Sample records for factors affecting susceptibility

  1. ENVIRONMENTAL FACTORS AFFECTING BREAST CANCER SUSCEPTIBILITY

    EPA Science Inventory

    Environmental Factors Affecting Breast Cancer Susceptibility
    Suzanne. E. Fenton
    US EPA, ORD, MD-67 NHEERL, Reproductive Toxicology Division, Research Triangle Park, NC 27711.

    Breast cancer is still the most common malignancy afflicting women in the Western world. Alt...

  2. FACTORS AFFECTING SUSCEPTIBILITY OF THE CORAL MONTASTRAEA FAVEOLATE TO BLACK-BAND DISEASE

    EPA Science Inventory

    Black-band disease affects many species of tropical reef-building corals, but it is unclear what factors contribute to the disease-susceptibility of individual corals or how the disease is transmitted between colonies. Studies have suggested that the ability of black-band disease...

  3. The Role of Abcb5 Alleles in Susceptibility to Haloperidol-Induced Toxicity in Mice and Humans

    PubMed Central

    Zheng, Ming; Zhang, Haili; Dill, David L.; Clark, J. David; Tu, Susan; Yablonovitch, Arielle L.; Tan, Meng How; Zhang, Rui; Rujescu, Dan; Wu, Manhong; Tessarollo, Lino; Vieira, Wilfred; Gottesman, Michael M.; Deng, Suhua; Eberlin, Livia S.; Zare, Richard N.; Billard, Jean-Martin; Gillet, Jean-Pierre; Li, Jin Billy; Peltz, Gary

    2015-01-01

    Background We know very little about the genetic factors affecting susceptibility to drug-induced central nervous system (CNS) toxicities, and this has limited our ability to optimally utilize existing drugs or to develop new drugs for CNS disorders. For example, haloperidol is a potent dopamine antagonist that is used to treat psychotic disorders, but 50% of treated patients develop characteristic extrapyramidal symptoms caused by haloperidol-induced toxicity (HIT), which limits its clinical utility. We do not have any information about the genetic factors affecting this drug-induced toxicity. HIT in humans is directly mirrored in a murine genetic model, where inbred mouse strains are differentially susceptible to HIT. Therefore, we genetically analyzed this murine model and performed a translational human genetic association study. Methods and Findings A whole genome SNP database and computational genetic mapping were used to analyze the murine genetic model of HIT. Guided by the mouse genetic analysis, we demonstrate that genetic variation within an ABC-drug efflux transporter (Abcb5) affected susceptibility to HIT. In situ hybridization results reveal that Abcb5 is expressed in brain capillaries, and by cerebellar Purkinje cells. We also analyzed chromosome substitution strains, imaged haloperidol abundance in brain tissue sections and directly measured haloperidol (and its metabolite) levels in brain, and characterized Abcb5 knockout mice. Our results demonstrate that Abcb5 is part of the blood-brain barrier; it affects susceptibility to HIT by altering the brain concentration of haloperidol. Moreover, a genetic association study in a haloperidol-treated human cohort indicates that human ABCB5 alleles had a time-dependent effect on susceptibility to individual and combined measures of HIT. Abcb5 alleles are pharmacogenetic factors that affect susceptibility to HIT, but it is likely that additional pharmacogenetic susceptibility factors will be discovered. Conclusions ABCB5 alleles alter susceptibility to HIT in mouse and humans. This discovery leads to a new model that (at least in part) explains inter-individual differences in susceptibility to a drug-induced CNS toxicity. PMID:25647612

  4. HLA non-class II genes may confer type I diabetes susceptibility in a Mapuche (Amerindian) affected family.

    PubMed

    Pérez-Bravo, Francisco; Martinez-Laso, Jorge; Martin-Villa, Jose M; Moscoso, Juan; Moreno, Almudena; Serrano-Vela, Juan I; Zamora, Jorge; Asenjo, Silvia; Gleisner, Andrea; Arnaiz-Villena, Antonio

    2006-01-01

    A rare case of type I diabetes is studied in an Amerindian (Mapuche) family from Chile, analyzing glutamic acid decarboxylase, islet-cell autoantibodies and human leukocyte antigen (HLA) genes. The affected sib is the only one that has one specific HLA haplotype combination that differs from the other sibs only in the HLA class I genes. It is concluded that HLA diabetes susceptibility factors may be placed outside the class II region or even that susceptibility factors do not exist in the HLA region in this Amerindian family.

  5. Adolescents' Susceptibility to Peer Pressure: Relations to Parent-Adolescent Relationship and Adolescents' Emotional Autonomy from Parents

    ERIC Educational Resources Information Center

    Chan, Siu Mui; Chan, Kwok-Wai

    2013-01-01

    Studies on factors affecting susceptibility to peer pressure are not plentiful although this susceptibility has been found to be associated with youth problems such as substance use and risky sexual behavior. The present study examined how adolescents' susceptibility to peer pressure is related to their relationships with mothers and emotional…

  6. Digital Dermatitis in Dairy Cows: A Review of Risk Factors and Potential Sources of Between-Animal Variation in Susceptibility

    PubMed Central

    Palmer, Maeve A.; O’Connell, Niamh E.

    2015-01-01

    Simple Summary Dairy cow lameness is a major problem for the industry, causing reduced animal welfare and economic loss. Digital dermatitis (DD) is a bacterial disease causing painful lesions, generally on the heels of the rear feet, and is an important cause of lameness. There appears to be individual variation between animals in susceptibility to this disease. Particular physical, physiological and behavioural factors might influence individual susceptibility, but further work is required to clarify the influence of these factors and to determine how this information could be used to develop breeding and management strategies to reduce DD prevalence. Abstract Digital dermatitis (DD) is a bacterial disease that primarily affects the skin on the heels of cattle. It is a major cause of lameness in dairy cows and a significant problem for the dairy industry in many countries, causing reduced animal welfare and economic loss. A wide range of infection levels has been found on infected farms, prompting investigations into both farm level and animal level risk factors for DD occurrence. There also appears to be individual variation between animals in susceptibility to the disease. The identification of factors affecting individual variation in susceptibility to DD might allow changes in breeding policies or herd management which could be used to reduce DD prevalence. Factors mentioned in the literature as possibly influencing individual variation in susceptibility to DD include physical factors such as hoof conformation and properties of the skin, physiological factors such as the efficacy of the immune response, and behavioural factors such as standing half in cubicles. Further work is required to determine the influence of these factors, identify the genetic basis of variation, clarify the level of heritability of DD susceptibility and to determine how this is correlated with production and health traits currently used in breeding programmes. PMID:26479371

  7. A combined oral contraceptive affects mucosal SHIV susceptibility factors in a pigtail macaque model

    PubMed Central

    Ostergaard, Sharon Dietz; Butler, Katherine; Ritter, Jana M.; Johnson, Ryan; Sanders, Jeanine; Powell, Nathaniel; Lathrop, George; Zaki, Sherif R.; McNicholl, Janet M.; Kersh, Ellen N.

    2015-01-01

    Background Injectable hormonal contraception may increase women’s risk of HIV acquisition, and can affect biological risk factors in animal models of HIV. We established, for the first time, a model to investigate whether combined oral contraceptives (COC) alter SHIV susceptibility in macaques. Methods Seven pigtail macaques were administered a monophasic levonorgestrel (LNG)/ethinyl estradiol (EE) COC at 33% or 66% of the human dose for 60 days. Menstrual cycling, vaginal epithelial thickness and other SHIV susceptibility factors were monitored for a mean of 18 weeks. Results Mean vaginal epithelial thicknesses was 290.8 μm at baseline and 186.2 μm during COC (p=0.0141, Mann Whitney test). Vaginal pH decreased from 8.5 during to 6.5 post- treatment (0.0176 two-tailed t-test). Measured microflora was unchanged. Conclusions COC caused thinning of the vaginal epithelium and vaginal pH changes, which may increase SHIV susceptibility. 0.033 mg LNG + 0.0066 mg EE appeared effective in suppressing ovulation. PMID:25536296

  8. Biomarkers of susceptibility: State of the art and implications for occupational exposure to engineered nanomaterials

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Iavicoli, Ivo, E-mail: ivo.iavicoli@unina.it

    Rapid advances and applications in nanotechnology are expected to result in increasing occupational exposure to nano-sized materials whose health impacts are still not completely understood. Scientific efforts are required to identify hazards from nanomaterials and define risks and precautionary management strategies for exposed workers. In this scenario, the definition of susceptible populations, which may be at increased risk of adverse effects may be important for risk assessment and management. The aim of this review is to critically examine available literature to provide a comprehensive overview on susceptibility aspects potentially affecting heterogeneous responses to nanomaterials workplace exposure. Genetic, genotoxic and epigeneticmore » alterations induced by nanomaterials in experimental studies were assessed with respect to their possible function as determinants of susceptibility. Additionally, the role of host factors, i.e. age, gender, and pathological conditions, potentially affecting nanomaterial toxicokinetic and health impacts, were also analysed. Overall, this review provides useful information to obtain insights into the nanomaterial mode of action in order to identify potentially sensitive, specific susceptibility biomarkers to be validated in occupational settings and addressed in risk assessment processes. The findings of this review are also important to guide future research into a deeper characterization of nanomaterial susceptibility in order to define adequate risk communication strategies. Ultimately, identification and use of susceptibility factors in workplace settings has both scientific and ethical issues that need addressing. - Highlights: • To define susceptible populations is important for risk assessment and management; • Genetic susceptibility may influence the individual response to nanomaterial exposure; • Susceptibility factors in workplace settings have both scientific and ethical issues.« less

  9. Innate Resistance and Susceptibility to Norovirus Infection

    DOE PAGES

    Nordgren, Johan; Sharma, Sumit; Kambhampati, Anita; ...

    2016-04-26

    The notion that certain individuals appear more or less susceptible to infections or to specific microbes is not new, but, until recently, it was assumed that clinical outcome of an infection was mainly owing to virulence factors of the microorganism. Relatively little attention has been given to host genetic factors involved in innate or adaptive immunity or expression of pathogen receptors. A remarkable example of susceptibility dependence is the strong Mendelian trait resistance to the most common noroviruses among individuals with a nonsense mutation in chromosome 19. Norovirus is recognized as the leading cause of gastroenteritis worldwide, affecting children andmore » adults alike. Noroviruses are highly contagious and genetically diverse RNA viruses, but not all individuals are susceptible to infection to the same norovirus genotypes. Presence of histo-blood group antigens (HBGAs) on gut epithelial surfaces is essential for susceptibility to many norovirus genotypes. The synthesis of these HBGAs, specifically of the ABH and Lewis families, requires the use of several fucosyl and glycosyltransferases encoded by the FUT2, FUT3, and ABH genes. Polymorphisms in these genes vary considerably depending on ethnicity, with a homozygous nonsense mutation (individuals called non-secretors) in the FUT2 gene occurring in approximately 5%–50% of different populations worldwide. Secretor status also affects gut microbiota composition, including HBGA-expressing bacteria and bacteria inducing fucosylation in the gut. These could be intermediary factors that govern norovirus susceptibility.« less

  10. Innate Resistance and Susceptibility to Norovirus Infection

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nordgren, Johan; Sharma, Sumit; Kambhampati, Anita

    The notion that certain individuals appear more or less susceptible to infections or to specific microbes is not new, but, until recently, it was assumed that clinical outcome of an infection was mainly owing to virulence factors of the microorganism. Relatively little attention has been given to host genetic factors involved in innate or adaptive immunity or expression of pathogen receptors. A remarkable example of susceptibility dependence is the strong Mendelian trait resistance to the most common noroviruses among individuals with a nonsense mutation in chromosome 19. Norovirus is recognized as the leading cause of gastroenteritis worldwide, affecting children andmore » adults alike. Noroviruses are highly contagious and genetically diverse RNA viruses, but not all individuals are susceptible to infection to the same norovirus genotypes. Presence of histo-blood group antigens (HBGAs) on gut epithelial surfaces is essential for susceptibility to many norovirus genotypes. The synthesis of these HBGAs, specifically of the ABH and Lewis families, requires the use of several fucosyl and glycosyltransferases encoded by the FUT2, FUT3, and ABH genes. Polymorphisms in these genes vary considerably depending on ethnicity, with a homozygous nonsense mutation (individuals called non-secretors) in the FUT2 gene occurring in approximately 5%–50% of different populations worldwide. Secretor status also affects gut microbiota composition, including HBGA-expressing bacteria and bacteria inducing fucosylation in the gut. These could be intermediary factors that govern norovirus susceptibility.« less

  11. Modeling landslide susceptibility in data-scarce environments using optimized data mining and statistical methods

    NASA Astrophysics Data System (ADS)

    Lee, Jung-Hyun; Sameen, Maher Ibrahim; Pradhan, Biswajeet; Park, Hyuck-Jin

    2018-02-01

    This study evaluated the generalizability of five models to select a suitable approach for landslide susceptibility modeling in data-scarce environments. In total, 418 landslide inventories and 18 landslide conditioning factors were analyzed. Multicollinearity and factor optimization were investigated before data modeling, and two experiments were then conducted. In each experiment, five susceptibility maps were produced based on support vector machine (SVM), random forest (RF), weight-of-evidence (WoE), ridge regression (Rid_R), and robust regression (RR) models. The highest accuracy (AUC = 0.85) was achieved with the SVM model when either the full or limited landslide inventories were used. Furthermore, the RF and WoE models were severely affected when less landslide samples were used for training. The other models were affected slightly when the training samples were limited.

  12. Personality factors in older women's perceived susceptibility to diseases of aging.

    PubMed

    Gerend, Mary A; Aiken, Leona S; West, Stephen G

    2004-04-01

    Personality correlates of older women's perceived susceptibility to breast cancer, heart disease, and osteoporosis were examined in a community sample of 312 women aged 40-86. A latent factor of general perceived susceptibility to disease was shown to underlie disease-specific perceptions of susceptibility. Affect-related personality traits (neuroticism, extraversion, optimism, worry, and self-deceptive enhancement) and internal and chance health locus of control predicted general perceived susceptibility. Perceived disease characteristics (e.g., perceived controllability, severity) and the use of cognitive heuristics (i.e., perceived similarity to those who contract each disease) also displayed marked consistency across the three distinct diseases. Finally, our results suggested that general beliefs about the characteristics of health threats and the use of cognitive heuristics may mediate the link between personality traits and perceived risk.

  13. A model to estimate effects of SNPs on host susceptibility and infectivity for an endemic infectious disease.

    PubMed

    Biemans, Floor; de Jong, Mart C M; Bijma, Piter

    2017-06-30

    Infectious diseases in farm animals affect animal health, decrease animal welfare and can affect human health. Selection and breeding of host individuals with desirable traits regarding infectious diseases can help to fight disease transmission, which is affected by two types of (genetic) traits: host susceptibility and host infectivity. Quantitative genetic studies on infectious diseases generally connect an individual's disease status to its own genotype, and therefore capture genetic effects on susceptibility only. However, they usually ignore variation in exposure to infectious herd mates, which may limit the accuracy of estimates of genetic effects on susceptibility. Moreover, genetic effects on infectivity will exist as well. Thus, to design optimal breeding strategies, it is essential that genetic effects on infectivity are quantified. Given the potential importance of genetic effects on infectivity, we set out to develop a model to estimate the effect of single nucleotide polymorphisms (SNPs) on both host susceptibility and host infectivity. To evaluate the quality of the resulting SNP effect estimates, we simulated an endemic disease in 10 groups of 100 individuals, and recorded time-series data on individual disease status. We quantified bias and precision of the estimates for different sizes of SNP effects, and identified the optimum recording interval when the number of records is limited. We present a generalized linear mixed model to estimate the effect of SNPs on both host susceptibility and host infectivity. SNP effects were on average slightly underestimated, i.e. estimates were conservative. Estimates were less precise for infectivity than for susceptibility. Given our sample size, the power to estimate SNP effects for susceptibility was 100% for differences between genotypes of a factor 1.56 or more, and was higher than 60% for infectivity for differences between genotypes of a factor 4 or more. When disease status was recorded 11 times on each animal, the optimal recording interval was 25 to 50% of the average infectious period. Our model was able to estimate genetic effects on susceptibility and infectivity. In future genome-wide association studies, it may serve as a starting point to identify genes that affect disease transmission and disease prevalence.

  14. Biomarkers of susceptibility: State of the art and implications for occupational exposure to engineered nanomaterials

    PubMed Central

    Iavicoli, Ivo; Leso, Veruscka; Schulte, Paul A.

    2016-01-01

    Rapid advances and applications in nanotechnology are expected to result in increasing occupational exposure to nano-sized materials whose health impacts are still not completely understood. Scientific efforts are required to identify hazards from nanomaterials and define risks and precautionary management strategies for exposed workers. In this scenario, the definition of susceptible populations, which may be at increased risk of adverse effects may be important for risk assessment and management. The aim of this review is to critically examine available literature to provide a comprehensive overview on susceptibility aspects potentially affecting heterogeneous responses to nanomaterials workplace exposure. Genetic, genotoxic and epigenetic alterations induced by nanomaterials in experimental studies were assessed with respect to their possible function as determinants of susceptibility. Additionally, the role of host factors, i.e. age, gender, and pathological conditions, potentially affecting nanomaterial toxicokinetic and health impacts, were also analysed. Overall, this review provides useful information to obtain insights into the nanomaterial mode of action in order to identify potentially sensitive, specific susceptibility biomarkers to be validated in occupational settings and addressed in risk assessment processes. The findings of this review are also important to guide future research into a deeper characterization of nanomaterial susceptibility in order to define adequate risk communication strategies. Ultimately, identification and use of susceptibility factors in workplace settings has both scientific and ethical issues that need addressing. PMID:26724381

  15. Effect of environmental and physiological factors on the antibacterial activity of Curvularia haloperoxidase system against Escherichia coli.

    PubMed

    Hansen, E H; Schäfer, T; Molin, S; Gram, L

    2005-01-01

    The aim of this study was to investigate the influence of environmental and physiological factors on the susceptibility of Escherichia coli to the Curvularia haloperoxidase system. The Curvularia haloperoxidase system is a novel enzyme system that produces reactive oxygen species which have an antimicrobial effect. Escherichia coli MG1655 was exposed to the Curvularia haloperoxidase system under different temperatures and NaCl concentrations and after exposure to different stress factors. Temperature clearly affected enzymatic activity with increasing antibacterial effect at increasing temperature. The presence of NaCl interfered with the enzyme system and in the presence of 1% NaCl, no antibacterial effect could be observed at pH 7. Cells grown at pH 8.0 were in one experiment more resistant than cells grown at pH 6.5, whereas cells grown in the presence of 2% NaCl were more susceptible to the Curvularia haloperoxidase system. Environmental and physiological factors can affect the antibacterial activity of the Curvularia haloperoxidase system. The study demonstrates a systematic approach in assessing the effect of environmental and physiological factors on microbial susceptibility to biocides. Such information is crucial for prediction of application as well as potential side-effects.

  16. Genetics of Paget's disease of bone

    PubMed Central

    Albagha, Omar ME

    2015-01-01

    Paget's disease of bone (PDB) is a common metabolic bone disease characterised by focal areas of increased bone turnover, which primarily affects people over the age of 55 years. Genetic factors have a fundamental role in the pathogenesis of PDB and are probably the main predisposing factor for the disease. The genetic contribution to PDB susceptibility ranges from rare pathogenic mutations in the single gene SQSTM1 to more common, small effect variants in at least seven genetic loci that predispose to the disease. These loci have additive effects on disease susceptibility and interact with SQSTM1 mutations to affect disease severity, making them a potentially useful tool in predicting disease risk and complication and in managing treatments. Many of these loci harbour genes that have important function in osteoclast differentiation such as CSF1, DCSTAMP and TNFRSF11A. Other susceptibility loci have highlighted new molecular pathways that have not been previously implicated in regulation of bone metabolism such as OPTN, which was recently found to negatively regulate osteoclast differentiation. PDB-susceptibility variants exert their effect either by affecting the protein coding sequence such as variants found in SQSTM1 and RIN3 or by influencing gene expression such as those found in OPTN and DCSTAMP. Epidemiological studies indicate that environmental triggers also have a key role in PDB and interact with genetic factors to influence manifestation and severity of the disease; however, further studies are needed to identify these triggers. PMID:26587225

  17. Biomarkers of susceptibility: State of the art and implications for occupational exposure to engineered nanomaterials.

    PubMed

    Iavicoli, Ivo; Leso, Veruscka; Schulte, Paul A

    2016-05-15

    Rapid advances and applications in nanotechnology are expected to result in increasing occupational exposure to nano-sized materials whose health impacts are still not completely understood. Scientific efforts are required to identify hazards from nanomaterials and define risks and precautionary management strategies for exposed workers. In this scenario, the definition of susceptible populations, which may be at increased risk of adverse effects may be important for risk assessment and management. The aim of this review is to critically examine available literature to provide a comprehensive overview on susceptibility aspects potentially affecting heterogeneous responses to nanomaterials workplace exposure. Genetic, genotoxic and epigenetic alterations induced by nanomaterials in experimental studies were assessed with respect to their possible function as determinants of susceptibility. Additionally, the role of host factors, i.e. age, gender, and pathological conditions, potentially affecting nanomaterial toxicokinetic and health impacts, were also analysed. Overall, this review provides useful information to obtain insights into the nanomaterial mode of action in order to identify potentially sensitive, specific susceptibility biomarkers to be validated in occupational settings and addressed in risk assessment processes. The findings of this review are also important to guide future research into a deeper characterization of nanomaterial susceptibility in order to define adequate risk communication strategies. Ultimately, identification and use of susceptibility factors in workplace settings has both scientific and ethical issues that need addressing. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. DIESEL EXHAUST ENHANCES INFLUENZA VIRUS INFECTIONS IN RESPIRATORY EPITHELIAL CELLS

    EPA Science Inventory

    Several factors, such as age and nutritional status can affect the susceptibility to influenza infections. Moreover, exposure to air pollutants, such as diesel exhaust (DE), has been shown to affect respiratory virus infections in rodent models. Influenza virus primarily infects ...

  19. Nutrition affects insect susceptibility to Bt toxins

    NASA Astrophysics Data System (ADS)

    Deans, Carrie A.; Behmer, Spencer T.; Tessnow, Ashley E.; Tamez-Guerra, Patricia; Pusztai-Carey, Marianne; Sword, Gregory A.

    2017-01-01

    Pesticide resistance represents a major challenge to global food production. The spread of resistance alleles is the primary explanation for observations of reduced pesticide efficacy over time, but the potential for gene-by-environment interactions (plasticity) to mediate susceptibility has largely been overlooked. Here we show that nutrition is an environmental factor that affects susceptibility to Bt toxins. Protein and carbohydrates are two key macronutrients for insect herbivores, and the polyphagous pest Helicoverpa zea self-selects and performs best on diets that are protein-biased relative to carbohydrates. Despite this, most Bt bioassays employ carbohydrate-biased rearing diets. This study explored the effect of diet protein-carbohydrate content on H. zea susceptibility to Cry1Ac, a common Bt endotoxin. We detected a 100-fold increase in LC50 for larvae on optimal versus carbohydrate-biased diets, and significant diet-mediated variation in survival and performance when challenged with Cry1Ac. Our results suggest that Bt resistance bioassays that use ecologically- and physiologically-mismatched diets over-estimate susceptibility and under-estimate resistance.

  20. AMBIENT COARSE PARTICULATE MATTER ASSOCIATED WITH HEMATOLOGIC FACTORS IN ADULT ASTHMATICS

    EPA Science Inventory

    Introduction: The elderly and those with cardiovascular disease are susceptible to particulate matter (PM) exposures. Asthmatics are thought to be primarily affected by PM via airway inflammation. We investigated whether factors in blood hemostasis change in response to fluctuat...

  1. Disease spread in age structured populations with maternal age effects.

    PubMed

    Clark, Jessica; Garbutt, Jennie S; McNally, Luke; Little, Tom J

    2017-04-01

    Fundamental ecological processes, such as extrinsic mortality, determine population age structure. This influences disease spread when individuals of different ages differ in susceptibility or when maternal age determines offspring susceptibility. We show that Daphnia magna offspring born to young mothers are more susceptible than those born to older mothers, and consider this alongside previous observations that susceptibility declines with age in this system. We used a susceptible-infected compartmental model to investigate how age-specific susceptibility and maternal age effects on offspring susceptibility interact with demographic factors affecting disease spread. Our results show a scenario where an increase in extrinsic mortality drives an increase in transmission potential. Thus, we identify a realistic context in which age effects and maternal effects produce conditions favouring disease transmission. © 2017 The Authors Ecology Letters published by CNRS and John Wiley & Sons Ltd.

  2. Cultural Contributors to Smoking Susceptibility Outcomes Among Latino Youth: The Padres Informados/Jovenes Preparados Participatory Trial.

    PubMed

    Allen, Michele L; Hurtado, G Ali; Garcia-Huidobro, Diego; Davey, Cynthia; Forster, Jean; Reynoso, Ursula; Alvarez de Davila, Silvia; Linares, Roxana; Gonzales, Nancy; Veronica Svetaz, María

    Padres Informados/Jovenes Preparados is a community-based participatory, family-focused tobacco prevention intervention for immigrant Latino families of adolescents. We conducted a participatory randomized controlled trial including 352 Latino families. Parents and youth in the intervention condition engaged in eight family skill building sessions. Participants completed baseline and 6-month postintervention surveys assessing smoking susceptibility and contextual factors. While the intervention did not affect smoking susceptibility overall, it resulted in lower smoking susceptibility among youth in families with less adherence to traditional Latino cultural values. This family cultural orientation is a key consideration for tobacco prevention interventions focused on Latino youth.

  3. Factors Contributing To Genetic Variation In Ice Damage Susceptibility In Shortleaf Pine

    Treesearch

    Ronald C. Schmidtling; Valerie Hipkins

    2002-01-01

    There are differences among species in susceptibility to ice damage (Williston 1974). There is also at least one report on within-species variation, where coastal Ioblolly pine was damaged more than interior seed sources in an ice storm (Jones and Wells 1969). Of ail the maladies affecting the growth and s&ival of southern pines. damage from ice storms is one of...

  4. Triglyceride level affecting shared susceptibility genes in metabolic syndrome and coronary artery disease.

    PubMed

    Kisfali, P; Polgár, N; Sáfrány, E; Sümegi, K; Melegh, B I; Bene, J; Wéber, A; Hetyésy, K; Melegh, B

    2010-01-01

    Metabolic syndrome is characterized primarily by abdominal obesity, high triglyceride- and low HDL cholesterol levels, elevated blood pressure, and increased fasting glucose levels, which are often associated with coronary heart diseases. Several factors, such as physical inactivity, age, and several endocrine and genetic factors can increase the risk of the development of the disease. Gathered evidence shows, that metabolic syndrome is not only a risk factor for cardiovascular disease, but often both of them have the same shared susceptibility genes, as several genetic variants have shown a predisposition to both diseases. Due to the spread of robust genome wide association studies, the number of candidate genes in metabolic syndrome and coronary heart disease susceptibility increases very rapidly. From the growing spectrum of the genes influencing lipid metabolism (like the LPL; PPARA; APOE; APOAI/CIII/AIV genecluster and APOAS5), the current review focuses on shared susceptibility variants involved in triglyceride metabolism and consequently the effects on the circulating triglyceride levels. As the elevated levels of triglycerides can be associated with disease phenotypes, some of these SNPs can have susceptibility features in both metabolic syndrome and in coronary heart disease, thereby some of them can even represent a kind of susceptibility link between metabolic syndrome and coronary artery disease.

  5. Relationships between microstructure and microfissuring in alloy 718

    NASA Technical Reports Server (NTRS)

    Thompson, R. G.

    1985-01-01

    Microfissures which occur in the weld heat affected zone of alloy 718 can be a limiting factor in the material's weldability. Several studies have attempted to relate microfissuring susceptibility to processing conditions, microstructure, and/or heat-to-heat chemistry differences. The present investigation studies the relationships between microstructure and microfissuring by isolating a particular microstructural feature and measuring microfissuring as a function of that feature. Results to date include the identification of a microstructure-microfissure sequence, microfissuring susceptibility as a function of grain size, and microfissuring susceptibility as a function of solution annealing time.

  6. New Genetic Susceptibility Factors for Sjögren's Syndrome Revealed

    MedlinePlus

    ... 5, 2014 The most common symptoms of Sjögren’s syndrome are dry eyes and mouth, but the disease can affect other ... is difficult to diagnose because its main characteristics—dry eyes and ... Sjögren’s syndrome affects ten times more women than men, suggesting ...

  7. Landslide susceptibility mapping using a bivariate statistical model in a tropical hilly area of southeastern Brazil

    NASA Astrophysics Data System (ADS)

    Araújo, J. P. C.; DA Silva, L. M.; Dourado, F. A. D.; Fernandes, N.

    2015-12-01

    Landslides are the most damaging natural hazard in the mountainous region of Rio de Janeiro State in Brazil, responsible for thousands of deaths and important financial and environmental losses. However, this region has currently few landslide susceptibility maps implemented on an adequate scale. Identification of landslide susceptibility areas is fundamental in successful land use planning and management practices to reduce risk. This paper applied the Bayes' theorem based on weight of evidence (WoE) using 8 landslide-related factors in a geographic information system (GIS) for landslide susceptibility mapping. 378 landslide locations were identified and mapped on a selected basin in the city of Nova Friburgo, triggered by the January 2011 rainfall event. The landslide scars were divided into two subsets: training and validation subsets. The 8 landslide-related factors weighted by WoE were performed using chi-square test to indicate which variables are conditionally independent of each other to be used in the final map. Finally, the maps of weighted factors were summed up to construct the landslide susceptibility map and validated by the validation landslide subset. According to the results, slope, aspect and contribution area showed the higher positive spatial correlation with landslides. In the landslide susceptibility map, 21% of the area presented very low and low susceptibilities with 3% of the validation scars, 41% presented medium susceptibility with 22% of the validation scars and 38% presented high and very high susceptibilities with 75% of the validation scars. The very high susceptibility class stands for 16% of the basin area and has 54% of the all scars. The approach used in this study can be considered very useful since 75% of the area affected by landslides was included in the high and very high susceptibility classes.

  8. Hydrogen Embrittlement Susceptibility and Safety Control of Reheated CGHAZ in X80 Welded Pipeline

    NASA Astrophysics Data System (ADS)

    Deng, Qiushi; Zhao, Weimin; Jiang, Wei; Zhang, Timing; Li, Tingting; Zhao, Yujiao

    2018-03-01

    Coarse-grained heat-affected zone (CGHAZ) exhibits the highest hydrogen embrittlement (HE) susceptibility, which changes under the influence of thermal cycle. In this study, slow strain rate tension (SSRT) tests were conducted to investigate the HE susceptibility of reheated CGHAZs and the critical hydrogen pressure for fracture failure. Results show that intercritically reheated CGHAZ (ICCGHAZ) possesses the lowest HE resistance. Analyses of HE index and fracture indicate that the critical hydrogen pressure is 3.5 MPa. Microstructure analysis reveals that HE susceptibility is associated with multiple factors, such as phase composition, grain coarsening, HAB density, and MA constituent. Blocky necklace-like MA constituent along prior austenite boundaries plays a predominant role in intensifying the HE susceptibility of ICCGHAZ.

  9. Impact of Herbicides on Heterodera glycines Susceptible and Resistant Soybean Cultivars.

    PubMed

    Bradley, C A; Noel, G R; Grau, C R; Gaska, J M; Kurtzweil, N C; Macguidwin, A E; Wax, L M; Hartman, G L; Pedersen, W L

    2003-03-01

    Several abiotic and biotic stresses can affect soybean in a growing season. Heterodera glycines, soybean cyst nematode, reduces yield of soybean more than any other pathogen in the United States. Field and greenhouse studies were conducted to determine whether preemergence and postemergence herbicides modified the reproduction of H. glycines, and to determine the effects of possible interactive stresses caused by herbicides and H. glycines on soybean growth and yield. Heterodera glycines reproduction factor (Rf) generally was less on resistant than susceptible cultivars, resulting in a yield advantage for resistant cultivars. The yield advantage of resistant cultivars was due to more pods per plant on resistant than susceptible cultivars. Pendimethalin reduced H. glycines Rf on the susceptible cultivars in 1998 at Champaign, Illinois, and in greenhouse studies reduced dry root weight of H. glycines-resistant and susceptible cultivars, therefore reducing Rf on the susceptible cultivars. The interactive stresses from acifluorfen or imazethapyr and H. glycines reduced the dry shoot weight of the resistant cultivar Jack in a greenhouse study. Herbicides did not affect resistant cultivars' ability to suppress H. glycines Rf; therefore, growers planting resistant cultivars should make herbicide decisions based on weeds present and cultivar tolerance to the herbicide.

  10. Predictors of youth e-cigarette use susceptibility in a U.S. nationally representative sample.

    PubMed

    Kwon, Elizabeth; Seo, Dong-Chul; Lin, Hsien-Chang; Chen, Zhongxue

    2018-07-01

    Given that nicotine is one of the most addictive substances and that adolescents who are exposed to nicotine via e-cigarettes can progress to conventional cigarette smoking, there is a need to identify youth who are susceptible to e-cigarette use and prevent them from initiating e-cigarette use. Susceptibility to e-cigarette use, defined as the absence of a firm decision not to use e-cigarettes, is a useful concept that can be used to predict e-cigarette initiation and identify youth who have high risk of initiating e-cigarettes. This study was conducted to investigate factors that affect youth susceptibility to e-cigarette use. Youth who have never smoked conventional cigarettes and who had seen or heard of e-cigarettes but never used them (N = 9853) were drawn from the Population Assessment of Tobacco and Health (PATH) Study Wave 1 youth dataset collected from 2013 to 2014. Data were analyzed using logistic regression to investigate intrapersonal and environmental determinants of youth susceptibility to e-cigarette use. Overall, 24.2% (n = 2410) of youth who have never used e-cigarettes were susceptible to e-cigarette use. Psychological problems and rebelliousness were associated with increased susceptibility. Ever use of alcohol, marijuana, and other substances and household secondhand smoke exposure were found to be risk factors. Perceptions of e-cigarettes as addictive and harmful worked as protective factors. The results revealed determinants of e-cigarette use susceptibility. Multi-level intervention approach is needed to prevent youth from being susceptible to e-cigarette initiation. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Imperative of preventive measures addressing the life-cycle.

    PubMed

    Yajnik, Chittaranjan S

    2009-01-01

    The epidemiological characteristics of chronic non-communicable diseases (NCD) are fast changing. The prevalence has risen to unprecedented levels, and the young and the underprivileged are increasingly affected. The classic view of the etiology of NCD consists of a genetic susceptibility which is precipitated by aging and modern lifestyle. In a virtual absence of any methods to tackle genetic susceptibility, the preventive approach has so far been focused on the control of lifestyle factors in those at high risk (old, and those with positive family history and elevated risk factors). Such an approach might help high risk individuals, but is unlikely to curtail the burgeoning epidemic of obesity and diabetes. Recent research has suggested that susceptibility to NCD originates in early life through non-genetic mechanisms (fetal programming). Tackling these may offer an exciting opportunity to control the NCD epidemic by influencing the susceptibility in a more durable manner than only controlling the lifestyle factors in adult life. The imperative is to address the life cycle rather than concentrate on the end stages. Copyright (c) 2009 S. Karger AG, Basel.

  12. Cultural Contributors to Smoking Susceptibility Outcomes Among Latino Youth: The Padres Informados/Jovenes Preparados Participatory Trial

    PubMed Central

    Hurtado, G. Ali; Garcia-Huidobro, Diego; Davey, Cynthia; Forster, Jean; Reynoso, Ursula; de Davila, Silvia Alvarez; Linares, Roxana; Gonzales, Nancy; Svetaz, María Veronica

    2017-01-01

    Introduction Padres Informados/Jovenes Preparados (PIJP) is a community-based participatory, family-focused tobacco prevention intervention for immigrant Latino families of adolescents. Design A participatory randomized controlled trial including 352 Latino families. Parents and youth of intervention families engaged in family skill-building sessions. Outcomes Participants completed baseline and six month post-intervention surveys assessing smoking susceptibility and contextual factors. Results While the intervention did not affect smoking susceptibility overall, it resulted in lower smoking susceptibility among youth in families with less adherence to traditional Latino cultural values. Conclusions Family cultural orientation is a key consideration for tobacco prevention interventions focused on Latino youth. PMID:28207680

  13. Adolescent Neurobiological Susceptibility to Social Context

    PubMed Central

    Schriber, Roberta A.; Guyer, Amanda E.

    2016-01-01

    Adolescence has been characterized as a period of heightened sensitivity to social contexts. However, adolescents vary in how their social contexts affect them. According to neurobiological susceptibility models, endogenous, biological factors confer some individuals, relative to others, with greater susceptibility to environmental influences, whereby more susceptible individuals fare the best or worst of all individuals, depending on the environment they encounter (e.g., high vs. low parental warmth). Until recently, research guided by these theoretical frameworks has not incorporated direct measures of brain structure or function to index this sensitivity. Drawing on prevailing models of adolescent neurodevelopment and a growing number of neuroimaging studies on the interrelations among social contexts, the brain, and developmental outcomes, we review research that supports the idea of adolescent neurobiological susceptibility to social context for understanding why and how adolescents differ in development and well-being. We propose that adolescent development is shaped in part by brain-based individual differences in sensitivity to social contexts – be they positive or negative – such as those created through relationships with parents/caregivers and peers. As such, we recommend that future research measure brain function and structure to operationalize susceptibility factors that moderate the influence of social contexts on developmental outcomes. PMID:26773514

  14. Susceptibility to Phytophthora ramorum in a key infectious host: landscape variation in host genotype, host phenotype, and environmental factors.

    PubMed

    Anacker, Brian L; Rank, Nathan E; Hüberli, Daniel; Garbelotto, Matteo; Gordon, Sarah; Harnik, Tami; Whitkus, Richard; Meentemeyer, Ross

    2008-01-01

    Sudden oak death is an emerging forest disease caused by the invasive pathogen Phytophthora ramorum. Genetic and environmental factors affecting susceptibility to P. ramorum in the key inoculum-producing host tree Umbellularia californica (bay laurel) were examined across a heterogeneous landscape in California, USA. Laboratory susceptibility trials were conducted on detached leaves and assessed field disease levels for 97 host trees from 12 225-m(2) plots. Genotype and phenotype characteristics were assessed for each tree. Effects of plot-level environmental conditions (understory microclimate, amount of solar radiation and topographic moisture potential) on disease expression were also evaluated. Susceptibility varied significantly among U. californica trees, with a fivefold difference in leaf lesion size. Lesion size was positively related to leaf area, but not to other phenotypic traits or to field disease level. Genetic diversity was structured at three spatial scales, but primarily among individuals within plots. Lesion size was significantly related to amplified fragment length polymorphism (AFLP) markers, but local environment explained most variation in field disease level. Thus, substantial genetic variation in susceptibility to P. ramorum occurs in its principal foliar host U. californica, but local environment mediates expression of susceptibility in nature.

  15. Factors that affect proliferation of Salmonella in tomatoes post-harvest: the roles of seasonal effects, irrigation regime, crop and pathogen genotype.

    PubMed

    Marvasi, Massimiliano; Hochmuth, George J; Giurcanu, Mihai C; George, Andrée S; Noel, Jason T; Bartz, Jerry; Teplitski, Max

    2013-01-01

    Fresh fruits and vegetables become increasingly recognized as vehicles of human salmonellosis. Physiological, ecological, and environmental factors are all thought to contribute to the ability of Salmonella to colonize fruits and vegetables pre- and post-harvest. The goal of this study was to test how irrigation levels, fruit water congestion, crop and pathogen genotypes affect the ability of Salmonella to multiply in tomatoes post-harvest. Fruits from three tomato varieties, grown over three production seasons in two Florida locations, were infected with seven strains of Salmonella and their ability to multiply post-harvest in field-grown tomatoes was tested. The field experiments were set up as a two-factor factorial split plot experiment, with the whole-plot treatments arranged in a randomized complete-block design. The irrigation treatment (at three levels) was the whole-plot factor, and the split-plot factor was tomato variety, with three levels. The significance of the main, two-way, and three-way interaction effects was tested using the (type III) F-tests for fixed effects. Mean separation for each significant fixed effect in the model was performed using Tukey's multiple comparison testing procedure. The irrigation regime per se did not affect susceptibility of the crop to post-harvest proliferation of Salmonella. However, Salmonella grew significantly better in water-congested tissues of green tomatoes. Tomato maturity and genotype, Salmonella genotype, and inter-seasonal differences were the strongest factors affecting proliferation. Red ripe tomatoes were significantly and consistently more conducive to proliferation of Salmonella. Tomatoes harvested in the driest, sunniest season were the most conducive to post-harvest proliferation of the pathogen. Statistically significant interactions between production conditions affected post-harvest susceptibility of the crop to the pathogen. UV irradiation of tomatoes post-harvest promoted Salmonella growth.

  16. A Geomorphological Approach To Landslide Susceptibility Assessment and Its Application To The Virginio River Basin

    NASA Astrophysics Data System (ADS)

    Casagli, N.; Catani, F.; Delmonaco, G.; Ermini, L.; Margottini, C.; Puglisi, C.

    The present note presents the results of a research project aimed at developing a ge- omorphology based method for the assessment of landslide susceptibility. The work has been carried out in the Virginio River basin, a tributary of the Arno river with confluence located 20 km downstream from Florence (Italy). Starting from a detailed landslide inventory, essentially carried out by aerial-photograph survey, the first phase of the research was directed to geomorphic field investigations, aimed at determining those hillslope factors influencing landslide triggering. This analysis was carried out for a significant sub-sample of the inventoried landslides, allowing the distinction of the most relevant hillslope factors affecting each type of mass movement. Selected factors are a) the past slope gradient in which landslide originated, b) litology and 3) land use. Once defined as thematic vector data, these factors have been handled by GIS overlay mapping, allowing to single out, for the entire Virginio River basin, homogeneous domains (Unique Condition Units) that contain, for each landslide ty- pology, unique combinations of the selected hillslope factors. Those domains are the basic Terrain Units for the following phase of landslide susceptibility assessment and mapping. The hillslope factors not selected in the first phase, however playing an im- portant role in contributing to the activation of the mass movements, have been taken into account for the definition of a landslide susceptibility function. This function is es- sentially a logic function based on the presence/absence of preparatory factors within the previous selected Unique Condition Terrain Units. The final mapping of the ar- eas characterized by different landslide susceptibility levels was performed by vector and raster based GIS techniques on the basis of the number and rank of predisposing factors. These landslide susceptibility classes, defined by a logic and easily replicable function, can be useful in the decision making procedures connected with territorial planning.

  17. Does a Rater's Familiarity with a Candidate's Pronunciation Affect the Rating in Oral Proficiency Interviews?

    ERIC Educational Resources Information Center

    Carey, Michael D.; Mannell, Robert H.; Dunn, Peter K.

    2011-01-01

    This study investigated factors that could affect inter-examiner reliability in the pronunciation assessment component of speaking tests. We hypothesized that the rating of pronunciation is susceptible to variation in assessment due to the amount of exposure examiners have to nonnative English accents. An inter-rater variability analysis was…

  18. Nature vs. nurture in dental caries.

    PubMed

    Mandel, I D

    1994-10-01

    Why are some people more resistant to dental caries than others? Certainly diet plays a part, but are there hereditary factors that affect caries development? This report explores genetic components that appear related to caries resistance and susceptibility.

  19. Exploring Genetic Susceptibility to Fibromyalgia

    PubMed Central

    Park, Dong-Jin; Kang, Ji-Hyoun; Yim, Yi-Rang; Kim, Ji-Eun; Lee, Jeong-Won; Lee, Kyung-Eun; Wen, Lihui; Kim, Tae-Jong; Park, Yong-Wook

    2015-01-01

    Fibromyalgia (FM) affects 1% to 5% of the population, and approximately 90% of the affected individuals are women. FM patients experience impaired quality of life and the disorder places a considerable economic burden on the medical care system. With the recognition of FM as a major health problem, many recent studies have evaluated the pathophysiology of FM. Although the etiology of FM remains unknown, it is thought to involve some combination of genetic susceptibility and environmental exposure that triggers further alterations in gene expression. Because FM shows marked familial aggregation, most previous research has focused on genetic predisposition to FM and has revealed associations between genetic factors and the development of FM, including specific gene polymorphisms involved in the serotonergic, dopaminergic, and catecholaminergic pathways. The aim of this review was to discuss the current evidence regarding genetic factors that may play a role in the development and symptom severity of FM. PMID:26306300

  20. Effect of the irrigation regime on the susceptibility of pepper and tomato to post-harvest proliferation of Salmonella enterica.

    PubMed

    Marvasi, Massimiliano; George, Andrée S; Giurcanu, Mihai C; Hochmuth, George J; Noel, Jason T; Teplitski, Max

    2015-04-01

    Raw produce is increasingly recognized as a vehicle of human gastroenteritis. Non-typhoidal Salmonella, pathogenic Escherichia coli, and other human pathogens have been isolated from fruits and vegetables in the field and in the marketplace, which led to the hypothesis that these microbes can use plants as alternate hosts. However, environmental and physiological factors that facilitate persistence of these bacteria in the crop production environment and make produce more vulnerable to post-harvest contamination have not been fully delineated. This study tested the effect of irrigation regimes on the susceptibility of peppers and tomatoes to post-harvest proliferation of Salmonella. The experiments were carried out over three experimental seasons in two locations using seven strains of Salmonella. The irrigation regime per se did not affect susceptibility of tomatoes and peppers to post-harvest proliferation of Salmonella; however, in some of the seasons, irrigation regime-dependent differences were observed. Red peppers and tomatoes were more conducive to proliferation of Salmonella than green fruit in all seasons. Inter-seasonal differences were the strongest factors affecting proliferation of Salmonella in peppers. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Factors Affecting Survival of Longleaf Pine Seedlings

    Treesearch

    John S. Kush; Ralph S. Meldahl; William D. Boyer

    2004-01-01

    Longleaf pine may be managed most efficiently in large even-aged stands. Past research has shown that the effect of trees surrounding the openings (gaps) or the use of fire is a complicating factor, especially with small openings. Longleaf seedlings are considered more susceptible to fire under and nearer to standing trees, and seedling size, kind of fire, soil type,...

  2. The Role of Prenatal, Obstetric and Neonatal Factors in the Development of Autism

    ERIC Educational Resources Information Center

    Dodds, Linda; Fell, Deshayne B.; Shea, Sarah; Armson, B. Anthony; Allen, Alexander C.; Bryson, Susan

    2011-01-01

    We conducted a linked database cohort study of infants born between 1990 and 2002 in Nova Scotia, Canada. Diagnoses of autism were identified from administrative databases with relevant diagnostic information to 2005. A factor representing genetic susceptibility was defined as having an affected sibling or a mother with a history of a psychiatric…

  3. Caffeine does not affect susceptibility to cortical spreading depolarization in mice.

    PubMed

    Yalcin, Nilufer; Chen, Shih-Pin; Yu, Esther S; Liu, Tzu-Ting; Yen, Jiin-Cherng; Atalay, Yahya B; Qin, Tao; Celik, Furkan; van den Maagdenberg, Arn Mjm; Moskowitz, Michael A; Ayata, Cenk; Eikermann-Haerter, Katharina

    2018-01-01

    Several factors that modulate migraine, a common primary headache disorder, also affect susceptibility to cortical spreading depolarization (CSD). CSD is a wave of neuronal and glial depolarization and thought to underlie the migraine aura and possibly headache. Here, we tested whether caffeine, known to alleviate or trigger headache after acute exposure or chronic use/withdrawal, respectively, modulates CSD. We injected C57BL/6J mice with caffeine (30, 60, or 120 mg/kg; i.p.) once (acute) or twice per day for one or two weeks (chronic). Susceptibility to CSD was evaluated by measuring the electrical CSD threshold and by assessing KCl-induced CSD. Simultaneous laser Doppler flowmetry was used to assess CSD-induced cortical blood flow changes. Recordings were performed 15 min after caffeine/vehicle administration, or 24 h after the last dose of chronic caffeine in the withdrawal group. The latter paradigm was also tested in mice carrying the familial hemiplegic migraine type 1 R192Q missense mutation, considered a valid migraine model. Neither acute/chronic administration nor withdrawal of caffeine affected CSD susceptibility or related cortical blood flow changes, either in WT or R192Q mice. Hence, adverse or beneficial effects of caffeine on headache seem unrelated to CSD pathophysiology, consistent with the non-migrainous clinical presentation of caffeine-related headache.

  4. PrPC Governs Susceptibility to Prion Strains in Bank Vole, While Other Host Factors Modulate Strain Features

    PubMed Central

    Espinosa, J. C.; Nonno, R.; Di Bari, M.; Aguilar-Calvo, P.; Pirisinu, L.; Fernández-Borges, N.; Vanni, I.; Vaccari, G.; Marín-Moreno, A.; Frassanito, P.; Lorenzo, P.; Agrimi, U.

    2016-01-01

    ABSTRACT Bank vole is a rodent species that shows differential susceptibility to the experimental transmission of different prion strains. In this work, the transmission features of a panel of diverse prions with distinct origins were assayed both in bank vole expressing methionine at codon 109 (Bv109M) and in transgenic mice expressing physiological levels of bank vole PrPC (the BvPrP-Tg407 mouse line). This work is the first systematic comparison of the transmission features of a collection of prion isolates, representing a panel of diverse prion strains, in a transgenic-mouse model and in its natural counterpart. The results showed very similar transmission properties in both the natural species and the transgenic-mouse model, demonstrating the key role of the PrP amino acid sequence in prion transmission susceptibility. However, differences in the PrPSc types propagated by Bv109M and BvPrP-Tg407 suggest that host factors other than PrPC modulate prion strain features. IMPORTANCE The differential susceptibility of bank voles to prion strains can be modeled in transgenic mice, suggesting that this selective susceptibility is controlled by the vole PrP sequence alone rather than by other species-specific factors. Differences in the phenotypes observed after prion transmissions in bank voles and in the transgenic mice suggest that host factors other than the PrPC sequence may affect the selection of the substrain replicating in the animal model. PMID:27654300

  5. Genetic Factors of Autoimmune Thyroid Diseases in Japanese

    PubMed Central

    Ban, Yoshiyuki

    2012-01-01

    Autoimmune thyroid diseases (AITDs), including Graves' disease (GD) and Hashimoto's thyroiditis (HT), are caused by immune response to self-thyroid antigens and affect approximately 2–5% of the general population. Genetic susceptibility in combination with external factors, such as smoking, viral/bacterial infection, and chemicals, is believed to initiate the autoimmune response against thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITDs. Various techniques have been employed to identify genes contributing to the etiology of AITDs, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions) that are linked to AITDs, and, in some of these loci, putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to GD and HT and some are common to both diseases, indicating that there is a shared genetic susceptibility to GD and HT. Known AITD-susceptibility genes are classified into three groups: HLA genes, non-HLA immune-regulatory genes (e.g., CTLA-4, PTPN22, and CD40), and thyroid-specific genes (e.g., TSHR and Tg). In this paper, we will summarize the latest findings on AITD susceptibility genes in Japanese. PMID:22242199

  6. Multilevel Analysis of Neighborhood Characteristics and Prostate Cancer

    DTIC Science & Technology

    2012-09-01

    widely by a number of key factors that may influence one’s well-being, stress level, lifestyle , and ultimately, disease susceptibility. These factors...outcomes, our work is helping to identify many neighborhood affects on prostate cancer, which include SES and lifestyle factors. The mechanisms of...Charnita Zeigler-Johnson 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail: czj@mail.med.upenn.edu 5f. WORK UNIT NUMBER 7. PERFORMING

  7. Natural Hazard Susceptibility Assessment for Road Planning Using Spatial Multi-Criteria Analysis

    NASA Astrophysics Data System (ADS)

    Karlsson, Caroline S. J.; Kalantari, Zahra; Mörtberg, Ulla; Olofsson, Bo; Lyon, Steve W.

    2017-11-01

    Inadequate infrastructural networks can be detrimental to society if transport between locations becomes hindered or delayed, especially due to natural hazards which are difficult to control. Thus determining natural hazard susceptible areas and incorporating them in the initial planning process, may reduce infrastructural damages in the long run. The objective of this study was to evaluate the usefulness of expert judgments for assessing natural hazard susceptibility through a spatial multi-criteria analysis approach using hydrological, geological, and land use factors. To utilize spatial multi-criteria analysis for decision support, an analytic hierarchy process was adopted where expert judgments were evaluated individually and in an aggregated manner. The estimates of susceptible areas were then compared with the methods weighted linear combination using equal weights and factor interaction method. Results showed that inundation received the highest susceptibility. Using expert judgment showed to perform almost the same as equal weighting where the difference in susceptibility between the two for inundation was around 4%. The results also showed that downscaling could negatively affect the susceptibility assessment and be highly misleading. Susceptibility assessment through spatial multi-criteria analysis is useful for decision support in early road planning despite its limitation to the selection and use of decision rules and criteria. A natural hazard spatial multi-criteria analysis could be used to indicate areas where more investigations need to be undertaken from a natural hazard point of view, and to identify areas thought to have higher susceptibility along existing roads where mitigation measures could be targeted after in-situ investigations.

  8. Natural Hazard Susceptibility Assessment for Road Planning Using Spatial Multi-Criteria Analysis.

    PubMed

    Karlsson, Caroline S J; Kalantari, Zahra; Mörtberg, Ulla; Olofsson, Bo; Lyon, Steve W

    2017-11-01

    Inadequate infrastructural networks can be detrimental to society if transport between locations becomes hindered or delayed, especially due to natural hazards which are difficult to control. Thus determining natural hazard susceptible areas and incorporating them in the initial planning process, may reduce infrastructural damages in the long run. The objective of this study was to evaluate the usefulness of expert judgments for assessing natural hazard susceptibility through a spatial multi-criteria analysis approach using hydrological, geological, and land use factors. To utilize spatial multi-criteria analysis for decision support, an analytic hierarchy process was adopted where expert judgments were evaluated individually and in an aggregated manner. The estimates of susceptible areas were then compared with the methods weighted linear combination using equal weights and factor interaction method. Results showed that inundation received the highest susceptibility. Using expert judgment showed to perform almost the same as equal weighting where the difference in susceptibility between the two for inundation was around 4%. The results also showed that downscaling could negatively affect the susceptibility assessment and be highly misleading. Susceptibility assessment through spatial multi-criteria analysis is useful for decision support in early road planning despite its limitation to the selection and use of decision rules and criteria. A natural hazard spatial multi-criteria analysis could be used to indicate areas where more investigations need to be undertaken from a natural hazard point of view, and to identify areas thought to have higher susceptibility along existing roads where mitigation measures could be targeted after in-situ investigations.

  9. Dietary factors affecting susceptibility to urinary tract infection.

    PubMed

    Kontiokari, Tero; Nuutinen, Matti; Uhari, Matti

    2004-04-01

    Urinary tract infection (UTI) is usually an ascending infection caused by bacteria derived from stools. Since the bacterial composition of stools is dependent on the diet, it is likely that the risk of UTI will change with changes in the diet. Most data describing diet as a risk factor for UTI come from epidemiological and interventional trials. It has been shown in a case-control setting that frequent consumption of fresh berry or fruit juices and fermented milk products containing probiotic bacteria decreases the risk for UTI recurrence in women. Several interventional trials have found Vaccinium berry products to provide protection from UTI recurrence. Probiotics have not been able to prevent UTI in interventional trials. However, the lack of an effect may be related to too low a dose or to the use of non-optimal products in these trials. Limited data are available on the effects of nutrition on UTI in children. However, there is no reason to expect that children would be different from adults in this respect. In this review, we discuss the dietary factors affecting the susceptibility to UTI.

  10. Correlates of smoking among youth: the role of parents, friends, attitudes/beliefs, and demographics.

    PubMed

    Dietz, Noella A; Arheart, Kristopher L; Sly, David F; Lee, David J; McClure, Laura A

    2016-01-01

    Family engagement has been shown to play a crucial role in youth cigarette use prevention and uptake. We examine cross-sectional and longitudinal data to determine whether changes in parental monitoring factors influence changes in smoking susceptibility. Two cross-sectional surveys of Florida youth (12-17 years) were conducted in 2009, with a follow-up survey in 2010. Multivariable analyses examined demographics, parent characteristics, family engagement, and parental monitoring on youth susceptibility to smoke. Cross-sectional data show eating together 6+ times/week and doing something for fun 5+ times/week were related to an increased likelihood of Very Low and decreased likelihood of High susceptibility, respectively. Parental monitoring factors and parents tell on a friend who smokes was significantly related to having Very Low susceptibility in both surveys. Mother's education, parent smokes, family engagement factors, and parental monitoring were significant in both survey rounds. Longitudinal analyses showed change in eating together did not significantly affect the odds of change in smoking susceptibility; however, change in the frequency of doing things for fun with a parent showed decreased odds of susceptibility (OR = .63 [.49-.82]), opposite of the hypothesized direction. Lastly, as youth aged, they were more likely to experience a greater odds of decreased susceptibility (OR14-15y = 1.47 [1.08-1.99] and OR≥16y = 1.40 [1.05-1.84], respectively) and less likely to experience an increased odds of susceptibility (OR14-15y = .65 [.49-.86] and OR≥16y = .72 [.56-.93], respectively). We found mixed results for family engagement and parental monitoring on changes in youth smoking susceptibility. Cross-sectional data showed general associations in the expected direction; however, longitudinal analyses showed family engagement variables had significance, but in the opposite hypothesized direction.

  11. PHYSICAL AND BIOLOGICAL CONTROLS ON DISSOLVED OXYGEN DYNAMICS IN PENSACOLA BAY, FL

    EPA Science Inventory

    Nutrient enrichment of estuaries and coastal waters can contribute to hypoxia (low dissolved oxygen) by increasing primary production and biological oxygen demand. Other factors, however, contribute to hypoxia and affect the susceptibility of coastal waters to hypoxia. Hypoxia fo...

  12. Temporal interactions facilitate endemicity in the susceptible-infected-susceptible epidemic model

    NASA Astrophysics Data System (ADS)

    Speidel, Leo; Klemm, Konstantin; Eguíluz, Víctor M.; Masuda, Naoki

    2016-07-01

    Data of physical contacts and face-to-face communications suggest temporally varying networks as the media on which infections take place among humans and animals. Epidemic processes on temporal networks are complicated by complexity of both network structure and temporal dimensions. Theoretical approaches are much needed for identifying key factors that affect dynamics of epidemics. In particular, what factors make some temporal networks stronger media of infection than other temporal networks is under debate. We develop a theory to understand the susceptible-infected-susceptible epidemic model on arbitrary temporal networks, where each contact is used for a finite duration. We show that temporality of networks lessens the epidemic threshold such that infections persist more easily in temporal networks than in their static counterparts. We further show that the Lie commutator bracket of the adjacency matrices at different times is a key determinant of the epidemic threshold in temporal networks. The effect of temporality on the epidemic threshold, which depends on a data set, is approximately predicted by the magnitude of a commutator norm.

  13. Determinants of Rotavirus Transmission: A Lag Nonlinear Time Series Analysis.

    PubMed

    van Gaalen, Rolina D; van de Kassteele, Jan; Hahné, Susan J M; Bruijning-Verhagen, Patricia; Wallinga, Jacco

    2017-07-01

    Rotavirus is a common viral infection among young children. As in many countries, the infection dynamics of rotavirus in the Netherlands are characterized by an annual winter peak, which was notably low in 2014. Previous study suggested an association between weather factors and both rotavirus transmission and incidence. From epidemic theory, we know that the proportion of susceptible individuals can affect disease transmission. We investigated how these factors are associated with rotavirus transmission in the Netherlands, and their impact on rotavirus transmission in 2014. We used available data on birth rates and rotavirus laboratory reports to estimate rotavirus transmission and the proportion of individuals susceptible to primary infection. Weather data were directly available from a central meteorological station. We developed an approach for detecting determinants of seasonal rotavirus transmission by assessing nonlinear, delayed associations between each factor and rotavirus transmission. We explored relationships by applying a distributed lag nonlinear regression model with seasonal terms. We corrected for residual serial correlation using autoregressive moving average errors. We inferred the relationship between different factors and the effective reproduction number from the most parsimonious model with low residual autocorrelation. Higher proportions of susceptible individuals and lower temperatures were associated with increases in rotavirus transmission. For 2014, our findings suggest that relatively mild temperatures combined with the low proportion of susceptible individuals contributed to lower rotavirus transmission in the Netherlands. However, our model, which overestimated the magnitude of the peak, suggested that other factors were likely instrumental in reducing the incidence that year.

  14. PrPC Governs Susceptibility to Prion Strains in Bank Vole, While Other Host Factors Modulate Strain Features.

    PubMed

    Espinosa, J C; Nonno, R; Di Bari, M; Aguilar-Calvo, P; Pirisinu, L; Fernández-Borges, N; Vanni, I; Vaccari, G; Marín-Moreno, A; Frassanito, P; Lorenzo, P; Agrimi, U; Torres, J M

    2016-12-01

    Bank vole is a rodent species that shows differential susceptibility to the experimental transmission of different prion strains. In this work, the transmission features of a panel of diverse prions with distinct origins were assayed both in bank vole expressing methionine at codon 109 (Bv109M) and in transgenic mice expressing physiological levels of bank vole PrP C (the BvPrP-Tg407 mouse line). This work is the first systematic comparison of the transmission features of a collection of prion isolates, representing a panel of diverse prion strains, in a transgenic-mouse model and in its natural counterpart. The results showed very similar transmission properties in both the natural species and the transgenic-mouse model, demonstrating the key role of the PrP amino acid sequence in prion transmission susceptibility. However, differences in the PrP Sc types propagated by Bv109M and BvPrP-Tg407 suggest that host factors other than PrP C modulate prion strain features. The differential susceptibility of bank voles to prion strains can be modeled in transgenic mice, suggesting that this selective susceptibility is controlled by the vole PrP sequence alone rather than by other species-specific factors. Differences in the phenotypes observed after prion transmissions in bank voles and in the transgenic mice suggest that host factors other than the PrP C sequence may affect the selection of the substrain replicating in the animal model. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  15. Space adaptation syndrome: multiple etiological factors and individual differences

    NASA Technical Reports Server (NTRS)

    Lackner, J. R.; DiZio, P.

    1991-01-01

    Space motion sickness is a significant operational concern in the American and Soviet space programs. Nearly 70% of all astronauts and cosmonauts are affected to some degree during their first several days of flight. It is now beginning to appear that space motion sickness like terrestrial motion sickness is the consequence of multiple etiological factors. As we come to understand basic mechanisms of spatial orientation and sensory-motor adaptation we can begin to predict etiological factors in different motion environments. Individuals vary greatly in the extent to which they are susceptible to these different factors. However, individuals seem to be relatively self-consistent in terms of their rates of adaptation to provocative stimulation and their retention of adaptation. Attempts to relate susceptibility to motion sickness during the microgravity phases of parabolic flight maneuvers to vestibular function under 1G and 0G test conditions are described.

  16. Factors That Affect Proliferation of Salmonella in Tomatoes Post-Harvest: The Roles of Seasonal Effects, Irrigation Regime, Crop and Pathogen Genotype

    PubMed Central

    Marvasi, Massimiliano; Hochmuth, George J.; Giurcanu, Mihai C.; George, Andrée S.; Noel, Jason T.; Bartz, Jerry; Teplitski, Max

    2013-01-01

    Main Objectives Fresh fruits and vegetables become increasingly recognized as vehicles of human salmonellosis. Physiological, ecological, and environmental factors are all thought to contribute to the ability of Salmonella to colonize fruits and vegetables pre- and post-harvest. The goal of this study was to test how irrigation levels, fruit water congestion, crop and pathogen genotypes affect the ability of Salmonella to multiply in tomatoes post-harvest. Experimental Design Fruits from three tomato varieties, grown over three production seasons in two Florida locations, were infected with seven strains of Salmonella and their ability to multiply post-harvest in field-grown tomatoes was tested. The field experiments were set up as a two-factor factorial split plot experiment, with the whole-plot treatments arranged in a randomized complete-block design. The irrigation treatment (at three levels) was the whole-plot factor, and the split-plot factor was tomato variety, with three levels. The significance of the main, two-way, and three-way interaction effects was tested using the (type III) F-tests for fixed effects. Mean separation for each significant fixed effect in the model was performed using Tukey’s multiple comparison testing procedure. Most Important Discoveries and Significance The irrigation regime per se did not affect susceptibility of the crop to post-harvest proliferation of Salmonella. However, Salmonella grew significantly better in water-congested tissues of green tomatoes. Tomato maturity and genotype, Salmonella genotype, and inter-seasonal differences were the strongest factors affecting proliferation. Red ripe tomatoes were significantly and consistently more conducive to proliferation of Salmonella. Tomatoes harvested in the driest, sunniest season were the most conducive to post-harvest proliferation of the pathogen. Statistically significant interactions between production conditions affected post-harvest susceptibility of the crop to the pathogen. UV irradiation of tomatoes post-harvest promoted Salmonella growth. PMID:24324640

  17. Risk of Human Papillomavirus Infection in Cancer-Prone Individuals: What We Know

    PubMed Central

    Khoury, Ruby; Sauter, Sharon; Butsch Kovacic, Melinda; Nelson, Adam S.; Myers, Kasiani C.; Mehta, Parinda A.; Davies, Stella M.; Wells, Susanne I.

    2018-01-01

    Human papillomavirus (HPV) infections cause a significant proportion of cancers worldwide, predominantly squamous cell carcinomas (SCC) of the mucosas and skin. High-risk HPV types are associated with SCCs of the anogenital and oropharyngeal tract. HPV oncogene activities and the biology of SCCs have been intensely studied in laboratory models and humans. What remains largely unknown are host tissue and immune-related factors that determine an individual’s susceptibility to infection and/or carcinogenesis. Such susceptibility factors could serve to identify those at greatest risk and spark individually tailored HPV and SCC prevention efforts. Fanconi anemia (FA) is an inherited DNA repair disorder that is in part characterized by extreme susceptibility to SCCs. An increased prevalence of HPV has been reported in affected individuals, and molecular and functional connections between FA, SCC, and HPV were established in laboratory models. However, the presence of HPV in some human FA tumors is controversial, and the extent of the etiological connections remains to be established. Herein, we discuss cellular, immunological, and phenotypic features of FA, placed into the context of HPV pathogenesis. The goal is to highlight this orphan disease as a unique model system to uncover host genetic and molecular HPV features, as well as SCC susceptibility factors. PMID:29361695

  18. Utility of R0 as a predictor of disease invasion in structured populations

    USGS Publications Warehouse

    Cross, P.C.; Johnson, P.L.F.; Lloyd-Smith, James O.; Getz, W.M.

    2007-01-01

    Early theoretical work on disease invasion typically assumed large and well-mixed host populations. Many human and wildlife systems, however, have small groups with limited movement among groups. In these situations, the basic reproductive number, R0, is likely to be a poor predictor of a disease pandemic because it typically does not account for group structure and movement of individuals among groups. We extend recent work by combining the movement of hosts, transmission within groups, recovery from infection and the recruitment of new susceptibles into a stochastic model of disease in a host metapopulation. We focus on how recruitment of susceptibles affects disease invasion and how population structure can affect the frequency of superspreading events (SSEs). We show that the frequency of SSEs may decrease with the reduced movement and the group sizes due to the limited number of susceptible individuals available. Classification tree analysis of the model results illustrates the hierarchical nature of disease invasion in host metapopulations. First, the pathogen must effectively transmit within a group (R0 > 1), and then the pathogen must persist within a group long enough to allow for movement among the groups. Therefore, the factors affecting disease persistence - such as infectious period, group size and recruitment of new susceptibles - are as important as the local transmission rates in predicting the spread of pathogens across a metapopulation. ?? 2006 The Royal Society.

  19. Utility of R0 as a predictor of disease invasion in structured populations.

    PubMed

    Cross, Paul C; Johnson, Philip L F; Lloyd-Smith, James O; Getz, Wayne M

    2007-04-22

    Early theoretical work on disease invasion typically assumed large and well-mixed host populations. Many human and wildlife systems, however, have small groups with limited movement among groups. In these situations, the basic reproductive number, R0, is likely to be a poor predictor of a disease pandemic because it typically does not account for group structure and movement of individuals among groups. We extend recent work by combining the movement of hosts, transmission within groups, recovery from infection and the recruitment of new susceptibles into a stochastic model of disease in a host metapopulation. We focus on how recruitment of susceptibles affects disease invasion and how population structure can affect the frequency of superspreading events (SSEs). We show that the frequency of SSEs may decrease with the reduced movement and the group sizes due to the limited number of susceptible individuals available. Classification tree analysis of the model results illustrates the hierarchical nature of disease invasion in host metapopulations. First, the pathogen must effectively transmit within a group (R0>1), and then the pathogen must persist within a group long enough to allow for movement among the groups. Therefore, the factors affecting disease persistence--such as infectious period, group size and recruitment of new susceptibles--are as important as the local transmission rates in predicting the spread of pathogens across a metapopulation.

  20. Susceptibility of Pacific herring to viral hemorrhagic septicemia is influenced by diet

    USGS Publications Warehouse

    Beaulaurier, Joshua; Bickford, N.; Gregg, J.L.; Grady, C.A.; Gannam, A.L.; Winton, J.R.; Hershberger, P.K.

    2012-01-01

    Groups of specific-pathogen-free Pacific herring Clupea pallasii were highly susceptible to infection by viral hemorrhagic septicemia virus (VHSV); however, the level of mortality was influenced by diet during the 40–71 d before, during, and after the first exposure to the virus. Cumulative mortality was highest among the herring maintained on an experimental soy-based pellet, intermediate among those maintained on a commercially available fish-meal-based pellet, and lowest among those maintained on a second commercially available fish-meal-based pellet containing ß-glucans. Additionally, the herring maintained on the experimental soy-based feed demonstrated less growth than those on the commercially available feeds. The results indicate the importance of standardizing diet during empirical determinations of disease susceptibility and provide insights into the risk factors affecting VHS susceptibility in wild populations.

  1. Impacts of geology and land use on magnetic susceptibility and selected heavy metals in surface soils of Mashhad plain, northeastern Iran

    NASA Astrophysics Data System (ADS)

    Karimi, Alireza; Haghnia, Gholam Hosain; Ayoubi, Shamsollah; Safari, Tayebeh

    2017-03-01

    Magnetic susceptibility is a fast, inexpensive and reliable technique for estimating and monitoring the anthropogenic contamination of soil with heavy metals. However, it is essential to determine the factors affecting magnetic susceptibility before applying this technique to environmental studies. The objectives of this study were to investigate i) the effect of parent materials and land use on the magnetic susceptibility and concentrations of Fe, Ni, Pb and Zn, and ii) capability of magnetic susceptibility as an indicator of anthropogenic heavy metals contamination of soil in Mashhad plain, northeastern Iran. One hundred seventy-eight composite surface soil samples (0-10 cm) were taken. The aqua-regia extractable concentrations of Fe, Ni, Zn and Pb were determined by atomic absorption spectroscopy. Magnetic susceptibility at low and high frequency (χlf and χhf) were measured and frequency dependent susceptibility (χfd) was calculated. The average concentrations of Fe, Ni, Pb and Zn were 22,812, 61.4, 74.1 and 31.6 mg kg- 1, respectively. The highest contents of Pb (69.1 mg kg- 1) and Zn (149 mg kg- 1) were observed in urban area. The highest concentration of Ni was 41,538 mg kg- 1 observed in the soils developed from ultramafic rocks. Magnetic susceptibility varied from 20.3 on marly sediments to 311.8 × 10- 8 m3 kg- 1 on ultramafic rocks. A positive strong correlation (Pvalue < 0.01, r = 0.88) was obtained between Ni and χlf. There were no significant relationships between Zn and Pb with χlf, therefore it seems that magnetic susceptibility has not been affected significantly by anthropogenic activities which enhanced Pb and Zn concentrations in urban soils. The results indicated that magnetic susceptibility was mainly controlled by Ni containing minerals with lithogenic origin. Therefore, in the soils studied, magnetic susceptibility could not be employed as indicator of anthropogenic contamination of soil with heavy metals.

  2. Genome-wide association study identifies two new susceptibility loci for atopic dermatitis in the Chinese Han population.

    PubMed

    Sun, Liang-Dan; Xiao, Feng-Li; Li, Yang; Zhou, Wen-Ming; Tang, Hua-Yang; Tang, Xian-Fa; Zhang, Hui; Schaarschmidt, Heidi; Zuo, Xian-Bo; Foelster-Holst, Regina; He, Su-Min; Shi, Mei; Liu, Qiang; Lv, Yong-Mei; Chen, Xi-Lan; Zhu, Kun-Ju; Guo, Yi-Feng; Hu, Da-Yan; Li, Ming; Li, Min; Zhang, Yan-Hong; Zhang, Xin; Tang, Jian-Ping; Guo, Bi-Rong; Wang, Hua; Liu, Yuan; Zou, Xiao-Yan; Zhou, Fu-Sheng; Liu, Xiao-Yan; Chen, Gang; Ma, Lin; Zhang, Shu-Mei; Jiang, Ai-Ping; Zheng, Xiao-Dong; Gao, Xing-Hua; Li, Pan; Tu, Cai-Xia; Yin, Xian-Yong; Han, Xiu-Ping; Ren, Yun-Qing; Song, Shun-Peng; Lu, Zhi-Yong; Zhang, Xing-Lian; Cui, Yong; Chang, Jing; Gao, Min; Luo, Xiao-Yan; Wang, Pei-Guang; Dai, Xing; Su, Wei; Li, Hui; Shen, Chun-Pin; Liu, Sheng-Xiu; Feng, Xiao-Bo; Yang, Chun-Jun; Lin, Guo-Shu; Wang, Zai-Xing; Huang, Jian-Qing; Fan, Xing; Wang, Yan; Bao, Yi-Xiao; Yang, Sen; Liu, Jian-Jun; Franke, Andre; Weidinger, Stephan; Yao, Zhi-Rong; Zhang, Xue-Jun

    2011-06-12

    Atopic dermatitis is a chronic, relapsing form of inflammatory skin disorder that is affected by genetic and environmental factors. We performed a genome-wide association study of atopic dermatitis in a Chinese Han population using 1,012 affected individuals (cases) and 1,362 controls followed by a replication study in an additional 3,624 cases and 12,197 controls of Chinese Han ethnicity, as well as 1,806 cases and 3,256 controls from Germany. We identified previously undescribed susceptibility loci at 5q22.1 (TMEM232 and SLC25A46, rs7701890, P(combined) = 3.15 × 10(-9), odds ratio (OR) = 1.24) and 20q13.33 (TNFRSF6B and ZGPAT, rs6010620, P(combined) = 3.0 × 10(-8), OR = 1.17) and replicated another previously reported locus at 1q21.3 (FLG, rs3126085, P(combined) = 5.90 × 10(-12), OR = 0.82) in the Chinese sample. The 20q13.33 locus also showed evidence for association in the German sample (rs6010620, P = 2.87 × 10(-5), OR = 1.25). Our study identifies new genetic susceptibility factors and suggests previously unidentified biological pathways in atopic dermatitis.

  3. Genetics and epigenetics of obesity.

    PubMed

    Herrera, Blanca M; Keildson, Sarah; Lindgren, Cecilia M

    2011-05-01

    Obesity results from interactions between environmental and genetic factors. Despite a relatively high heritability of common, non-syndromic obesity (40-70%), the search for genetic variants contributing to susceptibility has been a challenging task. Genome wide association (GWA) studies have dramatically changed the pace of detection of common genetic susceptibility variants. To date, more than 40 genetic variants have been associated with obesity and fat distribution. However, since these variants do not fully explain the heritability of obesity, other forms of variation, such as epigenetics marks, must be considered. Epigenetic marks, or "imprinting", affect gene expression without actually changing the DNA sequence. Failures in imprinting are known to cause extreme forms of obesity (e.g. Prader-Willi syndrome), but have also been convincingly associated with susceptibility to obesity. Furthermore, environmental exposures during critical developmental periods can affect the profile of epigenetic marks and result in obesity. We review the most recent evidence for genetic and epigenetic mechanisms involved in the susceptibility and development of obesity. Only a comprehensive understanding of the underlying genetic and epigenetic mechanisms, and the metabolic processes they govern, will allow us to manage, and eventually prevent, obesity. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  4. Factors affecting low summer dissolved oxygen concentrations in Mississippi Delta bayous

    USDA-ARS?s Scientific Manuscript database

    Streams in watersheds supporting intensive row-crop agriculture are vulnerable to ecological degradation due to non-point source pollutants such as nutrients. Low gradient streams such as bayous are especially susceptible to pollutants due to increased water residence time, and they often exhibit po...

  5. Issue Paper on Physiological and Behavioral Changes in Pregnant and Lactating Women and Available Exposure Factors

    EPA Science Inventory

    This issue paper provides a summary of information from the published literature related to behavioral and physiological changes during pregnancy and lactation that may affect women’s exposure or susceptibility to environmental contaminants, provides potentially useful exposur...

  6. Factors affecting low summer dissolved oxygen concentrations in Mississippi Delta bayous

    USDA-ARS?s Scientific Manuscript database

    Streams in watersheds supporting intensive row-crop agriculture are vulnerable to ecological degradation due to non-point source discharge of pollutants such as nutrients. Low gradient streams such as bayous are especially susceptible due to increased water residence time, and often result in poor w...

  7. SUSCEPTIBILITY OF A GULF OF MEXICO ESTUARY TO HYPOXIA: AN ANALYSIS USING BOX MODELS

    EPA Science Inventory

    The extent of hypoxia and the physical factors affecting development and maintenance of hypoxia were examined for Pensacola Bay, Florida (USA) by conducting monthly water quality surveys for 3 years and by constructing salt-and-water balance box models using the resulting data. W...

  8. Differential serotonergic mediation of aggression in roosters selected for resistance and susceptibility to Marek's disease

    USDA-ARS?s Scientific Manuscript database

    Serotonin (5-HT) is a primary regulating neurotransmitter involved in aggressive and impulsive behaviors in mammals. Previous studies have also demonstrated the function of serotonergic system in regulating aggression is affected by both genetic and environmental factors. The serotonergic system m...

  9. Differential serotonergic mediation of aggression in roosters selected for resistance and susceptibility to Marek’s disease

    USDA-ARS?s Scientific Manuscript database

    1. Serotonin (5-HT) is a primary regulating neurotransmitter involved in aggressive and impulsive behaviors in mammals and birds. Previous studies have also demonstrated the function of serotonergic system in regulating aggression is affected by both genetic and environmental factors. 2. Our obje...

  10. INFLUENCE OF SUMMER STREAM TEMPERATURES ON BLACK SPOT INFESTATION OF JUVENILE COHO SALMON IN THE OREGON COAST RANGE

    EPA Science Inventory

    High summer water temperatures can adversely affect stream salmonids in numerous ways. The direct effects of temperature associated with increased metabolic demand can be exacerbated by other factors, including decreased resistance to disease and increased susceptibility to para...

  11. Photodynamic treatment of epithelial tissue derived from patients with endometrial cancer: a contribution to the role of laminin and epidermal growth factor receptor in photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Ziolkowski, Piotr P.; Symonowicz, Krzysztof; Osiecka, Beata J.; Rabczynski, Jerzy; Gerber, Jerzy

    1999-07-01

    Photodynamic therapy (PDT) was used to treat endometrial G1 cancer tissue derived from patients who had undergone a total hysterectomy and bilateral salpingo-oophorectomy. After surgical treatment the cancerous tissue was kept in a medium containing Dulbecco solution, fetal calf serum, and antibiotics. The tissue was then exposed to hematoporphyrin derivative (0.1 mg/l) and 24 h later exposed to light (total light dose--18 J/sq cm). Necrosis depth was evaluated 24 h later using a light microscope. In order to assess the possible role of the basal membrane component laminin, as well as epidermal growth factor receptor susceptibility to PDT, immunohistochemical studies were carried out. Additionally, nucleolar organizer regions evaluation was performed. Our experiment confirmed that PDT results in the necrosis in the treated endometrial cancer, while not affecting the laminin in the cancerous tissue. In contrast, PDT strongly affects the epidermal growth factor receptor and nucleolar organizer regions in cancer cells. We suggest that laminin may contribute to the prevention of cancer dissemination in the cases where PDT has to be repeated, and that after PDT the cells become less susceptible to a mitogen, like, e.g., epidermal growth factor.

  12. The G1/S Specific Cyclin D2 Is a Regulator of HIV-1 Restriction in Non-proliferating Cells

    PubMed Central

    Badia, Roger; Pujantell, Maria; Riveira-Muñoz, Eva; Puig, Teresa; Torres-Torronteras, Javier; Martí, Ramón; Clotet, Bonaventura; Ampudia, Rosa M.; Ballana, Ester

    2016-01-01

    Macrophages are a heterogeneous cell population strongly influenced by differentiation stimuli that become susceptible to HIV-1 infection after inactivation of the restriction factor SAMHD1 by cyclin-dependent kinases (CDK). Here, we have used primary human monocyte-derived macrophages differentiated through different stimuli to evaluate macrophage heterogeneity on cell activation and proliferation and susceptibility to HIV-1 infection. Stimulation of monocytes with GM-CSF induces a non-proliferating macrophage population highly restrictive to HIV-1 infection, characterized by the upregulation of the G1/S-specific cyclin D2, known to control early steps of cell cycle progression. Knockdown of cyclin D2, enhances HIV-1 replication in GM-CSF macrophages through inactivation of SAMHD1 restriction factor by phosphorylation. Co-immunoprecipitation experiments show that cyclin D2 forms a complex with CDK4 and p21, a factor known to restrict HIV-1 replication by affecting the function of the downstream cascade that leads to SAMHD1 deactivation. Thus, we demonstrate that cyclin D2 acts as regulator of cell cycle proteins affecting SAMHD1-mediated HIV-1 restriction in non-proliferating macrophages. PMID:27541004

  13. Innate immunity and genetic determinants of urinary tract infection susceptibility

    PubMed Central

    Godaly, Gabriela; Ambite, Ines; Svanborg, Catharina

    2015-01-01

    Purpose of review Urinary tract infections (UTIs) are common, dangerous and interesting. Susceptible individuals experience multiple, often clustered episodes, and in a subset of patients, infections progress to acute pyelonephritis (APN), sometimes accompanied by uro-sepsis. Others develop asymptomatic bacteriuria (ABU). Here, we review the molecular basis for these differences, with the intention to distinguish exaggerated host responses that drive disease from attenuated responses that favour protection and to highlight the genetic basis for these extremes, based on knock-out mice and clinical studies. Recent findings The susceptibility to UTI is controlled by specific innate immune signalling and by promoter polymorphisms and transcription factors that modulate the expression of genes controlling these pathways. Gene deletions that disturb innate immune activation either favour asymptomatic bacteriuria or create acute morbidity and disease. Promoter polymorphisms and transcription factor variants affecting those genes are associated with susceptibility in UTI-prone patients. Summary It is time to start using genetics in UTI-prone patients, to improve diagnosis and to assess the risk for chronic sequels such as renal malfunction, hypertension, spontaneous abortions, dialysis and transplantation. Furthermore, the majority of UTI patients do not need follow-up, but for lack of molecular markers, they are unnecessarily investigated. PMID:25539411

  14. XVI European Charcot Foundation Lecture: Nutrition and environment, can MS be prevented?

    PubMed Central

    Simon, Kelly Claire; Munger, Kassandra L; Ascherio, Alberto

    2012-01-01

    Multiple sclerosis is a relatively common debilitating neurologic disease that affects people in early adulthood. While the characteristic pathology of MS has been well described, the etiology of the disease is not well understood, despite decades of research and the identification of strong genetic and environmental candidates for susceptibility. A question central to all diseases, but posed specifically for MS at the XVI European Charcot Foundation Lecture, was ‘Can MS be prevented?’ To address this question, we have evaluated the available data regarding nutritional and environmental factors that may be related to MS susceptibility and suggest the extent to which a potential intervention may reduce disease burden. It is our opinion that intervention, particularly supplementation with vitamin D, could have a dramatic impact on disease prevalence. Understanding that any intervention or behavioral modification will surely act in the context of genetic susceptibility and unidentified stochastic events, it is likely that not all MS is ‘preventable’. Epidemiologic observation has provided key insights into environmental and nutritional factors that may alter one’s susceptibility to MS, however, there are still many questions in unraveling the etiology of this complex disease. PMID:21975017

  15. The Role of Environment and Lifestyle in Determining the Risk of Multiple Sclerosis.

    PubMed

    Hedström, Anna Karin; Olsson, Tomas; Alfredsson, Lars

    2015-01-01

    MS is a complex disease where both genetic and environmental factors contribute to disease susceptibility. The substantially increased risk of developing MS in relatives of affected individuals gives solid evidence for a genetic base for susceptibility, whereas the modest familial risk, most strikingly demonstrated in the twin studies, is a very strong argument for an important role of lifestyle/environmental factors in determining the risk of MS, sometimes interacting with MS risk genes. Lifestyle factors and environmental exposures are harder to accurately study and quantify than genetic factors. However, it is important to identify these factors since they, as opposed to risk genes, are potentially preventable. We have reviewed the evidence for environmental factors that have been repeatedly shown to influence the risk of MS: Epstein-Barr virus (EBV) infection, ultraviolet radiation (UVR) exposure habits /vitamin D status, and smoking. We have also reviewed a number of additional environmental factors, published in the past 5 years, that have been described to influence MS risk. Independent replication, preferably by a variety of methods, may give still more firm evidence for their involvement.

  16. Genetic variability in the tumor necrosis factor-lymphotoxin region influences susceptibility to rheumatoid arthritis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mulcahy, B.; Waldron-Lynch, F.; Adams, C.

