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Sample records for increases adult susceptibility

  1. INCREASED SUSCEPTIBILITY OF ADULTS FOLLOWING DEVELOPMENT EXPOSURE TO NEUROTOXICANTS: ANOTHER SUSCEPTIBLE POPULATION?

    EPA Science Inventory

    There is considerable public and regulatory interest in the adverse outcomes of developmental exposure to toxicants. The 1996 Food Quality Protection Act spurred research on understanding potential neurotoxic, immunotoxic, and endocrine outcomes in susceptible populations, parti...

  2. INCREASED SUSCEPTIBILITY OF ADULTS FOLLOWING DEVELOPMENT EXPOSURE TO NEUROTOXICANTS: ANOTHER SUSCEPTIBLE POPULATION?

    EPA Science Inventory

    There is considerable public and regulatory interest in the adverse outcomes of developmental exposure to toxicants. The 1996 Food Quality Protection Act spurred research on understanding potential neurotoxic, immunotoxic, and endocrine outcomes in susceptible populations, parti...

  3. Perinatal Nicotine Exposure Increases Obesity Susceptibility in Adult Male Rat Offspring by Altering Early Adipogenesis.

    PubMed

    Fan, Jie; Zhang, Wan-Xia; Rao, Yi-Song; Xue, Jing-Ling; Wang, Fei-Fei; Zhang, Li; Yan, You-E

    2016-11-01

    The present study aims to evaluate whether perinatal nicotine (NIC) exposure increases obesity susceptibility in adult male rat offspring by altering early adipogenesis. NIC was sc administered (2.0 mg/kg per day) to pregnant rats from gestational day 9 to the time of weaning (postnatal day 28). At weaning, NIC-exposed male pups had an increased body weight and inguinal sc fat mass and a decreased average cell area of adipocyte, which was accompanied by an overexpression of adipogenic and lipogenic genes in the epididymal white adipose tissue. Additionally, the hepatic lipogenic gene levels from NIC-exposed male pups were also affected. At 12 and 26 weeks of age, body weight and fat mass were increased, whereas there was no change in food intake in NIC-exposed male offspring. Adipogenic and lipogenic genes, glucose transporter 4, and leptin mRNA levels were increased, whereas adiponectin mRNA levels were decreased in the epididymal white adipose tissue of NIC-exposed males. The hepatic lipogenic gene expression of NIC-exposed males was increased. NIC-exposed male offspring showed normal glycemia and a higher serum insulin level, homeostasis model assessment of insulin resistance, and homeostasis model assessment of β-cell function. Furthermore, the NIC-exposed male offspring showed higher serum lipids and Castelli index I and lower nonesterified fatty acid. At 26 weeks, in the ip glucose and insulin tolerance tests, the glucose clearance was delayed, and the area under the curve was higher in the NIC-exposed male offspring. In conclusion, perinatal NIC exposure increased obesity susceptibility in adult male rat offspring by altering early adipogenesis.

  4. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats

    SciTech Connect

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2014-01-15

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE + ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE + HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE + HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a “two-programming” hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is “the first programming”, and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as “the second programming”. - Highlights: • Prenatal ethanol exposure increase the susceptibility of NAFLD in female offspring. • Prenatal ethanol exposure reprograms fetal liver’s glucose and lipid metabolism . • Prenatal ethanol exposure cause

  5. Changing Epidemiological Characteristics of Hepatitis A in Zhejiang Province, China: Increased Susceptibility in Adults.

    PubMed

    Wang, Zhifang; Chen, Yaping; Xie, Shuyun; Lv, Huakun

    2016-01-01

    Hepatitis A is a common acute hepatitis caused by hepatitis A virus (HAV). Annually, it affects 1.4 million people worldwide. Between 1991 and 1994, HAV infections were highly endemic in Zhejiang Province (China), with 78,720 reported HAV infections per year. Hepatitis A vaccine came on the market in 1995 and was implemented for voluntary immunization. Since 2008, hepatitis A vaccine has been integrated into the national childhood routine immunization program. To understand the current epidemiological profile of hepatitis A in Zhejiang Province since hepatitis A vaccine has been available for nearly two decades. This study used the 2005-2014 National Notifiable Diseases Reporting System data to evaluate the incidence rate of notified hepatitis A cases in Zhejiang Province. The overall trend of incidence rate of notified hepatitis A cases significantly decreased from 2005 to 2014 (P< 0.001). During the study period, the reported incidence rate in individuals aged ≤19 years declined to the historically lowest record in 2014. Compared with individuals aged ≤19 years, those aged ≥20 years showed the highest incidence rate (P< 0.001). Majority of HAV infected cases were Laborers, accounting for approximately 70% of reported cases. Childhood immunization strategy with hepatitis A vaccine seemed to be effective in decreasing notified hepatitis A incidence rate in individuals aged ≤19 years. Those aged ≥20 years were observed to be the most susceptible population. The vast majority of hepatitis A cases were notified among Laborers. Therefore, we strongly suggest that future preventive and control measures should focus more on adults, particularly Laborers, in addition to the current childhood hepatitis A vaccination programme.

  6. Changing Epidemiological Characteristics of Hepatitis A in Zhejiang Province, China: Increased Susceptibility in Adults

    PubMed Central

    Wang, Zhifang; Chen, Yaping; Xie, Shuyun; Lv, Huakun

    2016-01-01

    Background Hepatitis A is a common acute hepatitis caused by hepatitis A virus (HAV). Annually, it affects 1.4 million people worldwide. Between 1991 and 1994, HAV infections were highly endemic in Zhejiang Province (China), with 78,720 reported HAV infections per year. Hepatitis A vaccine came on the market in 1995 and was implemented for voluntary immunization. Since 2008, hepatitis A vaccine has been integrated into the national childhood routine immunization program. Objective To understand the current epidemiological profile of hepatitis A in Zhejiang Province since hepatitis A vaccine has been available for nearly two decades. Methods This study used the 2005–2014 National Notifiable Diseases Reporting System data to evaluate the incidence rate of notified hepatitis A cases in Zhejiang Province. Results The overall trend of incidence rate of notified hepatitis A cases significantly decreased from 2005 to 2014 (P< 0.001). During the study period, the reported incidence rate in individuals aged ≤19 years declined to the historically lowest record in 2014. Compared with individuals aged ≤19 years, those aged ≥20 years showed the highest incidence rate (P< 0.001). Majority of HAV infected cases were Laborers, accounting for approximately 70% of reported cases. Conclusions Childhood immunization strategy with hepatitis A vaccine seemed to be effective in decreasing notified hepatitis A incidence rate in individuals aged ≤19 years. Those aged ≥20 years were observed to be the most susceptible population. The vast majority of hepatitis A cases were notified among Laborers. Therefore, we strongly suggest that future preventive and control measures should focus more on adults, particularly Laborers, in addition to the current childhood hepatitis A vaccination programme. PMID:27093614

  7. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats.

    PubMed

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2014-01-15

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE+ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE+HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE+HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a "two-programming" hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is "the first programming", and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as "the second programming".

  8. A Strong Immune Response in Young Adult Honeybees Masks Their Increased Susceptibility to Infection Compared to Older Bees

    PubMed Central

    Bull, James C.; Ryabov, Eugene V.; Prince, Gill; Mead, Andrew; Zhang, Cunjin; Baxter, Laura A.; Pell, Judith K.; Osborne, Juliet L.; Chandler, Dave

    2012-01-01

    Honeybees, Apis mellifera, show age-related division of labor in which young adults perform maintenance (“housekeeping”) tasks inside the colony before switching to outside foraging at approximately 23 days old. Disease resistance is an important feature of honeybee biology, but little is known about the interaction of pathogens and age-related division of labor. We tested a hypothesis that older forager bees and younger “house” bees differ in susceptibility to infection. We coupled an infection bioassay with a functional analysis of gene expression in individual bees using a whole genome microarray. Forager bees treated with the entomopathogenic fungus Metarhizium anisopliae s.l. survived for significantly longer than house bees. This was concomitant with substantial differences in gene expression including genes associated with immune function. In house bees, infection was associated with differential expression of 35 candidate immune genes contrasted with differential expression of only two candidate immune genes in forager bees. For control bees (i.e. not treated with M. anisopliae) the development from the house to the forager stage was associated with differential expression of 49 candidate immune genes, including up-regulation of the antimicrobial peptide gene abaecin, plus major components of the Toll pathway, serine proteases, and serpins. We infer that reduced pathogen susceptibility in forager bees was associated with age-related activation of specific immune system pathways. Our findings contrast with the view that the immunocompetence in social insects declines with the onset of foraging as a result of a trade-off in the allocation of resources for foraging. The up-regulation of immune-related genes in young adult bees in response to M. anisopliae infection was an indicator of disease susceptibility; this also challenges previous research in social insects, in which an elevated immune status has been used as a marker of increased disease

  9. A strong immune response in young adult honeybees masks their increased susceptibility to infection compared to older bees.

    PubMed

    Bull, James C; Ryabov, Eugene V; Prince, Gill; Mead, Andrew; Zhang, Cunjin; Baxter, Laura A; Pell, Judith K; Osborne, Juliet L; Chandler, Dave

    2012-12-01

    Honeybees, Apis mellifera, show age-related division of labor in which young adults perform maintenance ("housekeeping") tasks inside the colony before switching to outside foraging at approximately 23 days old. Disease resistance is an important feature of honeybee biology, but little is known about the interaction of pathogens and age-related division of labor. We tested a hypothesis that older forager bees and younger "house" bees differ in susceptibility to infection. We coupled an infection bioassay with a functional analysis of gene expression in individual bees using a whole genome microarray. Forager bees treated with the entomopathogenic fungus Metarhizium anisopliae s.l. survived for significantly longer than house bees. This was concomitant with substantial differences in gene expression including genes associated with immune function. In house bees, infection was associated with differential expression of 35 candidate immune genes contrasted with differential expression of only two candidate immune genes in forager bees. For control bees (i.e. not treated with M. anisopliae) the development from the house to the forager stage was associated with differential expression of 49 candidate immune genes, including up-regulation of the antimicrobial peptide gene abaecin, plus major components of the Toll pathway, serine proteases, and serpins. We infer that reduced pathogen susceptibility in forager bees was associated with age-related activation of specific immune system pathways. Our findings contrast with the view that the immunocompetence in social insects declines with the onset of foraging as a result of a trade-off in the allocation of resources for foraging. The up-regulation of immune-related genes in young adult bees in response to M. anisopliae infection was an indicator of disease susceptibility; this also challenges previous research in social insects, in which an elevated immune status has been used as a marker of increased disease resistance and

  10. Susceptibility to the Flash-Beep Illusion Is Increased in Children Compared to Adults

    ERIC Educational Resources Information Center

    Innes-Brown, Hamish; Barutchu, Ayla; Shivdasani, Mohit N.; Crewther, David P.; Grayden, David B.; Paolini, Antonio

    2011-01-01

    Audio-visual integration was studied in children aged 8-17 (N = 30) and adults (N = 22) using the "flash-beep illusion" paradigm, where the presentation of two beeps causes a single flash to be perceived as two flashes ("fission" illusion), and a single beep causes two flashes to be perceived as one flash ("fusion" illusion). Children reported…

  11. Susceptibility to the Flash-Beep Illusion Is Increased in Children Compared to Adults

    ERIC Educational Resources Information Center

    Innes-Brown, Hamish; Barutchu, Ayla; Shivdasani, Mohit N.; Crewther, David P.; Grayden, David B.; Paolini, Antonio

    2011-01-01

    Audio-visual integration was studied in children aged 8-17 (N = 30) and adults (N = 22) using the "flash-beep illusion" paradigm, where the presentation of two beeps causes a single flash to be perceived as two flashes ("fission" illusion), and a single beep causes two flashes to be perceived as one flash ("fusion" illusion). Children reported…

  12. Increased susceptibility to metabolic alterations in young adult females exposed to early malnutrition.

    PubMed

    Miñana-Solis, María del Carmen; Escobar, Carolina

    2006-10-05

    Early malnutrition during gestation and lactation modifies growth and metabolism permanently. Follow up studies using a nutritional rehabilitation protocol have reported that early malnourished rats exhibit hyperglycemia and/or hyperinsulinemia, suggesting that the effects of early malnutrition are permanent and produce a "programming" effect on metabolism. Deleterious effects have mainly been observed when early-malnutrition is followed by a high-carbohydrate or a high-fat diet. The aim of this study was to evaluate whether following a balanced diet subsequent to malnutrition can deter the expression of metabolic disease and lead rats to exhibit metabolic responses, similar to those of well-nourished controls. Young rats, born from dams malnourished during gestation and lactation with a low protein diet, were provided with a regular balanced chow diet upon weaning. At 90 days of age, the effects of rehabilitation were determined under three different feeding conditions: ad libitum, fasting or fasting-reefed satiated.Early-malnourished rats showed an increased rate of body weight gain. Males under ad libitum conditions showed an elevated concentration of hepatic glycogen and low values of insulin. In the fasting-reefed satiated condition, only early-malnourished females showed an alteration in glucose response and glucagon level, compared with their well-nourished controls. Data indicate that a balanced diet along life after early malnutrition can mask the expression of metabolic disorders and that a metabolic challenges due to a prolonged fasting and reefed state unmask metabolic deficiencies in early-malnourished females.

  13. Increased Susceptibility to Metabolic Alterations in Young Adult Females Exposed to Early Malnutrition

    PubMed Central

    del Carmen Miñana-Solis, María; Escobar, Carolina

    2007-01-01

    Early malnutrition during gestation and lactation modifies growth and metabolism permanently. Follow up studies using a nutritional rehabilitation protocol have reported that early malnourished rats exhibit hyperglycemia and/or hyperinsulinemia, suggesting that the effects of early malnutrition are permanent and produce a “programming” effect on metabolism. Deleterious effects have mainly been observed when early-malnutrition is followed by a high-carbohydrate or a high-fat diet. The aim of this study was to evaluate whether following a balanced diet subsequent to malnutrition can deter the expression of metabolic disease and lead rats to exhibit metabolic responses, similar to those of well-nourished controls. Young rats, born from dams malnourished during gestation and lactation with a low protein diet, were provided with a regular balanced chow diet upon weaning. At 90 days of age, the effects of rehabilitation were determined under three different feeding conditions: ad libitum, fasting or fasting-reefed satiated. Early-malnourished rats showed an increased rate of body weight gain. Males under ad libitum conditions showed an elevated concentration of hepatic glycogen and low values of insulin. In the fasting-reefed satiated condition, only early-malnourished females showed an alteration in glucose response and glucagon level, compared with their well-nourished controls. Data indicate that a balanced diet along life after early malnutrition can mask the expression of metabolic disorders and that a metabolic challenges due to a prolonged fasting and reefed state unmask metabolic deficiencies in early-malnourished females. PMID:17200687

  14. Intrauterine metabolic programming alteration increased susceptibility to non-alcoholic adult fatty liver disease in prenatal caffeine-exposed rat offspring.

    PubMed

    Wang, Linlong; Shen, Lang; Ping, Jie; Zhang, Li; Liu, Zhongfen; Wu, Yong; Liu, Yansong; Huang, Hegui; Chen, Liaobin; Wang, Hui

    2014-01-30

    An increase in susceptibility to metabolic syndromes (MetS) in rat offspring that experienced prenatal caffeine exposure (PCE) has been previously demonstrated. The present study aimed to clarify this increased susceptibility and elucidate the mechanism of foetal origin that causes or contributes to adult non-alcoholic fatty liver disease (NAFLD) as a result of PCE. Based on the results from both foetal and adult studies of rats that experienced PCE (120 mg/kgd), the foetal weight and serum triglyceride levels decreased significantly and hepatocellular ultrastructure was altered. Foetal livers exhibited inhibited insulin-like growth factor-1 (IGF-1), enhanced lipogenesis and reduced lipid output. In adult female offspring of PCE+lab chow, lipid synthesis, oxidation and output were enhanced, whereas lipogenesis was inhibited in their male conterparters. Furthermore, in adult offspring of PCE+ high-fat diet, catch-up growth appeared obvious with enhanced hepatic IGF-1, especially in females. Both males and females showed increased lipid synthesis and reduced output, which were accompanied by elevated serum triglyceride. Severe NAFLD appeared with higher Kleiner scores. Gluconeogenesis was continuously enhanced in females. Therefore, increased susceptibility to diet-induced NAFLD in PCE offspring was confirmed, and it appears to be mediated by intrauterine glucose and alterations in lipid metabolic programming. This altered programming enhanced foetal hepatic lipogenesis and reduced lipid output in utero, which continued into the postnatal phase and reappeared in adulthood with the introduction of a high-fat diet, thereby aggravating hepatic lipid accumulation and causing NAFLD.

  15. In utero exposure to diesel exhaust air pollution promotes adverse intrauterine conditions, resulting in weight gain, altered blood pressure, and increased susceptibility to heart failure in adult mice.

    PubMed

    Weldy, Chad S; Liu, Yonggang; Liggitt, H Denny; Chin, Michael T

    2014-01-01

    Exposure to fine particulate air pollution (PM₂.₅) is strongly associated with cardiovascular morbidity and mortality. Exposure to PM₂.₅ during pregnancy promotes reduced birthweight, and the associated adverse intrauterine conditions may also promote adult risk of cardiovascular disease. Here, we investigated the potential for in utero exposure to diesel exhaust (DE) air pollution, a major source of urban PM₂.₅, to promote adverse intrauterine conditions and influence adult susceptibility to disease. We exposed pregnant female C57Bl/6J mice to DE (≈300 µg/m³ PM₂.₅, 6 hrs/day, 5 days/week) from embryonic day (E) 0.5 to 17.5. At E17.5 embryos were collected for gravimetric analysis and assessed for evidence of resorption. Placental tissues underwent pathological examination to assess the extent of injury, inflammatory cell infiltration, and oxidative stress. In addition, some dams that were exposed to DE were allowed to give birth to pups and raise offspring in filtered air (FA) conditions. At 10-weeks of age, body weight and blood pressure were measured. At 12-weeks of age, cardiac function was assessed by echocardiography. Susceptibility to pressure overload-induced heart failure was then determined after transverse aortic constriction surgery. We found that in utero exposure to DE increases embryo resorption, and promotes placental hemorrhage, focal necrosis, compaction of labyrinth vascular spaces, inflammatory cell infiltration and oxidative stress. In addition, we observed that in utero DE exposure increased body weight, but counterintuitively reduced blood pressure without any changes in baseline cardiac function in adult male mice. Importantly, we observed these mice to have increased susceptibility to pressure-overload induced heart failure, suggesting this in utero exposure to DE 'reprograms' the heart to a heightened susceptibility to failure. These observations provide important data to suggest that developmental exposure to air

  16. Administration of anabolic steroid during adolescence induces long-term cardiac hypertrophy and increases susceptibility to ischemia/reperfusion injury in adult Wistar rats.

    PubMed

    Seara, Fernando de Azevedo Cruz; Barbosa, Raiana Andrade Quintanilha; de Oliveira, Dahienne Ferreira; Gran da Silva, Diorney Luiz Souza; Carvalho, Adriana Bastos; Freitas Ferreira, Andrea Claudia; Matheus Nascimento, José Hamilton; Olivares, Emerson Lopes

    2017-07-01

    Chronic administration of anabolic androgenic steroids (AAS) in adult rats results in cardiac hypertrophy and increased susceptibility to myocardial ischemia/reperfusion (IR) injury. Molecular analyses demonstrated that hyperactivation of type 1 angiotensin II (AT1) receptor mediates cardiac hypertrophy induced by AAS and also induces down-regulation of myocardial ATP-sensitive potassium channel (KATP), resulting in loss of exercise-induced cardioprotection. Exposure to AAS during adolescence promoted long-term cardiovascular dysfunctions, such as dysautonomia. We tested the hypothesis that chronic AAS exposure in the pre/pubertal phase increases the susceptibility to myocardial ischemia/reperfusion (IR) injury in adult rats. Male Wistar rats (26day old) were treated with vehicle (Control, n=12) or testosterone propionate (TP) (AAS, 5mgkg(-1) n=12) 5 times/week during 5 weeks. At the end of AAS exposure, rats underwent 23days of washout period and were submitted to euthanasia. Langendorff-perfused hearts were submitted to IR injury and evaluated for mechanical dysfunctions and infarct size. Molecular analysis was performed by mRNA levels of α-myosin heavy chain (MHC), βMHC and brain-derived natriuretic peptide (BNP), ryanodine receptor (RyR2) and sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) by quantitative RT-PCR (qRT-PCR). The expression of AT1 receptor and KATP channel subunits (Kir6.1 and SURa) was analyzed by qRT-PCR and Western Blot. NADPH oxidase (Nox)-related reactive oxygen species generation was assessed by spectrofluorimetry. The expression of antioxidant enzymes was measured by qRT-PCR in order to address a potential role of redox unbalance. AAS exposure promoted long-term cardiac hypertrophy characterized by increased expression of βMHC and βMHC/αMHC ratio. Baseline derivative of pressure (dP/dt) was impaired by AAS exposure. Postischemic recovery of mechanical properties was impaired (decreased left ventricle [LV] developed pressure and

  17. The aging kidney: increased susceptibility to nephrotoxicity.

    PubMed

    Wang, Xinhui; Bonventre, Joseph V; Parrish, Alan R

    2014-09-01

    Three decades have passed since a series of studies indicated that the aging kidney was characterized by increased susceptibility to nephrotoxic injury. Data from these experimental models is strengthened by clinical data demonstrating that the aging population has an increased incidence and severity of acute kidney injury (AKI). Since then a number of studies have focused on age-dependent alterations in pathways that predispose the kidney to acute insult. This review will focus on the mechanisms that are altered by aging in the kidney that may increase susceptibility to injury, including hemodynamics, oxidative stress, apoptosis, autophagy, inflammation and decreased repair.

  18. The Aging Kidney: Increased Susceptibility to Nephrotoxicity

    PubMed Central

    Wang, Xinhui; Bonventre, Joseph V.; Parrish, Alan R.

    2014-01-01

    Three decades have passed since a series of studies indicated that the aging kidney was characterized by increased susceptibility to nephrotoxic injury. Data from these experimental models is strengthened by clinical data demonstrating that the aging population has an increased incidence and severity of acute kidney injury (AKI). Since then a number of studies have focused on age-dependent alterations in pathways that predispose the kidney to acute insult. This review will focus on the mechanisms that are altered by aging in the kidney that may increase susceptibility to injury, including hemodynamics, oxidative stress, apoptosis, autophagy, inflammation and decreased repair. PMID:25257519

  19. Maternal hypoxia increases the susceptibility of adult rat male offspring to high-fat diet-induced nonalcoholic fatty liver disease.

    PubMed

    Su, Yi-Ming; Lv, Guo-Rong; Xie, Jing-Xian; Wang, Zhen-Hua; Lin, Hui-Tong

    2013-11-01

    Exposure to an adverse intrauterine environment increases the risk for adult metabolic syndrome. However, the influence of prenatal hypoxia on the risk of fatty liver disease in offspring is unclear. The purpose of the present study was to evaluate the role of reduced fetal oxygen on the development and severity of high-fat (HF) diet-induced nonalcoholic fatty liver disease (NAFLD). Based on design implicating 2 factors, ie, maternal hypoxia (MH) and postnatal HF diet, blood lipid and insulin levels, hepatic histology, and potential molecular targets were evaluated in male Sprague Dawley rat offspring. MH associated with postnatal HF diet caused a significant increase in plasma concentration of triglycerides, free fatty acids, low-density lipoprotein cholesterol, and insulin. Histologically, a more severe form of NAFLD with hepatic inflammation, hepatic resident macrophage infiltration, and progression toward nonalcoholic steatohepatitis was observed. The lipid homeostasis changes and insulin resistance caused by MH plus HF were accompanied by a significant down-regulation of insulin receptor substrate 2 (IRS-2), phosphoinositide-3 kinase p110 catalytic subunit, and protein kinase B. In MH rats, insulin-stimulated IRS-2 and protein kinase B (AKT) phosphorylation were significantly blunted as well as insulin suppression of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Meanwhile, a significant up-regulation of lipogenic pathways was noticed, including sterol-regulatory element-binding protein-1 and fatty acid synthase in liver. Our results indicate that maternal hypoxia enhances dysmetabolic liver injury in response to an HF diet. Therefore, the offspring born in the context of maternal hypoxia may require special attention and follow-up to prevent the early development of NAFLD.

  20. Polytrauma Increases Susceptibility to Pseudomonas Pneumonia in Mature Mice.

    PubMed

    Turnbull, Isaiah R; Ghosh, Sarbani; Fuchs, Anja; Hilliard, Julia; Davis, Christopher G; Bochicchio, Grant V; Southard, Robert E

    2016-05-01

    Pneumonia is the most common complication observed in patients with severe injuries. Although the average age of injured patients is 47 years, existing studies of the effect of injury on the susceptibility to infectious complications have focused on young animals, equivalent to a late adolescent human. We hypothesized that mature adult animals are more susceptible to infection after injury than younger counterparts. To test this hypothesis, we challenged 6 to 8-month-old mature mice to a polytrauma injury followed by Pseudomonas aeruginosa pneumonia and compared them to young (8-10-week-old) animals. We demonstrate that polytrauma injury increases mortality from pneumonia in mature animals (sham-pneumonia 21% vs. polytrauma-pneumonia 62%) but not younger counterparts. After polytrauma, pneumonia in mature mice is associated with higher bacterial burden in lung, increased incidence of bacteremia, and elevated levels of bacteria in the blood, demonstrating that injury decreases the ability to control the infectious challenge. We further find that polytrauma did not induce elevations in circulating cytokine levels (TNF-alpha, IL-6, KC, and IL-10) 24  h after injury. However, mature mice subjected to polytrauma demonstrated an exaggerated circulating inflammatory cytokine response to subsequent Pseudomonas pneumonia. Additionally, whereas prior injury increases LPS-stimulated IL-6 production by peripheral blood leukocytes from young (8-10-week-old) mice, injury does not prime IL-6 production by cell from mature adult mice. We conclude that in mature mice polytrauma results in increased susceptibility to Pseudomonas pneumonia while priming an exaggerated but ineffective inflammatory response.

  1. Antibiotics in neonatal life increase murine susceptibility to experimental psoriasis

    PubMed Central

    Zanvit, Peter; Konkel, Joanne E.; Jiao, Xue; Kasagi, Shimpei; Zhang, Dunfang; Wu, Ruiqing; Chia, Cheryl; Ajami, Nadim J.; Smith, Daniel P.; Petrosino, Joseph F.; Abbatiello, Brittany; Nakatsukasa, Hiroko; Chen, Qianming; Belkaid, Yasmine; Chen, Zi-Jiang; Chen, WanJun

    2015-01-01

    Psoriasis is an inflammatory skin disease affecting ∼2% of the world's population, but the aetiology remains incompletely understood. Recently, microbiota have been shown to differentially regulate the development of autoimmune diseases, but their influence on psoriasis is incompletely understood. We show here that adult mice treated with antibiotics that target Gram-negative and Gram-positive bacteria develop ameliorated psoriasiform dermatitis induced by imiquimod, with decreased pro-inflammatory IL-17- and IL-22-producing T cells. Surprisingly, mice treated neonatally with these antibiotics develop exacerbated psoriasis induced by imiquimod or recombinant IL-23 injection when challenged as adults, with increased IL-22-producing γδ+ T cells. 16S rRNA gene compositional analysis reveals that neonatal antibiotic-treatment dysregulates gut and skin microbiota in adults, which is associated with increased susceptibility to experimental psoriasis. This link between neonatal antibiotic-mediated imbalance in microbiota and development of experimental psoriasis provides precedence for further investigation of its specific aetiology as it relates to human psoriasis. PMID:26416167

  2. Blocking miRNA Biogenesis in Adult Forebrain Neurons Enhances Seizure Susceptibility, Fear Memory, and Food Intake by Increasing Neuronal Responsiveness.

    PubMed

    Fiorenza, Anna; Lopez-Atalaya, Jose P; Rovira, Victor; Scandaglia, Marilyn; Geijo-Barrientos, Emilio; Barco, Angel

    2016-04-01

    The RNase Dicer is essential for the maturation of most microRNAs, a molecular system that plays an essential role in fine-tuning gene expression. To gain molecular insight into the role of Dicer and the microRNA system in brain function, we conducted 2 complementary RNA-seq screens in the hippocampus of inducible forebrain-restricted Dicer1 mutants aimed at identifying the microRNAs primarily affected by Dicer loss and their targets, respectively. Functional genomics analyses predicted the main biological processes and phenotypes associated with impaired microRNA maturation, including categories related to microRNA biology, signal transduction, seizures, and synaptic transmission and plasticity. Consistent with these predictions, we found that, soon after recombination, Dicer-deficient mice exhibited an exaggerated seizure response, enhanced induction of immediate early genes in response to different stimuli, stronger and more stable fear memory, hyperphagia, and increased excitability of CA1 pyramidal neurons. In the long term, we also observed slow and progressive excitotoxic neurodegeneration. Overall, our results indicate that interfering with microRNA biogenesis causes an increase in neuronal responsiveness and disrupts homeostatic mechanisms that protect the neuron against overactivation, which may explain both the initial and late phenotypes associated with the loss of Dicer in excitatory neurons.

  3. Developmental PCB Exposure Increases Susceptibility to Audiogenic Seizures in Adulthood

    PubMed Central

    Poon, Emily; Bandara, Suren B.; Allen, Jont B.; Sadowski, Renee N.; Schantz, Susan L.

    2014-01-01

    Developmental exposure to polychlorinated biphenyls (PCBs) causes auditory deficits. Thus, we recently conducted a study to investigate if developmental PCB exposure would exacerbate noise-induced hearing loss in adulthood. Unexpectedly, some PCB-exposed rats exhibited seizure-like behaviors when exposed to loud noise. Therefore, we conducted the current experiment to determine if adult rats perinatally exposed to PCBs are more susceptible to audiogenic seizures when tested in a standard audiogenic seizure paradigm. Adult male and female rats exposed to PCBs during gestation and lactation (0, 1, 3 or 6 mg/kg/day) and previously tested in the noise-induced hearing loss study were presented with a 100dB noise stimulus. If they did not exhibit clonus in response to the 100dB noise, they were exposed to a 105dB stimulus 24-48 hours later. This was followed by an 110dB stimulus 24-48 hours later if they did not exhibit clonus at 105 dB. Female and male rats exposed to either 3 or 6 mg/kg PCBs exhibited a significantly higher incidence of audiogenic seizures, shorter latency to onset of seizures, and greater severity of seizures compared to controls. Thyroxine measured in littermates at weaning was significantly lower in all PCB groups compared to controls, suggesting a potential mechanism for the increased incidence of audiogenic seizures. This is the first study to show that developmental PCB exposure increases the susceptibility to audiogenic seizures in adulthood. PMID:25543072

  4. Correlates of Susceptibility to Scams in Older Adults Without Dementia

    PubMed Central

    James, Bryan D.; Boyle, Patricia A.; Bennett, David A.

    2013-01-01

    This study examined correlates of susceptibility to scams in 639 community-dwelling older adults without dementia from a cohort study of aging. Regression models adjusted for age, sex, education, and income were used to examine associations between susceptibility to scams, measured by 5-item self-report measure, and a number of potential correlates. Susceptibility was positively associated with age and negatively associated with income, cognition, psychological well being, social support, and literacy. Fully adjusted models indicated that older age and lower levels of cognitive function, decreased psychological well-being, and lower literacy in particular may be markers of susceptibility to financial victimization in old age. PMID:24499279

  5. Diesel Exhaust Exposure Increases Susceptibility to Influenza ...

    EPA Pesticide Factsheets

    Mice were necropsied at day 1, 4, 8 and 14 post-infection and lung tissue was assessed for virus titers by TCID50, lung injury and inflammation. Lung and lymph node DC populations (CD11c+, MHCII, CD45+, CD80+ and CD86+) were identified by flow cytometry. Prior exposure to DE significantly increased viral titers in the lung at 4 and 8 days post infection in association with increased neutrophil influx and lung injury. Pro-inflammatory cytokines including IP-10, MCP-1, GM-CSF, and IL-1β, and the antiviral cytokine IFN-β were also increased at days 1, 4 and 8 post infection compared to air/flu controls. The number of DCs in the lung was not affected with previous exposure to DE, however the lymph nodes had increased number of mature DCs at 1, 4, and 8 days post infection compared to the air/flu controls. We conclude that exposure to DE prior to an influenza infection increases pulmonary inflammation, viral titers, and stimulates more DCs to migrate to the lymph nodes and mature as a consequence of the DE-enhanced influenza infection. Numerous studies have shown that diesel exhaust (DE) decreases resistance to respiratory infection and can alter the maturation and migration of dendritic cells (DCs). The purpose of this study was to evaluate the effects of DE exposure on susceptibilty to influenza infection in mice and to determine if this correlated with changes in the pulmonary DC populations. BALB/c mice were exposed to air or 0.5 mg/m3 DE from a diesel-power

  6. Diesel Exhaust Exposure Increases Susceptibility to Influenza ...

    EPA Pesticide Factsheets

    Mice were necropsied at day 1, 4, 8 and 14 post-infection and lung tissue was assessed for virus titers by TCID50, lung injury and inflammation. Lung and lymph node DC populations (CD11c+, MHCII, CD45+, CD80+ and CD86+) were identified by flow cytometry. Prior exposure to DE significantly increased viral titers in the lung at 4 and 8 days post infection in association with increased neutrophil influx and lung injury. Pro-inflammatory cytokines including IP-10, MCP-1, GM-CSF, and IL-1β, and the antiviral cytokine IFN-β were also increased at days 1, 4 and 8 post infection compared to air/flu controls. The number of DCs in the lung was not affected with previous exposure to DE, however the lymph nodes had increased number of mature DCs at 1, 4, and 8 days post infection compared to the air/flu controls. We conclude that exposure to DE prior to an influenza infection increases pulmonary inflammation, viral titers, and stimulates more DCs to migrate to the lymph nodes and mature as a consequence of the DE-enhanced influenza infection. Numerous studies have shown that diesel exhaust (DE) decreases resistance to respiratory infection and can alter the maturation and migration of dendritic cells (DCs). The purpose of this study was to evaluate the effects of DE exposure on susceptibilty to influenza infection in mice and to determine if this correlated with changes in the pulmonary DC populations. BALB/c mice were exposed to air or 0.5 mg/m3 DE from a diesel-power

  7. Porins Increase Copper Susceptibility of Mycobacterium tuberculosis

    PubMed Central

    Speer, Alexander; Rowland, Jennifer L.; Haeili, Mehri; Niederweis, Michael

    2013-01-01

    Copper resistance mechanisms are crucial for many pathogenic bacteria, including Mycobacterium tuberculosis, during infection because the innate immune system utilizes copper ions to kill bacterial intruders. Despite several studies detailing responses of mycobacteria to copper, the pathways by which copper ions cross the mycobacterial cell envelope are unknown. Deletion of porin genes in Mycobacterium smegmatis leads to a severe growth defect on trace copper medium but simultaneously increases tolerance for copper at elevated concentrations, indicating that porins mediate copper uptake across the outer membrane. Heterologous expression of the mycobacterial porin gene mspA reduced growth of M. tuberculosis in the presence of 2.5 μM copper by 40% and completely suppressed growth at 15 μM copper, while wild-type M. tuberculosis reached its normal cell density at that copper concentration. Moreover, the polyamine spermine, a known inhibitor of porin activity in Gram-negative bacteria, enhanced tolerance of M. tuberculosis for copper, suggesting that copper ions utilize endogenous outer membrane channel proteins of M. tuberculosis to gain access to interior cellular compartments. In summary, these findings highlight the outer membrane as the first barrier against copper ions and the role of porins in mediating copper uptake in M. smegmatis and M. tuberculosis. PMID:24013632

  8. Porins increase copper susceptibility of Mycobacterium tuberculosis.

    PubMed

    Speer, Alexander; Rowland, Jennifer L; Haeili, Mehri; Niederweis, Michael; Wolschendorf, Frank

    2013-11-01

    Copper resistance mechanisms are crucial for many pathogenic bacteria, including Mycobacterium tuberculosis, during infection because the innate immune system utilizes copper ions to kill bacterial intruders. Despite several studies detailing responses of mycobacteria to copper, the pathways by which copper ions cross the mycobacterial cell envelope are unknown. Deletion of porin genes in Mycobacterium smegmatis leads to a severe growth defect on trace copper medium but simultaneously increases tolerance for copper at elevated concentrations, indicating that porins mediate copper uptake across the outer membrane. Heterologous expression of the mycobacterial porin gene mspA reduced growth of M. tuberculosis in the presence of 2.5 μM copper by 40% and completely suppressed growth at 15 μM copper, while wild-type M. tuberculosis reached its normal cell density at that copper concentration. Moreover, the polyamine spermine, a known inhibitor of porin activity in Gram-negative bacteria, enhanced tolerance of M. tuberculosis for copper, suggesting that copper ions utilize endogenous outer membrane channel proteins of M. tuberculosis to gain access to interior cellular compartments. In summary, these findings highlight the outer membrane as the first barrier against copper ions and the role of porins in mediating copper uptake in M. smegmatis and M. tuberculosis.

  9. Neuropsychological status in older adults influences susceptibility to false memories.

    PubMed

    Meade, Michelle L; Geraci, Lisa D; Roediger, Henry L

    2012-01-01

    In 2 experiments we examined the influence of frontal lobe function on older adults' susceptibility to false memory in a categorized list paradigm. Using a neuropsychological battery of tests developed by Glisky, Polster, and Routhieaux (1995), we designated older adults as having high- or low-frontal function. Young and older adults studied and were tested on categorized lists using free report cued recall and forced report cued recall instructions, with the latter requiring participants to produce responses even if they had to guess. Under free report cued recall instructions, frontal lobe function was a strong predictor of false memories in older adults: Older adults who scored low on tests of frontal functioning demonstrated much higher levels of false recall than younger adults, whereas levels of false recall in high-frontal older adults were more similar to those of young adults. However, after forced report cued recall, high- and low-frontal older adults performed similarly to each other, and both demonstrated higher levels of false recall than young adults. On a final recognition test, high-frontal older adults in both the free report cued recall and forced report cued recall conditions were more successful than low-frontal older adults in using source information to reduce memory errors. The results indicate that older adults show higher levels of false recall than younger adults, but type of test (free report or forced report) and neuropsychological status of older adults mediate these effects. Low-frontal older adults are particularly susceptible to producing false memories on free report tests that entail source monitoring.

  10. Tobacco Marketing, E-cigarette Susceptibility, and Perceptions among Adults.

    PubMed

    Nicksic, Nicole E; Snell, L Morgan; Rudy, Alyssa K; Cobb, Caroline O; Barnes, Andrew J

    2017-09-01

    Understanding the impact of tobacco marketing on e-cigarette (EC) susceptibility and perceptions is essential to inform efforts to mitigate tobacco product burden on public health. Data were collected online in 2016 from 634 conventional cigarette (CC) smokers and 393 non-smokers using a convenience sample from Amazon Mechanical Turk. Logistic regression models, stratified by smoking status and adjusted for socio-demographics, examined the relationship among tobacco advertisements and coupons, EC and CC susceptibility, and EC perceptions. Among non-smokers, increased exposure to tobacco advertising and receiving tobacco coupons was significantly related to measures of EC and CC susceptibility (p < .05). Older, more educated non-smokers had decreased odds of EC susceptibility (p < .05). Additionally, increased exposure to tobacco advertising was significantly associated with the perceptions of EC not containing nicotine and being less addictive than CC among smokers (p < .05). Increased exposure to tobacco advertising outlets could influence future EC and CC use in non-smokers and perceptions in smokers, while receiving coupons could affect EC and CC susceptibility among non-smokers. Future research is needed to determine whether policies to minimize exposure to tobacco marketing reduce EC use by decreasing susceptibility.

  11. Atrazine increases ranavirus susceptibility in the tiger salamander, Ambystoma tigrinum.

    PubMed

    Forson, Diane Denise; Storfer, Andrew

    2006-12-01

    Pathogenic diseases and environmental contaminants are two of the leading hypotheses for global amphibian declines, yet few studies have examined the influence of contaminants on disease susceptibility. In this study, we examined effects of ecologically relevant doses of atrazine (0, 1.6, 16, and 160 microg/L), sodium nitrate (0, 6.8, 68 mg/L), and their interactions on susceptibility of four laboratory-bred tiger salamander families to Ambystoma tigrinum virus (ATV), a pathogen implicated in global amphibian die-offs. Salamanders were from Arizona populations where a coevolutionary history with ATV is supported, and thus cofactors rather than recent introduction may contribute to disease epizootics. Use of atrazine and nitrogenous fertilizers are ubiquitous; therefore, the impact of these cofactors on disease susceptibility is an important consideration. Atrazine and sodium nitrate significantly decreased peripheral leukocyte levels, suggesting an impact of these contaminants on the immune system. As expected from this result, atrazine significantly increased susceptibility of larvae to ATV infection. In contrast, nitrate had a marginally significant main effect and significantly decreased infection rate at the highest level. However, neither atrazine nor sodium nitrate had significant effects on viral copy number per individual. These results suggest that ecologically relevant concentrations of atrazine and nitrates have immunosuppressive effects, and atrazine may contribute to ATV epizootics, raising concerns about the influence of contaminants on diseases in general.

  12. Simulated microgravity disrupts intestinal homeostasis and increases colitis susceptibility.

    PubMed

    Li, Pingping; Shi, Junxiu; Zhang, Peng; Wang, Ke; Li, Jinglong; Liu, Hongju; Zhou, Yu; Xu, Xi; Hao, Jie; Sun, Xiuyuan; Pang, Xuewen; Li, Yan; Wu, Hounan; Chen, Xiaoping; Ge, Qing

    2015-08-01

    The immune systems can be altered by spaceflight in many aspects, but microgravity-related mucosal immune changes and its clinical significance have not been well studied. The purpose of this study was to investigate whether simulated microgravity influences the intestinal homeostasis and increases the susceptibility to colon inflammation. The hindlimb unloading (HU) mouse model was used to simulate the microgravity condition. Three percent dextran sulfate sodium (DSS) was given to mice to induce colitis. Compared to ground control (Ctrl) mice, the HU ones revealed an impaired intestinal homeostasis and increased susceptibility to DSS-induced colitis. This includes an early-onset, 4-fold expansion of segmented filamentous bacteria (SFB), more than 2-fold decrease in regulatory T (Treg) cell numbers and IL-10 production, ∼2-fold increase in colonic IL-1β expression, 2-fold increase in circulating neutrophils, and colonic neutrophil infiltration. The application of antibiotics ameliorated the Treg and IL-10 reductions but did not significantly dampen neutrophilia and elevated expression of colonic IL-1β. These results indicate that the intestinal microflora and innate immune system both respond to simulated microgravity and together, contribute to the proinflammatory shift in the gut microenvironment. The data also emphasize the necessity for evaluating the susceptibility to inflammatory bowel diseases (IBDs) in distant space travels.

  13. Increased Susceptibility to Chemical Toxicity with (Pre-existing ...

    EPA Pesticide Factsheets

    Numerous host and environmental factors may modulate vulnerability and risk. An area of increasing interest to risk assessors is the potential for chemicals to interact with pre-existing diseases and aging that may yield cumulative damage, altered chemical response, and increased disease susceptibility. We evaluated the relationships between chemicals and pre-existing disease and identified the type of information needed to evaluate the relationships of interest. This is for presentation at the 54th Society of Toxicology Annual Meeting and ToxExpo 2015.

