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https://www.readbyqxmd.com/read/28088192/nucleotide-diversity-inflation-as-a-genome-wide-response-to-experimental-lifespan-extension-in-drosophila-melanogaster
#1
Pawel Michalak, Lin Kang, Pernille M Sarup, Mads F Schou, Volker Loeschcke
BACKGROUND: Evolutionary theory predicts that antagonistically selected alleles, such as those with divergent pleiotropic effects in early and late life, may often reach intermediate population frequencies due to balancing selection, an elusive process when sought out empirically. Alternatively, genetic diversity may increase as a result of positive frequency-dependent selection and genetic purging in bottlenecked populations. RESULTS: While experimental evolution systems with directional phenotypic selection typically result in at least local heterozygosity loss, we report that selection for increased lifespan in Drosophila melanogaster leads to an extensive genome-wide increase of nucleotide diversity in the selected lines compared to replicate control lines, pronounced in regions with no or low recombination, such as chromosome 4 and centromere neighborhoods...
January 14, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28087594/a-human-proteome-array-approach-to-identifying-key-host-proteins-targeted-by-toxoplasma-kinase-rop18
#2
Zhaoshou Yang, Yongheng Hou, Taofang Hao, Hee-Sool Rho, Jun Wan, Yizhao Luan, Xin Gao, Jianping Yao, Aihua Pan, Zhi Xie, Jiang Qian, Wanqin Liao, Heng Zhu, Xingwang Zhou
Toxoplasma kinase ROP18 is a key molecule responsible for the virulence of Toxoplasma gondii; however, the mechanisms by which ROP18 exerts parasite virulence via interaction with host proteins remain limited to a small number of identified substrates. To identify a broader array of ROP18 substrates we successfully purified bioactive mature ROP18 and used it to probe a human proteome array. Sixty-eight new putative host targets were identified. Functional annotation analysis suggested that these proteins have a variety of functions including metabolic process, kinase activity and phosphorylation, cell growth, apoptosis and cell death, and immunity, indicating a pleiotropic role of ROP18 kinase...
January 13, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28087332/exo-mfa-a-13c-metabolic-flux-analysis-to-dissect-tumor-microenvironment-secreted-exosome-contributions-towards-cancer-cell-metabolism
#3
Abhinav Achreja, Hongyun Zhao, Lifeng Yang, Tae Hyun Yun, Juan Marini, Deepak Nagrath
Dissecting the pleiotropic roles of tumor micro-environment (TME) on cancer progression has been brought to the foreground of research on cancer pathology. Extracellular vesicles such as exosomes, transport proteins, lipids, and nucleic acids, to mediate intercellular communication between TME components and have emerged as candidates for anti-cancer therapy. We previously reported that cancer-associated fibroblast (CAF) derived exosomes (CDEs) contain metabolites in their cargo that are utilized by cancer cells for central carbon metabolism and promote cancer growth...
January 10, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28087294/bioactive-metabolites-of-docosahexaenoic-acid
#4
REVIEW
Ondrej Kuda
Docosahexaenoic acid (DHA) is an essential fatty acid that is recognized as a beneficial dietary constituent and as a source of the anti-inflammatory specialized proresolving mediators (SPM): resolvins, protectins and maresins. Apart from SPMs, other metabolites of DHA also exert potent biological effects. This article summarizes current knowledge on the metabolic pathways involved in generation of DHA metabolites. Over 70 biologically active metabolites have been described, but are often discussed separately within specific research areas...
January 10, 2017: Biochimie
https://www.readbyqxmd.com/read/28087255/unknown-face-of-known-drugs-what-else-can-we-expect-from-angiotensin-converting-enzyme-inhibitors
#5
REVIEW
Anna Wzgarda, Robert Kleszcz, Monika Prokop, Katarzyna Regulska, Milosz Regulski, Jaroslaw Paluszczak, Beata J Stanisz
The renin-angiotensin system (RAS) is one of important systems among homeostatic mechanisms that controls the function of cardiovascular, renal and adrenal systems. As RAS has a very complex nature, it has been also found as related to the control of cell migration and apoptosis. Angiotensin-converting enzyme inhibitors (ACEI) are drugs most commonly used in the modulation of RAS activity. ACEI have been extensively described as effective in the treatment of hypertension among adults, but also as drugs delaying progression in diabetic nephropathy and reducing mortality in left ventricular dysfunction and congestive heart failure...
