Abstract
We conclude the following: i) overexpression of ΔNp63 contributes to salivary tumorigenesis, ii) ΔNp63 plays a dominant negative effect on the TA isoform in the modulation of cell migration and invasion, and iii) the ΔN isoform plays an oncogenic role and may represent an attractive target for th...
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PMID: 21703418
PDF is available here.
Abstract
We were able to showed that PGC1-α expression is dramatically reduced in GRMD compared to healthy muscle. Collectively, these results provide novel insights into the molecular pathology of the clinically relevant animal model of DMD, and indicate that defective energy metabolism is a central hallma...
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PMID: 21410286
PDF is available here.
Abstract
We show that AFCs express pluripotency markers (Nanog, Sox2, and Oct3/4) as well as retinal transcription factor genes (Et, Lhx2, Tll1, Six6, Otx2, Pax6, and Fgf15). AFCs from amniotic fluid of Fgf15.gfp, Nrl.gfp, and Crx.gfp embryos cultured in retinal proliferation and differentiation conditions f...
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PMID: 20939691
PDF is available here.
Abstract
We describe two complete ssDNA phage genomes that were reconstructed from a viral metagenome from 80 m depth at the Bermuda Atlantic Time-series Study (BATS) site in the northwestern Sargasso Sea and examine their spatial and temporal distributions. Both genomes (SARssφ1 and SARssφ2) exhibited s...
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PMID: 21124487
PDF is available here.
Abstract
We demonstrate that differentiation into the T(H)1 and T(H)17 subsets of helper T cells was selectively regulated by signaling from mTOR complex 1 (mTORC1) that was dependent on the small GTPase Rheb. Rheb-deficient T cells failed to generate T(H)1 and T(H)17 responses in vitro and in vivo and did n...
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PMID: 21358638
PDF is available here.
Abstract
We have developed a directed differentiation protocol to obtain insulin-producing cells from ESCs. The ESCs are first induced towards a homogeneous monolayer of definitive endoderm-like cells by co-culture with primary hepatocytes. Pancreatic commitment is induced by plating the ESC-derived endoderm...
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PMID: 20717889
PDF is available here.
Shulin Ju,
Daniel F Tardiff,
Haesun Han,
Kanneganti Divya,
Quan Zhong,
Lynne E Maquat,
Daryl A Bosco,
Lawrence J Hayward,
Robert H Brown,
Susan Lindquist,
Dagmar Ringe and
Gregory A Petsko
Abstract
We report a yeast model of human FUS/TLS expression that recapitulates multiple salient features of the pathology of the disease-causing mutant proteins, including nuclear to cytoplasmic translocation, inclusion formation, and cytotoxicity. Protein domain analysis indicates that the carboxyl-terminu...
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PMID: 21541368
PDF is available here.
Abstract
We identify a new parkin interacting substrate, PARIS (ZNF746), whose levels are regulated by the ubiquitin proteasome system via binding to and ubiquitination by the E3 ubiquitin ligase, parkin. PARIS is a KRAB and zinc finger protein that accumulates in models of parkin inactivation and in human P...
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PMID: 21376232
PDF is available here.
Abstract
A substantial proportion of patients with rheumatoid arthritis do not respond to tumor necrosis factor blocking therapy. Results of a large genome-wide association study demonstrate evidence of novel genetic factors that determine response to treatment, which could provide a basis fo...
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PMID: 21304506
PDF is available here.
Gregor B Deutsch,
Elisabeth M Zielonka,
Daniel Coutandin,
Tobias A Weber,
Birgit Schäfer,
Jens Hannewald,
Laura M Luh,
Florian G Durst,
Mohamed Ibrahim,
Jan Hoffmann,
Frank H Niesen,
Aycan Sentürk,
Hana Kunkel,
Bernd Brutschy,
Enrico Schleiff,
Stefan Knapp,
Amparo Acker-Palmer,
Manuel Grez,
Frank McKeon and
Volker Dötsch
Abstract
We show that TAp63α is kept in an inactive dimeric state. We reveal that relief of inhibition leads to tetramer formation with ∼20-fold higher DNA affinity. In vivo, phosphorylation-triggered tetramerization of TAp63α is not reversible by dephosphorylation. Furthermore, we show that a helix in t...
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PMID: 21335238
PDF is available here.
