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This page shows you the most recent publications within this specialty of the MedWorm directory. This is page number 34.

Prrx1 Inhibits Adipogenesis through TGF{beta} [Metabolism]
In this study, we identify Prrx1a and Prrx1b as negative regulators of adipogenesis. We show that Prrx1a and Prrx1b are down-regulated during adipogenesis in vitro and in vivo. Stable knockdown of Prrx1a/b enhances adipogenesis, with increased expression of peroxisome proliferator-activated receptor-γ, CCAAT/enhancer-binding protein-α and FABP4 and increased secretion of the adipokines adiponectin and chemerin. Although stable low-level expression of Prrx1a, Prrx1b, or Prrx2 does not affect 3T3-L1 adipogenesis, transient overexpression of Prrx1a or Prrx1b inhibits peroxisome proliferator-activated receptor-γ activity. P...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Du, B., Cawthorn, W. P., Su, A., Doucette, C. R., Yao, Y., Hemati, N., Kampert, S., McCoin, C., Broome, D. T., Rosen, C. J., Yang, G., MacDougald, O. A. Tags: Cell Biology Source Type: research

Regulation of the GPR-G{alpha}i Signaling Complex [Cell Biology]
Group II activators of G-protein signaling (AGS) serve as binding partners for Gαi/o/t via one or more G-protein regulatory (GPR) motifs. GPR-Gα signaling modules may be differentially regulated by cell surface receptors or by different nonreceptor guanine nucleotide exchange factors. We determined the effect of the nonreceptor guanine nucleotide exchange factors AGS1, GIV/Girdin, and Ric-8A on the interaction of two distinct GPR proteins, AGS3 and AGS4, with Gαil in the intact cell by bioluminescence resonance energy transfer (BRET) in human embryonic kidney 293 cells. AGS3-Rluc-Gαi1-YFP and AGS4-Rluc-Gαi1-YFP BRET w...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Oner, S. S., Maher, E. M., Gabay, M., Tall, G. G., Blumer, J. B., Lanier, S. M. Tags: Signal Transduction Source Type: research

Duration of STAT3 Activation Encodes Specific Cytokine Responses [Immunology]
Paradoxically, the pro-inflammatory cytokine IL-6 and the anti-inflammatory cytokine IL-10 both activate STAT3, yet generate nearly opposing cellular responses. Here, we show that the temporal pattern of STAT3 activation codes for the specific cytokine response. A computational model of IL-6 and IL-10 signaling predicted that IL-6 stimulation results in transient activation of STAT3, with a rapid decline in phosphorylation and nuclear localization. In contrast, simulated IL-10 signaling resulted in sustained STAT3 activation. The predicted STAT3 patterns produced by each cytokine were confirmed experimentally in human dend...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Braun, D. A., Fribourg, M., Sealfon, S. C. Tags: Cell Biology Source Type: research

The Role of rpS3 and TRAF2 in Radioresistance of NSCLC Cells [Cell Biology]
In this study, to elucidate radioresistance mechanism in lung cancer, we compared radiation responses in two types of non-small cell lung cancer (NSCLC) cells with different radiosensitivity and identified key molecules conferring radioresistance. In radioresistant NSCLC cells, ionizing radiation (IR) led to casein kinase 2α (CK2α)- and PKC-mediated phosphorylation of rpS3 and TRAF2, respectively, which induced dissociation of rpS3-TRAF2 complex and NF-κB activation, resulting in significant up-regulation of prosurvival genes (cIAP1, cIAP2, and survivin). Also, dissociated phospho-rpS3 translocated into nucleus and boun...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Yang, H. J., Youn, H., Seong, K. M., Jin, Y.-W., Kim, J., Youn, B. Tags: Signal Transduction Source Type: research

A Novel Apoptotic Mechanism in Response to Calcium Overload♦ [Papers of the Week]
♦ See referenced article, J. Biol. Chem. 2013, 288, 2952–2963 Heart failure, brain ischemia, and strokes are pathological conditions that have one thing in common: an intracellular overload of calcium. The overload of calcium is caused by a hyperactivation of acid-sensing ion channels, including the degenerin/epithelial amiloride-sensitive sodium (DEG/ENaC) channels. The hyperactivation of DEG/ENaC channels has been shown to lead to apoptosis in mammalian cells, but the mechanism remains unclear. In this Paper of the Week, a team led by Wei-Xing Zong at Stony Brook University in New York demonstrated that the hyperacti...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Tags: Cell Biology Source Type: research

