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https://www.readbyqxmd.com/read/28812720/antagonistic-pleiotropy-and-mutation-accumulation-influence-human-senescence-and-disease
#1
Juan Antonio Rodríguez, Urko M Marigorta, David A Hughes, Nino Spataro, Elena Bosch, Arcadi Navarro
Senescence has long been a public health challenge as well as a fascinating evolutionary problem. There is neither a universally accepted theory for its ultimate causes, nor a consensus about what may be its impact on human health. Here we test the predictions of two evolutionary explanations of senescence-mutation accumulation and antagonistic pleiotropy-which postulate that genetic variants with harmful effects in old ages can be tolerated, or even favoured, by natural selection at early ages. Using data from genome-wide association studies (GWAS), we study the effects of genetic variants associated with diseases appearing at different periods in life, when they are expected to have different impacts on fitness...
January 30, 2017: Nature ecology & evolution
https://www.readbyqxmd.com/read/28812210/increased-il-6-expression-on-thp-1-by-il-34-stimulation-up-regulated-rheumatoid-arthritis-th17-cells
#2
Bing Wang, Yawei Tang, Xiaotong Sun, Xunli Ouyang, Han Li, Jing Wei, Yan Zhang, Xia Li
IL-34 is a pleiotropic cytokine, which is a key regulator of monocytes/macrophages and might participate in the pathogenesis of RA. In this study, we aimed to explore the effect of IL-34 on the monocyte-like cell line THP-1 and the quantitative variation of Th17 cells in THP-1 and RA CD4(+)T cells coculture system. CD4(+)T cells were purified from RA PBMC using immunomagnetic beads. THP-1 were cultured with RA CD4(+)T cells. The frequency of Th17 cells was determined by FACS. Fluorscence indensity and expression of ROS were detected by FACS and cell staining, respectively...
August 15, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28811884/factors-contributing-to-the-accumulation-of-reproductive-isolation-a-mixed-model-approach
#3
Dean M Castillo
The analysis of large datasets describing reproductive isolation between species has been extremely influential in the study of speciation. However, the statistical methods currently used for these data limit the ability to make direct inferences about the factors predicting the evolution of reproductive isolation. As a result, our understanding of iconic patterns and rules of speciation rely on indirect analyses that have clear statistical limitations. Phylogenetic mixed models are commonly used in ecology and evolution, but have not been applied to studies of reproductive isolation...
August 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/28810834/multiple-trait-qtl-mapping-and-genomic-prediction-for-wool-traits-in-sheep
#4
Sunduimijid Bolormaa, Andrew A Swan, Daniel J Brown, Sue Hatcher, Nasir Moghaddar, Julius H van der Werf, Michael E Goddard, Hans D Daetwyler
BACKGROUND: The application of genomic selection to sheep breeding could lead to substantial increases in profitability of wool production due to the availability of accurate breeding values from single nucleotide polymorphism (SNP) data. Several key traits determine the value of wool and influence a sheep's susceptibility to fleece rot and fly strike. Our aim was to predict genomic estimated breeding values (GEBV) and to compare three methods of combining information across traits to map polymorphisms that affect these traits...
August 15, 2017: Genetics, Selection, Evolution: GSE
https://www.readbyqxmd.com/read/28810704/yeast-kch1-and-kch2-membrane-proteins-play-a-pleiotropic-role-in-membrane-potential-establishment-and-monovalent-cation-homeostasis-regulation
#5
Kristina Felcmanova, Petra Neveceralova, Hana Sychrova, Olga Zimmermannova
The Kch1 and Kch2 plasma-membrane proteins were identified in Saccharomyces cerevisiae as being essential for the activation of a high-affinity Ca2+ influx system. We searched for Kch proteins roles in the maintenance of cation homeostasis and tested the effect of kch1 and/or kch2 deletions on various physiological parameters. Compared to wild-type, kch1 kch2 mutant cells were smaller, relatively hyperpolarised, grew better under limited K+ conditions and exhibited altered growth in the presence of monovalent cations...
August 1, 2017: FEMS Yeast Research
https://www.readbyqxmd.com/read/28808890/vitamin-d-activity-and-metabolism-in-bone
#6
REVIEW
Paul H Anderson
PURPOSE OF REVIEW: In addition to the actions of the endocrine hormone, 1alpha,25-dihydroxyvitamin D (1,25(OH)2D) in stimulating intestinal calcium absorption, the regulation of bone mineral metabolism by 1,25(OH)2D is also considered an important contributor to calcium homeostasis. However, recent evidence suggest that 1,25(OH)2D acting either via endocrine or autocrine pathways plays varied roles in bone, which suggests that vitamin D contributes to the maintenance of bone mineral in addition to its catabolic roles...
