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https://www.readbyqxmd.com/read/28817124/directed-differentiation-and-long-term-maintenance-of-epicardial-cells-derived-from-human-pluripotent-stem-cells-under-fully-defined-conditions
#1
Xiaoping Bao, Xiaojun Lian, Tongcheng Qian, Vijesh J Bhute, Tianxiao Han, Sean P Palecek
Here, we describe how to efficiently direct human pluripotent stem cells (hPSCs) differentiation into self-renewing epicardial cells in a completely defined, xeno-free system by temporal modulation of regulators of canonical Wnt signaling. Appropriate differentiation-stage-specific application of Gsk3 inhibitor, Wnt inhibitor, and Gsk3 inhibitor (GiWiGi) is sufficient to produce cells expressing epicardial markers and exhibiting epicardial phenotypes with a high yield and purity from multiple hPSC lines in 16 d...
September 2017: Nature Protocols
https://www.readbyqxmd.com/read/28816949/whole-exome-sequencing-identifies-a-kcnj12-mutation-as-a-cause-of-familial-dilated-cardiomyopathy
#2
Hai-Xin Yuan, Kai Yan, Dong-Yan Hou, Zhi-Yong Zhang, Hua Wang, Xin Wang, Juan Zhang, Xiao-Rong Xu, Yan-Hong Liang, Wen-Shu Zhao, Lin Xu, Lin Zhang
Dilated cardiomyopathy (DCM) is characterized by left ventricular dilation, and is associated with systolic dysfunction and increased action potential duration. Approximately 50% of DCM cases are caused by inherited gene mutations with genetic and phenotypic heterogeneity. Next generation sequencing may be useful in screening unknown mutations in such cases.A family was identified with DCM, in which the affected family members developed heart failure, arrhythmia, and sudden death. Probands and 4 affected family members underwent whole exome sequencing (WES), bioinformatics methods, and gene annotation to identify potentially causative variants...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28816234/novel-mutations-of-tcirg1-cause-a-malignant-and-mild-phenotype-of-autosomal-recessive-osteopetrosis-aro-in-four-chinese-families
#3
Xiao-Ya Zhang, Jin-Wei He, Wen-Zhen Fu, Chun Wang, Zhen-Lin Zhang
Human autosomal recessive osteopetrosis (ARO), also known as infantile malignant osteopetrosis, is a rare genetic bone disorder that often causes death. Mutations in T-cell immune regulator 1 (TCIRG1) are a frequent cause of human ARO. Six additional genes (TNFSF11, TNFRSF11A, CLCN7, OSTM1, SNX10, PLEKHM1) were also found to be associated with human ARO. In order to expand the mutation spectrum and clinical diversity for a better understanding of the ARO phenotype and to further investigate the clinical characteristics of benign subjects with ARO, we here report five individuals with ARO from four unrelated Chinese families...
August 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28815346/unilateral-cancer-associated-retinopathy-diagnosis-serology-and-treatment
#4
Dimitri Roels, Shinji Ueno, Cornelia D Talianu, Dafina Draganova, Mineo Kondo, Bart P Leroy
PURPOSE: To report a case of unilateral cancer-associated retinopathy (CAR) with clinical, serological and electroretinogram (ERG) normalization after aggressive cancer treatment combined with steroids and rituximab. METHODS: Work-up included extensive clinical and electrophysiological testing. Also, serological work-up for antiretinal antibodies and oncological screening was organized. RESULTS: A 45-year-old female presented with progressive photopsias, photophobia and relative central scotoma in the right eye since 6 weeks prior...
August 16, 2017: Documenta Ophthalmologica. Advances in Ophthalmology
https://www.readbyqxmd.com/read/28813631/rapid-and-targeted-introgression-of-fgr-gene-through-marker-assisted-backcrossing-in-rice-oryza-sativa-l
#5
Acga Cheng, Ismanizan Ismail, Mohamad Osman, Habibuddin Hashim, Nur Samahah Mohd Zainual
While it is crucial for developing countries like Malaysia to achieve self-sufficiency in rice (Oryza sativa L.), it is equally critical to be able to produce high-quality rice, specifically fragrant rice, which demands are often met through importation. The present study was aimed at developing high-yielding fragrant rice, in a timely and cost-effective manner. A marker-assisted backcross (MABC) approach was optimised to introgress the fragrance gene (fgr) into two high-yielding Malaysian varieties; MR84 and MR219, within two years utilising less than fifty molecular markers...