MDEG Hyperactivation Induces Caspase-8 Activation [Molecular Bases of Disease]
Intracellular calcium overload plays a critical role in numerous pathological syndromes such as heart failure, brain ischemia, and stroke. Hyperactivation of the acid-sensing ion channels including degenerin/epithelial amiloride-sensitive sodium (DEG/ENaC) channels has been shown to elevate intracellular calcium and cause subsequent neuronal cell death that is independent of the canonical Egl-1/Ced-9/Ced-4/Ced-3 apoptotic pathway in Caenorhabditis elegans. In mammalian cells, hyperactivation of the DEG/ENaC channels can also lead to cell death, although the underlying mechanism remains largely unknown. Here, we use a tetra...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Pan, J.-A., Fan, Y., Gandhirajan, R. K., Madesh, M., Zong, W.-X. Tags: Cell Biology Source Type: research

MEK1/2 Inhibitor Regulation of Proliferation [Cell Biology]
The Ras-MEK1/2-ERK1/2 kinase signaling pathway regulates proliferation, survival, and differentiation and, because it is often aberrant in tumors, is a popular target for small molecule inhibition. A novel metabolic analysis that measures the real-time oxidation state of NAD(H) and the hemes of the electron transport chain and oxygen consumption within intact, living cells found that structurally distinct MEK1/2 inhibitors had an immediate, dose-dependent effect on mitochondrial metabolism. The inhibitors U0126, MIIC and PD98059 caused NAD(H) reduction, heme oxidation, and decreased oxygen consumption, characteristic of co...
Source: Journal of Biological Chemistry - February 1, 2013 Category: Chemistry Authors: Ripple, M. O., Kim, N., Springett, R. Tags: Metabolism Source Type: research

[Clinico-pathological and molecular aspects of diagnostic and prognostic value in gliomas].
CONCLUSIONS. The study of proteomics and molecular biomarkers should complement the histopathological analysis and sometimes allows to determine direct or indirect predictive factors as well as the study of affected pathways which may become selective therapeutic targets. PMID: 23359078 [PubMed - in process]
Source: Revista de Neurologia - February 1, 2013 Category: Neurology Authors: Ortega-Aznar A, Jimenez-Leon P, Martinez E, Romero-Vidal FJ Tags: Rev Neurol Source Type: research

Replication of a carcinogenic nitropyrene DNA lesion by human Y-family DNA polymerase
Nitrated polycyclic aromatic hydrocarbons are common environmental pollutants, of which many are mutagenic and carcinogenic. 1-Nitropyrene is the most abundant nitrated polycyclic aromatic hydrocarbon, which causes DNA damage and is carcinogenic in experimental animals. Error-prone translesion synthesis of 1-nitropyrene–derived DNA lesions generates mutations that likely play a role in the etiology of cancer. Here, we report two crystal structures of the human Y-family DNA polymerase iota complexed with the major 1-nitropyrene DNA lesion at the insertion stage, incorporating either dCTP or dATP nucleotide opposite th...
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: Kirouac, K. N., Basu, A. K., Ling, H. Tags: Structural Biology Source Type: research

A small molecule directly inhibits the p53 transactivation domain from binding to replication protein A
Replication protein A (RPA), essential for DNA replication, repair and DNA damage signalling, possesses six ssDNA-binding domains (DBDs), including DBD-F on the N-terminus of the largest subunit, RPA70. This domain functions as a binding site for p53 and other DNA damage and repair proteins that contain amphipathic alpha helical domains. Here, we demonstrate direct binding of both ssDNA and the transactivation domain 2 of p53 (p53TAD2) to DBD-F, as well as DBD-F-directed dsDNA strand separation by RPA, all of which are inhibited by fumaropimaric acid (FPA). FPA binds directly to RPA, resulting in a conformational shift as ...
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: Glanzer, J. G., Carnes, K. A., Soto, P., Liu, S., Parkhurst, L. J., Oakley, G. G. Tags: Structural Biology Source Type: research

Guanine base stacking in G-quadruplex nucleic acids
In this study, we investigate how guanine base stacking influences the stability of G-quadruplexes and their stacked higher-order structures. A structural survey of the Protein Data Bank is conducted to characterize experimentally observed guanine base stacking geometries within the core of G-quadruplexes and at the interface between stacked G-quadruplex structures. We couple this survey with a systematic computational examination of stacked G-tetrad energy landscapes using quantum mechanical computations. Energy calculations of stacked G-tetrads reveal large energy differences of up to 12 kcal/mol between experimentally o...
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: Lech, C. J., Heddi, B., Phan, A. T. Tags: Structural Biology Source Type: research

