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https://www.readbyqxmd.com/read/28749585/mir3954-is-a-trigger-of-phasirnas-that-affects-flowering-time-in-citrus
#1
Yuanlong Liu, Lili Ke, Guizhi Wu, Yuantao Xu, Xiaomeng Wu, Rui Xia, Xiuxin Deng, Qiang Xu
In plant, a few 22 nt miRNAs direct cleavages of their targets and trigger the biogenesis of phased small interfering RNAs (phasiRNAs) in plant. In this study, we characterized a miRNA triggering phasiRNAs generation, miR3954, and explored its downstream target genes and potential function. Our results demonstrated that miR3954 showed specific expression in the flowers of citrus species and it targeted a NAC transcription factor (Cs7g22460) and two non-coding RNA transcripts (lncRNAs, Cs1g09600 and Cs1g09635)...
July 27, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28749570/hepatocyte-derived-exosomes-promote-t-follicular-regulatory-cell-expansion-during-hcv-infection
#2
Dustin A Cobb, Lucy Golden-Mason, Hugo R Rosen, Young S Hahn
Hepatitis C virus (HCV) is a global health concern that can cause severe liver disease such as cirrhosis and hepatocellular carcinoma. Control of HCV requires vigorous T cell responses, yet CD4(+) T cells in chronic HCV patients are dysfunctional. T follicular regulatory (Tfr) cells are a subset of regulatory T cells that suppress T follicular helper (Tfh) cells and the generation of high affinity antibody-producing B cells. In this study, we examined the accumulation of Tfr cells in the liver compartment during chronic HCV infection and defined the cellular and molecular mechanisms underlying their expansion...
July 27, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28749477/mapping-the-genomic-landscape-of-inherited-retinal-disease-genes-prioritizes-genes-prone-to-coding-and-noncoding-copy-number-variations
#3
Kristof Van Schil, Sarah Naessens, Stijn Van de Sompele, Marjolein Carron, Alexander Aslanidis, Caroline Van Cauwenbergh, Anja Kathrin Mayer, Mattias Van Heetvelde, Miriam Bauwens, Hannah Verdin, Frauke Coppieters, Michael E Greenberg, Marty G Yang, Marcus Karlstetter, Thomas Langmann, Katleen De Preter, Susanne Kohl, Timothy J Cherry, Bart P Leroy, Elfride De Baere
PurposePart of the hidden genetic variation in heterogeneous genetic conditions such as inherited retinal diseases (IRDs) can be explained by copy-number variations (CNVs). Here, we explored the genomic landscape of IRD genes listed in RetNet to identify and prioritize those genes susceptible to CNV formation.MethodsRetNet genes underwent an assessment of genomic features and of CNV occurrence in the Database of Genomic Variants and literature. CNVs identified in an IRD cohort were characterized using targeted locus amplification (TLA) on extracted genomic DNA...
July 27, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28749469/zinc-oxide-nanoparticles-harness-autophagy-to-induce-cell-death-in-lung-epithelial-cells
#4
Jun Zhang, Xia Qin, Bin Wang, Ge Xu, Zhexue Qin, Jian Wang, Lanxiang Wu, Xiangwu Ju, Diptiman D Bose, Feng Qiu, Honghao Zhou, Zhen Zou
Although zinc oxide nanoparticles (ZnONPs) are widely used, they have raised concerns of toxicity in humans. Previous studies have indicated that reactive oxygen species (ROS) and autophagy are involved in the cytotoxicity of ZnONPs, but the regulatory mechanisms between autophagy and ROS remain to be elucidated. Herein, we comprehensively investigated the regulatory mechanism of autophagy and the link between autophagy and ROS in ZnONPs-treated lung epithelial cells. We demonstrated that ZnONPs could induce autophagy, and this process could enhance the dissolution of ZnONPs in lysosomes to release zinc ions...
July 27, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28749464/the-cohesin-complex-prevents-myc-induced-replication-stress
#5
Sara Rohban, Aurora Cerutti, Marco J Morelli, Fabrizio d'Adda di Fagagna, Stefano Campaner
The cohesin complex is mutated in cancer and in a number of rare syndromes collectively known as Cohesinopathies. In the latter case, cohesin deficiencies have been linked to transcriptional alterations affecting Myc and its target genes. Here, we set out to understand to what extent the role of cohesins in controlling cell cycle is dependent on Myc expression and activity. Inactivation of the cohesin complex by silencing the RAD21 subunit led to cell cycle arrest due to both transcriptional impairment of Myc target genes and alterations of replication forks, which were fewer and preferentially unidirectional...
