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This page shows you the most recent publications within this specialty of the MedWorm directory. This is page number 6.

NQO1 Regulates Host Susceptibility to Ozone via A2-isoP [Cell Biology]
NADPH:quinone oxidoreductase 1 (NQO1) is recognized as a major susceptibility gene for ozone-induced pulmonary toxicity. In the absence of NQO1 as can occur by genetic mutation, the human airway is protected from harmful effects of ozone. We recently reported that NQO1-null mice are protected from airway hyperresponsiveness and pulmonary inflammation following ozone exposure. However, NQO1 regenerates intracellular antioxidants and therefore should protect the individual from oxidative stress. To explain this paradox, we tested whether in the absence of NQO1 ozone exposure results in increased generation of A2-isoprostane,...
Source: Journal of Biological Chemistry - February 15, 2013 Category: Chemistry Authors: Kummarapurugu, A. B., Fischer, B. M., Zheng, S., Milne, G. L., Ghio, A. J., Potts-Kant, E. N., Foster, W. M., Soderblom, E. J., Dubois, L. G., Moseley, M. A., Thompson, J. W., Voynow, J. A. Tags: Gene Regulation Source Type: research

Ca2+- and ROS-induced Activation of Superoxide Flashes [Membrane Biology]
Mitochondrial superoxide flashes reflect a quantal, bursting mode of reactive oxygen species (ROS) production that arises from stochastic, transient opening of the mitochondrial permeability transition pore (mPTP) in many types of cells and in living animals. However, the regulatory mechanisms and the exact nature of the flash-coupled mPTP remain poorly understood. Here we demonstrate a profound synergistic effect between mitochondrial Ca2+ uniport and elevated basal ROS production in triggering superoxide flashes in intact cells. Hyperosmotic stress potently augmented the flash activity while simultaneously elevating mito...
Source: Journal of Biological Chemistry - February 15, 2013 Category: Chemistry Authors: Hou, T., Zhang, X., Xu, J., Jian, C., Huang, Z., Ye, T., Hu, K., Zheng, M., Gao, F., Wang, X., Cheng, H. Tags: Cell Biology Source Type: research

Neutrophil Lyso-PS Regulates Tissue Neutrophilia [Lipids]
Resolution of neutrophilia characteristic of acute inflammation requires cessation of neutrophil recruitment and removal of tissue neutrophils. Based on in vitro studies, a role in these events was hypothesized for oxidant-generated lysophosphatidylserine (lyso-PS) on recruited neutrophils signaling via the G2A receptor on macrophages. Peritoneal exudate neutrophils harvested from wild type (WT) mice had 5-fold more lyso-PS (lyso-PShigh) than those of gp91phox−/− (lyso-PSlow) mice. Ex vivo engulfment of lyso-PShigh neutrophils (95% viable) by WT peritoneal macrophages was quantitatively similar to UV-irradiated apoptot...
Source: Journal of Biological Chemistry - February 15, 2013 Category: Chemistry Authors: Frasch, S. C., Fernandez-Boyanapalli, R. F., Berry, K. A. Z., Murphy, R. C., Leslie, C. C., Nick, J. A., Henson, P. M., Bratton, D. L. Tags: Cell Biology Source Type: research

Role of FAM57B in Adipocyte Differentiation [Lipids]
This report identifies a novel gene encoding Fam57b (family with sequence similarity 57, member B) as a novel peroxisome proliferator-activated receptor γ (PPARγ)-responsive transmembrane gene that is related to obesity. The gene was identified based on an integrated bioinformatics analysis of the following three expression profiling data sets: adipocyte differentiation of mouse stromal cells (ST2 cells), adipose tissues from obesity mice, and siRNA-mediated knockdown of Pparγ using ST2 cells. Fam57b consists of three variants expressed from different promoters and contains a Tram-Lag1-CLN8 domain that is related to cer...
Source: Journal of Biological Chemistry - February 15, 2013 Category: Chemistry Authors: Yamashita-Sugahara, Y., Tokuzawa, Y., Nakachi, Y., Kanesaki-Yatsuka, Y., Matsumoto, M., Mizuno, Y., Okazaki, Y. Tags: Cell Biology Source Type: research