August 16, 2017: Genome Génome / Conseil National de Recherches Canada
https://www.readbyqxmd.com/read/28812395/current-research-on-circular-rnas-associated-with-colorectal-cancer
#6
Penghui Wang, Xiaodong He
Representing a novel type of endogenous noncoding RNAs, circular RNAs (circRNAs) have recently gained much attention for their involvement in multiple biological processes. CircRNAs are ubiquitously expressed in eukaryotic cells and modulate gene expression by acting as sponges of microRNAs (miRNAs) or other proteins, such as RNA-binding proteins (RBPs). Due to their unique structure, circRNAs are more stable than linear RNAs. Expression profiles of circRNAs are associated with clinicopathological characteristics of colorectal cancer patients, such as differentiation, TNM classification and distant metastasis...
August 16, 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28811895/long-term-rearrangement-of-retinal-structures-in-a-novel-mutation-of-x-linked-retinoschisis
#7
Stefano Piermarocchi, Stefania Miotto, Davide Colavito, Elda Del Giudice, Alberta Leon, Veronica Maritan, Rita Piermarocchi, Alma Patrizia Tormene
The aim of the present study was to report a novel mutation in the retinoschisin 1 (RS1) gene in a Caucasian family affected by X-linked juvenile retinoschisis (XLRS) and to describe the long-term modification of retinal structure. Two brothers with an early onset maculopathy were diagnosed with XLRS. Fundus photography, fluorescein angiography, spectral domain optical coherence tomography and electroretinogram analyses were performed. Their sister was also examined. All subjects were screened for mutations in the RS1 gene...
September 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28811825/ethanol-extract-of-mylabris-phalerata-inhibits-m2-polarization-induced-by-recombinant-il-4-and-il-13-in-murine-macrophages
#8
Hwan-Suck Chung, Bong-Seon Lee, Jin Yeul Ma
Mylabris phalerata (MP) is an insect used in oriental herbal treatments for tumor, tinea infections, and stroke. Recent studies have shown that tumor-associated macrophages (TAM) have detrimental roles such as tumor progression, angiogenesis, and metastasis. Although TAM has phenotypes and characteristics in common with M2-polarized macrophages, M1 macrophages have tumor suppression and immune stimulation effects. Medicines polarizing macrophages to M1 have been suggested to have anticancer effects via the modulation of the tumor microenvironment...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28811128/a-newly-synthesized-ligustrazine-stilbene-derivative-inhibits-pdgf-bb-induced-vascular-smooth-muscle-cell-phenotypic-switch-and-proliferation-via-delaying-cell-cycle-progression
#9
Chunlian Peng, Siming Zhang, Haixin Liu, Yanxiao Jiao, Guifa Su, Yan Zhu
Vascular Smooth muscle cells (VSMCs) possess remarkable phenotype plasticity that allows it to rapidly adapt to fluctuating environmental cues, including the period of development and progression of vascular diseases such as atherosclerosis and restenosis subsequent to vein grafting or coronary intervention. Although VSMC phenotypic switch is an attractive target, there is no effective drug so far. Using rat aortic VSMCs, we investigate the effects of Ligustrazine and its synthetic derivatives on platelet-derived growth factor-BB (PDGF-BB) induced proliferation and phenotypic switch by a cell image-based screening of 60 Ligustrazine stilbene derivatives...
August 12, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28810864/molecular-determination-of-antimicrobial-resistance-in-escherichia-coli-isolated-from-raw-meat-in-addis-ababa-and-bishoftu-ethiopia
#10
Yohannes Equar Messele, Reta Duguma Abdi, Shimels Tikuye Yalew, Desiye Tesfaye Tegegne, Bezina Arega Emeru, Gebremeskel Mamu Werid
BACKGROUND: Consumption of meat contaminated by E. coli causes a serious illness and even death to affected individuals. Recently the emerging of antibiotic resistant foodborne E. coli poses serious public health risks worldwide. However, little is known about the antibiotic resistance profile of E. coli in Ethiopia. This study aimed to determine the prevalence and Antimicrobial resistance (AMR) status of E. coli isolated from different type of meat. METHODS: Overall 292 samples were collected from December 2015 to April 2016 from slaughterhouses to determine the prevalence and AMR of E...