Solution conformations of early intermediates in Mos1 transposition
DNA transposases facilitate genome rearrangements by moving DNA transposons around and between genomes by a cut-and-paste mechanism. DNA transposition proceeds in an ordered series of nucleoprotein complexes that coordinate pairing and cleavage of the transposon ends and integration of the cleaved ends at a new genomic site. Transposition is initiated by transposase recognition of the inverted repeat sequences marking each transposon end. Using a combination of solution scattering and biochemical techniques, we have determined the solution conformations and stoichiometries of DNA-free Mos1 transposase and of the transposas...
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: Cuypers, M. G., Trubitsyna, M., Callow, P., Forsyth, V. T., Richardson, J. M. Tags: Structural Biology Source Type: research

Magnetic tweezers measurements of the nanomechanical stability of DNA against denaturation at various conditions of pH and ionic strength
The opening of DNA double strands is extremely relevant to several biological functions, such as replication and transcription or binding of specific proteins. Such opening phenomenon is particularly sensitive to the aqueous solvent conditions in which the DNA molecule is dispersed, as it can be observed by considering the classical dependence of DNA melting temperature on pH and salt concentration. In the present work, we report a single-molecule study of the stability of DNA against denaturation when subjected to changes in solvent. We investigated the appearance of DNA instability under specific external applied force a...
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: Tempestini, A., Cassina, V., Brogioli, D., Ziano, R., Erba, S., Giovannoni, R., Cerrito, M. G., Salerno, D., Mantegazza, F. Tags: Structural Biology Source Type: research

Structures of the Escherichia coli transcription activator and regulator of diauxie, XylR: an AraC DNA-binding family member with a LacI/GalR ligand-binding domain
Escherichia coli can rapidly switch to the metabolism of l-arabinose and d-xylose in the absence of its preferred carbon source, glucose, in a process called carbon catabolite repression. Transcription of the genes required for l-arabinose and d-xylose consumption is regulated by the sugar-responsive transcription factors, AraC and XylR. E. coli represents a promising candidate for biofuel production through the metabolism of hemicellulose, which is composed of d-xylose and l-arabinose. Understanding the l-arabinose/d-xylose regulatory network is key for such biocatalyst development. Unlike AraC, which is a well-studied pr...
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: Ni, L., Tonthat, N. K., Chinnam, N., Schumacher, M. A. Tags: Structural Biology Source Type: research

Sleeping Beauty transposon-based system for cellular reprogramming and targeted gene insertion in induced pluripotent stem cells
The discovery of direct cell reprogramming and induced pluripotent stem (iPS) cell technology opened up new avenues for the application of non-viral, transposon-based gene delivery systems. The Sleeping Beauty (SB) transposon is highly advanced for versatile genetic manipulations in mammalian cells. We established iPS cell reprogramming of mouse embryonic fibroblasts and human foreskin fibroblasts by transposition of OSKM (Oct4, Sox2, Klf4 and c-Myc) and OSKML (OSKM + Lin28) expression cassettes mobilized by the SB100X hyperactive transposase. The efficiency of iPS cell derivation with SB transposon system was in the range...
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: Grabundzija, I., Wang, J., Sebe, A., Erdei, Z., Kajdi, R., Devaraj, A., Steinemann, D., Szuhai, K., Stein, U., Cantz, T., Schambach, A., Baum, C., Izsvak, Z., Sarkadi, B., Ivics, Z. Tags: Molecular Biology Source Type: research

Transcription blockage by homopurine DNA sequences: role of sequence composition and single-strand breaks
The ability of DNA to adopt non-canonical structures can affect transcription and has broad implications for genome functioning. We have recently reported that guanine-rich (G-rich) homopurine-homopyrimidine sequences cause significant blockage of transcription in vitro in a strictly orientation-dependent manner: when the G-rich strand serves as the non-template strand [Belotserkovskii et al. (2010) Mechanisms and implications of transcription blockage by guanine-rich DNA sequences., Proc. Natl Acad. Sci. USA, 107, 12816–12821]. We have now systematically studied the effect of the sequence composition and single-stra...
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: Belotserkovskii, B. P., Neil, A. J., Saleh, S. S., Shin, J. H. S., Mirkin, S. M., Hanawalt, P. C. Tags: Molecular Biology Source Type: research

