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https://www.readbyqxmd.com/read/28640878/genetic-loci-associated-with-coronary-artery-disease-harbor-evidence-of-selection-and-antagonistic-pleiotropy
#1
Sean G Byars, Qin Qin Huang, Lesley-Ann Gray, Andrew Bakshi, Samuli Ripatti, Gad Abraham, Stephen C Stearns, Michael Inouye
Traditional genome-wide scans for positive selection have mainly uncovered selective sweeps associated with monogenic traits. While selection on quantitative traits is much more common, very few signals have been detected because of their polygenic nature. We searched for positive selection signals underlying coronary artery disease (CAD) in worldwide populations, using novel approaches to quantify relationships between polygenic selection signals and CAD genetic risk. We identified new candidate adaptive loci that appear to have been directly modified by disease pressures given their significant associations with CAD genetic risk...
June 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28636950/structural-evidence-of-quercetin-multi-target-bioactivity-a-reverse-virtual-screening-strategy
#2
Diego Carvalho, Margot Paulino, Fabio Polticelli, Florencia Arredondo, Robert J Williams, Juan A Abin-Carriquiry
The ubiquitous flavonoid quercetin is broadly recognized for showing diverse biological and health-promoting effects, such as anti-cancer, anti-inflammatory and cytoprotective activities. The therapeutic potential of quercetin and similar compounds for preventing such diverse oxidative stress-related pathologies has been generally attributed to their direct antioxidant properties. Nevertheless, accumulated evidence indicates that quercetin is also able to interact with multiple cellular targets influencing the activity of diverse signaling pathways...
June 18, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28636232/a-genetic-stochastic-process-model-for-genome-wide-joint-analysis-of-biomarker-dynamics-and-disease-susceptibility-with-longitudinal-data
#3
Liang He, Ilya Zhbannikov, Konstantin G Arbeev, Anatoliy I Yashin, Alexander M Kulminski
Unraveling the underlying biological mechanisms or pathways behind the effects of genetic variations on complex diseases remains one of the major challenges in the post-GWAS (where GWAS is genome-wide association study) era. To further explore the relationship between genetic variations, biomarkers, and diseases for elucidating underlying pathological mechanism, a huge effort has been placed on examining pleiotropic and gene-environmental interaction effects. We propose a novel genetic stochastic process model (GSPM) that can be applied to GWAS and jointly investigate the genetic effects on longitudinally measured biomarkers and risks of diseases...
June 21, 2017: Genetic Epidemiology
https://www.readbyqxmd.com/read/28634856/estrogen-receptor-%C3%AE-gene-polymorphism-and-vascular-complications-in-girls-with-type-1-diabetes-mellitus
#4
Bartosz Słomiński, Jolanta Myśliwska, Monika Ryba-Stanisławowska, Maria Skrzypkowska, Małgorzata Myśliwiec
The effect of estrogens is mediated by activation of estrogen receptors (ERs). Because ER-α gene polymorphisms may exert different effects in childhood, we analyzed the associations between the IVS1 -397T>C (PvuII) polymorphism and systemic inflammatory state, proangiogenic factors, frequency of monocyte subsets, lipid profile, blood pressure, and vascular complications in girls with type 1 diabetes mellitus (DM1). We examined 180 young girls with DM1 and 120 healthy age-matched controls. The analysis concerned PvuII polymorphism of the ER-α gene as well as the levels of serum inflammatory markers (CRP, IL-6, TNF-α), proangiogenic factors (VEGF, angiogenin), 17β-estradiol, values of monocyte subsets (CD14(++)CD16(-) and CD14(+)CD16(+)), lipid profile, and blood pressure...
June 20, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28634745/prolactin-function-and-putative-expression-in-the-brain
#5
REVIEW
Erika Alejandra Cabrera-Reyes, Ofelia Limón-Morales, Nadia Alejandra Rivero-Segura, Ignacio Camacho-Arroyo, Marco Cerbón
INTRODUCTION: Prolactin is a peptide hormone mainly synthetized and secreted by the anterior pituitary gland, but also by extrapituitary tissues, such as mammary gland, decidua, prostate, skin, and possibly the brain. Similarly, prolactin receptor is expressed in the pituitary gland, many peripheral tissues, and in contrast to prolactin, its receptor has been consistently detected in several brain regions, such as cerebral cortex, olfactory bulb, hypothalamus, hippocampus, amygdala, among others...
