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https://www.readbyqxmd.com/read/27936513/probing-the-structural-dynamics-of-the-crispr-cas9-rna-guided-dna-cleavage-system-by-coarse-grained-modeling
#1
Wenjun Zheng
In the adaptive immune systems of many bacteria and archaea, the Cas9 endonuclease forms a complex with specific guide/scaffold RNA to identify and cleave complementary target sequences in foreign DNA. This DNA targeting machinery has been exploited in numerous applications of genome editing and transcription control. However, the molecular mechanism of the Cas9 system is still obscure. Recently, high-resolution structures have been solved for Cas9 in different structural forms (e.g., unbound forms, RNA-bound binary complexes, and RNA-DNA-bound tertiary complexes, corresponding to an inactive state, a pre-target-bound state, and a cleavage-competent or product state), which offered key structural insights to the Cas9 mechanism...
December 9, 2016: Proteins
https://www.readbyqxmd.com/read/27936423/optimising-the-community-based-approach-to-healthcare-improvement-comparative-case-studies-of-the-clinical-community-model-in-practice
#2
Emma-Louise Aveling, Graham Martin, Georgia Herbert, Natalie Armstrong
Community-based approaches to healthcare improvement are receiving increasing attention. Such approaches could offer an infrastructure for efficient knowledge-sharing and a potent means of influencing behaviours, but their potential is yet to be optimised. After briefly reviewing challenges to community-based approaches, we describe in detail the clinical community model. Through exploring clinical communities in practice, we seek to identify practical lessons for optimising this community-based approach to healthcare improvement...
November 22, 2016: Social Science & Medicine
https://www.readbyqxmd.com/read/27936422/social-network-types-among-older-korean-adults-associations-with-subjective-health
#3
Sung Yun Sohn, Won-Tak Joo, Woo Jung Kim, Se Joo Kim, Yoosik Youm, Hyeon Chang Kim, Yeong-Ran Park, Eun Lee
With population aging now a global phenomenon, the health of older adults is becoming an increasingly important issue. Because the Korean population is aging at an unprecedented rate, preparing for public health problems associated with old age is particularly salient in this country. As the physical and mental health of older adults is related to their social relationships, investigating the social networks of older adults and their relationship to health status is important for establishing public health policies...
December 1, 2016: Social Science & Medicine
https://www.readbyqxmd.com/read/27936411/a-network-analysis-of-dsm-5-posttraumatic-stress-disorder-symptoms-and-correlates-in-u-s-military-veterans
#4
Cherie Armour, Eiko I Fried, Marie K Deserno, Jack Tsai, Robert H Pietrzak
OBJECTIVE: Recent developments in psychometrics enable the application of network models to analyze psychological disorders, such as PTSD. Instead of understanding symptoms as indicators of an underlying common cause, this approach suggests symptoms co-occur in syndromes due to causal interactions. The current study has two goals: (1) examine the network structure among the 20 DSM-5 PTSD symptoms, and (2) incorporate clinically relevant variables to the network to investigate whether PTSD symptoms exhibit differential relationships with suicidal ideation, depression, anxiety, physical functioning/quality of life (QoL), mental functioning/QoL, age, and sex...
November 27, 2016: Journal of Anxiety Disorders
https://www.readbyqxmd.com/read/27936376/peer-network-counseling-as-brief-treatment-for-urban-adolescent-heavy-cannabis-users
#5
Michael J Mason, Roy Sabo, Nikola M Zaharakis
OBJECTIVE: A small body of evidence supports targeting adolescents who are heavy users of cannabis with brief interventions, yet more research is needed to confirm the effectiveness of these studies. We conducted a secondary analysis of our Peer Network Counseling (PNC) study (Mason et al., 2015), focusing on 46 adolescents of the sample of 119 who reported heavy cannabis use at baseline. METHOD: Urban adolescents (91% African American) presenting for primary health care were randomized to intervention or control conditions and followed for 6 months...
January 2017: Journal of Studies on Alcohol and Drugs
https://www.readbyqxmd.com/read/27936374/testing-a-matching-hypothesis-for-emerging-adults-in-project-match-during-treatment-and-one-year-outcomes
#6
Jordan P Davis, Brandon G Bergman, Douglas C Smith, John F Kelly
OBJECTIVE: Compared with older adults, emerging adults (18-29 years old) entering treatment typically have less severe alcohol use consequences. Also, their unique clinical presentations (e.g., modest initial abstinence motivation) and developmental contexts (e.g., drinking-rich social networks) may make a straightforward implementation of treatments developed for adults less effective. Yet, this has seldom been examined empirically. This study was a secondary analysis of Project MATCH (Matching Alcoholism Treatments to Client Heterogeneity) data examining (a) overall differences between emerging adults and older adults (≥30 years old) on outcomes during treatment and at 1-year follow-up, and (b) whether emerging adults had poorer outcomes on any of the three Project MATCH treatments in particular...