    The major histocompatibility complex class H1 tumor necrosis factor-tymphotoxin (TNF-LT) region (6p21.3) was investigated as a possible susceptibility locus for rheumatoid arthritis (RA). Inheritance of five TNF microsatellite markers was determined in 50 multiplex families. Overall, 47 different haplotypes were observed. One of these, the TNF a6, b5, c1, d3, e3 (H1) haplotype, was present in 35.3% of affected, but in only 20.5% of unaffected, individuals (P < .005). This haplotype accounted for 21.5% of the parental haplotypes transmitted to affected offspring and only 7.3 % not transmitted to affected offspring (P = .0003). The TNF a6 and TNF c1more » alleles were individually associated with RA (P = .0005 and .0008, respectively), as were the HLA-DRB1 {open_quotes}shared epitope{close_quotes} (SE) (P = .0001) and HLA-DRB1*0401 (P = .0018). Both univariate and bivariate conditional logistic regression analysis showed significant effects of TNF c1 and SE in increasing risk to RA (P < .001). Stratification by the presence of SE indicated an independent effect of the TNFc1 allele (P = .0003) and the HLA A1, BS, DR3 extended haplotype (always TNFa2, b3, c1, d1, e3) (P = .0027) in SE heterozygotes, while the H1 haplotype was associated with RA in SE homozygotes (P = .0018). The TNF-LT region appears to influence susceptibility to RA, distinct from HLA-DR. 50 refs., 1 fig., 1 tab.« less

  17. Factors that affect self-care behaviour of female high school students with dysmenorrhoea: a cluster sampling study.

    PubMed

    Chang, Shu-Fang; Chuang, Mei-hua

    2012-04-01

    The purpose of this study was to identify factors that affect the self-care behaviour of female high school students with dysmenorrhoea. This cross-sectional study utilized a questionnaire-based survey to understand the self-care behaviour of female high school students dysmenorrhoeal, along with the factors that affect this behaviour. A cluster random sampling method was adopted and questionnaires were used for data collection. Study participants experienced a moderate level of discomfort from dysmenorrhoea, and perceived dysmenorrhoea as serious. This investigation finds that cues to action raised perceived susceptibility to dysmenorrhoea and the perceived effectiveness of self-care behaviour and, therefore, increased the adoption of self-care behaviour. Hence, school nurses should offer female high school students numerous resources to apply correct self-care behaviour. © 2012 Blackwell Publishing Asia Pty Ltd.

  18. A new-old approach for shallow landslide analysis and susceptibility zoning in fine-grained weathered soils of southern Italy

    NASA Astrophysics Data System (ADS)

    Cascini, Leonardo; Ciurleo, Mariantonietta; Di Nocera, Silvio; Gullà, Giovanni

    2015-07-01

    Rainfall-induced shallow landslides involve several geo-environmental contexts and different types of soils. In clayey soils, they affect the most superficial layer, which is generally constituted by physically weathered soils characterised by a diffuse pattern of cracks. This type of landslide most commonly occurs in the form of multiple-occurrence landslide phenomena simultaneously involving large areas and thus has several consequences in terms of environmental and economic damage. Indeed, landslide susceptibility zoning is a relevant issue for land use planning and/or design purposes. This study proposes a multi-scale approach to reach this goal. The proposed approach is tested and validated over an area in southern Italy affected by widespread shallow landslides that can be classified as earth slides and earth slide-flows. Specifically, by moving from a small (1:100,000) to a medium scale (1:25,000), with the aid of heuristic and statistical methods, the approach identifies the main factors leading to landslide occurrence and effectively detects the areas potentially affected by these phenomena. Finally, at a larger scale (1:5000), deterministic methods, i.e., physically based models (TRIGRS and TRIGRS-unsaturated), allow quantitative landslide susceptibility assessment, starting from sample areas representative of those that can be affected by shallow landslides. Considering the reliability of the obtained results, the proposed approach seems useful for analysing other case studies in similar geological contexts.

  19. An In-Depth Characterization of the Major Psoriasis Susceptibility Locus Identifies Candidate Susceptibility Alleles within an HLA-C Enhancer Element

    PubMed Central

    Clop, Alex; Bertoni, Anna; Spain, Sarah L.; Simpson, Michael A.; Pullabhatla, Venu; Tonda, Raul; Hundhausen, Christian; Di Meglio, Paola; De Jong, Pieter; Hayday, Adrian C.; Nestle, Frank O.; Barker, Jonathan N.; Bell, Robert J. A.; Capon, Francesca; Trembath, Richard C.

    2013-01-01

    Psoriasis is an immune-mediated skin disorder that is inherited as a complex genetic trait. Although genome-wide association scans (GWAS) have identified 36 disease susceptibility regions, more than 50% of the genetic variance can be attributed to a single Major Histocompatibility Complex (MHC) locus, known as PSORS1. Genetic studies indicate that HLA-C is the strongest PSORS1 candidate gene, since markers tagging HLA-Cw*0602 consistently generate the most significant association signals in GWAS. However, it is unclear whether HLA-Cw*0602 is itself the causal PSORS1 allele, especially as the role of SNPs that may affect its expression has not been investigated. Here, we have undertaken an in-depth molecular characterization of the PSORS1 interval, with a view to identifying regulatory variants that may contribute to disease susceptibility. By analysing high-density SNP data, we refined PSORS1 to a 179 kb region encompassing HLA-C and the neighbouring HCG27 pseudogene. We compared multiple MHC sequences spanning this refined locus and identified 144 candidate susceptibility variants, which are unique to chromosomes bearing HLA-Cw*0602. In parallel, we investigated the epigenetic profile of the critical PSORS1 interval and uncovered three enhancer elements likely to be active in T lymphocytes. Finally we showed that nine candidate susceptibility SNPs map within a HLA-C enhancer and that three of these variants co-localise with binding sites for immune-related transcription factors. These data indicate that SNPs affecting HLA-Cw*0602 expression are likely to contribute to psoriasis susceptibility and highlight the importance of integrating multiple experimental approaches in the investigation of complex genomic regions such as the MHC. PMID:23990973

  20. Comparison of Passively Transferred Antibodies in Bighorn and Domestic Lambs Reveals One Factor in Differential Susceptibility of These Species to Mannheimia haemolytica-Induced Pneumonia ▿

    PubMed Central

    Herndon, Caroline N.; Shanthalingam, Sudarvili; Knowles, Donald P.; Call, Douglas R.; Srikumaran, Subramaniam

    2011-01-01

    Mannheimia haemolytica consistently causes fatal bronchopneumonia in bighorn sheep (BHS; Ovis canadensis) under natural and experimental conditions. Leukotoxin is the primary virulence factor of this organism. BHS are more susceptible to developing fatal pneumonia than the related species Ovis aries (domestic sheep [DS]). In BHS herds affected by pneumonia, lamb recruitment is severely impaired for years subsequent to an outbreak. We hypothesized that a lack of maternally derived antibodies (Abs) against M. haemolytica provides an immunologic basis for enhanced susceptibility of BH lambs to population-limiting pneumonia. Therefore, the objective of this study was to determine the titers of Abs directed against M. haemolytica in the sera of BH and domestic lambs at birth through 12 weeks of age. Results revealed that BH lambs had approximately 18-fold lower titers of Ab against surface antigens of M. haemolytica and approximately 20-fold lower titers of leukotoxin-neutralizing Abs than domestic lambs. The titers of leukotoxin-neutralizing Abs in the serum and colostrum samples of BH ewes were approximately 157- and 50-fold lower than those for domestic ewes, respectively. Comparatively, the higher titers of parainfluenza 3 virus-neutralizing Abs in the BH lambs ruled out the possibility that these BHS had an impaired ability to passively transfer Abs to their lambs. These results suggest that lower levels of leukotoxin-neutralizing Abs in the sera of BH ewes, and resultant low Ab titers in their lambs, may be a critical factor in the poor lamb recruitment in herds affected by pneumonia. PMID:21613459

  1. Controlled field and laboratory studies on VHS and Ichtyophonus in Pacific herring: Section II in Investigations of disease factors affecting declines of Pacific herring populations in Prince William Sound

    USGS Publications Warehouse

    Kocan, Richard M.; Hershberger, Paul K.; Winton, James R.

    1999-01-01

    No evidence for increased susceptibility, mortality or loss of disease resistance was observed in wild or laboratory-reared herring exposed to oil or synthetic corticosteroids, either prior to or following exposure to VHSV.

  2. The transmission of oak wilt.

    Treesearch

    J.N. Gibbs; D.W. French

    1980-01-01

    Provides an up-to-date review of factors affecting the transmission of oak wilt, Ceratocystis fagacearum. Discusses the history and severity of the disease, the saprophytic existence of the fungus in the dying tree, seasonal susceptibility of trees to infection, overland and underground spread, the role of animals and insects as vectors or tree wounders, and the...

  3. Patterns of Sensitivity to Parenting and Peer Environments: Early Temperament and Adolescent Externalizing Behavior.

    PubMed

    Tung, Irene; Noroña, Amanda N; Morgan, Julia E; Caplan, Barbara; Lee, Steve S; Baker, Bruce L

    2018-03-14

    Although parenting behavior and friendship quality predict adolescent externalizing behaviors (EBs), individual differences in temperament may differentially affect susceptibility to these factors over time. In a multi-method and multi-informant study of 141 children followed prospectively from toddlerhood to adolescence, we tested the independent and interactive associations of age 3 reactive temperament (e.g., negative emotionality) and age 13 observed parenting (i.e., positive and negative behavior) and friendship (i.e., conflict and warmth), with multi-informant ratings of age 15 aggression and rule-breaking behavior. Negative parenting predicted growth in parent-rated EB, but only for adolescents with early reactive temperament. Temperament did not affect sensitivity to positive parenting or friendship. Results are discussed in the context of differential susceptibility theory and intervention implications for adolescents. © 2018 Society for Research on Adolescence.

  4. Arsenic in Drinking Water in Bangladesh: Factors Affecting Child Health

    PubMed Central

    Aziz, Sonia N.; Aziz, Khwaja M. S.; Boyle, Kevin J.

    2014-01-01

    The focus of this paper is to present an empirical model of factors affecting child health by observing actions households take to avoid exposure to arsenic in drinking water. Millions of Bangladeshis face multiple health hazards from high levels of arsenic in drinking water. Safe water sources are either expensive or difficult to access, affecting people’s individuals’ time available for work and ultimately affecting the health of household members. Since children are particularly susceptible and live with parents who are primary decision makers for sustenance, parental actions linking child health outcomes is used in the empirical model. Empirical results suggest that child health is significantly affected by the age and gender of the household water procurer. Adults with a high degree of concern for children’s health risk from arsenic contamination, and who actively mitigate their arsenic contaminated water have a positive effect on child health. PMID:24982854

  5. An innovative tool for landslide susceptibility mapping in Kyrgyzstan, Central Asia

    NASA Astrophysics Data System (ADS)

    Saponaro, Annamaria; Pilz, Marco; Wieland, Marc; Bindi, Dino; Parolai, Stefano

    2013-04-01

    Kyrgyzstan is among the most exposed countries in the world to landslide susceptibility. The high seismicity of the area, the presence of high mountain ridges and topographic relieves, the geology of the local materials and the occurrence of heavy precipitations represent the main factors responsible for slope failures. In particular, the large variability of material properties and slope conditions as well as the difficulties in forecasting heavy precipitations locally and in quantifying the level of ground shaking call for harmonized procedures for reducing the negative impact of these factors. Several studies have recently been carried out aiming at preparing landslide susceptibility and hazard maps; however, some of them - qualitative-based - suffer from the application of subjective decision rules from experts in the classification of parameters that influence the occurrence of a landslide. On the other hand, statistical methods provide objectivity over qualitative ones since they allow a numerical evaluation of landslide spatial distribution with landslide potential factors. For this reason, we will make use of a bivariate technique known as Weight-Of-Evidence method to evaluate the influence of landslide predictive factors. The aim of this study is to identify areas in Kyrgyzstan being more prone to earthquake-triggered landslides. An innovative approach which exploits the new advances of GIS technology together with statistical concepts is presented. A range of conditioning factors and their potential impact on landslide activation is quantitatively assessed on the basis of landslide spatial distribution and seismic zonation. Results show areas which are more susceptible to landslides induced by earthquakes. Our approach can be used to fill the gap of subjectivity that typically affects already performed qualitative analysis. The resulting landslide susceptibility map represents a potentially supportive tool for disaster management and planning activities at regional level; furthermore, it can be used as a starting point for further constraining the analysis which might also consider meteorological influences and for carrying out an extension to all Central Asian countries in the framework of cross-border activities.

  6. Factors Affecting Intention among Students to Be Vaccinated against A/H1N1 Influenza: A Health Belief Model Approach

    PubMed Central

    Teitler-Regev, Sharon; Shahrabani, Shosh; Benzion, Uri

    2011-01-01

    The outbreak of A/H1N1 influenza (henceforth, swine flu) in 2009 was characterized mainly by morbidity rates among young people. This study examined the factors affecting the intention to be vaccinated against the swine flu among students in Israel. Questionnaires were distributed in December 2009 among 387 students at higher-education institutions. The research questionnaire included sociodemographic characteristics and Health Belief Model principles. The results show that the factors positively affecting the intention to take the swine flu vaccine were past experience with seasonal flu shot and three HBM categories: higher levels of perceived susceptibility for catching the illness, perceived seriousness of illness, and lower levels of barriers. We conclude that offering the vaccine at workplaces may raise the intention to take the vaccine among young people in Israel. PMID:22229099

  7. Arabidopsis HIPP27 is a host susceptibility gene for the beet cyst nematode Heterodera schachtii.

    PubMed

    Radakovic, Zoran S; Anjam, Muhammad Shahzad; Escobar, Elizabeth; Chopra, Divykriti; Cabrera, Javier; Silva, Ana Cláudia; Escobar, Carolina; Sobczak, Miroslaw; Grundler, Florian M W; Siddique, Shahid

    2018-02-22

    Sedentary plant-parasitic cyst nematodes are obligate biotrophs that infect the roots of their host plant. Their parasitism is based on the modification of root cells to form a hypermetabolic syncytium from which the nematodes draw their nutrients. The aim of this study was to identify nematode susceptibility genes in Arabidopsis thaliana and to characterize their roles in supporting the parasitism of Heterodera schachtii. By selecting genes that were most strongly upregulated in response to cyst nematode infection, we identified HIPP27 (HEAVY METAL-ASSOCIATED ISOPRENYLATED PLANT PROTEIN 27) as a host susceptibility factor required for beet cyst nematode infection and development. Detailed expression analysis revealed that HIPP27 is a cytoplasmic protein and that HIPP27 is strongly expressed in leaves, young roots and nematode-induced syncytia. Loss-of-function Arabidopsis hipp27 mutants exhibited severely reduced susceptibility to H. schachtii and abnormal starch accumulation in syncytial and peridermal plastids. Our results suggest that HIPP27 is a susceptibility gene in Arabidopsis whose loss of function reduces plant susceptibility to cyst nematode infection without increasing the susceptibility to other pathogens or negatively affecting the plant phenotype. © 2018 UNIVERSITY BONN. MOLECULAR PLANT PATHOLOGY © 2018 BSPP AND JOHN WILEY & SONS LTD.

  8. Sex differences in chronic stress responses and Alzheimer's disease.

    PubMed

    Yan, Yan; Dominguez, Sky; Fisher, Daniel W; Dong, Hongxin

    2018-02-01

    Clinical studies indicate that Alzheimer's disease (AD) disproportionately affects women in both disease prevalence and severity, but the mechanisms underlying this sex divergence are unknown. Though some have suggested this difference in risk is a reflection of known differences in longevity between men and women, mounting clinical and preclinical evidence supports women also having intrinsic susceptibilities towards the disease. While a number of potential risk factors have been hypothesized to affect these differences in risks, none have been definitively verified. In this review, we discuss a novel hypothesis whereby women's susceptibility to chronic stress also mediates increased risk for AD. As stress is a risk factor for AD, and women are twice as likely to develop mood disorders where stress is a major etiology, it is possible that sex dimorphisms in stress responses contribute to the increase in women with AD. In line with this, sex divergence in biochemical responses to stress have been noted along the hypothalamic-pituitary-adrenal (HPA) axis and among known molecular effectors of AD, with crosstalk between these processes also being likely. In addition, activation of the cortical corticotrophin-releasing factor receptor 1 (CRF1) signaling pathway leads to distinct female-biased increases in molecules associated with AD pathogenesis. Therefore, the different biochemical responses to stress between women and men may represent an intrinsic, sex-dependent risk factor for AD.

  9. The Differential Expression of Immune Genes between Water Buffalo and Yellow Cattle Determines Species-Specific Susceptibility to Schistosoma japonicum Infection

    PubMed Central

    Yang, Jianmei; Fu, Zhiqiang; Hong, Yang; Wu, Haiwei; Jin, Yamei; Zhu, Chuangang; Li, Hao; Lu, Ke; Shi, Yaojun; Yuan, Chunxiu; Cheng, Guofeng; Feng, Xingang; Liu, Jinming; Lin, Jiaojiao

    2015-01-01

    Water buffalo are less susceptible to Schistosoma japonicum infection than yellow cattle. The factors that affect such differences in susceptibility remain unknown. A Bos taurus genome-wide gene chip was used to analyze gene expression profiles in the peripheral blood of water buffalo and yellow cattle pre- and post-infection with S. japonicum. This study showed that most of the identified differentially expressed genes(DEGs) between water buffalo and yellow cattle pre- and post-infection were involved in immune-related processes, and the expression level of immune genes was lower in water buffalo. The unique DEGs (390) in yellow cattle were mainly associated with inflammation pathways, while the unique DEGs (2,114) in water buffalo were mainly associated with immune-related factors. The 83 common DEGs may be the essential response genes during S. japonicum infection, the highest two gene ontology (GO) functions were associated with the regulation of fibrinolysis. The pathway enrichment analysis showed that the DEGs constituted similar immune-related pathways pre- and post-infection between the two hosts. This first analysis of the transcriptional profiles of natural hosts has enabled us to gain new insights into the mechanisms that govern their susceptibility or resistance to S. japonicum infections. PMID:26125181

  10. To quit or not: Vulnerability of women to smoking tobacco.

    PubMed

    Park, Se-Jung; Yi, Bitna; Lee, Ho-Sun; Oh, Woo-Yeon; Na, Hyun-Kyung; Lee, Minjeong; Yang, Mihi

    2016-01-01

    Tobacco smoking is currently on the rise among women, and can pose a greater health risk. In order to understand the nature of the increase in smoking prevalence among women, we focused on the vulnerability of women to smoking behaviors--smoking cessation or tobacco addiction--and performed a systematic review of the socioeconomic and intrinsic factors as well as tobacco ingredients that affect women's susceptibility to smoking tobacco. We observed that nicotine and other tobacco components including cocoa-relatives, licorice products, and menthol aggravate tobacco addiction in women rather than in men. Various genetic and epigenetic alterations in dopamine pathway and the pharmaco-kinetics and -dynamic factors of nicotine also showed potential evidences for high susceptibility to tobacco addiction in women. Therefore, we suggest systemic approaches to prevent tobacco smoking-related health risks, considering gene-environment-gender interaction.

  11. Multiple factors affect pest and pathogen damage on 31 Populus clones in South Carolina

    Treesearch

    David R. Coyle; Mark D. Coleman; Jaclin A. Durant; Lee A. Newman

    2006-01-01

    Populus species and hybrids have many practical applications, but there is a paucity of data regarding selections that perform well in the southeastern US. We compared pest susceptibility of 31 Populus clones over 3 years in South Carolina, USA. Cuttings were planted in spring 2001 on two study sites. Clones planted in the...

  12. Predictors of change on the smoking uptake continuum among adolescents.

    PubMed

    Kaufman, Nancy J; Castrucci, Brian C; Mowery, Paul D; Gerlach, Karen K; Emont, Seth; Orleans, C Tracy

    2002-06-01

    Understanding how advertising and other risk and demographic factors affect adolescent susceptibility to smoking would allow for the development of more effective youth-targeted tobacco prevention and cessation programs and policies. To examine the effect of various demographic and risk factors on different stages of smoking among adolescents. A nationally representative cross-sectional survey, The Robert Wood Johnson Foundation's Survey of Tobacco Price Sensitivity, Behavior, and Attitudes Among Teenagers and Young Adults. The Robert Wood Johnson Foundation's Survey of Tobacco Price Sensitivity, Behavior, and Attitudes Among Teenagers and Young Adults included 17,287 adolescent respondents (aged, 13-19 years) in 1996. Stage of susceptibility and correlates of progression toward regular smoking. Of all never [corrected] smoking adolescents, 32% were susceptible smokers (have never smoked, but might) with younger adolescents almost 3 times more likely than older adolescents to be susceptible. Female subjects were 50% [corrected] more likely than male subjects to be susceptible. In addition to exposure to others' smoking, owning or willingness to own tobacco promotional items, having a favorite cigarette advertisement, skipping school, poor school performance, and lack of attendance in religious activities were associated with progression along the uptake continuum. Improved understanding of the tobacco use trajectories of adolescents and the risk factors associated with progression will help clinicians and tobacco control advocates create effective youth-targeted interventions and policies. Findings suggest that physicians and other health care providers should redouble their efforts to ask preadolescents and young adults about smoking or the likelihood of their smoking. Nonsmokers should also be advised about the addictive nature of tobacco products and the resulting loss of control that accompanies addiction.

  13. The interaction between temperament and the family environment in adolescent substance use and externalizing behaviors: Support for diathesis–stress or differential susceptibility?

    PubMed Central

    Rioux, Charlie; Castellanos-Ryan, Natalie; Parent, Sophie; Séguin, Jean R.

    2016-01-01

    Both individual and environmental factors predict externalizing behaviors and substance use (EB-SU); however, different patterns of interaction among these factors may have different implications. This review first examines how temperament and the family environment interact in the prediction of adolescent EB-SU. Second, studies are reviewed according to two theoretical models: (1) diathesis–stress, i.e., certain individual characteristics are linked to vulnerability and later problems in adverse environments; (2) differential susceptibility, i.e., these characteristics are linked to susceptibility, predicting problems in adverse environments, but also better than average outcomes in good environments. Fourteen studies focusing on the prediction of EB-SU at ages 12–18 were selected through a literature search. Results showed that certain temperament traits (high levels of impulsivity and disinhibition; low levels of effortful control, negative affect, fearfulness and shyness), hereby designated as “adventurous” disposition, were associated with higher levels of EB-SU in adverse family environments. Some studies also showed that children with “adventurous” temperament traits in positive environments had the lowest levels of EB-SU. This suggests that prevention of EB-SU might target family factors such as parenting and focus on children with “adventurous” temperament traits. Further, studies that supported the differential susceptibility model were those assessing temperament and the family environment in childhood and studies that supported the diathesis–stress model assessed these variables in adolescence. It is thus possible that some of these “adventurous” temperament traits, with regard to EB-SU, would be indicators of susceptibility to both enriched and adverse environments in childhood but no longer in adolescence, when they would only be indicators of vulnerability to adverse environments. PMID:27413247

  14. Family-based linkage and association mapping reveals novel genes affecting Plum pox virus infection in Arabidopsis thaliana.

    PubMed

    Pagny, Gaëlle; Paulstephenraj, Pauline S; Poque, Sylvain; Sicard, Ophélie; Cosson, Patrick; Eyquard, Jean-Philippe; Caballero, Mélodie; Chague, Aurélie; Gourdon, Germain; Negrel, Lise; Candresse, Thierry; Mariette, Stéphanie; Decroocq, Véronique

    2012-11-01

    Sharka is a devastating viral disease caused by the Plum pox virus (PPV) in stone fruit trees and few sources of resistance are known in its natural hosts. Since any knowledge gained from Arabidopsis on plant virus susceptibility factors is likely to be transferable to crop species, Arabidopsis's natural variation was searched for host factors essential for PPV infection. To locate regions of the genome associated with susceptibility to PPV, linkage analysis was performed on six biparental populations as well as on multiparental lines. To refine quantitative trait locus (QTL) mapping, a genome-wide association analysis was carried out using 147 Arabidopsis accessions. Evidence was found for linkage on chromosomes 1, 3 and 5 with restriction of PPV long-distance movement. The most relevant signals occurred within a region at the bottom of chromosome 3, which comprises seven RTM3-like TRAF domain-containing genes. Since the resistance mechanism analyzed here is recessive and the rtm3 knockout mutant is susceptible to PPV infection, it suggests that other gene(s) present in the small identified region encompassing RTM3 are necessary for PPV long-distance movement. In consequence, we report here the occurrence of host factor(s) that are indispensable for virus long-distance movement. © 2012 INRA. New Phytologist © 2012 New Phytologist Trust.

  15. Acute withdrawal, protracted abstinence and negative affect in alcoholism: Are they linked?

    PubMed Central

    Heilig, M.; Egli, M.; Crabbe, J.C.; Becker, H.C.

    2012-01-01

    The role of withdrawal-related phenomena in development and maintenance of alcohol addiction remains under debate. A “self-medication” framework postulates that emotional changes are induced by a history of alcohol use, persist into abstinence, and are a major factor in maintaining alcoholism. This view initially focused on negative emotional states during early withdrawal: these are pronounced, occur in the vast majority of alcohol dependent patients, and are characterized by depressed mood and elevated anxiety. This concept lost popularity with the realization that, in most patients, these symptoms abate over 3 – 6 weeks of abstinence, while relapse risk persists long beyond this period. More recently, animal data have established that a prolonged history of alcohol dependence induces more subtle neuroadaptations. These confer altered emotional processing that persists long into protracted abstinence. The resulting behavioral phenotype is characterized by excessive voluntary alcohol intake and increased behavioral sensitivity to stress. Emerging human data support the clinical relevance of negative emotionality for protracted abstinence and relapse. These developments prompt a series of research questions: 1) Are processes observed during acute withdrawal, while transient in nature, mechanistically related to those that remain during protracted abstinence? 2) Is susceptibility to negative emotionality in acute withdrawal in part due to heritable factors, similar to what animal models have indicated for susceptibility to physical aspects of withdrawal? 3) To what extent is susceptibility to negative affect that persists into protracted abstinence heritable? PMID:20148778

  16. Novel Variants in ZNF34 and Other Brain-Expressed Transcription Factors are Shared Among Early-Onset MDD Relatives

    PubMed Central

    Subaran, Ryan L.; Odgerel, Zagaa; Swaminathan, Rajeswari; Glatt, Charles E.; Weissman, Myrna M.

    2018-01-01

    There are no known genetic variants with large effects on susceptibility to major depressive disorder (MDD). Although one proposed study approach is to increase sensitivity by increasing sample sizes, another is to focus on families with multiple affected individuals to identify genes with rare or novel variants with strong effects. Choosing the family-based approach, we performed whole-exome analysis on affected individuals (n = 12) across five MDD families, each with at least five affected individuals, early onset, and prepubertal diagnoses. We identified 67 genes where novel deleterious variants were shared among affected relatives. Gene ontology analysis shows that of these 67 genes, 18 encode transcriptional regulators, eight of which are expressed in the human brain, including four KRAB-A box-containing Zn2+ finger repressors. One of these, ZNF34, has been reported as being associated with bipolar disorder and as differentially expressed in bipolar disorder patients compared to healthy controls. We found a novel variant—encoding a non-conservative P17R substitution in the conserved repressor domain of ZNF34 protein—segregating completely with MDD in all available individuals in the family in which it was discovered. Further analysis showed a common ZNF34 coding indel segregating with MDD in a separate family, possibly indicating the presence of an unobserved, linked, rare variant in that particular family. Our results indicate that genes encoding transcription factors expressed in the brain might be an important group of MDD candidate genes and that rare variants in ZNF34 might contribute to susceptibility to MDD and perhaps other affective disorders. PMID:26823146

  17. The association of folate pathway and DNA repair polymorphisms with susceptibility to childhood acute lymphoblastic leukemia.

    PubMed

    Goričar, Katja; Erčulj, Nina; Faganel Kotnik, Barbara; Debeljak, Maruša; Hovnik, Tinka; Jazbec, Janez; Dolžan, Vita

    2015-05-15

    Genetic factors may play an important role in susceptibility to childhood acute lymphoblastic leukemia (ALL). The aim of our study was to evaluate the associations of genetic polymorphisms in folate pathway and DNA repair genes with susceptibility to ALL. In total, 121 children with ALL and 184 unrelated healthy controls of Slovenian origin were genotyped for 14 polymorphisms in seven genes of folate pathway, base excision repair and homologous recombination repair (TYMS, MTHFR, OGG1, XRCC1, NBN, RAD51, and XRCC3). In addition, the exon 6 of NBN was screened for the presence of mutations using denaturing high performance liquid chromatography. Twelve polymorphisms were in Hardy-Weinberg equilibrium in controls and their genotype frequencies were in agreement with those reported in other Caucasian populations. Among the investigated polymorphisms and mutations, NBN Glu185Gln significantly decreased susceptibility to B-cell ALL (p=0.037), while TYMS 3R allele decreased susceptibility to T-cell ALL (p=0.011). Moreover, significantly decreased susceptibility to ALL was observed for MTHFR TA (p=0.030) and RAD51 GTT haplotypes (p=0.016). Susceptibility to ALL increased with the increasing number of risk alleles (ptrend=0.007). We also observed significant influence of hOGG-RAD51 and NBN-RAD51 interactions on susceptibility to ALL. Our results suggest that combination of several polymorphisms in DNA repair and folate pathways may significantly affect susceptibility to childhood ALL. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Effects of nitrogen and potassium fertilization on the susceptibility of tomatoes to post-harvest proliferation of Salmonella enterica.

    PubMed

    Marvasi, Massimiliano; George, Andrée S; Giurcanu, Mihai; Hochmuth, George J; Noel, Jason T; Gause, Elizabeth; Teplitski, Max

    2014-10-01

    Fresh fruits and vegetables are increasingly recognized as vehicles of salmonellosis. Pre- and post-harvest environmental conditions, and physiological, and genetic factors are thought to contribute to the ability of human pathogens to persist in the production environment, attach to, colonize and proliferate in and on raw produce. How field production conditions affect the post-harvest food safety outcomes is not entirely understood. This study tested how varying nitrogen and potassium fertilization levels affected the "susceptibility" of tomatoes to Salmonella infections following the harvest of fruits. Two tomato varieties grown over three seasons under high, medium, and low levels of nitrogen and potassium fertilization in two locations were inoculated with seven strains of Salmonella. Even though the main effects of nitrogen and potassium fertilization on the susceptibility of tomatoes to infections with Salmonella enterica were not statistically significant overall, differences in nitrogen concentrations in plant tissues correlated with the susceptibility of partially ripe tomatoes (cv. Solar Fire) to Salmonella. Tomato maturity and the season in which tomatoes were produced had the strongest effect on the ability of Salmonella to multiply in tomatoes. Tomato phenolics, accumulation of which is known to correlate with rates of the N fertilization, did not inhibit growth of Salmonella in vitro. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Barley disease susceptibility factor RACB acts in epidermal cell polarity and positioning of the nucleus

    PubMed Central

    Scheler, Björn; Schnepf, Vera; Galgenmüller, Carolina; Ranf, Stefanie; Hückelhoven, Ralph

    2016-01-01

    RHO GTPases are regulators of cell polarity and immunity in eukaryotes. In plants, RHO-like RAC/ROP GTPases are regulators of cell shaping, hormone responses, and responses to microbial pathogens. The barley (Hordeum vulgare L.) RAC/ROP protein RACB is required for full susceptibility to penetration by Blumeria graminis f.sp. hordei (Bgh), the barley powdery mildew fungus. Disease susceptibility factors often control host immune responses. Here we show that RACB does not interfere with early microbe-associated molecular pattern-triggered immune responses such as the oxidative burst or activation of mitogen-activated protein kinases. RACB also supports rather than restricts expression of defence-related genes in barley. Instead, silencing of RACB expression by RNAi leads to defects in cell polarity. In particular, initiation and maintenance of root hair growth and development of stomatal subsidiary cells by asymmetric cell division is affected by silencing expression of RACB. Nucleus migration is a common factor of developmental cell polarity and cell-autonomous interaction with Bgh. RACB is required for positioning of the nucleus near the site of attack from Bgh. We therefore suggest that Bgh profits from RACB’s function in cell polarity rather than from immunity-regulating functions of RACB. PMID:27056842

  20. Barley disease susceptibility factor RACB acts in epidermal cell polarity and positioning of the nucleus.

    PubMed

    Scheler, Björn; Schnepf, Vera; Galgenmüller, Carolina; Ranf, Stefanie; Hückelhoven, Ralph

    2016-05-01

    RHO GTPases are regulators of cell polarity and immunity in eukaryotes. In plants, RHO-like RAC/ROP GTPases are regulators of cell shaping, hormone responses, and responses to microbial pathogens. The barley (Hordeum vulgare L.) RAC/ROP protein RACB is required for full susceptibility to penetration by Blumeria graminis f.sp. hordei (Bgh), the barley powdery mildew fungus. Disease susceptibility factors often control host immune responses. Here we show that RACB does not interfere with early microbe-associated molecular pattern-triggered immune responses such as the oxidative burst or activation of mitogen-activated protein kinases. RACB also supports rather than restricts expression of defence-related genes in barley. Instead, silencing of RACB expression by RNAi leads to defects in cell polarity. In particular, initiation and maintenance of root hair growth and development of stomatal subsidiary cells by asymmetric cell division is affected by silencing expression of RACB. Nucleus migration is a common factor of developmental cell polarity and cell-autonomous interaction with Bgh RACB is required for positioning of the nucleus near the site of attack from Bgh We therefore suggest that Bgh profits from RACB's function in cell polarity rather than from immunity-regulating functions of RACB. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  1. Recommendations for Optimizing Tuberculosis Treatment: Therapeutic Drug Monitoring, Pharmacogenetics, and Nutritional Status Considerations

    PubMed Central

    Choi, Rihwa; Jeong, Byeong-Ho

    2017-01-01

    Although tuberculosis is largely a curable disease, it remains a major cause of morbidity and mortality worldwide. Although the standard 6-month treatment regimen is highly effective for drug-susceptible tuberculosis, the use of multiple drugs over long periods of time can cause frequent adverse drug reactions. In addition, some patients with drug-susceptible tuberculosis do not respond adequately to treatment and develop treatment failure and drug resistance. Response to tuberculosis treatment could be affected by multiple factors associated with the host-pathogen interaction including genetic factors and the nutritional status of the host. These factors should be considered for effective tuberculosis control. Therefore, therapeutic drug monitoring (TDM), which is individualized drug dosing guided by serum drug concentrations during treatment, and pharmacogenetics-based personalized dosing guidelines of anti-tuberculosis drugs could reduce the incidence of adverse drug reactions and increase the likelihood of successful treatment outcomes. Moreover, assessment and management of comorbid conditions including nutritional status could improve anti-tuberculosis treatment response. PMID:28028995

  2. Interaction Between Allergy and Middle Ear Infection.

    PubMed

    Oh, Jeong-Hoon; Kim, Woo Jin

    2016-09-01

    Recent studies have attempted to identify interactions among the causes of otitis media with effusion (OME). This review discusses the interaction between allergy and infection with regard to host and environmental factors in terms of the development of OME. Protection of the upper airway against microbial invasion requires active interaction between the defense mechanisms of the respiratory epithelium, including innate and adaptive immunity, and mechanical factors. The impairment of these defenses due to allergy and/or increased bacterial resistance may lead to increased susceptibility to infectious organisms in the respiratory tract and middle ear mucosa. Recent genetic studies have provided valuable information about the association of Toll-like receptor signaling variations with clinical phenotypes and the risk of infection in the middle ear. Among the causal factors of OME, allergy not only induces an inflammatory reaction in the middle ear cavity but also facilitates the invasion of infectious pathogens. There is also evidence that allergy can affect the susceptibility of patients to infection of the upper respiratory tract, including the middle ear cavity.

  3. Recommendations for Optimizing Tuberculosis Treatment: Therapeutic Drug Monitoring, Pharmacogenetics, and Nutritional Status Considerations.

    PubMed

    Choi, Rihwa; Jeong, Byeong Ho; Koh, Won Jung; Lee, Soo Youn

    2017-03-01

    Although tuberculosis is largely a curable disease, it remains a major cause of morbidity and mortality worldwide. Although the standard 6-month treatment regimen is highly effective for drug-susceptible tuberculosis, the use of multiple drugs over long periods of time can cause frequent adverse drug reactions. In addition, some patients with drug-susceptible tuberculosis do not respond adequately to treatment and develop treatment failure and drug resistance. Response to tuberculosis treatment could be affected by multiple factors associated with the host-pathogen interaction including genetic factors and the nutritional status of the host. These factors should be considered for effective tuberculosis control. Therefore, therapeutic drug monitoring (TDM), which is individualized drug dosing guided by serum drug concentrations during treatment, and pharmacogenetics-based personalized dosing guidelines of anti-tuberculosis drugs could reduce the incidence of adverse drug reactions and increase the likelihood of successful treatment outcomes. Moreover, assessment and management of comorbid conditions including nutritional status could improve anti-tuberculosis treatment response.

  4. Variations in the susceptibility to landslides, as a consequence of land cover changes: A look to the past, and another towards the future.

    PubMed

    Pisano, L; Zumpano, V; Malek, Ž; Rosskopf, C M; Parise, M

    2017-12-01

    Land cover is one of the most important conditioning factors in landslide susceptibility analysis. Usually it is considered as a static factor, but it has proven to be dynamic, with changes occurring even in few decades. In this work the influence of land cover changes on landslide susceptibility are analyzed for the past and for future scenarios. For the application, an area representative of the hilly-low mountain sectors of the Italian Southern Apennines was chosen (Rivo basin, in Molise Region). With this purpose landslide inventories and land cover maps were produced for the years 1954, 1981 and 2007. Two alternative future scenarios were created for 2050, one which follows the past trend (2050-trend), and another one more extreme, foreseeing a decrease of forested and cultivated areas (2050-alternative). The landslide susceptibility analysis was performed using the Spatial Multi-Criteria Evaluation method for different time steps, investigating changes to susceptibility over time. The results show that environmental dynamics, such as land cover change, affect slope stability in time. In fact there is a decrease of susceptibility in the past and in the future 2050-trend scenario. This is due to the increase of forest or cultivated areas, that is probably determined by a better land management, water and soil control respect to other land cover types such as shrubland, pasture or bareland. Conversely the results revealed by the alternative scenario (2050-alternative), show how the decrease in forest and cultivated areas leads to an increase in landslide susceptibility. This can be related to the assumed worst climatic condition leading to a minor agricultural activity and lower extension of forested areas, possibly associated also to the effects of forest fires. The results suggest that conscious landscape management might contribute to determine a significant reduction in landslide susceptibility. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Synaptic consolidation as a temporally variable process: Uncovering the parameters modulating its time-course.

    PubMed

    Casagrande, Mirelle A; Haubrich, Josué; Pedraza, Lizeth K; Popik, Bruno; Quillfeldt, Jorge A; de Oliveira Alvares, Lucas

    2018-04-01

    Memories are not instantly created in the brain, requiring a gradual stabilization process called consolidation to be stored and persist in a long-lasting manner. However, little is known whether this time-dependent process is dynamic or static, and the factors that might modulate it. Here, we hypothesized that the time-course of consolidation could be affected by specific learning parameters, changing the time window where memory is susceptible to retroactive interference. In the rodent contextual fear conditioning paradigm, we compared weak and strong training protocols and found that in the latter memory is susceptible to post-training hippocampal inactivation for a shorter period of time. The accelerated consolidation process triggered by the strong training was mediated by glucocorticoids, since this effect was blocked by pre-training administration of metyrapone. In addition, we found that pre-exposure to the training context also accelerates fear memory consolidation. Hence, our results demonstrate that the time window in which memory is susceptible to post-training interferences varies depending on fear conditioning intensity and contextual familiarity. We propose that the time-course of memory consolidation is dynamic, being directly affected by attributes of the learning experiences. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Early Childhood Caries: A Review.

    PubMed

    Alazmah, Abdulfatah

    2017-08-01

    To review and update the current knowledge about early childhood caries (ECC) and its etiology, prevalence, risk factors, management, and preventive strategies. Early childhood caries is a disease affecting significantly both well-developed and industrial nations. The ECC can significantly affect the child's quality of life, as it may lead to infection, swelling, pain, and other symptoms. The ECC affects children after eruption of primary teeth until age of around 5 years. The ECC affects all parts of the tooth including the smooth surface. Upper anterior teeth and primary molars are usually affected. The lower anterior teeth are less likely affected. The risk factors for ECC are diet, bacteria, and host susceptibility. The additional factors, such as presence of enamel defect and the feeding practices also contribute to the initiation and progress of ECC. Dentists must focus on utilizing existing techniques to distinguish indications of right on time and propelled caries and give guidance on the best way to counteract and control caries in children. Approaches should be directed to preventive caries control strategies among children. Preventing and controlling the development of ECC among children is important to maintain effective eating, speech development, and formation of a positive self-image.

  7. An Evaluation of the Reliability and Construct Validity of Eating Disorder Measures in White and Black Women

    ERIC Educational Resources Information Center

    Kelly, Nichole R.; Mitchell, Karen S.; Gow, Rachel W.; Trace, Sara E.; Lydecker, Janet A.; Bair, Carrie E.; Mazzeo, Suzanne

    2012-01-01

    Most measures of eating disorder symptoms and risk factors were developed in predominantly White female samples. Yet eating disorders affect individuals of all racial and ethnic backgrounds. Black women appear more vulnerable to certain forms of eating pathology, such as binge eating, and less susceptible to other eating disorder symptoms and risk…

  8. Factors affecting nurses' decision to get the flu vaccine.

    PubMed

    Shahrabani, Shosh; Benzion, Uri; Yom Din, Gregory

    2009-05-01

    The objective of this study was to identify factors that influence the decision whether or not to get the influenza (flu) vaccine among nurses in Israel by using the health belief model (HBM). A questionnaire distributed among 299 nurses in Israel in winter 2005/2006 included (1) socio-demographic information; (2) variables based on the HBM, including susceptibility, seriousness, benefits, barriers and cues to action; and (3) knowledge about influenza and the vaccine, and health motivation. A probit model was used to analyze the data. In Israel, the significant HBM categories affecting nurses' decision to get a flu shot are the perceived benefits from vaccination and cues to action. In addition, nurses who are vaccinated have higher levels of (1) knowledge regarding the vaccine and influenza, (2) perceived seriousness of the illness, (3) perceived susceptibility, and (4) health motivation than do those who do not get the vaccine. Immunization of healthcare workers may reduce the risk of flu outbreaks in all types of healthcare facilities and reduce morbidity and mortality among high-risk patients. In order to increase vaccination rates among nurses, efforts should be made to educate them regarding the benefits of vaccination and the potential health consequences of influenza for their patients, and themselves.

  9. Genetic Susceptibility to ANCA-Associated Vasculitis: State of the Art

    PubMed Central

    Bonatti, Francesco; Reina, Michele; Neri, Tauro Maria; Martorana, Davide

    2014-01-01

    ANCA-associated vasculitis (AAV) is a group of disorders that is caused by inflammation affecting small blood vessels. Both arteries and veins are affected. AAV includes microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA) renamed from Wegener’s granulomatosis, and eosinophilic granulomatosis with polyangiitis (EGPA), renamed from Churg–Strauss syndrome. AAV is primarily due to leukocyte migration and resultant damage. Despite decades of research, the mechanisms behind AAV disease etiology are still not fully understood, although it is clear that genetic and environmental factors are involved. To improve the understanding of the disease, the genetic component has been extensively studied by candidate association studies and two genome-wide association studies. The majority of the identified genetic AAV risk factors are common variants. These have uncovered information that still needs further investigation to clarify its importance. In this review, we summarize and discuss the results of the genetic studies in AAV. We also present the novel approaches to identifying the causal variants in complex susceptibility loci and disease mechanisms. Finally, we discuss the limitations of current methods and the challenges that we still have to face in order to incorporate genomic and epigenomic data into clinical practice. PMID:25452756

  10. Prevalence, Predictors, and Prevention of Motion Sickness in Zero-G Parabolic Flights.

    PubMed

    Golding, John F; Paillard, Aurore C; Normand, Hervé; Besnard, Stéphane; Denise, Pierre

    2017-01-01

    Zero-G parabolic flight reproduces the weightlessness of space for short periods. However, motion sickness may affect some fliers. The aim was to assess the extent of this problem and to find possible predictors and modifying factors. Airbus zero-G flights consist of 31 parabolas performed in blocks. Each parabola consisted of 20 s of 0 g sandwiched by 20 s of hypergravity of 1.5-1.8 g. The survey covered N = 246 person-flights (193 men, 53 women), ages (M ± SD) 36.0 ± 11.3 yr. An anonymous questionnaire included motion sickness rating (1 = OK to 6 = vomiting), Motion Sickness Susceptibility Questionnaire (MSSQ), antimotion sickness medication, prior zero-G experience, anxiety level, and other characteristics. Participants had lower MSSQ percentile scores (27.4 ± 28.0) than the population norm of 50. Motion sickness was experienced by 33% and 12% vomited. Less motion sickness was predicted by older age, greater prior zero-G flight experience, medication with scopolamine, lower MSSQ scores, but not gender or anxiety. Sickness ratings in fliers pretreated with scopolamine (1.81 ± 1.58) were lower than for nonmedicated fliers (2.93 ± 2.16), and incidence of vomiting in fliers using scopolamine treatment was reduced by half to a third. Possible confounding factors including age, sex, flight experience, and MSSQ could not account for this. Motion sickness affected one-third of zero-G fliers despite being intrinsically less motion sickness susceptible compared to the general population. Susceptible individuals probably try to avoid such a provocative environment. Risk factors for motion sickness included younger age and higher MSSQ scores. Protective factors included prior zero-G flight experience (habituation) and antimotion sickness medication.Golding JF, Paillard AC, Normand H, Besnard S, Denise P. Prevalence, predictors, and prevention of motion sickness in zero-G parabolic flights. Aerosp Med Hum Perform. 2017; 88(1):3-9.

  11. Cancer susceptibility and reproductive trade-offs: a model of the evolution of cancer defences

    PubMed Central

    Boddy, Amy M.; Kokko, Hanna; Breden, Felix; Wilkinson, Gerald S.; Aktipis, C. Athena

    2015-01-01

    The factors influencing cancer susceptibility and why it varies across species are major open questions in the field of cancer biology. One underexplored source of variation in cancer susceptibility may arise from trade-offs between reproductive competitiveness (e.g. sexually selected traits, earlier reproduction and higher fertility) and cancer defence. We build a model that contrasts the probabilistic onset of cancer with other, extrinsic causes of mortality and use it to predict that intense reproductive competition will lower cancer defences and increase cancer incidence. We explore the trade-off between cancer defences and intraspecific competition across different extrinsic mortality conditions and different levels of trade-off intensity, and find the largest effect of competition on cancer in species where low extrinsic mortality combines with strong trade-offs. In such species, selection to delay cancer and selection to outcompete conspecifics are both strong, and the latter conflicts with the former. We discuss evidence for the assumed trade-off between reproductive competitiveness and cancer susceptibility. Sexually selected traits such as ornaments or large body size require high levels of cell proliferation and appear to be associated with greater cancer susceptibility. Similar associations exist for female traits such as continuous egg-laying in domestic hens and earlier reproductive maturity. Trade-offs between reproduction and cancer defences may be instantiated by a variety of mechanisms, including higher levels of growth factors and hormones, less efficient cell-cycle control and less DNA repair, or simply a larger number of cell divisions (relevant when reproductive success requires large body size or rapid reproductive cycles). These mechanisms can affect intra- and interspecific variation in cancer susceptibility arising from rapid cell proliferation during reproductive maturation, intrasexual competition and reproduction. PMID:26056364

  12. Predictive susceptibility analysis of typhoon induced landslides in Central Taiwan

    NASA Astrophysics Data System (ADS)

    Shou, Keh-Jian; Lin, Zora

    2017-04-01

    Climate change caused by global warming affects Taiwan significantly for the past decade. The increasing frequency of extreme rainfall events, in which concentrated and intensive rainfalls generally cause geohazards including landslides and debris flows. The extraordinary, such as 2004 Mindulle and 2009 Morakot, hit Taiwan and induced serious flooding and landslides. This study employs rainfall frequency analysis together with the atmospheric general circulation model (AGCM) downscaling estimation to understand the temporal rainfall trends, distributions, and intensities in the adopted Wu River watershed in Central Taiwan. To assess the spatial hazard of the landslides, landslide susceptibility analysis was also applied. Different types of rainfall factors were tested in the susceptibility models for a better accuracy. In addition, the routes of typhoons were also considered in the predictive analysis. The results of predictive analysis can be applied for risk prevention and management in the study area.

  13. Genome-Wide Association Analysis of Blood Biomarkers in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Kim, Deog Kyeom; Cho, Michael H.; Hersh, Craig P.; Lomas, David A.; Miller, Bruce E.; Kong, Xiangyang; Bakke, Per; Gulsvik, Amund; Agustí, Alvar; Wouters, Emiel; Celli, Bartolome; Coxson, Harvey; Vestbo, Jørgen; MacNee, William; Yates, Julie C.; Rennard, Stephen; Litonjua, Augusto; Qiu, Weiliang; Beaty, Terri H.; Crapo, James D.; Riley, John H.; Tal-Singer, Ruth

    2012-01-01

    Rationale: A genome-wide association study (GWAS) for circulating chronic obstructive pulmonary disease (COPD) biomarkers could identify genetic determinants of biomarker levels and COPD susceptibility. Objectives: To identify genetic variants of circulating protein biomarkers and novel genetic determinants of COPD. Methods: GWAS was performed for two pneumoproteins, Clara cell secretory protein (CC16) and surfactant protein D (SP-D), and five systemic inflammatory markers (C-reactive protein, fibrinogen, IL-6, IL-8, and tumor necrosis factor-α) in 1,951 subjects with COPD. For genome-wide significant single nucleotide polymorphisms (SNPs) (P < 1 × 10−8), association with COPD susceptibility was tested in 2,939 cases with COPD and 1,380 smoking control subjects. The association of candidate SNPs with mRNA expression in induced sputum was also elucidated. Measurements and Main Results: Genome-wide significant susceptibility loci affecting biomarker levels were found only for the two pneumoproteins. Two discrete loci affecting CC16, one region near the CC16 coding gene (SCGB1A1) on chromosome 11 and another locus approximately 25 Mb away from SCGB1A1, were identified, whereas multiple SNPs on chromosomes 6 and 16, in addition to SNPs near SFTPD, had genome-wide significant associations with SP-D levels. Several SNPs affecting circulating CC16 levels were significantly associated with sputum mRNA expression of SCGB1A1 (P = 0.009–0.03). Several SNPs highly associated with CC16 or SP-D levels were nominally associated with COPD in a collaborative GWAS (P = 0.001–0.049), although these COPD associations were not replicated in two additional cohorts. Conclusions: Distant genetic loci and biomarker-coding genes affect circulating levels of COPD-related pneumoproteins. A subset of these protein quantitative trait loci may influence their gene expression in the lung and/or COPD susceptibility. Clinical trial registered with www.clinicaltrials.gov (NCT 00292552). PMID:23144326

  14. Elucidating the Links Between Endocrine Disruptors and Neurodevelopment

    PubMed Central

    Blawas, Ashley M.; Gray, Kimberly; Heindel, Jerrold J.; Lawler, Cindy P.

    2015-01-01

    Recent data indicate that approximately 12% of children in the United States are affected by neurodevelopmental disorders, including attention deficit hyperactivity disorder, learning disorders, intellectual disabilities, and autism spectrum disorders. Accumulating evidence indicates a multifactorial etiology for these disorders, with social, physical, genetic susceptibility, nutritional factors, and chemical toxicants acting together to influence risk. Exposure to endocrine-disrupting chemicals during the early stages of life can disrupt normal patterns of development and thus alter brain function and disease susceptibility later in life. This article highlights research efforts and pinpoints approaches that could shed light on the possible associations between environmental chemicals that act on the endocrine system and compromised neurodevelopmental outcomes. PMID:25714811

  15. Elongation factor P is dispensable in Escherichia coli and Pseudomonas aeruginosa.

    PubMed

    Balibar, Carl J; Iwanowicz, Dorothy; Dean, Charles R

    2013-09-01

    Elongation factor P (EF-P) is a highly conserved ribosomal initiation factor responsible for stimulating formation of the first peptide bond. Its essentiality has been debated and may differ depending on the organism. Here, we demonstrate that EF-P is dispensable in Escherichia coli and Pseudomonas aeruginosa under laboratory growth conditions. Although knockouts are viable, growth rates are diminished compared with wild-type strains. Despite this cost in fitness, these mutants are not more susceptible to a wide range of antibiotics; including ribosome targeting antibiotics, such as lincomycin, chloramphenicol, and streptomycin, which have been shown previously to disrupt EF-P function in vitro. In Pseudomonas, knockout of efp leads to an upregulation of mexX, a phenotype previously observed with other genetic lesions affecting ribosome function and that can be induced by the treatment with antibiotics affecting protein synthesis.

  16. Seborrheic Dermatitis and Dandruff: A Comprehensive Review

    PubMed Central

    Borda, Luis J.; Wikramanayake, Tongyu C.

    2016-01-01

    Seborrheic Dermatitis (SD) and dandruff are of a continuous spectrum of the same disease that affects the seborrheic areas of the body. Dandruff is restricted to the scalp, and involves itchy, flaking skin without visible inflammation. SD can affect the scalp as well as other seborrheic areas, and involves itchy and flaking or scaling skin, inflammation and pruritus. Various intrinsic and environmental factors, such as sebaceous secretions, skin surface fungal colonization, individual susceptibility, and interactions between these factors, all contribute to the pathogenesis of SD and dandruff. In this review, we summarize the current knowledge on SD and dandruff, including epidemiology, burden of disease, clinical presentations and diagnosis, treatment, genetic studies in humans and animal models, and predisposing factors. Genetic and biochemical studies and investigations in animal models provide further insight on the pathophysiology and strategies for better treatment. PMID:27148560

  17. Using the Health Belief Model to Illustrate Factors That Influence Risk Assessment during Pregnancy and Implications for Prenatal Education about Endocrine Disruptors

    ERIC Educational Resources Information Center

    Qiu, Xing; Chen, Shaw-Ree; Barrett, Emily S.; Velez, Marissa; Conn, Kelly; Heinert, Sara

    2014-01-01

    Endocrine disrupting chemicals (EDCs) such as Bisphenol A (BPA) and phthalates are ubiquitous in our environment and a growing body of research indicates that EDCs may adversely affect human development. Fetal development is particularly susceptible to EDC exposure, and prenatal care providers are being asked to educate women about the risks of…

  18. SLC11A1 polymorphisms and host susceptibility to cutaneous leishmaniasis in Pakistan.

    PubMed

    Sophie, Mariam; Hameed, Abdul; Muneer, Akhtar; Samdani, Azam J; Saleem, Saima; Azhar, Abid

    2017-01-07

    The vector-borne cutaneous leishmaniasis (CL) is endemic in several regions of Pakistan mainly affecting poor populations. Host genetic factors, particularly SLC11A1 (solute carrier transmembrane protein) within macrophages, play a crucial role in disease pathology and susceptibility. Association of SLC11A1 with cutaneous leishmaniasis, a neglected tropical disease, is not well established. Inconsistencies have been observed within different populations worldwide with respect to genetic susceptibility. This study was designed to investigate genetic variation(s) in SLC11A1 and to assess possible association with cutaneous leishmaniasis in Pakistan. Eight polymorphisms (rs2276631, rs3731864, rs2290708, rs2695342, rs201565523, rs17215556, rs17235409, rs17235416) were genotyped across SLC11A1 in 274 patients and 119 healthy controls. Six polymorphisms were studied by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing. Two single nucleotide polymorphisms were analyzed with newly designed semi-nested PCR assays. Case-control analysis showed no association between selected polymorphisms in SLC11A1 and cutaneous leishmaniasis. No significant difference was observed in the distribution of alleles between leishmaniasis patients and healthy individuals. Strong pairwise linkage disequilibrium was observed between rs2276631 and rs2290708 (r 2  = 64); and rs17235409 and rs17235416 (r 2  = 78). This study shows that genetic variations in the candidate gene SLC11A1 do not affect susceptibility to cutaneous leishmaniasis in the sample population from Pakistan.

  19. Transcriptome analysis reveals regulatory networks underlying differential susceptibility to Botrytis cinerea in response to nitrogen availability in Solanum lycopersicum

    PubMed Central

    Vega, Andrea; Canessa, Paulo; Hoppe, Gustavo; Retamal, Ignacio; Moyano, Tomas C.; Canales, Javier; Gutiérrez, Rodrigo A.; Rubilar, Joselyn

    2015-01-01

    Nitrogen (N) is one of the main limiting nutrients for plant growth and crop yield. It is well documented that changes in nitrate availability, the main N source found in agricultural soils, influences a myriad of developmental programs and processes including the plant defense response. Indeed, many agronomical reports indicate that the plant N nutritional status influences their ability to respond effectively when challenged by different pathogens. However, the molecular mechanisms involved in N-modulation of plant susceptibility to pathogens are poorly characterized. In this work, we show that Solanum lycopersicum defense response to the necrotrophic fungus Botrytis cinerea is affected by plant N availability, with higher susceptibility in nitrate-limiting conditions. Global gene expression responses of tomato against B. cinerea under contrasting nitrate conditions reveals that plant primary metabolism is affected by the fungal infection regardless of N regimes. This result suggests that differential susceptibility to pathogen attack under contrasting N conditions is not only explained by a metabolic alteration. We used a systems biology approach to identify the transcriptional regulatory network implicated in plant response to the fungus infection under contrasting nitrate conditions. Interestingly, hub genes in this network are known key transcription factors involved in ethylene and jasmonic acid signaling. This result positions these hormones as key integrators of nitrate and defense against B. cinerea in tomato plants. Our results provide insights into potential crosstalk mechanisms between necrotrophic defense response and N status in plants. PMID:26583019

  20. Single Nucleotide Polymorphisms in IL8 and TLR4 Genes as Candidates for Digital Dermatitis Resistance/Susceptibility in Holstein Cattle.

    PubMed

    El-Shafaey, El-Sayed; Ateya, Ahmed; Ramadan, Hazem; Saleh, Rasha; Elseady, Yousef; Abo El Fadl, Eman; El-Khodery, Sabry

    2017-04-03

    Relatedness between single nucleotide polymorphisms in IL8 and TLR4 genes and digital dermatitis resistance/susceptibility was investigated in seventy Holstein dairy cows. Animals were assigned into two groups, affected group (n = 35) and resistant group (n = 35) based on clinical signs and previous history of farm clinical records. Blood samples were collected for DNA extraction to ampliy fragments of 267-bp and 382-bp for IL8 and TLR4 genes, respectively. PCR-DNA sequencing revealed three SNPs in each of IL8 and TLR4 genes. The identified SNPs associated with digital dermatitis resistance were C94T, A220G, and T262A for IL8 and C118T for TLR4. However, the G349C and C355A SNPs in TLR4 gene were associated with digital dermatitis susceptibility. Chi-square analysis for comparison the distribution of all identified SNPs in both IL8 and TLR4 genes between resistant and affected animals showed no significant variation among the identified SNPs in IL8 gene. Meanwhile, there was a significant variation in case of TLR4 gene. As a pilot study, the present results revealed that identified SNPs in IL8 and TLR4 genes can be used as a genetic marker and predisposing factor for resistance/susceptibility to digital dermatitis in dairy cows. However, TLR4 gene may be a potential candidate for such disease.

  1. Effects of natural and human factors on groundwater quality of basin-fill aquifers in the southwestern United States-conceptual models for selected contaminants

    USGS Publications Warehouse

    Bexfield, Laura M.; Thiros, Susan A.; Anning, David W.; Huntington, Jena M.; McKinney, Tim S.

    2011-01-01

    As part of the U.S. Geological Survey National Water-Quality Assessment (NAWQA) Program, the Southwest Principal Aquifers (SWPA) study is building a better understanding of the factors that affect water quality in basin-fill aquifers in the Southwestern United States. The SWPA study area includes four principal aquifers of the United States: the Basin and Range basin-fill aquifers in California, Nevada, Utah, and Arizona; the Rio Grande aquifer system in New Mexico and Colorado; and the California Coastal Basin and Central Valley aquifer systems in California. Similarities in the hydrogeology, land- and water-use practices, and water-quality issues for alluvial basins within the study area allow for regional analysis through synthesis of the baseline knowledge of groundwater-quality conditions in basins previously studied by the NAWQA Program. Resulting improvements in the understanding of the sources, movement, and fate of contaminants are assisting in the development of tools used to assess aquifer susceptibility and vulnerability.This report synthesizes previously published information about the groundwater systems and water quality of 15 information-rich basin-fill aquifers (SWPA case-study basins) into conceptual models of the primary natural and human factors commonly affecting groundwater quality with respect to selected contaminants, thereby helping to build a regional understanding of the susceptibility and vulnerability of basin-fill aquifers to those contaminants. Four relatively common contaminants (dissolved solids, nitrate, arsenic, and uranium) and two contaminant classes (volatile organic compounds (VOCs) and pesticide compounds) were investigated for sources and controls affecting their occurrence and distribution above specified levels of concern in groundwater of the case-study basins. Conceptual models of factors that are important to aquifer vulnerability with respect to those contaminants and contaminant classes were subsequently formed. The conceptual models are intended in part to provide a foundation for subsequent development of regional-scale statistical models that relate specific constituent concentrations or occurrence in groundwater to natural and human factors.

  2. Ontology driven modeling for the knowledge of genetic susceptibility to disease.

    PubMed

    Lin, Yu; Sakamoto, Norihiro

    2009-05-12

    For the machine helped exploring the relationships between genetic factors and complex diseases, a well-structured conceptual framework of the background knowledge is needed. However, because of the complexity of determining a genetic susceptibility factor, there is no formalization for the knowledge of genetic susceptibility to disease, which makes the interoperability between systems impossible. Thus, the ontology modeling language OWL was used for formalization in this paper. After introducing the Semantic Web and OWL language propagated by W3C, we applied text mining technology combined with competency questions to specify the classes of the ontology. Then, an N-ary pattern was adopted to describe the relationships among these defined classes. Based on the former work of OGSF-DM (Ontology of Genetic Susceptibility Factors to Diabetes Mellitus), we formalized the definition of "Genetic Susceptibility", "Genetic Susceptibility Factor" and other classes by using OWL-DL modeling language; and a reasoner automatically performed the classification of the class "Genetic Susceptibility Factor". The ontology driven modeling is used for formalization the knowledge of genetic susceptibility to complex diseases. More importantly, when a class has been completely formalized in an ontology, the OWL reasoning can automatically compute the classification of the class, in our case, the class of "Genetic Susceptibility Factors". With more types of genetic susceptibility factors obtained from the laboratory research, our ontologies always needs to be refined, and many new classes must be taken into account to harmonize with the ontologies. Using the ontologies to develop the semantic web needs to be applied in the future.

  3. Homozygous parent affected sib pair method for detecting disease predisposing variants: application to insulin dependent diabetes mellitus.

    PubMed

    Robinson, W P; Barbosa, J; Rich, S S; Thomson, G

    1993-01-01

    For complex genetic diseases involving incomplete penetrance, genetic heterogeneity, and multiple disease genes, it is often difficult to determine the molecular variant(s) responsible for the disease pathogenesis. Linkage and association studies may help identify genetic regions and molecular variants suspected of being directly responsible for disease predisposition or protection, but, especially for complex diseases, they are less useful for determining when a predisposing molecular variant has been identified. In this paper, we expand upon the simple concept that if a genetic factor predisposing to disease has been fully identified, then a parent homozygous for this factor should transmit either of his/her copies at random to any affected children. Closely linked markers are used to determine identity by descent values in affected sib pairs from a parent homozygous for a putative disease predisposing factor. The expected deviation of haplotype sharing from 50%, when not all haplotypes carrying this factor are in fact equally predisposing, has been algebraically determined for a single locus general disease model. Equations to determine expected sharing for multiple disease alleles or multiple disease locus models have been formulated. The recessive case is in practice limiting and therefore can be used to estimate the maximum proportion of putative susceptibility haplotypes which are in fact predisposing to disease when the mode of inheritance of a disease is unknown. This method has been applied to 27 DR3/DR3 parents and 50 DR4/DR4 parents who have at least 2 children affected with insulin dependent diabetes mellitus (IDDM). The transmission of both DR3 and DR4 haplotypes is statistically different from 50% (P < 0.05 and P < 0.001, respectively). An upper estimate for the proportion of DR3 haplotypes associated with a high IDDM susceptibility is 49%, and for DR4 haplotypes 38%. Our results show that the joint presence of non-Asp at DQ beta position 57 and Arg at DQ alpha position 52, which has been proposed as a strong IDDM predisposing factor, is insufficient to explain the HLA component of IDDM predisposition.

  4. Children's differential susceptibility to parenting: An experimental test of "for better and for worse".

    PubMed

    Slagt, Meike; Dubas, Judith Semon; van Aken, Marcel A G; Ellis, Bruce J; Deković, Maja

    2017-02-01

    Differential susceptibility theory proposes that a subset of individuals exist who display enhanced susceptibility to both negative (risk-promoting) and positive (development-enhancing) environments. This experiment represents the first attempt to directly test this assumption by exposing children in the experimental group to both negative and positive feedback using puppet role-plays. It thereby serves as an empirical test as well as a methodological primer for testing differential susceptibility. Dutch children (N=190, 45.3% girls) between the ages of 4 and 6years participated. We examined whether negative and positive feedback would differentially affect changes in positive and negative affect, in prosocial and antisocial intentions and behavior, depending on children's negative emotionality. Results show that on hearing negative feedback, children in the experimental group increased in negative affect and decreased in positive affect more strongly than children in the control group. On hearing positive feedback, children in the experimental group tended to increase in positive affect and decrease in prosocial behavior. However, changes in response to negative or positive feedback did not depend on children's negative emotionality. Moreover, using reliable change scores, we found support for a subset of "vulnerable" children but not for a subset of "susceptible" children. The findings offer suggestions to guide future differential susceptibility experiments. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. New Alzheimer's disease locus on chromosome 8.

    PubMed

    Giedraitis, V; Hedlund, M; Skoglund, L; Blom, E; Ingvast, S; Brundin, R; Lannfelt, L; Glaser, A

    2006-12-01

    Family history is one of the most consistent risk factors for dementia. Therefore, analysis of families with a distinct inheritance pattern of disease can be a powerful approach for the identification of previously unknown disease genes. To map susceptibility regions for Alzheimer's disease. A complete genome scan with 369 microsatellite markers was carried out in 12 extended families collected in Sweden. Age at disease onset ranged from 53 to 78 years, but in 10 of the families there was at least one member with age at onset of < or =65 years. Mutations in known early-onset Alzheimer's disease susceptibility genes have been excluded. All people were genotyped for APOE, but no clear linkage with the epsilon4 allele was observed. Although no common disease locus could be found in all families, in two families an extended haplotype was identified on chromosome 8q shared by all affected members. In one of the families, a non-parametric multimarker logarithm of the odds (LOD) score of 4.2 (p = 0.004) was obtained and analysis based on a dominant model showed a parametric LOD score of 2.4 for this region. All six affected members of this family shared a haplotype of 10 markers spanning about 40 cM. Three affected members in another family also shared a haplotype in the same region. On the basis of our data, we propose the existence of a dominantly acting Alzheimer's disease susceptibility locus on chromosome 8.

  6. Microglial activation, increased TNF and SERT expression in the prefrontal cortex define stress-altered behaviour in mice susceptible to anhedonia.

    PubMed

    Couch, Yvonne; Anthony, Daniel C; Dolgov, Oleg; Revischin, Alexander; Festoff, Barry; Santos, Ana Isabel; Steinbusch, Harry W; Strekalova, Tatyana

    2013-03-01

    A chronic stress paradigm comprising exposure to predation, tail suspension and restraint induces a depressive syndrome in C57BL/6J mice that occurs in some, but not all, animals. Here, we sought to extend our behavioural studies to investigate how susceptibility (sucrose preference<65%) or resilience (sucrose preference>65%) to stress-induced anhedonia affects the 5HT system and the expression of inflammation-related genes. All chronically stressed animals, displayed increased level of anxiety, but susceptible mice exhibited an increased propensity to float in the forced swim test and demonstrate hyperactivity under stressful lighting conditions. These changes were not present in resilient or acutely stressed animals. Compared to resilient animals, susceptible mice showed elevated expression of tumour necrosis factor alpha (TNF) and the 5-HT transporter (SERT) in the pre-frontal area. Enhanced expression of 5HT(2A) and COX-1 in the pre-frontal area was observed in all stressed animals. In turn, indoleamine-2,3-dioxygenase (IDO) was significantly unregulated in the raphe of susceptible animals. At the cellular level, increased numbers of Iba-1-positive microglial cells were also present in the prefrontal area of susceptible animals compared to resilient animals. Consequently, the susceptible animals display a unique molecular profile when compared to resilient, but anxious, animals. Unexpectedly, this altered profile provides a rationale for exploring anti-inflammatory, and possibly, TNF-targeted therapy for major depression. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Lateral Asymmetry and Spatial Difference of Iron Deposition in the Substantia Nigra of Patients with Parkinson Disease Measured with Quantitative Susceptibility Mapping.

    PubMed

    Azuma, M; Hirai, T; Yamada, K; Yamashita, S; Ando, Y; Tateishi, M; Iryo, Y; Yoneda, T; Kitajima, M; Wang, Y; Yamashita, Y

    2016-05-01

    Quantitative susceptibility mapping is useful for assessing iron deposition in the substantia nigra of patients with Parkinson disease. We aimed to determine whether quantitative susceptibility mapping is useful for assessing the lateral asymmetry and spatial difference in iron deposits in the substantia nigra of patients with Parkinson disease. Our study population comprised 24 patients with Parkinson disease and 24 age- and sex-matched healthy controls. They underwent 3T MR imaging by using a 3D multiecho gradient-echo sequence. On reconstructed quantitative susceptibility mapping, we measured the susceptibility values in the anterior, middle, and posterior parts of the substantia nigra, the whole substantia nigra, and other deep gray matter structures in both hemibrains. To identify the more and less affected hemibrains in patients with Parkinson disease, we assessed the severity of movement symptoms for each hemibrain by using the Unified Parkinson's Disease Rating Scale. In the posterior substantia nigra of patients with Parkinson disease, the mean susceptibility value was significantly higher in the more than the less affected hemibrain substantia nigra (P < .05). This value was significantly higher in both the more and less affected hemibrains of patients with Parkinson disease than in controls (P < .05). Asymmetry of the mean susceptibility values was significantly greater for patients than controls (P < .05). Receiver operating characteristic analysis showed that quantitative susceptibility mapping of the posterior substantia nigra in the more affected hemibrain provided the highest power for discriminating patients with Parkinson disease from the controls. Quantitative susceptibility mapping is useful for assessing the lateral asymmetry and spatial difference of iron deposition in the substantia nigra of patients with Parkinson disease. © 2016 by American Journal of Neuroradiology.

  8. Arabidopsis GOLDEN2-LIKE (GLK) transcription factors activate jasmonic acid (JA)-dependent disease susceptibility to the biotrophic pathogen Hyaloperonospora arabidopsidis, as well as JA-independent plant immunity against the necrotrophic pathogen Botrytis cinerea.

    PubMed

    Murmu, Jhadeswar; Wilton, Michael; Allard, Ghislaine; Pandeya, Radhey; Desveaux, Darrell; Singh, Jas; Subramaniam, Rajagopal

    2014-02-01

    Arabidopsis thaliana GOLDEN2-LIKE (GLK1 and 2) transcription factors regulate chloroplast development in a redundant manner. Overexpression of AtGLK1 (35S:AtGLK1) in Arabidopsis also confers resistance to the cereal pathogen Fusarium graminearum. To further elucidate the role of GLK transcription factors in plant defence, the Arabidopsis glk1 glk2 double-mutant and 35S:AtGLK1 plants were challenged with the virulent oomycete pathogen Hyaloperonospora arabidopsidis (Hpa) Noco2. Compared with Col-0, glk1 glk2 plants were highly resistant to Hpa Noco2, whereas 35S:AtGLK1 plants showed enhanced susceptibility to this pathogen. Genetic studies suggested that AtGLK-mediated plant defence to Hpa Noco2 was partially dependent on salicylic acid (SA) accumulation, but independent of the SA signalling protein NONEXPRESSOR OF PATHOGENESIS-RELATED 1 (NPR1). Pretreatment with jasmonic acid (JA) dramatically reversed Hpa Noco2 resistance in the glk1 glk2 double mutant, but only marginally affected the 35S:AtGLK1 plants. In addition, overexpression of AtGLK1 in the JA signalling mutant coi1-16 did not increase susceptibility to Hpa Noco2. Together, our GLK gain-of-function and loss-of-function experiments suggest that GLK acts upstream of JA signalling in disease susceptibility to Hpa Noco2. In contrast, glk1 glk2 plants were more susceptible to the necrotrophic fungal pathogen Botrytis cinerea, whereas 35S:AtGLK1 plants exhibited heightened resistance which could be maintained in the absence of JA signalling. Together, the data reveal that AtGLK1 is involved in JA-dependent susceptibility to the biotrophic pathogen Hpa Noco2 and in JA-independent resistance to the necrotrophic pathogen B. cinerea. © 2013 HER MAJESTY THE QUEEN IN RIGHT OF CANADA. MOLECULAR PLANT PATHOLOGY © 2013 BSPP. REPRODUCED WITH THE PERMISSION OF THE MINISTER OF AGRICULTURE AND AGRI-FOOD CANADA.

  9. An Evolutionary Perspective on Family Studies: Differential Susceptibility to Environmental Influences.

    PubMed

    Hartman, Sarah; Belsky, Jay

    2016-12-01

    An evolutionary perspective of human development provides the basis for the differential-susceptibility hypothesis which stipulates that individuals should differ in their susceptibility to environmental influences, with some being more affected than others by both positive and negative developmental experiences and environmental exposures. This paper reviews evidence consistent with this claim while revealing that temperamental and genetic characteristics play a role in distinguishing more and less susceptible individuals. The differential-susceptibility framework under consideration is contrasted to the traditional diathesis-stress view that "vulnerability" traits predispose some to being disproportionately affected by (only) adverse experiences. We raise several issues stimulated by the literature that need to be clarified in further research. Lastly, we suggest that therapy may differ in its effects depending on an individual's susceptibility. © 2015 Family Process Institute.

  10. Examining the relationship between personality and affect-related attributes and adolescents' intentions to try smoking using the Substance Use Risk Profile Scale.

    PubMed

    Memetovic, Jasmina; Ratner, Pamela A; Gotay, Carolyn; Richardson, Christopher G

    2016-05-01

    Assessments of adolescents' smoking intentions indicate that many are susceptible to smoking initiation because they do not have resolute intentions to abstain from trying smoking in the future. Although researchers have developed personality and affect-related risk factor profiles to understand risk for the initiation of substance use and abuse (e.g., alcohol), few have examined the extent to which these risk factors are related to the tobacco use intentions of adolescents who have yet to try tobacco smoking. The objective of this study was to examine the relationships between personality and affect-related risk factors measured by the Substance Use Risk Profile Scale (SURPS) and smoking intentions in a sample of adolescents who have not experimented with tobacco smoking. Data is based on responses from 1352 participants in the British Columbia Adolescent Substance Use Survey (56% female, 76% in Grade 8) who had never tried smoking tobacco. Of these 1352 participants, 29% (n=338) were classified as not having resolute intentions to not try smoking. Generalized estimating equations were used to examine the relationship between each SURPS dimension (Anxiety Sensitivity, Hopelessness, Impulsivity and Sensation Seeking) and the intention to try cigarettes in the future. Hopelessness (AOR 1.06, 95% CI [1.03, 1.10], p<.001), Impulsivity (AOR 1.07 [1.03, 1.11], p<.001) and Sensation Seeking (AOR 1.05 95% CI [1.02, 1.09], p<.01) had independent statistically significant associations with having an intention to try smoking. These findings may be used to inform a prevention-oriented framework to reduce susceptibility to tobacco smoking. Copyright © 2016. Published by Elsevier Ltd.

  11. Beyond medical risk: investigating the psychological factors underlying women's perceptions of susceptibility to breast cancer, heart disease, and osteoporosis.

    PubMed

    Gerend, Mary A; Aiken, Leona S; West, Stephen G; Erchull, Mindy J

    2004-05-01

    The relationships of epidemiological (objective) risk indices, perceived disease characteristics, and cognitive heuristics to women's perceived susceptibility to breast cancer, heart disease, and osteoporosis in a community sample of 312 women ages 40-86 were examined. Epidemiological indices accounted for a small to moderate proportion of the variance in perceived susceptibility. Psychological factors (perceived similarity to women who contract the target disease and perceived disease prevalence) predicted perceived susceptibility above and beyond medical risk factors. Opposite to actual risk, age correlated negatively with perceived susceptibility to all 3 diseases. Exploratory analyses suggested that perceived similarity, perceived prevalence, and absent/exempt beliefs might mediate this relationship. Confirmatory factor analyses verified that measures of absolute and direct comparative risk assess the same underlying construct of perceived susceptibility. ((c) 2004 APA, all rights reserved)

  12. A Pharmacogenetic Discovery: Cystamine Protects Against Haloperidol-Induced Toxicity and Ischemic Brain Injury.

    PubMed

    Zhang, Haili; Zheng, Ming; Wu, Manhong; Xu, Dan; Nishimura, Toshihiko; Nishimura, Yuki; Giffard, Rona; Xiong, Xiaoxing; Xu, Li Jun; Clark, J David; Sahbaie, Peyman; Dill, David L; Peltz, Gary

    2016-05-01

    Haloperidol is an effective antipsychotic agent, but it causes Parkinsonian-like extrapyramidal symptoms in the majority of treated subjects. To address this treatment-limiting toxicity, we analyzed a murine genetic model of haloperidol-induced toxicity (HIT). Analysis of a panel of consomic strains indicated that a genetic factor on chromosome 10 had a significant effect on susceptibility to HIT. We analyzed a whole-genome SNP database to identify allelic variants that were uniquely present on chromosome 10 in the strain that was previously shown to exhibit the highest level of susceptibility to HIT. This analysis implicated allelic variation within pantetheinase genes (Vnn1 and Vnn3), which we propose impaired the biosynthesis of cysteamine, could affect susceptibility to HIT. We demonstrate that administration of cystamine, which is rapidly metabolized to cysteamine, could completely prevent HIT in the murine model. Many of the haloperidol-induced gene expression changes in the striatum of the susceptible strain were reversed by cystamine coadministration. Since cystamine administration has previously been shown to have other neuroprotective actions, we investigated whether cystamine administration could have a broader neuroprotective effect. Cystamine administration caused a 23% reduction in infarct volume after experimentally induced cerebral ischemia. Characterization of this novel pharmacogenetic factor for HIT has identified a new approach for preventing the treatment-limiting toxicity of an antipsychotic agent, which could also be used to reduce the extent of brain damage after stroke. Copyright © 2016 by the Genetics Society of America.

  13. A Pharmacogenetic Discovery: Cystamine Protects Against Haloperidol-Induced Toxicity and Ischemic Brain Injury

    PubMed Central

    Zhang, Haili; Zheng, Ming; Wu, Manhong; Xu, Dan; Nishimura, Toshihiko; Nishimura, Yuki; Giffard, Rona; Xiong, Xiaoxing; Xu, Li Jun; Clark, J. David; Sahbaie, Peyman; Dill, David L.; Peltz, Gary

    2016-01-01

    Haloperidol is an effective antipsychotic agent, but it causes Parkinsonian-like extrapyramidal symptoms in the majority of treated subjects. To address this treatment-limiting toxicity, we analyzed a murine genetic model of haloperidol-induced toxicity (HIT). Analysis of a panel of consomic strains indicated that a genetic factor on chromosome 10 had a significant effect on susceptibility to HIT. We analyzed a whole-genome SNP database to identify allelic variants that were uniquely present on chromosome 10 in the strain that was previously shown to exhibit the highest level of susceptibility to HIT. This analysis implicated allelic variation within pantetheinase genes (Vnn1 and Vnn3), which we propose impaired the biosynthesis of cysteamine, could affect susceptibility to HIT. We demonstrate that administration of cystamine, which is rapidly metabolized to cysteamine, could completely prevent HIT in the murine model. Many of the haloperidol-induced gene expression changes in the striatum of the susceptible strain were reversed by cystamine coadministration. Since cystamine administration has previously been shown to have other neuroprotective actions, we investigated whether cystamine administration could have a broader neuroprotective effect. Cystamine administration caused a 23% reduction in infarct volume after experimentally induced cerebral ischemia. Characterization of this novel pharmacogenetic factor for HIT has identified a new approach for preventing the treatment-limiting toxicity of an antipsychotic agent, which could also be used to reduce the extent of brain damage after stroke. PMID:26993135

  14. Genetic and Functional Evidence Supports LPAR1 as a Susceptibility Gene for Hypertension.

    PubMed

    Xu, Ke; Ma, Lu; Li, Yang; Wang, Fang; Zheng, Gu-Yan; Sun, Zhijun; Jiang, Feng; Chen, Yundai; Liu, Huirong; Dang, Aimin; Chen, Xi; Chun, Jerold; Tian, Xiao-Li

    2015-09-01

    Essential hypertension is a complex disease affected by genetic and environmental factors and serves as a major risk factor for cardiovascular diseases. Serum lysophosphatidic acid correlates with an elevated blood pressure in rats, and lysophosphatidic acid interacts with 6 subtypes of receptors. In this study, we assessed the genetic association of lysophosphatidic acid receptors with essential hypertension by genotyping 28 single-nucleotide polymorphisms from genes encoding for lysophosphatidic acid receptors, LPAR1, LPAR2, LPAR3, LPAR4, LPAR5, and LPAR6 and their flanking sequences, in 3 Han Chinese cohorts consisting of 2630 patients and 3171 controls in total. We identified a single-nucleotide polymorphism, rs531003 in the 3'-flanking genomic region of LPAR1, associated with hypertension (the Bonferroni corrected P=1.09×10(-5), odds ratio [95% confidence interval]=1.23 [1.13-1.33]). The risk allele C of rs531003 is associated with the increased expression of LPAR1 and the susceptibility of hypertension, particularly in those with a shortage of sleep (P=4.73×10(-5), odds ratio [95% confidence interval]=1.75 [1.34-2.28]). We further demonstrated that blood pressure elevation caused by sleep deprivation and phenylephrine-induced vasoconstriction was both diminished in LPAR1-deficient mice. Together, we show that LPAR1 is a novel susceptibility gene for human essential hypertension and that stress, such as shortage of sleep, increases the susceptibility of patients with risk allele to essential hypertension. © 2015 American Heart Association, Inc.

  15. Combination of geo- pedo- and technogenic magnetic and geochemical signals in soil profiles - Diversification and its interpretation: A new approach.

    PubMed

    Szuszkiewicz, Marcin; Łukasik, Adam; Magiera, Tadeusz; Mendakiewicz, Maria

    2016-07-01

    Magnetic and geochemical parameters of soils are determined with respect to geology, pedogenesis and anthropopression. Depending on local conditions these factors affect magnetic and geochemical signals simultaneously or in various configurations. We examined four type of soils (Entic Podzol, Eutric Cambisol, Humic Cambisol and Dystric Cambisol) developed on various bedrock (the Tumlin Sandstone, basaltoid, amphibolite and serpentinite, respectively). Our primary aim was to characterize the origin and diversification of the magnetic and geochemical signal in soils in order to distinguish the most reliable methods for correct interpretation of measured parameters. Presented data include selected parameters, both magnetic (mass magnetic susceptibility - χ, frequency-dependent magnetic susceptibility - χfd and thermomagnetic susceptibility measurement - TSM), and geochemical (selected heavy metal contents: Co, Cr, Cu, Fe, Mn, Ni, Pb, Zn). Additionally, the enrichment factor (EF) and index of geoaccumulation (Igeo) were calculated. Our results suggest the following: (1) the χ/Fe ratio may be a reliable indicator for determining changes of magnetic signal origin in soil profiles; (2) magnetic and geochemical signals are simultaneously higher (the increment of χ and lead and zinc was noted) in topsoil horizons because of the deposition of technogenic magnetic particles (TMPs); (3) EF and Igeo evaluated for lead and zinc unambiguously showed anthropogenic influence in terms of increasing heavy metal contents in topsoil regardless of bedrock or soil type; (4) magnetic susceptibility measurements supported by TSM curves for soil samples of different genetic horizons are a helpful tool for interpreting the origin and nature of the mineral phases responsible for the changes of magnetic susceptibility values. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Genetic susceptibility for Alzheimer disease neuritic plaque pathology.

    PubMed

    Shulman, Joshua M; Chen, Kewei; Keenan, Brendan T; Chibnik, Lori B; Fleisher, Adam; Thiyyagura, Pradeep; Roontiva, Auttawut; McCabe, Cristin; Patsopoulos, Nikolaos A; Corneveaux, Jason J; Yu, Lei; Huentelman, Matthew J; Evans, Denis A; Schneider, Julie A; Reiman, Eric M; De Jager, Philip L; Bennett, David A

    2013-09-01

    While numerous genetic susceptibility loci have been identified for clinical Alzheimer disease (AD), it is important to establish whether these variants are risk factors for the underlying disease pathology, including neuritic plaques. To investigate whether AD susceptibility loci from genome-wide association studies affect neuritic plaque pathology and to additionally identify novel risk loci for this trait. Candidate analysis of single-nucleotide polymorphisms and genome-wide association study in a joint clinicopathologic cohort, including 725 deceased subjects from the Religious Orders Study and the Rush Memory and Aging Project (2 prospective, community-based studies), followed by targeted validation in an independent neuroimaging cohort, including 114 subjects from multiple clinical and research centers. A quantitative measure of neuritic plaque pathologic burden, based on assessments of silver-stained tissue averaged from multiple brain regions. Validation based on β-amyloid load by immunocytochemistry, and replication with fibrillar β-amyloid positron emission tomographic imaging with Pittsburgh Compound B or florbetapir. Besides the previously reported APOE and CR1 loci, we found that the ABCA7 (rs3764650; P = .02) and CD2AP (rs9349407; P = .03) AD susceptibility loci are associated with neuritic plaque burden. In addition, among the top results of our genome-wide association study, we discovered a novel variant near the amyloid precursor protein gene (APP, rs2829887) that is associated with neuritic plaques (P = 3.3 × 10-6). This polymorphism was associated with postmortem β-amyloid load as well as fibrillar β-amyloid in 2 independent cohorts of adults with normal cognition. These findings enhance understanding of AD risk factors by relating validated susceptibility alleles to increased neuritic plaque pathology and implicate common genetic variation at the APP locus in the earliest, presymptomatic stages of AD.

  17. Risk Factors for Varicella Susceptibility Among Refugees to Toronto, Canada.

    PubMed

    Cadieux, Geneviève; Redditt, Vanessa; Graziano, Daniela; Rashid, Meb

    2017-02-01

    Several outbreaks of varicella have occurred among refugees. We aimed to estimate the prevalence of varicella susceptibility among refugees, and identify risk factors for varicella susceptibility. All refugees rostered at Crossroads Clinic in Toronto, Canada in 2011-2014 were included in our study. Varicella serology was assessed at the initial visit. Refugees' age, sex, education, time since arrival, and climate and population density of birth country were abstracted from the chart. Multivariate logistic regression was used to identify risk factors for varicella susceptibility. 1063 refugees were rostered at Crossroads Clinic during the study; 7.9 % (95 % CI 6.1, 9.7) were susceptible to varicella. Tropical climate (OR 3.20, 95 % CI 1.53, 6.69) and younger age (OR per year of age 0.92, 95 % CI 0.88-0.96) were associated with increased varicella susceptibility. These risk factors for varicella susceptibility should be taken into account to maximize the cost-effectiveness of varicella prevention strategies among refugees.

