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Modeling gene regulation

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https://www.readbyqxmd.com/read/28527130/pulse-generation-in-the-quorum-machinery-of-pseudomonas-aeruginosa
#1
Cicik Alfiniyah, Martin A Bees, A Jamie Wood
Pseudomonas aeruginosa is a Gram-negative bacterium that is responsible for a wide range of infections in humans. Colonies employ quorum sensing (QS) to coordinate gene expression, including for virulence factors, swarming motility and complex social traits. The QS signalling system of P. aeruginosa is known to involve multiple control components, notably the las, rhl and pqs systems. In this paper, we examine the las system and, in particular, the repressive interaction of rsaL, an embedded small regulative protein, employing recent biochemical information to aid model construction...
May 19, 2017: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/28526615/lung-inflammation-after-bleomycin-treatment-in-mice-selection-of-an-accurate-normalization-strategy-for-gene-expression-analysis-in-an-ex-vivo-and-in-vitro-model
#2
Veronica Della Latta, Manuela Cabiati, Silvia Burchielli, Giada Frenzilli, Margherita Bernardeschi, Antonella Cecchettini, Federica Viglione, Maria-Aurora Morales, Silvia Del Ry
Pulmonary fibrosis (PF) is the most common and aggressive interstitial lung disease, characterized by a patchy development of fibrosis leading to progressive destruction of the normal lung architecture which is preceded by an inflammatory process. Gene expression studies are important to understand the development of PF but the accuracy and reproducibility of Real-Time PCR depend on appropriate normalization strategies. This study aimed to analyze the expression variability of eight commonly used reference genes during the initial inflammatory phase of bleomycin-induced PF in a mouse model and to verify whether the selected reference genes could be applied to an in-vitro model of BLM-treated primary murine lung fibroblasts...
May 16, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28526608/microrna-analysis-of-taenia-crassiceps-cysticerci-under-praziquantel-treatment-and-genome-wide-identification-of-taenia-solium-mirnas
#3
Matías Gastón Pérez, Natalia Macchiaroli, Gabriel Lichtenstein, Gabriela Conti, Sebastián Asurmendi, Diego Humberto Milone, Georgina Stegmayer, Laura Kamenetzky, Marcela Cucher, Mara Cecilia Rosenzvit
MicroRNAs (miRNAs) are small non-coding RNAs that have emerged as important regulators of gene expression and perform critical functions in development and disease. In spite of the increased interest in miRNAs from helminth parasites, no information is available on miRNAs from Taenia solium, the causative agent of cysticercosis, a neglected disease affecting millions of people worldwide. Here we performed a comprehensive analysis of miRNAs from Taenia crassiceps, a laboratory model for T. solium studies, and identified miRNAs in the T...
May 16, 2017: International Journal for Parasitology
https://www.readbyqxmd.com/read/28526573/transcriptomic-variation-of-locally-infected-skin-of-epinephelus-coioides-reveals-the-mucosal-immune-mechanism-against-cryptocaryon-irritans
#4
Yazhou Hu, Anxing Li, Yang Xu, Biao Jiang, Geling Lu, Xiaochun Luo
Fish skin is the largest immunologically active mucosal organ, providing first-line defense against external pathogens. However, the skin-associated immune mechanisms of fish are still unclear. Cryptocaryon irritans is an obligate ectoparasitic ciliated protozoan that infects almost all marine fish, and is believed to be an excellent pathogen model to study fish mucosal immunity. In this study, a de novo transcriptome assembly of Epinephelus coioides skin post C. irritans tail-infection was performed for the first time using the Illumina HiSeq™ 2500 system...
May 16, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28526450/the-association-of-single-nucleotide-polymorphisms-in-the-oxytocin-receptor-and-g-protein-coupled-receptor-kinase-6-grk6-genes-with-oxytocin-dosing-requirements-and-labor-outcomes
#5
Chad A Grotegut, Emily Ngan, Melanie E Garrett, Marie Lynn Miranda, Allison E Ashley-Koch, Geeta K Swamy
BACKGROUND: Oxytocin is a potent uterotonic agent that is widely used for induction and augmentation of labor. Oxytocin has a narrow therapeutic index and the optimal dosing for any individual woman varies widely. OBJECTIVE: The objective of this study was to determine if genetic variation in the oxytocin receptor (OXTR) or in the gene encoding G protein-coupled receptor kinase 6 (GRK6), which regulates desensitization of the OXTR, could explain variation in oxytocin dosing and labor outcomes among women being induced near term...
