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https://www.readbyqxmd.com/read/29053968/multiscale-3d-genome-rewiring-during-mouse-neural-development
#1
Boyan Bonev, Netta Mendelson Cohen, Quentin Szabo, Lauriane Fritsch, Giorgio L Papadopoulos, Yaniv Lubling, Xiaole Xu, Xiaodan Lv, Jean-Philippe Hugnot, Amos Tanay, Giacomo Cavalli
Chromosome conformation capture technologies have revealed important insights into genome folding. Yet, how spatial genome architecture is related to gene expression and cell fate remains unclear. We comprehensively mapped 3D chromatin organization during mouse neural differentiation in vitro and in vivo, generating the highest-resolution Hi-C maps available to date. We found that transcription is correlated with chromatin insulation and long-range interactions, but dCas9-mediated activation is insufficient for creating TAD boundaries de novo...
October 19, 2017: Cell
https://www.readbyqxmd.com/read/29053667/assay-development-for-high-content-quantification-of-sod1-mutant-protein-aggregate-formation-in-living-cells
#2
Honggun Lee, Constantin Radu, Jeung Whan Han, Regis Grailhe
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that can be caused by inherited mutations in the gene encoding copper-zinc superoxide dismutase 1 (SOD1). The structural instability of SOD1 and the detection of SOD1-positive inclusions in familial-ALS patients supports a potential causal role for misfolded and/or aggregated SOD1 in ALS pathology. In this study, we describe the development of a cell-based assay designed to quantify the dynamics of SOD1 aggregation in living cells by high content screening approaches...
October 4, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29053466/classification-of-single-cell-gene-expression-trajectories-from-incomplete-and-noisy-data
#3
Alireza Karbalayghareh, Ulisses Braga-Neto, Edward Russell Dougherty
This paper studies classification of gene-expression trajectories coming from two classes, healthy and mutated (cancerous) using Boolean networks with perturbation (BNps) to model the dynamics of each class at the state level. Each class has its own BNp, which is partially known based on gene pathways. We employ a Gaussian model at the observation level to show the expression values of the genes given the hidden binary states at each time point. We use expectation maximization (EM) to learn the BNps and the unknown model parameters, derive closed-form updates for the parameters, and propose a learning algorithm...
October 16, 2017: IEEE/ACM Transactions on Computational Biology and Bioinformatics
https://www.readbyqxmd.com/read/29053389/mrpl53-a-new-candidate-gene-for-orofacial-clefting-identified-using-an-eqtl-approach
#4
C Masotti, L A Brito, A C Nica, K U Ludwig, K Nunes, C P Savastano, C Malcher, S G Ferreira, G S Kobayashi, D F Bueno, N Alonso, D Franco, A Rojas-Martinez, S E Dos Santos, P A Galante, D Meyer, T Hünemeier, E Mangold, E T Dermitzakis, M R Passos-Bueno
A valuable approach to understand how individual and population genetic differences can predispose to disease is to assess the impact of genetic variants on cellular functions (e.g., gene expression) of cell and tissue types related to pathological states. To understand the genetic basis of nonsyndromic cleft lip with or without cleft palate (NSCL/P) susceptibility, a complex and highly prevalent congenital malformation, we searched for genetic variants with a regulatory role in a disease-related tissue, the lip muscle (orbicularis oris muscle [OOM]), of affected individuals...
October 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/29052597/syk-expression-in-monomorphic-epitheliotropic-intestinal-t-cell-lymphoma
#5
Grit Mutzbauer, Katja Maurus, Clara Buszello, Jordan Pischimarov, Sabine Roth, Andreas Rosenwald, Andreas Chott, Eva Geissinger
Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), formerly known as type II enteropathy associated T-cell lymphoma (type II EATL), is a rare, aggressive primary intestinal T-cell lymphoma with a poor prognosis and an incompletely understood pathogenesis. We collected 40 cases of MEITL and 27 cases of EATL, formerly known as type I EATL, and comparatively investigated the T-cell receptor (TCR) itself and associated signaling molecules using immunohistochemistry, amplicon deep sequencing and bisulfite pyrosequencing...