Abstract
We show that both AMPK and calcineurin modulate longevity exclusively through post-translational modification of CRTC-1, the sole C. elegans CRTC. We demonstrate that CRTC-1 is a direct AMPK target, and interacts with the CREB homologue-1 (CRH-1) transcription factor in vivo. The pro-longevity effec...
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PMID: 21331044
PDF is available here.
Abstract
Pancreatic islets contain low activities of catalase, selenium-dependent glutathione peroxidase 1 (GPX1), and Cu,Zn-superoxide dismutase 1 (SOD1). Thus, enhancing expression of these enzymes in islets has been unquestionably favored. However, such an attempt has produced variable met...
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PMID: 20618069
PDF is available here.
Abstract
We used both shRNA and siRNA to examine the effect of fra-1 knockdown in GBM cells over-expressing Fra-1. Furthermore, we analyzed both the expression of JunB and its knockdown, a previously identified target for Fra-1, and also examined its potential association with Fra-1. When using fra-1 shRNA a...
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PMID: 21088499
PDF is available here.
Abstract
The availability of targeted therapies has created a need for precise subtyping of non-small cell lung carcinomas (NSCLCs). The aim of this study was to assess the utility of immunohistochemical markers in subtyping poorly differentiated NSCLC and to compare the results of immunohistochemical staini...
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PMID: 21164283
PDF is available here.
Abstract
We investigated the possible mechanisms underlying AGE-related suppression of insulin synthesis. In the rat pancreatic β-cell line INS-1, we found that AGEs induced dephosphorylation of Foxo1 and increased its accumulation in the nucleus. The translocation of Foxo1 subsequently inhibited pancreatic...
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PMID: 21533167
PDF is available here.
Abstract
We describe a set of luminescent reporters, which could be used in high, medium or low throughput format, for the discovery and validation of agonists or antagonists of the Las QS system of Pseudomonas aeruginosa. These nearly isogenic reporters contain truncations or point mutations in the AHL bind...
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PMID: 21031308
PDF is available here.
Abstract
We describe the usage of reporter strains consisting of a lasB-gfp or rhlA-gfp fusion in P. aeruginosa for qualitative and quantitative evaluation of the inhibition of the two major QS pathways, monitored as reduced expression of green fluorescence. By the use of an in vitro flow cell system it is p...
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PMID: 21031317
PDF is available here.
Abstract
Sertoli cells (SCs) provide an immunoprotective environment to pancreatic islet grafts for treatment of insulin-dependent diabetes. Aim of this work was to verify whether intraperitoneal graft of SCs, enveloped in barium alginate-based microcapsules, would reverse overt spontaneous diabetes in nonob...
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PMID: 21197711
PDF is available here.
Abstract
We observed retrovirus-induced RXRα–Nurr1 heterodimer interactions with, and transactivation of, the TH promoter region in cultured rat embryonic neural precursor cells. Interestingly, forced expression of RXRα with Nurr1 remarkably reduced Nurr1 activity in TH+ dopaminergic neuron generation an...
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PMID: 22066143
PDF is available here.
Abstract
The expression of a variety of cytoprotective genes is regulated by short cis-acting elements in their promoters, called antioxidant response elements (AREs). A central regulator of ARE-mediated gene expression is the NF-E2-related factor 2 (Nrf2). Human hepatitis B virus (HBV) induces a strong acti...
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PMID: 20956535
PDF is available here.
Abstract
Our results suggest that TAp63 may play a compensatory role in cell cycle regulation and DNA damage repair in p53-deficient cancer cells.
Copyright © 2010 Elsevier Inc. All rights reserved....
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PMID: 21075072
PDF is available here.
Abstract
We will discuss the regulation of each CRL using the Cul3-Keap1-E3 ligase complex as the primary focus. The substrates of CRLs are involved in many signaling pathways. Therefore, deregulation of CRLs affects several cellular processes, including cell cycle arrest, DNA repair, cell proliferation, sen...
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PMID: 20486766
PDF is available here.
Abstract
We identified CSCs in primary GBC and in the cell line GBC-SD using the cell surface markers CD44 and CD133. The percentages of CD44+CD133+ cells were 1.76-3.05% in primary tumors and 40.29% in GBC-SD cells. These cells showed stem cell properties, including self-renewal, differentiation potential,...
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PMID: 20948317
PDF is available here.
