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Modeling gene regulation

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https://www.readbyqxmd.com/read/28324111/arap1-deficiency-causes-photoreceptor-degeneration-in-mice
#1
Ala Moshiri, Devin Humpal, Brian C Leonard, Denise M Imai, Addy Tham, Lynette Bower, Dave Clary, Thomas M Glaser, K C Kent Lloyd, Christopher J Murphy
Purpose: Small guanosine triphosphatase (GTPase) ADP-ribosylation factors (Arfs) regulate membrane traffic and actin reorganization under the control of GTPase-activating proteins (GAPs). Arap1 is an Arf-directed GAP that inhibits the trafficking of epidermal growth factor receptor (EGFR) to the early endosome, but the diversity of its functions is incompletely understood. The aim of this study was to determine the role of Arap1 in the mammalian retina. Methods: Genetically engineered Arap1 knockout mice were screened for ocular abnormalities in the National Institutes of Health Knockout Mouse Production and Phenotyping (KOMP2) Project...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28324024/thyroid-hormone-receptor-%C3%AE-controls-developmental-timing-and-regulates-the-rate-and-coordination-of-tissue-specific-metamorphosis-in-xenopus-tropicalis
#2
Luan Wen, Yuki Shibata, Dan Su, Liezhen Fu, Nga Luu, Yun-Bo Shi
Thyroid hormone (T3) receptor (TR) mediates the effects of T3 on organ metabolism and animal development. There are two TR genes, TRα and TRβ, in all vertebrates. During animal development, TRα expression is activated earlier than zygotic T3 synthesis and secretion into the plasma, implicating a developmental role of TRα both in the presence and absence of T3. Using T3-dependend amphibian metamorphosis as a model, we have previously proposed a dual functional model for TRs, in particular TRα, during development...
March 14, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323945/coordinated-regulation-among-progesterone-prostaglandins-and-egf-like-factors-in-human-ovulatory-follicles
#3
Yohan Choi, Kalin Wilson, Patrick R Hannon, Katherine L Rosewell, Mats Brännström, James W Akin, Thomas E Curry, Misung Jo
CONTEXT: In animal models, the LH surge increases progesterone (P4)/its receptor (PGR), prostaglandins (PTGs), and epidermal growth factor (EGF)-like factors that play essential roles in ovulation. However, little is known about the expression, regulation, and function of these key ovulatory mediators in humans. OBJECTIVES: To determine when and how these key ovulatory mediators are induced after the luteinizing hormone surge in human ovaries. DESIGN AND PARTICIPANTS: Timed periovulatory follicles were obtained from cycling women...
March 9, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323939/tac1-gene-products-regulate-pituitary-hormone-secretion-and-gene-expression-in-prepubertal-grass-carp-pituitary-cells
#4
Guangfu Hu, Mulan He, Wendy K W Ko, Anderson O L Wong
Tachykinin 1 (TAC1) is known to have diverse functions in mammals but similar information is scarce in lower vertebrates including fish species. Using grass carp as a model, the pituitary actions, receptor specificity and post-receptor signaling of TAC1 gene products, namely substance P (SP) and neurokinin A (NKA), were examined. As a first step, TAC1 encoding carp SP and NKA as well as tachykinin receptors NK1R and NK2R were cloned in carp pituitary. Expression studies revealed that the newly cloned receptors were functional and with pharmacological properties similar to mammalian counterparts...
March 13, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323888/lzts2-and-pten-collaboratively-regulate-%C3%A3-catenin-in-prostatic-tumorigenesis
#5
Eun-Jeong Yu, Erika Hooker, Daniel T Johnson, Mi Kyung Kwak, Kang Zou, Richard Luong, Yongfeng He, Zijie Sun
The leucine zipper tumor suppressor 2 (LZTS2) was identified as a tumor susceptibility gene within the 10q24.3 chromosomal region, and is approximately 15Mb from the PTEN locus. This region containing the both loci is frequently deleted in a variety of human malignancies, including prostate cancer. LZTS2 is a ß-catenin-binding protein and a negative regulator of Wnt signaling. Overexpression of PTEN in prostate cancer cell lines reduces ß-catenin-mediated transcriptional activity. In this study, we examined the collaborative effect of PTEN and LZTS2 using multiple in vitro and in vivo approaches...
