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https://www.readbyqxmd.com/read/28817833/fmnl2-destabilises-commd10-to-activate-nf-%C3%AE%C2%BAb-pathway-in-invasion-and-metastasis-of-colorectal-cancer
#1
S S Yang, X M Li, M Yang, X L Ren, J L Hu, X H Zhu, F F Wang, Z C Zeng, J Y Li, Z Q Cheng, W T Liao, Y Q Ding, J Guan, L Liang
BACKGROUND: Diaphanous-related formins (DRFs), actin necleator, have been known to participate in the progression of cancer cells. We previously reported that FMNL2 (Formin-like2), a member of DRFs, was a positive regulator in colorectal cancer (CRC) metastasis, yet proteins and pathways required for the function of this pro-invasive DRFs remain to be identified. METHODS: The relationship between FMNL2 and COMMD10 was examined using Co-IP, GST pull-down, immunofluorescence and in vitro ubiquitination assay...
August 17, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28816449/paralog-specificity-determines-subcellular-distribution-action-mechanism-and-anticancer-activity-of-trap1-inhibitors
#2
Hye-Kyung Park, Hanbin Jeong, Eunhwa Ko, Geumwoo Lee, Ji-Eun Lee, Sang Kwang Lee, An-Jung Lee, Jin Young Im, Sung Hu, Seong Heon Kim, Ji Hoon Lee, Changwook Lee, Soosung Kang, Byoung Heon Kang
Although Hsp90 inhibitors can inhibit multiple tumorigenic pathways in cancer cells, their anticancer activity has been disappointingly modest. However, by forcing Hsp90 inhibitors into the mitochondria with mitochondrial delivery vehicles, they were converted into potent drugs targeting the mitochondrial Hsp90 paralog TRAP1. Here, to improve mitochondrial drug accumulation without using the mitochondrial delivery vehicle, we increased freely available drug concentrations in the cytoplasm by reducing the binding of the drugs to the abundant cytoplasmic Hsp90...
August 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28815376/evaluation-of-genetic-and-non-genetic-factors-on-foot-and-mouth-disease-fmd-virus-vaccine-elicited-immune-response-in-hardhenu-bos-taurus-x-bos-indicus-cattle
#3
Manjeet, B L Pander, R Sharma, S S Dhaka, Ankit Magotra, Kapil Dev
Foot and mouth disease (FMD) is the most contagious disease of mammals and a major threat to animal husbandry sector. In India, vaccination with the inactivated trivalent (O, A and Asia1) vaccine is one proven way for protecting the livestock from FMD. However, many outbreaks have been reported in different parts of the country. Therefore, present study was aimed at elucidating the effects of genetic and non-genetic factors on FMD viral vaccine-elicited immune response in Hardhenu cattle. The effect of season of vaccination was not consistent...
August 16, 2017: Tropical Animal Health and Production
https://www.readbyqxmd.com/read/28810240/efficient-statistical-method-for-association-analysis-of-x-linked-variants
#4
Heejin Jin, Taesung Park, Sungho Won
BACKGROUND/AIMS: Unlike the gene-poor Y chromosome, the X chromosome contains over 1,000 genes that are essential for viability of cells. Females have 2 X chromosomes, and thus female X-linked gene expression would be expected to be twice that of males. To adjust this imbalance, one of the 2 X-linked genes is often inactivated, and this is known as X-chromosome inactivation (XCI). However, recent studies described that a gene can be nonrandomly selected for inactivation from 2 X-linked genes and that XCI is not observed in some X-linked genes...
August 16, 2017: Human Heredity
https://www.readbyqxmd.com/read/28806168/mapping-the-mouse-allelome-reveals-tissue-specific-regulation-of-allelic-expression
#5
Daniel Andergassen, Christoph P Dotter, Daniel Wenzel, Verena Sigl, Philipp C Bammer, Markus Muckenhuber, Daniela Mayer, Tomasz M Kulinski, Hans-Christian Theussl, Josef M Penninger, Christoph Bock, Denise P Barlow, Florian M Pauler, Quanah J Hudson
To determine the dynamics of allelic-specific expression during mouse development, we analyzed RNA-seq data from 23 F1 tissues from different developmental stages, including 19 female tissues allowing X chromosome inactivation (XCI) escapers to also be detected. We demonstrate that allelic expression arising from genetic or epigenetic differences is highly tissue-specific. We find that tissue-specific strain-biased gene expression may be regulated by tissue-specific enhancers or by post-transcriptional differences in stability between the alleles...
