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Spheroid Formation and Neural Induction in Human Adipose-Derived Stem Cells on a Chitosan-Coated Surfaceemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Cells Tissues Organs (DOI:10.1159/000332045) (Source: Cells Tissues Organs)
Source: Cells Tissues Organs - February 6, 2012 Category: Cytology Source Type: research

Structural analysis of proteins in living eukaryotic cells using magnetic resonance spectroscopy.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Abstract Three-dimensional structures of proteins are often critical in understanding proteins functions. However, structures or states of proteins in cells undergo dynamical changes in response to interactions with other proteins and/or biological molecules. In addition, post-translational modification such as phosphorylation, methylation and ubiquitination can drastically change the structure and hence the properties of proteins. Therefore, to precisely correlate structure data of proteins with cell biology data, the structure information should be collected in living cells preferably at atomic level. In addition...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - February 6, 2012 Category: Drugs & Pharmacology Authors: Tochio H, Shirakawa M Tags: Yakugaku Zasshi Source Type: research

Gene-Gene Interactions Between Interleukin-12A and Interleukin-12B with the Risk of Brain Tumoremail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
DNA and Cell Biology Feb 2012, Vol. 31, No. 2: 219-223. (Source: DNA and Cell Biology)
Source: DNA and Cell Biology - February 6, 2012 Category: Cytology Tags: article Source Type: research

Bronchoscopy in Rural Areas?email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Quality of bronchoscopy performed by one single pulmonologist in a scarcely populated subarctic area was compared to the guidelines provided by the British Thoracic Society (BTS). 103 patients underwent bronchoscopy. Diagnostic yield was increased to 76.6% when the first bronchoscopy was supplemented by bronchial washing fluid and brush cytology and to 86.7% (BTS guidelines >80%) after a second bronchoscopy. Median time from referral to bronchoscopy was 10 days and 8 days from positive bronchoscopy to operative referral to another hospital. 1% of patients that underwent transbronchial lung biopsy had minor complica...
Source: Advances in Urology - February 6, 2012 Category: Urology & Nephrology Source Type: research

Polo-like kinase 1 (Plk1): an Unexpected Player in DNA Replicationemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Regulation of cell cycle progression is important for the maintenance of genome integrity, and Polo-like kinases (Plks) have been identified as key regulators of this process. It is well established that Polo-like kinase 1 (Plk1) plays critical roles in mitosis but little is known about its functions at other stages of the cell cycle. Here we summarize the functions of Plk1 during DNA replication, focusing on the molecular events related to Origin Recognition Complex (ORC), the complex that is essential for the initiation of DNA replication. Within the context of Plk1 phosphorylation of Orc2, we also emphasize regulation o...
Source: Cell Division - February 6, 2012 Category: Cytology Authors: Bing SongX. LiuXiaoqi Liu Source Type: research

Denaturation of HIV-1 Protease (PR) Monomer by Acetic Acid: Mechanistic and Trajectory Insights from Molecular Dynamics Simulations and NMR.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
In this study, all-atom MD simulations in explicit solvent and NMR relaxation studies were performed on HIV-1 Protease (PR) in 9 M acetic acid (AcOH) (the commonly used denaturant during PR preparation). Following previous reports that denaturation proceeds via dissociation of the dimer into monomers, unfolding of the monomer by acetic acid has been explicitly investigated here. Direct visualization of the denaturation process and evidence for the mechanism of denaturation have been presented. Our simulations reveal that the denaturation of the PR monomer is caused due to direct interaction between acetic acid molecules an...
Source: Cell Research - February 5, 2012 Category: Cytology Authors: Borkar A, Rout MK, Hosur RV Tags: J Biomol Struct Dyn Source Type: research

Protocols, Toolboxes and Resource papers.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Abstract In the August 2009 issue of Autophagy, I indicated that we were launching a new category of article, Protocols. At that time, I noted that we would ultimately be placing these articles on a new site online. Well, that time has finally arrived (see www.landesbioscience.com/journals/autophagy/protocols/ for links to these papers). Therefore, it seems appropriate for me to briefly distinguish among three types of community-oriented papers, Protocol, Toolbox and Resource. PMID: 22301999 [PubMed - as supplied by publisher] (Source: Autophagy)
Source: Autophagy - February 5, 2012 Category: Cytology Authors: Klionsky DJ Tags: Autophagy Source Type: research

PKD at the crossroads of necrosis and autophagy.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Abstract Reactive oxygen species (ROS) that accumulate under oxidative pressure cause severe damage to cellular components, and induce various cellular responses, including apoptosis, programmed necrosis and autophagy, depending on the cellular setting. Various studies have described ROS-induced autophagy, but only a few direct factors that regulate autophagy under oxidative stress are known to date. We have identified DAPK and PKD as such regulators by demonstrating their role in the process of autophagy in general, and specifically during oxidative stress. PKD acts as a downstream effector of DAPk in the regulati...
Source: Autophagy - February 5, 2012 Category: Cytology Authors: Eisenberg-Lerner A, Kimchi A Tags: Autophagy Source Type: research