2017: PloS One
https://www.readbyqxmd.com/read/28323859/diacerein-inhibits-the-pro-atherogenic-pro-inflammatory-effects-of-il-1-on-human-keratinocytes-endothelial-cells
#6
Girish C Mohan, Huayi Zhang, Lei Bao, Benjamin Many, Lawrence S Chan
We investigated IL-1-induced regulation of genes related to inflammation and atherogenesis in human keratinocytes and endothelial cells, and if 'diacerein', an oral IL-1 inhibiting drug currently approved for use in osteoarthritis, would reverse IL-1's effects on these cells. Primary human keratinocytes and coronary artery endothelial cells were treated with either IL-1α or IL-1β, with and without diacerein. Using PCR-array, we assessed differential gene-expression regulated by IL-1 and diacerein. We identified 34 pro-atherogenic genes in endothelial cells and 68 pro-inflammatory genes in keratinocytes significantly (p<0...
2017: PloS One
https://www.readbyqxmd.com/read/28323406/affinity-selection-mass-spectrometry-identifies-a-novel-antibacterial-rna-polymerase-inhibitor
#7
Scott S Walker, David Degen, Elliott Nickbarg, Donna Carr, Aileen Soriano, Mihir Baran Mandal, Ronald E Painter, Payal R Sheth, Li Xiao, Xinwei Sher, Nicholas Murgolo, Jing Su, David B Olsen, Richard H Ebright, Katherine Young
The growing prevalence of drug-resistant Gram-negative bacteria is a significant global threat to human health. Rifampicin, an RNA polymerase-targeting agent, is an important part of the antibacterial armamentarium; however the emergence of resistance requires that it be used against only certain infections and usually in combination with another antibiotic. While rifampicin has significant clinical limitations, it does show that bacterial RNA polymerase can be an effective target for antibacterial intervention...
March 21, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28320085/down-regulation-of-microrna-142-5p-attenuates-oxygen-glucose-deprivation-and-reoxygenation-induced-neuron-injury-through-up-regulating-nrf2-are-signaling-pathway
#8
Ning Wang, Lingmin Zhang, Yang Lu, Mingxin Zhang, Zhenni Zhang, Kui Wang, Jianrui Lv
MicroRNAs (miRNAs) play vital roles in regulating neuron survival during cerebral ischemia/reperfusion injury. miR-142-5p is reported to be an important regulator of cellular survival. However, little is known about the role of miR-142-5p in regulating neuron survival during cerebral ischemia/reperfusion injury. In this study, we aimed to investigate the precise function and mechanism of miR-142-5p in the regulation of neuron ischemia/reperfusion injury using a cellular model of oxygen-glucose deprivation and reoxygenation (OGD/R)-induced injury in hippocampal neurons in vitro...
March 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28319609/developmental-alterations-in-huntington-s-disease-neural-cells-and-pharmacological-rescue-in-cells-and-mice
#9
(no author information available yet)
Neural cultures derived from Huntington's disease (HD) patient-derived induced pluripotent stem cells were used for 'omics' analyses to identify mechanisms underlying neurodegeneration. RNA-seq analysis identified genes in glutamate and GABA signaling, axonal guidance and calcium influx whose expression was decreased in HD cultures. One-third of gene changes were in pathways regulating neuronal development and maturation. When mapped to stages of mouse striatal development, the profiles aligned with earlier embryonic stages of neuronal differentiation...
March 20, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28319529/the-notch-signaling-system-is-involved-in-the-regulation-of-reparative-angiogenesis-in-the-zone-of-stasis
#10
Ozan Luay Abbas, Orhan Özatik, Yunus Kasm Terzi, Fikriye Yasemin Özatik, Rukiye Nar, Gamze Turna
The Notch pathway ligand Delta-like 4 (Dll4) functions as an antiangiogenic factor, inhibiting vascular endothelial growth factor (VEGF)-induced angiogenesis. This function is documented in tumor and embryonic vasculature. However, its implication in burn wounds remains unexplored. Our objective was to explore the involvement of the Notch in the healing of zone of stasis burns. We hypothesized that anti-Dll4 therapy would prevent progressive necrosis in the stasis zone by promoting angiogenesis. Burns were created in 21 rats using the comb burn model...