May 16, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28525535/sexual-dimorphism-and-aging-differentially-regulate-adaptive-homeostasis
#6
Laura C D Pomatto, John Tower, Kelvin J A Davies
External and internal stimuli cause modifications to gene and biochemical pathways. In turn, demonstrating that biological systems continuously make short-term adaptations both to set-points, and to the range of "normal" capacity, due to mild conditional changes, or to subtoxic, nondamaging levels of chemical agents. This is termed as "Adaptive Homeostasis," defined with the following: "The transient expansion or contraction of the homeostatic range in response to exposure to sub-toxic, nondamaging, signaling molecules or events, or the removal or cessation of such molecules or events...
May 18, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28524834/wild-type-p53-induced-phosphatase-1-deficiency-exacerbates-myocardial-infarction-induced-ischemic-injury
#7
Ke-Mei Liu, Hai-Hong Zhang, Ya-Nan Wang, Lian-Mei Wang, Hong-Yu Chen, Cai-Feng Long, Lian-Feng Zhang, Hong-Bing Zhang, Hong-Bing Yan
BACKGROUND: Myocardial infarction (MI) is a major disease burden. Wild-type p53-induced phosphatase 1 (Wip1) has been studied extensively in the context of cancer and the regulation of different types of stem cells, but the role of Wip1 in cardiac adaptation to MI is unknown. We investigated the significance of Wip1 in a mouse model of MI. METHODS: The study began in June 2014 and was completed in July 2016. We compared Wip1-knockout (Wip1-KO) mice and wild-type (WT) mice to determine changes in cardiac function and survival in response to MI...
June 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28524599/modulation-of-nuclear-rest-by-alternative-splicing-a-potential-therapeutic-target-for-huntington-s-disease
#8
Guo-Lin Chen, Qi Ma, Dharmendra Goswami, Jianyu Shang, Gregory M Miller
Huntington's disease (HD) is caused by a genetically mutated huntingtin (mHtt) protein with expanded polyQ stretch, which impairs cytosolic sequestration of the repressor element-1 silencing transcription factor (REST), resulting in excessive nuclear REST and subsequent repression of neuronal genes. We recently demonstrated that REST undergoes extensive, context-dependent alternative splicing, of which exon-3 skipping (∆E3 )-a common event in human and nonhuman primates-causes loss of a motif critical for REST nuclear targeting...
May 19, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28524180/aberrant-epigenetic-regulation-of-gabrp-associates-with-aggressive-phenotype-of-ovarian-cancer
#9
Hye Youn Sung, San-Duk Yang, Woong Ju, Jung-Hyuck Ahn
Metastasis is a major cause of therapeutic failure in ovarian cancer. To elucidate molecular mechanisms of ovarian cancer metastasis, we previously established a metastatic xenograft mouse model using human ovarian carcinoma SK-OV-3 cells. Using gene expression profiling, we found that γ-aminobutyric acid (GABA)A receptor π subunit (GABRP) expression was upregulated (>4-fold) in metastatic tissues from our xenograft mice compared with SK-OV-3 cells. Importantly, GABRP knockdown diminished the migration and invasion of SK-OV-3 cells, and reduced extracellular signal-regulated kinase (ERK) activation while overexpression of GABRP exhibited significantly increased cell migration, invasion and ERK activation...
May 19, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28523739/mechanisms-of-peptide-sex-pheromone-regulation-of-conjugation-in-enterococcus-faecalis
#10
Yuqing Chen, Arpan Bandyopadhyay, Briana K Kozlowicz, Heather A H Haemig, Albert Tai, Wei-Shou Hu, Gary M Dunny
In many gram positive bacteria, horizontal transfer and virulence are regulated by peptide-mediated cell-cell signaling. The heptapeptide cCF10 (C) activates conjugative transfer of the Enterococcus faecalis plasmid pCF10, whereas the iCF10 (I) peptide inhibits transfer. Both peptides bind to the same domain of the master transcription regulator PrgX, a repressor of transcription of the prgQ operon encoding conjugation genes. We show that repression of prgQ by PrgX tetramers requires formation of a pCF10 DNA loop where each of two PrgX DNA-binding sites is occupied by a dimer...
