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https://www.readbyqxmd.com/read/28453927/tir-domain-containing-adapter-inducing-interferon-%C3%AE-trif-forms-filamentous-structures-whose-pro-apoptotic-signalling-is-terminated-by-autophagy
#1
I E Gentle, K T McHenry, A Weber, A Metz, O Kretz, D Porter, G Häcker
The formation of amyloid-like protein structures has recently emerged as a feature in signal transduction, particularly in innate immunity. These structures appear to depend on defined domains for their formation but likely also require dedicated ways to terminate signalling. We here define the innate immunity protein/Toll-like receptor adaptor TRIF as a novel platform of fibril formation and probe signal initiation through TRIF as well as its termination in toll-like receptor 3 (TLR3)-stimulated melanoma cells...
April 28, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28453520/wdr23-regulates-nrf2-independently-of-keap1
#2
Jacqueline Y Lo, Brett N Spatola, Sean P Curran
Cellular adaptation to stress is essential to ensure organismal survival. NRF2/NFE2L2 is a key determinant of xenobiotic stress responses, and loss of negative regulation by the KEAP1-CUL3 proteasome system is implicated in several chemo- and radiation-resistant cancers. Advantageously using C. elegans alongside human cell culture models, we establish a new WDR23-DDB1-CUL4 regulatory axis for NRF2 activity that operates independently of the canonical KEAP1-CUL3 system. WDR23 binds the DIDLID sequence within the Neh2 domain of NRF2 to regulate its stability; this regulation is not dependent on the KEAP1-binding DLG or ETGE motifs...
April 28, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28453376/control-of-the-unfolded-protein-response-in-health-and-disease
#3
Dimitrios Doultsinos, Tony Avril, Stéphanie Lhomond, Nicolas Dejeans, Philippe Guédat, Eric Chevet
The unfolded protein response (UPR) is an integrated, adaptive biochemical process that is inextricably linked with cell homeostasis and paramount to maintenance of normal physiological function. Prolonged accumulation of improperly folded proteins in the endoplasmic reticulum (ER) leads to stress. This is the driving stimulus behind the UPR. As such, prolonged ER stress can push the UPR past beneficial functions such as reduced protein production and increased folding and clearance to apoptotic signaling. The UPR is thus contributory to the commencement, maintenance, and exacerbation of a multitude of disease states, making it an attractive global target to tackle conditions sorely in need of novel therapeutic intervention...
April 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28449351/long-term-plasticity-of-corticostriatal-synapses-is-modulated-by-pathway-specific-co-release-of-opioids-through-kappa-opioid-receptors
#4
Sarah L Hawes, Armando G Salinas, David M Lovinger, Kim T Blackwell
Synaptic plasticity in striatum adjusts behaviour adaptively during skill learning, or maladaptively in the case of addiction. Just as dopamine plays a critical role in synaptic plasticity underlying normal skill learning and addiction, endogenous and exogenous opiates also modulate learning and addiction-related striatal plasticity. Though the role of opioid receptors in long-term depression in striatum has been characterized, their effect on long-term potentiation (LTP) remains unknown. In particular, direct pathway (Dopamine D1 Receptor containing; D1R) - spiny projection neurons (SPNs) co-release the opioid neuropeptide dynorphin, which acts at presynaptic kappa opioid receptors (KORs) on dopaminergic afferents and can negatively regulate dopamine release...
April 27, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28448516/natural-variation-of-pirna-expression-affects-immunity-to-transposable-elements
#5
Sergei Ryazansky, Elizaveta Radion, Anastasia Mironova, Natalia Akulenko, Yuri Abramov, Valeriya Morgunova, Maria Y Kordyukova, Ivan Olovnikov, Alla Kalmykova
In the Drosophila germline, transposable elements (TEs) are silenced by PIWI-interacting RNA (piRNA) that originate from distinct genomic regions termed piRNA clusters and are processed by PIWI-subfamily Argonaute proteins. Here, we explore the variation in the ability to restrain an alien TE in different Drosophila strains. The I-element is a retrotransposon involved in the phenomenon of I-R hybrid dysgenesis in Drosophila melanogaster. Genomes of R strains do not contain active I-elements, but harbour remnants of ancestral I-related elements...