August 14, 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/28808141/a-critical-role-for-plasma-kallikrein-in-the-pathogenesis-of-autoantibody-induced-arthritis
#7
Aizhen Yang, Junsong Zhou, Bo Wang, Jihong Dai, Robert W Colman, Wenchao Song, Yi Wu
The plasma kallikrein-kinin system (KKS) consists of serine proteases, prekallikrein (pKal) and factor XII (FXII), and a cofactor, high-MW kininogen (HK). Upon activation, activated pKal and FXII cleave HK to release bradykinin. Activation of this system has been noted in patients with rheumatoid arthritis, and its pathogenic role has been characterized in animal arthritic models. In this study, we generated 2 knockout mouse strains that lacked pKal and HK and determined the role of KKS in autoantibody-induced arthritis...
August 14, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28808135/mutations-in-eif5b-confer-thermosensitive-and-pleiotropic-phenotypes-via-translation-defects-in-arabidopsis-thaliana
#8
Liyuan Zhang, Xinye Liu, Kishor Gaikwad, Xiaoxia Kou, Fei Wang, Xuejun Tian, Mingming Xin, Zhongfu Ni, Qixin Sun, Huiru Peng, Elizabeth Vierling
The conserved eukaryotic translation initiation factor 5B, eIF5B, is a GTPase that acts late in translation initiation. We found that an Arabidopsis thaliana mutant sensitive to hot temperatures 3 (hot3-1), which behaves as wild type in the absence of stress but is unable to acclimate to high temperature, carries a missense mutation in eIF5B1 gene (At1g76810),, producing a temperature sensitive protein. A more severe, T-DNA insertion allele (hot3-2) causes pleiotropic developmental phenotypes. Surprisingly, Arabidopsis has three other eIF5B genes that do not substitute for eIF5B1; two of these appear to be in the process of pseudogenization...
August 14, 2017: Plant Cell
https://www.readbyqxmd.com/read/28808036/reducing-posttreatment-relapse-in-cleft-lip-palatal-expansion-using-an-injectable-estrogen-nanodiamond-hydrogel
#9
Christine Hong, Dayoung Song, Dong-Keun Lee, Lawrence Lin, Hsin Chuan Pan, Deborah Lee, Peng Deng, Zhenqing Liu, Danny Hadaya, Hye-Lim Lee, Abdulaziz Mohammad, Xinli Zhang, Min Lee, Cun-Yu Wang, Dean Ho
Patients with cleft lip and/or palate (CLP), who undergo numerous medical interventions from infancy, can suffer from lifelong debilitation caused by underdeveloped maxillae. Conventional treatment approaches use maxillary expansion techniques to develop normal speech, achieve functional occlusion for nutrition intake, and improve esthetics. However, as patients with CLP congenitally lack bone in the cleft site with diminished capacity for bone formation in the expanded palate, more than 80% of the patient population experiences significant postexpansion relapse...
August 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28805808/constraints-and-consequences-of-the-emergence-of-amino-acid-repeats-in-eukaryotic-proteins
#10
Sreenivas Chavali, Pavithra L Chavali, Guilhem Chalancon, Natalia Sanchez de Groot, Rita Gemayel, Natasha S Latysheva, Elizabeth Ing-Simmons, Kevin J Verstrepen, Santhanam Balaji, M Madan Babu
Proteins with amino acid homorepeats have the potential to be detrimental to cells and are often associated with human diseases. Why, then, are homorepeats prevalent in eukaryotic proteomes? In yeast, homorepeats are enriched in proteins that are essential and pleiotropic and that buffer environmental insults. The presence of homorepeats increases the functional versatility of proteins by mediating protein interactions and facilitating spatial organization in a repeat-dependent manner. During evolution, homorepeats are preferentially retained in proteins with stringent proteostasis, which might minimize repeat-associated detrimental effects such as unregulated phase separation and protein aggregation...
