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https://www.readbyqxmd.com/read/28813417/cmtm6-maintains-the-expression-of-pd-l1-and-regulates-anti-tumour-immunity
#1
Marian L Burr, Christina E Sparbier, Yih-Chih Chan, James C Williamson, Katherine Woods, Paul A Beavis, Enid Y N Lam, Melissa A Henderson, Charles C Bell, Sabine Stolzenburg, Omer Gilan, Stuart Bloor, Tahereh Noori, David W Morgens, Michael C Bassik, Paul J Neeson, Andreas Behren, Phillip K Darcy, Sarah-Jane Dawson, Ilia Voskoboinik, Joseph A Trapani, Jonathan Cebon, Paul J Lehner, Mark A Dawson
Cancer cells exploit the expression of the programmed death-1 (PD-1) ligand 1 (PD-L1) to subvert T-cell-mediated immunosurveillance. The success of therapies that disrupt PD-L1-mediated tumour tolerance has highlighted the need to understand the molecular regulation of PD-L1 expression. Here we identify the uncharacterized protein CMTM6 as a critical regulator of PD-L1 in a broad range of cancer cells, by using a genome-wide CRISPR-Cas9 screen. CMTM6 is a ubiquitously expressed protein that binds PD-L1 and maintains its cell surface expression...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28813411/mammals-divert-endogenous-genotoxic-formaldehyde-into-one-carbon-metabolism
#2
Guillermo Burgos-Barragan, Niek Wit, Johannes Meiser, Felix A Dingler, Matthias Pietzke, Lee Mulderrig, Lucas B Pontel, Ivan V Rosado, Thomas F Brewer, Rebecca L Cordell, Paul S Monks, Christopher J Chang, Alexei Vazquez, Ketan J Patel
The folate-driven one-carbon (1C) cycle is a fundamental metabolic hub in cells that enables the synthesis of nucleotides and amino acids and epigenetic modifications. This cycle might also release formaldehyde, a potent protein and DNA crosslinking agent that organisms produce in substantial quantities. Here we show that supplementation with tetrahydrofolate, the essential cofactor of this cycle, and other oxidation-prone folate derivatives kills human, mouse and chicken cells that cannot detoxify formaldehyde or that lack DNA crosslink repair...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28813025/association-between-promoter-methylation-of-gene-ercc3-and-benzene-hematotoxicity
#3
Min Zheng, Feiliang Lin, Fenxia Hou, Guilan Li, Caiying Zhu, Peiyu Xu, Caihong Xing, Qianfei Wang
Benzene is a primary industrial chemical and a ubiquitous environmental pollutant. ERCC3 is a key player in nucleotide excision repair. Recent studies suggested that site-specific methylation is a possible mechanism of the transcriptional dysregulation by blocking transcription factors binding. We previously found that the average promoter methylation level of ERCC3 was increased in benzene-exposed workers. In order to test whether specific CpG sites of ERCC3 play an important role in benzene-induced epigenetic changes and whether the specific methylation patterns are associated with benzene hematotoxicity, we analyzed the promoter methylation levels of individual CpG sites, transcription factor binding motif and the correlation between aberrant CpG methylation and hematotoxicity in 76 benzene-exposed workers and 24 unexposed controls in China...
August 16, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28812568/gene-expression-plasticity-as-a-mechanism-of-coral-adaptation-to-a-variable-environment
#4
Carly D Kenkel, Mikhail V Matz
Local adaptation is ubiquitous, but the molecular mechanisms that give rise to this ecological phenomenon remain largely unknown. A year-long reciprocal transplant of mustard hill coral (Porites astreoides) between a highly environmentally variable inshore habitat and a more stable offshore habitat demonstrated that populations exhibit phenotypic signatures that are consistent with local adaptation. We characterized the genomic basis of this adaptation in both coral hosts and their intracellular symbionts (Symbiodinium sp...