Autophagic proteins: New facets of the oxygen paradox.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Abstract Oxygen (O 2), while essential for aerobic life, can also cause metabolic toxicity through the excess generation of reactive oxygen species (ROS). Pathological changes in ROS production can originate through the partial reduction of O 2 during mitochondrial electron transport, as well as from enzymatic sources. This phenomenon, termed the oxygen paradox, has been implicated in aging and disease, and is especially evident in critical care medicine. Whereas high O 2 concentrations are utilized as a life-sustaining therapeutic for respiratory insufficiency, they in turn can cause acute lung injury. Alveolar ep...
Source: Autophagy - February 5, 2012 Category: Cytology Authors: Jin Y, Tanaka A, Choi AM, Ryter SW Tags: Autophagy Source Type: research

Maternal inheritance of mitochondrial DNA: Degradation of paternal mitochondria by allogeneic organelle autophagy, allophagy.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Abstract Maternal inheritance of mitochondrial DNA (mtDNA) is generally observed in many eukaryotes. Sperm-derived paternal mitochondria and their mtDNA enter the oocyte cytoplasm upon fertilization and then normally disappear during early embryogenesis. However, the mechanism underlying this clearance of paternal mitochondria has remained largely unknown. Recently, we showed that autophagy is required for the elimination of paternal mitochondria in Caenorhabditis elegans embryos. Shortly after fertilization, autophagosomes are induced locally around the penetrated sperm components. These autophagosomes engulf pate...
Source: Autophagy - February 5, 2012 Category: Cytology Authors: Sato M, Sato K Tags: Autophagy Source Type: research

Carotenoid deficiency triggers autophagy in the model green alga Chlamydomonas reinhardtii.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
In this study we used the unicellular green alga Chlamydomonas reinhardtii to demonstrate that defects in carotenoid biosynthesis lead to the activation of autophagy, a membrane-trafficking process that participates in the recycling and degradation of damaged or toxic cellular components. Carotenoid depletion caused by either the mutation of phytoene synthase or the inhibition of phytoene desaturase by the herbicide norflurazon, resulted in a strong induction of autophagy. We found that high light transiently activates autophagy in wild-type Chlamydomonas cells as part of an adaptation response to this stress. Our results ...
Source: Autophagy - February 5, 2012 Category: Cytology Authors: Pérez-Pérez ME, Couso I, Crespo JL Tags: Autophagy Source Type: research

A high-throughput FRET-based assay for determination of Atg4 activity.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
In this study, a sensitive and specific method to measure the activity of two Atg4 homologs in mammalian cells, Atg4A and Atg4B, was developed using a fluorescence resonance energy transfer (FRET)-based approach. Thus LC3B and GATE-16, two substrates that could be differentially cleaved by Atg4A and Atg4B, were fused with CFP and YFP at the N- and C-terminus, respectively, allowing FRET to occur. The FRET signals decreased in proportion to the Atg4-mediated cleavage, which separated the two fluorescent proteins. This method is highly efficient for measuring the enzymatic activity and kinetics of Atg4A and Atg4B under in vi...
Source: Autophagy - February 5, 2012 Category: Cytology Authors: Li M, Chen X, Ye QZ, Vogt A, Yin XM Tags: Autophagy Source Type: research

Andrographolide sensitizes cisplatin-induced apoptosis via suppression of autophagosome-lysosome fusion in human cancer cells.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
In this study, we sought to examine the effect of Andro on autophagy, and to evaluate whether such effect is relevant to the sensitization effect of Andro on apoptosis induced by DNA damage agents in cancer cells. First, we found that Andro is able to significantly enhance autophagic markers in various cancer cell lines, including GFP-LC3 puncta and LC3-II level. Interestingly, Andro treatment also led to marked increase of p62 protein level and addition of chloroquine (CQ) failed to further enhance either LC3-II or p62 level, indicating that Andro is likely to suppress autophagic flux at the maturation and degradation sta...
Source: Autophagy - February 5, 2012 Category: Cytology Authors: Zhou J, Hu SE, Tan SH, Cao R, Chen Y, Xia D, Zhu X, Yang XF, Ong CN, Shen HM Tags: Autophagy Source Type: research

