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Peter Vegh, Muzlifah Haniffa
Application of single-cell genomics technologies has revolutionized our approach to study the immune system. Unravelling the functional diversity of immune cells and their coordinated response is key to understanding immunity. Single-cell transcriptomics technologies provide high-dimensional assessment of the transcriptional states of immune cells and have been successfully applied to discover new immune cell types, reveal haematopoietic lineages, identify gene modules dictating immune responses and investigate lymphocyte antigen receptor diversity...
March 14, 2018: Briefings in Functional Genomics
Xu Chen, Stefan Gustafsson, Thomas Whitington, Yan Borné, Erik Lorentzen, Jitong Sun, Peter Almgren, Jun Su, Robert Karlsson, Jie Song, Yi Lu, Yiqiang Zhan, Sara Hägg, Per Svensson, Karin E Smedby, Susan L Slager, Erik Ingelsson, Cecilia M Lindgren, Andrew P Morris, Olle Melander, Thomas Karlsson, Ulf de Faire, Kenneth Caidahl, Gunnar Engström, Lars Lind, Mikael C I Karlsson, Nancy L Pedersen, Johan Frostegård, Patrik K E Magnusson
Phosphorylcholine (PC) is an epitope on oxidized low-density lipoprotein (oxLDL), apoptotic cells and several pathogens like Streptococcus pneumoniae. Immunoglobulin M against PC (IgM anti-PC) has the ability to inhibit uptake of oxLDL by macrophages and increase clearance of apoptotic cells. From our genome-wide association studies (GWAS) in four European-ancestry cohorts, six SNPs in 11q24.1 were discovered (in 3002 individuals) and replicated (in 646 individuals) to be associated with serum level of IgM anti-PC (the leading SNP rs35923643-G, combined beta=0...
March 14, 2018: Human Molecular Genetics
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
Clément Niel, Christine Sinoquet, Christian Dina, Ghislain Rocheleau
Motivation: Large scale genome-wide association studies (GWAS) are tools of choice for discovering associations between genotypes and phenotypes. To date, many studies rely on univariate statistical tests for association between the phenotype and each assayed single nucleotide polymorphism (SNP). However, interaction between SNPs, namely epistasis, must be considered when tackling the complexity of underlying biological mechanisms. Epistasis analysis at large scale entails a prohibitive computational burden when addressing the detection of more than two interacting SNPs...
March 14, 2018: Bioinformatics
Kelsey A Herrmann, Heather T Broihier
Although retrograde neurotrophin signaling has provided an immensely influential paradigm for understanding growth factor signaling in the nervous system, recent studies indicate that growth factors also signal via cell-autonomous, or autocrine, mechanisms. Autocrine signals have been discovered in many neuronal contexts, providing insights into their regulation and function. The growing realization of the importance of cell-autonomous signaling stems from advances in both conditional genetic approaches and in sophisticated analyses of growth factor dynamics, which combine to enable rigorous in vivo dissection of signaling pathways...
March 13, 2018: Current Opinion in Neurobiology
Gregory D Bowden, Kirkwood M Land, Roberta M O'Connor, Heather M Fritz
The apicomplexan parasite Sarcocystis neurona is the primary etiologic agent of equine protozoal myeloencephalitis (EPM), a serious neurologic disease of horses. Many horses in the U.S. are at risk of developing EPM; approximately 50% of all horses in the U.S. have been exposed to S. neurona and treatments for EPM are 60-70% effective. Advancement of treatment requires new technology to identify new drugs for EPM. To address this critical need, we developed, validated, and implemented a high-throughput screen to test 725 FDA-approved compounds from the NIH clinical collections library for anti-S...
February 16, 2018: International Journal for Parasitology, Drugs and Drug Resistance
Julia K Nussbacher, Gene W Yeo
RNA binding proteins (RBPs) interact with primary, precursor, and mature microRNAs (miRs) to influence mature miR levels, which in turn affect critical aspects of human development and disease. To understand how RBPs contribute to miR biogenesis, we analyzed human enhanced UV crosslinking followed by immunoprecipitation (eCLIP) datasets for 126 RBPs to discover miR-encoding genomic loci that are statistically enriched for RBP binding. We find that 92% of RBPs interact directly with at least one miR locus, and that some interactions are cell line specific despite expression of the miR locus in both cell lines evaluated...