August 14, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28804221/s1p-provokes-tumor-lymphangiogenesis-via-macrophage-derived-mediators-such-as-il-1%C3%AE-or-lipocalin-2
#11
REVIEW
Shahzad N Syed, Michaela Jung, Andreas Weigert, Bernhard Brüne
A pleiotropic signaling lipid, sphingosine-1-phosphate (S1P), has been implicated in various pathophysiological processes supporting tumor growth and metastasis. However, there are only a few descriptive studies suggesting a role of S1P in tumor lymphangiogenesis, which is critical for tumor growth and dissemination. Corroborating own data, the literature suggests that apoptotic tumor cell-derived S1P alters the phenotype of tumor-associated macrophages (TAMs) to gain protumor functions. However, mechanistically, the role of TAM-induced lymphangiogenesis has only been poorly described, mostly linked to the production of lymphangiogenic factors such as vascular endothelial growth factor C (VEGF-C) and VEGF-D, or transdifferentiation into lymphatic endothelial cells...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28801380/vitamin-d-and-immunomodulation-is-it-time-to-change-the-reference-values
#12
Giulia Bivona, Luisa Agnello, Marcello Ciaccio
The term "vitamin D" refers to two chemical compounds - ergosterol, or vitamin D2, and cholecalciferol, or vitamin D3. Active vitamin D3 is correctly regarded as a neurohormone due to its pleiotropic biological activities. Although the relation between vitamin D and calcium-phosphorus metabolism has never been discussed, the knowledge on many other roles vitamin D plays is growing fast. Briefly, vitamin D immunomodulation includes attenuation and stimulation of Th1 and Th2 cell proliferation, respectively. Similarly, vitamin D can induce or inhibit the synthesis, secretion, and release of anti- inflammatory (IL-4 and IL-10) and pro-inflammatory (IL-1, TNF-α, IFN-γ) cytokines, respectively...
August 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/28801314/macrophage-migration-inhibitory-factor-limits-renal-inflammation-and-fibrosis-by-counteracting-tubular-cell-cycle-arrest
#13
Sonja Djudjaj, Ina V Martin, Eva M Buhl, Nina J Nothofer, Lin Leng, Marta Piecychna, Jürgen Floege, Jürgen Bernhagen, Richard Bucala, Peter Boor
Renal fibrosis is a common underlying process of progressive kidney diseases. We investigated the role of macrophage migration inhibitory factor (MIF), a pleiotropic proinflammatory cytokine, in this process. In mice subjected to unilateral ureteral obstruction, genetic deletion or pharmacologic inhibition of MIF aggravated fibrosis and inflammation, whereas treatment with recombinant MIF was beneficial, even in established fibrosis. In two other models of progressive kidney disease, global Mif deletion or MIF inhibition also worsened fibrosis and inflammation and associated with worse kidney function...
August 11, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28800709/the-major-outer-membrane-protein-mopb-is-required-for-twitching-movement-and-affects-biofilm-formation-and-virulence-in-two-xylella-fastidiosa-strains
#14
Hongyu Chen, Prem Prasad Kandel, Luisa Fernanda Cruz, Paul Anthony Cobine, Leonardo De La Fuente
MopB is a major outer membrane protein in Xylella fastidiosa, a bacterial plant pathogen that causes losses on many economically important crops. Based on in silico analysis, the uncharacterized MopB protein of X. fastidiosa contains a β-barrel structure with an OmpA-like domain and a predicted calcium-binding motif. Here, MopB function was studied by mutational analysis taking advantage of the natural competence of X. fastidiosa. Mutants of mopB were constructed in two different X. fastidiosa strains, the type strain 'Temecula' and the more virulent 'WM1-1'...
August 11, 2017: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/28799796/immune-modulation-by-curcumin-the-role-of-interleukin-10
#15
Hamid Mollazadeh, Arrigo F G Cicero, Christopher N Blesso, Matteo Pirro, Muhammed Majeed, Amirhossein Sahebkar
Cytokines are small secreted proteins released by different types of cells with specific effects on cellular signaling and communication via binding to their receptors on the cell surface. IL-10 is known to be a pleiotropic and potent anti-inflammatory and immunosuppressive cytokine that is produced by both innate and adaptive immunity cells including dendritic cells, macrophages, mast cells, natural killer cells, eosinophils, neutrophils, B cells, CD8(+) T cells, and TH1, TH2, and TH17 and regulatory T cells...