  18. Segregation of a Latent High Adiposity Phenotype in Families with a History of Type 2 Diabetes Mellitus Implicates Rare Obesity-Susceptibility Genetic Variants with Large Effects in Diabetes-Related Obesity

    PubMed Central

    Jenkins, Arthur B.; Batterham, Marijka; Samocha-Bonet, Dorit; Tonks, Katherine; Greenfield, Jerry R.; Campbell, Lesley V.

    2013-01-01

    Background We recently reported significantly greater weight gain in non-diabetic healthy subjects with a 1st degree family history (FH+) of type 2 diabetes mellitus (T2DM) than in a matched control group without such history (FH−) during voluntary overfeeding, implying co-inheritance of susceptibilities to T2DM and obesity. We have estimated the extent and mode of inheritance of susceptibility to increased adiposity in FH+. Methods Normoglycaemic participants were categorised either FH+ (≥1 1st degree relative with T2DM, 50F/30M, age 45±14 (SD) yr) or FH− (71F/51M, age 43±14 yr). Log-transformed anthropometric measurements (height, hip and waist circumferences) and lean, bone and fat mass (Dual Energy X-ray Absorptiometry) data were analysed by rotated Factor Analysis. The age- and gender-adjusted distributions of indices of adiposity in FH+ were assessed by fits to a bimodal model and by relative risk ratios (RR, FH+/FH−) and interpreted in a purely genetic model of FH effects. Results The two orthogonal factors extracted, interpretable as Frame and Adiposity accounted for 80% of the variance in the input data. FH+ was associated with significantly higher Adiposity scores (p<0.01) without affecting Frame scores. Adiposity scores in FH+ conformed to a bimodal normal distribution, consistent with dominant expression of major susceptibility genes with 59% (95% CI 40%, 74%) of individuals under the higher mode. Calculated risk allele frequencies were 0.09 (0.02, 0.23) in FH−, 0.36 (0.22, 0.48) in FH+ and 0.62 (0.36, 0.88) in unobserved T2DM-affected family members. Conclusions The segregation of Adiposity in T2DM-affected families is consistent with dominant expression of rare risk variants with major effects, which are expressed in over half of FH+ and which can account for most T2DM-associated obesity in our population. The calculated risk allele frequency in FH− suggests that rare genetic variants could also account for a substantial fraction of the prevalent obesity in this society. PMID:23950934

  19. Accumulation of anthocyanins in tomato skin extends shelf life.

    PubMed

    Bassolino, Laura; Zhang, Yang; Schoonbeek, Henk-Jan; Kiferle, Claudia; Perata, Pierdomenico; Martin, Cathie

    2013-11-01

    Shelf life is one of the most important traits for the tomato (Solanum lycopersicum) industry. Two key factors, post-harvest over-ripening and susceptibility to post-harvest pathogen infection, determine tomato shelf life. Anthocyanins accumulate in the skin of Aft/Aft atv/atv tomatoes, the result of introgressing alleles affecting anthocyanin biosynthesis in fruit from two wild relatives of tomato, which results in extended fruit shelf life. Compared with ordinary, anthocyanin-less tomatoes, the fruits of Aft/Aft atv/atv keep longer during storage and are less susceptible to Botrytis cinerea, a major tomato pathogen, post-harvest. Using genetically modified tomatoes over-producing anthocyanins, we confirmed that skin-specific accumulation of anthocyanins in tomato is sufficient to reduce the susceptibility of fruit to Botrytis cinerea. Our data indicate that accumulation of anthocyanins in tomato fruit, achieved either by traditional breeding or genetic engineering can be an effective way to extend tomato shelf life. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

  20. Mapping debris flow susceptibility using analytical network process in Kodaikkanal Hills, Tamil Nadu (India)

    NASA Astrophysics Data System (ADS)

    Sujatha, Evangelin Ramani; Sridhar, Venkataramana

    2017-12-01

    Rapid debris flows, a mixture of unconsolidated sediments and water travelling at speeds > 10 m/s are the most destructive water related mass movements that affect hill and mountain regions. The predisposing factors setting the stage for the event are the availability of materials, type of materials, stream power, slope gradient, aspect and curvature, lithology, land use and land cover, lineament density, and drainage. Rainfall is the most common triggering factor that causes debris flow in the Palar subwatershed and seismicity is not considered as it is a stable continental region and moderate seismic zone. Also, there are no records of major seismic activities in the past. In this study, one of the less explored heuristic methods known as the analytical network process (ANP) is used to map the spatial propensity of debris flow. This method is based on top-down decision model and is a multi-criteria, decision-making tool that translates subjective assessment of relative importance to weights or scores and is implemented in the Palar subwatershed which is part of the Western Ghats in southern India. The results suggest that the factors influencing debris flow susceptibility in this region are the availability of material on the slope, peak flow, gradient of the slope, land use and land cover, and proximity to streams. Among all, peak discharge is identified as the chief factor causing debris flow. The use of micro-scale watersheds demonstrated in this study to develop the susceptibility map can be very effective for local level planning and land management.

  1. Prioritizing plant defence over growth through WRKY regulation facilitates infestation by non-target herbivores.

    PubMed

    Li, Ran; Zhang, Jin; Li, Jiancai; Zhou, Guoxin; Wang, Qi; Bian, Wenbo; Erb, Matthias; Lou, Yonggen

    2015-06-17

    Plants generally respond to herbivore attack by increasing resistance and decreasing growth. This prioritization is achieved through the regulation of phytohormonal signaling networks. However, it remains unknown how this prioritization affects resistance against non-target herbivores. In this study, we identify WRKY70 as a specific herbivore-induced, mitogen-activated protein kinase-regulated rice transcription factor that physically interacts with W-box motives and prioritizes defence over growth by positively regulating jasmonic acid (JA) and negatively regulating gibberellin (GA) biosynthesis upon attack by the chewing herbivore Chilo suppressalis. WRKY70-dependent JA biosynthesis is required for proteinase inhibitor activation and resistance against C. suppressalis. In contrast, WRKY70 induction increases plant susceptibility against the rice brown planthopper Nilaparvata lugens. Experiments with GA-deficient rice lines identify WRKY70-dependent GA signaling as the causal factor in N. lugens susceptibility. Our study shows that prioritizing defence over growth leads to a significant resistance trade-off with important implications for the evolution and agricultural exploitation of plant immunity.

  2. Hierarchical Status Predicts Behavioral Vulnerability and Nucleus Accumbens Metabolic Profile Following Chronic Social Defeat Stress.

    PubMed

    Larrieu, Thomas; Cherix, Antoine; Duque, Aranzazu; Rodrigues, João; Lei, Hongxia; Gruetter, Rolf; Sandi, Carmen

    2017-07-24

    Extensive data highlight the existence of major differences in individuals' susceptibility to stress [1-4]. While genetic factors [5, 6] and exposure to early life stress [7, 8] are key components for such neurobehavioral diversity, intriguing observations revealed individual differences in response to stress in inbred mice [9-12]. This raised the possibility that other factors might be critical in stress vulnerability. A key challenge in the field is to identify non-invasively risk factors for vulnerability to stress. Here, we investigated whether behavioral factors, emerging from preexisting dominance hierarchies, could predict vulnerability to chronic stress [9, 13-16]. We applied a chronic social defeat stress (CSDS) model of depression in C57BL/6J mice to investigate the predictive power of hierarchical status to pinpoint which individuals will exhibit susceptibility to CSDS. Given that the high social status of dominant mice would be the one particularly challenged by CSDS, we predicted and found that dominant individuals were the ones showing a strong susceptibility profile as indicated by strong social avoidance following CSDS, while subordinate mice were not affected. Data from 1 H-NMR spectroscopy revealed that the metabolic profile in the nucleus accumbens (NAc) relates to social status and vulnerability to stress. Under basal conditions, subordinates show lower levels of energy-related metabolites compared to dominants. In subordinates, but not dominants, levels of these metabolites were increased after exposure to CSDS. To the best of our knowledge, this is the first study that identifies non-invasively the origin of behavioral risk factors predictive of stress-induced depression-like behaviors associated with metabolic changes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Evolutionary clade affects resistance of Clostridium difficile spores to Cold Atmospheric Plasma

    NASA Astrophysics Data System (ADS)

    Connor, Mairéad; Flynn, Padrig B.; Fairley, Derek J.; Marks, Nikki; Manesiotis, Panagiotis; Graham, William G.; Gilmore, Brendan F.; McGrath, John W.

    2017-02-01

    Clostridium difficile is a spore forming bacterium and the leading cause of colitis and antibiotic associated diarrhoea in the developed world. Spores produced by C. difficile are robust and can remain viable for months, leading to prolonged healthcare-associated outbreaks with high mortality. Exposure of C. difficile spores to a novel, non-thermal atmospheric pressure gas plasma was assessed. Factors affecting sporicidal efficacy, including percentage of oxygen in the helium carrier gas admixture, and the effect on spores from different strains representing the five evolutionary C. difficile clades was investigated. Strains from different clades displayed varying resistance to cold plasma. Strain R20291, representing the globally epidemic ribotype 027 type, was the most resistant. However all tested strains displayed a ~3 log reduction in viable spore counts after plasma treatment for 5 minutes. Inactivation of a ribotype 078 strain, the most prevalent clinical type seen in Northern Ireland, was further assessed with respect to surface decontamination, pH, and hydrogen peroxide concentration. Environmental factors affected plasma activity, with dry spores without the presence of organic matter being most susceptible. This study demonstrates that cold atmospheric plasma can effectively inactivate C. difficile spores, and highlights factors that can affect sporicidal activity.

  4. Tooth quality in dental fluorosis genetic and environmental factors.

    PubMed

    Vieira, A P G F; Hanocock, R; Eggertsson, H; Everett, E T; Grynpas, M D

    2005-01-01

    Dental fluorosis (DF) affects the appearance and structure of tooth enamel and can occur following ingestion of excess fluoride during critical periods of amelogenesis. This tooth malformation may, depending on its severity, influence enamel and dentin microhardness and dentin mineralization. Poor correlation between tooth fluoride (F) concentration and DF severity was shown in some studies, but even when a correlation was present, tooth fluoride concentration explained very little of DF severity. This fact calls into question the generally accepted hypothesis that the main factor responsible for DF severity is tooth fluoride concentration. It has been shown previously that genetic factors (susceptibility to DF) play an important role in DF severity although DF severity relates to individual susceptibility to fluoride exposure (genetics), tooth fluoride concentration relates to fluoride ingestion (environmental). The objective of this study was to investigate the correlation between tooth fluoride concentration, DF severity, and tooth mechanical and materials properties. Three strains of mice (previously shown to have different susceptibility to DF) at weaning were treated with four different levels of F in their water (0, 25, 50, and 100 ppm) for 6 weeks. Mice teeth were tested for fluoride by instrumental neutron activation analysis (INAA), DF severity determined by quantitative light-induced fluorescence [QLF], and tooth quality (enamel and dentin microhardness and dentin mineralization). Tooth fluoride concentration (environment factor) correlated positively with DF severity (QLF) (rs=0.608), fluoride treatment group (rs=0.952). However, tooth fluoride concentration correlated negatively with enamel microhardness (rs=-0.587), dentin microhardness (rs=-0.268) and dentin mineralization (rs=-0.245). Dental fluorosis (genetic factor) severity (QLF) correlated positively with fluoride treatment (rs=0.608) and tooth fluoride concentration (rs=0.583). DF severity correlated negatively with enamel microhardness (rs=-0.564) and dentin microhardness (rs=-0.356). Genetic factors (DF severity) and the environmental factor (fluoride concentration in tooth structure) have similar influence on tooth biomechanical properties, whereas only the environmental factor has an influence on tooth material property (mineralization).

  5. Methodology for Elaborating Regional Susceptibility Maps of Slope Instability: the State of Guerrero (mexico) Case Study

    NASA Astrophysics Data System (ADS)

    González Huesca, A. E.; Ferrés, D.; Domínguez-M, L.

    2013-05-01

    Numerous cases of different types of slope instability occur every year in the mountain areas of México. Sometimes these instabilities severely affect the exposed communities, roads and infrastructure, causing deaths and serious material damage, mainly in the states of Puebla, Veracruz, Oaxaca, Guerrero and Chiapas, at the central and south sectors of the country. The occurrence of the slope instability is the result of the combination of climatic, geologic, hydrologic, geomorphologic and anthropogenic factors. The National Center for Disaster Prevention (CENAPRED) is developing several projects in order to offer civil protection authorities of the Mexican states some methodologies to address the hazard assessment for different natural phenomena in a regional level. In this framework, during the past two years, a methodology was prepared to construct susceptibility maps for slope instability at regional (≤ 1:100 000) and national (≤ 1:1 000 000) levels. This research was addressed in accordance to the criteria established by the International Association of Engineering Geology, which is the highest international authority in this topic. The state of Guerrero has been taken as a pilot scheme to elaborate the susceptibility map for slope instability at a regional level. The major constraints considered in the methodology to calculate susceptibility are: a) the slope of the surface, b) the geology and c) the land use, which were integrated using a Geographic Information System (GIS). The arithmetic sum and weighting factors to obtain the final susceptibility map were based on the average values calculated in the individual study of several cases of slope instability occurred in the state in the past decade. For each case, the evaluation format proposed by CENAPRED in 2006 in the "Guía Básica para la elaboración de Atlas Estatales y Municipales de Peligros y Riesgos" to evaluate instabilities in a local level, was applied. The resulting susceptibility map shows that the central and east-central sectors of the state of Guerrero are those with higher values of susceptibility to slope instability. Future work will elaborate the hazard maps of slope instability for the state of Guerrero using and combining the information of susceptibility obtained with the data of the trigger factors, such as precipitation and seismicity, for different periods of recurrence. The final goal is that this methodology can be applied to other states of the country, in order to nourish and enhance their Atlas of hazards and risk.

  6. Characterisation of virulence genes in methicillin susceptible and resistant Staphylococcus aureus isolates from a paediatric population in a university hospital of Medellín, Colombia.

    PubMed

    Jiménez, Judy Natalia; Ocampo, Ana María; Vanegas, Johanna Marcela; Rodríguez, Erika Andrea; Garcés, Carlos Guillermo; Patiño, Luz Adriana; Ospina, Sigifredo; Correa, Margarita María

    2011-12-01

    Virulence and antibiotic resistance are significant determinants of the types of infections caused by Staphylococcus aureus and paediatric groups remain among the most commonly affected populations. The goal of this study was to characterise virulence genes of methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) strains isolated from a paediatric population of a Colombian University Hospital during 2009. Sixty MSSA and MRSA isolates were obtained from paediatric patients between zero-14 years. We identified the genes encoding virulence factors, which included Panton-Valentine leucocidine (PVL), staphylococcal enterotoxins A-E, exfoliative toxins A and B and toxic shock syndrome toxin 1. Typing of the staphylococcal chromosome cassette mec (SCCmec) was performed in MRSA strains. The virulence genes were more diverse and frequent in MSSA than in MRSA isolates (83% vs. 73%). MRSA strains harboured SCCmec types IVc (60%), I (30%), IVa (7%) and V (3%). SCCmec type IVc isolates frequently carried the PVL encoding genes and harboured virulence determinants resembling susceptible strains while SCCmec type I isolates were often negative. PVL was not exclusive to skin and soft tissue infections. As previously suggested, these differences in the distribution of virulence factor genes may be due to the fitness cost associated with methicillin resistance.

  7. Microbiome and Food Allergy

    PubMed Central

    Blázquez, Ana B.; Berin, M. Cecilia

    2016-01-01

    Food allergy is a common disease affecting approximately 8% of children and 5% of adults. The prevalence has increased over the last two decades, suggesting an important environmental contribution to susceptibility. Studies have identified mode of birth, pet exposure, and having older siblings as being significant risk modifying factors in the development of food allergy. With the discovery that these factors significantly impact the composition of the intestinal microbiome, which is known to play a critical role in shaping the immune system, recent studies have begun to address the role of the intestinal microbiota in the development of food allergy. Studies in human cohorts support a dysbiosis in food allergy, and limited data suggest that this dysbiosis occurs early in life, preceding the onset of sensitization. Studies from animal models have clearly shown that the composition of the intestinal microbiota confers susceptibility to food allergy, and that there are organisms such as Clostridia species that are protective in the development of food allergy. Our understanding of microbial regulation of food allergy is in its nascency, but the state of the field supports an important contribution of intestinal microbes to susceptibility. Challenges going forward are to identify commensal-derived microorganisms that could be used therapeutically to prevent or perhaps treat food allergy. PMID:27686718

  8. Association between EN1 rs4144782 and susceptibility of knee osteoarthritis: A case-control study.

    PubMed

    Li, Haohuan; Zhang, Xiaolong; Cao, Yiping; Hu, Song; Peng, Fei; Zhou, Jianlin; Li, Jianping

    2017-05-30

    Osteoarthritis (OA) is a complex disease that affects the whole joint, resulting from the combined influence of biomechanical factors and genetic factors. The heritable component for primary OA accounts for about 60% of variation in population liability to the disease. So far, genome-wide association studies (GWAS) and candidate gene studies have established many OA-related loci. However, these findings account for only a rather small fraction of the genetic component. To further reveal the genetic architecture of OA, we conducted this case-control study to explore the association of locus EN1 rs4144782 and knee OA susceptibility in a Chinese population. EN1 rs4144782 was significantly associated with increased risk of knee OA (OR=1.26; 95% CI: 1.05-1.50, P value=0.012). In dominant model, compared with carriers of GG genotype, those with AG or AA genotype have an 1.44-fold increased risk of OA (OR: 1.44; 95% CI: 1.10-1.88; P value=0.008). Subgroup analyses didn't change the results materially. This should be the first association study of EN1 locus on risk of OA, and our finding suggested that the EN1 rs4144782 might contribute to the susceptibility of knee OA.

  9. Parental genetic diversity of brown trout (Salmo trutta m. fario) brood stock affects offspring susceptibility to whirling disease.

    PubMed

    Eszterbauer, Edit; Forró, Barbara; Tolnai, Zoltán; Guti, Csaba Ferenc; Zsigmond, Gergely; Hoitsy, György; Kallert, Dennis Marc

    2015-03-03

    Whirling disease, caused by the myxozoan parasite Myxobolus cerebralis, has high economical and ecological importance worldwide. Susceptibility to the disease varies considerably among salmonid species. In brown trout (Salmo trutta) the infection is usually subclinical with low mortality, which increases the risk of parasite dissemination, especially when farm fish are used for stocking natural habitats. The influence of intraspecific genetic differences (especially the level of homozygosity) on susceptibility is unknown. Therefore, we examined the possible correlations between parental genetic diversity and offspring susceptibility of brown trout stocks to whirling disease. Two brown trout brood stocks from a German and a Hungarian fish farm were genetically characterized using microsatellite and lineage-specific genetic markers. The individual inbreeding coefficient f and pairwise relatedness factor r were estimated based on eight microsatellite markers. Brood stock populations were divided into groups according to low and high f and r value estimates and subjected to selective fertilization. The offspring from these separate groups were exposed to M. cerebralis actinospores, and the infection prevalence and intensity was measured and statistically analysed. The analysis of phylogeographic lineage heritage revealed high heterogeneity in the Hungarian brood stock since > 50% of individuals were Atlantic-Danubian hybrids, while only pure Atlantic-descending specimens were detected in the German population. Based on f msat and r msat estimations, classified non-inbred (NIB), inbred (IB) and a group of closely related fish (REL) were created. The susceptibility of their offspring varied considerably. Although there was no significant difference in the prevalence of M. cerebralis infection, the mean intensity of infection differed significantly between NIB and IB groups. In REL and IB groups, a high variability was observed in infection intensity. No external clinical signs were observed in the exposed brown trout groups. Our findings indicate that the allelic diversity of brown trout brood stock may constitute a significant factor in disease susceptibility, i.e. the intensity of parasite infection in the subsequent generation.

  10. A Systematic Review on Sasang Constitutional Type-Associated Susceptibility to Disorders in Korea.

    PubMed

    Lee, Hyun-Yong; Lee, Woo-Jin; Kim, Hae-Won; Jang, Eun-Su; Ahn, Yo-Chan; Ku, Bon-Cho; Kang, Weechang; Lee, Si-Woo; Son, Chang-Gue

    2016-12-01

    Sasang constitutional medicine is a component of traditional Korean medicine that classifies individuals into four Sasang constitutional types (SCTs) by their physical and psychological traits. Each SCT is known to show different susceptibilities to disorders. This systematic review investigated the effect of SCT as a risk factor for various disorders. A systematic literature survey was conducted by searching seven databases for all articles on the prevalence rates of disorders according to SCT and sex. From 14,272 relevant articles, 15 studies (13 disorders) were ultimately identified to verify different prevalence rates by SCT. Of the 13 disorders, 6 (prehypertension, general obesity, abdominal obesity, metabolic syndrome, diabetes mellitus, and irritable bowel syndrome [IBS]) had a significantly different prevalence by SCT. Metabolic syndrome and its associated disorders showed the highest prevalence in Taeumin-type individuals, whereas IBS was most prevalent in Soeumin-type individuals. In general, these findings were consistent with the results obtained in an analysis of male and female participants. This study revealed that susceptibility to disorders was affected by SCT to some extent. Further studies are needed to determine the concrete features of SCT-related susceptibility, which may be helpful in preventive medicine with Sasang constitutional practice.

  11. Regulatory T cells control strain specific resistance to Experimental Autoimmune Prostatitis

    PubMed Central

    Breser, Maria L.; Lino, Andreia C.; Motrich, Ruben D.; Godoy, Gloria J.; Demengeot, Jocelyne; Rivero, Virginia E.

    2016-01-01

    Susceptibility to autoimmune diseases results from the encounter of a complex and long evolved genetic context with a no less complex and changing environment. Major actors in maintaining health are regulatory T cells (Treg) that primarily dampen a large subset of autoreactive lymphocytes escaping thymic negative selection. Here, we directly asked whether Treg participate in defining susceptibility and resistance to Experimental Autoimmune Prostatitis (EAP). We analyzed three common laboratory strains of mice presenting with different susceptibility to autoimmune prostatitis upon immunization with prostate proteins. The NOD, the C57BL/6 and the BALB/c mice that can be classified along a disease score ranging from severe, mild and to undetectable, respectively. Upon mild and transient depletion of Treg at the induction phase of EAP, each model showed an increment along this score, most remarkably with the BALB/c mice switching from a resistant to a susceptible phenotype. We further show that disease associates with the upregulation of CXCR3 expression on effector T cells, a process requiring IFNγ. Together with recent advances on environmental factors affecting Treg, these findings provide a likely cellular and molecular explanation to the recent rise in autoimmune diseases incidence. PMID:27624792

  12. Age is not a determinant factor in susceptibility of broilers to H5N2 clade 2.3.4.4 high pathogenicity avian influenza virus

    USDA-ARS?s Scientific Manuscript database

    In 2014–2015, the US experienced an unprecedented outbreak of H5 clade 2.3.4.4 highly pathogenic avian influenza (HPAI) virus. The H5N2 HPAI virus outbreak in the Midwest in 2015 affected commercial turkey and layer farms, but not broiler farms. To assess any potential genetic resistance of broilers...

  13. The interobserver-validated relevance of intervertebral spacer materials in MRI artifacting

    PubMed Central

    Heidrich, G.; Bruening, T.; Krefft, S.; Buchhorn, G.; Klinger, H.M.

    2006-01-01

    Intervertebral spacers for anterior spine fusion are made of different materials, such as titanium, carbon or cobalt-chrome, which can affect the post-fusion MRI scans. Implant-related susceptibility artifacts can decrease the quality of MRI scans, thwarting proper evaluation. This cadaver study aimed to demonstrate the extent that implant-related MRI artifacting affects the post-fusion evaluation of intervertebral spacers. In a cadaveric porcine spine, we evaluated the post-implantation MRI scans of three intervertebral spacers that differed in shape, material, surface qualities and implantation technique. A spacer made of human cortical bone was used as a control. The median sagittal MRI slice was divided into 12 regions of interest (ROI). No significant differences were found on 15 different MRI sequences read independently by an interobserver-validated team of specialists (P>0.05). Artifact-affected image quality was rated on a score of 0-1-2. A maximum score of 24 points (100%) was possible. Turbo spin echo sequences produced the best scores for all spacers and the control. Only the control achieved a score of 100%. The carbon, titanium and cobalt-chrome spacers scored 83.3, 62.5 and 50%, respectively. Our scoring system allowed us to create an implant-related ranking of MRI scan quality in reference to the control that was independent of artifact dimensions. The carbon spacer had the lowest percentage of susceptibility artifacts. Even with turbo spin echo sequences, the susceptibility artifacts produced by the metallic spacers showed a high degree of variability. Despite optimum sequencing, implant design and material are relevant factors in MRI artifacting. PMID:16463200

  14. Confirmation of prior evidence of genetic susceptibility to alcoholism in a genome-wide association study of comorbid alcoholism and bipolar disorder.

    PubMed

    Lydall, Gregory John; Bass, Nicholas J; McQuillin, Andrew; Lawrence, Jacob; Anjorin, Adebayo; Kandaswamy, Radhika; Pereira, Ana; Guerrini, Irene; Curtis, David; Vine, Anna E; Sklar, Pamela; Purcell, Shaun M; Gurling, Hugh Malcolm Douglas

    2011-12-01

    Alcoholism and affective disorders are both strongly comorbid and heritable. We have investigated the genetic comorbidity between bipolar affective disorder and alcoholism. A genome-wide allelic association study of 506 patients from the University College London bipolar disorder case-control sample and 510 ancestrally matched supernormal controls. One hundred forty-three of the bipolar patients fulfilled the Research Diagnostic Criteria diagnosis of alcoholism. A total of 372 193 single nucleotide polymorphisms (SNPs) were genotyped. Genes previously shown to be associated with alcoholism and addiction phenotypes were then tested for association in the bipolar alcoholic sample using gene-wise permutation tests of all SNPs genotyped within a 50-kb region flanking each gene. Several central nervous system genes showed significant (P<0.05) gene-wise evidence of association with bipolar alcoholism. The genes implicated, which replicated genes previously shown to be associated with alcoholism were: cadherin 11, collagen type 11 α2, neuromedin U receptor 2, exportin7, and semaphorin-associated protein 5A. The SNPs most strongly implicated in bipolar alcoholism, but, which did not meet conventional genome-wide significance criteria were the insulin-like growth factor-binding protein 7, carboxypeptidase O, cerebellin 2, and the cadherin 12 genes. We have confirmed the role of some genes previously shown to be associated with alcoholism in the comorbid bipolar alcoholism subgroup. In this subgroup, bipolar disorder may lower the threshold for the phenotypic expression of these alcoholism susceptibility genes. We also show that some genes may independently increase susceptibility to affective disorder and alcoholism.

  15. Increased susceptibility of skin from HERDA (Hereditary Equine Regional Dermal Asthenia)-affected horses to bacterial collagenase degradation: a potential contributing factor to the clinical signs of HERDA.

    PubMed

    Rashmir-Raven, Ann; Lavagnino, Michael; Sedlak, Aleksa; Gardner, Keri; Arnoczky, Steven

    2015-12-01

    Hereditary equine regional dermal asthenia (HERDA) is a genetic disorder of collagen resulting in fragile, hyper-extensible skin and ulcerative lesions. The predominance of skin lesions have been shown to occur on the dorsum of HERDA-affected horses. While this has been postulated to be due to increased exposure to sunlight of these areas, the precise pathological mechanism which causes this to occur is unclear. We hypothesized that an increase in collagenase activity, that has been associated with the exposure of dermal fibroblasts to sunlight, will significantly degrade the material properties of skin from HERDA-affected horses when compared to unaffected controls. Six unaffected and seven HERDA-affected horses, all euthanized for other reasons. Full-thickness skin samples from similar locations on each horse were collected and cut into uniform strips and their material properties (tensile modulus) determined by mechanical testing before (n = 12 samples/horse) or after (n = 12 samples/horse) incubation in bacterial collagenase at 37°C for 6 h. The change in modulus following treatment was then compared between HERDA-affected and unaffected horses using a Student's t-test. The modulus of skin from HERDA-affected horses decreased significantly more than that from unaffected horses following collagenase treatment (54 ± 7% versus 30 ± 16%, P = 0.004). The significant decrease in the modulus of skin from HERDA-affected horses following collagenase exposure suggests that their altered collagen microarchitecture is more susceptible to enzymatic degradation and may explain the localization of skin lesions in HERDA-affected horses to those areas of the body most exposed to sunlight. These findings appear to support the previously reported benefits of sunlight restriction in HERDA-affected horses. © 2015 ESVD and ACVD.

  16. Lithology and Bedrock Geotechnical Properties in Controlling Rock and Ice Mass Movements in Mountain Cryosphere

    NASA Astrophysics Data System (ADS)

    Karki, A.; Kargel, J. S.

    2017-12-01

    Landslides and ice avalanches kill >5000 people annually (D. Petley, 2012, Geology http://dx.doi.org/10.1130/G33217.1); destroy or damage homes and infrastructure; and create secondary hazards, such as flooding due to blocked rivers. Critical roles of surface slope, earthquake shaking, soil characteristics and saturation, river erosional undercutting, rainfall intensity, snow loading, permafrost thaw, freeze-thaw and frost shattering, debuttressing of unstable masses due to glacier thinning, and vegetation burn or removal are well-known factors affecting landslides and avalanches. Lithology-dependent bedrock physicochemical-mechanical properties—especially brittle elastic and shear strength, and chemical weathering properties that affect rock strength, are also recognized controls on landsliding and avalanching, but are not commonly considered in detail in landslide susceptibility assessment. Lithology controls the formation of weakened, weathered bedrock; the formation and accumulation of soils; soil saturation-related properties of grain size distribution, porosity, and permeability; and soil creep related to soil wetting-drying and freeze-thaw. Lithology controls bedrock abrasion and glacial erosion and debris production rates, the formation of rough or smoothed bedrock surface by glaciation, fluvial, and freeze-thaw processes. Lithologic variability (e.g., bedding; fault and joint structure) affects contrasts in chemical weathering rates, porosity, and susceptibility to frost shattering and chemical weathering, hence formation of overhanging outcrops and weakened slip planes. The sudden failure of bedrock or sudden slip of ice on bedrock, and many other processes depend on rock lithology, microstructure (porosity and permeability), and macrostructure (bedding; faults). These properties are sometimes considered in gross terms for landslide susceptibility assessment, but in detailed applications to specific development projects, and in detailed mapping over large areas, the details of rock lithology, weathering state, and structure are rarely considered. We have initiated a geological and rock mechanical properties approach to landslide susceptibility assessments in areas of high concern for human and infrastructure safety.

  17. Empiric systemic antibiotics for hospitalized patients with severe odontogenic infections.

    PubMed

    Zirk, Matthias; Buller, Johannes; Goeddertz, Peter; Rothamel, Daniel; Dreiseidler, Timo; Zöller, Joachim E; Kreppel, Matthias

    2016-08-01

    Odontogenic infections may lead to severe head and neck infections with potentially great health risk. Age, location of purulent affected sites and beta-lactam allergy are some mentionable factors regarding patients' in-hospital stay and course of disease. Are there new challenges regarding bacteria' antibiotic resistance for empiric treatment and what influences do they have on patients' clinical course? We analyzed in a 4-year retrospective study the medical records of 294 in-hospital patients with severe odontogenic infections. On a routine base bacteria were identified and susceptibility testing was performed. Length of stay in-hospital was evaluated regarding patients' age, beta-lactam allergy profile, affected sites and bacteria susceptibility to empiric antibiotics. Length of stay in-hospital was detected to be associated with affected space and penicillin allergy as well (p < 0.05). Isolates presented large amounts of aerobic gram-positive bacteria (64.2%), followed by facultative anaerobic bacteria (gram+/15.8%, gram-/12.7%). Tested ampicillin in combination with sulbactam (or without) and cephalosporins displayed high susceptibility rates, revealing distinguished results regarding clindamycin (p < 0.05). Co-trimoxazol and moxifloxacin showed high overall susceptibility rates (MOX: 94.7%, COTRIM: 92.6%). This study demonstrates ampicillin/sulbactam in addition to surgical intervention is a good standard in treatment of severe odontogenic neck infections. Cephalosporins seem to be a considerable option as well. If beta-lactam allergy is diagnosed co-trimoxazol and moxifloxacin represent relevant alternatives. Age, allergic profile and bacteria' resistance patterns for empiric antibiotics have an influence on patients in-hospital stay. Ampicillin/sulbactam proves itself to be good for empiric antibiosis in severe odontogenic infections. Furthermore cephalosporins could be considered as another option in treatment. However moxifloxacin and co-trimoxazol deserves further investigation as empiric antibiosis in odontogenic infections if beta-lactam allergy is diagnosed. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  18. Effects of Inventory Bias on Landslide Susceptibility Calculations

    NASA Technical Reports Server (NTRS)

    Stanley, T. A.; Kirschbaum, D. B.

    2017-01-01

    Many landslide inventories are known to be biased, especially inventories for large regions such as Oregon's SLIDO or NASA's Global Landslide Catalog. These biases must affect the results of empirically derived susceptibility models to some degree. We evaluated the strength of the susceptibility model distortion from postulated biases by truncating an unbiased inventory. We generated a synthetic inventory from an existing landslide susceptibility map of Oregon, then removed landslides from this inventory to simulate the effects of reporting biases likely to affect inventories in this region, namely population and infrastructure effects. Logistic regression models were fitted to the modified inventories. Then the process of biasing a susceptibility model was repeated with SLIDO data. We evaluated each susceptibility model with qualitative and quantitative methods. Results suggest that the effects of landslide inventory bias on empirical models should not be ignored, even if those models are, in some cases, useful. We suggest fitting models in well-documented areas and extrapolating across the study region as a possible approach to modeling landslide susceptibility with heavily biased inventories.

  19. Effects of Inventory Bias on Landslide Susceptibility Calculations

    NASA Technical Reports Server (NTRS)

    Stanley, Thomas; Kirschbaum, Dalia B.

    2017-01-01

    Many landslide inventories are known to be biased, especially inventories for large regions such as Oregons SLIDO or NASAs Global Landslide Catalog. These biases must affect the results of empirically derived susceptibility models to some degree. We evaluated the strength of the susceptibility model distortion from postulated biases by truncating an unbiased inventory. We generated a synthetic inventory from an existing landslide susceptibility map of Oregon, then removed landslides from this inventory to simulate the effects of reporting biases likely to affect inventories in this region, namely population and infrastructure effects. Logistic regression models were fitted to the modified inventories. Then the process of biasing a susceptibility model was repeated with SLIDO data. We evaluated each susceptibility model with qualitative and quantitative methods. Results suggest that the effects of landslide inventory bias on empirical models should not be ignored, even if those models are, in some cases, useful. We suggest fitting models in well-documented areas and extrapolating across the study region as a possible approach to modelling landslide susceptibility with heavily biased inventories.

  20. Does thinning affect gypsy moth dynamics?

    Treesearch

    Andrew M. Liebhold; Rose-Marie Muzika; Kurt W. Gottschalk

    1998-01-01

    In northeastern U.S. forests there is considerable variation in susceptibility (defoliation potential) and vulnerability (tree mortality) to gypsy moth (Lymantria dispar [L.]). Thinning has been suggested as a way to reduce susceptibility and/or vulnerability. We evaluated how thinning affected the dynamics of gypsy moth populations by experimentally...

  1. PWSCC Susceptibility in Heat Affected Zones of Alloy 600

    NASA Astrophysics Data System (ADS)

    Couvant, Thierry; Brossier, Thomas; Cossange, Christian

    The recent field experience and several experimental results have shown the possible deleterious effect of a heat affected zone (HAZ) induced by welding on the susceptibility to the stress corrosion cracking (SCC) of Alloy 600 of bottom penetrations exposed to primary water of PWRs. This work tried to quantify the increasing susceptibility to initiation and crack propagation in 600/182 HAZ. The rolled plate did not exhibit any susceptibility to SCC except for a cold work higher than 10% typically. By contrast, the weld metal was well known for its high susceptibility to SCC. Metallurgical and mechanical characterizations of the HAZ indicated a slight gradient of Vickers micro hardness close to the fusion line (up to few mm) and a lack of intergranular precipitates up to 500 µm from the fusion line. SCC tests clearly demonstrated that a non-susceptible plate may exhibit a significant susceptibility to SCC propagation in the HAZ. Results of initiation tests did not allow to observe any SCC in the base metal, due to the high susceptibility to SCC of the weld.

  2. Field-based landslide susceptibility assessment in a data-scarce environment: the populated areas of the Rwenzori Mountains

    NASA Astrophysics Data System (ADS)

    Jacobs, Liesbet; Dewitte, Olivier; Poesen, Jean; Sekajugo, John; Nobile, Adriano; Rossi, Mauro; Thiery, Wim; Kervyn, Matthieu

    2018-01-01

    The inhabited zone of the Ugandan Rwenzori Mountains is affected by landslides, frequently causing loss of life, damage to infrastructure and loss of livelihood. This area of ca. 1230 km2 is characterized by contrasting geomorphologic, climatic and lithological patterns, resulting in different landslide types. In this study, the spatial pattern of landslide susceptibility is investigated based on an extensive field inventory constructed for five representative areas within the region (153 km2) and containing over 450 landslides. To achieve a reliable susceptibility assessment, the effects of (1) using different topographic data sources and spatial resolutions and (2) changing the scale of assessment by comparing local and regional susceptibility models on the susceptibility model performances are investigated using a pixel-based logistic regression approach. Topographic data are extracted from different digital elevation models (DEMs) based on radar interferometry (SRTM and TanDEM-X) and optical stereophotogrammetry (ASTER DEM). Susceptibility models using the radar-based DEMs tend to outperform the ones using the ASTER DEM. The model spatial resolution is varied between 10, 20, 30 and 90 m. The optimal resolution depends on the location of the investigated area within the region but the lowest model resolution (90 m) rarely yields the best model performances while the highest model resolution (10 m) never results in significant increases in performance compared to the 20 m resolution. Models built for the local case studies generally have similar or better performances than the regional model and better reflect site-specific controlling factors. At the regional level the effect of distinguishing landslide types between shallow and deep-seated landslides is investigated. The separation of landslide types allows us to improve model performances for the prediction of deep-seated landslides and to better understand factors influencing the occurrence of shallow landslides such as tangent curvature and total rainfall. Finally, the landslide susceptibility assessment is overlaid with a population density map in order to identify potential landslide risk hotspots, which could direct research and policy action towards reduced landslide risk in this under-researched, landslide-prone region.

  3. Comparison between monitored and modeled pore water pressure and safety factor in a slope susceptible to shallow landslides

    NASA Astrophysics Data System (ADS)

    Bordoni, Massimiliano; Meisina, Claudia; Zizioli, Davide; Valentino, Roberto; Bittelli, Marco; Chersich, Silvia

    2014-05-01

    Shallow landslides can be defined as slope movements affecting superficial deposits of small thicknesses which are usually triggered due to extreme rainfall events, also very concentrated in time. Shallow landslides are hazardous phenomena: in particular, if they happen close to urbanized areas they could cause significant damages to cultivations, structures, infrastructures and, sometimes, human losses. The triggering mechanism of rainfall-induced shallow landslides is strictly linked with the hydrological and mechanical responses of usually unsaturated soils to rainfall events. For this reason, it is fundamental knowing the intrinsic hydro-mechanical properties of the soils in order to assess both susceptibility and hazard of shallow landslide and to develop early-warning systems at large scale. The hydrological data collected by a 20 months monitoring on a slope susceptible to shallow landslides in an area of the North -Eastern Oltrepo Pavese (Northern Apennines, Italy) were used to identify the hydrological behaviors of the investigated soils towards rainfall events. Field conditions under different rainfall trends have also been modeled by using both hydrological and physically-based stability models for the evaluation of the slope safety factor . The main objectives of this research are: (a) to compare the field measured pore water pressures at different depths with results of hydrological models, in order to evaluate the efficiency of the tested models and to determine how precipitations affect pore pressure development; (b) to compare the time trends of the safety factor that have been obtained by applying different stability models; (c) to evaluate, through a sensitivity analysis, the effects of soil hydrological properties on modeling pore water pressure and safety factor. The test site slope where field measurements were acquired is representative of other sites in Northern Apennines affected by shallow landslides and is characterized by medium-high topographic gradient (ranging from 22 to 35°). The bedrock is made up of gravel, sand and poorly cemented conglomerates; superficial soils, derived by the weathered bedrock, are prevalently clayey-sandy silts and clayey-silty sands with different amounts of pebbles and carbonate concretions. A geotechnical, mechanical, pedological and mineralogical characterization of superficial deposits was performed. Laboratory reconstruction of hysteretic soil water characteristic curves was also carried out to determine the main soil hydrological properties. The experimental station consists in a pluviometer, a thermo-hygrometer, a barometer, an anemometer and a net radiometer. Six TDR probes equipped with a multiplexer are installed at 0.2, 0.4, 0.6, 1, 1.2, 1.4 m from ground level to measure volumetric water content; to measure pore water pressure, three tensiometers and three heat dissipation sensors are installed at 0.2, 0.6, 1.2 m from ground level. The data are collected by a CR1000 datalogger (Campbell Sci. Inc.) each 10 minutes. In this work the results of the comparison between monitored and modeled pore water pressures and the safety factor in different conditions are analyzed in order to understand the hydro-mechanical properties that could predispose the triggering mechanism of shallow instabilities and the processes that have to be taken into account in the evaluation of shallow landslides susceptibility.

  4. Medical hypothesis: xenoestrogens as preventable causes of breast cancer.

    PubMed Central

    Davis, D L; Bradlow, H L; Wolff, M; Woodruff, T; Hoel, D G; Anton-Culver, H

    1993-01-01

    Changes in documented risk factors for breast cancer and rates of screening cannot completely explain recent increases in incidence or mortality. Established risk factors for breast cancer, including genetics, account for at best 30% of cases. Most of these risk factors can be linked to total lifetime exposure to bioavailable estrogens. Experimental evidence reveals that compounds such as some chlorinated organics, polycyclic aromatic hydrocarbons (PAHs), triazine herbicides, and pharmaceuticals affect estrogen production and metabolism and thus function as xenoestrogens. Many of these xenoestrogenic compounds also experimentally induce mammary carcinogenesis. Recent epidemiologic studies have found that breast fat and serum lipids of women with breast cancer contain significantly elevated levels of some chlorinated organics compared with noncancer controls. As the proportion of inherited breast cancer in the population is small, most breast cancers are due to acquired mutations. Thus, the induction of breast cancer in the majority of cases stems from interactions between host factors, including genetics and environmental carcinogens. We hypothesize that substances such as xenoestrogens increase the risk of breast cancer by mechanisms which include interaction with breast-cancer susceptibility genes. A series of major epidemiologic studies need to be developed to evaluate this hypothesis, including studies of estrogen metabolism, the role of specific xenoestrogenic substances in breast cancer, and relevant genetic-environmental interactions. In addition, experimental studies are needed to evaluate biologic markers of suspect xenoestrogens and biologic markers of host susceptibility and identify pathways of estrogenicity that affect the development of breast cancer. If xenoestrogens do play a role in breast cancer, reductions in exposure will provide an opportunity for primary prevention of this growing disease.(ABSTRACT TRUNCATED AT 250 WORDS) Images p372-a Figure 1. PMID:8119245

  5. Inflammatory Bowel Disease: Genetics, Epigenetics, and Pathogenesis

    PubMed Central

    Loddo, Italia; Romano, Claudio

    2015-01-01

    Inflammatory bowel diseases (IBDs) are complex, multifactorial disorders characterized by chronic relapsing intestinal inflammation. Although etiology remains largely unknown, recent research has suggested that genetic factors, environment, microbiota, and immune response are involved in the pathogenesis. Epidemiological evidence for a genetic contribution is defined: 15% of patients with Crohn’s Disease (CD) have an affected family member with IBD, and twin studies for CD have shown 50% concordance in monozygotic twins compared to <10% in dizygotics. The most recent and largest genetic association studies, which employed genome-wide association data for over 75,000 patients and controls, identified 163 susceptibility loci for IBD. More recently, a trans-ethnic analysis, including over 20,000 individuals, identified an additional 38 new IBD loci. Although most cases are correlated with polygenic contribution toward genetic susceptibility, there is a spectrum of rare genetic disorders that can contribute to early-onset IBD (before 5 years) or very early onset IBD (before 2 years). Genetic variants that cause these disorders have a wide effect on gene function. These variants are so rare in allele frequency that the genetic signals are not detected in genome-wide association studies of patients with IBD. With recent advances in sequencing techniques, ~50 genetic disorders have been identified and associated with IBD-like immunopathology. Monogenic defects have been found to alter intestinal immune homeostasis through many mechanisms. Candidate gene resequencing should be carried out in early-onset patients in clinical practice. The evidence that genetic factors contribute in small part to disease pathogenesis confirms the important role of microbial and environmental factors. Epigenetic factors can mediate interactions between environment and genome. Epigenetic mechanisms could affect development and progression of IBD. Epigenomics is an emerging field, and future studies could provide new insight into the pathogenesis of IBD. PMID:26579126

  6. Predisposing factors and susceptibility assessment for deep-seated gravitational slope deformations (DSGSDs): a case study (NW Alps, Italy)

    NASA Astrophysics Data System (ADS)

    Lo Russo, S.; Forno, M. G.; Taddia, G.; Gnavi, L.

    2012-04-01

    KEY WORDS: Deep-seated gravitational slope deformation (DSGSD); Risk; Hazard; Susceptibility; Piemonte; Italy Deep-seated gravitational slope deformations (DSGSDs) and "sackung" deformations are complex processes of gravitational movement that involve large volumes of rock, often several tens of meters thick and several kilometers long. The development and characteristics of deep-seated gravitational slope deformations (DSGSDs) have not yet been fully explained. If unrecognized, these deformations can cause serious damage to rigid infrastructures such as dams, tunnels, and water conduits. Early identification of these phenomena and their predisposing factors through detailed geological and geomorphological surveys is therefore necessary for the correct location, construction, and expansion of fixed infrastructures. The hazard evaluation component of landslide risk assessment combines measures of susceptibility and triggering variables. This approach may not be applicable to DSGSDs, given the difficulty of quantifying the probability of occurrence within a specified period of time without well-defined DSGSD triggering factors. Evaluation of DSGSDs should thus be restricted to the assessment of susceptibility. Zones of DSGSD susceptibility can be identified through geological and geomorphological analysis, by overlapping maps of the four main predisposing factors (lithology, neotectonic activity, relief energy, morphological deglaciation evidence). The attribution of a susceptibility level to a certain zone cannot replace a hazard evaluation, but it can be a good index of the potential presence of a DSGSD. A DSGSD is most likely in a territory characterized by the worst combination of predisposing factors (high susceptibility): poor rock mechanics, intense neotectonic activity (high seismicity, active faults), high energy relief, and evidence of past glacialism. The probability of a DSGSD correspondingly decreases if one or more of the predisposing factors are absent (low susceptibility). A case study of two DSGSDs located in the Rodoretto Valley (northwestern Alps, Italy) has been examined. After detailed field survey provided morphological identification of these features, the authors conducted a back-analysis to assess the susceptibility of the entire valley. Each main predisposing factor has been independently mapped, and the level of susceptibility to DSGSD has been identified through geographic information system (GIS) overlapping of the four maps. The results confirm the combined presence of four main predisposing factors for the examined DGSDs, indicating high susceptibility.

  7. Can a systems biology approach unlock the mysteries of Kawasaki disease?

    PubMed

    Rowley, Anne H

    2013-01-01

    Kawasaki disease (KD) is a systemic inflammatory illness of childhood that particularly affects the coronary arteries. It can lead to coronary artery aneurysms, myocardial infarction, and sudden death. Clinical and epidemiologic data support an infectious cause, and the etiology remains unknown, but recent data support infection with a 'new' virus. Genetic factors influence KD susceptibility; the incidence is 10-fold higher in children of Asian when compared with Caucasian ethnicity. Recent research has identified genes affecting immune response that are associated with KD susceptibility and outcome. A re-examination of the pathologic features of KD has yielded a three process model of KD vasculopathy, providing a framework for understanding the KD arterial immune response and the damage it inflicts and for identifying new therapeutic targets for KD patients with coronary artery abnormalities. The researcher is faced with many challenges in determining the pathogenesis of KD. A systems biology approach incorporating genomics, proteomics, transcriptomics, and microbial bioinformatics analysis of high-throughput sequence data from KD tissues could provide the keys to unlocking the mysteries of this potentially fatal illness of childhood. Copyright © 2013 Wiley Periodicals, Inc.

  8. Predicting Natural Neuroprotection in Marine Mammals: Environmental and Biological Factors Affecting the Vulnerability to Acoustically Mediated Tissue Trauma in Marine Species

    DTIC Science & Technology

    2013-09-30

    comparing both globin deposition profiles from carcasses ranging in age from neonates to adults, as well as the change in mass-specific metabolic demands...to acoustically mediated trauma, 1) molecular and biochemical evaluation of neuroprotection at the tissue level, and 2) whole animal /physiological...Noren, UCSC.) The second component of this study examined the susceptibility of marine mammals to decompression illness at the whole animal

  9. The Brain-Derived Neurotrophic Factor Gene Confers Susceptibility to Bipolar Disorder: Evidence from a Family-Based Association Study

    PubMed Central

    Neves-Pereira, Maria; Mundo, Emanuela; Muglia, Pierandrea; King, Nicole; Macciardi, Fabio; Kennedy, James L.

    2002-01-01

    Bipolar disorder (BP) is a severe psychiatric disease, with a strong genetic component, that affects 1% of the population worldwide and is characterized by recurrent episodes of mania and depression. Brain-derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of mood disorders, and the aim of the present study was to test for the presence of linkage disequilibrium between two polymorphisms in the BDNF gene and BP in 283 nuclear families. Family-based association test (FBAT) results for the dinucleotide repeat (GT)N polymorphism at position −1040 bp showed that allele A3 was preferentially transmitted to the affected individuals (Z=2.035 and P=.042). FBAT results for the val66met SNP showed a significant association for allele G (Z=3.415 and P=.00064). Transmission/disequilibrium test (TDT) haplotype analysis showed a significant result for the 3-G allele combination (P=.000394), suggesting that a DNA variant in the vicinity of the BDNF locus confers susceptibility to BP. Given that there is no direct evidence that either of the polymorphisms we examined alters function, it is unlikely that the actual risk-conferring allele is from these two sites. Rather, the causative site is likely nearby and in linkage disequilibrium with the 3-G haplotype that we have identified. PMID:12161822

  10. RABBIT POX

    PubMed Central

    Greene, Harry S. N.

    1935-01-01

    The epidemiological significance of age, race, sex, genetic constitution and physiological status were studied by means of a differential analysis of the mortality data derived from a devastating epidemic of rabbit pox and, with the exception of sex, were found to be factors of the utmost importance in the determination of susceptibility. Young animals were more susceptible than adults and although the most susceptible age varied with the epidemic phase, it corresponded in general with the period of weaning. The influence of physiological status was further indicated by the increased susceptibility incident to lactation. Racial variations in susceptibility were obscured by age factors in young animals, but were of profound importance in the adult population and formed the most significant feature of the analysis. A high degree of conformity was found in the susceptibility of racially related breeds, and this similarity in behavior increased with the proximity of relationship. Moreover, a study of the hybrids obtained from the crossing of pure breeds showed that two separable groups of hereditary factors were concerned in the determination of breed susceptibility, one group consisting of essential racial characters, the other of constitutional factors incorporated in the stock by chance association, and that the final expression of susceptibility or resistance was the result of their combined interaction. PMID:19870417

  11. Travel-associated faecal colonization with ESBL-producing Enterobacteriaceae: incidence and risk factors.

    PubMed

    Ostholm-Balkhed, Ase; Tärnberg, Maria; Nilsson, Maud; Nilsson, Lennart E; Hanberger, Håkan; Hällgren, Anita

    2013-09-01

    To study the acquisition of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) among the faecal flora during travel, with a focus on risk factors, antibiotic susceptibility and ESBL-encoding genes. An observational prospective multicentre cohort study of individuals attending vaccination clinics in south-east Sweden was performed, in which the submission of faecal samples and questionnaires before and after travelling outside Scandinavia was requested. Faecal samples were screened for ESBL-PE by culturing on ChromID ESBL and an in-house method. ESBL-PE was confirmed by phenotypic and genotypic methods. Susceptibility testing was performed with the Etest. Individuals who acquired ESBL-PE during travel (travel-associated carriers) were compared with non-carriers regarding risk factors, and unadjusted and adjusted ORs after manual stepwise elimination were calculated using logistic regression. Of 262 enrolled individuals, 2.4% were colonized before travel. Among 226 evaluable participants, ESBL-PE was detected in the post-travel samples from 68 (30%) travellers. The most important risk factor in the final model was the geographic area visited: Indian subcontinent (OR 24.8, P < 0.001), Asia (OR 8.63, P < 0.001) and Africa north of the equator (OR 4.94, P = 0.002). Age and gastrointestinal symptoms also affected the risk significantly. Multiresistance was seen in 77 (66%) of the ESBL-PE isolates, predominantly a combination of reduced susceptibility to third-generation cephalosporins, trimethoprim/sulfamethoxazole and aminoglycosides. The most common species and ESBL-encoding gene were Escherichia coli (90%) and CTX-M (73%), respectively. Acquisition of multiresistant ESBL-PE among the faecal flora during international travel is common. The geographical area visited has the highest impact on ESBL-PE acquisition.

  12. Venous Thromboembolism and Varicose Veins Share Familial Susceptibility: A Nationwide Family Study in Sweden

    PubMed Central

    Zöller, Bengt; Ji, Jianguang; Sundquist, Jan; Sundquist, Kristina

    2014-01-01

    Background Varicose veins (VVs) have been associated with venous thromboembolism (VTE), but whether these diseases share familial susceptibility has not been determined. This nationwide study aimed to determine whether VTE shares familial susceptibility with VVs. Methods and Results Swedish Multigeneration Register data for persons aged 0 to 76 years during the period 1964–2008 were linked to the Swedish Inpatient and Outpatient Registers. Familial risks (standardized incidence ratios [SIRs]) of VTE and VVs were examined in 2 ways (ie, bidirectionally): risk of VTE in subjects whose siblings had been diagnosed with VVs and risk of VVs in persons whose siblings had been diagnosed with VTE. The analyses were repeated for spouses to determine the importance of shared adult family environment. In total, 96 810 siblings had VVs and 87 564 had VTE. An increased risk of VTE was observed in persons whose siblings had VVs (SIR 1.30, 95% CI 1.26 to 1.33), whereas persons whose siblings had VTE had an increased risk of VVs (SIR 1.30, 95% CI 1.27 to 1.34). If 2 or more siblings were affected by VTE, the risk for VVs was 1.70 (95% CI 1.53 to 1.88). Conversely, if 2 or more siblings were affected by VVs, the risk for VTE was 1.52 (95% CI 1.38 to 1.67). In spouses of VTE patients, a minor increased risk of VVs was observed (SIR 1.05 for husbands, SIR 1.06 for wives). The risk of VTE in spouses of VV patients was similarly small (SIR 1.01 for husbands, SIR 1.05 for wives). Conclusions VVs and VTE share familial susceptibility. This novel finding suggests the existence of shared familial and possibly genetic factors. PMID:25158864

  13. Unexpected effects of azole transporter inhibitors on antifungal susceptibility in Candida glabrata and other pathogenic Candida species

    PubMed Central

    Nagayoshi, Yohsuke; Shimamura, Shintaro; Nakayama, Hironobu; Minematsu, Asuka; Yamauchi, Shunsuke; Takazono, Takahiro; Nakamura, Shigeki; Yanagihara, Katsunori; Kohno, Shigeru; Mukae, Hiroshi; Izumikawa, Koichi

    2017-01-01

    The pathogenic fungus Candida glabrata is often resistant to azole antifungal agents. Drug efflux through azole transporters, such as Cdr1 and Cdr2, is a key mechanism of azole resistance and these genes are under the control of the transcription factor Pdr1. Recently, the monoamine oxidase A (MAO-A) inhibitor clorgyline was shown to inhibit the azole efflux pumps, leading to increased azole susceptibility in C. glabrata. In the present study, we have evaluated the effects of clorgyline on susceptibility of C. glabrata to not only azoles, but also to micafungin and amphotericin B, using wild-type and several mutant strains. The addition of clorgyline to the culture media increased fluconazole susceptibility of a C. glabrata wild-type strain, whereas micafungin and amphotericin B susceptibilities were markedly decreased. These phenomena were also observed in other medically important Candida species, including Candida albicans, Candida parapsilosis, Candida tropicalis, and Candida krusei. Expression levels of CDR1, CDR2 and PDR1 mRNAs and an amount of Cdr1 protein in the C. glabrata wild-type strain were highly increased in response to the treatment with clorgyline. However, loss of Cdr1, Cdr2, Pdr1, and a putative clorgyline target (Fms1), which is an ortholog of human MAO-A, or overexpression of CDR1 did not affect the decreased susceptibility to micafungin and amphotericin B in the presence of clorgyline. The presence of other azole efflux pump inhibitors including milbemycin A4 oxime and carbonyl cyanide 3-chlorophenylhydrazone also decreased micafungin susceptibility in C. glabrata wild-type, Δcdr1, Δcdr2, and Δpdr1 strains. These findings suggest that azole efflux pump inhibitors increase azole susceptibility but concurrently induce decreased susceptibility to other classes of antifungals independent of azole transporter functions. PMID:28700656

  14. Unexpected effects of azole transporter inhibitors on antifungal susceptibility in Candida glabrata and other pathogenic Candida species.

    PubMed

    Nagayoshi, Yohsuke; Miyazaki, Taiga; Shimamura, Shintaro; Nakayama, Hironobu; Minematsu, Asuka; Yamauchi, Shunsuke; Takazono, Takahiro; Nakamura, Shigeki; Yanagihara, Katsunori; Kohno, Shigeru; Mukae, Hiroshi; Izumikawa, Koichi

    2017-01-01

    The pathogenic fungus Candida glabrata is often resistant to azole antifungal agents. Drug efflux through azole transporters, such as Cdr1 and Cdr2, is a key mechanism of azole resistance and these genes are under the control of the transcription factor Pdr1. Recently, the monoamine oxidase A (MAO-A) inhibitor clorgyline was shown to inhibit the azole efflux pumps, leading to increased azole susceptibility in C. glabrata. In the present study, we have evaluated the effects of clorgyline on susceptibility of C. glabrata to not only azoles, but also to micafungin and amphotericin B, using wild-type and several mutant strains. The addition of clorgyline to the culture media increased fluconazole susceptibility of a C. glabrata wild-type strain, whereas micafungin and amphotericin B susceptibilities were markedly decreased. These phenomena were also observed in other medically important Candida species, including Candida albicans, Candida parapsilosis, Candida tropicalis, and Candida krusei. Expression levels of CDR1, CDR2 and PDR1 mRNAs and an amount of Cdr1 protein in the C. glabrata wild-type strain were highly increased in response to the treatment with clorgyline. However, loss of Cdr1, Cdr2, Pdr1, and a putative clorgyline target (Fms1), which is an ortholog of human MAO-A, or overexpression of CDR1 did not affect the decreased susceptibility to micafungin and amphotericin B in the presence of clorgyline. The presence of other azole efflux pump inhibitors including milbemycin A4 oxime and carbonyl cyanide 3-chlorophenylhydrazone also decreased micafungin susceptibility in C. glabrata wild-type, Δcdr1, Δcdr2, and Δpdr1 strains. These findings suggest that azole efflux pump inhibitors increase azole susceptibility but concurrently induce decreased susceptibility to other classes of antifungals independent of azole transporter functions.

  15. On the use of sibling recurrence risks to select environmental factors liable to interact with genetic risk factors.

    PubMed

    Kazma, Rémi; Bonaïti-Pellié, Catherine; Norris, Jill M; Génin, Emmanuelle

    2010-01-01

    Gene-environment interactions are likely to be involved in the susceptibility to multifactorial diseases but are difficult to detect. Available methods usually concentrate on some particular genetic and environmental factors. In this paper, we propose a new method to determine whether a given exposure is susceptible to interact with unknown genetic factors. Rather than focusing on a specific genetic factor, the degree of familial aggregation is used as a surrogate for genetic factors. A test comparing the recurrence risks in sibs according to the exposure of indexes is proposed and its power is studied for varying values of model parameters. The Exposed versus Unexposed Recurrence Analysis (EURECA) is valuable for common diseases with moderate familial aggregation, only when the role of exposure has been clearly outlined. Interestingly, accounting for a sibling correlation for the exposure increases the power of EURECA. An application on a sample ascertained through one index affected with type 2 diabetes is presented where gene-environment interactions involving obesity and physical inactivity are investigated. Association of obesity with type 2 diabetes is clearly evidenced and a potential interaction involving this factor is suggested in Hispanics (P=0.045), whereas a clear gene-environment interaction is evidenced involving physical inactivity only in non-Hispanic whites (P=0.028). The proposed method might be of particular interest before genetic studies to help determine the environmental risk factors that will need to be accounted for to increase the power to detect genetic risk factors and to select the most appropriate samples to genotype.

  16. Molecular Neuro-Pathomechanism of Neurocysticercosis: How Host Genetic Factors Influence Disease Susceptibility.

    PubMed

    Arora, Naina; Tripathi, Shweta; Sao, Reshma; Mondal, Prosenjit; Mishra, Amit; Prasad, Amit

    2018-02-01

    Neurocysticercosis (NCC) is one of the most neglected tropical diseases among widely endemic neurological diseases. It is caused by cysticerci of Taenia solium. The clinical symptom for the outcome of infection and progression of disease is pleomorphic and its neuro-pathomechanism is still illusive. Identification of host genetic factors and their association with disease susceptibility is one of the most important areas of research towards personalized medicine in the era of omics. Several genes and their allelic variations had been identified to be associated with various neurological disorders; however, the information for parasitic diseases affecting the central nervous system is very limited. Both Th1 and Th2 arms of the immune system are reported to be active at different stages of T. solium infection in the brain. Recently, several papers had been published, where the role of host genetic makeup with NCC had been explored. Increased frequency of HLA-A28, HLA-B63, HLA-B58, TLR 4 Asp299Gly, sICAM-1 gene K469E, GSTM1, and GSTT1 were found to be associated with increased risk of NCC occurrence, while HLA-DQW2 and HLA-A11 were shown to be providing protection from disease. In this review, we have summarized these findings and analyzed the influence of host genetic polymorphism on the susceptibility/resistance of host to NCC.

  17. The genetics of sports injuries and athletic performance

    PubMed Central

    Maffulli, Nicola; Margiotti, Katia; Longo, Umile Giuseppe; Loppini, Mattia; Fazio, Vito Michele; Denaro, Vincenzo

    2013-01-01

    Summary Purpose: in the last two decades, several evidences have been provided to support the relationship between single nucleotide polymorphisms and the susceptibility to develop injuries participating in sport and performance related to sports activity. We report up-to-date review of the genetics factors involved in tendon injuries and athletic performance. Methods: we searched PubMed using the terms “sports injuries”, “athletic performance” and “genetics” over the period 1990 to the present day. We also included non-English journals. Results: most of the currently established or putative tendinopathy susceptibility loci have been analyzed by candidate gene studies. The genes currently associated with tendon injuries include gene encoding for collagen, matrix metallopeptidase, tenascin and growth factors. Several genes have been related to the physical performance phenotypes affecting endurance capacity and muscle performance. The most studied include ACE and ACTN3 genes. Conclusions: genetics determines the response of an individual to the surrounding environment. Recently, some of the individual genetic variations contributing to the athletic performance and the onset of musculoskeletal injuries, particularly in tendon and ligament tissues, have been identified. However, the identification of the genetic background related to susceptibility to injuries and physical performance of the athletes is challenging yet and further studies must be performed to establish the specific role of each gene and the potential effect of the interaction of these. PMID:24367777

  18. Effect of Inoculum and of Beta-Lactamase on the Anti-Staphylococcal Activity of Thirteen Penicillins and Cephalosporins

    PubMed Central

    Sabath, L. D.; Garner, Carol; Wilcox, Clare; Finland, Maxwell

    1975-01-01

    Because there are few persuasive data for selecting one semisynthetic penicillin or cephalosporin over another for treatment of serious staphylococcal infections, 118 recent clinical isolates of Staphylococcus aureus were studied to determine to what extent the presence of β-lactamase affected the relative anti-staphylococcal activity of six penicillins and seven cephalosporins. In addition, the effect of inoculum was studied for its possible effect on the anti-staphylococcal activity of the 13 β-lactam antibiotics. By all criteria, methicillin and nafcillin were clearly more resistant to both the inoculum effect and the production of staphylococcal β-lactamase, whereas benzylpenicillin and cephaloridine (especially benzyl-penicillin) were the most susceptible to these effects. Cephazolin was clearly more susceptible to staphylococcal β-lactamase and heavy inocula than the other cephalosporins (with the exception of cephaloridine), whereas cephalothin was the most resistant cephalosporin to these factors. The minimal inhibitory concentration for benzylpenicillin for tests with undiluted inoculum, compared to results with inoculum diluted 10−4, differed by a factor up to 16,384, whereas with methicillin and nafcillin the differences were rarely more than twofold. Ratios for the other 10 antibiotics fell between these extremes. These results suggest that methicillin or nafcillin is most stable to staphylococcal β-lactamase, and that benzylpenicillin and cephaloridine are the most susceptible. PMID:1167043

  19. Effects of cocoa powder and dark chocolate on LDL oxidative susceptibility and prostaglandin concentrations in humans.

    PubMed

    Wan, Y; Vinson, J A; Etherton, T D; Proch, J; Lazarus, S A; Kris-Etherton, P M

    2001-11-01

    Flavonoids are polyphenolic compounds of plant origin with antioxidant effects. Flavonoids inhibit LDL oxidation and reduce thrombotic tendency in vitro. Little is known about how cocoa powder and dark chocolate, rich sources of polyphenols, affect these cardiovascular disease risk factors. We evaluated the effects of a diet high in cocoa powder and dark chocolate (CP-DC diet) on LDL oxidative susceptibility, serum total antioxidant capacity, and urinary prostaglandin concentrations. We conducted a randomized, 2-period, crossover study in 23 healthy subjects fed 2 diets: an average American diet (AAD) controlled for fiber, caffeine, and theobromine and an AAD supplemented with 22 g cocoa powder and 16 g dark chocolate (CP-DC diet), providing approximately 466 mg procyanidins/d. LDL oxidation lag time was approximately 8% greater (P = 0.01) after the CP-DC diet than after the AAD. Serum total antioxidant capacity measured by oxygen radical absorbance capacity was approximately 4% greater (P = 0.04) after the CP-DC diet than after the AAD and was positively correlated with LDL oxidation lag time (r = 0.32, P = 0.03). HDL cholesterol was 4% greater after the CP-DC diet (P = 0.02) than after the AAD; however, LDL-HDL ratios were not significantly different. Twenty-four-hour urinary excretion of thromboxane B(2) and 6-keto-prostaglandin F(1)(alpha) and the ratio of the 2 compounds were not significantly different between the 2 diets. Cocoa powder and dark chocolate may favorably affect cardiovascular disease risk status by modestly reducing LDL oxidation susceptibility, increasing serum total antioxidant capacity and HDL-cholesterol concentrations, and not adversely affecting prostaglandins.

  20. Confirmation of prior evidence of genetic susceptibility to alcoholism in a genome wide association study of comorbid alcoholism and bipolar disorder

    PubMed Central

    Lydall, Gregory J; Bass, Nicholas J; McQuillin, Andrew; Lawrence, Jacob; Anjorin, Adebayo; Kandaswamy, Radhika; Pereira, Ana; Guerrini, Irene; Curtis, David; Vine, Anna E; Sklar, Pamela; Purcell, Shaun M; Gurling, Hugh MD

    2012-01-01

    Objectives Alcoholism and affective disorders are both strongly comorbid and heritable. We have investigated the genetic comorbidity between bipolar affective disorder and alcoholism. Methods A genome-wide allelic association study of 506 patients from the University College London (UCL) bipolar disorder case control sample and 510 ancestrally-matched supernormal controls. 143 of the bipolar subjects fulfilled the research diagnostic criteria (RDC) diagnosis of alcoholism. 372,193 single nucleotide polymorphisms (SNPs) were genotyped. Genes previously shown to be associated with alcoholism and addiction phenotypes were then tested for association in the bipolar alcoholic sample using gene wise permutation tests of all SNPs genotyped within a 50kb region flanking each gene. Results Several CNS genes showed significant (p<0.05) gene wise evidence of association with bipolar alcoholism. The genes implicated which replicated previously identified associations with alcoholism were: cadherin 11 (CDH11), collagen type XI alpha 2 (COL11A2), neuromedin U receptor 2 (NMUR2), exportin7 (XP07) and semaphorin associated protein 5A (SEMA5A). The SNPs most strongly implicated in bipolar alcoholism, but which did not meet conventional genome-wide significance criteria were the insulin-like growth factor binding protein 7 (IGFBP7), carboxypeptidase O (CPO), cerebellin 2 (CBLN2), and the cadherin 12 (CDH12) genes. Conclusions We have confirmed the role of some genes previously shown to be associated with alcoholism in the comorbid bipolar alcoholism subgroup. In this subgroup bipolar disorder may lower the threshold for the phenotypic expression of these alcoholism susceptibility genes. We also show that some genes may independently increase susceptibility to affective disorder and alcoholism. PMID:21876473

  1. The life cycle of chondrocytes in the developing skeleton

    PubMed Central

    Shum, Lillian; Nuckolls, Glen

    2002-01-01

    Cartilage serves multiple functions in the developing embryo and in postnatal life. Genetic mutations affecting cartilage development are relatively common and lead to skeletal malformations, dysfunction or increased susceptibility to disease or injury. Characterization of these mutations and investigation of the molecular pathways in which these genes function have contributed to an understanding of the mechanisms regulating skeletal patterning, chondrogenesis, endochondral ossification and joint formation. Extracellular growth and differentiation factors including bone morphogenetic proteins, fibroblast growth factors, parathyroid hormone-related peptide, extracellular matrix components, and members of the hedgehog and Wnt families provide important signals for the regulation of cell proliferation, differentiation and apoptosis. Transduction of these signals within the developing mesenchymal cells and chondrocytes results in changes in gene expression mediated by transcription factors including Smads, Msx2, Sox9, signal transducer and activator of transcription (STAT), and core-binding factor alpha 1. Further investigation of the interactions of these signaling pathways will contribute to an understanding of cartilage growth and development, and will allow for the development of strategies for the early detection, prevention and treatment of diseases and disorders affecting the skeleton. PMID:11879545

  2. Season mediates herbivore effects on litter and soil microbial abundance and activity in a semi-arid woodland

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Classen, Aimee T; Overby, Stephen; Hart, Stephen C

    2007-01-01

    Herbivores can directly impact ecosystem function by altering litter quality entering an ecosystem or indirectly by affecting a shift in the microbial community that mediate nutrient processes. We examine herbivore susceptibility and resistance effects on litter microarthropod and soil microbial communities to test the general hypothesis that herbivore driven changes in litter inputs will feedback to the microbial community. Our study population consisted of individual trees that are susceptible or resistant to the stem-boring moth (Dioryctria albovittella) and trees that herbivores have been manually removed since 1982. Moth herbivory increased pi on litter nitrogen concentrations (16%) and canopy precipitation infiltrationmore » (28%), both significant factors influencing litter and soil microbial populations. Our research resulted in three major conclusions: 1) In spite of an increase in litter quality, herbivory does not change litter microarthropod abundance or species richness. 2) Herbivore susceptibility alters bulk soil microbial communities, but not soil properties. 3) Season has a strong influence on microbial communities, and their response to herbivore inputs, in this semi-arid ecosystem.« less

  3. Interactions between the impacts of ultraviolet radiation, elevated CO2, and nutrient limitation on marine primary producers.

    PubMed

    Beardall, John; Sobrino, Cristina; Stojkovic, Slobodanka

    2009-09-01

    It is well known that UV radiation can cause deleterious effects to the physiological performance, growth and species assemblages of marine primary producers. In this review we describe the range of interactions observed between these impacts of ultraviolet radiation (UVR, 280-400 nm) with other environmental factors such as the availability of photosynthetically active radiation (PAR), nutrient status and levels of dissolved CO2, all of which can, in turn, be influenced by global climate change. Thus, increases in CO2 levels can affect the sensitivity of some species to UV-B radiation (UV-B), while others show no such impact on UV-B susceptibility. Both nitrogen- and phosphorus-limitation can have direct interactive effects on the susceptibility of algal cells and communities to UVR, though such effects are somewhat variable. Nutrient depletion can also potentially lead to a dominance of smaller celled species, which may be less able to screen out and are thus likely to be more susceptible to UVR-induced damage. The variability of responses to such interactions can lead to alterations in the species composition of algal assemblages.

  4. How to control hydrogen level in (super) duplex stainless steel weldments using the GTAW or GMAW process

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mee, V.V.D.; Meelker, H.; Schelde, R.V.D.

    1999-01-01

    In this investigation, an attempt is made to further the understanding of factors influencing the hydrogen content in duplex stainless steel gas tungsten arc (GTA) and gas metal arc (GMA) welds as well as to what extent it affects hydrogen-induced cracking susceptibility. The results indicated that susceptibility to hydrogen cracking using the GTA or GMA process appears to be limited. In practice, maintaining a moisture level below 10 ppm in the shielding gas is of less importance than the choice of welding parameters. Even a moisture level of 1000 ppm in the shielding gas, in combination with the correct weldingmore » parameters, will result in a sufficient low hydrogen content in the weld. Similarly, a moisture level in the shielding gas below 10 ppm does not necessarily result in low hydrogen content in the weld metal. Although very high ferrite levels were combined with high restrain and high hydrogen content, none of the GMA and GTA welds cracked. Susceptibility to hydrogen cracking is concluded to be limited.« less

  5. Adult bacterial meningitis: aetiology, penicillin susceptibility, risk factors, prognostic factors and guidelines for empirical antibiotic treatment.

    PubMed

    Meyer, C N; Samuelsson, I S; Galle, M; Bangsborg, J M

    2004-08-01

    Episodes of adult bacterial meningitis (ABM) at a Danish hospital in 1991-2000 were identified from the databases of the Department of Clinical Microbiology, and compared with data from the Danish National Patient Register and the Danish National Notification System. Reduced penicillin susceptibility occurred in 21 (23%) of 92 cases of known aetiology, compared to an estimated 6% in nationally notified cases (p < 0.001). Ceftriaxone plus penicillin as empirical treatment was appropriate in 97% of ABM cases in the study population, and in 99.6% of nationally notified cases. The notification rate was 75% for penicillin-susceptible episodes, and 24% for penicillin-non-susceptible episodes (p < 0.001). Cases involving staphylococci, Pseudomonas spp. and Enterobacteriaceae were under-reported. Among 51 ABM cases with no identified risk factors, nine of 11 cases with penicillin-non-susceptible bacteria were community-acquired. Severe sequelae correlated independently with age, penicillin non-susceptibility, mechanical ventilation and non-transferral to a tertiary hospital (p < 0.05; logistic regression). Other factors that correlated with severe sequelae by univariate analysis only were inappropriate clinical handling, abnormal consciousness, convulsions and nosocomial infection. Overall, the data indicated that neither age alone, community-acquired infection nor absence of identified risk factors can predict susceptibility to penicillin accurately. Recommendations for empirical antibiotic treatment for ABM should not be based exclusively on clinical notification systems with possible unbalanced under-reporting.

  6. Magnetic field effects on charge structure factors of gapped graphene structure

    NASA Astrophysics Data System (ADS)

    Rezania, Hamed; Tawoose, Nasrin

    2018-02-01

    We present the behaviors of dynamical and static charge susceptibilities of undoped gapped graphene using the Green's function approach in the context of tight binding model Hamiltonian. Specially, the effects of magnetic field on the plasmon modes of gapped graphene structure are investigated via calculating correlation function of charge density operators. Our results show the increase of magnetic field leads to disappear high frequency plasmon mode for gapped case. We also show that low frequency plasmon mode has not affected by increase of magnetic field and chemical potential. Finally the temperature dependence of static charge structure factor of gapp graphene structure is studied. The effects of both magnetic field and gap parameter on the static structure factor are discusses in details.

  7. Assessment of flood susceptible areas using spatially explicit, probabilistic multi-criteria decision analysis

    NASA Astrophysics Data System (ADS)

    Tang, Zhongqian; Zhang, Hua; Yi, Shanzhen; Xiao, Yangfan

    2018-03-01

    GIS-based multi-criteria decision analysis (MCDA) is increasingly used to support flood risk assessment. However, conventional GIS-MCDA methods fail to adequately represent spatial variability and are accompanied with considerable uncertainty. It is, thus, important to incorporate spatial variability and uncertainty into GIS-based decision analysis procedures. This research develops a spatially explicit, probabilistic GIS-MCDA approach for the delineation of potentially flood susceptible areas. The approach integrates the probabilistic and the local ordered weighted averaging (OWA) methods via Monte Carlo simulation, to take into account the uncertainty related to criteria weights, spatial heterogeneity of preferences and the risk attitude of the analyst. The approach is applied to a pilot study for the Gucheng County, central China, heavily affected by the hazardous 2012 flood. A GIS database of six geomorphological and hydrometeorological factors for the evaluation of susceptibility was created. Moreover, uncertainty and sensitivity analysis were performed to investigate the robustness of the model. The results indicate that the ensemble method improves the robustness of the model outcomes with respect to variation in criteria weights and identifies which criteria weights are most responsible for the variability of model outcomes. Therefore, the proposed approach is an improvement over the conventional deterministic method and can provides a more rational, objective and unbiased tool for flood susceptibility evaluation.

  8. Developmental Neurotoxicity of Traffic-Related Air Pollution: Focus on Autism.

    PubMed

    Costa, Lucio G; Chang, Yu-Chi; Cole, Toby B

    2017-06-01

    Epidemiological and animal studies suggest that air pollution may negatively affect the central nervous system (CNS) and contribute to CNS diseases. Traffic-related air pollution is a major contributor to global air pollution, and diesel exhaust (DE) is its most important component. Several studies suggest that young individuals may be particularly susceptible to air pollution-induced neurotoxicity and that perinatal exposure may cause or contribute to developmental disabilities and behavioral abnormalities. In particular, a number of recent studies have found associations between exposures to traffic-related air pollution and autism spectrum disorders (ASD), which are characterized by impairment in socialization and in communication and by the presence of repetitive and unusual behaviors. The cause(s) of ASD are unknown, and while it may have a hereditary component, environmental factors are increasingly suspected as playing a pivotal role in its etiology, particularly in genetically susceptible individuals. Autistic children present higher levels of neuroinflammation and systemic inflammation, which are also hallmarks of exposure to traffic-related air pollution. Gene-environment interactions may play a relevant role in determining individual susceptibility to air pollution developmental neurotoxicity. Given the worldwide presence of elevated air pollution, studies on its effects and mechanisms on the developing brain, genetic susceptibility, role in neurodevelopmental disorders, and possible therapeutic interventions are certainly warranted.

  9. Osteomyelitis: a descriptive study.

    PubMed

    Prieto-Pérez, Laura; Pérez-Tanoira, Ramón; Petkova-Saiz, Elizabet; Pérez-Jorge, Concepción; Lopez-Rodriguez, Cristina; Alvarez-Alvarez, Beatriz; Polo-Sabau, Jorge; Esteban, Jaime

    2014-03-01

    To analyze the incidence and clinical-microbiological characteristics of osteomyelitis (OM) in a tertiary Spanish hospital. All cases diagnosed with OM between January 2007 and December 2010 were retrospectively reviewed. The variables examined include epidemiological characteristics, risk factors, affected bone, radiographic changes, histology, microbiological culture results, antibiotic treatment, and the need for surgery. Sixty-three cases of OM were diagnosed. Twenty-six patients (41.3%) had acute OM whereas 37 patients (58.7%) were classified as chronic OM. OM may result from haematogenous or contiguous microbial seeding. In this group, 49 patients (77.8%) presented with OM secondary to a contiguous source of infection and 14 patients had hematogenous OM (22.2%). Staphylococcus aureus was the most commonly found microorganism. OM mainly affected patients with risk factors related to the presence of vascular diseases. Antibiotic treatment must be guided by susceptibility patterns of individual microorganisms, although it must be performed together with surgery in most of the cases.

  10. Dermatoglyphic anomalies and neurocognitive deficits in sibling pairs discordant for schizophrenia spectrum disorders.

    PubMed

    Rosa, Araceli; Cuesta, Manuel J; Peralta, Víctor; Zarzuela, Amalia; Serrano, Fermín; Martínez-Larrea, Alfredo; Fañanás, Lourdes

    2005-12-15

    The neurodevelopmental hypothesis of schizophrenia suggests that adverse genetic loading in conjunction with environmental factors early in fetal life causes a disruption of neural development, decades before the symptomatic manifestation of the disease. Neurocognitive deficits have been observed early on the course of schizophrenia, and their association with an early developmental brain lesion has been postulated. Dermatoglyphics have been analyzed in schizophrenia as markers of prenatal brain injury because of their early fetal ontogenesis and susceptibility to the same environmental factors that can also affect cerebral development. The aim of our study was to conduct a comparative examination of neurocognitive functions and dermatoglyphic variables in 89 sibling pairs discordant for schizophrenia spectrum disorders. Therefore, we investigated the association between these two markers to explore the prenatal origin of cognitive deficits in schizophrenia. The affected siblings were significantly impaired on all the cognitive variables assessed (Wisconsin Card Sorting Test, Trail Making Test and Continuous Performance Test) and had a greater number of dermatoglyphic anomalies. These results suggest the influence of intrauterine environmental factors in the siblings affected with schizophrenia. However, we did not detect a significant association between these two vulnerability markers in the schizophrenic patients, suggesting the role of genetic or late environmental factors in the origin of the neurocognitive deficits found in these patients.

  11. The effect of water contamination and host-related factors on ectoparasite load in an insectivorous bat.

    PubMed

    Korine, Carmi; Pilosof, Shai; Gross, Amit; Morales-Malacara, Juan B; Krasnov, Boris R

    2017-09-01

    We examined the effects of sex, age, and reproductive state of the insectivorous bat Pipistrellus kuhlii on the abundance and prevalence of arthropod ectoparasites (Macronyssidae and Cimicidae) in habitats with either sewage-polluted or natural bodies of water, in the Negev Desert, Israel. We chose water pollution as an environmental factor because of the importance of water availability in desert environments, particularly for P. kuhlii, which needs to drink on a daily basis. We predicted that parasite infestation rates would be affected by both environment and demographic cohort of the host. We found that female bats in the polluted site harbored significantly more mites than female bats in the natural site and that juveniles in the polluted site harbored significantly more cimicid individuals than juveniles in the natural site. We further found that age and sex (host-related factors) affected ectoparasite prevalence and intensity (i.e., the abundance of parasites) in the polluted site. Our results may suggest that the interaction between host-related and environment-related factors affected parasite infestations, with females and young bats being more susceptible to ectoparasites when foraging over polluted water. This effect may be particularly important for bats that must drink or forage above water for other wildlife that depend on drinking water for survival.

  12. Interaction between IL-6 and TNF-α genotypes associated with bacteremia in multiple myeloma patients submitted to autologous stem cell transplantation (ASCT).

    PubMed

    Trigo, Fernanda M B; Luizon, Marcelo R; Dutra, Hélio S; Maiolino, Angelo; Nucci, Márcio; Simões, Belinda P

    2014-01-01

    Stem cell transplantation affects patient׳s vulnerability to infections due to immunological changes related to chemotherapy. Multiple myeloma is characterized by susceptibility to infections, and IL-6 and TNF-α increased levels affect immune response (IR). Polymorphisms in promoter region of cytokine genes may alter expression levels and affect IR. We performed interaction analysis of IL-6 (-174G/C) and TNF-α (-308G/A) polymorphisms with infection susceptibility in 148 patients classified accordingly to infection status and found an interaction when compared groups with and without bacteremia (p=0.0380). The interaction may be more important than single effects for the IR associated with the infection susceptibility in ASCT.

  13. Peripartum Antibiotics Promote Gut Dysbiosis, Loss of Immune Tolerance, and Inflammatory Bowel Disease in Genetically Prone Offspring.

    PubMed

    Miyoshi, Jun; Bobe, Alexandria M; Miyoshi, Sawako; Huang, Yong; Hubert, Nathaniel; Delmont, Tom O; Eren, A Murat; Leone, Vanessa; Chang, Eugene B

    2017-07-11

    Factors affecting the developing neonatal gut microbiome and immune networks may increase the risk of developing complex immune disorders such as inflammatory bowel diseases (IBD). In particular, peripartum antibiotics have been suggested as risk factors for human IBD, although direct evidence is lacking. Therefore, we examined the temporal impact of the commonly used antibiotic cefoperazone on both maternal and offspring microbiota when administered to dams during the peripartum period in the IL-10-deficient murine colitis model. By rigorously controlling for cage, gender, generational, and murine pathobiont confounders, we observed that offspring from cefoperazone-exposed dams develop a persistent gut dysbiosis into adulthood associated with skewing of the host immune system and increased susceptibility to spontaneous and chemically dextran sodium sulfate (DSS)-induced colitis. Thus, early life exposure to antibiotic-induced maternal dysbiosis during a critical developmental window for gut microbial assemblage and immune programming elicits a lasting impact of increased IBD risk on genetically susceptible offspring. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  14. Prioritizing plant defence over growth through WRKY regulation facilitates infestation by non-target herbivores

    PubMed Central

    Li, Ran; Zhang, Jin; Li, Jiancai; Zhou, Guoxin; Wang, Qi; Bian, Wenbo; Erb, Matthias; Lou, Yonggen

    2015-01-01

    Plants generally respond to herbivore attack by increasing resistance and decreasing growth. This prioritization is achieved through the regulation of phytohormonal signaling networks. However, it remains unknown how this prioritization affects resistance against non-target herbivores. In this study, we identify WRKY70 as a specific herbivore-induced, mitogen-activated protein kinase-regulated rice transcription factor that physically interacts with W-box motifs and prioritizes defence over growth by positively regulating jasmonic acid (JA) and negatively regulating gibberellin (GA) biosynthesis upon attack by the chewing herbivore Chilo suppressalis. WRKY70-dependent JA biosynthesis is required for proteinase inhibitor activation and resistance against C. suppressalis. In contrast, WRKY70 induction increases plant susceptibility against the rice brown planthopper Nilaparvata lugens. Experiments with GA-deficient rice lines identify WRKY70-dependent GA signaling as the causal factor in N. lugens susceptibility. Our study shows that prioritizing defence over growth leads to a significant resistance trade-off with important implications for the evolution and agricultural exploitation of plant immunity. DOI: http://dx.doi.org/10.7554/eLife.04805.001 PMID:26083713

  15. Spontaneous abortion and functional polymorphism (Val16Ala) in the manganese SOD gene.

    PubMed

    Eskafi Sabet, E; Salehi, Z; Khodayari, S; Sabouhi Zarafshan, S; Zahiri, Z

    2015-02-01

    Spontaneous abortion is the most common complication of early pregnancy. Genetic factors have been hypothesised to play a role in spontaneous abortion. Since it is possible that the balance of oxidants and antioxidants can be affected by different genetic variants, gene polymorphisms have been proposed as a susceptibility factor that increases the chance of miscarriage. Manganese superoxide dismutase is an important antioxidant enzyme encoded by manganese superoxide dismutase (MnSOD) gene. The aim of this experiment was to assess whether Val16Ala polymorphism of MnSOD gene is associated with miscarriage in northern Iran. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for genotyping. Statistical analyses were conducted using the χ(2)-test. The genetic distributions did not differ significantly between cases and controls, however slightly more Val/Val genotypes were found among the patients compared with control subjects (p = 0.059). No correlation was observed between susceptibility to abortion and MnSOD Val16Ala polymorphism. Larger population-based studies are needed for clarifying the relationship between abortion and MnSOD genotypes.