March 15, 2018: Molecular Cell
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
Jared T Hammill, Daniel C Scott, Jaeki Min, Michele C Connelly, Gloria Holbrook, Fangyi Zhu, Amy Matheny, Lei Yang, Bhuvanesh Singh, Brenda A Schulman, R Kiplin Guy
We previously discovered and validated a class of piperidinyl ureas that regulate defective in cullin neddylation 1 (DCN1)-dependent neddylation of cullins. Here, we report preliminary structure-activity relationship studies aimed at advancing our high-throughput screen hit into a tractable tool compound for dissecting the effects of acute DCN1-UBE2M inhibition on the NEDD8/cullin pathway. Structure-enabled optimization led to a 100-fold increase in biochemical potency and modestly increased solubility and permeability as compared to our initial hit...
March 16, 2018: Journal of Medicinal Chemistry
Xiang Jiao, Wen Liu, Hovsep Mahdessian, Patrick Bryant, Jenny Ringdahl, Maria Timofeeva, Susan M Farrington, Malcolm Dunlop, Annika Lindblom
Genome-wide association studies (GWAS) have identified dozens of common genetic variants associated with risk of colorectal cancer (CRC). However, the majority of CRC heritability remains unclear. In order to discover low-frequency, high-risk CRC susceptibility variants in Swedish population, we genotyped 1 515 CRC patients enriched for familial cases, and 12 108 controls. Case/control association analysis suggested eight novel variants associated with CRC risk (OR 2.0-17.6, p-value < 2.0E-07), comprised of seven coding variants in genes RAB11FIP5, POTEA, COL27A1, MUC5B, PSMA8, MYH7B, and PABPC1L as well as one variant downstream of NEU1 gene...
2018: PloS One
Elodie Alessandri-Gradt, Fabienne De Oliveira, Marie Leoz, Véronique Lemee, David L Robertson, Felix Feyertag, Paul-Alain Ngoupo, Philippe Mauclere, François Simon, Jean-Christophe Plantier
OBJECTIVES: HIV/1 group P (HIV-1/P) is the last HIV/1 group discovered and to date, comprises only two strains. To obtain new insights into this divergent group, we screened for new infections by developing specific tools, and analysed phenotypic and genotypic properties of the prototypic strain RBF168. In addition, the follow-up of the unique patient monitored so far, has raised the knowledge of the natural history of this infection and its therapeutic management. DESIGN/METHODS: We developed an HIV-1/P specific sero-molecular strategy and screened over 29,498 specimen samples...
March 15, 2018: AIDS
Yimin Wang, Fang Ye, Chanyan Huang, Faling Xue, Yingyuan Li, Shaowei Gao, Zeting Qiu, Si Li, Qinchang Chen, Huaqiang Zhou, Yiyan Song, Wenqi Huang, Wulin Tan, Zhongxing Wang
BACKGROUND: Neuropathic pain is one of the common complications after spinal cord injury (SCI), affecting patients' life quality. The molecular mechanism for neuropathic pain after SCI is still unclear. We aimed to discover potential genes and MicroRNAs(miRNAs) related to neuropathic pain by bioinformatics method. METHODS: Microarray data of GSE69901 were obtained from Gene Expression Omnibus (GEO) database. Peripheral blood samples from patients with or without neuropathic pain after spinal cord injury (SCI) were collected...
March 15, 2018: Clinical Journal of Pain
Kyle L Brown, Billy G Hudson, Paul A Voziyan
PURPOSE OF REVIEW: The purpose of this review is to highlight recent advances in understanding the molecular assembly of basement membranes, as exemplified by the glomerular basement membrane (GBM) of the kidney filtration apparatus. In particular, an essential role of halogens in the basement membrane formation has been discovered. RECENT FINDINGS: Extracellular chloride triggers a molecular switch within non collagenous domains of collagen IV that induces protomer oligomerization and scaffold assembly outside the cell...
March 15, 2018: Current Opinion in Nephrology and Hypertension
G Satta, N Mascia, T Serra, A Salis, L Saba, S Sanna, M G Zucca, E Angelucci, A Gabbas, F Culurgioni, P Pili, E Mura, M Cappai, M G Ennas, P Cocco
We investigated the association between environmental exposure to radiofrequency electromagnetic fields (RF-EMF) and risk of lymphoma subtypes in a case-control study comprised of 322 patients and 444 individuals serving as controls in Sardinia, Italy in 1998-2004. Questionnaire information included the self-reported distance of the three longest held residential addresses from fixed radio-television transmitters and mobile phone base stations. We georeferenced the residential addresses of all study subjects and obtained the spatial coordinates of mobile phone base stations...
