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https://www.readbyqxmd.com/read/29346770/integrative-analyses-of-de-novo-mutations-provide-deeper-biological-insights-into-autism-spectrum-disorder
#1
Atsushi Takata, Noriko Miyake, Yoshinori Tsurusaki, Ryoko Fukai, Satoko Miyatake, Eriko Koshimizu, Itaru Kushima, Takashi Okada, Mako Morikawa, Yota Uno, Kanako Ishizuka, Kazuhiko Nakamura, Masatsugu Tsujii, Takeo Yoshikawa, Tomoko Toyota, Nobuhiko Okamoto, Yoko Hiraki, Ryota Hashimoto, Yuka Yasuda, Shinji Saitoh, Kei Ohashi, Yasunari Sakai, Shouichi Ohga, Toshiro Hara, Mitsuhiro Kato, Kazuyuki Nakamura, Aiko Ito, Chizuru Seiwa, Emi Shirahata, Hitoshi Osaka, Ayumi Matsumoto, Saoko Takeshita, Jun Tohyama, Tomoko Saikusa, Toyojiro Matsuishi, Takumi Nakamura, Takashi Tsuboi, Tadafumi Kato, Toshifumi Suzuki, Hirotomo Saitsu, Mitsuko Nakashima, Takeshi Mizuguchi, Fumiaki Tanaka, Norio Mori, Norio Ozaki, Naomichi Matsumoto
Recent studies have established important roles of de novo mutations (DNMs) in autism spectrum disorders (ASDs). Here, we analyze DNMs in 262 ASD probands of Japanese origin and confirm the "de novo paradigm" of ASDs across ethnicities. Based on this consistency, we combine the lists of damaging DNMs in our and published ASD cohorts (total number of trios, 4,244) and perform integrative bioinformatics analyses. Besides replicating the findings of previous studies, our analyses highlight ATP-binding genes and fetal cerebellar/striatal circuits...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346371/identification-of-novel-leishmanicidal-molecules-by-virtual-and-biochemical-screenings-targeting-leishmania-eukaryotic-initiation-factor-4a
#2
Emna Harigua-Souiai, Yosser Zina Abdelkrim, Imen Bassoumi-Jamoussi, Ons Zakraoui, Guillaume Bouvier, Khadija Essafi-Benkhadir, Josette Banroques, Nathan Desdouits, Hélène Munier-Lehmann, Mourad Barhoumi, N Kyle Tanner, Michael Nilges, Arnaud Blondel, Ikram Guizani
Leishmaniases are neglected parasitic diseases in spite of the major burden they inflict on public health. The identification of novel drugs and targets constitutes a research priority. For that purpose we used Leishmania infantum initiation factor 4A (LieIF), an essential translation initiation factor that belongs to the DEAD-box proteins family, as a potential drug target. We modeled its structure and identified two potential binding sites. A virtual screening of a diverse chemical library was performed for both sites...
January 18, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29346286/a-more-efficient-transportable-and-scalable-system-for-real-time-activities-and-exercises-recognition
#3
Kévin Chapron, Valère Plantevin, Florentin Thullier, Kévin Bouchard, Elise Duchesne, Sébastien Gaboury
Many people in the world are affected by muscle wasting, especially the population hits by myotonic dystrophy type 1 (DM1). Those people are usually given a program of multiple physical exercises to do. While DM1 and many other people have difficulties attending commercial centers to realize their program, a solution is to develop such a program completable at home. To this end, we developed a portable system that patients could bring home. This prototype is an improved version of the previous one using Wi-Fi, as this new prototype runs on BLE technology...
January 18, 2018: Sensors
https://www.readbyqxmd.com/read/29346071/identification-of-potential-inhibitors-against-nuclear-dam1-complex-subunit-ask1-of-candida-albicans-using-virtual-screening-and-md-simulations
#4
Himanshu Tripathi, Feroz Khan
Identification of hit compounds against specific target form the starting point for a drug discovery program. A consistent decline of new chemical entities (NCEs) in recent years prompted a challenge to explore newer approaches to discover potential hit compounds that in turn can be converted into leads, and ultimately drug with desired therapeutic efficacy. The vast amount of omics and activity data available in public databases offers an opportunity to identify novel targets and their potential inhibitors...