June 20, 2017: Endocrine
https://www.readbyqxmd.com/read/28634570/to-use-or-not-to-use-metformin-in-cerebral-ischemia-a-review-of-the-application-of-metformin-in-stroke-rodents
#6
REVIEW
Isaac Arbeláez-Quintero, Mauricio Palacios
Ischemic strokes are major causes of death and disability. Searching for potential therapeutic strategies to prevent and treat stroke is necessary, given the increase in overall life expectancy. Epidemiological reports indicate that metformin is an oral antidiabetic medication that can reduce the incidence of ischemic events in patients with diabetes mellitus. Its mechanism of action has not been elucidated, but metformin pleiotropic effects involve actions in addition to glycemic control. AMPK activation has been described as one of the pharmacological mechanisms that explain the action of metformin and that lead to neuroprotective effects...
2017: Stroke Research and Treatment
https://www.readbyqxmd.com/read/28630940/fluconazole-induced-ploidy-change-in-cryptococcus-neoformans-results-from-the-uncoupling-of-cell-growth-and-nuclear-division
#7
Sophie Altamirano, Diana Fang, Charles Simmons, Shreyas Sridhar, Peipei Wu, Kaustuv Sanyal, Lukasz Kozubowski
Cryptococcus neoformans is a pathogenic yeast that causes lethal cryptococcal meningitis in immunocompromised patients. One of the challenges in treating cryptococcosis is the development of resistance to azole antifungals. Previous studies linked azole resistance to elevated numbers of copies of critical resistance genes in aneuploid cells. However, how aneuploidy is formed in the presence of azole drugs remains unclear. This study showed that treatment with inhibitory concentrations of an azole drug, fluconazole (FLC), resulted in a significant population of cells with increased DNA content, through the following defects: inhibition of budding, premature mitosis, and inhibition of cytokinesis followed by replication in the mother cell...
May 2017: MSphere
https://www.readbyqxmd.com/read/28629524/endogenous-erythropoietin
#8
Steven J Korzeniewski, Athina Pappas
We sought to briefly describe current models of endogenous erythropoietin (EPO) pleiotropic properties to make four points clear. First, endogenous EPO regulates erythroid cell apoptosis so that red blood cell production is balanced against the number of cells destroyed in order to maintain optimal tissue oxygen levels (i.e., consistent with provision of homeostatic functional signaling information). Second, preclinical and clinical studies alike provide additional evidence of other (i.e., extraerythropoietic) immune-related and growth/trophic properties...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28628558/genetics-of-pleiotropic-effects-of-dexamethasone
#9
Laura B Ramsey, Stan Pounds, Cheng Cheng, Xueyuan Cao, Wenjian Yang, Colton Smith, Seth E Karol, Chengcheng Liu, John C Panetta, Hiroto Inaba, Jeffrey E Rubnitz, Monika L Metzger, Raul C Ribeiro, John T Sandlund, Sima Jeha, Ching-Hon Pui, William E Evans, Mary V Relling
OBJECTIVES: Glucocorticoids such as dexamethasone have pleiotropic effects, including desired antileukemic, anti-inflammatory, or immunosuppressive effects, and undesired metabolic or toxic effects. The most serious adverse effects of dexamethasone among patients with acute lymphoblastic leukemia are osteonecrosis and thrombosis. To identify inherited genomic variation involved in these severe adverse effects, we carried out genome-wide association studies (GWAS) by analyzing 14 pleiotropic glucocorticoid phenotypes in 391 patients with acute lymphoblastic leukemia...
June 16, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28625994/a-small-protein-hemp-is-a-transcriptional-activator-for-hemin-uptake-operon-in-burkholderia-multivorans-atcc-17616
#10
Takuya Sato, Shouta Nonoyama, Akane Kimura, Yuji Nagata, Yoshiyuki Ohtsubo, Masataka Tsuda
Iron and heme play very important roles in various metabolic functions in bacteria, and their intracellular homeostasis is maintained because high concentrations of free forms of these molecules greatly facilitate the Fenton reaction-mediated production of large amounts of reactive oxygen species that severely damage various biomolecules. Ferric uptake regulator (Fur) from Burkholderiamultivorans ATCC 17616 is an iron-responsive global transcriptional regulator, and its fur deletant exhibits pleiotropic phenotypes...