October 20, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29052520/upregulation-of-dars2-by-hbv-promotes-hepatocarcinogenesis-through-the-mir-30e-5p-mapk-nfat5-pathway
#6
Xian Qin, Changsheng Li, Tao Guo, Jing Chen, Hai-Tao Wang, Yi-Tao Wang, Yu-Sha Xiao, Jun Li, Pengpeng Liu, Zhi-Su Liu, Quan-Yan Liu
BACKGROUND: Infection with the hepatitis B virus (HBV) is closely associated with the development of hepatocellular carcinoma (HCC). The osmoregulatory transcription factor nuclear factor of activated T-cells 5 (NFAT5) has been shown to play an important role in the development of many types of human cancers. The role of NFAT5 in HBV-associated HCC has never previously been investigated. METHODS: We compared expression profiles of NFAT5, DARS2 and miR-30e-5p in HCC samples, adjacent nontumor tissues and different hepatoma cell lines by quantitative real-time polymerase chain reaction and /or Western blot...
October 19, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29052331/piwis-pirnas-and-retrotransposons-complex-battles-during-reprogramming-in-gametes-and-early-embryos
#7
REVIEW
S J Russell, L Stalker, J LaMarre
Gamete and embryo development are indispensable processes for successful reproduction. Cells involved in these processes acquire pluripotency, the ability to differentiate into multiple different cell types, through a series of events known as reprogramming that lead to profound changes in histone and DNA methylation. While essential for pluripotency, this epigenetic remodelling removes constraints that normally limit the expression of genomic sequences known as transposable elements (TEs). Unconstrained TE expression can lead to many deleterious consequences including infertility, so organisms have evolved complex and potent mechanistic arsenals to target and suppress TE expression during reprogramming...
October 2017: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/29052317/defective-ciliogenesis-in-inpp5e-related-joubert-syndrome
#8
Isabel Hardee, Ariane Soldatos, Mariska Davids, Thierry Vilboux, Camilo Toro, Karen L David, Carlos R Ferreira, Michele Nehrebecky, Joseph Snow, Audrey Thurm, Theo Heller, Ellen F Macnamara, Meral Gunay-Aygun, Wadih M Zein, William A Gahl, May Christine V Malicdan
Joubert syndrome is a neurodevelopmental disorder, characterized by malformation of the mid and hindbrain leading to the pathognomonic molar tooth appearance of the brainstem and cerebellum on axial MRI. Core clinical manifestations include hypotonia, tachypnea/apnea, ataxia, ocular motor apraxia, and developmental delay of varying degrees. In addition, a subset of patients has retinal dystrophy, chorioretinal colobomas, hepatorenal fibrocystic disease, and polydactyly. Joubert syndrome exhibits genetic heterogeneity, with mutations identified in more than 30 genes, including INPP5E, a gene encoding inositol polyphosphate 5-phosphatase E, which is important in the development and stability of the primary cilium...
October 20, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/29052269/control-of-biotin-biosynthesis-in-mycobacteria-by-a-pyruvate-carboxylase-dependent-metabolic-signal
#9
Nathaniel Lazar, Allison Fay, Madhumitha Nandakumar, Kerry E Boyle, Joao Xavier, Kyu Rhee, Michael S Glickman
Biotin is an essential cofactor utilized by all domains of life, but only synthesized by bacteria, fungi and plants, making biotin biosynthesis a target for antimicrobial development. To understand biotin biosynthesis in mycobacteria, we executed a genetic screen in Mycobacterium smegmatis for biotin auxotrophs and identified pyruvate carboxylase (Pyc) as required for biotin biosynthesis. The biotin auxotrophy of the pyc::tn strain is due to failure to transcriptionally induce late stage biotin biosynthetic genes in low biotin conditions...