November 7, 2016: Nature ecology & evolution
https://www.readbyqxmd.com/read/28812395/current-research-on-circular-rnas-associated-with-colorectal-cancer
#5
Penghui Wang, Xiaodong He
Representing a novel type of endogenous noncoding RNAs, circular RNAs (circRNAs) have recently gained much attention for their involvement in multiple biological processes. CircRNAs are ubiquitously expressed in eukaryotic cells and modulate gene expression by acting as sponges of microRNAs (miRNAs) or other proteins, such as RNA-binding proteins (RBPs). Due to their unique structure, circRNAs are more stable than linear RNAs. Expression profiles of circRNAs are associated with clinicopathological characteristics of colorectal cancer patients, such as differentiation, TNM classification and distant metastasis...
August 16, 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28811740/multiple-testing-in-the-context-of-gene-discovery-in-sickle-cell-disease-using-genome-wide-association-studies
#6
Kevin H M Kuo
The issue of multiple testing, also termed multiplicity, is ubiquitous in studies where multiple hypotheses are tested simultaneously. Genome-wide association study (GWAS), a type of genetic association study that has gained popularity in the past decade, is most susceptible to the issue of multiple testing. Different methodologies have been employed to address the issue of multiple testing in GWAS. The purpose of the review is to examine the methodologies employed in dealing with multiple testing in the context of gene discovery using GWAS in sickle cell disease complications...
2017: Genomics Insights
https://www.readbyqxmd.com/read/28811649/spin-selective-transmission-and-devisable-chirality-in-two-layer-metasurfaces
#7
Zhancheng Li, Wenwei Liu, Hua Cheng, Shuqi Chen, Jianguo Tian
Chirality is a nearly ubiquitous natural phenomenon. Its minute presence in most naturally occurring materials makes it incredibly difficult to detect. Recent advances in metasurfaces indicate that they exhibit devisable chirality in novel forms; this finding offers an effective opening for studying chirality and its features in such nanostructures. These metasurfaces display vast possibilities for highly sensitive chirality discrimination in biological and chemical systems. Here, we show that two-layer metasurfaces based on twisted nanorods can generate giant spin-selective transmission and support engineered chirality in the near-infrared region...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811506/an-amphibian-chemical-defense-phenotype-is-inducible-across-life-history-stages
#8
Gary M Bucciarelli, H Bradley Shaffer, David B Green, Lee B Kats
Inducible phenotypic responses to environmental variation are ubiquitous across the tree of life, but it remains an open question whether amphibian chemical defense phenotypes are inducible. Tetrodotoxin (TTX) is a key chemical defense trait in North American and Eurasian newts (Salamandridae). We tested if TTX can be induced by exposing populations of adult and larval California newts (Taricha torosa) to sustained stressful conditions while longitudinally quantifying TTX concentrations. Adult newts rapidly increased chemical defenses in response to simulated predator attacks and consistently maintained elevated TTX concentrations relative to wild, non-captive individuals...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811364/mechanosensing-drives-acuity-of-%C3%AE-%C3%AE-t-cell-recognition
#9
Yinnian Feng, Kristine N Brazin, Eiji Kobayashi, Robert J Mallis, Ellis L Reinherz, Matthew J Lang
T lymphocytes use surface [Formula: see text] T-cell receptors (TCRs) to recognize peptides bound to MHC molecules (pMHCs) on antigen-presenting cells (APCs). How the exquisite specificity of high-avidity T cells is achieved is unknown but essential, given the paucity of foreign pMHC ligands relative to the ubiquitous self-pMHC array on an APC. Using optical traps, we determine physicochemical triggering thresholds based on load and force direction. Strikingly, chemical thresholds in the absence of external load require orders of magnitude higher pMHC numbers than observed physiologically...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28811226/characterization-and-expression-analysis-of-six-interleukin-17-receptor-genes-in-grouper-epinephelus-coioides-after-cryptocaryon-irritans-infection
#10
Biao Jiang, Yan-Wei Li, Ya-Zhou Hu, Heng-Li Luo, An-Xing Li
Interleukin-17 receptors (IL17Rs) mediate the activation of several downstream signal pathways to induce inflammatory response and contribute to the pathology of many autoimmune diseases. In this study, six IL17Rs (IL17RA1, RA2, RB, RC, RD and RE) were cloned and characterized from Epinephelus coioides, an orange-spotted grouper. Multiple sequence alignment and structural analysis revealed that all members of IL17Rs were low in sequence identity with each other. But their structures were conservative in grouper, which contain signal peptide, extracellular FNIII domain (IL17RA1/RA2/RB) or IL-17_R_N domain (IL17RC/RD/RE), transmembrane domain and SEFIR domain in their intracellular region...