Amino Acid-induced GLP-1 Secretion in GLUTag Cells [Signal Transduction]
Although amino acids are dietary nutrients that evoke the secretion of glucagon-like peptide 1 (GLP-1) from intestinal L cells, the precise molecular mechanism(s) by which amino acids regulate GLP-1 secretion from intestinal L cells remains unknown. Here, we show that the G protein-coupled receptor (GPCR), family C group 6 subtype A (GPRC6A), is involved in amino acid-induced GLP-1 secretion from the intestinal L cell line GLUTag. Application of l-ornithine caused an increase in intracellular Ca2+ concentration ([Ca2+]i) in GLUTag cells. Application of a GPRC6A receptor antagonist, a phospholipase C inhibitor, or an IP3 re...
Source: Journal of Biological Chemistry - February 15, 2013 Category: Chemistry Authors: Oya, M., Kitaguchi, T., Pais, R., Reimann, F., Gribble, F., Tsuboi, T. Tags: Cell Biology Source Type: research

Noninvasive tool for the diagnosis of polyomavirus BK–associated nephropathy in renal transplant recipients
Abstract: Noninvasive methods can facilitate early diagnosis of BK virus (BKV) replication and guide the evaluation of BKV-associated nephropathy (BKVAN). We developed 3 noninvasive methods for BKVAN screening including quantitative polymerase chain reaction (PCR) assay for BKV DNA load in urine and plasma, and quantitative assay of urine cytology by light microscopy or electron microscopy, and used these assays concurrently with renal transplant biopsies for the evaluation of 338 patients. BKVAN was diagnosed in 24 (7.1%) of 338 renal recipients. The median level of the 3 methods was the highest in pattern B of BKVAN (P <...
Source: Diagnostic Microbiology and Infectious Disease - February 14, 2013 Category: Microbiology Authors: Gang Huang, Wen-fang Chen, Chang-xi Wang, Ji-guang Fei, Su-xiong Deng, Jiang Qiu, Li-zhong Chen Tags: Virology Source Type: research

A high resolution view of the fly actin cytoskeleton lacking a functional WAVE complex
Summary The development of multicellular organisms involves a series of morphogenetic processes coordinating a highly dynamic and organized interplay between cells and their environment. Thus, the generation of forces that drive cellular and intracellular movements is prerequisite to shape single cells into tissues and organs. The actin cytoskeleton represents a highly dynamic filamentous system providing cell structure and mechanical forces to drive membrane protrusion, cell migration and vesicle trafficking. Here, we apply the structured‐illumination microscopy (SIM) technique to analyse the actin cytoskeleton in fixed...
Source: Journal of Microscopy - February 14, 2013 Category: Laboratory Medicine Authors: T. ZOBEL, S. BOGDAN Source Type: research

Cotransin induces accumulation of a cytotoxic clusterin variant that cotranslationally rerouted to the cytosol.
Abstract Although clusterin (CLU) was originally identified as a secreted glycoprotein that plays cytoprotective role, several intracellular CLU variants have been recently identified in the diverse pathological conditions. The mechanistic basis of these variants is now believed to be alternative splicing and retrotranslocation. Here, we uncovered, an unglycosylated and signal sequence-unprocessed, CLU variant in the cytosol. This variant proved to be a product that cotranslationally rerouted to the cytosol during translocation. Cytosolic CLU was prone to aggregation at peri-nuclear region of cells and induced cell...
Source: Experimental Cell Research - February 14, 2013 Category: Cytology Authors: Choi I, Kim J, Park JY, Kang SW Tags: Exp Cell Res Source Type: research

Generation and characterization of a spontaneously immortalized endothelial cell line from mice microcirculation.
Abstract Endothelial cells from microvasculature are directly involved in a large number of vascular diseases; however, culture of these cells is problematic since most methodologies employ proteolytic enzymes or mechanical techniques, leading to cell damage and contamination of endothelial cultures with other cellular types. Besides, primary cultured cells have a short life span in vitro and undergo replicative senescence after 3-4 passages, limiting long-term studies. In the present work we report the generation of a spontaneously immortalized endothelial culture obtained from mice pulmonary capillaries. Firstly,...
Source: Experimental Cell Research - February 14, 2013 Category: Cytology Authors: Loiola RA, Torres TC, Aburaya CM, Landgraf MA, Landgraf RG, Bosco Pesquero J, Fernandes L Tags: Exp Cell Res Source Type: research

MiR-30d induces apoptosis and is regulated by the Akt/FOXO pathway in renal cell carcinoma.
In this study, we identified miR-30d as a downstream effector of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway in renal cell carcinoma (RCC) cells. We show that Akt inhibition transcriptionally up-regulates miR-30d expression through activation of the transcription factor forkhead box O (FOXO) 3A. Functional analysis revealed that miR-30d overexpression suppresses cell proliferation and induces apoptosis in RCC cells, suggesting that miR-30d acts as a tumor suppressor. In searching for downstream targets of miR-30d, we found that miR-30d post-transcriptionally suppresses expression of the oncoprotein metadheri...
Source: Cellular Signalling - February 14, 2013 Category: Cytology Authors: Wu C, Jin B, Chen L, Zhuo D, Zhang Z, Gong K, Mao Z Tags: Cell Signal Source Type: research