January 1, 2018: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/29345217/statistical-analysis-of-human-microarray-data-shows-that-dietary-intervention-with-n-3-fatty-acids-flavonoids-and-resveratrol-enriches-for-immune-response-and-disease-pathways
#5
Alix Warburton, Olga Vasieva, Peter Quinn, James P Stewart, John P Quinn
n-3 Fatty acids, flavonoids and resveratrol are well publicised for their beneficial effects on human health and wellbeing. Identifying common, underlying biological mechanisms targeted by these functional foods would therefore be informative for the public health sector for advising on nutritional health and disease, food and drug product development and consumer interest. The aim of this study was to explore the potential effects of gene expression changes associated with n-3 fatty acids EPA and DHA, flavonoids and resveratrol on modifying biological systems and disease pathways...
January 18, 2018: British Journal of Nutrition
https://www.readbyqxmd.com/read/29345009/choosing-non-redundant-representative-subsets-of-protein-sequence-data-sets-using-submodular-optimization
#6
Maxwell W Libbrecht, Jeffrey A Bilmes, William Stafford Noble
Selecting a non-redundant representative subset of sequences is a common step in many bioinformatics workflows, such as the creation of non-redundant training sets for sequence and structural models or selection of "operational taxonomic units" from metagenomics data. Previous methods for this task, such as CD-HIT, PISCES and UCLUST, apply a heuristic threshold-based algorithm that has no theoretical guarantees. We propose a new approach based on submodular optimization. Submodular optimization, a discrete analogue to continuous convex optimization, has been used with great success for other representative set selection problems...
January 18, 2018: Proteins
https://www.readbyqxmd.com/read/29343831/novel-hydrogenases-from-deep-sea-hydrothermal-vent-metagenomes-identified-by-a-recently-developed-activity-based-screen
#7
Nicole Adam, Mirjam Perner
Hydrogen is one of the most common elements on Earth. The enzymes converting molecular hydrogen into protons and electrons are the hydrogenases. Hydrogenases are ubiquitously distributed in all three domains of life where they play a central role in cell metabolism. So far, the recovery of hydrogenases has been restricted to culture-dependent and sequence-based approaches. We have recently developed the only activity-based screen for seeking H2-uptake enzymes from metagenomes without having to rely on enrichment and isolation of hydrogen-oxidizing microorganisms or prior metagenomic sequencing...
January 17, 2018: ISME Journal
https://www.readbyqxmd.com/read/29342416/identification-of-novel-quinazolinedione-derivatives-as-ror%C3%AE-t-inverse-agonist
#8
Yoshiyuki Fukase, Ayumu Sato, Yoshihide Tomata, Atsuko Ochida, Mitsunori Kono, Kazuko Yonemori, Keiko Koga, Toshitake Okui, Masashi Yamasaki, Yasushi Fujitani, Hideyuki Nakagawa, Ryoukichi Koyama, Masaharu Nakayama, Robert Skene, Bi-Ching Sang, Isaac Hoffman, Junya Shirai, Satoshi Yamamoto
Novel small molecules were synthesized and evaluated as retinoic acid receptor-related orphan receptor-gamma t (RORγt) inverse agonists for the treatment of inflammatory and autoimmune diseases. A hit compound, 1, was discovered by high-throughput screening of our compound library. The structure-activity relationship (SAR) study of compound 1 showed that the introduction of a chlorine group at the 3-position of 4-cyanophenyl moiety increased the potency and a 3-methylpentane-1,5-diamide linker is favorable for the activity...