August 14, 2017: ELife
https://www.readbyqxmd.com/read/28801450/genomic-analysis-of-hairy-cell-leukemia-identifies-novel-recurrent-genetic-alterations
#6
Benjamin H Durham, Bartlomiej Getta, Sascha Dietrich, Justin Taylor, Helen Won, James M Bogenberger, Sasinya Scott, Eunhee Kim, Young Rock Chung, Stephen S Chung, Jennifer Hüllein, Tatjana Walther, Lu Wang, Sydney X Lu, Christopher C Oakes, Raoul Tibes, Torsten Haferlach, Barry S Taylor, Martin S Tallman, Michael F Berger, Jae H Park, Thorsten Zenz, Omar Abdel-Wahab
Classical hairy cell leukemia (cHCL) is characterized by a near 100% frequency of the BRAFV600E mutation while ~30% of variant HCL (vHCL) have MAP2K1 mutations. However, recurrent genetic alterations cooperating with BRAFV600E or MAP2K1 mutations in HCL, as well as those in MAP2K1- wildtype vHCL, are not well defined. We therefore performed deep targeted mutational and copy number analysis of cHCL (n=53) and vHCL (n=8). The most common genetic alteration in cHCL outside of BRAFV600E was heterozygous loss of chromosome 7q, the minimally deleted region of which targeted wildtype BRAF, subdividing cHCL into those hemizygous versus heterozygous for the BRAFV600E mutation...
August 11, 2017: Blood
https://www.readbyqxmd.com/read/28796844/genome-wide-identification-of-autosomal-genes-with-allelic-imbalance-of-chromatin-state
#7
Andrej J Savol, Peggy I Wang, Yesu Jeon, David Colognori, Eda Yildirim, Stefan F Pinter, Bernhard Payer, Jeannie T Lee, Ruslan I Sadreyev
In mammals, monoallelic gene expression can result from X-chromosome inactivation, genomic imprinting, and random monoallelic expression (RMAE). Epigenetic regulation of RMAE is not fully understood. Here we analyze allelic imbalance in chromatin state of autosomal genes using ChIP-seq in a clonal cell line. We identify approximately 3.7% of autosomal genes that show significant differences between chromatin states of two alleles. Allelic regulation is represented among several functional gene categories including histones, chromatin modifiers, and multiple early developmental regulators...
2017: PloS One
https://www.readbyqxmd.com/read/28794184/post-transcriptional-regulation-of-mouse-neurogenesis-by-pumilio-proteins
#8
Meng Zhang, Dong Chen, Jing Xia, Wenqi Han, Xiekui Cui, Nils Neuenkirchen, Gretchen Hermes, Nenad Sestan, Haifan Lin
Despite extensive studies on mammalian neurogenesis, its post-transcriptional regulation remains under-explored. Here we report that neural-specific inactivation of two murine post-transcriptional regulators, Pumilio 1 (Pum1) and Pum2, severely reduced the number of neural stem cells (NSCs) in the postnatal dentate gyrus (DG), drastically increased perinatal apoptosis, altered DG cell composition, and impaired learning and memory. Consistently, the mutant DG neurospheres generated fewer NSCs with defects in proliferation, survival, and differentiation, supporting a major role of Pum1 and Pum2 in hippocampal neurogenesis and function...
August 9, 2017: Genes & Development
https://www.readbyqxmd.com/read/28783177/autophagy-dependent-generation-of-axin2-cancer-stem-like-cells-promotes-hepatocarcinogenesis-in-liver-cirrhosis
#9
J Li, S B Hu, L Y Wang, X Zhang, X Zhou, B Yang, J H Li, J Xiong, N Liu, Y Li, Y Z Wu, Q C Zheng
Autophagy is a pathophysiological phenomenon in liver cirrhosis that can further progress into hepatocarcinoma. Liver cancer stem cells (CSCs) are believed to initiate hepatocarcinogenesis. To investigate the precise mechanism related to the origin of CSCs in liver cirrhosis and hepatocarcinogenesis, we labeled Axin2+ hepatic cells with EGFP in Axin2Cre;Rosa26EGFP transgenic rats, and then stratified clinical and rat liver cirrhosis samples by autophagy flux. Clinical follow-up and lineage tracing in transgenic rat liver cirrhosis revealed that while Axin2/EGFP+ hepatic cells were present in normal livers and cirrhotic livers without aberrant autophagy, hepatic Axin2/EGFP+CD90+ cells were generated exclusively in cirrhotic livers with aberrant autophagy and promoted hepatocarcinogenesis...