Abstract
We show that type I interferon (IFN) induction but not its downstream signaling is blocked by HBV replication in HepG2.2.15 cells. This effect may be partially due to HBV X protein (HBx), which impairs IFNβ promoter activation by both Sendai virus (SeV) and components implicated in signaling by vir...
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PMID: 21213104
PDF is available here.
Abstract
We first studied homologous genes to OAF1 and PIP2 of Saccharomyces cerevisiae, but their disruption did not change growth on oleic acid at all. We next characterized a Y. lipolytica gene, POR1 (primary oleate regulator 1), an ortholog of farA encoding a transcriptional activator that regulates fatt...
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PMID: 20977884
PDF is available here.
Abstract
We show here that ChREBP inactivation in clonal pancreatic MIN6 β-cells results in an increase in Pdx-1 expression at low glucose and to a small, but significant, increase in Ins2, GcK and MafA gene expression at high glucose concentrations. Conversely, adenovirus-mediated over-expression of ChREBP...
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PMID: 20934404
PDF is available here.
Abstract
We report that the WWP1 E3 ubiquitin ligase binds specifically to ΔNp63 isoform but it does not trigger ΔNp63 proteasome-dependent degradation. Accordingly, we found that WWP1-dependent ubiquitylation of ΔNp63 occurs through the formation of Lys63-linked poly-ubiquitin chains. Importantly, we fou...
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PMID: 20951678
PDF is available here.
Abstract
We report that PKG-I stimulates myocardin/serum response factor (SRF)-dependent gene expression in vascular SMCs. The expression of PKG in PKG-deficient cells enhanced myocardin-induced SM22 promoter activity in a concentration-dependent fashion. However, neither SRF nor myocardin expression was aff...
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PMID: 20802137
PDF is available here.
Abstract
We report the reciprocal effect on keratin expression of ΔNp63, pivotal in normal epidermal morphogenesis and maintenance, and Skn-1a/Oct-11, a POU transcription factor that triggers and regulates the differentiation of keratinocytes. The expression of Skn-1a markedly downregulated ΔNp63-driven K1...
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PMID: 20888799
PDF is available here.
Abstract
We show that the number of CREB-binding sites (CREs) affects whether the related histone acetyltransferases (HATs) CREB-binding protein (CBP) and p300 are required for endogenous gene transcription. Fibroblasts with both CBP and p300 knocked-out had strongly attenuated histone H4 acetylation at CREB...
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PMID: 20859256
PDF is available here.
Abstract
We introduced an shRNA into mouse insulinoma MIN6 cells to deplete Pdx1 and found that expression of proapoptotic genes, including NIP3-like protein X (Nix), was increased. Forced Nix expression in MIN6 and pancreatic islet β cells induced programmed cell death by simultaneously activating apoptoti...
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PMID: 20978346
PDF is available here.
Xiaohua Su,
Deepavali Chakravarti,
Min Soon Cho,
Lingzhi Liu,
Young Jin Gi,
Yu-Li Lin,
Marco L Leung,
Adel El-Naggar,
Chad J Creighton,
Milind B Suraokar,
Ignacio Wistuba and
Elsa R Flores
Abstract
We show that TAp63, a p53 family member, suppresses tumorigenesis and metastasis, and coordinately regulates Dicer and miR-130b to suppress metastasis. Metastatic mouse and human tumours deficient in TAp63 express Dicer at very low levels, and we found that modulation of expression of Dicer and miR-...
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PMID: 20962848
PDF is available here.
Abstract
We observed that the cell-proliferation-related phosphoinositide 3-kinase/Akt pathway is activated by HBx in vivo and in vitro. Increased ROS were detected by HBx. Tumor suppressor PTEN, via dephosphorylation of Akt, was oxidized and inactivated by increased ROS. Increased oxidized PTEN activated th...
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PMID: 20954279
PDF is available here.
Abstract
We show that the replication-associated proteins (Rep: a rolling-circle replication initiator protein) encoded by these alphasatellites interact with the Rep and C4 proteins encoded by their helper begomovirus, Cotton leaf curl Rajasthan virus (CLCuRaV), in a yeast two-hybrid assay. Both the alphasa...
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PMID: 20598726
PDF is available here.