October 20, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/29052189/cell-type-specific-profiling-of-chromatin-modifications-and-associated-proteins
#10
Ana Karina Morao, Erwann Caillieux, Vincent Colot, François Roudier
Progression of a cell along a differentiation path is characterized by changes in gene expression profiles. Alterations of these transcriptional programs result from cell type-specific transcription factors that act in a dynamic chromatin environment. Understanding the precise contribution of these molecular factors during the differentiation process requires accessing specific cell types within a developing organ. This chapter describes a streamlined and alternative version of INTACT, a method enabling the isolation of specific cell populations by affinity-purification of tagged nuclei and the subsequent analysis of gene expression, transcription factor binding profiles, as well as chromatin state at a genome-wide scale...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29052182/profiling-developmentally-and-environmentally-controlled-chromatin-reprogramming
#11
Clara Bourbousse, Moussa Benhamed, Fredy Barneche
Dynamic reshuffling of the chromatin landscape is a recurrent theme orchestrated in many, if not all, plant developmental transitions and adaptive responses. Spatiotemporal variations of the chromatin properties on regulatory genes and on structural genomic elements trigger the establishment of distinct transcriptional contexts, which in some instances can epigenetically be inherited. Studies on plant cell plasticity during the differentiation of stem cells, including gametogenesis, or the specialization of vegetative cells in various organs, as well as the investigation of allele-specific gene regulation have long been impaired by technical challenges in generating specific chromatin profiles in complex or hardly accessible cell populations...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29052178/hmga1-is-a-novel-transcriptional-regulator-of-the-foxo1-gene
#12
Biagio Arcidiacono, Eusebio Chiefari, Sebastiano Messineo, Francesco L Bilotta, Ida Pastore, Domenica M Corigliano, Daniela P Foti, Antonio Brunetti
PURPOSE: The forkhead transcription factor (FoxO1) is a master transcriptional regulator of fundamental cellular processes ranging from cell proliferation and differentiation to inflammation and metabolism. However, despite its relevance, the mechanism(s) underlying FoxO1 gene regulation are largely unknown. We have previously shown that the chromatin factor high-mobility group A1 (HMGA1) plays a key role in the transcriptional regulation of glucose-responsive genes, including some that are involved in FoxO1-mediated glucose metabolism...
October 19, 2017: Endocrine
https://www.readbyqxmd.com/read/29052140/prion-protein-family-contributes-to-tumorigenesis-via-multiple-pathways
#13
Xiaowen Yang, Zhijun Cheng, Lihua Zhang, Guiru Wu, Run Shi, Zhenxing Gao, Chaoyang Li
A wealth of evidence suggests that proteins from prion protein (PrP) family contribute to tumorigenesis in many types of cancers, including pancreatic ductal adenocarcinoma (PDAC), breast cancer, glioblastoma, colorectal cancer, gastric cancer, melanoma, etc. It is well documented that PrP is a biomarker for PDAC, breast cancer, and gastric cancer. However, the underlying mechanisms remain unclear. The major reasons for cancer cell-caused patient death are metastasis and multiple drug resistance, both of which connect to physiological functions of PrP expressing in cancer cells...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29052095/grass-phasirnas-and-male-fertility
#14
REVIEW
Yang Yu, Yanfei Zhou, Yuchan Zhang, Yueqin Chen
Recent studies have indicated that a special type of small noncoding RNAs, phased small-interfering RNAs (phasiRNAs) play crucial roles in many cellular processes of plant development. PhasiRNAs are generated from long RNA precursors at intervals of 21 or 24 nt in plants, and they are produced from both protein-coding gene and long noncoding RNA genes. Different from those in eudicots, grass phasiRNAs include a special class of small RNAs that are specifically expressed in reproductive organs. These grass phasiRNAs are associated with gametogenesis, especially with anther development and male fertility...
October 18, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/29052022/udp-arabinopyranose-mutase-gene-expressions-are-required-for-the-biosynthesis-of-the-arabinose-side-chain-of-both-pectin-and-arabinoxyloglucan-and-normal-leaf-expansion-in-nicotiana-tabacum
#15
Hideyuki Honta, Takuya Inamura, Teruko Konishi, Shinobu Satoh, Hiroaki Iwai
Plant cell walls are composed of polysaccharides such as cellulose, hemicelluloses, and pectins, whose location and function differ depending on plant type. Arabinose is a constituent of many different cell wall components, including pectic rhamnogalacturonan I (RG-I) and II (RG-II), glucuronoarabinoxylans (GAX), and arabinoxyloglucan (AXG). Arabinose is found predominantly in the furanose rather than in the thermodynamically more stable pyranose form. The UDP-arabinopyranose mutases (UAMs) have been demonstrated to convert UDP-arabinopyranose (UDP-Arap) to UDP-arabinofuranose (UDP-Araf) in rice (Oryza sativa L...