January 2017: Journal of Studies on Alcohol and Drugs
https://www.readbyqxmd.com/read/27936164/transcriptome-and-metabolome-analyses-in-exogenous-fabp4-and-fabp5-treated-adipose-derived-stem-cells
#7
Tokunori Yamamoto, Masato Furuhashi, Takeshi Sugaya, Tsuyoshi Oikawa, Megumi Matsumoto, Yasuhito Funahashi, Yoshihisa Matsukawa, Momokazu Gotoh, Tetsuji Miura
Adipose-derived stem cells (ADSC), which exist near adipocytes in adipose tissue, have been used as a potential tool of regenerative medicine. Lipid chaperones, fatty acid-binding protein 4 (FABP4) and 5 (FABP5), are abundantly expressed in adipocytes. FABP4 has recently been shown to be secreted from adipocytes during lipolysis in a non-classical pathway and may act as an adipokine. Here, we investigated the role of exogenous FABP4 and FABP5 in transcriptional and metabolic regulation in ADSC. FABP4 and FABP5 were little expressed in ADSC...
2016: PloS One
https://www.readbyqxmd.com/read/27936142/gene-co-expression-network-analysis-unraveling-transcriptional-regulation-of-high-altitude-adaptation-of-tibetan-pig
#8
Cunling Jia, Xiaoyan Kong, James E Koltes, Xiao Gou, Shuli Yang, Dawei Yan, Shaoxiong Lu, Zehui Wei
Tibetan pigs have survived at high altitude for millennia and they have a suite of adaptive features to tolerate the hypoxic environment. However, the molecular mechanisms underlying the regulation of hypoxia-adaptive phenotypes have not been completely elucidated. In this study, we analyzed differentially expressed genes (DEGs), biological pathways and constructed co-expression regulation networks using whole-transcriptome microarrays from lung tissues of Tibetan and Duroc pigs both at high and low altitude...
2016: PloS One
https://www.readbyqxmd.com/read/27936098/analysis-of-hiv-diversity-in-hiv-infected-black-men-who-have-sex-with-men-hptn-061
#9
Iris Chen, Gordon Chau, Jing Wang, William Clarke, Mark A Marzinke, Vanessa Cummings, Autumn Breaud, Oliver Laeyendecker, Sheldon D Fields, Sam Griffith, Hyman M Scott, Steven Shoptaw, Carlos Del Rio, Manya Magnus, Sharon Mannheimer, Hong-Van Tieu, Darrell P Wheeler, Kenneth H Mayer, Beryl A Koblin, Susan H Eshleman
BACKGROUND: HIV populations often diversify in response to selective pressures, such as the immune response and antiretroviral drug use. We analyzed HIV diversity in Black men who have sex with men who were enrolled in the HIV Prevention Trials Network 061 study. METHODS: A high resolution melting (HRM) diversity assay was used to measure diversity in six regions of the HIV genome: two in gag, one in pol, and three in env. HIV diversity was analyzed for 146 men who were HIV infected at study enrollment, including three with acute infection and 13 with recent infection (identified using a multi-assay algorithm), and for 21 men who seroconverted during the study...
2016: PloS One
https://www.readbyqxmd.com/read/27936063/hydrophobins-in-the-life-cycle-of-the-ectomycorrhizal-basidiomycete-tricholoma-vaccinum
#10
Dominik Sammer, Katrin Krause, Matthias Gube, Katharina Wagner, Erika Kothe
Hydrophobins-secreted small cysteine-rich, amphipathic proteins-foster interactions of fungal hyphae with hydrophobic surfaces, and are involved in the formation of aerial hyphae. Phylogenetic analyses of Tricholoma vaccinum hydrophobins showed a grouping with hydrophobins of other ectomycorrhizal fungi, which might be a result of co-evolution. Further analyses indicate angiosperms as likely host trees for the last common ancestor of the genus Tricholoma. The nine hydrophobin genes in the T. vaccinum genome were investigated to infer their individual roles in different stages of the life cycle, host interaction, asexual and sexual development, and with respect to different stresses...