April 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28448515/chronic-cocaine-induces-hif-vegf-pathway-activation-along-with-angiogenesis-in-the-brain
#6
Wei Yin, Kevin Clare, Qiujia Zhang, Nora D Volkow, Congwu Du
Cocaine induces vasoconstriction in cerebral vessels, which with repeated use can result in transient ischemic attacks and cerebral strokes. However, the neuroadaptations that follow cocaine's vasoconstricting effects are not well understood. Here, we investigated the effects of chronic cocaine exposure (2 and 4 weeks) on markers of vascular function and morphology in the rat brain. For this purpose we measured nitric oxide (NO) concentration in plasma, brain neuronal nitric oxide synthase (nNOS or NOS1), HIF-1α, and VEGF expression in different brain regions, i...
2017: PloS One
https://www.readbyqxmd.com/read/28448019/a-tandem-liquid-chromatography-mass-spectrometry-based-approach-for-metabolite-analysis-of-staphylococcus-aureus
#7
David J Samuels, Zhe Wang, Kyu Y Rhee, Shaun R Brinsmade
In an effort to thwart bacterial pathogens, hosts often limit the availability of nutrients at the site of infection. This limitation can alter the abundances of key metabolites to which regulatory factors respond, adjusting cellular metabolism. In recent years, a number of proteins and RNA have emerged as important regulators of virulence gene expression. For example, the CodY protein responds to levels of branched-chain amino acids and GTP and is widely conserved in low G+C Gram-positive bacteria. As a global regulator in Staphylococcus aureus, CodY controls the expression of dozens of virulence and metabolic genes...
March 28, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28447887/cyclopiazonic-acid-is-a-pathogenicity-factor-for-aspergillus-flavus-and-a-promising-target-for-screening-germplasm-for-ear-rot-resistance
#8
Subbaiah C Chalivendra, Catherine DeRobertis, Perng-Kuang Chang, Kenneth E Damann
Aspergillus flavus, an opportunistic pathogen, contaminates maize and other key crops with carcinogenic aflatoxins (AFs). Besides AFs, A. flavus makes many more secondary metabolites (SMs) whose toxicity in insects or vertebrates has been studied. However, the role of SMs in the invasion of plant hosts by A. flavus remains to be investigated. Cyclopiazonic acid (CPA), a neurotoxic SM made by A. flavus, is a nanomolar inhibitor of endoplasmic reticulum calcium ATPases (ECAs) and a potent inducer of cell death in plants...
April 24, 2017: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/28447400/genome-wide-identification-of-pathogenicity-conidiation-and-colony-sectorization-genes-in-metarhizium-robertsii
#9
Guohong Zeng, Xiaoxuan Chen, Xing Zhang, Qiangqiang Zhang, Chuan Xu, Wubin Mi, Na Guo, Hong Zhao, Yue You, Farah-Jade Dryburgh, Michael J Bidochka, Raymond J St Leger, Lei Zhang, Weiguo Fang
Metarhizium robertsii occupies a wide array of ecological niches and has diverse lifestyle options (saprophyte, insect pathogen and plant symbiont), that renders it an unusually effective model for studying genetic mechanisms for fungal adaptation. Here we screened over 20,000 M. robertsii T-DNA mutants in order to elucidate genetic mechanism by which M. robertsii replicates and persists in diverse niches. We identified 287 conidiation, colony sectorization or pathogenicity loci, many of which have not been reported in other fungi...
April 26, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28447364/the-ja-and-aba-signaling-pathways-crosstalk-during-one-but-not-repeated-dehydration-stresses-a-non-specific-panicky-or-a-meaningful-response
#10
Zoya Avramova
Experiencing diverse and recurring biotic and abiotic stresses throughout life, plants have evolved mechanisms to respond, survive and, eventually, adapt to changing habitats. The initial response to drought involves a large number of genes that are involved also in response to other stresses. According to current models, this initial response is non-specific, becoming stress-specific only at later time points. The question, then, is whether non-specific activation of various stress-signaling systems leading to the expression of numerous stresses-regulated genes is a false-alarm ('panicky') response or whether it has biologically relevant consequences for the plant...
April 26, 2017: Plant, Cell & Environment
https://www.readbyqxmd.com/read/28446542/a-proteolytic-regulator-controlling-chalcone-synthase-stability-and-flavonoid-biosynthesis-in-arabidopsis
#11
Xuebin Zhang, Carolina Abrahan, Thomas A Colquhoun, Chang-Jun Liu
Flavonoids represent a large family of specialized metabolites involved in plant growth, development and adaptation. Chalcone synthase (CHS) catalyzes the first step of flavonoid biosynthesis by directing carbon flux from general phenylpropanoid metabolism to flavonoid pathway. Despite extensive characterization on its function and transcriptional regulation, the molecular basis governing its post-translational modification is enigmatic. Here, we report the discovery of a proteolytic regulator of CHS, namely KFBCHS, a Kelch domain-containing F-box protein in Arabidopsis...