Enhancing lysosome biogenesis attenuates BNIP3-induced cardiomyocyte death.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Abstract Hypoxia-inducible pro-death protein BNIP3 (BCL-2/adenovirus E1B 19-kDa interacting protein 3), provokes mitochondrial permeabilization causing cardiomyocyte death in ischemia-reperfusion injury. Inhibition of autophagy accelerates BNIP3-induced cell death, by preventing removal of damaged mitochondria. We tested the hypothesis that stimulating autophagy will attenuate BNIP3-induced cardiomyocyte death. Neonatal rat cardiac myocytes (NRCMs) were adenovirally transduced with BNIP3 (or LacZ as control; at multiplicity of infection = 100); and autophagy was stimulated with rapamycin (100 nM). Cell death was as...
Source: Autophagy - February 5, 2012 Category: Cytology Authors: Ma X, Godar RJ, Liu H, Diwan A Tags: Autophagy Source Type: research

The fibroblast growth factor signaling axis controls cardiac stem cell differentiation through regulating autophagy.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Abstract The fibroblast growth factor (FGF) signaling axis plays important roles in heart development. Yet, the molecular mechanism by which the FGF regulates cardiogenesis is not fully understood. Using genetically engineered mouse and in vitro cultured embryoid body (EB) models, we demonstrate that FGF signaling suppresses premature differentiation of heart progenitor cells, as well as autophagy in outflow tract (OFT) myocardiac cells. The FGF also promotes mesoderm differentiation in embryonic stem cells (ESCs) but inhibits cardiomyocyte differentiation of the mesoderm cells at later stages. Furthermore, inhibit...
Source: Autophagy - February 5, 2012 Category: Cytology Authors: Zhang J, Liu J, Liu L, McKeehan WL, Wang F Tags: Autophagy Source Type: research

Autophagy: A cyto-protective mechanism which prevents primary human hepatocyte apoptosis during oxidative stress.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Abstract The role of autophagy in the response of human hepatocytes to oxidative stress remains unknown. Understanding this process may have important implications for the understanding of basic liver epithelial cell biology and the responses of hepatocytes during liver disease. To address this we isolated primary hepatocytes from human liver tissue and exposed them ex vivo to hypoxia and hypoxia-reoxygenation (H-R). We showed that oxidative stress increased hepatocyte autophagy in a reactive oxygen species (ROS) and class III PtdIns3K-dependent manner. Specifically, mitochondrial ROS and NADPH oxidase were found t...
Source: Autophagy - February 5, 2012 Category: Cytology Authors: Bhogal RH, Weston CJ, Curbishley SM, Adams DH, Afford SC Tags: Autophagy Source Type: research

A novel method for autophagy detection in primary cells: Impaired levels of macroautophagy in immunosenescent T cells.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Abstract Autophagy is a conserved constitutive cellular process, responsible for the degradation of dysfunctional proteins and organelles. Autophagy plays a role in many diseases such as neurodegeneration and cancer; however, to date, conventional autophagy detection techniques are not suitable for clinical samples. We have developed a high throughput, statistically robust technique that quantitates autophagy in primary human leukocytes using the Image stream, an imaging flow cytometer. We validate this method on cell lines and primary cells knocked down for essential autophagy genes. Also, using this method we sho...
Source: Autophagy - February 5, 2012 Category: Cytology Authors: Phadwal K, Alegre-Abarrategui J, Watson AS, Pike L, Anbalagan S, Hammond EM, Wade-Martins R, McMichael A, Klenerman P, Simon AK Tags: Autophagy Source Type: research

Critical role of mTOR in calcineurin inhibitor-induced renal cancer progression.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Abstract Comment on: Basu A, et al. PLoS One 2011; 6:e23919. PMID: 22293493 [PubMed - as supplied by publisher] (Source: Cell Cycle)
Source: Cell Cycle - February 5, 2012 Category: Cytology Authors: Basu A, Banerjee P, Pal S Tags: Cell Cycle Source Type: research

The induction of polyploidy or apoptosis by the Aurora A kinase inhibitor MK8745 is p53-dependent.email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
In conclusion, our studies show p53 as a determining factor for induction of apoptosis vs. polyploidy upon inhibition of Aurora A. PMID: 22293494 [PubMed - as supplied by publisher] (Source: Cell Cycle)
Source: Cell Cycle - February 5, 2012 Category: Cytology Authors: Nair JS, Ho AL, Schwartz GK Tags: Cell Cycle Source Type: research

