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Maxime Lamontagne, Jean-Christophe Bérubé, Ma'en Obeidat, Michael H Cho, Brian D Hobbs, Phuwanat Sakornsakolpat, Kim de Jong, H Marike Boezen, David Nickle, Ke Hao, Wim Timens, Maarten van den Berge, Philippe Joubert, Michel Laviolette, Don D Sin, Peter D Paré, Yohan Bossé
Causal genes of chronic obstructive pulmonary disease (COPD) remain elusive. The current study aims at integrating genome-wide association studies (GWAS) and lung expression quantitative loci (eQTL) data to map COPD candidate causal genes and gain biological insights into the recently discovered COPD susceptibility loci. Two complementary genomic datasets on COPD were studied. First, the lung eQTL dataset which included whole-genome gene expression and genotyping data from 1,038 individuals. Second, the largest COPD GWAS to date from the International COPD Genetics Consortium (ICGC) with 13,710 cases and 38,062 controls...
March 14, 2018: Human Molecular Genetics
Jiawei Wang, Bingjiao Yang, André Leier, Tatiana T Marquez-Lago, Morihiro Hayashida, Andrea Rocker, Zhang Yanju, Tatsuya Akutsu, Kuo-Chen Chou, Richard A Strugnell, Jiangning Song, Trevor Lithgow
Motivation: Many Gram-negative bacteria use type VI secretion systems (T6SS) to export effector proteins into adjacent target cells. These secreted effectors (T6SEs) play vital roles in the competitive survival in bacterial populations, as well as pathogenesis of bacteria. Although various computational analyses have been previously applied to identify effectors secreted by certain bacterial species, there is no universal method available to accurately predict T6SS effector proteins from the growing tide of bacterial genome sequence data...
March 14, 2018: Bioinformatics
Elif Şenkuytu, Esra Tanrıverdi Eçik
In the study, the new hexa-bodipy functionalized dendrimeric cyclotriphosphazene conjugates (HBCP 1 and 2) have been successfully synthesized and characterized by using general spectroscopic techniques such as1 H,13 C and31 P NMR spectroscopies. The photophysical and metal sensing properties in THF solutions of dendrimeric cyclotriphosphazene conjugates (HBCP 1 and 2) were investigated by UV-Vis and fluorescence spectroscopies in dilute tetrahydrofuran solutions. These dendrimers showed strong absorption bands 501 and 641nm at low concentration with high molar extinction coefficients...
March 9, 2018: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
Mario Alberto Flores-Valdez, Cristian Alfredo Segura-Cerda, Jorge Gaona-Bernal
Effective prevention of tuberculosis (Tb) would undoubtedly be of paramount relevance in the control of its global burden, which resulted in more than 6 million new cases in 2016. Research aimed to improve the current vaccine, Bacillus Calmette- Guérin (BCG), or directed to develop new candidates, has taken into account the interaction between the host and Mycobacterium tuberculosis (Mtb). Recently, autophagy, an intracellular process of the host, has been shown to act as a mechanism that contributes to bacilli clearance in vitro and in vivo...
March 13, 2018: Molecular Immunology
Melissa Tomkins, Adi Kliot, Athanasius Fm Marée, Saskia A Hogenhout
Members of the Candidatus genus Phytoplasma are small bacterial pathogens that hijack their plant hosts via the secretion of virulence proteins (effectors) leading to a fascinating array of plant phenotypes, such as witch's brooms (stem proliferations) and phyllody (retrograde development of flowers into vegetative tissues). Phytoplasma depend on insect vectors for transmission, and interestingly, these insect vectors were found to be (in)directly attracted to plants with these phenotypes. Therefore, phytoplasma effectors appear to reprogram plant development and defence to lure insect vectors, similarly to social engineering malware, which employs tricks to lure people to infected computers and webpages...
March 13, 2018: Current Opinion in Plant Biology
Julianne Teresa Djordjevic, Sophie Lev
Invasive fungal diseases pose a serious threat, and new drugs are urgently needed. In this issue of Cell Chemical Biology, Pries et al. (2018) identified benzamide- and picolinamide-based small-molecule inhibitors with antifungal properties, including some active against pathogenic Candida species. These compounds target an essential component of the fungal secretion machinery, suggesting a new approach to antifungal development.
March 15, 2018: Cell Chemical Biology
Anna Pellattiero, Luca Scorrano
Despite the significance of mitochondrial dynamics in many diseases, drugs that modulate it are lacking. In this issue of Cell Chemical Biology, Miret-Casals et al. (2018) use a phenotypic high-throughput screen to discover a pro-fusion role for the anti-inflammatory drug Leflunomide, paving the way to screen for mitochondrial pro-fusion drug candidates.