A novel mechanism of eukaryotic translation initiation that is neither m7G-cap-, nor IRES-dependent
Resistance of translation of some eukaryotic messenger RNAs (mRNAs) to inactivation of the cap-binding factor eIF4E under unfavorable conditions is well documented. To date, it is the mechanism of internal ribosome entry that is predominantly thought to underlay this stress tolerance. However, many cellular mRNAs that had been considered to contain internal ribosome entry sites (IRESs) failed to pass stringent control tests for internal initiation, thus raising the question of how they are translated under stress conditions. Here, we show that inserting an eIF4G-binding element from a virus IRES into 5'-UTRs of strongly ca...
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: Terenin, I. M., Andreev, D. E., Dmitriev, S. E., Shatsky, I. N. Tags: Molecular Biology Source Type: research

AT-rich sequence elements promote nascent transcript cleavage leading to RNA polymerase II termination
RNA Polymerase II (Pol II) termination is dependent on RNA processing signals as well as specific terminator elements located downstream of the poly(A) site. One of the two major terminator classes described so far is the Co-Transcriptional Cleavage (CoTC) element. We show that homopolymer A/T tracts within the human β-globin CoTC-mediated terminator element play a critical role in Pol II termination. These short A/T tracts, dispersed within seemingly random sequences, are strong terminator elements, and bioinformatics analysis confirms the presence of such sequences in 70% of the putative terminator regions (PTRs) genome-wide.
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: White, E., Kamieniarz-Gdula, K., Dye, M. J., Proudfoot, N. J. Tags: Molecular Biology Source Type: research

Identification of RNA targets for the nuclear multidomain cyclophilin atCyp59 and their effect on PPIase activity
AtCyp59 is a multidomain cyclophilin containing a peptidyl-prolyl cis/trans isomerase (PPIase) domain and an evolutionarily highly conserved RRM domain. Deregulation of this class of cyclophilins has been shown to affect transcription and to influence phosphorylation of the C-terminal repeat domain of the largest subunit of the RNA polymerase II. We used a genomic SELEX method for identifying RNA targets of AtCyp59. Analysis of the selected RNAs revealed an RNA-binding motif (G[U/C]N[G/A]CC[A/G]) and we show that it is evolutionarily conserved. Binding to this motif was verified by gel shift assays in vitro and by RNA immu...
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: Bannikova, O., Zywicki, M., Marquez, Y., Skrahina, T., Kalyna, M., Barta, A. Tags: Molecular Biology Source Type: research

Competition between the GlnR and PhoP regulators for the glnA and amtB promoters in Streptomyces coelicolor
Interaction of regulatory networks is a subject of great interest in systems biology of bacteria. Phosphate control of metabolism in Streptomyces is mediated by the two-component system PhoR–PhoP. Similarly, the utilization of different nitrogen sources is controlled by the regulator GlnR. Transcriptomic and biochemical analysis revealed that glnA (encoding a glutamine synthetase), glnR and other nitrogen metabolism genes are under PhoP control. DNA-binding experiments showed that PhoP binds to other nitrogen-regulated genes (SCO0255, SCO01863 and ureA). Using the glnA promoter as model, we observed that PhoP and Gln...
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: Sola-Landa, A., Rodriguez-Garcia, A., Amin, R., Wohlleben, W., Martin, J. F. Tags: Molecular Biology Source Type: research

Deregulation of poly(A) polymerase I in Escherichia coli inhibits protein synthesis and leads to cell death
Polyadenylation plays important roles in RNA metabolism in both prokaryotes and eukaryotes. Surprisingly, deregulation of polyadenylation by poly(A) polymerase I (PAP I) in Escherichia coli leads to toxicity and cell death. We show here that mature tRNAs, which are normally not substrates for PAP I in wild-type cells, are rapidly polyadenylated as PAP I levels increase, leading to dramatic reductions in the fraction of aminoacylated tRNAs, cessation of protein synthesis and cell death. The toxicity associated with PAP I is exacerbated by the absence of either RNase T and/or RNase PH, the two major 3' -> 5' exonucleases ...
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: Mohanty, B. K., Kushner, S. R. Tags: Molecular Biology Source Type: research

Improving detection of copy-number variation by simultaneous bias correction and read-depth segmentation
We present a novel read-depth–based method, GENSENG, which uses a hidden Markov model and negative binomial regression framework to identify regions of discrete copy-number changes while simultaneously accounting for the effects of multiple confounders. Based on extensive calibration using multiple HTS data sets, we conclude that our method outperforms existing read-depth–based CNV detection algorithms. The concept of simultaneous bias correction and CNV detection can serve as a basis for combining read-depth with other types of information such as read-pair or split-read in a single analysis. A user-friendly a...
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: Szatkiewicz, J. P., Wang, W., Sullivan, P. F., Wang, W., Sun, W. Tags: Computational Methods, Genomics Computational Biology Source Type: research

