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https://www.readbyqxmd.com/read/28723843/no-superior-adaptations-to-carbohydrate-periodization-in-elite-endurance-athletes
#1
Kasper Degn Gejl, Line Thams, Mette Hansen, Torben Rokkedal-Lausch, Peter Plomgaard, Lars Nybo, Filip J Larsen, Daniele A Cardinale, Kurt Jensen, Hans-Christer Holmberg, Kristian Vissing, Niels Ørtenblad
PURPOSE: The present study investigated the effects of periodic CHO restriction on endurance performance and metabolic markers in elite endurance athletes. METHODS: Twenty-six male elite endurance athletes (VO2max: 65.0 ml O2[BULLET OPERATOR]kg[BULLET OPERATOR]min) completed 4 weeks of regular endurance training, while matched and randomized into two groups training with (Low) or without (High) carbohydrate (CHO) manipulation three days a week. The CHO manipulation days consisted of a 1-hr high intensity bike session in the morning, recovery for 7 hrs while consuming isocaloric diets containing either high CHO (414±2...
July 19, 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/28723564/the-lysine-acetyltransferase-gcn5-is-required-for-inkt-cell-development-through-egr2-acetylation
#2
Yajun Wang, Chawon Yun, Beixue Gao, Yuanming Xu, Yana Zhang, Yiming Wang, Qingfei Kong, Fang Zhao, Chyung-Ru Wang, Sharon Y R Dent, Jian Wang, Xiangping Xu, Hua-Bin Li, Deyu Fang
The development of CD1d-restricted invariant natural killer T (iNKT) cells, a population that is critical for both innate and adaptive immunity, is regulated by multiple transcription factors, but the molecular mechanisms underlying how the transcriptional activation of these factors are regulated during iNKT development remain largely unknown. We found that the histone acetyltransferase general control non-derepressible 5 (GCN5) is essential for iNKT cell development during the maturation stage. GCN5 deficiency blocked iNKT cell development in a cell-intrinsic manner...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28723416/unravelling-the-pharmacologic-opportunities-and-future-directions-for-targeted-therapies-in-gastro-intestinal-cancers-part-2-neuroendocrine-tumours-hepatocellular-carcinoma-and-gastro-intestinal-stromal-tumours
#3
REVIEW
Cindy Neuzillet, Louis de Mestier, Benoît Rousseau, Olivier Mir, Mohamed Hebbar, Hemant M Kocher, Philippe Ruszniewski, Christophe Tournigand
Until the 1990s, cytotoxic chemotherapy has been the cornerstone of medical therapy for gastrointestinal (GI) cancers. Better understanding of the cancer cell molecular biology has led to the therapeutic revolution of targeted therapies, i.e. monoclonal antibodies or small molecule inhibitors directed against proteins that are specifically overexpressed or mutated in cancer cells. These agents, being more specific to cancer cells, were expected to be less toxic than conventional cytotoxic agents. However, their effects have sometimes been disappointing, due to intrinsic or acquired resistance mechanisms, or to an activity restricted to some tumour settings, illustrating the importance of patient selection and early identification of predictive biomarkers of response to these therapies...
July 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28723241/the-effects-of-stretch-activation-on-ionic-selectivity-of-the-trek-2-k2p-k-channel
#4
Ehsan Nematian-Ardestani, Viwan Jarerattanachat, Prafulla Aryal, Mark S P Sansom, Stephen J Tucker
The TREK-2 (KCNK10) K2P potassium channel can be regulated by variety of polymodal stimuli including pressure. In a recent study, we demonstrated that this mechanosensitive K(+) channel responds to changes in membrane tension by undergoing a major structural change from its 'down' state to the more expanded 'up' state conformation. These changes are mostly restricted to the lower part of the protein within the bilayer, but are allosterically coupled to the primary gating mechanism located within the selectivity filter...
July 19, 2017: Channels
https://www.readbyqxmd.com/read/28722543/comparison-of-ovalbumin-and-ovalbumin-epitope-peptide-for-transdermal-delivery-and-vaccination-mediated-by-the-photothermal-effect-of-gold-nanorods
#5
Aung Thu Haine, Yuji Miyamoto, Taishi Higashi, Keiichi Motoyama, Hidetoshi Arima, Takuro Niidome
Transdermal protein delivery is a powerful and attractive method for protein therapy and dermal vaccination compared with other administrations. However, this delivery method is restricted by the low permeability of the stratum corneum, a hydrophobic barrier that restricts the entry of hydrophilic molecules such as proteins. In this study, we developed an improved gel patch system carrying ovalbumin and ovalbumin epitope peptide, and then compared their permeability into the skin. First, the gel patch was placed on mouse skin to allow contact with the polymer coated gold nanorods and then irradiated by a continuous-wave laser...