March 16, 2018: Radiation Research
Hirofumi Akamatsu, Yakun Yuan, Vladimir A Stoica, Greg Stone, Tiannan Yang, Zijian Hong, Shiming Lei, Yi Zhu, Ryan C Haislmaier, John W Freeland, Long-Qing Chen, Haidan Wen, Venkatraman Gopalan
Using time- and spatially resolved hard x-ray diffraction microscopy, the striking structural and electrical dynamics upon optical excitation of a single crystal of BaTiO_{3} are simultaneously captured on subnanoseconds and nanoscale within individual ferroelectric domains and across walls. A large emergent photoinduced electric field of up to 20×10^{6}  V/m is discovered in a surface layer of the crystal, which then drives polarization and lattice dynamics that are dramatically distinct in a surface layer versus bulk regions...
March 2, 2018: Physical Review Letters
Maria J Gonzalez-Moa, Bieke Van Dorst, Ole Lagatie, Ann Verheyen, Lieven Stuyver, Marco A Biamonte
Three O. volvulus immunogenic peptide sequences recently discovered by peptide microarray were adapted to a lateral flow assay (LFA). The LFA employs gold nanoshells as novel high-contrast reporter nanoparticles and detects a serological response against the 3 peptides, found in OvOC9384, OvOC198, and OvOC5528, respectively. When tested on 118 sera from O. volvulus infected patients and 208 control sera, the LFA was 90, 63, and 98% sensitive for each peptide, respectively, and 99-100% specific vs. samples from healthy volunteers...
March 16, 2018: ACS Infectious Diseases
Chang-Hui Tsao, Chien-Chun Chen, Chen-Han Lin, Hao-Yu Yang, Suewei Lin
The fruit fly can evaluate its energy state and decide whether to pursue food-related cues. Here, we reveal that the mushroom body (MB) integrates hunger and satiety signals to control food-seeking behavior. We have discovered five pathways in the MB essential for hungry flies to locate and approach food. Blocking the MB-intrinsic Kenyon cells (KCs) and the MB output neurons (MBONs) in these pathways impairs food-seeking behavior. Starvation bi-directionally modulates MBON responses to a food odor, suggesting that hunger and satiety controls occur at the KC-to-MBON synapses...
March 16, 2018: ELife
Lisa Wirihana, Anthony Welch, Moira Williamson, Martin Christensen, Shannon Bakon, Judy Craft
BACKGROUND: Phenomenology is a useful methodological approach in qualitative nursing research. It enables researchers to put aside their perceptions of a phenomenon and give meaning to a participant's experiences. Exploring the experiences of others enables previously unavailable insights to be discovered. AIM: To delineate the implementation of Colaizzi's ( 1978 ) method of data analysis in descriptive phenomenological nursing research. DISCUSSION: The use of Colaizzi's method of data analysis enabled new knowledge to be revealed and provided insights into the experiences of nurse academics teaching on satellite campuses...
March 16, 2018: Nurse Researcher
Lorenzo Baronti, Hampus Karlsson, Maja Marušič, Katja Petzold
RNA is becoming more important as an increasing number of functions, both regulatory and enzymatic, are being discovered on a daily basis. As the RNA boom has just begun, most techniques are still in development and changes occur frequently. To understand RNA functions, revealing the structure of RNA is of utmost importance, which requires sample preparation. We review the latest methods to produce and purify a variation of RNA molecules for different purposes with the main focus on structural biology and biophysics...
March 15, 2018: Analytical and Bioanalytical Chemistry
Jean-Nicolas Audet, Lima Kayello, Simon Ducatez, Sara Perillo, Laure Cauchard, Jason T Howard, Lauren A O'Connell, Erich D Jarvis, Louis Lefebvre
Problem solving and innovation are key components of intelligence. We compare wild-caught individuals from two species that are close relatives of Darwin's finches, the innovative Loxigilla barbadensis , and its most closely related species in Barbados, the conservative Tiaris bicolor . We found an all-or-none difference in the problem-solving capacity of the two species. Brain RNA sequencing analyses revealed interspecific differences in genes related to neuronal and synaptic plasticity in the intrapallial neural populations (mesopallium and nidopallium), especially in the nidopallium caudolaterale, a structure functionally analogous to the mammalian prefrontal cortex...
March 2018: Science Advances
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