  14. Ozone solubilizes elastin and increases its susceptibility to elastase

    SciTech Connect

    Winters, R.S.; Johnson, D.A. )

    1991-03-11

    Ozone is a powerful oxidant gas that may contribute to lung diseases such as emphysema. Because the hallmark of emphysema is destruction of the elastin rich alveoli of the lung, ozonization of elastin was studied in vitro to examine the effects of ozone on elastin structure and susceptibility to proteolysis. Samples of bovine ligamentum nuchae elastin were suspended in 15 ml PBS and bubbled with 13.7 ppm ozone in argon at a flow rate of 3.5 ml/min. Ozone treatment resulted in the solubilization of elastin as evidenced by a visual decrease in turbidity and an increase in the 225 nm absorbance of the supernatant fraction after centrifugation to pellet the insoluble elastin. Insoluble elastin recovered from exposed suspensions was examined for proteolytic susceptibility with human neutrophil elastase (HNE), by incubating 600 {mu}g samples in 1 ml of 50 mM Tris-HCl, 200 mM NaCl, pH 8.0 with 3 {mu}g HNE for various times at room temp. Elastin proteolysis was followed by measuring the 225 nm absorbance of solubilized peptides in supernatant fractions. Ozone exposed elastin, which had been previously ozonized to 5% solubility was found to be approximately twice as susceptible to proteolysis as native elastin.

  15. Association between adult height, genetic susceptibility and risk of glioma

    PubMed Central

    Kitahara, Cari M; Wang, Sophia S; Melin, Beatrice S; Wang, Zhaoming; Braganza, Melissa; Inskip, Peter D; Albanes, Demetrius; Andersson, Ulrika; Beane Freeman, Laura E; Buring, Julie E; Carreón, Tania; Feychting, Maria; Gapstur, Susan M; Gaziano, J Michael; Giles, Graham G; Hallmans, Goran; Hankinson, Susan E; Henriksson, Roger; Hsing, Ann W; Johansen, Christoffer; Linet, Martha S; McKean-Cowdin, Roberta; Michaud, Dominique S; Peters, Ulrike; Purdue, Mark P; Rothman, Nathaniel; Ruder, Avima M; Sesso, Howard D; Severi, Gianluca; Shu, Xiao-Ou; Stevens, Victoria L; Visvanathan, Kala; Waters, Martha A; White, Emily; Wolk, Alicja; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Hoover, Robert; Fraumeni, Joseph F; Chatterjee, Nilanjan; Yeager, Meredith; Chanock, Stephen J; Hartge, Patricia; Rajaraman, Preetha

    2012-01-01

    Background Some, but not all, observational studies have suggested that taller stature is associated with a significant increased risk of glioma. In a pooled analysis of observational studies, we investigated the strength and consistency of this association, overall and for major sub-types, and investigated effect modification by genetic susceptibility to the disease. Methods We standardized and combined individual-level data on 1354 cases and 4734 control subjects from 13 prospective and 2 case–control studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for glioma and glioma sub-types were estimated using logistic regression models stratified by sex and adjusted for birth cohort and study. Pooled ORs were additionally estimated after stratifying the models according to seven recently identified glioma-related genetic variants. Results Among men, we found a positive association between height and glioma risk (≥190 vs 170–174 cm, pooled OR = 1.70, 95% CI: 1.11–2.61; P-trend = 0.01), which was slightly stronger after restricting to cases with glioblastoma (pooled OR = 1.99, 95% CI: 1.17–3.38; P-trend = 0.02). Among women, these associations were less clear (≥175 vs 160–164 cm, pooled OR for glioma = 1.06, 95% CI: 0.70–1.62; P-trend = 0.22; pooled OR for glioblastoma = 1.36, 95% CI: 0.77–2.39; P-trend = 0.04). In general, we did not observe evidence of effect modification by glioma-related genotypes on the association between height and glioma risk. Conclusion An association of taller adult stature with glioma, particularly for men and stronger for glioblastoma, should be investigated further to clarify the role of environmental and genetic determinants of height in the etiology of this disease. PMID:22933650

  16. Developmental Trajectory of McGurk Effect Susceptibility in Children and Adults With Amblyopia.

    PubMed

    Narinesingh, Cindy; Goltz, Herbert C; Raashid, Rana Arham; Wong, Agnes M F

    2015-03-05

    The McGurk effect is an audiovisual illusion that involves the concurrent presentation of a phoneme (auditory syllable) and an incongruent viseme (visual syllable). Adults with amblyopia show less susceptibility to this illusion than visually normal controls, even when viewing binocularly. The present study investigated the developmental trajectory of McGurk effect susceptibility in adults, older children (10-17 years), and younger children (4-9 years) with amblyopia. A total of 62 participants with amblyopia (22 adults, 12 older children, 28 younger children) and 66 visually normal controls (25 adults, 17 older children, 24 younger children) viewed videos that combined phonemes and visemes, and were asked to report what they heard. Videos with congruent (auditory and visual matching) and incongruent (auditory and visual not matching) stimuli were presented. Incorrect responses on incongruent trials correspond to high McGurk effect susceptibility, indicating that the viseme influenced the phoneme. Participants with amblyopia (28.0% ± 3.3%) demonstrated a less consistent McGurk effect than visually normal controls (15.2% ± 2.3%) across all age groups (P = 0.0024). Effect susceptibility increased with age (P = 0.0003) for amblyopic participants and controls. Both groups showed a similar response pattern to different speakers and syllables, but amblyopic participants invariably demonstrated a less consistent effect. Amblyopia is associated with reduced McGurk effect susceptibility in children and adults. Our findings indicate that the differences do not simply indicate delayed development in children with amblyopia; rather, they represent permanent alterations that persist into adulthood. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

  17. Wolbachia increases the susceptibility of a parasitoid wasp to hyperparasitism.

    PubMed

    van Nouhuys, Saskya; Kohonen, Minna; Duplouy, Anne

    2016-10-01

    The success of maternally transmitted endosymbiotic bacteria, such as Wolbachia, is directly linked to their host reproduction but in direct conflict with other parasites that kill the host before it reaches reproductive maturity. Therefore, symbionts that have evolved strategies to increase their host's ability to evade lethal parasites may have high penetrance, while detrimental symbionts would be selected against, leading to lower penetrance or extinction from the host population. In a natural population of the parasitoid wasp Hyposoter horticola in the Åland Islands (Finland), the Wolbachia strain wHho persists at an intermediate prevalence (∼50%). Additionally, there is a negative correlation between the prevalence of Wolbachia and a hyperparasitoid wasp, Mesochorus cf. stigmaticus, in the landscape. Using a manipulative field experiment, we addressed the persistence of Wolbachia at this intermediate level, and tested whether the observed negative correlation could be due to Wolbachia inducing either susceptibility or resistance to parasitism. We show that infection with Wolbachia does not influence the ability of the wasp to parasitize its butterfly host, Melitaea cinxia, but that hyperparasitism of the wasp increases in the presence of wHho. Consequently, the symbiont is detrimental, and in order to persist in the host population, must also have a positive effect on fitness that outweighs the costly burden of susceptibility to widespread parasitism. © 2016. Published by The Company of Biologists Ltd.

  18. Chlorine gas exposure increases susceptibility to invasive lung fungal infection

    PubMed Central

    Gessner, Melissa A.; Doran, Stephen F.; Yu, Zhihong; Dunaway, Chad W.; Matalon, Sadis

    2013-01-01

    Chlorine (Cl2) is a highly irritating and reactive gas with potential occupational and environmental hazards. Acute exposure to Cl2 induces severe epithelial damage, airway hyperreactivity, impaired alveolar fluid clearance, and pulmonary edema in the presence of heightened inflammation and significant neutrophil accumulation in the lungs. Herein, we investigated whether Cl2 exposure affected the lung antimicrobial immune response leading to increased susceptibility to opportunistic infections. Mice exposed to Cl2 and challenged intratracheally 24 h thereafter with the opportunistic mold Aspergillus fumigatus demonstrated an >500-fold increase in A. fumigatus lung burden 72 h postchallenge compared with A. fumigatus mice exposed to room air. Cl2-exposed A. fumigatus challenged mice also demonstrated significantly higher lung resistance following methacholine challenge and increased levels of plasma proteins (albumin and IgG) in the bronchoalveolar lavage fluid. Despite enhanced recruitment of inflammatory cells to the lungs of Cl2-exposed A. fumigatus challenged mice, these cells (>60% of which were neutrophils) demonstrated a profound impairment in generating superoxide. Significantly higher A. fumigatus burden in the lungs of Cl2 exposed mice correlated with enhanced production of IL-6, TNF-α, CXCL1, CCL2, and CCL3. Surprisingly, however, Cl2-exposed A. fumigatus challenged mice had a specific impairment in the production of IL-17A and IL-22 in the lungs compared with mice exposed to room air and challenged with A. fumigatus. In summary, our results indicate that Cl2 exposure markedly impairs the antimicrobial activity and inflammatory reactivity of myeloid cells in the lung leading to increased susceptibility to opportunistic pathogens. PMID:23564508

  19. Increased Susceptibility to Chemical Toxicity with Pre-existing ...

    EPA Pesticide Factsheets

    Numerous host and environmental factors may modulate vulnerability and risk. An area of increasing interest to risk assessors is the potential for chemicals to interact with pre-existing diseases and aging that may yield cumulative damage, altered chemical response, and increased disease susceptibility. We evaluated the relationships between chemicals and pre-existing disease and identify the type of information needed to evaluate the relationships of interest. Key among these is the existence of a clinically relevant and easy to measure biomarker of disease risk which is also modulated by a particular chemical of interest. This biomarker may be a physiological, biochemical, or genetic indicator that corresponds to a phase of the disease process and may be an indicator of where an individual is on the continuum of disease or health status. The relationship between chemical exposure and a biomarker may then be used to predict how preexisting conditions may modify health risks of chemical exposures. Several case studies are explored to describe the toxic chemical, the clinical biomarker, the impacted disease and the evidence that the chemical enhances disease risk: fine particulate matter/decreased heart rate variability/increased cardiopulmonary events; cadmium/decreased glomerular filtration ate/increased chronic kidney disease; methyl mercury/decreased paraoxonase-1/increased cardiovascular risk; Trichloroethylene/increased anti-nuclear antibody/autoimmunit

  20. CDYL Deficiency Disrupts Neuronal Migration and Increases Susceptibility to Epilepsy.

    PubMed

    Qin, Rui; Cao, Shuai; Lyu, Tianjie; Qi, Cai; Zhang, Weiguang; Wang, Yun

    2017-01-10

    During brain development, the correct migration of newborn neurons is one of the determinants of circuit formation, and neuronal migration defects may lead to neurological and psychiatric disorders. The molecular mechanisms underlying neuronal migration and related disorders are poorly understood. Here, we report that Chromodomain Y-like (CDYL) is critical for neuronal migration in mice. Knocking down CDYL caused neuronal migration defects and disrupted both mobility and multipolar-to-bipolar transition of migrating neurons. We find that CDYL regulates neuronal migration by transcriptionally repressing RhoA. In addition, CDYL deficiency increased the excitability of cortical pyramidal neurons and the susceptibility of mice to convulsant-induced seizures. These results demonstrate that CDYL is a regulator of neuronal migration and shed light on the pathogenesis of seizure-related neurodevelopmental disorders. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  1. Ozone increases susceptibility to antigen inhalation in allergic dogs

    SciTech Connect

    Yanai, M.; Ohrui, T.; Aikawa, T.; Okayama, H.; Sekizawa, K.; Maeyama, K.; Sasaki, H.; Takishima, T. )

    1990-06-01

    To determine whether O3 exposure increased airway responsiveness to antigen inhalation, we studied airway responsiveness to acetylcholine (ACh) and Ascaris suum antigen (AA) before and after O3 in dogs both sensitive and insensitive to AA. Airway responsiveness was assessed by determining the provocative concentration of ACh and AA aerosols that increased respiratory resistance (Rrs) to twice the base-line value. O3 (3 parts per million) increased airway responsiveness to ACh in dogs both sensitive and insensitive to AA, and it significantly decreased the ACh provocation concentration from 0.541 +/- 0.095 to 0.102 +/- 0.047 (SE) mg/ml (P less than 0.01; n = 10). AA aerosols, even at the highest concentration in combination with O3, did not increase Rrs in dogs insensitive to AA. However, O3 increased airway responsiveness to AA in AA-sensitive dogs and significantly decreased log AA provocation concentration from 2.34 +/- 0.22 to 0.50 +/- 0.17 (SE) log protein nitrogen units/ml (P less than 0.01; n = 7). O3-induced hyperresponsiveness to ACh returned to the base-line level within 2 wk, but hyperresponsiveness to AA continued for greater than 2 wk. The plasma histamine concentration after AA challenge was significantly higher after than before O3 (P less than 0.01). Intravenous infusion of OKY-046 (100 micrograms.kg-1.min-1), an inhibitor of thromboxane synthesis, inhibited the O3-induced increase in responsiveness to ACh, but it had no effects on the O3-induced increase in responsiveness to AA and the increase in the plasma histamine concentration. These results suggest that O3 increases susceptibility to the antigen in sensitized dogs via a different mechanism from that of O3-induced muscarinic hyperresponsiveness.

  2. 5-Lipoxygenase Activity Increases Susceptibility to Experimental Paracoccidioides brasiliensis Infection

    PubMed Central

    Tristão, Fabrine Sales Massafera; Rocha, Fernanda Agostini; Moreira, Ana Paula; Cunha, Fernando Queiroz; Rossi, Marcos Antonio

    2013-01-01

    Paracoccidioidomycosis (PCM) is a systemic mycosis caused by the thermodimorphic fungus Paracoccidioides brasiliensis. Leukotrienes and lipoxins are lipid mediators produced after 5-lipoxygenase (5-LO) activation that exhibit pro- and anti-inflammatory roles, respectively. Here, we have investigated the contribution of 5-LO enzymatic activity in PCM using an experimental model of P. brasiliensis infection. B6.129 wild-type (B6.129) and 5-LO-deficient (5-LO−/−) mice were intravenously inoculated with a virulent strain of P. brasiliensis (Pb18), and the survival rate of the infected mice was investigated on different days after yeast infection. 5-LO−/− mice exhibited an increased survival rate associated with a decreased number of CFU. The resistance of 5-LO−/− during PCM was associated with augmented nitric oxide (NO) production and the formation of compact granulomas. In addition, the absence of 5-LO was associated with a diminished number of CD4+ CD25+ regulatory T cells, higher levels of gamma interferon and interleukin-12, and increased T-bet (a T-box transcription factor that directs Th1 lineage commitment) mRNA levels in the lungs. Taken together, our results show for the first time that 5-LO enzymatic activity increases susceptibility to P. brasiliensis, suggesting that this pathway may be a potential target for therapeutic intervention during PCM. PMID:23381993

  3. Heterozygote loss of ACE2 is sufficient to increase the susceptibility to heart disease.

    PubMed

    Wang, Wang; Patel, Vaibhav B; Parajuli, Nirmal; Fan, Dong; Basu, Ratnadeep; Wang, Zuocheng; Ramprasath, Tharmarajan; Kassiri, Zamaneh; Penninger, Josef M; Oudit, Gavin Y

    2014-08-01

    Angiotensin-converting enzyme 2 (ACE2) metabolizes Ang II into Ang 1-7 thereby negatively regulating the renin-angiotensin system. However, heart disease in humans and in animal models is associated with only a partial loss of ACE2. ACE2 is an X-linked gene; and as such, we tested the clinical relevance of a partial loss of ACE2 by using female ACE2(+/+) (wildtype) and ACE2(+/-) (heterozygote) mice. Pressure overload in ACE2(+/-) mice resulted in greater LV dilation and worsening systolic and diastolic dysfunction. These changes were associated with increased myocardial fibrosis, hypertrophy, and upregulation of pathological gene expression. In response to Ang II infusion, there was increased NADPH oxidase activity and myocardial fibrosis resulting in the worsening of Ang II-induced diastolic dysfunction with a preserved systolic function. Ang II-mediated cellular effects in cultured adult ACE2(+/-) cardiomyocytes and cardiofibroblasts were exacerbated. Ang II-mediated pathological signaling worsened in ACE2(+/-) hearts characterized by an increase in the phosphorylation of ERK1/2 and JNK1/2 and STAT-3 pathways. The ACE2(+/-) mice showed an exacerbated pressor response with increased vascular fibrosis and stiffness. Vascular superoxide and nitrotyrosine levels were increased in ACE2(+/-) vessels consistent with increased vascular oxidative stress. These changes occurred with increased renal fibrosis and superoxide production. Partial heterozygote loss of ACE2 is sufficient to increase the susceptibility to heart disease secondary to pressure overload and Ang II infusion. Heart disease in humans with idiopathic dilated cardiomyopathy is associated with a partial loss of ACE2. Heterozygote female ACE2 mutant mice showed enhanced susceptibility to pressure overload-induced heart disease. Heterozygote female ACE2 mutant mice showed enhanced susceptibility to Ang II-induced heart and vascular diseases. Partial loss of ACE2 is sufficient to enhance the susceptibility to

  4. Wolbachia increases susceptibility to Plasmodium infection in a natural system

    PubMed Central

    Zélé, F.; Nicot, A.; Berthomieu, A.; Weill, M.; Duron, O.; Rivero, A.

    2014-01-01

    Current views about the impact of Wolbachia on Plasmodium infections are almost entirely based on data regarding artificially transfected mosquitoes. This work has shown that Wolbachia reduces the intensity of Plasmodium infections in mosquitoes, raising the exciting possibility of using Wolbachia to control or limit the spread of malaria. Whether natural Wolbachia infections have the same parasite-inhibiting properties is not yet clear. Wolbachia–mosquito combinations with a long evolutionary history are, however, key for understanding what may happen with Wolbachia-transfected mosquitoes after several generations of coevolution. We investigate this issue using an entirely natural mosquito–Wolbachia–Plasmodium combination. In contrast to most previous studies, which have been centred on the quantification of the midgut stages of Plasmodium, we obtain a measurement of parasitaemia that relates directly to transmission by following infections to the salivary gland stages. We show that Wolbachia increases the susceptibility of Culex pipiens mosquitoes to Plasmodium relictum, significantly increasing the prevalence of salivary gland stage infections. This effect is independent of the density of Wolbachia in the mosquito. These results suggest that naturally Wolbachia-infected mosquitoes may, in fact, be better vectors of malaria than Wolbachia-free ones. PMID:24500167

  5. Wolbachia increases susceptibility to Plasmodium infection in a natural system.

    PubMed

    Zélé, F; Nicot, A; Berthomieu, A; Weill, M; Duron, O; Rivero, A

    2014-03-22

    Current views about the impact of Wolbachia on Plasmodium infections are almost entirely based on data regarding artificially transfected mosquitoes. This work has shown that Wolbachia reduces the intensity of Plasmodium infections in mosquitoes, raising the exciting possibility of using Wolbachia to control or limit the spread of malaria. Whether natural Wolbachia infections have the same parasite-inhibiting properties is not yet clear. Wolbachia-mosquito combinations with a long evolutionary history are, however, key for understanding what may happen with Wolbachia-transfected mosquitoes after several generations of coevolution. We investigate this issue using an entirely natural mosquito-Wolbachia-Plasmodium combination. In contrast to most previous studies, which have been centred on the quantification of the midgut stages of Plasmodium, we obtain a measurement of parasitaemia that relates directly to transmission by following infections to the salivary gland stages. We show that Wolbachia increases the susceptibility of Culex pipiens mosquitoes to Plasmodium relictum, significantly increasing the prevalence of salivary gland stage infections. This effect is independent of the density of Wolbachia in the mosquito. These results suggest that naturally Wolbachia-infected mosquitoes may, in fact, be better vectors of malaria than Wolbachia-free ones.

  6. ON pathway mutations increase susceptibility to form-deprivation myopia

    PubMed Central

    Chakraborty, Ranjay; Park, Han na; Hanif, Adam M.; Sidhu, Curran; Iuvone, P. Michael; Pardue, Machelle T.

    2015-01-01

    The ON pathway mutation in nob mice is associated with altered refractive development, and an increased susceptibility to form-deprivation (FD) myopia. In this study, we used mGluR6−/− mice, another ON pathway mutant, to determine whether the nob phenotype was due to the Nyx mutation or abnormal ON pathway transmission. Refractive development under a normal visual environment for mGluR6−/− and age-matched wild-type (WT) mice was measured every 2 weeks from 4 to 16 weeks of age. The response to monocular FD from 4 weeks of age was measured weekly in a separate cohort of mice. Refraction and ocular biometry were obtained using a photorefractor and optical coherence tomography. Retinas were harvested at 16 weeks, and analyzed for dopamine (DA) and DOPAC using high-performance liquid chromatography. Under normal conditions, mGluR6−/− mice were significantly more myopic than their WT controls (refraction at 12 weeks; WT: 9.40 ± 0.16 D, mGluR6−/−: 6.91 ± 0.38 D). Similar to nob mice, two weeks of FD resulted in a significant myopic shift of −5.57 ± 0.72 D in mGluR6−/− mice compared to −1.66 ± 0.19 D in WT animals. No significant axial length changes were observed with either normal or FD visual conditions. At 16 weeks, mGluR6−/− retinas showed significantly lower DOPAC levels (111.2 ± 33.0 pg/mg) compared to their WT counterparts (197.5 ± 11.2 pg/mg). Retinal DA levels were similar between the different genotypes. Our results indicate that reduced retinal DA metabolism/turnover may be associated with increased susceptibility to myopia in mice with ON pathway defect mutations. PMID:26072023

  7. Asthma is associated with increased susceptibility to infection.

    PubMed

    Patella, V; Bocchino, M; Steinhilber, G

    2015-08-01

    Asthma is a chronic inflammatory disorder of the airways characterized by airway hyperresponsiveness and airflow limitation. Despite respiratory symptoms may be episodic, progressive changes occur in the structure of the airway, leading to its irreversible remodeling. Changes include mucus hypersecretion, injury to epithelial cells, smooth muscle hypertrophy, sub-basement membrane fibrosis and angiogenesis. The risk factors for developing asthma are a combination of genetic predisposition along with environmental exposure to inhaled substances and particles that may provoke allergic reactions or irritate the airways, such as in- and out-door allergens, tobacco smoke, chemical irritants in the workplace and air pollution. Asthma is a clinically heterogeneous entity due to the complexity of its pathogenetic substrate. Recent evidence suggests asthma to be associated with a sort of immunodeficiency accounting for an increased susceptibility to infection in asthmatic patients. The role of infections as triggers and promoters of disease progression is well established. Conversely, the impact of asthma as a predisposing condition to infection has not clearly been addressed. Such a topic will be the focus of the present review.

  8. INCREASED SUSCEPTIBILITY TO INFLUENZA INFECTION AFTER DIESEL EXHAUST EXPOSURE.

    EPA Science Inventory

    Inhaled environmental pollutants have a possible role in modulating the susceptibility of humans to respiratory infections. Diesel exhaust (DE) is a major component of urban air pollution and their effects on pulmonary infections is of great concern. Influenza infections cause ...

  9. INCREASED SUSCEPTIBILITY TO INFLUENZA INFECTION AFTER DIESEL EXHAUST EXPOSURE

    EPA Science Inventory

    Inhaled environmental pollutants have a possible role in modulating the susceptibility of humans to respiratory infections. Diesel exhaust (DE) is a major component of urban air pollution and their effects on pulmonary infections is of great concern. Influenza infections cause ...

  10. INCREASED SUSCEPTIBILITY TO INFLUENZA INFECTION AFTER DIESEL EXHAUST EXPOSURE.

    EPA Science Inventory

    Inhaled environmental pollutants have a possible role in modulating the susceptibility of humans to respiratory infections. Diesel exhaust (DE) is a major component of urban air pollution and their effects on pulmonary infections is of great concern. Influenza infections cause ...

  11. INCREASED SUSCEPTIBILITY TO INFLUENZA INFECTION AFTER DIESEL EXHAUST EXPOSURE

    EPA Science Inventory

    Inhaled environmental pollutants have a possible role in modulating the susceptibility of humans to respiratory infections. Diesel exhaust (DE) is a major component of urban air pollution and their effects on pulmonary infections is of great concern. Influenza infections cause ...

  12. Susceptibility to inhaled flame-generated ultrafine soot in neonatal and adult rat lungs.

    PubMed

    Chan, Jackie K W; Fanucchi, Michelle V; Anderson, Donald S; Abid, Aamir D; Wallis, Christopher D; Dickinson, Dale A; Kumfer, Benjamin M; Kennedy, Ian M; Wexler, Anthony S; Van Winkle, Laura S

    2011-12-01

    Over a quarter of the U.S. population is exposed to harmful levels of airborne particulate matter (PM) pollution, which has been linked to development and exacerbation of respiratory diseases leading to morbidity and mortality, especially in susceptible populations. Young children are especially susceptible to PM and can experience altered anatomic, physiologic, and biological responses. Current studies of ambient PM are confounded by the complex mixture of soot, metals, allergens, and organics present in the complex mixture as well as seasonal and temporal variance. We have developed a laboratory-based PM devoid of metals and allergens that can be replicated to study health effects of specific PM components in animal models. We exposed 7-day-old postnatal and adult rats to a single 6-h exposure of fuel-rich ultrafine premixed flame particles (PFPs) or filtered air. These particles are high in polycyclic aromatic hydrocarbons content. Pulmonary cytotoxicity, gene, and protein expression were evaluated at 2 and 24 h postexposure. Neonates were more susceptible to PFP, exhibiting increased lactate dehydrogenase activity in bronchoalveolar lavage fluid and ethidium homodimer-1 cellular staining in the lung in situ as an index of cytotoxicity. Basal gene expression between neonates and adults differed for a significant number of antioxidant, oxidative stress, and proliferation genes and was further altered by PFP exposure. PFP diminishes proliferation marker PCNA gene and protein expression in neonates but not adults. We conclude that neonates have an impaired ability to respond to environmental exposures that increases lung cytotoxicity and results in enhanced susceptibility to PFP, which may lead to abnormal airway growth.

  13. Susceptibility to Inhaled Flame-Generated Ultrafine Soot in Neonatal and Adult Rat Lungs

    PubMed Central

    Chan, Jackie K. W.; Fanucchi, Michelle V.; Anderson, Donald S.; Abid, Aamir D.; Wallis, Christopher D.; Dickinson, Dale A.; Kumfer, Benjamin M.; Kennedy, Ian M.; Wexler, Anthony S.; Van Winkle, Laura S.

    2011-01-01

    Over a quarter of the U.S. population is exposed to harmful levels of airborne particulate matter (PM) pollution, which has been linked to development and exacerbation of respiratory diseases leading to morbidity and mortality, especially in susceptible populations. Young children are especially susceptible to PM and can experience altered anatomic, physiologic, and biological responses. Current studies of ambient PM are confounded by the complex mixture of soot, metals, allergens, and organics present in the complex mixture as well as seasonal and temporal variance. We have developed a laboratory-based PM devoid of metals and allergens that can be replicated to study health effects of specific PM components in animal models. We exposed 7-day-old postnatal and adult rats to a single 6-h exposure of fuel-rich ultrafine premixed flame particles (PFPs) or filtered air. These particles are high in polycyclic aromatic hydrocarbons content. Pulmonary cytotoxicity, gene, and protein expression were evaluated at 2 and 24 h postexposure. Neonates were more susceptible to PFP, exhibiting increased lactate dehydrogenase activity in bronchoalveolar lavage fluid and ethidium homodimer-1 cellular staining in the lung in situ as an index of cytotoxicity. Basal gene expression between neonates and adults differed for a significant number of antioxidant, oxidative stress, and proliferation genes and was further altered by PFP exposure. PFP diminishes proliferation marker PCNA gene and protein expression in neonates but not adults. We conclude that neonates have an impaired ability to respond to environmental exposures that increases lung cytotoxicity and results in enhanced susceptibility to PFP, which may lead to abnormal airway growth. PMID:21914721

  14. Increased apoptosis susceptibility in mesangial cells from spontaneously hypertensive rats.

    PubMed

    Rodríguez-López, A M; Flores, O; Martínez-Salgado, C; Eleno, N; López-Novoa, J M; Arévalo, M

    2000-01-01

    We have examined the susceptibility to apoptosis in mesangial cells from spontaneously hypertensive rats (SHR) or from normotensive rats (WKY) and the possible involvement of nitric oxide in this process. Mesangial cells monolayers from either SHR or normal rats were incubated for 12 h in medium with or without fetal calf serum (FCS) and with or without thapsigargin (Tg, 10(-6) M). A series of cultures from rats of both groups was treated with N(G)-nitro-l-arginine methyl ester (l-NAME, 10(-4) M). We assessed apoptosis by propidium iodide staining, by TUNEL nitrite production (Griess reaction), by inducible nitric oxide synthase (iNOS) and Bcl-2 and Bax by Western blot. Incubated with a FCS-free medium, cells from SHR showed a significantly higher apoptotic rate (10.7 +/- 2.0) than with 10% FCS (10% FCS, 4.7 +/- 0.3), while WKY cells did not show this increment (10% FCS, 4.7 +/- 0.3; 0% FCS, 5.9 +/- 0. 3). Apoptosis in cells from WKY increased when incubated with thapsigargin in FCS-free medium (0% FCS+ Tg, 17.7 +/- 2.9%) and increased even more in SHR cells (0% FCS+ Tg, 19.7 +/- 2.9%). Treatment with l-NAME decreased thapsigargin-induced apoptosis in both SHR (8.2 +/- 2.4%) and WKY cells (9.3 +/- 2.4%). An increase in nitrite production and iNOS expression was detected in groups in which the apoptosis rate was elevated. A high rate of apoptosis was also associated with a decrease in the Bcl-2/Bax ratio. Our results indicate that in SHR cells, short-term serum deprivation and the increase in intracellular free calcium concentration with thapsigargin are able to enhance the apoptosis rate in primary cultures and that the expression of iNOS, and hence NO production, is involved in this effect. Copyright 2000 Academic Press.

  15. Susceptibility of adult pigeons and hybrid falcons to experimental aspergillosis.

    PubMed

    Van Waeyenberghe, L; Fischer, D; Coenye, T; Ducatelle, R; Haesebrouck, F; Pasmans, F; Lierz, M; Martel, A

    2012-12-01

    Aspergillosis caused by Aspergillus fumigatus seems to be more prevalent in some avian species than in others. We compared the development of aspergillosis in 8-month-old Gyr-Saker hybrid falcons and 8-month-old pigeons after a single intratracheal inoculation of different dosages of A. fumigatus conidia (10(7), 10(5) and 10(3)). Clinical signs, including vomiting, discoloration of the urates, loss of appetite and dyspnoea, were observed in four out of five falcons and in four out of five pigeons inoculated with 10(7) A. fumigatus conidia. Necropsy revealed the presence of granulomas in the air sacs and/or lungs in four out of five falcons and in four out of five pigeons in the high dosage group. A. fumigatus was isolated from these granulomas in three falcons and in three pigeons. The presence of fungal hyphae was detected with Periodic acid Shiff reagent staining in three out of five falcons and in three out of five pigeons in the high dosage group. Avian respiratory macrophages were clearly present in and around the fungal granulomas. In the other dosage groups, no granulomas, positive A. fumigatus cultures or fungal hyphae were present, except for one falcon in the middle dosage group in which a sterile granuloma without fungal hyphae was noticed. In conclusion, the study shows that adult falcons and pigeons are susceptible to aspergillosis after inoculation of a single dose of conidia intratracheally.

  16. Investigation of infectivity of neonates and adults from different rat strains to Toxoplasma gondii Prugniaud shows both variation which correlates with iNOS and Arginase-1 activity and increased susceptibility of neonates to infection.

    PubMed

    Gao, Jiang-Mei; Yi, Si-Qi; Wu, Ming-Shui; Geng, Guo-Qing; Shen, Ji-Long; Lu, Fang-Li; Hide, Geoff; Lai, De-Hua; Lun, Zhao-Rong

    2015-02-01

    Mouse models differ considerably from humans with regard to clinical symptoms of toxoplasmosis caused by Toxoplasma gondii and, by comparison, the rat model is more representative of this disease in humans. In the present study, we found that different strains of adult and newborn rats (Lewis, Wistar, Sprague Dawley, Brown Norway and Fischer 344) exhibited remarkable variation in the number of brain cysts following inoculation with the T.gondii Prugniaud strain. In adult rats, large numbers of cysts (1231 ± 165.6) were observed in Fischer 344, but none in the other four. This situation was different in newborn rats aged from 5 to 20 days old. All Fischer 344 and Brown Norway newborns were cyst-positive while cyst-positive infection in Sprague Dawley neonates ranged from 54.5% to 60% depending on their age at infection. In Wistar and Lewis rat neonates, however, cyst-positivity rates of 0-42.9% and 0-25% were found respectively. To investigate whether rat strain differences in infectivity could be related to inherent strain and genetic differences in the host immune response, we correlated our data with previously reported strain differences in iNOS/Arginase ratio in adult rats and found them to be linked. These results show that interactions between host genetic background and age of rat influence T.gondii infection. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Ceftobiprole and ampicillin increase daptomycin susceptibility of daptomycin-susceptible and -resistant VRE.

    PubMed

    Werth, Brian J; Barber, Katie E; Tran, Kieu-Nhi T; Nonejuie, P; Sakoulas, G; Pogliano, J; Rybak, Michael J

    2015-02-01

    The synergistic combination of daptomycin plus ampicillin has proven to be effective against VRE including daptomycin-non-susceptible strains. Ceftobiprole is a cephalosporin with broad binding affinity for enterococcal PBP subtypes including PBP5. Given the synergy between β-lactams and daptomycin against VRE, it was of interest to determine whether ceftobiprole offered any synergistic advantage with daptomycin compared with ampicillin. MICs were determined by broth microdilution in the presence and absence of ampicillin or ceftobiprole for 20 ampicillin-resistant VRE. Six strains, including two isogenic pairs of vancomycin-resistant Enterococcus faecium and two vancomycin-resistant Enterococcus faecalis, were evaluated for synergy using time-kill methods. Synergy was defined as a ≥2 log10 cfu/mL reduction of the combination over the most active single agent. Binding of daptomycin-bodipy in the presence and absence of ceftobiprole was quantified. Daptomycin MICs ranged from 2 to 256 mg/L. The addition of ceftobiprole and ampicillin reduced daptomycin MICs by a median of 3 and 4 log2 dilutions, respectively. In time-kill studies, daptomycin plus either ceftobiprole or ampicillin was synergistic against four of six strains, but not the same strains. Both combinations were synergistic against the vancomycin-resistant E. faecalis strains. Ceftobiprole exposure increased daptomycin-bodipy binding by 2.8 times (P<0.0001). Ceftobiprole appears to offer a similar degree of synergistic activity to ampicillin when combined with daptomycin against VRE. Further research should explore the genetic and phenotypic qualities of strains that respond preferentially to ceftobiprole as opposed to ampicillin. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Toll-like Receptor 1 Polymorphisms Increase Susceptibility to Candidemia

    PubMed Central

    Plantinga, Theo S.; Johnson, Melissa D.; Scott, William K.; van de Vosse, Esther; Velez Edwards, Digna R.; Smith, P. Brian; Alexander, Barbara D.; Yang, John C.; Kremer, Dennis; Laird, Gregory M.; Oosting, Marije; Joosten, Leo A. B.; van der Meer, Jos W. M.; van Dissel, Jaap T.; Walsh, Thomas J.; Perfect, John R.; Kullberg, Bart Jan

    2012-01-01

    (See the editorial commentary by Bagni and Whitby, on pages 873–4.) Background. Candidemia is a severe invasive fungal infection with high mortality. Recognition of Candida species is mediated through pattern recognition receptors such as Toll-like receptors (TLRs). This study assessed whether genetic variation in TLR signaling influences susceptibility to candidemia. Methods. Thirteen mostly nonsynonymous single nucleotide polymorphisms (SNPs) in genes encoding TLRs and signaling adaptors MyD88 and Mal/TIRAP were genotyped in 338 patients (237 white, 93 African American, 8 other race) with candidemia and 351 noninfected controls (263 white, 88 African American). The SNPs significant in univariate analysis were further analyzed with multivariable logistic regression to determine association with clinical outcomes. Functional consequences of these polymorphisms were assessed via in vitro stimulation assays. Results. Analyses of TLR SNPs revealed that 3 TLR1 SNPs (R80T, S248N, I602S) were significantly associated with candidemia susceptibility in whites. This association was not found in African Americans, likely due to lower power in this smaller study population. Furthermore, these TLR1 polymorphisms displayed impaired cytokine release by primary monocytes. No associations with susceptibility to candidemia were observed for SNPs in TLR2, TLR4, TLR6, TLR9, MyD88, or TIRAP. Conclusions. Nonsynonymous SNPs in TLR1 are associated with impaired TLR1 function, decreased cytokine responses, and predisposition to candidemia in whites. PMID:22301633

  19. Immature mice are more susceptible than adult mice to acetaminophen-induced acute liver injury

    PubMed Central

    Lu, Yan; Zhang, Cheng; Chen, Yuan-Hua; Wang, Hua; Zhang, Zhi-Hui; Chen, Xi; Xu, De-Xiang

    2017-01-01

    Acetaminophen (APAP) overdose induces acute liver injury. The aim of the present study was to analyze the difference of susceptibility between immature and adult mice to APAP-induced acute liver injury. Weanling immature and adult mice were injected with APAP (300 mg/kg). As expected, immature mice were more susceptible than adult mice to APAP-induced acute liver injury. APAP-evoked hepatic c-Jun N-terminal kinase phosphorylation was stronger in immature mice than in adult mice. Hepatic receptor-interacting protein (RIP)1 was obviously activated at APAP-exposed immature and adult mice. Interestingly, hepatic RIP3 activation was more obvious in APAP-treated immature mice than adult mice. Although there was no difference on hepatic GSH metabolic enzymes between immature and adult mice, immature mice were more susceptible than adult mice to APAP-induced hepatic GSH depletion. Of interest, immature mice expressed a much higher level of hepatic Cyp2e1 and Cyp3a11 mRNAs than adult mice. Correspondingly, immature mice expressed a higher level of hepatic CYP2E1, the key drug metabolic enzyme that metabolized APAP into the reactive metabolite NAPQI. These results suggest that a higher level of hepatic drug metabolic enzymes in immature mice than adult mice might contribute to the difference of susceptibility to APAP-induced acute liver injury. PMID:28205631

  20. Microbicide excipients can greatly increase susceptibility to genital herpes transmission in the mouse

    PubMed Central

    2010-01-01

    Background Several active ingredients proposed as vaginal microbicides have been shown paradoxically to increase susceptibility to infection in mouse genital herpes (HSV-2) vaginal susceptibility models and in clinical trials. In addition, "inactive ingredients" (or excipients) used in topical products to formulate and deliver the active ingredient might also cause epithelial toxicities that increase viral susceptibility. However, excipients have not previously been tested in susceptibility models. Methods Excipients commonly used in topical products were formulated in a non-toxic vehicle (the "HEC universal placebo"), or other formulations as specified. Twelve hours after exposure to the excipient or a control treatment, mice were challenged with a vaginal dose of HSV-2, and three days later were assessed for infection by vaginal lavage culture to assess susceptibility. Results The following excipients markedly increased susceptibility to HSV-2 after a single exposure: 5% glycerol monolaurate (GML) formulated in K-Y® Warming Jelly, 5% GML as a colloidal suspension in phosphate buffered saline, K-Y Warming Jelly alone, and both of its humectant/solvent ingredients (neat propylene glycol and neat PEG-8). For excipients formulated in the HEC vehicle, 30% glycerin significantly increased susceptibility, and a trend toward increased HSV-2 susceptibility was observed after 10% glycerin, and 0.1% disodium EDTA, but not after 0.0186% disodium EDTA. The following excipients did not increase susceptibility: 10% propylene glycol, 0.18%, methylparaben plus 0.02% propylparaben, and 1% benzyl alcohol. Conclusions As reported with other surfactants, the surfactant/emulsifier GML markedly increased susceptibility to HSV-2. Glycerin at 30% significantly increased susceptibility, and, undiluted propylene glycol and PEG-8 greatly increased susceptibility. PMID:21087496

  1. Does MAOA increase susceptibility to prenatal stress in young children?

    PubMed

    Massey, Suena H; Hatcher, Amalia E; Clark, Caron A C; Burns, James L; Pine, Daniel S; Skol, Andrew D; Mroczek, Daniel K; Espy, Kimberly A; Goldman, David; Cook, Edwin; Wakschlag, Lauren S

    2017-05-01

    We previously demonstrated a gene-by-prenatal-environment interaction whereby the monoamine oxidase A gene (MAOA) modified the impact of prenatal tobacco exposure (PTE) on adolescent disruptive behavior (DB), with the MAOA risk genotype varying by sex. We extend this work by examining whether this mechanism is evident with another common adversity, prenatal stress exposure (PSE), and whether sex differences are present earlier in development in closer proximity to exposure. Participants were 281 mothers and their 285 children derived from a prenatal cohort with in-depth prospective measures of PSE and PTE. We assessed DB at age 5 via dimensional developmentally-sensitive measurement. Analyses were stratified by sex based on prior evidence for sex differences. Concurrent stress exposure predicted DB in children (β=0.310, p=0.001), while main effects of prenatal exposures were seen only in boys. We found a three-way interaction of MAOA×PSE×sex on DB (β=0.813, p=0.022). Boys with MAOA-H had more DB as a function of PSE, controlling for PTE (β=0.774, p=0.015), and as a function of PTE, controlling for PSE (β=0.362, p=0.037). Boys with MAOA-L did not show this susceptibility. MAOA did not interact with PSE (β=-0.133, p=0.561) nor PTE (β=-0.144; p=0.505) in predicting DB in girls. Examination of gene-environment correlation (rGE) showed a correlation between paternal MAOA-L and daughters' concurrent stress exposure (r=-0.240, p=0.013). Findings underscore complex mechanisms linking genetic susceptibility and early adverse exposures. Replication in larger cohorts followed from the pregnancy through adolescence is suggested to elucidate mechanisms that appear to have varying developmental expression. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Waterpipe Tobacco Smoking and Susceptibility to Cigarette Smoking Among Young Adults in the United States, 2012–2013

    PubMed Central

    Haider, M. Rifat; Barnett, Tracey E.; Guo, Yi; Getz, Kayla R.; Thrasher, James F.; Maziak, Wasim

    2016-01-01

    Introduction Waterpipe tobacco smoking, also known as hookah and shisha, has surged in popularity among young people in the United States. Waterpipe is also increasingly becoming the first tobacco product that young people try. Given the limited access to and limited portability of waterpipes, waterpipe smokers who become more nicotine dependent over time may be more likely to turn to cigarettes. This study examined the relationship between waterpipe tobacco smoking and susceptibility to cigarette smoking among young adults in the United States. Methods Using data from the 2012–2013 National Adult Tobacco Survey, a nationally representative sample of US adults, we reported rates of current waterpipe smoking and susceptibility to cigarette smoking by demographic characteristics and by use of other tobacco products among survey participants aged 18 to 24 years. Multivariable logistic regression was used to examine the relationship between current waterpipe smoking and susceptibility to cigarette smoking, defined as the lack of a firm intention not to smoke soon or within the next year. Results Of 2,528 young adults who had never established cigarette smoking, 15.7% (n = 398) reported being waterpipe smokers (every day or some days [n = 97; 3.8%] or rarely [n = 301; 11.9%]); 44.2% (176/398) of waterpipe smokers reported being susceptible to cigarette smoking. Those who smoked waterpipe rarely were 2.3 times as susceptible to cigarette smoking as those who were not current waterpipe smokers (OR = 2.3; 95% CI, 1.6–3.4). Conclusion Current waterpipe smoking is associated with susceptibility to cigarette smoking among young adults in the United States. Longitudinal studies are needed to demonstrate causality between waterpipe smoking and initiation of cigarette smoking. PMID:26890407

  3. Waterpipe Tobacco Smoking and Susceptibility to Cigarette Smoking Among Young Adults in the United States, 2012-2013.

    PubMed

    Salloum, Ramzi G; Haider, M Rifat; Barnett, Tracey E; Guo, Yi; Getz, Kayla R; Thrasher, James F; Maziak, Wasim

    2016-02-18

    Waterpipe tobacco smoking, also known as hookah and shisha, has surged in popularity among young people in the United States. Waterpipe is also increasingly becoming the first tobacco product that young people try. Given the limited access to and limited portability of waterpipes, waterpipe smokers who become more nicotine dependent over time may be more likely to turn to cigarettes. This study examined the relationship between waterpipe tobacco smoking and susceptibility to cigarette smoking among young adults in the United States. Using data from the 2012-2013 National Adult Tobacco Survey, a nationally representative sample of US adults, we reported rates of current waterpipe smoking and susceptibility to cigarette smoking by demographic characteristics and by use of other tobacco products among survey participants aged 18 to 24 years. Multivariable logistic regression was used to examine the relationship between current waterpipe smoking and susceptibility to cigarette smoking, defined as the lack of a firm intention not to smoke soon or within the next year. Of 2,528 young adults who had never established cigarette smoking, 15.7% (n = 398) reported being waterpipe smokers (every day or some days [n = 97; 3.8%] or rarely [n = 301; 11.9%]); 44.2% (176/398) of waterpipe smokers reported being susceptible to cigarette smoking. Those who smoked waterpipe rarely were 2.3 times as susceptible to cigarette smoking as those who were not current waterpipe smokers (OR = 2.3; 95% CI, 1.6-3.4). Current waterpipe smoking is associated with susceptibility to cigarette smoking among young adults in the United States. Longitudinal studies are needed to demonstrate causality between waterpipe smoking and initiation of cigarette smoking.