Abstract
We characterized the functional domains of BFV BTas. BTas contains two major functional domains: the N-terminal DNA-binding domain (residues 1-133) and the C-terminal activation domain (residues 198-249). The complete BTas responsive regions were mapped to the positions -380/-140 of LTR and 9205/927...
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PMID: 20615521
PDF is available here.
Abstract
We suggest that decreased stability of Tra1-L3733A accounts for the phenotypes since intragenic suppressors of tra1-L3733A restored Tra1 levels, and reducing wild-type Tra1 led to comparable growth defects. Also supporting a key role for the FATC domain in the structure/function of Tra1, addition of...
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PMID: 20635087
PDF is available here.
Abstract
We investigate the consequences of desmosome loss for carcinogenesis by analyzing conditional knockout mice lacking Perp, a p53/p63 regulated gene that encodes an important component of desmosomes. Analysis of Perp-deficient mice in a UVB-induced squamous cell skin carcinoma model reveals that Perp...
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PMID: 20975948
PDF is available here.
Abstract
Mitochondrial dysfunction is a common hallmark of ageing-related diseases involving neurodegeneration. Huntington's disease (HD) is one of the most common monogenetic forms of neurodegenerative disorders and shares many salient features with the major sporadic disease of neurodegeneration, such as a...
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PMID: 20840068
PDF is available here.
Abstract
We show that Pcif1 targets Pdx1 for ubiquitination and proteasomal degradation. Silencing of Pcif1 increased Pdx1 protein levels in cultured mouse β cells, and Pcif1 heterozygosity normalized Pdx1 protein levels in Pdx1(+/-) mouse islets, thereby increasing expression of key Pdx1 transcriptional ta...
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PMID: 20811152
PDF is available here.
Abstract
Progress has been made towards the development of agents targeting tyrosine kinase receptors and other molecules involved in signalling pathways important for cell proliferation, motility, and apoptosis. Inhibitor molecules designed to be highly specific with the aim of decreasing toxicity have prov...
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PMID: 20533896
PDF is available here.
Abstract
We identify the dSTRIPAK PP2A complex as a major regulator of Hpo signaling. dSTRIPAK depletion leads to increased Hpo activatory phosphorylation and repression of Yki target genes in vivo, suggesting this phosphatase complex prevents Hpo activation during development.
Copyright (c)...
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PMID: 20797625
PDF is available here.
Weidong Jiang,
Xin Wei Wang,
Tamar Unger,
Marshonna Forgues,
Jin Woo Kim,
S Perwez Hussain,
Elise Bowman,
Elisa A Spillare,
Michael M Lipsky,
Jeanne M Meck,
Luciane R Cavalli,
Bassem R Haddad and
Curtis C Harris
Abstract
We have reported that tumor-derived HBx variants encoded by HBV exhibited attenuated transactivation and proapoptotic functions but retained their ability to block p53-mediated apoptosis. These results indicate that mutations in HBx may contribute to the development of HCC. In this study, we determi...
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PMID: 20017137
PDF is available here.
Abstract
We report on a novel human RING finger protein, ZNF645, which contains a C3HC4 RING finger domain, a C2H2 zinc-finger domain, and a proline-rich region, indicating that it has a structure similar to that of the c-Cbl-like protein Hakai. ZNF645 was exclusively expressed in normal human testicular tis...
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PMID: 20657603
PDF is available here.
Abstract
This study is to construct a lentiviral vector harbouring an RNA interference (RNAi) sequence that targets the gene encoding the human high-mobility group nucleosomal binding protein 1 (NSBP1); to study its role in inducing G(2)/M phase arrest and apoptosis in prostate cancer (PCa) DU145 cells; and...
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PMID: 20531280
PDF is available here.
Abstract
We show that MEF is modulated by p53 in human cells and mice tissues. MEF expression and promoter activity were suppressed by p53. While we found that MEF promoter does not contain p53 response elements, intriguingly, it contains E2F consensus sites. Subsequently, we determined that E2F1 specificall...
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PMID: 20805247
PDF is available here.
Abstract
We have used a modular approach to determine the crystal structures of the structured domains in the EBF family. The DNA binding domain reveals a striking resemblance to the DNA binding domains of the Rel homology superfamily of transcription factors but contains a unique zinc binding structure, ter...
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PMID: 20592035
PDF is available here.