Genes involved in host-parasite interactions can be revealed by their correlated expression
Molecular interactions between a parasite and its host are key to the ability of the parasite to enter the host and persist. Our understanding of the genes and proteins involved in these interactions is limited. To better understand these processes it would be advantageous to have a range of methods to predict pairs of genes involved in such interactions. Correlated gene expression profiles can be used to identify molecular interactions within a species. Here we have extended the concept to different species, showing that genes with correlated expression are more likely to encode proteins, which directly or indirectly part...
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: Reid, A. J., Berriman, M. Tags: Computational Biology Source Type: research

Development and application of a DNA microarray-based yeast two-hybrid system
The yeast two-hybrid (Y2H) system is the most widely applied methodology for systematic protein–protein interaction (PPI) screening and the generation of comprehensive interaction networks. We developed a novel Y2H interaction screening procedure using DNA microarrays for high-throughput quantitative PPI detection. Applying a global pooling and selection scheme to a large collection of human open reading frames, proof-of-principle Y2H interaction screens were performed for the human neurodegenerative disease proteins huntingtin and ataxin-1. Using systematic controls for unspecific Y2H results and quantitative benchm...
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: Suter, B., Fontaine, J.-F., Yildirimman, R., Rasko, T., Schaefer, M. H., Rasche, A., Porras, P., Vazquez-Alvarez, B. M., Russ, J., Rau, K., Foulle, R., Zenkner, M., Saar, K., Herwig, R., Andrade-Navarro, M. A., Wanker, E. E. Tags: Protein-protein interaction, Microarray Technology Computational Biology Source Type: research

Candidate RNA structures for domain 3 of the foot-and-mouth-disease virus internal ribosome entry site
The foot-and-mouth-disease virus (FMDV) utilizes non-canonical translation initiation for viral protein synthesis, by forming a specific RNA structure called internal ribosome entry site (IRES). Domain 3 in FMDV IRES is phylogenetically conserved and highly structured; it contains four-way junctions where intramolecular RNA–RNA interactions serve as a scaffold for the RNA to fold for efficient IRES activity. Although the 3D structure of domain 3 is crucial to exploring and deciphering the initiation mechanism of translation, little is known. Here, we employ a combination of various modeling approaches to propose cand...
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: Jung, S., Schlick, T. Tags: Computational Biology Source Type: research

Highly similar structural frames link the template tunnel and NTP entry tunnel to the exterior surface in RNA-dependent RNA polymerases
In this study, we made structure-based comparisons that are independent of sequence composition using a recently developed algorithm. We identified residue-to-residue correspondences of multiple protein structures and created (two-dimensional) structure-based alignment maps of 37 polymerase structures that provide both sequence and structure details. Using these maps, we determined that ~75% of each polymerase species consists of seven protein segments, each of which has high structural similarity to segments in other species, though they are widely divergent in sequence composition and order. We define each of these segme...
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: Lang, D. M., Zemla, A. T., Zhou, C. L. E. Tags: Computational Biology Source Type: research

Transcription factor and chromatin features predict genes associated with eQTLs
Cell type–specific gene expression in humans involves complex interactions between regulatory factors and DNA at enhancers and promoters. Mapping studies for expression quantitative trait loci (eQTLs), transcription factors (TFs) and chromatin markers have become widely used tools for identifying gene regulatory elements, but prediction of target genes remains a major challenge. Here, we integrate genome-wide data on TF-binding sites, chromatin markers and functional annotations to predict genes associated with human eQTLs. Using the random forest classifier, we found that genomic proximity plus five TF and chromatin...
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: Wang, D., Rendon, A., Wernisch, L. Tags: Computational Methods, Chromatin and Epigenetics, Genomics Computational Biology Source Type: research

The twilight zone of cis element alignments
Sequence alignment of proteins and nucleic acids is a routine task in bioinformatics. Although the comparison of complete peptides, genes or genomes can be undertaken with a great variety of tools, the alignment of short DNA sequences and motifs entails pitfalls that have not been fully addressed yet. Here we confront the structural superposition of transcription factors with the sequence alignment of their recognized cis elements. Our goals are (i) to test TFcompare (http://floresta.eead.csic.es/tfcompare), a structural alignment method for protein–DNA complexes; (ii) to benchmark the pairwise alignment of regulator...
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: Sebastian, A., Contreras-Moreira, B. Tags: Computational Methods, Genomics Computational Biology Source Type: research