August 7, 2017: Oncogene
https://www.readbyqxmd.com/read/28777483/skewed-x-inactivation-in-a-family-with-dlg3-associated-x-linked-intellectual-disability
#10
Laura Gieldon, Luisa Mackenroth, Elitza Betcheva-Krajcir, Andreas Rump, Stefanie Beck-Wödl, Jens Schallner, Nataliya Di Donato, Evelin Schröck, Andreas Tzschach
Mutations in DLG3 are a rare cause of non-syndromic X-linked intellectual disability (XLID) (MRX90, OMIM *300189). Only ten DLG3 mutations have been reported to date. The majority of female heterozygous mutation carriers was healthy and had random X-inactivation patterns. We report on an XLID family with a novel DLG3 mutation. The 12-year-old male index patient had moderate intellectual disability (ID) and dysmorphic features. The mutation was also present in four female relatives. A maternal aunt had moderate ID and significantly skewed X-inactivation favorably inactivating the normal DLG3 allele...
August 4, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28771462/a-tetrad-of-chromatin-interactions-for-chromosome-pairing-in-x-inactivation
#11
Ivan Krivega, Ann Dean
No abstract text is available yet for this article.
August 3, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28768854/presence-of-a-shared-5-leader-sequence-in-ancestral-human-and-mammalian-retroviruses-and-its-transduction-into-feline-leukemia-virus
#12
Junna Kawasaki, Maki Kawamura, Yoshiharu Ohsato, Jumpei Ito, Kazuo Nishigaki
Recombination events induce significant genetic changes, and this process can result in virus genetic diversity or in the generation of novel pathogenicity. We discovered a new recombinant feline leukemia virus (FeLV) gag gene harboring an unrelated insertion, termed the "X-region", which was derived from FcERV-gamma4, a feline endogenous gammaretrovirus. The identified FcERV-gamma4 proviruses have lost their coding capability, but some can express their viral RNA in feline tissues. Although the X-region-carrying recombinant FeLVs appeared to be replication-defective viruses, they were detected in 6...
August 2, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28768204/single-cell-landscape-of-transcriptional-heterogeneity-and-cell-fate-decisions-during-mouse-early-gastrulation
#13
Hisham Mohammed, Irene Hernando-Herraez, Aurora Savino, Antonio Scialdone, Iain Macaulay, Carla Mulas, Tamir Chandra, Thierry Voet, Wendy Dean, Jennifer Nichols, John C Marioni, Wolf Reik
The mouse inner cell mass (ICM) segregates into the epiblast and primitive endoderm (PrE) lineages coincident with implantation of the embryo. The epiblast subsequently undergoes considerable expansion of cell numbers prior to gastrulation. To investigate underlying regulatory principles, we performed systematic single-cell RNA sequencing (seq) of conceptuses from E3.5 to E6.5. The epiblast shows reactivation and subsequent inactivation of the X chromosome, with Zfp57 expression associated with reactivation and inactivation together with other candidate regulators...
August 1, 2017: Cell Reports
https://www.readbyqxmd.com/read/28767436/rnai-mediated-knockdown-of-parp1-does-not-improve-the-development-of-female-cloned-mouse-embryos
#14
Guang-Yu Bai, Si-Hang Song, Rui-Zhen Sun, Zi-Hui Zhang, Jingyu Li, Zhen-Dong Wang, Zhong-Hua Liu, Lei Lei
Somatic cell nuclear transfer is an important technique for life science research, but its efficiency is still extremely low, and most genes that are important during early development, such as X chromosome-linked genes, are not appropriately expressed during this process. Poly (ADP-ribose) polymerase (PARP) is an enzyme that transfers ADP ribose clusters to target proteins. PARP family members such as PARP1 participate in cellular signalling pathways through poly (ADP-ribosylation) (PARylation), which ultimately promotes changes in chromatin structure, gene expression, and the localization and activity of proteins that mediate signalling responses...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28766050/unique-xci-evolution-in-tokudaia-initial-xci-of-the-neo-x-chromosome-in-tokudaia-muenninki-and-function-loss-of-xist-in-tokudaia-osimensis
#15
Hideki Zushi, Chie Murata, Shusei Mizushima, Chizuko Nishida, Asato Kuroiwa
X chromosome inactivation (XCI) is an essential mechanism to compensate gene dosage in mammals. Here, we show that XCI has evolved differently in two species of the genus Tokudaia. The Amami spiny rat, Tokudaia osimensis, has a single X chromosome in males and females (XO/XO). By contrast, the Okinawa spiny rat, Tokudaia muenninki, has XX/XY sex chromosomes like most mammals, although the X chromosome has acquired a neo-X region by fusion with an autosome. BAC clones containing the XIST gene, which produces the long non-coding RNA XIST required for XCI, were obtained by screening of T...