  16. Linear and nonlinear susceptibilities from diffusion quantum Monte Carlo: application to periodic hydrogen chains.

    PubMed

    Umari, P; Marzari, Nicola

    2009-09-07

    We calculate the linear and nonlinear susceptibilities of periodic longitudinal chains of hydrogen dimers with different bond-length alternations using a diffusion quantum Monte Carlo approach. These quantities are derived from the changes in electronic polarization as a function of applied finite electric field--an approach we recently introduced and made possible by the use of a Berry-phase, many-body electric-enthalpy functional. Calculated susceptibilities and hypersusceptibilities are found to be in excellent agreement with the best estimates available from quantum chemistry--usually extrapolations to the infinite-chain limit of calculations for chains of finite length. It is found that while exchange effects dominate the proper description of the susceptibilities, second hypersusceptibilities are greatly affected by electronic correlations. We also assess how different approximations to the nodal surface of the many-body wave function affect the accuracy of the calculated susceptibilities.

  17. [Will climate and demography have a major impact on malaria in sub-Saharan Africa in the next 20 years?].

    PubMed

    Saugeon, C; Baldet, T; Akogbeto, M; Henry, M C

    2009-04-01

    The purpose of this review of the literature is to present factors possibly affecting the spread of malaria in sub-Saharan Africa over the next 20 years. Malaria is a vector-borne disease that depends on environmental and human constraints. The main environmental limitations involve susceptibility of the vector (mosquitoes of the Anopheles genus) and parasite (Plasmodium falciparum) to climate. Malaria is a stable, endemic disease over most of the African continent. Climatic change can only affect a few regions on the fringes of stable zones (e.g. altitude areas or Sahel) where malaria is an unstable, epidemic disease. Higher temperatures could induce a decrease of malaria transmission in regions of the Sahel or an increase in the highlands. The extent of these overall trends will depend on the unpredictable occurrence of major meteorological phenomenon as well as on human activities affecting the environment that could lead to dramatic but limited outbreaks in some locations. The most influential human factors could be runaway demographic growth and urban development. Estimations based on modeling studies indicate that urbanization will lead to a 53.5% drop in exposure to malaria by 2030. However this reduction could be less than expected because of adaptation of Anopheles gambiae and An. arabiensis, the main vectors of malaria in sub-Saharan Africa, to the urban environment as well as increasing vector resistance to insecticides. Another unforeseeable factor that could induce unexpected malaria epidemics is mass migration due to war or famine. Finally immunosuppressive illnesses (e.g. HIV and malnutrition) could alter individual susceptibility to malaria. Social constraints also include human activities that modify land use. In this regard land use (e.g. forest clearance and irrigation) is known to influence the burden of malaria that is itself dependent on local determinants of transmission. Overall the most important social constraint for the population will be access to malarial prevention and implementation action to control this scourge.

  18. Human susceptibility to legionnaires' disease.

    PubMed

    Berrington, William R; Hawn, Thomas R

    2013-01-01

    Legionella pneumophila is a facultative intracellular pathogen that is an important cause of pneumonia. Although host factors that may predispose to acquisition of Legionnaire's Disease (LD) include comorbid illnesses (e.g., diabetes, chronic lung disease), age, male sex, and smoking, many individuals have no identifiable risk factors. Some studies suggest that genetic factors may enhance susceptibility to LD. In this chapter we discuss current techniques and scientific methods to identify genetic susceptibility factors. These genetic studies provide insight into the human immune response to intracellular pathogens and may improve strategies for treatment and vaccine development.

  19. Evidence, from family studies, for linkage disequilibrium between TGFA and a gene for nonsyndromic cleft lip with or without cleft palate

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Feng, Hongshu; Lee, A.; Gasser, D.L.

    1994-11-01

    The inheritance of alleles of the transforming growth factor alpha (TGFA) locus has been studied in families affected with cleft lip with or without cleft palate (CL/P), by using the transmission/disequilibrium test described by Spielman and colleagues. Only heterozygous parents with an affected child can be included in this test, but within such families a significantly greater frequency of C2 alleles were transmitted to affected children than would be expected by chance. There was no evidence that the total number of C2 alleles transmitted to affected and unaffected children differed significantly from random segregation. These data provide evidence from withinmore » families that a gene for susceptibility to CL/P is in significant linkage disequilibrium with the C2 allele of the TGFA locus. 30 refs., 1 fig., 2 tabs.« less

  20. Gender Stereotype Susceptibility

    PubMed Central

    Pavlova, Marina A.; Weber, Susanna; Simoes, Elisabeth; Sokolov, Alexander N.

    2014-01-01

    Gender affects performance on a variety of cognitive tasks, and this impact may stem from socio-cultural factors such as gender stereotyping. Here we systematically manipulated gender stereotype messages on a social cognition task on which no initial gender gap has been documented. The outcome reveals: (i) Stereotyping affects both females and males, with a more pronounced impact on females. Yet an explicit negative message for males elicits a striking paradoxical deterioration in performance of females. (ii) Irrespective of gender and directness of message, valence of stereotype message affects performance: negative messages have stronger influence than positive ones. (iii) Directness of stereotype message differentially impacts performance of females and males: females tend to be stronger affected by implicit than explicit negative messages, whereas in males this relationship is opposite. The data are discussed in the light of neural networks underlying gender stereotyping. The findings provide novel insights into the sources of gender related fluctuations in cognition and behavior. PMID:25517903

  1. Gender stereotype susceptibility.

    PubMed

    Pavlova, Marina A; Weber, Susanna; Simoes, Elisabeth; Sokolov, Alexander N

    2014-01-01

    Gender affects performance on a variety of cognitive tasks, and this impact may stem from socio-cultural factors such as gender stereotyping. Here we systematically manipulated gender stereotype messages on a social cognition task on which no initial gender gap has been documented. The outcome reveals: (i) Stereotyping affects both females and males, with a more pronounced impact on females. Yet an explicit negative message for males elicits a striking paradoxical deterioration in performance of females. (ii) Irrespective of gender and directness of message, valence of stereotype message affects performance: negative messages have stronger influence than positive ones. (iii) Directness of stereotype message differentially impacts performance of females and males: females tend to be stronger affected by implicit than explicit negative messages, whereas in males this relationship is opposite. The data are discussed in the light of neural networks underlying gender stereotyping. The findings provide novel insights into the sources of gender related fluctuations in cognition and behavior.

  2. Modulating effects of plasma containing anti-malarial antibodies on in vitro anti-malarial drug susceptibility in Plasmodium falciparum.

    PubMed

    Monatrakul, Preeyaporn; Mungthin, Mathirut; Dondorp, Arjen M; Krudsood, Srivicha; Udomsangpetch, Rachanee; Wilairatana, Polrat; White, Nicholas J; Chotivanich, Kesinee

    2010-11-16

    The efficacy of anti-malarial drugs is determined by the level of parasite susceptibility, anti-malarial drug bioavailability and pharmacokinetics, and host factors including immunity. Host immunity improves the in vivo therapeutic efficacy of anti-malarial drugs, but the mechanism and magnitude of this effect has not been characterized. This study characterized the effects of 'immune' plasma to Plasmodium falciparumon the in vitro susceptibility of P. falciparum to anti-malarial drugs. Titres of antibodies against blood stage antigens (mainly the ring-infected erythrocyte surface antigen [RESA]) were measured in plasma samples obtained from Thai patients with acute falciparum malaria. 'Immune' plasma was selected and its effects on in vitro parasite growth and multiplication of the Thai P. falciparum laboratory strain TM267 were assessed by light microscopy. The in vitro susceptibility to quinine and artesunate was then determined in the presence and absence of 'immune' plasma using the 3H-hypoxanthine uptake inhibition method. Drug susceptibility was expressed as the concentrations causing 50% and 90% inhibition (IC50 and IC90), of 3H-hypoxanthine uptake. Incubation with 'immune' plasma reduced parasite maturation and decreased parasite multiplication in a dose dependent manner. 3H-hypoxanthine incorporation after incubation with 'immune' plasma was decreased significantly compared to controls (median [range]; 181.5 [0 to 3,269] cpm versus 1,222.5 [388 to 5,932] cpm) (p= 0.001). As a result 'immune' plasma reduced apparent susceptibility to quinine substantially; median (range) IC50 6.4 (0.5 to 23.8) ng/ml versus 221.5 (174.4 to 250.4) ng/ml (p = 0.02), and also had a borderline effect on artesunate susceptibility; IC50 0.2 (0.02 to 0.3) ng/ml versus 0.8 (0.2 to 2.3) ng/ml (p = 0.08). Effects were greatest at low concentrations, changing the shape of the concentration-effect relationship. IC90 values were not significantly affected; median (range) IC90 448.0 (65 to > 500) ng/ml versus 368.8 (261 to 501) ng/ml for quinine (p > 0.05) and 17.0 (0.1 to 29.5) ng/ml versus 7.6 (2.3 to 19.5) ng/ml for artesunate (p = 0.4). 'Immune' plasma containing anti-malarial antibodies inhibits parasite development and multiplication and increases apparent in vitro anti-malarial drug susceptibility of P. falciparum. The IC90 was much less affected than the IC50 measurement.

  3. Research progress in the genetics of hyperuricaemia and gout.

    PubMed

    Zheng, Min; Ma, Jun-wu

    2016-04-01

    Gout is one of the most common inflammatory arthritis caused by hyperuricaemia, which is affected by both genetic factors and environmental factors. Early researches show that a few of rare monogenic mutations, such as PRPS1 and HPRT1 mutations, lead to abnormal purine anabolism and then cause hyperuricaemia and gout. In recent years, genome-wide association studies (GWAS) have identified dozens of susceptibility loci and/or candidate genes associated with hyperuricemia and gout. Loss-of-function mutations in SLC2A9, SLC22A11, and SLC22A12 cause hereditary hypouricaemia, while their overexpression may increase the reabsorption of uric acid. In contrast, loss-of-function mutations in ABCG2, SLC17A1, and SLC17A3 cause urate underexcretion of renal and intestinal. These variations leading to blood uric acid excretion disorder (excess reabsorption and underexcretion) are the main genetic factors affecting hyperuicemia and gout. Moreover, to some degree, inhibins-activins growth factor system, transcription factors, cytoskeleton and gene-environment interaction can also affect the level of blood uric acid. In addition, two risk genes, RFX3 and KCNQ1, which might impair immune response and lead to functional deficiency of beta cell were recently discovered to influence hyperuiceamia and gout in Han Chinese. This paper systematically reviews genetic studies on hyperuricaemia and gout to improve our understanding of pathogenesis of hyperuricaemia and gout.

  4. Progress in national-scale landslide susceptibility mapping in Romania using a combined statistical-heuristical approach

    NASA Astrophysics Data System (ADS)

    Bălteanu, Dan; Micu, Mihai; Malet, Jean-Philippe; Jurchescu, Marta; Sima, Mihaela; Kucsicsa, Gheorghe; Dumitrică, Cristina; Petrea, Dănuţ; Mărgărint, Ciprian; Bilaşco, Ştefan; Văcăreanu, Radu; Georgescu, Sever; Senzaconi, Francisc

    2017-04-01

    Landslide processes represent a very widespread geohazard in Romania, affecting mainly the hilly and plateau regions as well as the mountain sectors developed on flysch formations. Two main projects provided the framework for improving the existing national landslide susceptibility map (Bălteanu et al. 2010): the ELSUS (Pan-European and nation-wide landslide susceptibility assessment, EC-CERG) and the RO-RISK (Disaster Risk Evaluation at National Level, ESF-POCA) projects. The latter one, a flagship project aiming at strengthening risk prevention and management in Romania, focused on a national-level evaluation of the main risks in the country including landslides. The strategy for modeling landslide susceptibility was designed based on the experience gained from continental and national level assessments conducted in the frame of the International Programme on Landslides (IPL) project IPL-162, the European Landslides Expert Group - JRC and the ELSUS project. The newly proposed landslide susceptibility model used as input a reduced set of landslide conditioning factor maps available at scales of 1:100,000 - 1:200,000 and consisting of lithology, slope angle and land cover. The input data was further differentiated for specific natural environments, defined here as morpho-structural units in order to incorporate differences induced by elevation (vertical climatic zonation), morpho-structure as well as neotectonic features. In order to best discern the specific landslide conditioning elements, the analysis has been carried out for one single process category, namely slides. The existence of a landslide inventory covering the whole country's territory ( 30,000 records, Micu et al. 2014), although affected by incompleteness and lack of homogeneity, allowed for the application of a semi-quantitative, mixed statistical-heuristical approach having the advantage of combining the objectivity of statistics with expert-knowledge in calibrating class and factor weights. The maps obtained for the different units were subjected to evaluation and validation using both expert judgment and two additional landslide inventories with national coverage. Expert evaluations were provided for several parts of the country, where possible also using available regional zonations, and derived knowledge was subsequently used for map improvements. The external landslide datasets allowed for validation of the maps through prediction-rate curves (PRC). An improved national landslide susceptibility map of Romania (100 m resolution) resulted from merging the various unit maps and classifying them according to the PRC-thresholds. The final map reveals good performance for most areas. Finally, improvements compared to the previous version of the national map as well as model limitations and possible enhancement requirements are discussed. This study is part of the RO-RISK project (2016) coordinated by the Romanian General Inspectorate for Emergency Situations (IGSU) and supported by the European Social Fund through the Operational Programme for Administrative Capacity (POCA).

  5. Modification of the effect of ambient air pollution on pediatric asthma emergency visits: susceptible subpopulations

    PubMed Central

    Strickland, Matthew J; Klein, Mitchel; Flanders, W Dana; Chang, Howard H; Mulholland, James A; Tolbert, Paige E; Darrow, Lyndsey A

    2016-01-01

    Background Children may have differing susceptibility to ambient air pollution concentrations depending on various background characteristics of the children. Methods Using emergency department (ED) data linked with birth records from Atlanta, Georgia, we identified ED visits for asthma or wheeze among children aged 2–16 years from 1 January 2002 through 30 June 2010 (n=109,758). We stratified by preterm delivery, term low birth weight, maternal race, Medicaid status, maternal education, maternal smoking, delivery method, and history of a bronchiolitis ED visit. Population-weighted daily average concentrations were calculated for 1-hour maximum carbon monoxide and nitrogen dioxide; 8-hour maximum ozone; and 24-hour average particulate matter less than 10 microns in diameter, particulate matter less than 2.5 microns in diameter (PM2.5), and the PM2.5 components sulfate, nitrate, ammonium, elemental carbon, and organic carbon, using measurements from stationary monitors. Poisson time-series models were used to estimate rate ratios for associations between three-day moving average pollutant concentrations and daily ED visit counts and to investigate effect-measure modification by the stratification factors. Results Associations between pollutant concentrations and asthma exacerbations were larger among children born preterm and among children born to African American mothers. Stratification by race and preterm status together suggested that both factors affected susceptibility. The largest estimated effect size (for an interquartile-range increase in pollution) was observed for ozone among preterm births to African American mothers: rate ratio=1.138 (95% confidence interval=1.077–1.203). In contrast, the rate ration for the ozone association among full-term births to mothers of other races was 1.025 (0.970–1.083). Conclusions Results support the hypothesis that children vary in their susceptibility to ambient air pollutants. PMID:25192402

  6. Vancomycin-Resistance Enterococci Infections in the Department of the Defense: Annual Report 2014

    DTIC Science & Technology

    2015-07-22

    change in 2014 as VRE continues to predominately affect elderly females and manifest as urinary tract infections ( UTIs ). In addition, antibiotic...urinary tract infections ( UTIs ). In addition, antibiotic susceptibility patterns did not substantially change in 2014. Daptomycin, linezolid and...the infection continues to predominately affect elderly females and manifest as UTIs . In addition, antibiotic susceptibility patterns did not

  7. The effects of learning about one's own genetic susceptibility to alcoholism: a randomized experiment.

    PubMed

    Dar-Nimrod, Ilan; Zuckerman, Miron; Duberstein, Paul R

    2013-02-01

    Increased accessibility of direct-to-consumer personalized genetic reports raises the question: how are people affected by information about their own genetic predispositions? Participants were led to believe that they had entered a study on the genetics of alcoholism and sleep disorders. Participants provided a saliva sample purportedly to be tested for the presence of relevant genes. While awaiting the results, they completed a questionnaire assessing their emotional state. They subsequently received a bogus report about their genetic susceptibility and completed a questionnaire about their emotional state and items assessing perceived control over drinking, relevant future drinking-related intentions, and intervention-related motivation and behavior. Participants who were led to believe that they had a gene associated with alcoholism showed an increase in negative affect, decrease in positive affect, and reduced perceived personal control over drinking. Reported intentions for alcohol consumption in the near future were not affected; however, individuals were more likely to enroll in a "responsible drinking" workshop after learning of their alleged genetic susceptibility. The first complete randomized experiment to examine the psychological and behavioral effects of receiving personalized genetic susceptibility information indicates some potential perils and benefits of direct-to-consumer genetic tests.

  8. Spatial Resolution Effects of Digital Terrain Models on Landslide Susceptibility Analysis

    NASA Astrophysics Data System (ADS)

    Chang, K. T.; Dou, J.; Chang, Y.; Kuo, C. P.; Xu, K. M.; Liu, J. K.

    2016-06-01

    The purposes of this study are to identify the maximum number of correlated factors for landslide susceptibility mapping and to evaluate landslide susceptibility at Sihjhong river catchment in the southern Taiwan, integrating two techniques, namely certainty factor (CF) and artificial neural network (ANN). The landslide inventory data of the Central Geological Survey (CGS, MOEA) in 2004-2014 and two digital elevation model (DEM) datasets including a 5-meter LiDAR DEM and a 30-meter Aster DEM were prepared. We collected thirteen possible landslide-conditioning factors. Considering the multi-collinearity and factor redundancy, we applied the CF approach to optimize these thirteen conditioning factors. We hypothesize that if the CF values of the thematic factor layers are positive, it implies that these conditioning factors have a positive relationship with the landslide occurrence. Therefore, based on this assumption and positive CF values, seven conditioning factors including slope angle, slope aspect, elevation, terrain roughness index (TRI), terrain position index (TPI), total curvature, and lithology have been selected for further analysis. The results showed that the optimized-factors model provides a better accuracy for predicting landslide susceptibility in the study area. In conclusion, the optimized-factors model is suggested for selecting relative factors of landslide occurrence.

  9. Chronic obstructive pulmonary disease in women: exploring gender differences.

    PubMed

    Varkey, Anita B

    2004-03-01

    Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality throughout the world. This major public health threat is ranked twelfth as a worldwide burden of disease and is projected to rank fifth by the year 2020 as a cause of lost quantity and quality of life. The impact of this disease in women is significantly understudied but the evidence that does exist reveals potentially substantial gender differences in the susceptibility to, severity of, and response to management of COPD. The best known risk factor for the development of COPD is tobacco smoking. While smoking rates in women have largely stabilized in developed countries, the rates are continuing to climb in developing countries. While it is not clear whether women are more susceptible to the toxic effects of cigarette smoke than men, it is known that the incidence and prevalence of COPD will continue to climb as more women smoke. Other known risk factors for the development of COPD include air pollution, infections, occupational exposures, and genetic factors. Air pollution, particularly fine particulate indoor air pollution from biomass fuels disproportionately affects women. Infections such as human immunodeficiency virus (HIV) and tuberculosis (TB) disproportionately affect vulnerable populations such as poor women and occupational exposures to various dusts and toxins are often gender specific. Genetic factors are still being explored but there seems a preponderance of women who are affected by early-onset and non-smoking related COPD. Women with COPD also seem to be underdiagnosed by physicians and may have different responses to medical treatment, smoking cessation interventions, and pulmonary rehabilitation programs. Chronic obstructive pulmonary disease in women is an understudied subject but is gaining attention as a significant public health threat. In developed countries, efforts at preventing the initiation of tobacco smoking and targeting smoking cessation programs in women are needed. In developing countries, efforts to promote cleaner fuels, improved stoves, better home ventilation, reduce toxic dust and fume exposures, combat infectious diseases such as TB and HIV, and improve nutrition are all ways in which the lung health of women can be improved.

  10. Novel disease susceptibility factors for fungal necrotrophic pathogens in Arabidopsis.

    PubMed

    Dobón, Albor; Canet, Juan Vicente; García-Andrade, Javier; Angulo, Carlos; Neumetzler, Lutz; Persson, Staffan; Vera, Pablo

    2015-04-01

    Host cells use an intricate signaling system to respond to invasions by pathogenic microorganisms. Although several signaling components of disease resistance against necrotrophic fungal pathogens have been identified, our understanding for how molecular components and host processes contribute to plant disease susceptibility is rather sparse. Here, we identified four transcription factors (TFs) from Arabidopsis that limit pathogen spread. Arabidopsis mutants defective in any of these TFs displayed increased disease susceptibility to Botrytis cinerea and Plectosphaerella cucumerina, and a general activation of non-immune host processes that contribute to plant disease susceptibility. Transcriptome analyses revealed that the mutants share a common transcriptional signature of 77 up-regulated genes. We characterized several of the up-regulated genes that encode peptides with a secretion signal, which we named PROVIR (for provirulence) factors. Forward and reverse genetic analyses revealed that many of the PROVIRs are important for disease susceptibility of the host to fungal necrotrophs. The TFs and PROVIRs identified in our work thus represent novel genetic determinants for plant disease susceptibility to necrotrophic fungal pathogens.

  11. The interactive effects of genetic polymorphisms within LFA-1/ICAM-1/GSK-3β pathway and environmental hazards on the development of Graves' opthalmopathy.

    PubMed

    Yang, Ge; Fu, Yang; Lu, Xiaoyan; Wang, Menghua; Dong, Hongtao; Li, Qiuming

    2018-05-22

    The purpose of this investigation was to explore the combined effects of single nucleotide polymorphisms (SNPs) within LFA-1/ICAM-1/GSK-3β pathway and environmental hazards on susceptibility to Graves' opthalmopathy (GO) among a Chinese Han population. Altogether 305 GO patients and 283 Graves' disease (GD) subjects were recruited. Information relevant to the participants' age, gender, body mass index (BMI), regular physical activity, smoking history, alcohol intake, stressful work environment, stress at work, family history of thyroid disease and 131 I treatment were summarized, and the participants' related SNPs of LFA-1/ICAM-1/GSK-3β were also detected. Then the gene-gene and gene-environment interactions were evaluated by logistic regression model and multi-factor dimensionality reduction (MDR) modeling. The results exhibited that age, BMI, smoking history, stressful work, stress at home, family history of thyroid disease and 131 I treatment appeared as potential indicators regulating GO risk, when either univariate or multivariate regression analysis was performed (all P < 0.05). Moreover, rs12716977 (T > C) and rs2230433 (G > C) of LFA-1, rs1799969 (G > A) and rs5498 (A > G) of ICAM-1, as well as rs6438552 (T > C) and rs334558 (T > C) of GSK-3β were significantly associated with altered susceptibility to GO under the allelic models (all P < 0.05). Also haplotype TGAATC acted as a protective factor against GO risk (P < 0.05), whereas haplotype CGAACC largely elevated risk of GO (P < 0.05). Besides, logistic regression analysis demonstrated that rs12716927, rs5498 and rs6438552 all would affect the influences exerted by age, BMI, smoking history, stressful work, stress at home, family history of thyroid disease or 131 I treatment on GO susceptibility (all P < 0.05). MDR modeling implied that the combined model of rs12716977, rs2230433 and rs1799969 was the supreme interactive model when BMI was co-assessed, and the interactive model of rs12716977, rs334558 and rs5491 was the most desirable among the smoking population. In conclusion, gene-gene and gene-environment interactions served as a crucial manner in affecting susceptibility to GO, providing solid evidences for screening effective GO-susceptible biomarkers and exploring potential GO treatment strategies. Copyright © 2018. Published by Elsevier Ltd.

  12. Hepatitis C virus utilizes VLDLR as a novel entry pathway.

    PubMed

    Ujino, Saneyuki; Nishitsuji, Hironori; Hishiki, Takayuki; Sugiyama, Kazuo; Takaku, Hiroshi; Shimotohno, Kunitada

    2016-01-05

    Various host factors are involved in the cellular entry of hepatitis C virus (HCV). In addition to the factors previously reported, we discovered that the very-low-density lipoprotein receptor (VLDLR) mediates HCV entry independent of CD81. Culturing Huh7.5 cells under hypoxic conditions significantly increased HCV entry as a result of the expression of VLDLR, which was not expressed under normoxic conditions in this cell line. Ectopic VLDLR expression conferred susceptibility to HCV entry of CD81-deficient Huh7.5 cells. Additionally, VLDLR-mediated HCV entry was not affected by the knockdown of cellular factors known to act as HCV receptors or HCV entry factors. Because VLDLR is expressed in primary human hepatocytes, our results suggest that VLDLR functions in vivo as an HCV receptor independent of canonical CD81-mediated HCV entry.

  13. Familial aggregation of gout and relative genetic and environmental contributions: a nationwide population study in Taiwan

    PubMed Central

    Kuo, Chang-Fu; Grainge, Matthew J; See, Lai-Chu; Yu, Kuang-Hui; Luo, Shue-Fen; Valdes, Ana M; Zhang, Weiya; Doherty, Michael

    2015-01-01

    Objective To examine familial aggregation of gout and to estimate the heritability and environmental contributions to gout susceptibility in the general population. Methods Using data from the National Health Insurance (NHI) Research Database in Taiwan, we conducted a nationwide cross-sectional study of data collected from 22 643 748 beneficiaries of the NHI in 2004; among them 1 045 059 individuals had physician-diagnosed gout. We estimated relative risks (RR) of gout in individuals with affected first-degree and second-degree relatives and relative contributions of genes (heritability), common environment shared by family members and non-shared environment to gout susceptibility. Results RRs for gout were significantly higher in individuals with affected first-degree relatives (men, 1.91 (95% CI 1.90 to 1.93); women, 1.97 (95% CI 1.94 to 1.99)) and also in those with affected second-degree relatives (men, 1.27 (95% CI 1.23 to 1.31); women, 1.40 (95% CI 1.35 to 1.46)). RRs (95% CIs) for individuals with an affected twin, sibling, offspring, parent, grandchild, nephew/niece, uncle/aunt and grandparent were 8.02 (6.95 to 9.26), 2.59 (2.54 to 2.63), 1.96 (1.95 to 1.97), 1.93 (1.91 to 1.94), 1.48 (1.43 to 1.53), 1.40 (1.32 to 1.47), 1.31 (1.24 to 1.39), and 1.26 (1.21 to 1.30), respectively. The relative contributions of heritability, common and non-shared environmental factors to phenotypic variance of gout were 35.1, 28.1 and 36.8% in men and 17.0, 18.5 and 64.5% in women, respectively. Conclusions This population-based study confirms that gout aggregates within families. The risk of gout is higher in people with a family history. Genetic and environmental factors contribute to gout aetiology, and the relative contributions are sexually dimorphic. PMID:24265412

  14. Effect Measure Modification of Blood Lead-Air Lead Slope Factors

    EPA Science Inventory

    Background: There is abundant literature finding that blood lead (PbB) levels are directly influenced by susceptibility factors including race and ethnicity, age, and housing. However, no study has explored how susceptibility factors influence the PbB-air lead (PbA) relationship...

  15. Interaction of Chlamydia trachomatis organisms and HeLa 229 cells.

    PubMed Central

    Kuo, C C; Grayston, T

    1976-01-01

    The infection of HeLa 229 cells in monolayer culture with trachoma (B/TW-5/OT) and lymphogranuloma venereum (LGV) (L2/434/Bu) organism was studied in terms of two parameters: radioactivity counts of cell-associated tritium labeled organisms at the initial stage of inoculation for measurement of attachment, and inclusion counts of infection cells after incubation for measurement of growth. Factors affecting attachment and inclusion formation and correlation of the two are presented. It was shown that attachment is an important initial step in infection by Chlamydia trachomatis. The rate of attachment was temperature dependent. The attachment of LGV organisms was affected more profoundly by temperature than was that of trachoma organisms. Attachment and inclusion formation of trachoma and LGV organisms were inhibited by heparin. Diethylaminoethyl-dextran was again shown to enhance attachment and inclusion formation of trachoma but not LGV organisms. NaF had no effect on attachment, but inhibited inclusion formation of both trachoma and LGV organisms. Both attachment and inclusion formation of trachoma organisms were strongly enhanced by centrifugation of the inoculum onto the cell monolayer. Although inclusion formation of trachoma organism was much greater in susceptible cells (HeLa 229) than relatively insusceptible cells (fetal tonsil), attachment was only slightly greater. The results based on the test of two cell lines suggested that attachment prpbably is not a critical factor in determing a cell line's susceptibility to infection with trachoma organisms. PMID:179950

  16. Use of molecular approaches in hydrogeological studies: the case of carbonate aquifers in southern Italy

    NASA Astrophysics Data System (ADS)

    Bucci, Antonio; Petrella, Emma; Celico, Fulvio; Naclerio, Gino

    2017-06-01

    Waterborne pathogens represent a significant health risk in both developed and developing countries with sensitive sub-populations including children, the elderly, neonates, and immune-compromised people, who are particularly susceptible to enteric infections. Annually, approximately 1.8 billion people utilize a faecally contaminated water source, and waterborne diseases are resulting in up to 2.1 million human mortalities globally. Although groundwater has traditionally been considered less susceptible to contamination by enteric pathogens than surface water due to natural attenuation by overlying strata, the degree of microbial removal attributable to soils and aquifers can vary significantly depending on several factors. Thus, accurate assessment of the variable presence and concentration of microbial contaminants, and the relative importance of potentially causative factors affecting contaminant ingress, is critical in order to develop effective source (well) and resource (aquifer) protection strategies. "Traditional" and molecular microbiological study designs, when coupled with hydrogeological, hydrochemical, isotopic, and geophysical methods, have proven useful for analysis of numerous aspects of subsurface microbial dynamics. Accordingly, this overview paper presents the principal microbial techniques currently being employed (1) to predict and identify sources of faecal contamination in groundwater, (2) to elucidate the dynamics of contaminant migration, and (3) to refine knowledge about the hydrogeological characteristics and behaviours of aquifer systems affected by microbial contamination with an emphasis on carbonate aquifers, which represent an important global water supply. Previous investigations carried out in carbonate aquifers in southern Italy are discussed.

  17. Effects of antibiotic resistance (AR) and microbiota shifts on Campylobacter jejuni-mediated diseases.

    PubMed

    Brooks, Phillip T; Mansfield, Linda S

    2017-12-01

    Campylobacter jejuni is an important zoonotic pathogen recently designated a serious antimicrobial resistant (AR) threat. While most patients with C. jejuni experience hemorrhagic colitis, serious autoimmune conditions can follow including inflammatory bowel disease (IBD) and the acute neuropathy Guillain Barré Syndrome (GBS). This review examines inter-relationships among factors mediating C. jejuni diarrheal versus autoimmune disease especially AR C. jejuni and microbiome shifts. Because both susceptible and AR C. jejuni are acquired from animals or their products, we consider their role in harboring strains. Inter-relationships among factors mediating C. jejuni colonization, diarrheal and autoimmune disease include C. jejuni virulence factors and AR, the enteric microbiome, and host responses. Because AR C. jejuni have been suggested to affect the severity of disease, length of infections and propensity to develop GBS, it is important to understand how these interactions occur when strains are under selection by antimicrobials. More work is needed to elucidate host-pathogen interactions of AR C. jejuni compared with susceptible strains and how AR C. jejuni are maintained and evolve in animal reservoirs and the extent of transmission to humans. These knowledge gaps impair the development of effective strategies to prevent the emergence of AR C. jejuni in reservoir species and human populations.

  18. Genetic factors affecting EBV copy number in lymphoblastoid cell lines derived from the 1000 Genome Project samples.

    PubMed

    Mandage, Rajendra; Telford, Marco; Rodríguez, Juan Antonio; Farré, Xavier; Layouni, Hafid; Marigorta, Urko M; Cundiff, Caitlin; Heredia-Genestar, Jose Maria; Navarro, Arcadi; Santpere, Gabriel

    2017-01-01

    Epstein-Barr virus (EBV), human herpes virus 4, has been classically associated with infectious mononucleosis, multiple sclerosis and several types of cancers. Many of these diseases show marked geographical differences in prevalence, which points to underlying genetic and/or environmental factors. Those factors may include a different susceptibility to EBV infection and viral copy number among human populations. Since EBV is commonly used to transform B-cells into lymphoblastoid cell lines (LCLs) we hypothesize that differences in EBV copy number among individual LCLs may reflect differential susceptibility to EBV infection. To test this hypothesis, we retrieved whole-genome sequenced EBV-mapping reads from 1,753 LCL samples derived from 19 populations worldwide that were sequenced within the context of the 1000 Genomes Project. An in silico methodology was developed to estimate the number of EBV copy number in LCLs and validated these estimations by real-time PCR. After experimentally confirming that EBV relative copy number remains stable over cell passages, we performed a genome wide association analysis (GWAS) to try detecting genetic variants of the host that may be associated with EBV copy number. Our GWAS has yielded several genomic regions suggestively associated with the number of EBV genomes per cell in LCLs, unraveling promising candidate genes such as CAND1, a known inhibitor of EBV replication. While this GWAS does not unequivocally establish the degree to which genetic makeup of individuals determine viral levels within their derived LCLs, for which a larger sample size will be needed, it potentially highlighted human genes affecting EBV-related processes, which constitute interesting candidates to follow up in the context of EBV related pathologies.

  19. Urban air pollution and meteorological factors affect emergency department visits of elderly patients with chronic obstructive pulmonary disease in Taiwan.

    PubMed

    Ding, Pei-Hsiou; Wang, Gen-Shuh; Guo, Yue-Leon; Chang, Shuenn-Chin; Wan, Gwo-Hwa

    2017-05-01

    Both air pollution and meteorological factors in metropolitan areas increased emergency department (ED) visits from people with chronic obstructive pulmonary disease (COPD). Few studies investigated the associations between air pollution, meteorological factors, and COPD-related health disorders in Asian countries. This study aimed to investigate the relationship between the environmental factors and COPD-associated ED visits of susceptible elderly population in the largest Taiwanese metropolitan area (Taipei area, including Taipei city and New Taipei city) between 2000 and 2013. Data of air pollutant concentrations (PM 10 , PM 2.5 , O 3 , SO 2 , NO 2 and CO), meteorological factors (daily temperature, relative humidity and air pressure), and daily COPD-associated ED visits were collected from Taiwan Environmental Protection Administration air monitoring stations, Central Weather Bureau stations, and the Taiwan National Health Insurance database in Taipei area. We used a case-crossover study design and conditional logistic regression models with odds ratios (ORs), and 95% confidence intervals (CIs) for evaluating the associations between the environmental factors and COPD-associated ED visits. Analyses showed that PM 2.5 , O 3 , and SO 2 had significantly greater lag effects (the lag was 4 days for PM 2.5 , and 5 days for O 3 and SO 2 ) on COPD-associated ED visits of the elderly population (65-79 years old). In warmer days, a significantly greater effect on elderly COPD-associated ED visits was estimated for PM 2.5 with coexistence of O 3 . Additionally, either O 3 or SO 2 combined with other air pollutants increased the risk of elderly COPD-associated ED visits in the days of high relative humidity and air pressure difference, respectively. This study showed that joint effect of urban air pollution and meteorological factors contributed to the COPD-associated ED visits of the susceptible elderly population in the largest metropolitan area in Taiwan. Government authorities should review existing air pollution policies, and strengthen health education propaganda to ensure the health of the susceptible elderly population. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Violent video game effects on aggression, empathy, and prosocial behavior in eastern and western countries: a meta-analytic review.

    PubMed

    Anderson, Craig A; Shibuya, Akiko; Ihori, Nobuko; Swing, Edward L; Bushman, Brad J; Sakamoto, Akira; Rothstein, Hannah R; Saleem, Muniba

    2010-03-01

    Meta-analytic procedures were used to test the effects of violent video games on aggressive behavior, aggressive cognition, aggressive affect, physiological arousal, empathy/desensitization, and prosocial behavior. Unique features of this meta-analytic review include (a) more restrictive methodological quality inclusion criteria than in past meta-analyses; (b) cross-cultural comparisons; (c) longitudinal studies for all outcomes except physiological arousal; (d) conservative statistical controls; (e) multiple moderator analyses; and (f) sensitivity analyses. Social-cognitive models and cultural differences between Japan and Western countries were used to generate theory-based predictions. Meta-analyses yielded significant effects for all 6 outcome variables. The pattern of results for different outcomes and research designs (experimental, cross-sectional, longitudinal) fit theoretical predictions well. The evidence strongly suggests that exposure to violent video games is a causal risk factor for increased aggressive behavior, aggressive cognition, and aggressive affect and for decreased empathy and prosocial behavior. Moderator analyses revealed significant research design effects, weak evidence of cultural differences in susceptibility and type of measurement effects, and no evidence of sex differences in susceptibility. Results of various sensitivity analyses revealed these effects to be robust, with little evidence of selection (publication) bias.

  1. The global susceptibility of coastal forage fish to competition by large jellyfish

    PubMed Central

    Mariani, Patrizio

    2016-01-01

    Competition between large jellyfish and forage fish for zooplankton prey is both a possible cause of jellyfish increases and a concern for the management of marine ecosystems and fisheries. Identifying principal factors affecting this competition is therefore important for marine management, but the lack of both good quality data and a robust theoretical framework have prevented general global analyses. Here, we present a general mechanistic food web model that considers fundamental differences in feeding modes and predation pressure between fish and jellyfish. The model predicts forage fish dominance at low primary production, and a shift towards jellyfish with increasing productivity, turbidity and fishing. We present an index of global ecosystem susceptibility to shifts in fish–jellyfish dominance that compares well with data on jellyfish distributions and trends. The results are a step towards better understanding the processes that govern jellyfish occurrences globally and highlight the advantage of considering feeding traits in ecosystem models. PMID:28120793

  2. Factors influencing message dissemination through social media

    NASA Astrophysics Data System (ADS)

    Zheng, Zeyu; Yang, Huancheng; Fu, Yang; Fu, Dianzheng; Podobnik, Boris; Stanley, H. Eugene

    2018-06-01

    Online social networks strongly impact our daily lives. An internet user (a "Netizen") wants messages to be efficiently disseminated. The susceptible-infected-recovered (SIR) dissemination model is the traditional tool for exploring the spreading mechanism of information diffusion. We here test our SIR-based dissemination model on open and real-world data collected from Twitter. We locate and identify phase transitions in the message dissemination process. We find that message content is a stronger factor than the popularity of the sender. We also find that the probability that a message will be forwarded has a threshold that affects its ability to spread, and when the probability is above the threshold the message quickly achieves mass dissemination.

  3. Periodontology: past, present, perspectives.

    PubMed

    Slots, Jørgen

    2013-06-01

    Periodontitis is an infectious disease that affects the tooth-supporting tissues and exhibits a wide range of clinical, microbiological and immunological manifestations. The disease is associated with and is probably caused by a multifaceted dynamic interaction of specific infectious agents, host immune responses, harmful environmental exposure and genetic susceptibility factors. This volume of Periodontology 2000 covers key subdisciplines of periodontology, ranging from etiopathogeny to therapy, with emphasis on diagnosis, classification, epidemiology, risk factors, microbiology, immunology, systemic complications, anti-infective therapy, reparative treatment, self-care and affordability issues. Learned and unlearned concepts of periodontitis over the past 50 years have shaped our current understanding of the etiology of the disease and of clinical practice. © 2013 John Wiley & Sons A/S.

  4. Genome-wide analysis of genetic susceptibility to language impairment in an isolated Chilean population

    PubMed Central

    Villanueva, Pia; Newbury, Dianne F; Jara, Lilian; De Barbieri, Zulema; Mirza, Ghazala; Palomino, Hernán M; Fernández, María Angélica; Cazier, Jean-Baptiste; Monaco, Anthony P; Palomino, Hernán

    2011-01-01

    Specific language impairment (SLI) is an unexpected deficit in the acquisition of language skills and affects between 5 and 8% of pre-school children. Despite its prevalence and high heritability, our understanding of the aetiology of this disorder is only emerging. In this paper, we apply genome-wide techniques to investigate an isolated Chilean population who exhibit an increased frequency of SLI. Loss of heterozygosity (LOH) mapping and parametric and non-parametric linkage analyses indicate that complex genetic factors are likely to underlie susceptibility to SLI in this population. Across all analyses performed, the most consistently implicated locus was on chromosome 7q. This locus achieved highly significant linkage under all three non-parametric models (max NPL=6.73, P=4.0 × 10−11). In addition, it yielded a HLOD of 1.24 in the recessive parametric linkage analyses and contained a segment that was homozygous in two affected individuals. Further, investigation of this region identified a two-SNP haplotype that occurs at an increased frequency in language-impaired individuals (P=0.008). We hypothesise that the linkage regions identified here, in particular that on chromosome 7, may contain variants that underlie the high prevalence of SLI observed in this isolated population and may be of relevance to other populations affected by language impairments. PMID:21248734

  5. Knockout Mice for Dyslexia Susceptibility Gene Homologs KIAA0319 and KIAA0319L have Unaffected Neuronal Migration but Display Abnormal Auditory Processing

    PubMed Central

    Guidi, Luiz G; Mattley, Jane; Martinez-Garay, Isabel; Monaco, Anthony P; Linden, Jennifer F; Velayos-Baeza, Antonio

    2017-01-01

    Abstract Developmental dyslexia is a neurodevelopmental disorder that affects reading ability caused by genetic and non-genetic factors. Amongst the susceptibility genes identified to date, KIAA0319 is a prime candidate. RNA-interference experiments in rats suggested its involvement in cortical migration but we could not confirm these findings in Kiaa0319-mutant mice. Given its homologous gene Kiaa0319L (AU040320) has also been proposed to play a role in neuronal migration, we interrogated whether absence of AU040320 alone or together with KIAA0319 affects migration in the developing brain. Analyses of AU040320 and double Kiaa0319;AU040320 knockouts (dKO) revealed no evidence for impaired cortical lamination, neuronal migration, neurogenesis or other anatomical abnormalities. However, dKO mice displayed an auditory deficit in a behavioral gap-in-noise detection task. In addition, recordings of click-evoked auditory brainstem responses revealed suprathreshold deficits in wave III amplitude in AU040320-KO mice, and more general deficits in dKOs. These findings suggest that absence of AU040320 disrupts firing and/or synchrony of activity in the auditory brainstem, while loss of both proteins might affect both peripheral and central auditory function. Overall, these results stand against the proposed role of KIAA0319 and AU040320 in neuronal migration and outline their relationship with deficits in the auditory system. PMID:29045729

  6. Weights of Evidence Method for Landslide Susceptibility Mapping in Takengon, Central Aceh, Indonesia

    NASA Astrophysics Data System (ADS)

    Pamela; Sadisun, Imam A.; Arifianti, Yukni

    2018-02-01

    Takengon is an area prone to earthquake disaster and landslide. On July 2, 2013, Central Aceh earthquake induced large numbers of landslides in Takengon area, which resulted in casualties of 39 people. This location was chosen to assess the landslide susceptibility of Takengon, using a statistical method, referred to as the weight of evidence (WoE). This WoE model was applied to indicate the main factors influencing the landslide susceptible area and to derive landslide susceptibility map of Takengon. The 251 landslides randomly divided into two groups of modeling/training data (70%) and validation/test data sets (30%). Twelve thematic maps of evidence are slope degree, slope aspect, lithology, land cover, elevation, rainfall, lineament, peak ground acceleration, curvature, flow direction, distance to river and roads used as landslide causative factors. According to the AUC, the significant factor controlling the landslide is the slope, the slope aspect, peak ground acceleration, elevation, lithology, flow direction, lineament, and rainfall respectively. Analytical result verified by using test data of landslide shows AUC prediction rate is 0.819 and AUC success rate with all landslide data included is 0.879. This result showed the selective factors and WoE method as good models for assessing landslide susceptibility. The landslide susceptibility map of Takengon shows the probabilities, which represent relative degrees of susceptibility for landslide proneness in Takengon area.

  7. Recent advances in Takayasu arteritis.

    PubMed

    Terao, Chikashi; Yoshifuji, Hajime; Mimori, Tsuneyo

    2014-03-01

    Takayasu arteritis (TAK) is a relatively rare systemic vasculitis mainly affecting the aorta and its large branches. While patients with TAK are more frequently observed in Asian countries, we can find patients with TAK all over the world. This limited number of patients has made it difficult to collect large numbers of patients and perform detailed studies. However, recent progresses have led to the identification of susceptibility genes and novel susceptibility human leukocyte antigen (HLA) alleles as well as accumulation of clues for the pathophysiology of TAK. IL12B was shown to be a susceptibility gene beyond ethnicity. MLX and FCGR2A/3A were shown to be associated with TAK in Japanese and Turkish/American populations, respectively. HLA-B*52:01 and *67:01 are susceptibility alleles to TAK, and the 171st and 67th amino acid residues of HLA-B protein are suggested important for TAK susceptibility. HLA-DQB1/DRB1 is recently reported as an independent susceptibility locus. Although there are no standardized serum markers or composite measures for disease activity of TAK, Japanese and Italian groups showed pentraxin 3 as a novel biomarker for detecting and monitoring patients with TAK. Recently, an Indian group proposed a novel scoring system called ITAS to evaluate disease activity of TAK. Standardization of assessing disease activity would lead to clinical studies with high quality. Several groups reported results of treatment for refractory TAK with biological agents targeting tumor necrosis factor or interleukin-6R. The recent accumulation of research data should improve understanding of the basic pathophysiology of TAK and lead to better management of patients with TAK. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  8. Air pollution increases forest susceptibility to wildfires: a case study for the San Bernardino Mountains in southern California

    Treesearch

    N.E. Grulke; R.A. Minnich; T. Paine; P. Riggan

    2010-01-01

    Many factors increase susceptibility of forests to wildfire. Among them are increases in human population, changes in land use, fire suppression, and frequent droughts. These factors have been exacerbating forest susceptibility to wildfires over the last century in southern California. Here we report on the significant role that air pollution has on increasing forest...

  9. microRNAs: Novel Breast Cancer Susceptibility Factors in Caucasian and African American Women

    DTIC Science & Technology

    2012-06-01

    Susceptibility Factors in Caucasian and African American Women PRINCIPAL INVESTIGATOR: Hua Zhao, Ph.D. CONTRACTING ORGANIZATION: Roswell ...5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER Roswell Park...cancer incidence . It is most likely that residual genetic susceptibility is driven by variants at many loci, each conferring a moderately risk of the

  10. Early Life Precursors, Epigenetics, and the Development of Food Allergy1

    PubMed Central

    Hong, Xiumei; Wang, Xiaobin

    2012-01-01

    Food allergy (FA), a major clinical and public health concern worldwide, is caused by a complex interplay of environmental exposures, genetic variants, gene-environment interactions, and epigenetic alterations. This review summarizes recent advances surrounding these key factors, with a particular focus on the potential role of epigenetics in the development of FA. Epidemiologic studies have reported a number of non-genetic factors that may influence the risk of FA, such as timing of food introduction and feeding pattern, diet/nutrition, exposure to environmental tobacco smoking, prematurity and low birthweight, microbial exposure, and race/ethnicity. Current studies on the genetics of FA are mainly conducted using candidate gene approaches, which have linked more than 10 genes to the genetic susceptibility of FA. Studies on gene-environment interactions of FA are very limited. Epigenetic alteration has been proposed as one of the mechanisms to mediate the influence of early-life environmental exposures and gene-environment interactions on the development of diseases later in life. The role of epigenetics in the regulation of the immune system and the epigenetic effects of some FA-associated environmental exposures are discussed in this review. There is a particular lack of large-scale prospective birth cohort studies that simultaneously assess the inter-relationships of early life exposures, genetic susceptibility, epigenomic alterations and the development of FA. The identification of these key factors and their independent and joint contributions to FA will allow us to gain important insight into the biological mechanisms by which environmental exposures and genetic susceptibility affect the risk of FA, and will provide essential information to develop more effective new paradigms in the diagnosis, prevention and management of FA. PMID:22777545

  11. Map making in the 21st century: charting breast cancer susceptibility pathways in rodent models.

    PubMed

    Blackburn, Anneke C; Jerry, D Joseph

    2011-04-01

    Genetic factors play an important role in determining risk and resistance to increased breast cancer. Recent technological advances have made it possible to analyze hundreds of thousands of single nucleotide polymorphisms in large-scale association studies in humans and have resulted in identification of alleles in over 20 genes that influence breast cancer risk. Despite these advances, the challenge remains in identifying what the functional polymorphisms are that confer the increased risk, and how these genetic variants interact with each other and with environmental factors. In rodents, the incidence of mammary tumors varies among strains, such that they can provide alternate ideas for candidate pathways involved in humans. Mapping studies in animals have unearthed numerous loci for breast cancer susceptibility that have been validated in human populations. In a reciprocal manner, knockin and knockout mice have been used to validate the tumorigenicity of risk alleles found in population studies. Rodent studies also underscore the complexity of interactions among alleles. The fact that genes affecting risk and resistance to mammary tumors in rodents depend greatly upon the carcinogenic challenge emphasizes the importance of gene x environment interactions. The challenge to rodent geneticists now is to capitalize on the ability to control the genetics and environment in rodent models of tumorigenesis to better understand the biology of breast cancer development, to identify those polymorphisms most relevant to human susceptibility and to identify compensatory pathways that can be targeted for improved prevention in women at highest risk of developing breast cancer.

  12. Impact of Spodoptera frugiperda neonate pretreatment conditions on Vip3Aa19 insecticidal protein activity and laboratory bioassay variation.

    PubMed

    Da Silva, Karen F; Spencer, Terence A; Camargo Gil, Carolina; Siegfried, Blair D; Walters, Frederick S

    2016-04-01

    Variation in response to insecticidal proteins is common upon repetition of insect bioassays. Understanding this variation is a prerequisite to detecting biologically important differences. We tracked neonate Spodoptera frugiperda (J.E. Smith) susceptibility to Vip3Aa19 over 17 generations using standardized bioassay methods. Five larval pretreatment conditions and one bioassay condition were tested to determine whether susceptibility was affected. These included: storage time; prefeeding; storage at reduced temperature; storage at reduced humidity; colony introgression of field-collected individuals. Extremes of photoperiod during the bioassay itself were also examined. LC50 values for two strains of S. frugiperda varied 6.6-fold or 8.8-fold over 17 generations. Storage time and humidity had no impact on Vip3Aa19 susceptibility, whereas prefeeding significantly reduced subsequent mortality (by 27%). Storage at reduced temperature increased mortality for one colony (from 45.6 to 73.0%) but not for the other. Introgression of field-collected individuals affected susceptibility at the first generation but not for subsequent generations. A 24 h bioassay photophase significantly reduced susceptibility (by 26%) for both colonies. Certain pretreatment and bioassay conditions were identified that can affect S. frugiperda Vip3Aa19 susceptibility, but innate larval heterogeneity was also present. Our observations should help to increase the consistency of insecticidal protein bioassay results. © 2015 Syngenta Crop Protection, LLC. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

  13. Quantitative and qualitative evaluation of dermal elastin of draught horses with chronic progressive lymphoedema.

    PubMed

    De Cock, H E V; Van Brantegem, L; Affolter, V K; Oosterlinck, M; Ferraro, G L; Ducatelle, R

    2009-01-01

    Chronic progressive lymphoedema (CPL) in horses, a disease of certain draught breeds, is associated with altered elastin metabolism. The characteristic lesions are seen in the skin of the lower (distal) limbs. This study was based on horses of susceptible breeds, with and without CPL, and on horses of a non-susceptible breed. Skin samples were obtained for examination from the neck (considered a non-affected region) and from the distal limb. The skin lesions were characterized histologically and the dermal elastic fibres were evaluated morphologically and quantitatively. In all horses the mean elastin concentrations were highest in the superficial dermis, gradually decreasing in the mid-dermis and deep dermis. As compared with horses of a non-susceptible breed, affected horses had increased amounts of dermal elastin in both the distal limb and neck, while non-affected horses of a susceptible breed had decreased amounts. The findings support an earlier hypothesis that CPL of horses is a generalized disease. Reduced efficiency of the elastic network in supporting the dermal lymphatics may explain the development of CPL.

  14. Negative (but not Positive) Parenting Interacts with Infant Negative Affect to Predict Infant Approach: Evidence of Diathesis-Stress.

    PubMed

    Holzman, Jacob B; Burt, Nicole M; Edwards, Erin S; Rosinski, Leanna D; Bridgett, David J

    2018-01-01

    Temperament by parenting interactions may reflect that individuals with greater risk are more likely to experience negative outcomes in adverse contexts (diathesis-stress) or that these individuals are more susceptible to contextual influences in a 'for better or for worse' pattern (differential susceptibility). Although such interactions have been identified for a variety of child outcomes, prior research has not examined approach characteristics - excitement and approach toward pleasurable activities - in the first year of life. Therefore, the current study investigated whether 6-month maternal reported infant negative affect - a phenotypic marker of risk/susceptibility - interacted with 8-month observed parenting behaviors (positive parenting, negative parenting) to predict 12-month infant behavioral approach. Based a sample of mothers and their infants ( N =150), results indicated that negative parenting was inversely associated with subsequent approach for infants with high, but not low, levels of early negative affect. Similar results did not occur regarding positive parenting. These findings better fit a diathesis-stress model rather than a differential susceptibility model. Implications and limitations of these findings are discussed.

  15. Environmental influences on development of type 2 diabetes and obesity: challenges in personalizing prevention and management.

    PubMed

    Ershow, Abby G

    2009-07-01

    Recent epidemic increases in the U.S. prevalence of obesity and diabetes are a consequence of widespread environmental changes affecting energy balance and its regulation. These environmental changes range from exposure to endocrine disrupting pollutants to shortened sleep duration to physical inactivity to excess caloric intake. Overall, we need a better understanding of the factors affecting individual susceptibility and resistance to adverse exposures and behaviors and of determinants of individual response to treatment. Obesity and diabetes prevention will require responding to two primary behavioral risk factors: excess energy intake and insufficient energy expenditure. Adverse food environments (external, nonphysiological influences on eating behaviors) contribute to excess caloric intake but can be countered through behavioral and economic approaches. Adverse built environments, which can be modified to foster more physical activity, are promising venues for community-level intervention. Techniques to help people to modulate energy intake and increase energy expenditure must address their personal situations: health literacy, psychological factors, and social relationships. Behaviorally oriented translational research can help in developing useful interventions and environmental modifications that are tailored to individual needs. Copyright 2009 Diabetes Technology Society.

  16. The effect of sub-inhibitory concentrations of rifaximin on urease production and on other virulence factors expressed by Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa and Staphylococcus aureus.

    PubMed

    Ricci, Annalisa; Coppo, Erika; Barbieri, Ramona; Debbia, Eugenio A; Marchese, Anna

    2017-04-01

    Rifaximin, a topical derivative of rifampin, inhibited urease production and other virulence factors at sub-MIC concentrations in strains involved in hepatic encephalopathy and the expression of methicillin resistance in Staphylococcus aureus. In particular, urease production was affected in all Proteus mirabilis and Klebsiella pneumoniae strains as well as in all tested Pseudomonas aeruginosa isolates. Other exotoxins, synthesized by P. aeruginosa, such as protease, gelatinase, lipase, lecithinase and DNAse were also not metabolized in the presence of rifaximin. This antibiotic inhibited pigment production in both P. aeruginosa and Chromobacterium violaceum, a biosensor control strain. Lastly, rifaximin affected haemolysin production in S. aureus and was able to restore cefoxitin susceptibility when the strain was cultured in the presence of sub-MICs of the drug. The present findings confirm and extend previous observations about the beneficial effects of rifaximin for the treatment of gastrointestinal diseases, since in this anatomic site, it reaches a large array of concentrations which prevents enterobacteria from thriving and/or producing their major virulence factors.

  17. The nature of genetic susceptibility to multiple sclerosis: constraining the possibilities.

    PubMed

    Goodin, Douglas S

    2016-04-27

    Epidemiological observations regarding certain population-wide parameters (e.g., disease-prevalence, recurrence-risk in relatives, gender predilections, and the distribution of common genetic-variants) place important constraints on the possibilities for the genetic-basis underlying susceptibility to multiple sclerosis (MS). Using very broad range-estimates for the different population-wide epidemiological parameters, a mathematical model can help elucidate the nature and the magnitude of these constraints. For MS no more than 8.5 % of the population can possibly be in the "genetically-susceptible" subset (defined as having a life-time MS-probability at least as high as the overall population average). Indeed, the expected MS-probability for this subset is more than 12 times that for every other person of the population who is not in this subset. Moreover, provided that those genetically susceptible persons (genotypes), who carry the well-established MS susceptibility allele (DRB1*1501), are equally or more likely to get MS than those susceptible persons, who don't carry this allele, then at least 84 % of MS-cases must come from this "genetically susceptible" subset. Finally, because men, compared to women, are at least as likely (and possibly more likely) to be susceptible, it can be demonstrated that women are more responsive to the environmental factors that are involved in MS-pathogenesis (whatever these are) and, thus, susceptible women are more likely actually to develop MS than susceptible men. Finally, in contrast to genetic susceptibility, more than 70 % of men (and likely also women) must have an environmental experience (including all of the necessary factors), which is sufficient to produce MS in a susceptible individual. As a result, because of these constraints, it is possible to distinguish two classes of persons, indicating either that MS can be caused by two fundamentally different pathophysiological mechanisms or that the large majority of the population is at no risk of the developing this disease regardless of their environmental experience. Moreover, although environmental-factors would play a critical role in both mechanisms (if both exist), there is no reason to expect that these factors are the same (or even similar) between the two.

  18. Restriction fragment length polymorphism mapping of quantitative trait loci for malaria parasite susceptibility in the mosquito Aedes aegypti

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Severson, D.W.; Thathy, V.; Mori, A.

    Susceptibility of the mosquito Aedes aegypti to the malarial parasite Plasmodium gallinaceum was investigated as a quantitative trait using restriction fragment length polymorphisms (RFLP). Two F{sub 2} populations of mosquitoes were independently prepared from pairwise matings between a highly susceptible and a refractory strain of A. aegypti. RFLP were tested for association with oocyst development on the mosquito midgut. Two putative quantitative trait loci (QTL) were identified that significantly affect susceptibility. One QTL, pgs [2,LF98], is located on chromosome 2 and accounted for 65 and 49% of the observed phenotypic variance in the two populations, respectively. A second QTL, pgs[3,MalI],more » is located on chromosome 3 and accounted for 14 and 10% of the observed phenotypic variance in the two populations, respectively. Both QTL exhibit a partial dominance effect on susceptibility, wherein the dominance effect is derived from the refractory parent. No indication of epistasis between these QTL was detected. Evidence suggests that either a tightly linked cluster of independent genes or a single locus affecting susceptibility to various mosquito-borne parasites and pathogens has evolved near the LF98 locus; in addition to P. gallinaceum susceptibility, this general genome region has previously been implicated in susceptibility to the filaria nematode Brugia malayi and the yellow fever virus. 35 refs., 2 figs., 3 tabs.« less

  19. Developmental neurotoxicity of traffic-related air pollution: focus on autism

    PubMed Central

    Costa, Lucio G.; Chang, Yu-Chi; Cole, Toby B.

    2018-01-01

    Purpose of Review Epidemiological and animal studies suggest that air pollution may negatively affect the central nervous system (CNS) and contribute to CNS diseases. Traffic-related air pollution is a major contributor to global air pollution, and diesel exhaust (DE) is its most important component. Recent findings Several studies suggest that young individuals may be particularly susceptible to air pollution-induced neurotoxicity, and that perinatal exposure may cause or contribute to developmental disabilities and behavioral abnormalities. In particular, a number of recent studies have found associations between exposures to traffic-related air pollution and autism spectrum disorders (ASD), which are characterized by impairment in socialization and in communication, and by the presence of repetitive and unusual behaviors. The cause(s) of ASD are unknown, and while it may have a hereditary component, environmental factors are increasingly suspected as playing a pivotal role in its etiology, particularly in genetically susceptible individuals. Summary Autistic children present higher levels of neuroinflammation and systemic inflammation, which are also hallmarks of exposure to traffic-related air pollution. Gene-environment interactions may play a relevant role in determining individual susceptibility to air pollution developmental neurotoxicity. Given the worldwide presence of elevated air pollution, studies on its effects and mechanisms on the developing brain, genetic susceptibility, role in neurodevelopmental disorders, and possible therapeutic interventions, are certainly warranted. PMID:28417440

  20. Susceptibility and tolerance of human gut culturable aerobic microbiota to wine polyphenols.

    PubMed

    Cueva, Carolina; Bartolomé, Begoña; Moreno-Arribas, M Victoria; Bustos, Irene; Requena, Teresa; González-Manzano, Susana; Santos-Buelga, Celestino; Turrientes, María-Carmen; del Campo, Rosa

    2015-02-01

    Diet is one of the main factors that could affect quantitatively and qualitatively the stability of the gut microbiota. Polyphenols are abundantly present in the human diet and have an antimicrobial effect inducing selective changes in the microbiota composition, with potential beneficial effects for the human health. Our aim was to determine the human gut microbiota susceptibility toward wine polyphenols. Susceptibility to two commercial wine phenolic extracts (Vitaflavan(®) and Provinols™) was determined in isolates from fecal samples from 36 gastrointestinal healthy volunteers. To select the polyphenol-resistant isolates, feces were seeded in plates containing 1 mg/ml of phenolic extract. The minimal inhibitory concentration to polyphenols in the collected isolates was assessed by the agar dilution method. Overall results showed that Gram-negative isolates are most tolerant to the presence of both grape seed and red wine extracts. Furthermore, we purified to homogeneity the phenolic fractions by high-performance liquid chromatography (HPLC) to determine their antimicrobial effect and their influence on bacterial growth in four selected ATCC strains using the BioScreen apparatus. Results showed that the antimicrobial activity of the wine polyphenols is the result of the interaction of both the flavan-3-ol type and the bacteria. Bacterial Intraspecies differences in the phenolic susceptibility suggest the existence of polyphenol-resistant mechanisms that are uncharacterized as yet.

  1. Blue light treatment of Pseudomonas aeruginosa: Strong bactericidal activity, synergism with antibiotics and inactivation of virulence factors.

    PubMed

    Fila, Grzegorz; Kawiak, Anna; Grinholc, Mariusz Stanislaw

    2017-08-18

    Pseudomonas aeruginosa is among the most common pathogens responsible for both acute and chronic infections of high incidence and severity. Additionally, P. aeruginosa resistance to conventional antimicrobials has increased rapidly over the past decade. Therefore, it is crucial to explore new therapeutic options, particularly options that specifically target the pathogenic mechanisms of this microbe. The ability of a pathogenic bacterium to cause disease is dependent upon the production of agents termed 'virulence factors', and approaches to mitigate these agents have gained increasing attention as new antibacterial strategies. Although blue light irradiation is a promising alternative approach, only limited and preliminary studies have described its effect on virulence factors. The current study aimed to investigate the effects of lethal and sub-lethal doses of blue light treatment (BLT) on P. aeruginosa virulence factors. We analyzed the inhibitory effects of blue light irradiation on the production/activity of several virulence factors. Lethal BLT inhibited the activity of pyocyanin, staphylolysin, pseudolysin and other proteases, but sub-lethal BLT did not affect the production/expression of proteases, phospholipases, and flagella- or type IV pili-associated motility. Moreover, a eukaryotic cytotoxicity test confirmed the decreased toxicity of blue light-treated extracellular P. aeruginosa fractions. Finally, the increased antimicrobial susceptibility of P. aeruginosa treated with sequential doses of sub-lethal BLT was demonstrated with a checkerboard test. Thus, this work provides evidence-based proof of the susceptibility of drug-resistant P. aeruginosa to BLT-mediated killing, accompanied by virulence factor reduction, and describes the synergy between antibiotics and sub-lethal BLT.

  2. Optimization of Causative Factors for Landslide Susceptibility Evaluation Using Remote Sensing and GIS Data in Parts of Niigata, Japan.

    PubMed

    Dou, Jie; Tien Bui, Dieu; Yunus, Ali P; Jia, Kun; Song, Xuan; Revhaug, Inge; Xia, Huan; Zhu, Zhongfan

    2015-01-01

    This paper assesses the potentiality of certainty factor models (CF) for the best suitable causative factors extraction for landslide susceptibility mapping in the Sado Island, Niigata Prefecture, Japan. To test the applicability of CF, a landslide inventory map provided by National Research Institute for Earth Science and Disaster Prevention (NIED) was split into two subsets: (i) 70% of the landslides in the inventory to be used for building the CF based model; (ii) 30% of the landslides to be used for the validation purpose. A spatial database with fifteen landslide causative factors was then constructed by processing ALOS satellite images, aerial photos, topographical and geological maps. CF model was then applied to select the best subset from the fifteen factors. Using all fifteen factors and the best subset factors, landslide susceptibility maps were produced using statistical index (SI) and logistic regression (LR) models. The susceptibility maps were validated and compared using landslide locations in the validation data. The prediction performance of two susceptibility maps was estimated using the Receiver Operating Characteristics (ROC). The result shows that the area under the ROC curve (AUC) for the LR model (AUC = 0.817) is slightly higher than those obtained from the SI model (AUC = 0.801). Further, it is noted that the SI and LR models using the best subset outperform the models using the fifteen original factors. Therefore, we conclude that the optimized factor model using CF is more accurate in predicting landslide susceptibility and obtaining a more homogeneous classification map. Our findings acknowledge that in the mountainous regions suffering from data scarcity, it is possible to select key factors related to landslide occurrence based on the CF models in a GIS platform. Hence, the development of a scenario for future planning of risk mitigation is achieved in an efficient manner.

  3. Optimization of Causative Factors for Landslide Susceptibility Evaluation Using Remote Sensing and GIS Data in Parts of Niigata, Japan

    PubMed Central

    Dou, Jie; Tien Bui, Dieu; P. Yunus, Ali; Jia, Kun; Song, Xuan; Revhaug, Inge; Xia, Huan; Zhu, Zhongfan

    2015-01-01

    This paper assesses the potentiality of certainty factor models (CF) for the best suitable causative factors extraction for landslide susceptibility mapping in the Sado Island, Niigata Prefecture, Japan. To test the applicability of CF, a landslide inventory map provided by National Research Institute for Earth Science and Disaster Prevention (NIED) was split into two subsets: (i) 70% of the landslides in the inventory to be used for building the CF based model; (ii) 30% of the landslides to be used for the validation purpose. A spatial database with fifteen landslide causative factors was then constructed by processing ALOS satellite images, aerial photos, topographical and geological maps. CF model was then applied to select the best subset from the fifteen factors. Using all fifteen factors and the best subset factors, landslide susceptibility maps were produced using statistical index (SI) and logistic regression (LR) models. The susceptibility maps were validated and compared using landslide locations in the validation data. The prediction performance of two susceptibility maps was estimated using the Receiver Operating Characteristics (ROC). The result shows that the area under the ROC curve (AUC) for the LR model (AUC = 0.817) is slightly higher than those obtained from the SI model (AUC = 0.801). Further, it is noted that the SI and LR models using the best subset outperform the models using the fifteen original factors. Therefore, we conclude that the optimized factor model using CF is more accurate in predicting landslide susceptibility and obtaining a more homogeneous classification map. Our findings acknowledge that in the mountainous regions suffering from data scarcity, it is possible to select key factors related to landslide occurrence based on the CF models in a GIS platform. Hence, the development of a scenario for future planning of risk mitigation is achieved in an efficient manner. PMID:26214691

  4. Effects of a Cancer Prevention Advertisement on Beliefs and Knowledge about Cancer Prevention.

    PubMed

    Kye, Su Yeon; Yoo, Jisu; Lee, Min Hee; Jun, Jae Kwan

    2015-01-01

    Outcome-expectation beliefs and knowledge may ultimately influence behavior for cancer prevention. The aims of this study were to measure changes in knowledge and beliefs about cancer prevention before and after viewing a television advertisement and identify the factors affecting receptivity to its messages. A one-group pretest-posttest design was used in this study of 1,000 individuals aged 20 to 65 years who were recruited online in November 2014. The outcome variables included cancer prevention beliefs based on the Health Belief Model (five items) and knowledge about risk factors for cancer (seven items). Perceived susceptibility, perceived benefits, and self-efficacy increased significantly and their perceived severity and perceived barriers decreased significantly, after participants viewed the television advertisement. Correct responses to questions about risk factors also increased significantly, except for smoking. The main factors affecting changes in the outcome variables were age, interest in cancer prevention, social network, satisfaction with the ad, and pretest scores. Television advertisements with positive frameworks can be an efficient channel of improving beliefs and knowledge about cancer prevention in a short period. The continuous development of intervention materials that consider the demographics, needs, and satisfaction of the target group will be necessary for future studies.

  5. Genetic factors affecting dental caries risk.

    PubMed

    Opal, S; Garg, S; Jain, J; Walia, I

    2015-03-01

    This article reviews the literature on genetic aspects of dental caries and provides a framework for the rapidly changing disease model of caries. The scope is genetic aspects of various dental factors affecting dental caries. The PubMed database was searched for articles with keywords 'caries', 'genetics', 'taste', 'diet' and 'twins'. This was followed by extensive handsearching using reference lists from relevant articles. The post-genomic era will present many opportunities for improvement in oral health care but will also present a multitude of challenges. We can conclude from the literature that genes have a role to play in dental caries; however, both environmental and genetic factors have been implicated in the aetiology of caries. Additional studies will have to be conducted to replicate the findings in a different population. Identification of genetic risk factors will help screen and identify susceptible patients to better understand the contribution of genes in caries aetiopathogenesis. Information derived from these diverse studies will provide new tools to target individuals and/or populations for a more efficient and effective implementation of newer preventive measures and diagnostic and novel therapeutic approaches in the management of this disease. © 2015 Australian Dental Association.

  6. Novel Disease Susceptibility Factors for Fungal Necrotrophic Pathogens in Arabidopsis

    PubMed Central

    García-Andrade, Javier; Angulo, Carlos; Neumetzler, Lutz; Persson, Staffan; Vera, Pablo

    2015-01-01

    Host cells use an intricate signaling system to respond to invasions by pathogenic microorganisms. Although several signaling components of disease resistance against necrotrophic fungal pathogens have been identified, our understanding for how molecular components and host processes contribute to plant disease susceptibility is rather sparse. Here, we identified four transcription factors (TFs) from Arabidopsis that limit pathogen spread. Arabidopsis mutants defective in any of these TFs displayed increased disease susceptibility to Botrytis cinerea and Plectosphaerella cucumerina, and a general activation of non-immune host processes that contribute to plant disease susceptibility. Transcriptome analyses revealed that the mutants share a common transcriptional signature of 77 up-regulated genes. We characterized several of the up-regulated genes that encode peptides with a secretion signal, which we named PROVIR (for provirulence) factors. Forward and reverse genetic analyses revealed that many of the PROVIRs are important for disease susceptibility of the host to fungal necrotrophs. The TFs and PROVIRs identified in our work thus represent novel genetic determinants for plant disease susceptibility to necrotrophic fungal pathogens. PMID:25830627

  7. Water erosion susceptibility mapping by applying Stochastic Gradient Treeboost to the Imera Meridionale River Basin (Sicily, Italy)

    NASA Astrophysics Data System (ADS)

    Angileri, Silvia Eleonora; Conoscenti, Christian; Hochschild, Volker; Märker, Michael; Rotigliano, Edoardo; Agnesi, Valerio

    2016-06-01

    Soil erosion by water constitutes a serious problem affecting various countries. In the last few years, a number of studies have adopted statistical approaches for erosion susceptibility zonation. In this study, the Stochastic Gradient Treeboost (SGT) was tested as a multivariate statistical tool for exploring, analyzing and predicting the spatial occurrence of rill-interrill erosion and gully erosion. This technique implements the stochastic gradient boosting algorithm with a tree-based method. The study area is a 9.5 km2 river catchment located in central-northern Sicily (Italy), where water erosion processes are prevalent, and affect the agricultural productivity of local communities. In order to model soil erosion by water, the spatial distribution of landforms due to rill-interrill and gully erosion was mapped and 12 environmental variables were selected as predictors. Four calibration and four validation subsets were obtained by randomly extracting sets of negative cases, both for rill-interrill erosion and gully erosion models. The results of validation, based on receiving operating characteristic (ROC) curves, showed excellent to outstanding accuracies of the models, and thus a high prediction skill. Moreover, SGT allowed us to explore the relationships between erosion landforms and predictors. A different suite of predictor variables was found to be important for the two models. Elevation, aspect, landform classification and land-use are the main controlling factors for rill-interrill erosion, whilst the stream power index, plan curvature and the topographic wetness index were the most important independent variables for gullies. Finally, an ROC plot analysis made it possible to define a threshold value to classify cells according to the presence/absence of the two erosion processes. Hence, by heuristically combining the resulting rill-interrill erosion and gully erosion susceptibility maps, an integrated water erosion susceptibility map was created. The adopted method offers the advantages of an objective and repeatable procedure, whose result is useful for local administrators to identify the areas that are most susceptible to water erosion and best allocate resources for soil conservation strategies.

  8. Androgenic alopecia may have evolved to protect men from prostate cancer by increasing skin exposure to ultraviolet radiation.

    PubMed

    Kabai, Peter

    2008-01-01

    Androgenic alopecia affects populations adapted to colder climate, and individuals at an age and hormonal status susceptible to prostate cancer. Male pattern baldness enhances absorption of UV radiation on the top of the head, an area directly exposed to sunlight during everyday activities. Ultraviolet radiation is reported to reduce the risk of advanced prostate cancer. Here I propose that progression of androgenic alopecia rather than being a risk factor is a finely tuned mechanism evolved to protect against prostate cancer.

  9. A gene for familial psoriasis susceptibility maps to the distal end of human chromosome 17q

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bowcock, A.; Tomfohrde, J.; Barnes, R.

    1994-09-01

    Psoriasis is a chronic inflammatory dermatosis that affects approximately 2% of the population. A gene for psoriasis susceptibility was localized to the distal region of human chromosome 17q as a result of a genome wide linkage-analysis with polymorphic microsatellites and eight multiply affected psoriasis kindreds. With one large kindred a maximum two-point lod score with D17S784 was 5.70 at 15% recombination. Heterogeneity testing indicated that psoriasis susceptibility in 50% of the families was linked to distal 17q. Susceptibility to psoriasis has repeatedly been found to be associated with HLA-Cw6 and associated HLA alleles. We therefore genotyped the families for locimore » within and flanking HLA; these included PCR assays for susceptibility alleles. By lod score analysis no evidence of linkage of psoriasis susceptibility to HLA was detected. The distribution of HLA-Cw6 and HLA-Class II alleles showed that HLA-Cw6 was frequent among patients, particularly in 4 of the 5 unlinked families. All affected members of two of these unlinked families carried HLA-Cw6 (empirical P values of 0.027 and 0.004). In 2 other families 4 of 6 and 6 of 7 had HLA-Cw6. In some of these families, an inability to detect linkage to HLA may have been due to the occurrence of multiple haplotypes carrying the psoriasis associated allele, HLA-Cw6. Contrasting with these findings, we observed a lack of association between HLA-Cw6 and psoriasis in the 3 families in which 17q markers were linked to susceptibility. The ability to detect linkage to 17q confirms that some forms of familial psoriasis are due to molecular defects at a single major genetic locus other than HLA.« less

  10. The immunoproteasome-specific inhibitor ONX 0914 reverses susceptibility to acute viral myocarditis.

    PubMed

    Althof, Nadine; Goetzke, Carl Christoph; Kespohl, Meike; Voss, Karolin; Heuser, Arnd; Pinkert, Sandra; Kaya, Ziya; Klingel, Karin; Beling, Antje

    2018-02-01

    Severe heart pathology upon virus infection is closely associated with the immunological equipment of the host. Since there is no specific treatment available, current research focuses on identifying new drug targets to positively modulate predisposing immune factors. Utilizing a murine model with high susceptibility to coxsackievirus B3-induced myocarditis, this study describes ONX 0914-an immunoproteasome-specific inhibitor-as highly protective during severe heart disease. Represented by reduced heart infiltration of monocytes/macrophages and diminished organ damage, ONX 0914 treatment reversed fulminant pathology. Virus-induced immune response features like overwhelming pro-inflammatory cytokine and chemokine production as well as a progressive loss of lymphocytes all being reminiscent of a sepsis-like disease course were prevented by ONX 0914. Although the viral burden was only minimally affected in highly susceptible mice, resulting maintenance of immune homeostasis improved the cardiac output, and saved animals from severe illness as well as high mortality. Altogether, this could make ONX 0914 a potent drug for the treatment of severe virus-mediated inflammation of the heart and might rank immunoproteasome inhibitors among drugs for preventing pathogen-induced immunopathology. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

  11. Suppression of epidemic spreading in complex networks by local information based behavioral responses.

    PubMed

    Zhang, Hai-Feng; Xie, Jia-Rong; Tang, Ming; Lai, Ying-Cheng

    2014-12-01

    The interplay between individual behaviors and epidemic dynamics in complex networks is a topic of recent interest. In particular, individuals can obtain different types of information about the disease and respond by altering their behaviors, and this can affect the spreading dynamics, possibly in a significant way. We propose a model where individuals' behavioral response is based on a generic type of local information, i.e., the number of neighbors that has been infected with the disease. Mathematically, the response can be characterized by a reduction in the transmission rate by a factor that depends on the number of infected neighbors. Utilizing the standard susceptible-infected-susceptible and susceptible-infected-recovery dynamical models for epidemic spreading, we derive a theoretical formula for the epidemic threshold and provide numerical verification. Our analysis lays on a solid quantitative footing the intuition that individual behavioral response can in general suppress epidemic spreading. Furthermore, we find that the hub nodes play the role of "double-edged sword" in that they can either suppress or promote outbreak, depending on their responses to the epidemic, providing additional support for the idea that these nodes are key to controlling epidemic spreading in complex networks.

  12. Landslide Susceptibility Analysis along Li-Shing Mountain Road in Nantou County, Taiwan

    NASA Astrophysics Data System (ADS)

    Yeh, J. H.; Chan, H. C.; Chen, B. A.

    2016-12-01

    Slopeland hazards are frequently occurred during typhoon periods in the mountain areas of Taiwan. The Li-Shing Mountain Road was suffered from the landslide and erosion of road foundation due to its fragile geological structure, overuse of land, and heavy rainfall. Transportation of agricultural produce in Li-Shing areas was seriously affected while the Li-Shing Mountain Road was blocked by the landslides. To evaluate the landslide susceptibilities along the Li-Shing Mountain Road, this study collected the landslide inventories from Typhoon Mindulle in July, 2004 and Typhoon Kalmaegi in July, 2008. By combining the landslide inventories with hydrological and geological factors, such as rainfall, distance to river, geology, and land slope and aspect, the Instability Index Method was used to specify the landslide susceptibilities of the slopes along the Li-Shing Mountain Road. The accuracy of the present model was evaluated by comparison of the predicted and the typhoon triggered landslides. Finally, the high landslide potential slopes along the Li-Shing Mountain Road were identified. It is expected to provide the information for landslide warning system and engineering countermeasures planning along the Li-Shing Mountain Road. Keywords: Landslide, Instability Index Method, Li-Shing Mountain Road

  13. Suppression of epidemic spreading in complex networks by local information based behavioral responses

    NASA Astrophysics Data System (ADS)

    Zhang, Hai-Feng; Xie, Jia-Rong; Tang, Ming; Lai, Ying-Cheng

    2014-12-01

    The interplay between individual behaviors and epidemic dynamics in complex networks is a topic of recent interest. In particular, individuals can obtain different types of information about the disease and respond by altering their behaviors, and this can affect the spreading dynamics, possibly in a significant way. We propose a model where individuals' behavioral response is based on a generic type of local information, i.e., the number of neighbors that has been infected with the disease. Mathematically, the response can be characterized by a reduction in the transmission rate by a factor that depends on the number of infected neighbors. Utilizing the standard susceptible-infected-susceptible and susceptible-infected-recovery dynamical models for epidemic spreading, we derive a theoretical formula for the epidemic threshold and provide numerical verification. Our analysis lays on a solid quantitative footing the intuition that individual behavioral response can in general suppress epidemic spreading. Furthermore, we find that the hub nodes play the role of "double-edged sword" in that they can either suppress or promote outbreak, depending on their responses to the epidemic, providing additional support for the idea that these nodes are key to controlling epidemic spreading in complex networks.

  14. Susceptibility to Yersinia pestis experimental infection in wild Rattus rattus, reservoir of plague in Madagascar.

    PubMed

    Tollenaere, C; Rahalison, L; Ranjalahy, M; Duplantier, J-M; Rahelinirina, S; Telfer, S; Brouat, C

    2010-06-01

    In Madagascar, the black rat, Rattus rattus, is the main reservoir of plague (Yersinia pestis infection), a disease still responsible for hundreds of cases each year in this country. This study used experimental plague challenge to assess susceptibility in wild-caught rats to better understand how R. rattus can act as a plague reservoir. An important difference in plague resistance between rat populations from the plague focus (central highlands) and those from the plague-free zone (low altitude area) was confirmed to be a widespread phenomenon. In rats from the plague focus, we observed that sex influenced plague susceptibility, with males slightly more resistant than females. Other individual factors investigated (weight and habitat of sampling) did not affect plague resistance. When infected at high bacterial dose (more than 10⁵ bacteria injected), rats from the plague focus died mainly within 3-5 days and produced specific antibodies, whereas after low-dose infection (< 5,000 bacteria), delayed mortality was observed and surviving seronegative rats were not uncommon. These results concerning plague resistance level and the course of infection in the black rat would contribute to a better understanding of plague circulation in Madagascar.

  15. Empiric antibiotic therapy in urinary tract infection in patients with risk factors for antibiotic resistance in a German emergency department.

    PubMed

    Bischoff, Sebastian; Walter, Thomas; Gerigk, Marlis; Ebert, Matthias; Vogelmann, Roger

    2018-01-26

    The aim of this study was to identify clinical risk factors for antimicrobial resistances and multidrug resistance (MDR) in urinary tract infections (UTI) in an emergency department in order to improve empirical therapy. UTI cases from an emergency department (ED) during January 2013 and June 2015 were analyzed. Differences between patients with and without resistances towards Ciprofloxacin, Piperacillin with Tazobactam (Pip/taz), Gentamicin, Cefuroxime, Cefpodoxime and Ceftazidime were analyzed with Fisher's exact tests. Results were used to identify risk factors with logistic regression modelling. Susceptibility rates were analyzed in relation to risk factors. One hundred thirty-seven of four hundred sixty-nine patients who met the criteria of UTI had a positive urine culture. An MDR pathogen was found in 36.5% of these. Overall susceptibility was less than 85% for standard antimicrobial agents. Logistic regression identified residence in nursing homes, male gender, hospitalization within the last 30 days, renal transplantation, antibiotic treatment within the last 30 days, indwelling urinary catheter and recurrent UTI as risk factors for MDR or any of these resistances. For patients with no risk factors Ciprofloxacin had 90%, Pip/taz 88%, Gentamicin 95%, Cefuroxime 98%, Cefpodoxime 98% and Ceftazidime 100% susceptibility. For patients with 1 risk factor Ciprofloxacin had 80%, Pip/taz 80%, Gentamicin 88%, Cefuroxime 78%, Cefpodoxime 78% and Ceftazidime 83% susceptibility. For 2 or more risk factors Ciprofloxacin drops its susceptibility to 52%, Cefuroxime to 54% and Cefpodoxime to 61%. Pip/taz, Gentamicin and Ceftazidime remain at 75% and 77%, respectively. We identified several risk factors for resistances and MDR in UTI. Susceptibility towards antimicrobials depends on these risk factors. With no risk factor cephalosporins seem to be the best choice for empiric therapy, but in patients with risk factors the beta-lactam penicillin Piperacillin with Tazobactam is an equal or better choice compared to fluoroquinolones, cephalosporins or gentamicin. This study highlights the importance of monitoring local resistance rates and its risk factors in order to improve empiric therapy in a local environment.

  16. A Mendelian locus on chromosome 16 determines susceptibility to doxorubicin nephropathy in the mouse

    PubMed Central

    Zheng, Zongyu; Schmidt-Ott, Kai M.; Chua, Streamson; Foster, Kirk A.; Frankel, Rachelle Z.; Pavlidis, Paul; Barasch, Jonathan; D'Agati, Vivette D.; Gharavi, Ali G.