July 19, 2017: Journal of Biomaterials Science. Polymer Edition
https://www.readbyqxmd.com/read/28722471/simulated-annealing-molecular-dynamics-and-ligand-receptor-contacts-analysis-for-pharmacophore-modeling
#6
Ma'mon M Hatmal, Mutasem O Taha
AIM: Ligand-based pharmacophore modeling requires long list of inhibitors, while pharmacophores based on single ligand-receptor crystallographic structure can be too restricted or promiscuous. METHODOLOGY: This prompted us to combine simulated annealing molecular dynamics (SAMD) with ligand-receptor contacts analysis as means to construct pharmacophore model(s) from single ligand-receptor complex. Ligand-receptor contacts that survive numerous heating-cooling SAMD cycles are considered critical and are used to guide pharmacophore development...
July 19, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28721198/brd4-inhibition-for-the-treatment-of-pathological-organ-fibrosis
#7
REVIEW
Matthew S Stratton, Saptarsi M Haldar, Timothy A McKinsey
Fibrosis is defined as excess deposition of extracellular matrix, resulting in tissue scarring and organ dysfunction. It is estimated that 45% of deaths in the developed world are due to fibrosis-induced organ failure. Despite the well-accepted role of fibrosis in the pathogenesis of numerous diseases, there are only two US Food and Drug Administration-approved anti-fibrotic therapies, both of which are currently restricted to the treatment of pulmonary fibrosis. Thus, organ fibrosis represents a massive unmet medical need...
2017: F1000Research
https://www.readbyqxmd.com/read/28717316/induced-pluripotent-stem-cell-a-headway-in-reprogramming-with-promising-approach-in-regenerative-biology
#8
REVIEW
N Rawat, M K Singh
Since the embryonic stem cells have knocked the doorsteps, they have proved themselves in the field of science, research, and medicines, but the hovered restrictions confine their application in human welfare. Alternate approaches used to reprogram the cells to the pluripotent state were not up to par, but the innovation of induced pluripotent stem cells (iPSCs) paved a new hope for the researchers. Soon after the discovery, iPSCs technology is undergoing renaissance day by day, i.e., from the use of genetic material to recombinant proteins and now only chemicals are employed to convert somatic cells to iPSCs...
June 2017: Veterinary World
https://www.readbyqxmd.com/read/28717241/sca-1-identifies-a-trophoblast-population-with-multipotent-potential-in-the-mid-gestation-mouse-placenta
#9
Bryony V Natale, Christina Schweitzer, Martha Hughes, Maria A Globisch, Ramie Kotadia, Emilie Tremblay, Priscilla Vu, James C Cross, David R C Natale
Trophoblast stem (TS) cells in the mouse derive from the polar trophectoderm of the blastocyst and persist through early gestation (to E8.5) to support placental development. Further development and growth is proposed to rely on layer-restricted progenitor cells. Stem cell antigen (Sca) -1 is a member of the Ly6 gene family and a known marker of stem cells in both hematopoietic and non-hematopoietic mouse tissues. Having identified that Sca-1 mRNA was highly expressed in mouse TS cells in culture, we found that it was also expressed in a subset of trophoblast within the chorion and labyrinth layer of the mouse placenta...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28717216/random-mutagenesis-analysis-and-identification-of-a-novel-c2h2-type-transcription-factor-from-the-nematode-trapping-fungus-arthrobotrys-oligospora
#10
Dewei Jiang, Jing Zhou, Guizhen Bai, Xinjing Xing, Liyan Tang, Xuewei Yang, Juan Li, Ke-Qin Zhang, Jinkui Yang
Arthrobotrys oligospora is a typical nematode-trapping fungus. In this study, 37 transformants of A. oligospora were obtained by REMI (restriction enzyme mediated integration) method and phenotypic properties of nine transformants were analyzed. The nine transformants showed differences in growth, conidiation, trap formation, stress tolerance, and/or pathogenicity among each other and with those of the parental wild-type strain (WT). The insertional sites of the hph cassette were identified in transformants X5 and X13...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28717032/th17-mediated-cross-protection-against-pneumococcal-carriage-by-vaccination-with-a-variable-antigen
#11
Kirsten Kuipers, Wouter S P Jong, Christa E van der Gaast-de Jongh, Diane Houben, Fred van Opzeeland, Elles Simonetti, Saskia van Selm, Ronald de Groot, Marije I Koenders, Taj Azarian, Elder Pupo, Peter van der Ley, Jeroen D Langereis, Aldert Zomer, Joen Luirink, Marien I de Jonge
Serotype-specific protection against a Streptococcus pneumoniae is an important limitation of the current polysaccharide-based vaccines. To prevent serotype replacement, reduce transmission and limit emergence of new variants, it is essential to induce broad protection and restrict pneumococcal colonization. In this study, we used a prototype vaccine formulation consisting of LPS-detoxified outer membrane vesicles (OMVs) from Salmonella Typhimurium displaying the variable N-terminus of PspA (α1α2) for intranasal vaccination, which induced strong Th17 immunity associated with substantial reduction of pneumococcal colonization...