May 19, 2017: MicrobiologyOpen
https://www.readbyqxmd.com/read/28523551/epigenetic-mechanisms-of-gene-regulation-in-amyotrophic-lateral-sclerosis
#11
Alba Jimenez-Pacheco, Jaime M Franco, Soledad Lopez, Juan Miguel Gomez-Zumaquero, Maria Magdalena Leal-Lasarte, Diana E Caballero-Hernandez, Marta Cejudo-Guillén, David Pozo
Despite being clinically described 150 years ago, the mechanisms underlying amyotrophic lateral sclerosis (ALS) pathogenesis have not yet been fully understood. Studies in both animal models of ALS and human patients reveal a plethora of alterations such as increased glutamate-mediated excitotoxicity, redox stress, increased apoptosis, defective axonal transport, protein-misfolding events, mitochondrial impairment and sustained unregulated immune responses. Regardless of being sporadic or familiar ALS, the final outcome at the cellular level is the death of upper and lower motor neurons, and once diagnosed, ALS is typically lethal within the next 5 years...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28523548/noncoding-rnas-in-depression
#12
Rixing Lin, Gustavo Turecki
Major depressive disorder (MDD) is a common psychiatric disorder affecting millions of people worldwide, yet its etiology remains elusive. The last decades have seen great advances in our understanding of the genome structure and functional organization. Noncoding RNAs (ncRNAs) are RNAs that do not code for proteins but have important regulatory roles. The investigation of ncRNAs as regulators of gene expression has been a topic of growing interest in health research, including in studies investigating etiological and therapeutic factors in major depression...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28522730/11%C3%AE-hsd1-suppresses-cardiac-fibroblast-cxcl2-cxcl5-and-neutrophil-recruitment-to-the-heart-post-mi
#13
Katie J Mylonas, Neil A Turner, Sumia A Bageghni, Christopher J Kenyon, Christopher I White, Kieran McGregor, Robert A Kimmitt, Richard Sulston, Valerie Kelly, Brian R Walker, Karen E Porter, Karen E Chapman, Gillian A Gray
We have previously demonstrated that neutrophil recruitment to the heart following myocardial infarction (MI) is enhanced in mice lacking 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) that regenerates active glucocorticoid within cells from intrinsically inert metabolites. The present study aimed to identify the mechanism of regulation. In a mouse model of MI, neutrophil mobilization to blood and recruitment to the heart were higher in 11β-HSD1-deficient (Hsd11b1(-)(/)(-) ) relative to wild-type (WT) mice, despite similar initial injury and circulating glucocorticoid...
June 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28522594/sphingomyelin-synthase-2-deficiency-inhibits-the-induction-of-murine-colitis-associated-colon-cancer
#14
Toshio Ohnishi, Chieko Hashizume, Makoto Taniguchi, Hidehiro Furumoto, Jia Han, Rongfen Gao, Shinichi Kinami, Takeo Kosaka, Toshiro Okazaki
Sphingomyelin synthase 2 (SMS2) is the synthetic enzyme of sphingomyelin (SM), which regulates membrane fluidity and microdomain structure. SMS2 plays a role in LPS-induced lung injury and inflammation; however, its role in inflammation-mediated tumorigenesis is unclear. We investigated the effect of SMS2 deficiency on dextran sodium sulfate (DSS)-induced murine colitis and found inhibition of DSS-induced inflammation in SMS2-deficient (SMS2(-/-)) mice. DSS treatment induced a significant increase in ceramide levels, with a decrease of SM levels in SMS2(-/-) colon tissue, and demonstrated attenuation of the elevation of both inflammation-related gene expression and proinflammatory cytokines and chemokines, leukocyte infiltration, and MAPK and signal transducer and activator of transcription 3 activation...
May 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28522584/cooperative-targets-of-combined-mtor-hdac-inhibition-promote-myc-degradation
#15
John K Simmons, Aleksandra M Michalowski, Benjamin J Gamache, Wendy DuBois, Jyoti Patel, Ke Zhang, Joy Gary, Shuling Zhang, Snehal Gaikwad, Daniel Connors, Nicholas Watson, Elena Leon, Jin-Qiu Chen, W Michael Kuehl, Maxwell P Lee, Adriana Zingone, Ola Landgren, Peter Ordentlich, Jing Huang, Beverly A Mock
Cancer treatments often require combinations of molecularly targeted agents to be effective. mTORi (rapamycin) and HDACi (MS-275/entinostat) inhibitors have been shown to be effective in limiting tumor growth, and here we define part of the cooperative action of this drug combination. More than 60 human cancer cell lines responded synergistically (CI<1) when treated with this drug combination compared to single agents.  In addition, a breast cancer patient-derived xenograft, and a BCL-XL plasmacytoma mouse model both showed enhanced responses to the combination compared to single agents...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28521882/cholesterol-metabolites-alleviate-injured-liver-function-and-decrease-mortality-in-an-lps-induced-mouse-model
#16
Yanxia Ning, Jin Kyung Kim, Hae-Ki Min, Shunlin Ren
BACKGROUND: Oxysterol sulfation plays a fundamental role in the regulation of many biological events. Its products, 25-hydroxycholesterol 3-sulfate (25HC3S) and 25-hydroxycholesterol 3, 25-disulfate (25HCDS), have been demonstrated to be potent regulators of lipid metabolism, inflammatory response, cell apoptosis, and cell survival. In the present study, we tested these products' potential to treat LPS-induced acute liver failure in a mouse model. METHODS: Acute liver failure mouse model was established by intravenous injection with LPS...