July 27, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28749339/pten-controls-glandular-morphogenesis-through-a-juxtamembrane-%C3%AE-arrestin1-arhgap21-scaffolding-complex
#6
Arman Javadi, Ravi K Deevi, Emma Evergren, Elodie Blondel-Tepaz, George S Baillie, Mark Gh Scott, Frederick Charles Campbell
PTEN controls three-dimensional (3D) glandular morphogenesis by coupling juxtamembrane signalling to mitotic spindle machinery. While molecular mechanisms remain unclear, PTEN interacts through its C2 membrane-binding domain with the scaffold protein β-Arrestin1. Because β-Arrestin1 binds and suppresses the Cdc42 GTPase-activating protein ARHGAP21, we hypothesize that PTEN controls Cdc42-dependent morphogenic processes through a β-Arrestin1-ARHGAP21 complex. Here we show that PTEN knockdown (KD) impairs β-Arrestin1 membrane localization, β-Arrestin1-ARHGAP21 interactions, Cdc42 activation, mitotic spindle orientation and 3D glandular morphogenesis...
July 27, 2017: ELife
https://www.readbyqxmd.com/read/28749311/reconstitution-of-the-peripheral-immune-repertoire-following-withdrawal-of-fingolimod
#7
Mahtab Ghadiri, Leslie Fitz-Gerald, Ayman Rezk, Rui Li, Mukanthu Nyirenda, David Haegert, Paul Steven Giacomini, Amit Bar-Or, Jack Antel
BACKGROUND: Following fingolimod cessation, immune reconstitution or lack thereof may have consequences for disease rebound or safety of commencing alternative therapies. OBJECTIVE: To examine the degree and profile of peripheral blood lymphocyte reconstitution following fingolimod withdrawal. METHODS: Total lymphocyte counts (TLC) and CD4+/CD8+ T-cell counts were measured in 18 multiple sclerosis (MS) patients pre-treatment, on fingolimod, and up to 8-9 months post-cessation...
August 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28749240/epigenetic-dysregulation-of-the-erythropoietic-transcription-factor-klf1-and-the-beta-like-globin-locus-in-juvenile-myelomonocytic-leukemia
#8
Silvia Fluhr, Christopher Felix Krombholz, Angelina Meier, Thomas Epting, Oliver Mücke, Christoph Plass, Charlotte M Niemeyer, Christian Flotho
Increased levels of fetal hemoglobin (HbF) are a hallmark of more than half of the children diagnosed with juvenile myelomonocytic leukemia (JMML). Elevated HbF levels in JMML are associated with DNA hypermethylation of distinct gene promoter regions in leukemic cells. Since the regulation of globin gene transcription is known to be under epigenetic control, we set out to study the relation of DNA methylation patterns at β-/γ-globin promoters, mRNA and protein expression of globins, and epigenetic modifications of genes encoding the globin-regulatory transcription factors BCL11A and KLF1 in nucleated erythropoietic precursor cells of patients with JMML...
July 27, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28749197/cardiovascular-benefits-and-safety-of-non-insulin-medications-used-in-the-treatment-of-type-2-diabetes-mellitus
#9
Srikanth Yandrapalli, George Jolly, Adam Horblitt, Abdallah Sanaani, Wilbert S Aronow
Diabetes mellitus is a growing in exponential proportions. If the current growth trend continues, it may result in every third adult in the United States having diabetes mellitus by 2050, and every 10(th) adult worldwide. Type 2 diabetes mellitus (T2DM) confers a 2- to 3-fold increased risk of cardiovascular (CV) events compared with non-diabetic patients, and CV mortality is responsible for around 80% mortality in this population. Patients with T2DM can have other features of insulin resistance-metabolic syndrome like hypertension, lipid abnormalities, and obesity which are all associated with increased CV disease and stroke risk even in the absence of T2DM...