  4. An acute social defeat stressor in early puberty increases susceptibility to social defeat in adulthood.

    PubMed

    Rosenhauer, Anna M; McCann, Katharine E; Norvelle, Alisa; Huhman, Kim L

    2017-04-05

    Syrian hamsters readily display territorial aggression; if they lose even a single agonistic encounter, however, hamsters show striking reductions in aggressive behavior and increases in submissive behavior, a distinct behavioral change that we have previously termed conditioned defeat. This acute social defeat stressor is primarily psychological and is effective in both males and females. Therefore, we maintain that this procedure presents an ideal model for studying behavioral and physiological responses to social stress. Here, we demonstrate that social avoidance following social defeat is a particularly useful dependent measure because of its sensitivity and stability between sexes and across the estrous cycle. In addition, we demonstrate that peripubertal hamsters exposed to a single, 15min social defeat exhibit significantly more social avoidance 24h later when compared with no-defeat controls. Later, defeated and non-defeated hamsters displayed similar agonistic behavior in adulthood indicating that the peripubertal defeat did not alter adult territorial aggression. After experiencing an additional social defeat in adulthood, however, the hamsters that experienced the pubertal defeat responded to the adult defeat with increased social avoidance when compared with hamsters that were defeated only in adulthood and with no-defeat controls. These data are the first to show that a single social defeat in puberty increases susceptibility to later social defeat in both males and females.

  5. Gender difference in acquired seizure susceptibility in adult rats after early complex febrile seizures.

    PubMed

    Dai, Yun-Jian; Xu, Zheng-Hao; Feng, Bo; Xu, Ceng-Lin; Zhao, Hua-Wei; Wu, Deng-Chang; Hu, Wei-Wei; Chen, Zhong

    2014-12-01

    Gender differences are involved in many neurological disorders including epilepsy. However, little is known about the effect of gender difference on the risk of epilepsy in adults with a specific early pathological state such as complex febrile seizures (FSs) in infancy. Here we used a well-established complex FS model in rats and showed that: (1) the susceptibility to seizures induced by hyperthermia, pentylenetetrazol (PTZ), and maximal electroshock (MES) was similar in male and female rat pups, while males were more susceptible to PTZ- and MES-induced seizures than age-matched females in normal adult rats; (2) adult rats with complex FSs in infancy acquired higher seizure susceptibility than normal rats; importantly, female FS rats were more susceptible to PTZ and MES than male FS rats; and (3) the protein expression of interleukin-1β, an inflammatory factor associated with seizure susceptibility, was higher in adult FS females than in males, which may reflect a gender-difference phenomenon of seizure susceptibility. Our results provide direct evidence that the acquired seizure susceptibility after complex FSs is gender-dependent.

  6. Increased False-Memory Susceptibility After Mindfulness Meditation.

    PubMed

    Wilson, Brent M; Mickes, Laura; Stolarz-Fantino, Stephanie; Evrard, Matthew; Fantino, Edmund

    2015-10-01

    The effect of mindfulness meditation on false-memory susceptibility was examined in three experiments. Because mindfulness meditation encourages judgment-free thoughts and feelings, we predicted that participants in the mindfulness condition would be especially likely to form false memories. In two experiments, participants were randomly assigned to either a mindfulness induction, in which they were instructed to focus attention on their breathing, or a mind-wandering induction, in which they were instructed to think about whatever came to mind. The overall number of words from the Deese-Roediger-McDermott paradigm that were correctly recalled did not differ between conditions. However, participants in the mindfulness condition were significantly more likely to report critical nonstudied items than participants in the control condition. In a third experiment, which tested recognition and used a reality-monitoring paradigm, participants had reduced reality-monitoring accuracy after completing the mindfulness induction. These results demonstrate a potential unintended consequence of mindfulness meditation in which memories become less reliable.

  7. Aging increases the susceptibility to motor memory interference and reduces off-line gains in motor skill learning.

    PubMed

    Roig, Marc; Ritterband-Rosenbaum, Anina; Lundbye-Jensen, Jesper; Nielsen, Jens Bo

    2014-08-01

    Declines in the ability to learn motor skills in older adults are commonly attributed to deficits in the encoding of sensorimotor information during motor practice. We investigated whether aging also impairs motor memory consolidation by assessing the susceptibility to memory interference and off-line gains in motor skill learning after practice in children, young, and older adults. Subjects performed a ballistic task (A) followed by an accuracy-tracking task (B) designed to disrupt the consolidation of A. Retention tests of A were performed immediately and 24 hours after B. Older adults showed greater susceptibility to memory interference and no off-line gains in motor skill learning. Performing B produced memory interference and reduced off-line gains only in the older group. However, older adults also showed deficits in memory consolidation independent of the interfering effects of B. Age-related declines in motor skill learning are not produced exclusively by deficits in the encoding of sensorimotor information during practice. Aging also increases the susceptibility to memory interference and reduces off-line gains in motor skill learning after practice.

  8. Exposure to celebrity-endorsed small cigar promotions and susceptibility to use among young adult cigarette smokers.

    PubMed

    Sterling, Kymberle L; Moore, Roland S; Pitts, Nicole; Duong, Melissa; Ford, Kentya H; Eriksen, Michael P

    2013-01-01

    Small cigar smoking among young adult cigarette smokers may be attributed to their exposure to its advertisements and promotions. We examined the association between exposure to a celebrity music artist's endorsement of a specific brand of small cigars and young adult cigarette smokers' susceptibility to smoking that brand. Venue-based sampling procedures were used to select and survey a random sample of 121 young adult cigarette smokers, aged 18-35. Fourteen percent reported exposure to the artist's endorsement of the small cigar and 45.4% reported an intention to smoke the product in the future. The odds of small cigar smoking susceptibility increased threefold for those who reported exposure to the endorsement compared to those not exposed (OR = 3.64, 95% CI 1.06 to 12.54). Past 30-day small cigar use (OR = 3.30, 95% CI 1.24 to 8.74) and past 30-day cigar use (OR = 5.08, 95% CI 1.23, 21.08) were also associated with susceptibility to smoke a small cigar. An association between young adult cigarette smokers' exposure to the music artist's small cigar endorsement and their susceptibility to smoke small cigars was found. This association underscores the importance of monitoring small cigar promotions geared toward young people and their impact on small cigar product smoking.

  9. Exposure to Celebrity-Endorsed Small Cigar Promotions and Susceptibility to Use among Young Adult Cigarette Smokers

    PubMed Central

    Sterling, Kymberle L.; Moore, Roland S.; Pitts, Nicole; Duong, Melissa; Ford, Kentya H.; Eriksen, Michael P.

    2013-01-01

    Small cigar smoking among young adult cigarette smokers may be attributed to their exposure to its advertisements and promotions. We examined the association between exposure to a celebrity music artist's endorsement of a specific brand of small cigars and young adult cigarette smokers' susceptibility to smoking that brand. Venue-based sampling procedures were used to select and survey a random sample of 121 young adult cigarette smokers, aged 18–35. Fourteen percent reported exposure to the artist's endorsement of the small cigar and 45.4% reported an intention to smoke the product in the future. The odds of small cigar smoking susceptibility increased threefold for those who reported exposure to the endorsement compared to those not exposed (OR = 3.64, 95% CI 1.06 to 12.54). Past 30-day small cigar use (OR = 3.30, 95% CI 1.24 to 8.74) and past 30-day cigar use (OR = 5.08, 95% CI 1.23, 21.08) were also associated with susceptibility to smoke a small cigar. An association between young adult cigarette smokers' exposure to the music artist's small cigar endorsement and their susceptibility to smoke small cigars was found. This association underscores the importance of monitoring small cigar promotions geared toward young people and their impact on small cigar product smoking. PMID:24371444

  10. Increased Myofilament Ca2+-Sensitivity and Arrhythmia Susceptibility

    PubMed Central

    Huke, Sabine; Knollmann, Bjorn C.

    2010-01-01

    Increased myofilament Ca2+ sensitivity, a common attribute of inherited and acquired cardiomyopathies, is often associated with cardiac arrhythmias. Accumulating evidence supports that increased myofilament Ca2+ sensitivity is an independent risk factor for arrhythmias, but the underlying molecular mechanism remains unclear. This review focuses on potential mechanisms how myofilament Ca2+ sensitivity may affect cardiac excitation and leads to the generation of arrhythmias. We discuss in detail the downstream effects of increased myofilament Ca2+ sensitivity, i.e. altered Ca2+ buffering/handling, impaired energy metabolism and increased mechanical stretch, and how they may contribute to the proarrhythmic effect. PMID:20097204

  11. Kv4.2 knockout mice demonstrate increased susceptibility to convulsant stimulation

    PubMed Central

    Barnwell, L. Forbes S.; Lugo, Joaquin N.; Lee, Wai Ling; Willis, Sarah E.; Gertz, Shira J.; Hrachovy, Richard A.; Anderson, Anne E.

    2010-01-01

    Purpose Kv4.2 subunits contribute to the pore-forming region of channels that express a transient, A-type K+ current (A-current) in hippocampal CA1 pyramidal cell dendrites. Here, the A-current plays an important role in signal processing and synaptic integration. Kv4.2 knockout mice show a near elimination of the A-current in area CA1 dendrites producing increased excitability in this region. In these studies, we evaluated young adult Kv4.2 knockout mice for spontaneous seizures and the response to convulsant stimulation in the whole animal in vivo and in hippocampal slices in vitro. Methods Electroencephalogram electrode-implanted Kv4.2 knockout and wildtype mice were observed for spontaneous behavioral and electrographic seizures. The latency to seizure and status epilepticus onset in Kv4.2 knockout and wildtype mice was assessed following intraperitoneal injection of kainate. Extracellular field potential recordings were performed in hippocampal slices from Kv4.2 knockout and wildtype mice following the bath application of bicuculline. Results No spontaneous behavioral or electrographic seizures were observed in Kv4.2 knockout mice. Following kainate, Kv4.2 knockout mice demonstrated a decreased seizure and status epilepticus latency as well as increased mortality compared to wildtype littermates. The background strain modified the seizure susceptibility phenotype in Kv4.2 knockout mice. In response to bicuculline, slices from Kv4.2 knockout mice exhibited an increase in epileptiform bursting in area CA1 as compared to wildtype littermates. Discussion These studies show that loss of Kv4.2 channels is associated with enhanced susceptibility to convulsant stimulation, supporting the concept that Kv4.2 deficiency may contribute to aberrant network excitability and regulate seizure threshold. PMID:19453702

  12. Heterozygous caveolin-3 mice show increased susceptibility to palmitate-induced insulin resistance.

    PubMed

    Talukder, M A Hassan; Preda, Marilena; Ryzhova, Larisa; Prudovsky, Igor; Pinz, Ilka M

    2016-03-01

    Insulin resistance and diabetes are comorbidities of obesity and affect one in 10 adults in the United States. Despite the high prevalence, the mechanisms of cardiac insulin resistance in obesity are still unclear. We test the hypothesis that the insulin receptor localizes to caveolae and is regulated through binding to caveolin-3 (CAV3). We further test whether haploinsufficiency forCAV3 increases the susceptibility to high-fat-induced insulin resistance. We used in vivo and in vitro studies to determine the effect of palmitate exposure on global insulin resistance, contractile performance of the heart in vivo, glucose uptake in the heart, and on cellular signaling downstream of theIR We show that haploinsufficiency forCAV3 increases susceptibility to palmitate-induced global insulin resistance and causes cardiomyopathy. On the basis of fluorescence energy transfer (FRET) experiments, we show thatCAV3 andIRdirectly interact in cardiomyocytes. Palmitate impairs insulin signaling by a decrease in insulin-stimulated phosphorylation of Akt that corresponds to an 87% decrease in insulin-stimulated glucose uptake inHL-1 cardiomyocytes. Despite loss of Akt phosphorylation and lower glucose uptake, palmitate increased insulin-independent serine phosphorylation ofIRS-1 by 35%. In addition, we found lipid induced downregulation ofCD36, the fatty acid transporter associated with caveolae. This may explain the problem the diabetic heart is facing with the simultaneous impairment of glucose uptake and lipid transport. Thus, these findings suggest that loss ofCAV3 interferes with downstream insulin signaling and lipid uptake, implicatingCAV3 as a regulator of theIRand regulator of lipid uptake in the heart. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  13. A Period of Increased Susceptibility to Cigarette Smoking among High School Students.

    ERIC Educational Resources Information Center

    Filice, Gregory A.; Hannan, Peter J.; Lando, Harry A.; Joseph, Ann M.

    2003-01-01

    Assessed susceptibility to cigarette smoking among high school students who never smoked. Students participated in voluntary extracurricular anti-tobacco activities throughout the school year. Pre- and post-intervention surveys indicated that among 9th grade nonsmokers, susceptibility increased over the year, while it decreased for 10th-12th grade…

  14. Susceptibility of adult mosquitoes to insecticides in aqueous sucrose baits.

    PubMed

    Allan, Sandra A

    2011-06-01

    Mosquitoes characteristically feed on plant-derived carbohydrates and honeydew just after emergence and intermittently during their lives. Development of toxic baits focusing on this carbohydrate-seeking behavior may potentially contribute to localized control. In the present study, ten insecticides were fed to female Culex quinquefasciatus, Anopheles quadrimaculatus, and Aedes taeniorhynchus in a 10% sucrose solution. Active ingredients representative of five classes of insecticides (pyrethroids, phenylpyroles, pyrroles, neonicotinoids, and macrocyclic lactones) were selected for comparison with commercial formulations used to facilitate incorporation of active ingredients into aqueous sucrose solutions. Sucrose as a phagostimulant significantly enhanced mortality to toxicants. In general, the most effective active ingredients were fipronil, deltamethrin and imidacloprid, followed by spinosad, thiamethoxam, bifenthrin, permethrin, and cyfluthrin. The least effective ingredients were chlorfenapyr and ivermectin. For some of the ingredients tested, Cx. quinquefasciatus was the least susceptible species. One-day-old male Cx. quinquefasciatus were more susceptible than females; however, no differences existed between one- and seven-day-old mosquitoes. There were no differences in susceptibility between unfed and gravid ten-day-old female Cx. quinquefasciatus to bifenthrin. In conclusion, several pesticides from different classes of compounds have potential for use in development of toxic baits for mosquitoes.

  15. Iron increases the susceptibility of multiple myeloma cells to bortezomib

    PubMed Central

    Campanella, Alessandro; Santambrogio, Paolo; Fontana, Francesca; Frenquelli, Michela; Cenci, Simone; Marcatti, Magda; Sitia, Roberto; Tonon, Giovanni; Camaschella, Clara

    2013-01-01

    Multiple myeloma is a malignant still incurable plasma cell disorder. Pharmacological treatment based on proteasome inhibition has improved patient outcome; however, bortezomib-resistance remains a major clinical problem. Inhibition of proteasome functionality affects cellular iron homeostasis and iron is a potent inducer of reactive oxygen species and cell death, unless safely stored in ferritin. We explored the potential role of iron in bortezomib-resistance. We analyzed iron proteins, oxidative status and cell viability in 7 multiple myeloma cell lines and in plasma cells from 5 patients. Cells were treated with increasing bortezomib concentrations with or without iron supplementation. We reduced ferritin levels by both shRNA technology and by drug-induced iron starvation. Multiple myeloma cell lines are characterized by distinct ferritin levels, which directly correlate with bortezomib resistance. We observed that iron supplementation upon bortezomib promotes protein oxidation and cell death, and that iron toxicity inversely correlates with basal ferritin levels. Bortezomib prevents ferritin upregulation in response to iron, thus limiting the ability to buffer reactive oxygen species. Consequently, reduction of basal ferritin levels increases both bortezomib sensitivity and iron toxicity. In patients’ cells, we confirmed that bortezomib prevents ferritin increase, that iron supplementation upon bortezomib increases cell death and that ferritin reduction overcomes bortezomib resistance. Bortezomib affects iron homeostasis, sensitizing cells to oxidative damage. Modulation of iron status is a strategy worth exploring to improve the efficacy of proteasome inhibition therapies. PMID:23242599

  16. Prenatal ethanol exposure increases osteoarthritis susceptibility in female rat offspring by programming a low-functioning IGF-1 signaling pathway

    NASA Astrophysics Data System (ADS)

    Ni, Qubo; Tan, Yang; Zhang, Xianrong; Luo, Hanwen; Deng, Yu; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-10-01

    Epidemiological evidence indicates that osteoarthritis (OA) and prenatal ethanol exposure (PEE) are both associated with low birth weight but possible causal interrelationships have not been investigated. To investigate the effects of PEE on the susceptibility to OA in adult rats that experienced intrauterine growth retardation (IUGR), and to explore potential intrauterine mechanisms, we established the rat model of IUGR by PEE and dexamethasone, and the female fetus and 24-week-old adult offspring subjected to strenuous running for 6 weeks were sacrificed. Knee joints were collected from fetuses and adult offspring for histochemistry, immunohistochemistry and qPCR assays. Histological analyses and the Mankin score revealed increased cartilage destruction and accelerated OA progression in adult offspring from the PEE group compared to the control group. Immunohistochemistry showed reduced expression of insulin-like growth factor-1 (IGF-1) signaling pathway components. Furthermore, fetuses in the PEE group experienced IUGR but exhibited a higher postnatal growth rate. The expression of many IGF-1 signaling components was downregulated, which coincided with reduced amounts of type II collagen in the epiphyseal cartilage of fetuses in the PEE group. These results suggest that PEE enhances the susceptibility to OA in female adult rat offspring by down-regulating IGF-1 signaling and retarding articular cartilage development.

  17. Prenatal ethanol exposure increases osteoarthritis susceptibility in female rat offspring by programming a low-functioning IGF-1 signaling pathway.

    PubMed

    Ni, Qubo; Tan, Yang; Zhang, Xianrong; Luo, Hanwen; Deng, Yu; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-10-05

    Epidemiological evidence indicates that osteoarthritis (OA) and prenatal ethanol exposure (PEE) are both associated with low birth weight but possible causal interrelationships have not been investigated. To investigate the effects of PEE on the susceptibility to OA in adult rats that experienced intrauterine growth retardation (IUGR), and to explore potential intrauterine mechanisms, we established the rat model of IUGR by PEE and dexamethasone, and the female fetus and 24-week-old adult offspring subjected to strenuous running for 6 weeks were sacrificed. Knee joints were collected from fetuses and adult offspring for histochemistry, immunohistochemistry and qPCR assays. Histological analyses and the Mankin score revealed increased cartilage destruction and accelerated OA progression in adult offspring from the PEE group compared to the control group. Immunohistochemistry showed reduced expression of insulin-like growth factor-1 (IGF-1) signaling pathway components. Furthermore, fetuses in the PEE group experienced IUGR but exhibited a higher postnatal growth rate. The expression of many IGF-1 signaling components was downregulated, which coincided with reduced amounts of type II collagen in the epiphyseal cartilage of fetuses in the PEE group. These results suggest that PEE enhances the susceptibility to OA in female adult rat offspring by down-regulating IGF-1 signaling and retarding articular cartilage development.

  18. Prenatal ethanol exposure increases osteoarthritis susceptibility in female rat offspring by programming a low-functioning IGF-1 signaling pathway

    PubMed Central

    Ni, Qubo; Tan, Yang; Zhang, Xianrong; Luo, Hanwen; Deng, Yu; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-01-01

    Epidemiological evidence indicates that osteoarthritis (OA) and prenatal ethanol exposure (PEE) are both associated with low birth weight but possible causal interrelationships have not been investigated. To investigate the effects of PEE on the susceptibility to OA in adult rats that experienced intrauterine growth retardation (IUGR), and to explore potential intrauterine mechanisms, we established the rat model of IUGR by PEE and dexamethasone, and the female fetus and 24-week-old adult offspring subjected to strenuous running for 6 weeks were sacrificed. Knee joints were collected from fetuses and adult offspring for histochemistry, immunohistochemistry and qPCR assays. Histological analyses and the Mankin score revealed increased cartilage destruction and accelerated OA progression in adult offspring from the PEE group compared to the control group. Immunohistochemistry showed reduced expression of insulin-like growth factor-1 (IGF-1) signaling pathway components. Furthermore, fetuses in the PEE group experienced IUGR but exhibited a higher postnatal growth rate. The expression of many IGF-1 signaling components was downregulated, which coincided with reduced amounts of type II collagen in the epiphyseal cartilage of fetuses in the PEE group. These results suggest that PEE enhances the susceptibility to OA in female adult rat offspring by down-regulating IGF-1 signaling and retarding articular cartilage development. PMID:26434683

  19. Increasing risk awareness and facilitating safe sexual activity among older adults in senior housing.

    PubMed

    Gedin, Tonii C; Resnick, Barbara

    2014-01-01

    The prevalence of HIV in older adults is rising. This increase can be attributed to inconsistent condom use, low perceived disease susceptibility, and a sexual health knowledge gap found in older adults. Yet, little to no health promotion for older adults focuses on sex education. This study sought to determine the feasibility of a group-based educational program in senior housing settings and consider the utility of a self-efficacy based group education program on knowledge of disease risk and preventive techniques among older adults living in senior housing.

  20. Susceptibility of germfree or antibiotic-treated adult mice to Cryptosporidium parvum.

    PubMed

    Harp, J A; Wannemuehler, M W; Woodmansee, D B; Moon, H W

    1988-08-01

    Adult mice are more resistant than neonatal mice to intestinal colonization with the protozoan parasite Cryptosporidium parvum. Development of a mature intestinal flora may play a role in this resistance. We compared susceptibilities to colonization with C. parvum in adult conventional mice, adult germfree mice, and adult conventional mice treated with oral antibiotics to deplete the intestinal flora. Germfree mice of both CD1 and BALB/c strains were colonized at day 7 following inoculation with C. parvum oocysts isolated from the feces of an infected, diarrheic calf. Age-matched conventional mice of the same strains were comparatively resistant to colonization. Conventional mice treated with antibiotics remained resistant to colonization. These results suggest that the microflora in the intestine was not the sole determinant of resistance or susceptibility to colonization. The germfree adult mouse as an experimental model of cryptosporidiosis is discussed.

  1. Deltamethrin Increases Candida albicans infection susceptibility in mice.

    PubMed

    Rehman, H; Mohan, A; Tabassum, H; Ahmad, F; Rahman, S; Parvez, S; Raisuddin, S

    2011-05-01

    Deltamethrin, an alpha-cyano type II synthetic pyrethroid insecticide, is used to control a wide range of insects on a variety of crops and vectors of diseases. Deltamethrin has been previously reported for its immunotoxic effects and therefore its exposure may affect the host resistance to infection and tumour challenge. Effect of exposure of deltamethrin on host resistance to Candida albicans infection was examined in Swiss albino mice. The objective of this study was to investigate the modulatory action of deltamethrin in C. albicans infected mice. The dose of deltamethrin was initially tested and selected from our previous study (18 mg/kg). Percentage of infection in deltamethrin treated animals increased faster when compared to that of the controls. Deltamethrin exposure along with C. albicans infection caused alteration of humoral immune response. The number of colony forming unit in liver and spleen were also found to be significantly increased in the treated group. The results from our present study suggest that deltamethrin exhibits an immunosuppressive effect and has a negative impact on host resistance to C. albicans infection. © 2011 The Authors. Scandinavian Journal of Immunology © 2011 Blackwell Publishing Ltd.

  2. Application of spinosad increases the susceptibility of insecticide-resistant Alphitobius diaperinus (Coleoptera: Tenebrionidae) to pyrethroids.

    PubMed

    Lambkin, Trevor A; Furlong, Michael J

    2014-08-01

    The effect of spinosad exposure on the susceptibility of pyrethroid- and organophosphate-resistant populations of lesser mealworm, Alphitobius diaperinus (Panzer) (Coleoptera: Tenebrionidae), to insecticides was investigated in broiler house farm and laboratory studies. A field pyrethroid- and organophosphate-resistant population showed a 3.6-fold increase in susceptibility to gamma-cyhalothrin following spinosad treatment. Overall, cyfluthrin- and fenitrothion-resistant field populations were more susceptible to these insecticides following spinosad treatments, but populations that were not resistant showed no change in susceptibility following spinosad treatment. In a related study, three broiler farm beetle populations with very similar levels of cyfluthrin and gamma-cyhalothrin resistance and similar susceptibilities to spinosad were used to investigate temporal effects of spinosad field treatments on the susceptibility to pyrethroids. Farm insecticide regimes applied at the start of each flock differed: the control broiler house received no insecticide applications, another house was systematically treated with cyfluthrin at the start of each study flock, and the third house was systematically treated with spinosad at the start of five flocks. Afterwards, treatments reverted to cyfluthrin on all farms. At the end of flocks, beetles were tested with cyfluthrin, gamma-cyhalothrin, and spinosad. The control and cyfluthrin house beetles did not change susceptibility to pyrethroids over the period of the study. In the spinosad house, spinosad had no effect on spinosad susceptibility but dramatically increased cyfluthrin and gamma-cyhalothrin susceptibilities. These new susceptibilities were maintained while spinosad applications continued, but pyrethroid susceptibility declined once spinosad applications ceased. This study provides evidence of a synergistic interaction between spinosad and pyrethroids in pyrethroid-resistant beetles. This evidence has significant

  3. Hypertriglyceridemia increases mitochondrial resting respiration and susceptibility to permeability transition.

    PubMed

    Alberici, Luciane C; Oliveira, Helena C F; Bighetti, Eliete J B; de Faria, Eliana C; Degaspari, Giovana R; Souza, Claudio T; Vercesi, Anibal E

    2003-10-01

    High plasma level of triglycerides (TGs) is a common feature in atherosclerosis, obesity, diabetes, alcoholism, stress, and infection. Since mitochondria have been implicated in cell death under a variety of metabolic disorders, we examined liver mitochondrial functions in hypertriglyceridemic transgenic mice. Hypertriglyceridemia increased resting respiration and predisposed to mitochondrial permeability transition (MPT). Ciprofibrate therapy reduced plasma TG levels, normalized respiration, and prevented MPT. The higher resting respiration in transgenic mitochondria remained in the presence of the adenine nucleotide carrier inhibitor, carboxyatractyloside, bovine serum albumin, and the uncoupling proteins (UCPs) inhibitor, GDP. UCP2 content was similar in both control and transgenic mitochondria. We propose that faster resting respiration represents a regulated adaptation to oxidize excess free fatty acid in the transgenic mice.

  4. The Susceptibility of Older Adults to Environmental Hazards

    EPA Science Inventory

    This rapid growth in the number of older Americans has many implications for public health, including the need to better understand the health risks posed by environmental exposures to older adults. This paper describes the need to link environmental exposures, the processing of...

  5. The Susceptibility of Older Adults to Environmental Hazards

    EPA Science Inventory

    This rapid growth in the number of older Americans has many implications for public health, including the need to better understand the health risks posed by environmental exposures to older adults. This paper describes the need to link environmental exposures, the processing of...

  6. Inventory and recently increasing GLOF susceptibility of glacial lakes in Sikkim, Eastern Himalaya

    NASA Astrophysics Data System (ADS)

    Aggarwal, Suruchi; Rai, S. C.; Thakur, P. K.; Emmer, Adam

    2017-10-01

    Climatic changes alter the climate system, leading to a decrease of glacier mass volumes and swelling glacial lakes. This study provides a new inventory of glacial and high-altitude lakes for Sikkim, Eastern Himalaya, and evaluates the susceptibility of lakes to Glacial Lake Outburst Flood (GLOF). By using satellite data of high spatial resolution (5 m), we obtain 1104 glacial and high-altitude lakes with total area 30.498 km2, of which 472 have an area > 0.01 km2. Applying pre-defined GLOF susceptibility criteria on these 472 lakes yields 21 lakes susceptible to GLOF, which all increased in area from 1972-2015. Using Analytic Hierarchy Processes (AHP), the pairwise comparison matrix further reveals that 5 of these glacial lakes have low, 14 have medium and 2 have high GLOF susceptibility. Especially these 16 glacial lakes with high and medium GLOF susceptibility may threaten downstream communities and infrastructure and need further attention.

  7. Increased susceptibility to amyloid-β toxicity in rat brain microvascular endothelial cells under hyperglycemic conditions.

    PubMed

    Carvalho, Cristina; Katz, Paige S; Dutta, Somhrita; Katakam, Prasad V G; Moreira, Paula I; Busija, David W

    2014-01-01

    We hypothesized that hyperglycemia-induced mitochondrial dysfunction and oxidative stress are closely associated with amyloid-β peptide (Aβ) toxicity in endothelial cells. Brain microvascular endothelial cells from rat (RBMEC) and mice (MBMEC) were isolated from adult Sprague-Dawley rats and homozygous db/db (Leprdb/Leprdb) and heterozygous (Dock7m/Leprdb) mice, and cultured under normo- and hyperglycemic conditions for 7 d followed by 24 h exposure to Aβ1-40. Some experiments were also performed with two mitochondrial superoxide (O2•-) scavengers, MitoTempo and Peg-SOD. Cell viability was measured by the Alamar blue assay and mitochondrial membrane potential (ΔΨm) by confocal microscopy. Mitochondrial O2•- and hydrogen peroxide (H2O2) production was assessed by fluorescence microscopy and H2O2 production was confirmed by microplate reader. Hyperglycemia or Aβ1-40 alone did not affect cell viability in RBMEC. However, the simultaneous presence of high glucose and Aβ1-40 reduced cell viability and ΔΨm, and enhanced mitochondrial O2•- and H2O2 production. MitoTempo and PEG-SOD prevented Aβ1-40 toxicity. Interestingly, MBMEC presented a similar pattern of alterations with db/db cultures presenting higher susceptibility to Aβ1-40. Overall, our results show that high glucose levels increase the susceptibility of brain microvascular endothelial cells to Aβ toxicity supporting the idea that hyperglycemia is a major risk factor for vascular injury associated with AD.

  8. Thermomechanical processing of 5083 aluminum to increase strength without increasing susceptibility to stress corrosion cracking

    SciTech Connect

    Edstrom, C. M.; Blakeslee, J. J.

    1980-09-30

    5083 aluminium with 25% cold work must be processed above 215/sup 0/C or below 70/sup 0/C to avoid forming continuous precipitate in the grain boundaries which makes the material susceptible to stress corrosion cracking. Time at temperature above 215/sup 0/C should be held to minimum (less than 30 min) to retain some strength from the 25% cold work.

  9. Increased Seizure Susceptibility in Mice 30 Days after Fluid Percussion Injury

    PubMed Central

    Mukherjee, Sanjib; Zeitouni, Suzanne; Cavarsan, Clarissa Fantin; Shapiro, Lee A.

    2013-01-01

    Traumatic brain injury (TBI) has been reported to increase seizure susceptibility and also contribute to the development of epilepsy. However, the mechanistic basis of the development of increased seizure susceptibility and epilepsy is not clear. Though there is substantial work done using rats, data are lacking regarding the use of mice in the fluid percussion injury (FPI) model. It is unclear if mice, like rats, will experience increased seizure susceptibility following FPI. The availability of a mouse model of increased seizure susceptibility after FPI would provide a basis for the use of genetically modified mice to study mechanism(s) of the development of post-traumatic epilepsy. Therefore, this study was designed to test the hypothesis that, mice subjected to a FPI develop increased seizure susceptibility to a subconvulsive dose of the chemoconvulsant, pentylenetetrazole (PTZ). Three groups of mice were used: FPI, sham, and naïve controls. On day 30 after FPI, mice from the three groups were injected with PTZ. The results showed that FPI mice exhibited an increased severity, frequency, and duration of seizures in response to PTZ injection compared with the sham and naïve control groups. Histopathological assessment was used to characterize the injury at 1, 3, 7, and 30 days after FPI. The results show that mice subjected to the FPI had a pronounced lesion and glial response that was centered at the FPI focus and peaked at 3 days. By 30 days, only minimal evidence of a lesion is observed, although there is evidence of a chronic glial response. These data are the first to demonstrate an early increase in seizure susceptibility following FPI in mice. Therefore, future studies can incorporate transgenic mice into this model to further elucidate mechanisms of TBI-induced increases in seizure susceptibility. PMID:23519723

  10. Perinatal Exposure to Oestradiol and Bisphenol A Alters the Prostate Epigenome and Increases Susceptibility to Carcinogenesis

    PubMed Central

    Prins, Gail S.; Tang, Wan-Yee; Belmonte, Jessica; Ho, Shuk-Mei

    2010-01-01

    An important and controversial health concern is whether low-dose exposures to hormonally active environmental oestrogens such as bisphenol A can promote human diseases including prostate cancer. Our studies in rats have shown that pharmacological doses of oestradiol administered during the critical window of prostate development result in marked prostate pathology in adulthood that progress to neoplastic lesions with ageing. Our recent studies have also demonstrated that transient developmental exposure of rats to low, environmentally relevant doses of bisphenol A or oestradiol increases prostate gland susceptibility to adult-onset precancerous lesions and hormonal carcinogenesis. These findings indicate that a wide range of oestrogenic exposures during development can predispose to prostatic neoplasia that suggests a potential developmental basis for this adult disease. To identify a molecular basis for oestrogen imprinting, we screened for DNA methylation changes over time in the exposed prostate glands. We found permanent alterations in DNA methylation patterns of multiple cell signalling genes suggesting an epigenetic mechanism of action. For phosphodiesterase type 4 variant 4 (PDE4D4), an enzyme responsible for intracellular cyclic adenosine monophosphate breakdown, a specific methylation cluster was identified in the 5′-flanking CpG island that was gradually hypermethylated with ageing in normal prostates resulting in loss of gene expression. However, in prostates exposed to neonatal oestradiol or bisphenol A, this region became hypomethylated with ageing resulting in persistent and elevated PDE4D4 expression. In total, these findings indicate that low-dose exposures to ubiquitous environmental oestrogens impact the prostate epigenome during development and in so doing, promote prostate disease with ageing. PMID:18226066

  11. Characterizing Young Adults' Susceptibility to Waterpipe Tobacco Use and Their Reactions to Messages About Product Harms and Addictiveness.

    PubMed

    Lipkus, Isaac M; Mays, Darren; P Tercyak, Kenneth

    2017-10-01

    There is very little insight into the psychosocial characteristics of young adults susceptible to waterpipe tobacco use and their reactions to messages about harms of waterpipe tobacco smoking (WTS). We investigated how young adults who were or were not susceptible to WTS differed on various characteristics and their reactions to messages about WTS harms. Young adults ages 18 to 30 who had never used waterpipe tobacco were recruited through an online crowdsourcing site. Participants were stratified on susceptibility status (susceptible or not) and randomized to receive messages about harms and addictiveness of WTS or a control condition that received no messages. Participants' perceptions of risk and worry, their attitudes toward, and willingness/curiosity to try WTS were assessed. Compared to nonsusceptible participants, susceptible participants perceived themselves to be at lower risk and worried less about harms and addictiveness of WTS, had more positive attitudes toward use, and expressed a greater willingness and curiosity to try it. Among susceptible participants, messages decreased willingness/curiosity to try WTS; messages had no effect on nonsusceptible participants. The message effects among susceptible participants were explained by more negative attitudes and less ambivalence toward WTS. Susceptible young adults' psychosocial characteristics place them at high risk for future uptake of WTS. Brief public health messages about harm and addiction may deter susceptible young adults' willingness to try WTS and prevent WTS initiation and progression. Findings suggest that in order to curb the initiation of WTS among susceptible young adults, interventions should target risk appraisals and attitudes toward WTS.

  12. Periadolescent rats (P41-50) exhibit increased susceptibility to D-methamphetamine-induced long-term spatial and sequential learning deficits compared to juvenile (P21-30 or P31-40) or adult rats (P51-60).

    PubMed

    Vorhees, Charles V; Reed, Tracy M; Morford, LaRonda L; Fukumura, Masao; Wood, Sandra L; Brown, Carrie A; Skelton, Matthew R; McCrea, Anne E; Rock, Stephanie L; Williams, Michael T

    2005-01-01

    We have previously shown that P11-20 treatment with d-methamphetamine (MA) induces impaired spatial navigation in the Morris water maze (MWM), whereas P1-10 treatment does not. Little is known about the long-term behavioral consequences of MA during juvenile, adolescent, and early adult brain development. In dose-response experiments, we tested successive 10-day intervals of exposure to MA in rats (P21-30, P31-40, P41-50, and P51-60; four doses per day). MA dosing prior to P21 produces little or no toxicity; however, we observed an increased toxicity with advancing age. Across-age comparisons revealed no MWM acquisition or Cincinnati water maze (CWM) effects after MA treatment on P21-30 (2.5-10 mg/kg/dose), P31-40 (1.25-7.5 mg/kg/dose), or P51-60 (1.25-5.0 mg/kg/dose); however, significantly impaired MWM acquisition was observed after P41-50 MA treatment at the highest dose (6.25 mg/kg/dose). Learning in the CWM was also impaired in this group. No effects were seen at 1.25, 2.5, or 5 mg/kg/dose following P41-50 MA treatment. MWM reversal learning trials after P41-50 treatment showed a trend towards longer latency in all MA dose groups, but no effect on double-reversal trials. Reversal and double-reversal also showed no effects at the other exposure ages. No differences in straight channel swimming or cued learning in the MWM were seen after MA treatment at any exposure age. P41-50 is the periadolescent stage of brain development in rodents. The effects observed at this age may suggest a previously unrecognized period of susceptibility for MA-induced cognitive deficits.

  13. Low birth weight increases susceptibility to renal injury in a rat model of mild ischemia-reperfusion.

    PubMed

    Ojeda, Norma B

    2011-08-01

    Renal injury due to ischemia-reperfusion (I/R) is the major cause of acute kidney injury. Whether enhanced susceptibility to renal injury due to I/R can be programmed during fetal life is unknown. Epidemiological studies indicate that low birth weight (LBW) individuals are more susceptible to renal injury than normal birth weight (NBW) individuals. Thus, the aim of this study was to test the hypothesis that LBW is associated with an increased susceptibility to renal injury induced by mild renal I/R (15-min ischemia). Systemic and renal hemodynamic parameters were determined in NBW and LBW adult male rats after mild renal I/R; renal superoxide production and tubular injury were also assessed. A subgroup was pretreated with tempol, a superoxide dismutase mimetic, initiated 15 min before ischemia. Mild renal I/R did not alter renal hemodynamic parameters, induce tubular injury, or induce superoxide production in NBW rats. However, renal hemodynamic parameters declined, superoxide production increased, and histological indicators of tubular injury were present following mild renal I/R in LBW rats. Acute treatment with tempol prevented these alterations in LBW rats subjected to mild renal I/R. Thus, these findings suggest that adverse conditions during fetal life can compromise the renal response to subtle insults leading to an increased susceptibility to renal injury, suggesting that LBW individuals may be an "at risk" population for renal disease. Additionally, the outcome of tempol treatment proposes a possible mechanistic pathway involved in mediating enhanced susceptibility to renal injury programmed during fetal life.

  14. Increasing Employment Opportunities for Disadvantaged Young Adults

    ERIC Educational Resources Information Center

    Hossain, Farhana; Terwelp, Emily

    2015-01-01

    In the past four decades, profound changes in the U.S. economy--including falling wages, widening inequality, and the polarization of jobs at the top and bottom of the education and wage distributions--have had dramatic implications for the labor-market fortunes of young adults. Only about half of young people ages 16 to 24 held jobs in 2014, and…

  15. Pubertal and adult windows of susceptibility to a high animal fat diet in Trp53-null mammary tumorigenesis.

    PubMed

    Zhu, Yirong; Aupperlee, Mark D; Zhao, Yong; Tan, Ying Siow; Kirk, Erin L; Sun, Xuezheng; Troester, Melissa A; Schwartz, Richard C; Haslam, Sandra Z

    2016-12-13

    Premenopausal breast cancer is associated with increased animal fat consumption among normal weight, but not overweight women (Farvid et al., 2014). Our previous findings in obesity-resistant BALB/c mice similarly showed promotion of carcinogen-induced mammary tumorigenesis by a diet high in saturated animal fat (HFD). This effect was specific to pubertal versus adult HFD. This study identifies the effects of HFD during puberty versus adulthood in Trp53-null transplant BALB/c mice and investigates its mechanism of enhancing tumorigenesis. Either pubertal or adult HFD is sufficient to increase incidence of Trp53-null mammary tumors. Puberty-restricted HFD exposure promoted tumor cell proliferation, increased angiogenesis, and increased recruitment of total and M2 macrophages in epithelial tumors. Adult-restricted exposure to HFD similarly increased proliferation, angiogenesis, recruitment of total and M2 macrophages, and additionally reduced apoptosis. Adult HFD also increased incidence of spindle cell carcinomas resembling claudin-low breast cancer, and thus adult HFD in the Trp53-null transplantation system may be a useful model for human claudin low breast cancer. Importantly, these results on Trp53-null and our prior studies on DMBA-induced mammary tumorigenesis demonstrate a pubertal window of susceptibility to the promotional effects of HFD, indicating the potential of early life dietary intervention to reduce breast cancer risk.