Abstract
We show that Sin1, an essential component of mTOR complex 2 (mTORC2), regulates B cell development. Sin1 deficiency results in increased IL-7 receptor (il7r) and RAG recombinase (rag1 and rag2) gene expression, leading to enhanced pro-B cell survival and augmented V(D)J recombinase activity. We furt...
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PMID: 20705244
PDF is available here.
Abstract
The CDX2 transcription factor is known to play a crucial role in inhibiting proliferation, promoting differentiation and the expression of intestinal specific genes in intestinal cells. The overall effect of CDX2 in intestinal cells has previously been investigated in conditional knock-out mice, reve...
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PMID: 20551321
PDF is available here.
Abstract
We show here that physiological concentrations (nM) of ouabain enhance phosphorylation of EGFR on tyr-845, stimulate Ca(2+) influx and induce the acrosome reaction in sperm. These effects could be seen only in the presence of very low concentrations of EGF (0.1 ng/ml or 0.016 nM) added together with...
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PMID: 20580701
PDF is available here.
Abstract
We describe a link between transposition of IS608 and ISDra2, both members of the IS200/IS605 family, which uses obligatory single-stranded DNA intermediates, and the host replication fork. Replication direction through the IS plays a crucial role in excision: activity is maximal when the "top" IS s...
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PMID: 20691900
PDF is available here.
Abstract
We show that basal cells from primary benign human prostate tissue can initiate prostate cancer in immunodeficient mice. The cooperative effects of AKT, ERG, and androgen receptor in basal cells recapitulated the histological and molecular features of human prostate cancer, with loss of basal cells...
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PMID: 20671189
PDF is available here.
Abstract
I (SMARD1). However, the mechanism of regulation of IGHMBP2 gene expression remains unclear. In the present study, a 2.0-kb fragment of the 5'-flanking (promoter) region of the human IGHMBP2 gene was isolated from the HL-60 genome by PCR and ligated into a luciferase (Luc) expression vector, pGL3, t...
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PMID: 20441787
PDF is available here.
Abstract
Chronic hepatitis B (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). Most HCCs complicate the evolution of an active or inactive cirrhosis. However, some tumors occur on livers with minimal histological changes; the prevalence of such cases varies from one geographical regi...
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PMID: 20667665
PDF is available here.
Abstract
We find that when the strains being compared have the same thyA allele (wild type or mutant), flhD mutations have no effect on growth....
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PMID: 20546312
PDF is available here.
Abstract
We show that dimethyl sulfoxide (DMSO) inhibits Salmonella hilA expression and that this inhibition is stronger under anaerobiosis. Because DMSO can be reduced to dimethyl sulfide (DMS) during anaerobic growth, we hypothesized that DMS was responsible for hilA inhibition. Indeed, DMS strongly inhibi...
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PMID: 20562287
PDF is available here.
Abstract
Zebrafish models have significantly contributed to our understanding of vertebrate development and, more recently, human disease. The growing number of genetic tools available in zebrafish research has resulted in the identification of many genes involved in developmental and disease...
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PMID: 20679337
PDF is available here.
Abstract
To investigate whether AMP-activated protein kinase (AMPK) regulates the expression of pancreatic duodenal homeobox-1 (PDX-1), a beta-cell-specific transcription factor and whether PPARalpha/gamma is involved in the regulation of pancreatic beta-cell lines after acute stimulation....
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PMID: 20644547
PDF is available here.
Abstract
We define a subset of signaling markers closely associated with albuminuria. Mammalian target of rapamycin complex 2 (mTORC2)::IRS complexes may play a role in the nuclear accumulation, and possible downstream transcriptional effects, of p-PKC. The activity and apparent safety of nephrilin in rodent...
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PMID: 20545557
PDF is available here.
Kah Poh Tan,
Bernice Wang,
Mingdong Yang,
Paul C Boutros,
Jane Macaulay,
Haibo Xu,
Andrew I Chuang,
Kazuhiro Kosuge,
Mika Yamamoto,
Shinichiro Takahashi,
Alex M L Wu,
Douglas D Ross,
Patricia A Harper and
Shinya Ito
Abstract
We show that BCRP induction by AHR ligands occurs in human intestinal, liver, and mammary carcinoma cells and in primary colonocytes and hepatocytes. Increased BCRP transporter activity consistent with gene induction was also evident in the Caco2 subclone C2bbe1 cells. Using RNA interference and ect...
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PMID: 20460431
PDF is available here.