January 10, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28086956/differential-expression-of-e-type-prostanoid-receptors-2-and-4-in-microglia-stimulated-with-lipopolysaccharide
#6
Ester Bonfill-Teixidor, Amaia Otxoa-de-Amezaga, Miriam Font-Nieves, M Glòria Sans-Fons, Anna M Planas
BACKGROUND: Cyclooxygenase-2 (COX-2) is induced under inflammatory conditions, and prostaglandin E2 (PGE2) is one of the products of COX activity. PGE2 has pleiotropic actions depending on the activation of specific E-type prostanoid EP1-4 receptors. We investigated the involvement of PGE2 and EP receptors in glial activation in response to an inflammatory challenge induced by LPS. METHODS: Cultures of mouse microglia or astroglia cells were treated with LPS in the presence or absence of COX-2 inhibitors, and the production of PGE2 was measured by ELISA...
January 5, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28081224/resveratrol-impairs-glioma-stem-cells-proliferation-and-motility-by-modulating-the-wnt-signaling-pathway
#7
Chiara Cilibrasi, Gabriele Riva, Gabriele Romano, Massimiliano Cadamuro, Riccardo Bazzoni, Valentina Butta, Laura Paoletta, Leda Dalprà, Mario Strazzabosco, Marialuisa Lavitrano, Roberto Giovannoni, Angela Bentivegna
Glioblastoma multiforme (GBM) is a grade IV astrocytoma and the most common form of malignant brain tumor in adults. GBM remains one of the most fatal and least successfully treated solid tumors: current therapies provide a median survival of 12-15 months after diagnosis, due to the high recurrence rate. Glioma Stem Cells (GSCs) are believed to be the real driving force of tumor initiation, progression and relapse. Therefore, better therapeutic strategies GSCs-targeted are needed. Resveratrol is a polyphenolic phytoalexin found in fruits and vegetables displaying pleiotropic health benefits...
2017: PloS One
https://www.readbyqxmd.com/read/28081206/identifying-pleiotropic-genes-in-genome-wide-association-studies-for-multivariate-phenotypes-with-mixed-measurement-scales
#8
James J Yang, L Keoki Williams, Anne Buu
We propose a multivariate genome-wide association test for mixed continuous, binary, and ordinal phenotypes. A latent response model is used to estimate the correlation between phenotypes with different measurement scales so that the empirical distribution of the Fisher's combination statistic under the null hypothesis is estimated efficiently. The simulation study shows that our proposed correlation estimation methods have high levels of accuracy. More importantly, our approach conservatively estimates the variance of the test statistic so that the type I error rate is controlled...
2017: PloS One
https://www.readbyqxmd.com/read/28079060/intranasal-lactoferrin-enhances-%C3%AE-secretase-dependent-amyloid-precursor-protein-processing-via-the-erk1-2-creb-and-hif-1%C3%AE-pathways-in-an-alzheimer-s-disease-mouse-model
#9
Chuang Guo, Zhao-Hui Yang, Shuai Zhang, Rui Chai, Han Xue, Yan-Hui Zhang, Jia-Yi Li, Zhan-You Wang
Growing evidence suggests that lactoferrin (Lf), an iron-binding glycoprotein, is a pleiotropic functional nutrient. Additionally, Lf was recently implicated as a neuroprotective agent. These properties make Lf a valuable therapeutic candidate for the treatment of Alzheimer's disease (AD). However, the mechanisms regulating the physiological roles of Lf in the pathologic condition of AD remain unknown. In the present study, an APPswe/PS1DE9 transgenic mouse model of AD was used. We explored whether intranasal human Lf (hLf) administration could reduce β-amyloid (Aβ) deposition and ameliorate cognitive decline in this AD model...
January 12, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28078746/a-gly65val-substitution-in-an-actin-ghact_li1-disrupts-cell-polarity-and-f-actin-organization-resulting-in-dwarf-lintless-cotton-plants
#10
Gregory N Thyssen, David D Fang, Rickie B Turley, Christopher B Florane, Ping Li, Christopher P Mattison, Marina Naoumkina
Actin polymerizes to form part of the cytoskeleton and organize polar growth in all eukaryotic cells. Species with numerous actin genes are especially useful for the dissection of actin molecular function due to redundancy and neofunctionalization. Here, we investigated the role of a cotton (Gossypium hirsutum) actin gene in the organization of actin filaments in lobed cotyledon pavement cells and the highly-elongated single-celled trichomes that comprise cotton lint fibers. Using mapping-by-sequencing, virus-induced gene silencing, and molecular modeling, we identified the causative mutation of the dominant dwarf Ligon-lintless Li1 short fiber mutant as a single Gly65Val amino acid substitution in a polymerization domain of an actin gene, GhACT_LI1 (Gh_D04G0865)...