  16. Pubertal and adult windows of susceptibility to a high animal fat diet in Trp53-null mammary tumorigenesis

    PubMed Central

    Zhu, Yirong; Aupperlee, Mark D.; Zhao, Yong; Tan, Ying Siow; Kirk, Erin L.; Sun, Xuezheng; Troester, Melissa A.; Schwartz, Richard C.; Haslam, Sandra Z.

    2016-01-01

    Premenopausal breast cancer is associated with increased animal fat consumption among normal weight, but not overweight women (Farvid et al., 2014). Our previous findings in obesity-resistant BALB/c mice similarly showed promotion of carcinogen-induced mammary tumorigenesis by a diet high in saturated animal fat (HFD). This effect was specific to pubertal versus adult HFD. This study identifies the effects of HFD during puberty versus adulthood in Trp53-null transplant BALB/c mice and investigates its mechanism of enhancing tumorigenesis. Either pubertal or adult HFD is sufficient to increase incidence of Trp53-null mammary tumors. Puberty-restricted HFD exposure promoted tumor cell proliferation, increased angiogenesis, and increased recruitment of total and M2 macrophages in epithelial tumors. Adult-restricted exposure to HFD similarly increased proliferation, angiogenesis, recruitment of total and M2 macrophages, and additionally reduced apoptosis. Adult HFD also increased incidence of spindle cell carcinomas resembling claudin-low breast cancer, and thus adult HFD in the Trp53-null transplantation system may be a useful model for human claudin low breast cancer. Importantly, these results on Trp53-null and our prior studies on DMBA-induced mammary tumorigenesis demonstrate a pubertal window of susceptibility to the promotional effects of HFD, indicating the potential of early life dietary intervention to reduce breast cancer risk. PMID:27825136

  17. Transient increase of interleukin-1β after prolonged febrile seizures promotes adult epileptogenesis through long-lasting upregulating endocannabinoid signaling.

    PubMed

    Feng, Bo; Tang, Yangshun; Chen, Bin; Xu, Cenglin; Wang, Yi; Dai, Yunjian; Wu, Dengchang; Zhu, Junmin; Wang, Shuang; Zhou, Yudong; Shi, Liyun; Hu, Weiwei; Zhang, Xia; Chen, Zhong

    2016-02-23

    It remains unclear how infantile febrile seizures (FS) enhance adult seizure susceptibility. Here we showed that the transient increase of interleukin-1β (IL-1β) after prolonged FS promoted adult seizure susceptibility, which was blocked by interleukin-1 receptor antagonist (IL-1Ra) within a critical time window. Postnatal administered IL-1β alone mimicked the effect of FS on adult seizure susceptibility. IL-1R1 knockout mice were not susceptible to adult seizure after prolonged FS or IL-1β treatment. Prolonged FS or early-life IL-1β treatment increased the expression of cannabinoid type 1 receptor (CB1R) for over 50 days, which was blocked by IL-1Ra or was absent in IL-1R1 knockout mice. CB1R antagonist, knockdown and endocannabinoid synthesis inhibitor abolished FS or IL-1β-enhanced seizure susceptibility. Thus, this work identifies a pathogenic role of postnatal IL-1β/IL-1R1 pathway and subsequent prolonged prominent increase of endocannabinoid signaling in adult seizure susceptibility following prolonged FS, and highlights IL-1R1 as a potential therapeutic target for preventing the development of epilepsy after infantile FS.

  18. Transient increase of interleukin-1β after prolonged febrile seizures promotes adult epileptogenesis through long-lasting upregulating endocannabinoid signaling

    PubMed Central

    Feng, Bo; Tang, Yangshun; Chen, Bin; Xu, Cenglin; Wang, Yi; Dai, Yunjian; Wu, Dengchang; Zhu, Junmin; Wang, Shuang; Zhou, Yudong; Shi, Liyun; Hu, Weiwei; Zhang, Xia; Chen, Zhong

    2016-01-01

    It remains unclear how infantile febrile seizures (FS) enhance adult seizure susceptibility. Here we showed that the transient increase of interleukin-1β (IL-1β) after prolonged FS promoted adult seizure susceptibility, which was blocked by interleukin-1 receptor antagonist (IL-1Ra) within a critical time window. Postnatal administered IL-1β alone mimicked the effect of FS on adult seizure susceptibility. IL-1R1 knockout mice were not susceptible to adult seizure after prolonged FS or IL-1β treatment. Prolonged FS or early-life IL-1β treatment increased the expression of cannabinoid type 1 receptor (CB1R) for over 50 days, which was blocked by IL-1Ra or was absent in IL-1R1 knockout mice. CB1R antagonist, knockdown and endocannabinoid synthesis inhibitor abolished FS or IL-1β-enhanced seizure susceptibility. Thus, this work identifies a pathogenic role of postnatal IL-1β/IL-1R1 pathway and subsequent prolonged prominent increase of endocannabinoid signaling in adult seizure susceptibility following prolonged FS, and highlights IL-1R1 as a potential therapeutic target for preventing the development of epilepsy after infantile FS. PMID:26902320

  19. A period of increased susceptibility to cigarette smoking among high school students.

    PubMed

    Filice, Gregory A; Hannan, Peter J; Lando, Harry A; Joseph, Anne M

    2003-09-01

    Cross-sectional surveys of randomly selected high school students were conducted in October 1999 and in May 2000 to measure awareness of youth-led tobacco prevention efforts. A secondary goal of the surveys was to learn about tobacco use and attitudes. Respondents who never smoked cigarettes were asked if they had made a firm commitment to not smoke, and respondents who had not made such a commitment were considered susceptible. Among ninth graders, susceptibility increased from 31% in October to 47% in May, while susceptibility decreased from October to May for students in more advanced grades (p = 0.03, interaction of linear trends). Susceptibility was more common among students who felt smoking produced social benefits (OR 1.59, 95% CI 1.22-2.08) or who were tolerant of tobacco company behavior (OR 1.65, 95% CI 1.23-2.21), and less common among students who felt short-term adverse effects of cigarette smoking on health or hygiene were important to them (OR 0.74, 95% CI 0.56-0.97). Further studies should confirm the increase in susceptibility and its underlying mechanisms. Whether associated with ninth grade or with the first year in a new school, this previously unrecognized period of heightened susceptibility might represent an important opportunity for prevention.

  20. Seizure-induced disinhibition of the HPA axis increases seizure susceptibility.

    PubMed

    O'Toole, Kate K; Hooper, Andrew; Wakefield, Seth; Maguire, Jamie

    2014-01-01

    Stress is the most commonly reported precipitating factor for seizures. The proconvulsant actions of stress hormones are thought to mediate the effects of stress on seizure susceptibility. Interestingly, epileptic patients have increased basal levels of stress hormones, including corticotropin-releasing hormone (CRH) and corticosterone, which are further increased following seizures. Given the proconvulsant actions of stress hormones, we proposed that seizure-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis may contribute to future seizure susceptibility. Consistent with this hypothesis, our data demonstrate that pharmacological induction of seizures in mice with kainic acid or pilocarpine increases circulating levels of the stress hormone, corticosterone, and exogenous corticosterone administration is sufficient to increase seizure susceptibility. However, the mechanism(s) whereby seizures activate the HPA axis remain unknown. Here we demonstrate that seizure-induced activation of the HPA axis involves compromised GABAergic control of CRH neurons, which govern HPA axis function. Following seizure activity, there is a collapse of the chloride gradient due to changes in NKCC1 and KCC2 expression, resulting in reduced amplitude of sIPSPs and even depolarizing effects of GABA on CRH neurons. Seizure-induced activation of the HPA axis results in future seizure susceptibility which can be blocked by treatment with an NKCC1 inhibitor, bumetanide, or blocking the CRH signaling with Antalarmin. These data suggest that compromised GABAergic control of CRH neurons following an initial seizure event may cause hyperexcitability of the HPA axis and increase future seizure susceptibility.

  1. Bacterial Manipulation of NK Cell Regulatory Activity Increases Susceptibility to Listeria monocytogenes Infection

    PubMed Central

    Guthrie, Brandon S.; Schmidt, Rebecca L.; Jamieson, Amanda; Merkel, Patricia; Knight, Vijaya; Cole, Caroline M.; Raulet, David H.; Lenz, Laurel L.

    2016-01-01

    Natural killer (NK) cells produce interferon (IFN)-γ and thus have been suggested to promote type I immunity during bacterial infections. Yet, Listeria monocytogenes (Lm) and some other pathogens encode proteins that cause increased NK cell activation. Here, we show that stimulation of NK cell activation increases susceptibility during Lm infection despite and independent from robust NK cell production of IFNγ. The increased susceptibility correlated with IL-10 production by responding NK cells. NK cells produced IL-10 as their IFNγ production waned and the Lm virulence protein p60 promoted induction of IL-10 production by mouse and human NK cells. NK cells consequently exerted regulatory effects to suppress accumulation and activation of inflammatory myeloid cells. Our results reveal new dimensions of the role played by NK cells during Lm infection and demonstrate the ability of this bacterial pathogen to exploit the induction of regulatory NK cell activity to increase host susceptibility. PMID:27295349

  2. Epigenetic Modification of TLRs in Leukocytes Is Associated with Increased Susceptibility to Salmonella enteritidis in Chickens

    PubMed Central

    Zhao, Guiping; Zheng, Maiqing; Li, Peng; Wang, Huihua; Zhu, Yun; Chen, Jilan; Wen, Jie

    2012-01-01

    Toll-like receptors (TLRs) signaling pathways are the first lines in defense against Salmonella enteritidis (S. enteritidis) infection but the molecular mechanism underlying susceptibility to S. enteritidis infection in chicken remains unclear. SPF chickens injected with S. enteritidis were partitioned into two groups, one consisted of those from Salmonella-susceptible chickens (died within 5 d after injection, n = 6), the other consisted of six Salmonella-resistant chickens that survived for 15 d after injection. The present study shows that the bacterial load in susceptible chickens was significantly higher than that in resistant chickens and TLR4, TLR2-1 and TLR21 expression was strongly diminished in the leukocytes of susceptible chickens compared with those of resistant chickens. The induction of expression of pro-inflammatory cytokine genes, IL-6 and IFN-β, was greatly enhanced in the resistant but not in susceptible chickens. Contrasting with the reduced expression of TLR genes, those of the zinc finger protein 493 (ZNF493) gene and Toll-interacting protein (TOLLIP) gene were enhanced in the susceptible chickens. Finally, the expression of TLR4 in peripheral blood mononuclear cells (PBMCs) infected in vitro with S. enteritidis increased significantly as a result of treatment with 5-Aza-2-deoxycytidine (5-Aza-dc) while either 5-Aza-dc or trichostatin A was effective in up-regulating the expression of TLR21 and TLR2-1. DNA methylation, in the predicted promoter region of TLR4 and TLR21 genes, and an exonic CpG island of the TLR2-1 gene was significantly higher in the susceptible chickens than in resistant chickens. Taken together, the results demonstrate that ZNF493-related epigenetic modification in leukocytes probably accounts for increased susceptibility to S. enteritidis in chickens by diminishing the expression and response of TLR4, TLR21 and TLR2-1. PMID:22438967

  3. Self-Rated Health in Healthy Adults and Susceptibility to the Common Cold.

    PubMed

    Cohen, Sheldon; Janicki-Deverts, Denise; Doyle, William J

    2015-01-01

    To explore the association of self-rated health (SRH) with host resistance to illness after exposure to a common cold virus and identify mechanisms linking SRH to future health status. We analyzed archival data from 360 healthy adults (mean [standard deviation] age = 33.07 [10.69] years, 45.6% women). Each person completed validated questionnaires that assessed SRH (excellent, very good, good, fair, poor), socioemotional factors, and health practices and was subsequently exposed to a common cold virus and monitored for 5 days for clinical illness (infection and objective signs of illness). Poorer SRH was associated in a graded fashion with greater susceptibility to developing clinical illness (good/fair versus excellent: odds ratio = 3.21, 95% confidence interval = 1.47-6.99; very good versus excellent: odds ratio = 2.60, 95% confidence interval = 1.27-5.32), independent of age, sex, race, prechallenge immunity (specific antibody), body mass, season, education, and income. Greater illness risk was not attributable to infection, but to increased likelihood of developing objective signs of illness once infected. Poorer SRH also correlated with poorer health practices, increased stress, lower positive emotions, and other socioemotional factors. However, none of these (alone or together) accounted for the association between SRH and host resistance. Additional data (separate study) indicated that history of having colds was unrelated to susceptibility and hence also did not account for the SRH link with immunocompetence. Poorer SRH is associated with poorer immunocompetence, possibly reflecting sensitivity to sensations associated with premorbid immune dysfunction. In turn, poorer immune function may be a major contributing mechanism linking SRH to future health.

  4. Self-Rated Health in Healthy Adults and Susceptibility to the Common Cold

    PubMed Central

    Cohen, Sheldon; Janicki-Deverts, Denise; Doyle, William J.

    2015-01-01

    Objectives Explore the association of self-rated health (SRH) with host-resistance to illness following exposure to a common cold virus and identify mechanisms linking SRH to future health status. Methods We analyzed archival data from 360 healthy adults (mean age = 33.07, SD = 10.69; 45.6% women). Each completed validated questionnaires assessing SRH (excellent, very good, good, fair, poor), socio-emotional factors and health practices; was subsequently exposed to a virus that causes the common cold; and monitored for 5 days for clinical illness (infection + objective signs of illness). Results Poorer SRH was associated in a graded fashion with greater susceptibility to developing clinical illness (good/fair vs. excellent: odds ratio [OR]=3.21, 95% confidence interval [CI]=1.47-6.99]; very good vs. excellent: OR=2.60, 95% CI=1.27-5.32), independent of age, sex, race, pre-challenge immunity (specific antibody), body mass, season, education, and income. Greater illness risk was not attributable to infection, but to increased likelihood of developing objective signs of illness once infected. Poorer SRH also correlated with poorer health practices, increased stress, lower positive emotions, and other socio-emotional factors. However, none of these (alone or together) accounted for the association between SRH and host-resistance. Additional data (separate study) indicated that history of having colds was unrelated to susceptibility and hence also did not account for the SRH link with immunocompetence. Conclusions Poorer SRH is associated with poorer immunocompetence, possibly reflecting sensitivity to sensations associated with premorbid immune dysfunction. In turn poorer immune function may be a major contributing mechanism linking SRH with future health. PMID:26397938

  5. Suppression of Adult Neurogenesis Increases the Acute Effects of Kainic Acid

    PubMed Central

    Iyengar, Sloka S.; LaFrancois, John J.; Friedman, Daniel; Drew, Liam J.; Denny, Christine A.; Burghardt, Nesha S.; Wu, Melody V.; Hsieh, Jenny; Hen, René; Scharfman, Helen E.

    2016-01-01

    Adult neurogenesis, the generation of new neurons in the adult brain, occurs in the hippocampal dentate gyrus (DG) and the olfactory bulb (OB) of all mammals, but the functions of these new neurons are not entirely clear. Originally, adult-born neurons were considered to have excitatory effects on the DG network, but recent studies suggest a net inhibitory effect. Therefore, we hypothesized that selective removal of newborn neurons would lead to increased susceptibility to the effects of a convulsant. This hypothesis was tested by evaluating the response to the chemoconvulsant kainic acid (KA) in mice with reduced adult neurogenesis, produced either by focal X-irradiation of the DG, or by pharmacogenetic deletion of dividing radial glial precursors. In the first 4 hrs after KA administration, when mice have the most robust seizures, mice with reduced adult neurogenesis had more severe convulsive seizures, exhibited either as a decreased latency to the first convulsive seizure, greater number of convulsive seizures, or longer convulsive seizures. Nonconvulsive seizures did not appear to change or they decreased. Four-21 hrs after KA injection, mice with reduced adult neurogenesis showed more interictal spikes (IIS) and delayed seizures than controls. Effects were greater when the anticonvulsant ethosuximide was injected 30 min prior to KA administration; ethosuximide allows forebrain seizure activity to be more easily examined in mice by suppressing seizures dominated by the brainstem. These data support the hypothesis that reduction of adult-born neurons increases the susceptibility of the brain to effects of KA. PMID:25476494

  6. Grey matter correlates of susceptibility to scams in community-dwelling older adults.

    PubMed

    Duke Han, S; Boyle, Patricia A; Yu, Lei; Arfanakis, Konstantinos; James, Bryan D; Fleischman, Debra A; Bennett, David A

    2016-06-01

    Susceptibility to scams is a significant issue among older adults, even among those with intact cognition. Age-related changes in brain macrostructure may be associated with susceptibility to scams; however, this has yet to be explored. Based on previous work implicating frontal and temporal lobe functioning as important in decision making, we tested the hypothesis that susceptibility to scams is associated with smaller grey matter volume in frontal and temporal lobe regions in a large community-dwelling cohort of non-demented older adults. Participants (N = 327, mean age = 81.55, mean education = 15.30, 78.9 % female) completed a self-report measure used to assess susceptibility to scams and an MRI brain scan. Results indicated an inverse association between overall grey matter and susceptibility to scams in models adjusted for age, education, and sex; and in models further adjusted for cognitive function. No significant associations were observed for white matter, cerebrospinal fluid, or total brain volume. Models adjusted for age, education, and sex revealed seven clusters showing smaller grey matter in the right parahippocampal/hippocampal/fusiform, left middle temporal, left orbitofrontal, right ventromedial prefrontal, right middle temporal, right precuneus, and right dorsolateral prefrontal regions. In models further adjusted for cognitive function, results revealed three significant clusters showing smaller grey matter in the right parahippocampal/hippocampal/fusiform, right hippocampal, and right middle temporal regions. Lower grey matter concentration in specific brain regions may be associated with susceptibility to scams, even after adjusting for cognitive ability. Future research is needed to determine whether grey matter reductions in these regions may be a biomarker for susceptibility to scams in old age.

  7. Increase in fluoroquinolone non-susceptibility among clinical Streptococcus pyogenes in Belgium during 2007-10.

    PubMed

    Van Heirstraeten, Liesbet; Leten, Gert; Lammens, Christine; Goossens, Herman; Malhotra-Kumar, Surbhi

    2012-11-01

    To study the temporal evolution of fluoroquinolone non-susceptibility among Streptococcus pyogenes during 2007-10 in Belgium. S. pyogenes (n = 4690) recovered from patients with tonsillopharyngitis or skin, wound or invasive infections were screened for fluoroquinolone non-susceptibility. A selection of fluoroquinolone-non-susceptible strains was investigated for resistance mechanisms: reserpine-sensitive efflux and mutations in topoisomerase genes parC and gyrA. Clonality was determined by emm typing. Fluoroquinolone non-susceptibility (ciprofloxacin MIC ≥2 mg/L) was identified in 535 (11.4%) of 4690 S. pyogenes recovered during 2007-10 in Belgium. The proportion of fluoroquinolone-non-susceptible S. pyogenes increased significantly from 4.3% (2008) to 10.9% (2009) to 21.6% (2010) and coincided with a significant increase in emm6 strains among fluoroquinolone-non-susceptible S. pyogenes. Ciprofloxacin MICs of 2-8 mg/L correlated with first-step ParC substitutions. Two high-level fluoroquinolone-resistant S. pyogenes strains (ciprofloxacin MICs 32 mg/L) showed second-step substitutions in GyrA (Ser-81→Phe or Tyr) in addition to first-step mutations in parC. Reserpine-sensitive efflux was not observed. We report an unprecedented increase in fluoroquinolone-non-susceptible S. pyogenes in Belgium, a country with high quinolone use, as well as emergence of two high-level fluoroquinolone-resistant S. pyogenes strains with second-step mutations in gyrA, warning us of the need for more prudent use of fluoroquinolones and for continued resistance surveillance.

  8. Reduced susceptibility to chlorhexidine in staphylococci: is it increasing and does it matter?

    PubMed

    Horner, Carolyne; Mawer, Damien; Wilcox, Mark

    2012-11-01

    Antiseptic agents are increasingly used for hand hygiene and skin decolonization as key tools for the prevention of healthcare-associated infections. Chlorhexidine, a divalent, cationic biguanide, has a broad spectrum of activity and is one of the most frequently used topical antiseptic agents. Notably, there are an increasing number of prevalence studies that report reduced levels of susceptibility to chlorhexidine. In contrast to bacterial resistance to antibiotics, using parameters such as the MIC to define resistance to antiseptics, including chlorhexidine, is not straightforward. A range of methods have been used for the detection of reduced susceptibility to chlorhexidine, but, importantly, there is no standardized method and no consensus on the definition of chlorhexidine 'resistance'. In this review we have assessed the methods available for the detection of reduced susceptibility to chlorhexidine and the prevalence of coresistance to other antimicrobial agents. We have focused on the development of reduced susceptibility to chlorhexidine and the presence of efflux-mediated resistance genes in staphylococci, and have reviewed the clinical significance of this phenomenon. Lastly, we have identified unanswered questions to further our understanding of this emergent threat. We anticipate that clinical use of chlorhexidine will continue to increase, and it will be important to be alert to the possibility that this may lead to the emergence of new clones with reduced susceptibility. Indiscriminate chlorhexidine use in the absence of efficacy data should be discouraged.

  9. Increased susceptibility to fungal disease accompanies adaptation to drought in Brassica rapa

    PubMed Central

    O’Hara, Niamh B.; Rest, Joshua S.; Franks, Steven J.

    2016-01-01

    Recent studies have demonstrated adaptive evolutionary responses to climate change, but little is known about how these responses may influence ecological interactions with other organisms, including natural enemies. We used a resurrection experiment in the greenhouse to examine the effect of evolutionary responses to drought on the susceptibility of Brassica rapa plants to a fungal pathogen, Alternaria brassicae. In agreement with previous studies in this population, we found an evolutionary shift to earlier flowering post-drought, which was previously shown to be adaptive. Here we report the novel finding that post-drought descendant plants were also more susceptible to disease, indicating a rapid evolutionary shift to increased susceptibility. This was accompanied by an evolutionary shift to increased specific leaf area (thinner leaves) following drought. We found that flowering time and disease susceptibility displayed plastic responses to experimental drought treatments, but that this plasticity did not match the direction of evolution, indicating that plastic and evolutionary responses to changes in climate can be opposed. The observed evolutionary shift to increased disease susceptibility accompanying adaptation to drought provides evidence that even if populations can rapidly adapt in response to climate change, evolution in other traits may have ecological effects that could make species more vulnerable. PMID:26648585

  10. Inhibition of LpxC Increases Antibiotic Susceptibility in Acinetobacter baumannii

    PubMed Central

    García-Quintanilla, Meritxell; Caro-Vega, José M.; Pulido, Marina R.; Moreno-Martínez, Patricia; Pachón, Jerónimo

    2016-01-01

    LpxC inhibitors have generally shown poor in vitro activity against Acinetobacter baumannii. We show that the LpxC inhibitor PF-5081090 inhibits lipid A biosynthesis, as determined by silver staining and measurements of endotoxin levels, and significantly increases cell permeability. The presence of PF-5081090 at 32 mg/liter increased susceptibility to rifampin, vancomycin, azithromycin, imipenem, and amikacin but had no effect on susceptibility to ciprofloxacin and tigecycline. Potentiating existing antibiotics with LpxC inhibitors may represent an alternative treatment strategy for multidrug-resistant A. baumannii. PMID:27270288

  11. Gastric bypass surgery does not increase susceptibility to Helicobacter pylori infection in the stomach of rat or mouse.

    PubMed

    Stenström, Björn; Løseth, Kirsti; Bevanger, Lars; Sturegård, Erik; Wadström, Torkel; Chen, Duan

    2005-01-01

    Gastric bypass is a clinical option for obesity surgery. An increased susceptibility to Helicobacter pylori infection in the bypassed stomach has been speculated. The aim of the present study was to examine the susceptibility of the bypassed stomach to H. pylori infection in rats and mice. Adult Sprague-Dawley and Wistar rats and NMRI mice were subjected to either gastric bypass or laparotomy only as control. The animals were inoculated with the CagA- and VacA- positive H. pylori strain 67/21 (not mouse-adapted) in the first experiment and with 9 additional isolates in the second, by injection into the bypassed stomach or the control stomach during surgery. The stomach of each animal was collected for H. pylori culture 2-3 weeks later. While all the rats were H. pylori negative, 54% of gastric bypassed mice and 75% of controls were positive (P = 0.4). We conclude that susceptibility to H. pylori infection in the stomach is not increased by gastric bypass surgery.

  12. Adults as Learners. Increasing Participation and Facilitating Learning.

    ERIC Educational Resources Information Center

    Cross, K. Patricia

    The literature on adult learners is reviewed, and two models of adult learning are developed. Demographic, social, and technological trends that stimulate the increasing demand for learning opportunities are examined, and the views of those who see dangers in new pressures on adults to participate in organized learning activities are considered.…

  13. Ozone, but not nitrogen dioxide, fragments elastin and increases its susceptibility to proteolysis.

    PubMed

    Winters, R S; Burnette-Vick, B A; Johnson, D A

    1994-10-01

    The effects of ozone (O3) and nitrogen dioxide (NO2) on the solubility and proteolytic susceptibility of elastin were examined to better understand how these oxidant air pollutants might damage the lung. In vitro O3 exposures at pH 7.4 resulted in the complete solubilization of elastin, but NO2 had no effect on solubility. The initial solubilization rate was 65 micrograms/mumol of O3, which increased to 150 micrograms/mumol in the midregion of a sigmoidal solubilization curve. Peptide fragments of the O3-solubilized elastin ranged in size from 5 to 20 kD. The conversion of insoluble elastin into soluble fragments by O3 was not due to the destruction of desmosine crosslinks. The effect of O3 on the proteolytic susceptibility of elastin was measured using insoluble elastin recovered from exposures that resulted in 5.3%, 12.8%, and 26.3% solubilization. Human neutrophil elastase (HNE) digested the remaining insoluble elastin samples 4.3, 6.0, and 9.8 times faster than unexposed elastin. In contrast, NO2-exposed elastin was no more susceptible to digestion by HNE. Ascorbate, EDTA, and uric acid reduced the proteolytic susceptibility of O3-exposed elastin, but mannitol afforded no protection. These findings indicate that the inhalation of O3 may contribute to lung disease by directly damaging elastin and by increasing its susceptibility to proteolysis, whereas NO2 probably damages lungs via alternative mechanisms.

  14. Differences in the Molecular Epidemiology and Antibiotic Susceptibility of Clostridium difficile Isolates in Pediatric and Adult Patients.

    PubMed

    Kociolek, Larry K; Gerding, Dale N; Osmolski, James R; Patel, Sameer J; Snydman, David R; McDermott, Laura A; Hecht, David W

    2016-08-01

    The rising incidence of Clostridium difficile infections (CDIs) in adults is partly related to the global spread of fluoroquinolone-resistant strains, namely, BI/NAP1/027. Although CDIs are also increasingly diagnosed in children, BI/NAP1/027 is relatively uncommon in children. Little is known about the antibiotic susceptibility of pediatric CDI isolates. C. difficile was cultured from tcdB-positive stools collected from children diagnosed with CDI between December 2012 and December 2013 at an academic children's hospital. CDI isolates were grouped by restriction endonuclease analysis (REA). MICs were measured by agar dilution method for 7 antibiotics. Susceptibility breakpoints were based on guidelines from CLSI and/or the European Committee on Antimicrobial Susceptibility Testing (EUCAST). MICs and REA groupings of C. difficile isolates from 74 adult patients (29 isolates underwent REA) from a temporally and geographically similar adult cohort were compared to those of pediatric isolates. Among 122 pediatric and 74 adult isolates, respectively, the rates of resistance were as follows: metronidazole, 0% and 0%; vancomycin, 0% and 8% (P = 0.003); rifaximin, 1.6% and 6.7% (P = 0.11); clindamycin, 18.9% and 25.3% (P = 0.29); and moxifloxacin, 2.5% and 36% (P = <0.0001). Only 1 of 122 (0.8%) BI/NAP1/027 isolates was identified among the children, compared to 9 of 29 (31%) isolates identified among the adults (P = <0.0001). The 3 moxifloxacin-resistant pediatric isolates were of REA groups BI and CF and a nonspecific group. The 2 rifaximin-resistant pediatric isolates were of REA groups DH and Y. The 21 clindamycin-resistant pediatric isolates were distributed among 9 REA groups (groups A, CF, DH, G, L, M, and Y and 2 unique nonspecific REA groups). These data suggest that a diverse array of relatively antibiotic-susceptible C. difficile strains predominate in a cohort of children with CDI compared to adults. Copyright © 2016, American Society for Microbiology. All

  15. Does reactivating a witnessed memory increase its susceptibility to impairment by subsequent misinformation?

    PubMed

    Rindal, Eric J; DeFranco, Rachel M; Rich, Patrick R; Zaragoza, Maria S

    2016-10-01

    In a recent PNAS article, Chan and LaPaglia (2013) provided arguments and evidence to support the claim that reactivating a witnessed memory (by taking a test) renders the memory labile and susceptible to impairment by subsequent misinformation. In the current article, we argue that Chan and LaPaglia’s (2013) findings are open to alternative interpretations, and further test the hypothesis that reactivation increases a witnessed memory’s susceptibility to impairment. To this end, the current studies used a different set of materials and a different measure of memory impairment, the Modified Recognition Test (McCloskey & Zaragoza, 1985). In Experiment 1a, we established that our reactivation manipulation was effective by showing that we could replicate the well-established retrieval enhanced suggestibility effect with our materials. However, when we assessed potential impairment of the witnessed memory with the Modified Recognition Test (Experiments 1a and 1b), we failed to find evidence that reactivating the witnessed memory prior to misinformation impaired memory for the originally witnessed event. In Experiment 2, we replicated Chan and LaPaglia’s (2013) findings when we used their memory impairment measure (misinformation-free True/False Recognition Test) and showed why that test does not permit clear inferences about memory impairment. Collectively, the results showed that, although the reactivation manipulation increased susceptibility to suggestion (i.e., as evidenced by increased reporting of suggested misinformation), there was no evidence that reactivation through testing increased the original memory’s susceptibility to impairment.

  16. Dietary stress increases the susceptibility of Tribolium castaneum to Beauveria bassiana

    USDA-ARS?s Scientific Manuscript database

    Sanitation being an important component of chemical-free management of stored-products pests, the nutritional stress that results from a clean environment may prove advantageous to the use of microbial controls. Dietary stress by food deprivation or suboptimal diet increased susceptibility of the re...

  17. Not just little adults: candidemia epidemiology, molecular characterization, and antifungal susceptibility in neonatal and pediatric patients.

    PubMed

    Blyth, Christopher C; Chen, Sharon C A; Slavin, Monica A; Serena, Carol; Nguyen, Quoc; Marriott, Deborah; Ellis, David; Meyer, Wieland; Sorrell, Tania C

    2009-05-01

    The purpose of this work was to identify differences in incidence, risk factors, microbiology, treatment, and clinical outcome of candidemia in neonates, children, and adults that might impact on management. Cases of candidemia in Australia were identified prospectively by blood culture surveillance over 3 years. Episodes of candidemia in neonatal, pediatric, and adult age groups were analyzed and compared. Of 1005 incident cases, 33 occurred in neonates, 110 in children, and 862 in adults. The respective annual age-specific incidences were 4.4, 0.9, and 1.8 per 100,000 population. Prematurity and ICU admission were major risk factors in neonates. Hematologic malignancy and neutropenia were significantly more frequent in children than in neonates and adults. Diabetes, renal disease, hemodialysis, and recent surgery were more common in adults. Candidemia was attributed to a vascular access device in 58% of neonates, 70% of children, and 44% of adults. Candida albicans caused approximately 48% of cases in all of the age groups. Candida parapsilosis was significantly more common in neonates and children (42% and 38% vs 15%). Candida glabrata was infrequent in neonates and children (9% and 3% vs 17%). Significantly more isolates from children were susceptible to fluconazole compared with those from adults (95% vs 75%). Fluconazole-resistant candidal isolates were infrequent in all of the age groups. Neonates and children were more likely to receive amphotericin B compared with adults. Adults were more likely to receive fluconazole. Survival rates at 30 days were 78% in neonates, 90% in children, and 70% in adults. This study identifies significant differences in candidemia in neonates, children, and adults. Neonatologists and pediatricians must consider age-specific differences when interpreting adult studies and developing treatment and prevention guidelines.

  18. Deletion of nudB causes increased susceptibility to antifolates in Escherichia coli and Salmonella enterica.

    PubMed

    Li, Kun; Li, Ting; Yang, Shan-Shan; Wang, Xu-De; Gao, Lei-Xin; Wang, Rui-Qi; Gu, Jing; Zhang, Xian-En; Deng, Jiao-Yu

    2017-02-21

    Co-trimoxazole, a fixed-dose combination of sulfamethoxazole (SMX) and trimethoprim (TMP), has been used for the treatment of bacterial infections since the 1960s. Since it has long been assumed that the synergistic effects between SMX and TMP are the consequence of targeting 2 different enzymes of bacterial folate biosynthesis, 2 genes (pabB and nudB) involved in the folate biosynthesis of Escherichia coli were deleted, and their effects on the susceptibility to antifolates were tested. The results showed that the deletion of nudB resulted in a lag of growth in minimal medium, and increased susceptibility to both SMX and TMP. Moreover, deletion of nudB also greatly enhanced the bactericidal effect of TMP. To elucidate the mechanism of how the deletion of nudB affects the bacterial growth and susceptibility to antifolates, 7, 8-dihydroneopterin and 7, 8-dihydropteroate were supplemented into the growth medium. Although those metabolites could restore bacterial growth, they had no effect on the susceptibility to the antifolates. Reverse mutants of the nudB deletion strain were isolated to further study the mechanism of how the deletion of nudB affects the susceptibility to antifolates. Targeted sequencing and subsequent genetic studies revealed that the disruption of the tetrahydromonapterin biosynthesis pathway could reverse the phenotype caused by the nudB deletion. Meanwhile, overexpression of folM could also lead to increased susceptibility to both SMX and TMP. These data suggested that the deletion of nudB resulted in the excess production of tetrahydromonapterin, which then caused the increased susceptibility to antifolates. In addition, we found that the deletion of nudB also resulted in the increased susceptibility to both SMX and TMP in Salmonella enterica Since dihydroneopterin triphosphate hydrolase is an important component of bacterial folate biosynthesis and the tetrahydromonapterin biosynthesis pathway also exists in a variety of bacteria, it will be

  19. Prenatal Dexamethasone Exposure Increases the Susceptibility to Autoimmunity in Offspring Rats by Epigenetic Programing of Glucocorticoid Receptor.

    PubMed

    Sun, Yanhong; Wan, Xiaoyan; Ouyang, Juan; Xie, Renfeng; Wang, Xueping; Chen, Peisong

    2016-01-01

    Objective. Prenatal glucocorticoids (GC) can induce long term effects on offspring health. However, reports and related studies regarding the prolonged effects of prenatal GC on the development of autoimmunity are limited. Here, we aimed to explore the immunological effects of dexamethasone (DEX) exposure on young adults and whether glucocorticoid receptor (GR) is involved in this process. Methods. Wistar rats were given DEX during pregnancy. Susceptibility to autoimmunity in offspring was assessed using experimental autoimmune encephalomyelitis (EAE) and adjuvant-induced arthritis (AIA) animal models. To reveal the possible mechanism, glucocorticoid response, GR expression, and methylation status were measured in peripheral blood mononuclear cells (PBMCs). Results. Our results showed that the DEX-treated rats had greater susceptibility to EAE (100% versus 62.5%, P < 0.05) and AIA (63.6% versus 0%, P < 0.05) than saline control group. Glucocorticoid response and GR expression were decreased in DEX rats. Significant difference was also found in the methylation levels of GR exon 1-10 to exon 1-11 region. Conclusions. Prenatal DEX administration increases the susceptibility to autoimmune diseases, which is potentially mediated by programming GR methylation status and glucocorticoid sensitivity.

  20. Prenatal Dexamethasone Exposure Increases the Susceptibility to Autoimmunity in Offspring Rats by Epigenetic Programing of Glucocorticoid Receptor

    PubMed Central

    Sun, Yanhong; Ouyang, Juan; Xie, Renfeng; Wang, Xueping

    2016-01-01

    Objective. Prenatal glucocorticoids (GC) can induce long term effects on offspring health. However, reports and related studies regarding the prolonged effects of prenatal GC on the development of autoimmunity are limited. Here, we aimed to explore the immunological effects of dexamethasone (DEX) exposure on young adults and whether glucocorticoid receptor (GR) is involved in this process. Methods. Wistar rats were given DEX during pregnancy. Susceptibility to autoimmunity in offspring was assessed using experimental autoimmune encephalomyelitis (EAE) and adjuvant-induced arthritis (AIA) animal models. To reveal the possible mechanism, glucocorticoid response, GR expression, and methylation status were measured in peripheral blood mononuclear cells (PBMCs). Results. Our results showed that the DEX-treated rats had greater susceptibility to EAE (100% versus 62.5%, P < 0.05) and AIA (63.6% versus 0%, P < 0.05) than saline control group. Glucocorticoid response and GR expression were decreased in DEX rats. Significant difference was also found in the methylation levels of GR exon 1-10 to exon 1-11 region. Conclusions. Prenatal DEX administration increases the susceptibility to autoimmune diseases, which is potentially mediated by programming GR methylation status and glucocorticoid sensitivity. PMID:28078304

  1. Susceptibility of cat fleas (Siphonaptera: Pulicidae) to fipronil and imidacloprid using adult and larval bioassays.

    PubMed

    Rust, M K; Vetter, R; Denholm, I; Blagburn, B; Williamson, M S; Kopp, S; Coleman, G; Hostetler, J; Davis, W; Mencke, N; Rees, R; Foit, S; Tetzner, K

    2014-05-01

    The monitoring of the susceptibility offleas to insecticides has typically been conducted by exposing adults on treated surfaces. Other methods such as topical applications of insecticides to adults and larval bioassays on treated rearing media have been developed. Unfortunately, baseline responses of susceptible strains of cat flea, Ctenocephalides felis (Bouchè), except for imidacloprid, have not been determined for all on-animal therapies and new classes of chemistry now being used. However, the relationship between adult and larval bioassays of fleas has not been previously investigated. The adult and larval bioassays of fipronil and imidacloprid were compared for both field-collected isolates and laboratory strains. Adult topical bioassays of fipronil and imidacloprid to laboratory strains and field-collected isolates demonstrated that LD50s of fipronil and imidacloprid ranged from 0.11 to 0.40 nanograms per flea and 0.02 to 0.18 nanograms per flea, respectively. Resistance ratios for fipronil and imidacloprid ranged from 0.11 to 2.21. Based on the larval bioassay published for imidacloprid, a larval bioassay was established for fipronil and reported in this article. The ranges of the LC50s of fipronil and imidacloprid in the larval rearing media were 0.07-0.16 and 0.11-0.21 ppm, respectively. Resistance ratios for adult and larval bioassays ranged from 0.11 to 2.2 and 0.58 to 1.75, respectively. Both adult and larval bioassays provided similar patterns for fipronil and imidacloprid. Although the adult bioassays permitted a more precise dosage applied, the larval bioassays allowed for testing isolates without the need to maintain on synthetic or natural hosts.

  2. Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation.

    PubMed

    Sahay, Amar; Scobie, Kimberly N; Hill, Alexis S; O'Carroll, Colin M; Kheirbek, Mazen A; Burghardt, Nesha S; Fenton, André A; Dranovsky, Alex; Hen, René

    2011-04-28

    Adult hippocampal neurogenesis is a unique form of neural circuit plasticity that results in the generation of new neurons in the dentate gyrus throughout life. Neurons that arise in adults (adult-born neurons) show heightened synaptic plasticity during their maturation and can account for up to ten per cent of the entire granule cell population. Moreover, levels of adult hippocampal neurogenesis are increased by interventions that are associated with beneficial effects on cognition and mood, such as learning, environmental enrichment, exercise and chronic treatment with antidepressants. Together, these properties of adult neurogenesis indicate that this process could be harnessed to improve hippocampal functions. However, despite a substantial number of studies demonstrating that adult-born neurons are necessary for mediating specific cognitive functions, as well as some of the behavioural effects of antidepressants, it is unknown whether an increase in adult hippocampal neurogenesis is sufficient to improve cognition and mood. Here we show that inducible genetic expansion of the population of adult-born neurons through enhancing their survival improves performance in a specific cognitive task in which two similar contexts need to be distinguished. Mice with increased adult hippocampal neurogenesis show normal object recognition, spatial learning, contextual fear conditioning and extinction learning but are more efficient in differentiating between overlapping contextual representations, which is indicative of enhanced pattern separation. Furthermore, stimulation of adult hippocampal neurogenesis, when combined with an intervention such as voluntary exercise, produces a robust increase in exploratory behaviour. However, increasing adult hippocampal neurogenesis alone does not produce a behavioural response like that induced by anxiolytic agents or antidepressants. Together, our findings suggest that strategies that are designed to increase adult hippocampal

  3. Varicella susceptibility and vaccine use among young adults enlisting in the United States Navy.

    PubMed

    Ryan, Margaret A K; Smith, Tyler C; Honner, William K; Gray, Gregory C

    2003-01-01

    Primary varicella infection, or chicken pox, is a threat to all young adults who join the United States (U.S.) military if they fail to develop immunity prior to enlistment. Historically, outbreaks of chicken pox have caused marked morbidity and impaired military readiness. In December 1996, the U.S. Navy began performing serologic testing for varicella among all new recruits, and vaccinating those found to be sero-negative. We evaluated results of the screening program in its first 4 years, and used multivariable logistic regression modeling to describe factors associated with varicella susceptibility. Cases of chicken pox were tracked among all military services before and after program implementation. More than 190,000 young adults enlisted in the U.S. Navy between 1997 and 2000. Recruits originated from all 50 states and several foreign countries; 84% were male, and their average age was 19 years. Seven percent were found to be susceptible (sero-negative) to varicella. In multivariable modeling, race/ethnicity was associated with susceptibility, but age, gender, and home state were not. The overall incidence of chicken pox in the Navy was reduced by more than 80% after initiation of the screening-vaccination program. A successful varicella screening-vaccination program has been implemented in the U.S. Navy. Results of serologic screening undertaken on this large number of young adults may be useful in tracking the changing epidemiology of varicella in the general population in the post-vaccine era.

  4. Gestational ketogenic diet programs brain structure and susceptibility to depression & anxiety in the adult mouse offspring.

    PubMed

    Sussman, Dafna; Germann, Jurgen; Henkelman, Mark

    2015-02-01

    The ketogenic diet (KD) has seen an increase in popularity for clinical and non-clinical purposes, leading to rise in concern about the diet's impact on following generations. The KD is known to have a neurological effect, suggesting that exposure to it during prenatal brain development may alter neuro-anatomy. Studies have also indicated that the KD has an anti-depressant effect on the consumer. However, it is unclear whether any neuro-anatomical and/or behavioral changes would occur in the offspring and persist into adulthood. To fill this knowledge gap we assessed the brain morphology and behavior of 8-week-old young-adult CD-1 mice, who were exposed to the KD in utero, and were fed only a standard-diet (SD) in postnatal life. Standardized neuro-behavior tests included the Open-Field, Forced-Swim, and Exercise Wheel tests, and were followed by post-mortem Magnetic Resonance Imaging (MRI) to assess brain anatomy. The adult KD offspring exhibit reduced susceptibility to anxiety and depression, and elevated physical activity level when compared with controls exposed to the SD both in utero and postnatally. Many neuro-anatomical differences exist between the KD offspring and controls, including, for example, a cerebellar volumetric enlargement by 4.8%, a hypothalamic reduction by 1.39%, and a corpus callosum reduction by 4.77%, as computed relative to total brain volume. These results suggest that prenatal exposure to the KD programs the offspring neuro-anatomy and influences their behavior in adulthood.