    2005-01-01

    The development of kidney disease is influenced by both genetic and environmental factors. Searching for models of glomerulopathy that display strong gene–environment interaction, we examined the determinants of anthracycline-induced nephropathy, a classic, strain-dependent experimental model applied to rodents in the past four decades. We produced three crosses derived from mice with contrasting susceptibility to doxorubicin (DOX) nephropathy and, surprisingly, we found that this widely studied model segregates as a single-gene defect with recessive inheritance. By genome-wide analysis of linkage, we mapped the trait locus to chromosome 16A1-B1 (DOXNPH locus) in all three crosses [peak logarithm of odds (lod) score of 92.7, P = 1 × 10-65]; this interval represents a susceptibility locus for nephropathy. Gene expression analysis indicated that susceptibility alleles at the DOXNPH locus are associated with blunted expression of protein arginine methyltransferase 7 (Prmt7) on chromosome 8, a protein previously implicated in cellular sensitivity to chemotherapeutic agents (lod = 12.4, P = 0.0001). Therefore, Prmt7 expression serves as a molecular marker for susceptibility to DOX nephropathy. Finally, increased variation in the severity of kidney disease among affected mice motivated a second genome-wide search, identifying a locus on chromosome 9 that influences the severity and progression of nephropathy (DOXmod, peak lod score 4.3, P = 0.0018). These data provide genetic and molecular characterization of a previously unrecognized Mendelian trait. Elucidation of DOX nephropathy may simultaneously provide insight into the pathogenesis of renal failure and mechanisms of cytotoxicity induced by chemotherapeutic agents. PMID:15699352

  17. A Mendelian locus on chromosome 16 determines susceptibility to doxorubicin nephropathy in the mouse.

    PubMed

    Zheng, Zongyu; Schmidt-Ott, Kai M; Chua, Streamson; Foster, Kirk A; Frankel, Rachelle Z; Pavlidis, Paul; Barasch, Jonathan; D'Agati, Vivette D; Gharavi, Ali G

    2005-02-15

    The development of kidney disease is influenced by both genetic and environmental factors. Searching for models of glomerulopathy that display strong gene-environment interaction, we examined the determinants of anthracycline-induced nephropathy, a classic, strain-dependent experimental model applied to rodents in the past four decades. We produced three crosses derived from mice with contrasting susceptibility to doxorubicin (DOX) nephropathy and, surprisingly, we found that this widely studied model segregates as a single-gene defect with recessive inheritance. By genome-wide analysis of linkage, we mapped the trait locus to chromosome 16A1-B1 (DOXNPH locus) in all three crosses [peak logarithm of odds (lod) score of 92.7, P = 1 x 10(-65)]; this interval represents a susceptibility locus for nephropathy. Gene expression analysis indicated that susceptibility alleles at the DOXNPH locus are associated with blunted expression of protein arginine methyltransferase 7 (Prmt7) on chromosome 8, a protein previously implicated in cellular sensitivity to chemotherapeutic agents (lod = 12.4, P = 0.0001). Therefore, Prmt7 expression serves as a molecular marker for susceptibility to DOX nephropathy. Finally, increased variation in the severity of kidney disease among affected mice motivated a second genome-wide search, identifying a locus on chromosome 9 that influences the severity and progression of nephropathy (DOXmod, peak lod score 4.3, P = 0.0018). These data provide genetic and molecular characterization of a previously unrecognized Mendelian trait. Elucidation of DOX nephropathy may simultaneously provide insight into the pathogenesis of renal failure and mechanisms of cytotoxicity induced by chemotherapeutic agents.

  18. Will inundation and salinity levels associated with projected sea level rise reduce the survival, growth, and reproductive capacity of Sarcocornia pacifica (pickleweed)?

    USGS Publications Warehouse

    Woo, I.; Takekawa, John Y.

    2012-01-01

    In the San Francisco Bay Estuary, CA, USA, sea level rise (SLR) is projected to increase by 1.4 m during the next 90 years resulting in increased inundation and salt water intrusion up-estuary. Since inundation and salinity are critical factors that drive vegetation structure and composition in coastal wetlands, we asked whether inundation and salinity levels associated with SLR would reduce the survival, growth, and reproductive capacity of a dominant halophyte, Sarcocornia pacifica (pickleweed). We conducted a 4 × 4 factorial greenhouse experiment to examine the effects of a range of inundation periods (25, 50, 75, and 100%) and water salinities (0, 10, 20, 30 psu) on individual S. pacifica adults and seedlings. We found that inundation and salinity treatments affected the height of adults and seedlings combined. When examined separately, adult height was negatively affected by inundation ≥75%, while seedling height was affected by the interaction of both inundation and salinity. Adult belowground biomass was negatively affected by complete inundation. Seedling aboveground biomass decreased 46% at the highest salinity (30 psu) and belowground biomass decreased at salinities ≥20 psu. Adult flower production was not affected by treatments but was reduced by 38% at 30 psu salinity for seedlings. While adult survival was 99%, seedling survival was 56% with greatest mortality at low (25%) inundation, possibly because their roots were more susceptible to desiccation. Vegetation structure of the marsh platform comprised of S. pacifica adults will be susceptible to greater inundation rates associated with SLR. Our results suggest that adults may grow less tall, thus altering the vegetation structure and likely the tidal marsh wildlife that rely on these habitats.

  19. The Vascular Pathogen Verticillium longisporum Does Not Affect Water Relations and Plant Responses to Drought Stress of Its Host, Brassica napus.

    PubMed

    Lopisso, Daniel Teshome; Knüfer, Jessica; Koopmann, Birger; von Tiedemann, Andreas

    2017-04-01

    Verticillium longisporum is a host-specific vascular pathogen of oilseed rape (Brassica napus L.) that causes economic crop losses by impairing plant growth and inducing premature senescence. This study investigates whether plant damage through Verticillium stem striping is due to impaired plant water relations, whether V. longisporum affects responses of a susceptible B. napus variety to drought stress, and whether drought stress, in turn, affects plant responses to V. longisporum. Two-factorial experiments on a susceptible cultivar of B. napus infected or noninfected with V. longisporum and exposed to three watering levels (30, 60, and 100% field capacity) revealed that drought stress and V. longisporum impaired plant growth by entirely different mechanisms. Although both stresses similarly affected plant growth parameters (plant height, hypocotyl diameter, and shoot and root dry matter), infection of B. napus with V. longisporum did not affect any drought-related physiological or molecular genetic plant parameters, including transpiration rate, stomatal conductance, photosynthesis rate, water use efficiency, relative leaf water content, leaf proline content, or the expression of drought-responsive genes. Thus, this study provides comprehensive physiological and molecular genetic evidence explaining the lack of wilt symptoms in B. napus infected with V. longisporum. Likewise, drought tolerance of B. napus was unaffected by V. longisporum, as was the level of disease by drought conditions, thus excluding a concerted action of both stresses in the field. Although it is evident that drought and vascular infection with V. longisporum impair plant growth by different mechanisms, it remains to be determined by which other factors V. longisporum causes crop loss.

  20. Negative Urgency Is Associated With Heightened Negative Affect and Urge During Tobacco Abstinence in Regular Smokers

    PubMed Central

    Park, Annie D.; Farrahi, Layla N.; Pang, Raina D.; Guillot, Casey R.; Aguirre, Claudia G.; Leventhal, Adam M.

    2016-01-01

    Objective: Negative urgency—the tendency to act rashly during negative affective states—is a risk factor for regular cigarette smoking. This human laboratory study tested a novel theoretical model of the underlying mechanisms linking negative urgency and smoking motivation, which purports that smokers with high negative urgency are at increased susceptibility to abstinence-induced increases in negative affect, which, in turn, provokes the urge to smoke to suppress negative affect. Method: Smokers (N = 180, >10 cigarettes/day) attended a baseline session at which they completed self-report measures of negative urgency and other co-factors and subsequently attended two counterbalanced within-subject experimental sessions (i.e., 16 hours of smoking abstinence or smoking as usual). At both experimental sessions, self-reported tobacco withdrawal symptoms, affect, and smoking urge were assessed. Results: Negative urgency was associated with larger abstinence-induced increases in tobacco withdrawal symptoms, negative affect, and urge to smoke to alleviate negative affect, both with and without controlling for anxiety, depression, tobacco dependence, and sensation seeking (βs > .18, ps < .05). The association between negative urgency and abstinence-induced increases in urge to smoke to alleviate negative affect was mediated by greater abstinence-induced increases in negative affect (βs > .062, ps = .01). Conclusions: These results provide initial support of this model by providing evidence that smokers with higher (vs. lower) negative urgency may be more prone to greater negative affect during withdrawal, which in turn may promote urge to smoke to suppress negative emotion. Research extending this model to other settings, measures, and methodological approaches may be fruitful. PMID:27588535

  1. Negative Urgency Is Associated With Heightened Negative Affect and Urge During Tobacco Abstinence in Regular Smokers.

    PubMed

    Park, Annie D; Farrahi, Layla N; Pang, Raina D; Guillot, Casey R; Aguirre, Claudia G; Leventhal, Adam M

    2016-09-01

    Negative urgency-the tendency to act rashly during negative affective states-is a risk factor for regular cigarette smoking. This human laboratory study tested a novel theoretical model of the underlying mechanisms linking negative urgency and smoking motivation, which purports that smokers with high negative urgency are at increased susceptibility to abstinence-induced increases in negative affect, which, in turn, provokes the urge to smoke to suppress negative affect. Smokers (N = 180, >10 cigarettes/day) attended a baseline session at which they completed self-report measures of negative urgency and other co-factors and subsequently attended two counterbalanced within-subject experimental sessions (i.e., 16 hours of smoking abstinence or smoking as usual). At both experimental sessions, self-reported tobacco withdrawal symptoms, affect, and smoking urge were assessed. Negative urgency was associated with larger abstinence-induced increases in tobacco withdrawal symptoms, negative affect, and urge to smoke to alleviate negative affect, both with and without controlling for anxiety, depression, tobacco dependence, and sensation seeking (βs > .18, ps < .05). The association between negative urgency and abstinence-induced increases in urge to smoke to alleviate negative affect was mediated by greater abstinence-induced increases in negative affect (βs > .062, ps = .01). These results provide initial support of this model by providing evidence that smokers with higher (vs. lower) negative urgency may be more prone to greater negative affect during withdrawal, which in turn may promote urge to smoke to suppress negative emotion. Research extending this model to other settings, measures, and methodological approaches may be fruitful.

  2. Temperature and population density: interactional effects of environmental factors on phenotypic plasticity, immune defenses, and disease resistance in an insect pest.

    PubMed

    Silva, Farley W S; Elliot, Simon L

    2016-06-01

    Temperature and crowding are key environmental factors mediating the transmission and epizooty of infectious disease in ectotherm animals. The host physiology may be altered in a temperature-dependent manner and thus affects the pathogen development and course of diseases within an individual and host population, or the transmission rates (or infectivity) of pathogens shift linearly with the host population density. To our understanding, the knowledge of interactive and synergistic effects of temperature and population density on the host-pathogen system is limited. Here, we tested the interactional effects of these environmental factors on phenotypic plasticity, immune defenses, and disease resistance in the velvetbean caterpillar Anticarsia gemmatalis . Upon egg hatching, caterpillars were reared in thermostat-controlled chambers in a 2 × 4 factorial design: density (1 or 8 caterpillars/pot) and temperature (20, 24, 28, or 32°C). Of the immune defenses assessed, encapsulation response was directly affected by none of the environmental factors; capsule melanization increased with temperature in both lone- and group-reared caterpillars, although the lone-reared ones presented the most evident response, and hemocyte numbers decreased with temperature regardless of the population density. Temperature, but not population density, affected considerably the time from inoculation to death of velvetbean caterpillar. Thus, velvetbean caterpillars succumbed to Anticarsia gemmatalis multiple nucleopolyhedrovirus (AgMNPV) more quickly at higher temperatures than at lower temperatures. As hypothesized, temperature likely affected caterpillars' movement rates, and thus the contact between conspecifics, which in turn affected the phenotypic expression of group-reared caterpillars. Our results suggest that environmental factors, mainly temperature, strongly affect both the course of disease in velvetbean caterpillar population and its defenses against pathogens. As a soybean pest, velvetbean caterpillar may increase its damage on soybean fields under a scenario of global warming as caterpillars may reach the developmental resistance faster, and thus decrease their susceptibility to biological control by AgMNPV.

  3. Environmental and Biological Factors Influencing Culex pipiens quinquefasciatus Say (Diptera: Culicidae) Vector Competence for Saint Louis Encephalitis Virus

    PubMed Central

    Richards, Stephanie L.; Lord, Cynthia C.; Pesko, Kendra; Tabachnick, Walter J.

    2009-01-01

    Complex interactions between environmental and biological factors influence the susceptibility of Culex pipiens quinquefasciatus to St. Louis encephalitis virus and could affect the epidemiology of virus transmission. Similar interactions could have epidemiologic implications for other vector-virus systems. We conducted an experiment to examine four such factors in combination: mosquito age, extrinsic incubation temperature (EIT), virus dose, and colony. The proportion of mosquitoes with body infections or disseminated infections varied between colonies, and was dependant on age, EIT, and dose. We also show that the probability of a body or leg infection interacted in complex ways between colonies, ages, EITs, and doses. The complex interactive effects of environmental and biological factors must be taken into account for studies of vector competence and epidemiology, especially when laboratory studies are used to generalize to natural transmission dynamics where the extent of variation is largely unknown. PMID:19635881

  4. Environmental and biological factors influencing Culex pipiens quinquefasciatus Say (Diptera: Culicidae) vector competence for Saint Louis encephalitis virus.

    PubMed

    Richards, Stephanie L; Lord, Cynthia C; Pesko, Kendra; Tabachnick, Walter J

    2009-08-01

    Complex interactions between environmental and biological factors influence the susceptibility of Culex pipiens quinquefasciatus to St. Louis encephalitis virus and could affect the epidemiology of virus transmission. Similar interactions could have epidemiologic implications for other vector-virus systems. We conducted an experiment to examine four such factors in combination: mosquito age, extrinsic incubation temperature (EIT), virus dose, and colony. The proportion of mosquitoes with body infections or disseminated infections varied between colonies, and was dependant on age, EIT, and dose. We also show that the probability of a body or leg infection interacted in complex ways between colonies, ages, EITs, and doses. The complex interactive effects of environmental and biological factors must be taken into account for studies of vector competence and epidemiology, especially when laboratory studies are used to generalize to natural transmission dynamics where the extent of variation is largely unknown.

  5. The influence of the social environment on youth smoking status.

    PubMed

    Bellatorre, Anna; Choi, Kelvin; Bernat, Debra

    2015-12-01

    Youth smoking is complex with multilevel influences. While much is known about certain levels of influence on youth smoking, the lack of focus on institutional influences is notable. This study evaluated the effects of ambient smoking attitudes and behaviors in schools on individual youth smoking. Data from the 2012 Florida Youth Tobacco Survey (n=67,460) were analyzed. Multinomial logistic regression was used to investigate individual and aggregated school-level factors that were associated with a youth being classified as a "susceptible nonsmoker" (SN) or "current smoker" (CS) relative to a "non-susceptible nonsmoker" (NN). The aggregated percentage of regular smokers at a school, ambient school level positive smoking perceptions, and the standardized difference between individual and school-level positive smoking perceptions were statistically significant in the fully adjusted model. We also found an increased risk of being a SN relative to a NN for Hispanic youth. Moreover, our approach to modeling institutional-level factors raised the pseudo r-squared from 0.05 to 0.14. These findings suggest the importance of ambient smoking attitudes and behaviors on youth smoking. Prevention efforts affecting ambient smoking attitudes may be beneficial. Published by Elsevier Inc.

  6. Cholinergic Basal Forebrain Lesion Decreases Neurotrophin Signaling without Affecting Tau Hyperphosphorylation in Genetically Susceptible Mice.

    PubMed

    Turnbull, Marion T; Coulson, Elizabeth J

    2017-01-01

    Alzheimer's disease (AD) is a progressive, irreversible neurodegenerative disease that destroys memory and cognitive function. Aggregates of hyperphosphorylated tau protein are a prominent feature in the brain of patients with AD, and are a major contributor to neuronal toxicity and disease progression. However, the factors that initiate the toxic cascade that results in tau hyperphosphorylation in sporadic AD are unknown. Here we investigated whether degeneration of basal forebrain cholinergic neurons (BFCNs) and/or a resultant decrease in neurotrophin signaling cause aberrant tau hyperphosphorylation. Our results reveal that the loss of BFCNs in pre-symptomatic pR5 (P301L) tau transgenic mice results in a decrease in hippocampal brain-derived neurotrophic factor levels and reduced TrkB receptor activation. However, there was no exacerbation of the levels of phosphorylated tau or its aggregation in the hippocampus of susceptible mice. Furthermore the animals' performance in a hippocampal-dependent learning and memory task was unaltered, and no changes in hippocampal synaptic markers were observed. This suggests that tau pathology is likely to be regulated independently of BFCN degeneration and the corresponding decrease in hippocampal neurotrophin levels, although these features may still contribute to disease etiology.

  7. Susceptibility to exertional heat illness and hospitalisation risk in UK military personnel

    PubMed Central

    Stacey, Michael J; Parsons, Iain T; Woods, David R; Taylor, Peter N; Ross, David; J Brett, Stephen

    2015-01-01

    Background Susceptibility to exertional heat illness (EHI) is considered multifactorial in nature. The aims of this study were to (1) review traditional susceptibility factors identified in cases of EHI and (2) determine how they are related to risk of hospitalisation. Methods Review of an electronic database of EHI reported in the British Army between 1 September 2007 and 31 December 2014. Cases were categorised by demographic, situational and susceptibility variables. Univariate and multivariate logistic regression was performed for the OR for hospitalisation by risk factor. Results 361 reports were included in the analysis. 33.5% of cases occurred in hot climates, 34.6% in temperate climates during summer months and 31.9% in temperate climates outside of summer months. Traditional susceptibility factors were reported in 193 but entirely absent from 168 cases. 137 cases (38.0%) were admitted to hospital. Adjusted OR for hospitalisation was lower for recruits (OR 0.42, 95% CI 0.18 to 0.99, p<0.05) and for personnel wearing occlusive dress (OR 0.56, 95% CI 0.34 to 0.93, p<0.05) or unacclimatised to heat (OR 0.31, 95% CI 0.15 to 0.66, p<0.01). Conclusions The global, year-round threat of EHI is highlighted. Absence of susceptibility factors in nearly half of reports highlights the challenge of identifying EHI-prone individuals. Paradoxical association of traditional susceptibility factors with reduced hospitalisation risk may reflect the contemporary contexts in which severe EHI occurs. These findings also suggest a need for better evidence to inform guidelines that aim to prevent severe EHI concurrent to reducing overall morbidity. PMID:27900138

  8. NIEHS/EPA CEHCs: Center for Child Environmental Health Risks Research - University of Washington

    EPA Pesticide Factsheets

    This center aims to understand why some children are more susceptible than others to the harmful effects of pesticides and are trying to identify how this susceptibility affects growth, development and learning.

  9. Potential of 3D City Models to assess flood vulnerability

    NASA Astrophysics Data System (ADS)

    Schröter, Kai; Bochow, Mathias; Schüttig, Martin; Nagel, Claus; Ross, Lutz; Kreibich, Heidi

    2016-04-01

    Vulnerability, as the product of exposure and susceptibility, is a key factor of the flood risk equation. Furthermore, the estimation of flood loss is very sensitive to the choice of the vulnerability model. Still, in contrast to elaborate hazard simulations, vulnerability is often considered in a simplified manner concerning the spatial resolution and geo-location of exposed objects as well as the susceptibility of these objects at risk. Usually, area specific potential flood loss is quantified on the level of aggregated land-use classes, and both hazard intensity and resistance characteristics of affected objects are represented in highly simplified terms. We investigate the potential of 3D City Models and spatial features derived from remote sensing data to improve the differentiation of vulnerability in flood risk assessment. 3D City Models are based on CityGML, an application scheme of the Geography Markup Language (GML), which represents the 3D geometry, 3D topology, semantics and appearance of objects on different levels of detail. As such, 3D City Models offer detailed spatial information which is useful to describe the exposure and to characterize the susceptibility of residential buildings at risk. This information is further consolidated with spatial features of the building stock derived from remote sensing data. Using this database a spatially detailed flood vulnerability model is developed by means of data-mining. Empirical flood damage data are used to derive and to validate flood susceptibility models for individual objects. We present first results from a prototype application in the city of Dresden, Germany. The vulnerability modeling based on 3D City Models and remote sensing data is compared i) to the generally accepted good engineering practice based on area specific loss potential and ii) to a highly detailed representation of flood vulnerability based on a building typology using urban structure types. Comparisons are drawn in terms of affected building area and estimated loss for a selection of inundation scenarios.

  10. Susceptibility of ground water to surface and shallow sources of contamination, Orange County, North Carolina

    USGS Publications Warehouse

    Terziotti, Silvia; Eimers, J.L.

    1999-01-01

    In 1998, the relative susceptibility of ground water in Orange County, North Carolina,to contamination from surface and shallow sources was evaluated. A geographic information system was used to build three county-wide layers--soil permeability, land use/land cover, and land-surface slope. The harmonic mean permeability of soil layers was used to estimate a location's capacity to transmit water through the soil. Values for each of these three factors were categorized and ranked from 1 to 10 according to relative potential for contamination. Each factor was weighted to reflect its relative potential contribution to ground-water contamination, then the factors were combined to create a relative susceptibility index. The relative susceptibility index was categorized to reflect lowest, low, moderate, high, and highest potential for ground-water contamination. The relative susceptibility index for about 12 percent of the area in Orange County was categorized as high or highest. The high and highest range areas have highly permeable soils, land cover or land-use activities that have a high contamination potential, and low to moderate slopes. Most of the county is within the moderate category of relative susceptibility to ground-water contamination. About 21 percent of the county is ranked as low or lowest relative susceptibility to ground-water contamination.

  11. The epidemic of Tuberculosis on vaccinated population

    NASA Astrophysics Data System (ADS)

    Syahrini, Intan; Sriwahyuni; Halfiani, Vera; Meurah Yuni, Syarifah; Iskandar, Taufiq; Rasudin; Ramli, Marwan

    2017-09-01

    Tuberculosis is an infectious disease which has caused a large number of mortality in Indonesia. This disease is caused by Mycrobacterium tuberculosis. Besides affecting lung, this disease also affects other organs such as lymph gland, intestine, kidneys, uterus, bone, and brain. This article discusses the epidemic of tuberculosis through employing the SEIR model. Here, the population is divided into four compartments which are susceptible, exposed, infected and recovered. The susceptible population is further grouped into two which are vaccinated group and unvaccinated group. The behavior of the epidemic is investigated through analysing the equilibrium of the model. The result shows that administering vaccine to the susceptible population contributes to the reduction of the tuberculosis epidemic rate.

  12. Spatial analysis for susceptibility of second-time karst sinkholes: A case study of Jili Village in Guangxi, China

    NASA Astrophysics Data System (ADS)

    Zhou, Guoqing; Yan, Hongbo; Chen, Kunhua; Zhang, Rongting

    2016-04-01

    After a big karst sinkhole happened in Jili Village of Guangxi, China, the local government was eager to quantitatively analyze and map susceptible areas of the potential second-time karst sinkholes in order to make timely decisions whether the residents living in the first-time sinkhole areas should move. For this reason, karst sinkholes susceptibility geospatial analysis is investigated using multivariate spatial data, logistic regression model (LRM) and Geographical Information System (GIS). Ten major karst sinkholes related factors, including (1) formation lithology, (2) soil structure, (3) profile curvature, (4) groundwater depth, (5) fluctuation of groundwater level, (6) percolation rate of soil, (7) degree of karst development, (8) distance from fault, (9) distance from the traffic route, and (10) overburden thickness were selected, and then each of factors was classified and quantitated with the three or four levels. The LRM was applied to evaluate which factor makes significant contributions to sinkhole. The results demonstrated that formation lithology, soil structure, profile curvature, groundwater depth, ground water level, percolation rate of soil, and degree of karst development, the distance from fault, and overburden thickness are positive, while one factor, the distance from traffic routes is negative, which is deleted from LRM model. The susceptibility of the potential sinkholes in the study area is estimated and mapped using the solved impact factors. The susceptible degrees of the study area are classified into five levels, very high, high, moderate, low, and ignore susceptibility. It has been found that that both very high and high susceptibility areas are along Datou Hill and the foothills of the study area. This finding is verified by field observations. With the investigations conducted in this paper, it can be concluded that the susceptibility maps produced in this paper are reliable and accurate, and useful as a reference for local governments to make decisions regarding whether or not residents living within sinkhole areas should move.

  13. Threat processing in generalized social phobia: an investigation of interpretation biases in ambiguous facial affect.

    PubMed

    Jusyte, Aiste; Schönenberg, Michael

    2014-06-30

    Facial affect is one of the most important information sources during the course of social interactions, but it is susceptible to distortion due to the complex and dynamic nature. Socially anxious individuals have been shown to exhibit alterations in the processing of social information, such as an attentional and interpretative bias toward threatening information. This may be one of the key factors contributing to the development and maintenance of anxious psychopathology. The aim of the current study was to investigate whether a threat-related interpretation bias is evident for ambiguous facial stimuli in a population of individuals with a generalized Social Anxiety Disorder (gSAD) as compared to healthy controls. Participants judged ambiguous happy/fearful, angry/fearful and angry/happy blends varying in intensity and rated the predominant affective expression. The results obtained in this study do not indicate that gSAD is associated with a biased interpretation of ambiguous facial affect. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Susceptibility to Classmates' Influence on Delinquency during Early Adolescence

    ERIC Educational Resources Information Center

    Müller, Christoph M.; Hofmann, Verena; Arm, Sybille

    2017-01-01

    Early adolescents vary in their susceptibility to peer influence on delinquency. However, it is still less clear which factors explain this variation and how these factors relate to each other. In this study, 10 factors that may moderate peer influence were investigated. A sample of 868 participants was followed across six occasions from seventh…

  15. Mathematical Model for Dengue Epidemics with Differential Susceptibility and Asymptomatic Patients Using Computer Algebra

    NASA Astrophysics Data System (ADS)

    Saldarriaga Vargas, Clarita

    When there are diseases affecting large populations where the social, economic and cultural diversity is significant within the same region, the biological parameters that determine the behavior of the dispersion disease analysis are affected by the selection of different individuals. Therefore and because of the variety and magnitude of the communities at risk of contracting dengue disease around all over the world, suggest defining differentiated populations with individual contributions in the results of the dispersion dengue disease analysis. In this paper those conditions were taken in account when several epidemiologic models were analyzed. Initially a stability analysis was done for a SEIR mathematical model of Dengue disease without differential susceptibility. Both free disease and endemic equilibrium states were found in terms of the basic reproduction number and were defined in the Theorem (3.1). Then a DSEIR model was solved when a new susceptible group was introduced to consider the effects of important biological parameters of non-homogeneous populations in the spreading analysis. The results were compiled in the Theorem (3.2). Finally Theorems (3.3) and (3.4) resumed the basic reproduction numbers for three and n different susceptible groups respectively, giving an idea of how differential susceptibility affects the equilibrium states. The computations were done using an algorithmic method implemented in Maple 11, a general-purpose computer algebra system.

  16. Phenotype overlap in Xylella fastidiosa is controlled by the cyclic di-GMP phosphodiesterase Eal in response to antibiotic exposure and diffusible signal factor-mediated cell-cell signaling.

    PubMed

    de Souza, Alessandra A; Ionescu, Michael; Baccari, Clelia; da Silva, Aline M; Lindow, Steven E

    2013-06-01

    Eal is an EAL domain protein in Xylella fastidiosa homologous to one involved in resistance to tobramycin in Pseudomonas aeruginosa. EAL and HD-GYP domain proteins are implicated in the hydrolysis of the secondary messenger bis-(3'-5')-cyclic dimeric GMP (cyclic di-GMP). Cell density-dependent communication mediated by a Diffusible Signal Factor (DSF) also modulates cyclic di-GMP levels in X. fastidiosa, thereby controlling the expression of virulence genes and genes involved in insect transmission. The possible linkage of Eal to both extrinsic factors such as antibiotics and intrinsic factors such as quorum sensing, and whether both affect virulence, was thus addressed. Expression of eal was induced by subinhibitory concentrations of tobramycin, and an eal deletion mutant was more susceptible to this antibiotic than the wild-type strain and exhibited phenotypes similar to those of an rpfF deletion mutant blocked in DSF production, such as hypermotility, reduced biofilm formation, and hypervirulence to grape. Consistent with that, the rpfF mutant was more susceptible than the wild-type strain to tobramycin. Therefore, we propose that cell-cell communication and antibiotic stress can apparently lead to similar modulations of cyclic di-GMP in X. fastidiosa, resulting in similar phenotypes. However, the effect of cell density is dominant compared to that of antibiotic stress, since eal is suppressed by RpfF, which may prevent inappropriate behavioral changes in response to antibiotic stress when DSF accumulates.

  17. Antimicrobial susceptibility of Histophilus somni isolated from clinically affected cattle in Australia.

    PubMed

    Goldspink, Lauren K; Mollinger, Joanne L; Barnes, Tamsin S; Groves, Mitchell; Mahony, Timothy J; Gibson, Justine S

    2015-02-01

    This study investigated antimicrobial resistance traits, clonal relationships and epidemiology of Histophilus somni isolated from clinically affected cattle in Queensland and New South Wales, Australia. Isolates (n = 53) were subjected to antimicrobial susceptibility testing against six antimicrobial agents (ceftiofur, enrofloxacin, florfenicol, tetracycline, tilmicosin and tulathromycin) using disc diffusion and minimum inhibitory concentration (MIC) assays. Clonal relationships were assessed using repetitive sequence PCR and descriptive epidemiological analysis was performed. The H. somni isolates appeared to be geographically clonal, with 27/53 (47%) isolates grouping in one cluster from one Australian state. On the basis of disc diffusion, 34/53 (64%) isolates were susceptible to all antimicrobial agents tested; there was intermediate susceptibility to tulathromycin in 12 isolates, tilmicosin in seven isolates and resistance to tilmicosin in one isolate. Using MIC, all but one isolate was susceptible to all antimicrobial agents tested; the non-susceptible isolate was resistant to tetracycline, but this MIC result could not be compared to disc diffusion, since there are no interpretative guidelines for disc diffusion for H. somni against tetracycline. In this study, there was little evidence of antimicrobial resistance in H. somni isolates from Australian cattle. Disc diffusion susceptibility testing results were comparable to MIC results for most antimicrobial agents tested; however, results for isolates with intermediate susceptibility or resistance to tilmicosin and tulathromycin on disc diffusion should be interpreted with caution in the absence of MIC results. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Animal Viruses, Bacteria, and Cancer: A Brief Commentary

    PubMed Central

    Efird, Jimmy T.; Davies, Stephen W.; O’Neal, Wesley T.; Anderson, Ethan J.

    2014-01-01

    Animal viruses and bacteria are ubiquitous in the environment. However, little is known about their mode of transmission and etiologic role in human cancers, especially among high-risk groups (e.g., farmers, veterinarians, poultry plant workers, pet owners, and infants). Many factors may affect the survival, transmissibility, and carcinogenicity of these agents, depending on the animal-host environment, hygiene practices, climate, travel, herd immunity, and cultural differences in food consumption and preparation. Seasonal variations in immune function also may increase host susceptibility at certain times of the year. The lack of objective measures, inconsistent study designs, and sources of epidemiologic bias (e.g., residual confounding, recall bias, and non-randomized patient selection) are some of the factors that complicate a clear understanding of this subject. PMID:24592380

  19. On post-weld heat treatment cracking in tig welded superalloy ATI 718Plus

    NASA Astrophysics Data System (ADS)

    Asala, G.; Ojo, O. A.

    The susceptibility of heat affected zone (HAZ) to cracking in Tungsten Inert Gas (TIG) welded Allvac 718Plus superalloy during post-weld heat treatment (PWHT) was studied. Contrary to the previously reported case of low heat input electron beam welded Allvac 718Plus, where HAZ cracking occurred during PWHT, the TIG welded alloy is crack-free after PWHT, notwithstanding the presence of similar micro-constituents that caused cracking in the low input weld. Accordingly, the formation of brittle HAZ intergranular micro-constituents may not be a sufficient factor to determine cracking propensity, the extent of heat input during welding may be another major factor that influences HAZ cracking during PWHT of the aerospace superalloy Allvac 718Plus.

  20. Landslide Susceptibility Assessment Using Spatial Multi-Criteria Evaluation Model in Rwanda.

    PubMed

    Nsengiyumva, Jean Baptiste; Luo, Geping; Nahayo, Lamek; Huang, Xiaotao; Cai, Peng

    2018-01-31

    Landslides susceptibility assessment has to be conducted to identify prone areas and guide risk management. Landslides in Rwanda are very deadly disasters. The current research aimed to conduct landslide susceptibility assessment by applying Spatial Multi-Criteria Evaluation Model with eight layers of causal factors including: slope, distance to roads, lithology, precipitation, soil texture, soil depth, altitude and land cover. In total, 980 past landslide locations were mapped. The relationship between landslide factors and inventory map was calculated using the Spatial Multi-Criteria Evaluation. The results revealed that susceptibility is spatially distributed countrywide with 42.3% of the region classified from moderate to very high susceptibility, and this is inhabited by 49.3% of the total population. In addition, Provinces with high to very high susceptibility are West, North and South (40.4%, 22.8% and 21.5%, respectively). Subsequently, the Eastern Province becomes the peak under low susceptibility category (87.8%) with no very high susceptibility (0%). Based on these findings, the employed model produced accurate and reliable outcome in terms of susceptibility, since 49.5% of past landslides fell within the very high susceptibility category, which confirms the model's performance. The outcomes of this study will be useful for future initiatives related to landslide risk reduction and management.

  1. Manifestation of a neuro-fuzzy model to produce landslide susceptibility map using remote sensing data derived parameters

    NASA Astrophysics Data System (ADS)

    Pradhan, Biswajeet; Lee, Saro; Buchroithner, Manfred

    Landslides are the most common natural hazards in Malaysia. Preparation of landslide suscep-tibility maps is important for engineering geologists and geomorphologists. However, due to complex nature of landslides, producing a reliable susceptibility map is not easy. In this study, a new attempt is tried to produce landslide susceptibility map of a part of Cameron Valley of Malaysia. This paper develops an adaptive neuro-fuzzy inference system (ANFIS) based on a geographic information system (GIS) environment for landslide susceptibility mapping. To ob-tain the neuro-fuzzy relations for producing the landslide susceptibility map, landslide locations were identified from interpretation of aerial photographs and high resolution satellite images, field surveys and historical inventory reports. Landslide conditioning factors such as slope, plan curvature, distance to drainage lines, soil texture, lithology, and distance to lineament were extracted from topographic, soil, and lineament maps. Landslide susceptible areas were analyzed by the ANFIS model and mapped using the conditioning factors. Furthermore, we applied various membership functions (MFs) and fuzzy relations to produce landslide suscep-tibility maps. The prediction performance of the susceptibility map is checked by considering actual landslides in the study area. Results show that, triangular, trapezoidal, and polynomial MFs were the best individual MFs for modelling landslide susceptibility maps (86

  2. Landslide Susceptibility Assessment Using Spatial Multi-Criteria Evaluation Model in Rwanda

    PubMed Central

    Nsengiyumva, Jean Baptiste; Luo, Geping; Nahayo, Lamek; Huang, Xiaotao; Cai, Peng

    2018-01-01

    Landslides susceptibility assessment has to be conducted to identify prone areas and guide risk management. Landslides in Rwanda are very deadly disasters. The current research aimed to conduct landslide susceptibility assessment by applying Spatial Multi-Criteria Evaluation Model with eight layers of causal factors including: slope, distance to roads, lithology, precipitation, soil texture, soil depth, altitude and land cover. In total, 980 past landslide locations were mapped. The relationship between landslide factors and inventory map was calculated using the Spatial Multi-Criteria Evaluation. The results revealed that susceptibility is spatially distributed countrywide with 42.3% of the region classified from moderate to very high susceptibility, and this is inhabited by 49.3% of the total population. In addition, Provinces with high to very high susceptibility are West, North and South (40.4%, 22.8% and 21.5%, respectively). Subsequently, the Eastern Province becomes the peak under low susceptibility category (87.8%) with no very high susceptibility (0%). Based on these findings, the employed model produced accurate and reliable outcome in terms of susceptibility, since 49.5% of past landslides fell within the very high susceptibility category, which confirms the model’s performance. The outcomes of this study will be useful for future initiatives related to landslide risk reduction and management. PMID:29385096

  3. Anopheles sinensis mosquito insecticide resistance: comparison of three mosquito sample collection and preparation methods and mosquito age in resistance measurements.

    PubMed

    Xu, Tielong; Zhong, Daibin; Tang, Linhua; Chang, Xuelian; Fu, Fengyang; Yan, Guiyun; Zheng, Bin

    2014-01-28

    Insecticide resistance monitoring in malaria mosquitoes is essential for guiding the rational use of insecticides in vector control programs. Resistance bioassay is the first step for insecticide monitoring and it lays an important foundation for molecular examination of resistance mechanisms. In the literature, various mosquito sample collection and preparation methods have been used, but how mosquito sample collection and preparation methods affect insecticide susceptibility bioassay results is largely unknown. The objectives of this study were to determine whether mosquito sample collection and preparation methods affected bioassay results, which may cause incorrect classification of mosquito resistance status. The study was conducted in Anopheles sinensis mosquitoes in two study sites in central China. Three mosquito sample collection and preparation methods were compared for insecticide susceptibility, kdr frequencies and metabolic enzyme activities: 1) adult mosquitoes collected from the field; 2) F1 adults from field collected, blood-fed mosquitoes; and 3) adult mosquitoes reared from field collected larvae. Mosquito sample collection and preparation methods significantly affected mortality rates in the standard WHO tube resistance bioassay. Mortality rate of field-collected female adults was 10-15% higher than in mosquitoes reared from field-collected larvae and F1 adults from field collected blood-fed females. This pattern was consistent in mosquitoes from the two study sites. High kdr mutation frequency (85-95%) with L1014F allele as the predominant mutation was found in our study populations. Field-collected female adults consistently exhibited the highest monooxygenase and GST activities. The higher mortality rate observed in the field-collected female mosquitoes may have been caused by a mixture of mosquitoes of different ages, as older mosquitoes were more susceptible to deltamethrin than younger mosquitoes. Female adults reared from field-collected larvae in resistance bioassays are recommended to minimize the effect of confounding factors such as mosquito age and blood feeding status so that more reliable and reproducible mortality may be obtained.

  4. Planning of geological investigations in areas affected by anthropogenic sinkholes: the case of densely urbanised area northeast of Naples (Italy)

    NASA Astrophysics Data System (ADS)

    Guarino, Paolo Maria; Santo, Antonio

    2013-04-01

    In the last years, many studies about sinkholes have been produced. These sudden phenomena can be generated from natural or artificial causes: the first ones are developed in soluble rocks like carbonate or sulphates, the second are linked to the presence of artificial caves or mines. In Italy both the typologies are widely present, but more often the anthropogenic sinkholes are cause of most damages and fatalities, because many ancient city center were built using the local rock, giving rise to complex and widespread networks of underground cavities, whose collapse brings about the formation of sinkholes. Examples are the Lazio, Toscana, Umbria, Campania, Puglia and Sicily regions, where important towns like Rome, Naples and Palermo are frequently affected by sinkholes. Identifying and analyzing natural and anthropogenic predisposing and triggering factors are essential steps for evaluating susceptibility to sinkholes; nevertheless, the susceptibility zoning must be considered the starting point towards further detailed studies. This study aims to provide a contribution to the definition of a more accurate planning of geological studies at the municipality scale, in order to mitigate the risk in densely urbanized areas affected by anthropogenic sinkholes. The considered study area includes the metropolitan area northeast of Naples (Italy), where sinkholes are very frequent because of the widespread presence of artificial caves dug in pyroclastic rocks. In a first phase, data and information relative to stratigraphic logs, presence and distribution of cavities and sinkholes phenomena were collected and organized in a GIS associated database. Thereafter, the processing of contour maps of tuff top surface and caves depth has been realized, as well as fully detailed cross sections, in order to recognize different characteristics and genesis of sinkholes. At the end, with reference to high susceptibility areas, a list of possible geological surveys and monitoring systems as well early warning activities were reported in order to mitigate the risk.

  5. Fetal alcohol exposure and mammary tumorigenesis in offspring: role of the estrogen and insulin-like growth factor systems.

    PubMed

    Cohick, Wendie S; Crismale-Gann, Catina; Stires, Hillary; Katz, Tiffany A

    2015-01-01

    Fetal alcohol spectrum disorders affect a significant number of live births each year, indicating that alcohol consumption during pregnancy is an important public health issue. Environmental exposures and lifestyle choices during pregnancy may affect the offspring's risk of disease in adulthood, leading to the idea that a woman's risk of breast cancer may be pre-programmed prior to birth. Exposure of pregnant rats to alcohol increases tumorigenesis in the adult offspring in response to mammary carcinogens. The estrogen and insulin-like growth factor (IGF-I) axes occupy central roles in normal mammary gland development and breast cancer. 17-β estradiol (E2) and IGF-I synergize to regulate formation of terminal end buds and ductal elongation during pubertal development. The intracellular signaling pathways mediated by the estrogen and IGF-I receptors cross-talk at multiple levels through both genomic and non-genomic mechanisms. Several components of the E2 and IGF-I systems are altered in early development in rat offspring exposed to alcohol in utero, therefore, these changes may play a role in the enhanced susceptibility to mammary carcinogens observed in adulthood. Alcohol exposure in utero induces a number of epigenetic alterations in non-mammary tissues in the offspring and other adverse in utero exposures induce epigenetic modifications in the mammary gland. Future studies will determine if fetal alcohol exposure can induce epigenetic modifications in genes that regulate E2/IGF action at key phases of mammary development, ultimately leading to changes in susceptibility to carcinogens.

  6. Landslides susceptibility change over time according to terrain conditions in a mountain area of the tropic region.

    PubMed

    Pineda, M C; Viloria, J; Martínez-Casasnovas, J A

    2016-04-01

    Susceptibility to landslides in mountain areas results from the interaction of various factors related to relief formation and soil development. The assessment of landslide susceptibility has generally taken into account individual events, or it has been aimed at establishing relationships between landslide-inventory maps and maps of environmental factors, without considering that such relationships can change in space and time. In this work, temporal and space changes in landslides were analysed in six different combinations of date and geomorphological conditions, including two different geological units, in a mountainous area in the north-centre of Venezuela, in northern South America. Landslide inventories from different years were compared with a number of environmental factors by means of logistic regression analysis. The resulting equations predicted landslide susceptibility from a range of geomorphometric parameters and a vegetation index, with diverse accuracy, in the study area. The variation of the obtained models and their prediction accuracy between geological units and dates suggests that the complexity of the landslide processes and their explanatory factors changed over space and time in the studied area. This calls into question the use of a single model to evaluate landslide susceptibility over large regions.

  7. PTGER4 Expression-Modulating Polymorphisms in the 5p13.1 Region Predispose to Crohn's Disease and Affect NF-κB and XBP1 Binding Sites

    PubMed Central

    Czamara, Darina; Pasciuto, Giulia; Diegelmann, Julia; Wetzke, Martin; Olszak, Torsten; Wolf, Christiane; Müller-Myhsok, Bertram; Balschun, Tobias; Achkar, Jean-Paul; Kamboh, M. Ilyas; Franke, Andre; Duerr, Richard H.; Brand, Stephan

    2012-01-01

    Background Genome-wide association studies identified a PTGER4 expression-modulating region on chromosome 5p13.1 as Crohn's disease (CD) susceptibility region. The study aim was to test this association in a large cohort of patients with inflammatory bowel disease (IBD) and to elucidate genotypic and phenotypic interactions with other IBD genes. Methodology/Principal Findings A total of 7073 patients and controls were genotyped: 844 CD and 471 patients with ulcerative colitis and 1488 controls were analyzed for the single nucleotide polymorphisms (SNPs) rs4495224 and rs7720838 on chromosome 5p13.1. The study included two replication cohorts of North American (CD: n = 684; controls: n = 1440) and of German origin (CD: n = 1098; controls: n = 1048). Genotype-phenotype, epistasis and transcription factor binding analyses were performed. In the discovery cohort, an association of rs4495224 (p = 4.10×10−5; 0.76 [0.67–0.87]) and of rs7720838 (p = 6.91×10−4; 0.81 [0.71–0.91]) with susceptibility to CD was demonstrated. These associations were confirmed in both replication cohorts. In silico analysis predicted rs4495224 and rs7720838 as essential parts of binding sites for the transcription factors NF-κB and XBP1 with higher binding scores for carriers of the CD risk alleles, providing an explanation of how these SNPs might contribute to increased PTGER4 expression. There was no association of the PTGER4 SNPs with IBD phenotypes. Epistasis detected between 5p13.1 and ATG16L1 for CD susceptibility in the discovery cohort (p = 5.99×10−7 for rs7720838 and rs2241880) could not be replicated in both replication cohorts arguing against a major role of this gene-gene interaction in the susceptibility to CD. Conclusions/Significance We confirmed 5p13.1 as a major CD susceptibility locus and demonstrate by in silico analysis rs4495224 and rs7720838 as part of binding sites for NF-κB and XBP1. Further functional studies are necessary to confirm the results of our in silico analysis and to analyze if changes in PTGER4 expression modulate CD susceptibility. PMID:23300802

  8. PTGER4 expression-modulating polymorphisms in the 5p13.1 region predispose to Crohn's disease and affect NF-κB and XBP1 binding sites.

    PubMed

    Glas, Jürgen; Seiderer, Julia; Czamara, Darina; Pasciuto, Giulia; Diegelmann, Julia; Wetzke, Martin; Olszak, Torsten; Wolf, Christiane; Müller-Myhsok, Bertram; Balschun, Tobias; Achkar, Jean-Paul; Kamboh, M Ilyas; Franke, Andre; Duerr, Richard H; Brand, Stephan

    2012-01-01

    Genome-wide association studies identified a PTGER4 expression-modulating region on chromosome 5p13.1 as Crohn's disease (CD) susceptibility region. The study aim was to test this association in a large cohort of patients with inflammatory bowel disease (IBD) and to elucidate genotypic and phenotypic interactions with other IBD genes. A total of 7073 patients and controls were genotyped: 844 CD and 471 patients with ulcerative colitis and 1488 controls were analyzed for the single nucleotide polymorphisms (SNPs) rs4495224 and rs7720838 on chromosome 5p13.1. The study included two replication cohorts of North American (CD: n = 684; controls: n = 1440) and of German origin (CD: n = 1098; controls: n = 1048). Genotype-phenotype, epistasis and transcription factor binding analyses were performed. In the discovery cohort, an association of rs4495224 (p = 4.10×10⁻⁵; 0.76 [0.67-0.87]) and of rs7720838 (p = 6.91×10⁻⁴; 0.81 [0.71-0.91]) with susceptibility to CD was demonstrated. These associations were confirmed in both replication cohorts. In silico analysis predicted rs4495224 and rs7720838 as essential parts of binding sites for the transcription factors NF-κB and XBP1 with higher binding scores for carriers of the CD risk alleles, providing an explanation of how these SNPs might contribute to increased PTGER4 expression. There was no association of the PTGER4 SNPs with IBD phenotypes. Epistasis detected between 5p13.1 and ATG16L1 for CD susceptibility in the discovery cohort (p = 5.99×10⁻⁷ for rs7720838 and rs2241880) could not be replicated in both replication cohorts arguing against a major role of this gene-gene interaction in the susceptibility to CD. We confirmed 5p13.1 as a major CD susceptibility locus and demonstrate by in silico analysis rs4495224 and rs7720838 as part of binding sites for NF-κB and XBP1. Further functional studies are necessary to confirm the results of our in silico analysis and to analyze if changes in PTGER4 expression modulate CD susceptibility.

  9. Is susceptibility to tuberculosis acquired or inherited?

    PubMed

    Schurr, E

    2007-02-01

    Tuberculosis is an ongoing major public health problem on a global scale. One of the striking features of the disease is that only an estimated 10% of immunocompetent persons infected by the causative pathogen Mycobacterium tuberculosis will develop clinical signs of disease. This well-established epidemiological observation has prompted an intense search for the factors that trigger advancement of infection to disease in the small proportion of susceptible individuals. Central to this search is the questions if tuberculosis patients are inherently susceptible to the disease or if disease development is promoted by specific environmental factors. It is known that genetic and non-genetic factors of both the bacterium and the host have impact on the host response to M. tuberculosis. Yet, little is known about the interaction of these different factors and the resulting impact on disease development. Recent work suggests that in addition to common host susceptibility genes a second group of susceptibility loci exists the action of which strongly depends on the individual's clinical and exposure history. The latter genes may have a very strong effect on promoting advancement from infection to disease only in specific epidemiological settings. These findings suggest that a more detailed knowledge of gene-environment interactions in tuberculosis is necessary to understand why a small proportion of individuals are susceptible to the disease whilst the majority of humans are naturally resistant to tuberculosis.

  10. Differential Response of Coral Assemblages to Thermal Stress Underscores the Complexity in Predicting Bleaching Susceptibility.

    PubMed

    Chou, Loke Ming; Toh, Tai Chong; Toh, Kok Ben; Ng, Chin Soon Lionel; Cabaitan, Patrick; Tun, Karenne; Goh, Eugene; Afiq-Rosli, Lutfi; Taira, Daisuke; Du, Rosa Celia Poquita; Loke, Hai Xin; Khalis, Aizat; Li, Jinghan; Song, Tiancheng

    2016-01-01

    Coral bleaching events have been predicted to occur more frequently in the coming decades with global warming. The susceptibility of corals to bleaching during thermal stress episodes is dependent on many factors and an understanding of these underlying drivers is crucial for conservation management. In 2013, a mild bleaching episode ensued in response to elevated sea temperature on the sediment-burdened reefs in Singapore. Surveys of seven sites highlighted variable bleaching susceptibility among coral genera-Pachyseris and Podabacia were the most impacted (31% of colonies of both genera bleached). The most susceptible genera such as Acropora and Pocillopora, which were expected to bleach, did not. Susceptibility varied between less than 6% and more than 11% of the corals bleached, at four and three sites respectively. Analysis of four of the most bleached genera revealed that a statistical model that included a combination of the factors (genus, colony size and site) provided a better explanation of the observed bleaching patterns than any single factor alone. This underscored the complexity in predicting the coral susceptibility to future thermal stress events and the importance of monitoring coral bleaching episodes to facilitate more effective management of coral reefs under climate change.

  11. Differential Response of Coral Assemblages to Thermal Stress Underscores the Complexity in Predicting Bleaching Susceptibility

    PubMed Central

    Toh, Kok Ben; Ng, Chin Soon Lionel; Cabaitan, Patrick; Tun, Karenne; Goh, Eugene; Afiq-Rosli, Lutfi; Taira, Daisuke; Du, Rosa Celia Poquita; Loke, Hai Xin; Khalis, Aizat; Li, Jinghan; Song, Tiancheng

    2016-01-01

    Coral bleaching events have been predicted to occur more frequently in the coming decades with global warming. The susceptibility of corals to bleaching during thermal stress episodes is dependent on many factors and an understanding of these underlying drivers is crucial for conservation management. In 2013, a mild bleaching episode ensued in response to elevated sea temperature on the sediment-burdened reefs in Singapore. Surveys of seven sites highlighted variable bleaching susceptibility among coral genera–Pachyseris and Podabacia were the most impacted (31% of colonies of both genera bleached). The most susceptible genera such as Acropora and Pocillopora, which were expected to bleach, did not. Susceptibility varied between less than 6% and more than 11% of the corals bleached, at four and three sites respectively. Analysis of four of the most bleached genera revealed that a statistical model that included a combination of the factors (genus, colony size and site) provided a better explanation of the observed bleaching patterns than any single factor alone. This underscored the complexity in predicting the coral susceptibility to future thermal stress events and the importance of monitoring coral bleaching episodes to facilitate more effective management of coral reefs under climate change. PMID:27438593

  12. A simple landslide susceptibility analysis for hazard and risk assessment in developing countries

    NASA Astrophysics Data System (ADS)

    Guinau, M.; Vilaplana, J. M.

    2003-04-01

    In recent years, a number of techniques and methodologies have been developed for mitigating natural disasters. The complexity of these methodologies and the scarcity of material and data series justify the need for simple methodologies to obtain the necessary information for minimising the effects of catastrophic natural phenomena. The work with polygonal maps using a GIS allowed us to develop a simple methodology, which was developed in an area of 473 Km2 in the Departamento de Chinandega (NW Nicaragua). This area was severely affected by a large number of landslides (mainly debris flows), triggered by the Hurricane Mitch rainfalls in October 1998. With the aid of aerial photography interpretation at 1:40.000 scale, amplified to 1:20.000, and detailed field work, a landslide map at 1:10.000 scale was constructed. The failure zones of landslides were digitized in order to obtain a failure zone digital map. A terrain unit digital map, in which a series of physical-environmental terrain factors are represented, was also used. Dividing the studied area into two zones (A and B) with homogeneous physical and environmental characteristics, allows us to develop the proposed methodology and to validate it. In zone A, the failure zone digital map is superimposed onto the terrain unit digital map to establish the relationship between the different terrain factors and the failure zones. The numerical expression of this relationship enables us to classify the terrain by its landslide susceptibility. In zone B, this numerical relationship was employed to obtain a landslide susceptibility map, obviating the need for a failure zone map. The validity of the methodology can be tested in this area by using the degree of superposition of the susceptibility map and the failure zone map. The implementation of the methodology in tropical countries with physical and environmental characteristics similar to those of the study area allows us to carry out a landslide susceptibility analysis in areas where landslide records do not exist. This analysis is essential to landslide hazard and risk assessment, which is necessary to determine the actions for mitigating landslide effects, e.g. land planning, emergency aid actions, etc.

  13. Susceptibility Evaluation and Mapping of CHINA'S Landslide Disaster Based on Multi-Temporal Ground and Remote Sensing Satellite Data

    NASA Astrophysics Data System (ADS)

    Liu, C.; Li, W.; Lu, P.; Sang, K.; Hong, Y.; Li, R.

    2012-07-01

    Under the circumstances of global climate change, nowadays landslide occurs in China more frequently than ever before. The landslide hazard and risk assessment remains an international focus on disaster prevention and mitigation. It is also an important approach for compiling and quantitatively characterizing landslide damages. By integrating empirical models for landslide disasters, and through multi-temporal ground data and remote sensing data, this paper will perform a landslide susceptibility assessment throughout China. A landslide susceptibility (LS) map will then be produced, which can be used for disaster evaluation, and provide basis for analyzing China's major landslide-affected regions. Firstly, based on previous research of landslide susceptibility assessment, this paper collects and analyzes the historical landslide event data (location, quantity and distribution) of past sixty years in China as a reference for late-stage studies. Secondly, this paper will make use of regional GIS data of the whole country provided by the National Geomatics Centre and China Meteorological Administration, including regional precipitation data, and satellite remote sensing data such as from TRMM and MODIS. By referring to historical landslide data of past sixty years, it is possible to develop models for assessing LS, including producing empirical models for prediction, and discovering both static and dynamic key factors, such as topography and landforms (elevation, curvature and slope), geologic conditions (lithology of the strata), soil type, vegetation cover, hydrological conditions (flow distribution). In addition, by analyzing historical data and combining empirical models, it is possible to synthesize a regional statistical model and perform a LS assessment. Finally, based on the 1km×1km grid, the LS map is then produced by ANN learning and multiplying the weighted factor layers. The validation is performed with reference to the frequency and distribution of historical data. This research reveals the spatiotemporal distribution of landslide disasters in China. The study develops a complete algorithm of data collecting, processing, modelling and synthesizing, which fulfils the assessment of landslide susceptibility, and provides theoretical basis for prediction and forecast of landslide disasters throughout China.

  14. Variation in the miRNA-433 Binding Site of FGF20 Confers Risk for Parkinson Disease by Overexpression of α-Synuclein

    PubMed Central

    Wang, Gaofeng; van der Walt, Joelle M.; Mayhew, Gregory; Li, Yi-Ju; Züchner, Stephan; Scott, William K.; Martin, Eden R.; Vance, Jeffery M.

    2008-01-01

    Parkinson disease (PD) is a common neurodegenerative disorder caused by environmental and genetic factors. We have previously shown linkage of PD to chromosome 8p. Subsequently, fibroblast growth factor 20 (FGF20) at 8p21.3–22 was identified as a risk factor in several association studies. To identify the risk-conferring polymorphism in FGF20, we performed genetic and functional analysis of single-nucleotide polymorphisms within the gene. In a sample of 729 nuclear families with 1089 affected and 1165 unaffected individuals, the strongest evidence of association came from rs12720208 in the 3′ untranslated region of FGF20. We show in several functional assays that the risk allele for rs12720208 disrupts a binding site for microRNA-433, increasing translation of FGF20 in vitro and in vivo. In a cell-based system and in PD brains, this increase in translation of FGF20 is correlated with increased α-synuclein expression, which has previously been shown to cause PD through both overexpression and point mutations. We suggest a novel mechanism of action for PD risk in which the modulation of the susceptibility gene's translation by common variations interfere with the regulation mechanisms of microRNA. We propose this is likely to be a common mechanism of genetic modulation of individual susceptibility to complex disease. PMID:18252210

  15. Perceptions of Heat-Susceptibility in Older Persons: Barriers to Adaptation

    PubMed Central

    Hansen, Alana; Bi, Peng; Nitschke, Monika; Pisaniello, Dino; Newbury, Jonathan; Kitson, Alison

    2011-01-01

    The increase in the frequency of very hot weather that is a predicted consequence of climate change poses an emerging threat to public health. Extreme heat can be harmful to the health of older persons who are known to be amongst the most vulnerable in the community. This study aimed to investigate factors influencing the ability of older persons to adapt to hot conditions, and barriers to adaptation. A qualitative study was conducted in Adelaide, Australia, involving focus groups and interviews with stakeholders including key personnel involved in aged care, community services, government sectors, emergency services and policy making. Findings revealed a broad range of factors that underpin the heat-susceptibility of the aged. These were categorized into four broad themes relating to: physiology and an age-related decline in health; socioeconomic factors, particularly those influencing air conditioning use; psychological issues including fears and anxieties about extreme heat; and adaptive strategies that could be identified as both enablers and barriers. As a consequence, the ability and willingness to undertake behavior change during heatwaves can therefore be affected in older persons. Additionally, understanding the control panels on modern air conditioners can present challenges for the aged. Improving heat-health knowledge and addressing the social and economic concerns of the older population will assist in minimizing heat-related morbidity and mortality in a warming climate. PMID:22408598

  16. Transcription factor NFAT5 promotes macrophage survival in rheumatoid arthritis

    PubMed Central

    Choi, Susanna; Choi, Soo Youn; Kwon, H. Moo; Hwang, Daehee; Park, Yune-Jung; Cho, Chul-Soo

    2017-01-01

    Defective apoptotic death of activated macrophages has been implicated in the pathogenesis of rheumatoid arthritis (RA). However, the molecular signatures defining apoptotic resistance of RA macrophages are not fully understood. Here, global transcriptome profiling of RA macrophages revealed that the osmoprotective transcription factor nuclear factor of activated T cells 5 (NFAT5) critically regulates diverse pathologic processes in synovial macrophages including the cell cycle, apoptosis, and proliferation. Transcriptomic analysis of NFAT5-deficient macrophages revealed the molecular networks defining cell survival and proliferation. Proinflammatory M1-polarizing stimuli and hypoxic conditions were responsible for enhanced NFAT5 expression in RA macrophages. An in vitro functional study demonstrated that NFAT5-deficient macrophages were more susceptible to apoptotic death. Specifically, CCL2 secretion in an NFAT5-dependent fashion bestowed apoptotic resistance to RA macrophages in vitro. Injection of recombinant CCL2 into one of the affected joints of Nfat5+/– mice increased joint destruction and macrophage infiltration, demonstrating the essential role of the NFAT5/CCL2 axis in arthritis progression in vivo. Moreover, after intra-articular injection, NFAT5-deficient macrophages were more susceptible to apoptosis and less efficient at promoting joint destruction than were NFAT5-sufficient macrophages. Thus, NFAT5 regulates macrophage survival by inducing CCL2 secretion. Our results provide evidence that NFAT5 expression in macrophages enhances chronic arthritis by conferring apoptotic resistance to activated macrophages. PMID:28192374

  17. Oral and intestinal mucositis - causes and possible treatments.

    PubMed

    Duncan, M; Grant, G

    2003-11-01

    Chemotherapy and radiotherapy, whilst highly effective in the treatment of neoplasia, can also cause damage to healthy tissue. In particular, the alimentary tract may be badly affected. Severe inflammation, lesioning and ulceration can occur. Patients may experience intense pain, nausea and gastro-enteritis. They are also highly susceptible to infection. The disorder (mucositis) is a dose-limiting toxicity of therapy and affects around 500 000 patients world-wide annually. Oral and intestinal mucositis is multi-factorial in nature. The disruption or loss of rapidly dividing epithelial progenitor cells is a trigger for the onset of the disorder. However, the actual dysfunction that manifests and its severity and duration are greatly influenced by changes in other cell populations, immune responses and the effects of oral/gut flora. This complexity has hampered the development of effective palliative or preventative measures. Recent studies have concentrated on the use of bioactive/growth factors, hormones or interleukins to modify epithelial metabolism and reduce the susceptibility of the tract to mucositis. Some of these treatments appear to have considerable potential and are at present under clinical evaluation. This overview deals with the cellular changes and host responses that may lead to the development of mucositis of the oral cavity and gastrointestinal tract, and the potential of existing and novel palliative measures to limit or prevent the disorder. Presently available treatments do not prevent mucositis, but can limit its severity if used in combination. Poor oral health and existing epithelial damage predispose patients to mucositis. The elimination of dental problems or the minimization of existing damage to the alimentary tract, prior to the commencement of therapy, lowers their susceptibility. Measures that reduce the flora of the tract, before therapy, can also be helpful. Increased production of free radicals and the induction of inflammation are early events in the onset of mucositis. Prophylactic administration of scavengers or anti-inflammatories can partially counteract or limit some of these therapy-mediated effects, as can the use of cryotherapy. The regular use of mouthwashes, mouth coatings, antibiotics and analgesics is essential, prior to and during loss and ablation of the epithelial layer. Granulocyte-macrophage colony-stimulating factor/granulocyte colony-stimulating factor or the use of laser light therapy may aid restitution and repair. Glutamine supplements may be beneficial in the repair/recovery phase.

  18. Naval Survivability and Susceptibility Reduction Study-Surface Ship

    DTIC Science & Technology

    2012-09-01

    the ship, causing damage. There are four properties affecting the susceptibility of a ship. The first property is the ease at which the ship can be...will affect how easily she can be detected. The second property is the ease at which the ship can be effective tracked, identified and classified by...being tracked by the active sensor after the she had been detected (PT|D). The third property is the ability to avoid being targeted. Again this is

  19. Sensitivity to Secondhand Smoke Exposure Predicts Future Smoking Susceptibility

    PubMed Central

    Wahlgren, Dennis R.; Liles, Sandy; Ji, Ming; Hughes, Suzanne C.; Winickoff, Jonathan P.; Jones, Jennifer A.; Swan, Gary E.; Hovell, Melbourne F.

    2011-01-01

    OBJECTIVE: Susceptibility to cigarette smoking in tobacco-naive youth is a strong predictor of smoking initiation. Identifying mechanisms that contribute to smoking susceptibility provide information about early targets for smoking prevention. This study investigated whether sensitivity to secondhand smoke exposure (SHSe) contributes to smoking susceptibility. PARTICIPANTS AND METHODS: Subjects were high-risk, ethnically diverse 8- to 13-year-old subjects who never smoked and who lived with at least 1 smoker and who participated in a longitudinal SHSe reduction intervention trial. Reactions (eg, feeling dizzy) to SHSe were assessed at baseline, and smoking susceptibility was assessed at baseline and 3 follow-up measurements over 12 months. We examined the SHSe reaction factor structure, association with demographic characteristics, and prediction of longitudinal smoking susceptibility status. RESULTS: Factor analysis identified “physically unpleasant” and “pleasant” reaction factors. Reported SHSe reactions did not differ across gender or family smoking history. More black preteens reported feeling relaxed and calm, and fewer reported feeling a head rush or buzz compared with non-Hispanic white and Hispanic white counterparts. Longitudinally, 8.5% of subjects tracked along the trajectory for high (versus low) smoking susceptibility. Reporting SHSe as “unpleasant or gross” predicted a 78% reduction in the probability of being assigned to the high–smoking susceptibility trajectory (odds ratio: 0.22 [95% confidence interval: 0.05–0.95]), after covariate adjustment. CONCLUSIONS: Assessment of SHSe sensitivity is a novel approach to the study of cigarette initiation etiology and informs prevention interventions. PMID:21746728

  20. Landslide susceptibility mapping by combining the three methods Fuzzy Logic, Frequency Ratio and Analytical Hierarchy Process in Dozain basin

    NASA Astrophysics Data System (ADS)

    Tazik, E.; Jahantab, Z.; Bakhtiari, M.; Rezaei, A.; Kazem Alavipanah, S.

    2014-10-01

    Landslides are among the most important natural hazards that lead to modification of the environment. Therefore, studying of this phenomenon is so important in many areas. Because of the climate conditions, geologic, and geomorphologic characteristics of the region, the purpose of this study was landslide hazard assessment using Fuzzy Logic, frequency ratio and Analytical Hierarchy Process method in Dozein basin, Iran. At first, landslides occurred in Dozein basin were identified using aerial photos and field studies. The influenced landslide parameters that were used in this study including slope, aspect, elevation, lithology, precipitation, land cover, distance from fault, distance from road and distance from river were obtained from different sources and maps. Using these factors and the identified landslide, the fuzzy membership values were calculated by frequency ratio. Then to account for the importance of each of the factors in the landslide susceptibility, weights of each factor were determined based on questionnaire and AHP method. Finally, fuzzy map of each factor was multiplied to its weight that obtained using AHP method. At the end, for computing prediction accuracy, the produced map was verified by comparing to existing landslide locations. These results indicate that the combining the three methods Fuzzy Logic, Frequency Ratio and Analytical Hierarchy Process method are relatively good estimators of landslide susceptibility in the study area. According to landslide susceptibility map about 51% of the occurred landslide fall into the high and very high susceptibility zones of the landslide susceptibility map, but approximately 26 % of them indeed located in the low and very low susceptibility zones.

  1. Association of IRF5 polymorphisms with susceptibility to macrophage activation syndrome in patients with juvenile idiopathic arthritis.

    PubMed

    Yanagimachi, Masakatsu; Naruto, Takuya; Miyamae, Takako; Hara, Takuma; Kikuchi, Masako; Hara, Ryoki; Imagawa, Tomoyuki; Mori, Masaaki; Sato, Hidenori; Goto, Hiroaki; Yokota, Shumpei

    2011-04-01

    Systemic-onset juvenile idiopathic arthritis (systemic JIA) and macrophage activation syndrome (MAS), the most devastating complication of systemic JIA, are characterized by abnormal levels of proinflammatory cytokines. Interferon regulatory factor 5 (IRF5) is a member of the IRF family of transcription factors, and acts as a master transcription factor in the activation of genes encoding proinflammatory cytokines. Polymorphisms in the IRF5 gene have been associated with susceptibility to autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. Our aim was to assess associations of IRF5 gene polymorphisms with susceptibility to systemic JIA and MAS. Three IRF5 single-nucleotide polymorphisms (rs729302, rs2004640, and rs2280714) were genotyped using TaqMan assays in 81 patients with systemic JIA (33 with MAS, 48 without) and 190 controls. There were no associations of the IRF5 gene polymorphisms or haplotypes under study with susceptibility to systemic JIA. There was a significant association of the rs2004640 T allele with MAS susceptibility (OR 4.11; 95% CI 1.84, 9.16; p = 0.001). The IRF5 haplotype (rs729302 A, rs2004640 T, and rs2280714 T), which was reported as conferring an increased risk of SLE, was significantly associated with MAS susceptibility in patients with systemic JIA (OR 4.61; 95% CI 1.73, 12.3; p < 0.001). IRF5 gene polymorphism is a genetic factor influencing susceptibility to MAS in patients with systemic JIA, and IRF5 contributes to the pathogenesis of MAS in these patients.

  2. Predicted disease susceptibility in a Panamanian amphibian assemblage based on skin peptide defenses.

    PubMed

    Woodhams, Douglas C; Voyles, Jamie; Lips, Karen R; Carey, Cynthia; Rollins-Smith, Louise A

    2006-04-01

    Chytridiomycosis is an emerging infectious disease of amphibians caused by a chytrid fungus, Batrachochytrium dendrobatidis. This panzootic does not equally affect all amphibian species within an assemblage; some populations decline, others persist. Little is known about the factors that affect disease resistance. Differences in behavior, life history, biogeography, or immune function may impact survival. We found that an innate immune defense, antimicrobial skin peptides, varied significantly among species within a rainforest stream amphibian assemblage that has not been exposed to B. dendrobatidis. If exposed, all amphibian species at this central Panamanian site are at risk of population declines. In vitro pathogen growth inhibition by peptides from Panamanian species compared with species with known resistance (Rana pipiens and Xenopus laevis) or susceptibility (Bufo boreas) suggests that of the nine species examined, two species (Centrolene prosoblepon and Phyllomedusa lemur) may demonstrate strong resistance, and the other species will have a higher risk of disease-associated population declines. We found little variation among geographically distinct B. dendrobatidis isolates in sensitivity to an amphibian skin peptide mixture. This supports the hypothesis that B. dendrobatidis is a generalist pathogen and that species possessing an innate immunologic defense at the time of disease emergence are more likely to survive.

  3. Dietary factors and epigenetic regulation for prostate cancer prevention.

    PubMed

    Ho, Emily; Beaver, Laura M; Williams, David E; Dashwood, Roderick H

    2011-11-01

    The role of epigenetic alterations in various human chronic diseases has gained increasing attention and has resulted in a paradigm shift in our understanding of disease susceptibility. In the field of cancer research, e.g., genetic abnormalities/mutations historically were viewed as primary underlying causes; however, epigenetic mechanisms that alter gene expression without affecting DNA sequence are now recognized as being of equal or greater importance for oncogenesis. Methylation of DNA, modification of histones, and interfering microRNA (miRNA) collectively represent a cadre of epigenetic elements dysregulated in cancer. Targeting the epigenome with compounds that modulate DNA methylation, histone marks, and miRNA profiles represents an evolving strategy for cancer chemoprevention, and these approaches are starting to show promise in human clinical trials. Essential micronutrients such as folate, vitamin B-12, selenium, and zinc as well as the dietary phytochemicals sulforaphane, tea polyphenols, curcumin, and allyl sulfur compounds are among a growing list of agents that affect epigenetic events as novel mechanisms of chemoprevention. To illustrate these concepts, the current review highlights the interactions among nutrients, epigenetics, and prostate cancer susceptibility. In particular, we focus on epigenetic dysregulation and the impact of specific nutrients and food components on DNA methylation and histone modifications that can alter gene expression and influence prostate cancer progression.

  4. ALS Patient Stem Cells for Unveiling Disease Signatures of Motoneuron Susceptibility: Perspectives on the Deadly Mitochondria, ER Stress and Calcium Triad

    PubMed Central

    Kaus, Anjoscha; Sareen, Dhruv

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a largely sporadic progressive neurodegenerative disease affecting upper and lower motoneurons (MNs) whose specific etiology is incompletely understood. Mutations in superoxide dismutase-1 (SOD1), TAR DNA-binding protein 43 (TARDBP/TDP-43) and C9orf72, have been identified in subsets of familial and sporadic patients. Key associated molecular and neuropathological features include ubiquitinated TDP-43 inclusions, stress granules, aggregated dipeptide proteins from mutant C9orf72 transcripts, altered mitochondrial ultrastructure, dysregulated calcium homeostasis, oxidative and endoplasmic reticulum (ER) stress, and an unfolded protein response (UPR). Such impairments have been documented in ALS animal models; however, whether these mechanisms are initiating factors or later consequential events leading to MN vulnerability in ALS patients is debatable. Human induced pluripotent stem cells (iPSCs) are a valuable tool that could resolve this “chicken or egg” causality dilemma. Relevant systems for probing pathophysiologically affected cells from large numbers of ALS patients and discovering phenotypic disease signatures of early MN susceptibility are described. Performing unbiased ‘OMICS and high-throughput screening in relevant neural cells from a cohort of ALS patient iPSCs, and rescuing mitochondrial and ER stress impairments, can identify targeted therapeutics for increasing MN longevity in ALS. PMID:26635528

  5. A histopathological survey of the razor clam Ensis macha (Pharidae) along the Patagonian Argentina coast.

    PubMed

    Vázquez, Nuria; Bruno, Elizabeth Perez; Márquez, Federico; Van der Molen, Silvina; Gilardoni, Carmen; Cremonte, Florencia

    2013-03-01

    This is the first study performed to determine the health status of the razor clam, Ensis macha, including six different populations along Argentina Patagonian coast and one of Chile. The parasites and pathologies affecting E. macha were analyzed and their prevalence and mean intensity values were calculated. To establish which factors affect the presence and intensity of infection, Generalized Linear Models (GLMs) were applied. Basophilic inclusions, ciliates, coccidians protozoans and turbellarians were found. We report an Aporocotylidae digenean and hemocyte infiltrations. None of the parasites is OIE (World Organisation for Animal Health) notifiable, and none seemed to be pathogenic, with the exception of the digenean. The prevalence of the parasites was affected mainly by environmental factors (such as site of sampling and season) instead of intrinsic conditions of the clam (such as size, condition index, sex and gonadal stage). On the other hand, the maximum intensity of parasites was not only related with cold seasons but also with the partially spawned gonadal stage of E. macha. During this stage, the clams would need to store energy for the next gametogenesis cycle, might be more susceptible to infection by the parasites. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Periodontal abscess during supportive periodontal therapy: a review of the literature.

    PubMed

    Silva, Geraldo L M; Soares, Rodrigo V; Zenóbio, Elton G

    2008-09-01

    The aim of this review is to present the current status of the occurrence and management of a periodontal abscess during supportive periodontal therapy (SPT). A periodontal abscess depicts typical features and has been described in patients under SPT in clinical trials. Common periodontal pathogens have been observed in this lesion and some etiologic factors may be responsible for its recurrence. This condition can be isolated or associated with factors that can change the prognosis of affected teeth. Although it has been frequently noticed in untreated periodontitis, the periodontal abscess can also occur in patients under SPT and has been regarded as one of the possible complications of SPT. Patients with a high susceptibility to periodontal disease lost more teeth than those with a healthy periodontium. Early diagnosis and appropriate intervention for periodontal abscesses in patients under SPT are extremely important for the management of the periodontal abscess since this condition can lead to loss of the involved tooth. A single case of a tooth diagnosed with periodontal abscess that responds favorably to adequate treatment does not seem to affect its longevity. An accurate diagnosis and adequate treatment can preserve the longevity of affected teeth.

  7. Genetic susceptibility to Grave's disease.

    PubMed

    Li, Hong; Chen, Qiuying

    2013-06-01

    The variety of clinical presentations of eye changes in patients with Graves' disease (GD) suggests that complex interactions between genetic, environmental, endogenous and local factors influence the severity of Graves' ophthalmopathy (GO). It is thought that the development of GO might be influenced by genetic factors and environmental factors, such as cigarette smoking. At present, however, the role of genetic factors in the development of GO is not known. On the basis of studies with candidate genes and other genetic approaches, several susceptibility loci in GO have been proposed, including immunological genes, human leukocyte antigen (HLA), cytotoxic T-lymphocyte antigen-4 (CTLA-4), regulatory T-cell genes and thyroid-specific genes. This review gives a brief overview of the current range of major susceptibility genes found for GD.

  8. Identification of a functional variant in SPLUNC1 associated with nasopharyngeal carcinoma susceptibility among Malaysian Chinese.

    PubMed

    Yew, Poh-Yin; Mushiroda, Taisei; Kiyotani, Kazuma; Govindasamy, Gopala Krishnan; Yap, Lee-Fah; Teo, Soo-Hwang; Lim, Paul Vey-Hong; Govindaraju, Selvaratnam; Ratnavelu, Kananathan; Sam, Choon-Kook; Yap, Yoke-Yeow; Khoo, Alan Soo-Beng; Pua, Kin-Choo; Nakamura, Yusuke; Ng, Ching-Ching

    2012-10-01

    Nasopharyngeal carcinoma (NPC) is a multifactorial and polygenic disease with high incidence in Asian countries. Epstein-Barr virus infection, environmental and genetic factors are believed to be involved in the tumorigenesis of NPC. The association of single nucleotide polymorphisms (SNPs) in LPLUNC1 and SPLUNC1 genes with NPC was investigated by performing a two-stage case control association study in a Malaysian Chinese population. The initial screening consisted of 81 NPC patients and 147 healthy controls while the replication study consisted of 366 NPC patients and 340 healthy controls. The combined analysis showed that a SNP (rs2752903) of SPLUNC1 was significantly associated with the risk of NPC (combined P = 0.00032, odds ratio = 1.62, 95% confidence interval = 1.25-2.11). In the subsequent dense fine mapping of SPLUNC1 locus, 36 SNPs in strong linkage disequilibrium with rs2752903 (r(2) ≥ 0.85) were associated with NPC susceptibility. Screening of these variants by electrophoretic mobility shift and luciferase reporter assays showed that rs1407019 located in intron 3 (r(2)  = 0.994 with rs2752903) caused allelic difference in the binding of specificity protein 1 (Sp1) transcription factor and affected luciferase activity. This SNP may consequently alter the expression of SPLUNC1 in the epithelial cells. In summary, our study suggested that rs1407019 in intronic enhancer of SPLUNC1 is associated with NPC susceptibility in which its A allele confers an increased risk of NPC in the Malaysian Chinese population. Copyright © 2011 Wiley Periodicals, Inc.

  9. Genetics and genomics of susceptibility and immune response to necrotic enteritis in chicken: a review.

    PubMed

    Zahoor, Imran; Ghayas, Abdul; Basheer, Atia

    2018-02-01

    Global poultry production is facing many challenges and is currently under pressure due to the presence of several diseases like Necrotic Enteritis (NE). It is estimated that NE-caused global economic losses has increased from 2 billion to 6 billion US$ in 2015 because it is not easy to diagnose and control disease at the earlier stage of occurrence. Additionally, ban on the in-feed antibiotics and some other genetic and non-genetic predisposing factors affect the occurrence of the disease. Though the incidence of the disease can be reduced by minimizing the predisposing factors and through immunization of birds but there is no single remedy to control the disease. Therefore, we suggest that there is need to find out the genetic variants that could help to select the birds resistant to NE. The current review details the pertinent features about the genetic and genomics of susceptibility and immune response of birds to Necrotic Enteritis. We report here the list of candidate gene reported for their involvement with the susceptibility and/or resistance to the disease. However, most of these genes are involved in immune-related functions. For better understanding of the role of Clostridium perfringens and its toxins in the pathogenesis of disease there is need to unveil the association between any specific genetic variation and clinical status of NE. However, the presence of substantial genetic variations among different breeds/strains of chicken shows that it is possible to develop broiler strain with genetic resistant against NE. It would help in the cost-effective and sustainable production of safe broiler meat.

  10. Susceptibility of the individual caseins in reconstituted skim milk to cross-linking by transglutaminase: influence of temperature, pH and mineral equilibria.

    PubMed

    Hinz, Katharina; Huppertz, Thom; Kelly, Alan L

    2012-11-01

    The susceptibility of total casein and the individual caseins in reconstituted skim milk to transglutaminase (TGase)-induced cross-linking was studied as a function of incubation temperature (5-40 °C), pH (5·0-7·0) and mineral addition. Within the ranges studied, the level of total casein cross-linked increased with increasing temperature, pH and concentration of added trisodium citrate, whereas adding calcium chloride had the opposite effect. These effects can be largely related to the effects of these parameters on TGase activity. In addition, the parameters were also found to influence the susceptibility of κ-casein, and to a lesser extent β-casein, to cross-linking, whereas the susceptibility of αs1-casein was not affected. The susceptibility of κ-casein to cross-linking increased with increasing temperature and calcium chloride addition, but decreased with increasing pH and citrate content, whereas the susceptibility of β-casein to TGase-induced cross-linking decreased with increasing temperature, but was not affected by other parameters. These findings highlight the fact that selection of environmental conditions during cross-linking can be applied to tailor the surface, and hence possibly colloidal stability, of casein micelles in TGase-treated milk.

  11. Correlation of Alzheimer's disease death rates with historical per capita personal income in the USA.

    PubMed

    Stępkowski, Dariusz; Woźniak, Grażyna; Studnicki, Marcin

    2015-01-01

    Alzheimer's disease (AD) is a progressive degenerating disease of complex etiology. A variety of risk factors contribute to the chance of developing AD. Lifestyle factors, such as physical, mental and social activity, education, and diet all affect the susceptibility to developing AD. These factors are in turn related to the level of personal income. Lower income usually coincides with lower level of education, lesser mental, leisure-social and physical activity, and poorer diet. In the present paper, we have analyzed the correlation of historical (1929-2011) per capita personal income (PCPI) for all states of the USA with corresponding age-adjusted AD death rates (AADR) for years 2000, 2005 and 2008. We found negative correlations in all cases, the highest one (R ≈ -0.65) for the PCPIs in the year 1970 correlated against the AADRs in 2005. From 1929 to 2005 the R value varies in an oscillatory manner, with the strongest correlations in 1929, 1970, 1990 and the weakest in 1950, 1980, 1998. Further analysis indicated that this oscillatory behavior of R is not artificially related to the economic factors but rather to delayed biological consequences associated with personal income. We conclude that the influence of the income level on the AD mortality in 2005 was the highest in the early years of life of the AD victims. Overall, the income had a significant, lifelong, albeit constantly decreasing, influence on the risk of developing AD. We postulate that the susceptibility of a population to late-onset AD (LOAD) is determined to a large extent by the history of income-related modifiable lifestyle risk factors. Among these risk factors, inappropriate diet has a significant contribution.

  12. Correlation of Alzheimer’s Disease Death Rates with Historical Per Capita Personal Income in the USA

    PubMed Central

    Stępkowski, Dariusz; Woźniak, Grażyna; Studnicki, Marcin

    2015-01-01

    Alzheimer’s disease (AD) is a progressive degenerating disease of complex etiology. A variety of risk factors contribute to the chance of developing AD. Lifestyle factors, such as physical, mental and social activity, education, and diet all affect the susceptibility to developing AD. These factors are in turn related to the level of personal income. Lower income usually coincides with lower level of education, lesser mental, leisure—social and physical activity, and poorer diet. In the present paper, we have analyzed the correlation of historical (1929–2011) per capita personal income (PCPI) for all states of the USA with corresponding age-adjusted AD death rates (AADR) for years 2000, 2005 and 2008. We found negative correlations in all cases, the highest one (R ≈ -0.65) for the PCPIs in the year 1970 correlated against the AADRs in 2005. From 1929 to 2005 the R value varies in an oscillatory manner, with the strongest correlations in 1929, 1970, 1990 and the weakest in 1950, 1980, 1998. Further analysis indicated that this oscillatory behavior of R is not artificially related to the economic factors but rather to delayed biological consequences associated with personal income. We conclude that the influence of the income level on the AD mortality in 2005 was the highest in the early years of life of the AD victims. Overall, the income had a significant, lifelong, albeit constantly decreasing, influence on the risk of developing AD. We postulate that the susceptibility of a population to late-onset AD (LOAD) is determined to a large extent by the history of income-related modifiable lifestyle risk factors. Among these risk factors, inappropriate diet has a significant contribution. PMID:25961738

  13. Rethinking the Heterosexual Infectivity of HIV-1: A Systematic Review and Meta-analysis

    PubMed Central

    Powers, Kimberly A.; Poole, Charles; Pettifor, Audrey E.; Cohen, Myron S.

    2009-01-01

    Background Studies of cumulative HIV incidence suggest that co-factors such as genital ulcer disease (GUD), HIV disease stage, and circumcision influence HIV transmission; however, the heterosexual infectivity of HIV-1 is commonly cited as a fixed value (∼0·001, or 1 transmission per thousand contacts). We sought to estimate transmission co-factor effects on the heterosexual infectivity of HIV-1 and to quantify the extent to which study methods have affected infectivity estimates. Methods We conducted a systematic search (through April 2008) of PubMed, Web of Science, and relevant bibliographies to identify articles estimating the heterosexual infectivity of HIV-1. We used meta-regression and stratified random-effects meta-analysis to assess differences in infectivity by co-factors and study methods. Findings Infectivity estimates were extremely heterogeneous, ranging from zero transmissions after more than 100 penile-vaginal contacts in some sero-discordant couples to one transmission for every 3·1 episodes of heterosexual anal intercourse. Estimates were only weakly associated with study methods. Infectivity differences (95% confidence intervals), expressed as number of transmissions per 1000 contacts, were 8 (0-16) comparing uncircumcised to circumcised male susceptibles, 6 (3-9) comparing susceptible individuals with and without GUD, 2 (1-3) comparing late-stage to mid-stage index cases, and 3 (0-5) comparing early-stage to mid-stage index cases. Interpretation A single value for the heterosexual infectivity of HIV-1 fails to reflect the variation associated with important co-factors. The commonly cited value of ∼0·001 was estimated among stable couples with low prevalences of high-risk co-factors, and represents a lower bound. Co-factor effects are important to include in epidemic models, policy considerations, and prevention messages. PMID:18684670

  14. Utilizing the Dog Genome in the Search for Novel Candidate Genes Involved in Glioma Development—Genome Wide Association Mapping followed by Targeted Massive Parallel Sequencing Identifies a Strongly Associated Locus

    PubMed Central

    Dickinson, Peter; Xiong, Anqi; York, Daniel; Jayashankar, Kartika; Pielberg, Gerli; Koltookian, Michele; Murén, Eva; Fuxelius, Hans-Henrik; Weishaupt, Holger; Andersson, Göran; Hedhammar, Åke; Bongcam-Rudloff, Erik; Forsberg-Nilsson, Karin

    2016-01-01

    Gliomas are the most common form of malignant primary brain tumors in humans and second most common in dogs, occurring with similar frequencies in both species. Dogs are valuable spontaneous models of human complex diseases including cancers and may provide insight into disease susceptibility and oncogenesis. Several brachycephalic breeds such as Boxer, Bulldog and Boston Terrier have an elevated risk of developing glioma, but others, including Pug and Pekingese, are not at higher risk. To identify glioma-associated genetic susceptibility factors, an across-breed genome-wide association study (GWAS) was performed on 39 dog glioma cases and 141 controls from 25 dog breeds, identifying a genome-wide significant locus on canine chromosome (CFA) 26 (p = 2.8 x 10−8). Targeted re-sequencing of the 3.4 Mb candidate region was performed, followed by genotyping of the 56 SNVs that best fit the association pattern between the re-sequenced cases and controls. We identified three candidate genes that were highly associated with glioma susceptibility: CAMKK2, P2RX7 and DENR. CAMKK2 showed reduced expression in both canine and human brain tumors, and a non-synonymous variant in P2RX7, previously demonstrated to have a 50% decrease in receptor function, was also associated with disease. Thus, one or more of these genes appear to affect glioma susceptibility. PMID:27171399

  15. Allelic Variation in the Toll-Like Receptor Adaptor Protein Ticam2 Contributes to SARS-Coronavirus Pathogenesis in Mice.