August 2, 2017: Chromosoma
https://www.readbyqxmd.com/read/28764922/tissue-specific-mineralization-defects-in-the-periodontium-of-the-hyp-mouse-model-of-x-linked-hypophosphatemia
#16
Benjamin R Coyac, Guillaume Falgayrac, Brigitte Baroukh, Lotfi Slimani, Jérémy Sadoine, Guillaume Penel, Martin Biosse-Duplan, Thorsten Schinke, Agnès Linglart, Marc D McKee, Catherine Chaussain, Claire Bardet
X-linked hypophosphatemia (XLH) is a dento-osseous disorder caused by inactivating mutations in the PHEX gene, leading to renal phosphate wasting and hypophosphatemia, and impaired mineralization of bones and teeth. In the oral cavity, recent reports suggest a higher susceptibility of XLH patients to periodontitis, where patients present with impaired tooth cementum - a bone-like tissue involved in tooth attachment to the jaw bones and post-eruption tooth positioning - and a higher frequency of intrabony defects...
July 29, 2017: Bone
https://www.readbyqxmd.com/read/28760982/low-frequency-hippocampal-cortical-activity-drives-brain-wide-resting-state-functional-mri-connectivity
#17
Russell W Chan, Alex T L Leong, Leon C Ho, Patrick P Gao, Eddie C Wong, Celia M Dong, Xunda Wang, Jufang He, Ying-Shing Chan, Lee Wei Lim, Ed X Wu
The hippocampus, including the dorsal dentate gyrus (dDG), and cortex engage in bidirectional communication. We propose that low-frequency activity in hippocampal-cortical pathways contributes to brain-wide resting-state connectivity to integrate sensory information. Using optogenetic stimulation and brain-wide fMRI and resting-state fMRI (rsfMRI), we determined the large-scale effects of spatiotemporal-specific downstream propagation of hippocampal activity. Low-frequency (1 Hz), but not high-frequency (40 Hz), stimulation of dDG excitatory neurons evoked robust cortical and subcortical brain-wide fMRI responses...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28760675/alkaline-hydrolysis-to-increase-the-selectivity-of-colorimetric-determination-of-polysorbate
#18
Andrea Engelmaier, Heinz Anderle, Alfred Weber
Here, we describe a straightforward sample pretreatment step for the colorimetric cobaltthiocyanate determination of polysorbate, which circumvents the assay's shortcomings due to interference of protein and does not require complex instrumentation. Protein-containing test samples are hydrolyzed with strong alkali at 100 °C, neutralized and clarified by filtration before applying the colorimetric assay. The modified method performs with appropriate accuracy and precision, allowing specific polysorbate measurement in the presence of Triton X-100 during virus inactivation, determination of residual amounts of polysorbate in the final products and measurement of polysorbate 80 in final formulated products...
July 28, 2017: Biologicals: Journal of the International Association of Biological Standardization
https://www.readbyqxmd.com/read/28759216/allosteric-inhibitors-crystallography-and-comparative-analysis-reveal-network-of-coordinated-movement-across-human-herpesvirus-proteases
#19
Timothy M Acker, Jonathan E Gable, Markus-Frederik Bohn, Priyadarshini Jaishankar, Michael C Thompson, James S Fraser, Adam R Renslo, Charles S Craik
Targeting of cryptic binding sites represents an attractive but underexplored approach to modulating protein function with small molecules. Using the dimeric protease (Pr) from Kaposi's sarcoma-associated herpesvirus (KSHV) as a model system, we sought to dissect a putative allosteric network linking a cryptic site at the dimerization interface to enzyme function. Five cryogenic x-ray structures were solved of the monomeric protease with allosteric inhibitors bound to the dimer interface site. Distinct coordinated movements captured by the allosteric inhibitors were also revealed as alternative states in room temperature X-ray data and comparative analyses of other dimeric herpesvirus proteases...
July 31, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28759203/structural-and-functional-characterization-of-the-histidine-phosphatase-domains-of-human-sts-1-and-sts-2
#20
Weijie Zhou, Yue Yin, Alexandra S Weinheimer, Neena Kaur, Nick Carpino, Jarrod B French
The suppressor of T-cell signaling (Sts) proteins, Sts-1 and Sts-2, are homologous phosphatases that negatively regulate signaling pathways downstream of the T-cell receptor. Functional inactivation of Sts-1 and Sts-2 in a murine model leads to resistance to systemic infection by the opportunistic pathogen, C. albicans. This suggests that modulation of the host immune response by inhibiting Sts function may be a viable strategy to treat these deadly fungal pathogen infections. To better understand the molecular determinants of function and structure, we characterized the structure and steady-state kinetics of the histidine phosphatase domains of human Sts-1 (Sts-1HP) and Sts-2 (Sts-2HP)...
July 31, 2017: Biochemistry
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