Ephedrine induced Thioredoxin-1 expression through β-adrenergic receptors/Cyclic AMP/protein kinase A/dopamine- and Cyclic AMP-regulated phosphoprotein signaling pathway.
In this study, we found that Eph induced Trx-1 expression, which was inhibited by propranolol (β-adrenergic receptors inhibitor), but not by phenoxybenzamine (α-adrenergic receptors inhibitor) in rat pheochromocytoma PC12 cells. Moreover, the increase of Trx-1 expression was inhibited by SQ22536 (adenylyl cyclase inhibitor) and H-89 (protein kinase A inhibitor). Interestingly, the effect of Eph on dopamine- and Cyclic AMP-regulated phosphoprotein (DARPP-32) was similar to Trx-1. Thus, the relationship between Trx-1 and DARPP-32 was further studied. The DARPP-32 siRNA significantly reduced Trx-1 expression, but Trx-1 siRN...
Source: Cellular Signalling - February 14, 2013 Category: Cytology Authors: Jia JJ, Zeng XS, Li Y, Ma S, Bai J Tags: Cell Signal Source Type: research

The multiple roles for Sox2 in stem cell maintenance and tumorigenesis.
Abstract The Sry-containing protein Sox2 initially was known to regulate the self-renewal of the mouse and human embryonic stem cells (ESCs). It is also important for the maintenance of stem cells in multiple adult tissues including the brain and trachea, and it is one of the key transcription factors for establishing induced pluripotent stem cells. Recently, overexpression and gene amplification of Sox2 has been associated with the development of squamous cell carcinoma in multiple tissues such as the lung and esophagus. These different roles for Sox2 involve a complicated regulatory networks consisting of microRN...
Source: Cellular Signalling - February 14, 2013 Category: Cytology Authors: Liu K, Lin B, Zhao M, Yang X, Chen M, Gao A, Liu F, Que J, Lan X Tags: Cell Signal Source Type: research

Long non-coding RNA ANRIL (CDKN2B-AS) is induced by the ATM-E2F1 signaling pathway.
Abstract The maintenance of genome integrity is essential for the proper function and survival of all organisms. Human cells have evolved prompt and efficient DNA damage response to eliminate the detrimental effects of DNA lesions. The DNA damage response involves a complex network of processes that detect and repair DNA damage, in which long non-coding (lncRNAs), a new class of regulatory RNAs, may play important roles. Recent studies have identified a large number of lncRNAs in mammalian transcriptomes. However, little is known about the regulation and function of lncRNAs in the DNA damage response. In the presen...
Source: Cellular Signalling - February 14, 2013 Category: Cytology Authors: Wan G, Mathur R, Hu X, Liu Y, Zhang X, Peng G, Lu X Tags: Cell Signal Source Type: research

Autophagy during Mycobacterium tuberculosis infection and implications for future tuberculosis medications.
Abstract Autophagy is a cellular homeostasis mechanism to eliminate unwanted or excessive organelles, or for the turnover of long-life cytosolic macromolecules. During Mycobacterium tuberculosis infection, autophagy represents not only an antimicrobial mechanism for the clearance of the intracelluar pathogen, but also prevents excessive inflammation, avoiding the adverse effects on host. Here we focus on the anti-tuberculosis autophagy and signal pathways involved, attempt to depict an integrative map of the interaction between autophagy and cytokine, ROS production, vitamin D, and inflammatory response. Novel auto...
Source: Cellular Signalling - February 14, 2013 Category: Cytology Authors: Yu X, Li C, Hong W, Pan W, Xie J Tags: Cell Signal Source Type: research

RGS19 inhibits Ras signaling through Nm23H1/2-mediated phosphorylation of the kinase suppressor of Ras.
This study demonstrates that expression of RGS19 can suppress Ras-mediated signaling via upregulation of Nm23. PMID: 23416464 [PubMed - as supplied by publisher]
Source: Cellular Signalling - February 14, 2013 Category: Cytology Authors: Tso PH, Wang Y, Yung LY, Tong Y, Lee MM, Wong YH Tags: Cell Signal Source Type: research

Post-translational Regulation of mTOR Complex 1 in Hypoxia and Reoxygenation.
In conclusion, our results suggest that mTORC1 can respond rapidly to changes in oxygen concentrations via a post-translational mechanism that may involve a heme containing protein. PMID: 23416465 [PubMed - as supplied by publisher]
Source: Cellular Signalling - February 14, 2013 Category: Cytology Authors: Tan CY, Hagen T Tags: Cell Signal Source Type: research