Myeloid Elf‐1‐like factor stimulates adipogenic differentiation through the induction of peroxisome proliferator‐activated receptor γ expression in bone marrowemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
AbstractMyeloid Elf‐1 like factor (MEF) is one of the Ets transcription factors known to regulate cell proliferation and differentiation. A previous report has shown that osteoblast‐specific MEF transgenic mice (Col1a1‐MEF‐TG mice) have low bone mass but high bone marrow adiposity. In the present study, we explored a previously unappreciated mechanism whereby MEF promotes adipogenesis in bone marrow. An adipogenic colony forming unit assay showed that bone marrow cells derived from Col1a1‐MEF‐TG mice had a higher adipogenic differentiation potential compared to those from wild‐type. The levels of adipogenic m...
Source: Journal of Cellular Physiology - February 4, 2012 Category: Cytology Authors: Kyunghwa BaekJe‐Yoel ChoHyo Rin HwangArang KwonHye‐Lim LeeHyun‐Jung ParkAbdul S QadirHyun‐Mo RyooKyung Mi WooJeong‐Hwa Baek Tags: Original Research Article Source Type: research

CCND1 G870A Polymorphism with Altered Cyclin D1 Transcripts Expression Is Associated with the Risk of Glioma in a Chinese Populationemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
DNA and Cell Biology , Vol. 0, No. 0. (Source: DNA and Cell Biology)
Source: DNA and Cell Biology - February 3, 2012 Category: Cytology Tags: article Source Type: research

Dynamics of expression patterns of AQP4, dystroglycan, agrin and matrix metalloproteinases in human glioblastomaemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Abstract  In human glioblastoma, the blood–brain barrier (BBB) is disturbed. According to our concept, the glio-vascular relationships and thus the control of the BBB are essentially dependent on the polarity of astroglial cells. This polarity is characterized by the uneven distribution of the water channel protein aquaporin-4 (AQP4), dystroglycan and other molecules. Recently, we were able to show that the extracellular matrix component agrin is important for the construction and localization of the so-called orthogonal arrays of particles (OAPs), which consist in AQP4. Here, combining freeze-fracture elec...
Source: Cell and Tissue Research - February 3, 2012 Category: Cytology Tags: Cell and Tissue Research Source Type: research

Cell Biology: Push Me Pull Youemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
A contractile ring composed of actin and myosin promotes cytokinesis—the final stage of cell division when daughter cells are physically separated from one another. The small GTPase RhoA regulates the … [Read more] (Source: Editors' Choice)
Source: Editors' Choice - February 3, 2012 Category: Science Authors: Stewart Wills (mailto:swills at aaas.org) Source Type: research

[News & Analysis] Cell Biology: Donation Spurs a Cell Observatory—And Bigger Plansemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
The Broad Institute received a $32.5 million gift last week to take on one of the biggest challenges in biology: mapping the molecular "circuitry" inside several kinds of mammalian cells.Author: Jocelyn Kaiser (Source: Science: Current Issue)
Source: Science: Current Issue - February 3, 2012 Category: Science Authors: Jocelyn Kaiser Source Type: research

Editors' Choiceemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Astronomy: A Comet Dates Jupiter | Sociology: I Liked You From the Start | Genetics: Wrapped Up Right | Climate Science: Here's Looking at You | Cell Biology: Push Me Pull You | Chemistry: Sacrifices at the Surface | Education: Science Illustrated (Source: Science: Current Issue)
Source: Science: Current Issue - February 3, 2012 Category: Science Authors: Stewart Wills (mailto:swills at aaas.org) Source Type: research

Expression and distribution of creatine transporter and creatine kinase (brain isoform) in developing and mature rat cochlear tissuesemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
This study postulates that this CRT is developmentally regulated in the rat cochlea. CRT expression was measured by quantitative real-time RT-PCR and immunohistochemistry in the postnatal (P0–P14) and adult (P22–P56) rat cochlea. The maximum CRT expression was reached at the onset of hearing (P12), and this level was maintained through to adulthood. CRT immunoreactivity was strongest in the sensory inner hair cells, supporting cells and the spiral ganglion neurons. Cochlear distribution of the CK brain isoform (CKB) was also assessed by immunohistochemistry and compared with the distribution of CRT in the developi...
Source: Histochemistry and Cell Biology - February 3, 2012 Category: Biomedical Science Tags: Histochemistry and Cell Biology Source Type: research

Functional Characterization of Genetic Polymorphisms Identified in the Promoter Region of the Bovine PEPS Geneemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
DNA and Cell Biology , Vol. 0, No. 0. (Source: DNA and Cell Biology)
Source: DNA and Cell Biology - February 3, 2012 Category: Cytology Tags: article Source Type: research

Response to Pan's Letteremail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
DNA and Cell Biology , Vol. 0, No. 0. (Source: DNA and Cell Biology)
Source: DNA and Cell Biology - February 3, 2012 Category: Cytology Tags: article Source Type: research

Functional Polymorphism Located in MMP-9 Gene Promoter Is Strongly Associated with Obesityemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
DNA and Cell Biology , Vol. 0, No. 0. (Source: DNA and Cell Biology)
Source: DNA and Cell Biology - February 3, 2012 Category: Cytology Tags: article Source Type: research