March 15, 2018: Cell Chemical Biology
Pascal Fleurkens, Agnes van Minnen, Eni S Becker, Iris van Oostrom, Anne Speckens, Mike Rinck, Janna N Vrijsen
Depression risk genes in combination with childhood events have been associated with biased processing as an intermediate phenotype for depression. The aim of the present conceptual replication study was to investigate the role of biased automatic approach-avoidance tendencies as a candidate intermediate phenotype for depression, in the context of genes (5-HTTLPR polymorphism) and childhood trauma. A naturalistic remitted depressed patients sample (N = 209) performed an Approach-Avoidance Task (AAT) with facial expressions (angry, sad, happy and neutral)...
2018: PloS One
Souheil El-Chemaly, Kevin J O'Brien, Steven D Nathan, Gerald L Weinhouse, Hilary J Goldberg, Jean M Connors, Ye Cui, Todd L Astor, Philip C Camp, Ivan O Rosas, Merte Lemma, Vladislav Speransky, Melissa A Merideth, William A Gahl, Bernadette R Gochuico
Pulmonary fibrosis is a progressive, fatal manifestation of Hermansky-Pudlak syndrome (HPS). Some patients with advanced HPS pulmonary fibrosis undergo lung transplantation despite their disease-associated bleeding tendency; others die while awaiting donor organs. The objective of this study is to determine the clinical management and outcomes of a cohort with advanced HPS pulmonary fibrosis who were evaluated for lung transplantation. Six patients with HPS-1 pulmonary fibrosis were evaluated at the National Institutes of Health Clinical Center and one of two regional lung transplant centers...
2018: PloS One
Hirofumi Chiba, Yoichi Kakuta, Yoshitaka Kinouchi, Yosuke Kawai, Kazuhiro Watanabe, Munenori Nagao, Takeo Naito, Motoyuki Onodera, Rintaro Moroi, Masatake Kuroha, Yoshitake Kanazawa, Tomoya Kimura, Hisashi Shiga, Katsuya Endo, Kenichi Negoro, Masao Nagasaki, Michiaki Unno, Tooru Shimosegawa
BACKGROUND: Inflammatory bowel disease (IBD) has an unknown etiology; however, accumulating evidence suggests that IBD is a multifactorial disease influenced by a combination of genetic and environmental factors. The influence of genetic variants on DNA methylation in cis and cis effects on expression have been demonstrated. We hypothesized that IBD susceptibility single-nucleotide polymorphisms (SNPs) regulate susceptibility gene expressions in cis by regulating DNA methylation around SNPs...
2018: PloS One
Marcin Maździarz, Adam Mrozek, Wacław Kuś, Tadeusz Burczyński
A potentially new, single-atom thick semiconducting 2D- graphene -like material, called Anisotropic-cyclicgraphene , has been generated by the two stage searching strategy linking molecular and ab initio approach. The candidate was derived from the evolutionary-based algorithm and molecular simulations was then profoundly analysed using first-principles density functional theory from the structural, mechanical, phonon, and electronic properties point of view. The proposed polymorph of graphene ( rP16 -P1m1) is mechanically, dynamically, and thermally stable and can achieve semiconducting with a direct band gap of 0...
March 16, 2018: Materials
Thomas Joshua Pasvol, Caroline Foster, Sarah Fidler
PURPOSE OF REVIEW: Successful roll-out of paediatric antiretroviral therapy (ART) has led to a significant increase in survival of adolescents and young people growing up with HIV. Those on suppressive ART since childhood represent a unique group particularly well positioned to interrupt ART and achieve post-treatment control (PTC), or HIV remission. This maybe a consequence of early and sustained treatment since infancy, the small size of the HIV reservoir, the presence of a functioning thymus and a more 'flexible' immune system better able to respond to novel immune therapeutic interventions when compared with adults who acquired HIV at a time of immunological maturity and thymic involution...
March 14, 2018: Current Opinion in HIV and AIDS
N De Neve, B Vlaeminck, F Gadeyne, E Claeys, P Van der Meeren, V Fievez
Previously, polyunsaturated fatty acids (PUFA) from linseed oil were effectively protected (>80%) against biohydrogenation through polyphenol-oxidase-mediated protein crosslinking of an emulsion, prepared with polyphenol oxidase (PPO) extract from potato tuber peelings. However, until now, emulsions of only 2 wt% oil have been successfully protected, which implies serious limitations both from a research perspective (e.g. in vivo trials) as well as for further upscaling toward practical applications. Therefore, the aim of this study was to increase the oil/PPO ratio...