June 16, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28624884/age-at-menarche-and-lung-function-a-mendelian-randomization-study
#11
Dipender Gill, Nuala A Sheehan, Matthias Wielscher, Nick Shrine, Andre F S Amaral, John R Thompson, Raquel Granell, Bénédicte Leynaert, Francisco Gómez Real, Ian P Hall, Martin D Tobin, Juha Auvinen, Susan M Ring, Marjo-Riitta Jarvelin, Louise V Wain, John Henderson, Deborah Jarvis, Cosetta Minelli
A trend towards earlier menarche in women has been associated with childhood factors (e.g. obesity) and hypothesised environmental exposures (e.g. endocrine disruptors present in household products). Observational evidence has shown detrimental effects of early menarche on various health outcomes including adult lung function, but these might represent spurious associations due to confounding. To address this we used Mendelian randomization where genetic variants are used as proxies for age at menarche, since genetic associations are not affected by classical confounding...
June 17, 2017: European Journal of Epidemiology
https://www.readbyqxmd.com/read/28624810/the-p38-pathway-a-major-pleiotropic-cascade-that-transduces-stress-and-metastatic-signals-in-endothelial-cells
#12
REVIEW
Isabelle Corre, François Paris, Jacques Huot
By gating the traffic of molecules and cells across the vessel wall, endothelial cells play a central role in regulating cardiovascular functions and systemic homeostasis and in modulating pathophysiological processes such as inflammation and immunity. Accordingly, the loss of endothelial cell integrity is associated with pathological disorders that include atherosclerosis and cancer. The p38 mitogen-activated protein kinase (MAPK) cascades are major signaling pathways that regulate several functions of endothelial cells in response to exogenous and endogenous stimuli including growth factors, stress and cytokines...
May 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28621039/wbla-a-pleiotropic-regulatory-gene-modulating-morphogenesis-and-daptomycin-production-in-streptomyces-roseosporus
#13
Xingwei Huang, Tingmei Ma, Jun Tian, Lan Shen, Hua Zuo, Changhua Hu, Guojian Liao
AIMS: The wblA gene, encoding a homolog of the WhiB family protein, was identified in the sequenced genome of daptomycin producer S.roseosporus. To explore the function of wblA, we construct wblA disruption strains, complemented strains and overexpression strains to test whether it can affect the production of secondary metabolites and morphogenesis. METHODS AND RESULTS: We constructed disruption strains by homologous recombination in S.roseosporus. The disruption mutant of wblA could block aerial mycelium sporulation and enhance the production of daptomycin by 51%...
June 16, 2017: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/28620008/pten-dicer1-fh-and-their-associated-tumor-susceptibility-syndromes-clinical-features-genetics-and-surveillance-recommendations-in-childhood
#14
REVIEW
Kris Ann P Schultz, Surya P Rednam, Junne Kamihara, Leslie Doros, Maria Isabel Achatz, Jonathan D Wasserman, Lisa R Diller, Laurence Brugières, Harriet Druker, Katherine A Schneider, Rose B McGee, William D Foulkes
PTEN hamartoma tumor syndrome (PHTS), DICER1 syndrome, and hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome are pleiotropic tumor predisposition syndromes that include benign and malignant neoplasms affecting adults and children. PHTS includes several disorders with shared and distinct clinical features. These are associated with elevated lifetime risk of breast, thyroid, endometrial, colorectal, and renal cancers as well as melanoma. Thyroid cancer represents the predominant cancer risk under age 20 years...
June 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28620004/cancer-and-central-nervous-system-tumor-surveillance-in-pediatric-neurofibromatosis-1
#15
REVIEW
D Gareth R Evans, Hector Salvador, Vivian Y Chang, Ayelet Erez, Stephan D Voss, Kami Wolfe Schneider, Hamish S Scott, Sharon E Plon, Uri Tabori
Although the neurofibromatoses consist of at least three autosomal dominantly inherited disorders, neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and schwannomatosis, NF1 represents a multisystem pleiotropic condition very different from the other two. NF1 is a genetic syndrome first manifesting in childhood; affecting multiple organs, childhood development, and neurocognitive status; and presenting the clinician with often complex management decisions that require a multidisciplinary approach. Molecular genetic testing (see article for detailed discussion) is recommended to confirm NF1, particularly in children fulfilling only pigmentary features of the diagnostic criteria...