TEAK: Topology Enrichment Analysis frameworK for detecting activated biological subpathways
To mine gene expression data sets effectively, analysis frameworks need to incorporate methods that identify intergenic relationships within enriched biologically relevant subpathways. For this purpose, we developed the Topology Enrichment Analysis frameworK (TEAK). TEAK employs a novel in-house algorithm and a tailor-made Clique Percolation Method to extract linear and nonlinear KEGG subpathways, respectively. TEAK scores subpathways using the Bayesian Information Criterion for context specific data and the Kullback-Leibler divergence for case–control data. In this article, we utilized TEAK with experimental studies...
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: Judeh, T., Johnson, C., Kumar, A., Zhu, D. Tags: Computational Methods, Genomics Computational Biology Source Type: research

One size does not fit all: On how Markov model order dictates performance of genomic sequence analyses
The structural simplicity and ability to capture serial correlations make Markov models a popular modeling choice in several genomic analyses, such as identification of motifs, genes and regulatory elements. A critical, yet relatively unexplored, issue is the determination of the order of the Markov model. Most biological applications use a predetermined order for all data sets indiscriminately. Here, we show the vast variation in the performance of such applications with the order. To identify the ‘optimal’ order, we investigated two model selection criteria: Akaike information criterion and Bayesian informati...
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: Narlikar, L., Mehta, N., Galande, S., Arjunwadkar, M. Tags: Computational Biology Source Type: research

PreCisIon: PREdiction of CIS-regulatory elements improved by gene's positION
This study demonstrates that respective gene positioning carries significant information. This novel type of information is combined with traditional sequence information by a machine learning algorithm called PreCisIon. To optimize this combination, PreCisIon builds a strong gene target classifier by adaptively combining weak classifiers based on either local binding sequence or global gene position. This strategy generically paves the way to the optimized incorporation of any future advances in gene target prediction based on local sequence, genome layout or on novel criteria. With the current state of the art, PreCisIon...
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: Elati, M., Nicolle, R., Junier, I., Fernandez, D., Fekih, R., Font, J., Kepes, F. Tags: Computational Methods, Genomics Computational Biology Source Type: research

Categorical spectral analysis of periodicity in human and viral genomes
This article applies the rigorous method of spectral envelope to systematically characterize the contributions of codon bias, AA bias and protein structural motifs to the three-base periodicity of coding sequences. The method is also used to classify CpG islands in the human genome. In addition, we show how spectral envelope can be used to trace the evolution of viral genomes and monitor global sequence changes without having to align to previously known genomes. This approach also detects reassortment events, such as those that led to the 2009 pandemic H1N1 virus.
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: Howe, E. D., Song, J. S. Tags: Computational Biology Source Type: research

Improved nucleic acid descriptors for siRNA efficacy prediction
Although considerable progress has been made recently in understanding how gene silencing is mediated by the RNAi pathway, the rational design of effective sequences is still a challenging task. In this article, we demonstrate that including three-dimensional descriptors improved the discrimination between active and inactive small interfering RNAs (siRNAs) in a statistical model. Five descriptor types were used: (i) nucleotide position along the siRNA sequence, (ii) nucleotide composition in terms of presence/absence of specific combinations of di- and trinucleotides, (iii) nucleotide interactions by means of a modified a...
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: Sciabola, S., Cao, Q., Orozco, M., Faustino, I., Stanton, R. V. Tags: Computational Methods, Targeted inhibition of gene function, Genomics Computational Biology Source Type: research

miRNA target enrichment analysis reveals directly active miRNAs in health and disease
microRNAs (miRNAs) are short non-coding regulatory RNA molecules. The activity of a miRNA in a biological process can often be reflected in the expression program that characterizes the outcome of the activity. We introduce a computational approach that infers such activity from high-throughput data using a novel statistical methodology, called minimum-mHG (mmHG), that examines mutual enrichment in two ranked lists. Based on this methodology, we provide a user-friendly web application that supports the statistical assessment of miRNA target enrichment analysis (miTEA) in the top of a ranked list of genes or proteins. Using...
Source: Nucleic Acids Research - February 1, 2013 Category: Research Authors: Steinfeld, I., Navon, R., Ach, R., Yakhini, Z. Tags: Computational Methods, Genomics Methods Online Source Type: research

The Science of Early Life Toxic Stress for Pediatric Practice and Advocacy
In this report, we provide an overview of the science of toxic stress. We summarize the development of the neuroendocrine-immune network, how its function is altered by early life adversity, and how these alterations then increase vulnerability to disease. The fact that early environments shape and calibrate the functioning of biological systems very early in life is both a cautionary tale about overlooking critical periods in development and reason for optimism about the promise of intervention. Even in the most extreme cases of adversity, well-timed changes to children’s environments can improve outcomes. Pediatric...
Source: PEDIATRICS - February 1, 2013 Category: Pediatrics Authors: Johnson, S. B., Riley, A. W., Granger, D. A., Riis, J. Tags: Developmental/Behavior State-of-the-Art Review Article Source Type: research