March 16, 2018: Animal: An International Journal of Animal Bioscience
Diego Jaramillo-Cano, Maud Formanek, Christos N Likos, Manuel Camargo
Star block-copolymers (SBCs) have been demonstrated to constitute self-assembling building blocks with specific softness, functionalization, shape and flexibility. In this work we study the behaviour of an isolated SBC under shear flow by means of particle-based multi-scale simulations. We systematically analyse the conformational properties of low-functionality stars as well as the formation of attractive patches on their corona as a function of the shear rate. We cover a wide range of system parameters, including functionality, amphiphilicity and solvent quality...
March 16, 2018: Journal of Physical Chemistry. B
Nick Zwart, Shan Li Nio, Corine J Houtman, Jacob De Boer, Jeroen Kool, Timo Hamers, Marja H Lamoree
Effect-Directed Analysis (EDA) is a commonly used approach for effect-based identification of endocrine disruptive chemicals in complex (environmental) mixtures. For routine toxicity assessment of e.g. water samples however, current EDA approaches are considered time consuming and laborious. We achieved faster EDA and identification, by downscaling of sensitive cell-based hormone reporter gene assays and increasing fractionation resolution to allow testing of smaller fractions with reduced complexity. The high-resolution EDA approach is demonstrated by analysis of four environmental passive sampler extracts...
March 16, 2018: Environmental Science & Technology
Lucia Romero, Jordi Cano, Julio Gomis-Tena, Beatriz Trenor, Ferran Sanz, Manuel Pastor, Javier Saiz
Drug-induced proarrhythmicity is a major concern for regulators and pharmaceutical companies. For novel drug candidates, the standard assessment involves the evaluation of the potassium hERG channels block and the in vivo prolongation of the QT interval. However, this method is known to be too restrictive and to stop the development of potentially valuable therapeutic drugs. The aim of this work is to create an in silico tool for early detection of drug-induced proarrhythmic risk. The system is based on simulations of how different compounds affect the action potential duration (APD) of isolated endocardial, midmyocardial, and epicardial cells as well as the QT prolongation in a virtual tissue...
March 16, 2018: Journal of Chemical Information and Modeling
Eric M Hill, Christian P Petersen
Most animals undergo homeostatic tissue maintenance, yet those capable of robust regeneration in adulthood use mechanisms significantly overlapping with homeostasis. Here we show in planarians that modulations to body-wide patterning systems shift the target site for eye regeneration while still enabling homeostasis of eyes outside this region. The uncoupling of homeostasis and regeneration, which can occur during normal positional rescaling after axis truncation, is not due to altered injury signaling or stem cell activity, nor specific to eye tissue...
March 16, 2018: ELife
Da Li, Yu-Ming Jiao, Liang Wang, Fu-Xin Lin, Jun Wu, Xian-Zeng Tong, Shuo Wang, Yong Cao
OBJECTIVE Surgical management of brainstem lesions is challenging due to the highly compact, eloquent anatomy of the brainstem. This study aimed to evaluate the safety and efficacy of preoperative diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) in brainstem cavernous malformations (CMs). METHODS A prospective randomized controlled clinical trial was performed by using stratified blocked randomization. The primary eligibility criterion of the study was being a surgical candidate for brainstem CMs (with informed consent)...
March 16, 2018: Journal of Neurosurgery
Ningning Wang, Xueyan Li, Qi Zhang, Hao Zhang, Li Zhou, Nan Wu, Ming Jin, Changchun Qiu, Keyong Zhang
Angiotensin I converting enzyme (ACE) gene is one of the most-studied candidate genes related to essential hypertension (EH). Pulse pressure (PP) may reflect vascular stiffness, especially in patients with EH, and has been used to predict EH. Previous evidence has indicated that obesity is a traditional risk factor of hypertension. The aim of the present study was to investigate the interaction between the obesity status and ACE gene polymorphisms on the development of high level of PP. A total of 1980 adults (1024 hypertensive and 956 normotensive) were included in this study and genotyped for ACE gene polymorphisms...
March 16, 2018: Clinical and Experimental Hypertension: CHE
Ying Hu, Zhonghai Fang, Yichen Yang, Ting Fan, Ju Wang
Nicotine dependence is the primary addictive stage of cigarette smoking. Although a lot of studies have been performed to explore the molecular mechanism underlying nicotine dependence, our understanding on this disorder is still far from complete. Over the past decades, an increasing number of candidate genes involved in nicotine dependence have been identified by different technical approaches, including the genetic association analysis. In this study, we performed a comprehensive collection of candidate genes reported to be genetically associated with nicotine dependence...
March 16, 2018: Journal of Biomolecular Structure & Dynamics
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