July 27, 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28749078/vitamin-d-insufficiency-correlates-with-peripheral-b10-cells-in-patients-with-pituitary-tumours
#10
Weimin Wang, Li Fu, Shengli Li, Zhiming Xu, Peng Qiu, Tong-Jiang Xu, Wei Yang, Yu-Bao Zhang, Guang-Ming Xu, Xiang-Dong Lu, Xinggang Li
The mechanism of pituitary gland tumour (PGT) is unclear. Aberrant immune tolerance is associated with the pathogenesis of tumour. Vitamin D and vitamin D receptor (VDR) are involved in the immune regulation. Interleukin (IL)-10 is one of the important immune regulatory molecules. This study aims to elucidate the role of VDR in the regulation of IL-10 in peripheral B cells of PGT patients. In this study, the peripheral blood samples were collected from PGT patients and healthy subjects. B cells were purified from the blood samples and analysed by RT-qPCR and Western blotting...
July 2017: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/28749013/physiological-versus-pharmacological-signalling-to-myosin-phosphorylation-in-airway-smooth-muscle
#11
Ning Gao, Ming-Ho Tsai, Audrey N Chang, Weiqi He, Cai-Ping Chen, Minsheng Zhu, Kristine E Kamm, James T Stull
Ca(2+) /calmodulin activation of myosin light chain kinase (MLCK) initiates myosin regulatory light chain (RLC) phosphorylation for smooth muscle contraction with subsequent dephosphorylation for relaxation by myosin light chain phosphatase (MLCP) containing regulatory (MYPT1) and catalytic (PP1cδ) subunits. RLC phosphorylation-dependent force development is regulated by distinct signalling modules involving protein phosphorylations. We investigated responses to cholinergic agonist treatment versus neurostimulation by electric field stimulation (EFS) in bovine tracheal smooth muscle...
July 27, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28748720/blunting-of-cardioprotective-actions-of-estrogen-in-female-rodent-heart-linked-to-altered-expression-of-cardiac-tissue-chymase-and-ace2
#12
Jacqueline S da Silva, Daniele Gabriel-Costa, Hao Wang, Sarfaraz Ahmad, Xuming Sun, Jasmina Varagic, Roberto T Sudo, Carlos M Ferrario, Louis J Dell Italia, Gisele-Zapata Sudo, Leanne Groban
BACKGROUND: Diastolic dysfunction develops in response to hypertension and estrogen (E2) loss and is a forerunner to heart failure (HF) in women. The cardiac renin-angiotensin system (RAS) contributes to diastolic dysfunction, but its role with respect to E2 and blood pressure remain unclear. METHODS: We compared the effects of ovariectomy (OVX) or sham surgery on the cardiac RAS, left ventricular (LV) structure/function, and systemic/intracardiac pressures of spontaneously hypertensive rats (SHRs: n = 6 intact and 6 OVX) and age-matched Wistar-Kyoto (WKY: n = 5 intact and 4 OVX) controls...
July 2017: Journal of the Renin-angiotensin-aldosterone System: JRAAS
https://www.readbyqxmd.com/read/28748589/the-role-of-medical-abortion-in-the-implementation-of-the-law-on-voluntary-termination-of-pregnancy-in-uruguay
#13
Verónica Fiol, Leticia Rieppi, Rafael Aguirre, María Nozar, Mónica Gorgoroso, Francisco Coppola, Leonel Briozzo
OBJECTIVE: To evaluate the implementation of the law that liberalizes voluntary abortion in Uruguay and enables health services to offer these services to the population. METHODS: The legal and regulatory provisions are described and the national data-provided by the Ministry of Public Health's National Information System (SINADI)-on the number of voluntary terminations of pregnancy, the abortion method (medical or surgical), and whether it was performed as an outpatient or inpatient are analyzed...
August 2016: International Journal of Gynaecology and Obstetrics
https://www.readbyqxmd.com/read/28748534/mir-130b-directly-targets-arhgap1-to-drive-activation-of-a-metastatic-cdc42-pak1-ap1-positive-feedback-loop-in-ewing-sarcoma
#14
Laura Satterfield, Ryan Shuck, Lyazat Kurenbekova, Wendy Allen-Rhoades, Dean Edwards, Shixia Huang, Kimal Rajapakshe, Cristian Coarfa, Lawrence A Donehower, Jason T Yustein
Ewing Sarcoma (ES) is a highly aggressive bone tumor with peak incidence in the adolescent population. It has a high propensity to metastasize, which is associated with dismal survival rates of approximately 25%. To further understand mechanisms of metastasis we investigated microRNA regulatory networks in ES. Our studies focused on miR-130b due to our analysis that enhanced expression of this microRNA has clinical relevance in multiple sarcomas, including ES. Our studies provide insights into a novel positive feedback network involving the direct regulation of miR-130b and activation of downstream signaling events contributing towards sarcoma metastasis...