June 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28619711/igfbp7-deletion-promotes-hepatocellular-carcinoma
#16
Maaged Akiel, Chunqing Guo, Xia Li, Devaraja Rajasekaran, Rachel G Mendoza, Chadia L Robertson, Nidhi Jariwala, Fang Yuan, Mark A Subler, Jolene Windle, Dawn K Garcia, Zhao Lai, Hung-I Harry Chen, Yidong Chen, Shah Giashuddin, Paul B Fisher, Xiang-Yang Wang, Devanand Sarkar
Activation of IGF signaling is a major oncogenic event in diverse cancers, including hepatocellular carcinoma (HCC). In this setting, the insulin-like growth factor binding protein IGFBP7 inhibits IGF signaling by binding the IGF-1 receptor (IGF-1R), functioning as a candidate tumor suppressor. IGFBP7 abrogates tumors by inhibiting angiogenesis and inducing cancer-specific senescence and apoptosis. Here we report that Igfbp7-deficient mice exhibit constitutively active IGF signaling, presenting with pro-inflammatory and immunosuppressive microenvironments and spontaneous liver and lung tumors occurring with increased incidence in carcinogen-treated subjects...
June 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28616771/androgen-supplementation-improves-some-but-not-all-aspects-of-immune-senescence-in-aged-male-macaques
#17
Maham Rais, Randall M Wilson, Henryk F Urbanski, Ilhem Messaoudi
Aging leads to a progressive decline in immune function commonly referred to as immune senescence, which results in increased incidence and severity of infection. In addition, older males experience a significant disruption in their levels of circulating androgens, notably testosterone and dehydroepiandrosterone (DHEA), which has been linked to sarcopenia, osteoporosis, cardiovascular disease, and diabetes. Since sex steroid levels modulate immune function, it is possible that the age-related decline in androgen levels can also affect immune senescence...
June 14, 2017: GeroScience
https://www.readbyqxmd.com/read/28615731/the-role-of-il-6-in-host-defence-against-infections-immunobiology-and-clinical-implications
#18
REVIEW
Stefan Rose-John, Kevin Winthrop, Leonard Calabrese
IL-6 is a pleiotropic cytokine with broad-ranging effects within the integrated immune response. One of the roles of IL-6 is to support immunocompetence, defined as the ability of a host to respond to infections. Understanding the precise role of this cytokine in immunocompetence requires a critical appraisal of data derived from both preclinical and clinical studies. Primary immunodeficiency diseases involving IL-6 or its signalling pathways reveal that IL-6 is critical in the defence against numerous types of pathogens...
July 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28615697/remodeling-of-the-cycling-transcriptome-of-the-oyster-crassostrea-gigas-by-the-harmful-algae-alexandrium-minutum
#19
Laura Payton, Mickael Perrigault, Claire Hoede, Jean-Charles Massabuau, Mohamedou Sow, Arnaud Huvet, Floriane Boullot, Caroline Fabioux, Hélène Hegaret, Damien Tran
As a marine organism, the oyster Crassostrea gigas inhabits a complex biotope governed by interactions between the moon and the sun cycles. We used next-generation sequencing to investigate temporal regulation of oysters under light/dark entrainment and the impact of harmful algal exposure. We found that ≈6% of the gills' transcriptome exhibits circadian expression, characterized by a nocturnal and bimodal pattern. Surprisingly, a higher number of ultradian transcripts were also detected under solely circadian entrainment...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28615505/topological-features-of-a-gene-co-expression-network-predict-patterns-of-natural-diversity-in-environmental-response
#20
David L Des Marais, Rafael F Guerrero, Jesse R Lasky, Samuel V Scarpino
Molecular interactions affect the evolution of complex traits. For instance, adaptation may be constrained by pleiotropic or epistatic effects, both of which can be reflected in the structure of molecular interaction networks. To date, empirical studies investigating the role of molecular interactions in phenotypic evolution have been idiosyncratic, offering no clear patterns. Here, we investigated the network topology of genes putatively involved in local adaptation to two abiotic stressors-drought and cold-in Arabidopsis thaliana Our findings suggest that the gene-interaction topologies for both cold and drought stress response are non-random, with genes that show genetic variation in drought expression response (eGxE) being significantly more peripheral and cold response genes being significantly more central than genes which do not show GxE...
June 14, 2017: Proceedings. Biological Sciences
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