2016: PloS One
https://www.readbyqxmd.com/read/27936058/modeling-the-role-of-lanthionine-synthetase-c-like-2-lancl2-in-the-modulation-of-immune-responses-to-helicobacter-pylori-infection
#11
Andrew Leber, Josep Bassaganya-Riera, Nuria Tubau-Juni, Victoria Zoccoli-Rodriguez, Monica Viladomiu, Vida Abedi, Pinyi Lu, Raquel Hontecillas
Immune responses to Helicobacter pylori are orchestrated through complex balances of host-bacterial interactions, including inflammatory and regulatory immune responses across scales that can lead to the development of the gastric disease or the promotion of beneficial systemic effects. While inflammation in response to the bacterium has been reasonably characterized, the regulatory pathways that contribute to preventing inflammatory events during H. pylori infection are incompletely understood. To aid in this effort, we have generated a computational model incorporating recent developments in the understanding of H...
2016: PloS One
https://www.readbyqxmd.com/read/27936056/spatial-temporal-analysis-of-environmental-data-of-north-beijing-district-using-hilbert-huang-transform
#12
Yu Xiang, Xuezhi Wang, Lihua He, Wenyong Wang, William Moran
Temperature, solar radiation and water are major important variables in ecosystem models which are measurable via wireless sensor networks (WSN). Effective data analysis is necessary to extract significant spatial and temporal information. In this work, information regarding the long term variation of seasonal field environment conditions is explored using Hilbert-Huang transform (HHT) based analysis on the wireless sensor network data collection. The data collection network, consisting of 36 wireless nodes, covers an area of 100 square kilometres in Yanqing, the northwest of Beijing CBD, in China and data collection involves environmental parameter observations taken over a period of three months in 2011...
2016: PloS One
https://www.readbyqxmd.com/read/27936040/a-high-throughput-strategy-for-dissecting-mammalian-genetic-interactions
#13
Victoria B Stockman, Lila Ghamsari, Gorka Lasso, Barry Honig, Sagi D Shapira, Harris H Wang
Comprehensive delineation of complex cellular networks requires high-throughput interrogation of genetic interactions. To address this challenge, we describe the development of a multiplex combinatorial strategy to assess pairwise genetic interactions using CRISPR-Cas9 genome editing and next-generation sequencing. We characterize the performance of combinatorial genome editing and analysis using different promoter and gRNA designs and identified regions of the chimeric RNA that are compatible with next-generation sequencing preparation and quantification...
2016: PloS One
https://www.readbyqxmd.com/read/27936036/the-rs3957357c-t-snp-in-gsta1-is-associated-with-a-higher-risk-of-occurrence-of-hepatocellular-carcinoma-in-european-individuals
#14
Hanane Akhdar, Said El Shamieh, Orlando Musso, Romain Désert, Wissam Joumaa, Dominique Guyader, Caroline Aninat, Anne Corlu, Fabrice Morel
Glutathione S-transferases (GSTs) detoxify toxic molecules by conjugation with reduced glutathione and regulate cell signaling. Single nucleotide polymorphisms (SNPs) of GST genes have been suggested to affect GST functions and thus to increase the risk of human hepatocellular carcinoma (HCC). As GSTA1 is expressed in hepatocytes and the rs3957357C>T (TT) SNP is known to downregulate GSTA1 mRNA expression, the aims of this study were: (i) to explore the relationship between the TT SNP in GSTA1 and the occurrence of HCC; (ii) to measure GSTA1 mRNA expression in HCCs...
2016: PloS One
https://www.readbyqxmd.com/read/27935958/synchronization-and-random-triggering-of-lymphatic-vessel-contractions
#15
James W Baish, Christian Kunert, Timothy P Padera, Lance L Munn
The lymphatic system is responsible for transporting interstitial fluid back to the bloodstream, but unlike the cardiovascular system, lacks a centralized pump-the heart-to drive flow. Instead, each collecting lymphatic vessel can individually contract and dilate producing unidirectional flow enforced by intraluminal check valves. Due to the large number and spatial distribution of such pumps, high-level coordination would be unwieldy. This leads to the question of how each segment of lymphatic vessel responds to local signals that can contribute to the coordination of pumping on a network basis...