August 15, 2017: Annals of Clinical Microbiology and Antimicrobials
https://www.readbyqxmd.com/read/28809826/high-throughput-screening-for-protein-based-inheritance-in-s-cerevisiae
#11
James S Byers, Daniel F Jarosz
The encoding of biological information that is accessible to future generations is generally achieved via changes to the DNA sequence. Long-lived inheritance encoded in protein conformation (rather than sequence) has long been viewed as paradigm-shifting but rare. The best characterized examples of such epigenetic elements are prions, which possess a self-assembling behavior that can drive the heritable manifestation of new phenotypes. Many archetypal prions display a striking N/Q-rich sequence bias and assemble into an amyloid fold...
August 8, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28808997/target-identification-using-cell-permeable-and-cleavable-chloroalkane-derivatized-small-molecules
#12
Jacqui L Mendez-Johnson, Danette L Daniels, Marjeta Urh, Rachel Friedman Ohana
An important aspect for gaining functional insight into the activity of small molecules revealed through phenotypic screening is the identification of their interacting proteins. Yet, isolating and validating these interacting proteins remains difficult. Here, we present a new approach utilizing a chloroalkane (CA) moiety capture handle, which can be chemically attached to small molecules to isolate their respective protein targets. Derivatization of small molecules with the CA moiety has been shown to not significantly impact their cell permeability or potency, allowing for phenotypic validation of the derivatized small molecule prior to capture...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28808971/high-throughput-screening-for-identification-of-novel-innate-immune-activators
#13
Bryan J Gall, Victor R DeFilippis
Modern drug discovery has embraced in vitro platforms that enable investigation of large numbers of compounds within tractable timeframes and for feasible costs. These endeavors have been greatly aided in recent years by advances in molecular and cell-based methods such as gene delivery and editing technology, advanced imaging, robotics, and quantitative analysis. As such, the examination of phenotypic impacts of novel molecules may only be limited by the size of the compound collection. Innate immune signaling processes in mammalian cells are especially amenable to high-throughput screening platforms since the cellular responses elicited by their activation often result in high level transcription that can be harnessed in the form of bioluminescent or fluorescent signal...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28808861/epidemiology-of-sleep-disordered-breathing-and-heart-failure-what-drives-what
#14
REVIEW
Sushma M Dharia, Lee K Brown
PURPOSE OF REVIEW: The bidirectional relationships that have been demonstrated between heart failure (HF) and central sleep apnea (CSA) demand further exploration with respect to the implications that each condition has for the other. This review discusses the body of literature that has accumulated on these relationships and how CSA and its potential treatment may affect outcomes in patients with CSA. RECENT FINDINGS: Obstructive sleep apnea (OSA) can exacerbate hypertension, type 2 diabetes, obesity, and atherosclerosis, which are known predicates of HF...
August 14, 2017: Current Heart Failure Reports
https://www.readbyqxmd.com/read/28808002/optimized-strategy-for-in-vivo-cas9-activation-in-drosophila
#15
Ben Ewen-Campen, Donghui Yang-Zhou, Vitória R Fernandes, Delfina P González, Lu-Ping Liu, Rong Tao, Xingjie Ren, Jin Sun, Yanhui Hu, Jonathan Zirin, Stephanie E Mohr, Jian-Quan Ni, Norbert Perrimon
While several large-scale resources are available for in vivo loss-of-function studies in Drosophila, an analogous resource for overexpressing genes from their endogenous loci does not exist. We describe a strategy for generating such a resource using Cas9 transcriptional activators (CRISPRa). First, we compare a panel of CRISPRa approaches and demonstrate that, for in vivo studies, dCas9-VPR is the most optimal activator. Next, we demonstrate that this approach is scalable and has a high success rate, as >75% of the lines tested activate their target gene...
August 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28807931/identification-of-novel-growth-regulators-in-plant-populations-expressing-random-peptides
#16
Zhilong Bao, Maureen A Clancy, Raquel F Carvalho, Kiona Elliott, Kevin M Folta
The use of chemical genomics approaches allows the identification of small molecules that integrate into biological systems, thereby changing discrete processes that influence growth, development or metabolism. Libraries of chemicals are applied to living systems, and changes in phenotype are observed, potentially leading to the identification of new growth regulators. This work describes an approach that is the nexus of chemical-genomics and synthetic biology. Here each plant in an extensive population synthesizes a unique small peptide arising from a transgene composed of a randomized nucleic acid sequence core, flanked by translational start, stop, and cysteine-encoding (for disulfide cyclization) sequences...