March 13, 2017: Journal of Burn Care & Research: Official Publication of the American Burn Association
https://www.readbyqxmd.com/read/28319438/systemic-deregulation-of-autophagy-upon-loss-of-als-and-ftd-linked-c9orf72
#11
Yon Ji, Janet Ugolino, Nathan Ryan Brady, Anne Hamacher-Brady, Jiou Wang
A genetic mutation in the C9orf72 gene causes the most common forms of neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The C9orf72 protein, predicted to be a DENN-family protein, is reduced in ALS and FTD, but its functions remain poorly understood. Using a 3110043O21Rik/C9orf72 knockout mouse model, as well as cellular analysis, we have found that loss of C9orf72 causes alterations in the signaling states of central autophagy regulators. In particular, C9orf72 depletion leads to reduced activity of MTOR, a negative regulator of macroautophagy/autophagy, and concomitantly increased TFEB levels and nuclear translocation...
March 20, 2017: Autophagy
https://www.readbyqxmd.com/read/28319320/the-endochondral-bone-protein-chm1-sustains-an-undifferentiated-invasive-phenotype-promoting-lung-metastasis-in-ewing-sarcoma
#12
Kristina von Heyking, Julia Calzada-Wack, Stefanie Göllner, Frauke Neff, Oxana Schmidt, Tim Hensel, David Schirmer, Annette Fasan, Irene Esposito, Carsten Müller-Tidow, Poul H Sorensen, Stefan Burdach, Günther H S Richter
Ewing sarcomas (ES) are highly malignant, osteolytic bone or soft tissue tumors, which are characterized by EWS-ETS translocations and early metastasis to lung and bone. In this study, we investigated the role of the BRICHOS chaperone domain-containing endochondral bone protein chondromodulin I (CHM1) in ES pathogenesis. CHM1 is significantly over-expressed in ES, and chromosome immunoprecipitation (ChIP) data demonstrate CHM1 to be directly bound by an EWS-ETS translocation, EWS-FLI1. Using RNA interference we observed that CHM1 promoted chondrogenic differentiation capacity of ES cells but decreased the expression of osteolytic genes such as HIF1A, IL6, JAG1 and VEGF...
March 20, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28319066/nucleus-accumbens-associated-protein-1-promotes-glycolysis-and-survival-of-hypoxic-tumor-cells-via-the-hdac4-hif-1%C3%AE-axis
#13
Y Zhang, Y-J Ren, L-C Guo, C Ji, J Hu, H-H Zhang, Q-H Xu, W-D Zhu, Z-J Ming, Y-S Yuan, X Ren, J Song, J-M Yang
Nucleus accumbens-associated protein-1 (NAC1), a nuclear factor of the BTB/POZ gene family, has emerging roles in cancer. In this study, we identified the NAC1-HDAC4-HIF-1α axis as an important pathway in regulating glycolysis and hypoxic adaptation in tumor cells. We show that nuclear NAC1 binds to histone deacetylase type 4 (HDAC4), hindering phosphorylation of HDAC4 at Ser(246) and preventing its nuclear export that leads to cytoplasmic degradation of the deacetylase. Accumulation of HDAC4 in the nuclei results in an attenuation of HIF-1α acetylation, enhancing the stabilization and transcriptional activity of HIF-1α and strengthening adaptive response of cells to hypoxia...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28319047/isocitrate-dehydrogenase-mutations-suppress-stat1-and-cd8-t-cell-accumulation-in-gliomas
#14
Gary Kohanbash, Diego A Carrera, Shruti Shrivastav, Brian J Ahn, Naznin Jahan, Tali Mazor, Zinal S Chheda, Kira M Downey, Payal B Watchmaker, Casey Beppler, Rolf Warta, Nduka A Amankulor, Christel Herold-Mende, Joseph F Costello, Hideho Okada
Mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 are among the first genetic alterations observed during the development of lower-grade glioma (LGG). LGG-associated IDH mutations confer gain-of-function activity by converting α-ketoglutarate to the oncometabolite R-2-hydroxyglutarate (2HG). Clinical samples and gene expression data from The Cancer Genome Atlas (TCGA) demonstrate reduced expression of cytotoxic T lymphocyte-associated genes and IFN-γ-inducible chemokines, including CXCL10, in IDH-mutated (IDH-MUT) tumors compared with IDH-WT tumors...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28318534/a-multidrug-and-toxic-compound-extrusion-transporter-mediates-berberine-accumulation-into-vacuoles-in-coptis-japonica
#15
Kojiro Takanashi, Yasuyuki Yamada, Takayuki Sasaki, Yoko Yamamoto, Fumihiko Sato, Kazufumi Yazaki
Plants produce a large variety of alkaloids, which have diverse chemical structures and biological activities. Many of these alkaloids accumulate in vacuoles. Although some membrane proteins on tonoplasts have been identified as alkaloid uptake transporters, few have been characterized to date, and relatively little is known about the mechanisms underlying alkaloid transport and accumulation in plant cells. Berberine is a model alkaloid. Although all genes involved in berberine biosynthesis, as well as the master regulator, have been identified, the gene responsible for the final accumulation of berberine at tonoplasts has not been determined...