January 12, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28077800/oxidative-stress-induced-by-se-deficient-high-energy-diet-implicates-neutrophil-dysfunction-via-nrf2-pathway-suppression-in-swine
#11
Tianshu Yang, Zeping Zhao, Tianqi Liu, Ziwei Zhang, Pengzu Wang, Shiwen Xu, Xin Gen Len, Anshan Shan
The mechanism of the interaction between Se deficiency and high energy remains limited. The aim of the current study was to identify whether Se-deficient, high-energy diet can induce oxidative stress, and downregulate the Nrf2 pathway and phagocytic dysfunction of neutrophils. We detected the phagocytic activity, ROS production, protein levels of Nrf2 and Nrf2 downstream target genes, and the mRNA levels of 25 selenoproteins, heat shock proteins, and cytokines in neutrophils. Cytokine ELISA kits were used to measure the serum cytokines...
January 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28076367/a-chemogenomic-screen-reveals-novel-snf1p-ampk-independent-regulators-of-acetyl-coa-carboxylase
#12
Bruno L Bozaquel-Morais, Juliana B Madeira, Thiago M Venâncio, Thiago Pacheco-Rosa, Claudio A Masuda, Monica Montero-Lomeli
Acetyl-CoA carboxylase (Acc1p) is a key enzyme in fatty acid biosynthesis and is essential for cell viability. To discover new regulators of its activity, we screened a Saccharomyces cerevisiae deletion library for increased sensitivity to soraphen A, a potent Acc1p inhibitor. The hits identified in the screen (118 hits) were filtered using a chemical-phenotype map to exclude those associated with pleiotropic drug resistance. This enabled the identification of 82 ORFs that are genetic interactors of Acc1p. The main functional clusters represented by these hits were "transcriptional regulation", "protein post-translational modifications" and "lipid metabolism"...
2017: PloS One
https://www.readbyqxmd.com/read/28075554/an-engineered-allele-of-afsq1-facilitates-the-discovery-and-investigation-of-cryptic-natural-products
#13
Martin Daniel-Ivad, Nabeela Hameed, Stephanie Tan, Rachna Dhanjal, Daniel Socko, Patricia Pak, Tomas Gverzdys, Marie A Elliot, Justin R Nodwell
New approaches to antimicrobial discovery are needed to address the growing threat of antibiotic resistance. The Streptomyces genus, a proven source of antibiotics, is recognized as having a large reservoir of untapped secondary metabolic genes, many of which are likely to produce uncharacterized compounds. However, most of these compounds are currently inaccessible, as they are not expressed under standard laboratory conditions. Here we present a novel methodology for activating these 'cryptic' metabolites by heterologously expressing a constitutively active pleiotropic regulator...
January 11, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28074822/pleiotropic-effects-of-statins-in-the-perioperative-setting
#14
REVIEW
George Galyfos, Argyri Sianou, Konstantinos Filis
Statins belong to a specific group of drugs that have been described for their ability to control hyperlipidemia as well as for other pleiotropic effects such as improving vascular endothelial function, inhibition of oxidative stress pathways, and anti-inflammatory actions. Accumulating clinical evidence strongly suggests that statins also have a beneficial effect on perioperative morbidity and mortality. Therefore, this review aims to present all recent and pooled data on statin treatment in the perioperative setting as well as to highlight considerations regarding their indications and therapeutic application...
January 2017: Annals of Cardiac Anaesthesia
https://www.readbyqxmd.com/read/28070752/absence-of-macrophage-migration-inhibitory-factor-reduces-proliferative-retinopathy-in-a-mouse-model
#15
Jing Wang, Jihong Lin, Ulrike Kaiser, Paulus Wohlfart, Hans-Peter Hammes
AIMS: Ischemia-induced neovascularization is the key feature of proliferative diabetic retinopathy. Macrophage migration inhibitory factor (MIF) is a pleiotropic proinflammatory and proangiogenic cytokine, and its levels are elevated in the vitreous of patients with proliferative diabetic retinopathy. In this study, we aimed at investigating the relative potential of MIF in the ischemia-induced retinal neovascularization. METHODS: Both WT and MIF-knockout mice were subjected to the retinopathy of prematurity (ROP) model...
