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https://www.readbyqxmd.com/read/28549777/p32-is-required-for-appropriate-interleukin-6-production-upon-lps-stimulation-and-protects-mice-from-endotoxin-shock
#1
Katsuhiko Sasaki, Kazuhito Gotoh, Sho Miake, Daiki Setoyama, Mikako Yagi, Ko Igami, Takeshi Uchiumi, Donchon Kang
Sepsis is a major cause of morbidity and mortality in seriously ill patients and mitochondrial dysfunction is associated with poor outcomes in septic patients. Although interleukin-6 (IL-6) is a good prognostic marker for sepsis, the relationship between mitochondrial dysfunction and IL-6 remains poorly understood. We identified p32/C1QBP/HABP1 as a regulator of IL-6 production in response to lipopolysaccharide (LPS). LPS induced IL-6 overproduction in p32 deficient mouse embryonic fibroblasts (MEFs) through NF-κB independent but activating transcription factor (ATF) 4 dependent pathways...
May 11, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28548965/inhibition-of-colorectal-cancer-genomic-copy-number-alterations-and-chromosomal-fragile-site-tumor-suppressor-fhit-and-wwox-deletions-by-dna-mismatch-repair
#2
Sohail Jahid, Jian Sun, Ozkan Gelincik, Pedro Blecua, Winfried Edelmann, Raju Kucherlapati, Kathy Zhou, Maria Jasin, Zeynep H Gümüş, Steven M Lipkin
Homologous recombination (HR) enables precise DNA repair after DNA double strand breaks (DSBs) using identical sequence templates, whereas homeologous recombination (HeR) uses only partially homologous sequences. Homeologous recombination introduces mutations through gene conversion and genomic deletions through single-strand annealing (SSA). DNA mismatch repair (MMR) inhibits HeR, but the roles of mammalian MMR MutL homologues (MLH1, PMS2 and MLH3) proteins in HeR suppression are poorly characterized. Here, we demonstrate that mouse embryonic fibroblasts (MEFs) carrying Mlh1, Pms2, and Mlh3 mutations have higher HeR rates, by using 7,863 uniquely mapping paired direct repeat sequences (DRs) in the mouse genome as endogenous gene conversion and SSA reporters...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548876/the-constitutive-lipid-droplet-protein-plin2-regulates-autophagy-in-liver
#3
Tsung-Huang Tsai, Elaine Chen, Lan Li, Pradip Saha, Hsiao-Ju Lee, Li-Shin Huang, Gregory S Shelness, Lawrence Chan, Benny Hung-Junn Chang
Excess triglyceride (TG) accumulation in the liver underlies fatty liver disease, a highly prevalent ailment. TG occurs in the liver sequestered in lipid droplets, the major lipid storage organelle. Lipid droplets are home to the lipid droplet proteins, the most abundant of which are the perilipins (PLINs), encoded by 5 different genes, Plin1 to Plin5. Of the corresponding gene products, PLIN2 is the only constitutive and ubiquitously expressed lipid droplet protein that has been used as a protein marker for lipid droplets...
May 26, 2017: Autophagy
https://www.readbyqxmd.com/read/28541373/the-histone-acetylation-mediated-by-gcn5-regulates-the-hoxc11-gene-expression-in-mefs
#4
Ji Hoon Oh, Ji-Yeon Lee, Kyoung-Ah Kong, Jie Min Kim, Myoung Hee Kim
Hox genes are responsible for encoding transcription factors that are essential for anterior-posterior body patterning at early stages of embryogenesis. However, detailed mechanisms of Hox genes are yet to be defined. Protein kinase B alpha (Akt1) was previously identified as a possible upstream regulator of Hox genes. Furthermore, the Hoxc11 gene has been upregulated in Akt1 null (Akt1-/-) mouse embryonic fibroblasts (MEFs), while repressed in wild-type MEFs. In this study, we propose to investigate the role of Gcn5, a histone acetyltransferase, in the regulation of Hoxc11 expression in MEFs...