Abnormal male meiosis explains pollen sterility in the polyploid medicinal plant Pinellia ternata (Araceae).email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Abnormal male meiosis explains pollen sterility in the polyploid medicinal plant Pinellia ternata (Araceae). Genet Mol Res. 2012;11(1):112-20 Authors: Liu Y, Hui RK, Deng RN, Wang JJ, Wang M, Li ZY Abstract Pinellia ternata is an important traditional Chinese medicinal plant. Its different populations in China have various ploidy levels, based on x = 13, as well as extensive aneuploid series. The microsporogenesis process was observed in specimens from three populations from three regions of Hubei Province; they were characterized by normal and abnormal meiotic divisions in pollen mother cells (PMCs) at all...
Source: Genetics and Molecular Research - February 3, 2012 Category: Genetics & Stem Cells Authors: Liu Y, Hui RK, Deng RN, Wang JJ, Wang M, Li ZY Tags: Genet Mol Res Source Type: research

Rearranging the Cell's Skeleton- 2/1/12email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Cell biologists at Johns Hopkins have identified key steps in how certain molecules alter a cell’s skeletal shape and drive the cell’s movement. (Source: Johns Hopkins Medicine News)
Source: Johns Hopkins Medicine News - February 3, 2012 Category: Research Source Type: news

Functional Relationship of BAR/SH3 Domains of Endophilin [Membrane Biology]email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Bin/Amphiphysin/Rvs (BAR) domain-containing proteins are essential players in the dynamics of intracellular compartments. The BAR domain is an evolutionarily conserved dimeric module characterized by a crescent-shaped structure whose intrinsic curvature, flexibility, and ability to assemble into highly ordered oligomers contribute to inducing the curvature of target membranes. Endophilins, diverging into A and B subgroups, are BAR and SH3 domain-containing proteins. They exert activities in membrane dynamic processes such as endocytosis, autophagy, mitochondrial dynamics, and permeabilization during apoptosis. Here, we rep...
Source: Journal of Biological Chemistry - February 3, 2012 Category: Chemistry Authors: Gortat, A., San-Roman, M. J., Vannier, C., Schmidt, A. A. Tags: Cell Biology Source Type: research

PARP1 Poisoning Sensitizes to Topoisomerase I Inhibitors [Cell Biology]email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
In this study we evaluated the ability of the PARP inhibitor veliparib to enhance the cytotoxicity of the topoisomerase I poisons topotecan and camptothecin (CPT). Veliparib increased the cell cycle and cytotoxic effects of topotecan in multiple cell line models. Importantly, this sensitization occurred at veliparib concentrations far below those required to substantially inhibit poly(ADP-ribose) polymer synthesis and at least an order of magnitude lower than those involved in selective killing of homologous recombination-deficient cells. Further studies demonstrated that veliparib enhanced the effects of CPT in wild-type ...
Source: Journal of Biological Chemistry - February 3, 2012 Category: Chemistry Authors: Patel, A. G., Flatten, K. S., Schneider, P. A., Dai, N. T., McDonald, J. S., Poirier, G. G., Kaufmann, S. H. Tags: Cell Biology Source Type: research

Reduced Adipose Fibrosis in 11{beta}HSD1 Deficiency [Cell Biology]email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
In obesity, rapidly expanding adipose tissue becomes hypoxic, precipitating inflammation, fibrosis, and insulin resistance. Compensatory angiogenesis may prevent these events. Mice lacking the intracellular glucocorticoid-amplifying enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1−/−) have “healthier” adipose tissue distribution and resist metabolic disease with diet-induced obesity. Here we show that adipose tissues of 11βHSD1−/− mice exhibit attenuated hypoxia, induction of hypoxia-inducible factor (HIF-1α) activation of the TGF-β/Smad3/α-smooth muscle actin (α-SMA) signaling pathway, and fibrog...
Source: Journal of Biological Chemistry - February 3, 2012 Category: Chemistry Authors: Michailidou, Z., Turban, S., Miller, E., Zou, X., Schrader, J., Ratcliffe, P. J., Hadoke, P. W. F., Walker, B. R., Iredale, J. P., Morton, N. M., Seckl, J. R. Tags: Molecular Bases of Disease Source Type: research

miR-30a Sensitizes Tumor Cells to cis-Platinum [Cell Biology]email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
In conclusion, our results demonstrate for the first time that miR-30a can sensitize tumor cells to cis-DDP via reducing beclin 1-mediated autophagy and that increasing miR-30a level in tumor cells represents a novel approach to enhance the efficacy of chemotherapy during cancer treatment. (Source: Journal of Biological Chemistry)
Source: Journal of Biological Chemistry - February 3, 2012 Category: Chemistry Authors: Zou, Z., Wu, L., Ding, H., Wang, Y., Zhang, Y., Chen, X., , Zhang, C.-Y., Zhang, Q., Zen, K. Tags: Molecular Bases of Disease Source Type: research