January 9, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28069944/soluble-klotho-binds-monosialoganglioside-to-regulate-membrane-microdomains-and-growth-factor-signaling
#16
George Dalton, Sung-Wan An, Saif I Al-Juboori, Nicole Nischan, Joonho Yoon, Evgenia Dobrinskikh, Donald W Hilgemann, Jian Xie, Kate Luby-Phelps, Jennifer J Kohler, Lutz Birnbaumer, Chou-Long Huang
Soluble klotho, the shed ectodomain of the antiaging membrane protein α-klotho, is a pleiotropic endocrine/paracrine factor with no known receptors and poorly understood mechanism of action. Soluble klotho down-regulates growth factor-driven PI3K signaling, contributing to extension of lifespan, cardioprotection, and tumor inhibition. Here we show that soluble klotho binds membrane lipid rafts. Klotho binding to rafts alters lipid organization, decreases membrane's propensity to form large ordered domains for endocytosis, and down-regulates raft-dependent PI3K/Akt signaling...
January 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28069795/intraflagellar-transport-88-ift88-is-crucial-for-craniofacial-development-in-mice-and-is-a-candidate-gene-for-human-cleft-lip-and-palate
#17
Hua Tian, Jifan Feng, Jingyuan Li, Thach-Vu Ho, Yuan Yuan, Yang Liu, Frederick Brindopke, Jane C Figueiredo, William Magee, Pedro A Sanchez-Lara, Yang Chai
Ciliopathies are pleiotropic human diseases resulting from defects of the primary cilium, and these patients often have cleft lip and palate. IFT88 is required for the assembly and function of the primary cilia, which mediate the activity of key developmental signaling pathways. Through whole exome sequencing of a family of three affected siblings with isolated cleft lip and palate, we discovered that they share a novel missense mutation in IFT88 (c.915G>C, p.E305D), suggesting this gene should be considered a candidate for isolated orofacial clefting...
January 9, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28069396/multi-level-evaluation-of-escherichia-coli-polyphosphate-related-mutants-using-global-transcriptomic-proteomic-and-phenomic-analyses
#18
Macarena Varas, Camilo Valdivieso, Cecilia Mauriaca, Javiera Ortíz-Severín, Alberto Paradela, Ignacio Poblete-Castro, Ricardo Cabrera, Francisco P Chávez
BACKGROUND: Polyphosphate (polyP) is a linear biopolymer found in all living cells. In bacteria, mutants lacking polyphosphate kinase 1 (PPK1), the enzyme responsible for synthesis of most polyP, have many structural and functional defects. However, little is known about the causes of these pleiotropic alterations. The link between ppk1 deletion and those numerous phenotypes observed can be the result of complex molecular interactions that can be elucidated via a systems biology approach...
January 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28068529/impact-of-high-dose-statins-on-vitamin-d-levels-and-platelet-function-in-patients-with-coronary-artery-disease
#19
Monica Verdoia, Patrizia Pergolini, Roberta Rolla, Matteo Nardin, Alon Schaffer, Lucia Barbieri, Veronica Daffara, Paolo Marino, Giorgio Bellomo, Harry Suryapranata, Giuseppe De Luca
BACKGROUND: Statins represent a pivotal treatment in coronary artery disease, offering a reduction in cardiovascular risk even beyond their lipid-lowering action. However, the mechanism of these "pleiotropic" benefits of statins is poorly understood. Vitamin D has been suggested as a potential mediator of the anti-inflammatory, anti-thrombotic and vascular protecting effects of statins. Aim of present study was to assess the impact of a high-intensity statin therapy on vitamin D levels and platelet function in patients with coronary artery disease...
December 28, 2016: Thrombosis Research
https://www.readbyqxmd.com/read/28068429/functional-requirements-for-heparan-sulfate-biosynthesis-in-morphogenesis-and-nervous-system-development-in-c-elegans
#20
Cassandra R Blanchette, Andrea Thackeray, Paola N Perrat, Siegfried Hekimi, Claire Y Bénard
The regulation of cell migration is essential to animal development and physiology. Heparan sulfate proteoglycans shape the interactions of morphogens and guidance cues with their respective receptors to elicit appropriate cellular responses. Heparan sulfate proteoglycans consist of a protein core with attached heparan sulfate glycosaminoglycan chains, which are synthesized by glycosyltransferases of the exostosin (EXT) family. Abnormal HS chain synthesis results in pleiotropic consequences, including abnormal development and tumor formation...
January 2017: PLoS Genetics
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