RKIP Regulates MAP Kinase Signaling in Cells with Defective B-Raf Activity.
Abstract MAP kinase (MAPK) signaling results from activation of Raf kinases in response to external or internal stimuli. Here, we demonstrate that Raf Kinase Inhibitory Protein (RKIP) regulates the activation of MAPK when B-Raf signaling is defective. We used multiple models including mouse embryonic fibroblasts (MEFs) and primary keratinocytes from RKIP- or Raf-deficient mice as well as allografts in mice to investigate the mechanism. Loss of B-Raf protein or activity significantly reduces MAPK activation in these cells. We show that RKIP depletion can rescue the compromised ERK activation and promote proliferatio...
Source: Cellular Signalling - February 14, 2013 Category: Cytology Authors: Zeng L, Ehrenreiter K, Menon J, Menard R, Kern F, Nakazawa Y, Bevilacqua E, Imamoto A, Baccarini M, Rosner MR Tags: Cell Signal Source Type: research

Expression of human BRCA1Δ17-19 alternative splicing variant with a truncated BRCT domain in MCF-7 cells results in impaired assembly of DNA repair complexes and aberrant DNA damage response.
In this study, we examined the influence of the BRCA1Δ17-19 ASV, which lacks a portion of the BRCT domain, on DNA repair capacity using human MCF-7 BC cell clones with stably modified BRCA1 expression. Our results show that overexpression of BRCA1Δ17-19 impairs homologous recombination repair (sensitizes cells to mitomycin C), delays repair of ionizing radiation-induced DNA damage and dynamics of the ionizing radiation-induced foci (IRIF) formation, and undermines also the non-homologous end joining repair (NHEJ) activity. Mechanistically, BRCA1Δ17-19 cannot interact with the partner proteins Abraxas and CtIP, thus prev...
Source: Cellular Signalling - February 14, 2013 Category: Cytology Authors: Sevcik J, Falk M, Macurek L, Kleiblova P, Lhota F, Hojny J, Stefancikova L, Janatova M, Bartek J, Stribrna J, Hodny Z, Jezkova L, Pohlreich P, Kleibl Z Tags: Cell Signal Source Type: research

The human adenylate kinase 9 is a nucleoside mono- and diphosphate kinase.
Abstract Adenylate kinases regulate adenine nucleotide levels and are present in different intracellular compartments. These enzymes also participate in the activation of pharmacologically active nucleoside and nucleotide analogs. We have in the present study identified the ninth isoform of the adenylate kinase family of enzymes and accordingly named the protein adenylate kinase 9 (AK9). Initially a full-length cDNA of a hypothetical protein containing a predicted adenylate kinase domain was identified and subsequently cloned and expressed in Escherichia coli. The substrate specificity of the recombinant protein sh...
Source: The International Journal of Biochemistry and Cell Biology - February 14, 2013 Category: Biochemistry Authors: Amiri M, Conserva F, Panayiotou C, Karlsson A, Solaroli N Tags: Int J Biochem Cell Biol Source Type: research

Knockdown of creatine kinase B inhibits ovarian cancer progression by decreasing glycolysis.
Abstract Creatine kinase plays a key role in the energy homeostasis of vertebrate cells. Creatine kinase B (CKB), a cytosolic isoform of creatine kinase, shows upregulated expression in a variety of cancers. In this research, we confirmed that some ovarian cancer tissues had elevated CKB expression at the protein level. The functions of CKB in ovarian cancer progression were investigated in the ovarian cancer cell line Skov3, which has a high CKB expression. It was found that CKB knockdown inhibited Skov3 cell proliferation and induced apoptosis under hypoxia or hypoglycemia conditions. CKB depletion also sensitize...
Source: The International Journal of Biochemistry and Cell Biology - February 14, 2013 Category: Biochemistry Authors: Li XH, Chen XJ, Ou WB, Zhang Q, Lv ZR, Zhan Y, Ma L, Huang T, Yan YB, Zhou HM Tags: Int J Biochem Cell Biol Source Type: research

Peroxisome Formation and Maintenance Are Dependent on the Endoplasmic Reticulum.
Abstract Looks can be deceiving. Although peroxisomes appear to be simple organelles, their formation and maintenance pose unique challenges for the cell. The birth of new peroxisomes starts at the endoplasmic reticulum (ER), which delivers lipids and membrane proteins. To form a new peroxisomal compartment, ER-derived preperoxisomal vesicles carrying different membrane proteins fuse, allowing the assembly of the peroxisomal translocon. To complete formation, peroxisomes import their soluble proteins directly from the cytosol using the newly assembled translocon. Together with the ER-derived biogenic route, peroxis...
Source: Annual Review of Biochemistry - February 14, 2013 Category: Biochemistry Authors: Tabak HF, Braakman I, van der Zand A Tags: Annu Rev Biochem Source Type: research