The 22nd annual meeting of the European Tissue Repair Society (ETRS) in Athens, Greece
The 22nd Annual Meeting of the European Tissue Repair Society, Athens, Greece, October 4 to 5, 2012 informed about pathophysiological mechanisms in tissue repair and on the development of clinical treatments of chronic wounds, fibrosis, and cancer, considering recent advances in molecular biology and biotechnology.
Source: BioMed Central - February 1, 2013 Category: Journals (General) Authors: Boris HinzMagda UlrichHilde BeeleDimitris Kletsas Source Type: research

Endothelial barrier dysfunction in diabetic conduit arteries: a novel method to quantify filtration
In conclusion, the Lp of a conduit artery can be accurately and reproducibly measured using a novel isovolumic method, which in diabetic rats is hyperpermeable. This is likely due to disruption of the endothelial glycocalyx.
Source: AJP: Heart and Circulatory Physiology - February 1, 2013 Category: Cardiology Authors: Lu, X., Huxley, V. H., Kassab, G. S. Tags: VASCULAR BIOLOGY AND MICROCIRCULATION Source Type: research

Circulating humanin levels are associated with preserved coronary endothelial function
Humanin is a small endogenous antiapoptotic peptide, originally identified as protective against Alzheimer's disease, but subsequently also found on human endothelium as well as carotid artery plaques. Endothelial dysfunction is a precursor to the development of atherosclerotic plaques, which are characterized by a highly proinflammatory, reactive oxygen species, and apoptotic milieu. Previous animal studies demonstrated that humanin administration may improve endothelial function. Thus the aim of this study was to test the hypothesis that patients with coronary endothelial dysfunction have reduced systemic levels of human...
Source: AJP: Heart and Circulatory Physiology - February 1, 2013 Category: Cardiology Authors: Widmer, R. J., Flammer, A. J., Herrmann, J., Rodriguez-Porcel, M., Wan, J., Cohen, P., Lerman, L. O., Lerman, A. Tags: VASCULAR BIOLOGY AND MICROCIRCULATION Source Type: research

Endothelial 12(S)-HETE vasorelaxation is mediated by thromboxane receptor inhibition in mouse mesenteric arteries
Arachidonic acid (AA) metabolites mediate endothelium-dependent relaxation in many vascular beds. Previously, we identified the major AA 12/15-lipoxygenase (12/15-LO) metabolite of mouse arteries as 12-hydroxyeicosatetraenoic acid (12-HETE). The goal was to determine the stereospecific configuration of mouse vascular 12-HETE and characterize the role of 12-HETE stereoisomers in the regulation of vascular tone. Using normal, reverse phase, and chiral HPLC, the stereospecific configuration was identified as 12(S)-HETE. 12(S)-HETE relaxed U46619-, carbocyclic thromboxane A2-, PGF2α-, and 8-iso PGF2α-preconstricted...
Source: AJP: Heart and Circulatory Physiology - February 1, 2013 Category: Cardiology Authors: Siangjong, L., Gauthier, K. M., Pfister, S. L., Smyth, E. M., Campbell, W. B. Tags: VASCULAR BIOLOGY AND MICROCIRCULATION Source Type: research

AMP-activated protein kinase inhibits vascular smooth muscle cell proliferation and migration and vascular remodeling following injury
Vascular smooth muscle cell (VSMC) activation promotes a synthetic phenotype that underlies many vessel growth disorders. In this regard it has been suggested that the metabolic sensor adenosine 5'-monophosphate-activated protein kinase (AMPK) has significant antigrowth and antimetastatic properties and may serve as a viable therapeutic target. In the current study we hypothesized that AMPK reduces neointima formation following balloon injury and that this occurs through reduction in VSMC proliferation and migration. Data reveal that local or systemic dosing with the AMPK agonist 5-aminoimidazole-4-carboxamide-1-β-d-r...
Source: AJP: Heart and Circulatory Physiology - February 1, 2013 Category: Cardiology Authors: Stone, J. D., Narine, A., Shaver, P. R., Fox, J. C., Vuncannon, J. R., Tulis, D. A. Tags: VASCULAR BIOLOGY AND MICROCIRCULATION Source Type: research