April 26, 2017: Plant Cell
https://www.readbyqxmd.com/read/28446242/activity-of-distinct-growth-factor-receptor-network-components-in-breast-tumors-uncovers-two-biologically-relevant-subtypes
#12
Mumtahena Rahman, Shelley M MacNeil, David F Jenkins, Gajendra Shrestha, Sydney R Wyatt, Jasmine A McQuerry, Stephen R Piccolo, Laura M Heiser, Joe W Gray, W Evan Johnson, Andrea H Bild
BACKGROUND: The growth factor receptor network (GFRN) plays a significant role in driving key oncogenic processes. However, assessment of global GFRN activity is challenging due to complex crosstalk among GFRN components, or pathways, and the inability to study complex signaling networks in patient tumors. Here, pathway-specific genomic signatures were used to interrogate GFRN activity in breast tumors and the consequent phenotypic impact of GRFN activity patterns. METHODS: Novel pathway signatures were generated in human primary mammary epithelial cells by overexpressing key genes from GFRN pathways (HER2, IGF1R, AKT1, EGFR, KRAS (G12V), RAF1, BAD)...
April 26, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28446138/assessing-the-complexity-of-interventions-within-systematic-reviews-development-content-and-use-of-a-new-tool-icat_sr
#13
Simon Lewin, Maggie Hendry, Jackie Chandler, Andrew D Oxman, Susan Michie, Sasha Shepperd, Barnaby C Reeves, Peter Tugwell, Karin Hannes, Eva A Rehfuess, Vivien Welch, Joanne E Mckenzie, Belinda Burford, Jennifer Petkovic, Laurie M Anderson, Janet Harris, Jane Noyes
BACKGROUND: Health interventions fall along a spectrum from simple to more complex. There is wide interest in methods for reviewing 'complex interventions', but few transparent approaches for assessing intervention complexity in systematic reviews. Such assessments may assist review authors in, for example, systematically describing interventions and developing logic models. This paper describes the development and application of the intervention Complexity Assessment Tool for Systematic Reviews (iCAT_SR), a new tool to assess and categorise levels of intervention complexity in systematic reviews...
April 26, 2017: BMC Medical Research Methodology
https://www.readbyqxmd.com/read/28445987/context-dependent-mir-204-and-mir-211-affect-the-biological-properties-of-amelanotic-and-melanotic-melanoma-cells
#14
Marianna Vitiello, Andrea Tuccoli, Romina D'Aurizio, Samanta Sarti, Laura Giannecchini, Simone Lubrano, Andrea Marranci, Monica Evangelista, Silvia Peppicelli, Chiara Ippolito, Ivana Barravecchia, Elena Guzzolino, Valentina Montagnani, Michael Gowen, Elisa Mercoledi, Alberto Mercatanti, Laura Comelli, Salvatore Gurrieri, Lawrence W Wu, Omotayo Ope, Keith Flaherty, Genevieve M Boland, Marc R Hammond, Lawrence Kwong, Mario Chiariello, Barbara Stecca, Gao Zhang, Alessandra Salvetti, Debora Angeloni, Letizia Pitto, Lido Calorini, Giovanna Chiorino, Marco Pellegrini, Meenhard Herlyn, Iman Osman, Laura Poliseno
Despite increasing amounts of experimental evidence depicting the involvement of non-coding RNAs in cancer, the study of BRAFV600E-regulated genes has thus far focused mainly on protein-coding ones. Here, we identify and study the microRNAs that BRAFV600E regulates through the ERK pathway.By performing small RNA sequencing on A375 melanoma cells and a vemurafenib-resistant clone that was taken as negative control, we discover miR-204 and miR-211 as the miRNAs most induced by vemurafenib. We also demonstrate that, although belonging to the same family, these two miRNAs have distinctive features...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445834/light-harvesting-antenna-complexes-in-the-moss-physcomitrella-patens-implications-for-the-evolutionary-transition-from-green-algae-to-land-plants
#15
REVIEW
Masakazu Iwai, Makio Yokono
Plants have successfully adapted to a vast range of terrestrial environments during their evolution. To elucidate the evolutionary transition of light-harvesting antenna proteins from green algae to land plants, the moss Physcomitrella patens is ideally placed basally among land plants. Compared to the genomes of green algae and land plants, the P. patens genome codes for more diverse and redundant light-harvesting antenna proteins. It also encodes Lhcb9, which has characteristics not found in other light-harvesting antenna proteins...