May 24, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28537904/cnot2-promotes-degradation-of-p62-sqstm1-as-a-negative-regulator-in-atg5-dependent-autophagy
#5
Kwon Jeong, Hee Young Kwon, Myoung Seok Jeong, Eun Jung Sohn, Sung-Hoon Kim
Though CNOT2 is involved in regulation of adipogenic differentiation, apoptotic cell death and metastasis, the underlying autophagic mechanism of CNOT2 was unknown until now. Thus, in the present study, the critical role of CNOT2 in autophagy was elucidated in association with p62/SQSTM1 signaling. CNOT2 depletion induced p62/SQSTM1 accumulation and LC3B-II conversion, and also increased the number of puncta with impaired autophagic flux. In contrast, CNOT2 overexpression induced downregulation and ubiquitination of p62/SQSTM1 in HEK293 QBI...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28531208/phylogenetic-analysis-of-emergent-streptococcus-pneumoniae-serotype-22f-causing-invasive-pneumococcal-disease-using-whole-genome-sequencing
#6
Walter H B Demczuk, Irene Martin, Linda Hoang, Paul Van Caeseele, Brigitte Lefebvre, Greg Horsman, David Haldane, Jonathan Gubbay, Sam Ratnam, Gregory German, Jennifer Daley Bernier, Lori Strudwick, Allison McGeer, George G Zhanel, Gary Van Domselaar, Morag Graham, Michael R Mulvey
Since implementation of the 13-valent polyvalent conjugate vaccine (PCV13) in Canada during 2010, the proportion of PCV13 serotypes causing invasive pneumococcal disease (IPD) has declined from 55% (n = 1492) in 2010 to 31% (n = 764) in 2014. A concurrent increase of non-PCV13 serotypes has occurred and 22F has become the most prevalent serotype in Canada increasing from 7% (n = 183) to 11% (n = 283). Core single nucleotide variant phylogenetic analysis was performed on 137 Streptococcus pneumoniae serotype 22F isolates collected across Canada from 2005-2015...
2017: PloS One
https://www.readbyqxmd.com/read/28530706/akt-is-indispensable-for-coordinating-par-4-jnk-cross-talk-in-p21-downmodulation-during-er-stress
#7
R U Rasool, D Nayak, S Chakraborty, M M Faheem, B Rah, P Mahajan, V Gopinath, A Katoch, Z Iqra, S K Yousuf, D Mukherjee, L D Kumar, A Nargotra, A Goswami
The double-edged role of p21 to command survival and apoptosis is emerging. The current investigation highlights ER stress-mediated JNK activation that plausibly triggers cell death by attenuating endogenous p21 level. Here, we demonstrated that ER stress activator 3-AWA diminishes the p21 levels in cancer cells by averting the senescent phenotype to commence G2/M arrest. In essence, the deceleration in p21 level occurs through ER stress/JNK/Caspase-3 axis via activation/induction of proapoptotic Par-4 and inhibition of AKT...
May 22, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28525382/sulfatase-1-overexpression-indicates-poor-prognosis-in-urothelial-carcinoma-of-the-urinary-bladder-and-upper-tract
#8
Hsiang-Ying Lee, Bi-Wen Yeh, Ti-Chun Chan, Kei-Fu Yang, Wei-Ming Li, Chun-Nung Huang, Hung-Lung Ke, Ching-Chia Li, Hsin-Chih Yeh, Peir-In Liang, Yow-Ling Shiue, Wen-Jeng Wu, Chien-Feng Li
Urothelial carcinoma (UC), arising from the urothelium of the urinary tract, can occur in the upper (UTUC) and the urinary bladder (UBUC). A representative molecular aberration for UC characteristics and prognosis remains unclear. Data mining of Gene Expression Omnibus focusing on UBUC, we identified sulfatase-1 (SULF1) upregulation is associated with UC progression. SULF1 controls the sulfation status of heparan sulfate proteoglycans and plays a role in tumor growth and metastasis, while its role is unexplored in UC...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28523267/a-novel-role-for-the-bmp-antagonist-noggin-in-sensitizing-cells-to-non-canonical-wnt-5a-ror2-disheveled-pathway-activation
#9
Ondrej Bernatik, Tomasz Radaszkiewicz, Martin Behal, Zankruti Dave, Florian Witte, Annika Mahl, Nicole H Cernohorsky, Pavel Krejci, Sigmar Stricker, Vitezslav Bryja
Mammalian limb development is driven by the integrative input from several signaling pathways; a failure to receive or a misinterpretation of these signals results in skeletal defects. The brachydactylies, a group of overlapping inherited human hand malformation syndromes, are mainly caused by mutations in BMP signaling pathway components. Two closely related forms, Brachydactyly type B2 (BDB2) and BDB1 are caused by mutations in the BMP antagonist Noggin (NOG) and the atypical receptor tyrosine kinase ROR2 that acts as a receptor in the non-canonical Wnt pathway...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28516842/serotype-distribution-antimicrobial-resistance-and-prevalence-of-pilus-islets-in-pneumococci-following-the-use-of-conjugate-vaccines
#10
Mitsuyo Kawaguchiya, Noriko Urushibara, Meiji Soe Aung, Masaaki Shinagawa, Satoshi Takahashi, Nobumichi Kobayashi
PURPOSE: In Japan, the 7-valent pneumococcal vaccine (PCV7) was introduced in 2010 and, in 2013, the PCV7 was replaced with the 13-valent pneumococcal vaccine (PCV13). This study was conducted to investigate serotypes, antimicrobial resistance and prevalence of pilus islets in pneumococcal isolates from inpatients in a Japanese tertiary hospital. METHODOLOGY: From April 2011 to February 2016, 151 isolates [95 (18 children, 77 adults) and 56 (19 children, 37 adults) in the PCV7 and PCV13 periods, respectively] were collected...