    PubMed

    Gralinski, Lisa E; Menachery, Vineet D; Morgan, Andrew P; Totura, Allison L; Beall, Anne; Kocher, Jacob; Plante, Jessica; Harrison-Shostak, D Corinne; Schäfer, Alexandra; Pardo-Manuel de Villena, Fernando; Ferris, Martin T; Baric, Ralph S

    2017-06-07

    Host genetic variation is known to contribute to differential pathogenesis following infection. Mouse models allow direct assessment of host genetic factors responsible for susceptibility to Severe Acute Respiratory Syndrome coronavirus (SARS-CoV). Based on an assessment of early stage lines from the Collaborative Cross mouse multi-parent population, we identified two lines showing highly divergent susceptibilities to SARS-CoV: the resistant CC003/Unc and the susceptible CC053/Unc. We generated 264 F2 mice between these strains, and infected them with SARS-CoV. Weight loss, pulmonary hemorrhage, and viral load were all highly correlated disease phenotypes. We identified a quantitative trait locus of major effect on chromosome 18 (27.1-58.6 Mb) which affected weight loss, viral titer and hemorrhage. Additionally, each of these three phenotypes had distinct quantitative trait loci [Chr 9 (weight loss), Chrs 7 and 12 (virus titer), and Chr 15 (hemorrhage)]. We identified Ticam2 , an adaptor protein in the TLR signaling pathways, as a candidate driving differential disease at the Chr 18 locus. Ticam2 -/- mice were highly susceptible to SARS-CoV infection, exhibiting increased weight loss and more pulmonary hemorrhage than control mice. These results indicate a critical role for Ticam2 in SARS-CoV disease, and highlight the importance of host genetic variation in disease responses. Copyright © 2017 Gralinski et al.

  16. Allelic Variation in the Toll-Like Receptor Adaptor Protein Ticam2 Contributes to SARS-Coronavirus Pathogenesis in Mice

    PubMed Central

    Gralinski, Lisa E.; Menachery, Vineet D.; Morgan, Andrew P.; Totura, Allison L.; Beall, Anne; Kocher, Jacob; Plante, Jessica; Harrison-Shostak, D. Corinne; Schäfer, Alexandra; Pardo-Manuel de Villena, Fernando; Ferris, Martin T.; Baric, Ralph S.

    2017-01-01

    Host genetic variation is known to contribute to differential pathogenesis following infection. Mouse models allow direct assessment of host genetic factors responsible for susceptibility to Severe Acute Respiratory Syndrome coronavirus (SARS-CoV). Based on an assessment of early stage lines from the Collaborative Cross mouse multi-parent population, we identified two lines showing highly divergent susceptibilities to SARS-CoV: the resistant CC003/Unc and the susceptible CC053/Unc. We generated 264 F2 mice between these strains, and infected them with SARS-CoV. Weight loss, pulmonary hemorrhage, and viral load were all highly correlated disease phenotypes. We identified a quantitative trait locus of major effect on chromosome 18 (27.1–58.6 Mb) which affected weight loss, viral titer and hemorrhage. Additionally, each of these three phenotypes had distinct quantitative trait loci [Chr 9 (weight loss), Chrs 7 and 12 (virus titer), and Chr 15 (hemorrhage)]. We identified Ticam2, an adaptor protein in the TLR signaling pathways, as a candidate driving differential disease at the Chr 18 locus. Ticam2−/− mice were highly susceptible to SARS-CoV infection, exhibiting increased weight loss and more pulmonary hemorrhage than control mice. These results indicate a critical role for Ticam2 in SARS-CoV disease, and highlight the importance of host genetic variation in disease responses. PMID:28592648

  17. Identification of Cd101 as a susceptibility gene for Novosphingobium aromaticivorans - induced liver autoimmunity

    PubMed Central

    Mohammed, Javid P.; Fusakio, Michael E.; Rainbow, Daniel B.; Moule, Carolyn; Fraser, Heather I.; Clark, Jan; Todd, John A.; Peterson, Laurence B.; Savage, Paul B.; Wills-Karp, Marsha; Ridgway, William M.; Wicker, Linda S.; Mattner, Jochen

    2011-01-01

    Environmental and genetic factors define the susceptibility of an individual to autoimmune disease. Although common genetic pathways affect general immunological tolerance mechanisms in autoimmunity, the effects of such genes could vary under distinct immune challenges within different tissues. Here we demonstrate this by observing that autoimmune type 1 diabetes (T1D) protective haplotypes at the susceptibility region 10 (Idd10) introgressed from chromosome 3 of B6 and A/J mice onto the NOD background increase the severity of autoimmune primary biliary cirrhosis (PBC) induced by infection with Novosphingobium aromaticivorans (N. aro), an ubiquitous alphaproteobacterium, when compared to mice having the NOD and NOD.CAST Idd10 T1D susceptible haplotypes. Substantially increased liver pathology in mice having the B6 and A/J Idd10 haplotypes correlates with reduced expression of CD101 on dendritic cells (DCs), macrophages and granulocytes following infection, delayed clearance of N. aro and the promotion of overzealous, IFN-γ- and IL-17-dominated T cell responses essential for the adoptive transfer of liver lesions. CD101-knockout mice generated on the B6 background also exhibit substantially more severe N.aro-induced liver disease correlating with increased IFN-γ and IL-17 responses compared to wild type mice. These data strongly support the hypothesis that allelic variation of the Cd101 gene, located in the Idd10 region, alters the severity of liver autoimmunity induced by N. aro. PMID:21613619

  18. A BRIEF TARGETED REVIEW OF SUSCEPTIBILITY FACTORS, ENVIRONMENTAL EXPOSURES, ASHTMA INCIDENCE, AND RECOMMENDATIONS FOR FUTURE ASHTMA INCIDENCE RESEARCH

    EPA Science Inventory

    Genetics, obesity, age, and lifestyle are major susceptibility factors in the induction of asthma and can interact with environmental exposures either synergistically or antagonistically. Different environmental exposures that increase or decrease the likelihood of developing as...

  19. Molecular epidemiology of acute leukemia in children: causal model, interaction of three factors-susceptibility, environmental exposure and vulnerability period.

    PubMed

    Mejía-Aranguré, Juan Manuel

    Acute leukemias have a huge morphological, cytogenetic and molecular heterogeneity and genetic polymorphisms associated with susceptibility. Every leukemia presents causal factors associated with the development of the disease. Particularly, when three factors are present, they result in the development of acute leukemia. These phenomena are susceptibility, environmental exposure and a period that, for this model, has been called the period of vulnerability. This framework shows how the concepts of molecular epidemiology have established a reference from which it is more feasible to identify the environmental factors associated with the development of leukemia in children. Subsequently, the arguments show that only susceptible children are likely to develop leukemia once exposed to an environmental factor. For additional exposure, if the child is not susceptible to leukemia, the disease does not develop. In addition, this exposure should occur during a time window when hematopoietic cells and their environment are more vulnerable to such interaction, causing the development of leukemia. This model seeks to predict the time when the leukemia develops and attempts to give a context in which the causality of childhood leukemia should be studied. This information can influence and reduce the risk of a child developing leukemia. Copyright © 2016 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  20. Moraine-dammed lake failures in Patagonia and assessment of outburst susceptibility in the Baker Basin

    NASA Astrophysics Data System (ADS)

    Iribarren Anacona, P.; Norton, K. P.; Mackintosh, A.

    2014-07-01

    Glacier retreat since the Little Ice Age has resulted in the development or expansion of hundreds of glacial lakes in Patagonia. Some of these lakes have produced large (≥106 m3) Glacial Lake Outburst Floods (GLOFs) damaging inhabited areas. GLOF hazard studies in Patagonia have been mainly based on the analysis of short-term series (≤50 years) of flood data and until now no attempt has been made to identify the relative susceptibility of lakes to failure. Power schemes and associated infrastructure are planned for Patagonian basins that have historically been affected by GLOFs, and we now require a thorough understanding of the characteristics of dangerous lakes in order to assist with hazard assessment and planning. In this paper, the conditioning factors of 16 outbursts from moraine dammed lakes in Patagonia were analysed. These data were used to develop a classification scheme designed to assess outburst susceptibility, based on image classification techniques, flow routine algorithms and the Analytical Hierarchy Process. This scheme was applied to the Baker Basin, Chile, where at least 7 moraine-dammed lakes have failed in historic time. We identified 386 moraine-dammed lakes in the Baker Basin of which 28 were classified with high or very high outburst susceptibility. Commonly, lakes with high outburst susceptibility are in contact with glaciers and have moderate (>8°) to steep (>15°) dam outlet slopes, akin to failed lakes in Patagonia. The proposed classification scheme is suitable for first-order GLOF hazard assessments in this region. However, rapidly changing glaciers in Patagonia make detailed analysis and monitoring of hazardous lakes and glaciated areas upstream from inhabited areas or critical infrastructure necessary, in order to better prepare for hazards emerging from an evolving cryosphere.

  1. Moraine-dammed lake failures in Patagonia and assessment of outburst susceptibility in the Baker Basin

    NASA Astrophysics Data System (ADS)

    Iribarren Anacona, P.; Norton, K. P.; Mackintosh, A.

    2014-12-01

    Glacier retreat since the Little Ice Age has resulted in the development or expansion of hundreds of glacial lakes in Patagonia. Some of these lakes have produced large (≥ 106 m3) Glacial Lake Outburst Floods (GLOFs) damaging inhabited areas. GLOF hazard studies in Patagonia have been mainly based on the analysis of short-term series (≤ 50 years) of flood data and until now no attempt has been made to identify the relative susceptibility of lakes to failure. Power schemes and associated infrastructure are planned for Patagonian basins that have historically been affected by GLOFs, and we now require a thorough understanding of the characteristics of dangerous lakes in order to assist with hazard assessment and planning. In this paper, the conditioning factors of 16 outbursts from moraine-dammed lakes in Patagonia were analysed. These data were used to develop a classification scheme designed to assess outburst susceptibility, based on image classification techniques, flow routine algorithms and the Analytical Hierarchy Process. This scheme was applied to the Baker Basin, Chile, where at least seven moraine-dammed lakes have failed in historic time. We identified 386 moraine-dammed lakes in the Baker Basin of which 28 were classified with high or very high outburst susceptibility. Commonly, lakes with high outburst susceptibility are in contact with glaciers and have moderate (> 8°) to steep (> 15°) dam outlet slopes, akin to failed lakes in Patagonia. The proposed classification scheme is suitable for first-order GLOF hazard assessments in this region. However, rapidly changing glaciers in Patagonia make detailed analysis and monitoring of hazardous lakes and glaciated areas upstream from inhabited areas or critical infrastructure necessary, in order to better prepare for hazards emerging from an evolving cryosphere.

  2. Multiple Sclerosis: Epidemiologic, Clinical, and Therapeutic Aspects.

    PubMed

    Vidal-Jordana, Angela; Montalban, Xavier

    2017-05-01

    Multiple sclerosis (MS) is a chronic autoimmune and degenerative disease of the central nervous system that affects young people. MS develops in genetically susceptible individuals exposed to different unknown triggering factors. Different phenotypes are described. About 15% of patients present with a primary progressive course and 85% with a relapsing-remitting course. An increasing number of disease-modifying treatments has emerged. Although encouraging, the number of drugs challenges the neurologist because each treatment has its own risk-benefit profile. Patients should be involved in the decision-making process to ensure good treatment and safety monitoring adherence. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Biorhythms and space experiments with nonhuman primates

    NASA Technical Reports Server (NTRS)

    Winget, C. M.

    1977-01-01

    Man's response to exposure to spaceflight and weightlessness is expressed in physiological adjustments which involve his health and ability to function. The amplitude and periodicity of fluctuations in biological processes affect various functions and responses to provocative stimuli. Primates and other species are subjected to tests to determine the consequences of an altered biorhythm on work and performance, emotional stability, biomedical evaluation in space, the ability to cope with the unexpected, and susceptibility to infection, toxicity, radiation, drugs, and stress. Factors in the environment or operational setup which can change the physiological baseline must be determined and controlled.

  4. Is motivation for marathon a protective factor or a risk factor of injury?

    PubMed

    Chalabaev, A; Radel, R; Ben Mahmoud, I; Massiera, B; Deroche, T; d'Arripe-Longueville, F

    2017-12-01

    This research investigated whether and how self-determined motivation predicts perceived susceptibility to injury during competition (marathon). Two correlational studies including 378 (Study 1) and 339 (Study 2) marathon runners were conducted. Participants filled out a questionnaire the day before the race measuring self-determined motivation, perceived susceptibilities to marathon-related injury and to keep running through pain, and control variables. Study 1 showed that self-determined motivation was negatively related to perceived susceptibility to marathon-related injury. Study 2 replicated this finding and showed that this relationship was partially mediated by perceived susceptibility to keep running through pain during the race. Moreover, results indicated that the predictive role of self-determination was mostly driven by controlled forms of motivation, and more particularly external regulation. These results suggest that self-determined motivation for sport is a protective factor of injury. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Phenotypic responses to microbial volatiles render a mold fungus more susceptible to insect damage.

    PubMed

    Caballero Ortiz, Silvia; Trienens, Monika; Pfohl, Katharina; Karlovsky, Petr; Holighaus, Gerrit; Rohlfs, Marko

    2018-04-01

    In decomposer systems, fungi show diverse phenotypic responses to volatile organic compounds of microbial origin (volatiles). The mechanisms underlying such responses and their consequences for the performance and ecological success of fungi in a multitrophic community context have rarely been tested explicitly. We used a laboratory-based approach in which we investigated a tripartite yeast-mold-insect model decomposer system to understand the possible influence of yeast-borne volatiles on the ability of a chemically defended mold fungus to resist insect damage. The volatile-exposed mold phenotype (1) did not exhibit protein kinase A-dependent morphological differentiation, (2) was more susceptible to insect foraging activity, and (3) had reduced insecticidal properties. Additionally, the volatile-exposed phenotype was strongly impaired in secondary metabolite formation and unable to activate "chemical defense" genes upon insect damage. These results suggest that volatiles can be ecologically important factors that affect the chemical-based combative abilities of fungi against insect antagonists and, consequently, the structure and dynamics of decomposer communities.

  6. Responses to Cytokines and Interferons that Depend upon JAKs and STATs.

    PubMed

    Stark, George R; Cheon, HyeonJoo; Wang, Yuxin

    2018-01-02

    Many cytokines and all interferons activate members of a small family of kinases (the Janus kinases [JAKs]) and a slightly larger family of transcription factors (the signal transducers and activators of transcription [STATs]), which are essential components of pathways that induce the expression of specific sets of genes in susceptible cells. JAK-STAT pathways are required for many innate and acquired immune responses, and the activities of these pathways must be finely regulated to avoid major immune dysfunctions. Regulation is achieved through mechanisms that include the activation or induction of potent negative regulatory proteins, posttranslational modification of the STATs, and other modulatory effects that are cell-type specific. Mutations of JAKs and STATs can result in gains or losses of function and can predispose affected individuals to autoimmune disease, susceptibility to a variety of infections, or cancer. Here we review recent developments in the biochemistry, genetics, and biology of JAKs and STATs. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

  7. Natural Selection in a Bangladeshi Population from the Cholera-Endemic Ganges River Delta

    PubMed Central

    Karlsson, Elinor K.; Harris, Jason B.; Tabrizi, Shervin; Rahman, Atiqur; Shlyakhter, Ilya; Patterson, Nick; O'Dushlaine, Colm; Schaffner, Stephen F.; Gupta, Sameer; Chowdhury, Fahima; Sheikh, Alaullah; Shin, Ok Sarah; Ellis, Crystal; Becker, Christine E.; Stuart, Lynda M.; Calderwood, Stephen B.; Ryan, Edward T.; Qadri, Firdausi; Sabeti, Pardis C.; LaRocque, Regina C.

    2015-01-01

    As an ancient disease with high fatality, cholera has likely exerted strong selective pressure on affected human populations. We performed a genome-wide study of natural selection in a population from the Ganges River Delta, the historic geographic epicenter of cholera. We identified 305 candidate selected regions using the Composite of Multiple Signals (CMS) method. The regions were enriched for potassium channel genes involved in cyclic AMP-mediated chloride secretion and for components of the innate immune system involved in NF-κB signaling. We demonstrate that a number of these strongly selected genes are associated with cholera susceptibility in two separate cohorts. We further identify repeated examples of selection and association in an NF-kB / inflammasome-dependent pathway that is activated in vitro by Vibrio cholerae. Our findings shed light on the genetic basis of cholera resistance in a population from the Ganges River Delta and present a promising approach for identifying genetic factors influencing susceptibility to infectious diseases. PMID:23825302

  8. A family of rare-earth-based single chain magnets: playing with anisotropy.

    PubMed

    Bernot, Kevin; Bogani, Lapo; Caneschi, Andrea; Gatteschi, Dante; Sessoli, Roberta

    2006-06-21

    The first family of rare-earth-based single chain magnets is presented. Compounds of general formula [M(hfac)3(NITPhOPh)], where M = Eu, Gd, Tb, Dy, Ho, Er, or Yb, and PhOPh is the nitronyl-nitroxide radical (2,4'-benzoxo-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide), have been structurally characterized and found to be isostructural. The characterization of both static and dynamic magnetic properties of the whole family is reported. Dy, Tb, and Ho compounds display slow relaxation of the magnetization, and ac susceptibility shows a thermally activated regime with energy barriers of 69, 45, and 34 K for Dy, Tb, and Ho compounds, respectively, while only a frequency-dependent susceptibility is observed for Er below 2.0 K. In Gd and Yb derivatives, antiferromagnetic interactions dominate. The pre-exponential factors differ by about 4 orders of magnitude. Finite size effects, due to naturally occurring defects, affect the static and dynamic properties of the compounds differently.

  9. Host-Microbiome Cross-talk in Oral Mucositis

    PubMed Central

    Vasconcelos, R.M.; Sanfilippo, N.; Paster, B.J.; Kerr, A.R.; Li, Y.; Ramalho, L.; Queiroz, E.L.; Smith, B.; Sonis, S.T.; Corby, P.M.

    2016-01-01

    Oral mucositis (OM) is among the most common, painful, and debilitating toxicities of cancer regimen–related treatment, resulting in the formation of ulcers, which are susceptible to increased colonization of microorganisms. Novel discoveries in OM have focused on understanding the host-microbial interactions, because current pathways have shown that major virulence factors from microorganisms have the potential to contribute to the development of OM and may even prolong the existence of already established ulcerations, affecting tissue healing. Additional comprehensive and disciplined clinical investigation is needed to carefully characterize the relationship between the clinical trajectory of OM, the local levels of inflammatory changes (both clinical and molecular), and the ebb and flow of the oral microbiota. Answering such questions will increase our knowledge of the mechanisms engaged by the oral immune system in response to mucositis, facilitating their translation into novel therapeutic approaches. In doing so, directed clinical strategies can be developed that specifically target those times and tissues that are most susceptible to intervention. PMID:27053118

  10. Are leftists more emotion-driven than rightists? The interactive influence of ideology and emotions on support for policies.

    PubMed

    Pliskin, Ruthie; Bar-Tal, Daniel; Sheppes, Gal; Halperin, Eran

    2014-12-01

    Although emotions and ideology are important factors guiding policy support in conflict, their interactive influence remains unclear. Based on prior findings that ideological leftists' beliefs are more susceptible to change than rightists' beliefs, we tested a somewhat counterintuitive extension that leftists would be more susceptible to influence by their emotional reactions than rightists. In three laboratory studies, inducing positive and negative emotions affected Jewish-Israeli leftists', but not rightists', support for conciliatory policies toward an adversarial (Studies 1 and 3) and a non-adversarial (Study 2) outgroup. Three additional field studies showed that positive and negative emotions were related to leftists', but not rightists', policy support in positive as well as highly negative conflict-related contexts, among both Jewish (Studies 4 and 5) and Palestinian (Study 6) citizens of Israel. Across different conflicts, emotions, conflict-related contexts, and even populations, leftists' policy support changed in accordance with emotional reactions more than rightists' policy support. © 2014 by the Society for Personality and Social Psychology, Inc.

  11. Positive association of vitamin D receptor gene variations with multiple sclerosis in South East Iranian population.

    PubMed

    Narooie-Nejad, Mehrnaz; Moossavi, Maryam; Torkamanzehi, Adam; Moghtaderi, Ali

    2015-01-01

    Among the factors postulated to play a role in MS susceptibility, the role of vitamin D is outstanding. Since the function of vitamin D receptor (VDR) represents the effect of vitamin D on the body and genetic variations in VDR gene may affect its function, we aim to highlight the association of two VDR gene polymorphisms with MS susceptibility. In current study, we recruited 113 MS patients and 122 healthy controls. TaqI (rs731236) and ApaI (rs7975232) genetic variations in these two groups were evaluated using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. All genotype and allele frequencies in both variations showed association with the disease status. However, to find the definite connection between genetic variations in VDR gene and MS disease in a population of South East of Iran, more researches on gene structure and its function with regard to patients' conditions are required.

  12. The global susceptibility of coastal forage fish to competition by large jellyfish.

    PubMed

    Schnedler-Meyer, Nicolas Azaña; Mariani, Patrizio; Kiørboe, Thomas

    2016-11-16

    Competition between large jellyfish and forage fish for zooplankton prey is both a possible cause of jellyfish increases and a concern for the management of marine ecosystems and fisheries. Identifying principal factors affecting this competition is therefore important for marine management, but the lack of both good quality data and a robust theoretical framework have prevented general global analyses. Here, we present a general mechanistic food web model that considers fundamental differences in feeding modes and predation pressure between fish and jellyfish. The model predicts forage fish dominance at low primary production, and a shift towards jellyfish with increasing productivity, turbidity and fishing. We present an index of global ecosystem susceptibility to shifts in fish-jellyfish dominance that compares well with data on jellyfish distributions and trends. The results are a step towards better understanding the processes that govern jellyfish occurrences globally and highlight the advantage of considering feeding traits in ecosystem models. © 2016 The Author(s).

  13. Human Gut Microbiota Predicts Susceptibility to Vibrio cholerae Infection.

    PubMed

    Midani, Firas S; Weil, Ana A; Chowdhury, Fahima; Begum, Yasmin A; Khan, Ashraful I; Debela, Meti D; Durand, Heather K; Reese, Aspen T; Nimmagadda, Sai N; Silverman, Justin D; Ellis, Crystal N; Ryan, Edward T; Calderwood, Stephen B; Harris, Jason B; Qadri, Firdausi; David, Lawrence A; LaRocque, Regina C

    2018-04-12

    Cholera is a public health problem worldwide and the risk factors for infection are only partially understood. We prospectively studied household contacts of cholera patients to compare those who were infected with those who were not. We constructed predictive machine learning models of susceptibility using baseline gut microbiota data. We identified bacterial taxa associated with susceptibility to Vibrio cholerae infection and tested these taxa for interactions with V. cholerae in vitro. We found that machine learning models based on gut microbiota predicted V. cholerae infection as well as models based on known clinical and epidemiological risk factors. A 'predictive gut microbiota' of roughly 100 bacterial taxa discriminated between contacts who developed infection and those who did not. Susceptibility to cholera was associated with depleted levels of microbes from the phylum Bacteroidetes. By contrast, a microbe associated with cholera by our modeling framework, Paracoccus aminovorans, promoted the in vitro growth of V. cholerae. Gut microbiota structure, clinical outcome, and age were also linked. These findings support the hypothesis that abnormal gut microbial communities are a host factor related to V. cholerae susceptibility.

  14. Use of Satellite Remote Sensing Data in the Mapping of Global Landslide Susceptibility

    NASA Technical Reports Server (NTRS)

    Hong, Yang; Adler, Robert F.; Huffman, George J.

    2007-01-01

    Satellite remote sensing data has significant potential use in analysis of natural hazards such as landslides. Relying on the recent advances in satellite remote sensing and geographic information system (GIS) techniques, this paper aims to map landslide susceptibility over most of the globe using a GIs-based weighted linear combination method. First , six relevant landslide-controlling factors are derived from geospatial remote sensing data and coded into a GIS system. Next, continuous susceptibility values from low to high are assigned to each of the six factors. Second, a continuous scale of a global landslide susceptibility index is derived using GIS weighted linear combination based on each factor's relative significance to the process of landslide occurrence (e.g., slope is the most important factor, soil types and soil texture are also primary-level parameters, while elevation, land cover types, and drainage density are secondary in importance). Finally, the continuous index map is further classified into six susceptibility categories. Results show the hot spots of landslide-prone regions include the Pacific Rim, the Himalayas and South Asia, Rocky Mountains, Appalachian Mountains, Alps, and parts of the Middle East and Africa. India, China, Nepal, Japan, the USA, and Peru are shown to have landslide-prone areas. This first-cut global landslide susceptibility map forms a starting point to provide a global view of landslide risks and may be used in conjunction with satellite-based precipitation information to potentially detect areas with significant landslide potential due to heavy rainfall. 1

  15. An Unbiased Assessment of the Role of Imprinted Genes in an Intergenerational Model of Developmental Programming

    PubMed Central

    Radford, Elizabeth J.; Isganaitis, Elvira; Jimenez-Chillaron, Josep; Schroeder, Joshua; Molla, Michael; Andrews, Simon; Didier, Nathalie; Charalambous, Marika; McEwen, Kirsten; Marazzi, Giovanna; Sassoon, David; Patti, Mary-Elizabeth; Ferguson-Smith, Anne C.

    2012-01-01

    Environmental factors during early life are critical for the later metabolic health of the individual and of future progeny. In our obesogenic environment, it is of great socioeconomic importance to investigate the mechanisms that contribute to the risk of metabolic ill health. Imprinted genes, a class of functionally mono-allelic genes critical for early growth and metabolic axis development, have been proposed to be uniquely susceptible to environmental change. Furthermore, it has also been suggested that perturbation of the epigenetic reprogramming of imprinting control regions (ICRs) may play a role in phenotypic heritability following early life insults. Alternatively, the presence of multiple layers of epigenetic regulation may in fact protect imprinted genes from such perturbation. Unbiased investigation of these alternative hypotheses requires assessment of imprinted gene expression in the context of the response of the whole transcriptome to environmental assault. We therefore analyse the role of imprinted genes in multiple tissues in two affected generations of an established murine model of the developmental origins of health and disease using microarrays and quantitative RT–PCR. We demonstrate that, despite the functional mono-allelicism of imprinted genes and their unique mechanisms of epigenetic dosage control, imprinted genes as a class are neither more susceptible nor protected from expression perturbation induced by maternal undernutrition in either the F1 or the F2 generation compared to other genes. Nor do we find any evidence that the epigenetic reprogramming of ICRs in the germline is susceptible to nutritional restriction. However, we propose that those imprinted genes that are affected may play important roles in the foetal response to undernutrition and potentially its long-term sequelae. We suggest that recently described instances of dosage regulation by relaxation of imprinting are rare and likely to be highly regulated. PMID:22511876

  16. Familial aggregation of gout and relative genetic and environmental contributions: a nationwide population study in Taiwan.

    PubMed

    Kuo, Chang-Fu; Grainge, Matthew J; See, Lai-Chu; Yu, Kuang-Hui; Luo, Shue-Fen; Valdes, Ana M; Zhang, Weiya; Doherty, Michael

    2015-02-01

    To examine familial aggregation of gout and to estimate the heritability and environmental contributions to gout susceptibility in the general population. Using data from the National Health Insurance (NHI) Research Database in Taiwan, we conducted a nationwide cross-sectional study of data collected from 22 643 748 beneficiaries of the NHI in 2004; among them 1 045 059 individuals had physician-diagnosed gout. We estimated relative risks (RR) of gout in individuals with affected first-degree and second-degree relatives and relative contributions of genes (heritability), common environment shared by family members and non-shared environment to gout susceptibility. RRs for gout were significantly higher in individuals with affected first-degree relatives (men, 1.91 (95% CI 1.90 to 1.93); women, 1.97 (95% CI 1.94 to 1.99)) and also in those with affected second-degree relatives (men, 1.27 (95% CI 1.23 to 1.31); women, 1.40 (95% CI 1.35 to 1.46)). RRs (95% CIs) for individuals with an affected twin, sibling, offspring, parent, grandchild, nephew/niece, uncle/aunt and grandparent were 8.02 (6.95 to 9.26), 2.59 (2.54 to 2.63), 1.96 (1.95 to 1.97), 1.93 (1.91 to 1.94), 1.48 (1.43 to 1.53), 1.40 (1.32 to 1.47), 1.31 (1.24 to 1.39), and 1.26 (1.21 to 1.30), respectively. The relative contributions of heritability, common and non-shared environmental factors to phenotypic variance of gout were 35.1, 28.1 and 36.8% in men and 17.0, 18.5 and 64.5% in women, respectively. This population-based study confirms that gout aggregates within families. The risk of gout is higher in people with a family history. Genetic and environmental factors contribute to gout aetiology, and the relative contributions are sexually dimorphic. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  17. Fire Severity Controlled Susceptibility to a 1940s Spruce Beetle Outbreak in Colorado, USA

    PubMed Central

    Kulakowski, Dominik; Veblen, Thomas T.; Bebi, Peter

    2016-01-01

    The frequency, magnitude, and size of forest disturbances are increasing globally. Much recent research has focused on how the occurrence of one disturbance may affect susceptibility to subsequent disturbances. While much has been learned about such linked disturbances, the strength of the interactions is likely to be contingent on the severity of disturbances as well as climatic conditions, both of which can affect disturbance intensity and tree resistance to disturbances. Subalpine forests in western Colorado were affected by extensive and severe wildfires in the late 19th century and an extensive and severe outbreak of spruce beetle (Dendroctonus rufipennis) in the 1940s. Previous research found that most, but not all, of the stands that burned and established following the late 19th century fires were not susceptible to the 1940s outbreak as beetles preferentially attack larger trees and stands in advanced stages of development. However, previous research also left open the possibility that some stands that burned and established following the 19th century fires may have been attacked during the 1940s outbreak. Understanding how strongly stand structure, as shaped by disturbances of varying severity, affected susceptibility to past outbreaks is important to provide a baseline for assessing the degree to which recent climate change may be relaxing the preferences of beetles for larger trees and for stands in latter stages of structural development and thereby changing the nature of linked disturbances. Here, dendroecological methods were used to study disturbance history and tree age of stands in the White River National Forest in Western Colorado that were identified in historical documents or remotely-sensed images as having burned in the 19th century and having been attacked by spruce beetle in the 1940s. Dendroecological reconstructions indicate that in young post-fire stands only old remnant trees that survived the otherwise stand-replacing fires were killed in the 1940s outbreak. No young post-fire trees (< ca. 128 years) were susceptible to the 1940s outbreak, implying that under the relatively cool and wet conditions of the mid-20th century, susceptibility to and spatial patterns of spruce beetle outbreak were most likely controlled by variations in severity of prior disturbance by fire. This study provides a baseline for comparing linked disturbances under the relatively warmer and drier conditions of recent (e.g. post-1990) outbreaks in order to assess how climate mitigates the degree to which pre-disturbance history and structure affect susceptibility to disturbances. PMID:27438289

  18. Fire Severity Controlled Susceptibility to a 1940s Spruce Beetle Outbreak in Colorado, USA.

    PubMed

    Kulakowski, Dominik; Veblen, Thomas T; Bebi, Peter

    2016-01-01

    The frequency, magnitude, and size of forest disturbances are increasing globally. Much recent research has focused on how the occurrence of one disturbance may affect susceptibility to subsequent disturbances. While much has been learned about such linked disturbances, the strength of the interactions is likely to be contingent on the severity of disturbances as well as climatic conditions, both of which can affect disturbance intensity and tree resistance to disturbances. Subalpine forests in western Colorado were affected by extensive and severe wildfires in the late 19th century and an extensive and severe outbreak of spruce beetle (Dendroctonus rufipennis) in the 1940s. Previous research found that most, but not all, of the stands that burned and established following the late 19th century fires were not susceptible to the 1940s outbreak as beetles preferentially attack larger trees and stands in advanced stages of development. However, previous research also left open the possibility that some stands that burned and established following the 19th century fires may have been attacked during the 1940s outbreak. Understanding how strongly stand structure, as shaped by disturbances of varying severity, affected susceptibility to past outbreaks is important to provide a baseline for assessing the degree to which recent climate change may be relaxing the preferences of beetles for larger trees and for stands in latter stages of structural development and thereby changing the nature of linked disturbances. Here, dendroecological methods were used to study disturbance history and tree age of stands in the White River National Forest in Western Colorado that were identified in historical documents or remotely-sensed images as having burned in the 19th century and having been attacked by spruce beetle in the 1940s. Dendroecological reconstructions indicate that in young post-fire stands only old remnant trees that survived the otherwise stand-replacing fires were killed in the 1940s outbreak. No young post-fire trees (< ca. 128 years) were susceptible to the 1940s outbreak, implying that under the relatively cool and wet conditions of the mid-20th century, susceptibility to and spatial patterns of spruce beetle outbreak were most likely controlled by variations in severity of prior disturbance by fire. This study provides a baseline for comparing linked disturbances under the relatively warmer and drier conditions of recent (e.g. post-1990) outbreaks in order to assess how climate mitigates the degree to which pre-disturbance history and structure affect susceptibility to disturbances.

  19. Changes in insulin-like growth factor signaling alter phenotypes in Fragile X Mice.

    PubMed

    Wise, T L

    2017-02-01

    Fragile X syndrome (FXS) is an inherited form of intellectual disability that is usually caused by expansion of a polymorphic CGG repeat in the 5' untranslated region of the X-linked FMR1 gene, which leads to hypermethylation and transcriptional silencing. Two non-neurological phenotypes of FXS are enlarged testes and connective tissue dysplasia, which could be caused by alterations in a growth factor signaling pathway. FXS patients also frequently have autistic-like symptoms, suggesting that the signaling pathways affected in FXS may overlap with those affected in autism. Identifying these pathways is important for both understanding the effects of FMR1 inactivation and developing treatments for both FXS and autism. Here we show that decreasing the levels of the insulin-like growth factor (Igf) receptor 1 corrects a number of phenotypes in the mouse model of FXS, including macro-orchidism, and that increasing the levels of IGF2 exacerbates the seizure susceptibility phenotype. These results suggest that the pathways altered by the loss of the FMR1-encoded protein (FMRP) may overlap with the pathways affected by changes in Igf signaling or that one or more of the proteins that play a role in Igf signaling could interact with FMRP. They also indicate a new set of potential targets for drug treatment of FXS and autism spectrum disorders. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  20. The redox-sensing gene Nrf2 affects intestinal homeostasis, insecticide resistance, and Zika virus susceptibility in the mosquito Aedes aegypti.

    PubMed

    Bottino-Rojas, Vanessa; Talyuli, Octavio A C; Carrara, Luana; Martins, Ademir J; James, Anthony A; Oliveira, Pedro L; Paiva-Silva, Gabriela O

    2018-06-08

    Production and degradation of reactive oxygen species (ROS) are extensively regulated to ensure proper cellular responses to various environmental stimuli and stresses. Moreover, physiologically generated ROS function as secondary messengers that can influence tissue homeostasis. The cap'n'collar transcription factor known as nuclear factor erythroid-derived factor 2 (Nrf2) coordinates an evolutionarily conserved transcriptional activation pathway that mediates antioxidant and detoxification responses in many animal species, including insects and mammals. Here, we show that Nrf2-mediated signaling affects embryo survival, midgut homeostasis, and redox biology in Aedes aegypti , a mosquito species vector of dengue, Zika, and other disease-causing viruses. We observed that AeNrf2 silencing increases ROS levels and stimulates intestinal stem cell proliferation. Because ROS production is a major aspect of innate immunity in mosquito gut, we found that a decrease in Nrf2 signaling results in reduced microbiota growth and Zika virus infection. Moreover, we provide evidence that AeNrf2 signaling also controls transcriptional adaptation of A. aegypti to insecticide challenge. Therefore, we conclude that Nrf2-mediated response regulates assorted gene clusters in A. aegypti that determine cellular and midgut redox balance, affecting overall xenobiotic resistance and vectorial adaptation of the mosquito. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Deuterium content of water increases depression susceptibility: the potential role of a serotonin-related mechanism.

    PubMed

    Strekalova, Tatyana; Evans, Matthew; Chernopiatko, Anton; Couch, Yvonne; Costa-Nunes, João; Cespuglio, Raymond; Chesson, Lesley; Vignisse, Julie; Steinbusch, Harry W; Anthony, Daniel C; Pomytkin, Igor; Lesch, Klaus-Peter

    2015-01-15

    Environmental factors can significantly affect disease prevalence, including neuropsychiatric disorders such as depression. The ratio of deuterium to protium in water shows substantial geographical variation, which could affect disease susceptibility. Thus the link between deuterium content of water and depression was investigated, both epidemiologically, and in a mouse model of chronic mild stress. We performed a correlation analysis between deuterium content of tap water and rates of depression in regions of the USA. Next, we used a 10-day chronic stress paradigm to test whether 2-week deuterium-depleted water treatment (91 ppm) affects depressive-like behavior and hippocampal SERT. The effect of deuterium-depletion on sleep electrophysiology was also evaluated in naïve mice. There was a geographic correlation between a content of deuterium and the prevalence of depression across the USA. In the chronic stress model, depressive-like features were reduced in mice fed with deuterium-depleted water, and SERT expression was decreased in mice treated with deuterium-treated water compared with regular water. Five days of predator stress also suppressed proliferation in the dentate gyrus; this effect was attenuated in mice fed with deuterium-depleted water. Finally, in naïve mice, deuterium-depleted water treatment increased EEG indices of wakefulness, and decreased duration of REM sleep, phenomena that have been shown to result from the administration of selective serotonin reuptake inhibitors (SSRI). Our data suggest that the deuterium content of water may influence the incidence of affective disorder-related pathophysiology and major depression, which might be mediated by the serotoninergic mechanisms. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  2. Selection of Functional Quorum Sensing Systems by Lysogenic Bacteriophages in Pseudomonas aeruginosa

    PubMed Central

    Saucedo-Mora, Miguel A.; Castañeda-Tamez, Paulina; Cazares, Adrián; Pérez-Velázquez, Judith; Hense, Burkhard A.; Cazares, Daniel; Figueroa, Wendy; Carballo, Marco; Guarneros, Gabriel; Pérez-Eretza, Berenice; Cruz, Nelby; Nishiyama, Yoshito; Maeda, Toshinari; Belmont-Díaz, Javier A.; Wood, Thomas K.; García-Contreras, Rodolfo

    2017-01-01

    Quorum sensing (QS) in Pseudomonas aeruginosa coordinates the expression of virulence factors, some of which are used as public goods. Since their production is a cooperative behavior, it is susceptible to social cheating in which non-cooperative QS deficient mutants use the resources without investing in their production. Nevertheless, functional QS systems are abundant; hence, mechanisms regulating the amount of cheating should exist. Evidence that demonstrates a tight relationship between QS and the susceptibility of bacteria against the attack of lytic phages is increasing; nevertheless, the relationship between temperate phages and QS has been much less explored. Therefore, in this work, we studied the effects of having a functional QS system on the susceptibility to temperate bacteriophages and how this affects the bacterial and phage dynamics. We find that both experimentally and using mathematical models, that the lysogenic bacteriophages D3112 and JBD30 select QS-proficient P. aeruginosa phenotypes as compared to the QS-deficient mutants during competition experiments with mixed strain populations in vitro and in vivo in Galleria mellonella, in spite of the fact that both phages replicate better in the wild-type background. We show that this phenomenon restricts social cheating, and we propose that temperate phages may constitute an important selective pressure toward the conservation of bacterial QS. PMID:28912771

  3. Schizophrenia, vitamin D, and brain development.

    PubMed

    Mackay-Sim, Alan; Féron, François; Eyles, Darryl; Burne, Thomas; McGrath, John

    2004-01-01

    Schizophrenia research is invigorated at present by the recent discovery of several plausible candidate susceptibility genes identified from genetic linkage and gene expression studies of brains from persons with schizophrenia. It is a current challenge to reconcile this gathering evidence for specific candidate susceptibility genes with the "neurodevelopmental hypothesis," which posits that schizophrenia arises from gene-environment interactions that disrupt brain development. We make the case here that schizophrenia may result not from numerous genes of small effect, but a few genes of transcriptional regulation acting during brain development. In particular we propose that low vitamin D during brain development interacts with susceptibility genes to alter the trajectory of brain development, probably by epigenetic regulation that alters gene expression throughout adult life. Vitamin D is an attractive "environmental" candidate because it appears to explain several key epidemiological features of schizophrenia. Vitamin D is an attractive "genetic" candidate because its nuclear hormone receptor regulates gene expression and nervous system development. The polygenic quality of schizophrenia, with linkage to many genes of small effect, maybe brought together via this "vitamin D hypothesis." We also discuss the possibility of a broader set of environmental and genetic factors interacting via the nuclear hormone receptors to affect the development of the brain leading to schizophrenia.

  4. A theoretical framework to model DSC-MRI data acquired in the presence of contrast agent extravasation

    NASA Astrophysics Data System (ADS)

    Quarles, C. C.; Gochberg, D. F.; Gore, J. C.; Yankeelov, T. E.

    2009-10-01

    Dynamic susceptibility contrast (DSC) MRI methods rely on compartmentalization of the contrast agent such that a susceptibility gradient can be induced between the contrast-containing compartment and adjacent spaces, such as between intravascular and extravascular spaces. When there is a disruption of the blood-brain barrier, as is frequently the case with brain tumors, a contrast agent leaks out of the vasculature, resulting in additional T1, T2 and T*2 relaxation effects in the extravascular space, thereby affecting the signal intensity time course and reducing the reliability of the computed hemodynamic parameters. In this study, a theoretical model describing these dynamic intra- and extravascular T1, T2 and T*2 relaxation interactions is proposed. The applicability of using the proposed model to investigate the influence of relevant MRI pulse sequences (e.g. echo time, flip angle), and physical (e.g. susceptibility calibration factors, pre-contrast relaxation rates) and physiological parameters (e.g. permeability, blood flow, compartmental volume fractions) on DSC-MRI signal time curves is demonstrated. Such a model could yield important insights into the biophysical basis of contrast-agent-extravasastion-induced effects on measured DSC-MRI signals and provide a means to investigate pulse sequence optimization and appropriate data analysis methods for the extraction of physiologically relevant imaging metrics.

  5. Inflammation-associated alterations to the intestinal microbiota reduce colonization resistance against non-typhoidal Salmonella during concurrent malaria parasite infection.

    PubMed

    Mooney, Jason P; Lokken, Kristen L; Byndloss, Mariana X; George, Michael D; Velazquez, Eric M; Faber, Franziska; Butler, Brian P; Walker, Gregory T; Ali, Mohamed M; Potts, Rashaun; Tiffany, Caitlin; Ahmer, Brian M M; Luckhart, Shirley; Tsolis, Renée M

    2015-10-05

    Childhood malaria is a risk factor for disseminated infections with non-typhoidal Salmonella (NTS) in sub-Saharan Africa. While hemolytic anemia and an altered cytokine environment have been implicated in increased susceptibility to NTS, it is not known whether malaria affects resistance to intestinal colonization with NTS. To address this question, we utilized a murine model of co-infection. Infection of mice with Plasmodium yoelii elicited infiltration of inflammatory macrophages and T cells into the intestinal mucosa and increased expression of inflammatory cytokines. These mucosal responses were also observed in germ-free mice, showing that they are independent of the resident microbiota. Remarkably, P. yoelii infection reduced colonization resistance of mice against S. enterica serotype Typhimurium. Further, 16S rRNA sequence analysis of the intestinal microbiota revealed marked changes in the community structure. Shifts in the microbiota increased susceptibility to intestinal colonization by S. Typhimurium, as demonstrated by microbiota reconstitution of germ-free mice. These results show that P. yoelii infection, via alterations to the microbial community in the intestine, decreases resistance to intestinal colonization with NTS. Further they raise the possibility that decreased colonization resistance may synergize with effects of malaria on systemic immunity to increase susceptibility to disseminated NTS infections.

  6. Inflammation-associated alterations to the intestinal microbiota reduce colonization resistance against non-typhoidal Salmonella during concurrent malaria parasite infection

    PubMed Central

    Mooney, Jason P.; Lokken, Kristen L.; Byndloss, Mariana X.; George, Michael D.; Velazquez, Eric M.; Faber, Franziska; Butler, Brian P.; Walker, Gregory T.; Ali, Mohamed M.; Potts, Rashaun; Tiffany, Caitlin; Ahmer, Brian M. M.; Luckhart, Shirley; Tsolis, Renée M.

    2015-01-01

    Childhood malaria is a risk factor for disseminated infections with non-typhoidal Salmonella (NTS) in sub-Saharan Africa. While hemolytic anemia and an altered cytokine environment have been implicated in increased susceptibility to NTS, it is not known whether malaria affects resistance to intestinal colonization with NTS. To address this question, we utilized a murine model of co-infection. Infection of mice with Plasmodium yoelii elicited infiltration of inflammatory macrophages and T cells into the intestinal mucosa and increased expression of inflammatory cytokines. These mucosal responses were also observed in germ-free mice, showing that they are independent of the resident microbiota. Remarkably, P. yoelii infection reduced colonization resistance of mice against S. enterica serotype Typhimurium. Further, 16S rRNA sequence analysis of the intestinal microbiota revealed marked changes in the community structure. Shifts in the microbiota increased susceptibility to intestinal colonization by S. Typhimurium, as demonstrated by microbiota reconstitution of germ-free mice. These results show that P. yoelii infection, via alterations to the microbial community in the intestine, decreases resistance to intestinal colonization with NTS. Further they raise the possibility that decreased colonization resistance may synergize with effects of malaria on systemic immunity to increase susceptibility to disseminated NTS infections. PMID:26434367

  7. TRAF3IP2 gene and systemic lupus erythematosus: association with disease susceptibility and pericarditis development.

    PubMed

    Perricone, Carlo; Ciccacci, Cinzia; Ceccarelli, Fulvia; Di Fusco, Davide; Spinelli, Francesca Romana; Cipriano, Enrica; Novelli, Giuseppe; Valesini, Guido; Conti, Fabrizio; Borgiani, Paola

    2013-10-01

    Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease. Although genetic factors confer susceptibility to the disease, only 15 % of the genetic contribution has been identified. TRAF3IP2 gene, associated with susceptibility to psoriatic arthritis and psoriasis, encodes for Act1, a negative regulator of adaptive immunity and a positive signaling adaptor in IL-17-mediated immune responses. The aim of this study was to assess the role of TRAF3IP2 gene variability in SLE susceptibility and disease phenotype in an Italian population. Two hundred thirty-nine consecutive SLE patients were enrolled. Study protocol included complete physical examination; the clinical and laboratory data were collected. Two hundred seventy-eight age- and ethnicity-matched healthy subjects served as controls. TRAF3IP2 polymorphisms (rs33980500, rs13190932, and rs13193677) were analyzed in both cases and controls. Genotype analysis was performed by allelic discrimination assays. A case-control association study and a genotype-phenotype correlation were performed. The rs33980500 and rs13193677 resulted significantly associated with SLE susceptibility (P = 0.021, odds ratio (OR) = 1.71, and P = 0.046, OR = 1.73, respectively). All three TRAF3IP2 single nucleotide polymorphisms resulted associated with the development of pericarditis; in particular, rs33980500 showed the strongest association (P = 0.002, OR 2.59). This association was further highlighted by binary logistic regression analysis. In conclusion, our data show for the first time the contribution of TRAF3IP2 genetic variability in SLE susceptibility, providing further suggestions that common variation in genes that function in the adaptive and innate arms of the immune system are important in establishing SLE risk. Our study also shows that this gene may affect disease phenotype and, particularly, the occurrence of pericarditis.

  8. Expression-associated polymorphisms of CAV1-CAV2 affect intraocular pressure and high-tension glaucoma risk

    PubMed Central

    Kim, Sewon; Kim, Kyunglan; Heo, Dong Won; Kim, Jong-Sung; Park, Chan Kee; Kim, Chang-sik

    2015-01-01

    Purpose The human CAV1-CAV2 locus has been associated with susceptibility to primary open-angle glaucoma in four studies of Caucasian, Chinese, and Pakistani populations, although not in several other studies of non-Korean populations. In this study with Korean participants, the CAV1-CAV2 locus was investigated for associations with susceptibility to primary open-angle glaucoma accompanied by elevated intraocular pressure (IOP), namely, high-tension glaucoma (HTG), as well as with IOP elevation, which is a strong risk factor for glaucoma. Methods Two single nucleotide polymorphisms (SNPs) were genotyped in 1,161 Korean participants including 229 patients with HTG and 932 healthy controls and statistically examined for association with HTG susceptibility and IOP. One SNP was rs4236601 G>A, which had been reported in the original study, and the other SNP was rs17588172 T>G, which was perfectly correlated (r2=1) with another reported SNP rs1052990. Expression quantitative trait loci (eQTL) analysis was performed using GENe Expression VARiation (Genevar) data. Results Both SNPs were associated with HTG susceptibility, but the rs4236601 association disappeared when adjusted for the rs17588172 genotype and not vice versa. The minor allele G of rs17588172 was associated significantly with 1.5-fold increased susceptibility to HTG (p=0.0069) and marginally with IOP elevation (p=0.043) versus the major allele T. This minor allele was also associated with decreased CAV1 and CAV2 mRNA in skin and adipose according to the Genevar eQTL analysis. Conclusions The minor allele G of rs17588172 in the CAV1-CAV2 locus is associated with decreased expression of CAV1 and CAV2 in some tissues, marginally with IOP elevation, and consequently with increased susceptibility to HTG. PMID:26015768

  9. Community acquired pneumonia: genetic variants influencing systemic inflammation.

    PubMed

    Ferrer Agüero, J M; Millán, S; Rodríguez de Castro, F; Martín-Loeches, I; Solé Violán, J

    2014-01-01

    The inflammatory response depends on several factors, including pathogenicity and duration of the stimulus, and also on the balance between inflammatory and antiinflammatory response. Several studies have presented evidence of the importance of genetic factors in severe infections. The innate immune response prevents the invasion and spread of pathogens during the first hours after infection. Each of the different processes involved in innate immunity may be affected by genetic polymorphisms, which can result in susceptibility or resistance to infection. The results obtained in the different studies do not irrefutably prove the role or function of a gene in the pathogenesis of respiratory infections. However, they can generate new hypotheses, suggest new candidate genes based on their role in the inflammatory response, and constitute a first step in understanding the underlying genetic factors. Copyright © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.

  10. Personalized nutrition and obesity.

    PubMed

    Qi, Lu

    2014-08-01

    The past few decades have witnessed a rapid rise in nutrition-related disorders such as obesity in the United States and over the world. Traditional nutrition research has associated various foods and nutrients with obesity. Recent advances in genomics have led to identification of the genetic variants determining body weight and related dietary factors such as intakes of energy and macronutrients. In addition, compelling evidence has lent support to interactions between genetic variations and dietary factors in relation to obesity and weight change. Moreover, recently emerging data from other 'omics' studies such as epigenomics and metabolomics suggest that more complex interplays between the global features of human body and dietary factors may exist at multiple tiers in affecting individuals' susceptibility to obesity; and a concept of 'personalized nutrition' has been proposed to integrate this novel knowledge with traditional nutrition research, with the hope ultimately to endorse person-centric diet intervention to mitigate obesity and related disorders.

  11. Personalized nutrition and obesity

    PubMed Central

    Qi, Lu

    2017-01-01

    The past few decades have witnessed a rapid rise in nutrition-related disorders such as obesity in the United States and over the world. Traditional nutrition research has associated various foods and nutrients with obesity. Recent advances in genomics have led to identification of the genetic variants determining body weight and related dietary factors such as intakes of energy and macronutrients. In addition, compelling evidence has lent support to interactions between genetic variations and dietary factors in relation to obesity and weight change. Moreover, recently emerging data from other ‘omics’ studies such as epigenomics and metabolomics suggest that more complex interplays between the global features of human body and dietary factors may exist at multiple tiers in affecting individuals’ susceptibility to obesity; and a concept of ‘personalized nutrition’ has been proposed to integrate this novel knowledge with traditional nutrition research, with the hope ultimately to endorse person-centric diet intervention to mitigate obesity and related disorders. PMID:24716734

  12. Genetics of Alcoholism.

    PubMed

    Zhu, Ena C; Soundy, Timothy J; Hu, Yueshan

    2017-05-01

    Consuming excessive amounts of alcohol has the potential to modify an individual's brain and lead to alcohol dependence. Alcohol use leads to 88,000 deaths every year in the U.S. alone and can lead to other health issues including cancers, such as colorectal cancer, and mental health problems. While drinking behavior varies due to environmental factors, genetic factors also contribute to the risk of alcoholism. Certain genes affecting alcohol metabolism and neurotransmitters have been found to contribute to or inhibit the risk. Geneenvironment interactions may also play a role in the susceptibility of alcoholism. With a better understanding of the different components that can contribute to alcoholism, more personalized treatment could cater to the individual. This review discusses the major genetic factors and some small variants in other genes that contribute to alcoholism, as well as considers the gene-environmental interactions. Copyright© South Dakota State Medical Association.

  13. Assessments on landslide susceptibility in the Tseng-wen reservoir watershed, Taiwan

    NASA Astrophysics Data System (ADS)

    Chen, Yu-Chin; Chen, Yung-Chau; Chen, Wen-Fu

    2014-05-01

    Typhoon Morakot under the strong influence of southwestern monsoon wind struck Taiwan on 8 August 2009, and dumped record-breaking rains in southern Taiwan. It triggered enormous landslides in mountains and severe flooding in low-lying areas. In addition, it destroyed or damaged houses, agricultural fields, roads, bridges, and other infrastructure facilities, causing massive economic loss and, more tragically, human casualties. In order to evaluate landslide hazard and risk assessment, it is important to understand the potential sites of landslide and their spatial distribution. Multi-temporal satellite images and geo-spatial data are used to build landslide susceptibility map for the post-disaster in the Tseng-wen reservoir watershed in this research. Elevation, slope, aspect, NDVI (normalized differential vegetation index), relief, roughness, distance to river, and distance to road are the considered factors for estimating landslide susceptibility. Maximum hourly rainfall and total rainfall, accompanied with typhoon event, are selected as the trigger factors of landslide events. Logistic regression analysis is adopted as the statistical method to model landslide susceptibility. The assessed susceptibility is represented in 4 levels which are high, high-intermediate, intermediate, and low level, respectively. Landslide spatial distribution can be depicted as a landslide susceptibility map with respect to each considered influence factors for a specified susceptible level. The landslide areas are about 358 ha and 1,485 ha before and after typhoon Morakot. The new landslide area, induced by typhoon Morakot, is as almost 4 times as the landslide area before typhoon Morakot. In addition, there is about 44.56% landslide area elevation ranging from 500m to 1000m and about 57.22% average slope ranging from 30° to 45° of landslide area. Furthermore, the devastating landslides were happened at those sites close to rivers, exposed area, and area with big land cover change (high human development). Among considered factors, slope, distance to river, NDVI, and maximum hourly rainfall are the major influence factors for landslide susceptibility. The results show that the accuracy of predicted landslide area is 74.74% and AUC is 0.82 corresponding to typhoon Morakot. Comparing model predicted with actual landslide areas, it shows that the predicted accuracy is 93% for high or high-intermediate level landslide area. It suggests that a landslide susceptibility map, depicted by this assessment model, is applicable on landslide prediction.

  14. Risk factors for persisting measles susceptibility: a case-control study among unvaccinated orthodox Protestants.

    PubMed

    de Munter, Anne C; Tostmann, Alma; Hahné, Susan J M; Spaan, D Henri; van Ginkel, Rijk; Ruijs, Wilhelmina L M

    2018-04-30

    Measles is an infectious disease providing lifelong immunity. Epidemics periodically occur among unvaccinated orthodox Protestants in the Netherlands. During the 2013/2014 epidemic, 17% of the reported patients was over 14 years old. Apparently, they did not catch measles during the previous 1999/2000 epidemic and remained susceptible. We wanted to identify risk factors for this so-called persisting measles susceptibility, and thus risk factors for acquiring measles at older age with increased risk of complications. A case-control study was performed among unvaccinated orthodox Protestants born between 1988 and 1998; cases had measles in 2013/2014, controls during or before 1999/2000. Associations between demographic, geographical and religion-related determinants and persisting measles susceptibility were determined using univariate and multivariable logistic regression. Analyses were stratified in two age-groups: infants/toddlers and primary school-aged children during the 1999/2000 measles epidemic. In total, 204 cases and 563 controls were included. Risk factors for persisting measles susceptibility for infants/toddlers in 1999/2000 were belonging to a moderately conservative church, absence of older siblings and residency outside low vaccination coverage (LVC)-municipalities. Risk factors for primary school-aged children were residency outside LVC-municipalities and attendance of non-orthodox Protestant primary school. Unvaccinated orthodox Protestant adolescents and adults who resided outside the LVC-municipalities, did not attend an orthodox Protestant primary school, had no older siblings and belonged to a moderately conservative church were at risk for persisting measles susceptibility and, thus, for acquiring measles at older age with increased risk of complications. For this subgroup of orthodox Protestants targeted information on vaccination is recommended.

  15. Cardiovascular disease risk factors and the perception of general health among male law enforcement officers: encouraging behavioral change.

    PubMed

    Ramey, Sandra L

    2003-05-01

    The relationship among cardiovascular disease (CVD) morbidity, risk factors (including stress), and the perception of health among male law enforcement officers (LEOs) compared to men in the general population were examined in this study. Self reported prevalence of CVD and CVD risk factors among currently employed male LEOs from nine states (n = 2,818) were compared to those of other men in the same states (n = 9,650 for CVD risk factors, n = 3,147 for CVD prevalence). Perceived stress in LEOs was assessed to determine if it affected the relationship between CVD prevalence and CVD risk factors. Cross tabulated simple percentages showed CVD was less prevalent in the LEO group than among the general population. The best predictor variables for CVD were perceived stress, time in the profession, and hypertension. The LEO group had greater prevalence of hypercholesterolemia, overweight, and tobacco use than the general population. However, a greater percentage of LEOs perceived their health as "good to excellent" compared to men in the general population. Using multivariate analysis of variance (MANOVA) it was determined that perceived stress was associated with CVD in the LEO group and three CVD risk factors (i.e., cholesterol, hypertension, physical activity) were significantly affected by perceived stress. Among susceptible officers, stress may contribute to CVD development as well as potentiate several CVD risk factors. However, an apparent lack of association exists between perception of general health and CVD risk in LEOs.

  16. A Novel Technique for Performing PID Susceptibility Screening during the Solar Cell Fabrication Process

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Oh, Jaewon; Dahal, Som; Dauksher, Bill

    2016-11-21

    Various characterization techniques have historically been developed in order to screen potential induced degradation (PID)-susceptible cells, but those techniques require final solar cells. We present a new characterization technique for screening PID-susceptible cells during the cell fabrication process. Illuminated Lock-In Thermography (ILIT) was used to image PID shunting of the cell without metallization and clearly showed PID-affected areas. PID-susceptible cells can be screened by ILIT, and the sample structure can advantageously be simplified as long as the sample has the silicon nitride antireflection coating and an aluminum back surface field.

  17. Landslide Susceptibility Analysis by the comparison and integration of Random Forest and Logistic Regression methods; application to the disaster of Nova Friburgo - Rio de Janeiro, Brasil (January 2011)

    NASA Astrophysics Data System (ADS)

    Esposito, Carlo; Barra, Anna; Evans, Stephen G.; Scarascia Mugnozza, Gabriele; Delaney, Keith

    2014-05-01

    The study of landslide susceptibility by multivariate statistical methods is based on finding a quantitative relationship between controlling factors and landslide occurrence. Such studies have become popular in the last few decades thanks to the development of geographic information systems (GIS) software and the related improved data management. In this work we applied a statistical approach to an area of high landslide susceptibility mainly due to its tropical climate and geological-geomorphological setting. The study area is located in the south-east region of Brazil that has frequently been affected by flood and landslide hazard, especially because of heavy rainfall events during the summer season. In this work we studied a disastrous event that occurred on January 11th and 12th of 2011, which involved Região Serrana (the mountainous region of Rio de Janeiro State) and caused more than 5000 landslides and at least 904 deaths. In order to produce susceptibility maps, we focused our attention on an area of 93,6 km2 that includes Nova Friburgo city. We utilized two different multivariate statistic methods: Logistic Regression (LR), already widely used in applied geosciences, and Random Forest (RF), which has only recently been applied to landslide susceptibility analysis. With reference to each mapping unit, the first method (LR) results in a probability of landslide occurrence, while the second one (RF) gives a prediction in terms of % of area susceptible to slope failure. With this aim in mind, a landslide inventory map (related to the studied event) has been drawn up through analyses of high-resolution GeoEye satellite images, in a GIS environment. Data layers of 11 causative factors have been created and processed in order to be used as continuous numerical or discrete categorical variables in statistical analysis. In particular, the logistic regression method has frequent difficulties in managing numerical continuous and discrete categorical variables together; therefore in our work we tried different methods to process categorical variables , until we obtained a statistically significant model. The outcomes of the two statistical methods (RF and LR) have been tested with a spatial validation and gave us two susceptibility maps. The significance of the models is quantified in terms of Area Under ROC Curve (AUC resulted in 0.81 for RF model and in 0.72 for LR model). In the first instance, a graphical comparison of the two methods shows a good correspondence between them. Further, we integrated results in a unique susceptibility map which maintains both information of probability of occurrence and % of area of landslide detachment, resulting from LR and RF respectively. In fact, in view of a landslide susceptibility classification of the study area, the former is less accurate but gives easily classifiable results, while the latter is more accurate but the results can be only subjectively classified. The obtained "integrated" susceptibility map preserves information about the probability that a given % of area could fail for each mapping unit.

  18. Individual Differences in Susceptibility to Inattentional Blindness

    ERIC Educational Resources Information Center

    Seegmiller, Janelle K.; Watson, Jason M.; Strayer, David L.

    2011-01-01

    Inattentional blindness refers to the finding that people do not always see what appears in their gaze. Though inattentional blindness affects large percentages of people, it is unclear if there are individual differences in susceptibility. The present study addressed whether individual differences in attentional control, as reflected by…

  19. Influence of Some Hypnotist and Subject Variables on Hypnotic Susceptibility

    ERIC Educational Resources Information Center

    Greenberg, Robert P.; Land, Jay M.

    1971-01-01

    As predicted, subjects run by the objectively warmer, more competent appearing hypnosis obtained significantly higher susceptibility scores. Structured warmth produced significant differences only in subjects run by the objectively less warm hypnotists. Both structured warmth and experience affected subjects' subjective impressions of whether they…

  20. Isolation method (direct plating or enrichment) does not affect antimicrobial susceptibility of Campylobacter from chicken carcasses

    USDA-ARS?s Scientific Manuscript database

    To determine if Campylobacter isolation method influenced antimicrobial susceptibility results, the minimum inhibitory concentrations (MIC) of nine antimicrobials were compared for 291 pairs of Campylobacter isolates recovered from chicken carcass rinse samples using direct plating and an enrichment...

  1. A qualitative study of factors affecting mental health amongst low-income working mothers in Bangalore, India.

    PubMed

    Travasso, Sandra Mary; Rajaraman, Divya; Heymann, Sally Jody

    2014-02-07

    Low-income urban working mothers face many challenges in their domestic, environmental, and working conditions that may affect their mental health. In India, a high prevalence of mental health disorders has been recorded in young women, but there has been little research to examine the factors that affect their mental health at home and work. Through a primarily qualitative approach, we studied the relationship between work, caring for family, spousal support, stress relief strategies and mental health amongst forty eight low-income working mothers residing in urban slums across Bangalore, India. Participants were construction workers, domestic workers, factory workers and fruit and vegetable street vendors. Qualitative data analysis themes included state of mental health, factors that affected mental health positively or negatively, manifestations and consequences of stress and depression, and stress mitigators. Even in our small sample of women, we found evidence of extreme depression, including suicidal ideation and attempted suicide. Women who have an alcoholic and/or abusive husband, experience intimate partner violence, are raising children with special needs, and lack adequate support for child care appear to be more susceptible to severe and prolonged periods of depression and suicide attempts. Factors that pointed towards reduced anxiety and depression were social support from family, friends and colleagues and fulfilment from work. This qualitative study raises concerns that low-income working mothers in urban areas in India are at high risk for depression, and identifies common factors that create and mitigate stress in this population group. We discuss implications of the findings for supporting the mental health of urban working women in the Indian context. The development of the national mental health policy in India and its subsequent implementation should draw on existing research documenting factors associated with negative mental health amongst specific population groups in order to ensure greater impact.

  2. A qualitative study of factors affecting mental health amongst low-income working mothers in Bangalore, India

    PubMed Central

    2014-01-01

    Background Low-income urban working mothers face many challenges in their domestic, environmental, and working conditions that may affect their mental health. In India, a high prevalence of mental health disorders has been recorded in young women, but there has been little research to examine the factors that affect their mental health at home and work. Methods Through a primarily qualitative approach, we studied the relationship between work, caring for family, spousal support, stress relief strategies and mental health amongst forty eight low-income working mothers residing in urban slums across Bangalore, India. Participants were construction workers, domestic workers, factory workers and fruit and vegetable street vendors. Qualitative data analysis themes included state of mental health, factors that affected mental health positively or negatively, manifestations and consequences of stress and depression, and stress mitigators. Results Even in our small sample of women, we found evidence of extreme depression, including suicidal ideation and attempted suicide. Women who have an alcoholic and/or abusive husband, experience intimate partner violence, are raising children with special needs, and lack adequate support for child care appear to be more susceptible to severe and prolonged periods of depression and suicide attempts. Factors that pointed towards reduced anxiety and depression were social support from family, friends and colleagues and fulfilment from work. Conclusion This qualitative study raises concerns that low-income working mothers in urban areas in India are at high risk for depression, and identifies common factors that create and mitigate stress in this population group. We discuss implications of the findings for supporting the mental health of urban working women in the Indian context. The development of the national mental health policy in India and its subsequent implementation should draw on existing research documenting factors associated with negative mental health amongst specific population groups in order to ensure greater impact. PMID:24502531

  3. Modeling and analyzing malware propagation in social networks with heterogeneous infection rates

    NASA Astrophysics Data System (ADS)

    Jia, Peng; Liu, Jiayong; Fang, Yong; Liu, Liang; Liu, Luping

    2018-10-01

    With the rapid development of social networks, hackers begin to try to spread malware more widely by utilizing various kinds of social networks. Thus, studying malware epidemic dynamics in these networks is becoming a popular subject in the literature. Most of the previous works focus on the effects of factors, such as network topology and user behavior, on malware propagation. Some researchers try to analyze the heterogeneity of infection rates, but the common problem of their works is the factors they mentioned that could affect the heterogeneity are not comprehensive enough. In this paper, focusing on the effects of heterogeneous infection rates, we propose a novel model called HSID (heterogeneous-susceptible-infectious-dormant model) to characterize virus propagation in social networks, in which a connection factor is presented to evaluate the heterogeneous relationships between nodes, and a resistance factor is introduced to represent node's mutable resistant ability. We analyzed how key parameters in the two factors affect the heterogeneity and then performed simulations to explore the effects in three real-world social networks. The results indicate: heterogeneous relationship could lead to wider diffusion in directed network, and heterogeneous security awareness could lead to wider diffusion in both directed and undirected networks; heterogeneous relationship could restrain the outbreak of malware but heterogeneous initial security awareness would increase the probability; furthermore, the increasing resistibility along with infected times would lead to malware's disappearance in social networks.

  4. Moisture and vegetation controls on decadal-scale accrual of soil organic carbon and total nitrogen in restored grasslands

    USGS Publications Warehouse

    O'Brien, S. L.; Jastrow, J.D.; Grimley, D.A.; Gonzalez-Meler, M. A.

    2010-01-01

    Revitalization of degraded landscapes may provide sinks for rising atmospheric CO2, especially in reconstructed prairies where substantial belowground productivity is coupled with large soil organic carbon (SOC) deficits after many decades of cultivation. The restoration process also provides opportunities to study the often-elusive factors that regulate soil processes. Although the precise mechanisms that govern the rate of SOC accrual are unclear, factors such as soil moisture or vegetation type may influence the net accrual rate by affecting the balance between organic matter inputs and decomposition. A resampling approach was used to assess the control that soil moisture and plant community type each exert on SOC and total nitrogen (TN) accumulation in restored grasslands. Five plots that varied in drainage were sampled at least four times over two decades to assess SOC, TN, and C4- and C3-derived C. We found that higher long-term soil moisture, characterized by low soil magnetic susceptibility, promoted SOC and TN accrual, with twice the SOC and three times the TN gain in seasonally saturated prairies compared with mesic prairies. Vegetation also influenced SOC and TN recovery, as accrual was faster in the prairies compared with C3-only grassland, and C4-derived C accrual correlated strongly to total SOC accrual but C3-C did not. High SOC accumulation at the surface (0-10 cm) combined with losses at depth (10-20 cm) suggested these soils are recovering the highly stratified profiles typical of remnant prairies. Our results suggest that local hydrology and plant community are critical drivers of SOC and TN recovery in restored grasslands. Because these factors and the way they affect SOC are susceptible to modification by climate change, we contend that predictions of the C-sequestration performance of restored grasslands must account for projected climatic changes on both soil moisture and the seasonal productivity of C4 and C3 plants. ?? 2009 Blackwell Publishing Ltd.

  5. Niemann-Pick Type C2 Protein Regulates Free Cholesterol Accumulation and Influences Hepatic Stellate Cell Proliferation and Mitochondrial Respiration Function.

    PubMed

    Wang, Yuan-Hsi; Twu, Yuh-Ching; Wang, Chung-Kwe; Lin, Fu-Zhen; Lee, Chun-Ya; Liao, Yi-Jen

    2018-06-05

    Liver fibrosis is the first step toward the progression to cirrhosis, portal hypertension, and hepatocellular carcinoma. A high-cholesterol diet is associated with liver fibrosis via the accumulation of free cholesterol in hepatic stellate cells (HSCs). Niemann-Pick type C2 (NPC2) plays an important role in the regulation of intracellular free cholesterol homeostasis via direct binding with free cholesterol. Previously, we reported that NPC2 was downregulated in liver cirrhosis tissues. Loss of NPC2 enhanced the accumulation of free cholesterol in HSCs and made them more susceptible to transforming growth factor (TGF)-β1. In this study, we showed that knockdown of NPC2 resulted in marked increases in platelet-derived growth factor BB (PDGF-BB)-induced HSC proliferation through enhanced extracellular signal-regulated kinases (ERK), p38, c-Jun N-terminal kinases (JNK), and protein kinase B (AKT) phosphorylation. In contrast, NPC2 overexpression decreased PDGF-BB-induced cell proliferation by inhibiting p38, JNK, and AKT phosphorylation. Although NPC2 expression did not affect caspase-related apoptosis, the autophagy marker light chain 3β (LC3B) was decreased in NPC2 knockdown, and free cholesterol accumulated in the HSCs. The mitochondrial respiration functions (such as oxygen consumption rate, ATP production, and maximal respiratory capacity) were decreased in NPC2 knockdown, and free cholesterol accumulated in the HSCs, while NPC2-overexpressed cells remained normal. In addition, NPC2 expression did not affect the susceptibility of HSCs to lipopolysaccharides (LPS), and U18666A treatment induced free cholesterol accumulation, which enhanced LPS-induced Toll-like receptor 4 (TLR4), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 phosphorylation, interleukin (IL)-1 and IL-6 expression. Our study demonstrated that NPC2-mediated free cholesterol homeostasis controls HSC proliferation and mitochondrial function.

  6. Mannan-binding lectin (MBL) gene polymorphisms in ulcerative colitis and Crohn's disease.

    PubMed

    Rector, A; Lemey, P; Laffut, W; Keyaerts, E; Struyf, F; Wollants, E; Vermeire, S; Rutgeerts, P; Van Ranst, M

    2001-10-01

    The inflammatory bowel diseases (IBD), Crohn's disease (CD), and ulcerative colitis (UC), are complex multifactorial traits involving both environmental and genetic factors. Mannan-binding lectin (MBL) plays an important role in non-specific immunity and complement activation. Point mutations in codons 52, 54 and 57 of exon 1 of the MBL gene are associated with decreased MBL plasma concentrations and increased susceptibility to various infectious diseases. If these MBL mutations could lead to susceptibility to putative IBD-etiological microbial agents, or could temper the complement-mediated mucosal damage in IBD, MBL could function as the link between certain microbial, immunological and genetic factors in IBD. In this study, we investigated the presence of the codon 52, 54 and 57 mutations of the MBL gene in 431 unrelated IBD patients, 112 affected and 141 unaffected first-degree relatives, and 308 healthy control individuals. In the group of sporadic IBD patients (n = 340), the frequency of the investigated MBL variants was significantly lower in UC patients when compared with CD patients (P = 0.01) and with controls (P = 0.02). These results suggest that MBL mutations which decrease the formation of functional MBL could protect against the clinical development of sporadic UC, but not of CD. This could be explained by the differential T-helper response in both diseases.

  7. Genetic variation in the vascular endothelial growth factor gene is associated with biliary atresia.

    PubMed

    Lee, Hung-Chang; Chang, Tzu-Yang; Yeung, Chun-Yan; Chan, Wai-Tao; Jiang, Chuen-Bin; Chen, Wei-Fang; Chan, Hui-Wen; Liu, Hsin-Fu; Lin, Marie; Lee, Yann-Jinn

    2010-02-01

    Biliary atresia (BA) is a chronic inflammatory disease of the bile ducts resulting in biliary cirrhosis. Vascular endothelial growth factor (VEGF) has been implicated in cell-mediated inflammatory reactions. We aimed to study the relationship between genetic variations of the VEGF gene and susceptibility to BA using both case-control and family-based methodologies. A total of 45 Taiwanese children with BA, 160 ethnically matched healthy controls, and 40 families (consisting of parents, affected children, and unaffected siblings) were studied. Three functional VEGF polymorphisms (-2578 A/C, -634 G/C, and +936 C/T) were assessed by using TaqMan assay. The +936 CC genotype [odds ratio (OR) 3.51, 95% confidence interval 1.54-8.01, P(c)=0.006] and C allele (OR 3.19, 95% confidence interval 1.48-6.90, P(c)=0.004) were significantly associated with increased risk of BA. The association of the +936 C allele with BA was also confirmed in a family-based association study (OR 5.7, chi2=9.8, P(c)=0.005). None of the haplotypes studied significantly influenced the risk to BA in either the case-control or family data sets. The VEGF +936 C/T polymorphism and particularly the C allele are associated with BA, possibly conferring increased susceptibility to the disease.

  8. GENOMIC IDENTIFICATION OF POTENTIAL RISK FACTORS DURING ACETAMINOPHEN-INDUCED LIVER DISEASE IN SUSCEPTIBLE AND RESISTANT STRAINS OF MICE

    EPA Science Inventory

    Drug-induced liver disease (DILD) continues to cause significant morbidity and mortality and impair new drug development. Mounting evidence suggests that DILD is a complex, multifactorial disease in which no one factor is likely to be an absolute indicator of susceptibility. As a...

  9. Cardiovascular Disease Susceptibility and Resistance in Circumpolar Inuit Populations.

    PubMed

    Tvermosegaard, Maria; Dahl-Petersen, Inger K; Nielsen, Nina Odgaard; Bjerregaard, Peter; Jørgensen, Marit Eika

    2015-09-01

    Cardiovascular disease (CVD) is a major public health issue in indigenous populations in the Arctic. These diseases have emerged concomitantly with profound social changes over the past 60 years. The aim of this study was to summarize the literature on CVD risk among Arctic Inuit. Literature on prevalence, incidence, and time trends for CVD and its risk factors in Arctic Inuit populations was reviewed. Most evidence supports a similar incidence of coronary heart disease and a higher incidence of cerebrovascular disease among Arctic Inuit than seen in western populations. Factors that may increase CVD risk include aging of the population, genetic susceptibility, and a rapid increase in obesity, diabetes, and hypertension in parallel with decreasing physical activity and deterioration of the lipid profile. In contrast, and of great importance, there has been a decrease in smoking and alcohol intake (at least documented in Greenland), and contaminant levels are declining. Although there have been marked socioeconomic and dietary changes, it remains unsolved and to some extent controversial how this may have influenced cardiovascular risk among Arctic Inuit. The increase in life expectancy, in combination with improved prognosis for patients with manifest CVD, will inevitably lead to a large increase in absolute numbers of individuals affected by CVD in Arctic Inuit populations, exacerbated by the rise in most CVD risk factors over the past decades. For preventive purposes and for health care planning, it is crucial to carefully monitor disease incidence and trends in risk factors in these vulnerable Arctic populations. Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  10. Genetic Factors Affecting Late-Onset Alzheimer's Disease Susceptibility.

    PubMed

    Rezazadeh, Maryam; Khorrami, Aziz; Yeghaneh, Tarlan; Talebi, Mahnaz; Kiani, Seyed Jalal; Heshmati, Yaser; Gharesouran, Jalal

    2016-03-01

    Alzheimer's disease is considered a progressive brain disease in the older population. Late-onset Alzheimer's disease (LOAD) as a multifactorial dementia has a polygenic inheritance. Age, environment, and lifestyle along with a growing number of genetic factors have been reported as risk factors for LOAD. Our aim was to present results of LOAD association studies that have been done in northwestern Iran, and we also explored possible interactions with apolipoprotein E (APOE) status. We re-evaluated the association of these markers in dominant, recessive, and additive models. In all, 160 LOAD and 163 healthy control subjects of Azeri Turkish ethnicity were studied. The Chi-square test with Yates' correction and Fisher's exact test were used for statistical analysis. A Bonferroni-corrected p value, based on the number of statistical tests, was considered significant. Our results confirmed that chemokine receptor type 2 (CCR2), estrogen receptor 1 (ESR1), toll-like receptor 2 (TLR2), tumor necrosis factor alpha (TNF α), APOE, bridging integrator 1 (BIN1), and phosphatidylinositol-binding clathrin assembly protein (PICALM) are LOAD susceptibility loci in Azeri Turk ancestry populations. Among them, variants of CCR2, ESR1, TNF α, and APOE revealed associations in three different genetic models. After adjusting for APOE, the association (both allelic and genotypic) with CCR2, BIN1, and ESRα (PvuII) was evident only among subjects without the APOE ε4, whereas the association with CCR5, without Bonferroni correction, was significant only among subjects carrying the APOE ε4 allele. This result is an evidence of a synergistic and antagonistic effect of APOE on variant associations with LOAD.

  11. Phenotype Overlap in Xylella fastidiosa Is Controlled by the Cyclic Di-GMP Phosphodiesterase Eal in Response to Antibiotic Exposure and Diffusible Signal Factor-Mediated Cell-Cell Signaling

    PubMed Central

    de Souza, Alessandra A.; Ionescu, Michael; Baccari, Clelia; da Silva, Aline M.

    2013-01-01

    Eal is an EAL domain protein in Xylella fastidiosa homologous to one involved in resistance to tobramycin in Pseudomonas aeruginosa. EAL and HD-GYP domain proteins are implicated in the hydrolysis of the secondary messenger bis-(3′-5′)-cyclic dimeric GMP (cyclic di-GMP). Cell density-dependent communication mediated by a Diffusible Signal Factor (DSF) also modulates cyclic di-GMP levels in X. fastidiosa, thereby controlling the expression of virulence genes and genes involved in insect transmission. The possible linkage of Eal to both extrinsic factors such as antibiotics and intrinsic factors such as quorum sensing, and whether both affect virulence, was thus addressed. Expression of eal was induced by subinhibitory concentrations of tobramycin, and an eal deletion mutant was more susceptible to this antibiotic than the wild-type strain and exhibited phenotypes similar to those of an rpfF deletion mutant blocked in DSF production, such as hypermotility, reduced biofilm formation, and hypervirulence to grape. Consistent with that, the rpfF mutant was more susceptible than the wild-type strain to tobramycin. Therefore, we propose that cell-cell communication and antibiotic stress can apparently lead to similar modulations of cyclic di-GMP in X. fastidiosa, resulting in similar phenotypes. However, the effect of cell density is dominant compared to that of antibiotic stress, since eal is suppressed by RpfF, which may prevent inappropriate behavioral changes in response to antibiotic stress when DSF accumulates. PMID:23542613

  12. Novel Gentic Variations Contributing to Asthma Susceptability in Saudi Arabia

    ClinicalTrials.gov

    2014-04-13

    Collection of Clinical Data That Will be Used in This Study and Will Form a Data Bank for Asthma in Saudi Arabia; Identify Known and NOVEL Genetic Risk Factors Contributing to Asthma Susceptibility; Study the Mechanistic Roles of the Genetic Variants Within Major Asthma Susceptibility Genes

  13. Nurses and Dietitians Differ in Food Safety Information Provided to Highly Susceptible Clients

    ERIC Educational Resources Information Center

    Buffer, Janet; Kendall, Patricia; Medeiros, Lydia; Schroeder, Mary; Sofos, John

    2013-01-01

    Objective: To determine content, education channels, and motivational factors that influence what health professionals teach about safe food handling to populations who are highly susceptible for foodborne illnesses. To assess the differences in information provided by health professionals to highly susceptible populations. Design: Descriptive,…

  14. A NATIONAL STUDY TO ASSESS SUSCEPTIBILITY, VULNERABILITY, AND EFFECT MODIFICATION OF AIR POLLUTION HEALTH RISKS

    EPA Science Inventory

    Identifying factors that explain heterogeneity of risks will help to identify: 1) the populations that are more susceptible/vulnerable to air pollution; and 2) the emission sources, pollutants and pollutant mixtures that are more toxic. The characterization of susceptibility f...

  15. Contrasting amino acid profiles among permissive and non-permissive hosts of Candidatus Liberibacter asiaticus, putative causal agent of Huanglongbing

    PubMed Central

    Alabi, Olufemi J.; Simpson, Catherine R.; Jifon, John L.

    2017-01-01

    Huanglongbing is a devastating disease of citrus. In this study, a comprehensive profile of phloem sap amino acids (AA) in four permissive host plants of Candidatus Liberibacter asiaticus (CLas) and three non-permissive Rutaceae plants was conducted to gain a better understanding of host factors that may promote or suppress the bacterium. The AA profiles of Diaphorina citri nymphs and adults were similarly analyzed. A total of 38 unique AAs were detected in phloem sap of the various plants and D. citri samples, with phloem sap of young shoots containing more AAs and at higher concentrations than their mature counterparts. All AAs detected in phloem sap of non-permissive plants were also present in CLas -permissive hosts plus additional AAs in the latter class of plants. However, the relative composition of 18 commonly shared AAs varied between CLas -permissive hosts and non-permissive plants. Multivariate analysis with a partial least square discriminant methodology revealed a total of 12 AAs as major factors affecting CLas host status, of which seven were positively related to CLas tolerance/resistance and five positively associated with CLas susceptibility. Most of the AAs positively associated with CLas susceptibility were predominantly of the glutamate family, notably stressed-induced AAs such as arginine, GABA and proline. In contrast, AAs positively correlated with CLas tolerance/resistance were mainly of the serine family. Further analysis revealed that whereas the relative proportions of AAs positively associated with CLas susceptibility did not vary with host developmental stages, those associated with CLas tolerance/resistance increased with flush shoot maturity. Significantly, the proline-to-glycine ratio was determined to be an important discriminating factor for CLas permissivity with higher values characteristic of CLas -permissive hosts. This ratio could be exploited as a biomarker in HLB-resistance breeding programs. PMID:29236706

  16. Susceptibility to varicella-zoster infection in individuals 1 to 29 years of age in Mexico.

    PubMed

    Alvarez y Muñoz, M T; Torres, J; Damasio-Santana, L; Gómez, A; Fernández-Quintanilla, G; Tapia-Conyer, R; Muñoz, O

    1999-01-01

    The prevalence of varicella zoster virus (VZV) infection has been poorly studied in Latin America. The aim of this work was to study the seroprevalence of antibody to VZV infection in Mexico. Infection was determined in 3,737 individuals. Samples were collected during a national serologic survey performed during 1987-1988 and represented individuals 1- to 29-years-old from all socioeconomic levels and from rural and urban communities throughout the country. Antibodies anti-VZV were measured with a commercially available enzyme-linked immunosorbent assay (VARELISA Merck, Germany). In the population studied, 464 individuals (12.4%) were seronegative or susceptible to infection, whereas about 17.0% of individuals 1- to 19-years-old were susceptible to infection. Between the ages of 20 to 24 years, 8.4% were susceptible and between 25 to 29 years, 5.0% of persons were still susceptible to infection. Socioeconomic level, density of population, crowding, and gender were not found as risk factors for susceptibility to VZV infection in adolescents and young adults. Low educational level was found as a risk factor for susceptibility. High proportions of adolescents and young adults in Mexico are susceptible to VZV infection and should receive special attention when designing vaccination programs.

  17. Determinants of physical activity in middle-aged woman in Isfahan using the health belief model.

    PubMed

    Hosseini, Habibollah; Moradi, Razieh; Kazemi, Ashraf; Shahshahani, Maryam Sadat

    2017-01-01

    Nowadays with respect to the automation of the lifestyle, immobility statistics in middle-aged women has increased and they are at risk for complications of immobility. One of the models used to identify factors associated with physical activity is Health Belief Model utilized in different age and different cultural backgrounds and different results have been obtained from those studies. The purpose of this study was to investigate the factors affecting on physical activity in middle-aged women using Health Belief Model. This descriptive-correlation study was conducted on 224 middle-aged women referring to health centers in Isfahan. Health Belief Model structures including perceived susceptibility and severity, perceived barriers and benefits, and self-efficacy were measured by questionnaire and physical activity was assessed using the international physical activity questionnaire. Collected data were analyzed using descriptive statistics and Pearson correlation coefficient test and regression analysis. There wasn't significant correlation between perceived susceptibility ( P = 0.263, r = 0.075) and perceived severity with physical activity duration ( P = 0.127, r = 0.058) but there was positive and weak correlation between physical activity duration with perceived benefits ( P = 0.001 and r = 0.26) and perceived self-efficacy ( P = 0.001, r = 0.54) and had weak and inverse correlation with perceived barriers ( P = 0.001, r = -0.25). Regression analysis also showed that from among all the Health Belief Model structures just self-efficacy structure has influenced on behavior independently and other structures are affected by it. The obtained results implied on a correlation between benefits, barriers and perceived self-efficacy with and moderate physical activity. Therefore it is necessary to develop appropriate educational programs with emphasis on structures of Health Belief Model that has the maximum impact on physical activity in middle-aged women.

