MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Current Opinion in Genetics and Development' source. Thu, 09 Feb 2012 09:43:31 +0100 http://www.medworm.com/index.php?rid=5636043&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22265936%26dopt%3DAbstract Authors: McIntyre RE, van der Weyden L, Adams DJ Abstract Developments in high-throughput genome analysis and in computational tools have made it possible to rapidly profile entire cancer genomes with basepair resolution. In parallel with these advances, mouse models of cancer have evolved into powerful tools for cancer gene discovery. Here we discuss some of the approaches that may be used for cancer gene identification in the mouse and discuss how a cross-species 'oncogenomics' approach to cancer gene discovery represents a powerful strategy for finding genes that drive tumorigenesis. PMID: 22265936 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Development) Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5636043 Fri, 20 Jan 2012 05:00:00 +0100 5636043 http://www.medworm.com/index.php?rid=5636045&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22265226%26dopt%3DAbstract Authors: Dostie J, Bickmore WA Abstract For more than a century, developments in light microscopy drove forward our understanding of how chromosomes are organized in the cell nucleus. Now, derivatives of the chromosome conformation capture (3C) technique have harnessed the power of molecular biology to provide more genome-wide perspectives on the spatial relationships of DNA sequences, both within and between chromosomes. Here we consider what new insights into chromosome territory organization and mechanisms of gene regulation these innovative tools are providing, and the extent to which the visual and the molecular approaches give consistent or differing views of chromosome territory organization. PMID: 22265226 [PubMed - as supplied by publisher] (Source: Current Opinion in ... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5636045 Thu, 19 Jan 2012 05:00:00 +0100 5636045 http://www.medworm.com/index.php?rid=5636044&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22265227%26dopt%3DAbstract Authors: Yang J, Corces VG Abstract Insulators are DNA-protein complexes that can mediate interactions in cis or trans between different regions of the genome. Although originally defined on the basis of their ability to block enhancer-promoter communication or to serve as barriers against the spreading of heterochromatin in reporter systems, recent information suggests that their function is more nuanced and depends on the nature of the sequences brought together by contacts between specific insulator sites. Here we provide an overview of new evidence that has uncovered a wide range of functions for these sequences in addition to their two classical roles. PMID: 22265227 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Development) Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5636044 Thu, 19 Jan 2012 05:00:00 +0100 5636044 http://www.medworm.com/index.php?rid=5617806&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22243696%26dopt%3DAbstract Authors: Reyes-Turcu FE, Grewal SI Abstract The assembly of heterochromatin in eukaryotic genomes is critical for diverse chromosomal events including regulation of gene expression, silencing of repetitive DNA elements, proper segregation of chromosomes and maintenance of genomic integrity. Previous studies have shown that noncoding RNAs and the RNA interference (RNAi) machinery promote the assembly of heterochromatin that serves as a multipurpose platform for targeting effectors involved in various chromosomal processes. Recent work has revealed that RNAi-independent mechanisms, involving RNA processing activities that utilize both noncoding and coding RNAs, operate in the assembly of heterochromatin. These findings have established that, in addition to coding for proteins, mRNAs ... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5617806 Wed, 11 Jan 2012 05:00:00 +0100 5617806 http://www.medworm.com/index.php?rid=5543674&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22195775%26dopt%3DAbstract Authors: Abramowitz LK, Bartolomei MS Abstract Genomic imprinting is an epigenetic process resulting in the monoallelic parent-of-origin-specific expression of a subset of genes in the mammalian genome. The parental alleles are differentially marked by DNA methylation during gametogenesis when the genomes are in separate compartments. How methylation machinery recognizes and differentially modifies these imprinted regions in germ cells remains a key question in the field. While studies have focused on determining a sequence signature that alone could distinguish imprinted regions from the rest of the genome, recent reports do not support such a hypothesis. Rather, it is becoming clear that features such as transcription, histone modifications and higher order chromatin are employed... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5543674 Wed, 21 Dec 2011 05:00:00 +0100 5543674 http://www.medworm.com/index.php?rid=5523540&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22178420%26dopt%3DAbstract Authors: Pirrotta V, Li HB Abstract Polycomb group (PcG) proteins are concentrated in nuclear foci called PcG bodies. Although some of these foci are due to the tendency of PcG binding sites in the genome to occur in linear clusters, distant PcG sites can contact one another and in some cases congregate in the same PcG body when they are repressed. Experiments using transgenes containing PcG binding sites reveal that co-localization depends on the presence of insulator elements rather than of Polycomb Response Elements (PREs) and that it can occur also when the transgenes are in the active state. A model is proposed according to which insulator proteins mediate shuttling of PcG target genes between PcG bodies when repressed to transcription factories when transcriptionally active. ... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5523540 Fri, 16 Dec 2011 05:00:00 +0100 5523540 http://www.medworm.com/index.php?rid=5523539&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22178421%26dopt%3DAbstract Authors: Maddox PS, Corbett KD, Desai A Abstract Centromeres are epigenetically defined chromatin domains marked by the presence of the histone H3 variant CENP-A. Here we review recent structural and biochemical work on CENP-A, and advances in understanding the mechanisms that propagate and read centromeric chromatin domains. PMID: 22178421 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Development) Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5523539 Fri, 16 Dec 2011 05:00:00 +0100 5523539 http://www.medworm.com/index.php?rid=5523541&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22169023%26dopt%3DAbstract Authors: Krivega I, Dean A Abstract In metazoans, enhancers of gene transcription must often exert their effects over tens of kilobases of DNA. Over the past decade it has become clear that to do this, enhancers come into close proximity with target promoters with the looping away of intervening sequences. In a few cases proteins that are involved in the establishment or maintenance of these loops have been revealed but how the proper gene target is selected remains mysterious. Chromatin insulators had been appreciated as elements that play a role in enhancer fidelity through their enhancer blocking or barrier activity. However, recent work suggests more direct participation of insulators in enhancer-gene interactions. The emerging view begins to incorporate transcription activatio... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5523541 Mon, 12 Dec 2011 05:00:00 +0100 5523541 http://www.medworm.com/index.php?rid=5523542&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22155130%26dopt%3DAbstract Authors: Seitan VC, Merkenschlager M Abstract Cohesin defines the topology of chromosomes in mitosis and meiosis by holding sister chromatids together; more recently a role for cohesin in chromatin organisation and gene expression in interphase has emerged. PMID: 22155130 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Development) Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5523542 Fri, 09 Dec 2011 05:00:00 +0100 5523542 http://www.medworm.com/index.php?rid=5523543&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22154525%26dopt%3DAbstract Authors: Flynn RA, Chang HY Abstract Eukaryotic genomes are packaged into chromatin, where diverse histone modifications can demarcate chromatin domains that facilitate or block gene expression. While silent chromatin has been associated with long noncoding RNAs (lncRNAs) for some time, new studies suggest that noncoding RNAs also modulate the active chromatin state. Divergent, antisense, and enhancer-like intergenic noncoding RNAs can either activate or repress gene expression by altering histone H3 lysine 4 methylation. An emerging class of enhancer-like lncRNAs may link chromosome structure to chromatin state and establish active chromatin domains. The confluence of several new technologies promises to rapidly expand this fascinating topic of investigation. PMID: 22154525 [P... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5523543 Wed, 07 Dec 2011 05:00:00 +0100 5523543 http://www.medworm.com/index.php?rid=5409089&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22079435%26dopt%3DAbstract Authors: Perrimon N, Barkai N PMID: 22079435 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Development) Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5409089 Fri, 11 Nov 2011 05:00:00 +0100 5409089 http://www.medworm.com/index.php?rid=5409090&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22054717%26dopt%3DAbstract Authors: Gunsalus KC, Rhrissorrakrai K Abstract The network paradigm has become a pervasive theme in biology over the last decade, as increasingly large functional genomic datasets are being collected to interrogate regulatory influences, physical interactions, and genetic dependencies between genes, transcripts, and proteins. These 'molecular interaction' networks can be analyzed collectively and individually to define their global architecture and local patterns of connectivity. These structural features ultimately underlie functional properties such as robustness, modularity, component circuitry (e.g. feedback loops), dynamics, and responses to perturbations. This review focuses on recent progress in elucidating molecular interaction networks using different kinds of functional ... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5409090 Wed, 02 Nov 2011 04:00:00 +0100 5409090 http://www.medworm.com/index.php?rid=5409091&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22051606%26dopt%3DAbstract Authors: Balaban N Abstract When microorganisms are exposed to lethal agents, the initial exponential decay in survival is typically followed by a slower decrease. This tailing of the survival curve is due to persister cells that have differentiated into phenotypes with reduced sensitivity to the lethal agent. We review the environmental factors that have been shown to trigger such differentiation processes, as well as the network motifs that enable the co-existence of persistent and nonpersistent cells within genetically uniform populations. Threshold amplification of noise and bi-stability from positive feedback emerge as key motifs underlying persistence. PMID: 22051606 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Development) Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5409091 Tue, 01 Nov 2011 04:00:00 +0100 5409091 http://www.medworm.com/index.php?rid=5373575&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22033219%26dopt%3DAbstract Authors: Reuven P, Eldar A Abstract Bacterial phenotypic variability-the display of multiple distinct phenotypes in a genetically homogenous population of bacteria-emerges as an adaptive response to conflicting challenges. This creates an opportunity for social interactions which are able to dynamically redistribute cell fates within a community and to directly share the benefits of the different fates. While social interactions between cell fates can optimize community behavior, they also make the community vulnerable to exploitation. The aim of this review is to emphasize the social roles of phenotypic variability and introduce it as a communal rather than a single-cell property. Specifically, we present two prevalent perspectives on the forces shaping social interactions between... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5373575 Tue, 25 Oct 2011 04:00:00 +0100 5373575 http://www.medworm.com/index.php?rid=5373396&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22033220%26dopt%3DAbstract Authors: Nahmad M, Lander AD Abstract Few mechanistic ideas from the pre-molecular era of biology have had as enduring an impact as the morphogen concept. In the classical view, cells in developing embryos obtain positional information by measuring morphogen concentrations and comparing them with fixed concentration thresholds; as a result, graded morphogen distributions map into discrete spatial arrangements of gene expression. Recent studies on Hedgehog and other morphogens suggest that establishing patterns of gene expression may be less a function of absolute morphogen concentrations, than of the dynamics of signal transduction, gene expression, and gradient formation. The data point away from any universal model of morphogen interpretation and suggest that organisms use multip... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5373396 Tue, 25 Oct 2011 04:00:00 +0100 5373396 http://www.medworm.com/index.php?rid=5356859&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22005655%26dopt%3DAbstract Authors: Loewer A, Lahav G Abstract The human body is formed by trillions of individual cells. These cells work together with remarkable precision, first forming an adult organism out of a single fertilized egg, and then keeping the organism alive and functional for decades. To achieve this precision, one would assume that each individual cell reacts in a reliable, reproducible way to a given input, faithfully executing the required task. However, a growing number of studies investigating cellular processes on the level of single cells revealed large heterogeneity even among genetically identical cells of the same cell type. Here we discuss the sources of heterogeneity in mammalian systems; how cells ensure reliable processing of information despite fluctuations in their molecular ... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5356859 Sat, 15 Oct 2011 04:00:00 +0100 5356859 http://www.medworm.com/index.php?rid=5356860&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21996420%26dopt%3DAbstract Authors: Megason SG, Srinivas S, Dickinson ME, Hadjantonakis AK PMID: 21996420 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Development) Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5356860 Tue, 11 Oct 2011 04:00:00 +0100 5356860 http://www.medworm.com/index.php?rid=5306489&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21982413%26dopt%3DAbstract Authors: Grill SW Abstract Would it not be nice to understand the rules that govern how a small and round zygote reforms itself into a full blown three-dimensional and structured organism? The past decades have provided us with a wealth of knowledge about molecular mechanisms, intracellular behaviors, and tissue organization. However, we still do not know how to systematically integrate molecular mechanisms into descriptions that operate at larger scales involving higher-order structures such as the actomyosin cell cortex or an entire tissue. For development, it is the biophysical laws by which these structures deform, move, and restructure that are essential for morphogenetic rearrangements at developmental length- and time-scales. Recent years have seen the advent of systematic a... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5306489 Thu, 06 Oct 2011 04:00:00 +0100 5306489 http://www.medworm.com/index.php?rid=5293210&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21963791%26dopt%3DAbstract Authors: Weber M, Huisken J Abstract Within only a few short years, light sheet microscopy has contributed substantially to the emerging field of real-time developmental biology. Low photo-toxicity and high-speed multiview acquisition have made selective plane illumination microscopy (SPIM) a popular choice for studies of organ morphogenesis and function in zebrafish, Drosophila, and other model organisms. A multitude of different light sheet microscopes have emerged for the noninvasive imaging of specimens ranging from single molecules to cells, tissues, and entire embryos. In particular, developmental biology can benefit from the ability to watch developmental events occur in real time in an entire embryo, thereby advancing our understanding on how cells form tissues and organs. ... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5293210 Fri, 30 Sep 2011 04:00:00 +0100 5293210 http://www.medworm.com/index.php?rid=5293215&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21962441%26dopt%3DAbstract Authors: Ten Tusscher K, Scheres B Abstract Feedback and integration of information are of paramount importance for the robust functioning and dynamics of biological systems. In plant developmental biology, experimentation is increasingly combined with computational modeling to obtain a better understanding of how such regulatory interactions shape the systems' behavior. Here we highlight experimental and modeling studies on feedback loops and integration mechanisms involved in plant development. These studies have substantially expanded our understanding of previously characterized gene regulatory networks (GRNs). In addition, they illustrate the pervasiveness of regulatory interactions between seemingly unrelated processes and levels of organization. Modelers in plant development... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5293215 Thu, 29 Sep 2011 04:00:00 +0100 5293215 http://www.medworm.com/index.php?rid=5293214&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21962442%26dopt%3DAbstract Authors: Larina IV, Larin KV, Justice MJ, Dickinson ME Abstract Understanding the nature and mechanism of congenital defects of the different organ systems in humans has heavily relied on the analysis of the corresponding mutant phenotypes in rodent models. Optical Coherence Tomography (OCT) has recently emerged as a powerful tool to study early embryonic development. This non-invasive optical methodology does not require labeling and allows visualization of embryonic tissues with single cell resolution. Here, we will discuss how OCT can be applied for structural imaging of early mouse and rat embryos in static culture, cardiodynamic and blood flow analysis, and in utero embryonic imaging at later stages of gestation, demonstrating how OCT can be used to assess structural and funct... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5293214 Thu, 29 Sep 2011 04:00:00 +0100 5293214 http://www.medworm.com/index.php?rid=5293213&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21963131%26dopt%3DAbstract Authors: Soroldoni D, Oates AC Abstract Imaging rapidly changing gene expression during embryogenesis is a challenge for the development of probes and imaging techniques. The vertebrate Segmentation Clock is a genetic network that controls the subdivision of the elongating embryonic body axis into somites, the precursors of adult segmented structures, such as vertebrae. Because of its rapid oscillations, direct observation of gene expression in this system has proven difficult, and so is a benchmark for transgene design and imaging in vivo. Transgenic approaches using destabilized reporter cassettes in the mouse embryo have provided the first glimpses of this dynamic expression system. Nevertheless, improvements in temporal and spatial resolution, paired with the ability to make pr... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5293213 Wed, 28 Sep 2011 04:00:00 +0100 5293213 http://www.medworm.com/index.php?rid=5293212&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21963132%26dopt%3DAbstract Authors: Cheng KC, Xin X, Clark DP, La Riviere P Abstract Imaging can potentially make a major contribution to the Zebrafish Phenome Project, which will probe the functions of vertebrate genes through the generation and phenotyping of mutants. Imaging of whole animals at different developmental stages through adulthood will be used to infer biological function. Cell resolutions will be required to identify cellular mechanism and to detect a full range of organ effects. Light-based imaging of live zebrafish embryos is practical only up to ∼2 days of development, owing to increasing pigmentation and diminishing tissue lucency with age. The small size of the zebrafish makes possible whole-animal imaging at cell resolutions by histology and micron-scale tomography (microCT). The hist... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5293212 Wed, 28 Sep 2011 04:00:00 +0100 5293212 http://www.medworm.com/index.php?rid=5293211&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21963133%26dopt%3DAbstract Authors: Van Nostrand EL, Kim SK Abstract There has been a recent explosion in the wealth of genomic data available to C. elegans researchers, as efforts to characterize gene expression and its regulators at a molecular level have borne significant fruit. Detailed measurement of gene expression at a variety of developmental stages, and in numerous individual tissues, has dramatically increased our understanding of cell-type-specific gene expression networks. Characterization of the targets of transcription factors, chromatin-binding proteins, and miRNAs has provided genome-wide insights into the mechanisms governing gene expression. Development of new techniques have allowed this characterization to begin to shift from whole-organism studies to tissue-level, and even single-cell-le... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5293211 Wed, 28 Sep 2011 04:00:00 +0100 5293211 http://www.medworm.com/index.php?rid=5272327&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21959321%26dopt%3DAbstract Authors: Wartlick O, González-Gaitán M Abstract In the wing imaginal disc of Drosophila melanogaster, the morphogen Dpp controls growth, probably in an instructive manner. Many models for growth control by Dpp have been proposed and have been extensively discussed elsewhere. In this review, we speculate on how instructive growth control could provide a link between Dpp signaling and cell growth and/or cell cycle progression and so implement morphogenetic growth control on the cellular and molecular levels. PMID: 21959321 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Development) Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5272327 Tue, 27 Sep 2011 04:00:00 +0100 5272327 http://www.medworm.com/index.php?rid=5272329&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21955794%26dopt%3DAbstract Authors: Johnson JM, Jin M, Lew DJ Abstract Cell polarity is typically oriented by external cues such as cell-cell contacts, chemoattractants, or morphogen gradients. In the absence of such cues, however, many cells can spontaneously polarize in a random direction, suggesting the existence of an internal polarity-generating mechanism whose direction can be spatially biased by external cues. Spontaneous 'symmetry-breaking' polarization is likely to involve an autocatalytic process set off by small random fluctuations [1]. Here we review recent work on the nature of the autocatalytic process in budding yeast and on the question of why polarized cells only develop a single 'front'. PMID: 21955794 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Developm... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5272329 Mon, 26 Sep 2011 04:00:00 +0100 5272329 http://www.medworm.com/index.php?rid=5272328&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21955795%26dopt%3DAbstract Authors: Eaton S, Jülicher F Abstract Planar tissue polarity is a fundamental feature of many epithelia. Large-scale cell polarity patterns govern the orientation of external structures such as hairs and cilia. Tissue polarity patterns arise from the collective organization of cells, which are polarized individually. Such cell and tissue polarities are reflected in anisotropic distributions of proteins of the planar cell polarity (PCP) pathway. Here we give an overview on recent progress in understanding how large-scale patterns of tissue polarity are controlled. We highlight the role of active mechanical events in the organization of polarity patterns during the development of the pupal fly wing. Patterns of cell flow are generated by mechanical stresses exerted on the tissue as ... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5272328 Mon, 26 Sep 2011 04:00:00 +0100 5272328 http://www.medworm.com/index.php?rid=5272331&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21945001%26dopt%3DAbstract Authors: Sharpe J Abstract Recent developments in mesoscopic imaging-imaging at the level of tissues and organs, rather than the subcellular or molecular scale-are proving to be powerful for developmental biology. At the same time, these developments are also helping to emphasize an important distinction between two quite different approaches of how imaging is used. In the more traditional approach, images provide a direct insight into how a systems works-suggesting a mechanism or part of a mechanism. However an alternative approach is gaining ground, in which imaging is used to quantify the behaviour of a system, rather than directly assessing the mechanism. In this case the causal relationships of a system are inferred in a more indirect way-by comparing quantitative measurements... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5272331 Thu, 22 Sep 2011 04:00:00 +0100 5272331 http://www.medworm.com/index.php?rid=5272330&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21945002%26dopt%3DAbstract Authors: Folick A, Min W, Wang MC Abstract The recently developed Coherent Anti-stokes Raman Scattering (CARS) microscopy and Stimulated Raman Scattering (SRS) microscopy have provided new methods to visualize the localization and regulation of biological molecules without the use of invasive and potentially perturbative labels. They allow rapid imaging of specific molecules with high resolution and sensitivity. These tools have been effectively applied to the study of lipid metabolism using Caenorhabditis elegans as a genetic model, unraveling new lipid storage phenotypes and their regulatory mechanisms. Here we review the underlying principle of CARS and SRS microscopy, as well as their recent applications in lipid biology research in C. elegans. PMID: 21945002 [PubMed - as s... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5272330 Thu, 22 Sep 2011 04:00:00 +0100 5272330 http://www.medworm.com/index.php?rid=5256237&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21937218%26dopt%3DAbstract Authors: Plouhinec JL, Zakin L, De Robertis EM Abstract Embryonic morphogenetic programs coordinate cell behavior to ensure robust pattern formation. Having identified components of those programs by molecular genetics, developmental biology is now borrowing concepts and tools from systems biology to decode their regulatory logic. Dorsal-ventral (D-V) patterning of the frog gastrula by Bone Morphogenetic Proteins (BMPs) is one of the best studied examples of a self-regulating embryonic patterning system. Embryological analyses and mathematical modeling are revealing that the BMP activity gradient is maintained by a directed flow of BMP ligands towards the ventral side. Pattern robustness is ensured through feedback control of the levels of extracellular BMP pathway modulators that ... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5256237 Mon, 19 Sep 2011 04:00:00 +0100 5256237 http://www.medworm.com/index.php?rid=5256239&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21930371%26dopt%3DAbstract Authors: Blanchard GB, Adams RJ Abstract The elaborate changes in morphology of an organism during development are the result of mechanical contributions that are a mixture of those generated locally and those that influence from a distance. We would like to know how chemical and mechanical information is transmitted and transduced, how work is done to achieve robust morphogenesis and why it sometimes fails. We introduce a scheme for separating the influence of two classes of forces. Active intrinsic forces integrate up levels of scale to shape tissues. Counter-currently, extrinsic forces exert influence from higher levels downwards and feed back directly and indirectly upon the intrinsic behaviours. We identify the measurable signatures of different kinds of forces and identify th... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5256239 Sat, 17 Sep 2011 04:00:00 +0100 5256239 http://www.medworm.com/index.php?rid=5256238&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21930372%26dopt%3DAbstract Authors: He L, Wang X, Montell DJ Abstract Drosophila oogenesis is a powerful model for the study of numerous questions in cell and developmental biology. In addition to its longstanding value as a genetically tractable model of organogenesis, recently it has emerged as an excellent system in which to combine genetics and live imaging. Rapidly improving ex vivo culture conditions, new fluorescent biosensors and photo-manipulation tools, and advances in microscopy have allowed direct observation in real time of processes such as stem cell self-renewal, collective cell migration, and polarized mRNA and protein transport. In addition, entirely new phenomena have been discovered, including revolution of the follicle within the basement membrane and oscillating assembly and disassembly ... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5256238 Sat, 17 Sep 2011 04:00:00 +0100 5256238 http://www.medworm.com/index.php?rid=5256240&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21924603%26dopt%3DAbstract Authors: Mojzisova H, Vermot J Abstract The need for quantification and real time visualization of developmental processes has called for increasingly sophisticated imaging techniques. Among them, multiphoton microscopy reveals itself to be an extremely versatile tool owing to its unique ability to combine fluorescent imaging, laser ablation, and higher harmonic generation. Furthermore, recent advances in femtosecond lasers and optical parametric oscillators (OPO) are now opening doors for imaging at unprecedented wavelengths centered in the tissue transparency window. This Review describes promising multiphoton approaches using OPO and the growing number of useful applications of non-linear microscopy in the field of developmental biology. Basic characteristics associated with the... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5256240 Wed, 14 Sep 2011 04:00:00 +0100 5256240 http://www.medworm.com/index.php?rid=5224428&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21917444%26dopt%3DAbstract Authors: Supatto W, Truong TV, Débarre D, Beaurepaire E Abstract Multiphoton imaging is a promising approach for addressing current issues in systems biology and high-content investigation of embryonic development. Recent advances in multiphoton microscopy, including light-sheet illumination, optimized laser scanning, adaptive and label-free strategies, open new opportunities for embryo imaging. However, the literature is often unclear about which microscopy technique is most adapted for achieving specific experimental goals. In this review, we describe and discuss the key concepts of imaging speed, imaging depth, photodamage, and nonlinear contrast mechanisms in the context of recent advances in live embryo imaging. We illustrate the potentials of these new imaging approaches wit... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5224428 Mon, 12 Sep 2011 04:00:00 +0100 5224428 http://www.medworm.com/index.php?rid=5214616&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907568%26dopt%3DAbstract Authors: Nieman BJ, Wong MD, Henkelman RM Abstract Mammalian development is a sophisticated program coordinated by a complex set of genetic and physiological factors. Alterations in anatomy or morphology provide intrinsic measures of progress in or deviations from this program. Emerging three-dimensional imaging methods now allow for more sophisticated morphological assessment than ever before, enabling comprehensive phenotyping, visualization of anatomical context and patterns, automated and quantitative morphological analysis, as well as improved understanding of the developmental time course. Furthermore, these imaging tools are becoming increasingly available and will consequently play a prominent role in elucidating the factors that direct and influence mammalian development. ... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5214616 Thu, 08 Sep 2011 04:00:00 +0100 5214616 http://www.medworm.com/index.php?rid=5214620&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21893407%26dopt%3DAbstract Authors: Trier SM, Davidson LA Abstract The importance of mechanical signals during embryogenesis and development, through both intercellular and extracellular signals, is coming into focus. It is widely hypothesized that physical forces help to guide the shape, cellular differentiation and the patterning of tissues. To test these ideas many classical engineering principles and imaging technologies are being adapted. Recent advances in microscopy, mechanical testing and genetic and pharmacological techniques, alongside computational models are helping to dissect the activity of mechanical signals in development at the cellular and molecular level. These inroads are providing maps of mechanical changes in tissue structure and stiffness, and will permit deeper insights into the role ... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5214620 Sat, 03 Sep 2011 04:00:00 +0100 5214620 http://www.medworm.com/index.php?rid=5214619&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21893408%26dopt%3DAbstract Authors: Mohun TJ, Weninger WJ Abstract Development of the heart in vertebrate embryos is a complex process in which the organ is continually remodelled as chambers are formed, valves sculpted and connections established to the developing vascular system. Investigating the genetic programmes driving these changes and the environmental factors that may influence them is critical for our understanding of congenital heart disease. A recurrent challenge in this work is how to integrate studies as diverse as those of cardiac gene function and regulation with an appreciation of the localised interactions between cardiac tissues not to mention the manner in which both may be affected by cardiac function itself. Meeting this challenge requires an accurate way to analyse the changes in 3D m... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5214619 Sat, 03 Sep 2011 04:00:00 +0100 5214619 http://www.medworm.com/index.php?rid=5214618&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21893409%26dopt%3DAbstract Authors: Mason FM, Martin AC Abstract Throughout the lifespan of an organism, shape changes are necessary for cells to carry out their essential functions. Nowhere is this more dramatic than embryonic development and gastrulation, when cell shape changes drive large-scale rearrangements in tissue architecture to establish the body plan of the organism. A longstanding question for both cell and developmental biologists has been how are forces generated to change cell shape? Recent studies in both cell culture and developing embryos have combined live imaging, computational analysis, genetics, and biophysics to identify ratchet-like behaviors in actomyosin networks that operate to incrementally change cell shape, drive cell movement, and deform tissues. Our analysis of several cell s... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5214618 Sat, 03 Sep 2011 04:00:00 +0100 5214618 http://www.medworm.com/index.php?rid=5214617&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21893410%26dopt%3DAbstract Authors: Luengo-Oroz M, Ledesma-Carbayo M, Peyriéras N, Santos A Abstract The digital reconstruction of the embryogenesis of model organisms from 3D+time data is revolutionizing practices in quantitative and integrative Developmental Biology. A manual and fully supervised image analysis of the massive complex data acquired with new microscopy technologies is no longer an option and automated image processing methods are required to fully exploit the potential of imaging data for biological insights. Current developments and challenges in biological image processing include algorithms for microscopy multiview fusion, cell nucleus tracking for quasi-perfect lineage reconstruction, segmentation, and validation methodologies for cell membrane shape identification, single cell gene exp... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5214617 Sat, 03 Sep 2011 04:00:00 +0100 5214617 http://www.medworm.com/index.php?rid=5214621&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21889888%26dopt%3DAbstract Authors: Wunderlich Z, Depace AH Abstract Quantitative models of developmental processes can provide insights at multiple scales. Ultimately, models may be particularly informative for key questions about network level behavior during development such as how does the system respond to environmental perturbation, or operate reliably in different genetic backgrounds? The transcriptional networks that pattern the Drosophila embryo have been the subject of numerous quantitative experimental studies coupled to modeling frameworks in recent years. In this review, we describe three studies that consider these networks at different levels of molecular detail and therefore result in different types of insights. We also discuss other developmental transcriptional networks operating in Drosop... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5214621 Thu, 01 Sep 2011 04:00:00 +0100 5214621 http://www.medworm.com/index.php?rid=5214622&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21889328%26dopt%3DAbstract Authors: Leinwand SG, Chalasani SH Abstract Olfactory networks, comprised of sensory neurons and interneurons, detect and process changes in the chemical environment to drive animal behavior. Recent studies combining genetics with behavioral analyses and imaging in worms, flies and mice have revealed new insights into the mechanisms of olfaction. In this discussion, we focus on three interesting findings. First, sensory neuron responses to odor are modulated by neuropeptides. This modulation might serve to extend the range of responses of the sensory neurons and also to integrate internal state information into the chemosensory circuit. Second, genetic tracing studies in mice and flies have shown that the first layer of connections in chemosensory circuits from olfactory epithelium... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5214622 Wed, 31 Aug 2011 04:00:00 +0100 5214622 http://www.medworm.com/index.php?rid=5214623&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21873045%26dopt%3DAbstract Authors: Ben-Zvi D, Shilo BZ, Barkai N Abstract Individuals of the same or closely related species can vary substantially in size. Still, the proportions within and between tissues are precisely kept. This adaptation of pattern with size termed scaling, is receiving a growing attention. We review experimental evidence for scaling, and describe theoretical models for mechanisms that scale morphogen gradients. We particularly note the Expansion-Repression mechanism, in which a diffusible molecule that positively regulates the morphogen gradient width is repressed by morphogen signaling. The Expansion-Repression circuit provides scaling in a robust manner and is readily implemented by a host of molecular mechanisms. We suggest means for identifying such a circuit in a system of intere... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5214623 Fri, 26 Aug 2011 04:00:00 +0100 5214623 http://www.medworm.com/index.php?rid=5170194&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21862314%26dopt%3DAbstract Authors: Tomer R, Khairy K, Keller PJ Abstract Light sheet-based fluorescence microscopy (LSFM) is emerging as a powerful imaging technique for the life sciences. LSFM provides an exceptionally high imaging speed, high signal-to-noise ratio, low level of photo-bleaching and good optical penetration depth. This unique combination of capabilities makes light sheet-based microscopes highly suitable for live imaging applications. There is an outstanding potential in applying this technology to the quantitative study of embryonic development. Here, we provide an overview of the different basic implementations of LSFM, review recent technical advances in the field and highlight applications in the context of embryonic development. We conclude with a discussion of promising future directi... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5170194 Thu, 18 Aug 2011 23:00:00 +0100 5170194 http://www.medworm.com/index.php?rid=5170193&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21862315%26dopt%3DAbstract Authors: Chen S, Wang S, Xie T Abstract Germline stem cells (GSCs) were the first stem cells demonstrated to be regulated by the microenvironment or niche in the Drosophila ovary a decade ago. In the Drosophila ovary, as a stem cell divides, one daughter remaining in the niche continues to self-renew, and the other daughter positioned outside the niche undergoes differentiation. The niche produces bone morphogenetic proteins (BMPs) that only act within one cell diameter to ensure that at every division only one of two GSC daughters self-renews and thus maintains a stable GSC pool. Within the past decade, great progress has been made toward understanding how functions of BMP niche signals are restricted to GSCs. In this review, we have discussed multiple levels of control underlying... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5170193 Thu, 18 Aug 2011 23:00:00 +0100 5170193 http://www.medworm.com/index.php?rid=5170192&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21862316%26dopt%3DAbstract Authors: Shaya O, Sprinzak D Abstract Notch signaling is the canonical signaling pathway between neighboring cells. It plays an important role in fine-grained patterning processes such as the formation of checkerboard-like differentiation patterns and sharp boundaries between developing tissues. While detailed information about many of the genes and proteins involved have been identified, we still lack a quantitative mechanistic understanding of these processes. Here we discuss several recent studies that provide novel insights into Notch-dependent patterning by combining mathematical models with quantitative experimental results. Such approaches allow identification of mechanisms and design principles controlling how patterns are generated in a reproducible and robust manner. ... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5170192 Thu, 18 Aug 2011 23:00:00 +0100 5170192 http://www.medworm.com/index.php?rid=5170191&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21862317%26dopt%3DAbstract Authors: Larson DR Abstract Single-cell microscopy studies have the potential to provide an unprecedented view of gene expression with exquisite spatial and temporal sensitivity. However, there is a challenge to connect the holistic cellular view with a reductionist biochemical view. In particular, experimental efforts to characterize the in vivo regulation of transcription have focused primarily on measurements of the dynamics of transcription factors and chromatin modifying factors. Such measurements have elucidated the transient nature of many nuclear interactions. In the past few years, experimental approaches have emerged that allow for interrogation of the output of transcription at the single-molecule, single-cell level. Here, I summarize the experimental results and models ... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5170191 Thu, 18 Aug 2011 23:00:00 +0100 5170191 http://www.medworm.com/index.php?rid=5170190&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21862318%26dopt%3DAbstract Authors: Cheung LS, Schüpbach T, Shvartsman SY Abstract Spatial patterns of cell differentiation in developing tissues can be controlled by receptor tyrosine kinase (RTK) signaling gradients, which may form when locally secreted ligands activate uniformly expressed receptors. Graded activation of RTKs can span multiple cell diameters, giving rise to spatiotemporal patterns of signaling through the Extracellular Signal Regulated/Mitogen Activated Protein Kinase (ERK/MAPK), which connects receptor activation to multiple aspects of tissue morphogenesis. This general mechanism has been identified in numerous developmental contexts, from body axis specification in insects to patterning of the mammalian neocortex. We review recent quantitative studies of this mechanism in Drosophila oog... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5170190 Thu, 18 Aug 2011 23:00:00 +0100 5170190 http://www.medworm.com/index.php?rid=5170189&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21862319%26dopt%3DAbstract Authors: Das P Abstract The growth of tissues, organs or organisms derives from the coordinated activities of complex genetic regulatory networks. In addition to its molecular underpinnings, growth also generally involves significant changes in geometry. To fully understand morphogenesis in its molecular and physical contexts the development of an interdisciplinary approach is required associating biology, mathematics, and physics, which held together by computer science. Growth quantitation and digital simulations have been developed to generate and test the plausibilities of complex hypotheses. Increasingly, real-time live imaging protocols are becoming an essential part of this process. In this review, I discuss the evolution of imaging techniques in plant developmental biology ... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5170189 Thu, 18 Aug 2011 23:00:00 +0100 5170189 http://www.medworm.com/index.php?rid=5133776&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21840706%26dopt%3DAbstract Authors: Franze K While our understanding of the influence of biochemical signaling on cell functioning is increasing rapidly, the consequences of mechanical signaling are currently poorly understood. However, cells of the nervous system respond to their mechanical environment; their mechanosensitivity has important implications for development and disease. Atomic force microscopy provides a powerful technique to investigate the mechanical interaction of cells with their environment with high resolution. This method can be used to obtain high-resolution surface topographies, stiffness maps, and apply well-defined forces to samples at different length scales. This review summarizes recent advances of atomic force microscopy, provides an overview about state-of-the-art measurements, and ... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5133776 Thu, 11 Aug 2011 23:00:00 +0100 5133776 http://www.medworm.com/index.php?rid=5086931&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21764293%26dopt%3DAbstract Authors: Darnell J Recent data suggest that the levels of many synaptic proteins may be tightly controlled by the opposing processes of new translation and protein turnover in neurons. Alterations in this balance or in the levels of such dosage-sensitive proteins that result in altered stoichiometry of protein complexes at developing and remodeling synapses may underlie several human cognitive diseases including Fragile X Syndrome, autism spectrum disorders, Angelman syndrome and non-syndromic mental retardation. While a significant amount is known about the transduction of membrane signals to the translational apparatus through kinase cascades acting on general translation factors, much less is understood about how such signals may influence the activity of mRNA-specific regulators, t... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5086931 Thu, 14 Jul 2011 23:00:00 +0100 5086931 http://www.medworm.com/index.php?rid=5086915&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21764576%26dopt%3DAbstract Authors: Ishizu H, Nagao A, Siomi H RNA silencing pathways are now recognized to participate in essential cellular functions ranging from the regulation of mRNA turnover to the suppression of the activity of potentially deleterious transposable elements (TEs). Piwi-interacting RNAs (piRNAs) are germline-specific, small silencing RNAs that suppress TE activity and maintain genome integrity during germline development. In Drosophila ovarian somatic cells, piRNAs are processed from long single-stranded RNAs by a Dicer-independent pathway and are loaded onto Piwi in the cytoplasm. The Piwi-piRNA complexes are then transported into the nucleus to exert TE silencing. This mechanism involves gatekeepers for a functional Piwi-piRNA complex to be imported, which parallels with the Tetrahymena T... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5086915 Wed, 13 Jul 2011 23:00:00 +0100 5086915 http://www.medworm.com/index.php?rid=5037343&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21741823%26dopt%3DAbstract Authors: Richter JD, Treisman JE PMID: 21741823 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Development) Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=5037343 Wed, 06 Jul 2011 23:00:00 +0100 5037343 http://www.medworm.com/index.php?rid=4894180&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21636265%26dopt%3DAbstract Authors: Subramanyam D, Blelloch R MicroRNAs (miRNAs) are 22nt non-coding RNAs that regulate expression of downstream targets by messenger RNA (mRNA) destabilization and translational inhibition. A large number of eukaryotic mRNAs are targeted by miRNAs, with many individual mRNAs being targeted by multiple miRNAs. Further, a single miRNA can target hundreds of mRNAs, making these small RNAs powerful regulators of cell fate decisions. Such regulation by miRNAs has been observed in the maintenance of the embryonic stem cell (ESC) cell cycle and during ESC differentiation. MiRNAs can also promote the dedifferentiation of somatic cells to induced pluripotent stem cells. During this process they target multiple downstream genes, which represent important nodes of key cellular processes. He... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4894180 Mon, 30 May 2011 23:00:00 +0100 4894180 http://www.medworm.com/index.php?rid=4849071&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21592778%26dopt%3DAbstract Authors: Saj A, Lai EC A limited set of cell-cell signaling pathways presides over the vast majority of animal developmental events. The typical raison d'etre for signal transduction is to control the transcription of protein-coding genes. However, with the recent appreciation of microRNAs, growing attention has been paid towards understanding how signaling pathways intertwine with microRNA-mediated regulation. This review highlights recent studies that uncover unexpected modes of microRNA regulation by cell signaling pathways. Not only can miRNA transcription be positively or negatively regulated by cell signaling, the TGF-β/BMP pathways and Ras/MAPK pathways have now been shown to directly influence microRNA biogenesis to mediate substantial cellular phenotypes. PMID: 21592778 [... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4849071 Sun, 15 May 2011 23:00:00 +0100 4849071 http://www.medworm.com/index.php?rid=4849086&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21571521%26dopt%3DAbstract Authors: Silberberg G, Ohman M RNA editing is emerging as a wide-spread phenomenon both in coding and non-coding RNA regions. While the mechanisms underlying many of these post-transcriptional modifications have not been elucidated, RNA editing by nucleotide deamination has been known for over two decades as a mechanism to generate base substitutions. With the recently growing use of high throughput sequencing technologies, knowledge about the frequency and diversity of RNA nucleotide substitutions has vastly increased. In this review we will highlight recent findings within this field, and illustrate how novel technologies have made it possible to detect and measure the efficiency of editing in an unprecedented accuracy and robustness. Future prospects for the detection of important t... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4849086 Thu, 12 May 2011 23:00:00 +0100 4849086 http://www.medworm.com/index.php?rid=4849092&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21561760%26dopt%3DAbstract Authors: Siegel G, Saba R, Schratt G The regulation of synapse formation and plasticity in the developing and adult brain underlies a complex interplay of intrinsic genetic programs and extrinsic factors. Recent research identified microRNAs (miRNAs), a class of small non-coding RNAs, as a new functional layer in this regulatory network. Within only a few years, a network of synaptic miRNAs and their target genes has been extensively characterized, highlighting the importance of this mechanism for synapse development and physiology. Very recent data further provide insight into activity-dependent regulation of miRNAs, thereby connecting miRNAs with adaptive processes of neural circuits. First direct links between miRNA dysfunction and synaptic pathologies are emerging, raising the inte... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4849092 Sun, 08 May 2011 23:00:00 +0100 4849092 http://www.medworm.com/index.php?rid=4849129&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21550797%26dopt%3DAbstract Authors: Hwang J, Maquat LE Nonsense-mediated mRNA decay (NMD) is a well-studied cellular quality-control pathway. It decreases the half-lives of eukaryotic mRNAs that aberrantly contain premature termination codons and additionally regulates an estimated 10-20% of normal transcripts. NMD factors play crucial roles during embryogenesis in many animals. Here, we review data indicating that NMD factors are required for proper embryogenesis by discussing the abnormal developmental phenotypes that result when the abundance of individual NMD factors is either downregulated or completely eliminated. We conclude that while NMD per se affects the embryogenesis of all animals, it is required to avoid embryonic lethality in only some animals. The critical roles of many NMD factors in other metab... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4849129 Thu, 05 May 2011 23:00:00 +0100 4849129 http://www.medworm.com/index.php?rid=4794643&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21543223%26dopt%3DAbstract Authors: Stumpf CR, Ruggero D Deregulations in translational control are critical features of cancer initiation and progression. Activation of key oncogenic pathways promotes rapid and dramatic translational reprogramming, not simply by increasing overall protein synthesis, but also by modulating specific mRNA networks that promote cellular transformation. Additionally, ribosomopathies caused by mutations in ribosome components alter translational regulation leading to specific pathological features, including cancer susceptibility. Exciting advances in our understanding of translational control in cancer have illuminated a striking specificity innate to the translational apparatus. Characterizing this specificity will provide novel insights into how cells normally utilize translationa... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4794643 Sun, 01 May 2011 23:00:00 +0100 4794643 http://www.medworm.com/index.php?rid=4794646&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21536427%26dopt%3DAbstract Authors: Macdonald PM Localization of mRNAs to subcellular domains can enrich proteins at sites where they function. Coordination with translational control can ensure that the encoded proteins will not appear elsewhere, an important property for factors that control cell fate or body patterning. Here I focus on two aspects of mRNA localization. One is the question of how mRNAs that undergo directed transport by a shared mechanism are bound to the transport machinery, and why localization signals from these mRNAs have very diverse sequences. The second topic concerns the role of particles, in which localized mRNAs often appear. Recent evidence highlights the importance of such assemblies, and the possibility that close association of mRNAs confers community effects and a novel form of ... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4794646 Fri, 29 Apr 2011 23:00:00 +0100 4794646 http://www.medworm.com/index.php?rid=4794645&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21536428%26dopt%3DAbstract Authors: Villalba A, Coll O, Gebauer F Cytoplasmic polyadenylation is the process by which dormant, translationally inactive mRNAs become activated via the elongation of their poly(A) tails in the cytoplasm. This process is regulated by the conserved cytoplasmic polyadenylation element binding (CPEB) protein family. Recent studies have advanced our understanding of the molecular code that dictates the timing of CPEB-mediated poly(A) tail elongation and the extent of translational activation. In addition, evidence for CPEB-independent mechanisms has accumulated, and the breath of biological circumstances in which cytoplasmic polyadenylation plays a role has expanded. These observations underscore the versatility of CPEB as a translational regulator, and highlight the diversity of cytopl... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4794645 Fri, 29 Apr 2011 23:00:00 +0100 4794645 http://www.medworm.com/index.php?rid=4794644&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21536429%26dopt%3DAbstract Authors: Marín O, Gleeson JG PMID: 21536429 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Development) Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4794644 Fri, 29 Apr 2011 23:00:00 +0100 4794644 http://www.medworm.com/index.php?rid=4794650&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21530229%26dopt%3DAbstract Authors: Ambros V MicroRNAs regulate temporal transitions in gene expression associated with cell fate progression and differentiation throughout animal development. Genetic analysis of developmental timing in the nematode Caenorhabditis elegans identified two evolutionarily conserved microRNAs, lin-4/mir-125 and let-7, that regulate cell fate progression and differentiation in C. elegans cell lineages. MicroRNAs perform analogous developmental timing functions in other animals, including mammals. By regulating cell fate choices and transitions between pluripotency and differentiation, microRNAs help to orchestrate developmental events throughout the developing animal, and to play tissue homeostasis roles important for disease, including cancer. PMID: 21530229 [PubMed - as supplied... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4794650 Wed, 27 Apr 2011 23:00:00 +0100 4794650 http://www.medworm.com/index.php?rid=4794649&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21530230%26dopt%3DAbstract Authors: Jung H, O'Hare CM, Holt CE Axonal growth cones (GCs) steer in response to extrinsic cues using mechanisms that include local protein synthesis. This adaptive form of gene regulation occurs with spatial precision and depends on subcellular mRNA localisation. Recent genome-wide studies have shown unexpectedly complex and dynamically changing mRNA repertoires in growing axons and GCs. Axonal targeting of some transcripts seems to be highly selective and involves sequence diversity in non-coding regions generated by transcriptional and/or post-transcriptional mechanisms. New evidence reports direct coupling of a guidance receptor to the protein synthesis machinery and other findings demonstrate that some guidance cues can repress translation. The recent findings shed further light... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4794649 Tue, 26 Apr 2011 23:00:00 +0100 4794649 http://www.medworm.com/index.php?rid=4794648&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21530231%26dopt%3DAbstract Authors: Swanger SA, Bassell GJ Neurons are exquisitely polarized cells that extend intricate axonal and dendritic arbors. Developmental cues guide axons and dendrites into circuits by inducing rapid changes in local protein expression and cytoskeletal structure. Neurons can transduce these signals through local mRNA regulation. Here, we review the latest insights regarding post-transcriptional control of gene expression through mRNA transport and local protein synthesis in developing neurons. We focus on local mRNA regulation during axon growth and guidance, dendrite morphogenesis, and synapse formation and refinement. Dysregulated mRNA transport and translation in neurological disorders are also discussed. The collection of molecules and mechanisms reviewed includes sequence-specific... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4794648 Tue, 26 Apr 2011 23:00:00 +0100 4794648 http://www.medworm.com/index.php?rid=4794647&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21530232%26dopt%3DAbstract Authors: McManus CJ, Graveley BR Alternative splicing is a widespread means of increasing protein diversity and regulating gene expression in eukaryotes. Much progress has been made in understanding the proteins involved in regulating alternative splicing, the sequences they bind to, and how these interactions lead to changes in splicing patterns. However, several recent studies have identified other players involved in regulating alternative splicing. A major theme emerging from these studies is that RNA secondary structures play an under appreciated role in the regulation of alternative splicing. This review provides an overview of the basic aspects of splicing regulation and highlights recent progress in understanding the role of RNA secondary structure in this process. PMID: 21... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4794647 Tue, 26 Apr 2011 23:00:00 +0100 4794647 http://www.medworm.com/index.php?rid=4794651&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21514141%26dopt%3DAbstract Authors: Llorian M, Smith CW Muscle was one of the first tissues in which alternative splicing was widely observed. Cloning and sequencing of muscle-derived cDNAs in the early 1980's revealed that many of the abundant contractile proteins arise by alternative splicing of genes that are more widely expressed. Consequently alternative splicing events in contractile protein genes have long been used as models to dissect the mechanisms of alternative splicing. Transcriptomic and computational analyses have complemented traditional molecular analyses of alternative splicing in muscle and other tissues, illuminating the general underlying principles of coregulated splicing programs. This has culminated in the first attempt to computationally predict tissue-specific changes in splicing. Inves... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4794651 Tue, 19 Apr 2011 23:00:00 +0100 4794651 http://www.medworm.com/index.php?rid=4742721&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21511457%26dopt%3DAbstract Authors: Grabowski P The spatial and temporal control of alternative splicing is a major mechanism used to generate proteomic diversity in the brain. Microarray and Next Generation Sequencing approaches reveal mechanistic insights about networks of tissue-specific RNA binding proteins and micro RNAs that coordinate suites of alternative splicing patterns during neuronal differentiation. In the context of large-scale changes, one alternative splicing switch during embryonic brain development is crucial for neuronal migration and the laminar organization of the cerebral cortex. A major challenge to understand alternative splicing at the systems level is now being approached by the design of integrative modeling approaches that predict the combinatorial control of brain-specific exons. ... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4742721 Mon, 18 Apr 2011 23:00:00 +0100 4742721 http://www.medworm.com/index.php?rid=4742722&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21497503%26dopt%3DAbstract Authors: Luco RF, Misteli T Large portions of the genome undergo alternative pre-mRNA splicing in often intricate patterns. Alternative splicing regulation requires extensive control mechanisms since errors can have deleterious consequences and may lead to developmental defects and disease. Recent work has identified a complex network of regulatory RNA elements which guide splicing decisions. In addition, the discovery that transcription and splicing are intimately coupled has opened up new directions into alternative splicing regulation. Work at the interface of chromatin and RNA biology has revealed unexpected molecular links between histone modifications, the transcription machinery, and non-coding RNAs (ncRNAs) in the determination of alternative splicing patterns. PMID: 214975... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4742722 Wed, 13 Apr 2011 23:00:00 +0100 4742722 http://www.medworm.com/index.php?rid=4742724&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21497081%26dopt%3DAbstract Authors: Walser CB, Lipshitz HD In all animals, a key event in the transition from maternal control of development to control by products of the zygotic genome is the elimination of a significant fraction of the mRNAs loaded into the egg by the mother. Clearance of these maternal mRNAs is accomplished by two activities: the first is maternally encoded while the second requires zygotic transcription. Recent advances include identification of RNA-binding proteins that function as specificity factors to direct the maternal degradation machinery to its target mRNAs; small RNAs-most notably microRNAs-that function as components of the zygotically encoded activity; signaling pathways that trigger production and/or activation of the clearance mechanism in early embryos; and mechanisms for spa... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4742724 Tue, 12 Apr 2011 23:00:00 +0100 4742724 http://www.medworm.com/index.php?rid=4742723&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21497082%26dopt%3DAbstract Authors: Vlasova-St Louis I, Bohjanen PR The GU-rich element (GRE) was identified as a conserved sequence enriched in the 3' UTR of human transcripts that exhibited rapid mRNA turnover. In mammalian cells, binding to GREs by the protein CELF1 coordinates mRNA decay of networks of transcripts involved in cell growth, migration, and apoptosis. Depending on the context, GREs and CELF1 also regulate pre-mRNA splicing and translation. GREs are highly conserved throughout evolution and play important roles in the development of organisms ranging from worms to man. In humans, abnormal GRE-mediated regulation contributes to disease states and cancer. Thus, GREs and CELF proteins serve critical functions in gene expression regulation and define an important evolutionarily conserved posttranscri... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4742723 Tue, 12 Apr 2011 23:00:00 +0100 4742723 http://www.medworm.com/index.php?rid=4742725&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21474300%26dopt%3DAbstract Authors: Salz HK The gene regulatory networks that control sex determination vary between species. Despite these differences, comparative studies in insects have found that alternative splicing is reiteratively used in evolution to control expression of the key sex-determining genes. Sex determination is best understood in Drosophila where activation of the RNA binding protein-encoding gene Sex-lethal is the central female-determining event. Sex-lethal serves as a genetic switch because once activated it controls its own expression by a positive feedback splicing mechanism. Sex fate choice in is also maintained by self-sustaining positive feedback splicing mechanisms in other dipteran and hymenopteran insects, although different RNA binding protein-encoding genes function as the binary... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4742725 Mon, 04 Apr 2011 23:00:00 +0100 4742725 http://www.medworm.com/index.php?rid=4628405&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21420851%26dopt%3DAbstract Authors: Papai G, Weil PA, Schultz P The general transcription factor IID is a key player in the early events of gene expression. TFIID is a multisubunit complex composed of the TATA binding protein and at least 13 TBP associated factors (TAfs) which recognize the promoter of protein coding genes in an activator dependant way. This review highlights recent findings on the molecular architecture and dynamics of TFIID. The structural analysis of functional transcription complexes formed by TFIID, TFIIA, activators and/or promoter DNA illuminates the faculty of TFIID to adjust to various promoter architectures and highlights its role as a platform for preinitiation complex assembly. PMID: 21420851 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Development... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4628405 Fri, 18 Mar 2011 00:00:00 +0100 4628405 http://www.medworm.com/index.php?rid=4628406&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21411309%26dopt%3DAbstract Authors: Frappier L, Verrijzer CP Protein ubiquitylation is involved in the regulation of virtually all aspects of eukaryotic cell biology, including gene expression. The central function of E3 ubiquitin ligases in target selection is well established. More recently, it has become appreciated that deubiquitylating enzymes (DUBs) are crucial components of ubiquitin-regulated cellular switches. Here, we discuss advances in our understanding of how DUBs regulate chromatin dynamics and gene expression. DUBs are integral components of the transcription machinery, involved in both gene activation and repression. They modulate the ubiquitylation status of histones H2A and H2B, which play pivotal roles in a cascade of molecular events that determine chromatin status. A DUB module in the SAGA c... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4628406 Mon, 14 Mar 2011 00:00:00 +0100 4628406 http://www.medworm.com/index.php?rid=4628407&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21397493%26dopt%3DAbstract Authors: Godfrey C, Foley AR, Clement E, Muntoni F A common group of muscular dystrophies is associated with the aberrant glycosylation of α-dystroglycan. These clinically heterogeneous disorders, collectively termed dystroglycanopathies, are often associated with central nervous system and more rarely eye pathology. Defects in a total of eight putative and demonstrated glycosyltransferases or accessory proteins of glycosyltransferases have been shown to cause a dystroglycanopathy phenotype. In recent years the systematic analysis of large patient cohorts has uncovered a complex relationship between the underlying genetic defect and the resulting clinical phenotype. These studies have also drawn attention to the high proportion of patients that remain without a genetic diagnosis impli... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4628407 Thu, 10 Mar 2011 00:00:00 +0100 4628407 http://www.medworm.com/index.php?rid=4566441&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21377351%26dopt%3DAbstract Authors: Shilatifard A, Verrijzer P PMID: 21377351 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Development) Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4566441 Fri, 04 Mar 2011 00:00:00 +0100 4566441 http://www.medworm.com/index.php?rid=4566442&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21376566%26dopt%3DAbstract Authors: Rasetti R, Weinberger DR The small effect size of most individual risk factors for psychiatric disorders likely reflects biological heterogeneity and diagnostic imprecision, which has encouraged genetic studies of intermediate biological phenotypes that are closer to the molecular effects of risk genes than are the clinical symptoms. Neuroimaging-based intermediate phenotypes have emerged as particularly promising because they map risk associated gene effects onto physiological processes in brain that are altered in patients and in their healthy relatives. Recent evidence using this approach has elucidated discrete, dissociable biological mechanisms of risk genes at the level of neural circuitries, and their related cognitive functions. This approach may greatly contribute to ... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4566442 Wed, 02 Mar 2011 00:00:00 +0100 4566442 http://www.medworm.com/index.php?rid=4566443&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21371880%26dopt%3DAbstract Authors: Lambert JC, Amouyel P Alzheimer's disease (AD) is the prime cause of dementia and presents a strong genetic predisposition (60-80% of the attributable risk). In addition to APOE, a major recognized genetic determinant of AD, systematic, high-throughput genomic approaches have recently allowed the characterization of four new genetic determinants: CLU, CR1, PICALM and BIN1. Even if the complete picture of AD genetics is still not fully understood, the characterization of these new AD genetic determinants is probably going to strongly modify our perception of the pathophysiological process involved in AD. The new AD genetic landscape suggests that the common and late-onset forms of the disease are associated with a defect in peripheral Aβ peptide clearance, implying that the am... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4566443 Tue, 01 Mar 2011 00:00:00 +0100 4566443 http://www.medworm.com/index.php?rid=4566444&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21349696%26dopt%3DAbstract Authors: Maeda RK, Karch F In higher eukaryotes, individual genes are often intermingled with other genes and spread out across tens to hundreds of kilobases, even though only small portions of their sequence are devoted to protein coding. Yet, in this seemingly extended and tangled mess, the cell is able to precisely regulate gene expression in both time and space. Over the past few decades, numerous elements, like enhancers, silencers and insulators have been found that shed some light on how the precise control of gene expression is achieved. Through these discoveries, an additive model of gene expression was envisioned, where the addition of the patterning details imparted by regulatory elements would create the final pattern of gene expression. Although many genes can be described... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4566444 Tue, 22 Feb 2011 00:00:00 +0100 4566444 http://www.medworm.com/index.php?rid=4566445&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21345665%26dopt%3DAbstract Authors: Meister P, Mango SE, Gasser SM The differentiation of pluripotent or totipotent cells into various differentiated cell types is accompanied by a restriction of gene expression patterns, alteration in histone and DNA methylation, and changes in the gross nuclear organization of eu- and heterochromatic domains. Several recent studies have coupled genome-wide mapping of histone modifications with changes in gene expression. Other studies have examined changes in the subnuclear positioning of tissue-specific genes upon transcriptional induction or repression. Here we summarize intriguing correlations of the three phenomena, which suggest that in some cases causal relationships may exist. PMID: 21345665 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics an... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4566445 Mon, 21 Feb 2011 00:00:00 +0100 4566445 http://www.medworm.com/index.php?rid=4566446&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21342762%26dopt%3DAbstract Authors: Li G, Reinberg D Genomic DNA in the eukaryotic nucleus is hierarchically packaged by histones into chromatin to fit inside the nucleus. The dynamics of higher-order chromatin compaction play a crucial role in transcription and other biological processes inherent to DNA. Many factors, including histone variants, histone modifications, DNA methylation, and the binding of non-histone architectural proteins regulate the structure of chromatin. Although the structure of nucleosomes, the fundamental repeating unit of chromatin, is clear, there is still much discussion on the higher-order levels of chromatin structure. In this review, we focus on the recent progress in elucidating the structure of the 30-nm chromatin fiber. We also discuss the structural plasticity/dynamics and epige... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4566446 Sun, 20 Feb 2011 00:00:00 +0100 4566446 http://www.medworm.com/index.php?rid=4512552&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21330128%26dopt%3DAbstract Authors: Zediak VP, Wherry EJ, Berger SL Memory T lymphocytes are distinct from antigen-inexperienced naïve T cells in that memory T cells can respond more rapidly when they re-encounter a pathogen. Work over the past decade has begun to define the epigenetic underpinnings of the transcriptional component of the memory T cell response. An emerging theme is the persistence of an active chromatin signature at relevant gene loci in resting memory T cells, even when those genes are transcriptionally inactive. This gives strength to the concept of gene poising, and has shown that memory T lymphocytes are an ideal model in which to further define various mechanisms of epigenetic poising. PMID: 21330128 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Developm... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4512552 Tue, 15 Feb 2011 00:00:00 +0100 4512552 http://www.medworm.com/index.php?rid=4512550&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21330129%26dopt%3DAbstract Authors: Conaway RC, Conaway JW Over the past few years, advances in biochemical and genetic studies of the structure and function of the Mediator complex have shed new light on its subunit architecture and its mechanism of action in transcription by RNA polymerase II (pol II). The development of improved methods for reconstitution of recombinant Mediator subassemblies is enabling more in-depth analyses of basic features of the mechanisms by which Mediator interacts with and controls the activity of pol II and the general initiation factors. The discovery and characterization of multiple, functionally distinct forms of Mediator characterized by the presence or absence of the Cdk8 kinase module have led to new insights into how Mediator functions in both Pol II transcription activation ... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4512550 Tue, 15 Feb 2011 00:00:00 +0100 4512550 http://www.medworm.com/index.php?rid=4512549&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21330130%26dopt%3DAbstract Authors: Orom UA, Shiekhattar R Long non-coding RNAs (ncRNAs) are emerging as important regulatory factors in mammalian genomics. A number of reports within the last 2 years have identified thousands of actively expressed long ncRNA transcripts with distinct properties. The long ncRNAs show differential expression patterns and regulation in a wide variety of cells and tissues, adding significant complexity to the understanding of their biological role. Furthermore, genome-wide studies of transcriptional enhancers based on chromatin modifications and enhancer binding proteins have led to the identification of putative enhancers and provided insight into their tissue-specific regulation of gene expression. In an exciting turn of events, new evidence is indicating that long ncRNAs are ass... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4512549 Tue, 15 Feb 2011 00:00:00 +0100 4512549 http://www.medworm.com/index.php?rid=4512548&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21330131%26dopt%3DAbstract Authors: Calarco JP, Martienssen RA The movement of mobile small RNA signals between cells has garnered much interest over the last few years, and has recently been extended to germ cells during gamete development. Focusing on plants, we review mobile RNA signals that arise following reprogramming in the germline, and their effect on transposable element silencing on the one hand and on meiotic and apomictic germ cell fate on the other. A potential role for reprogramming and small RNA in hybrid formation and speciation is proposed. PMID: 21330131 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Development) Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4512548 Tue, 15 Feb 2011 00:00:00 +0100 4512548 http://www.medworm.com/index.php?rid=4512556&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21324670%26dopt%3DAbstract Authors: Li J, Gilmour DS The advent of methods for mapping the location of specific proteins across genomes is substantially enlightening our understanding of gene regulation. One recent discovery is that Pol II is concentrated at the 5' end of thousands of genes in mammalian and Drosophila cells. Before this, much research had focused on understanding how sequence-specific, DNA-binding proteins orchestrate the actions of regulators of chromatin structure and the general transcriptional machinery to control transcription initiation. The concentration of Pol II at the 5' ends of genes indicates that key steps regulating transcription occur after Pol II has associated with a gene's promoter. PMID: 21324670 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and ... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4512556 Mon, 14 Feb 2011 00:00:00 +0100 4512556 http://www.medworm.com/index.php?rid=4512555&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21324671%26dopt%3DAbstract Authors: Dorsett D Over the past decade it has emerged that the cohesin protein complex, which functions in sister chromatid cohesion, chromosome segregation, and DNA repair, also regulates gene expression and development. Even minor changes in cohesin activity alter several aspects of development. Genome-wide analysis indicates that cohesin directly regulates transcription of genes involved in cell proliferation, pluripotency, and differentiation through multiple mechanisms. These mechanisms are poorly understood, but involve both partial gene repression in concert with Polycomb group proteins, and facilitating long-range looping, both between enhancers and promoters, and between CTCF protein binding sites. PMID: 21324671 [PubMed - as supplied by publisher] (Source: Current Opinio... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4512555 Mon, 14 Feb 2011 00:00:00 +0100 4512555 http://www.medworm.com/index.php?rid=4512554&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21324672%26dopt%3DAbstract Authors: Baroux C, Raissig MT, Grossniklaus U Plants and animals reproduce sexually via specialized, highly differentiated gametes. Yet, gamete formation drastically differs between the two kingdoms. In flowering plants, the specification of cells destined to enter meiosis occurs late in development, gametic and accessory cells are usually derived from the same meiotic product, and two distinct female gametes involved in double fertilization differentiate. This poses fascinating questions in terms of gamete development and the associated epigenetic processes. Although studies in this area remain at their infancy, it becomes clear that large-scale epigenetic reprograming, involving RNA-directed DNA methylation, chromatin modifications, and nucleosome remodeling, contributes to the estab... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4512554 Mon, 14 Feb 2011 00:00:00 +0100 4512554 http://www.medworm.com/index.php?rid=4512553&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21324673%26dopt%3DAbstract Authors: Yusufzai T, Kadonaga JT The proper resolution of branched DNA molecules, which arise during processes such as DNA replication, DNA repair, and transcription, is critical for the maintenance of the genome. Disruption of this process can lead to genome instability and cancer progression. In this review, we describe recent progress on several interesting and biologically important enzymes that act upon different types of branched DNA substrates. PMID: 21324673 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Development) Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4512553 Mon, 14 Feb 2011 00:00:00 +0100 4512553 http://www.medworm.com/index.php?rid=4512557&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21316939%26dopt%3DAbstract Authors: Straub T, Becker PB Dosage compensation processes in flies and worms provide a unique opportunity to study common regulatory principles of thousands of genes. Technological advancement in the recent years has allowed for the comprehensive description of key aspects such as the targeting of the regulatory factors, the emerging chromatin structure changes and the ensuing subtle transcriptional alterations. With plenty of data at hand the challenge remains to integrate the findings into coherent models that appreciate the global nature of the underlying principles leaving the experimental anecdotes behind while avoiding the numerical burlesque. PMID: 21316939 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Development) Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4512557 Fri, 11 Feb 2011 00:00:00 +0100 4512557 http://www.medworm.com/index.php?rid=4512560&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21316215%26dopt%3DAbstract Authors: Galbraith MD, Espinosa JM Response to environmental stimuli is critical for cell survival and function and requires high fidelity signal transduction into the nucleus to facilitate the coordinated transcriptional regulation of appropriate gene networks. The cellular response to mitogenic stimuli provides an excellent paradigm to decipher the mechanisms mediating precise gene expression control at the transcriptional level. Here we review recent advances in our understanding of this so-called serum response network, which illuminate novel aspects of nuclear signaling mechanisms, combinatorial control by DNA binding proteins and regulation of RNA polymerase II (RNAPII) elongation. PMID: 21316215 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Dev... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4512560 Thu, 10 Feb 2011 00:00:00 +0100 4512560 http://www.medworm.com/index.php?rid=4512558&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21316216%26dopt%3DAbstract Authors: Fisher CL, Fisher AG The pluripotent state of embryonic stem cells is maintained by a core network of transcription factors, and by chromatin remodelling factors that support an environment permissive for transcription. Polycomb and trithorax Group proteins enable 'bivalent' chromatin to be established at lineage-specific genes within pluripotent cells that is thought to poise genes for rapid activation upon induction of differentiation. As differentiation proceeds, chromatin condenses and there is a genome-wide increase in the abundance of repressive histone modifications, alterations in the subnuclear organisation of particular genomic regions, and changes in DNA methylation profiles within genes. Reprogramming of somatic cells provides a platform to investigate the role of ... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4512558 Thu, 10 Feb 2011 00:00:00 +0100 4512558 http://www.medworm.com/index.php?rid=4455035&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21296568%26dopt%3DAbstract Authors: Mitchell KJ The processes by which cortical areas become specialized for high-level cognitive functions may be revealed by the study of familial developmental disorders such as dyslexia, dyscalculia, prosopagnosia, color agnosia and amusia. These disorders are characterised by the inability to integrate information across multiple areas and the consequent failure to develop representations of the knowledge of some category based on its associated attributes. In contrast, synesthesia may be seen as a hyper-associative condition, possibly due to a failure to properly segregate areas into distinct networks. Here, I consider recent advances in our understanding of the genetic and neurobiological bases of these conditions and the developmental mechanisms underlying the specializati... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4455035 Fri, 04 Feb 2011 00:00:00 +0100 4455035 http://www.medworm.com/index.php?rid=4455036&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21295966%26dopt%3DAbstract Authors: Rico B, Marín O Neuregulin-1 (Nrg1) and its receptor ErbB4 are encoded by genes that have been repeatedly linked to schizophrenia. Both genes are thought to play important roles in the development of brain circuitry, but their precise contribution to the disease process remains unknown. In this review, we summarize novel findings on the biological function of Nrg1 and ErbB4 in mice, with a focus on the development of inhibitory circuits in the cerebral cortex. We will also discuss how this basic knowledge may help us to understand the etiology of schizophrenia, and eventually lead to the development of novel therapies for treating the disorder. PMID: 21295966 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Development) Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4455036 Thu, 03 Feb 2011 00:00:00 +0100 4455036 http://www.medworm.com/index.php?rid=4455037&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21292473%26dopt%3DAbstract Authors: Tischfield MA, Cederquist GY, Gupta ML, Engle EC A spectrum of neurological disorders characterized by abnormal neuronal migration, differentiation, and axon guidance and maintenance have recently been attributed to missense and splice-site mutations in the genes that encode α-tubulin and β-tubulin isotypes TUBA1A, TUBA8, TUBB2B, and TUBB3, all of which putatively coassemble into neuronal microtubules. The resulting nervous system malformations can include different types of cortical malformations, defects in commissural fiber tracts, and degeneration of motor and sensory axons. Many clinical phenotypes and brain malformations are shared among the various mutations regardless of structural location and/or isotype, while others segregate with distinct amino acids or functiona... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4455037 Tue, 01 Feb 2011 00:00:00 +0100 4455037 http://www.medworm.com/index.php?rid=4455038&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21288712%26dopt%3DAbstract Authors: Manzini MC, Walsh CA The unique size and complexity of the human cerebral cortex are achieved via a long and precisely regulated developmental process controlling neurogenesis, neuronal migration and differentiation. Traditionally, disorders of cortical development have been classified on the basis of the most obvious defects in one of these developmental steps. However, the more we learn about the cellular biological roles of genes that are essential for cortical development, the more we realize that these functions map onto molecular processes, but not so cleanly onto anatomical processes. Essential genes might be involved in both proliferation and migration as well as differentiation, reflecting roles for underlying molecular mechanisms in different phases of development an... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4455038 Mon, 31 Jan 2011 00:00:00 +0100 4455038 http://www.medworm.com/index.php?rid=4455044&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21277190%26dopt%3DAbstract Authors: Poduri A, Lowenstein D Human epilepsy is a common and heterogeneous condition in which genetics play an important etiological role. We begin by reviewing the past history of epilepsy genetics, a field that has traditionally included studies of pedigrees with epilepsy caused by defects in ion channels and neurotransmitters. We highlight important recent discoveries that have expanded the field beyond the realm of channels and neurotransmitters and that have challenged the notion that single genes produce single disorders. Finally, we project toward an exciting future for epilepsy genetics as large-scale collaborative phenotyping studies come face to face with new technologies in genomic medicine. PMID: 21277190 [PubMed - as supplied by publisher] (Source: Current Opinion in... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4455044 Thu, 27 Jan 2011 00:00:00 +0100 4455044 http://www.medworm.com/index.php?rid=4455043&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21277191%26dopt%3DAbstract Authors: Girard SL, Xiong L, Dion PA, Rouleau GA On the basis of recent data from candidate region/gene and genome-wide association studies (GWAS) and their follow-up investigations, the number of genes potentially implicated in schizophrenia has been estimated to be over 1000. However, with regard to the identified odds ratio, it is likely that genetic variants with more definitive effect on schizophrenia phenotype are still missing. The hunt therefore remains open for the genetic variants that would explain the majority of the missing heritability of schizophrenia. This review aims at summarizing data from recent DNA microarray and target gene/region resequencing in order to propose new insights of where to look next. The review is divided into three sections: GWAS, copy-number varia... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4455043 Thu, 27 Jan 2011 00:00:00 +0100 4455043 http://www.medworm.com/index.php?rid=4455042&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21277192%26dopt%3DAbstract Authors: Melom JE, Littleton JT Recent insights into the genetic basis of neurological disease have led to the hypothesis that molecular pathways involved in synaptic growth, development, and stability are perturbed in a variety of mental disorders. Formation of a functional synapse is a complex process requiring stabilization of initial synaptic contacts by adhesive protein interactions, organization of presynaptic and postsynaptic specializations by scaffolding proteins, regulation of growth by intercellular signaling pathways, reorganization of the actin cytoskeleton, and proper endosomal trafficking of synaptic growth signaling complexes. Many neuropsychiatric disorders, including autism, schizophrenia, and intellectual disability, have been linked to inherited mutations which pert... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4455042 Thu, 27 Jan 2011 00:00:00 +0100 4455042 http://www.medworm.com/index.php?rid=4455041&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21277193%26dopt%3DAbstract Authors: State MW Tourette disorder (TD) is a childhood onset neuropsychiatric syndrome defined by persistent motor and vocal tics. Despite a long-standing consensus for a strong genetic contribution, the pace of discovery compared to other disorders of similar prevalence has been slow, due in part to a paucity of studies and both clinical heterogeneity and a complex genetic architecture. However, the potential for rapid progress is high. Recent rare variant findings have pointed to the importance of copy number variation, the overlap of risks among distinct diagnostic entities, the contribution of novel molecular mechanisms, and the value of family based studies. Finally, analysis of a cohort of sufficient size to identify common polymorphisms of plausible effect is underway, promisin... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4455041 Thu, 27 Jan 2011 00:00:00 +0100 4455041 http://www.medworm.com/index.php?rid=4455040&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21277194%26dopt%3DAbstract Authors: Cundiff PE, Anderson SA The derivation of pluripotent stem cells from somatic tissues has provided researchers with a source of patient-specific stem cells. The potential applications of this technology are truly momentous, and include cellular modeling of disease processes, drug discovery, and cell-based therapy. Here, we review the use of induced pluripotent stem cells (iPSCs) to study CNS disease. Since the iPSC field is still in its infancy, we also discuss some of the challenges that will need to be overcome before the potential of this technology to study and to treat neurological and psychiatric disorders can be fully harnessed. PMID: 21277194 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Development) Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4455040 Thu, 27 Jan 2011 00:00:00 +0100 4455040 http://www.medworm.com/index.php?rid=4455039&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21277195%26dopt%3DAbstract Authors: Reed-Geaghan EG, Maricich SM The somatosensory system processes information that organisms 'feel': joint position, muscle stretch, pain, pressure, temperature, and touch. The system is composed of a diverse array of peripheral nerve endings specialized to detect these sensory modalities. Several recent discoveries have shed light on the genetic pathways that control specification and differentiation of these neurons, how they accurately innervate their central and peripheral targets, and the molecules that enable them to detect mechanical stimuli. Here, we review the cadre of genes that control these processes, focusing on mechanosensitive neurons and support cells of the skin that mediate different aspects of the sense of touch. PMID: 21277195 [PubMed - as supplied by pub... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4455039 Thu, 27 Jan 2011 00:00:00 +0100 4455039 http://www.medworm.com/index.php?rid=4455045&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21273056%26dopt%3DAbstract Authors: Marshall C, Vousden K PMID: 21273056 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Development) Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4455045 Tue, 25 Jan 2011 00:00:00 +0100 4455045 http://www.medworm.com/index.php?rid=4455047&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21255997%26dopt%3DAbstract Authors: Brough R, Frankum JR, Costa-Cabral S, Lord CJ, Ashworth A The incentive to develop personalised therapy for cancer treatment is driven by the premise that it will increase therapeutic efficacy and reduce toxicity. Understanding the underlying cellular and molecular basis of the disease has been extremely important in the design of these novel therapies; however, identifying new drug targets for personalised therapies remains problematic. This review describes how the biological concept of synthetic lethality has been successfully implemented to identify new therapeutic approaches and targets in models from yeast through to human cells. We also discuss how recent technical advances combined with an increased understanding of the complexity of cellular networks may facilitate th... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4455047 Wed, 19 Jan 2011 00:00:00 +0100 4455047 http://www.medworm.com/index.php?rid=4455046&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21255998%26dopt%3DAbstract Authors: Mathew R, White E Autophagy is the mechanism by which cells consume parts of themselves to survive starvation and stress. This self-cannibalization limits cell death and tissue inflammation, recycles energy and biosynthetic substrates and removes damaged proteins and organelles, accumulation of which is toxic. In normal tissues, autophagy-mediated damage mitigation may suppress tumorigenesis, while in advanced tumors macromolecular recycling may support survival by buffering metabolic demand under stress. As a result, autophagy-activation in normal cells may suppress tumorigenesis, while autophagy inhibition may be beneficial for the therapy of established tumors. The mechanisms by which autophagy supports cancer cell metabolism are slowly emerging. As cancer is being increasi... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4455046 Wed, 19 Jan 2011 00:00:00 +0100 4455046 http://www.medworm.com/index.php?rid=4388860&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21251809%26dopt%3DAbstract Authors: Siegenthaler JA, Pleasure SJ The meninges have traditionally been viewed as specialized membranes surrounding and protecting the adult brain from injury. However, there is increasing evidence that the fetal meninges play important roles during brain development. Through the release of diffusible factors, the meninges influence the proliferative and migratory behaviors of neural progenitors and neurons in the forebrain and hindbrain. Meningeal cells also secrete and organize the pial basement membrane (BM), a critical anchor point for the radially oriented fibers of neuroepithelial stem cells. With its emerging role in brain development, the potential that defects in meningeal development may underlie certain congenital brain abnormalities in humans should be considered. In thi... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4388860 Tue, 18 Jan 2011 00:00:00 +0100 4388860 http://www.medworm.com/index.php?rid=4388859&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21251810%26dopt%3DAbstract Authors: Inman GJ TGFβ acts as a potent tumor suppressor and tumor promoter in a context dependent manner. Tumor suppressive functions include inhibition of cell proliferation, induction of apoptosis and regulation of autophagy. As tumors develop they switch their response to TGFβ and utilise this factor as a potent promoter of cell motility, invasion, metastasis and tumor stem cell maintenance. These multifactorial tumor influencing actions of TGFβ involve regulation of an increasing number of signal transduction pathways employing a diverse range of signaling molecules. Understanding the molecular mechanisms of how tumor cells respond to TGFβ and switch their response to this cytokine during disease progression is vital for both the development and the informed use of potentially... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4388859 Tue, 18 Jan 2011 00:00:00 +0100 4388859 http://www.medworm.com/index.php?rid=4388858&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21251811%26dopt%3DAbstract Authors: Kearney JA Genetic modifiers make an important contribution to neurological disease phenotypes. Significant progress has been made by studying genetic modifiers in model organisms. The ability to study complex genetic interactions in model systems contributes to our understanding of the genetic factors that influence neurological disease. This will lead to the development of novel therapeutic strategies and personalized treatment based on genetic risk. PMID: 21251811 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Development) Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4388858 Tue, 18 Jan 2011 00:00:00 +0100 4388858 http://www.medworm.com/index.php?rid=4388861&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21247752%26dopt%3DAbstract Authors: Baranzini SE For more than 30 years the only genetic factor associated with susceptibility to multiple sclerosis (MS) was the human leukocyte antigen (HLA) region. Recent advancements in genotyping platforms and the development of more effective statistical methods resulted in the identification of 16 more genes by genome-wide association studies (GWAS) in the last three years alone. While the effect of each of these genes is modest compared to that of HLA, this list is expected to grow significantly in the near future, thus defining a complex landscape in which susceptibility may be determined by a combination of allelic variants in different pathways according to ethnic background, disease sub-type, and specific environmental triggers. A considerable overlap of susceptibilit... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4388861 Mon, 17 Jan 2011 00:00:00 +0100 4388861 http://www.medworm.com/index.php?rid=4388863&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21236660%26dopt%3DAbstract Authors: McCormick F Mutant onco-proteins play a direct, causal role in cancer and are therefore considered attractive drug targets. Clinical experience has supported this view, with some exceptions. However, clinical benefit has often been restricted by rapid emergence of drug-resistant clones through several distinct mechanisms. This problem can, in principle, be addressed through cocktails containing several drugs. However, the number of tumors whose survival is dependent on a single, druggable mutant onco-protein is currently unknown. The majority of tumors may be driven either by single drivers that are un-druggable, or by combinations of drivers. In both cases, new approaches will be necessary. Development of systemic RNA interference may be a solution to these problems. PMID... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4388863 Wed, 12 Jan 2011 00:00:00 +0100 4388863 http://www.medworm.com/index.php?rid=4388862&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21236661%26dopt%3DAbstract Authors: Llambi F, Green DR The mitochondrial pathway of apoptosis constitutes one of the main safeguards against tumorigenesis. The BCL-2 family includes the central players of this pathway that regulate cell fate through the control of mitochondrial outer membrane permeabilization (MOMP), and important progress has been made in understanding the dynamic interactions between pro-apoptotic and anti-apoptotic BCL-2 proteins. In particular, recent studies have delineated a stepwise model for the induction of MOMP. BCL-2 proteins are often dysregulated in cancer, leading to increased survival of abnormal cells; however, recent studies have paradoxically shown that apoptosis induction can under some circumstances drive tumor formation, perhaps by inducing compensatory proliferation under c... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4388862 Wed, 12 Jan 2011 00:00:00 +0100 4388862 http://www.medworm.com/index.php?rid=4298866&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21145726%26dopt%3DAbstract Authors: Klein CA Unusually long latency periods between the treatment of primary tumors and metastatic recurrences are commonly thought to prove the existence and relevance of clinical tumor dormancy. However, careful consideration of disease courses and cancer growth rates leads to the conclusion that clinical dormancy may be everything from non-existent to much more frequent than originally thought. On the other hand, cellular dormancy defined as a non-productive state of disseminated tumor cells is very frequent, while homeostatic mechanisms such as angiogenic and immunological control contribute to the chronicity of cancer. This review attempts to provide a conceptual framework for the study of dormancy, which may guide clinical and experimental research. PMID: 21145726 [PubMe... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4298866 Wed, 08 Dec 2010 00:00:00 +0100 4298866 http://www.medworm.com/index.php?rid=4298867&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21144738%26dopt%3DAbstract Authors: Sansone P, Bromberg J Rudolf Virchow postulated that a critical feature of tumors was the presence of leukocytes, providing the first indication that inflammation may play a role in tumorigenesis. We now have a wealth of experimental and clinical data demonstrating a clear relationship between inflammatory responses and the roles they play at different stages of tumor development. The details of the dynamic relationship between tumor cells and specific subtypes of immune cells and mesenchymal cells are being revealed as critical to cancer progression which has led to the development of potential new targets for cancer treatment. This review describes some of the key molecular and cellular events demonstrating the critical role of inflammation on promoting tumorigenesis with at... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4298867 Mon, 06 Dec 2010 00:00:00 +0100 4298867 http://www.medworm.com/index.php?rid=4243644&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21123047%26dopt%3DAbstract Authors: Brognard J, Hunter T Protein kinases orchestrate the activation of signaling cascades in response to extracellular and intracellular stimuli to control cell growth, proliferation, and survival. The complexity of numerous intracellular signaling pathways is highlighted by the number of kinases encoded by the human genome (539) and the plethora of phosphorylation sites identified in phosphoproteomic studies. Perturbation of these signaling networks by mutations or abnormal protein expression underlies the cause of many diseases including cancer. Recent RNAi screens and cancer genomic sequencing studies have revealed that many more kinases than anticipated contribute to tumorigenesis and are potential targets for inhibitor drug development intervention. This review will highlight... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4243644 Mon, 29 Nov 2010 00:00:00 +0100 4243644 http://www.medworm.com/index.php?rid=4243645&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21112767%26dopt%3DAbstract Authors: Attard G, de Bono JS Circulating tumor cells (CTC) detected in the blood of cancer patients could be used for risk-stratification, molecular subclassification and as an intermediate end-point in therapeutic efficacy studies. Most studies to date have focused on enumeration of CTC in advanced cancer patients but further development of CTC evaluation technologies could allow expansion into early disease, monitoring of treatment response, and selection of patients for targeted therapies based on a CTC derived signature. This review discusses the challenges faced in achieving these goals, including the potential absence of CTC in patients with no blood-borne metastases, CTC intra-patient molecular heterogeneity, ex vivo loss of CTC viability, and the biological differences between... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4243645 Fri, 26 Nov 2010 00:00:00 +0100 4243645 http://www.medworm.com/index.php?rid=4243646&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21112206%26dopt%3DAbstract Authors: Berardi MJ, Fantin VR Malignant transformation is often a multistep process characterized by an initial period of avascular growth. Rapid cell proliferation creates areas within the emerging preneoplastic lesion with limited diffusion of oxygen and nutrients. In this context, activation of oncogenes, loss of tumor suppressors as well as additional adaptive mechanisms drive a profound metabolic rewiring to overcome the environmental constraints. The emerging cells are in principle better suited to proliferate and survive in the hostile tumor microenvironment. Furthermore, some of the acquired metabolic traits impact their metastatic behavior and response to therapy. It is becoming increasingly clear that malignant cells are highly dependent on certain nutrients, an Achilles' he... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4243646 Thu, 25 Nov 2010 00:00:00 +0100 4243646 http://www.medworm.com/index.php?rid=4243647&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21106363%26dopt%3DAbstract Authors: De Bock K, Cauwenberghs S, Carmeliet P As a result of excessive production of angiogenic molecules, tumor vessels become abnormal in structure and function. By impairing oxygen delivery, abnormal vessels fuel a vicious cycle of non-productive angiogenesis, which creates a hostile microenvironment from where tumor cells escape through leaky vessels and which renders tumors less responsive to chemoradiation. While anti-angiogenic strategies focused on inhibiting new vessel growth and destroying pre-existing vessels, clinical studies showed modest anti-tumor effects. For many solid tumors, anti-VEGF treatment offers greater clinical benefit when combined with chemotherapy. This is partly due to a normalization of the tumor vasculature, which improves cytotoxic drug delivery and e... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4243647 Mon, 22 Nov 2010 00:00:00 +0100 4243647 http://www.medworm.com/index.php?rid=4243648&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21093253%26dopt%3DAbstract Authors: Campisi J Cellular senescence arrests the proliferation of potential cancer cells, and so is a potent tumor suppressive mechanism, akin to apoptosis. Or is it? Why did cells evolve an anti-cancer mechanism that arrests, rather than kills, would-be tumor cells? Recent discoveries that senescent cells secrete growth factors, proteases and cytokines provide a shifting view-from senescence as a cell autonomous suppressor of tumorigenesis to senescence as a means to mobilize the systemic and local tissue milieu for repair. In some instances, this mobilization benefits the organism, but in others it can be detrimental. These discoveries provide potential mechanisms by which cellular senescence might contribute to the diverse, and seemingly incongruent, processes of tumor suppression... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4243648 Wed, 17 Nov 2010 00:00:00 +0100 4243648 http://www.medworm.com/index.php?rid=4197513&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21087854%26dopt%3DAbstract Authors: Cruickshanks HA, Adams PD To prevent cancer, mammals have evolved potent tumor suppression mechanisms, including senescence and apoptosis. These processes depend on regulation of chromatin. Chromatin-dependent tumor suppressor pathways are activated in premalignant cells and tissues harboring cancer-causing genetic alterations, and also in normal aged tissue, the latter likely due to accumulation of genetic and cellular damage. Paradoxically, however, disruption of chromatin structure may also promote cancer. Apparent defects in chromatin structure accumulate with age, the biggest single risk factor for cancer. Evidence suggests that these age-associated perturbations in chromatin structure contribute to the age-associated increase in incidence of cancer. Thus, alterations in ... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4197513 Wed, 17 Nov 2010 00:00:00 +0100 4197513 http://www.medworm.com/index.php?rid=4180563&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21074987%26dopt%3DAbstract Authors: Brahimi-Horn MC, Bellot G, Pouysségur J The hypoxia-inducible factor (HIF-1), in addition to genetic and epigenetic changes, is largely responsible for alterations in cell metabolism in hypoxic tumour cells. This transcription factor not only favours cell proliferation through the metabolic shift from oxidative phosphorylation to glycolysis and lactic acid production but also stimulates nutrient supply by mediating adaptive survival mechanisms. These include epithelial-mesenchymal transition, angiogenesis, autophagy, and synthesis and storage of lipid and glycogen. HIF-1 also ensures survival by correcting tumour acidosis via increased expression of the carbonic anhydrase CA IX and the lactate/H+ symporter MCT4. The targeting of key HIF-1-mediated steps, responsible for exace... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4180563 Thu, 11 Nov 2010 00:00:00 +0100 4180563 http://www.medworm.com/index.php?rid=4163649&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21071203%26dopt%3DAbstract Authors: Kirkin V, Dikic I Conjugation of ubiquitin to cellular proteins has emerged as a post-translational modification, which affects major cellular processes, including cell cycle, proliferation and apoptosis. The ubiquitin-mediated signaling is frequently altered in cancer cells, with several tumor suppressors and oncogenes representing enzymes of the ubiquitin conjugation and deconjugation pathways. Recently, ubiquitination has been involved into selective degradation of both proteins and mitochondria by autophagy. Studying this novel role of ubiquitin can shed light on autophagy as a tumor suppressor mechanism as well as provide insights into the role of autophagy in survival of tumor cells, thus aiding the design of better cancer therapies. PMID: 21071203 [PubMed - as suppl... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4163649 Tue, 09 Nov 2010 00:00:00 +0100 4163649 http://www.medworm.com/index.php?rid=4163650&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21051220%26dopt%3DAbstract Authors: Laxman S, Tu BP Over four decades ago, the first oscillations in metabolism in yeast cells were reported. Since then, multiple forms of oscillatory behavior have been observed in yeast grown under a variety of continuous culturing environments. The remarkable synchrony of cells undergoing such oscillations has made them ideal subjects for investigation using systems-based approaches. Herein, we briefly summarize previous work on the characterization of such oscillations using systems approaches, and present the long-period, Yeast Metabolic Cycle as an excellent model system for deciphering the temporal organization of fundamental cellular and metabolic processes at unprecedented resolution. PMID: 21051220 [PubMed - as supplied by publisher] (Source: Current Opinion in Gene... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4163650 Tue, 02 Nov 2010 00:00:00 +0100 4163650 http://www.medworm.com/index.php?rid=4134603&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21036033%26dopt%3DAbstract Authors: Hasty J, Hoffmann A, Golden S PMID: 21036033 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Development) Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4134603 Thu, 28 Oct 2010 00:00:00 +0100 4134603 http://www.medworm.com/index.php?rid=4106600&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20971631%26dopt%3DAbstract Authors: Cheong R, Levchenko A Oscillatory processes in biological signal transduction have come under progressively increasing scrutiny in terms of their functional significance and mechanisms of emergence and regulation. Since oscillatory processes can be a by-product of rapid adaptation and can also easily emerge if the feedback underlying adaptive processes is inadvertently artificially enhanced, one needs to exercise caution in both claiming the existence of in vivo oscillations and seeking to assign to them a specific functional significance. Nevertheless, oscillations can be a powerful means of encoding and transferring information both in time and in space, thus possessing important potential advantages for evolutionary selection and stabilization. Thus periodicity in the cell ... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4106600 Thu, 21 Oct 2010 23:00:00 +0100 4106600 http://www.medworm.com/index.php?rid=4106601&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20961750%26dopt%3DAbstract Authors: Glass L, Siegelmann HT Logical models provide insight about key control elements of biological networks. Based solely on the logical structure, we can determine state transition diagrams that give the allowed possible transitions in a coarse grained phase space. Attracting pathways and stable nodes in the state transition diagram correspond to robust attractors that would be found in several different types of dynamical systems that have the same logical structure. Attracting nodes in the state transition diagram correspond to stable steady states. Furthermore, the sequence of logical states appearing in biological networks with robust attracting pathways would be expected to appear also in Boolean networks, asynchronous switching networks, and differential equations having th... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4106601 Sun, 17 Oct 2010 23:00:00 +0100 4106601 http://www.medworm.com/index.php?rid=4106602&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20956081%26dopt%3DAbstract Authors: Behar M, Hoffmann A The health of organisms and cells depends on appropriate responses to diverse internal and external cues, stimuli, or challenges, such as changes in hormone or cytokine levels, or exposure to a pathogen. Cellular responses must be tailored to the identity and intensity of the stimulus and therefore intra-cellular signals must carry information about both. However, signaling mediators often form intricate networks that react to multiple stimuli yet manage to produce stimulus-specific responses. The multi-functionality ('functional pleiotropism') of signaling nodes suggests that biological networks have evolved ways of passing physiologically relevant stimulus information through shared channels. Increasing evidence supports the notion that this is achieved i... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4106602 Fri, 15 Oct 2010 23:00:00 +0100 4106602 http://www.medworm.com/index.php?rid=4074955&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20947336%26dopt%3DAbstract Authors: Pando BF, van Oudenaarden A Understanding how different cellular subsystems are coupled to each other is a fundamental question in the quest for reliably predicting the dynamic state of a cell. Coupling of oscillatory subsystems is especially interesting as dynamic interactions play an important role in cell physiology. Here we review recent efforts that investigate and quantify the coupling between the circadian and cell cycle clocks in cyanobacteria as a model system. We discuss studies that quantify the coupling from a systems point of view in which the oscillators are described in abstract terms. We also emphasize recent developments aimed at uncovering the molecular details underlying the coupling between these systems. Finally we review recent studies that describe a pot... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4074955 Mon, 11 Oct 2010 23:00:00 +0100 4074955 http://www.medworm.com/index.php?rid=4057801&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20934868%26dopt%3DAbstract Authors: Yamada Y, Forger D The field of systems biology studies how the interactions among individual components (e.g. genes and proteins) yield interesting and complex behavior. The circadian (daily) timekeeping system in mammals is an ideal system to study complexity because of its many biological scales (from genes to animal behavior). A wealth of data at each of these scales has recently been discovered. Within each scale, modeling can advance our understanding of challenging problems that arise in studying mammalian timekeeping. However, future work must focus on bridging the multiple spatial and temporal scales in the modeling of SCN network. Here we review recent advances, and then delve into a few areas that are promising research directions. We also discuss the flavor of mode... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4057801 Thu, 07 Oct 2010 23:00:00 +0100 4057801 http://www.medworm.com/index.php?rid=4057800&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20934869%26dopt%3DAbstract Authors: Mehta P, Gregor T From flocking birds, to organ generation, to swarming bacterial colonies, biological systems often exhibit collective behaviors. Here, we review recent advances in our understanding of collective dynamics in cell populations. We argue that understanding population-level oscillations requires examining the system under consideration at three different levels of complexity: at the level of isolated cells, homogenous populations, and spatially structured populations. We discuss the experimental and theoretical challenges this poses and highlight how new experimental techniques, when combined with conceptual tools adapted from physics, may help us overcome these challenges. PMID: 20934869 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetic... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4057800 Thu, 07 Oct 2010 23:00:00 +0100 4057800 http://www.medworm.com/index.php?rid=4057799&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20934870%26dopt%3DAbstract Authors: Dong G, Kim YI, Golden SS The circadian clock of the cyanobacterium Synechococcus elongatus PCC 7942 is built on a three-protein central oscillator that can be reconstituted in vitro, a redox-sensitive input for synchronization with the environment, and a bacterial two-component signal transduction pathway for global transcriptional regulation. This review covers the most recent progress in our understanding of the biological and biochemical mechanism of this bacterial clock, such as the discovery of a quinone-binding activity of the oscillator protein KaiA, the molecular mechanism of circadian control of cell division, and the global control of gene expression via modulation of DNA topology. PMID: 20934870 [PubMed - as supplied by publisher] (Source: Current Opinion in Ge... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4057799 Thu, 07 Oct 2010 23:00:00 +0100 4057799 http://www.medworm.com/index.php?rid=4057798&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20934871%26dopt%3DAbstract Authors: Mengel B, Hunziker A, Pedersen L, Trusina A, Jensen MH, Krishna S Oscillations are commonly observed in cellular behavior and span a wide range of timescales, from seconds in calcium signaling to 24 hours in circadian rhythms. In between lie oscillations with time periods of 1-5 hours seen in NF-κB, p53 and Wnt signaling, which play key roles in the immune system, cell growth/death and embryo development, respectively. In the first part of this article, we provide a brief overview of simple deterministic models of oscillations. In particular, we explain the mechanism of saturated degradation that has been used to model oscillations in the NF-κB, p53 and Wnt systems. The second part deals with the potential physiological role of oscillations. We use the simple models describe... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4057798 Thu, 07 Oct 2010 23:00:00 +0100 4057798 http://www.medworm.com/index.php?rid=4057802&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20934319%26dopt%3DAbstract Authors: Aubel D, Fussenegger M Inspired by natural time-keeping devices controlling the circadian clock, managing information processing in the brain and coordinating physiological activities on a daily (feeding and sleeping) or seasonal timescale (reproductive activity or hibernation), synthetic biologists have successfully assembled functional synthetic clocks from cataloged genetic components with standardized activities and arranging them in transcription circuits containing positive and negative feedback loops with integrated time-delay dynamics. While the positive feedback loop drives the clock like the (balance) spring in a mechanical watch the negative time-delay circuit represents the pulse generator defining a minimal time unit and precision of the clock like the pendulum fa... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4057802 Wed, 06 Oct 2010 23:00:00 +0100 4057802 http://www.medworm.com/index.php?rid=4057803&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20926286%26dopt%3DAbstract Authors: Baggs JE, Hogenesch JB The circadian clock is an endogenous oscillator that regulates daily rhythms in behavior and physiology. In recent years, systems biology and genomics approaches re-shaped our view of the clock. Our understanding of outputs that regulate behavior and physiology has been enhanced through gene expression profiling and proteomic analyses. Systems approaches uncovered underlying principles of transcriptional regulation and robustness of the oscillator through perturbation analysis and synthetic methods. Finally, new clock components and modifiers were identified through cell-based screening efforts and proteomics. PMID: 20926286 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Development) Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4057803 Sun, 03 Oct 2010 23:00:00 +0100 4057803 http://www.medworm.com/index.php?rid=4037692&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20889330%26dopt%3DAbstract Authors: McClung CR, Gutiérrez RA Whole-transcriptome analyses have established that the plant circadian clock regulates virtually every plant biological process and most prominently hormonal and stress response pathways. Systems biology efforts have successfully modeled the plant central clock machinery and an iterative process of model refinement and experimental validation has contributed significantly to the current view of the central clock machinery. The challenge now is to connect this central clock to the output pathways for understanding how the plant circadian clock contributes to plant growth and fitness in a changing environment. Undoubtedly, systems approaches will be needed to integrate and model the vastly increased volume of experimental data in order to extract meanin... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4037692 Thu, 30 Sep 2010 23:00:00 +0100 4037692 http://www.medworm.com/index.php?rid=4024275&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20851595%26dopt%3DAbstract Authors: Oikonomou C, Cross FR The cell cycle oscillator, based on a core negative feedback loop and modified extensively by positive feedback, cycles with a frequency that is regulated by environmental and developmental programs to encompass a wide range of cell cycle times. We discuss how positive feedback allows frequency tuning, how size and morphogenetic checkpoints regulate oscillator frequency, and how extrinsic oscillators such as the circadian clock gate cell cycle frequency. The master cell cycle regulatory oscillator in turn controls the frequency of peripheral oscillators controlling essential events. A recently proposed phase-locking model accounts for this coupling. PMID: 20851595 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Development... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4024275 Thu, 16 Sep 2010 23:00:00 +0100 4024275 http://www.medworm.com/index.php?rid=4024276&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20850963%26dopt%3DAbstract Authors: Paszek P, Jackson DA, White MR The emergence of biological function from the dynamic control of cellular signalling molecules is a fundamental process in biology. Key questions include: How do cells decipher noisy environmental cues, encode these signals to control fate decisions and propagate information through tissues? Recent advances in systems biology, and molecular and cellular biology, exemplified by analyses of signalling via the transcription factor Nuclear Factor kappaB (NF-κB), reveal a critical role of oscillatory control in the regulation of these biological functions. The emerging view is that the oscillatory dynamics of signalling molecules and the epigenetically regulated specificity for target genes contribute to robust regulation of biological function at ... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4024276 Wed, 15 Sep 2010 23:00:00 +0100 4024276 http://www.medworm.com/index.php?rid=4024277&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20846851%26dopt%3DAbstract Authors: Lee TK, Covert MW Single cells in a population often respond differently to perturbations in the environment. Live-cell microscopy has enabled scientists to observe these differences at the single-cell level. Some advantages of live-cell imaging over population-based methods include better time resolution, higher sensitivity, automation, and richer datasets. One specific area where live-cell microscopy has made a significant impact is the field of NF-κB signaling dynamics, and recent efforts have focused on making live-cell imaging of these dynamics more high-throughput. We highlight the major aspects of increasing throughput and describe a current system that can monitor, image and analyze the NF-κB activation of thousands of single cells in parallel. PMID: 20846851... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=4024277 Mon, 13 Sep 2010 23:00:00 +0100 4024277 http://www.medworm.com/index.php?rid=3960674&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20829031%26dopt%3DAbstract Authors: Bickmore W, Zaret KS PMID: 20829031 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Development) Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=3960674 Mon, 06 Sep 2010 23:00:00 +0100 3960674 http://www.medworm.com/index.php?rid=3933587&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20810275%26dopt%3DAbstract Authors: Shankaran H, Wiley HS The extracellular signal-regulated kinase (ERK) pathway is a central signaling pathway in development and disease and is regulated by multiple negative and positive feedback loops. Recent studies have shown negative feedback from ERK to upstream regulators can give rise to biochemical oscillations with a periodicity of between 15 and 30min. Feedback due to the stimulated transcription of negative regulators of the ERK pathway can also give rise to transcriptional oscillations with a periodicity of one to two hours. The biological significance of these oscillations is not clear, but recent evidence suggests that transcriptional oscillations participate in developmental processes, such as somite formation. Biochemical oscillations are more enigmatic, but co... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=3933587 Sun, 29 Aug 2010 23:00:00 +0100 3933587 http://www.medworm.com/index.php?rid=3933588&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20800472%26dopt%3DAbstract Authors: Fazzio TG, Panning B Embryonic stem (ES) cells are pluripotent cells that can self-renew indefinitely or be induced to differentiate into multiple cell lineages, and thus have the potential to be used in regenerative medicine. Pluripotency transcription factors (TFs), such as Oct4, Sox2, and Nanog, function in a regulatory circuit that silences the expression of key TFs required for differentiation and activates the expression of genes important for maintenance of pluripotency. In addition, proteins that remodel chromatin structure also play important roles in determining the ES cell-specific gene expression pattern. Here we review recent studies demonstrating the roles of enzymes that carry out one facet of chromatin regulation, nucleosome remodeling, in control of ES cell se... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=3933588 Tue, 24 Aug 2010 23:00:00 +0100 3933588 http://www.medworm.com/index.php?rid=3881284&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20702085%26dopt%3DAbstract Authors: Bruneau BG Heart development is a complex process that relies on networks of interacting transcription factors. Mutations in genes encoding some of these transcription factors result in many inherited congenital heart defects and point to the importance of these networks. Chromatin remodeling complexes are intimately associated with these transcriptional networks, adding an additional layer of complexity and fine-tuning to the regulation of heart development. Understanding these relationships will be crucial to understand fundamental concepts in tissue-specific gene regulation in organogenesis, in unraveling the mechanisms of congenital heart disease, as well as providing new avenues for reprogramming new cardiomyocytes for heart repair. PMID: 20702085 [PubMed - as supplie... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=3881284 Wed, 04 Aug 2010 23:00:00 +0100 3881284 http://www.medworm.com/index.php?rid=3818148&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20677359%26dopt%3DAbstract Authors: Watanabe T, Takahashi Y When different tissues successively emerge during development, they need to be morphologically segregated from each other. Morphological segregation of tissues is often accompanied by robust changes in cell shape, and these two events are precisely coordinated. We overview recent progress in understanding how such coordination is regulated at the cellular and molecular levels using vertebrate somitogenesis asa unique model. In the formation of the somitic gap and its concomitant cell epithelialization, Ephrin-Eph intercellular signals play a central role, with Ephrin transducing intracellular signals via suppression of Cdc42. These signals lead to the activation of integrin where the segment border of somites forms, which in turn induces the assembly of... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=3818148 Sat, 31 Jul 2010 23:00:00 +0100 3818148 http://www.medworm.com/index.php?rid=3773383&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20638836%26dopt%3DAbstract Authors: Smale ST Most studies of tissue-specific and developmental stage-specific transcription have focused on the DNA motifs, transcription factors, or chromatin events required for the active transcription of a gene in cells in which the gene is expressed, or for its active or heritable silencing in nonexpressing cells. However, accumulating evidence suggests that, in multicellular eukaryotes, enhancers or promoters for tissue-specific genes interact with pioneer transcription factors in embryonic stem cells and at other early stages of development, long before the genes are transcribed. These early interactions, which can lead to the presence of unmethylated CpG dinucleotides, histone modification signatures, and/or chromatin remodeling, may carry out different functions at differ... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=3773383 Thu, 15 Jul 2010 23:00:00 +0100 3773383 http://www.medworm.com/index.php?rid=3773382&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20638837%26dopt%3DAbstract Authors: Chubb JR, Liverpool TB With a developing appreciation of how noisy gene expression can be, and difficulties in deciphering conventional gene expression data into cell control mechanisms, it has become clear that single cell techniques for measuring transcription are necessary to illuminate basic cell regulation strategies. The resultant use of in situ hybridisation and live cell RNA visualisation approaches in single cells revealed transcription is not adequately reflected by the smooth, seamless process we tend to infer from standard measures of RNA level. When RNA production is measured in single cells, the process of transcription has been shown to occur in bursts, or pulses. This review will highlight the evidence for these phenomena, the proposed mechanisms underlying dis... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=3773382 Thu, 15 Jul 2010 23:00:00 +0100 3773382 http://www.medworm.com/index.php?rid=3758369&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20619631%26dopt%3DAbstract Authors: Kurimoto K, Saitou M Gene expression profiling at the single-cell level has been used to identify genes expressed in specific cell populations, in attempts to address various fundamental questions in multicellular organisms. In this article, we review the advance of single-cell cDNA amplification techniques in the last decade, and introduce a recently developed, reliable, quantitative method that is applicable to genome-wide transcriptional analyses with high-density oligonucleotide microarray and massively parallel sequencing. This method has been applied to a variety of biological studies, including developments of blastocyst inner cell mass, neurons, and primordial germ cells, to profile the molecular properties, dynamics during differentiation, and impacts of gene alterati... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=3758369 Tue, 06 Jul 2010 23:00:00 +0100 3758369 http://www.medworm.com/index.php?rid=3730801&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20598874%26dopt%3DAbstract Authors: Müller F, Zaucker A, Tora L The traditional model of transcription initiation nucleated by the TFIID complex has suffered significant erosion in the last decade. The discovery of cell-specific paralogs of TFIID subunits and a variety of complexes that replace TFIID in transcription initiation of protein coding genes have been paralleled by the description of diverse core promoter sequences. These observations suggest an additional level of regulation of developmental and tissue-specific gene expression at the core promoter level. Recent work suggests that this regulation may function through specific roles of distinct TBP-type factors and TBP-associated factors (TAFs), however the picture emerging is still far from complete. Here we summarize the proposed models of transcri... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=3730801 Wed, 30 Jun 2010 23:00:00 +0100 3730801 http://www.medworm.com/index.php?rid=3730800&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20598875%26dopt%3DAbstract Authors: Koh FM, Sachs M, Guzman-Ayala M, Ramalho-Santos M Open chromatin is a hallmark of pluripotent stem cells, but the underlying molecular mechanisms are only beginning to be unraveled. In this review we highlight recent studies that employ embryonic stem cells and induced pluripotent stem cells to investigate the regulation of open chromatin and its role in the maintenance and acquisition of pluripotency in vitro. We suggest that findings from in vitro studies using pluripotent stem cells are predictive of in vivo processes of epigenetic regulation of pluripotency, specifically in the development of the zygote and primordial germ cells. The combination of in vitro and in vivo approaches is expected to provide a comprehensive understanding of the epigenetic regulation of pluripote... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=3730800 Wed, 30 Jun 2010 23:00:00 +0100 3730800 http://www.medworm.com/index.php?rid=3730803&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20598522%26dopt%3DAbstract Authors: Buckingham M, Desplan C PMID: 20598522 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Development) Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=3730803 Tue, 29 Jun 2010 23:00:00 +0100 3730803 http://www.medworm.com/index.php?rid=3730802&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20598523%26dopt%3DAbstract Authors: Deng W, Blobel GA Control of gene expression involves the concerted action of multiple regulatory elements some of which can act over large genomic distances. Physical interaction among these elements can lead to looping of the chromatin fiber. Although posttranslational modifications of chromatin are thought to play a role in the conveyance of epigenetic information, it is largely unknown whether higher order chromatin organization such as looping contributes to epigenetic memory. A related unresolved question is whether chromatin loops are the cause or the effect of transcriptional regulation. Recent work on diverse organisms suggests a memory function for long-range chromatin interactions. It is proposed that higher order folding of the chromatin fiber can serve to maintain... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=3730802 Tue, 29 Jun 2010 23:00:00 +0100 3730802 http://www.medworm.com/index.php?rid=3718911&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20591646%26dopt%3DAbstract Authors: Ji Y, Tulin AV Cell growth and differentiation during developmental processes require the activation of many inducible genes. However, eukaryotic chromatin, which consists of DNA and histones, becomes a natural barrier impeding access to the functional transcription machinery. To break through the chromatin barrier, eukaryotic organisms have evolved the strategy of using poly(ADP-ribose) polymerase 1 (PARP1) to modulate chromatin structure and initiate the steps leading to gene expression control. As a structural protein in chromatin, enzymatically silent PARP1 inhibits transcription by contributing to the condensation of chromatin, which creates a barrier against gene transcription. However, once activated by environmental stimuli and developmental signals, PARP1 can modify i... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=3718911 Sun, 27 Jun 2010 23:00:00 +0100 3718911 http://www.medworm.com/index.php?rid=3718910&cid=s_35492_50_f&fid=35492&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20591647%26dopt%3DAbstract Authors: Kaestner KH The genetic analysis of the Foxa genes in both total and conditional mutant mice has clearly established that organogenesis of multiple systems is controlled by this subfamily of winged helix transcription factors. These discoveries followed the establishment of the conceptional framework of the mechanism of action of the FoxA proteins as 'pioneer factors' that can engage chromatin before other transcription factors. Recent molecular and genomic studies have also shown that FoxA proteins can facilitate binding of several nuclear receptors to their respective targets in a context-dependent manner, greatly increasing the range and importance of FoxA factors in biology. PMID: 20591647 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Dev... Current Opinion in Genetics and Development journals http://www.medworm.com/rss/comments.php?id=3718910 Sun, 27 Jun 2010 23:00:00 +0100 3718910