Aft1 Is Required for Pericentromeric Cohesin [Cell Biology]email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
The Saccharomyces cerevisiae iron-responsive transcription factor, Aft1, has a well established role in regulating iron homeostasis through the transcriptional induction of iron-regulon genes. However, recent studies have implicated Aft1 in other cellular processes independent of iron regulation such as chromosome stability. In addition, chromosome spreads and two-hybrid data suggest that Aft1 interacts with and co-localizes with kinetochore proteins; however, the cellular implications of this have not been established. Here, we demonstrate that Aft1 associates with the kinetochore complex through Iml3. Furthermore, like I...
Source: Journal of Biological Chemistry - February 3, 2012 Category: Chemistry Authors: Hamza, A., Baetz, K. Tags: DNA and Chromosomes Source Type: research

Structure and Function of Human Cdc45 [Cell Biology]email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
We report biochemical and structural data on the recombinant human Cdc45 protein, consistent with the proposed DHH family affiliation. Like the RecJ exonucleases, the human Cdc45 protein is able to bind single-stranded, but not double-stranded DNA. Small angle x-ray scattering data are consistent with a model compatible with the crystallographic structure of the RecJ/DHH family members. (Source: Journal of Biological Chemistry)
Source: Journal of Biological Chemistry - February 3, 2012 Category: Chemistry Authors: Krastanova, I., Sannino, V., Amenitsch, H., Gileadi, O., Pisani, F. M., Onesti, S. Tags: Protein Structure and Folding Source Type: research

B(a)P-induced {beta}2ADR-mediated Intracellular Ca2+ Increase [Cell Biology]email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Polycyclic aromatic hydrocarbons (PAHs) such as benzo(a)pyrene (B(a)P) are widely distributed environmental contaminants, known as potent ligands of the aryl hydrocarbon receptor (AhR). These chemicals trigger an early and transient increase of intracellular calcium concentration ([Ca2+]i), required for AhR-related effects of PAHs. The mechanisms involved in this calcium mobilization were investigated in the present study. We demonstrated that B(a)P-mediated [Ca2+]i induction was prevented in endothelial HMEC-1 cells by counteracting β2-adrenoreceptor (β2ADR) activity using pharmacological antagonists, anti-β2ADR antibo...
Source: Journal of Biological Chemistry - February 3, 2012 Category: Chemistry Authors: Mayati, A., Levoin, N., Paris, H., N'Diaye, M., Courtois, A., Uriac, P., Lagadic-Gossmann, D., Fardel, O., Le Ferrec, E. Tags: Signal Transduction Source Type: research

Autophagy Suppresses IL-1{beta} Signaling via Regulation of p62 Stability [Cell Biology]email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
In this study, we identified a novel function of ATG16L1, which suppresses signaling of the pro-inflammatory cytokine IL-1β. Deletion of ATG16L1 in mouse embryonic fibroblasts significantly amplifies IL-1β signal transduction cascades. This amplification is due to elevated p62 levels in ATG16L1-deficient cells. We found that ATG16L1 regulates p62 levels via both autolysosomal and proteasomal pathways. For proteasomal degradation, we found that Cullin-3 (Cul-3) is a E3 ubiquitin ligase of p62 and that ATG16L1 is essential for neddylation of Cul-3, a step required for Cul-3 activation. Taken together our data indicate that...
Source: Journal of Biological Chemistry - February 3, 2012 Category: Chemistry Authors: Lee, J., Kim, H. R., Quinley, C., Kim, J., Gonzalez-Navajas, J., Xavier, R., Raz, E. Tags: Signal Transduction Source Type: research

KCa1.1 Channels in RA-FLS [Cell Biology]email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Fibroblast-like synoviocytes (FLS) play important roles in the pathogenesis of rheumatoid arthritis (RA). Potassium channels have regulatory roles in many cell functions. We have identified the calcium- and voltage-gated KCa1.1 channel (BK, Maxi-K, Slo1, KCNMA1) as the major potassium channel expressed at the plasma membrane of FLS isolated from patients with RA (RA-FLS). We further show that blocking this channel perturbs the calcium homeostasis of the cells and inhibits the proliferation, production of VEGF, IL-8, and pro-MMP-2, and migration and invasion of RA-FLS. Our findings indicate a regulatory role of KCa1.1 chann...
Source: Journal of Biological Chemistry - February 3, 2012 Category: Chemistry Authors: Hu, X., Laragione, T., Sun, L., Koshy, S., Jones, K. R., Ismailov, I. I., Yotnda, P., Horrigan, F. T., Gulko, P. S., Beeton, C. Tags: Molecular Bases of Disease Source Type: research