December 28, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29341586/development-of-a-novel-cytopathic-effect-based-phenotypic-screening-assay-against-cryptosporidium
#9
Alexander T Chao, Boon Heng Lee, Kah Fei Wan, Jeremy Selva, Bin Zou, Peter Gedeck, David Beer, Thierry T Diagana, Ghislain Bonamy, Ujjini H Manjunatha
Cryptosporidiosis is a diarrheal disease predominantly caused by Cryptosporidium parvum (Cp) and Cryptosporidium hominis (Ch), apicomplexan parasites which infect the intestinal epithelial cells of their human hosts. The only approved drug for cryptosporidiosis is nitazoxanide, which shows limited efficacy in immunocompromised children, the most vulnerable patient population. Thus, new therapeutics and in vitro infection models are urgently needed to address the current unmet medical need. Toward this aim, we have developed novel cytopathic effect (CPE)-based Cp and Ch assays in human colonic tumor (HCT-8) cells and compared them to traditional imaging formats...
January 17, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29341130/mitochondrial-function-and-autophagy-integrating-proteotoxic-redox-and-metabolic-stress-in-parkinson-s-disease
#10
REVIEW
Jianhua Zhang, M Lillian Culp, Jason G Craver, Victor Darley-Usmar
Parkinson's disease (PD) is a movement disorder with widespread neurodegeneration in the brain. Significant oxidative, reductive, metabolic, and proteotoxic alterations have been observed in PD postmortem brains. The alterations of mitochondrial function resulting in decreased bioenergetic health is important and needs to be further examined to help develop biomarkers for PD severity and prognosis. It is now becoming clear that multiple hits on metabolic and signaling pathways are likely to exacerbate PD pathogenesis...
January 17, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29340039/integrative-molecular-network-analysis-identifies-emergent-enzalutamide-resistance-mechanisms-in-prostate-cancer
#11
Carly J King, Josha Woodward, Jacob Schwartzman, Daniel J Coleman, Robert Lisac, Nicholas J Wang, Kathryn Van Hook, Lina Gao, Joshua Urrutia, Mark A Dane, Laura M Heiser, Joshi J Alumkal
Recent work demonstrates that castration-resistant prostate cancer (CRPC) tumors harbor countless genomic aberrations that control many hallmarks of cancer. While some specific mutations in CRPC may be actionable, many others are not. We hypothesized that genomic aberrations in cancer may operate in concert to promote drug resistance and tumor progression, and that organization of these genomic aberrations into therapeutically targetable pathways may improve our ability to treat CRPC. To identify the molecular underpinnings of enzalutamide-resistant CRPC, we performed transcriptional and copy number profiling studies using paired enzalutamide-sensitive and resistant LNCaP prostate cancer cell lines...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339489/rogue-waves-and-large-deviations-in-deep-sea
#12
Giovanni Dematteis, Tobias Grafke, Eric Vanden-Eijnden
The appearance of rogue waves in deep sea is investigated by using the modified nonlinear Schrödinger (MNLS) equation in one spatial dimension with random initial conditions that are assumed to be normally distributed, with a spectrum approximating realistic conditions of a unidirectional sea state. It is shown that one can use the incomplete information contained in this spectrum as prior and supplement this information with the MNLS dynamics to reliably estimate the probability distribution of the sea surface elevation far in the tail at later times...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339272/an-old-friend-is-trouble-for-double-expressor-and-double-hit-lymphoma
#13
Michael Scordo
No abstract text is available yet for this article.
January 12, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29339184/a-novel-stress-hormone-response-gene-in-tadpoles-of-xenopus-tropicalis
#14
Katelin A Schneider, Leena H Shewade, Nicolas Buisine, Laurent M Sachs, Daniel R Buchholz
Previous work identified a transcribed locus, Str. 34945, induced by the frog stress hormone corticosterone (CORT) in Xenopus tropicalis tails. Because thyroid hormone had no influence on its expression, Str. 34945 was dubbed the first "CORT-only" gene known from tadpoles. Here, we examine the genomic annotation for this transcript, hormone specificity, time course of induction, tissue distribution, and developmental expression profile. The location of Str. 34945 on the X. tropicalis genome lies between the genes ush1g (Usher syndrome 1G) and fads6 (fatty acid desaturase 6)...