  5. Gestational ketogenic diet programs brain structure and susceptibility to depression & anxiety in the adult mouse offspring

    PubMed Central

    Sussman, Dafna; Germann, Jurgen; Henkelman, Mark

    2015-01-01

    Introduction The ketogenic diet (KD) has seen an increase in popularity for clinical and non-clinical purposes, leading to rise in concern about the diet's impact on following generations. The KD is known to have a neurological effect, suggesting that exposure to it during prenatal brain development may alter neuro-anatomy. Studies have also indicated that the KD has an anti-depressant effect on the consumer. However, it is unclear whether any neuro-anatomical and/or behavioral changes would occur in the offspring and persist into adulthood. Methods To fill this knowledge gap we assessed the brain morphology and behavior of 8-week-old young-adult CD-1 mice, who were exposed to the KD in utero, and were fed only a standard-diet (SD) in postnatal life. Standardized neuro-behavior tests included the Open-Field, Forced-Swim, and Exercise Wheel tests, and were followed by post-mortem Magnetic Resonance Imaging (MRI) to assess brain anatomy. Results The adult KD offspring exhibit reduced susceptibility to anxiety and depression, and elevated physical activity level when compared with controls exposed to the SD both in utero and postnatally. Many neuro-anatomical differences exist between the KD offspring and controls, including, for example, a cerebellar volumetric enlargement by 4.8%, a hypothalamic reduction by 1.39%, and a corpus callosum reduction by 4.77%, as computed relative to total brain volume. Conclusions These results suggest that prenatal exposure to the KD programs the offspring neuro-anatomy and influences their behavior in adulthood. PMID:25642385

  6. Repeated restraint stress increases seizure susceptibility by activation of hippocampal endoplasmic reticulum stress.

    PubMed

    Zhu, Xinjian; Dong, Jingde; Xia, Zhengrong; Zhang, Aifeng; Chao, Jie; Yao, Honghong

    2017-09-05

    A growing body of evidence suggests that stress triggers a variety of pathophysiological responses. Recent studies show that stress produces enduring effects on structure and function of hippocampus, which is one of the most important structures involved in epilepsy. In the present study, we determined the effect of repeated restraint stress exposure on the susceptibility of pentylenetetrazole (PTZ)-induced seizures and the possible mechanisms involved using a rodent model. Our results show that mice subjected to repeated restraint stress exhibited shorter latency to PTZ-induced tonic-clonic seizures and higher seizure severity, suggesting chronic restraint stress increases seizure susceptibility. Following repeated restraint stress, we observed an increased level of endoplasmic reticulum (ER) stress as well as oxidative stress in the hippocampus. Moreover, our results show that chronic restraint stress exposure causes neuron loss in the hippocampus. Inhibition of ER stress with chemical chaperone, tauroursodeoxycholic acid (TUDCA), however, protects against chronic restraint stress-induced neuron loss, suggesting repeated restraint stress-induced neuronal degeneration is dependent on ER stress activation. On the other hand, inhibition of ER stress with TUDCA suppresses restraint stress-induced seizure susceptibility. Taken together, these results indicate that repeated restraint stress increases seizure susceptibility by activation of hippocampal ER stress and ER stress mediated oxidative stress and neurodegeneration. Thus, attenuating ER stress may serve as a potential therapeutic strategy targeted to block stress-induced seizure activities. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Westernization of Chinese adults and increased subclinical atherosclerosis.

    PubMed

    Woo, K S; Chook, P; Raitakari, O T; McQuillan, B; Feng, J Z; Celermajer, D S

    1999-10-01

    Cardiovascular event rates are much lower in China compared with developed countries. "Westernization" of diet and lifestyle in the Chinese, however, may lead to an increased prevalence of atherosclerosis-related diseases. Because carotid intima-media thickness (IMT) is a marker of subclinical atherosclerosis, we examined IMT and vascular risk profile in community-based groups of rural Chinese, Westernized urban Chinese, and urban whites. Mean IMT of the common carotid artery was measured in 348 healthy adults, aged 42+/-13 years (range 21 to 71 years); 116 subjects from rural China, 116 urban Chinese subjects living in Hong Kong or in Australia, and 116 urban Caucasians living in Australia. These 3 groups were matched for age, sex, and cigarette smoke exposure. Urban Chinese subjects had slightly better risk factor profile (higher HDL-cholesterol and lower blood pressure) compared with rural Chinese subjects. Despite this, however, the mean IMT was lowest in rural Chinese (0.50+/-0.10 mm), intermediate in urban Chinese (0.56+/-0.12 mm), and highest in urban whites (0.64+/-0.13 mm) (P<0.001 for comparisons between all groups). These differences in IMT were not altered after adjustment for the major traditional cardiovascular risk factors (serum lipids, smoking, and blood pressure or for body mass index). The influence of vascular risk factors on atherosclerosis between urban versus rural Chinese subjects was studied by multivariate regression models and by comparing the steepness of regression slopes between risk factors and IMT in the subject groups. The effects of smoking, HDL-cholesterol, and triglycerides on IMT were significantly greater in the urban compared with the rural Chinese (P<0.01). These data suggest that Westernization of Chinese subjects is associated with greater susceptibility to the pro-atherogenic effects of traditional vascular risk factors, such as lipids and smoking, and with evidence of increased IMT as a marker of subclinical

  8. Diabetes Mellitus and Increased Tuberculosis Susceptibility: The Role of Short-Chain Fatty Acids.

    PubMed

    Lachmandas, Ekta; van den Heuvel, Corina N A M; Damen, Michelle S M A; Cleophas, Maartje C P; Netea, Mihai G; van Crevel, Reinout

    2016-01-01

    Type 2 diabetes mellitus confers a threefold increased risk for tuberculosis, but the underlying immunological mechanisms are still largely unknown. Possible mediators of this increased susceptibility are short-chain fatty acids, levels of which have been shown to be altered in individuals with diabetes. We examined the influence of physiological concentrations of butyrate on cytokine responses to Mycobacterium tuberculosis (Mtb) in human peripheral blood mononuclear cells (PBMCs). Butyrate decreased Mtb-induced proinflammatory cytokine responses, while it increased production of IL-10. This anti-inflammatory effect was independent of butyrate's well-characterised inhibition of HDAC activity and was not accompanied by changes in Toll-like receptor signalling pathways, the eicosanoid pathway, or cellular metabolism. In contrast blocking IL-10 activity reversed the effects of butyrate on Mtb-induced inflammation. Alteration of the gut microbiota, thereby increasing butyrate concentrations, can reduce insulin resistance and obesity, but further studies are needed to determine how this affects susceptibility to tuberculosis.

  9. Cardiac muscle ring finger-1 increases susceptibility to heart failure in vivo

    PubMed Central

    Willis, Monte S.; Schisler, Jonathan C.; Li, Luge; Rodríguez, Jessica E.; Hilliard, Eleanor G.; Charles, Peter C.; Patterson, Cam

    2009-01-01

    Muscle ring finger-1 (MuRF1) is a muscle-specific protein implicated in the regulation of cardiac myocyte size and contractility. MuRF2, a closely related family member, redundantly interacts with protein substrates, and hetero-dimerizes with MuRF1. Mice lacking either MuRF1 or MuRF2 are phenotypically normal whereas mice lacking both proteins develop a spontaneous cardiac and skeletal muscle hypertrophy indicating cooperative control of muscle mass by MuRF1 and MuRF2. In order to identify the unique role that MuRF1 plays in regulating cardiac hypertrophy in vivo, we created transgenic mice expressing increased amounts of cardiac MuRF1. Adult MuRF1 transgenic (Tg+) hearts exhibited a non-progressive thinning of the left ventricular wall and a concomitant decrease in cardiac function. Experimental induction of cardiac hypertrophy by trans-aortic constriction (TAC) induced rapid failure of MuRF1 Tg+ hearts. Microarray analysis identified that the levels of genes associated with metabolism (and in particular mitochondrial processes) were significantly altered in MuRF1 Tg+ hearts, both at baseline and during the development of cardiac hypertrophy. Surprisingly, ATP levels in MuRF1 Tg+ mice did not differ from wild type mice despite the depressed contractility following TAC. In comparing the level and activity of creatine kinase (CK) between wild type and MuRF1 Tg+ hearts we found that mCK and CK-M/B protein levels were unaffected in MuRF1 Tg+ hearts, however total CK activity was significantly inhibited. We conclude that increased expression of cardiac MuRF1 results in a broad disruption of primary metabolic functions, including alterations in CK activity that leads to increased susceptibility to heart failure following TAC. This study demonstrates for the first time a role for MuRF1 in the regulation of cardiac energetics in vivo. PMID:19498199

  10. The Type I Interferon Response Determines Differences in Choroid Plexus Susceptibility between Newborns and Adults in Herpes Simplex Virus Encephalitis.

    PubMed

    Wilcox, Douglas R; Folmsbee, Stephen S; Muller, William J; Longnecker, Richard

    2016-04-12

    Newborns are significantly more susceptible to severe viral encephalitis than adults, with differences in the host response to infection implicated as a major factor. However, the specific host signaling pathways responsible for differences in susceptibility and neurologic morbidity have remained unknown. In a murine model of HSV encephalitis, we demonstrated that the choroid plexus (CP) is susceptible to herpes simplex virus 1 (HSV-1) early in infection of the newborn but not the adult brain. We confirmed susceptibility of the CP to HSV infection in a human case of newborn HSV encephalitis. We investigated components of the type I interferon (IFN) response in the murine brain that might account for differences in cell susceptibility and found that newborns have a dampened interferon response and significantly lower basal levels of the alpha/beta interferon (IFN-α/β) receptor (IFNAR) than do adults. To test the contribution of IFNAR to restricting infection from the CP, we infected IFNAR knockout (KO) adult mice, which showed restored CP susceptibility to HSV-1 infection in the adult. Furthermore, reduced IFNAR levels did not account for differences we found in the basal levels of several other innate signaling proteins in the wild-type newborn and the adult, including protein kinase R (PKR), that suggested specific regulation of innate immunity in the developing brain. Viral targeting of the CP, a region of the brain that plays a critical role in neurodevelopment, provides a link between newborn susceptibility to HSV and long-term neurologic morbidity among survivors of newborn HSV encephalitis. Compared to adults, newborns are significantly more susceptible to severe disease following HSV infection. Over half of newborn HSV infections result in disseminated disease or encephalitis, with long-term neurologic morbidity in 2/3 of encephalitis survivors. We investigated differences in host cell susceptibility between newborns and adults that contribute to severe

  11. Adolescent but not adult-born neurons are critical for susceptibility to chronic social defeat

    PubMed Central

    Kirshenbaum, Greer S.; Lieberman, Sophie R.; Briner, Tamara J.; Leonardo, E. David; Dranovsky, Alex

    2014-01-01

    Recent evidence implicates adult hippocampal neurogenesis in regulating behavioral and physiologic responses to stress. Hippocampal neurogenesis occurs across the lifespan, however the rate of cell birth is up to 300% higher in adolescent mice compared to adults. Adolescence is a sensitive period in development where emotional circuitry and stress reactivity undergo plasticity establishing life-long set points. Therefore neurogenesis occurring during adolescence may be particularly important for emotional behavior. However, little is known about the function of hippocampal neurons born during adolescence. In order to assess the contribution of neurons born in adolescence to the adult stress response and depression-related behavior, we transiently reduced cell proliferation either during adolescence, or during adulthood in GFAP-Tk mice. We found that the intervention in adolescence did not change adult baseline behavioral response in the forced swim test, sucrose preference test or social affiliation test, and did not change adult corticosterone responses to an acute stressor. However following chronic social defeat, adult mice with reduced adolescent neurogenesis showed a resilient phenotype. A similar transient reduction in adult neurogenesis did not affect depression-like behaviors or stress induced corticosterone. Our study demonstrates that hippocampal neurons born during adolescence, but not in adulthood are important to confer susceptibility to chronic social defeat. PMID:25221485

  12. Differential Outcomes of Adult Education on Adult Learners' Increase in Social Inclusion

    ERIC Educational Resources Information Center

    de Greef, Maurice; Verté, Dominique; Segers, Mien

    2015-01-01

    To date a significant share of the European population can be considered at risk of social exclusion. It has been argued that adult education programmes are a powerful tool to support vulnerable adults increasing their social inclusion. This study aims to answer the question if and which subgroups of vulnerable adults experience an increase in…

  13. Differential Outcomes of Adult Education on Adult Learners' Increase in Social Inclusion

    ERIC Educational Resources Information Center

    de Greef, Maurice; Verté, Dominique; Segers, Mien

    2015-01-01

    To date a significant share of the European population can be considered at risk of social exclusion. It has been argued that adult education programmes are a powerful tool to support vulnerable adults increasing their social inclusion. This study aims to answer the question if and which subgroups of vulnerable adults experience an increase in…

  14. Increased susceptibility of aging gastric mucosa to injury: the mechanisms and clinical implications.

    PubMed

    Tarnawski, Andrzej S; Ahluwalia, Amrita; Jones, Michael K

    2014-04-28

    This review updates the current views on aging gastric mucosa and the mechanisms of its increased susceptibility to injury. Experimental and clinical studies indicate that gastric mucosa of aging individuals-"aging gastropathy"-has prominent structural and functional abnormalities vs young gastric mucosa. Some of these abnormalities include a partial atrophy of gastric glands, impaired mucosal defense (reduced bicarbonate and prostaglandin generation, decreased sensory innervation), increased susceptibility to injury by a variety of damaging agents such as ethanol, aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), impaired healing of injury and reduced therapeutic efficacy of ulcer-healing drugs. Detailed analysis of the above changes indicates that the following events occur in aging gastric mucosa: reduced mucosal blood flow and impaired oxygen delivery cause hypoxia, which leads to activation of the early growth response-1 (egr-1) transcription factor. Activation of egr-1, in turn, upregulates the dual specificity phosphatase, phosphatase and tensin homologue deleted on chromosome ten (PTEN) resulting in activation of pro-apoptotic caspase-3 and caspase-9 and reduced expression of the anti-apoptosis protein, survivin. The imbalance between pro- and anti-apoptosis mediators results in increased apoptosis and increased susceptibility to injury. This paradigm has human relevance since increased expression of PTEN and reduced expression of survivin were demonstrated in gastric mucosa of aging individuals. Other potential mechanisms operating in aging gastric mucosa include reduced telomerase activity, increase in replicative cellular senescence, and reduced expression of vascular endothelial growth factor and importin-α-a nuclear transport protein essential for transport of transcription factors to nucleus. Aging gastropathy is an important and clinically relevant issue because of: (1) an aging world population due to prolonged life span; (2) older

  15. Susceptibility to traumatic stress sensitizes the dopaminergic response to cocaine and increases motivation for cocaine.

    PubMed

    Brodnik, Zachary D; Black, Emily M; Clark, Meagan J; Kornsey, Kristen N; Snyder, Nathaniel W; España, Rodrigo A

    2017-10-01

    Patients with post-traumatic stress disorder have a heightened vulnerability to developing substance use disorders; however, the biological underpinnings of this vulnerability remain unresolved. We used the predator odor stress model of post-traumatic stress disorder with segregation of subjects as susceptible or resilient based on elevated plus maze behavior and context avoidance. We then determined behavioral and neurochemical differences across susceptible, resilient, and control populations using a panel of behavioral and neurochemical assays. Susceptible subjects showed a significant increase in the motoric and dopaminergic effects of cocaine, and this corresponded with heightened motivation to self-administer cocaine. Resilient subjects did not show differences in the motoric effects of cocaine, in dopamine signaling in vivo, or in any measure of cocaine self-administration. Nonetheless, we found that these animals displayed elevations in both the dopamine release-promoting effects of cocaine and dopamine autoreceptor sensitivity ex vivo. Our results suggest that the experience of traumatic stress may produce alterations in dopamine systems that drive elevations in cocaine self-administration behavior in susceptible subjects, but may also produce both active and passive forms of resilience that function to prevent gross changes in cocaine's reinforcing efficacy in resilient subjects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Larval application of sodium channel homologous dsRNA restores pyrethroid insecticide susceptibility in a resistant adult mosquito population.

    PubMed

    Bona, Ana Caroline Dalla; Chitolina, Rodrigo Faitta; Fermino, Marise Lopes; de Castro Poncio, Lisiane; Weiss, Avital; Lima, José Bento Pereira; Paldi, Nitzan; Bernardes, Emerson Soares; Henen, Jonathan; Maori, Eyal

    2016-07-14

    Mosquitoes host and pass on to humans a variety of disease-causing pathogens such as infectious viruses and other parasitic microorganisms. The emergence and spread of insecticide resistance is threatening the effectiveness of current control measures for common mosquito vector borne diseases, such as malaria, dengue and Zika. Therefore, the emerging resistance to the widely used pyrethroid insecticides is an alarming problem for public health. Herein we demonstrated the use of RNA interference (RNAi) to increase susceptibility of adult mosquitoes to a widely used pyrethroid insecticide. Experiments were performed on a field-collected pyrethroid resistant strain of Ae. aegypti (Rio de Janeiro; RJ). Larvae from the resistant Ae. aegypti population were soaked with double-stranded RNAs (dsRNAs) that correspond either to voltage-gate sodium channel (VGSC), P-glycoprotein, or P450 detoxification genes and reared to adulthood. Adult mortality rates in the presence of various Deltamethrin pyrethroid concentrations were used to assess mosquito insecticide susceptibility. We characterized the RJ Ae. aegypti strain with regard to its level of resistance to a pyrethroid insecticide and found that it was approximately 6 times more resistant to Deltamethrin compared to the laboratory Rockefeller strain. The RJ strain displayed a higher frequency of Val1016Ile and Phe1534Cys substitutions of the VGSC gene. The resistant strain also displayed a higher basal expression level of VGSC compared to the Rockefeller strain. When dsRNA-treated mosquitoes were subjected to a standard pyrethroid contact bioassay, only dsRNA targeting VGSC increased the adult mortality of the pyrethroid resistant strain. The dsRNA treatment proved effective in increasing adult mosquito susceptibility over a range of pyrethroid concentrations and these results were associated with dsRNA-specific small interfering RNAs in treated adults, and the corresponding specific down regulation of VGSC gene expression

  17. Increased susceptibility to Trichuris muris infection and exacerbation of colitis in Mdr1a-/- mice

    PubMed Central

    Bhardwaj, Ekta K; Else, Kathryn J; Rogan, Michael T; Warhurst, Geoffrey

    2014-01-01

    AIM: To investigate the influence of Trichuris muris (T. muris) infection in a mouse model of genetic susceptibility to inflammatory bowel disease, Mdr1a-/-. METHODS: Mdr1a-/- mice were housed under specific pathogen free conditions to slow the development of colitis and compared to congenic FVB controls. Mice were infected with approximately 200 embryonated ova from T. muris and assessed for worm burden and histological and functional markers of gut inflammation on day 19 post infection. RESULTS: Mdr1a-/- mice exhibited a marked increase in susceptibility to T. muris infection with a 10-fold increase in colonic worm count by day 19 pi compared to FVB controls. Prior to infection, Mdr1a-/- exhibited low-level mucosal inflammation with evidence of an enhanced Th1 environment. T. muris infection accelerated the progression of colitis in Mdr1a-/- as evidenced by marked increases in several indicators including histological damage score, mucosal CD4+ T-cell and DC infiltration and dramatically increased production of pro-inflammatory cytokines. CONCLUSION: These data provide further evidence of the complex interaction between T. muris and an inflammatory bowel disease (IBD)-susceptible host which may have relevance to the application of helminth therapy in the treatment of human IBD. PMID:24587657

  18. Increased susceptibility to Trichuris muris infection and exacerbation of colitis in Mdr1a-/- mice.

    PubMed

    Bhardwaj, Ekta K; Else, Kathryn J; Rogan, Michael T; Warhurst, Geoffrey

    2014-02-21

    To investigate the influence of Trichuris muris (T. muris) infection in a mouse model of genetic susceptibility to inflammatory bowel disease, Mdr1a-/-. Mdr1a-/- mice were housed under specific pathogen free conditions to slow the development of colitis and compared to congenic FVB controls. Mice were infected with approximately 200 embryonated ova from T. muris and assessed for worm burden and histological and functional markers of gut inflammation on day 19 post infection. Mdr1a-/- mice exhibited a marked increase in susceptibility to T. muris infection with a 10-fold increase in colonic worm count by day 19 pi compared to FVB controls. Prior to infection, Mdr1a-/- exhibited low-level mucosal inflammation with evidence of an enhanced Th1 environment. T. muris infection accelerated the progression of colitis in Mdr1a-/- as evidenced by marked increases in several indicators including histological damage score, mucosal CD⁺ T-cell and DC infiltration and dramatically increased production of pro-inflammatory cytokines. These data provide further evidence of the complex interaction between T. muris and an inflammatory bowel disease (IBD)-susceptible host which may have relevance to the application of helminth therapy in the treatment of human IBD.

  19. The incidence of melanoma is increasing in the susceptible young Australian population.

    PubMed

    Czarnecki, Douglas

    2014-09-01

    The number of melanomas removed from Australians is increasing. Despite this, it has been reported that the incidence of melanoma is decreasing in the young Australian population. However, the denominator for these estimates includes individuals at low risk of melanoma, and the proportion of such individuals has changed over recent decades due to immigration. In this study, the incidence was calculated for the susceptible young population. Data from the Australian Bureau of Statistics were analysed to determine the number of people younger than 30 years at low risk of developing melanoma in 1982 and 2009. Low risk people were defined as those born in Asia, the Pacific Islands, The Middle East, or Sub-Saharan Africa, or had parents born in these regions. There was a significant increase in the number of young Australians at low risk for melanoma. If these people are not included when calculating the crude rate of melanoma, the rate increased from 5.9 per 100,000 in 1982 to 6.3 in 2009. If the estimated number of young Maoris and young Aborigines is excluded from the susceptible population, the crude rate increased from 6.0 per 100,000 in 1982 to 6.8 in 2009. This is the first calculation of the rate of melanoma for the susceptible young Australian population.

  20. Larval stress alters dengue virus susceptibility in Aedes aegypti (L.) adult females.

    PubMed

    Kang, David S; Alcalay, Yehonatan; Lovin, Diane D; Cunningham, Joanne M; Eng, Matthew W; Chadee, Dave D; Severson, David W

    2017-10-01

    In addition to genetic history, environmental conditions during larval stages are critical to the development, success and phenotypic fate of the Aedes aegypti mosquito. In particular, previous studies have shown a strong genotype-by-environment component to adult mosquito body size in response to optimal vs stressed larval conditions. Here, we expand upon those results by investigating the effects of larval-stage crowding and nutritional limitation on the susceptibility of a recent field isolate of Aedes aegypti to dengue virus serotype-2. Interestingly, female mosquitoes from larvae subjected to a stressed regime exhibited significantly reduced susceptibility to disseminated dengue infection 14days post infection compared to those subjected to optimal regimes. Short term survivorship post-infected blood feeding was not significantly different. As with body size, dengue virus susceptibility of a mosquito population is determined by a combination of genetic and environmental factors and is likely maintained by balancing selection. Here, we provide evidence that under different environmental conditions, the innate immune response of field-reared mosquitoes exhibits a large range of phenotypic variability with regard to dengue virus susceptibility. Further, as with body size, our results suggest that mosquitoes reared under optimal laboratory conditions, as employed in all mosquito-pathogen studies to date, may not always be realistic proxies for natural populations. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Increased susceptibility to Salmonella infection in signal regulatory protein α-deficient mice.

    PubMed

    Li, Lin-Xi; Atif, Shaikh M; Schmiel, Shirdi E; Lee, Seung-Joo; McSorley, Stephen J

    2012-09-01

    Recent studies have shed light on the connection between elevated erythropoetin production/spleen erythropoiesis and increased susceptibility to Salmonella infection. In this article, we provide another mouse model, the SIRPα-deficient (Sirpα⁻/⁻) mouse, that manifests increased erythropoiesis as well as heightened susceptibility to Salmonella infection. Sirpα⁻/⁻ mice succumbed to systemic infection with attenuated Salmonella, possessing significantly higher bacterial loads in both the spleen and the liver. Moreover, Salmonella-specific Ab production and Ag-specific CD4 T cells were reduced in Sirpα⁻/⁻ mice compared with wild-type controls. To further characterize the potential mechanism underlying SIRPα-dependent Ag-specific CD4 T cell priming, we demonstrate that lack of SIRPα expression on dendritic cells results in less efficient Ag processing and presentation in vitro. Collectively, these findings demonstrate an indispensable role of SIRPα for protective immunity to Salmonella infection.

  2. Obesity-related abnormalities couple environmental triggers with genetic susceptibility in adult-onset T1D.

    PubMed

    Nguyen, K Hoa; Ande, Sudharsana R; Mishra, Suresh

    2016-01-29

    The incidence of adult-onset T1D in low-risk non-HLA type has increased several folds, whereas the contemporaneous incidence in high-risk HLA-type remains stable. Various factors behind this selective increase in T1D in young adults remain unclear. Obesity and its associated abnormalities appear to be an important determinant; however, the underlying mechanism involved is not understood. Recently, we have developed two novel transgenic obese mice models, Mito-Ob and m-Mito-Ob, by expressing a pleiotropic protein prohibitin (PHB) and a phospho mutant form of PHB (Y114F-PHB or m-PHB) from the aP2 gene promoter, respectively. Both mice models develop obesity in a sex-neutral manner, independent of diet; but obesity associated chronic low-grade inflammation and insulin resistance in a male sex-specific manner. Interestingly, on a high fat diet (HFD) only male m-Mito-Ob mice displayed marked mononuclear cell infiltration in pancreas and developed insulitis that mimic adult-onset T1D. Male Mito-Ob mice that share the metabolic phenotype of male m-Mito-Ob mice, and female m-Mito-Ob that harbor m-PHB similar to male m-Mito-Ob mice, did not develop insulitis. Thus, insulitis development in male m-Mito-Ob in response to HFD requires both, obesity-related abnormalities and m-PHB. Collectively, this data provides a proof-of-concept that obesity-associated abnormalities couple environmental triggers with genetic susceptibility in adult-onset T1D and reveals PHB as a potential susceptibility gene for T1D.

  3. Increased Susceptibility to Oxidative Death of Lymphocytes from Alzheimer Patients Correlates with Dementia Severity

    PubMed Central

    Ponce, Daniela P.; Salech, Felipe; SanMartin, Carol D.; Silva, Monica; Xiong, Chengjie; Roe, Catherine M.; Henriquez, Mauricio; Quest, Andrew F.; Behrens, Maria I.

    2015-01-01

    We previously reported on enhanced susceptibility to death of lymphocytes from Alzheimer’s disease (AD) patients when exposed to hydrogen peroxide (H2O2)-induced oxidative stress and an increased resistance to death in those of patients with a history of skin cancer. This is consistent with our hypothesis proposing that the cellular machinery controlling cell death is deregulated in opposite directions in Alzheimer’s disease (AD) and cancer, to explain the inverse association observed in epidemiological studies. Here we investigated whether the observed increased susceptibility correlates with the degree of dementia severity. Peripheral lymphocytes from 23 AD patients, classified using the Clinical Dementia Rating (CDR) into severe dementia (CDR 3, n=10) and mild-to-moderate dementia (CDR 1–2, n=13), and 15 healthy controls (HC) (CDR 0), were exposed to H2O2 for 20 hours. Lymphocyte death was determined by flow cytometry and propidium iodide staining. The greatest susceptibility to H2O2-induced death was observed for lymphocytes from severe dementia patients, whereas those with mild-to-moderate dementia exhibited intermediate values, compared to healthy controls. A significant increase in the apoptosis/necrosis ratio was found in AD patients. Poly (ADP-ribosyl) polymerase-1 (PARP-1) inhibition significantly protected from H2O2-induced death of lymphocytes, whereby a lower degree of protection was observed in severe AD patients. Moreover, inhibition of PARP-1 abolished the differences in apoptosis/necrosis ratios observed between the three groups of patients. These results support the notion that AD is a systemic disorder, whereby enhanced susceptibility to H2O2-induced death in peripheral lymphocytes correlates with dementia severity and enhanced death in AD patients is attributable to a PARP-dependent increase in the apoptosis/necrosis ratio. PMID:25274115

  4. Short-term secondhand smoke exposure decreases heart rate variability and increases arrhythmia susceptibility in mice.

    PubMed

    Chen, Chao-Yin; Chow, Drin; Chiamvimonvat, Nipavan; Glatter, Kathryn A; Li, Ning; He, Yuxia; Pinkerton, Kent E; Bonham, Ann C

    2008-08-01

    Exposure to secondhand smoke (SHS), a major indoor air pollutant, is linked to increased cardiovascular morbidity and mortality, including cardiac arrhythmias. However, the mechanisms underlying the epidemiological findings are not well understood. Impaired cardiac autonomic function, indexed by reduced heart rate variability (HRV), may represent an underlying cause. The present study takes advantage of well-defined short-term SHS exposure (3 days, 6 h/day) on HRV and the susceptibility to arrhythmia in mice. With the use of electrocardiograph telemetry recordings in conscious mice, HRV parameters in the time domain were measured during the night after each day of exposure and 24 h after 3 days of exposure to either SHS or filtered air. The susceptibility to arrhythmia was determined after 3 days of exposure. Exposure to a low concentration of SHS [total suspended particle (TSP), 2.4 +/- 3.2; and nicotine, 0.3 +/- 0.1 mg/m(3)] had no significant effect on HRV parameters. In contrast, the exposure to a higher but still environmentally relevant concentration of SHS (TSP, 30 +/- 1; and nicotine, 5 +/- 1 mg/m(3)) significantly reduced HRV starting after the first day of exposure and continuing 24 h after the last day of exposure. Moreover, the exposed mice showed a significant increase in ventricular arrhythmia susceptibility and atrioventricular block. The data suggest that SHS exposure decreased HRV beyond the exposure period and was associated with an increase in arrhythmia susceptibility. The data provide insights into possible mechanisms underlying documented increases in cardiovascular morbidity and mortality in humans exposed to SHS.

  5. 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...

  6. Increased Abundance of M Cells in the Gut Epithelium Dramatically Enhances Oral Prion Disease Susceptibility

    PubMed Central

    Sehgal, Anuj; Rios, Daniel

    2016-01-01

    Many natural prion diseases of humans and animals are considered to be acquired through oral consumption of contaminated food or pasture. Determining the route by which prions establish host infection will identify the important factors that influence oral prion disease susceptibility and to which intervention strategies can be developed. After exposure, the early accumulation and replication of prions within small intestinal Peyer’s patches is essential for the efficient spread of disease to the brain. To replicate within Peyer’s patches, the prions must first cross the gut epithelium. M cells are specialised epithelial cells within the epithelia covering Peyer’s patches that transcytose particulate antigens and microorganisms. M cell-development is dependent upon RANKL-RANK-signalling, and mice in which RANK is deleted only in the gut epithelium completely lack M cells. In the specific absence of M cells in these mice, the accumulation of prions within Peyer’s patches and the spread of disease to the brain was blocked, demonstrating a critical role for M cells in the initial transfer of prions across the gut epithelium in order to establish host infection. Since pathogens, inflammatory stimuli and aging can modify M cell-density in the gut, these factors may also influence oral prion disease susceptibility. Mice were therefore treated with RANKL to enhance M cell density in the gut. We show that prion uptake from the gut lumen was enhanced in RANKL-treated mice, resulting in shortened survival times and increased disease susceptibility, equivalent to a 10-fold higher infectious titre of prions. Together these data demonstrate that M cells are the critical gatekeepers of oral prion infection, whose density in the gut epithelium directly limits or enhances disease susceptibility. Our data suggest that factors which alter M cell-density in the gut epithelium may be important risk factors which influence host susceptibility to orally acquired prion diseases

  7. Increased Abundance of M Cells in the Gut Epithelium Dramatically Enhances Oral Prion Disease Susceptibility.

    PubMed

    Donaldson, David S; Sehgal, Anuj; Rios, Daniel; Williams, Ifor R; Mabbott, Neil A

    2016-12-01

    Many natural prion diseases of humans and animals are considered to be acquired through oral consumption of contaminated food or pasture. Determining the route by which prions establish host infection will identify the important factors that influence oral prion disease susceptibility and to which intervention strategies can be developed. After exposure, the early accumulation and replication of prions within small intestinal Peyer's patches is essential for the efficient spread of disease to the brain. To replicate within Peyer's patches, the prions must first cross the gut epithelium. M cells are specialised epithelial cells within the epithelia covering Peyer's patches that transcytose particulate antigens and microorganisms. M cell-development is dependent upon RANKL-RANK-signalling, and mice in which RANK is deleted only in the gut epithelium completely lack M cells. In the specific absence of M cells in these mice, the accumulation of prions within Peyer's patches and the spread of disease to the brain was blocked, demonstrating a critical role for M cells in the initial transfer of prions across the gut epithelium in order to establish host infection. Since pathogens, inflammatory stimuli and aging can modify M cell-density in the gut, these factors may also influence oral prion disease susceptibility. Mice were therefore treated with RANKL to enhance M cell density in the gut. We show that prion uptake from the gut lumen was enhanced in RANKL-treated mice, resulting in shortened survival times and increased disease susceptibility, equivalent to a 10-fold higher infectious titre of prions. Together these data demonstrate that M cells are the critical gatekeepers of oral prion infection, whose density in the gut epithelium directly limits or enhances disease susceptibility. Our data suggest that factors which alter M cell-density in the gut epithelium may be important risk factors which influence host susceptibility to orally acquired prion diseases.

  8. CREB1 gene polymorphisms combined with environmental risk factors increase susceptibility to major depressive disorder (MDD).

    PubMed

    Wang, Peng; Yang, Yanjie; Yang, Xiuxian; Qiu, Xiaohui; Qiao, Zhengxue; Wang, Lin; Zhu, Xiongzhao; Sui, Hong; Ma, Jingsong

    2015-01-01

    Major depressive disorder (MDD) is one of the most severe psychiatric disorders. The objective of this study was to explore the effects of CREB1 gene polymorphisms on risk of developing MDD and the joint effects of gene-environment interactions. Genotyping was performed by Taqman allelic discrimination assay among 586 patients and 586 healthy controls. A significant impact on rs6740584 genotype distribution was found for childhood trauma (P = 0.015). We did not find an association of CREB1 polymorphisms with MDD susceptibility. However, we found a significantly increased risk associated with the interactions of CREB1 polymorphisms and drinking (OR = 11.67, 95% CI = 2.52-54.18; OR = 11.52, 95% CI = 2.55-51.95 for rs11904814; OR = 4.18, 95% CI = 1.87-9.38; OR = 5.02, 95% CI = 2.27-11.14 for rs6740584; OR = 7.58, 95% CI = 2.05-27.98; OR = 7.59, 95% CI = 2.12-27.14 for rs2553206; OR = 8.37, 95% CI = 3.02-23.23; OR = 7.84, 95% CI = 2.93-20.98 for rs2551941). We also noted that CREB polymorphisms combined with family harmony and childhood trauma conferred increased susceptibility for MDD. In conclusion, polymorphisms in the CREB gene may not be independently associated with MDD risk, but they are likely to confer increased susceptibility by interacting with environmental risk factors in the Chinese population.

  9. Maternal stress during pregnancy increases neonatal allergy susceptibility: Role of glucocorticoids

    PubMed Central

    Lim, Robert; Fedulov, Alexey V.

    2014-01-01

    We sought to test experimentally whether maternal stress can promote susceptibility to development of asthma-like allergic airways disease in offspring. Normal pregnant mice (day 15) were subjected to a single restraint stress exposure. We subsequently tested their offspring for the development of airway hyperreactivity (AHR) and allergic airway inflammation (AI), after an intentionally suboptimal sensitization protocol. The offspring of stressed mothers showed levels of AI and enhanced airway responses to methacholine comparable to those seen in fully sensitized and challenged positive control animals; in contrast, minimal effects were seen in control offspring. Restraint stress caused a rapid and large increase in plasma corticosterone levels. Maternal treatment with dexamethasone on day 15 of pregnancy mimicked the stress effect and reproduced the AI and AHR outcomes, whereas blockade of the stress-induced corticosterone surge with metyrapone pretreatment of pregnant mice abrogated the effect. We conclude that stress-triggered glucocorticoids during pregnancy can increase susceptibility to allergy in offspring. Because inflammation typically includes a stress hormone response, the results also suggest a common pathway by which various injurious exposures during pregnancy might increase offspring susceptibility to asthma. PMID:24838749

  10. CREB1 gene polymorphisms combined with environmental risk factors increase susceptibility to major depressive disorder (MDD)

    PubMed Central

    Wang, Peng; Yang, Yanjie; Yang, Xiuxian; Qiu, Xiaohui; Qiao, Zhengxue; Wang, Lin; Zhu, Xiongzhao; Sui, Hong; Ma, Jingsong

    2015-01-01

    Major depressive disorder (MDD) is one of the most severe psychiatric disorders. The objective of this study was to explore the effects of CREB1 gene polymorphisms on risk of developing MDD and the joint effects of gene-environment interactions. Genotyping was performed by Taqman allelic discrimination assay among 586 patients and 586 healthy controls. A significant impact on rs6740584 genotype distribution was found for childhood trauma (P = 0.015). We did not find an association of CREB1 polymorphisms with MDD susceptibility. However, we found a significantly increased risk associated with the interactions of CREB1 polymorphisms and drinking (OR = 11.67, 95% CI = 2.52-54.18; OR = 11.52, 95% CI = 2.55-51.95 for rs11904814; OR = 4.18, 95% CI = 1.87-9.38; OR = 5.02, 95% CI = 2.27-11.14 for rs6740584; OR = 7.58, 95% CI = 2.05-27.98; OR = 7.59, 95% CI = 2.12-27.14 for rs2553206; OR = 8.37, 95% CI = 3.02-23.23; OR = 7.84, 95% CI = 2.93-20.98 for rs2551941). We also noted that CREB polymorphisms combined with family harmony and childhood trauma conferred increased susceptibility for MDD. In conclusion, polymorphisms in the CREB gene may not be independently associated with MDD risk, but they are likely to confer increased susceptibility by interacting with environmental risk factors in the Chinese population. PMID:25755794

  11. An interaction between NDE1 and high birth weight increases schizophrenia susceptibility.

    PubMed

    Wegelius, Asko; Pankakoski, Maiju; Tomppo, Liisa; Lehto, Ulriika; Lönnqvist, Jouko; Suvisaari, Jaana; Paunio, Tiina; Hennah, William

    2015-12-15

    Pre- and perinatal environmental factors have been shown to increase schizophrenia risk particularly when combined with genetic liability. The investigation of specific gene environment interactions in the etiology of psychiatric disorders has gained momentum. We used multivariate GEE regression modeling to investigate the interaction between genes of the DISC1 pathway and birth weight, in relation to schizophrenia susceptibility in a Finnish schizophrenia family cohort. The study sample consisted of 457 subjects with both genotype and birth weight information. Gender and place of birth were adjusted for in the models. We found a significant interaction between birth weight and two NDE1 markers in relation to increased schizophrenia risk: a four SNP haplotype spanning NDE1 (b=1.26, SE=0.5, p=0.012) and one of its constituent SNPs rs4781678 (b=1.33, SE=0.51, p=0.010). Specifically, high birth weight (>4000g) was associated with increased schizophrenia risk among subjects homozygous for the previously identified risk alleles. The study was based on a family study sample with high genetic loading for schizophrenia and thus our findings cannot directly be generalized as representing the general population. Our results suggest that the functions mediated by NDE1 during the early stages of neurodevelopment are susceptible to the additional disruptive effects of pre- and perinatal environmental factors associated with high birth weight, augmenting schizophrenia susceptibility.

  12. Maternal stress during pregnancy increases neonatal allergy susceptibility: role of glucocorticoids.

    PubMed

    Lim, Robert; Fedulov, Alexey V; Kobzik, Lester

    2014-07-15

    We sought to test experimentally whether maternal stress can promote susceptibility to development of asthma-like allergic airways disease in offspring. Normal pregnant mice (day 15) were subjected to a single restraint stress exposure. We subsequently tested their offspring for the development of airway hyperreactivity (AHR) and allergic airway inflammation (AI), after an intentionally suboptimal sensitization protocol. The offspring of stressed mothers showed levels of AI and enhanced airway responses to methacholine comparable to those seen in fully sensitized and challenged positive control animals; in contrast, minimal effects were seen in control offspring. Restraint stress caused a rapid and large increase in plasma corticosterone levels. Maternal treatment with dexamethasone on day 15 of pregnancy mimicked the stress effect and reproduced the AI and AHR outcomes, whereas blockade of the stress-induced corticosterone surge with metyrapone pretreatment of pregnant mice abrogated the effect. We conclude that stress-triggered glucocorticoids during pregnancy can increase susceptibility to allergy in offspring. Because inflammation typically includes a stress hormone response, the results also suggest a common pathway by which various injurious exposures during pregnancy might increase offspring susceptibility to asthma.

  13. Increasing age is a major risk factor for susceptibility to heat stress during physical activity.

    PubMed

    McGinn, Ryan; Poirier, Martin P; Louie, Jeffrey C; Sigal, Ronald J; Boulay, Pierre; Flouris, Andreas D; Kenny, Glen P

    2017-08-24

    We evaluated the extent to which age, cardiorespiratory fitness, and body fat can independently determine whole-body heat loss (WBHL) in 87 otherwise healthy adults. We show that increasing age is a major predictor for decreasing WBHL in otherwise healthy adults (aged 20-70 years), accounting for 40% of the variation in the largest study to date. While greater body fat also had a minor detrimental impact on WBHL, there was no significant role for cardiorespiratory fitness.

  14. Transgenic Arabidopsis thaliana containing increased levels of ATP and sucrose is more susceptible to Pseudomonas syringae

    PubMed Central

    Zhang, Renshan; Qi, Hua; Sun, Yuzhe; Xiao, Shi

    2017-01-01

    Disease resistance exerts a fitness cost on plants, presumably due to the extra consumption of energy and carbon. In this study, we examined whether transgenic Arabidopsis thaliana with increased levels of ATP and sucrose is more resistant or susceptible to pathogen infection. Lines of A. thaliana over-expressing purple acid phosphatase 2 (AtPAP2) (OE lines) contain increased levels of ATP and sucrose, with improved growth rate and seed production. Compared to wild type (WT) and pap2 lines, the OE lines were more susceptible to several Pseudomonas syringae pv. tomato (Pst) strains carrying AvrRpm1, AvrRpt2 AvrRps4, AvrPtoB, HrcC and WT strain DC3000. The increased susceptibility of the OE lines to Pst strains cannot solely be attributed to the suppressed expression of R-genes but must also be attributed to the suppression of downstream signaling components, such as MOS2, EDS1 and EDS5. Before infection, the levels of salicylic acid (SA) and jasmonic acid (JA) precursor OPDA were similar in the leaves of OE, pap2 and WT plants, whereas the levels of JA and its derivative JA-Ile were significantly lower in the leaves of OE lines and higher in the pap2 line. The expression of JA marker defense gene PDF1.2 was up-regulated in the OE lines compared to the WT prior to Pst DC3000 infection, but its expression was lower in the OE lines after infection. In summary, high fitness Arabidopsis thaliana exhibited altered JA metabolism and broad suppression of R-genes and downstream genes as well as a higher susceptibility to Pst infections. PMID:28152090

  15. Transgenic Arabidopsis thaliana containing increased levels of ATP and sucrose is more susceptible to Pseudomonas syringae.