May 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28516765/peptide-microarray-based-metal-enhanced-fluorescence-assay-for-multiple-profiling-matrix-metalloproteinases-activities
#11
Zhen Lei, Hua Zhang, Yaoqi Wang, Xianying Meng, Zhenxin Wang
Matrix metalloproteinases (MMPs) are closely associated with cancer cell invasion and metastasis. Herein, a fluorescence resonance energy transfer (FRET)-peptide microarray-based metal enhanced fluorescence (MEF) assay is proposed for multiple and sensitive profiling MMPs activities on a novel Au/Ag@SiO2 substrate. The Au/Ag@SiO2 substrate is prepared by electroless deposition of silver on gold nanoparticle (GNP) seeds, followed by SiO2 shell coating and surface functionalization. The specific FRET peptides are spotted on the Au/Ag@SiO2 substrate to sensitively detect MMPs (MMP-2, 3, 7, 9, 14) via fluorescence recovery by the MMP cleavage of quenched peptide motifs, and further enhanced by MEF...
May 18, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28516114/measurement-of-mrna-decay-in-mouse-embryonic-fibroblasts
#12
Lian-Qun Qiu, Wi S Lai, Deborah J Stumpo, Perry J Blackshear
mRNA stability control is a critical step in the post-transcriptional regulation of gene expression. Actinomycin D, an antibiotic initially used as an anti-cancer drug, has turned out to be a convenient tool for studying the turnover rates of transcripts in cells, due to its inhibition of mRNA synthesis. Here, we describe a protocol for the measurement of mRNA decay after adding actinomycin D into the medium of stable fibroblast cell lines derived from wild-type and tristetraprolin (TTP)-deficient mouse embryonic fibroblast (MEF) cultures, as well as a protocol for determining the relative transcript abundance using semi-quantitative real time RT-PCR...
July 5, 2016: Bio-protocol
https://www.readbyqxmd.com/read/28507462/comparative-analysis-of-non-viral-transfection-methods-in-mouse-embryonic-fibroblast-cells
#13
Migi Lee, Kathleen Chea, Rajyalakshmi Pyda, Melissa Chua, Isabel Dominguez
Mouse embryonic fibroblast (MEF) cells are an important in vitro model for developmental biology, disease, and reprogramming studies. However, as with other primary cells, they are challenging to transfect. Although viral gene-delivery methods achieve high gene-delivery efficiency, challenges with cell mutagenesis and safety among others have led to the use and improvement of non-viral gene-delivery methods in MEF cells. Despite the importance of gene delivery in MEF cells, there is limited comparison of method/reagent efficacy...
April 29, 2017: Journal of Biomolecular Techniques: JBT
https://www.readbyqxmd.com/read/28507276/dicer-protein-levels-elevated-by-mild-hyperthermia-promote-a-pro-survival-phenotype
#14
Anand S Devasthanam, Thomas B Tomasi
Cellular exposure to mild stress (39.5°C-41.5°C) induces thermotolerance, rendering cells resistant to a subsequent heat shock (>42°C) insult. We found that mild hyperthermia at 39.5°C leads to elevations in dicer, a protein well-known for its role in microRNA processing and for its role in cellular stress responses. However, whether elevated dicer protein levels play a role in sustaining a thermotolerant phenotype has, to our knowledge, not been reported. Here we demonstrate that elevated dicer protein is linked to a thermotolerant phenotype in the cervical carcinoma cell line HeLa and in murine embryonic fibroblasts (MEF), and demonstrate that dicer plays a role in mediating PKR and eIF2α phosphorylation...
April 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28504966/functional-characterization-of-the-lysosomal-membrane-protein-tmem192-in-mice
#15
Thuy Linh Nguyen, Janna Schneppenheim, Sönke Rudnik, Renate Lüllmann-Rauch, Christian Bernreuther, Irm Hermans-Borgmeyer, Markus Glatzel, Paul Saftig, Bernd Schröder
The Transmembrane protein 192 (TMEM192) is a lysosomal/late endosomal protein initially discovered by organellar proteomics. TMEM192 exhibits four transmembrane segments with cytosolic N- and C-termini and forms homodimers. Devoid of significant homologies, the molecular function of TMEM192 is currently unknown. Upon TMEM192 knockdown in hepatoma cells, a dysregulation of autophagy and increased apoptosis were reported. Here, we aimed to define the physiological role of TMEM192 by analysing consequences of TMEM192 ablation in mice...