January 12, 2018: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/29338922/alcohol-consumption-masculinity-and-alcohol-related-violence-and-anti-social-behaviour-in-sportspeople
#15
Kerry S O'Brien, Walter Forrest, Iain Greenlees, Daniel Rhind, Sophia Jowett, Ilana Pinsky, Albert Espelt, Marina Bosque-Prous, Anders Larrabee Sonderlund, Matteo Vergani, Muhammad Iqbal
OBJECTIVES: There is no research examining alcohol-related aggression and anti-social behaviour in UK or European sportspeople (athletes), and no research has examined relationships between masculinity, alcohol consumption, and alcohol-related aggression and antisocial behaviour in sportspeople (athletes). This study addresses this gap. DESIGN: Cross-sectional. METHODS: A sample (N=2048; women=892, 44%) of in season sportspeople enrolled at UK universities (response 83%), completed measures of masculinity, alcohol consumption, within-sport (on-field) violence, and having been the perpetrator and/or victim of alcohol-related violent/aggressive and antisocial behaviour (e...
July 4, 2017: Journal of Science and Medicine in Sport
https://www.readbyqxmd.com/read/29337966/drug-development-allosteric-inhibitors-hit-usp7-hard
#16
Wei Zhang, Sachdev S Sidhu
No abstract text is available yet for this article.
January 16, 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/29337950/quick-hits
#17
Yasemin Saplakoglu
No abstract text is available yet for this article.
January 16, 2018: Scientific American
https://www.readbyqxmd.com/read/29337878/tetrasubstituted-imidazolium-salts-as-potent-antiparasitic-agents-against-african-and-american-trypanosomiases
#18
Ouldouz Ghashghaei, Nicola Kielland, Marc Revés, Martin C Taylor, John M Kelly, Ornella Di Pietro, Diego Muñoz-Torrero, Belén Pérez, Rodolfo Lavilla
Imidazolium salts are privileged compounds in organic chemistry, and have valuable biological properties. Recent studies show that symmetric imidazolium salts with bulky moieties can display antiparasitic activity against T. cruzi. After developing a facile methodology for the synthesis of tetrasubstituted imidazolium salts from propargylamines and isocyanides, we screened a small library of these adducts against the causative agents of African and American trypanosomiases. These compounds display nanomolar activity against T...
January 16, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29337374/pooled-lentiviral-delivery-genetic-screens
#19
Federica Piccioni, Scott T Younger, David E Root
Pooled cell-based screens of mammalian genetic perturbations enable systematic large-scale, even genome-scale, evaluation of gene function. Pooled screens introduce genetic perturbations into a cell population through viral transduction such that each cell integrates into its DNA a single or small number of library perturbations with barcodes identifying the perturbations. One then selects and physically isolates the subset of cells that exhibit the phenotype of interest. Sequencing the barcodes in the hit cells reveals which genes favored or inhibited the hit phenotype...
January 16, 2018: Current Protocols in Molecular Biology
https://www.readbyqxmd.com/read/29336951/design-synthesis-and-evaluation-against-chikungunya-virus-of-novel-small-molecule-antiviral-agents
#20
Roberta Tardugno, Gilda Giancotti, Tine De Burghgraeve, Leen Delang, Johan Neyts, Pieter Leyssen, Andrea Brancale, Marcella Bassetto
Chikungunya virus is a re-emerging arbovirus transmitted to humans by mosquitoes, responsible for an acute flu-like illness associated with debilitating arthralgia, which can persist for several months or become chronic. In recent years, this viral infection has spread worldwide with a previously unknown virulence. To date, no specific antivirals treatments nor vaccines are available against this important pathogen. Starting from the structures of two antiviral hits previously identified in our research group with in silico techniques, this work describes the design and preparation of 31 novel structural analogues, with which different pharmacophoric features of the two hits have been explored and correlated with the inhibition of Chikungunya virus replication in cells...
January 6, 2018: Bioorganic & Medicinal Chemistry
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