August 14, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28807283/neospora-caninum-rop16-play-an-important-role-in-the-pathogenicity-by-phosphorylating-host-cell-stat3
#17
Lei Ma, Gongzhen Liu, Jing Liu, Muzi Li, Heng Zhang, Di Tang, Qun Liu
Neospora caninum is a common cause of abortions in cattle and nervous system dysfunctions in dogs. Our analysis shows that NcROP16 and TgROP16 have similar structures and may have similar functions. To our surprise, we found that similar to the T. gondii RH strain, the N. caninum Nc-1 strain could phosphorylate STAT3(Y705), but in contrast to T. gondii, N. caninum Nc-1 could not phosphorylate STAT6(Y641). We constructed a gene-knockout plasmid and screened ΔNcROP16 strains at the gene, protein and transcription levels...
August 30, 2017: Veterinary Parasitology
https://www.readbyqxmd.com/read/28806777/a-synthetic-sickness-screen-for-senescence-re-engagement-targets-in-mutant-cancer-backgrounds
#18
Claire J Cairney, Lauren S Godwin, Alan E Bilsland, Sharon Burns, Katrina H Stevenson, Lynn McGarry, John Revie, Jon D Moore, Ceri M Wiggins, Rebecca S Collinson, Clare Mudd, Elpida Tsonou, Mahito Sadaie, Dorothy C Bennett, Masashi Narita, Christopher J Torrance, W Nicol Keith
Senescence is a universal barrier to immortalisation and tumorigenesis. As such, interest in the use of senescence-induction in a therapeutic context has been gaining momentum in the past few years; however, senescence and immortalisation remain underserved areas for drug discovery owing to a lack of robust senescence inducing agents and an incomplete understanding of the signalling events underlying this complex process. In order to address this issue we undertook a large-scale morphological siRNA screen for inducers of senescence phenotypes in the human melanoma cell line A375P...
August 14, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28806602/exposure-of-european-sea-bass-dicentrarchus-labrax-to-chemically-dispersed-oil-has-a-chronic-residual-effect-on-hypoxia-tolerance-but-not-aerobic-scope
#19
Yangfan Zhang, Florian Mauduit, Anthony P Farrell, Denis Chabot, Hélène Ollivier, Adrien Rio-Cabello, Stéphane Le Floch, Guy Claireaux
We tested the hypothesis that the chronic residual effects of an acute exposure of European sea bass (Dicentrarchus labrax) to chemically dispersed crude oil is manifest in indices of hypoxic performance rather than aerobic performance. Sea bass were pre-screened with a hypoxia challenge test to establish their incipient lethal oxygen saturation (ILOS), but on discovering a wide breadth for individual ILOS values (2.6-11.0% O2 saturation), fish were subsequently subdivided into either hypoxia sensitive (HS) or hypoxia tolerant (HT) phenotypes, traits that were shown to be experimentally repeatable...
August 1, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28806050/linking-high-throughput-screens-to-identify-moas-and-novel-inhibitors-of-mycobacterium-tuberculosis-dihydrofolate-reductase
#20
John P Santa Maria, Yumi Park, Lihu Yang, Nicholas Murgolo, Michael D Altman, Paul Zuck, Greg Adam, Chad Chamberlin, Peter Saradjian, Peter Dandliker, Helena I M Boshoff, Clifton E Barry, Charles Garlisi, David B Olsen, Katherine Young, Meir Glick, Elliott Nickbarg, Peter S Kutchukian
Though phenotypic and target-based high-throughput screening approaches have been employed to discover new antibiotics, the identification of promising therapeutic candidates remains challenging. Each approach provides different information, and understanding their results can provide hypotheses for mechanism of action (MoA) and reveal actionable chemical matter. Here we describe a framework for identifying efficacy targets of bioactive compounds. High throughput biophysical profiling against a broad range of targets coupled with machine learning is employed to identify chemical features with predicted efficacy targets for a given phenotypic screen...
August 14, 2017: ACS Chemical Biology
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