    PubMed

    Zhang, Renshan; Qi, Hua; Sun, Yuzhe; Xiao, Shi; Lim, Boon Leong

    2017-01-01

    Disease resistance exerts a fitness cost on plants, presumably due to the extra consumption of energy and carbon. In this study, we examined whether transgenic Arabidopsis thaliana with increased levels of ATP and sucrose is more resistant or susceptible to pathogen infection. Lines of A. thaliana over-expressing purple acid phosphatase 2 (AtPAP2) (OE lines) contain increased levels of ATP and sucrose, with improved growth rate and seed production. Compared to wild type (WT) and pap2 lines, the OE lines were more susceptible to several Pseudomonas syringae pv. tomato (Pst) strains carrying AvrRpm1, AvrRpt2 AvrRps4, AvrPtoB, HrcC and WT strain DC3000. The increased susceptibility of the OE lines to Pst strains cannot solely be attributed to the suppressed expression of R-genes but must also be attributed to the suppression of downstream signaling components, such as MOS2, EDS1 and EDS5. Before infection, the levels of salicylic acid (SA) and jasmonic acid (JA) precursor OPDA were similar in the leaves of OE, pap2 and WT plants, whereas the levels of JA and its derivative JA-Ile were significantly lower in the leaves of OE lines and higher in the pap2 line. The expression of JA marker defense gene PDF1.2 was up-regulated in the OE lines compared to the WT prior to Pst DC3000 infection, but its expression was lower in the OE lines after infection. In summary, high fitness Arabidopsis thaliana exhibited altered JA metabolism and broad suppression of R-genes and downstream genes as well as a higher susceptibility to Pst infections.

  16. Enzymatic quorum quenching increases antibiotic susceptibility of multidrug resistant Pseudomonas aeruginosa

    PubMed Central

    Kiran, S; Sharma, P; Harjai, K; Capalash, N

    2011-01-01

    Background and Objectives There is increasing emergence of multidrug resistant Pseudomonas aeruginosa (MDRPA) strains and drug resistance is positively-correlated with biofilm-forming ability. Since about 10% of P. aeruginosa genome is controlled by quorum sensing (QS), alteration in its antibiotic susceptibility by targeting QS was the focus of the present study. Materials and Methods One day biofilms of PAO1 and three urinary tract infection MDRPA isolates (PA2, PA8 and PA18) were formed in 96-well microtiter plate. Biofilms were exposed to concentration gradient of ciprofloxacin and gentamicin to obtain Minimum Biofilm Eradication Concentration (MBEC) by direct enumeration method. Susceptibility of 24 h biofilms was evaluated by treatment with ciprofloxacin and gentamicin per se and in combination with lactonase. The effect was also examined on 72 h biofilms by Scanning Electron Microscopy. Results Lactonase treatment did not have any effect on growth of the selected strains but 73.42, 69.1, 77.34 and 72.5% reduction of biofilm was observed after lactonase (1 unit) treatment, respectively. Antibiotics in combination with lactonase (0.3 units) resulted in an increased susceptibility of the biofilm forms by>3.3, 4, 5 and 1.5 folds of MBEC, for ciprofloxacin and>6.67, 12.5, 6 and>2.5 folds, for gentamicin respectively, which could be due to the disruption of biofilm by lactonase treatment as shown by scanning electron microscopy. Also there was significant reduction (p<0.001) in virulence factor production by the strains. Conclusion Lactonase treatment increased antibiotic susceptibility of the biofilms of MDRPA isolates underscoring the potential of quorum quenching in antimicrobial therapeutics. PMID:22347576

  17. Susceptibility of black soldier fly (Diptera: Stratiomyidae) larvae and adults to four insecticides.

    PubMed

    Tomberlin, Jeffery K; Sheppard, D Craig; Joyce, John A

    2002-06-01

    Dosage-mortality regressions were determined for black soldier fly, Hermetia illucens (L.), larvae fed cyromazine or pyriproxifen treated media. Cyromazine LC50 for larvae dying before becoming prepupae ranged from 0.25 to 0.28 ppm with dosage-mortality regression slopes between 5.79 and 12.04. Cyromazine LC50s for larvae dying before emergence ranged from 0.13 to 0.19 ppm with dosage-mortality regression slopes between 3.94 and 7.69. Pyriproxifen dosage-mortality regressions were not generated for larvae failing to become prepupae since <32% mortality was recorded at the highest concentration of 1,857 ppm. LC50s for larvae failing to become adults ranged from 0.10 to 0.12 ppm with dosage mortality-regression slopes between 1.67 and 2.32. Lambda-cyhalothrin and permethrin dosage-mortality regressions were determined for wild adult black soldier flies and house flies, Musca domestica L., and for susceptible house flies. Our results indicate that the wild house fly, unlike the black soldier fly, population was highly resistant to each of these pyrethroids. Regression slopes for black soldier flies exposed to lambda-cyhalothrin were twice as steep as those determined for the wild house fly strain. Accordingly, LC50s for the black soldier fly and susceptible house fly were 10- to 30-fold lower than those determined for wild house flies. The differential sensitivity between wild black soldier flies and house flies might be due to behavioral differences. Adult house flies usually remain in animal facilities with the possibility of every adult receiving pesticide exposure, while black soldier fly adults are typically present only during emergence and oviposition thereby limiting their exposure.

  18. Foetal hypoxia increases cardiac AT2R expression and subsequent vulnerability to adult ischaemic injury

    PubMed Central

    Xue, Qin; Dasgupta, Chiranjib; Chen, Man; Zhang, Lubo

    2011-01-01

    Aims Hypoxia is a common stress to the foetus and results in increased cardiac vulnerability to adult ischaemic injury. This study tested the hypothesis that foetal hypoxia causes programming of increased AT2 receptor (AT2R) expression in the heart, resulting in the heightened cardiac susceptibility to adult ischaemic injury. Methods and results Time-dated pregnant rats were divided between normoxic and hypoxic (10.5% O2 from days 15 to 21 of gestation) groups. Hypoxia resulted in significantly increased AT2R in the heart of adult offspring. Multiple glucocorticoid response elements (GREs) were identified at the AT2R promoter, deletion of which increased the promoter activity. Consistently, ex vivo treatment of isolated foetal hearts with dexamethasone for 48 h decreased AT2R expression, which was inhibited by RU 486. Hypoxia decreased glucocorticoid receptors (GRs) in the hearts of foetal, 3-week-old and 3-month-old offspring, resulting in decreased GR binding to the GREs at the AT2R promoter. The inhibition of AT2R improved postischaemic recovery of left ventricular function and rescued the foetal hypoxia-induced cardiac ischaemic vulnerability in male adult animals. In contrast, the inhibition of AT1 receptors decreased the postischaemic recovery. Conclusion The results demonstrate that in utero hypoxia causes programming of increased AT2R gene expression in the heart by downregulating GR, which contributes to the increased cardiac vulnerability to adult ischaemic injury caused by prenatal hypoxic exposure. PMID:20870653

  19. Effect of nitrogen dioxide exposure on susceptibility to influenza A virus infection in healthy adults

    SciTech Connect

    Goings, S.A.; Kulle, T.J.; Bascom, R.; Sauder, L.R.; Green, D.J.; Hebel, J.R.; Clements, M.L.

    1989-05-01

    The effect of NO/sub 2/ exposure and human susceptibility to respiratory virus infection was investigated in a placebo-controlled, randomized, double-blind trial conducted in an environmentally controlled research chamber over 3 yr. Healthy, nonsmoking, young adult volunteers who were seronegative to influenza A/Korea/82 (H/sub 3/N/sub 2/) virus were randomly assigned to breathe either filtered clean air (control group) or NO/sub 2/ for 2 h/day for 3 consecutive days. The NO/sub 2/ concentrations were 2 ppm (Year 1), 3 ppm (Year 2), and 1 or 2 ppm (Year 3). Live, attenuated cold-adapted (ca) influenza A/Korea/82 reassortant virus was administered intranasally to all subjects immediately after the second exposure. Only one of the 152 volunteers had any symptoms; this person had a low grade fever. Pulmonary function measurements and nonspecific airway reactivity to methacholine were unchanged after NO/sub 2/ exposure, virus infection, or both. Infection was determined by virus recovery, a fourfold or greater increase in serum or nasal wash influenza-specific antibody titers, or both. The infection rates of the groups were 12/21 (2 ppm NO/sub 2/) versus 15/23 (clean air) in Year 1, 17/22 (3 ppm NO/sub 2/) versus 15/21 (clean air) in Year 2, and 20/22 (2 ppm) and 20/22 (1 ppm) versus 15/21 (clean air) in Year 3. Each group exposed to 1 or 2 ppm NO2 in the last year became infected more often (91%) than did the control group (71%), but the differences were not statistically significant.

  20. Long-range DHPS mutations unexpectedly increase Mycobacterium chimaera susceptibility to sulfonamides.

    PubMed

    Gotthard, Guillaume; Muhammed Ameen, Sirwan; Drancourt, Michel; Chabriere, Eric

    2013-12-01

    The two closely related mycobacteria, Mycobacterium intracellulare and Mycobacterium chimaera, exhibit a more than two-fold difference in their in vitro susceptibility to sulfonamides. Sulfonamides are antibiotics targeting the 6-hydroxymethyl-7,8-dihydropteroate synthase (DHPS) enzyme involved in the folate synthesis pathway. Comparing the DHPS gene sequence in six M. intracellulare and M. chimaera types trains and clinical isolates yielded only four amino acid changes. In silico structural modelling surprisingly indicated that these amino acids are not located in the active site of DHPS and do not interact directly with sulfonamides. Unexpectedly, these amino acids in distal positions may play a key role in the increased sulfonamide susceptibility observed in M. chimaera compared with M. intracellulare. This example illustrates how three-dimensional models could help to identify distal mutations capable of modulating enzymatic activity. Copyright © 2013 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

  1. Inbreeding increases susceptibility to powdery mildew (Oidium neolycopersici) infestation in horsenettle (Solanum carolinense L).

    PubMed

    Kariyat, Rupesh R; De Moraes, Consuelo M; Stephenson, Andrew G; Mescher, Mark C

    2012-07-01

    Inbreeding is common in flowering plants, but relatively few studies have examined its effects on interactions between plants and other organisms, such as herbivores and pathogens. In a recent paper, we documented effects of inbreeding depression on plant volatile signaling phenotypes, including elevated constitutive volatile emissions (and consequently greater herbivore recruitment to inbred plants) but reduced emission of key herbivore-induced volatiles that attract predatory and parasitic insects to damaged plants. While the effects of inbreeding on plant-insect interactions have been explored in only a few systems, even less is known about its effects on plant-pathogen interactions. Here we report the effects of inbreeding on horsenettle susceptibility to powdery mildew (Oidium neolycopersici), including more rapid onset of infection in inbred plants, particularly when plants were not previously damaged. These data suggest that inbreeding may increase plant susceptibility to pathogen infection and, therefore, may potentially facilitate pathogen establishment in natural populations.

  2. Active versus sedentary lifestyle from childhood to adult and susceptibility to ozone: An animal model

    EPA Science Inventory

    A pattern of sedentary lifestyle beginning in childhood is associated with obesity and related disorders such as type 2 diabetes. Obesity is associated with increased susceptibility to air pollutants and initiating regular exercise early in life should impact positively on respir...

  3. Active versus sedentary lifestyle from childhood to adult and susceptibility to ozone: An animal model

    EPA Science Inventory

    A pattern of sedentary lifestyle beginning in childhood is associated with obesity and related disorders such as type 2 diabetes. Obesity is associated with increased susceptibility to air pollutants and initiating regular exercise early in life should impact positively on respir...

  4. The BTNL2 G16071A gene polymorphism increases granulomatous disease susceptibility

    PubMed Central

    Tong, Xiang; Ma, Yao; Niu, Xundong; Yan, Zhipeng; Liu, Sitong; Peng, Bo; Peng, Shifeng; Fan, Hong

    2016-01-01

    G16071A gene polymorphism was truly associated with sarcoidosis susceptibility (A vs G, FPRP < 0.001). Additionally, the FPRP test confirmed that the BTNL2 G16071A gene polymorphism was associated only with granulomatous disease susceptibility among Caucasians (A vs G, FPRP < 0.001) at the level of a prior probability, which was 0.001. Conclusion: The meta-analysis indicated that BTNL2 G16071A gene polymorphism may as a likelihood factor contributed to granulomatous disease susceptibility, especially increasing the sarcoidosis susceptibility. In addition, the polymorphism may be greatly associated with likelihood of granulomatous diseases among Caucasians. PMID:27472712

  5. Susceptibility of captive adult winter-run Chinook salmon Oncorhynchus tshawytscha to waterborne exposures with infectious hematopoietic necrosis virus (IHNV).

    PubMed

    Arkush, K D; Mendonca, H L; McBride, A M; Hedrick, R P

    2004-06-11

    Sexually mature female Chinook salmon Oncorhynchus tshawytscha with no prior history of exposure to infectious hematopoietic necrosis virus (IHNV) were susceptible to experimental infection induced by additions of virus to the water. The resulting infections resembled those observed among naturally infected hatchery and wild populations of Chinook salmon. Virus was detected as early as 4 d post-exposure (p.e.) and subsequently in all virus-exposed fish that died or that were examined at 14 d p.e. when the study was terminated. The greatest concentrations of virus, up to 10(8) plaque-forming units (pfu) ml(-1), were found in the ovarian fluid at 13 to 14 d p.e., but the virus was also found in high concentrations in the gill, kidney/spleen and plasma. In contrast, the virus was not recovered from unexposed control adult salmon that died or were sampled at the end of the study. Despite detecting concentrations of IHNV in excess of 10(7) pfu g(-1) of tissue, no specific microscopic lesions were found in IHNV-exposed compared to unexposed control salmon. The results of this initial study suggest that virus in the spawning environment, either from adult salmon or other sources, may contribute to its rapid spread among adult Chinook salmon, thereby considerably increasing the prevalence of IHNV infection in both wild and hatchery populations of adult Chinook salmon.

  6. Does increased heat resistance result in higher susceptibility to predation? A test using Drosophila melanogaster selection and hardening.

    PubMed

    Hangartner, Sandra; Dworkin, Ian; DeNieu, Michael; Hoffmann, Ary A

    2017-04-07

    Heat resistance of ectotherms can be increased both by plasticity and evolution, but these effects may have trade-offs resulting from biotic interactions. Here we test for predation costs in Drosophila melanogaster populations with altered heat resistance produced by adult hardening and directional selection for increased heat resistance. In addition, we also tested for genetic trade-offs by testing heat resistance in lines that have evolved under increased predation risk. We show that while 35/37°C hardening increases heat resistance as expected, it does not increase predation risk from jumping spiders or mantids; in fact there was an indication that survival may have increased under predation following a triple 37°C compared to a single 35°C hardening treatment. Flies that survived a 39°C selection cycle showed lower survival under predation, suggesting a predation cost of exposure to a more severe heat stress. There was however no correlated response to selection because survival did not differ between control and selected lines after selection was relaxed for one or two generations. In addition, lines selected for increased predation risk did not differ in heat resistance. Our findings suggest independent evolutionary responses to predation and heat as measured in laboratory assays, and no costs of heat hardening on susceptibility to predation. This article is protected by copyright. All rights reserved.

  7. FGF-2 Overexpression Increases Excitability and Seizure Susceptibility but Decreases Seizure-Induced Cell Loss

    PubMed Central

    Zucchini, Silvia; Buzzi, Andrea; Barbieri, Mario; Rodi, Donata; Paradiso, Beatrice; Binaschi, Anna; Coffin, J. Douglas; Marzola, Andrea; Cifelli, Pierangelo; Belluzzi, Ottorino

    2008-01-01

    Fibroblast growth factor 2 (FGF-2) has multiple, pleiotropic effects on the nervous system that include neurogenesis, neuroprotection and neuroplasticity. Thus, alteration in FGF-2 expression patterns may have a profound impact in brain function, both in normal physiology and in pathology. Here, we used FGF-2 transgenic mice (TgFGF2) to study the effects of endogenous FGF-2 overexpression on susceptibility to seizures and to the pathological consequences of seizures. TgFGF2 mice display increased FGF-2 expression in hippocampal pyramidal neurons and dentate granule cells. Increased density of glutamatergic synaptic vesicles was observed in the hippocampus of TgFGF2 mice, and electrophysiological data (input/output curves and patch-clamp recordings in CA1) confirmed an increase in excitatory inputs in CA1, suggesting the presence of a latent hyperexcitability. Indeed, TgFGF2 mice displayed increased susceptibility to kainate-induced seizures compared with wild-type (WT) littermates, in that latency to generalized seizure onset was reduced, whereas behavioral seizure scores and lethality were increased. Finally, WT and TgFGF2 mice with similar seizure scores were used for examining seizure-induced cellular consequences. Neurogenesis and mossy fiber sprouting were not significantly different between the two groups. In contrast, cell damage (assessed with Fluoro-Jade B, silver impregnation and anti-caspase 3 immunohistochemistry) was significantly lower in TgFGF2 mice, especially in the areas of overexpression (CA1 and CA3), indicating reduction of seizure-induced necrosis and apoptosis. These data suggest that FGF-2 may be implicated in seizure susceptibility and in seizure-induced plasticity, exerting different, and apparently contrasting effects: favoring ictogenesis but reducing seizure-induced cell death. PMID:19052202

  8. Dividing attention lowers children's but increases adults' false memories.

    PubMed

    Otgaar, Henry; Peters, Maarten; Howe, Mark L

    2012-01-01

    The present study examined the impact of divided attention on children's and adults' neutral and negative true and false memories in a standard Deese/Roediger-McDermott paradigm. Children (7- and 11-year-olds; n = 126) and adults (n = 52) received 5 neutral and 5 negative Deese/Roediger-McDermott word lists; half of each group also received a divided attention task. The results showed that divided attention affected children's and adults' false memory levels differently but did not alter true memory differently. Our results revealed a developmental shift in that divided attention lowered children's false memory rates but increased adults' false memory rates, regardless of the nature of the material (i.e., neutral or negative). Our study indicates that manipulations that target conscious processing (e.g., divided attention) result in marked qualitative and quantitative differences between children's and adults' false memories but not true memories.

  9. Excess algal symbionts increase the susceptibility of reef corals to bleaching

    NASA Astrophysics Data System (ADS)

    Cunning, Ross; Baker, Andrew C.

    2013-03-01

    Rising ocean temperatures associated with global climate change are causing mass coral bleaching and mortality worldwide. Understanding the genetic and environmental factors that mitigate coral bleaching susceptibility may aid local management efforts to help coral reefs survive climate change. Although bleaching susceptibility depends partly on the genetic identity of a coral's algal symbionts, the effect of symbiont density, and the factors controlling it, remain poorly understood. By applying a new metric of symbiont density to study the coral Pocillopora damicornis during seasonal warming and acute bleaching, we show that symbiont cell ratio density is a function of both symbiont type and environmental conditions, and that corals with high densities are more susceptible to bleaching. Higher vulnerability of corals with more symbionts establishes a quantitative mechanistic link between symbiont density and the molecular basis for coral bleaching, and indicates that high densities do not buffer corals from thermal stress, as has been previously suggested. These results indicate that environmental conditions that increase symbiont densities, such as nutrient pollution, will exacerbate climate-change-induced coral bleaching, providing a mechanistic explanation for why local management to reduce these stressors will help coral reefs survive future warming.

  10. Increased susceptibility of spontaneously hypertensive rats to ventricular tachyarrhythmias in early hypertension

    PubMed Central

    Sovari, Ali A.; Pezhouman, Arash; Iyer, Shankar; Cao, Hong; Ko, Christopher Y.; Bapat, Aneesh; Vahdani, Nooshin; Ghanim, Mostafa; Fishbein, Michael C.

    2016-01-01

    Key points Hypertension is a risk factor for sudden cardiac death caused by ventricular tachycardia and fibrillation.Whether hypertension in its early stage is associated with an increased risk of ventricular tachyarrhythmias is not known.Based on experiments performed at the cellular and whole heart levels, we show that, even early in chronic hypertension, the hypertrophied and fibrotic ventricles of spontaneously hypertensive rats aged 5 to 6 months have already developed increased stress‐induced arrhythmogenicity, and this increased susceptibility to ventricular arrhythmias is primarily a result of tissue remodelling rather than cellular electrophysiological changes.Our findings highlight the need for early hypertension treatment to minimize myocardial fibrosis, ventricular hypertrophy, and arrhythmias. Abstract Hypertension is a risk factor for sudden cardiac death caused by ventricular tachycardia and fibrillation (VT/VF). We hypothesized that, in early hypertension, the susceptibility to stress‐induced VT/VF increases. We compared the susceptibility of 5‐ to 6‐month‐old male spontaneously hypertensive rats (SHR) and age/sex‐matched normotensive rats (NR) to VT/VF during challenge with oxidative stress (H2O2; 0.15 mmol l−1). We found that only SHR hearts exhibited left ventricular fibrosis and hypertrophy. H2O2 promoted VT in all 30 SHR but none of the NR hearts. In 33% of SHR cases, focal VT degenerated to VF within 3 s. Simultaneous voltage‐calcium optical mapping of Langendorff‐perfused SHR hearts revealed that H2O2‐induced VT/VF arose spontaneously from focal activations at the base and mid left ventricular epicardium. Microelectrode recording of SHR hearts showed that VT was initiated by early afterdepolarization (EAD)‐mediated triggered activity. However, despite the increased susceptibility of SHR hearts to VT/VF, patch clamped isolated SHR ventricular myocytes developed EADs and triggered activity to the same extent as NR

  11. Modelling increased landslide susceptibility near highways in the Andes of southern Ecuador

    NASA Astrophysics Data System (ADS)

    Brenning, Alexander; Muenchow, Jannes

    2016-04-01

    Modelling increased landslide susceptibility near highways in the Andes of southern Ecuador A. Brenning (1), J. Muenchow (1) (1) Department of Geography, Friedrich Schiller University Jena, Loebdergraben 32, 07743 Jena, Germany Mountain roads are affected by and also affect themselves landslide suceptibility. Especially in developing countries, inadequate drainage systems and mechanical destabilization of hillslopes by undercutting and overloading are known processes through which road construction and maintenance can enhance landslide activity within the immediate surroundings of road infrastructure. In the Andes of southern Ecuador, strong precipitation gradients as well as lithological differences provide an excellent study site in which the relationship between highways and landslide susceptibility and its regional differentiation can be studied. This study uses Generalized Additive Models (GAM) to investigate patterns of landslide susceptibility along two paved interurban highways in the tropical Andes of southern Ecuador. The relationship of landslides to distance from road is modeled while accounting for topographic, climatic and lithological predictors as possible confounders and modifiers, focusing on the odds ratio of landslide occurrence at 25 m versus 200 m distance from the highway. Spatial attention is given to uncertainties in estimated odds ratios of landslide occurrence using spatial block bootstrap techniques. The GAM is able to represent nonlinear additive terms as well as bivariate smooth interaction terms, providing a good tradeoff between model complexity and interpretability. The estimated odds of landslide occurrence were 18-21 times higher near the highway than at 200 m distance, based on different analyses, with lower 95% confidence limits always >13. (Semi-) parametric estimates confirmed this general range of values but suggests slightly higher odds ratios (95% confidence interval: 15.5-25.3). Highway-related effects were observed to

  12. Identification of Susceptibility Genes of Adult Asthma in French Canadian Women

    PubMed Central

    Bérubé, Jean-Christophe; Gaudreault, Nathalie; Lavoie-Charland, Emilie; Sbarra, Laura; Henry, Cyndi; Madore, Anne-Marie; Paré, Peter D.; van den Berge, Maarten; Nickle, David; Laviolette, Michel; Laprise, Catherine; Boulet, Louis-Philippe; Bossé, Yohan

    2016-01-01

    Susceptibility genes of asthma may be more successfully identified by studying subgroups of phenotypically similar asthma patients. This study aims to identify single nucleotide polymorphisms (SNPs) associated with asthma in French Canadian adult women. A pooling-based genome-wide association study was performed in 240 allergic asthmatic and 120 allergic nonasthmatic women. The top associated SNPs were selected for individual genotyping in an extended cohort of 349 asthmatic and 261 nonasthmatic women. The functional impact of asthma-associated SNPs was investigated in a lung expression quantitative trait loci (eQTL) mapping study (n = 1035). Twenty-one of the 38 SNPs tested by individual genotyping showed P values lower than 0.05 for association with asthma. Cis-eQTL analyses supported the functional contribution of rs17801353 associated with C3AR1 (P = 7.90E − 10). The asthma risk allele for rs17801353 is associated with higher mRNA expression levels of C3AR1 in lung tissue. In silico functional characterization of the asthma-associated SNPs also supported the contribution of C3AR1 and additional genes including SYNE1, LINGO2, and IFNG-AS1. This pooling-based GWAS in French Canadian adult women followed by lung eQTL mapping suggested C3AR1 as a functional locus associated with asthma. Additional susceptibility genes were suggested in this homogenous subgroup of asthma patients. PMID:27445529

  13. Identification of Susceptibility Genes of Adult Asthma in French Canadian Women.

    PubMed

    Bérubé, Jean-Christophe; Gaudreault, Nathalie; Lavoie-Charland, Emilie; Sbarra, Laura; Henry, Cyndi; Madore, Anne-Marie; Paré, Peter D; van den Berge, Maarten; Nickle, David; Laviolette, Michel; Laprise, Catherine; Boulet, Louis-Philippe; Bossé, Yohan

    2016-01-01

    Susceptibility genes of asthma may be more successfully identified by studying subgroups of phenotypically similar asthma patients. This study aims to identify single nucleotide polymorphisms (SNPs) associated with asthma in French Canadian adult women. A pooling-based genome-wide association study was performed in 240 allergic asthmatic and 120 allergic nonasthmatic women. The top associated SNPs were selected for individual genotyping in an extended cohort of 349 asthmatic and 261 nonasthmatic women. The functional impact of asthma-associated SNPs was investigated in a lung expression quantitative trait loci (eQTL) mapping study (n = 1035). Twenty-one of the 38 SNPs tested by individual genotyping showed P values lower than 0.05 for association with asthma. Cis-eQTL analyses supported the functional contribution of rs17801353 associated with C3AR1 (P = 7.90E - 10). The asthma risk allele for rs17801353 is associated with higher mRNA expression levels of C3AR1 in lung tissue. In silico functional characterization of the asthma-associated SNPs also supported the contribution of C3AR1 and additional genes including SYNE1, LINGO2, and IFNG-AS1. This pooling-based GWAS in French Canadian adult women followed by lung eQTL mapping suggested C3AR1 as a functional locus associated with asthma. Additional susceptibility genes were suggested in this homogenous subgroup of asthma patients.

  14. Increased susceptibility to Pseudomonas aeruginosa infection under hindlimb-unloading conditions

    NASA Technical Reports Server (NTRS)

    Aviles, Hernan; Belay, Tesfaye; Fountain, Kimberly; Vance, Monique; Sonnenfeld, Gerald

    2003-01-01

    It has been reported that spaceflight conditions alter the immune system and resistance to infection [Belay T, Aviles H, Vance M, Fountain K, and Sonnenfeld G. J Allergy Clin Immunol 170: 262-268, 2002; Hankins WR and Ziegelschmid JF. In: Biomedical Results of Apollo. Washington, DC: NASA, 1975, p. 43-81. (NASA Spec. Rep. SP-368)]. Ground-based models, including the hindlimb-unloading model, have become important tools for increasing understanding of how spaceflight conditions can influence physiology. The objective of the present study was to determine the effect of hindlimb unloading on the susceptibility of mice to Pseudomonas aeruginosa infection. Hindlimb-unloaded and control mice were subcutaneously infected with 1 LD50 of P. aeruginosa. Survival, bacterial organ load, and antibody and corticosterone levels were compared among the groups. Hindlimb unloading had detrimental effects for infected mice. Animals in the hindlimb-unloaded group, compared with controls, 1). showed significantly increased mortality and reduced time to death, 2). had increased levels of corticosterone, and 3). were much less able to clear bacteria from the organs. These results suggest that hindlimb unloading may induce the production of corticosterone, which may play a critical role in the modulation of the immune system leading to increased susceptibility to P. aeruginosa infection.

  15. Increased susceptibility to Pseudomonas aeruginosa infection under hindlimb-unloading conditions

    NASA Technical Reports Server (NTRS)

    Aviles, Hernan; Belay, Tesfaye; Fountain, Kimberly; Vance, Monique; Sonnenfeld, Gerald

    2003-01-01

    It has been reported that spaceflight conditions alter the immune system and resistance to infection [Belay T, Aviles H, Vance M, Fountain K, and Sonnenfeld G. J Allergy Clin Immunol 170: 262-268, 2002; Hankins WR and Ziegelschmid JF. In: Biomedical Results of Apollo. Washington, DC: NASA, 1975, p. 43-81. (NASA Spec. Rep. SP-368)]. Ground-based models, including the hindlimb-unloading model, have become important tools for increasing understanding of how spaceflight conditions can influence physiology. The objective of the present study was to determine the effect of hindlimb unloading on the susceptibility of mice to Pseudomonas aeruginosa infection. Hindlimb-unloaded and control mice were subcutaneously infected with 1 LD50 of P. aeruginosa. Survival, bacterial organ load, and antibody and corticosterone levels were compared among the groups. Hindlimb unloading had detrimental effects for infected mice. Animals in the hindlimb-unloaded group, compared with controls, 1). showed significantly increased mortality and reduced time to death, 2). had increased levels of corticosterone, and 3). were much less able to clear bacteria from the organs. These results suggest that hindlimb unloading may induce the production of corticosterone, which may play a critical role in the modulation of the immune system leading to increased susceptibility to P. aeruginosa infection.

  16. Susceptibility of the Adult Japanese Beetle, Popillia japonica to Entomopathogenic Nematodes

    PubMed Central

    Morris, E. Erin; Grewal, Parwinder S.

    2011-01-01

    To build upon prior research demonstrating the potential of entomopathogenic nematode dissemination by infected adult Japanese beetle, Popillia japonica, we evaluated susceptibility of the adult beetles to 20 strains of Steinernema and Heterorhabditis under laboratory conditions. The nematodes were applied at a rate of 10,000 infective juveniles per 10 adult beetles in 148 mL plastic cups containing autoclaved sand and sassafras leaves as a source of food for the beetles. All strains infected the beetles and caused 55% to 95% mortality. The most virulent strains that caused 50% beetle mortality in less than 5 days included a strain of H. georgiana (D61), three strains of Steinernema sp. (R54, R45, and FC48), and two strains of S. carpocapsae (All and D60). The ability of two strains of Steinernema sp. (R45 and R54) and two strains of Heterorhabditis bacteriophora (D98 and GPS11) to infect and reproduce in the beetle was further examined to assess the potential of infected beetles to disseminate nematodes upon their death. All four strains infected and killed the beetles, but only Steinernema strains reproduced in the cadavers. We conclude that both Heterorhabditis and Steinernema strains are able to cause mortality to adult Japanese beetle, but Steinernema strains may be effectively disseminated due to their reproduction in the beetle. PMID:23431080

  17. Susceptibility of the Adult Japanese Beetle, Popillia japonica to Entomopathogenic Nematodes.

    PubMed

    Morris, E Erin; Grewal, Parwinder S

    2011-09-01

    To build upon prior research demonstrating the potential of entomopathogenic nematode dissemination by infected adult Japanese beetle, Popillia japonica, we evaluated susceptibility of the adult beetles to 20 strains of Steinernema and Heterorhabditis under laboratory conditions. The nematodes were applied at a rate of 10,000 infective juveniles per 10 adult beetles in 148 mL plastic cups containing autoclaved sand and sassafras leaves as a source of food for the beetles. All strains infected the beetles and caused 55% to 95% mortality. The most virulent strains that caused 50% beetle mortality in less than 5 days included a strain of H. georgiana (D61), three strains of Steinernema sp. (R54, R45, and FC48), and two strains of S. carpocapsae (All and D60). The ability of two strains of Steinernema sp. (R45 and R54) and two strains of Heterorhabditis bacteriophora (D98 and GPS11) to infect and reproduce in the beetle was further examined to assess the potential of infected beetles to disseminate nematodes upon their death. All four strains infected and killed the beetles, but only Steinernema strains reproduced in the cadavers. We conclude that both Heterorhabditis and Steinernema strains are able to cause mortality to adult Japanese beetle, but Steinernema strains may be effectively disseminated due to their reproduction in the beetle.

  18. Decreased Polysaccharide Feruloylation Compromises Plant Cell Wall Integrity and Increases Susceptibility to Necrotrophic Fungal Pathogens

    PubMed Central

    Reem, Nathan T.; Pogorelko, Gennady; Lionetti, Vincenzo; Chambers, Lauran; Held, Michael A.; Bellincampi, Daniela; Zabotina, Olga A.

    2016-01-01

    The complexity of cell wall composition and structure determines the strength, flexibility, and function of the primary cell wall in plants. However, the contribution of the various components to cell wall integrity (CWI) and function remains unclear. Modifications of cell wall composition can induce plant responses known as CWI control. In this study, we used transgenic expression of the fungal feruloyl esterase AnFAE to examine the effect of post-synthetic modification of Arabidopsis and Brachypodium cell walls. Transgenic Arabidopsis plants expressing AnFAE showed a significant reduction of monomeric ferulic acid, decreased amounts of wall-associated extensins, and increased susceptibility to Botrytis cinerea, compared with wild type. Transgenic Brachypodium showed reductions in monomeric and dimeric ferulic acids and increased susceptibility to Bipolaris sorokiniana. Upon infection, transgenic Arabidopsis and Brachypodium plants also showed increased expression of several defense-related genes compared with wild type. These results demonstrate a role, in both monocot and dicot plants, of polysaccharide feruloylation in plant CWI, which contributes to plant resistance to necrotrophic pathogens. PMID:27242834

  19. Chronic stress shifts the GABA reversal potential in the hippocampus and increases seizure susceptibility

    PubMed Central

    MacKenzie, Georgina; Maguire, Jamie

    2014-01-01

    The most commonly reported precipitating factor for seizures is stress. However, the underlying mechanisms whereby stress triggers seizures are not yet fully understood. Here we demonstrate a potential mechanism underlying changes in neuronal excitability in the hippocampus following chronic stress, involving a shift in the reversal potential for GABA (EGABA) associated with a dephosphorylation of the potassium chloride co-transporter, KCC2. Mice subjected to chronic restraint stress (30 mins/day for 14 consecutive days) exhibit an increase in serum corticosterone levels which is associated with increased susceptibility to seizures induced with kainic acid (20 mg/kg). Following chronic stress, but not acute stress, we observe a dephosphorylation of KCC2 residue S940, which regulates KCC2 cell surface expression and function, in the hippocampus. To determine the impact of alterations in KCC2 expression following chronic stress, we performed gramicidin perforated patch recordings to measure changes in EGABA and neuronal excitability of principal hippocampal neurons. We observe a depolarizing shift in EGABA in hippocampal CA1 pyramidal neurons after chronic stress. In addition, there is an increase in the intrinsic excitability of CA1 pyramidal neurons, evident by a shift in the input-output curve which could be reversed with the NKCC1 inhibitor, bumetanide. These data uncover a potential mechanism involving chronic stress-induced plasticity in chloride homeostasis which may contribute to stress-induced seizure susceptibility. PMID:25524838

  20. Increasing trend of fluconazole-non-susceptible Cryptococcus neoformans in patients with invasive cryptococcosis: a 12-year longitudinal study.

    PubMed

    Chen, Yi-Chun; Chang, Tzu-Yao; Liu, Jien-Wei; Chen, Fang-Ju; Chien, Chun-Chih; Lee, Chen-Hsiang; Lu, Cheng-Hsien

    2015-07-22

    This study aimed to investigate the rate of fluconazole-non-susceptible Cryptococcus neoformans in Southern Taiwan for the period 2001-2012 and analyze the risk factors for acquiring it among patients with invasive cryptococcosis. All enrolled strains were isolated from blood or cerebrospinal fluid samples of the included patients. If a patient had multiple positive results for C. neoformans, only the first instance was enrolled. Susceptibility testing was performed using the Clinical and Laboratory Standards Institutes M27-A3 broth micro-dilution method. The MIC interpretative criteria for susceptibility to fluconazole were ≤ 8 μg/ml. A total of 89 patients were included. Patients (n = 59) infected by fluconazole-susceptible strains were compared with those (n = 30) infected by non-susceptible strains. The patients' demographic and clinical characteristics were analyzed. The rate of fluconazole-non-susceptible C. neoformans in the study period significantly increased over time (p < 0.001). The C. neoformans isolated in 2011-2012 (odds ratio: 10.68; 95 % confidence interval: 2.87-39.74; p < 0.001) was an independent predictive factor for the acquisition of fluconazole-non-susceptible C. neoformans. The rate of fluconazole-non-susceptible C. neoformans has significantly increased recently. Continuous and large-scale anti-fungal susceptibility tests for C. neoformans are warranted to confirm this trend.

  1. Alteration of the murine gastrointestinal microbiota by tigecycline leads to increased susceptibility to Clostridium difficile infection.

    PubMed

    Bassis, Christine M; Theriot, Casey M; Young, Vincent B

    2014-05-01

    Antibiotics can play dual roles in Clostridium difficile infection (CDI); antibiotic treatment increases the risk of CDI, and antibiotics are used to treat CDI. The glycylcycline antibiotic tigecycline has broad antimicrobial activity, yet it is rarely associated with the development of CDI, presumably due to its activity against C. difficile. In this study, we investigated how tigecycline treatment affects the structure of the gut microbiota and susceptibility to CDI by treating mice with tigecycline (n = 20) or saline (n = 8) for 10 days. A sequence analysis of the bacterial 16S rRNA gene amplicons was used to monitor changes in the fecal microbiota. A subset of the mice was followed for 5 weeks after the end of treatment. The remaining mice were challenged with C. difficile strain VPI 10463 spores 2 days after the tigecycline treatment ended. Tigecycline treatment resulted in major shifts in the gut microbiota, including large decreases in Bacteroidetes levels and large increases in Proteobacteria levels. Mice with tigecycline-altered microbial communities were susceptible to challenge with C. difficile spores and developed clinical signs of severe CDI. Five weeks after the cessation of tigecycline treatment, the recovery of the bacterial community was incomplete and diversity was lower than in the untreated controls. Antibiotics with intrinsic activity against C. difficile can still alter the microbiota in a way that leads to susceptibility to CDI after discontinuation of the drug. These results indicate that microbiotic dynamics are key in the development of CDI, and a better understanding of these dynamics may lead to better strategies to prevent and treat this disease.

  2. Increased Susceptibility to Aphids of Flowering Wheat Plants Exposed to Low Temperatures.

    PubMed

    Lacoste, C; Nansen, C; Thompson, S; Moir-Barnetson, L; Mian, A; McNee, M; Flower, K C

    2015-06-01

    Frost is known to directly affect flowering wheat plants (Triticum aestivum L.) and lead to reduced grain yield. Additionally, it may increase wheat susceptibility to economically important pests, such as aphids (Hemiptera: Aphididae). Wheat plants at flowering stage were exposed to one of the three temperature treatments: ambient (11-12°C), 0°C, and -3°C for 60 min. Preference (3-choice) and performance (no-choice) bioassays with aphids (Rhopalosiphum padi L.) were conducted 1, 3, 6, and 12 d after temperature treatments to assess effects of temperature-induced stress over time. As an initial feasibility study of using remote sensing technologies to detect frost-induced stress in flowering wheat plants, hyperspectral imaging data were acquired from wheat plants used in preference bioassays. Element analysis of wheat plants was included to determine the effect of temperature-induced stress on the nutritional composition of flowering wheat plants. The results from this study support the following cause-effect scenario: a 60-min exposure to low temperatures caused a significant decrease in potassium and copper content of wheat plants 6 d after temperature exposure, and it coincided with a marked increase in preference by aphids of wheat plants. The preference exhibited by aphids correlated positively with performance of aphids, so the preference-performance hypothesis was confirmed and possibly driven by potassium and copper content of wheat plants. In addition, we demonstrated that hyperspectral imaging data can be used to detect frost-induced susceptibility to aphid infestation in flowering wheat plants. These findings justify further research into airborne remote sensing of frost-induced stress and the possible secondary effects on crop susceptibility to arthropod pests. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Alteration of the Murine Gastrointestinal Microbiota by Tigecycline Leads to Increased Susceptibility to Clostridium difficile Infection

    PubMed Central

    Bassis, Christine M.; Young, Vincent B.

    2014-01-01

    Antibiotics can play dual roles in Clostridium difficile infection (CDI); antibiotic treatment increases the risk of CDI, and antibiotics are used to treat CDI. The glycylcycline antibiotic tigecycline has broad antimicrobial activity, yet it is rarely associated with the development of CDI, presumably due to its activity against C. difficile. In this study, we investigated how tigecycline treatment affects the structure of the gut microbiota and susceptibility to CDI by treating mice with tigecycline (n = 20) or saline (n = 8) for 10 days. A sequence analysis of the bacterial 16S rRNA gene amplicons was used to monitor changes in the fecal microbiota. A subset of the mice was followed for 5 weeks after the end of treatment. The remaining mice were challenged with C. difficile strain VPI 10463 spores 2 days after the tigecycline treatment ended. Tigecycline treatment resulted in major shifts in the gut microbiota, including large decreases in Bacteroidetes levels and large increases in Proteobacteria levels. Mice with tigecycline-altered microbial communities were susceptible to challenge with C. difficile spores and developed clinical signs of severe CDI. Five weeks after the cessation of tigecycline treatment, the recovery of the bacterial community was incomplete and diversity was lower than in the untreated controls. Antibiotics with intrinsic activity against C. difficile can still alter the microbiota in a way that leads to susceptibility to CDI after discontinuation of the drug. These results indicate that microbiotic dynamics are key in the development of CDI, and a better understanding of these dynamics may lead to better strategies to prevent and treat this disease. PMID:24590475

  4. Does abnormal glycogen structure contribute to increased susceptibility to seizures in epilepsy?

    PubMed Central

    DiNuzzo, Mauro; Mangia, Silvia; Maraviglia, Bruno; Giove, Federico

    2014-01-01

    Epilepsy is a family of brain disorders with a largely unknown etiology and high percentage of pharmacoresistance. The clinical manifestations of epilepsy are seizures, which originate from aberrant neuronal synchronization and hyperexcitability. Reactive astrocytosis, a hallmark of the epileptic tissue, develops into loss-of-function of glutamine synthetase, impairment of glutamate-glutamine cycle and increase in extracellular and astrocytic glutamate concentration. Here, we argue that chronically elevated intracellular glutamate level in astrocytes is instrumental to alterations in the metabolism of glycogen and leads to the synthesis of polyglucosans. Unaccessibility of glycogen-degrading enzymes to these insoluble molecules compromises the glycogenolysis-dependent reuptake of extracellular K+ by astrocytes, thereby leading to increased extracellular K+ and associated membrane depolarization. Based on current knowledge, we propose that the deterioration in structural homogeneity of glycogen particles is relevant to disruption of brain K+ homeostasis and increased susceptibility to seizures in epilepsy. PMID:24643875

  5. Leptin increases adult hippocampal neurogenesis in vivo and in vitro.

    PubMed

    Garza, Jacob C; Guo, Ming; Zhang, Wei; Lu, Xin-Yun

    2008-06-27

    Leptin, an adipose-derived hormone, has been implicated in several physiological processes involving the hippocampus. However, the role of leptin in adult hippocampal neurogenesis remains unknown. Here we show that leptin regulates neurogenesis in the dentate gyrus of adult mice as well as in cultured adult hippocampal progenitor cells. Chronic administration of leptin to adult mice increased cell proliferation without significant effects on the differentiation and the survival of newly proliferated cells in the dentate gyrus. The expression of the long form leptin receptor, LepRb, was detected in hippocampal progenitor cells by reverse transcription-PCR and immunohistochemistry. Leptin treatment also increased proliferation of cultured adult hippocampal progenitor cells. Analysis of signal transduction pathways revealed that leptin stimulated phosphorylation of Akt and STAT3 but not ERK1/2. Furthermore, pre-treating the cells with specific inhibitors of Akt or STAT3 attenuated leptin-induced cell proliferation in a dose-dependent manner. Taken together, our results support a role for leptin in adult hippocampal neurogenesis and suggest the involvement of the Akt and STAT3 signaling pathways in mediating the actions of leptin on neurogenesis.