August 12, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28810875/role-of-iqgap3-in-metastasis-and-epithelial-mesenchymal-transition-in-human-hepatocellular-carcinoma
#11
Yongjie Shi, Nan Qin, Qiang Zhou, Yanqiu Chen, Sicong Huang, Bo Chen, Gang Shen, Hongyun Jia
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide owing to its high rates of metastasis and recurrence. The oncogene IQ motif-containing GTPase activating protein 3 (IQGAP3) is ubiquitously overexpressed in several human cancers, including liver, ovary, lung, large intestine, gastric, bone marrow, and breast malignancies and is involved in the invasion and metastasis of cancer cells. Therefore, we aimed to determine the biological role and molecular mechanism of IQGAP3 in HCC...
August 15, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28810863/multiple-essential-functions-of-plasmodium-falciparum-actin-1-during-malaria-blood-stage-development
#12
Sujaan Das, Leandro Lemgruber, Chwen L Tay, Jake Baum, Markus Meissner
BACKGROUND: The phylum Apicomplexa includes intracellular parasites causing immense global disease burden, the deadliest of them being the human malaria parasite Plasmodium falciparum, which invades and replicates within erythrocytes. The cytoskeletal protein actin is well conserved within apicomplexans but divergent from mammalian actins, and was primarily reported to function during host cell invasion. However, novel invasion mechanisms have been described for several apicomplexans, and specific functions of the acto-myosin system are being reinvestigated...
August 15, 2017: BMC Biology
https://www.readbyqxmd.com/read/28810203/chemical-activity-and-distribution-of-emerging-pollutants-insights-from-a-multi-compartment-analysis-of-a-freshwater-system
#13
Pedro A Inostroza, Riccardo Massei, Romy Wild, Martin Krauss, Werner Brack
Emerging pollutants are ubiquitous in the aquatic system and may pose risks to aquatic ecosystems. The quantification and prediction of environmental partitioning of these chemicals in aquatic systems between water, sediment and biota is an important step in the comprehensive assessment of their sources and final fates in the environment. In this multi-compartment field study, we applied equilibrium partitioning theory and chemical activity estimates to investigate the predictability of concentrations in Gammarus pulex as a model invertebrate from water and sediment in a typical small central European river...
August 12, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28810045/scleral-buckle-infection-with-pseudallescheria-boydii
#14
Janice C Law, Mark P Breazzano, Dean Eliott
Pseudallescheria boydii is a ubiquitous fungus that infects soft tissues and is known to cause ocular disease, including keratitis and endophthalmitis, in rare cases. In immunocompromised hosts, P. boydii can disseminate to or from the eye and other organs with lethal consequences. Postoperative P. boydii infections have, in rare cases, complicated several types of ocular surgeries in immunocompetent patients, but never for a scleral buckle. The authors present the first case of an infected scleral buckle from P...
August 1, 2017: Ophthalmic Surgery, Lasers & Imaging Retina
https://www.readbyqxmd.com/read/28809841/measuring-neuromuscular-junction-functionality
#15
Emanuele Rizzuto, Simona Pisu, Carmine Nicoletti, Zaccaria Del Prete, Antonio Musarò
Neuromuscular junction (NMJ) functionality plays a pivotal role when studying diseases in which the communication between motor neuron and muscle is impaired, such as aging and amyotrophic lateral sclerosis (ALS). Here we describe an experimental protocol that can be used to measure NMJ functionality by combining two types of electrical stimulation: direct muscle membrane stimulation and the stimulation through the nerve. The comparison of the muscle response to these two different stimulations can help to define, at the functional level, potential alterations in the NMJ that lead to functional decline in muscle...