July 17, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28717010/phosphorylation-of-the-kainate-receptor-kar-auxiliary-subunit-neto2-at-serine-409-regulates-synaptic-targeting-of-the-kar-subunit-gluk1
#12
Richa Madan Lomash, Nengyin Sheng, Yan Li, Roger A Nicoll, Katherine W Roche
Synaptic strength at excitatory synapses is determined by the presence of glutamate receptors (i.e. AMPA, NMDA and kainate receptors) at the synapse. Synaptic strength is modulated by multiple factors including assembly of different receptor subunits, interaction with auxiliary subunits and post translational modifications of either the receptors or their auxiliary subunits. Using mass spectrometry, we find that the intracellular region of neuropilin and tolloid-like proteins (Neto)1 and Neto2, the auxiliary subunits of KARs are phosphorylated by multiple kinases in vitro...
July 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28716935/severe-viral-respiratory-infections-in-children-with-ifih1-loss-of-function-mutations
#13
Samira Asgari, Luregn J Schlapbach, Stéphanie Anchisi, Christian Hammer, Istvan Bartha, Thomas Junier, Geneviève Mottet-Osman, Klara M Posfay-Barbe, David Longchamp, Martin Stocker, Samuel Cordey, Laurent Kaiser, Thomas Riedel, Tony Kenna, Deborah Long, Andreas Schibler, Amalio Telenti, Caroline Tapparel, Paul J McLaren, Dominique Garcin, Jacques Fellay
Viral respiratory infections are usually mild and self-limiting; still they exceptionally result in life-threatening infections in previously healthy children. To investigate a potential genetic cause, we recruited 120 previously healthy children requiring support in intensive care because of a severe illness caused by a respiratory virus. Using exome and transcriptome sequencing, we identified and characterized three rare loss-of-function variants in IFIH1, which encodes an RIG-I-like receptor involved in the sensing of viral RNA...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28716924/insights-into-the-red-algae-and-eukaryotic-evolution-from-the-genome-of-porphyra-umbilicalis-bangiophyceae-rhodophyta
#14
Susan H Brawley, Nicolas A Blouin, Elizabeth Ficko-Blean, Glen L Wheeler, Martin Lohr, Holly V Goodson, Jerry W Jenkins, Crysten E Blaby-Haas, Katherine E Helliwell, Cheong Xin Chan, Tara N Marriage, Debashish Bhattacharya, Anita S Klein, Yacine Badis, Juliet Brodie, Yuanyu Cao, Jonas Collén, Simon M Dittami, Claire M M Gachon, Beverley R Green, Steven J Karpowicz, Jay W Kim, Ulrich Johan Kudahl, Senjie Lin, Gurvan Michel, Maria Mittag, Bradley J S C Olson, Jasmyn L Pangilinan, Yi Peng, Huan Qiu, Shengqiang Shu, John T Singer, Alison G Smith, Brittany N Sprecher, Volker Wagner, Wenfei Wang, Zhi-Yong Wang, Juying Yan, Charles Yarish, Simone Zäuner-Riek, Yunyun Zhuang, Yong Zou, Erika A Lindquist, Jane Grimwood, Kerrie W Barry, Daniel S Rokhsar, Jeremy Schmutz, John W Stiller, Arthur R Grossman, Simon E Prochnik
Porphyra umbilicalis (laver) belongs to an ancient group of red algae (Bangiophyceae), is harvested for human food, and thrives in the harsh conditions of the upper intertidal zone. Here we present the 87.7-Mbp haploid Porphyra genome (65.8% G + C content, 13,125 gene loci) and elucidate traits that inform our understanding of the biology of red algae as one of the few multicellular eukaryotic lineages. Novel features of the Porphyra genome shared by other red algae relate to the cytoskeleton, calcium signaling, the cell cycle, and stress-tolerance mechanisms including photoprotection...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28716903/autophagy-related-protein-vps34-controls-the-homeostasis-and-function-of-antigen-cross-presenting-cd8%C3%AE-dendritic-cells
#15
Vrajesh V Parekh, Sudheer K Pabbisetty, Lan Wu, Eric Sebzda, Jennifer Martinez, Jianhua Zhang, Luc Van Kaer
The class III PI3K Vacuolar protein sorting 34 (Vps34) plays a role in both canonical and noncanonical autophagy, key processes that control the presentation of antigens by dendritic cells (DCs) to naive T lymphocytes. We generated DC-specific Vps34-deficient mice to assess the contribution of Vps34 to DC functions. We found that DCs from these animals have a partially activated phenotype, spontaneously produce cytokines, and exhibit enhanced activity of the classic MHC class I and class II antigen-presentation pathways...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28716826/il-10-producing-infliximab-specific-t-cells-regulate-the-antidrug-t-cell-response-in-exposed-patients
#16
Alessandra Vultaggio, Francesca Nencini, Sara Pratesi, Daniele Cammelli, Maria Totaro, Sergio Romagnani, Enrico Maggi, Andrea Matucci
Infliximab (IFX) is a chimeric mAb that can lead to the appearance of anti-drug Abs. Recent research has identified the presence of circulating IFX-specific T cells in treated patients. The aim of the study was to analyze the functional characteristics of IFX-specific T cells, in particular their capability to produce biologically active regulatory cytokines. Drug-stimulated PBMCs or coculture systems were used to detect memory T cells in treated patients. The cytokines produced by IFX-specific T cells, T cell lines, and T cell clones were evaluated at the mRNA and protein levels...