  6. Increased susceptibility to RSV infection by exposure to inhaled diesel engine emissions.

    PubMed

    Harrod, Kevin S; Jaramillo, Richard J; Rosenberger, Cynthia L; Wang, Shan-Ze; Berger, Jennifer A; McDonald, Jacob D; Reed, Matthew D

    2003-04-01

    Although epidemiologic data strongly suggest a role for inhaled environmental pollutants in modulating the susceptibility to respiratory infection in humans, the underlying cellular and molecular mechanisms have not been well studied in experimental systems. The current study assessed the impact of inhaled diesel engine emissions (DEE) on the host response in vivo to a common pediatric respiratory pathogen, respiratory syncytial virus (RSV). Using a relatively resistant mouse model of RSV infection, prior exposure to either 30 microg/m3 particulate matter (PM) or 1,000 microg/m3 PM of inhaled DEE (6 h/d for seven consecutive days) increased lung inflammation to RSV infection as compared with air-exposed RSV-infected C57Bl/6 mice. Inflammatory cells in bronchoalveolar lavage fluid were increased in a dose-dependent manner with regard to the level of DEE exposure, concomitant with increased levels of inflammatory mediators. Lung histology analysis indicated pronounced peribronchial and peribronchiolar inflammation concordant with the level of DEE exposure during infection. Mucous cell metaplasia was markedly increased in the airway epithelium of DEE-exposed mice following RSV infection. Interestingly, both airway and alveolar host defense and immunomodulatory proteins were attenuated during RSV infection by prior DEE exposure. DEE-induced changes in inflammatory and lung epithelial responses to infection were associated with increased RSV gene expression in the lungs following DEE exposure. These findings are consistent with the concept that DEE exposure modulates the lung host defense to respiratory viral infections and may alter the susceptibility to respiratory infections leading to increased lung disease.

  7. Divalent cations increase lipid order in erythrocytes and susceptibility to secretory phospholipase A2.

    PubMed

    Vest, Rebekah S; Gonzales, Laurie J; Permann, Seth A; Spencer, Emily; Hansen, Lee D; Judd, Allan M; Bell, John D

    2004-04-01

    Elevated concentrations of intracellular calcium in erythrocytes increase membrane order and susceptibility to secretory phospholipase A2. We hypothesize that calcium aids the formation of domains of ordered lipids within erythrocyte membranes by interacting directly with the inner leaflet of the cell membrane. The interface of these domains with regions of more fluid lipids may create an environment with weakened neighbor-neighbor interactions that would facilitate phospholipid migration into the active site of bound secretory phospholipase A2. This hypothesis was investigated by determining the effects of seven other divalent ions on erythrocyte membrane properties. Changes in membrane order were assessed with steady-state fluorescence spectroscopy and two-photon microscopy with an environment-sensitive probe, laurdan. Each ion increased apparent membrane order in model membranes and in erythrocytes when introduced with an ionophore, suggesting that direct binding to the inner face of the membrane accounts for the effects of calcium on membrane fluidity. Furthermore, the degree to which ions affected membrane properties correlated with the ionic radius and electronegativity of the ions. Lastly, erythrocytes became more susceptible to enzyme hydrolysis in the presence of elevated intracellular levels of nickel and manganese, but not magnesium. These differences appeared related to the ability of the ions to induce a transition in erythrocyte shape.

  8. Telling true from false: cannabis users show increased susceptibility to false memories

    PubMed Central

    Riba, J; Valle, M; Sampedro, F; Rodríguez-Pujadas, A; Martínez-Horta, S; Kulisevsky, J; Rodríguez-Fornells, A

    2015-01-01

    Previous studies on the neurocognitive impact of cannabis use have found working and declarative memory deficits that tend to normalize with abstinence. An unexplored aspect of cognitive function in chronic cannabis users is the ability to distinguish between veridical and illusory memories, a crucial aspect of reality monitoring that relies on adequate memory function and cognitive control. Using functional magnetic resonance imaging, we show that abstinent cannabis users have an increased susceptibility to false memories, failing to identify lure stimuli as events that never occurred. In addition to impaired performance, cannabis users display reduced activation in areas associated with memory processing within the lateral and medial temporal lobe (MTL), and in parietal and frontal brain regions involved in attention and performance monitoring. Furthermore, cannabis consumption was inversely correlated with MTL activity, suggesting that the drug is especially detrimental to the episodic aspects of memory. These findings indicate that cannabis users have an increased susceptibility to memory distortions even when abstinent and drug-free, suggesting a long-lasting compromise of memory and cognitive control mechanisms involved in reality monitoring. PMID:25824306

  9. Telling true from false: cannabis users show increased susceptibility to false memories.

    PubMed

    Riba, J; Valle, M; Sampedro, F; Rodríguez-Pujadas, A; Martínez-Horta, S; Kulisevsky, J; Rodríguez-Fornells, A

    2015-06-01

    Previous studies on the neurocognitive impact of cannabis use have found working and declarative memory deficits that tend to normalize with abstinence. An unexplored aspect of cognitive function in chronic cannabis users is the ability to distinguish between veridical and illusory memories, a crucial aspect of reality monitoring that relies on adequate memory function and cognitive control. Using functional magnetic resonance imaging, we show that abstinent cannabis users have an increased susceptibility to false memories, failing to identify lure stimuli as events that never occurred. In addition to impaired performance, cannabis users display reduced activation in areas associated with memory processing within the lateral and medial temporal lobe (MTL), and in parietal and frontal brain regions involved in attention and performance monitoring. Furthermore, cannabis consumption was inversely correlated with MTL activity, suggesting that the drug is especially detrimental to the episodic aspects of memory. These findings indicate that cannabis users have an increased susceptibility to memory distortions even when abstinent and drug-free, suggesting a long-lasting compromise of memory and cognitive control mechanisms involved in reality monitoring.

  10. Role of HLA-DR Alleles to Increase Genetic Susceptibility to Onychomycosis in Nail Psoriasis

    PubMed Central

    Carrillo-Meléndrez, Hilda; Ortega-Hernández, Esteban; Granados, Julio; Arroyo, Sara; Barquera, Rodrigo; Arenas, Roberto

    2016-01-01

    Background Patients with nail psoriasis have an increased risk of onychomycosis. Previous studies suggest it may be due to structural changes of the nails. However, a genetic predisposition seems to be also at play. Objective To determine a genetic susceptibility for onychomycosis in nails with changes of psoriasis. Methods This is a prospective case-control study of patients with suggestive changes of nail psoriasis with onychomycosis (cases) and without onychomycosis (controls) confirmed by mycological tests. HLA typing was performed in all of them by sequence-specific primers. Results Twenty-five patients and 20 controls with a mean age of 50 years (range 37-72 years) were studied. HLA-DRB1*08 was found in 12 cases (48%) and only 3 controls (15%) [p < 0.033, odds ratio (OR) = 3.8, 95% confidence interval (CI): 0.9-19]. HLA-DR1 was found in 9 cases (36%) and only 1 control (5%) (p < 0.023, OR = 8.5, 95% CI: 1-188). Conclusion HLA-DR*08 and HLA-DR*01 probably increase the susceptibility to fungal infection in psoriasis-affected nails, but larger studies are required to confirm this observation. PMID:27843918

  11. Diabetes increases susceptibility of primary cultures of rat proximal tubular cells to chemically induced injury

    SciTech Connect

    Zhong Qing; Terlecky, Stanley R.; Lash, Lawrence H.

    2009-11-15

    Diabetic nephropathy is characterized by increased oxidative stress and mitochondrial dysfunction. In the present study, we prepared primary cultures of proximal tubular (PT) cells from diabetic rats 30 days after an ip injection of streptozotocin and compared their susceptibility to oxidants (tert-butyl hydroperoxide, methyl vinyl ketone) and a mitochondrial toxicant (antimycin A) with that of PT cells isolated from age-matched control rats, to test the hypothesis that PT cells from diabetic rats exhibit more cellular and mitochondrial injury than those from control rats when exposed to these toxicants. PT cells from diabetic rats exhibited higher basal levels of reactive oxygen species (ROS) and higher mitochondrial membrane potential, demonstrating that the PT cells maintain the diabetic phenotype in primary culture. Incubation with either the oxidants or mitochondrial toxicant resulted in greater necrotic and apoptotic cell death, greater evidence of morphological damage, greater increases in ROS, and greater decreases in mitochondrial membrane potential in PT cells from diabetic rats than in those from control rats. Pretreatment with either the antioxidant N-acetyl-L-cysteine or a catalase mimetic provided equivalent protection of PT cells from both diabetic and control rats. Despite the greater susceptibility to oxidative and mitochondrial injury, both cytoplasmic and mitochondrial glutathione concentrations were markedly higher in PT cells from diabetic rats, suggesting an upregulation of antioxidant processes in diabetic kidney. These results support the hypothesis that primary cultures of PT cells from diabetic rats are a valid model in which to study renal cellular function in the diabetic state.

  12. Polymorphisms in the RANTES gene increase susceptibility to active tuberculosis in Tunisia.

    PubMed

    Ben-Selma, Walid; Harizi, Hedi; Bougmiza, Iheb; Ben Kahla, Imen; Letaief, Mahmoud; Boukadida, Jalel

    2011-10-01

    RANTES plays a pivotal role in attracting and activating various leukocyte populations that control Mycobacterium tuberculosis infection. The present study investigated the relationship between the RANTES polymorphisms (-28C/G; rs2280788, and -403G/A; rs2107538) and susceptibility to active tuberculosis (TB) in Tunisian populations. A total of 168 patients with pulmonary TB (pTB), 55 with extrapulmonary TB (epTB), and 150 control subjects were studied. Genotype analyses were carried out using polymerase chain reaction-restriction fragment length polymorphism method. We found that the -28 GG genotype was significantly associated with susceptibility to pTB (odds ratio [OR]=11.19; 95% confidence intervals [CI], 5.14-25; P corrected for the number of genotypes [Pc]=10(-8)) and epTB (OR=11.67; 95% CI, 4.74-29.33; Pc=10(-8)). However, the -28 CC genotype was found to be significantly associated with resistance to pTB (OR=0.08; 95% CI, 0.04-0.16; Pc=10(-8)) and epTB development (OR=0.11; 95% CI, 0.05-0.27; Pc=10(-8)). -403A allele was associated with increased risk development of epTB (OR=2.21; 95% CI, 1.18-4.14; p=0.007). G-G and A-C haplotypes and the AG/GC diplotype were associated with increase susceptibility to pTB (OR=7.88, 95% CI, 5.38-11.55; Pc=3.10(-8); OR=2.32, 95% CI, 1.32-4.11; Pc=3.10(-3); OR=13.26, 95% CI, 6.06-29.89; Pc=3.10(-8); respectively) and epTB (OR=6.64, 95% CI, 4-11.05; Pc=3.10(-8); OR=2.6, 95% CI, 1.26-5.35; Pc=12.10(-3); OR=11.26, 95% CI, 4.44-29.28; Pc=3.10(-8); respectively). Collectively, our findings suggested an association of the RANTES -28C/G and -403G/A functional polymorphisms with susceptibility to Mycobacterium tuberculosis infection in Tunisian populations.

  13. Measles susceptibility in young Thai men suggests need for young adult measles vaccination: a cross sectional study.

    PubMed

    Gonwong, Siriphan; Chuenchitra, Thippawan; Khantapura, Patchariya; Islam, Dilara; Mason, Carl J

    2016-04-11

    Measles remains a major public health concern in Thailand despite the introduction of vaccination since 1984. Similar to other countries, Thailand has experienced numerous measles outbreaks including adult communities such as university student dormitories, prisons, refugee camps, and military recruit camps. These outbreaks raise questions on the seroprotective antibody level in Thai adults. To better understand measles susceptibility in young Thai adults, a retrospective measles seroprevalence study on repository serum specimens obtained with informed consent from young Thai men entering the Royal Thai Army (RTA) during 2007-2008 was conducted. A total of 7760 stratified randomized samples were chosen by residence province. Measles IgG titer was measured using a commercial IgG quantitative ELISA kit following the manufacturer's instructions. An antibody level ≥ 250 International Units per Liter (IU/L) was interpreted as seropositive. The overall measles seroprevalence was 78.5 % (95 % Confidence Interval: 77.6-79.4 %) with geometric mean titer of 738 IU/L (95 % Confidence Interval: 716-760 IU/L). The measles seroprevalence by province ranged from 59.6 % to 93.1 %. A trend of decreasing seroprevalence in the younger cohorts despite increasing immunization coverage was found. Lower seroprevalence than vaccination coverage was observed in the youngest age group. To achieve long term measles control and elimination, an integrated two doses vaccination strategy has been implemented in children in Thailand. This nationwide measles seroprevalence study in young adult RTA recruits found a measles seroprevalence lower than WHO's recommendation for measles outbreak prevention and elimination. These results raise concerns for measles control in Thailand. Supplementary immunization in young adults is essential especially in high-risk and densely populated communities to establish herd immunity for outbreak prevention and elimination.

  14. Are older adults more social than younger adults? Social importance increases older adults' prospective memory performance.

    PubMed

    Altgassen, Mareike; Kliegel, Matthias; Brandimonte, Maria; Filippello, Pina

    2010-05-01

    The purpose of this study was to explore the influence of social importance on prospective remembering in younger and older adults as a possible factor contributing to the age-prospective memory paradox. Using a between-subjects design, 40 younger and 40 older adults worked on a time-based prospective memory task in which social importance was varied. Overall, younger adults outperformed older adults in the prospective memory task. Importantly, in contrast to younger adults, older adults' prospective memory performance was significantly better in the social importance condition than in the standard condition. This interaction was not reflected in participants' time-monitoring behaviour. Findings are discussed in the context of recent prospective memory theories.

  15. The relationship of increased susceptibility of sperm DNA to denaturation and fertility in the stallion.

    PubMed

    Love, C C; Kenney, R M

    1998-10-15

    The relationship between fertility and susceptibility of sperm DNA to denaturation was determined in a group of 84 actively breeding, clinically fertile stallions. Susceptibility of DNA to denaturation was determined using the sperm chromatin structure assay (SCSA). The SCSA measures, mean of alpha-t (mean alpha t), standard deviation of alpha-t (SD alpha t), and the COMP of alpha-t (cells outside the main population)] were significantly correlated with the percentage seasonal pregnancy rate (SPR; mean alpha t, r = -0.24, P < or = 0.05; % COMP alpha t, r = -0.27, P < or = 0.05); percentage pregnant per first cycle (FCP; SD alpha t, r = -0.30, P < or = 0.01; % COMP alpha t, r = -0.42, P < or = 0.0001); and the percentage pregnant per cycle (PC; mean alpha t, r = -0.31, P < or = 0.01; SD alpha t, r = -0.32, P < or = 0.01; % COMP alpha t, r = -0.41, P < or = 0.0001). This study describes detectable intrinsic variation in sperm chromatin structure among fertile stallions (SPR, mean = 83%; FCP, mean = 58%; PC, mean = 57%) in an active breeding population (number of mares bred/stallion/year, mean = 37), in the absence of overt reproductive abnormalities and apparent diseases such that an increase in the susceptibility of sperm DNA to denaturation is associated with reduced fertility, both in terms of efficiency of reproduction (FCP and PC) and seasonal pregnancy rate (SPR). Both COMP alpha t and mean alpha t were useful indicators of fertility, with COMP alpha t being the only SCSA value able to identify mean differences between fertility groupings for SPR and FCP, and overall it was the most reliable indicator of fertility in this group of stallions. The SCSA is able to evaluate a compartment of the spermatozoa which is different from that of traditional tests for sperm quality such as motility and morphology.

  16. Human apolipoprotein E4 targeted replacement in mice reveals increased susceptibility to sleep disruption and intermittent hypoxia

    PubMed Central

    Kaushal, Navita; Ramesh, Vijay

    2012-01-01

    Intermittent hypoxia (IH) and sleep fragmentation (SF) are major manifestations of sleep apnea, a frequent condition in aging humans. Sleep perturbations are frequent in Alzheimer's disease (AD) and may underlie the progression of disease. We hypothesized that acute short-term IH, SF, and their combination (IH+SF) may reveal unique susceptibility in sleep integrity in a murine model of AD. The effects of acute IH, SF, and IH+SF on sleep architecture, delta power, sleep latency, and core body temperature were assessed in adult male human ApoE4-targeted replacement mice (hApoE4) and wild-type (WT) controls. Slow wave sleep (SWS) was significantly reduced, and rapid eye movement (REM) sleep was almost abolished during acute exposure to IH alone and IH+SF for 6 h in hApoE4, with milder effects in WT controls. Decreased delta power during SWS did not show postexposure rebound in hApoE4 unlike WT controls. IH and IH+SF induced hypothermia, which was more prominent in hApoE4 than WT controls. Mice subjected to SF also showed sleep deficits but without hypothermia. hApoE4 mice, unlike WT controls, exhibited increased sleep propensity, especially following IH and IH+SF, suggesting limited ability for sleep recovery in hApoE4 mice. These findings substantiate the potential impact of IH and SF in modulating sleep architecture and sleep homeostasis including maintenance of body temperature. Furthermore, the increased susceptibility and limited recovery ability of hApoE4 mice to sleep apnea suggests that early recognition and treatment of the latter in AD patients may restrict the progression and clinical manifestations of this frequent neurodegenerative disorder. PMID:22573105

  17. Projections of climate conditions that increase coral disease susceptibility and pathogen abundance and virulence

    NASA Astrophysics Data System (ADS)

    Maynard, Jeffrey; van Hooidonk, Ruben; Eakin, C. Mark; Puotinen, Marjetta; Garren, Melissa; Williams, Gareth; Heron, Scott F.; Lamb, Joleah; Weil, Ernesto; Willis, Bette; Harvell, C. Drew

    2015-07-01

    Rising sea temperatures are likely to increase the frequency of disease outbreaks affecting reef-building corals through impacts on coral hosts and pathogens. We present and compare climate model projections of temperature conditions that will increase coral susceptibility to disease, pathogen abundance and pathogen virulence. Both moderate (RCP 4.5) and fossil fuel aggressive (RCP 8.5) emissions scenarios are examined. We also compare projections for the onset of disease-conducive conditions and severe annual coral bleaching, and produce a disease risk summary that combines climate stress with stress caused by local human activities. There is great spatial variation in the projections, both among and within the major ocean basins, in conditions favouring disease development. Our results indicate that disease is as likely to cause coral mortality as bleaching in the coming decades. These projections identify priority locations to reduce stress caused by local human activities and test management interventions to reduce disease impacts.

  18. Aspirin increases susceptibility of Helicobacter pylori to metronidazole by augmenting endocellular concentrations of antimicrobials.

    PubMed

    Zhang, Xiao-Ping; Wang, Wei-Hong; Tian, Yu; Gao, Wen; Li, Jiang

    2009-02-28

    To investigate the mechanisms of aspirin increasing the susceptibility of Helicobacter pylori (H pylori) to metronidazole. H pylori reference strain 26695 and two metronidazole-resistant isolates of H pylori were included in this study. Strains were incubated in Brucella broth with or without aspirin (1 mmol/L). The rdxA gene of H pylori was amplified by PCR and sequenced. The permeability of H pylori to antimicrobials was determined by analyzing the endocellular radioactivity of the cells after incubated with [7-(3)H]-tetracycline. The outer membrane proteins (OMPs) of H pylori 26695 were depurated and analyzed by SDS-PAGE. The expression of 5 porins (hopA, hopB, hopC, hopD and hopE) and the putative RND efflux system (hefABC) of H pylori were analyzed using real-time quantitative PCR. The mutations in rdxA gene did not change in metronidazole resistant isolates treated with aspirin. The radioactivity of H pylori increased when treated with aspirin, indicating that aspirin improved the permeability of the outer membrane of H pylori. However, the expression of two OMP bands between 55 kDa and 72 kDa altered in the presence of aspirin. The expression of the mRNA of hopA, hopB, hopC, hopD, hopE and hefA, hefB, hefC of H pylori did not change when treated with aspirin. Although aspirin increases the susceptibility of H pylori to metronidazole, it has no effect on the mutations of rdxA gene of H pylori. Aspirin increases endocellular concentrations of antimicrobials probably by altering the OMP expression.

  19. Aspirin increases susceptibility of Helicobacter pylori to metronidazole by augmenting endocellular concentrations of antimicrobials

    PubMed Central

    Zhang, Xiao-Ping; Wang, Wei-Hong; Tian, Yu; Gao, Wen; Li, Jiang

    2009-01-01

    AIM: To investigate the mechanisms of aspirin increasing the susceptibility of Helicobacter pylori (H pylori) to metronidazole. METHODS: H pylori reference strain 26 695 and two metronidazole-resistant isolates of H pylori were included in this study. Strains were incubated in Brucella broth with or without aspirin (1 mmol/L). The rdxA gene of H pylori was amplified by PCR and sequenced. The permeability of H pylori to antimicrobials was determined by analyzing the endocellular radioactivity of the cells after incubated with [7-3H]-tetracycline. The outer membrane proteins (OMPs) of H pylori 26 695 were depurated and analyzed by SDS-PAGE. The expression of 5 porins (hopA, hopB, hopC, hopD and hopE) and the putative RND efflux system (hefABC) of H pylori were analyzed using real-time quantitative PCR. RESULTS: The mutations in rdxA gene did not change in metronidazole resistant isolates treated with aspirin. The radioactivity of H pylori increased when treated with aspirin, indicating that aspirin improved the permeability of the outer membrane of H pylori. However, the expression of two OMP bands between 55 kDa and 72 kDa altered in the presence of aspirin. The expression of the mRNA of hopA, hopB, hopC, hopD, hopE and hefA, hefB, hefC of H pylori did not change when treated with aspirin. CONCLUSION: Although aspirin increases the susceptibility of H pylori to metronidazole, it has no effect on the mutations of rdxA gene of H pylori. Aspirin increases endocellular concentrations of antimicrobials probably by altering the OMP expression. PMID:19248190

  20. Depletion of natural killer cells increases mice susceptibility in a Pseudomonas aeruginosa pneumonia model.

    PubMed

    Broquet, Alexis; Roquilly, Antoine; Jacqueline, Cédric; Potel, Gilles; Caillon, Jocelyne; Asehnoune, Karim

    2014-06-01

    Pseudomonas aeruginosa infection is a clinically relevant infection involved in pneumonia in ICUs. Understanding the type of immune response initiated by the host during pneumonia would help defining new strategies to interfere with the bacteria pathogenicity. In this setting, the role of natural killer cells remains controversial. We assessed the role of systemic natural killer cells in a Pseudomonas aeruginosa mouse pneumonia model. Experimental study. Research laboratory from a university hospital. RjOrl:SWISS and BALB/cJ mice (weight, 20-24 g). Lung injuries were assessed by bacterial load, myeloperoxidase activity, endothelial permeability (pulmonary edema), immune cell infiltrate (histological analysis), proinflammatory cytokine release, and Ly6-G immunohistochemistry. Bacterial loads were assessed in the lungs and spleen. Natural killer cell number and status were assessed in spleen (flow cytometry and quantitative polymerase chain reaction). Depletion of natural killer cells was achieved through an IV anti-asialo-GM1 antibody injection. Pseudomonas aeruginosa tracheal instillation led to an acute pneumonia with a rapid decrease of bacterial load in lungs and with an increase of endothelial permeability, proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β), and myeloperoxidase activity followed by Ly6-G positive cell infiltrate in lungs. Pseudomonas aeruginosa was detected in the spleen. Membrane markers of activation and maturation (CD69 and KLRG1 molecules) were increased in splenic natural killer cells during Pseudomonas aeruginosa infection. Splenic natural killer cells activated upon Pseudomonas aeruginosa infection produced interferon-γ but not interleukin-10. Ultimately, mice depleted of natural killer cells displayed an increased neutrophil numbers in the lungs and an increased mortality rate without bacterial load modifications in the lungs, indicating that mice depleted of natural killer cells were much more susceptible to

  1. Tumor Necrosis Factor B (TNFB) Genetic Variants and Its Increased Expression Are Associated with Vitiligo Susceptibility

    PubMed Central

    Laddha, Naresh C.; Dwivedi, Mitesh; Gani, Amina R.; Mansuri, Mohmmad Shoab; Begum, Rasheedunnisa

    2013-01-01

    Genetic polymorphisms in TNFB are involved in the regulation of its expression and are found to be associated with various autoimmune diseases. The aim of the present study was to determine whether TNFB +252A/G (rs909253) and exon 3 C/A (rs1041981) polymorphisms are associated with vitiligo susceptibility, and expression of TNFB and ICAM1 affects the disease onset and progression. We have earlier reported the role of TNFA in autoimmune pathogenesis of vitiligo, and we now show the involvement of TNFB in vitiligo pathogenesis. The two polymorphisms investigated in the TNFB were in strong linkage disequilibrium and significantly associated with vitiligo. TNFB and ICAM1 transcripts were significantly increased in patients compared to controls. Active vitiligo patients showed significant increase in TNFB transcripts compared to stable vitiligo. The genotype-phenotype analysis revealed that TNFB expression levels were higher in patients with GG and AA genotypes as compared to controls. Patients with the early age of onset and female patients showed higher TNFB and ICAM1 expression. Overall, our findings suggest that the increased TNFB transcript levels in vitiligo patients could result, at least in part, from variations at the genetic level which in turn leads to increased ICAM1 expression. For the first time, we show that TNFB +252A/G and exon 3 C/A polymorphisms are associated with vitiligo susceptibility and influence the TNFB and ICAM1 expression. Moreover, the study also emphasizes influence of TNFB and ICAM1 on the disease progression, onset and gender bias for developing vitiligo. PMID:24312346

  2. Perinatal hypoxia increases susceptibility to high-altitude polycythemia and attendant pulmonary vascular dysfunction

    PubMed Central

    Gonzales, Marcelino; Rodriguez, Armando; Bellido, Diva; Salmon, Carlos Salinas; Ladenburger, Anne; Reardon, Lindsay; Vargas, Enrique; Moore, Lorna G.

    2015-01-01

    Perinatal exposures exert a profound influence on physiological function, including developmental processes vital for efficient pulmonary gas transfer throughout the lifespan. We extend the concept of developmental programming to chronic mountain sickness (CMS), a debilitating syndrome marked by polycythemia, ventilatory impairment, and pulmonary hypertension that affects ∼10% of male high-altitude residents. We hypothesized that adverse perinatal oxygenation caused abnormalities of ventilatory and/or pulmonary vascular function that increased susceptibility to CMS in adulthood. Subjects were 67 male high-altitude (3,600–4,100 m) residents aged 18–25 yr with excessive erythrocytosis (EE, Hb concentration ≥18.3 g/dl), a preclinical form of CMS, and 66 controls identified from a community-based survey (n = 981). EE subjects not only had higher Hb concentrations and erythrocyte counts, but also lower alveolar ventilation, impaired pulmonary diffusion capacity, higher systolic pulmonary artery pressure, lower pulmonary artery acceleration time, and more frequent right ventricular hypertrophy, than controls. Compared with controls, EE subjects were more often born to mothers experiencing hypertensive complications of pregnancy and hypoxia during the perinatal period, with each increasing the risk of developing EE (odds ratio = 5.25, P = 0.05 and odds ratio = 6.44, P = 0.04, respectively) after other factors known to influence EE status were taken into account. Adverse perinatal oxygenation is associated with increased susceptibility to EE accompanied by modest abnormalities of the pulmonary circulation that are independent of increased blood viscosity. The association between perinatal hypoxia and EE may be due to disrupted alveolarization and microvascular development, leading to impaired gas exchange and/or pulmonary hypertension. PMID:26092986

  3. Perinatal hypoxia increases susceptibility to high-altitude polycythemia and attendant pulmonary vascular dysfunction.

    PubMed

    Julian, Colleen Glyde; Gonzales, Marcelino; Rodriguez, Armando; Bellido, Diva; Salmon, Carlos Salinas; Ladenburger, Anne; Reardon, Lindsay; Vargas, Enrique; Moore, Lorna G

    2015-08-15

    Perinatal exposures exert a profound influence on physiological function, including developmental processes vital for efficient pulmonary gas transfer throughout the lifespan. We extend the concept of developmental programming to chronic mountain sickness (CMS), a debilitating syndrome marked by polycythemia, ventilatory impairment, and pulmonary hypertension that affects ∼10% of male high-altitude residents. We hypothesized that adverse perinatal oxygenation caused abnormalities of ventilatory and/or pulmonary vascular function that increased susceptibility to CMS in adulthood. Subjects were 67 male high-altitude (3,600-4,100 m) residents aged 18-25 yr with excessive erythrocytosis (EE, Hb concentration ≥18.3 g/dl), a preclinical form of CMS, and 66 controls identified from a community-based survey (n = 981). EE subjects not only had higher Hb concentrations and erythrocyte counts, but also lower alveolar ventilation, impaired pulmonary diffusion capacity, higher systolic pulmonary artery pressure, lower pulmonary artery acceleration time, and more frequent right ventricular hypertrophy, than controls. Compared with controls, EE subjects were more often born to mothers experiencing hypertensive complications of pregnancy and hypoxia during the perinatal period, with each increasing the risk of developing EE (odds ratio = 5.25, P = 0.05 and odds ratio = 6.44, P = 0.04, respectively) after other factors known to influence EE status were taken into account. Adverse perinatal oxygenation is associated with increased susceptibility to EE accompanied by modest abnormalities of the pulmonary circulation that are independent of increased blood viscosity. The association between perinatal hypoxia and EE may be due to disrupted alveolarization and microvascular development, leading to impaired gas exchange and/or pulmonary hypertension. Copyright © 2015 the American Physiological Society.

  4. Increased susceptibility of IgA-deficient mice to pulmonary Francisella tularensis live vaccine strain infection.

    PubMed

    Furuya, Yoichi; Kirimanjeswara, Girish S; Roberts, Sean; Metzger, Dennis W

    2013-09-01

    Francisella tularensis, the causative agent of tularemia, is most deadly in the pneumonic form; therefore, mucosal immunity is an important first line of defense against this pathogen. We have now evaluated the lethality of primary F. tularensis live vaccine strain (LVS) pulmonary infection in mice that are defective in IgA (IgA(-/-) mice), the predominant mucosal Ig isotype. The results showed that IgA(-/-) mice were more susceptible than IgA(+/+) mice to intranasal F. tularensis LVS infection, despite developing higher levels of LVS-specific total, IgG, and IgM antibodies in the bronchoalveolar lavage specimens following infection. In addition, the absence of IgA resulted in a significant increase in bacterial loads and reduced survival. Interestingly, IgA(-/-) mice had lower pulmonary gamma interferon (IFN-γ) levels and decreased numbers of IFN-γ-secreting CD4(+) and CD8(+) T cells in the lung on day 9 postinfection compared to IgA(+/+) mice. Furthermore, IgA(-/-) mice displayed reduced interleukin 12 (IL-12) levels at early time points, and supplementing IgA(-/-) mice with IL-12 prior to LVS challenge induced IFN-γ production by NK cells and rescued them from mortality. Thus, IgA(-/-) mice are highly susceptible to primary pulmonary LVS infections not only because of IgA deficiency but also because of reduced IFN-γ responses.

  5. Selective Pharmacologic Inhibition of a PASTA Kinase Increases Listeria monocytogenes Susceptibility to β-Lactam Antibiotics

    PubMed Central

    Pensinger, Daniel A.; Aliota, Matthew T.; Schaenzer, Adam J.; Boldon, Kyle M.; Ansari, Israr-ul H.; Vincent, William J. B.; Knight, Benjamin; Reniere, Michelle L.; Striker, Rob

    2014-01-01

    While β-lactam antibiotics are a critical part of the antimicrobial arsenal, they are frequently compromised by various resistance mechanisms, including changes in penicillin binding proteins of the bacterial cell wall. Genetic deletion of the penicillin binding protein and serine/threonine kinase-associated protein (PASTA) kinase in methicillin-resistant Staphylococcus aureus (MRSA) has been shown to restore β-lactam susceptibility. However, the mechanism remains unclear, and whether pharmacologic inhibition would have the same effect is unknown. In this study, we found that deletion or pharmacologic inhibition of the PASTA kinase in Listeria monocytogenes by the nonselective kinase inhibitor staurosporine results in enhanced susceptibility to both aminopenicillin and cephalosporin antibiotics. Resistance to vancomycin, another class of cell wall synthesis inhibitors, or antibiotics that inhibit protein synthesis was unaffected by staurosporine treatment. Phosphorylation assays with purified kinases revealed that staurosporine selectively inhibited the PASTA kinase of L. monocytogenes (PrkA). Importantly, staurosporine did not inhibit a L. monocytogenes kinase without a PASTA domain (Lmo0618) or the PASTA kinase from MRSA (Stk1). Finally, inhibition of PrkA with a more selective kinase inhibitor, AZD5438, similarly led to sensitization of L. monocytogenes to β-lactam antibiotics. Overall, these results suggest that pharmacologic targeting of PASTA kinases can increase the efficacy of β-lactam antibiotics. PMID:24867981

  6. Antimicrobial susceptibilities of uropathogen Escherichia coli in renal transplant recipients: dramatic increase in ciprofloxacin resistance.

    PubMed

    Azap, Ö; Togan, T; Yesilkaya, A; Arslan, H; Haberal, M

    2013-04-01

    The urinary tract is the most common site of bacterial infections in renal transplant recipients. The management of urinary tract infections (UTI) in renal transplant recipients is becoming more difficult because of drug-resistant bacteria. The antimicrobial susceptibilities of uropathogen bacteria isolated from 398 patients who underwent renal transplantation between 2007 and 2011 were obtained from medical records. At least 1 UTI episode was diagnosed in 172 (43.2%) patients. Among the 703 bacteria isolated from these patients, Exherichia coli the most common pathogen, was isolated from 407/703 episodes (57.8%). Ciprofloxacin, co-trimoxazole, ceftriaxone, and gentamicin resistance rates were 59.4%, 85.7%, 40.7%, and 36.6%, respectively. Ninty six of 407 E. coli isolates (23.5%) were ESBL positive. Analysis of resistance rates in our center demonstrated ciprofloxacin resistance rate in uropathogenic E. coli to have increased gradually from 30.4% in 2003, 41.3% in 2007, and 59.4% in 2012. Instutional data regarding the etiologic agents and antimicrobial susceptibility results are important for proper management of patients with UTI.

  7. Primary immunodeficiency diseases associated with increased susceptibility to viral infections and malignancies.

    PubMed

    Rezaei, Nima; Hedayat, Mona; Aghamohammadi, Asghar; Nichols, Kim E

    2011-06-01

    Primary immunodeficiencies (PIDs) are commonly characterized by an increased susceptibility to specific infections and, in certain instances, a higher than usual incidence of malignancies. Although improved diagnosis and early treatment of PIDs have reduced early morbidity and mortality from infection, the development of cancer remains a significant cause of premature death. The emergence of cancer in patients with PIDs often results from impairments in the immune response that lead to weakened surveillance against oncogenic viruses, premalignant or malignant cells, or both. Here we review the clinical and biologic features of several PIDs associated with enhanced susceptibility to viral infections and cancer, including X-linked lymphoproliferative disease; IL-2-inducible T-cell kinase deficiency; epidermodysplasia verruciformis; warts, hypogammaglobulinemia, infections, and myelokathexis syndrome; autosomal recessive hyper-IgE syndrome; X-linked agammaglobulinemia; and common variable immunodeficiency. It is of importance that we gain in-depth insights into the fundamental molecular nature of these unique PIDs to better understand the pathogenesis of virus-associated malignancies and to develop innovative therapeutic strategies.

  8. Interleukin-10: Role in increasing susceptibility and pathogenesis of rheumatic fever/rheumatic heart disease.

    PubMed

    Sharma, Neha; Toor, Devinder

    2017-02-01

    Streptococcus pyogenes (group A streptococcus) causes rheumatic fever (RF) which later progresses towards rheumatic heart disease (RHD) in the susceptible individuals. RF and RHD both contribute towards increasing global burden of disease, especially in developing countries. RHD is one of the most common acquired heart diseases causing permanent damage to heart valves which ultimately leads to heart failure. In RHD, heart valve lesions are formed which are mediated by autoimmune reaction between streptococcal antigens (M protein and group A carbohydrate epitope GlcNAc) and heart tissues. On the other hand, inflammatory response generated by cytokines promotes chronicity of the disease. Varying concentrations of interleukin-10 (IL-10) in patients and controls are reported and are also found to be associated with IL-10 gene polymorphism in RF/RHD patients. Although the effect of IL-10 gene polymorphism on the functionality of IL-10 is unknown, many investigations suggest an important role of IL-10 and its polymorphism in immune regulation and progression of disease in RF/RHD. This review summarizes the studies based on association of interleukin-10 with RHD in different populations to understand the role of IL-10 in susceptibility and pathogenesis of the disease.

  9. Black and White adults' perspectives on the genetics of nicotine addiction susceptibility.

    PubMed

    Park, Elyse R; Kleimann, Susan; Youatt, Emily J; Lockhart, Abigail; Campbell, Eric G; Levy, Douglas E; Halbert, Chanita Hughes; Schmieder, Erin; Krishna, Rasika; Shields, Alexandra E

    2011-07-01

    Emerging research may soon lead to improved quit rates via genetically-tailored smoking cessation treatment. The purpose of this study was to explore individuals' beliefs and attitudes about genetic testing in this context, and how these may differ across racial groups. Two site qualitative study. Eleven focus groups were conducted in 2007 with 51 Black and 55 White adult participants in Montgomery, AL and Baltimore, MD. Questions were asked about smoking as an addiction, the role of genetics in nicotine addiction susceptibility, and undergoing genetic testing to receive tailored smoking cessation treatment. Data were analyzed using content analysis. Most participants believed that smoking was an addiction yet were unwilling to endorse the notion that genetics played a role in nicotine addiction susceptibility. However, 91% of White participants and 62% of Black participants indicated that they would likely take a genetic test that would match them to their optimal smoking cessation treatment. The primary potential benefit was a vague sense that additional knowledge about oneself would be of value. Primary barriers included disinterest and skepticism about the test, unwillingness to believe that genetics played a role in nicotine addiction or treatment response, and concerns about psychological consequences. The majority of participants, particularly Black participants, did not believe that genetics played a significant role in nicotine addiction susceptibility but were willing to undergo genetic testing. Participants identified some benefit to tailoring smoking treatment by genotype. However, participants also expressed skepticism about the test and concerns about its consequences; these issues would need to be addressed in the clinical encounter. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Impulsive social influence increases impulsive choices on a temporal discounting task in young adults.

    PubMed

    Gilman, Jodi M; Curran, Max T; Calderon, Vanessa; Stoeckel, Luke E; Evins, A Eden

    2014-01-01

    Adolescents and young adults who affiliate with friends who engage in impulsive behavior are more likely to engage in impulsive behaviors themselves, and those who associate with prosocial (i.e. more prudent, future oriented) peers are more likely to engage in prosocial behavior. However, it is difficult to disentangle the contribution of peer influence vs. peer selection (i.e., whether individuals choose friends with similar traits) when interpreting social behaviors. In this study, we combined a novel social manipulation with a well-validated delay discounting task assessing impulsive behavior to create a social influence delay discounting task, in which participants were exposed to both impulsive (smaller, sooner or SS payment) and non-impulsive (larger, later or LL payment) choices from their peers. Young adults in this sample, n = 51, aged 18-25 had a higher rate of SS choices after exposure to impulsive peer influence than after exposure to non-impulsive peer influence. Interestingly, in highly susceptible individuals, the rate of non-impulsive choices did not increase after exposure to non-impulsive influence. There was a positive correlation between self-reported suggestibility and degree of peer influence on SS choices. These results suggest that, in young adults, SS choices appear to be influenced by the choices of same-aged peers, especially for individuals who are highly susceptible to influence.

  11. Impulsive Social Influence Increases Impulsive Choices on a Temporal Discounting Task in Young Adults

    PubMed Central

    Gilman, Jodi M.; Curran, Max T.; Calderon, Vanessa; Stoeckel, Luke E.; Evins, A. Eden

    2014-01-01

    Adolescents and young adults who affiliate with friends who engage in impulsive behavior are more likely to engage in impulsive behaviors themselves, and those who associate with prosocial (i.e. more prudent, future oriented) peers are more likely to engage in prosocial behavior. However, it is difficult to disentangle the contribution of peer influence vs. peer selection (i.e., whether individuals choose friends with similar traits) when interpreting social behaviors. In this study, we combined a novel social manipulation with a well-validated delay discounting task assessing impulsive behavior to create a social influence delay discounting task, in which participants were exposed to both impulsive (smaller, sooner or SS payment) and non-impulsive (larger, later or LL payment) choices from their peers. Young adults in this sample, n = 51, aged 18–25 had a higher rate of SS choices after exposure to impulsive peer influence than after exposure to non-impulsive peer influence. Interestingly, in highly susceptible individuals, the rate of non-impulsive choices did not increase after exposure to non-impulsive influence. There was a positive correlation between self-reported suggestibility and degree of peer influence on SS choices. These results suggest that, in young adults, SS choices appear to be influenced by the choices of same-aged peers, especially for individuals who are highly susceptible to influence. PMID:24988440

  12. Susceptibility of Xenopus laevis tadpoles to infection by the ranavirus Frog-Virus 3 correlates with a reduced and delayed innate immune response in comparison with adult frogs.