August 11, 2017: Critical Reviews in Food Science and Nutrition
https://www.readbyqxmd.com/read/28798752/qtl-analysis-and-nested-association-mapping-for-adult-plant-resistance-to-powdery-mildew-in-two-bread-wheat-populations
#16
Yan Ren, Weixiu Hou, Caixia Lan, Bhoja R Basnet, Ravi P Singh, Wei Zhu, Xiyong Cheng, Dangqun Cui, Feng Chen
CIMMYT wheat (Triticum aestivum L.) lines Francolin#1 and Quaiu#3 displayed effective and stable adult plant resistance (APR) to Chinese Blumeria graminis f. sp. tritici isolates in the field. To elucidate their genetic basis of resistance, two recombinant inbred line (RIL) populations of their crosses with Avocet, the susceptible parent, were phenotyped in Zhengzhou and Shangqiu in the 2014-2015 and 2015-2016 cropping seasons. These populations were also genotyped with SSR (simple sequence repeat markers) and DArT (diversity arrays technology) markers...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28795382/liver-adipose-tissue-crosstalk-a-key-player-in-the-pathogenesis-of-glucolipid-metabolic-disease
#17
De-Wei Ye, Xiang-Lu Rong, Ai-Min Xu, Jiao Guo
Glucolipid metabolic disease (GLMD), a complex of interrelated disorders in glucose and lipid metabolism, has become one of the leading chronic diseases causing public and clinical problem worldwide. As the metabolism of lipid and glucose is a highly coordinated process under both physiological and diseased conditions, the impairment in the signals corresponding to the metabolism of either lipid or glucose represents the common mechanism underlying the pathogenesis of GLMD. The liver and adipose tissue are the major metabolic organs responsible for energy utilization and storage, respectively...
June 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28793350/ifnar2-dependent-gene-expression-profile-induced-by-ifn-%C3%AE-in-pteropus-alecto-bat-cells-and-impact-of-ifnar2-knockout-on-virus-infection
#18
Qian Zhang, Lei-Ping Zeng, Peng Zhou, Aaron T Irving, Shang Li, Zheng-Li Shi, Lin-Fa Wang
Bats are important reservoirs of many viruses, which are capable of infecting the host without inducing obvious clinical diseases. Interferon and the downstream interferon regulated genes (IRGs) are known to act as the first line of defense against viral infections. Little is known about the transcriptional profile of genes being induced by interferon in bats and their role in controlling virus infection. In this study, we constructed IFNAR2 knockout bat cell lines using CRISPR technology and further characterized gene expression profiles induced by the most abundant IFN-α (IFN-α3)...
2017: PloS One
https://www.readbyqxmd.com/read/28792545/contribution-of-independent-and-pleiotropic-genetic-effects-in-the-metabolic-syndrome-in-a-hypertensive-rat
#19
Man Chun John Ma, Janette M Pettus, Jessica A Jakoubek, Matthew G Traxler, Karen C Clark, Amanda K Mennie, Anne E Kwitek
Hypertension is a major risk factor for cardiovascular disease, Type 2 diabetes, and end organ failure, and is often found concomitant with disorders characteristic of the Metabolic Syndrome (MetS), including obesity, dyslipidemia, and insulin resistance. While the associated features often occur together, the pathway(s) or mechanism(s) linking hypertension in MetS are not well understood. Previous work determined that genetic variation on rat chromosome 17 (RNO17) contributes to several MetS-defining traits (including hypertension, obesity, and dyslipidemia) in the Lyon Hypertensive (LH) rat, a genetically determined MetS model...
2017: PloS One
https://www.readbyqxmd.com/read/28792098/identification-of-expression-quantitative-trait-loci-eqtls-in-human-peripheral-blood-mononuclear-cells-pbmcs-and-shared-with-liver-and-brain
#20
Pei He, Wei Xia, Lan Wang, Jian Wu, Yu-Fan Guo, Ke-Qin Zeng, Ming-Jun Wang, Peng-Fei Bing, Fang-Fei Xie, Xin Lu, Yong-Hong Zhang, Shu-Feng Lei, Fei-Yan Deng
PBMCs are essential for immunity and involved in various diseases. To identify genetic variations contributing to PBMCs transcriptome-wide gene expression, we performed a genome-wide eQTL analysis by using genome-wide SNPs data and transcriptome-wide mRNA expression data. To assess whether there are common regulation patterns shared among different tissues/organs, public datasets were utilized to identify common eQTLs shared with PBMCs in lymphoblastoid, monocytes, liver, and brain. Allelic expression imbalance (AEI) assay was employed to validate representative eQTLs identified...
August 9, 2017: Journal of Cellular Biochemistry
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