March 16, 2017: Phytochemistry
https://www.readbyqxmd.com/read/28318367/combinatorial-control-of-messenger-rnas-by-pumilio-nanos-and-brain-tumor-proteins
#16
René M Arvola, Chase A Weidmann, Traci M Tanaka Hall, Aaron C Goldstrohm
Eukaryotes possess a vast array of RNA-binding proteins (RBPs) that affect mRNAs in diverse ways to control protein expression. Combinatorial regulation of mRNAs by RBPs is emerging as the rule. No example illustrates this as vividly as the partnership of three Drosophila RBPs, Pumilio, Nanos and Brain Tumor, which have overlapping functions in development, stem cell maintenance and differentiation, fertility and neurological processes. Here we synthesize thirty years of research with new insights into their molecular functions and mechanisms of action...
March 20, 2017: RNA Biology
https://www.readbyqxmd.com/read/28317936/priming-of-transcriptional-memory-responses-via-the-chromatin-accessibility-landscape-in-t-cells
#17
Wen Juan Tu, Kristine Hardy, Christopher R Sutton, Robert McCuaig, Jasmine Li, Jenny Dunn, Abel Tan, Vedran Brezar, Melanie Morris, Gareth Denyer, Sau Kuen Lee, Stephen J Turner, Nabila Seddiki, Corey Smith, Rajiv Khanna, Sudha Rao
Memory T cells exhibit transcriptional memory and "remember" their previous pathogenic encounter to increase transcription on re-infection. However, how this transcriptional priming response is regulated is unknown. Here we performed global FAIRE-seq profiling of chromatin accessibility in a human T cell transcriptional memory model. Primary activation induced persistent accessibility changes, and secondary activation induced secondary-specific opening of previously less accessible regions associated with enhanced expression of memory-responsive genes...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28317486/abnormal-clock-gene-expression-and-locomotor-activity-rhythms-in-two-month-old-female-appswe-ps1de9-mice
#18
Olaide Oyegbami, Hilary M Collins, Marie C Pardon, Fran Jp Ebling, David M Heery, Paula M Moran
In addition to cognitive decline, Alzheimer's disease (AD) is also characterized by agitation and disruptions in activity and sleep. These symptoms typically occur in the evening or at night and have been referred to as 'sundowning'. These symptoms are especially difficult for carers and there are no specific drug treatments. There is increasing evidence that these symptoms reflect an underlying pathology of circadian rhythm generation and transmission. We investigated whether a transgenic mouse model relevant to AD (APPswe/PS1dE9) exhibits circadian alterations in locomotor activity and expression of clock genes involved in the regulation of the circadian cycle...
March 17, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28317260/comparative-proteomic-analysis-of-trophoblast-cell-models-reveals-their-differential-phenotypes-potential-uses-and-limitations
#19
Paulina B Szklanna, Kieran Wynne, Marie Nolan, Karl Egan, Fionnuala Ní Áinle, Patricia B Maguire
Trophoblastic cell lines are widely used in in vitro studies of placental function as a surrogate for primary trophoblasts. To date, no reference proteomics dataset exists to directly compare the shared and unique characteristics of these cells. Here, we performed comparative proteomic profiling of the BeWo and HTR8/SVneo cell lines using label-free quantitative mass spectrometry. 1557 proteins were identified, which included 338 uniquely attributed to BeWo cells, and a further 304 specifically identified in HTR8/SVneo cells...
March 20, 2017: Proteomics
https://www.readbyqxmd.com/read/28317029/listeriomics-an-interactive-web-platform-for-systems-biology-of-listeria
#20
Christophe Bécavin, Mikael Koutero, Nicolas Tchitchek, Franck Cerutti, Pierre Lechat, Nicolas Maillet, Claire Hoede, Hélène Chiapello, Christine Gaspin, Pascale Cossart
As for many model organisms, the amount of Listeria omics data produced has recently increased exponentially. There are now >80 published complete Listeria genomes, around 350 different transcriptomic data sets, and 25 proteomic data sets available. The analysis of these data sets through a systems biology approach and the generation of tools for biologists to browse these various data are a challenge for bioinformaticians. We have developed a web-based platform, named Listeriomics, that integrates different tools for omics data analyses, i...
March 2017: MSystems
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