Human Immunodeficiency Virus-Associated Lumbosacral Polyradiculopathy (P03.260)
CONCLUSIONS: This case represents the importance of considering HIV itself as a possible etiology of subacute lumbosacral polyradiculopathy.Disclosure: Dr. Maiser has nothing to disclose. Dr. Hartmann has nothing to disclose.
Source: Neurology - February 14, 2013 Category: Neurology Authors: Maiser, S., Hartmann, A. Tags: P03 Infections I Source Type: research

Is Non-Length-Dependant Small Fiber Sensory Neuropathy an Inflammatory Neuropathy? (P01.140)
CONCLUSIONS: NLD-SFSN occurs more commonly in younger female, onset is more likely acute and development appears to be more frequently associated with an immune mediated condition. This study confirms that NLD-SFSN is often associated with an inflammatory process.Disclosure: Dr. Laffon has nothing to disclose. Dr. Delmont has nothing to disclose. Dr. Alchaar has nothing to disclose. Dr. Lantéri Minet has nothing to disclose. Dr. Jeandel has nothing to disclose. Dr. Butori has nothing to disclose. Dr. Desnuelle has nothing to disclose.
Source: Neurology - February 14, 2013 Category: Neurology Authors: Laffon, M., Delmont, E., Alchaar, H., Lanteri Minet, M., Jeandel, P.-Y., Butori, C., Desnuelle, C. Tags: P01 Peripheral Nerve: Small Fiber and Painful Source Type: research

Isolated Bilateral Cranial Nerve Three Palsy as Unique Manifestation of CNS Spread of Burkitt Lymphoma (P01.058)
CONCLUSIONS: Thus, this case illustrates an atypical presentation of presumed CNS infiltration of Burkitt lymphoma, with a non-diagnostic work-up, which responded to radiation treatment. This may suggest a role for radiation therapy when CNS spread is suspected clinically despite a lack of positive confirmatory diagnostic testing.Disclosure: Dr. Damian has nothing to disclose. Dr. Lambert has nothing to disclose. Dr. Laneuville has nothing to disclose.
Source: Neurology - February 14, 2013 Category: Neurology Authors: Damian, A., Lambert, C., Laneuville, P. Tags: P01 Neurologic Manifestations: Therapeutics Source Type: research

Human Hsp40 proteins, DNAJA1 and DNAJA2, as potential targets of the immune response triggered by bacterial DnaJ in rheumatoid arthritis.
Abstract Hsp40 proteins of bacterial and human origin are suspected to be involved in the pathogenesis of rheumatoid arthritis (RA). It has been shown that sera of RA patients contain increased levels of antibodies directed to bacterial and human Hsp40s. The aim of this work was to explore immunological similarities between the bacterial (DnaJ) and human (DNAJA1 and DNAJA2) Hsp40 proteins in relation to their possible involvement in the RA. Using polyclonal antibodies directed against a full-length DnaJ or its domains, against DNAJA1 and DNAJA2, as well as monoclonal anti-DnaJ antibodies, we found immunological sim...
Source: Cell Stress and Chaperones - February 14, 2013 Category: Cytology Authors: Kotlarz A, Tukaj S, Krzewski K, Brycka E, Lipinska B Tags: Cell Stress Chaperones Source Type: research

Synthesis and screening of 3-MA derivatives for autophagy inhibitors.
In this study, we synthesized a library of small compounds by chemically modifying 3-MA and screened this library for autophagy inhibitors. Three 3-MA derivatives generated through this approach showed improved solubility and effectiveness in inhibiting autophagy. We demonstrated that chemical modification of an existing autophagy inhibitor is an effective method to generate improved autophagy inhibitors. PMID: 23412639 [PubMed - as supplied by publisher]
Source: Autophagy - February 14, 2013 Category: Cytology Authors: Wu Y, Wang X, Guo H, Zhang B, Zhang XB, Shi ZJ, Yu L Tags: Autophagy Source Type: research