April 23, 2017: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/28445535/microrna-125a-3p-is-regulated-by-myd88-in-legionella-pneumophila-infection-and-targets-ntan1
#16
Elisa Jentho, Malena Bodden, Christine Schulz, Anna-Lena Jung, Kerstin Seidel, Bernd Schmeck, Wilhelm Bertrams
BACKGROUND: Legionella pneumophila (L. pneumophila) is a causative agent of severe pneumonia. It is highly adapted to intracellular replication and manipulates host cell functions like vesicle trafficking and mRNA translation to its own advantage. However, it is still unknown to what extent microRNAs (miRNAs) are involved in the Legionella-host cell interaction. METHODS: WT and MyD88-/- murine bone marrow-derived macrophages (BMM) were infected with L. pneumophila, the transcriptome was analyzed by high throughput qPCR array (microRNAs) and conventional qPCR (mRNAs), and mRNA-miRNA interaction was validated by luciferase assays with 3´-UTR mutations and western blot...
2017: PloS One
https://www.readbyqxmd.com/read/28445522/revealing-phenotype-associated-functional-differences-by-genome-wide-scan-of-ancient-haplotype-blocks
#17
Ritsuko Onuki, Rui Yamaguchi, Tetsuo Shibuya, Minoru Kanehisa, Susumu Goto
Genome-wide scans for positive selection have become important for genomic medicine, and many studies aim to find genomic regions affected by positive selection that are associated with risk allele variations among populations. Most such studies are designed to detect recent positive selection. However, we hypothesize that ancient positive selection is also important for adaptation to pathogens, and has affected current immune-mediated common diseases. Based on this hypothesis, we developed a novel linkage disequilibrium-based pipeline, which aims to detect regions associated with ancient positive selection across populations from single nucleotide polymorphism (SNP) data...
2017: PloS One
https://www.readbyqxmd.com/read/28445142/potential-biomarkers-of-dna-replication-stress-in-cancer
#18
Liqun Ren, Long Chen, Wei Wu, Lorenza Garribba, Huanna Tian, Zihui Liu, Ivan Vogel, Chunhui Li, Ian D Hickson, Ying Liu
Oncogene activation is an established driver of tumorigenesis. An apparently inevitable consequence of oncogene activation is the generation of DNA replication stress (RS), a feature common to most cancer cells. RS, in turn, is a causal factor in the development of chromosome instability (CIN), a near universal feature of solid tumors. It is likely that CIN and RS are mutually reinforcing drivers that not only accelerate tumorigenesis, but also permit cancer cells to adapt to diverse and hostile environments...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28444662/early-mitochondrial-adaptations-in-skeletal-muscle-to-obesity-and-obesity-resistance-differentially-regulated-by-high-fat-diet
#19
Jingyu Sun, Tao Huang, Zhengtang Qi, Songhui You, Jingmei Dong, Chen Zhang, Lili Qin, Yunhe Zhou, Shuzhe Ding
The mechanism for different susceptibilities to obesity after short-term high-fat diet (HFD) feeding is largely unknown. Given the close association between obesity occurrence and mitochondrial dysfunction, the early events in skeletal muscle mitochondrial adaptations between HFD-induced obesity (DIO) and HFD-induced obesity resistant (DIO-R) lean phenotype under excess nutritional environment were explored.ICR/JCL male mice were randomly divided into 2 groups, as follows: low-fat diet (LFD) and HFD groups...
April 25, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28444390/characterisation-of-drug-specific-signalling-between-primary-human-hepatocytes-and-immune-cells
#20
Monday O Ogese, Lee Faulkner, Roz E Jenkins, Neil S French, Ian M Copple, Daniel J Antoine, Mohamed Elmasry, Hasan Malik, Christopher E Goldring, B Kevin Park, Catherine Betts, Dean J Naisbitt
It is now apparent that antigen-specific T-cells are activated in certain patients with drug-induced liver injury (DILI). Since cross-talk between hepatocytes and immune cells is likely to be critical in determining the outcome of drug exposure, the aim of this study was to profile the signals released by drug-treated hepatocytes and to characterise the impact of these molecules on dendritic cells. Human hepatocytes were exposed to three drugs (flucloxacillin, amoxicillin and isoniazid) associated with DILI potentially mediated by the adaptive immune system as drug-specific T-cells have been isolated from DILI patients, and the metabolite nitroso-sulfamethoxazole (SMX-NO)...
April 21, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
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