April 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28504692/mint3-mediated-l1cam-expression-in-fibroblasts-promotes-cancer-cell-proliferation-via-integrin-%C3%AE-5%C3%AE-1-and-tumour-growth
#16
H J Nakaoka, Z Tanei, T Hara, J S Weng, A Kanamori, T Hayashi, H Sato, A Orimo, K Otsuji, K Tada, T Morikawa, T Sasaki, M Fukayama, M Seiki, Y Murakami, T Sakamoto
Fibroblasts are some of the major cells in tumour tissues that influence tumour progression and drug resistance. However, our understanding on fibroblast-mediated tumour malignancy remains incomplete. Munc18-1-interacting protein 3 (Mint3) is known as an activator of hypoxia-inducible factor-1 (HIF-1) even during normoxia in cancer cells, macrophages and fibroblasts. Although Mint3 promotes ATP production via glycolysis by activating HIF-1 in cancer cells and macrophages, the biological role of Mint3-mediated HIF-1 activation in fibroblasts remains unclear...
May 15, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28502587/direct-and-indirect-activation-of-eukaryotic-elongation-factor-2-kinase-by-amp-activated-protein-kinase
#17
M Johanns, S Pyr Dit Ruys, A Houddane, D Vertommen, G Herinckx, L Hue, C G Proud, M H Rider
BACKGROUND: Eukaryotic elongation factor 2 (eEF2) kinase (eEF2K) is a key regulator of protein synthesis in mammalian cells. It phosphorylates and inhibits eEF2, the translation factor necessary for peptide translocation during the elongation phase of protein synthesis. When cellular energy demand outweighs energy supply, AMP-activated protein kinase (AMPK) and eEF2K become activated, leading to eEF2 phosphorylation, which reduces the rate of protein synthesis, a process that consumes a large proportion of cellular energy under optimal conditions...
May 11, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28500132/the-zinc-finger-e-box-binding-homeobox-1-zeb1-promotes-the-conversion-of-mouse-fibroblasts-into-functional-neurons
#18
Long Yan, Yue Li, Zixiao Shi, Xiaoyin Lu, Jiao Ma, Baoyang Hu, Jianwei Jiao, Hongmei Wang
The zinc finger E-box binding transcription factor Zeb1 plays a pivotal role in the epithelial-mesenchymal transition (EMT). Numerous studies have focused on the molecular mechanisms by which Zeb1 contributes to this process. However, the functions of Zeb1 beyond EMT remain largely elusive. Using a transdifferentiation system to convert mouse embryonic fibroblasts (MEFs) into functional neurons via the neuronal transcription factors Achaete-scute family bHLH transcription factor1 (Ascl1), POU class 3 homeobox 2 (POU3F2/Brn2) and Neurogenin 2 (Neurog2, Ngn2) (ABN), we found that Zeb1 was up-regulated during the early stages of transdifferentiation...
May 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28498911/different-chromatographic-methods-for-simultaneous-determination-of-mefenamic-acid-and-two-of-its-toxic-impurities
#19
Martha M Morcoss, Nada S Abdelwahab, Nouruddin W Ali, Mohammed T Elsaady
Two sensitive, accurate and precise chromatographic methods mentioned as TLC-densitometric method and RP-HPLC-DAD method, were developed and validated for the simultaneous determination of mefenamic acid (MEF) and its two toxic impurities, benzoic acid (BA) and 2,3-dimethylaniline (DMA). In the proposed TLC-densitometric method a developing system consisting of chloroform:acetone:acetic acid:ammonia solution(70:30:2:2, v/v/v/v) was used, TLC aluminum plates 60 F254 was used as a stationary phase and the separated bands were UV-scanned at 225 nm...
May 11, 2017: Journal of Chromatographic Science
https://www.readbyqxmd.com/read/28481879/cytoplasmic-e3-ubiquitin-ligase-cul9-controls-cell-proliferation-senescence-apoptosis-and-genome-integrity-through-p53
#20
Z Li, Y Xiong
CUL9 is a member of the cullin family of E3 ubiquitin ligases, and it localizes predominantly in the cytoplasm. Deletion of Cul9 in mice results in increased DNA damage, widespread aneuploidy, spontaneous tumor development, accelerated Eμ-Myc-induced lymphomagenesis and susceptibility to carcinogenesis. CUL9 binds to p53 and causes cell apoptosis when ectopically expressed. Whether the function of CUL9 in maintaining genomic integrity and suppressing tumorigenesis is linked to p53 has not been genetically tested...
May 8, 2017: Oncogene
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