Age-dependent changes in hippocampal synaptic transmission and plasticity in the PLB1(Triple) Alzheimer mouse.
Abstract Several genetically engineered models exist that mimic aspects of the pathological and cognitive hallmarks of Alzheimer's disease (AD). Here we report on a novel mouse model generated by targeted knock-in of transgenes containing mutated human amyloid precursor protein (APP) and microtubule-associated protein tau genes, inserted into the HPRT locus and controlled by the CaMKIIα regulatory element. These mice were crossed with an asymptomatic presenilin1(A246E) overexpressing line to generate PLB1(Triple) mice. Gene expression analysis and in situ hybridization confirmed stable, forebrain-specific, and gen...
Source: Cellular and Molecular Life Sciences : CMLS - February 14, 2013 Category: Cytology Authors: Koss DJ, Drever BD, Stoppelkamp S, Riedel G, Platt B Tags: Cell Mol Life Sci Source Type: research

miR-7 Suppresses Breast Cancer Metastasis
In this report, we found that CSCs (CD24−/CD44+/ESA+) isolated from metastatic breast cell lines are significantly more metastatic than non-CSC populations in an organ-specific manner. The results of our microRNA (miRNA) profile analysis for these cells revealed that CSCs that are highly metastatic to bone and brain expressed significantly lower level of miR-7 and that this miRNA was capable of modulating one of the essential genes for induced pluripotent stem cell, KLF4. Interestingly, high expression of KLF4 was significantly and inversely correlated to brain but not bone metastasis-free survival of patients with breas...
Source: Cancer Research - February 14, 2013 Category: Cancer & Oncology Authors: Okuda, H., Xing, F., Pandey, P. R., Sharma, S., Watabe, M., Pai, S. K., Mo, Y.-Y., Iiizumi-Gairani, M., Hirota, S., Liu, Y., Wu, K., Pochampally, R., Watabe, K. Tags: Tumor and Stem Cell Biology Source Type: research

Differential Hypoxic Response in Cancer Stem Cells
Tumor hypoxia is often linked to decreased survival in patients with breast cancer and current therapeutic strategies aim to target the hypoxic response. One way in which this is done is by blocking hypoxia-induced angiogenesis. Antiangiogenic therapies show some therapeutic potential with increased disease-free survival, but these initial promising results are short lived and followed by tumor progression. We hypothesized that this may be due to altered cancer stem cell (CSC) activity resulting from increased tumor hypoxia. We studied the effects of hypoxia on CSC activity, using in vitro mammosphere and holoclone assays ...
Source: Cancer Research - February 14, 2013 Category: Cancer & Oncology Authors: Harrison, H., Rogerson, L., Gregson, H. J., Brennan, K. R., Clarke, R. B., Landberg, G. Tags: Tumor and Stem Cell Biology Source Type: research

Autocrine Motility Factor Promotes HER2 Signaling
Trastuzumab (Herceptin) is an effective targeted therapy in HER2-overexpressing human breast carcinoma. However, many HER2-positive patients initially or eventually become resistant to this treatment, so elucidating mechanisms of trastuzumab resistance that emerge in breast carcinoma cells is clinically important. Here, we show that autocrine motility factor (AMF) binds to HER2 and induces cleavage to the ectodomain-deleted and constitutively active form p95HER2. Mechanistic investigations indicated that interaction of AMF with HER2 triggers HER2 phosphorylation and metalloprotease-mediated ectodomain shedding, activating ...
Source: Cancer Research - February 14, 2013 Category: Cancer & Oncology Authors: Kho, D. H., Nangia-Makker, P., Balan, V., Hogan, V., Tait, L., Wang, Y., Raz, A. Tags: Tumor and Stem Cell Biology Source Type: research

FGF-2 Disrupts Mitosis through CEP57
Malignant tumors with deregulated FGF-2 expression such as prostate cancer are also frequently aneuploid. Aneuploidy can be caused by cell division errors due to extra centrosomes and mitotic spindle poles. However, a link between FGF-2 overexpression and chromosome missegregation has so far been elusive. Here, we show that FGF-2 rapidly uncouples centrosome duplication from the cell division cycle in prostate cancer cells through CEP57, an intracellular FGF-2–binding and trafficking factor. CEP57 was initially identified as a regulator of centriole overduplication in an RNA interference screen. We subsequently found tha...
Source: Cancer Research - February 14, 2013 Category: Cancer & Oncology Authors: Cuevas, R., Korzeniewski, N., Tolstov, Y., Hohenfellner, M., Duensing, S. Tags: Tumor and Stem Cell Biology Source Type: research