Netrin-4 in Developmental Angiogenesis [Cell Biology]email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Netrins form a heterogeneous family of laminin-related molecules with multifunctional activities. Netrin-4, the most distant member of this family, is related to the laminin β chain and has recently been proposed to play an important role in embryonic and pathological angiogenesis. However, the data reported so far lead to the apparently contradictory conclusions supporting Netrin-4 as either a pro- or an anti-angiogenic factor. To elucidate this controversy, Netrin-4 was analyzed for a vascular activity in both cell-based models (human umbilical vein endothelial cells and human umbilical artery endothelial cells) and two...
Source: Journal of Biological Chemistry - February 3, 2012 Category: Chemistry Authors: Lambert, E., Coissieux, M.-M., Laudet, V., Mehlen, P. Tags: Developmental Biology Source Type: research

Direct Identification of miR-21 Targets in vSMCs [Cell Biology]email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
The bone morphogenetic protein 4 (BMP4) signaling pathway plays a critical role in the promotion and maintenance of the contractile phenotype in vascular smooth muscle cell (vSMC). Misexpression or inactivating mutations of the BMP receptor gene can lead to dedifferentiation of vSMC characterized by increased migration and proliferation that is linked to vascular proliferative disorders. Previously we demonstrated that vSMCs increase microRNA-21 (miR-21) biogenesis upon BMP4 treatment, which induces contractile gene expression by targeting programmed cell death 4 (PDCD4). To identify novel targets of miR-21 that are critic...
Source: Journal of Biological Chemistry - February 3, 2012 Category: Chemistry Authors: Kang, H., Davis-Dusenbery, B. N., Nguyen, P. H., Lal, A., Lieberman, J., Van Aelst, L., Lagna, G., Hata, A. Tags: Signal Transduction Source Type: research

EGR2 in Loading-related Gene Regulation in Bone Cells [Signal Transduction]email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Of the 1,328 genes revealed by microarray to be differentially regulated by disuse, or at 8 h following a single short period of osteogenic loading of the mouse tibia, analysis by predicting associated transcription factors from annotated affinities revealed the transcription factor EGR2/Krox-20 as being more closely associated with more pathways and functions than any other. Real time quantitative PCR confirmed up-regulation of Egr2 mRNA expression by loading of the tibia in vivo. In vitro studies where strain was applied to primary cultures of mouse tibia-derived osteoblastic cells and the osteoblast UMR106 cell line als...
Source: Journal of Biological Chemistry - February 3, 2012 Category: Chemistry Authors: Zaman, G., Sunters, A., Galea, G. L., Javaheri, B., Saxon, L. K., Moustafa, A., Armstrong, V. J., Price, J. S., Lanyon, L. E. Tags: Cell Biology Source Type: research

Novel Golgi Inhibitor Shows Potent Antitumor Activity [Cell Biology]email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
ADP-ribosylation factor 1 (Arf1) plays a major role in mediating vesicular transport. Brefeldin A (BFA), a known inhibitor of the Arf1-guanine nucleotide exchange factor (GEF) interaction, is highly cytotoxic. Therefore, interaction of Arf1 with ArfGEF is an attractive target for cancer treatment. However, BFA and its derivatives have not progressed beyond the pre-clinical stage of drug development because of their poor bioavailability. Here, we aimed to identify novel inhibitors of the Arf1-ArfGEF interaction that display potent antitumor activity in vivo but with a chemical structure distinct from that of BFA. We exploit...
Source: Journal of Biological Chemistry - February 3, 2012 Category: Chemistry Authors: Ohashi, Y., Iijima, H., Yamaotsu, N., Yamazaki, K., Sato, S., Okamura, M., Sugimoto, K., Dan, S., Hirono, S., Yamori, T. Tags: Cell Biology Source Type: research

APC Regulation of GSK-3 [Cell Biology]email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Glycogen synthase kinase-3 (GSK-3) is essential for many signaling pathways and cellular processes. As Adenomatous Polyposis Coli (APC) functions in many of the same processes, we investigated a role for APC in the regulation of GSK-3-dependent signaling. We find that APC directly enhances GSK-3 activity. Furthermore, knockdown of APC mimics inhibition of GSK-3 by reducing phosphorylation of glycogen synthase and by activating mTOR, revealing novel roles for APC in the regulation of these enzymes. Wnt signaling inhibits GSK-3 through an unknown mechanism, and this results in both stabilization of β-catenin and activation ...
Source: Journal of Biological Chemistry - February 3, 2012 Category: Chemistry Authors: Valvezan, A. J., Zhang, F., Diehl, J. A., Klein, P. S. Tags: Signal Transduction Source Type: research