  18. Noise sensitivity, rather than noise level, predicts the non-auditory effects of noise in community samples: a population-based survey.

    PubMed

    Park, Jangho; Chung, Seockhoon; Lee, Jiho; Sung, Joo Hyun; Cho, Seung Woo; Sim, Chang Sun

    2017-04-12

    Excessive noise affects human health and interferes with daily activities. Although environmental noise may not directly cause mental illness, it may accelerate and intensify the development of latent mental disorders. Noise sensitivity (NS) is considered a moderator of non-auditory noise effects. In the present study, we aimed to assess whether NS is associated with non-auditory effects. We recruited a community sample of 1836 residents residing in Ulsan and Seoul, South Korea. From July to November 2015, participants were interviewed regarding their demographic characteristics, socioeconomic status, medical history, and NS. The non-auditory effects of noise were assessed using the Center of Epidemiologic Studies Depression, Insomnia Severity index, State Trait Anxiety Inventory state subscale, and Stress Response Inventory-Modified Form. Individual noise levels were recorded from noise maps. A three-model multivariate logistic regression analysis was performed to identify factors that might affect psychiatric illnesses. Participants ranged in age from 19 to 91 years (mean: 47.0 ± 16.1 years), and 37.9% (n = 696) were male. Participants with high NS were more likely to have been diagnosed with diabetes and hyperlipidemia and to use psychiatric medication. The multivariable analysis indicated that even after adjusting for noise-related variables, sociodemographic factors, medical illness, and duration of residence, subjects in the high NS group were more than 2 times more likely to experience depression and insomnia and 1.9 times more likely to have anxiety, compared with those in the low NS group. Noise exposure level was not identified as an explanatory value. NS increases the susceptibility and hence moderates there actions of individuals to noise. NS, rather than noise itself, is associated with an elevated susceptibility to non-auditory effects.

  19. 4-aminobutyrate aminotransferase (ABAT): genetic and pharmacological evidence for an involvement in gastro esophageal reflux disease.

    PubMed

    Jirholt, Johan; Asling, Bengt; Hammond, Paul; Davidson, Geoffrey; Knutsson, Mikael; Walentinsson, Anna; Jensen, Jörgen M; Lehmann, Anders; Agreus, Lars; Lagerström-Fermer, Maria

    2011-04-28

    Gastro-esophageal reflux disease (GERD) is partly caused by genetic factors. The underlying susceptibility genes are currently unknown, with the exception of COL3A1. We used three independent GERD patient cohorts to identify GERD susceptibility genes. Thirty-six families, demonstrating dominant transmission of GERD were subjected to whole genome microsatellite genotyping and linkage analysis. Five linked regions were identified. Two families shared a linked region (LOD 3.9 and 2.0) on chromosome 16. We used two additional independent GERD patient cohorts, one consisting of 219 trios (affected child with parents) and the other an adult GERD case control cohort consisting of 256 cases and 485 controls, to validate individual genes in the linked region through association analysis. Sixty six single nucleotide polymorphism (SNP) markers distributed over the nine genes present in the linked region were genotyped in the independent GERD trio cohort. Transmission disequilibrium test analysis followed by multiple testing adjustments revealed a significant genetic association for one SNP located in an intron of the gene 4-aminobutyrate aminotransferase (ABAT) (P(adj) = 0.027). This association did not replicate in the adult case-control cohort, possibly due to the differences in ethnicity between the cohorts. Finally, using the selective ABAT inhibitor vigabatrin (γ-vinyl GABA) in a dog study, we were able to show a reduction of transient lower esophageal sphincter relaxations (TLESRs) by 57.3 ± 11.4 % (p = 0.007) and the reflux events from 3.1 ± 0.4 to 0.8 ± 0.4 (p = 0.007). Our results demonstrate the direct involvement of ABAT in pathways affecting lower esophageal sphincter (LES) control and identifies ABAT as a genetic risk factor for GERD.

  20. Chronic and catastrophic natural mortality of three common Caribbean reef corals

    NASA Astrophysics Data System (ADS)

    Bythell, J. C.; Gladfelter, E. H.; Bythell, M.

    1993-11-01

    Compared to catastrophic impacts from storms, disease epidemics and bleaching events, little is known about the effects of more routine chronic mortality in reef corals. To monitor this ongoing mortality, monthly visual assessments of the cause of tissue damage were related to mortality rates (changes in planar surface area) of tagged colonies of three common reef corals: Montastrea annularis, Porites astreoides and Diploria strigosa at Buck Island Reef National Monument, St. Croix, US Virgin Islands. During the study Hurricane Hugo, the most powerful cyclone to affect the area in at least 60 y, made a direct impact on the site. Effects of the hurricane were extremely localized, with certain exposed sites being almost completely razed while others showed no detectable changes in community structure. Mortality caused both by the hurricane and by other factors during the 26 month study varied between species and also between site locations around the island. Differences in susceptibility were not dependent solely on gross morphology, because two robust, massive species showed opposite responses to hurricane damage and chronic mortality. Diploria strigosa was virtually unaffected by chronic factors, but was heavily damaged at exposed sites during the hurricane. In contrast, mortality from predation and tissue necrosis was high in Montastrea annularis, but it largely escaped damage from the hurricane because it was absent from the most severely scoured locations. Porites astreoides, with populations dominated by much smaller colonies, was affected by both chronic and hurricanerelated mortality. Differences in susceptibility to the various types of natural disturbance among species, coupled with high spatial and temporal variability in the effects of such disturbances, may be critical to the maintenance of species diversity on the reef.

  1. Variants in Complement Factor H and Complement Factor H-Related Protein Genes, CFHR3 and CFHR1, Affect Complement Activation in IgA Nephropathy.

    PubMed

    Zhu, Li; Zhai, Ya-Ling; Wang, Feng-Mei; Hou, Ping; Lv, Ji-Cheng; Xu, Da-Min; Shi, Su-Fang; Liu, Li-Jun; Yu, Feng; Zhao, Ming-Hui; Novak, Jan; Gharavi, Ali G; Zhang, Hong

    2015-05-01

    Complement activation is common in patients with IgA nephropathy (IgAN) and associated with disease severity. Our recent genome-wide association study of IgAN identified susceptibility loci on 1q32 containing the complement regulatory protein-encoding genes CFH and CFHR1-5, with rs6677604 in CFH as the top single-nucleotide polymorphism and CFHR3-1 deletion (CFHR3-1∆) as the top signal for copy number variation. In this study, to explore the clinical effects of variation in CFH, CFHR3, and CFHR1 on IgAN susceptibility and progression, we enrolled two populations. Group 1 included 1178 subjects with IgAN and available genome-wide association study data. Group 2 included 365 subjects with IgAN and available clinical follow-up data. In group 1, rs6677604 was associated with mesangial C3 deposition by genotype-phenotype correlation analysis. In group 2, we detected a linkage between the rs6677604-A allele and CFHR3-1∆ and found that the rs6677604-A allele was associated with higher serum levels of CFH and lower levels of the complement activation split product C3a. Furthermore, CFH levels were positively associated with circulating C3 levels and negatively associated with mesangial C3 deposition. Moreover, serum levels of the pathogenic galactose-deficient glycoform of IgA1 were also associated with the degree of mesangial C3 deposition in patients with IgAN. Our findings suggest that genetic variants in CFH, CFHR3, and CFHR1 affect complement activation and thereby, predispose patients to develop IgAN. Copyright © 2015 by the American Society of Nephrology.

  2. Susceptibility and triggering scenarios at a regional scale for shallow landslides

    NASA Astrophysics Data System (ADS)

    Gullà, G.; Antronico, L.; Iaquinta, P.; Terranova, O.

    2008-07-01

    The work aims at identifying susceptible areas and pluviometric triggering scenarios at a regional scale in Calabria (Italy), with reference to shallow landsliding events. The proposed methodology follows a statistical approach and uses a database linked to a GIS that has been created to support the various steps of spatial data management and manipulation. The shallow landslide predisposing factors taken into account are derived from (i) the 40-m digital terrain model of the region, an ˜ 15,075 km 2 extension; (ii) outcropping lithology; (iii) soils; and (iv) land use. More precisely, a map of the slopes has been drawn from the digital terrain model. Two kinds of covers [prevalently coarse-grained (CG cover) or fine-grained (FG cover)] were identified, referring to the geotechnical characteristics of geomaterial covers and to the lithology map; soilscapes were drawn from soil maps; and finally, the land use map was employed without any prior processing. Subsequently, the inventory maps of some shallow landsliding events, totaling more than 30,000 instabilities of the past and detected by field surveys and photo aerial restitution, were employed to calibrate the relative importance of these predisposing factors. The use of single factors (first level analysis) therefore provides three different susceptibility maps. Second level analysis, however, enables better location of areas susceptible to shallow landsliding events by crossing the single susceptibility maps. On the basis of the susceptibility map obtained by the second level analysis, five different classes of susceptibility to shallow landsliding events have been outlined over the regional territory: 8.9% of the regional territory shows very high susceptibility, 14.3% high susceptibility, 15% moderate susceptibility, 3.6% low susceptibility, and finally, about 58% very low susceptibility. Finally, the maps of two significant shallow landsliding events of the past and their related rainfalls have been utilized to identify the relevant pluviometric triggering scenarios. By using 205 daily rainfall series, different triggering pluviometric scenarios have been identified with reference to CG and FG covers: a value of 365 mm of the total rainfall of the event and/or 170 mm/d of the rainfall maximum intensity and a value of 325 mm of the total rainfall of the event and/or 158 mm/d of the rainfall maximum intensity are able to trigger shallow landsliding events for CG and FG covers, respectively. The results obtained from this study can help administrative authorities to plan future development activities and mitigation measures in shallow landslide-prone areas. In addition, the proposed methodology can be useful in managing emergency situations at a regional scale for shallow landsliding events triggered by intense rainfalls; through this approach, the susceptibility and the pluviometric triggering scenario maps will be improved by means of finer calibration of the involved factors.

  3. The epidemiology of bovine respiratory disease: What is the evidence for predisposing factors?

    PubMed Central

    Taylor, Jared D.; Fulton, Robert W.; Lehenbauer, Terry W.; Step, Douglas L.; Confer, Anthony W.

    2010-01-01

    Bovine respiratory disease (BRD) is the most costly disease of beef cattle in North America. It is multi-factorial, with a variety of physical and physiological stressors combining to predispose cattle to pneumonia. However, efforts to discern which factors are most important have frequently failed to establish definitive answers. Calves are at highest risk shortly after transport. Risk factors include purchasing from sale barns and commingling. It is unclear whether or not these practices increase susceptibility, increase exposure, or are proxies for poor management. Lighter-weight calves appear to be at greater risk, although this has not been consistent. Persistent infection (PI) with bovine virus diarrhea virus increases BRD occurrence, but it is unclear if PI calves affect other cattle in the feedlot. The complexity of BRD has made it difficult to define involvement of individual factors. Stressors may play a role as “necessary but not sufficient” components, requiring additive effects to cause disease. PMID:21197200

  4. Back on the streets: Maturation and risk factors for recidivism among serious juvenile offenders.

    PubMed

    Leverso, John; Bielby, William; Hoelter, Lynette F

    2015-06-01

    This study examines how social and cognitive factors shape future criminal activity among serious juvenile offenders and assesses how adolescents' cognitive development affects the relative impact of those factors over time. The sample, from the Pathways to Desistance Study, is comprised of youth (aged 14-18 years) in the United States convicted of serious criminal offenses, and the outcome measure is self-reported crime. We rely on data collected when the youth were first interviewed (n = 1088) and 18-24 months later (n = 904). Logistic regression analyses reveal a strong relationship between impulsiveness and criminal behavior, regardless of age. Susceptibility to peer pressure and perceived risk that friends would be arrested were found to predict future criminal activity among younger adolescents, but have little impact at later ages. External factors such as amount of social support and gang membership have varying effects over time. Copyright © 2015 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  5. Retinopathy of prematurity: molecular pathology and therapeutic strategies.

    PubMed

    Mechoulam, Hadas; Pierce, Eric A

    2003-01-01

    Retinopathy of prematurity (ROP) is an ischemia-induced proliferative retinopathy, which affects premature infants with low birth weight. It is a leading cause of visual impairment and blindness in children, and shares pathophysiological characteristics with other common ocular diseases such as diabetic retinopathy, central vein occlusion, and age-related macular degeneration. Pathologically similar inherited diseases such as Norrie disease suggest a possible genetic component in the susceptibility to ROP. The process of retinal neovascularization in ROP and in animal models of oxygen-induced retinopathy is complex, and involves angiogenic factors, such as vascular endothelial growth factor, and basement membrane components. Potential medical therapies for ROP, including modulators of angiogenic factors, inhibitors of basement membrane changes, endogenous inhibitors such as pigment epithelium derived factor, and anti-inflammatory drugs, have shown efficacy against neovascularization in several animal models. Some of these therapies are in clinical trials now for diabetic retinopathy and age-related macular degeneration, and in the future may prove efficacious for the treatment of ROP.

  6. A comparison of non-typhoidal Salmonella from humans and food animals using pulsed-field gel electrophoresis and antimicrobial susceptibility patterns

    USDA-ARS?s Scientific Manuscript database

    Salmonellosis is one of the most important foodborne diseases affecting humans. To characterize the relationship between Salmonella causing human infections and their food animal reservoirs, we compared pulsed-field gel electrophoresis (PFGE) and antimicrobial susceptibility patterns of non-typhoida...

  7. Differential Susceptibility to Parenting and Quality Child Care

    ERIC Educational Resources Information Center

    Pluess, Michael; Belsky, Jay

    2010-01-01

    Research on differential susceptibility to rearing suggests that infants with difficult temperaments are disproportionately affected by parenting and child care quality, but a major U.S. child care study raises questions as to whether quality of care influences social adjustment. One thousand three hundred sixty-four American children from…

  8. Differential host susceptibility to Batrachochytrium dendrobatidis, an emerging amphibian pathogen

    Treesearch

    C.L. Searle; S.S. Gervasi; J. Hua; J.I. Hammond; R.A. Relyea; D.H. Olson; A.R. Blaustein

    2011-01-01

    The amphibian fungal pathogen Batrachochytrium dendrobatidis (Bd) has received considerable attention due to its role in amphibian population declines worldwide. Although many amphibian species appear to be affected by Bd, there is little information on species-specific differences in susceptibility to this pathogen. We used a comparative...

  9. Will all the trees fall? Variable resistance to an introduced forest disease in a highly susceptible host

    Treesearch

    K.J. Hayden; A. Nettel; R.S. Dodd; M. Garbelotto

    2011-01-01

    Although tanoak (Notholithocarpus densiflorus syn. Lithocarpus densiflorus) is the species most affected by the introduced pathogen Phytophthora ramorum, with demonstrable risk of extirpation, little is known about the origin, range or structuring of the tree's susceptibility. We examined variation in...

  10. Chronic Ethanol consumption modulates growth factor release, mucosal cytokine production and microRNA expression in nonhuman primates

    PubMed Central

    Asquith, Mark; Pasala, Sumana; Engelmann, Flora; Haberthur, Kristen; Meyer, Christine; Park, Byung; Grant, Kathleen A.; Messaoudi, Ilhem

    2013-01-01

    BACKGROUND Chronic alcohol consumption has been associated with enhanced susceptibility to both systemic and mucosal infections. However, the exact mechanisms underlying this enhanced susceptibility remain incompletely understood. METHODS Using a nonhuman primate model of ethanol self-administration, we examined the impact of chronic alcohol exposure on immune homeostasis, cytokine and growth factor production in peripheral blood, lung and intestinal mucosa following twelve months of chronic ethanol exposure. RESULTS Ethanol exposure inhibited activation-induced production of growth factors HGF, G-CSF and VEGF by peripheral blood mononuclear cells (PBMC). Moreover, ethanol significantly reduced the frequency of colonic Th1 and Th17 cells in a dose-dependent manner. In contrast, we did not observe differences in lymphocyte frequency or soluble factor production in the lung of ethanol-consuming animals. To uncover mechanisms underlying reduced growth factor and Th1/Th17 cytokine production, we compared expression levels of microRNAs in PBMC and intestinal mucosa. Our analysis revealed ethanol-dependent upregulation of distinct microRNAs in affected tissues (miR-181a and miR-221 in PBMC; miR-155 in colon). Moreover, we were able to detect reduced expression of the transcription factors STAT3 and ARNT, which regulate expression of VEGF, G-CSF and HGF and contain targets for these microRNAs. To confirm and extend these observations, PBMC were transfected with either mimics or antagomirs of miR181 and 221and protein levels of the transcription factors and growth factors were determined. Transfection of microRNA mimics led to a reduction in both STAT-3/ARNT as well as VEGF/HGF/G-CSF levels. The opposite outcome was observed when microRNA antagomirs were transfected CONCLUSION Chronic ethanol consumption significantly disrupts both peripheral and mucosal immune homeostasis, and this dysregulation may be mediated by changes in microRNA expression. PMID:24329418

  11. Genetic modification of risk assessment based on staging of preclinical type 1 diabetes in siblings of affected children.

    PubMed

    Mrena, S; Savola, K; Kulmala, P; Reijonen, H; Ilonen, J; Akerblom, H K; Knip, M

    2003-06-01

    We set out to study the association between human leukocyte antigen-defined genetic disease susceptibility and the stage of preclinical type 1 diabetes and whether genetic predisposition affects the natural course of preclinical diabetes in initially nondiabetic siblings of affected children. A total of 701 initially unaffected siblings were graded into four stages of preclinical type 1 diabetes based on the initial number of disease-associated autoantibodies detectable close to the time of diagnosis of the index case: no prediabetes (no antibodies), early (one antibody specificity), advanced (two antibodies), and late prediabetes (three or more antibodies). Another classification system covering 659 siblings was based on a combination of the initial number of antibodies and the first-phase insulin response (FPIR) to iv glucose: no prediabetes (no antibodies), early (one antibody specificity, normal FPIR), advanced (two or more antibodies, normal FPIR), and late prediabetes (at least one antibody, reduced FPIR). Genetic susceptibility to type 1 diabetes was defined by human leukocyte antigen identity and DR and DQ genotypes. There was a higher proportion of siblings with late prediabetes initially among those with strong genetic disease susceptibility than among those with decreased genetic predisposition (16.7% vs. 0.5%; P < 0.001 for DQB1 genotypes according to the first classification), whereas there was a higher proportion of siblings with no signs of prediabetes among those with genotypes conferring decreased risk (91.2% vs. 70.4% among those with high-risk DQB1 genotypes; P < 0.001 according to the first classification). Autoantibodies alone were more sensitive in the prediction of future diabetes in siblings than when combined with genetic susceptibility. Genetic susceptibility played a role in whether the initial prediabetic stage progressed (progression in 29.6% of the high-risk siblings compared with 6.6% of the siblings with DQB1 genotypes conferring decreased risk; P < 0.001 according to the first classification) and whether overt type 1 diabetes became manifest or not. Genetic susceptibility has an impact on both the initiation and progression of the autoimmune process leading to clinical diabetes in siblings of affected children.

  12. Susceptibility for thin ideal media and eating styles.

    PubMed

    Anschutz, Doeschka J; Engels, Rutger C M E; Van Strien, Tatjana

    2008-03-01

    This study examined the relations between susceptibility for thin ideal media and restrained, emotional and external eating, directly and indirectly through body dissatisfaction. Thin ideal media susceptibility, body dissatisfaction and eating styles were measured in a sample of 163 female students. Structural equation modelling was used for analyses, controlling for BMI. Higher susceptibility for thin ideal media was directly related to higher scores on all eating styles, and indirectly related to higher restrained and emotional eating through elevated levels of body dissatisfaction. So, thin ideal media susceptibility was not only related to restraint through body dissatisfaction, but also directly. Emotional eaters might be more vulnerable for negative affect, whereas external eaters might be more sensitive to external cues in general.

  13. Accurate Determination of the Q Quality Factor in Magnetoelastic Resonant Platforms for Advanced Biological Detection.

    PubMed

    Lopes, Ana Catarina; Sagasti, Ariane; Lasheras, Andoni; Muto, Virginia; Gutiérrez, Jon; Kouzoudis, Dimitris; Barandiarán, José Manuel

    2018-03-16

    The main parameters of magnetoelastic resonators in the detection of chemical (i.e., salts, gases, etc.) or biological (i.e., bacteria, phages, etc.) agents are the sensitivity S (or external agent change magnitude per Hz change in the resonance frequency) and the quality factor Q of the resonance. We present an extensive study on the experimental determination of the Q factor in such magnetoelastic resonant platforms, using three different strategies: (a) analyzing the real and imaginary components of the susceptibility at resonance; (b) numerical fitting of the modulus of the susceptibility; (c) using an exact mathematical expression for the real part of the susceptibility. Q values obtained by the three methods are analyzed and discussed, aiming to establish the most adequate one to accurately determine the quality factor of the magnetoelastic resonance.

  14. Accurate Determination of the Q Quality Factor in Magnetoelastic Resonant Platforms for Advanced Biological Detection

    PubMed Central

    Lopes, Ana Catarina; Sagasti, Ariane; Lasheras, Andoni; Muto, Virginia; Gutiérrez, Jon; Kouzoudis, Dimitris; Barandiarán, José Manuel

    2018-01-01

    The main parameters of magnetoelastic resonators in the detection of chemical (i.e., salts, gases, etc.) or biological (i.e., bacteria, phages, etc.) agents are the sensitivity S (or external agent change magnitude per Hz change in the resonance frequency) and the quality factor Q of the resonance. We present an extensive study on the experimental determination of the Q factor in such magnetoelastic resonant platforms, using three different strategies: (a) analyzing the real and imaginary components of the susceptibility at resonance; (b) numerical fitting of the modulus of the susceptibility; (c) using an exact mathematical expression for the real part of the susceptibility. Q values obtained by the three methods are analyzed and discussed, aiming to establish the most adequate one to accurately determine the quality factor of the magnetoelastic resonance. PMID:29547578

  15. Waterpipe Use and Susceptibility to Cigarette Smoking Among Never-Smoking Youth.

    PubMed

    Veeranki, Sreenivas P; Alzyoud, Sukaina; Kheirallah, Khalid A; Pbert, Lori

    2015-10-01

    Susceptibility to cigarette smoking, defined as the lack of a firm decision against smoking, is a strong predictor of regular smoking and addiction. Several modifiable risk factors have been identified among never cigarette smokers, and one potential factor of interest is waterpipe use. The purpose of this study is to determine the association of waterpipe use with susceptibility to cigarette smoking among never-smoking youth. In a pooled analysis of 17 Arab nations with nationally representative Global Youth Tobacco Surveys conducted during 2002-2011, tobacco-related information was obtained from 30,711 never-smoking adolescents representing 4,962,872 youth. Study outcome was susceptibility to cigarette smoking, and primary exposure was waterpipe use. Data were analyzed in 2014 using weighted logistic regression models, including stratified models by gender, to determine the odds of susceptibility to cigarette smoking with waterpipe use, adjusting for confounders. Overall, 20% of never-smoking youth were susceptible to cigarette smoking, ranging from 13.1% in Oman to 32.6% in Somalia; 5.2% currently used waterpipe, ranging from 0.3% in Morocco to 23.5% in Kuwait. The estimated odds of susceptibility to cigarette smoking were 2.5 (95% CI=1.9, 3.4) times higher for adolescents who used waterpipe in the past month compared with those who did not, controlling for confounders. Estimates were similar when stratified by gender. Waterpipe use is associated with susceptibility to cigarette smoking. Study findings identify a novel risk factor for never smokers to initiate smoking and will help the public health community develop and implement policies around waterpipe use prevention. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  16. Philometra floridensis (Nematoda: Philometridae) damages ovarian tissue without reducing host (Sciaenops ocellatus) fecundity.

    PubMed

    Bakenhaster, Micah D; Lowerre-Barbieri, Susan; Kiryu, Yasunari; Walters, Sarah; Fajer-Avila, Emma J

    2014-04-03

    The parasitic nematode Philometra floridensis infects the ovary of its only host, the economically important fish species Sciaenops ocellatus, but the factors influencing host susceptibility and potential pathogenic effects are unknown. Here we report new information on these topics from evaluations of infected and uninfected hosts collected from the northeastern Gulf of Mexico. Fish length and age were evaluated vis-à-vis nematode prevalence to check for ontogenetic differences in host susceptibility. To evaluate health and reproductive consequences of infection, we looked for effects in Fulton's condition factor (K) and batch fecundity estimates (BF), and we evaluated ovarian tissue histologically to check for oocyte atresia and other host responses. We observed localized pathological changes in fish ovarian tissue associated with female nematodes, including leucocytic exudates, granulomatous inflammation, and Langhans-type multinucleated giant cells; the hosts, however, appeared to maintain high fecundity and actually exhibited, on average, better health index scores and higher relative fecundity than did uninfected fish. These differences are likely explained by the parasite's tendency to disproportionately infect the largest, actively spawning fish and by the localization of pathogenic changes, which could have masked effects that otherwise would have been reflected in mass-based health indicators. Although we did not detect negative effects on measures of overall health or reproductive output, further research is needed to better elucidate the relationship between these parasites and other factors affecting host reproductive potential, such as egg quality.

  17. Periodontal diseases.

    PubMed

    Kinane, Denis F; Stathopoulou, Panagiota G; Papapanou, Panos N

    2017-06-22

    Periodontal diseases comprise a wide range of inflammatory conditions that affect the supporting structures of the teeth (the gingiva, bone and periodontal ligament), which could lead to tooth loss and contribute to systemic inflammation. Chronic periodontitis predominantly affects adults, but aggressive periodontitis may occasionally occur in children. Periodontal disease initiation and propagation is through a dysbiosis of the commensal oral microbiota (dental plaque), which then interacts with the immune defences of the host, leading to inflammation and disease. This pathophysiological situation persists through bouts of activity and quiescence, until the affected tooth is extracted or the microbial biofilm is therapeutically removed and the inflammation subsides. The severity of the periodontal disease depends on environmental and host risk factors, both modifiable (for example, smoking) and non-modifiable (for example, genetic susceptibility). Prevention is achieved with daily self-performed oral hygiene and professional removal of the microbial biofilm on a quarterly or bi-annual basis. New treatment modalities that are actively explored include antimicrobial therapy, host modulation therapy, laser therapy and tissue engineering for tissue repair and regeneration.

  18. Dual RNA-Sequencing of Eucalyptus nitens during Phytophthora cinnamomi Challenge Reveals Pathogen and Host Factors Influencing Compatibility

    PubMed Central

    Meyer, Febé E.; Shuey, Louise S.; Naidoo, Sitha; Mamni, Thandekile; Berger, Dave K.; Myburg, Alexander A.; van den Berg, Noëlani; Naidoo, Sanushka

    2016-01-01

    Damage caused by Phytophthora cinnamomi Rands remains an important concern on forest tree species. The pathogen causes root and collar rot, stem cankers, and dieback of various economically important Eucalyptus spp. In South Africa, susceptible cold tolerant Eucalyptus plantations have been affected by various Phytophthora spp. with P. cinnamomi considered one of the most virulent. The molecular basis of this compatible interaction is poorly understood. In this study, susceptible Eucalyptus nitens plants were stem inoculated with P. cinnamomi and tissue was harvested five days post inoculation. Dual RNA-sequencing, a technique which allows the concurrent detection of both pathogen and host transcripts during infection, was performed. Approximately 1% of the reads mapped to the draft genome of P. cinnamomi while 78% of the reads mapped to the Eucalyptus grandis genome. The highest expressed P. cinnamomi gene in planta was a putative crinkler effector (CRN1). Phylogenetic analysis indicated the high similarity of this P. cinnamomi CRN1 to that of Phytophthora infestans. Some CRN effectors are known to target host nuclei to suppress defense. In the host, over 1400 genes were significantly differentially expressed in comparison to mock inoculated trees, including suites of pathogenesis related (PR) genes. In particular, a PR-9 peroxidase gene with a high similarity to a Carica papaya PR-9 ortholog previously shown to be suppressed upon infection by Phytophthora palmivora was down-regulated two-fold. This PR-9 gene may represent a cross-species effector target during P. cinnamomi infection. This study identified pathogenicity factors, potential manipulation targets, and attempted host defense mechanisms activated by E. nitens that contributed to the susceptible outcome of the interaction. PMID:26973660

  19. Host pathogen interactions in Helicobacter pylori related gastric cancer

    PubMed Central

    Chmiela, Magdalena; Karwowska, Zuzanna; Gonciarz, Weronika; Allushi, Bujana; Stączek, Paweł

    2017-01-01

    Helicobacter pylori (H. pylori), discovered in 1982, is a microaerophilic, spiral-shaped gram-negative bacterium that is able to colonize the human stomach. Nearly half of the world's population is infected by this pathogen. Its ability to induce gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma has been confirmed. The susceptibility of an individual to these clinical outcomes is multifactorial and depends on H. pylori virulence, environmental factors, the genetic susceptibility of the host and the reactivity of the host immune system. Despite the host immune response, H. pylori infection can be difficult to eradicate. H. pylori is categorized as a group I carcinogen since this bacterium is responsible for the highest rate of cancer-related deaths worldwide. Early detection of cancer can be lifesaving. The 5-year survival rate for gastric cancer patients diagnosed in the early stages is nearly 90%. Gastric cancer is asymptomatic in the early stages but always progresses over time and begins to cause symptoms when untreated. In 97% of stomach cancer cases, cancer cells metastasize to other organs. H. pylori infection is responsible for nearly 60% of the intestinal-type gastric cancer cases but also influences the development of diffuse gastric cancer. The host genetic susceptibility depends on polymorphisms of genes involved in H. pylori-related inflammation and the cytokine response of gastric epithelial and immune cells. H. pylori strains differ in their ability to induce a deleterious inflammatory response. H. pylori-driven cytokines accelerate the inflammatory response and promote malignancy. Chronic H. pylori infection induces genetic instability in gastric epithelial cells and affects the DNA damage repair systems. Therefore, H. pylori infection should always be considered a pro-cancerous factor. PMID:28321154

  20. Evaluation of polymorphic variants in apoptotic genes and their role in susceptibility and clinical progression to systemic lupus erythematosus.

    PubMed

    Glesse, N; Vianna, P; Paim, L M G; Matte, M C C; Aguiar, A K K; Palhano, P L; Monticielo, O A; Brenol, C V; Xavier, R M; Chies, J A B

    2017-06-01

    Background Systemic lupus erythematosus (SLE) is an autoimmune disease marked by the disruption of the immune homeostasis. Patients exhibit a wide range of clinical manifestations, and environmental and genetic factors are involved in SLE pathogenesis. Evidence suggests that abnormalities in the cellular and molecular events that coordinate apoptosis may favour the generation of autoantigens involved in autoimmunity. In this way, the apoptotic deregulation may be affected by polymorphic variants in apoptotic-related genes. Methods We analyzed FAS, FASL, BCL-2 and BAX polymorphisms in order to correlate to SLE susceptibility and clinical features. A total of 427 SLE patients from the Hospital de Clínicas de Porto Alegre and 543 controls from southern Brazil were evaluated. Results We observed higher frequencies of the FASL -844CC genotype and -844C allele, as well as of the FASL-844C/IVS2nt-124A haplotype in African-derived SLE patients when compared to controls ( P < 0.001). FASL -844C, which is related to high FasL expression, could contribute to increased apoptosis and to the breakdown of immunological tolerance, favouring autoantibody production and inflammation. On the other hand, the BAX -248GA genotype and the -248A allele , related to low protein expression, were observed as a protective factor against SLE in this same population. The rate of apoptosis and cell death was evaluated in peripheral lymphocytes, and SLE patients presented a higher percentage of dead lymphocytes (CD3 + Annexin V + 7-AAD + ) compared to the control group. Conclusion Our data support a role for apoptosis in SLE susceptibility.

  1. Host pathogen interactions in Helicobacter pylori related gastric cancer.

    PubMed

    Chmiela, Magdalena; Karwowska, Zuzanna; Gonciarz, Weronika; Allushi, Bujana; Stączek, Paweł

    2017-03-07

    Helicobacter pylori ( H. pylori ), discovered in 1982, is a microaerophilic, spiral-shaped gram-negative bacterium that is able to colonize the human stomach. Nearly half of the world's population is infected by this pathogen. Its ability to induce gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma has been confirmed. The susceptibility of an individual to these clinical outcomes is multifactorial and depends on H. pylori virulence, environmental factors, the genetic susceptibility of the host and the reactivity of the host immune system. Despite the host immune response, H. pylori infection can be difficult to eradicate. H. pylori is categorized as a group I carcinogen since this bacterium is responsible for the highest rate of cancer-related deaths worldwide. Early detection of cancer can be lifesaving. The 5-year survival rate for gastric cancer patients diagnosed in the early stages is nearly 90%. Gastric cancer is asymptomatic in the early stages but always progresses over time and begins to cause symptoms when untreated. In 97% of stomach cancer cases, cancer cells metastasize to other organs. H. pylori infection is responsible for nearly 60% of the intestinal-type gastric cancer cases but also influences the development of diffuse gastric cancer. The host genetic susceptibility depends on polymorphisms of genes involved in H. pylori -related inflammation and the cytokine response of gastric epithelial and immune cells. H. pylori strains differ in their ability to induce a deleterious inflammatory response. H. pylori -driven cytokines accelerate the inflammatory response and promote malignancy. Chronic H. pylori infection induces genetic instability in gastric epithelial cells and affects the DNA damage repair systems. Therefore, H. pylori infection should always be considered a pro-cancerous factor.

  2. Biology of teeth and implants: Host factors - pathology, regeneration, and the role of stem cells.

    PubMed

    Eggert, F-Michael; Levin, Liran

    2018-01-01

    In chronic periodontitis and peri-implantitis, cells of the innate and adaptive immune systems are involved directly in the lesions within the tissues of the patient. Absence of a periodontal ligament around implants does not prevent a biologic process similar to that of periodontitis from affecting osseointegration. Our first focus is on factors in the biology of individuals that are responsible for the susceptibility of such individuals to chronic periodontitis and to peri-implantitis. Genetic factors are of significant importance in susceptibility to these diseases. Genetic factors of the host affect the composition of the oral microbiome in the same manner that they influence other microbiomes, such as those of the intestines and of the lungs. Our second focus is on the central role of stem cells in tissue regeneration, in the functioning of innate and adaptive immune systems, and in metabolism of bone. Epithelial cell rests of Malassez (ERM) are stem cells of epithelial origin that maintain the periodontal ligament as well as the cementum and alveolar bone associated with the ligament. The tissue niche within which ERM are found extends into the supracrestal areas of collagen fiber-containing tissues of the gingivae above the bony alveolar crest. Maintenance and regeneration of all periodontal tissues involves the activity of a variety of stem cells. The success of dental implants indicates that important groups of stem cells in the periodontium are active to enable that biologic success. Successful replantation of avulsed teeth and auto-transplantation of teeth is comparable to placing dental implants, and so must also involve periodontal stem cells. Biology of teeth and biology of implants represents the biology of the various stem cells that inhabit specialized niches within the periodontal tissues. Diverse biologic processes must function together successfully to maintain periodontal health. Osseointegration of dental implants does not involve formation of cementum or collagen fibers inserted into cementum - indicating that some stem cells are not active around dental implants or their niches are not available. Investigation of these similarities and differences between teeth and implants will help to develop a better understanding of the biology and physiologic functioning of the periodontium.

  3. The Integrative Studies of Genetic and Environmental Factors in Systemic Sclerosis

    DTIC Science & Technology

    2008-05-01

    15. SUBJECT TERMS Scleroderma (SSc), fibroblasts, fibrosis, silica, environmental particles, susceptibility. 16. SECURITY CLASSIFICATION OF...factors in a viable system - human fibroblasts. Fibroblasts with a scleroderma (SSc) susceptible genetic background may be more vulnerable to...for understanding environmental contributions to fibrosing diseases such as scleroderma (SSc). Third, in the studies of specific biological

  4. Risk factors for tobacco susceptibility in an orthodontic population: An exploratory study.

    PubMed

    Jashinsky, Jared Michael; Liles, Sandy; Schmitz, Katy; Ding, Ding; Hovell, Melbourne

    2017-08-01

    Tobacco use is related to increased periodontal disease, tooth loss, and decreased success of orthodontic appliances, and it may inhibit orthodontic tooth movement. Most smokers start during adolescence. Since most cessation attempts fail, prevention appears necessary. A cross-sectional sample of orthodontic patients reported hypothesized risk factors for smoking and susceptibility to tobacco use initiation. Exploratory analyses regressed susceptibility to tobacco initiation on each hypothesized predictor variable in a separate logistic model that included a standard set of covariates. Significant odds ratios (OR) were found for the presence of a smoker in the home (OR, 2.168; 95% confidence interval [CI], 1.144-4.107), a friend having no-smoking rules in his or her home and car (OR, 0.337; 95% CI, 0.128-0.886), having been offered a cigarette (OR, 4.526; 95% CI, 1.190-17.207), and exposure to tobacco advertisements (OR, 1.910; 95% CI, 1.044-3.496). Peer, family, and environmental factors appear to increase children's susceptibility to smoking in orthodontic populations. Attention to such factors could help dental clinicians to more effectively identify susceptible young patients in need of antismoking advice. Prospective and experimental studies are required to confirm the role that dental clinicians might play in youth smoking prevention. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  5. Frequencies of polymorphisms associated with BSE resistance differ significantly between Bos taurus, Bos indicus, and composite cattle

    PubMed Central

    Brunelle, Brian W; Greenlee, Justin J; Seabury, Christopher M; Brown, Charles E; Nicholson, Eric M

    2008-01-01

    Background Transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases that affect several mammalian species. At least three factors related to the host prion protein are known to modulate susceptibility or resistance to a TSE: amino acid sequence, atypical number of octapeptide repeats, and expression level. These factors have been extensively studied in breeds of Bos taurus cattle in relation to classical bovine spongiform encephalopathy (BSE). However, little is currently known about these factors in Bos indicus purebred or B. indicus × B. taurus composite cattle. The goal of our study was to establish the frequency of markers associated with enhanced susceptibility or resistance to classical BSE in B. indicus purebred and composite cattle. Results No novel or TSE-associated PRNP-encoded amino acid polymorphisms were observed for B. indicus purebred and composite cattle, and all had the typical number of octapeptide repeats. However, differences were observed in the frequencies of the 23-bp and 12-bp insertion/deletion (indel) polymorphisms associated with two bovine PRNP transcription regulatory sites. Compared to B. taurus, B. indicus purebred and composite cattle had a significantly lower frequency of 23-bp insertion alleles and homozygous genotypes. Conversely, B. indicus purebred cattle had a significantly higher frequency of 12-bp insertion alleles and homozygous genotypes in relation to both B. taurus and composite cattle. The origin of these disparities can be attributed to a significantly different haplotype structure within each species. Conclusion The frequencies of the 23-bp and 12-bp indels were significantly different between B. indicus and B. taurus cattle. No other known or potential risk factors were detected for the B. indicus purebred and composite cattle. To date, no consensus exists regarding which bovine PRNP indel region is more influential with respect to classical BSE. Should one particular indel region and associated genotypes prove more influential with respect to the incidence of classical BSE, differences regarding overall susceptibility and resistance for B. indicus and B. taurus cattle may be elucidated. PMID:18808703

  6. Sensitivity analysis of conditioning factors for landslide susceptibility evaluation in Santa Marta de Penaguiño (Douro valley - Portugal

    NASA Astrophysics Data System (ADS)

    Pereira, S.; Zêzere, J. L.; Bateira, C.

    2009-04-01

    The MapRisk project intends to develop a landslide hazard and risk analysis to support planning decisions at the municipal level. The municipality of Santa Marta de Penaguião (70 square kilometres) is one of the test sites of the project. The study area has been affected in recent years by destructive landslides that were responsible for deaths and house and roads destruction. Despite these losses, mitigation and zonation landslide programs are missing, and the land use planning at the municipal level did not solve yet the problem. The study area is located in the Douro Valley region, mainly composed by metamorphic rocks (e.g., schist and quartzites). These rocks are strongly fractured, and weathered materials are abundant in clayed schist, mainly in those areas with agricultural terraces. From the geomorphological point of view, the study area is characterized by a transition landscape between the Marão mountain and the transmontano plateau, with deep incised valleys, tectonic depressions and slopes controlled by the geological structure. This area is characterised by the vineyard monoculture cultivated in agricultural terraces over centuries to produce Oporto wine. The main landslide triggering factor is rainfall and the mean annual precipitation ranges from 2500 mm near Marão mountain to 700 mm in the Corgós Valley. In this area there are historical records of destructive landslides, although they were aggregated in a landslide geodatabase only recently. The most complete landslide inventory was performed in 2005-2008 using aerial photographs interpretation at 1/5.000 scale and field work verification. The geodatabase includes 725 landslides, most of shallow translational slide type (80% of total slope movements). The landslide density is 10.5 events/square kilometre, and the average landslide area is 535 square meters. In this work we present the results of GIS based landslide susceptibility assessment for the shallow translational slides using two bivariate statistical models: information value and fuzzy-logic. Success rate and prediction rate curves were calculated for susceptibility models performed with the total set of shallow translational slides, and using a landslide training group and a landslide test group, which were randomly defined, each corresponding to 50% of the complete landslide population. The obtained prediction rates are higher for the Information value method, in all experiences, when compared with the fuzzy logic. Using only the information value method, a sensitivity analysis was performed to identify the most important conditioning factors (8 spatial thematic layers) concerning the spatial distribution of shallow translational slides in the study area. Slope curvature, terrace structures build in slopes and lithology are the landslide conditioning factors that show the highest success rates. Susceptibility maps produced with different number of conditioning factors were tested and good results were achieved with only 4 factors (Slope curvature, terrace structures build in slopes, lithology and land use). The obtained results must be carefully analysed, because they result from few inventories and some landslides were erased in landscape due to reconstruction of terraces and roads, and seasonal soil ploughing. The land use changes rapidly in order to get more space for vineyard plantations and the slope structures that sustained the soil erosion are replaced for slopes without soil support structures. In this context, the conditioning factors and susceptibility maps have a short temporal validity and need to be regularly updated in response to changes in land use.

  7. Role of spontaneous physical activity in prediction of susceptibility to activity based anorexia in male and female rats

    PubMed Central

    Perez-Leighton, Claudio; Grace, Martha; Billington, Charles J.; Kotz, Catherine M.

    2015-01-01

    Anorexia nervosa (AN) is a chronic eating disorder affecting females and males, defined by body weight loss, higher physical activity levels and restricted food intake. Currently, the commonalities and differences between genders in etiology of AN are not well understood. Animal models of AN, such as activity-based anorexia (ABA), can be helpful in identifying factors determining individual susceptibility to AN. In ABA, rodents are given an access to a running wheel while food restricted, resulting in paradoxical increased physical activity levels and weight loss. Recent studies suggest that different behavioral traits, including voluntary exercise, can predict individual weight loss in ABA. A higher inherent drive for movement can promote development and severity of AN, but this hypothesis remains untested. In rodents and humans, drive for movement is defined as spontaneous physical activity (SPA), which is time spent in low-intensity, non-volitional movements. In this paper, we show that a profile of body weight history and behavioral traits, including SPA, can predict individual weight loss caused by ABA in male and female rats with high accuracy. Analysis of the influence of SPA on ABA susceptibility in males and females rats suggests that either high or low levels of SPA increase the probability of high weight loss in ABA, but with larger effects in males compared to females. These results suggest the same behavioral profile can identify individuals at-risk of AN for both male and female populations and that SPA has predictive value for susceptibility to AN. PMID:24912135

  8. Insulin Transactivator MafA Regulates Intrathymic Expression of Insulin and Affects Susceptibility to Type 1 Diabetes

    PubMed Central

    Noso, Shinsuke; Kataoka, Kohsuke; Kawabata, Yumiko; Babaya, Naru; Hiromine, Yoshihisa; Yamaji, Kaori; Fujisawa, Tomomi; Aramata, Shinsaku; Kudo, Takashi; Takahashi, Satoru; Ikegami, Hiroshi

    2010-01-01

    OBJECTIVE Tissue-specific self-antigens are ectopically expressed within the thymus and play an important role in the induction of central tolerance. Insulin is expressed in both pancreatic islets and the thymus and is considered to be the primary antigen for type 1 diabetes. Here, we report the role of the insulin transactivator MafA in the expression of insulin in the thymus and susceptibility to type 1 diabetes. RESEARCH DESIGN AND METHODS The expression profiles of transcriptional factors (Pdx1, NeuroD, Mafa, and Aire) in pancreatic islets and the thymus were examined in nonobese diabetic (NOD) and control mice. Thymic Ins2 expression and serum autoantibodies were examined in Mafa knockout mice. Luciferase reporter assay was performed for newly identified polymorphisms of mouse Mafa and human MAFA. A case-control study was applied for human MAFA polymorphisms. RESULTS Mafa, Ins2, and Aire expression was detected in the thymus. Mafa expression was lower in NOD thymus than in the control and was correlated with Ins2 expression. Targeted disruption of MafA reduced thymic Ins2 expression and induced autoantibodies against pancreatic islets. Functional polymorphisms of MafA were newly identified in NOD mice and humans, and polymorphisms of human MAFA were associated with susceptibility to type 1 diabetes but not to autoimmune thyroid disease. CONCLUSIONS These data indicate that functional polymorphisms of MafA are associated with reduced expression of insulin in the thymus and susceptibility to type 1 diabetes in the NOD mouse as well as human type 1 diabetes. PMID:20682694

  9. Role of spontaneous physical activity in prediction of susceptibility to activity based anorexia in male and female rats.

    PubMed

    Perez-Leighton, Claudio E; Grace, Martha; Billington, Charles J; Kotz, Catherine M

    2014-08-01

    Anorexia nervosa (AN) is a chronic eating disorder affecting females and males, defined by body weight loss, higher physical activity levels and restricted food intake. Currently, the commonalities and differences between genders in etiology of AN are not well understood. Animal models of AN, such as activity-based anorexia (ABA), can be helpful in identifying factors determining individual susceptibility to AN. In ABA, rodents are given an access to a running wheel while food restricted, resulting in paradoxical increased physical activity levels and weight loss. Recent studies suggest that different behavioral traits, including voluntary exercise, can predict individual weight loss in ABA. A higher inherent drive for movement may promote development and severity of AN, but this hypothesis remains untested. In rodents and humans, drive for movement is defined as spontaneous physical activity (SPA), which is time spent in low-intensity, non-volitional movements. In this paper, we show that a profile of body weight history and behavioral traits, including SPA, can predict individual weight loss caused by ABA in male and female rats with high accuracy. Analysis of the influence of SPA on ABA susceptibility in males and females rats suggests that either high or low levels of SPA increase the probability of high weight loss in ABA, but with larger effects in males compared to females. These results suggest that the same behavioral profile can identify individuals at-risk of AN for both male and female populations and that SPA has predictive value for susceptibility to AN. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Time-domain Response of a Metal Detector to a Target Buried in Soil with Frequency-dependent Magnetic Susceptibility

    DTIC Science & Technology

    2016-07-06

    The work reported in this paper is a part of on-going studies to clarify how and to what extent soil electromagnetic properties affect the...metallic sphere buried in a non-conducting soil half-space with frequency-dependent complex magnetic susceptibility. The sphere is chosen as a simple...prototype for the small metal parts in low-metal landmines, while soil with dispersive magnetic susceptibility is a good model for some soils that are

  11. The genetic and epigenetic landscapes of the epithelium in asthma.

    PubMed

    Moheimani, Fatemeh; Hsu, Alan C-Y; Reid, Andrew T; Williams, Teresa; Kicic, Anthony; Stick, Stephen M; Hansbro, Philip M; Wark, Peter A B; Knight, Darryl A

    2016-09-22

    Asthma is a global health problem with increasing prevalence. The airway epithelium is the initial barrier against inhaled noxious agents or aeroallergens. In asthma, the airway epithelium suffers from structural and functional abnormalities and as such, is more susceptible to normally innocuous environmental stimuli. The epithelial structural and functional impairments are now recognised as a significant contributing factor to asthma pathogenesis. Both genetic and environmental risk factors play important roles in the development of asthma with an increasing number of genes associated with asthma susceptibility being expressed in airway epithelium. Epigenetic factors that regulate airway epithelial structure and function are also an attractive area for assessment of susceptibility to asthma. In this review we provide a comprehensive discussion on genetic factors; from using linkage designs and candidate gene association studies to genome-wide association studies and whole genome sequencing, and epigenetic factors; DNA methylation, histone modifications, and non-coding RNAs (especially microRNAs), in airway epithelial cells that are functionally associated with asthma pathogenesis. Our aims were to introduce potential predictors or therapeutic targets for asthma in airway epithelium. Overall, we found very small overlap in asthma susceptibility genes identified with different technologies. Some potential biomarkers are IRAKM, PCDH1, ORMDL3/GSDMB, IL-33, CDHR3 and CST1 in airway epithelial cells. Recent studies on epigenetic regulatory factors have further provided novel insights to the field, particularly their effect on regulation of some of the asthma susceptibility genes (e.g. methylation of ADAM33). Among the epigenetic regulatory mechanisms, microRNA networks have been shown to regulate a major portion of post-transcriptional gene regulation. Particularly, miR-19a may have some therapeutic potential.

  12. Strain-specific outcomes of repeated social defeat and chronic fluoxetine treatment in the mouse.

    PubMed

    Razzoli, Maria; Carboni, Lucia; Andreoli, Michela; Michielin, Francesca; Ballottari, Alice; Arban, Roberto

    2011-01-01

    Social stress is a risk factor for affective disorders in vulnerable individuals. Although the biological nature of stress susceptibility/resilience remains to be elucidated, genetic variation is considered amongst the principal contributors to brain disorders. Furthermore, genetic predisposition may be determinant for the therapeutic outcome, as proposed for antidepressant treatments. In the present studies we compared the inherently diverse genetic backgrounds of 2 mouse strains by assessing the efficacy of a chronic antidepressant treatment in a repeated social stress procedure. C57BL/6J and BalbC mice underwent 10-day social defeats followed by 28-day fluoxetine treatment (10 mg/kg/mL, p.o.). In C57BL/6J, most of the social defeat-induced changes were of metabolic nature including persistently altered feed efficiency and decreased abdominal fat stores that were ameliorated by fluoxetine. BalbC mouse behavior was persistently affected by social defeat both in the social avoidance and the forced swim tests, and in either procedure it was restored by chronic fluoxetine, whereas their endocrine parameters were mostly unaffected. The highlighted strain-specific responsivity to the metabolic and behavioral consequences of social defeat and to the chronic antidepressant treatment offers a promising research tool to further explore the underlying neural mechanisms and genetic basis of stress susceptibility and treatment response. Copyright © 2010 Elsevier Inc. All rights reserved.

  13. Resist Globally, Infect Locally: A Transcontinental Test of Adaptation by Stickleback and Their Tapeworm Parasite.

    PubMed

    Weber, Jesse N; Kalbe, Martin; Shim, Kum Chuan; Erin, Noémie I; Steinel, Natalie C; Ma, Lei; Bolnick, Daniel I

    2017-01-01

    Parasite infections are a product of both ecological processes affecting host-parasite encounter rates and evolutionary dynamics affecting host susceptibility. However, few studies examine natural infection variation from both ecological and evolutionary perspectives. Here, we describe the ecological and evolutionary factors generating variation in infection rates by a tapeworm (Schistocephalus solidus) in a vertebrate host, the threespine stickleback (Gasterosteus aculeatus). To explore ecological aspects of infection, we measured tapeworm prevalence in Canadian stickleback inhabiting two distinct environments: marine and freshwater. Consistent with ecological control of infection, the tapeworm is very rare in marine environments, even though marine fish are highly susceptible. Conversely, commonly infected freshwater stickleback exhibit substantial resistance in controlled laboratory trials, suggesting that high exposure risk overwhelms their recently evolved resistance. We also tested for parasite adaptation to its host by performing transcontinental reciprocal infections, using stickleback and tapeworm populations from Europe and western Canada. More infections occurred in same-continent host-parasite combinations, indicating parasite "local" adaptation, at least on the scale of continents. However, the recently evolved immunity of freshwater hosts applies to both local and foreign parasites. The pattern of adaptation described here is not wholly compatible with either of the common models of host-parasite coevolution (i.e., matching infection or targeted recognition). Instead, we propose a hybrid, eco-evolutionary model to explain the remarkable pattern of global host resistance and local parasite infectivity.

  14. Multi-Collinearity Based Model Selection for Landslide Susceptibility Mapping: A Case Study from Ulus District of Karabuk, Turkey

    NASA Astrophysics Data System (ADS)

    Sahin, E. K.; Colkesen, I., , Dr; Kavzoglu, T.

    2017-12-01

    Identification of localities prone to landslide areas plays an important role for emergency planning, disaster management and recovery planning. Due to its great importance for disaster management, producing accurate and up-to-date landslide susceptibility maps is essential for hazard mitigation purpose and regional planning. The main objective of the present study was to apply multi-collinearity based model selection approach for the production of a landslide susceptibility map of Ulus district of Karabuk, Turkey. It is a fact that data do not contain enough information to describe the problem under consideration when the factors are highly correlated with each other. In such cases, choosing a subset of the original features will often lead to better performance. This paper presents multi-collinearity based model selection approach to deal with the high correlation within the dataset. Two collinearity diagnostic factors (Tolerance (TOL) and the Variance Inflation Factor (VIF)) are commonly used to identify multi-collinearity. Values of VIF that exceed 10.0 and TOL values less than 1.0 are often regarded as indicating multi-collinearity. Five causative factors (slope length, curvature, plan curvature, profile curvature and topographical roughness index) were found highly correlated with each other among 15 factors available for the study area. As a result, the five correlated factors were removed from the model estimation, and performances of the models including the remaining 10 factors (aspect, drainage density, elevation, lithology, land use/land cover, NDVI, slope, sediment transport index, topographical position index and topographical wetness index) were evaluated using logistic regression. The performance of prediction model constructed with 10 factors was compared to that of 15-factor model. The prediction performance of two susceptibility maps was evaluated by overall accuracy and the area under the ROC curve (AUC) values. Results showed that overall accuracy and AUC was calculated as 77.15% and 96.62% respectively for the model with 10 selected factors whilst they were estimated as 73.45% and 89.45% respectively for the model with all factors. It is clear that the multi-collinearity based model outperformed the conventional model in the mapping of landslide susceptibility.

  15. Microstructure and yield strength effects on hydrogen and tritium induced cracking in HERF (high-energy-rate-forged) stainless steel

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Morgan, M J; Tosten, M H

    1989-01-01

    Rising-load J-integral measurements and falling-load threshold stress intensity measurements were used to characterize hydrogen and tritium induced cracking in high-energy-rate-forged (HERF) 21-6-9 stainless steel. Samples having yield strengths in the range 517--930 MPa were thermally charged with either hydrogen or tritium and tested at room temperature in either air or high-pressure hydrogen gas. In general, the hydrogen isotopes reduced the fracture toughness by affecting the fracture process. Static recrystallization in the HERF microstructures affected the material's fracture toughness and its relative susceptibility to hydrogen and tritium induced fracture. In hydrogen-exposed samples, the reduction in fracture toughness was primarily dependent onmore » the susceptibility of the microstructure to intergranular fracture and only secondarily affected by strength in the range of 660 to 930 MPa. Transmission-electron microscopy observations revealed that the microstructures least susceptible to hydrogen-induced intergranular cracking contained patches of fully recrystallized grains. These grains are surrounded by highly deformed regions containing a high number density of dislocations. The microstructure can best be characterized as duplex'', with soft recrystallized grains embedded in a hard, deformed matrix. The microstructures most susceptible to hydrogen-induced intergranular fracture showed no well-developed recrystallized grains. The patches of recrystallized grains seemed to act as crack barriers to hydrogen-induced intergranular fracture. In tritium-exposed-and-aged samples, the amount of static recrystallization also affected the fracture toughness properties but to a lesser degree. 7 refs., 25 figs.« less

  16. Effects of host nutrition on virulence and fitness of entomopathogenic nematodes: Lipid- and protein-based supplements in Tenebrio molitor diets

    PubMed Central

    Shapiro-Ilan, David; Rojas, M. Guadalupe; Morales-Ramos, Juan A.; Lewis, Edwin E.; Tedders, W. Louis

    2008-01-01

    Entomopathogenic nematodes, Heterorhabditis indica and Steinernema riobrave, were tested for virulence and reproductive yield in Tenebrio molitor that were fed wheat bran diets with varying lipid- and protein-based supplements. Lipid supplements were based on 20% canola oil, peanut, pork or salmon, or a low lipid control (5% canola). Protein treatments consisted of basic supplement ingredients plus 0, 10, or 20% egg white; a bran-only control was also included. Some diet supplements had positive effects on nematode quality, whereas others had negative or neutral effects. All supplements with 20% lipids except canola oil caused increased T. molitor susceptibility to H. indica, whereas susceptibility to S. riobrave was not affected. Protein supplements did not affect host susceptibility, and neither lipid nor protein diet supplements affected reproductive capacity of either nematode species. Subsequently, we determined the pest control efficacy of progeny of nematodes that had been reared through T. molitor from different diets against Diaprepes abbreviatus and Otiorhynchus sulcatus. All nematode treatments reduced insect survival relative to the control (water only). Nematodes originating from T. molitor diets with the 0% or 20% protein exhibited lower efficacy versus D. abbreviatus than the intermediate level of protein (10%) or bran-only treatments. Nematodes originating from T. molitor lipid or control diets did not differ in virulence. Our research indicates that nutritional content of an insect host diet can affect host susceptibility to entomopathogenic nematodes and nematode fitness; therefore, host media could conceivably be optimized to increase in vivo nematode production efficiency. PMID:19259513

  17. Toddlers' Differential Susceptibility to the Effects of Coparenting on Social-Emotional Adjustment

    ERIC Educational Resources Information Center

    Altenburger, Lauren E.; Lang, Sarah N.; Schoppe-Sullivan, Sarah J.; Kamp Dush, Claire M.; Johnson, Susan

    2017-01-01

    The paper reports on a study which tested whether infants high in negative affectivity are differentially susceptible to observed coparenting behavior in relation to their subsequent social-emotional development. Data came from a longitudinal study of 182 US dual-earner, primiparous couples and their infant children. At nine-months postpartum,…

  18. Effect of Calcium, Magnesium, and Aluminum-Iron on the Susceptibility of Loblolly Pine Seedlings to Fusiform Rust

    Treesearch

    S.J. Rowan

    1979-01-01

    The susceptibility (percentage of seedlings infected) of Pinus taeda seedlings to infection by Cronartium quercuum f. sp. fusiforme was not affected by fertilization with calcium, magnesium, or aluminum-iron. Fertilization with Al as Al2(SO4)2,and Fe as FeCl

  19. Susceptibility of South Korea to Extremes Affecting the Global Food System

    NASA Technical Reports Server (NTRS)

    Chon, So Young; Puma, Michael J.

    2015-01-01

    Food security in South Korea is tightly linked to the global food system. The country's production of major grains declined from 5.8 million metric tons (mmt) in 1998 to 4.8 mmt in 2014, which caused the country's grain self suciency to decline from 31.4% to 24%. This decline is a consequence of several factors including reductions in domestic agricultural land, governmental policies supporting industry over agriculture, and a push towards trade liberalization. South Korea's self suciency is now one of the lowest among Organisation for Economic Co-operation and Development (OECD) countries, leaving it vulnerable to disruptions in the global food system.

  20. Stratigraphic correlations in mid- to late-Proterozoic carbonates of the Democratic Republic of Congo using magnetic susceptibility

    NASA Astrophysics Data System (ADS)

    Delpomdor, Franck R. A.; Devleeschouwer, Xavier; Spassov, Simo; Préat, Alain R.

    2017-04-01

    In this paper, we have tested the application of magnetic susceptibility measurements in Cu-Ag-Zn-Pb-(Fe)-mineralized carbonates of the BIe subgroup (Democratic Republic of Congo) as an efficient tool for regional and global high-resolution stratigraphic correlations in the Neoproterozoic marine carbonates. To achieve this goal, we integrate the low-field magnetic susceptibility (XLF) data with facies analyses, geochemistry and isotope stratigraphy. The microfacies analyses of two cores, Tshinyama#S70 and Kafuku#15, drilled in the early Neoproterozoic carbonates of the Mbuji-Mayi Supergroup reveal a deep carbonate ramp setting associated with a microbial/stromatolitic mid-ramp environment. High-resolution stratigraphic correlations using magnetic susceptibility and C-isotope curves established for both cores, 190 km apart, suggest a sedimentary hiatus at the base of the Tshinyama#S70 succession. C-O and Sr isotopes and Sr/Ca and Fe abundances show that a diagenetic meteoric overprint affected the series of the Tshinyama#S70 core and a thermal effect related to mineralizing fluids affected the Kafuku#15 core carbonates.

  1. Framing susceptibility in a risky choice game is altered by galvanic vestibular stimulation.

    PubMed

    Preuss, Nora; Kalla, Roger; Müri, Rene; Mast, Fred W

    2017-06-07

    Recent research provides evidence that galvanic vestibular stimulation (GVS) has a modulating effect on somatosensory perception and spatial cognition. However, other vestibular stimulation techniques have induced changes in affective control and decision making. The aim of this study was to investigate the effect of GVS on framing susceptibility in a risky-choice game. The participants were to decide between a safe and a risky option. The safe option was framed either positively or negatively. During the task, the participants were exposed to either left anodal/right cathodal GVS, right anodal/left cathodal GVS, or sham stimulation (control condition). While left anodal/right cathodal GVS activated more right-hemispheric vestibular brain areas, right anodal/left cathodal GVS resulted in more bilateral activation. We observed increased framing susceptibility during left anodal/right cathodal GVS, but no change in framing susceptibility during right anodal/left cathodal GVS. We propose that GVS results in increased reliance on the affect heuristic by means of activation of cortical and subcortical vestibular-emotional brain structures and that this effect is modulated by the lateralization of the vestibular cortex.

  2. Cognitive Factors in Hypnotic Susceptibility

    ERIC Educational Resources Information Center

    Palmer, Robert D.; Field, Peter B.

    1971-01-01

    This research explored the influence of cognitive variables on susceptibility to hypnosis. The three variables of concern in the present study are automatization, attention, and body experience. The results are summarized. (Author)

  3. Association of a Family History of Atrial Fibrillation With Incidence and Outcomes of Atrial Fibrillation: A Population-Based Family Cohort Study.

    PubMed

    Chang, Shang-Hung; Kuo, Chang-Fu; Chou, I-Jun; See, Lai-Chu; Yu, Kuang-Hui; Luo, Shue-Fen; Huang, Lu-Hsiang; Zhang, Weiya; Doherty, Michael; Wen, Ming-Shien; Kuo, Chi-Tai; Yeh, Yung-Hsin

    2017-08-01

    The heritability of atrial fibrillation (AF), the contribution of genetic and environmental factors, and the association of a family history of AF with prognosis are unclear. To measure genetic and environmental factors in the familial aggregation of AF and to estimate the association of a family history of AF with major adverse cardiovascular events (MACE). In this Taiwanese nationwide population-based study among more than 23 million people, a custom data set was obtained using the data of all patients having a diagnosis of AF recorded between January 1996 and December 2013 in the Taiwan National Health Insurance Research Database. The study population comprised all 23 422 955 individuals registered with the database in 2013, of whom 177 770 had a diagnosis of AF and were included in the heritability estimation. From the latter, a subgroup of patients having newly diagnosed AF with a first-degree relative affected by AF between 2000 and 2010 were selected and matched 1:4 to controls without a family history for estimating MACE-free survival. The dates of analysis were January 2010 to December 2013. The prevalence and relative risk of AF in relatives of patients with AF, as well as the relative contributions of heritability and shared and nonshared environmental factors to AF susceptibility. Also measured was MACE-free survival after AF was diagnosed. In total, 1510 patients (204 [13.5%] female; mean [SD] age, 57.9 [9.2] years) had newly diagnosed AF with a first-degree relative affected by AF. Individuals with a first-degree relative affected by AF had a relative risk of 1.92 (95% CI, 1.84-1.99) for AF. The accountability for the phenotypic variance of AF was 19.9% for genetic factors (heritability), 3.5% for shared environmental factors, and 76.6% for nonshared environmental factors. After matching for age, sex, hypertension, type 2 diabetes, previous stroke, and anticoagulation, incident AF patients with vs without an affected first-degree relative had similar MACE-free survival. Genetic and environmental factors were associated with AF, with nonshared environmental factors accounting for three-fourths of the phenotypic variance in Taiwan. Patients having AF with a first-degree relative affected by AF did not have more MACE. Therefore, family history may not be particularly informative in the diagnosis or management of AF.

  4. Genome-wide linkage meta-analysis identifies susceptibility loci at 2q34 and 13q31.3 for genetic generalized epilepsies.

    PubMed

    Leu, Costin; de Kovel, Carolien G F; Zara, Federico; Striano, Pasquale; Pezzella, Marianna; Robbiano, Angela; Bianchi, Amedeo; Bisulli, Francesca; Coppola, Antonietta; Giallonardo, Anna Teresa; Beccaria, Francesca; Trenité, Dorothée Kasteleijn-Nolst; Lindhout, Dick; Gaus, Verena; Schmitz, Bettina; Janz, Dieter; Weber, Yvonne G; Becker, Felicitas; Lerche, Holger; Kleefuss-Lie, Ailing A; Hallman, Kerstin; Kunz, Wolfram S; Elger, Christian E; Muhle, Hiltrud; Stephani, Ulrich; Møller, Rikke S; Hjalgrim, Helle; Mullen, Saul; Scheffer, Ingrid E; Berkovic, Samuel F; Everett, Kate V; Gardiner, Mark R; Marini, Carla; Guerrini, Renzo; Lehesjoki, Anna-Elina; Siren, Auli; Nabbout, Rima; Baulac, Stephanie; Leguern, Eric; Serratosa, Jose M; Rosenow, Felix; Feucht, Martha; Unterberger, Iris; Covanis, Athanasios; Suls, Arvid; Weckhuysen, Sarah; Kaneva, Radka; Caglayan, Hande; Turkdogan, Dilsad; Baykan, Betul; Bebek, Nerses; Ozbek, Ugur; Hempelmann, Anne; Schulz, Herbert; Rüschendorf, Franz; Trucks, Holger; Nürnberg, Peter; Avanzini, Giuliano; Koeleman, Bobby P C; Sander, Thomas

    2012-02-01

    Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3% with heritability estimates of 80%. A considerable proportion of families with siblings affected by GGEs presumably display an oligogenic inheritance. The present genome-wide linkage meta-analysis aimed to map: (1) susceptibility loci shared by a broad spectrum of GGEs, and (2) seizure type-related genetic factors preferentially predisposing to either typical absence or myoclonic seizures, respectively. Meta-analysis of three genome-wide linkage datasets was carried out in 379 GGE-multiplex families of European ancestry including 982 relatives with GGEs. To dissect out seizure type-related susceptibility genes, two family subgroups were stratified comprising 235 families with predominantly genetic absence epilepsies (GAEs) and 118 families with an aggregation of juvenile myoclonic epilepsy (JME). To map shared and seizure type-related susceptibility loci, both nonparametric loci (NPL) and parametric linkage analyses were performed for a broad trait model (GGEs) in the entire set of GGE-multiplex families and a narrow trait model (typical absence or myoclonic seizures) in the subgroups of JME and GAE families. For the entire set of 379 GGE-multiplex families, linkage analysis revealed six loci achieving suggestive evidence for linkage at 1p36.22, 3p14.2, 5q34, 13q12.12, 13q31.3, and 19q13.42. The linkage finding at 5q34 was consistently supported by both NPL and parametric linkage results across all three family groups. A genome-wide significant nonparametric logarithm of odds score of 3.43 was obtained at 2q34 in 118 JME families. Significant parametric linkage to 13q31.3 was found in 235 GAE families assuming recessive inheritance (heterogeneity logarithm of odds = 5.02). Our linkage results support an oligogenic predisposition of familial GGE syndromes. The genetic risk factor at 5q34 confers risk to a broad spectrum of familial GGE syndromes, whereas susceptibility loci at 2q34 and 13q31.3 preferentially predispose to myoclonic seizures or absence seizures, respectively. Phenotype- genotype strategies applying narrow trait definitions in phenotypic homogeneous subgroups of families improve the prospects of disentangling the genetic basis of common familial GGE syndromes. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

  5. Human genetic variation in VAC14 regulates Salmonella invasion and typhoid fever through modulation of cholesterol.

    PubMed

    Alvarez, Monica I; Glover, Luke C; Luo, Peter; Wang, Liuyang; Theusch, Elizabeth; Oehlers, Stefan H; Walton, Eric M; Tram, Trinh Thi Bich; Kuang, Yu-Lin; Rotter, Jerome I; McClean, Colleen M; Chinh, Nguyen Tran; Medina, Marisa W; Tobin, David M; Dunstan, Sarah J; Ko, Dennis C

    2017-09-12

    Risk, severity, and outcome of infection depend on the interplay of pathogen virulence and host susceptibility. Systematic identification of genetic susceptibility to infection is being undertaken through genome-wide association studies, but how to expeditiously move from genetic differences to functional mechanisms is unclear. Here, we use genetic association of molecular, cellular, and human disease traits and experimental validation to demonstrate that genetic variation affects expression of VAC14, a phosphoinositide-regulating protein, to influence susceptibility to Salmonella enterica serovar Typhi ( S Typhi) infection. Decreased VAC14 expression increased plasma membrane cholesterol, facilitating Salmonella docking and invasion. This increased susceptibility at the cellular level manifests as increased susceptibility to typhoid fever in a Vietnamese population. Furthermore, treating zebrafish with a cholesterol-lowering agent, ezetimibe, reduced susceptibility to S Typhi. Thus, coupling multiple genetic association studies with mechanistic dissection revealed how VAC14 regulates Salmonella invasion and typhoid fever susceptibility and may open doors to new prophylactic/therapeutic approaches.

  6. Human genetic variation in VAC14 regulates Salmonella invasion and typhoid fever through modulation of cholesterol

    PubMed Central

    Alvarez, Monica I.; Glover, Luke C.; Luo, Peter; Wang, Liuyang; Theusch, Elizabeth; Oehlers, Stefan H.; Walton, Eric M.; Tram, Trinh Thi Bich; Kuang, Yu-Lin; Rotter, Jerome I.; McClean, Colleen M.; Chinh, Nguyen Tran; Medina, Marisa W.; Dunstan, Sarah J.

    2017-01-01

    Risk, severity, and outcome of infection depend on the interplay of pathogen virulence and host susceptibility. Systematic identification of genetic susceptibility to infection is being undertaken through genome-wide association studies, but how to expeditiously move from genetic differences to functional mechanisms is unclear. Here, we use genetic association of molecular, cellular, and human disease traits and experimental validation to demonstrate that genetic variation affects expression of VAC14, a phosphoinositide-regulating protein, to influence susceptibility to Salmonella enterica serovar Typhi (S. Typhi) infection. Decreased VAC14 expression increased plasma membrane cholesterol, facilitating Salmonella docking and invasion. This increased susceptibility at the cellular level manifests as increased susceptibility to typhoid fever in a Vietnamese population. Furthermore, treating zebrafish with a cholesterol-lowering agent, ezetimibe, reduced susceptibility to S. Typhi. Thus, coupling multiple genetic association studies with mechanistic dissection revealed how VAC14 regulates Salmonella invasion and typhoid fever susceptibility and may open doors to new prophylactic/therapeutic approaches. PMID:28827342

  7. Assessment of sand encroachment in Kuwait using GIS

    NASA Astrophysics Data System (ADS)

    Al-Helal, Anwar B.; Al-Awadhi, Jasem M.

    2006-04-01

    Assessment of sand encroachment in Kuwait using Geographical Information System (GIS) technology has been formulated as a Multi-Criteria Decision Making problem. The Delphi method and Analytical Hierarchy Process were adopted as evaluating techniques, in which experts’ judgments were analyzed for objectively estimating and weighting control factors. Seven triggering factors, depicted in the form of maps, were identified and ordered according to their priority. These factors are (1) wind energy; (2) surface sediment; (3) vegetation density; (4) land use; (5) drainage density; (6) topographic change and (7) vegetation type. The factor maps were digitized, converted to raster data and overlaid to determine their possible spatial relationships. Applying a susceptibility model, a map of sand encroachment susceptibility in Kuwait was developed. The map showed that the areas of very high and high sand encroachment susceptibility are located within the main corridor of sand pathway that coincides with the northwesterly dominant wind direction.

  8. Sinkhole susceptibility mapping using the analytical hierarchy process (AHP) and magnitude-frequency relationships: A case study in Hamadan province, Iran

    NASA Astrophysics Data System (ADS)

    Taheri, Kamal; Gutiérrez, Francisco; Mohseni, Hassan; Raeisi, Ezzat; Taheri, Milad

    2015-04-01

    Since 1989, an increasing number of sinkhole occurrences have been reported in the Kabudar Ahang and Razan-Qahavand subcatchments (KRQ) of Hamadan province, western Iran. The sinkhole-related subsidence phenomenon poses a significant threat for people and human structures, including sensitive facilities like the Hamadan Power Plant. Groundwater over-exploitation from the thick alluvial cover and the underlying cavernous limestone has been identified as the main factor involved in sinkhole development. A sinkhole susceptibility model was produced in a GIS environment applying the analytical hierarchy process (AHP) approach and considering a selection of eight factors, each categorized into five classes: distance to faults (DF), water level decline (WLD), groundwater exploitation (GE), penetration of deep wells into karst bedrock (PKA), distance to deep wells (DDW), groundwater alkalinity (GA), bedrock lithology (BL), and alluvium thickness (AT). Relative weights were preliminarily assigned to each factor and to their different classes through systematic pairwise comparisons based on expert judgment. The resulting sinkhole susceptibility index (SSI) values were then classified into four susceptibility classes: low, moderate, high and very high susceptibility. Subsequently, the model was refined through a trial and error process involving changes in the relative weights and iterative evaluation of the prediction capability. Independent evaluation of the final model indicates that 55% and 45% of the subsidence events fall within the very high and high, susceptibility zones, respectively. The results of this study show that AHP can be a useful approach for susceptibility assessment if data on the main controlling factors have sufficient accuracy and spatial coverage. The limitations of the model are partly related to the difficulty of gathering data on some important geological factors, due to their hidden nature. The magnitude and frequency relationship constructed with the 41 sinkholes with chronological and morphometric data indicates maximum recurrence intervals of 1.17, 2.14 and 4.18 years for sinkholes with major axial lengths equal to or higher than 10 m, 20 m, and 30 m, respectively.

  9. Genetic architecture for susceptibility to gout in the KARE cohort study.

    PubMed

    Shin, Jimin; Kim, Younyoung; Kong, Minyoung; Lee, Chaeyoung

    2012-06-01

    This study aimed to identify functional associations of cis-regulatory regions with gout susceptibility using data resulted from a genome-wide association study (GWAS), and to show a genetic architecture for gout with interaction effects among genes within each of the identified functions. The GWAS was conducted with 8314 control subjects and 520 patients with gout in the Korea Association REsource cohort. However, genetic associations with any individual nucleotide variants were not discovered by Bonferroni multiple testing in the GWAS (P>1.42 × 10(-7)). Genomic regions enrichment analysis was employed to identify functional associations of cis-regulatory regions. This analysis revealed several biological processes associated with gout susceptibility, and they were quite different from those with serum uric acid level. Epistasis for susceptibility to gout was estimated using entropy decomposition with selected genes within each biological process identified by the genomic regions enrichment analysis. Some epistases among nucleotide sequence variants for gout susceptibility were found to be larger than their individual effects. This study provided the first evidence that genetic factors for gout susceptibility greatly differed from those for serum uric acid level, which may suggest that research endeavors for identifying genetic factors for gout susceptibility should not be heavily dependent on pathogenesis of uric acid. Interaction effects between genes should be examined to explain a large portion of phenotypic variability for gout susceptibility.

  10. Three periods of one and a half decade of ischemic stroke susceptibility gene research: lessons we have learned

    PubMed Central

    2010-01-01

    Candidate gene association studies, linkage studies and genome-wide association studies have highlighted the role of genetic factors in the development of ischemic stroke. This research started over a decade ago, and can be separated into three major periods of research. In the first wave classic susceptibility markers associated with other diseases (such as the Leiden mutation in Factor V and mutations in the prothrombin and 5,10-methylenetetrahydrofolate reductase (MTHFR) genes) were tested for their role in stroke. These first studies used just a couple of hundred samples or even less. The second and still ongoing period bridges the two other periods of research and has led to a rapid increase in the spectrum of functional variants of genes or genomic regions, discovered primarily in relation to other diseases, tested on larger stroke samples of clinically better stratified patients. Large numbers of these alleles were originally discovered by array-based genome-wide association studies. The third period of research involves the direct array screening of large samples; this approach represents significant progress for research in the field. Research into susceptibility genes for stroke has taught us that careful stratification of patients is critical, that susceptibility alleles are often shared between diseases, and that not all susceptibility factors that associate with clinical traits that are themselves risk factors for stroke (such as increase of triglycerides) necessarily represent susceptibility for stroke. Research so far has been mainly focused on large- and small-vessel associated stroke, and knowledge on other types of stroke, which represent much smaller population samples, is still very scarce. Although some susceptibility allele tests are on the palette of some direct-to-consumer companies, the clinical utility and clinical validity of these test results still do not support their use in clinical practice. PMID:20831840

  11. Integrating mechanistic and polymorphism data to characterize human genetic susceptibility for environmental chemical risk assessment in the 21st century

    EPA Science Inventory

    Response to environmental chemicals can vary widely among individuals and between population groups. In human health risk assessment, data on susceptibility can be utilized by deriving risk levels based on a study of a susceptible population and/or an uncertainty factor may be ap...

  12. Differential Susceptibility to Effects of the Home Environment on Motor Developmental Outcomes of Preschool Children: Low Birthweight Status as a Susceptibility Factor

    ERIC Educational Resources Information Center

    Wu, Jennifer Chun-Li; Chiang, Tung-liang

    2016-01-01

    Low birthweight (LBW) children tend to have higher risks of developmental problems. According to differential susceptibility hypothesis, these putatively vulnerable children may also disproportionately benefit from positive environmental exposure. This study aimed to examine whether LBW status moderates home environmental influences on…

  13. Changing Susceptibility to Non-Optimum Temperatures in Japan, 1972-2012: The Role of Climate, Demographic, and Socioeconomic Factors.

    PubMed

    Chung, Yeonseung; Yang, Daewon; Gasparrini, Antonio; Vicedo-Cabrera, Ana M; Fook Sheng Ng, Chris; Kim, Yoonhee; Honda, Yasushi; Hashizume, Masahiro

    2018-05-02

    Previous studies have shown that population susceptibility to non-optimum temperatures has changed over time, but little is known about the related time-varying factors that underlie the changes. Our objective was to investigate the changing population susceptibility to non-optimum temperatures in 47 prefectures of Japan over four decades from 1972 to 2012, addressing three aspects: minimum mortality temperature (MMT) and heat- and cold-related mortality risks. In addition, we aimed to examine how these aspects of susceptibility were associated with climate, demographic, and socioeconomic variables. We first used a two-stage time-series design with a time-varying distributed lag nonlinear model and multivariate meta-analysis to estimate the time-varying MMT, heat- and cold-related mortality risks. We then applied linear mixed effects models to investigate the association between each of the three time-varying aspects of susceptibility and various time-varying factors. MMT increased from 23.2 [95% confidence interval (CI): 23, 23.6] to 28.7 (27.0, 29.7) °C. Heat-related mortality risk [relative risk (RR) for the 99th percentile of temperature vs. the MMT] decreased from 1.18 (1.15, 1.21) to 1.01 (0.98, 1.04). Cold-related mortality risk (RR for the first percentile vs. the MMT) generally decreased from 1.48 (1.41, 1.54) to 1.35 (1.32, 1.40), with the exception of a few eastern prefectures that showed increased risk. The changing patterns in all three aspects differed by region, sex, and causes of death. Higher mean temperature was associated ( p <0.01) with lower heat risk, whereas higher humidity was associated with higher cold risk. A higher percentage of elderly people was associated with a higher cold risk, whereas higher economic strength of the prefecture was related to lower cold risk. Population susceptibility to heat has decreased over the last four decades in Japan. Susceptibility to cold has decreased overall except for several eastern prefectures where it has either increased or remained unchanged. Certain climate, demographic, and socioeconomic factors explored in the current study might underlie this changing susceptibility. https://doi.org/10.1289/EHP2546.

  14. Factors Infuencing Women in Pap Smear Uptake

    NASA Astrophysics Data System (ADS)

    Wijayanti, K. E.; Alam, I. G.

    2017-03-01

    Objective: Pap smear has proven can decrease death caused by cervical cancer. However, in Indonesia, only few woman who already did pap smear. The aim of this study was to investigate women’s knowledge about pap smear cervical cancer, and to investigate factors influence women to do pap smear test. Methods: Quantitative data colected through questionairre towards 31 women who did pap smear and 55 women who did not do pap smear. Questionairre was made using Health Belief model as a guideline to examine percieved susceptibility, perceived serioussnes, perceived benefits and perceived barriers. Chi square and multiple logistic regresion were used to investigate difference in knowledge and what the most factor that influence women to take pap smear test. Results: There’s significance knowledge difference betweeen women who did and did not do pap smear. But furthermore, by using Multiple Logistic Regression test, appearantly knowledge was not a strong predictor factor for women to take pap smear test (koefisiensi β = -0,164) Conclusion: Perceived barriers were factors that affected pap smear uptake in women in Indonesia. Few respondents get the wrong informations about pap smear, cevical cancer and its symptoms

  15. Epigenetic understanding of gene-environment interactions in psychiatric disorders: a new concept of clinical genetics

    PubMed Central

    2012-01-01

    Epigenetics is a mechanism that regulates gene expression independently of the underlying DNA sequence, relying instead on the chemical modification of DNA and histone proteins. Although environmental and genetic factors were thought to be independently associated with disorders, several recent lines of evidence suggest that epigenetics bridges these two factors. Epigenetic gene regulation is essential for normal development, thus defects in epigenetics cause various rare congenital diseases. Because epigenetics is a reversible system that can be affected by various environmental factors, such as drugs, nutrition, and mental stress, the epigenetic disorders also include common diseases induced by environmental factors. In this review, we discuss the nature of epigenetic disorders, particularly psychiatric disorders, on the basis of recent findings: 1) susceptibility of the conditions to environmental factors, 2) treatment by taking advantage of their reversible nature, and 3) transgenerational inheritance of epigenetic changes, that is, acquired adaptive epigenetic changes that are passed on to offspring. These recently discovered aspects of epigenetics provide a new concept of clinical genetics. PMID:22414323

  16. Factors affecting drug-induced liver injury: antithyroid drugs as instances

    PubMed Central

    Niknahad, Hossein; Jamshidzadeh, Akram; Abdoli, Narges

    2014-01-01

    Methimazole and propylthiouracil have been used in the management of hyperthyroidism for more than half a century. However, hepatotoxicity is one of the most deleterious side effects associated with these medications. The mechanism(s) of hepatic injury induced by antithyroid agents is not fully recognized yet. Furthermore, there are no specific tools for predicting the occurrence of hepatotoxicity induced by these drugs. The purpose of this article is to give an overview on possible susceptibility factors in liver injury induced by antithyroid agents. Age, gender, metabolism characteristics, alcohol consumption, underlying diseases, immunologic mechanisms, and drug interactions are involved in enhancing antithyroid drugs-induced hepatic damage. An outline on the clinically used treatments for antithyroid drugs-induced hepatotoxicity and the potential therapeutic strategies found to be effective against this complication are also discussed. PMID:25320726

  17. DNA methylation in inflammatory bowel disease and beyond

    PubMed Central

    Low, Daren; Mizoguchi, Atsushi; Mizoguchi, Emiko

    2013-01-01

    Inflammatory bowel disease (IBD) is a consequence of the complex, dysregulated interplay between genetic predisposition, environmental factors, and microbial composition in the intestine. Despite a great advancement in identifying host-susceptibility genes using genome-wide association studies (GWAS), the majority of IBD cases are still underrepresented. The immediate challenge in post-GWAS era is to identify other causative genetic factors of IBD. DNA methylation has received increasing attention for its mechanistical role in IBD pathogenesis. This stable, yet dynamic DNA modification, can directly affect gene expression that have important implications in IBD development. The alterations in DNA methylation associated with IBD are likely to outset as early as embryogenesis all the way until old-age. In this review, we will discuss the recent advancement in understanding how DNA methylation alterations can contribute to the development of IBD. PMID:23983426

  18. Contribution of Sex-linked Biology and Gender Roles to Disparities with Trachoma1

    PubMed Central

    West, Sheila K.

    2004-01-01

    Globally, trachoma is the leading infectious cause of blindness. Survey data consistently show that trachoma-related blindness is two to four times higher in women than men. Tracing the increased risk for trachoma and its consequences for women suggests that other factors besides biology may contribute. Understanding the reasons for the excess risk for and consequences of trachoma in girls and women requires examining a number of issues: Are girls and women more biologically susceptible to the consequences of infection with Chlamydia trachomatis? Could other factors help explain the excess of conjunctival scarring and trichiasis in women? Do gender roles affect the risk for trachoma and its consequences? Are women more likely to have recurrence after trichiasis surgery compared to men? This article explores the answers to these questions. PMID:15550216

  19. The effects of inbreeding on disease susceptibility: Gyrodactylus turnbulli infection of guppies, Poecilia reticulata.