“A high resolution view of the fly actin cytoskeleton lacking a functional WAVE complex”
Summary The development of multicellular organisms involves a series of morphogenetic processes coordinating a highly dynamic and organized interplay between cells and their environment. Thus, the generation of forces that drive cellular and intracellular movements is prerequisite to shape single cells into tissues and organs. The actin cytoskeleton represents a highly dynamic filamentous system providing cell structure and mechanical forces to drive membrane protrusion, cell migration and vesicle trafficking. Here, we apply the structured‐illumination microscopy (SIM) technique to analyse the actin cytoskeleton in fixed...
Source: Journal of Microscopy - February 14, 2013 Category: Laboratory Medicine Authors: T. ZOBEL, S. BOGDAN Source Type: research

Regulation of DNA Damage Responses by Ubiquitin and SUMO
Stephen P. Jackson, Daniel Durocher. Ubiquitylation and sumoylation, the covalent attachment of the polypeptides ubiquitin and SUMO, respectively, to target proteins, are pervasive mechanisms for controlling cellular functions. Here,....
Source: Molecular Cell - February 13, 2013 Category: Cytology Source Type: research

Cyclic Mechanical Reinforcement of Integrin–Ligand Interactions
Fang Kong, Zhenhai Li, William M. Parks, David W. Dumbauld, Andrés J. García, A. Paul Mould, Martin J. Humphries, Cheng Zhu. Cells regulate adhesion in response to internally generated and externally applied forces. Integrins connect the extracellular matrix to the cytoskeleton and provide cells with mechanical anchorag....
Source: Molecular Cell - February 13, 2013 Category: Cytology Source Type: research

Insights into FlaI Functions in Archaeal Motor Assembly and Motility from Structures, Conformations, and Genetics
Sophia Reindl, Abhrajyoti Ghosh, Gareth J. Williams, Kerstin Lassak, Tomasz Neiner, Anna-Lena Henche, Sonja-Verena Albers, John A. Tainer. Superfamily ATPases in type IV pili, type 2 secretion, and archaella (formerly archaeal flagella) employ similar sequences for distinct biological processes. Here, we structurally and functionally....
Source: Molecular Cell - February 13, 2013 Category: Cytology Source Type: research

Structure of a Ubiquitin E1-E2 Complex: Insights to E1-E2 Thioester Transfer
Shaun K. Olsen, Christopher D. Lima. Ubiquitin (Ub) conjugation is initiated by an E1 enzyme that catalyzes carboxy-terminal Ub adenylation, thioester bond formation to a catalytic cysteine in the E1 Cys domain, and thioester transfe....
Source: Molecular Cell - February 13, 2013 Category: Cytology Source Type: research

SnapShot: p38 MAPK Substrates
Natalia Trempolec, Natalia Dave-Coll, Angel R. Nebreda.
Source: Cell - February 13, 2013 Category: Cytology Source Type: research

Retraction Notice to: Imaging Activity-Dependent Regulation of Neurexin-Neuroligin Interactions Using trans-Synaptic Enzymatic Biotinylation
Amar Thyagarajan, Alice Y. Ting.
Source: Cell - February 13, 2013 Category: Cytology Source Type: research

Tit-for-Tat: Type VI Secretion System Counterattack during Bacterial Cell-Cell Interactions
Marek Basler, Brian T. Ho, John J. Mekalanos. The bacterial type VI secretion system (T6SS) is a dynamic organelle that bacteria use to target prey cells for inhibition via translocation of effector proteins. Time-lapse fluorescence microscop....
Source: Cell - February 13, 2013 Category: Cytology Source Type: research

DNA Synthesis Is Required for Reprogramming Mediated by Stem Cell Fusion
Tomomi Tsubouchi, Jorge Soza-Ried, Karen Brown, Francesco M. Piccolo, Irene Cantone, David Landeira, Hakan Bagci, Helfrid Hochegger, Matthias Merkenschlager, Amanda G. Fisher. Embryonic stem cells (ESCs) can instruct the conversion of differentiated cells toward pluripotency following cell-to-cell fusion by a mechanism that is rapid but poorly understood. Here, we used ....
Source: Cell - February 13, 2013 Category: Cytology Source Type: research

Regulation of Transcription through Acetylation of H3K122 on the Lateral Surface of the Histone Octamer
Philipp Tropberger, Sebastian Pott, Claudia Keller, Kinga Kamieniarz-Gdula, Matthieu Caron, Florian Richter, Guohong Li, Gerhard Mittler, Edison T. Liu, Marc Bühler, Raphael Margueron, Robert Schneider. Histone modifications are key regulators of chromatin function. However, little is known to what extent histone modifications can directly impact on chromatin. Here, we address how a modification ....
Source: Cell - February 13, 2013 Category: Cytology Source Type: research