July 27, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28748508/autophagy-enhancement-is-rendered-ineffective-in-presence-of-%C3%AE-synuclein-in-melanoma-cells
#15
Swapna Nandakumar, Bejoy Vijayan, Asha Kishore, Anoopkumar Thekkuveettil
Increased cellular concentration of α-synuclein (α-syn) predisposes it to misfolding and aggregation that in turn impair the degradation pathways. This poses a limitation to the use of overexpression models for studies on α-syn clearance by autophagy, which is widely investigated for its therapeutic potential. This limitation can be overcome with the use of endogenous models. In this study, SK-MEL-28, a melanoma cell model with endogenous α-syn expression, was employed to study α-syn clearance through autophagy...
July 26, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28748501/a-step-by-step-microrna-guide-to-cancer-development-and-metastasis
#16
REVIEW
Georgios S Markopoulos, Eugenia Roupakia, Maria Tokamani, Evangelia Chavdoula, Maria Hatziapostolou, Christos Polytarchou, Kenneth B Marcu, Athanasios G Papavassiliou, Raphael Sandaltzopoulos, Evangelos Kolettas
BACKGROUND: Cancer is one of the leading causes of mortality. The neoplastic transformation of normal cells to cancer cells is caused by a progressive accumulation of genetic and epigenetic alterations in oncogenes, tumor suppressor genes and epigenetic regulators, providing cells with new properties, collectively known as the hallmarks of cancer. During the process of neoplastic transformation cells progressively acquire novel characteristics such as unlimited growth potential, increased motility and the ability to migrate and invade adjacent tissues, the ability to spread from the tumor of origin to distant sites, and increased resistance to various types of stresses, mostly attributed to the activation of genetic stress-response programs...
July 26, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28748462/in-vivo-rat-t-lymphocyte-pig-a-assay-detection-and-expansion-of-cells-deficient-in-the-gpi-anchored-cd48-surface-marker-for-analysis-of-mutation-in-the-endogenous-pig-a-gene
#17
Vasily N Dobrovolsky, Javier Revollo, Dayton M Petibone, Robert H Heflich
The Pig-a assay is being developed as an in vivo gene mutation assay for regulatory safety assessments. The assay is based on detecting mutation in the endogenous Pig-a gene of treated rats by using flow cytometry to measure changes in cell surface markers of peripheral blood cells. Here we present a methodology for demonstrating that phenotypically mutant rat T-cells identified by flow cytometry contain mutations in the Pig-a gene, an important step for validating the assay. In our approach, the mutant phenotype T-cells are sorted into individual wells of 96-well plates and expanded into clones...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28748457/juvenile-nonclinical-safety-studies-in-support-of-pediatric-drug-development
#18
Paul C Barrow, Georg Schmitt
A pediatric assessment is now a required component of every drug marketing application in North America, Europe, and Japan, unless a waiver has been granted previously. Nonclinical juvenile toxicity studies are often required as part of this assessment. The protocols for juvenile toxicity studies are best devised in consultation with the regulatory authorities. It is important to submit the pediatric investigation plan (PIP) or pediatric study plan (PSP) early, in order not to delay the marketing authorization of the drug in adults...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28748456/nonclinical-development-of-combination-drugs
#19
Alberto Lodola
We define "combination drugs" as "fixed-dose combinations" (FDCs), that is, two or more drugs (marketed or not) combined in a single pill or two or more separate drugs packaged together. FDCs have been available commercially for many years but only relatively recently have nonclinical development guidelines been released by a number of regulatory authorities and the World Health Organization; as yet there are no ICH guidelines specific to combination drugs. In general however, the ICH guidelines for monotherapy development provide a framework for FDC development...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28748400/reconstructing-genetic-regulatory-networks-using-two-step-algorithms-with-the-differential-equation-models-of-neural-networks
#20
Chi-Kan Chen
BACKGROUND: The identification of genetic regulatory networks (GRNs) provides insights into complex cellular processes. A class of recurrent neural networks (RNNs) captures the dynamics of GRN. Algorithms combining the RNN and machine learning schemes were proposed to reconstruct small-scale GRNs using gene expression time series. RESULTS: We present new GRN reconstruction methods with neural networks. The RNN is extended to a class of recurrent multilayer perceptrons (RMLPs) with latent nodes...
July 26, 2017: Interdisciplinary Sciences, Computational Life Sciences
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