    PubMed

    Smallbone, Willow; van Oosterhout, Cock; Cable, Jo

    2016-08-01

    Inbreeding can threaten population persistence by reducing disease resistance through the accelerated loss of gene diversity (i.e. heterozygosity). Such inbreeding depression can affect many different fitness-related traits, including survival, reproductive success, and parasite susceptibility. Empirically quantifying the effects of inbreeding on parasite resistance is therefore important for ex-situ conservation of vertebrates. The present study evaluates the disease susceptibility of individuals bred under three different breeding regimes (inbred, crossed with full siblings; control, randomly crossed mating; and fully outbred). Specifically, we examined the relationship between inbreeding coefficient (F-coefficient) and susceptibility to Gyrodactylus turnbulli infection in a live bearing vertebrate, the guppy Poecilia reticulata. Host-breeding regime significantly affected the trajectories of parasite population growth on individual fish. Inbred fish showed significantly higher mean parasite intensity than fish from the control and outbred breeding regimes, and in addition, inbred fish were slower in purging their gyrodactylid infections. We discuss the role of inbreeding on the various arms of the immune system, and argue that the increased disease susceptibility of inbred individuals could contribute to the extinction vortex. This is one of the first studies to quantify the effects of inbreeding and breeding regime on disease susceptibility in a captive bred vertebrate of wild origin, and it highlights the risks faced by small (captive-bred) populations when exposed to their native parasites. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Magnetic mapping of distribution of wood ash used for fertilization of forest soil.

    PubMed

    Petrovský, Eduard; Remeš, Jiří; Kapička, Aleš; Podrázský, Vilém; Grison, Hana; Borůvka, Luboš

    2018-06-01

    The effect of wood-ash fertilization on forest soils has been assessed mainly through geochemical methods (e.g., content of soil organic matter or nutrients). However, a simple and fast method of determining the distribution of the ash and the extent of affected soil is missing. In this study we present the use of magnetic susceptibility, which is controlled by Fe-oxides, in comparing the fertilized soil in the forest plantation of pine and oak with intact forest soil. Spatial and vertical distribution of magnetic susceptibility was measured in an oak and pine plantation next to stems of young plants, where wood ash was applied as fertilizer. Pattern of the susceptibility distribution was compared with that in non-fertilized part of the plantation as well as with a spot of intact natural forest soil nearby. Our results show that the wood-ash samples contain significant amount of ferrimagnetic magnetite with susceptibility higher than that of typical forest soil. Clear differences were observed between magnetic susceptibility of furrows and ridges. Moreover, the dispersed ash remains practically on the surface, does not penetrate to deeper layers. Finally, our data suggest significant differences in surface values between the pine and oak plants. Based on this study we may conclude that magnetic susceptibility may represent a simple and approximate method of assessing the extent of soil affected by wood-ash. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. An EAR-motif-containing ERF transcription factor affects herbivore-induced signaling, defense and resistance in rice.

    PubMed

    Lu, Jing; Ju, Hongping; Zhou, Guoxin; Zhu, Chuanshu; Erb, Matthias; Wang, Xiaopeng; Wang, Peng; Lou, Yonggen

    2011-11-01

    Ethylene responsive factors (ERFs) are a large family of plant-specific transcription factors that are involved in the regulation of plant development and stress responses. However, little to nothing is known about their role in herbivore-induced defense. We discovered a nucleus-localized ERF gene in rice (Oryza sativa), OsERF3, that was rapidly up-regulated in response to feeding by the rice striped stem borer (SSB) Chilo suppressalis. Antisense and over-expression of OsERF3 revealed that it positively affects transcript levels of two mitogen-activated protein kinases (MAPKs) and two WRKY genes as well as concentrations of jasmonate (JA), salicylate (SA) and the activity of trypsin protease inhibitors (TrypPIs). OsERF3 was also found to mediate the resistance of rice to SSB. On the other hand, OsERF3 was slightly suppressed by the rice brown planthopper (BPH) Nilaparvata lugens (Stål) and increased susceptibility to this piercing sucking insect, possibly by suppressing H(2)O(2) biosynthesis. We propose that OsERF3 affects early components of herbivore-induced defense responses by suppressing MAPK repressors and modulating JA, SA, ethylene and H(2)O(2) pathways as well as plant resistance. Our results also illustrate that OsERF3 acts as a central switch that gears the plant's metabolism towards an appropriate response to chewing or piercing/sucking insects. © 2011 The Authors. The Plant Journal © 2011 Blackwell Publishing Ltd.

  2. Chronic ethanol consumption modulates growth factor release, mucosal cytokine production, and microRNA expression in nonhuman primates.

    PubMed

    Asquith, Mark; Pasala, Sumana; Engelmann, Flora; Haberthur, Kristen; Meyer, Christine; Park, Byung; Grant, Kathleen A; Messaoudi, Ilhem

    2014-04-01

    Chronic alcohol consumption has been associated with enhanced susceptibility to both systemic and mucosal infections. However, the exact mechanisms underlying this enhanced susceptibility remain incompletely understood. Using a nonhuman primate model of ethanol (EtOH) self-administration, we examined the impact of chronic alcohol exposure on immune homeostasis, cytokine, and growth factor production in peripheral blood, lung, and intestinal mucosa following 12 months of chronic EtOH exposure. EtOH exposure inhibited activation-induced production of growth factors hepatocyte growth factor (HGF), granulocyte colony-stimulating factor (G-CSF), and vascular-endothelial growth factor (VEGF) by peripheral blood mononuclear cells (PBMC). Moreover, EtOH significantly reduced the frequency of colonic Th1 and Th17 cells in a dose-dependent manner. In contrast, we did not observe differences in lymphocyte frequency or soluble factor production in the lung of EtOH-consuming animals. To uncover mechanisms underlying reduced growth factor and Th1/Th17 cytokine production, we compared expression levels of microRNAs in PBMC and intestinal mucosa. Our analysis revealed EtOH-dependent up-regulation of distinct microRNAs in affected tissues (miR-181a and miR-221 in PBMC; miR-155 in colon). Moreover, we were able to detect reduced expression of the transcription factors STAT3 and ARNT, which regulate expression of VEGF, G-CSF, and HGF and contain targets for these microRNAs. To confirm and extend these observations, PBMC were transfected with either mimics or antagomirs of miR-181 and miR-221, and protein levels of the transcription factors and growth factors were determined. Transfection of microRNA mimics led to a reduction in both STAT3/ARNT as well as VEGF/HGF/G-CSF levels. The opposite outcome was observed when microRNA antagomirs were transfected. Chronic EtOH consumption significantly disrupts both peripheral and mucosal immune homeostasis, and this dysregulation may be mediated by changes in microRNA expression. Copyright © 2013 by the Research Society on Alcoholism.

  3. Clinical characteristics and predictive factors of myasthenic crisis after thymectomy.

    PubMed

    Nam, Tai-Seung; Lee, Seung-Han; Kim, Byeong-Chae; Choi, Kang-Ho; Kim, Joon-Tae; Kim, Myeong-Kyu; Cho, Ki-Hyun; Lee, Min-Cheol

    2011-09-01

    The aims of this study were to assess the clinical characteristics of myasthenic crisis after thymectomy (MCAT) and to identify predictors affecting the occurrence of MCAT. Of 66 patients with myasthenia gravis (MG), MCAT occurred in 20 patients (30.3%). The median time interval from thymectomy to MCAT was 3.4 months. MCAT occurred in 65.0% of patients within the first 6 months of a thymectomy, and 35.0% after 6 months. A second MCAT occurred in nine (45.0%) patients who survived the first MCAT, and in seven (50.0%) of 14 patients with a history of a preoperative myasthenic crisis before thymectomy (MCBT). A history of MCBT, and clinical factors reflecting perioperative clinical severity at thymectomy, including preoperative Osserman's grade, bulbar symptoms, use of immunosuppressants, pulmonary function, and postoperative delayed ventilator weaning, were significantly correlated with the occurrence of MCAT on univariate analysis. However, a history of MCBT was the only independent factor affecting the occurrence of MCAT on multivariate logistic regression analysis (odds ratio, 17.9; 95% confidence interval, 4.019-79.873; p<0.001). Thus, the occurrence of MCAT may be correlated only with a history of MCBT rather than with factors reflecting perioperative clinical severity. MG patients with a history of MCBT are more susceptible to MCAT, particularly within the first 6 months of thymectomy. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Financial errors in dementia: Testing a neuroeconomic conceptual framework

    PubMed Central

    Chiong, Winston; Hsu, Ming; Wudka, Danny; Miller, Bruce L.; Rosen, Howard J.

    2013-01-01

    Financial errors by patients with dementia can have devastating personal and family consequences. We developed and evaluated a neuroeconomic conceptual framework for understanding financial errors across different dementia syndromes, using a systematic, retrospective, blinded chart review of demographically-balanced cohorts of patients with Alzheimer’s disease (AD, n=100) and behavioral variant frontotemporal dementia (bvFTD, n=50). Reviewers recorded specific reports of financial errors according to a conceptual framework identifying patient cognitive and affective characteristics, and contextual influences, conferring susceptibility to each error. Specific financial errors were reported for 49% of AD and 70% of bvFTD patients (p = 0.012). AD patients were more likely than bvFTD patients to make amnestic errors (p< 0.001), while bvFTD patients were more likely to spend excessively (p = 0.004) and to exhibit other behaviors consistent with diminished sensitivity to losses and other negative outcomes (p< 0.001). Exploratory factor analysis identified a social/affective vulnerability factor associated with errors in bvFTD, and a cognitive vulnerability factor associated with errors in AD. Our findings highlight the frequency and functional importance of financial errors as symptoms of AD and bvFTD. A conceptual model derived from neuroeconomic literature identifies factors that influence vulnerability to different types of financial error in different dementia syndromes, with implications for early diagnosis and subsequent risk prevention. PMID:23550884

  5. Combine bivariate statistics analysis and multivariate statistics analysis to assess landslide susceptibility in Chen-Yu-Lan watershed, Nantou, Taiwan.

    NASA Astrophysics Data System (ADS)

    Ngan Nguyen, Thi To; Liu, Cheng-Chien

    2013-04-01

    How landslides occurred and which factors triggered and sped up landslide occurrences were usually asked by researchers in the past decades. Many investigations carried out in many places in the world to finding out methods that predict and prevent damages from landslides phenomena. Chen-Yu-Lan River watershed is reputed as a 'hot pot' of landslide researches in Taiwan by its complicated geological structures with the significant tectonic fault systems and steeply mountainous terrain. Beside annual high precipitation concentration and the abrupt slopes, some natural disaster, as typhoons (Sinlaku-2008, Kalmaegi-2008, and Marakot-2009) and earthquake (Chi-Chi earthquake-1999) are also the triggered factors cause landslides with serious damages in this place. This research expresses the quantitative approaches to generate landslide susceptible map for Chen-Yu-Lan watershed, a mountainous area in the central Taiwan. Landslide inventories data, which were detected from the Formosat-2 imageries for eight years from 2004 to 2011, were applied to carry out landslide susceptibility mapping. Bivariate statistics analysis and multivariate statistics analysis would be applied to calculate susceptible index of landslides. The weights of parameters were computed based on landslide data for eight years from 2004 to 2011. To validate effective levels of factors to landslide occurrences, this method built some multivariate algorithms and compared these results with real landslide occurrences. Besides this method, the historical data of landslides were also used to assess and classify landslide susceptibility levels. From long-term landslide data, relation between landslide susceptibility levels and landslide repetition was assigned. The results demonstrated differently effective levels of potential factors, such as, slope gradient, drainage density, lithology and land use to landslide phenomena. The results also showed logical relationship between weights and characteristics of factors' classes. Depending on these results be able to help planning managers localize the high risk areas of landslide or safely areas by building and human activities.

  6. ramR mutations affecting fluoroquinolone susceptibility in epidemic multidrug-resistant Salmonella enterica serovar Kentucky ST198

    PubMed Central

    Baucheron, Sylvie; Le Hello, Simon; Doublet, Benoît; Giraud, Etienne; Weill, François-Xavier; Cloeckaert, Axel

    2013-01-01

    A screening for non-target mutations affecting fluoroquinolone susceptibility was conducted in epidemic multidrug-resistant Salmonella enterica serovar Kentucky ST198. Among a panel of representative isolates (n = 27), covering the epidemic, only three showed distinct mutations in ramR resulting in enhanced expression of genes encoding the AcrAB-TolC efflux system and low increase in ciprofloxacin MIC. No mutations were detected in other regulatory regions of this efflux system. Ciprofloxacin resistance in serovar Kentucky ST198 is thus currently mainly due to multiple target gene mutations. PMID:23914184

  7. Bemisia tabaci females from the Mediterranean (Q) species detect and avoid laying eggs in the presence of pyriproxyfen, a juvenile hormone analogue.

    PubMed

    Moshitzky, Pnina; Morin, Shai

    2014-10-01

    Pyriproxyfen, a juvenile hormone analogue, disrupts embryogenesis, metamorphosis and adult formation in Bemisia tabaci, but does not directly affect adult females. The effect of pyriproxyfen on egg-laying preference and performance of B. tabaci females and the influence of resistance to pyriproxyfen on these reproductive behaviours were studied. Choice experiments utilising cotton plants treated and not treated with pyriproxyfen revealed a significant preference for egg laying on non-treated plants both by resistant and susceptible females. No-choice assays indicated a reduction of ∼60% in the number of eggs laid on pyriproxyfen-treated plants by both resistant and susceptible females. The reduction in oviposition on treated plants was not accompanied with reduced expression of the vitellogenin gene or a delay in oocyte maturation, but significant accumulation of mature oocytes in the ovaries was observed, and could be reversed by transferring the females to non-treated plants. Pyriproxyfen caused reduced oviposition and enhanced mature oocyte accumulation in pyriproxyfen-resistant and pyriproxyfen-susceptible females. These findings can be explained by two alternative mechanisms: pyriproxyfen-regulated physiological arrest of oviposition, involving hormonal regulation of myotrophic factors, or the hierarchy-threshold behavioural theory of host choice, in which pyriproxyfen-treated plants are defined as low-quality hosts. Aspects of application are discussed. © 2013 Society of Chemical Industry.

  8. Differential susceptibility to environmental influences: the role of early temperament and parenting in the development of externalizing problems.

    PubMed

    Pitzer, Martina; Jennen-Steinmetz, Christine; Esser, Guenter; Schmidt, Martin H; Laucht, Manfred

    2011-01-01

    A difficult or undercontrolled temperament, as well as harsh parental discipline or a lack of warmth, has long been regarded as risk factors for the development of externalizing problems. In addition, it has been suggested that children with difficult temperament are especially susceptible to rearing influences. We investigated the impact of early temperament and parenting and their interactions on externalizing behavior at school age. Participants were 148 boys and 160 girls from a prospective longitudinal study on a high-risk sample. At ages 3 months and 2 years, temperament was assessed by a highly structured parent interview and standardized behavioral observations. Maternal parenting was assessed by videotaped behavioral observation and a parent questionnaire. Externalizing problems at age 8 years were measured by the Child Behavior Checklist. Using hierarchical linear regression analyses, we found that externalizing problems were predicted by psychosocial adversity and poor self-control, whereas no main effect for restrictive parenting or maternal empathy was found. Fearful-inhibited boys were positively affected by empathic and sensitive parenting, whereas girls who were low in self-control and/or fearful developed less externalizing problems with restrictive parenting. Our results partly support the differential susceptibility hypothesis. In addition, they point toward gender-specific pathways in the development of externalizing problems. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Why do animals differ in their susceptibility to geometrical illusions?

    PubMed

    Feng, Lynna C; Chouinard, Philippe A; Howell, Tiffani J; Bennett, Pauleen C

    2017-04-01

    In humans, geometrical illusions are thought to reflect mechanisms that are usually helpful for seeing the world in a predictable manner. These mechanisms deceive us given the right set of circumstances, correcting visual input where a correction is not necessary. Investigations of non-human animals' susceptibility to geometrical illusions have yielded contradictory results, suggesting that the underlying mechanisms with which animals see the world may differ across species. In this review, we first collate studies showing that different species are susceptible to specific illusions in the same or reverse direction as humans. Based on a careful assessment of these findings, we then propose several ecological and anatomical factors that may affect how a species perceives illusory stimuli. We also consider the usefulness of this information for determining whether sight in different species might be more similar to human sight, being influenced by contextual information, or to how machines process and transmit information as programmed. Future testing in animals could provide new theoretical insights by focusing on establishing dissociations between stimuli that may or may not alter perception in a particular species. This information could improve our understanding of the mechanisms behind illusions, but also provide insight into how sight is subjectively experienced by different animals, and the degree to which vision is innate versus acquired, which is difficult to examine in humans.

  10. Environmental determinants of allergy and asthma in early life.

    PubMed

    Burbank, Allison J; Sood, Amika K; Kesic, Matthew J; Peden, David B; Hernandez, Michelle L

    2017-07-01

    Allergic disease prevalence has increased significantly in recent decades. Primary prevention efforts are being guided by study of the exposome (or collective environmental exposures beginning during the prenatal period) to identify modifiable factors that affect allergic disease risk. In this review we explore the evidence supporting a relationship between key components of the external exposome in the prenatal and early-life periods and their effect on atopy development focused on microbial, allergen, and air pollution exposures. The abundance and diversity of microbial exposures during the first months and years of life have been linked with risk of allergic sensitization and disease. Indoor environmental allergen exposure during early life can also affect disease development, depending on the allergen type, dose, and timing of exposure. Recent evidence supports the role of ambient air pollution in allergic disease inception. The lack of clarity in the literature surrounding the relationship between environment and atopy reflects the complex interplay between cumulative environmental factors and genetic susceptibility, such that no one factor dictates disease development in all subjects. Understanding the effect of the summation of environmental exposures throughout a child's development is needed to identify cost-effective interventions that reduce atopy risk in children. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  11. Aluminium Involvement in Neurotoxicity

    PubMed Central

    Fulgenzi, Alessandro; Vietti, Daniele; Ferrero, Maria Elena

    2014-01-01

    The aetiology of neurodegenerative diseases (ND) seems to involve susceptibility genes and environmental factors. Toxic metals are considered major environmental pollutants. Following our study of a case of multiple sclerosis (MS) improvement due to removal of aluminium (Al) and other toxic metals, we have examined the possible relationship between Al intoxication and ND. We used the slow intravenous treatment with the chelating agent EDTA (calcium disodium ethylene diamine tetraacetic acid) (chelation test) to remove Al and detected it in the urine collected from the patients for 12 hours. Patients affected by MS represented 85.6% of total ND. Al was present in 44.8% of cases comprehensive of ND and healthy patients. Al levels were significantly higher in ND patients than in healthy subjects. We here show that treatment of patients affected by Al burden with ten EDTA chelation therapies (EDTA intravenous administration once a week) was able to significantly reduce Al intoxication. PMID:25243176

  12. Autoimmune mechanisms in pernicious anaemia & thyroid disease.

    PubMed

    Osborne, David; Sobczyńska-Malefora, Agata

    2015-09-01

    Pernicious anaemia (PA) and some types of thyroid disease result from autoimmune processes. The autoimmune mechanisms in these conditions have not been fully elucidated. This review discusses the autoimmune mechanisms involved in PA and how these affect diagnosis and disease progression. In addition to gastric antibodies, antibodies to the vitamin B12 binding protein transcobalamin which can result in high serum B12 levels are also addressed with regard to how they affect clinical practice. The role of autoimmune susceptibility is investigated by comparing PA to one of its most common comorbidities, autoimmune thyroid disease (AITD). Thyroid disease (although not exclusively AITD) and B12 deficiency are both also implicated in the pathology of hyperhomocysteinemia, an elevated homocysteine in plasma. Since hyperhomocysteinemia is a risk factor for cardiovascular occlusive disease, this review also addresses how thyroid disease in particular leads to changes in homocysteine levels. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Antagonism between phytohormone signalling underlies the variation in disease susceptibility of tomato plants under elevated CO2.

    PubMed

    Zhang, Shuai; Li, Xin; Sun, Zenghui; Shao, Shujun; Hu, Lingfei; Ye, Meng; Zhou, Yanhong; Xia, Xiaojian; Yu, Jingquan; Shi, Kai

    2015-04-01

    Increasing CO2 concentrations ([CO2]) have the potential to disrupt plant-pathogen interactions in natural and agricultural ecosystems, but the research in this area has often produced conflicting results. Variations in phytohormone salicylic acid (SA) and jasmonic acid (JA) signalling could be associated with variations in the responses of pathogens to plants grown under elevated [CO2]. In this study, interactions between tomato plants and three pathogens with different infection strategies were compared. Elevated [CO2] generally favoured SA biosynthesis and signalling but repressed the JA pathway. The exposure of plants to elevated [CO2] revealed a lower incidence and severity of disease caused by tobacco mosaic virus (TMV) and by Pseudomonas syringae, whereas plant susceptibility to necrotrophic Botrytis cinerea increased. The elevated [CO2]-induced and basal resistance to TMV and P. syringae were completely abolished in plants in which the SA signalling pathway nonexpressor of pathogenesis-related genes 1 (NPR1) had been silenced or in transgenic plants defective in SA biosynthesis. In contrast, under both ambient and elevated [CO2], the susceptibility to B. cinerea highly increased in plants in which the JA signalling pathway proteinase inhibitors (PI) gene had been silenced or in a mutant affected in JA biosynthesis. However, plants affected in SA signalling remained less susceptible to this disease. These findings highlight the modulated antagonistic relationship between SA and JA that contributes to the variation in disease susceptibility under elevated [CO2]. This information will be critical for investigating how elevated CO2 may affect plant defence and the dynamics between plants and pathogens in both agricultural and natural ecosystems. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  14. Antagonism between phytohormone signalling underlies the variation in disease susceptibility of tomato plants under elevated CO2

    PubMed Central

    Zhang, Shuai; Li, Xin; Sun, Zenghui; Shao, Shujun; Hu, Lingfei; Ye, Meng; Zhou, Yanhong; Xia, Xiaojian; Yu, Jingquan; Shi, Kai

    2015-01-01

    Increasing CO2 concentrations ([CO2]) have the potential to disrupt plant–pathogen interactions in natural and agricultural ecosystems, but the research in this area has often produced conflicting results. Variations in phytohormone salicylic acid (SA) and jasmonic acid (JA) signalling could be associated with variations in the responses of pathogens to plants grown under elevated [CO2]. In this study, interactions between tomato plants and three pathogens with different infection strategies were compared. Elevated [CO2] generally favoured SA biosynthesis and signalling but repressed the JA pathway. The exposure of plants to elevated [CO2] revealed a lower incidence and severity of disease caused by tobacco mosaic virus (TMV) and by Pseudomonas syringae, whereas plant susceptibility to necrotrophic Botrytis cinerea increased. The elevated [CO2]-induced and basal resistance to TMV and P. syringae were completely abolished in plants in which the SA signalling pathway nonexpressor of pathogenesis-related genes 1 (NPR1) had been silenced or in transgenic plants defective in SA biosynthesis. In contrast, under both ambient and elevated [CO2], the susceptibility to B. cinerea highly increased in plants in which the JA signalling pathway proteinase inhibitors (PI) gene had been silenced or in a mutant affected in JA biosynthesis. However, plants affected in SA signalling remained less susceptible to this disease. These findings highlight the modulated antagonistic relationship between SA and JA that contributes to the variation in disease susceptibility under elevated [CO2]. This information will be critical for investigating how elevated CO2 may affect plant defence and the dynamics between plants and pathogens in both agricultural and natural ecosystems. PMID:25657213

  15. Genetic resistance to rhabdovirus infection in teleost fish is paralleled to the derived cell resistance status.

    PubMed

    Verrier, Eloi R; Langevin, Christelle; Tohry, Corinne; Houel, Armel; Ducrocq, Vincent; Benmansour, Abdenour; Quillet, Edwige; Boudinot, Pierre

    2012-01-01

    Genetic factors of resistance and predisposition to viral diseases explain a significant part of the clinical variability observed within host populations. Predisposition to viral diseases has been associated to MHC haplotypes and T cell immunity, but a growing repertoire of innate/intrinsic factors are implicated in the genetic determinism of the host susceptibility to viruses. In a long-term study of the genetics of host resistance to fish rhabdoviruses, we produced a collection of double-haploid rainbow trout clones showing a wide range of susceptibility to Viral Hemorrhagic Septicemia Virus (VHSV) waterborne infection. The susceptibility of fibroblastic cell lines derived from these clonal fish was fully consistent with the susceptibility of the parental fish clones. The mechanisms determining the host resistance therefore did not associate with specific host immunity, but rather with innate or intrinsic factors. One cell line was resistant to rhabdovirus infection due to the combination of an early interferon IFN induction--that was not observed in the susceptible cells--and of yet unknown factors that hamper the first steps of the viral cycle. The implication of IFN was well consistent with the wide range of resistance of this genetic background to VSHV and IHNV, to the birnavirus IPNV and the orthomyxovirus ISAV. Another cell line was even more refractory to the VHSV infection through different antiviral mechanisms. This collection of clonal fish and isogenic cell lines provides an interesting model to analyze the relative contribution of antiviral pathways to the resistance to different viruses.

  16. Norovirus Gastroenteritis Outbreak with a Secretor-independent Susceptibility Pattern, Sweden

    PubMed Central

    Nordgren, Johan; Kindberg, Elin; Lindgren, Per-Eric; Matussek, Andreas

    2010-01-01

    Norovirus (NoV) is recognized as the commonest cause of acute gastroenteritis among adults. Susceptibility to disease has been associated with histo-blood group antigens and secretor status; nonsecretors are almost completely resistant to disease. We report a foodborne outbreak of GI.3 NoV gastroenteritis that affected 33/83 (40%) persons. Symptomatic disease was as likely to develop in nonsecretors as in secretors (odds ratio [OR] 1.41, 95% confidence interval [CI] 0.46–4.36 vs. OR 0.71, 95% CI 0.23–2.18, p = 0.57). Moreover, no statistical difference in susceptibility was found between persons of different Lewis or ABO phenotypes. The capsid gene of the outbreak strain shares high amino acid homology with the Kashiwa645 GI.3 strain, previously shown to recognize nonsecretor saliva, as well as synthetic Lewis a. This norovirus outbreak affected persons regardless of secretor status or Lewis or ABO phenotypes. PMID:20031047

  17. Influence of Incidental Discrete Emotions on Health Risk Perception and Persuasion.

    PubMed

    Nan, Xiaoli

    2017-06-01

    This research examines the effects of two incidental discrete emotions-fear and anger-on health risk perception (i.e., perceived susceptibility to a health problem) and persuasion. In two experiments, fear and anger were induced before participants were exposed to a public service announcement that advocated sun protection behaviors to prevent skin cancer (Experiment 1) or flossing to prevent gum diseases (Experiment 2). It was found that fearful participants perceived greater susceptibility to the health risk than angry participants and those who were in a neutral affective state. Angry participants did not differ from those in a neutral affective state in terms of perceived susceptibility. There was mixed evidence that fear exerted an indirect effect on attitude toward the recommended health behavior and intention to perform the health behavior through health risk perception. Theoretical and practical implications of the findings are discussed.

  18. Impact of I/D polymorphism of ACE gene on risk of development and course of chronic obstructive pulmonary disease.

    PubMed

    Mlak, Radosław; Homa-Mlak, Iwona; Powrózek, Tomasz; Mackiewicz, Barbara; Michnar, Marek; Krawczyk, Paweł; Dziedzic, Marcin; Rubinsztajn, Renata; Chazan, Ryszarda; Milanowski, Janusz; Małecka-Massalska, Teresa

    2016-04-01

    Chronic obstructive pulmonary disease (COPD) affects more than 10% of the world's population over 40 years of age. The main exogenous risk factor is cigarette smoking; however, only 20% of smokers develop COPD, indicating that some other factors, e.g. genetic, may play an important role in the disease pathogenesis. Recent research indicates that ACE (angiotensin-converting enzyme) may be a susceptibility gene for asthma or COPD. The aim of our study was to determine the influence of I/D (insertion/deletion) polymorphism of the ACE gene (AluYa5, rs4646994) on the risk and course of COPD. We investigated ACE I/D polymorphism in 206 COPD and 165 healthy Caucasian subjects. In the generalized linear model (GLZ) analysis of the influence of selected factors on presence of COPD we found a significant independent effect for male sex (repeatedly increases the risk of COPD, OR = 7.7, p = 0.049), as well as smoking or lower body mass index, but only in combination with older age (OR = 0.96, p = 0.003 and OR = 1.005, p = 0.04 respectively). Interestingly, analysis of factors which may influence the risk of a higher number of exacerbations demonstrated that occurrence of DD genotype, but only in men, is associated with a lower risk (OR = 0.7, p = 0.03) of this complication. We suggest that ACE may not be a susceptibility gene for the origin of COPD but a disease-modifying gene. Since the impact of I/D polymorphism of the ACE gene on COPD risk is moderate or negligible, other molecular changes, that will help predict the development of this disease, should still be sought.

  19. Genetic liability, prenatal health, stress and family environment: risk factors in the Harvard Adolescent Family High Risk for schizophrenia study.

    PubMed

    Walder, Deborah J; Faraone, Stephen V; Glatt, Stephen J; Tsuang, Ming T; Seidman, Larry J

    2014-08-01

    The familial ("genetic") high-risk (FHR) paradigm enables assessment of individuals at risk for schizophrenia based on a positive family history of schizophrenia in first-degree, biological relatives. This strategy presumes genetic transmission of abnormal traits given high heritability of the illness. It is plausible, however, that adverse environmental factors are also transmitted in these families. Few studies have evaluated both biological and environmental factors within a FHR study of adolescents. We conceptualize four precursors to psychosis pathogenesis: two biological (genetic predisposition, prenatal health issues (PHIs)) and two environmental (family environment, stressful life events (SLEs)). Participants assessed between 1998 and 2007 (ages 13-25) included 40 (20F/20M) adolescents at FHR for schizophrenia (FHRs) and 55 (31F/24M) community controls. 'Genetic load' indexed number of affected family members relative to pedigree size. PHI was significantly greater among FHRs, and family cohesion and expressiveness were less (and family conflict was higher) among FHRs; however, groups did not significantly differ in SLE indices. Among FHRs, genetic liability was significantly associated with PHI and family expressiveness. Prenatal and family environmental disruptions are elevated in families with a first-degree relative with schizophrenia. Findings support our proposed 'polygenic neurodevelopmental diathesis-stress model' whereby psychosis susceptibility (and resilience) involves the independent and synergistic confluence of (temporally-sensitive) biological and environmental factors across development. Recognition of biological and social environmental influences across critical developmental periods points to key issues relevant for enhanced identification of psychosis susceptibility, facilitation of more precise models of illness risk, and development of novel prevention strategies. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Basic helix-loop-helix transcription factor NEUROG1 and schizophrenia: effects on illness susceptibility, MRI brain morphometry and cognitive abilities.

    PubMed

    Ho, Beng-Choon; Epping, Eric; Wang, Kai; Andreasen, Nancy C; Librant, Amy; Wassink, Thomas H

    2008-12-01

    Transcription factors, including the basic helix-loop-helix (bHLH) family, regulate numerous genes and play vital roles in controlling gene expression. Consequently, transcription factor mutations can lead to phenotypic pleiotropy, and may be a candidate mechanism underlying the complex genetics and heterogeneous phenotype of schizophrenia. Neurogenin1 (NEUROG1; a.k.a. Ngn1 or Neurod3), a bHLH transcription factor encoded on a known schizophrenia linkage region in 5q31.1, induces glutamatergic and suppresses GABAergic neuronal differentiation during embryonic neurodevelopment. The goal of this study is to investigate NEUROG1 effects on schizophrenia risk and on phenotypic features of schizophrenia. We tested 392 patients with schizophrenia or schizoaffective disorder and 226 healthy normal volunteers for association with NEUROG1. Major alleles on two NEUROG1-associated SNPs (rs2344484-C-allele and rs8192558-G-allele) were significantly more prevalent among patients (p

  1. Proton Testing: Opportunities, Pitfalls and Puzzles

    NASA Technical Reports Server (NTRS)

    Ladbury, Raymond

    2017-01-01

    Although proton SEE testing can place constraints on some heavy-ion SEE susceptibilities, it is important to quantify residual risk that protons may not reveal all SEE susceptibilities in a system. We examine the relative strengths and limitations of proton and heavy-ion SEE testing and how these may be affected by technology scaling and high-Z materials in the device.

  2. Infant Temperament Moderates Relations between Maternal Parenting in Early Childhood and Children's Adjustment in First Grade

    ERIC Educational Resources Information Center

    Stright, Anne Dopkins; Gallagher, Kathleen Cranley; Kelley, Ken

    2008-01-01

    A differential susceptibility hypothesis proposes that children may differ in the degree to which parenting qualities affect aspects of child development. Infants with difficult temperaments may be more susceptible to the effects of parenting than infants with less difficult temperaments. Using latent change curve analyses to analyze data from the…

  3. Enhanced inflammation and attenuated tumor suppressor pathways are associated with oncogene-induced lung tumors in aged mice

    USDA-ARS?s Scientific Manuscript database

    Aging is often accompanied by a dramatic increase in cancer susceptibility. To gain insights into how aging affects tumor susceptibility, we generated a conditional mouse model in which oncogenic KrasG12D was activated specifically in lungs of young (3-5 months) and old (19-24 months) mice. Activati...

  4. Vector specificity of Trypanosoma catostomi and its infectivity to freshwater fishes.

    PubMed

    Jones, S R; Woo, P T

    1992-02-01

    Trypanosoma catostomi was found in 36.2% of 558 white suckers (Catostomus commersoni) from Ontario, Canada. The abundance of Actinobdella inequiannulata was 35% (68 leeches/197 suckers examined for leeches). The susceptibility of 3 species of leeches (Hemiclepsis marginata, Desserobdella phalera, and A. inequiannulata) and 7 species of fishes (C. commersoni, Amia calva, Anguilla rostrata, Ictalurus nebulosus, Oncorhynchus mykiss, Perca flavescens, and Esox lucius) to infection with T. catostomi was examined. Metatrypanosomes were found in the crop and proboscis sheath of 13 of 21 A. inequiannulata and in the crop of 10 of 12 H. marginata and 1 of 21 D. phalera. Only flagellates from A. inequiannulata were infective to C. commersoni. Cultured T. catostomi infected C. commersoni and A. calva but not any other fish species. Laboratory-reared C. commersoni were more susceptible than wild-caught specimens. Cultured Trypanosoma phaleri did not infect its natural host, A. calva. Host specificity should be established experimentally before a specific diagnosis is made. Cultures may be useful in simulating factors that affect development in the vector.

  5. Female Patient with Alport Syndrome and Concomitant Membranous Nephropathy: Susceptibility or Association of Two Diseases?

    PubMed

    Veloso, Mariana P; Neves, Precil D M M; Jorge, Lectícia B; Dias, Cristiane B; Yu, Luis; Pinheiro, Rafaela B B; Testagrossa, Leonardo A; Malheiros, Denise M; Balbo, Bruno E P; Lerário, Antônio M; Onuchic, Luiz F; Woronik, Viktoria

    2017-01-01

    Alport syndrome (AS) is a disorder of collagen IV, a component of glomerular basement membrane (GBM). The association of AS and immunocomplex nephropathies is uncommon. This is a case of a 37-year-old woman with family history of X-linked AS, including 4 affected sons. This patient developed full-blown nephrotic syndrome along a 3-month period, a presentation not consistent with AS progression. This scenario suggested an alternative diagnosis. A kidney biopsy was therefore performed, showing membranous nephropathy (MN) in addition to GBM structural alterations compatible with AS. Whole exome sequencing also confirmed the diagnosis of X-linked AS, revealing a heterozygous pathogenic mutation in COL4A5. While a negative serum anti-phospholipase A2 receptor did not rule out a primary form of MN, it was also uncertain whether positive serologic tests for syphilis could represent a secondary factor. It is currently unknown whether this unusual association represents AS susceptibility to immunocomplex-mediated diseases or simply an association of 2 disorders. © 2017 S. Karger AG, Basel.

  6. Don't let the flu catch you: agency assignment in printed educational materials about the H1N1 influenza virus.

    PubMed

    McGlone, Matthew S; Bell, Robert A; Zaitchik, Sarah T; McGlynn, Joseph

    2013-01-01

    In English and in other languages, the agency for viral transmission can be grammatically assigned to people (e.g., Thousands may contract H1N1) or to the virus itself (e.g., H1N1 may infect thousands). These assignment options shape different conceptions of transmission as attributable either to social contact within one's control or to pursuit of an active predator. The authors tested the effect of agency assignment and agentic images on young adults' (N = 246) reactions to educational materials about H1N1 influenza. The authors hypothesized that assigning agency to the virus would heighten perceived severity and personal susceptibility relative to human agency assignment. Results were consistent with this hypothesis, indicating that virus agency increased perceptions of severity, personal susceptibility, and reported intentions to seek vaccination relative to human agency. The image manipulation did not directly affect these factors. The findings suggest that strategic agency assignment can improve the effectiveness of educational materials about influenza and other health threats.

  7. Baseline heart rate, sensation seeking, and aggression in young adult women: a two-sample examination.

    PubMed

    Wilson, Laura C; Scarpa, Angela

    2013-01-01

    Although substantial literature discusses sensation seeking as playing a role in the relationship between baseline heart rate and aggression, few published studies have tested the relationships among these variables. Furthermore, most prior studies have focused on risk factors of aggression in men and have largely ignored this issue in women. Two samples (n = 104; n = 99) of young adult women completed measures of resting heart rate, sensation seeking, and aggression. Across the two samples of females there was no evidence for the relationships of baseline heart rate with sensation seeking or with aggression that has been consistently shown in males. Boredom susceptibility and disinhibition subscales of sensation seeking were consistently significantly correlated with aggression. The lack of significance and the small effect sizes indicate that other mechanisms are also at work in affecting aggression in young adult women. Finally, it is important to consider the type of sensation seeking in relation to aggression, as only boredom susceptibility and disinhibition were consistently replicated across samples. © 2013 Wiley Periodicals, Inc.

  8. A survey of Clostridium spiroforme antimicrobial susceptibility in rabbit breeding.

    PubMed

    Agnoletti, Fabrizio; Ferro, Tiziana; Guolo, Angela; Marcon, Barbara; Cocchi, Monia; Drigo, Ilenia; Mazzolini, Elena; Bano, Luca

    2009-04-14

    Rabbit meat breeding may be heavily affected by enterotoxaemia due to Clostridium spiroforme. Data on its antimicrobial susceptibility are insufficient, presumably because of difficulties in cultivating and identifying the pathogen. Our aim is therefore to provide this information to veterinary practitioners by focusing on a panel of therapeutics used in intensive rabbit units. Lincomycin was also checked in order to investigate the origin of resistance to macrolides. Minimal inhibitory concentrations (MICs) were determined with the agar dilution method according to the CLSI M11-A7 protocol (2007). MIC(50) and MIC(90) were, respectively, 64 and 64microg/ml for tiamulin, 32 and 32microg/ml for norfloxacin, 0.063 and 0.125microg/ml for amoxicillin, and 8 and 16microg/ml for doxycycline. MIC(50) and MIC(90) were 256microg/ml for sulphadimethoxine, spiramycin and lincomycin. Our results have shown that intrinsic or acquired antimicrobial resistances are diffuse in the C. spiroforme population and suggest focusing on prevention rather than on treatment of clostridial overgrowth, by reducing risk factors and using antimicrobials prudently.

  9. Copy Number Variants and Exome Sequencing Analysis in Six Pairs of Chinese Monozygotic Twins Discordant for Congenital Heart Disease.

    PubMed

    Xu, Yuejuan; Li, Tingting; Pu, Tian; Cao, Ruixue; Long, Fei; Chen, Sun; Sun, Kun; Xu, Rang

    2017-12-01

    Congenital heart disease (CHD) is one of the most common birth defects. More than 200 susceptibility loci have been identified for CHDs, yet a large part of the genetic risk factors remain unexplained. Monozygotic (MZ) twins are thought to be completely genetically identical; however, discordant phenotypes have been found in MZ twins. Recent studies have demonstrated genetic differences between MZ twins. We aimed to test whether copy number variants (CNVs) and/or genetic mutation differences play a role in the etiology of CHDs by using single nucleotide polymorphism (SNP) genotyping arrays and whole exome sequencing of twin pairs discordant for CHDs. Our goal was to identify mutations present only in the affected twins, which could identify novel candidates for CHD susceptibility loci. We present a comprehensive analysis for the CNVs and genetic mutation results of the selected individuals but detected no consistent differences within the twin pairs. Our study confirms that chromosomal structure or genetic mutation differences do not seem to play a role in the MZ twins discordant for CHD.

  10. Interplay between DISC1 and GABA signaling regulates neurogenesis in mice and risk for schizophrenia.

    PubMed

    Kim, Ju Young; Liu, Cindy Y; Zhang, Fengyu; Duan, Xin; Wen, Zhexing; Song, Juan; Feighery, Emer; Lu, Bai; Rujescu, Dan; St Clair, David; Christian, Kimberly; Callicott, Joseph H; Weinberger, Daniel R; Song, Hongjun; Ming, Guo-li

    2012-03-02

    How extrinsic stimuli and intrinsic factors interact to regulate continuous neurogenesis in the postnatal mammalian brain is unknown. Here we show that regulation of dendritic development of newborn neurons by Disrupted-in-Schizophrenia 1 (DISC1) during adult hippocampal neurogenesis requires neurotransmitter GABA-induced, NKCC1-dependent depolarization through a convergence onto the AKT-mTOR pathway. In contrast, DISC1 fails to modulate early-postnatal hippocampal neurogenesis when conversion of GABA-induced depolarization to hyperpolarization is accelerated. Extending the period of GABA-induced depolarization or maternal deprivation stress restores DISC1-dependent dendritic regulation through mTOR pathway during early-postnatal hippocampal neurogenesis. Furthermore, DISC1 and NKCC1 interact epistatically to affect risk for schizophrenia in two independent case control studies. Our study uncovers an interplay between intrinsic DISC1 and extrinsic GABA signaling, two schizophrenia susceptibility pathways, in controlling neurogenesis and suggests critical roles of developmental tempo and experience in manifesting the impact of susceptibility genes on neuronal development and risk for mental disorders. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Early-life adversity-induced long-term epigenetic programming associated with early onset of chronic physical aggression: Studies in humans and animals.

    PubMed

    Chistiakov, Dimitry A; Chekhonin, Vladimir P

    2017-06-05

    To examine whether chronic physical aggression (CPA) in adulthood can be epigenetically programmed early in life due to exposure to early-life adversity. Literature search of public databases such as PubMed/MEDLINE and Scopus. Children/adolescents susceptible for CPA and exposed to early-life abuse fail to efficiently cope with stress that in turn results in the development of CPA later in life. This phenomenon was observed in humans and animal models of aggression. The susceptibility to aggression is a complex trait that is regulated by the interaction between environmental and genetic factors. Epigenetic mechanisms mediate this interaction. Subjects exposed to stress early in life exhibited long-term epigenetic programming that can influence their behaviour in adulthood. This programming affects expression of many genes not only in the brain but also in other systems such as neuroendocrine and immune. The propensity to adult CPA behaviour in subjects experienced to early-life adversity is mediated by epigenetic programming that involves long-term systemic epigenetic alterations in a whole genome.

  12. Genetic risk factors of systemic lupus erythematosus in the Malaysian population: a minireview.

    PubMed

    Chai, Hwa Chia; Phipps, Maude Elvira; Chua, Kek Heng

    2012-01-01

    SLE is an autoimmune disease that is not uncommon in Malaysia. In contrast to Malays and Indians, the Chinese seem to be most affected. SLE is characterized by deficiency of body's immune response that leads to production of autoantibodies and failure of immune complex clearance. This minireview attempts to summarize the association of several candidate genes with risk for SLE in the Malaysian population and discuss the genetic heterogeneity that exists locally in Asians and in comparison with SLE in Caucasians. Several groups of researchers have been actively investigating genes that are associated with SLE susceptibility in the Malaysian population by screening possible reported candidate genes across the SLE patients and healthy controls. These candidate genes include MHC genes and genes encoding complement components, TNF, FcγR, T-cell receptors, and interleukins. However, most of the polymorphisms investigated in these genes did not show significant associations with susceptibility to SLE in the Malaysian scenario, except for those occurring in MHC genes and genes coding for TNF-α, IL-1β, IL-1RN, and IL-6.

  13. Genetic Risk Factors of Systemic Lupus Erythematosus in the Malaysian Population: A Minireview

    PubMed Central

    Chai, Hwa Chia; Phipps, Maude Elvira; Chua, Kek Heng

    2012-01-01

    SLE is an autoimmune disease that is not uncommon in Malaysia. In contrast to Malays and Indians, the Chinese seem to be most affected. SLE is characterized by deficiency of body's immune response that leads to production of autoantibodies and failure of immune complex clearance. This minireview attempts to summarize the association of several candidate genes with risk for SLE in the Malaysian population and discuss the genetic heterogeneity that exists locally in Asians and in comparison with SLE in Caucasians. Several groups of researchers have been actively investigating genes that are associated with SLE susceptibility in the Malaysian population by screening possible reported candidate genes across the SLE patients and healthy controls. These candidate genes include MHC genes and genes encoding complement components, TNF, FcγR, T-cell receptors, and interleukins. However, most of the polymorphisms investigated in these genes did not show significant associations with susceptibility to SLE in the Malaysian scenario, except for those occurring in MHC genes and genes coding for TNF-α, IL-1β, IL-1RN, and IL-6. PMID:21941582

  14. Pharmacogenetics and pathophysiology of CACNA1S mutations in malignant hyperthermia.

    PubMed

    Beam, Teresa A; Loudermilk, Emily F; Kisor, David F

    2017-02-01

    A review of the pharmacogenetics (PGt) and pathophysiology of calcium voltage-gated channel subunit alpha1 S (CACNA1S) mutations in malignant hyperthermia susceptibility type 5 (MHS5; MIM #60188) is presented. Malignant hyperthermia (MH) is a life-threatening hypermetabolic state of skeletal muscle usually induced by volatile, halogenated anesthetics and/or the depolarizing neuromuscular blocker succinylcholine. In addition to ryanodine receptor 1 (RYR1) mutations, several CACNA1S mutations are known to be risk factors for increased susceptibility to MH (MHS). However, the presence of these pathogenic CACNA1S gene variations cannot be used to positively predict MH since the condition is genetically heterogeneous with variable expression and incomplete penetrance. At present, one or at most six CACNA1S mutations display significant linkage or association either to clinically diagnosed MH or to MHS as determined by contracture testing. Additional pathogenic variants in CACNA1S, either alone or in combination with genes affecting Ca 2+ homeostasis, are likely to be discovered in association to MH as whole exome sequencing becomes more commonplace. Copyright © 2017 the American Physiological Society.

  15. [Serologic profile of toxoplasmosis in pregnant women attended at a teaching-hospital in Recife].

    PubMed

    Porto, Ana Maria Feitosa; Amorim, Melania Maria Ramos de; Coelho, Isabela Coutinho Neiva; Santos, Luiz Carlos

    2008-01-01

    To determine the serologic profile of toxoplasmosis and the main factors associated with susceptibility (patients without IgM and IgG antibodies) in pregnant women attended at a teaching-hospital in Recife, Brasil. A cross-sectional study was carried out, enrolling 503 pregnant women submitted to serology for toxoplasmosis at IMIP (Recife) from October 2004 to April 2005. Anti-Toxoplasma IgG and IgM antibodies were studied by IFA. A short questionnaire was administered to patients to provide identification, demographic and obstetrical characteristics, past history of morbidity, habits and dwelling conditions. The chi-square and Fisher-exact tests were used at a 5% level of significance. Immunity for toxoplasmosis was present in 74.7%, susceptibility in 22.5% and "possible" active infection in 2.8% of patients. No significant associations were observed between toxoplasmosis susceptibility and age, location, conditions of morbidity, habits, dwelling conditions and sewage system, living with animals, pregnancy and gestational age. A significant association between toxoplasmosis susceptibility and schooling was found, with a higher frequency of susceptibility among women with eight or more years of schooling. Susceptibility for toxoplasmosis was relatively low in these prenatal patients and schooling was the only identifiable predictive factor.

  16. Prevalence and determinants of susceptibility to cigarette smoking among school students in Pakistan: secondary analysis of Global Youth Tobacco Survey.

    PubMed

    Aslam, Syeda Kanwal; Zaheer, Sidra; Rao, Saadiyah; Shafique, Kashif

    2014-02-21

    Susceptibility to smoke has been recognized as a strong predictor of smoking experimentation and taking up regular smoking habit. The identification of smoking susceptible individuals and its determinants is important in the efforts to reduce future smoking prevalence. The aims of this study are to estimate prevalence of susceptibility to smoke among adolescents, and identify factors associated with it. Cross sectional data was obtained from Global Youth Tobacco Survey conducted in three cities of Pakistan in year 2004. Study population consisted of students in grades, 8th, 9th, and 10th; aged 13 to 15 years. Secondary analysis using univariate and multivariate logistic regression analyses were performed to estimate the associations between smoking susceptibility and co-variates. Descriptive statistics were reported in proportions, and adjusted odds ratios with 95% confidence interval were used to report logistic regression analyses. Approximately 12% of nonsmoking students were found susceptible to smoking. Students, who were females (OR = 1.53, 95% CI [1.24-1.89]); whose parents (OR = 1.64, 95% CI [1.35-1.99]); or close friend smoked (OR = 2.77, 95% CI [2.27- 3.40]) were more susceptible to cigarette smoking. Students who had good knowledge about harmful effects of smoking (OR = 0.54, 95% CI [0.43-0.69]); and had access to anti-smoking media (OR = 0.73, 95% CI [0.59-0.89]) were less likely to be susceptible to smoking. Students who were females, had smoking parents, friends or exposure to newspaper/magazines cigarette marketing, were more susceptible to cigarette smoking among Pakistani adolescents. While knowledge of harmful effects of smoking and access to anti-smoking media served as protective factors against susceptibility to smoking.

  17. Single nucleotide polymorphisms in the CD40 gene associate with the disease susceptibility and severity in knee osteoarthritis in the Chinese Han population: a case-control study.

    PubMed

    Deng, Zhen-Han; Sun, Ming-Hua; Li, Yu-Sheng; Luo, Wei; Zhang, Fang-Jie; Tian, Jian; Wu, Ping; Xiao, Wen-Feng

    2017-03-21

    This study explored the association between single nucleotide polymorphisms (SNPs) in the CD40 gene, rs4810485 G > T and rs1883832 C > T, as well as disease susceptibility and severity in knee osteoarthritis (KOA) in the Chinese Han population. Peripheral venous blood was collected from 133 KOA patients (KOA group) and 143 healthy people (control group) from December 2012 to November 2013. The patients in the KOA group were classified into mild, moderate and severe groups according to disease severity. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to test the genotypes of all subjects. Binary logistic regression analyses were performed to analyze the risk factors for KOA. The KOA group was significantly different from the control group in living environment (P < 0.05). The KOA group had a lower frequency of TT genotype and T allele distribution of rs4810485 G > T compared with the control group, and rs4810485 G > T TT genotype and T allele may associate with low incidence of KOA (all P < 0.05). Besides, T allele and mutant homozygous TT genotype of rs1883832 C > T increased the susceptibility to KOA. Genotype and allele distribution of rs4810485 G > T and rs1883832 C > T were significantly different among the mild, moderate and severe groups (P < 0.05). There were more patients with rs4810485 G > T GG genotype and rs1883832 C > T TT genotype in the severe group than other genotypes of these two SNPs. According to binary logistic regression analysis, rs4810485 G > T TT genotype could alleviate disease severity in KOA, rs1883832 C > T TT genotype increase the severity of KOA and living environment is an important external factor that affects KOA severity. These data provide evidences that rs4810485 G > T and rs1883832 C > T in the CD40 gene may be associated with disease susceptibility and severity in KOA.

  18. Using genetics to predict the natural history of asthma?

    PubMed

    Holloway, John W; Arshad, Syed H; Holgate, Stephen T

    2010-08-01

    Clinical practice reminds us that there is considerable variability in the course of asthma over time. Treatment of patients with asthma would be considerably improved if one could accurately predict the likely course of disease over the life course. Recently, with the advent of the era of genome-wide association studies, there has been a monumental shift in our understanding of the genetic factors that underlie inherited susceptibility to asthma. Genes have been identified that modulate many aspects of the natural history of asthma, such as susceptibility to atopy, altered lung development, and susceptibility to more severe disease. Heritability studies have even suggested a role for genetic factors in remission of asthma. However, although the discovery of novel genetic factors underlying disease susceptibility has undoubtedly improved our understanding of disease pathogenesis, whether these advances have improved the ability to predict the natural history in individual patients is questionable, and the application of genetic testing to clinical practice remains some way off. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  19. Impact of Maspin Polymorphism rs2289520 G/C and Its Interaction with Gene to Gene, Alcohol Consumption Increase Susceptibility to Oral Cancer Occurrence.

    PubMed

    Yang, Po-Yu; Miao, Nae-Fang; Lin, Chiao-Wen; Chou, Ying-Erh; Yang, Shun-Fa; Huang, Hui-Chuan; Chang, Hsiu-Ju; Tsai, Hsiu-Ting

    2016-01-01

    The purpose of this study was to identify gene polymorphisms of mammary serine protease inhibitor (Maspin) specific to patients with oral cancer susceptibility and clinicopathological status. Three single-nucleotide polymorphisms (SNPs) of the Maspin gene from 741 patients with oral cancer and 601 non-cancer controls were analyzed by real-time PCR. The participants with G/G homozygotes or with G/C heterozygotes of Maspin rs2289520 polymorphism had a 2.07-fold (p = 0.01) and a 2.01-fold (p = 0.02) risk of developing oral cancer compared to those with C/C homozygotes. Moreover, gene-gene interaction increased the risk of oral cancer susceptibility among subjects expose to oral cancer related risk factors, including areca, alcohol, and tobacco consumption. G allele of Maspin rs2289520 polymorphism may be a factor that increases the susceptibility to oral cancer. The interactions of gene to oral cancer-related environmental risk factors have a synergetic effect that can further enhance oral cancer development.

  20. Sinkhole Susceptibility Analysis for Karapinar/konya via Multi Criteria Decision

    NASA Astrophysics Data System (ADS)

    Sarı, F.

    2017-11-01

    Sinkholes are being a natural hazard which threads economic and human life. Sudden occurrence characteristic of sinkholes make it unable to escape. There are a lot of factor that activate sinkholes such as geology, irrigation, land use and human related factors. In Karapınar, Konya, there are over 200 sinkholes and this count is getting increased in recent years. Especially active agricultural lands, decreasing ground water level, extreme irrigation by 55267 water wells increase the risk factor of Karapınar. Nowadays, considering the economic contribution of Karapınar to Turkey economy in the field of agriculture, solar energy fields and thermal reactor which will be planned in next few years, prediction of sinkholes and searching for preventation ways are being more important issue. In this study, sinkhole susceptibility map via AHP was carried out for Karapınar in Konya. Slope, land use, elevation, geology, water wells, distance to roads and settlements criteria are included to determine susceptibility. The weights are calculated with AHP for each criterion and generated susceptibility map is overlapped with existing sinkholes. Suggestions and results are shared for this study.

  1. MR susceptibility imaging

    NASA Astrophysics Data System (ADS)

    Duyn, Jeff

    2013-04-01

    This work reviews recent developments in the use of magnetic susceptibility contrast for human MRI, with a focus on the study of brain anatomy. The increase in susceptibility contrast with modern high field scanners has led to novel applications and insights into the sources and mechanism contributing to this contrast in brain tissues. Dedicated experiments have demonstrated that in most of healthy brain, iron and myelin dominate tissue susceptibility variations, although their relative contribution varies substantially. Local variations in these compounds can affect both amplitude and frequency of the MRI signal. In white matter, the myelin sheath introduces an anisotropic susceptibility that has distinct effects on the water compartments inside the axons, between the myelin sheath, and the axonal space, and renders their signals dependent on the angle between the axon and the magnetic field. This offers opportunities to derive tissue properties specific to these cellular compartments.

  2. Combinatorial effects of diet and genetics on inflammatory bowel disease pathogenesis.

    PubMed

    Dixon, Laura J; Kabi, Amrita; Nickerson, Kourtney P; McDonald, Christine

    2015-04-01

    Inflammatory bowel disease (IBD) encompasses a group of disorders affecting the gastrointestinal tract characterized by acute and chronic inflammation. These are complex and multifactorial disorders that arise in part from a genetic predisposition. However, the increasing incidence of IBD in developing countries suggests that environmental factors, such as diet, are also critical components of disease susceptibility. Evidence suggests that consumption of a Western diet, enriched with saturated fat, refined carbohydrates, and food additives, is associated with increased IBD risk. Dietary components, such as omega-6 fatty acids, long-chain fatty acids, protein, and digestible carbohydrates, may contribute to IBD pathogenesis through altering intestinal microbiota, increasing intestinal permeability, and promoting inflammation; whereas omega-3 fatty acids, medium chain triglycerides, and nondigestible carbohydrates improve these parameters and intestinal health. However, the limited amount of prospective studies, small sample sizes, and the heterogeneity of disease subtype result in inconsistencies between studies and difficulty in conclusively determining the specific effects of diet on intestinal homeostasis. There are no standard clinical dietary recommendations for patients with IBD. However, exclusionary diet interventions have shown some efficacy in relieving symptoms or inducing remission, suggesting more research is needed to fully understand how diet influences disease behavior or combines with other IBD risk factors to promote disease. This review focuses on the associations of various dietary components and IBD risk in clinical studies and genetically susceptible IBD models.

  3. Combinatorial Effects of Diet and Genetics on Inflammatory Bowel Disease Pathogenesis

    PubMed Central

    Dixon, Laura J.; Kabi, Amrita; Nickerson, Kourtney P.; McDonald, Christine

    2014-01-01

    Inflammatory bowel disease (IBD) encompasses a group of disorders affecting the gastrointestinal tract characterized by acute and chronic inflammation. These are complex and multifactorial disorders that arise in part from a genetic predisposition. However, the increasing incidence of IBD in developing countries suggests that environmental factors, such as diet, are also critical components of disease susceptibility. Evidence suggests that consumption of a Western diet, enriched with saturated fat, refined carbohydrates, and food additives, is associated with increased IBD risk. Dietary components, such as omega-6 fatty acids, long chain fatty acids, protein, and digestible carbohydrates, may contribute to IBD pathogenesis through altering intestinal microbiota, increasing intestinal permeability, and promoting inflammation; whereas omega-3 fatty acids, medium chain triglycerides, and non-digestible carbohydrates improve these parameters and intestinal health. However, the limited amount of prospective studies, small sample sizes, and the heterogeneity of disease subtype result in inconsistencies between studies and difficulty in conclusively determining the specific effects of diet on intestinal homeostasis. There are no standard clinical dietary recommendations for IBD patients. However, exclusionary diet interventions have shown some efficacy in relieving symptoms or inducing remission, suggesting more research is needed to fully understand how diet influences disease behavior or combines with other IBD risk factors to promote disease. This review focuses on the associations of various dietary components and IBD risk in clinical studies and genetically susceptible IBD models. PMID:25581832

  4. The contrasting microRNA content of a drought tolerant and a drought susceptible wheat cultivar.

    PubMed

    Bakhshi, Behnam; Fard, Ehsan Mohseni; Gharechahi, Javad; Safarzadeh, Mahdieh; Nikpay, Nava; Fotovat, Reza; Azimi, Mohammad Reza; Salekdeh, Ghasem Hosseini

    2017-09-01

    Drought stress represents one of the most common stresses affecting the productivity of crop plants. A rather recently discovered component of the plant response to drought is the cellular population of microRNAs. Here, the microRNA content was revealed of two bread wheat cultivars contrasting strongly with respect to the ability to withstand drought stress. A total of 1813 miRNAs was identified, grouped into 106 families. Some 104 of these miRNAs were predicted to match 212 novel miRNA precursors. In the drought tolerant cultivar (SM), 105 (33 known and 72 novel) miRNAs were altered in abundance by the imposition of drought stress, while the equivalent number in the more sensitive cultivar (SW) was 51 (20 and 31). An in silico analysis predicted that these miRNAs target at least 1959 genes in SM and 1111 in SW, suggesting their broad contribution to the drought stress response. Among the target genes were several known stress-related genes, encoding, for example, superoxide dismutase, various MYB transcription factors, various ABA signaling proteins and various MADS-box transcription factors. In many cases, the more susceptible cultivar SW behaved in a contrasting manner. The suggestion is that miRNAs represent an important aspect of the drought stress response, post-transcriptionally regulating a range of stress-related genes. Copyright © 2017 Elsevier GmbH. All rights reserved.

  5. Interactions between C-reactive protein genotypes with markers of nutritional status in relation to inflammation.

    PubMed

    Nienaber-Rousseau, Cornelie; Swanepoel, Bianca; Dolman, Robin C; Pieters, Marlien; Conradie, Karin R; Towers, G Wayne

    2014-11-11

    Inflammation, as indicated by C-reactive protein concentrations (CRP), is a risk factor for chronic diseases. Both genetic and environmental factors affect susceptibility to inflammation. As dietary interventions can influence inflammatory status, we hypothesized that dietary effects could be influenced by interactions with single nucleotide polymorphisms (SNPs) in the CRP gene. We determined 12 CRP SNPs, as well as various nutrition status markers in 2010 black South Africans and analyzed their effect on CRP. Interactions were observed for several genotypes with obesity in determining CRP. Lipid intake modulated the pro-inflammatory effects of some SNPs, i.e., an increase in both saturated fatty acid and monounsaturated fatty acid intake in those homozygous for the polymorphic allele at rs2808630 was associated with a larger increase in CRP. Those harboring the minor alleles at rs3093058 and rs3093062 presented with significantly higher CRP in the presence of increased triglyceride or cholesterol intake. When harboring the minor allele of these SNPs, a high omega-6 to -3 ratio was, however, found to be anti-inflammatory. Carbohydrate intake also modulated CRP SNPs, as HbA1C and fasting glucose levels interacted with some SNPs to influence the CRP. This investigation highlights the impact that nutritional status can have on reducing the inherent genetic susceptibility to a heightened systemic inflammatory state.

  6. How Numeracy Influences Risk Comprehension and Medical Decision Making

    PubMed Central

    Reyna, Valerie F.; Nelson, Wendy L.; Han, Paul K.; Dieckmann, Nathan F.

    2009-01-01

    We review the growing literature on health numeracy, the ability to understand and use numerical information, and its relation to cognition, health behaviors, and medical outcomes. Despite the surfeit of health information from commercial and noncommercial sources, national and international surveys show that many people lack basic numerical skills that are essential to maintain their health and make informed medical decisions. Low numeracy distorts perceptions of risks and benefits of screening, reduces medication compliance, impedes access to treatments, impairs risk communication (limiting prevention efforts among the most vulnerable), and, based on the scant research conducted on outcomes, appears to adversely affect medical outcomes. Low numeracy is also associated with greater susceptibility to extraneous factors (i.e., factors that do not change the objective numerical information). That is, low numeracy increases susceptibility to effects of mood or how information is presented (e.g., as frequencies vs. percentages) and to biases in judgment and decision making (e.g., framing and ratio bias effects). Much of this research is not grounded in empirically supported theories of numeracy or mathematical cognition, which are crucial for designing evidence-based policies and interventions that are effective in reducing risk and improving medical decision making. To address this gap, we outline four theoretical approaches (psychophysical, computational, standard dual-process, and fuzzy trace theory), review their implications for numeracy, and point to avenues for future research. PMID:19883143

  7. Quantification of Urban Environment's Role in Slope Stability for Landslide Events.

    NASA Astrophysics Data System (ADS)

    Bozzolan, E.; Holcombe, E.; Wagener, T.; Pianosi, F.

    2017-12-01

    The combination of a rapid and unplanned urban development with a likely future climate change could significantly affect landslide occurrences in the humid tropics, where rainfall events of high intensity and duration are the dominant trigger for landslide risk. The attention of current landslide hazard studies is largely focussed on natural slope processes based on combinations of environmental factors, excluding the role of urbanisation on slope stability. This project aims to understand the relative influence of urbanisation features on local slope stability and to translate the findings to a wider region. Individual slopes are firstly analysed with the software CHASM, a physically based model which combines soil hydrology and slope stability assessment. Instead of relying on existing records, generally lacking for landslides, ranges of plausible preparatory (such as slope, cohesion, friction angles), triggering (rainfall) and aggravating factors (deforestation, house density and water network) are defined and possible combinations of these factors are created by sampling from those ranges. The influence of urban features on site hydrology and stability mechanisms are evaluated and then implemented in denser urban contexts, characteristic of unplanned settlements. The results of CHASMS can be transferred to regional maps in order to identify the areas belonging to the triggering combinations of factors previously found. In this way, areas susceptible to landslides can be detected not only in terms of natural factors but also in relation to the degree of urbanisation. Realistic scenarios can be extrapolated from the areas considered and then analysed again with CHASM. This permits to adapt (and improve) the initial variability ranges of the factors, creating a general-specific cycle able to identify the landslide susceptibility regions and outline a hazard map. Once the triggers are understood, possible consequences can be assessed and mitigation strategies can be evaluated. The ability to define local urban rainfall threshold for landslide slope stability helps the decision-making process to prioritize the areas of interest and locally define the main causes of instability.

  8. A GIS-based automated procedure for landslide susceptibility mapping by the Conditional Analysis method: the Baganza valley case study (Italian Northern Apennines)

    NASA Astrophysics Data System (ADS)

    Clerici, Aldo; Perego, Susanna; Tellini, Claudio; Vescovi, Paolo

    2006-08-01

    Among the many GIS based multivariate statistical methods for landslide susceptibility zonation, the so called “Conditional Analysis method” holds a special place for its conceptual simplicity. In fact, in this method landslide susceptibility is simply expressed as landslide density in correspondence with different combinations of instability-factor classes. To overcome the operational complexity connected to the long, tedious and error prone sequence of commands required by the procedure, a shell script mainly based on the GRASS GIS was created. The script, starting from a landslide inventory map and a number of factor maps, automatically carries out the whole procedure resulting in the construction of a map with five landslide susceptibility classes. A validation procedure allows to assess the reliability of the resulting model, while the simple mean deviation of the density values in the factor class combinations, helps to evaluate the goodness of landslide density distribution. The procedure was applied to a relatively small basin (167 km2) in the Italian Northern Apennines considering three landslide types, namely rotational slides, flows and complex landslides, for a total of 1,137 landslides, and five factors, namely lithology, slope angle and aspect, elevation and slope/bedding relations. The analysis of the resulting 31 different models obtained combining the five factors, confirms the role of lithology, slope angle and slope/bedding relations in influencing slope stability.

  9. Study of virulence factors of uropathogenic Escherichia coli and its antibiotic susceptibility pattern.

    PubMed

    Mittal, Seema; Sharma, Madhu; Chaudhary, Uma

    2014-01-01

    Urinary tract infection (UTI) is one of the most common nosocomial infections, caused by Escherichia coli. This study determined the presence of virulence factors in the organism and correlates it with the multi-drug resistance (MDR). The aim of the following study is to assess the virulence factors of uropathogenic E. coli and antibiotic susceptibility pattern. This was a prospective study conducted in the Department of Microbiology in PT. B. D. Sharma, PGIMS, Rohtak. The study was conducted over a period of 1 year. Urine samples received were processed as per standard microbiological procedures. Virulence factors such as hemolysin, hemagglutination, cell surface hydrophobicity, serum resistance, gelatinase and siderophore production were studied. The antimicrobial susceptibility was done as per Clinical and Laboratory Standard Institute Guidelines. The data was analyzed by using SPSS(Statistical Package for the social sciences) IBM Corporation version 17.0. A two sided P ≤ 0.05 was considered to be significant. Hemolysin production was seen in 47.4%, hemagglutination in 74.8%, cell surface hydrophobicity in 61%, serum resistance in 59%, gelatinase in 67.5% and siderophore production in 88% isolates. Nitrofurantoin was found to be most effective followed by, gatifloxacin and gentamicin. Twenty nine percent (29.62%) isolates were MDR. Therefore, the knowledge of virulence factors of E. coli and their antibiotic susceptibility pattern will help in better understanding of the organism and in the treatment of UTI.

  10. Prey Foraging Under Sublethal Lambda-Cyhalothrin Exposure on Pyrethroid-Susceptible and -Resistant Lady Beetles (Eriopis connexa (Coleoptera: Coccinelidae)).

    PubMed

    D'Ávila, V A; Reis, L C; Barbosa, W F; Cutler, G C; Torres, J B; Guedes, R N C

    2018-05-28

    Sublethal insecticide exposure may affect foraging of insects, including natural enemies, although the subject is usually neglected. The lady beetle Eriopis connexa (Germar, 1824) (Coleoptera: Coccinelidae) is an important predator of aphids with existing pyrethroid-resistant populations that are undergoing scrutiny for potential use in pest management systems characterized by frequent insecticide use. However, the potential effect of sublethal pyrethroid exposure on this predator's foraging activity has not yet been assessed and may compromise its use in biological control. Therefore, our objective was to assess the effect of sublethal lambda-cyhalothrin exposure on three components of the prey foraging activity (i.e., walking, and prey searching and handling), in both pyrethroid-susceptible and -resistant adults of E. connexa. Both lady beetle populations exhibited similar walking patterns without insecticide exposure in noncontaminated arenas, but in partially contaminated arenas walking differed between strains, such that the resistant insects exhibited greater walking activity. Behavioral avoidance expressed as repellence to lambda-cyhalothrin was not observed for either the susceptible or resistant populations of E. connexa, but the insecticide caused avoidance by means of inducing irritability in 40% of the individuals, irrespective of the strain. Insects remained in the insecticide-contaminated portion of the arena for extended periods resulting in greater exposure. Although lambda-cyhalothrin exposure did not affect prey searching by susceptible lady beetles, prey searching was extended for exposed resistant predators. In contrast, prey handling was not affected by population or by lambda-cyhalothrin exposure. Thus, sublethal exposure to the insecticide in conjunction with the insect resistance profile can affect prey foraging with pyrethroid-exposed resistant predators exhibiting longer prey searching time associated with higher walking activity reducing its predatory performance.

  11. Tissue preparation for immunocytochemistry.

    PubMed Central

    Williams, J H; Mepham, B L; Wright, D H

    1997-01-01

    AIMS: To investigate the effect of tissue preparation on immunostaining and to establish whether there is a standard tissue preparation schedule that allows optimal demonstration of all antigens. METHODS: Blocks of tonsil were subjected to variations to a standard fixation, processing, and section preparation schedule. The sections were stained with five antibodies-L26 (CD20), UCHL1 (CD45RO), CD3, vimentin, and anti-kappa light chain--using the streptavidinbiotin immunostaining technique. When further investigation was necessary, other tissues and antibodies were used and where weak immunostaining was obtained the use of microwave pretreatment to improve staining was tested. RESULTS: Several factors involved in fixation were found to affect immunoreactivity. These included the duration, pH, and type of fixative used. In tissue processing only temperature and the duration of the dehydration and wax infiltration steps affected immunoreactivity. Of all the factors investigated, the temperature and duration of the section drying had the greatest effect. In contrast, long term storage of cut sections before immunostaining had no effect on the reactivity of the antibodies tested. Antibodies were found to be affected by alterations to tissue preparation by varying degrees, UCHL1 and vimentin being the most susceptible to changes in fixation and L26 to changes in processing. Where weak staining occurred, microwave pretreatment was generally found to eliminate the problem. CONCLUSIONS: There is no standard tissue preparation schedule for the optimal demonstration of all antigens. Factors involved in all aspects of tissue preparation can affect immunoreactivity, so it is important that precise details of the preparation schedule are given when reporting immunocytochemical studies, rather than using the general term "routinely fixed and processed". Images PMID:9215127

  12. Preoperative Cerebral Oxygen Extraction Fraction Imaging Generated from 7T MR Quantitative Susceptibility Mapping Predicts Development of Cerebral Hyperperfusion following Carotid Endarterectomy.

    PubMed

    Nomura, J-I; Uwano, I; Sasaki, M; Kudo, K; Yamashita, F; Ito, K; Fujiwara, S; Kobayashi, M; Ogasawara, K

    2017-12-01

    Preoperative hemodynamic impairment in the affected cerebral hemisphere is associated with the development of cerebral hyperperfusion following carotid endarterectomy. Cerebral oxygen extraction fraction images generated from 7T MR quantitative susceptibility mapping correlate with oxygen extraction fraction images on positron-emission tomography. The present study aimed to determine whether preoperative oxygen extraction fraction imaging generated from 7T MR quantitative susceptibility mapping could identify patients at risk for cerebral hyperperfusion following carotid endarterectomy. Seventy-seven patients with unilateral internal carotid artery stenosis (≥70%) underwent preoperative 3D T2*-weighted imaging using a multiple dipole-inversion algorithm with a 7T MR imager. Quantitative susceptibility mapping images were then obtained, and oxygen extraction fraction maps were generated. Quantitative brain perfusion single-photon emission CT was also performed before and immediately after carotid endarterectomy. ROIs were automatically placed in the bilateral middle cerebral artery territories in all images using a 3D stereotactic ROI template, and affected-to-contralateral ratios in the ROIs were calculated on quantitative susceptibility mapping-oxygen extraction fraction images. Ten patients (13%) showed post-carotid endarterectomy hyperperfusion (cerebral blood flow increases of ≥100% compared with preoperative values in the ROIs on brain perfusion SPECT). Multivariate analysis showed that a high quantitative susceptibility mapping-oxygen extraction fraction ratio was significantly associated with the development of post-carotid endarterectomy hyperperfusion (95% confidence interval, 33.5-249.7; P = .002). Sensitivity, specificity, and positive- and negative-predictive values of the quantitative susceptibility mapping-oxygen extraction fraction ratio for the prediction of the development of post-carotid endarterectomy hyperperfusion were 90%, 84%, 45%, and 98%, respectively. Preoperative oxygen extraction fraction imaging generated from 7T MR quantitative susceptibility mapping identifies patients at risk for cerebral hyperperfusion following carotid endarterectomy. © 2017 by American Journal of Neuroradiology.

  13. Cell wall glycans and soluble factors determine the interactions between the hyphae of Candida albicans and Pseudomonas aeruginosa.

    PubMed

    Brand, Alexandra; Barnes, Julia D; Mackenzie, Kevin S; Odds, Frank C; Gow, Neil A R

    2008-10-01

    The fungus, Candida albicans, and the bacterium, Pseudomonas aeruginosa, are opportunistic human pathogens that have been coisolated from diverse body sites. Pseudomonas aeruginosa suppresses C. albicans proliferation in vitro and potentially in vivo but it is the C. albicans hyphae that are killed while yeast cells are not. We show that hyphal killing involves both contact-mediated and soluble factors. Bacterial culture filtrates contained heat-labile soluble factors that killed C. albicans hyphae. In cocultures, localized points of hyphal lysis were observed, suggesting that adhesion and subsequent bacteria-mediated cell wall lysis is involved in the killing of C. albicans hyphae. The glycosylation status of the C. albicans cell wall affected the rate of contact-dependent killing because mutants with severely truncated O-linked, but not N-linked, glycans were hypersensitive to Pseudomonas-mediated killing. Deletion of HWP1, ALS3 or HYR1, which encode major hypha-associated cell wall proteins, had no effect on fungal susceptibility.

  14. Natural variation in the parameters of innate immune cells is preferentially driven by genetic factors.

    PubMed

    Patin, Etienne; Hasan, Milena; Bergstedt, Jacob; Rouilly, Vincent; Libri, Valentina; Urrutia, Alejandra; Alanio, Cécile; Scepanovic, Petar; Hammer, Christian; Jönsson, Friederike; Beitz, Benoît; Quach, Hélène; Lim, Yoong Wearn; Hunkapiller, Julie; Zepeda, Magge; Green, Cherie; Piasecka, Barbara; Leloup, Claire; Rogge, Lars; Huetz, François; Peguillet, Isabelle; Lantz, Olivier; Fontes, Magnus; Di Santo, James P; Thomas, Stéphanie; Fellay, Jacques; Duffy, Darragh; Quintana-Murci, Lluís; Albert, Matthew L

    2018-03-01

    The quantification and characterization of circulating immune cells provide key indicators of human health and disease. To identify the relative effects of environmental and genetic factors on variation in the parameters of innate and adaptive immune cells in homeostatic conditions, we combined standardized flow cytometry of blood leukocytes and genome-wide DNA genotyping of 1,000 healthy, unrelated people of Western European ancestry. We found that smoking, together with age, sex and latent infection with cytomegalovirus, were the main non-genetic factors that affected variation in parameters of human immune cells. Genome-wide association studies of 166 immunophenotypes identified 15 loci that showed enrichment for disease-associated variants. Finally, we demonstrated that the parameters of innate cells were more strongly controlled by genetic variation than were those of adaptive cells, which were driven by mainly environmental exposure. Our data establish a resource that will generate new hypotheses in immunology and highlight the role of innate immunity in susceptibility to common autoimmune diseases.

  15. Effects of acute tryptophan depletion on affective processing in first-degree relatives of depressive patients and controls after exposure to uncontrollable stress.

    PubMed

    Firk, Christine; Markus, C Rob

    2008-08-01

    Individuals with a family history of depression may be more likely to develop depression due to an innate vulnerability of their serotonergic system. However, even though serotonergic vulnerability may constitute a risk factor in the development of depression, it does not seem to be sufficient to cause a depressive episode. Based on previous data, it is suggested that stress may be a mediating factor. This study examined the role of serotonin (5-HT) in stress coping in individuals with or without a family history of depression. Nineteen healthy first-degree relatives of depressive patients (FH+) and 19 healthy controls without a family history of depression (FH-) were tested in a double-blind placebo-controlled design for affective processing under acute stress exposure, following acute tryptophan depletion (ATD) or placebo. Significant negative effects were found of stress on affective processing in FH- and FH+. In addition, FH- responded slower to positive words after stress only following ATD, whereas FH+ responded marginally slower under stress already after placebo and before stress following ATD. Acute stress exposure reduces positive affective bias; supporting the role of stress as an important predecessor in the development of depression. Furthermore, FH+ may be more susceptible than FH- to the negative effects of stress as well as to the negative effects of ATD. The results support the assumption that the 5-HT system is involved in stress resilience and may be more vulnerable in first-degree relatives of depression.

  16. Identification of Aortic Arch-Specific Quantitative Trait Loci for Atherosclerosis by an Intercross of DBA/2J and 129S6 Apolipoprotein E-Deficient Mice

    PubMed Central

    Kayashima, Yukako; Makhanova, Natalia A.; Matsuki, Kota; Tomita, Hirofumi; Bennett, Brian J.; Maeda, Nobuyo

    2015-01-01

    The genetic background of apolipoprotein E (apoE) deficient mice influences atherosclerotic plaque development. We previously reported three quantitative trait loci (QTL), Aath1–Aath3, that affect aortic arch atherosclerosis independently of those in the aortic root in a cross between C57BL6 apoEKO mice (B6-apoE) and 129S6 apoEKO mice (129-apoE). To gain further insight into genetic factors that influence atherosclerosis at different vascular locations, we analyzed 335 F2 mice from an intercross between 129-apoE and apoEKO mice on a DBA/2J genetic background (DBA-apoE). The extent of atherosclerosis in the aortic arch was very similar in the two parental strains. Nevertheless, a genome-wide scan identified two significant QTL for plaque size in the aortic arch: Aath4 on Chromosome (Chr) 2 at 137 Mb and Aath5 on Chr 10 at 51 Mb. The DBA alleles of Aath4 and Aath5 respectively confer susceptibility and resistance to aortic arch atherosclerosis over 129 alleles. Both QTL are also independent of those affecting plaque size at the aortic root. Genome analysis suggests that athero-susceptibility of Aath4 in DBA may be contributed by multiple genes, including Mertk and Cd93, that play roles in phagocytosis of apoptotic cells and modulate inflammation. A candidate gene for Aath5 is Stab2, the DBA allele of which is associated with 10 times higher plasma hyaluronan than the 129 allele. Overall, our identification of two new QTL that affect atherosclerosis in an aortic arch-specific manner further supports the involvement of distinct pathological processes at different vascular locations. PMID:25689165

  17. Conspecific Plant-Soil Feedbacks of Temperate Tree Species in the Southern Appalachians, USA

    PubMed Central

    Reinhart, Kurt O.; Johnson, Daniel; Clay, Keith

    2012-01-01

    Many tree species have seedling recruitment patterns suggesting that they are affected by non-competitive distance-dependent sources of mortality. We conducted an experiment, with landscape-level replication, to identify cases of negative distance-dependent effects and whether variation in these effects corresponded with tree recruitment patterns in the southern Appalachian Mountains region. Specifically, soil was collected from 14 sites and used as inocula in a 62 day growth chamber experiment determining whether tree seedling growth was less when interacting with soil from conspecific (like) than heterospecific (other) tree species. Tests were performed on six tree species. Three of the tree species had been previously described as having greater recruitment around conspecifics (i.e. facilitator species group) compared to the other half (i.e. inhibitor species group). We were then able to determine whether variation in negative distance-dependent effects corresponded with recruitment patterns in the field. Across the six species, none were negatively affected by soil inocula from conspecific relative to heterospecific sources. Most species (four of six) were unaffected by soil source. Two species (Prunus serotina and Tsuga canadensis) had enhanced growth in pots inoculated with soil from conspecific trees vs. heterospecifics. Species varied in their susceptibility to soil pathogens, but trends across all species revealed that species classified as inhibitors were not more negatively affected by conspecific than heterospecific soil inocula or more susceptible to pathogenic effects than facilitators. Although plant-soil biota interactions may be important for individual species and sites, it may be difficult to scale these interactions over space or levels of ecological organization. Generalizing the importance of plant-soil feedbacks or other factors across regional scales may be especially problematic for hyperdiverse temperate forests where interactions may be spatially variable. PMID:22808231

  18. Conspecific plant-soil feedbacks of temperate tree species in the southern Appalachians, USA.

    PubMed

    Reinhart, Kurt O; Johnson, Daniel; Clay, Keith

    2012-01-01

    Many tree species have seedling recruitment patterns suggesting that they are affected by non-competitive distance-dependent sources of mortality. We conducted an experiment, with landscape-level replication, to identify cases of negative distance-dependent effects and whether variation in these effects corresponded with tree recruitment patterns in the southern Appalachian Mountains region. Specifically, soil was collected from 14 sites and used as inocula in a 62 day growth chamber experiment determining whether tree seedling growth was less when interacting with soil from conspecific (like) than heterospecific (other) tree species. Tests were performed on six tree species. Three of the tree species had been previously described as having greater recruitment around conspecifics (i.e. facilitator species group) compared to the other half (i.e. inhibitor species group). We were then able to determine whether variation in negative distance-dependent effects corresponded with recruitment patterns in the field. Across the six species, none were negatively affected by soil inocula from conspecific relative to heterospecific sources. Most species (four of six) were unaffected by soil source. Two species (Prunus serotina and Tsuga canadensis) had enhanced growth in pots inoculated with soil from conspecific trees vs. heterospecifics. Species varied in their susceptibility to soil pathogens, but trends across all species revealed that species classified as inhibitors were not more negatively affected by conspecific than heterospecific soil inocula or more susceptible to pathogenic effects than facilitators. Although plant-soil biota interactions may be important for individual species and sites, it may be difficult to scale these interactions over space or levels of ecological organization. Generalizing the importance of plant-soil feedbacks or other factors across regional scales may be especially problematic for hyperdiverse temperate forests where interactions may be spatially variable.

  19. Social withdrawal in children moderates the association between parenting styles and the children's own socioemotional development.

    PubMed

    Zarra-Nezhad, Maryam; Kiuru, Noona; Aunola, Kaisa; Zarra-Nezhad, Mansour; Ahonen, Timo; Poikkeus, Anna-Maija; Lerkkanen, Marja-Kristiina; Nurmi, Jari-Erik

    2014-11-01

    Social withdrawal in early childhood is a risk factor for later socioemotional difficulties. This study examined the joint effects of children's social withdrawal and mothers' and fathers' parenting styles on children's socioemotional development. Based on diatheses-stress, vantage sensitivity, and differential susceptibility models, socially withdrawn children were assumed to be more prone to parental influences than others. Teachers rated 314 children on prosocial skills, and internalizing and externalizing behaviors at three points in time between grades 1-3. Mothers (n = 279) and fathers (n = 182) filled in questionnaires measuring their affection, and their behavioral and psychological control at the same points in time. Teacher reports on children's level of social withdrawal were obtained at the end of kindergarten. Panel analysis showed that particularly those children who showed signs of social withdrawal were vulnerable to the negative effects of low maternal affection in terms of externalizing behavior. Moreover, among these children, mothers' and fathers' psychological control predicted high levels of internalizing problem but, at the same time, mothers' psychological control predicted also a high level of prosocial behavior and low levels of externalizing problem. The results supported the diathesis-stress model more than the differential susceptibility model. For example, socially withdrawn children were found to be particularly vulnerable to the negative effects of low maternal affection. Although maternal psychological control had positive effects on the prosocial skills of socially withdrawn children, and reduced the amount of externalizing problems, it was at the same time associated with an increase in their internalizing problems. In this way, socially withdrawn children seem to be at risk of pleasing their mothers at the cost of their own well-being. © 2014 The Authors. Journal of Child Psychology and Psychiatry. © 2014 Association for Child and Adolescent Mental Health.

  20. Losing the sugar coating: potential impact of perineuronal net abnormalities on interneurons in schizophrenia.

    PubMed

    Berretta, Sabina; Pantazopoulos, Harry; Markota, Matej; Brown, Christopher; Batzianouli, Eleni T

    2015-09-01

    Perineuronal nets (PNNs) were shown to be markedly altered in subjects with schizophrenia. In particular, decreases of PNNs have been detected in the amygdala, entorhinal cortex and prefrontal cortex. The formation of these specialized extracellular matrix (ECM) aggregates during postnatal development, their functions, and association with distinct populations of GABAergic interneurons, bear great relevance to the pathophysiology of schizophrenia. PNNs gradually mature in an experience-dependent manner during late stages of postnatal development, overlapping with the prodromal period/age of onset of schizophrenia. Throughout adulthood, PNNs regulate neuronal properties, including synaptic remodeling, cell membrane compartmentalization and subsequent regulation of glutamate receptors and calcium channels, and susceptibility to oxidative stress. With the present paper, we discuss evidence for PNN abnormalities in schizophrenia, the potential functional impact of such abnormalities on inhibitory circuits and, in turn, cognitive and emotion processing. We integrate these considerations with results from recent genetic studies showing genetic susceptibility for schizophrenia associated with genes encoding for PNN components, matrix-regulating molecules and immune system factors. Notably, the composition of PNNs is regulated dynamically in response to factors such as fear, reward, stress, and immune response. This regulation occurs through families of matrix metalloproteinases that cleave ECM components, altering their functions and affecting plasticity. Several metalloproteinases have been proposed as vulnerability factors for schizophrenia. We speculate that the physiological process of PNN remodeling may be disrupted in schizophrenia as a result of interactions between matrix remodeling processes and immune system dysregulation. In turn, these mechanisms may contribute to the dysfunction of GABAergic neurons. Copyright © 2015. Published by Elsevier B.V.

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