Mike Yeadon
Nature Reviews Drug Discovery 12, 96 (2013). doi:10.1038/nrd3936 When Pfizer announced the closure of its research operations in Sandwich, UK, former head of allergy and respiratory biology Mike Yeadon decided to form his own start-up company together with several former colleagues. His company, Ziarco, has licensed several former Pfizer compounds and recently secured UK£16.8 million in venture funding. Here, he talks to Charlotte Harrison about the challenges so far and the company's plans for the future.
Source: Nature Reviews Drug Discovery - February 1, 2013 Category: Drugs & Pharmacology Tags: News and Analysis Source Type: research

Vitamin D deficiency is associated with greater tumor size and poorer outcome in Merkel cell carcinoma patients
ConclusionThe association between vitamin D deficiency and MCC characteristics and outcome, together with detection of the VDR in MCC cells, suggest that vitamin D could influence the biology of MCC.
Source: Journal of the European Academy of Dermatology and Venereology - February 1, 2013 Category: Dermatology Authors: M. Samimi, A. Touzé, H. Laude, E. Bidre, F. Arnold, A. Carpentier, C. Gardair, A. Carlotti, E. Maubec, N. Dupin, F. Aubin, M.F. Avril, F. Rozenberg, M. Avenel‐Audran, S. Guyetant, G. Lorette, L. Machet, P. Coursaget Tags: Original Article Source Type: research

Genetically modified tobacco plants produce antibodies to treat rabies
(Federation of American Societies for Experimental Biology) Smoking tobacco is bad for your health, but a genetically altered version of the plant might provide an inexpensive cure for the deadly rabies virus. In a new report in The FASEB Journal, scientists produced a monoclonal antibody in transgenic tobacco plants shown to neutralize the rabies virus. This antibody works by preventing the virus from attaching to nerve endings around the bite site and keeping the virus from traveling to the brain.
Source: EurekAlert! - Medicine and Health - February 1, 2013 Category: Global & Universal Source Type: news

Primary immunodeficiencies: A rapidly evolving story
The characterization of primary immunodeficiencies (PIDs) in human subjects is crucial for a better understanding of the biology of the immune response. New achievements in this field have been possible in light of collaborative studies; attention paid to new phenotypes, infectious and otherwise; improved immunologic techniques; and use of exome sequencing technology. The International Union of Immunological Societies Expert Committee on PIDs recently reported on the updated classification of PIDs. However, new PIDs are being discovered at an ever-increasing rate. A series of 19 novel primary defects of immunity that have...
Source: Journal of Allergy and Clinical Immunology - February 1, 2013 Category: Allergy & Immunology Authors: Nima Parvaneh, Jean-Laurent Casanova, Luigi Daniele Notarangelo, Mary Ellen Conley Tags: Current perspectives Source Type: research

Humans put their eggs in more than one basket
Nature Cell Biology 15, 229 (2013). doi:10.1038/ncb2694 Author: Diana J. Laird
Source: Nature Cell Biology - February 1, 2013 Category: Cytology Authors: Diana J. Laird Tags: Corrigendum Source Type: research

Phosphorylation-enabled binding of SGO1–PP2A to cohesin protects sororin and centromeric cohesion during mitosis
Nature Cell Biology 15, 229 (2013). doi:10.1038/ncb2688 Author: Hong Liu, Susannah Rankin & Hongtao Yu
Source: Nature Cell Biology - February 1, 2013 Category: Cytology Authors: Hong LiuSusannah RankinHongtao Yu Tags: Erratum Source Type: research

Interrogating Lkb1 function
Nature Cell Biology 15, 141 (2013). doi:10.1038/ncb2692 Author: Emily J. Chenette
Source: Nature Cell Biology - February 1, 2013 Category: Cytology Authors: Emily J. Chenette Tags: Research Highlights Source Type: research

Scaling somitogenesis
Nature Cell Biology 15, 141 (2013). doi:10.1038/ncb2691 Author: Nathalie Le Bot
Source: Nature Cell Biology - February 1, 2013 Category: Cytology Authors: Nathalie Le Bot Tags: Research Highlights Source Type: research

Sorting Vangl2 at the Golgi
Nature Cell Biology 15, 141 (2013). doi:10.1038/ncb2687 Author: Christina Karlsson Rosenthal
Source: Nature Cell Biology - February 1, 2013 Category: Cytology Authors: Christina Karlsson Rosenthal Tags: Research Highlights Source Type: research

Focal adhesions tug at matrix for rigidity sensing
Nature Cell Biology 15, 141 (2013). doi:10.1038/ncb2686 Author: Alexia-Ileana Zaromytidou
Source: Nature Cell Biology - February 1, 2013 Category: Cytology Authors: Alexia-Ileana Zaromytidou Tags: Research Highlights Source Type: research