August 6, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28809666/biomolecular-network-controllability-with-drug-binding-information
#16
Lin Wu, Lingkai Tang, Min Li, Jianxin Wang, Fang-Xiang Wu
Complex networks are ubiquitous in nature. In biological systems, biomolecules interact with each other to form so-called biomolecular networks, which determine the cellular behaviors of living organisms. Controlling the cellular behaviors by regulating certain biomolecules in the network is one of the most concerned problems in systems biology. Recently, the connections between biological networks and structural control theory have been explored, uncovering some interesting biological phenomena. Some researchers have paid attentions to the structural controllability of networks in notion of the minimum steering sets (MSSs)...
July 2017: IEEE Transactions on Nanobioscience
https://www.readbyqxmd.com/read/28809018/fluorescent-quail-a-transgenic-model-system-for-the-dynamic-study-of-avian-development
#17
David Huss, Rusty Lansford
Real-time four-dimensional (4D, xyzt) imaging of cultured avian embryos is an ideal method for investigating the complex movements of cells and tissues during early morphogenesis. While methods that transiently label cells, such as electroporation, are highly useful for dynamic imaging, they can also be limiting due to the number and type of cells that can be effectively targeted. In contrast, the heritable, stable, and long-term expression of a fluorescent protein driven by the exogenous promoter of a transgene overcomes these challenges...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28808882/-1-h-13-c-and-15-n-chemical-shift-assignments-of-saccharomyces-cerevisiae-type-1-thioredoxin-in-the-oxidized-state-by-solution-nmr-spectroscopy
#18
Anwar Iqbal, Fabio C L Almeida
Thioredoxins (Trx) are ubiquitous proteins that regulate several biochemical processes inside the cell. Trx is an important player, displaying oxidoreductase activity and helping to keep and regulate the oxidative state of the cellular environment. Trx also participates in the regulation of many cellular functions, such as DNA synthesis, protection against oxidative stress, cell cycle and signal transduction. The oxidized Trx is the target for another set of proteins, such as thioredoxin reductase (TrR), which used the reductive potential of NADPH...
August 14, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28808553/parasite-and-host-elemental-content-and-parasite-effects-on-host-nutrient-excretion-and-metabolic-rate
#19
Nicole Chodkowski, Randall J Bernot
Ecological stoichiometry uses the mass balance of elements to predict energy and elemental fluxes across different levels of ecological organization. A specific prediction of ecological stoichiometry is the growth rate hypothesis (GRH), which states that organisms with faster growth or reproductive rates will require higher phosphorus content for nucleic acid and protein synthesis. Although parasites are found ubiquitously throughout ecosystems, little is understood about how they affect nutrient imbalances in ecosystems...
August 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/28808241/specific-calpain-inhibition-protects-kidney-against-inflammaging
#20
Guillaume Hanouna, Laurent Mesnard, Sophie Vandermeersch, Joëlle Perez, Sandrine Placier, Jean-Philippe Haymann, Fabien Campagne, Julien Moroch, Aurélien Bataille, Laurent Baud, Emmanuel Letavernier
Calpains are ubiquitous pro-inflammatory proteases, whose activity is controlled by calpastatin, their specific inhibitor. Transgenic mice over-expressing rabbit calpastatin (CalpTG) are protected against vascular remodelling and angiotensin II-dependent inflammation. We hypothesized that specific calpain inhibition would protect against aging-related lesions in arteries and kidneys. We analysed tissues from 2-months and 2-years-old CalpTG and wild-type mice and performed high throughput RNA-Sequencing of kidney tissue in aged mice...
August 14, 2017: Scientific Reports
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