October 19, 2017: Journal of Plant Research
https://www.readbyqxmd.com/read/29051706/investigation-of-the-tissue-distribution-and-physiological-roles-of-indoleamine-2-3-dioxygenase-2
#16
Felicita F Jusof, Supun M Bakmiwewa, Silvia Weiser, Lay Khoon Too, Richard Metz, George C Prendergast, Stuart T Fraser, Nicholas H Hunt, Helen J Ball
Indoleamine 2,3-dioxygenase-2 (IDO2) is 1 of the 3 enzymes that can catalyze the first step in the kynurenine pathway of tryptophan metabolism. Of the 2 other enzymes, tryptophan 2,3-dioxygenase is highly expressed in the liver and has a role in tryptophan homeostasis, whereas indoleamine 2,3-dioxygenase-1 (IDO1) expression is induced by inflammatory stimuli. Indoleamine 2,3-dioxygenase-2 is reportedly expressed comparatively narrow, including in liver, kidney, brain, and in certain immune cell types, and it does not appear to contribute significantly to systemic tryptophan catabolism under normal physiological conditions...
2017: International Journal of Tryptophan Research: IJTR
https://www.readbyqxmd.com/read/29051386/ets2-anchors-the-prometastatic-function-of-mutant-p53-in-osteosarcoma
#17
REVIEW
Daniel D Liu, Yibin Kang
Mutations in the tumor suppressor p53 occur in a majority of human cancers. Some gain-of-function (GOF) p53 mutations endow tumor cells with increased metastatic ability, although our understanding of the underlying mechanism remains incomplete. In this issue of Genes & Development, Pourebrahim and colleagues (pp. 1847-1857) develop a new mouse model of osteosarcoma in which a GOF mutant p53 allele is expressed specifically in osteoblasts, while the tumor microenvironment remains wild type for p53, allowing for the study of cell-autonomous functions...
September 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/29051230/iphemap-an-atlas-of-phenotype-to-genotype-relationships-of-human-ipsc-models-of-neurological%C3%A2-diseases
#18
Ethan W Hollingsworth, Jacob E Vaughn, Josh C Orack, Chelsea Skinner, Jamil Khouri, Sofia B Lizarraga, Mark E Hester, Fumihiro Watanabe, Kenneth S Kosik, Jaime Imitola
Disease modeling with induced pluripotent stem cells (iPSCs) is creating an abundance of phenotypic information that has become difficult to follow and interpret. Here, we report a systematic analysis of research practices and reporting bias in neurological disease models from 93 published articles. We find heterogeneity in current research practices and a reporting bias toward certain diseases. Moreover, we identified 663 CNS cell-derived phenotypes from 243 patients and 214 controls, which varied by mutation type and developmental stage in vitro We clustered these phenotypes into a taxonomy and characterized these phenotype-genotype relationships to generate a phenogenetic map that revealed novel correlations among previously unrelated genes...
October 19, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29051139/mining-the-stiffness-sensitive-transcriptome-in-human-vascular-smooth-muscle-cells-identifies-long-noncoding-rna-stiffness-regulators
#19
Christopher Yu, Tina Xu, Richard Assoian, Daniel J Rader
OBJECTIVE: Vascular extracellular matrix stiffening is a risk factor for aortic and coronary artery disease. How matrix stiffening regulates the transcriptome profile of human aortic and coronary vascular smooth muscle cells (VSMCs) is not well understood. Furthermore, the role of long noncoding RNAs (lncRNAs) in the cellular response to stiffening has never been explored. This study characterizes the stiffness-sensitive (SS) transcriptome of human aortic and coronary VSMCs and identifies potential key lncRNA regulators of stiffness-dependent VSMC functions...
October 19, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29050935/the-l1-adhesion-molecule-normalizes-neuritogenesis-in-rett-syndrome-derived-neural-precursor-cells
#20
Myungsik Yoo, Cassiano Carromeu, Ohyoon Kwon, Alysson Muotri, Melitta Schachner
Therapeutic intervention is an important need in ameliorating the severe consequences of Rett Syndrome (RTT), a neurological disorder caused by mutations in the X-linked gene methyl-CpG-binding protein-2 (MeCP2). Following previously observed morphological defects in induced pluripotent stem cell (iPSC)-derived neurons obtained from female RTT patients, we hypothesized transfection with the L1 cell adhesion molecule (L1) could contribute to normalizing a pathological male cell system bearing a nonsense mutation of MeCP2...
October 16, 2017: Biochemical and Biophysical Research Communications
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