June 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28521874/sirna-mediated-inhibition-of-srebp-cleavage-activating-protein-reduces-dyslipidemia-in-spontaneously-dysmetabolic-rhesus-monkeys
#17
Beth Ann Murphy, Marija Tadin-Strapps, Kristian Jensen, Robin Mogg, Andy Liaw, Kithsiri Herath, Gowri Bhat, David G McLaren, Stephen F Previs, Shirly Pinto
BACKGROUND: SREBP cleavage-activating protein (SCAP) is a cholesterol binding endoplasmic reticulum (ER) membrane protein that is required to activate SREBP transcription factors. SREBPs regulate genes involved in lipid biosynthesis. They also influence lipid clearance by modulating the expression of LDL receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. Inhibiting SCAP decreases circulating PCSK9, triglycerides (TG), and LDL-cholesterol (LDL-C), both in vitro and in vivo...
June 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28521784/functional-regression-method-for-whole-genome-eqtl-epistasis-analysis-with-sequencing-data
#18
Kelin Xu, Li Jin, Momiao Xiong
BACKGROUND: Epistasis plays an essential rule in understanding the regulation mechanisms and is an essential component of the genetic architecture of the gene expressions. However, interaction analysis of gene expressions remains fundamentally unexplored due to great computational challenges and data availability. Due to variation in splicing, transcription start sites, polyadenylation sites, post-transcriptional RNA editing across the entire gene, and transcription rates of the cells, RNA-seq measurements generate large expression variability and collectively create the observed position level read count curves...
May 18, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28520898/pyrenoid-loss-impairs-carbon-concentrating-mechanism-induction-and-alters-primary-metabolism-in-chlamydomonas-reinhardtii
#19
Madeline C Mitchell, Gergana Metodieva, Metodi V Metodiev, Howard Griffiths, Moritz T Meyer
Carbon-concentrating mechanisms (CCMs) enable efficient photosynthesis and growth in CO2-limiting environments, and in eukaryotic microalgae localisation of Rubisco to a microcompartment called the pyrenoid is key. In the model green alga Chlamydomonas reinhardtii, Rubisco preferentially relocalises to the pyrenoid during CCM induction and pyrenoid-less mutants lack a functioning CCM and grow very poorly at low CO2. The aim of this study was to investigate the CO2 response of pyrenoid-positive (pyr+) and pyrenoid-negative (pyr-) mutant strains to determine the effect of pyrenoid absence on CCM induction and gene expression...
May 18, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28520872/glucocerebrosidase-deficiency-in-dopaminergic-neurons-induces-microglial-activation-without-neurodegeneration
#20
Federico N Soria, Michel Engeln, Marta Martinez-Vicente, Christelle Glangetas, María José López-González, Sandra Dovero, Benjamin Dehay, Elisabeth Normand, Miquel Vila, Alexandre Favereaux, François Georges, Christophe Lo Bianco, Erwan Bezard, Pierre-Olivier Fernagut
Mutations in the GBA1 gene encoding the lysosomal enzyme glucocerebrosidase (GBA1) are important risk factors for Parkinson's disease (PD). In vitro, altered GBA1 activity promotes alpha-synuclein accumulation while elevated levels of alpha-synuclein compromise GBA1 function, thus supporting a pathogenic mechanism in PD. However, the mechanisms by which GBA1 deficiency is linked to increased risk of PD remains elusive, partially because of lack of aged models of GBA1 deficiency. Since knocking-out GBA1 in the entire brain induces massive neurodegeneration and early death, we generated a mouse model of GBA1 deficiency amenable to investigate the long-term consequences of compromised GBA1 function in dopaminergic neurons...
May 17, 2017: Human Molecular Genetics
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