C-terminal Modification of Osteopontin [Cell Biology]email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
In this study, we show that modification of the extreme C terminus of OPN plays an important regulatory role for the interaction with the αVβ3-integrin. It is demonstrated that highly phosphorylated OPN has a much reduced capability to promote cell adhesion via the αVβ3-integrin compared with lesser phosphorylated forms. The cell attachment promoted by highly phosphorylated OPN could be greatly increased by both dephosphorylation and proteolytic removal of the C terminus. Using recombinantly expressed OPN containing a tag in the N or C terminus, it is shown that a modification in the C-terminal part significantly reduc...
Source: Journal of Biological Chemistry - February 3, 2012 Category: Chemistry Authors: Christensen, B., Klaning, E., Nielsen, M. S., Andersen, M. H., Sorensen, E. S. Tags: Protein Structure and Folding Source Type: research

CYP17 Inhibitors Regulate AR Signaling [Cell Biology]email this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
TOK-001 and abiraterone are potent 17-heteroarylsteroid (17-HAS) inhibitors of Cyp17, one of the rate-limiting enzymes in the biosynthesis of testosterone from cholesterol in prostate cancer cells. Nevertheless, the molecular mechanism underlying the prevention of prostate cell growth by 17-HASs still remains elusive. Here, we assess the effects of 17-HASs on androgen receptor (AR) activity in LNCaP and LAPC-4 cells. We demonstrate that both TOK-001 and abiraterone reduced AR protein and mRNA expression, and antagonized AR-dependent promoter activation induced by androgen. TOK-001, but not abiraterone, is an effective appa...
Source: Journal of Biological Chemistry - February 3, 2012 Category: Chemistry Authors: Soifer, H. S., Souleimanian, N., Wu, S., Voskresenskiy, A. M., Kisaayak Collak, F., Cinar, B., Stein, C. A. Tags: Molecular Bases of Disease Source Type: research

Bypass of cell cycle arrest induced by transient DNMT1 post-transcriptional silencing triggers aneuploidy in human cellsemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
Conclusion: Our results suggest that DNMT1 depletion triggers a p14ARF/p53 dependent cell cycle arrest to counteract the aneuploidy induced by changes in DNA methylation. (Source: Cell Division)
Source: Cell Division - February 3, 2012 Category: Cytology Authors: Viviana BarraTiziana SchillaciLaura LentiniGiuseppe CostaAldo Di Leonardo Source Type: research

Gadd45a and Gadd45b modulate innate immune functions of granulocytes and macrophages by differential regulation of p38 and JNK signalingemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
This study shows that mice lacking either Gadd45a or Gadd45b are defective in the recruitment of granulocytes and macrophages to the intra‐peritoneal cavity following intra‐peritoneal administration of the bacterial cell‐wall PAMP lipopolysaccharide (LPS). Bone marrow (BM) derived granulocytes and macrophages lacking either Gadd45a or Gadd45b are shown to be impaired in their chemotactic response to LPS, as well as other inflammatory stimuli such as fMLP and IL‐8. Evidence was obtained also implicating Gadd45a and Gadd45b in other myeloid innate immune functions, including ROS production, phagocytosis, and adhesion...
Source: Journal of Cellular Physiology - February 3, 2012 Category: Cytology Authors: Dominic M. SalernoJennifer S. TrontBarbara HoffmanDan A. Liebermann Tags: Original Research Article Source Type: research

CIZ/NMP4 is expressed in B16 melanoma and forms a positive feedback loop with RANKL to promote migration of the melanoma cellsemail this articleEmail this article to a colleague. save this article to My ClippingsSave this article to My Clippings. discuss this articleDiscuss or comment on this article.
AbstractTumor metastasis to bone is a serious pathological situation that causes severe pain, and deterioration in locomoter function. However, the mechanisms underlying tumor metastasis is still incompletely understood. CIZ/NMP4 is a nucleocytoplasmic shuttling protein and its roles in tumor cells have not been known. We, therefore, hypothesized the role of CIZ/NMP4 in B16 melanoma cells that metastasize to bone. CIZ/NMP4 is expressed in B16 cells. The CIZ/NMP4 expression levels are correlated to the metastatic activity in divergent types of melanoma cells. Overexpression of CIZ/NMP4increased B16 cell migration in Trans...
Source: Journal of Cellular Physiology - February 3, 2012 Category: Cytology Authors: Tomomi SakumaTetsuya NakamotoHiroaki HemmiSohei KitazawaRiko KitazawaTakuya NotomiTadayosi HayataYoichi EzuraTeruo AmagasaMasaki Noda Tags: Rapid Communication Source Type: research