Beyond Secondary Structure: Primary-Sequence Determinants License Pri-miRNA Hairpins for Processing
Vincent C. Auyeung, Igor Ulitsky, Sean E. McGeary, David P. Bartel. To use microRNAs to downregulate mRNA targets, cells must first process these ∼22 nt RNAs from primary transcripts (pri-miRNAs). These transcripts form RNA hairpins important for processing, but a....
Source: Cell - February 13, 2013 Category: Cytology Source Type: research

SMARCA3, a Chromatin-Remodeling Factor, Is Required for p11-Dependent Antidepressant Action
Yong-Seok Oh, Pu Gao, Ko-Woon Lee, Ilaria Ceglia, Ji-Seon Seo, Xiaozhu Zhang, Jung-Hyuck Ahn, Brian T. Chait, Dinshaw J. Patel, Yong Kim, Paul Greengard. p11, through unknown mechanisms, is required for behavioral and cellular responses to selective serotonin reuptake inhibitors (SSRIs). We show that SMARCA3, a chromatin-remodeling factor, is a tar....
Source: Cell - February 13, 2013 Category: Cytology Source Type: research

Bacterial Nitric Oxide Extends the Lifespan of C. elegans
Ivan Gusarov, Laurent Gautier, Olga Smolentseva, Ilya Shamovsky, Svetlana Eremina, Alexander Mironov, Evgeny Nudler. Nitric oxide (NO) is an important signaling molecule in multicellular organisms. Most animals produce NO from L-arginine via a family of dedicated enzymes known as NO synthases (NOSes). A rare exc....
Source: Cell - February 13, 2013 Category: Cytology Source Type: research

A Genetic Program Promotes C. elegans Longevity at Cold Temperatures via a Thermosensitive TRP Channel
Rui Xiao, Bi Zhang, Yongming Dong, Jianke Gong, Tao Xu, Jianfeng Liu, X.Z. Shawn Xu. Both poikilotherms and homeotherms live longer at lower body temperatures, highlighting a general role of temperature reduction in lifespan extension. However, the underlying mechanisms remain unc....
Source: Cell - February 13, 2013 Category: Cytology Source Type: research

Dual Specificity Kinase DYRK3 Couples Stress Granule Condensation/Dissolution to mTORC1 Signaling
Frank Wippich, Bernd Bodenmiller, Maria Gustafsson Trajkovska, Stefanie W.a, Ruedi Aebersold, Lucas Pelkmans. Cytosolic compartmentalization through liquid-liquid unmixing, such as the formation of RNA granules, is involved in many cellular processes and might be used to regulate signal transduction. Howe....
Source: Cell - February 13, 2013 Category: Cytology Source Type: research

Branching Microtubule Nucleation in Xenopus Egg Extracts Mediated by Augmin and TPX2
Sabine Petry, Aaron C. Groen, Keisuke Ishihara, Timothy J. Mitchison, Ronald D. Vale. The microtubules that comprise mitotic spindles in animal cells are nucleated at centrosomes and by spindle assembly factors that are activated in the vicinity of chromatin. Indirect evidence has ....
Source: Cell - February 13, 2013 Category: Cytology Source Type: research

Structural Basis for Recruitment and Activation of the AP-1 Clathrin Adaptor Complex by Arf1
Xuefeng Ren, Ginny G. Farías, Bertram J. Canagarajah, Juan S. Bonifacino, James H. Hurley. AP-1 is a clathrin adaptor complex that sorts cargo between the trans-Golgi network and endosomes. AP-1 recruitment to these compartments requires Arf1-GTP. The crystal structure of the tet....
Source: Cell - February 13, 2013 Category: Cytology Source Type: research

The NeST Long ncRNA Controls Microbial Susceptibility and Epigenetic Activation of the Interferon-γ Locus
J. Antonio Gomez, Orly L. Wapinski, Yul W. Yang, Jean-François Bureau, Smita Gopinath, Denise M. Monack, Howard Y. Chang, Michel Brahic, Karla Kirkegaard. Long noncoding RNAs (lncRNAs) are increasingly appreciated as regulators of cell-specific gene expression. Here, an enhancer-like lncRNA termed NeST (nettoie Salmonella pas Th....
Source: Cell - February 13, 2013 Category: Cytology Source Type: research

Xist RNA Is a Potent Suppressor of Hematologic Cancer in Mice
Eda Yildirim, James E. Kirby, Diane E. Brown, Francois E. Mercier, Ruslan I. Sadreyev, David T. Scadden, Jeannie T. Lee. X chromosome aneuploidies have long been associated with human cancers, but causality has not been established. In mammals, X chromosome inactivation (XCI) is triggered by Xist RNA to equalize gen....
Source: Cell - February 13, 2013 Category: Cytology Source Type: research