July 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28716741/inferring-the-shallow-phylogeny-of-true-salamanders-salamandra-by-multiple-phylogenomic-approaches
#17
Ariel Rodríguez, James D Burgon, Mariana Lyra, Iker Irisarri, Denis Baurain, Leon Blaustein, Bayram Göcmen, Sven Künzel, Barbara Mable, Arne W Nolte, Michael Veith, Sebastian Steinfartz, Kathryn R Elmer, Hervé Philippe, Miguel Vences
The rise of high-throughput sequencing techniques provides the unprecedented opportunity to analyse controversial phylogenetic relationships in great depth, but also introduce the risk of being misinterpreted by high node support values influenced by unevenly distributed missing data or unrealistic model assumptions. Here, we use three largely independent phylogenomic data sets to reconstruct the controversial phylogeny of true salamanders of the genus Salamandra. a group of amphibians providing an intriguing model to study the evolution of aposematism and viviparity...
July 14, 2017: Molecular Phylogenetics and Evolution
https://www.readbyqxmd.com/read/28716408/molecular-and-biochemical-characterization-of-a-vigna-mungo-map-kinase-associated-with-mungbean-yellow-mosaic-india-virus-infection-and-deciphering-its-role-in-restricting-the-virus-multiplication
#18
Anju Patel, Nrisingha Dey, Shubho Chaudhuri, Amita Pal
Yellow Mosaic Disease caused by the begomovirus Mungbean Yellow Mosaic India Virus (MYMIV) severely affects many economically important legumes. Recent investigations in Vigna mungo - MYMIV incompatible interaction identified a MAPK homolog in the defense signaling pathway. An important branch of immunity involves phosphorylation by evolutionary conserved Mitogen-activated protein kinases (MAPK) that transduce signals of pathogen invasion to downstream molecules leading to diverse immune responses. However, most of the knowledge of MAPKs is derived from model crops, and functions of these versatile kinases are little explored in legumes...
September 2017: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/28716195/quantitative-assessment-of-social-and-economic-impact-of-african-swine-fever-outbreaks-in-northern-uganda
#19
Erika Chenais, Sofia Boqvist, Ulf Emanuelson, Claudia von Brömssen, Emily Ouma, Tonny Aliro, Charles Masembe, Karl Ståhl, Susanna Sternberg-Lewerin
African swine fever (ASF) is one of the most important pig diseases, causing high case fatality rate and trade restrictions upon reported outbreaks. In Uganda, a low-income country with the largest pig population in East Africa, ASF is endemic. Animal disease impact is multidimensional and include social and economic impact along the value chain. In low-income settings, this impact keep people poor and push those that have managed to escape poverty back again. If the diseases can be controlled, their negative consequences can be mitigated...
September 1, 2017: Preventive Veterinary Medicine
https://www.readbyqxmd.com/read/28715960/histone-methylation-by-set-domain-proteins-in-fungi
#20
Michael Freitag
Histone-modifying enzymes are responsible for regulating transcription, recombination, DNA repair, DNA replication, chromatid cohesion, and chromosome segregation. Fungi are ideally suited for comparative chromatin biology because sequencing of numerous genomes from many clades is coupled to existing rich methodology that allows truly holistic approaches, integrating evolutionary biology with mechanistic molecular biology and ecology, promising applications in medicine or plant pathology. While genome information is rich, mechanistic studies on histone modifications are largely restricted to two yeasts, Saccharomyces cerevisiae and Schizosaccharomyces pombe, and one filamentous fungus, Neurospora crassa-three species that arguably are not representative of this diverse kingdom...
July 17, 2017: Annual Review of Microbiology
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