December 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27935935/stimulus-driven-population-activity-patterns-in-macaque-primary-visual-cortex
#16
Benjamin R Cowley, Matthew A Smith, Adam Kohn, Byron M Yu
Dimensionality reduction has been applied in various brain areas to study the activity of populations of neurons. To interpret the outputs of dimensionality reduction, it is important to first understand its outputs for brain areas for which the relationship between the stimulus and neural response is well characterized. Here, we applied principal component analysis (PCA) to trial-averaged neural responses in macaque primary visual cortex (V1) to study two fundamental, population-level questions. First, we characterized how neural complexity relates to stimulus complexity, where complexity is measured using relative comparisons of dimensionality...
December 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27935212/hemophilia-liver-transplantation-observational-study-hots
#17
Margaret V Ragni, Abhinav Humar, Peter G Stock, Emily A Blumberg, Bijan Eghtesad, John J Fung, Valentina Stosor, Nicholas Nissen, Michael T Wong, Kenneth E Sherman, Donald M Stablein, Burc Barin
: Hepatitis C (HCV) infection is the leading cause of liver disease in hemophilia. In those with HIV/HCV co-infection, the rate of liver disease progression is greater than in HCV mono-infected individuals. Despite antiretroviral therapy which slows HCV liver disease progression, some require transplantation. Whether transplant outcomes are worse in hemophilic (H) than non-hemophilic (NH) candidates is unknown. In order to determine rates and predictors of pre- and post-transplant survival, we conducted a retrospective observational study utilizing United Network for Organ Sharing (UNOS) national transplant registry data, comparing HCV+ H and NH candidates...
December 9, 2016: Liver Transplantation
https://www.readbyqxmd.com/read/27934932/expression-profiling-and-functional-annotation-of-noncoding-genes-across-11-distinct-organs-in-rat-development
#18
Zhuo Wen, Geng Chen, Sibo Zhu, Jinhang Zhu, Bin Li, Yunjie Song, Suqing Li, Leming Shi, Yuanting Zheng, Menglong Li
Accumulating evidence suggests that noncoding RNAs (ncRNAs) have important regulatory functions. However, lacking of functional annotations for ncRNAs hampered us from carrying out the subsequent functional or predictive research. Here we dissected the expression profiles of 3,458 rat noncoding genes using rat bodymap RNA-sequencing data consisting of 11 solid organs over four developmental stages (juvenile, adolescent, adult and aged) from both sexes, and conducted a comprehensive analysis of differentially expressed noncoding genes (DEnGs) between various conditions...
December 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27934295/activity-based-protein-profiling-shows-heterogeneous-signaling-adaptations-to-braf-inhibition
#19
Ritin Sharma, Inna Fedorenko, Paige T Spence, Vernon K Sondak, Keiran S M Smalley, John M Koomen
Patients with BRAF V600E mutant melanoma are typically treated with targeted BRAF kinase inhibitors, such as vemurafenib and dabrafenib. Although these drugs are initially effective, they are not curative. Most of the focus to date has been upon genetic mechanisms of acquired resistance; therefore, we must better understand the global signaling adaptations that mediate escape from BRAF inhibition. In the current study, we have used activity-based protein profiling (ABPP) with ATP-analogue probes to enrich kinases and other enzyme classes that contribute to BRAF inhibitor (BRAFi) resistance in four paired isogenic BRAFi-naïve/resistant cell line models...
December 2, 2016: Journal of Proteome Research
https://www.readbyqxmd.com/read/27933965/first-structure-activity-relationship-of-17%C3%AE-hydroxysteroid-dehydrogenase-type-14-nonsteroidal-inhibitors-and-crystal-structures-in-complex-with-the-enzyme
#20
Florian Braun, Nicole Bertoletti, Gabriele Möller, Jerzy Adamski, Torsten Steinmetzer, Mohamed Salah, Ahmed S Abdelsamie, Chris J van Koppen, Andreas Heine, Gerhard Klebe, Sandrine Marchais-Oberwinkler
17β-HSD14 belongs to the SDR family and oxidizes the hydroxyl group at position 17 of estradiol and 5-androstenediol using NAD(+) as cofactor. The goal of this study was to identify and optimize 17β-HSD14 nonsteroidal inhibitors as well as to disclose their structure-activity relationship. In a first screen, a library of 17β-HSD1 and 17β-HSD2 inhibitors, selected with respect to scaffold diversity, was tested for 17β-HSD14 inhibition. The most interesting hit was taken as starting point for chemical modification applying a ligand-based approach...
December 8, 2016: Journal of Medicinal Chemistry
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