    PubMed

    De Jesús Andino, Francisco; Chen, Guangchun; Li, Zhenghui; Grayfer, Leon; Robert, Jacques

    2012-10-25

    Xenopus laevis adults mount effective immune responses to ranavirus Frog Virus 3 (FV3) infections and clear the pathogen within 2-3 weeks. In contrast, most tadpoles cannot clear FV3 and succumb to infections within a month. While larval susceptibility has been attributed to ineffective adaptive immunity, the contribution of innate immune components has not been addressed. Accordingly, we performed a comprehensive gene expression analysis on FV3-infected tadpoles and adults. In comparison to adults, leukocytes and tissues of infected tadpoles exhibited modest (10-100 time lower than adult) and delayed (3 day later than adult) increase in expression of inflammation-associated (TNF-α, IL-1β and IFN-γ) and antiviral (Mx1) genes. In contrast, these genes were readily and robustly upregulated in tadpoles upon bacterial stimulation. Furthermore, greater proportions of larval than adult PLs were infected by FV3. Our study suggests that tadpole susceptibility to FV3 infection is partially due to poor virus-elicited innate immune responses. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Susceptibility of Xenopus laevis tadpoles to infection by the ranavirus Frog-Virus 3 correlates with a reduced and delayed innate immune response in comparison with adult frogs

    PubMed Central

    De Jesús Andino, Francisco; Chen, Guangchun; Li, Zhenghui; Grayfer, Leon; Robert, Jacques

    2012-01-01

    Xenopus laevis adults mount effective immune responses to ranavirus Frog Virus 3 (FV3) infections and clear the pathogen within 2–3 weeks. In contrast, most tadpoles cannot clear FV3 and succumb to infections within a month. While larval susceptibility has been attributed to ineffective adaptive immunity, the contribution of innate immune components has not been addressed. Accordingly, we performed a comprehensive gene expression analysis on FV3-infected tadpoles and adults. In comparison to adults, leukocytes and tissues of infected tadpoles exhibited modest (10–100 time lower than adult) and delayed (3 day later than adult) increase in expression of inflammation-associated (TNF-α, IL-1β and IFN-γ) and antiviral (Mx1) genes. In contrast, these genes were readily and robustly upregulated in tadpoles upon bacterial stimulation. Furthermore, greater proportions of larval than adult PLs were infected by FV3. Our study suggests that tadpole susceptibility to FV3 infection is partially due to poor virus-elicited innate immune responses. PMID:22819836

  14. Increasing the Success of Adults from Diverse Populations.

    ERIC Educational Resources Information Center

    Sheckley, Barry G.; Keeton, Morris T.

    1995-01-01

    The following methods can increase the academic success of adults from diverse populations: focus on how educational circumstances are experienced by individuals, not broad groups; maximize time spent on tasks related to course/degree requirements; and reduce student costs in terms of time, money, frustration, and stress. (SK)

  15. Hunting increases adaptive auditory map plasticity in adult barn owls.

    PubMed

    Bergan, Joseph F; Ro, Peter; Ro, Daniel; Knudsen, Eric I

    2005-10-19

    The optic tectum (OT) of barn owls contains topographic maps of auditory and visual space. Barn owls reared with horizontally displacing prismatic spectacles (prisms) acquire a novel auditory space map in the OT that restores alignment with the prismatically displaced visual map. Although juvenile owls readily acquire alternative maps of auditory space as a result of experience, this plasticity is reduced greatly in adults. We tested whether hunting live prey, a natural and critically important behavior for barn owls, increases auditory map plasticity in adult owls. Two groups of naive adult owls were fit with prisms. The first group was fed dead mice during 10 weeks of prism experience, while the second group was required to hunt live prey for an identical period of time. When the owls hunted live prey, auditory maps shifted substantially farther (five times farther, on average) and the consistency of tuning curve shifts within each map increased. Only a short period of time in each day, during which the two groups experienced different conditions, accounts for this effect. In addition, increased map plasticity correlated with behavioral improvements in the owls' ability to strike and capture prey. These results indicate that the experience of hunting dramatically increases adult adaptive plasticity in this pathway.

  16. Thematic Solutions Using Young Adult Literature to Increase Reading Comprehension

    ERIC Educational Resources Information Center

    Adams, Jill; Bushman, John H.

    2006-01-01

    In this article, the authors discuss thematic solutions using young adult literature to increase reading comprehension. Here, they emphasize that prior knowledge plays a very important role in the reading process. As students read, they actively "construct meaning through the integration of existing and new knowledge and the flexible use of…

  17. Increasing Student/Older Adult Interaction by Life Review Assignments.

    ERIC Educational Resources Information Center

    Sumner, Edward D.; Haight, Barbara K.

    1993-01-01

    A method for increasing interaction between students and older adults in a geriatric pharmacy course uses an instructional module on stereotypes, age and personality, role changes, and nursing home living. The course requires students to conduct a life review of someone over age 65. The exercise improves student communication skills and…

  18. Lambda Interferon Restructures the Nasal Microbiome and Increases Susceptibility to Staphylococcus aureus Superinfection

    PubMed Central

    Planet, Paul J.; Parker, Dane; Cohen, Taylor S.; Smith, Hannah; Leon, Justinne D.; Ryan, Chanelle; Hammer, Tobin J.; Fierer, Noah; Chen, Emily I.

    2016-01-01

    ABSTRACT Much of the morbidity and mortality associated with influenza virus respiratory infection is due to bacterial coinfection with pathogens that colonize the upper respiratory tract such as methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pneumoniae. A major component of the immune response to influenza virus is the production of type I and III interferons. Here we show that the immune response to infection with influenza virus causes an increase and restructuring of the upper respiratory microbiota in wild-type (WT) mice but not in Il28r−/− mutant mice lacking the receptor for type III interferon. Mice lacking the IL-28 receptor fail to induce STAT1 phosphorylation and expression of its regulator, SOCS1. Il28r−/− mutant mice have increased expression of interleukin-22 (IL-22), as well as Ngal and RegIIIγ, in the nasal cavity, the source of organisms that would be aspirated to cause pneumonia. Proteomic analysis reveals changes in several cytoskeletal proteins that contribute to barrier function in the nasal epithelium that may contribute to the effects of IL-28 signaling on the microbiota. The importance of the effects of IL-28 signaling in the pathogenesis of MRSA pneumonia after influenza virus infection was confirmed by showing that WT mice nasally colonized before or after influenza virus infection had significantly higher levels of infection in the upper airways, as well as significantly greater susceptibility to MRSA pneumonia than Il28r−/− mutant mice did. Our results suggest that activation of the type III interferon in response to influenza virus infection has a major effect in expanding the upper airway microbiome and increasing susceptibility to lower respiratory tract infection. PMID:26861017

  19. Antepartum Antibiotic Treatment Increases Offspring Susceptibility to Experimental Colitis: A Role of the Gut Microbiota

    PubMed Central

    Munyaka, Peris Mumbi; Eissa, N.; Bernstein, Charles Noah; Khafipour, Ehsan; Ghia, Jean-Eric

    2015-01-01

    Background and aims Postnatal maturation of the immune system is largely driven by exposure to microbes, and thus the nature of intestinal colonization may be associated with development of childhood diseases that may persist into adulthood. We investigated whether antepartum antibiotic (ATB) therapy can increase offspring susceptibility to experimental colitis through alteration of the gut microbiota. Methods Pregnant C57Bl/6 mice were treated with cefazolin at 160 mg/kg body weight or with saline starting six days before due date. At 7 weeks, fecal samples were collected from male offspring after which they received 4% dextran sulfate sodium (DSS) in drinking water for 5 days. Disease activity index, histology, colonic IL-6, IL-1β and serum C-reactive protein (CRP) were determined. The V3-V4 region of colonic and fecal bacterial 16S rRNA was sequenced. Alpha-, beta-diversity and differences at the phylum and genus levels were determined, while functional pathways of classified bacteria were predicted. Results ATB influenced fecal bacterial composition and hence bacterial functional pathways before induction of colitis. After induction of colitis, ATB increased onset of clinical disease, histologic score, and colonic IL-6. In addition, ATB decreased fecal microbial richness, changed fecal and colon microbial composition, which was accompanied by a modification of microbial functional pathways. Also, several taxa were associated with ATB at lower taxonomical levels. Conclusions The results support the hypothesis that antepartum antibiotics modulate offspring intestinal bacterial colonization and increase susceptibility to develop colonic inflammation in a murine model of colitis, and may guide future interventions to restore physiologic intestinal colonization in offspring born by antibiotic-exposed mothers. PMID:26605545

  20. Antepartum Antibiotic Treatment Increases Offspring Susceptibility to Experimental Colitis: A Role of the Gut Microbiota.

    PubMed

    Munyaka, Peris Mumbi; Eissa, N; Bernstein, Charles Noah; Khafipour, Ehsan; Ghia, Jean-Eric

    2015-01-01

    Postnatal maturation of the immune system is largely driven by exposure to microbes, and thus the nature of intestinal colonization may be associated with development of childhood diseases that may persist into adulthood. We investigated whether antepartum antibiotic (ATB) therapy can increase offspring susceptibility to experimental colitis through alteration of the gut microbiota. Pregnant C57Bl/6 mice were treated with cefazolin at 160 mg/kg body weight or with saline starting six days before due date. At 7 weeks, fecal samples were collected from male offspring after which they received 4% dextran sulfate sodium (DSS) in drinking water for 5 days. Disease activity index, histology, colonic IL-6, IL-1β and serum C-reactive protein (CRP) were determined. The V3-V4 region of colonic and fecal bacterial 16S rRNA was sequenced. Alpha-, beta-diversity and differences at the phylum and genus levels were determined, while functional pathways of classified bacteria were predicted. ATB influenced fecal bacterial composition and hence bacterial functional pathways before induction of colitis. After induction of colitis, ATB increased onset of clinical disease, histologic score, and colonic IL-6. In addition, ATB decreased fecal microbial richness, changed fecal and colon microbial composition, which was accompanied by a modification of microbial functional pathways. Also, several taxa were associated with ATB at lower taxonomical levels. The results support the hypothesis that antepartum antibiotics modulate offspring intestinal bacterial colonization and increase susceptibility to develop colonic inflammation in a murine model of colitis, and may guide future interventions to restore physiologic intestinal colonization in offspring born by antibiotic-exposed mothers.

  1. Prenatal caffeine exposure induced high susceptibility to metabolic syndrome in adult female offspring rats and its underlying mechanisms.

    PubMed

    Pei, Lin-Guo; Yuan, Chao; Guo, Yi-Tian; Kou, Hao; Xia, Li-Ping; Zhang, Li; Yan, You-E; Xu, Dan; Wang, Hui

    2017-08-01

    Our previous studies have demonstrated that prenatal caffeine exposure (PCE) induced an intrauterine programming of hypothalamic-pituitary-adrenal axis (HPAA)-associated neuroendocrine metabolism in 3-month-old offspring rats. In this study, we aimed to confirm this programming disorder and high susceptibility to metabolic syndrome (MS) in 10-month-old female PCE offspring with postnatal catch-up growth. We found that PCE female offspring rats showed decreased bodyweight but a higher rate of weight gain after birth. Moreover, in the offspring, basal hyperinsulinemia and insulin resistance were observed before unpredictable chronic stress (UCS), but serum total cholesterol (TCH) levels and triglyceride/high-density lipoprotein-cholesterol (TG/HDL-C), TCH/HDL-C and low-density lipoprotein-cholesterol/HDL-C (LDL-C/HDL-C) ratio changes were increased after UCS, accompanied by morphological damage of the related tissues. These results suggested that PCE adult female offspring rats were highly susceptible to MS, which is related to HPAA-associated neuroendocrine-metabolic programming disorder. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Synergistic interaction between UVB radiation and temperature increases susceptibility to parasitic infection in a fish

    PubMed Central

    Cramp, Rebecca L.; Reid, Stefanie; Seebacher, Frank; Franklin, Craig E.

    2014-01-01

    Levels of UVB radiation (UVB) and mean temperatures have increased substantially over recent decades in many regions of the world. Both stressors independently can compromise immune function, disease resistance and fitness in fish. The impact of UVB can also be exacerbated by interactions with environmental temperatures. In this paper, we test the hypothesis that UVB and temperature act synergistically to influence patterns of energy consumption and susceptibility to disease. We exposed mosquitofish, Gambusia holbrooki, to a factorial design of low and high UVB levels and low (18°C) and high (25°C) temperatures. The combination of high UVB and high temperature interacted synergistically to suppress metabolism and exacerbate infection intensity by the fish pathogen whitespot (Ichtyhophthirius multifiliis). Given the rapid changes in the thermal environment globally, the interaction between UVB and temperatures on energy use and disease resistance could pose significant problems for aquatic animal health in the context of both pre-existing and emerging diseases. PMID:25252833

  3. Increased NHC Cells in the Peritoneal Cavity of Plasmacytoma Susceptible BALB/c Mouse

    PubMed Central

    Sánchez-González, Berenice; García-Vázquez, Francisco Javier; Farfán-Morales, José Eduardo; Jiménez-Zamudio, Luis Antonio

    2015-01-01

    BALB/c strain mice are unique in that they develop murine plasmacytoma (MPC) as a consequence of the inflammation induced by pristane oil injection in the peritoneal cavity. In this work the Treg, Th17, B1, B2, and NHC lymphocyte populations from the peritoneal environment of BALB/c, the susceptible strain, and C57BL/6 mice, which do not develop MPC after oil treatment, were studied. Both oil-treated strains showed decreased levels of Th17 lymphocytes, no significant variation in Treg lymphocytes, and a drastic decrease of all B lymphocyte populations. However, only oil-induced BALB/c showed increased levels of natural helper cells (NHC) which could be important in the myeloma induction. PMID:26504358

  4. Social stress increases the susceptibility to infection in the ant Harpegnathos saltator

    PubMed Central

    Schneider, Sebastian A.; Scharffetter, Charlotte; Wagner, Anika E.; Boesch, Christine; Bruchhaus, Iris; Rimbach, Gerald; Roeder, Thomas

    2016-01-01

    Aggressive interactions between members of a social group represent an important source of social stress with all its negative follow-ups. We used the ponerine ant Harpegnathos saltator to study the effects of frequent aggressive interactions on the resistance to different stressors. In these ants, removal or death of reproducing animals results in a period of social instability within the colony that is characterized by frequent ritualized aggressive interactions leading to the establishment of a new dominance structure. Animals are more susceptible to infections during this period, whereas their resistance against other stressors remained unchanged. This is associated with a shift from glutathione-S-transferase activities towards glutathione peroxidase activities, which increases the antioxidative capacity at the expense of their immune competence. PMID:27161621

  5. Smoking in Movies and Increased Smoking Among Young Adults

    PubMed Central

    Song, Anna V.; Ling, Pamela M.; Neilands, Torsten B.; Glantz, Stanton A.

    2010-01-01

    Objective This study assessed whether smoking in the movies was associated with smoking in young adults. Methods A national web-enabled cross-sectional survey of 1528 young adults, aged 18–25, was performed between September and November 2005. Logistic regression and path analysis using probit regression were used to assess relationships between exposure to smoking in the movies and smoking behavior. Analysis was completed in December 2006. Results Exposure to smoking in the movies predicted current smoking. The adjusted odds of current smoking increased by a factor of 1.21 for each quartile increase in exposure to smoking (p<0.01) in the movies, reaching 1.77 for the top exposure quartile. The unadjusted odds of established smoking (100+ cigarettes with current smoking) increased by 1.23 per quartile (p<0.001) of exposure, reaching 1.86 for the top quartile. This effect on established smoking was mediated by two factors related to smoking in the movies: positive expectations about smoking and exposure to friends and relatives who smoked, with positive expectations accounting for about two thirds of the effect. Conclusions The association between smoking in the movies and young adult smoking behavior exhibited a dose–response relationship; the more a young adult was exposed to smoking in the movies, the more likely he or she would have smoked in the past 30 days or have become an established smoker. PMID:17950405

  6. Increasing Susceptibility of the Global Network of Food Trade to Climate Disturbances

    NASA Astrophysics Data System (ADS)

    Puma, M. J.; Bose, S.; Chon, S.; Cook, B.

    2013-12-01

    Globalization of agriculture through trade liberalization has led to a dramatic transformation of the global network of food trade. The many benefits of this globalization include greater and more efficient global agricultural production, reduced variability of regional and global food supplies, and savings in global water resources. However, a potential hidden cost is an increasingly fragile network that is more susceptible to shocks or disruptions. Recent studies suggest that complex systems, like the global food trade network, may have architectural features typically associated with the existence of tipping points and susceptibility to collapse. Here we present evidence that this global agricultural network is increasingly connected, homogeneous, and in a state where network nodes (here countries) can flip between alternate states. We use production and trade data from 1986 to 2009 to identify shifts in national self sufficiency and to quantify changes in connectivity and homogeneity of the wheat, maize and rice trade. We then simulate the possible impacts of climate and crop-disease disruptions, which could potentially trigger a global food crisis through an export-restriction-induced domino effect. Changes in self-sufficiency ratio (SSR) over time for various country groups. The SSR is computed based on production and trade of cereals and starchy roots. (Top row) Time series of SSR for the Group of Eight + Five (G8+5) countries. The '+ Five' refers to the five leading emerging economies in the world. (Bottom row) Boxplots of average SSR over two periods (1986-1990 and 2005-2009) for countries designated as 'Annex I' and 'Least Developed Countries' (LDC) by the United Nations.

  7. Effects of maternal high-fat diet and sedentary lifestyle on susceptibility of adult offspring to ozone exposure in rats.

    PubMed

    Gordon, C J; Phillips, P M; Johnstone, A F M; Schmid, J; Schladweiler, M C; Ledbetter, A; Snow, S J; Kodavanti, U P

    2017-05-01

    Epidemiological and experimental data suggest that obesity exacerbates the health effects of air pollutants such as ozone (O3). Maternal inactivity and calorically rich diets lead to offspring that show signs of obesity. Exacerbated O3 susceptibility of offspring could thus be manifested by maternal obesity. Thirty-day-old female Long-Evans rats were fed a control (CD) or high-fat (HF) (60% calories) diet for 6 wks and then bred. GD1 rats were then housed with a running wheel (RW) or without a wheel (SED) until parturition, creating four groups of offspring: CD-SED, CD-RW, HF-SED and HF-RW. HF diet was terminated at PND 35 and all offspring were placed on CD. Body weight and %fat of dams were greatest in order; HF-SED > HF-RW > CD-SED > CD-RW. Adult offspring were exposed to O3 for two consecutive days (0.8 ppm, 4 h/day). Glucose tolerance tests (GTT), ventilatory parameters (plethysmography), and bronchoalveolar fluid (BALF) cell counts and protein biomarkers were performed to assess response to O3. Exercise and diet altered body weight and %fat of young offspring. GTT, ventilation and BALF cell counts were exacerbated by O3 with responses markedly exacerbated in males. HF diet and O3 led to significant exacerbation of several BALF parameters: total cell count, neutrophils and lymphocytes were increased in male HF-SED versus CD-SED. Males were hyperglycemic after O3 exposure and exhibited exacerbated GTT responses. Ventilatory dysfunction was also exacerbated in males. Maternal exercise had minimal effects on O3 response. The results of this exploratory study suggest a link between maternal obesity and susceptibility to O3 in their adult offspring in a sex-specific manner.

  8. Uncoupling Protein 2 Increases Susceptibility to Lipopolysaccharide-Induced Acute Lung Injury in Mice

    PubMed Central

    Wang, Qin; Wang, Jianchun; Hu, Mingdong; Yang, Yu; Guo, Liang; Xu, Jing; Lei, Chuanjiang; Jiao, Yan; Xu, JianCheng

    2016-01-01

    Uncoupling protein 2 (UCP2) is upregulated in patients with systemic inflammation and infection, but its functional role is unclear. We up- or downregulated UCP2 expression using UCP2 recombinant adenovirus or the UCP2 inhibitor, genipin, in lungs of mice, and investigated the mechanisms of UCP2 in ALI. UCP2 overexpression in mouse lungs increased LPS-induced pathological changes, lung permeability, lung inflammation, and lowered survival rates. Furthermore, ATP levels and mitochondrial membrane potential were decreased, while reactive oxygen species production was increased. Additionally, mitogen-activated protein kinases (MAPKs) activity was elevated, which increased the sensitivity to LPS-induced apoptosis and inflammation. LPS-induced apoptosis and release of inflammatory factors were alleviated by pretreatment of the Jun N-terminal kinase (JNK) inhibitor SP600125 or the p38 MAPK inhibitor SB203580, but not by the extracellular signal-regulated kinase (ERK) inhibitor PD98059 in UCP2-overexpressing mice. On the other hand, LPS-induced alveolar epithelial cell death and inflammation were attenuated by genipin. In conclusion, UCP2 increased susceptibility to LPS-induced cell death and pulmonary inflammation, most likely via ATP depletion and activation of MAPK signaling following ALI in mice. PMID:27057102

  9. Assessing increasing susceptibility to wildfire at the wildland-urban fringe in the western United States

    NASA Astrophysics Data System (ADS)

    Kinoshita, A. M.; Hogue, T. S.

    2013-05-01

    Much of the western U.S. is increasingly susceptible to wildfire activity due to drier conditions, elevated fuel loads, and expanding urbanization. As population increases, development pushes the urban boundary further into wildlands, creating more potential for human interaction at the wildland-urban interface (WUI), primarily from human ignitions and fire suppression policies. The immediate impacts of wildfires include vulnerability to debris flows, flooding, and impaired water quality. Fires also alter longer-term hydrological and ecosystem behavior. The current study utilizes geospatial datasets to investigate historical wildfire size and frequency relative to the WUI for a range of cities across western North America. California, the most populous state in the U.S., has an extensive fire history. The decennial population and acres burned for four major counties (Los Angeles, San Bernardino, San Diego, and Shasta) in California show that increasing wildfire size and frequency follow urbanization trends, with high correlation between the last decade of burned area, urban-fringe proximity, and increasing population. Ultimately, results will provide information on urban fringe communities that are most vulnerable to the risks associated with wildfire and post-fire impacts. In light of evolving land use policies (i.e. forest management and treatment, development at the urban-fringe) and climate change, it is critical to advance our knowledge of the implications that these conditions pose to urban centers, communicate risks to the public, and ultimately provide guidance for wildfire management.

  10. Nutrient enrichment can increase the susceptibility of reef corals to bleaching

    NASA Astrophysics Data System (ADS)

    Wiedenmann, Jörg; D'Angelo, Cecilia; Smith, Edward G.; Hunt, Alan N.; Legiret, François-Eric; Postle, Anthony D.; Achterberg, Eric P.

    2013-02-01

    Mass coral bleaching, resulting from the breakdown of coral-algal symbiosis has been identified as the most severe threat to coral reef survival on a global scale. Regionally, nutrient enrichment of reef waters is often associated with a significant loss of coral cover and diversity. Recently, increased dissolved inorganic nitrogen concentrations have been linked to a reduction of the temperature threshold of coral bleaching, a phenomenon for which no mechanistic explanation is available. Here we show that increased levels of dissolved inorganic nitrogen in combination with limited phosphate concentrations result in an increased susceptibility of corals to temperature- and light-induced bleaching. Mass spectrometric analyses of the algal lipidome revealed a marked accumulation of sulpholipids under these conditions. Together with increased phosphatase activities, this change indicates that the imbalanced supply of dissolved inorganic nitrogen results in phosphate starvation of the symbiotic algae. Based on these findings we introduce a conceptual model that links unfavourable ratios of dissolved inorganic nutrients in the water column with established mechanisms of coral bleaching. Notably, this model improves the understanding of the detrimental effects of coastal nutrient enrichment on coral reefs, which is urgently required to support knowledge-based management strategies to mitigate the effects of climate change.

  11. Increased susceptibility of Cantagalo virus to the antiviral effect of ST-246®.

    PubMed

    Santos-Fernandes, Élida; Beltrame, Cristiana O; Byrd, Chelsea M; Cardwell, Kara B; Schnellrath, Laila C; Medaglia, Maria Luiza G; Hruby, Dennis E; Jordan, Robert; Damaso, Clarissa R

    2013-03-01

    Cantagalo virus (CTGV) is the etiologic agent of a pustular disease in dairy cows and dairy workers in Brazil with important economical and occupational impacts. Nevertheless, no antiviral therapy is currently available. ST-246 is a potent inhibitor of orthopoxvirus egress from cells and has proved its efficacy in cell culture and in animal models. In this work, we evaluated the effect of ST-246 on CTGV replication. Plaque reduction assays indicated that CTGV is 6-38 times more susceptible to the drug than VACV-WR and cowpox virus, respectively, with an EC50 of 0.0086μM and a selective index of >11,600. The analysis of β-gal activity expressed by recombinant viruses in the presence of ST-246 confirmed these results. In addition, ST-246 had a greater effect on the reduction of CTGV spread in comet tail assays and on the production of extracellular virus relative to VACV-WR. Infection of mice with CTGV by tail scarification generated primary lesions at the site of scarification that appeared less severe than those induced by VACV-WR. Animals infected with CTGV and treated with ST-246 at 100mg/kg for 5days did not develop primary lesions and virus yields were inhibited by nearly 98%. In contrast, primary lesions induced by VACV-WR were not affected by ST-246. The analysis of F13 (p37) protein from CTGV revealed a unique substitution in residue 217 (D217N) not found in other orthopoxviruses. Construction of recombinant VACV-WR containing the D217N polymorphism did not lead to an increase in the susceptibility to ST-246. Therefore, it is still unknown why CTGV is more susceptible to the antiviral effects of ST-246 compared to VACV-WR. Nonetheless, our data demonstrates that ST-246 is a potent inhibitor of CTGV replication that should be further evaluated as a promising anti-CTGV therapy. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Factors associated with increased healthcare utilization among adults with asthma.

    PubMed

    Becerra, Monideepa Bhattacharya

    2017-05-01

    To evaluate determinants of increased emergency room (ER) visit and hospitalization among adults with asthma, with emphasis on the role of psychological distress, self-efficacy, and obesity. For analysis 2009, 2011/2012 California Health Interview Survey was used. Adults who reported lifetime asthma were selected. Association between ER and overnight hospital stay with population characteristics were conducted using chi-square analysis. Multivariable binary logistic regression models, taking into account control variables, were utilized to assess the relationship between ER visit or overnight hospital stay with that of psychological distress, self-efficacy, and obesity. Odds of ER visits were higher among those with mild-to-moderate psychological distress (adjusted odds ratio [aOR] = 1.94, 95% CI: 1.28, 2.94), and among those with serious psychological distress (aOR = 2.62, 95% CI: 1.65, 4.16). Mild-to-moderate distress was associated with two-fold increase in hospital overnight stay (aOR = 2.05, 95% CI: 1.29, 3.25). Adults with asthma who reported low self-efficacy had increased ER visits (aOR = 6.21, 95% CI: 3.63, 10.65) and hospitalization (aOR = 4.13, 95% CI: 2.63, 6.49). Finally, adults who had asthma and were obese had higher odds of ER visits (aOR = 1.60, 95% CI: 1.20, 2.13). Healthcare utilization is higher among asthma patients with psychological distress, low self-efficacy, and obesity. Interventions, such as incorporation of integrated care models, are critical to ensure early screening of mental health status among such patients. In addition, there is a need for patient education and improved weight management among adults with asthma.

  13. Prolonged pre-incubation increases the susceptibility of Galleria mellonella larvae to bacterial and fungal infection.

    PubMed

    Browne, Niall; Surlis, Carla; Maher, Amie; Gallagher, Clair; Carolan, James C; Clynes, Martin; Kavanagh, Kevin

    2015-01-01

    Galleria mellonella larvae are widely used for assessing the virulence of microbial pathogens and for measuring the in vivo activity of antimicrobial agents and produce results comparable to those that can be obtained using mammals. The aim of the work described here was to ascertain the effect of pre-incubation at 15°C for 1, 3, 6 or 10 weeks on the susceptibility of larvae to infection with Candida albicans and Staphylococcus aureus. Larvae infected with C. albicans after 1 week pre-incubation at 15°C showed 73.3 ± 3.3% survival at 24 hours post-infection while those infected after 10 weeks pre-incubation showed 30 ± 3.3% survival (P < 0.01). Larvae infected with S. aureus after 1 week pre-incubation showed 65.5 ± 3.3% survival after 24 hours while those infected after 10 weeks pre-incubation showed 13.3 ± 3.3% (P < 0.001). Analysis of the haemocyte density in larvae pre-incubated for 3-10 weeks showed a reduction in haemocytes over time but a proportionate increase in the density of granular haemocytes in the population as determined by FACS analysis. Proteomic analysis revealed decreased abundance of proteins associated with metabolic pathways (e.g. malate dehydrogenase, fructose-1,6-bisphosphatase, glyceraldehyde-3-phosphate dehydrogenase) and prophenoloxidase. G. mellonella larvae are a useful in vivo model system but the duration of the pre-incubation stage significantly affects their susceptibility to microbial pathogens possibly as a result of altered metabolism.

  14. Butylhydroxytoluene (BHT) increases susceptibility of transgenic rasH2 mice to lung carcinogenesis.

    PubMed

    Umemura, T; Kodama, Y; Hioki, K; Inoue, T; Nomura, T; Kurokawa, Y

    2001-10-01

    Transgenic mice carrying the human prototype c-Ha-ras gene (rasH2 mice) are highly susceptible to lung carcinogens. In order to investigate the possibility of developing a rapid in vivo assay for lung carcinogens, we examined whether the tumor-promoting activity of butylhydroxytoluene (BHT) is efficacious in rasH2 mice. rasH2 mice and wild littermates of both genders were pre-treated with carcinogens [urethane (UR), 4-nitroquinoline 1-oxide (4NQO) or diethylnitrosamine (DEN)], and, one day later, given a 400 mg/kg dose of BHT. Six weeks after the initiation treatment, evidence of carcinogenicity could be detected in male and female rasH2 mice that had received UR doses of > or = 250 mg/kg and > or = 125 mg/kg, respectively, prior to exposure to BHT, whereas only 500 mg/kg of UR was sufficient to induce tumors in female rasH2 mice given the carcinogen alone. The carcinogenicity of 15 mg/kg of 4NQO could be detected after 9 weeks in male rasH2 mice given the carcinogen followed by BHT. Similarly, the carcinogenicity of 60 mg/kg of DEN could be detected after 9 weeks and 6 weeks, respectively, in male and female rasH2 mice given the carcinogen followed by BHT. No carcinogenicity could be demonstrated through the experimental period with doses of 4NQO or DEN given alone. These results indicate that BHT administration increases the susceptibility of rasH2 mice to lung carcinogens, and suggest that the use of BHT in rasH2 mice might lead to the establishment of a rapid in vivo assay for lung carcinogens.

  15. CCL2-driven inflammation increases mammary gland stromal density and cancer susceptibility in a transgenic mouse model.

    PubMed

    Sun, Xuan; Glynn, Danielle J; Hodson, Leigh J; Huo, Cecilia; Britt, Kara; Thompson, Erik W; Woolford, Lucy; Evdokiou, Andreas; Pollard, Jeffrey W; Robertson, Sarah A; Ingman, Wendy V

    2017-01-11

    Macrophages play diverse roles in mammary gland development and breast cancer. CC-chemokine ligand 2 (CCL2) is an inflammatory cytokine that recruits macrophages to sites of injury. Although CCL2 has been detected in human and mouse mammary epithelium, its role in regulating mammary gland development and cancer risk has not been explored. Transgenic mice were generated wherein CCL2 is driven by the mammary epithelial cell-specific mouse mammary tumour virus 206 (MMTV) promoter. Estrous cycles were tracked in adult transgenic and non-transgenic FVB mice, and mammary glands collected at the four different stages of the cycle. Dissected mammary glands were assessed for cyclical morphological changes, proliferation and apoptosis of epithelium, macrophage abundance and collagen deposition, and mRNA encoding matrix remodelling enzymes. Another cohort of control and transgenic mice received carcinogen 7,12-Dimethylbenz(a)anthracene (DMBA) and tumour development was monitored weekly. CCL2 protein was also quantified in paired samples of human breast tissue with high and low mammographic density. Overexpression of CCL2 in the mammary epithelium resulted in an increased number of macrophages, increased density of stroma and collagen and elevated mRNA encoding matrix remodelling enzymes lysyl oxidase (LOX) and tissue inhibitor of matrix metalloproteinases (TIMP)3 compared to non-transgenic controls. Transgenic mice also exhibited increased susceptibility to development of DMBA-induced mammary tumours. In a paired sample cohort of human breast tissue, abundance of epithelial-cell-associated CCL2 was higher in breast tissue of high mammographic density compared to tissue of low mammographic density. Constitutive expression of CCL2 by the mouse mammary epithelium induces a state of low level chronic inflammation that increases stromal density and elevates cancer risk. We propose that CCL2-driven inflammation contributes to the increased risk of breast cancer observed in women

  16. Increased susceptibility to Klebsiella pneumonia and mortality in GSNOR-deficient mice.

    PubMed

    Tang, Chi-Hui; Seeley, Eric J; Huang, Xiaozhu; Wolters, Paul J; Liu, Limin

    2013-12-06

    S-nitrosoglutathione reductase (GSNOR) is a key denitrosylase and critically important for protecting immune and other cells from nitrosative stress. Pharmacological inhibition of GSNOR is being actively pursued as a therapeutic approach to increase S-nitrosoglutathione levels for the treatment of asthma and cystic fibrosis. In the present study, we employed GSNOR-deficient (GSNOR(-/-)) mice to investigate whether inactivation of GSNOR may increase susceptibility to pulmonary infection by Klebsiella pneumoniae, a common cause of nosocomial pneumonia. We found that compared to wild-type mice, bacterial colony forming units 48 h after intranasal infection with K. pneumoniae were increased over 4-folds in lung and spleen and strikingly, over a 1000-folds in blood of GSNOR(-/-) mice. Lung injury was comparable between infected wild-type and GSNOR(-/-) mice, but inflammation and injury was significantly elevated in spleen of GSNOR(-/-) mice. Whereas all wild-type mice survived 48 h after infection, 10 of 23 GSNOR(-/-) mice died. Thus, GSNOR appears to play a crucial role in controlling pulmonary and systemic infection by K. pneumoniae. Our results suggest that patients treated in clinical trials with inhibitors of GSNOR should be carefully monitored for signs of infection. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Acidosis increases the susceptibility of respiratory epithelial cells to Pseudomonas aeruginosa-induced cytotoxicity.

    PubMed

    Torres, Iviana M; Demirdjian, Sally; Vargas, Jennifer; Goodale, Britton C; Berwin, Brent

    2017-07-01

    Bacterial infection can lead to acidosis of the local microenvironment, which is believed to exacerbate disease pathogenesis; however, the mechanisms by which changes in pH alter disease progression are poorly understood. We test the hypothesis that acidosis enhances respiratory epithelial cell death in response to infection with Pseudomonas aeruginosa Our findings support the idea that acidosis in the context of P. aeruginosa infection results in increased epithelial cell cytotoxicity due to ExoU intoxication. Importantly, enforced maintenance of neutral pH during P. aeruginosa infection demonstrates that cytotoxicity is dependent on the acidosis. Investigation of the underlying mechanisms revealed that host cell cytotoxicity correlated with increased bacterial survival during an acidic infection that was due to reduced bactericidal activity of host-derived antimicrobial peptides. These findings extend previous reports that the activities of antimicrobial peptides are pH-dependent and provide novel insights into the consequences of acidosis on infection-derived pathology. Therefore, this report provides the first evidence that physiological levels of acidosis increase the susceptibility of epithelial cells to acute Pseudomonas infection and demonstrates the benefit of maintaining pH homeostasis during a bacterial infection. Copyright © 2017 the American Physiological Society.

  18. Mechanisms by which a CACNA1H mutation in epilepsy patients increases seizure susceptibility

    PubMed Central

    Eckle, Veit-Simon; Shcheglovitov, Aleksandr; Vitko, Iuliia; Dey, Deblina; Yap, Chan Choo; Winckler, Bettina; Perez-Reyes, Edward

    2014-01-01

    T-type calcium channels play essential roles in regulating neuronal excitability and network oscillations in the brain. Mutations in the gene encoding Cav3.2 T-type Ca2+ channels, CACNA1H, have been found in association with various forms of idiopathic generalized epilepsy. We and others have found that these mutations may influence neuronal excitability either by altering the biophysical properties of the channels or by increasing their surface expression. The goals of the present study were to investigate the excitability of neurons expressing Cav3.2 with the epilepsy mutation, C456S, and to elucidate the mechanisms by which it influences neuronal properties. We found that expression of the recombinant C456S channels substantially increased the excitability of cultured neurons by increasing the spontaneous firing rate and reducing the threshold for rebound burst firing. Additionally, we found that molecular determinants in the I–II loop (the region in which most childhood absence epilepsy-associated mutations are found) substantially increase the surface expression of T-channels but do not alter the relative distribution of channels into dendrites of cultured hippocampal neurons. Finally, we discovered that expression of C456S channels promoted dendritic growth and arborization. These effects were reversed to normal by either the absence epilepsy drug ethosuximide or a novel T-channel blocker, TTA-P2. As Ca2+-regulated transcription factors also increase dendritic development, we tested a transactivator trap assay and found that the C456S variant can induce changes in gene transcription. Taken together, our findings suggest that gain-of-function mutations in Cav3.2 T-type Ca2+ channels increase seizure susceptibility by directly altering neuronal electrical properties and indirectly by changing gene expression. PMID:24277868

  19. Developmental Exposure to Estradiol and Bisphenol A Increases Susceptibility to Prostate Carcinogenesis and Epigenetically Regulates Phosphodiesterase Type 4 Variant 4

    PubMed Central

    Ho, Shuk-Mei; Tang, Wan-Yee; de Frausto, Jessica Belmonte; Prins, Gail S.

    2008-01-01

    Early developmental perturbations have been linked to adult-onset prostate pathology, including excessive exposure to estrogenic compounds; however, the molecular basis for this imprinting event is not known. An important and controversial health concern is whether low-dose exposures to hormonally active environmental estrogens, such as bisphenol A, can promote human diseases, including prostate cancer. Here, we show that transient developmental exposure of rats to low, environmentally relevant doses of bisphenol A or estradiol increases prostate gland susceptibility to adult-onset precancerous lesions and hormonal carcinogenesis. We found permanent alterations in the DNA methylation patterns of multiple cell signaling genes, suggesting an epigenetic basis for estrogen imprinting. For phosphodiesterase type 4 variant 4 (PDE4D4), an enzyme responsible for cyclic AMP breakdown, a specific methylation cluster was identified in the 5′-flanking CpG island that was gradually hypermethylated with aging in normal prostates, resulting in loss of gene expression. Early and prolonged hypomethylation at this site following neonatal estradiol or bisphenol A exposure resulted in continued, elevated PDE4D4 expression. Cell line studies confirmed that site-specific methylation is involved in transcriptional silencing of the PDE4D4 gene and showed hypomethylation of this gene in prostate cancer cells. Importantly, the PDE4D4 alterations in the estrogen-exposed prostates were distinguishable before histopathologic changes of the gland, making PDE4D4 a candidate molecular marker for prostate cancer risk assessment as a result of endocrine disruptors. In total, these findings indicate that low-dose exposures to ubiquitous environmental estrogens affect the prostate epigenome during development and, in so doing, promote prostate disease with aging. PMID:16740699

  20. Some factors affecting an increase in magnetic susceptibility of cement dusts

    NASA Astrophysics Data System (ADS)

    Gołuchowska, Beata J.

    2001-09-01

    The aim of the research was to explain reasons of fluctuation in magnetic susceptibility of cement dusts and the consequences for the environment. The research comprised measurements of magnetic susceptibility and Fe content in dusts, and also in raw materials, additives, fuels, mixtures and clinkers used for cement production. The samples were taken in four cement plants located in Opole Province (southern Poland). In addition to this, the influence of two production methods (dry and wet) on magnetic susceptibility of dusts and some aspects of ferrimagnetic minerals formation in the process of clinker burning were considered. It was proven that magnetic susceptibility of dusts depends on raw materials and fuels but especially on additives used for cement production, method of production and the carbon monoxide content in gases from clinker rotary kilns. Statistically important linear correlations between magnetic susceptibility and Fe suggest that during clinker burning, ferrimagnetic minerals may be formed.

  1. Insulin-like Growth Factor 2 Overexpression Induces β-Cell Dysfunction and Increases Beta-cell Susceptibility to Damage*

    PubMed Central

    Casellas, Alba; Mallol, Cristina; Salavert, Ariana; Jimenez, Veronica; Garcia, Miquel; Agudo, Judith; Obach, Mercè; Haurigot, Virginia; Vilà, Laia; Molas, Maria; Lage, Ricardo; Morró, Meritxell; Casana, Estefania; Ruberte, Jesús; Bosch, Fatima

    2015-01-01

    The human insulin-like growth factor 2 (IGF2) and insulin genes are located within the same genomic region. Although human genomic studies have demonstrated associations between diabetes and the insulin/IGF2 locus or the IGF2 mRNA-binding protein 2 (IGF2BP2), the role of IGF2 in diabetes pathogenesis is not fully understood. We previously described that transgenic mice overexpressing IGF2 specifically in β-cells (Tg-IGF2) develop a pre-diabetic state. Here, we characterized the effects of IGF2 on β-cell functionality. Overexpression of IGF2 led to β-cell dedifferentiation and endoplasmic reticulum stress causing islet dysfunction in vivo. Both adenovirus-mediated overexpression of IGF2 and treatment of adult wild-type islets with recombinant IGF2 in vitro further confirmed the direct implication of IGF2 on β-cell dysfunction. Treatment of Tg-IGF2 mice with subdiabetogenic doses of streptozotocin or crossing these mice with a transgenic model of islet lymphocytic infiltration promoted the development of overt diabetes, suggesting that IGF2 makes islets more susceptible to β-cell damage and immune attack. These results indicate that increased local levels of IGF2 in pancreatic islets may predispose to the onset of diabetes. This study unravels an unprecedented role of IGF2 on β-cells function. PMID:25971976

  2. Insulin-like Growth Factor 2 Overexpression Induces β-Cell Dysfunction and Increases Beta-cell Susceptibility to Damage.

    PubMed

    Casellas, Alba; Mallol, Cristina; Salavert, Ariana; Jimenez, Veronica; Garcia, Miquel; Agudo, Judith; Obach, Mercè; Haurigot, Virginia; Vilà, Laia; Molas, Maria; Lage, Ricardo; Morró, Meritxell; Casana, Estefania; Ruberte, Jesús; Bosch, Fatima

    2015-07-03

    The human insulin-like growth factor 2 (IGF2) and insulin genes are located within the same genomic region. Although human genomic studies have demonstrated associations between diabetes and the insulin/IGF2 locus or the IGF2 mRNA-binding protein 2 (IGF2BP2), the role of IGF2 in diabetes pathogenesis is not fully understood. We previously described that transgenic mice overexpressing IGF2 specifically in β-cells (Tg-IGF2) develop a pre-diabetic state. Here, we characterized the effects of IGF2 on β-cell functionality. Overexpression of IGF2 led to β-cell dedifferentiation and endoplasmic reticulum stress causing islet dysfunction in vivo. Both adenovirus-mediated overexpression of IGF2 and treatment of adult wild-type islets with recombinant IGF2 in vitro further confirmed the direct implication of IGF2 on β-cell dysfunction. Treatment of Tg-IGF2 mice with subdiabetogenic doses of streptozotocin or crossing these mice with a transgenic model of islet lymphocytic infiltration promoted the development of overt diabetes, suggesting that IGF2 makes islets more susceptible to β-cell damage and immune attack. These results indicate that increased local levels of IGF2 in pancreatic islets may predispose to the onset of diabetes. This study unravels an unprecedented role of IGF2 on β-cells function. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Psychological comorbidity increases the risk for postinfectious IBS partly by enhanced susceptibility to develop infectious gastroenteritis.

    PubMed

    Wouters, Mira M; Van Wanrooy, Sander; Nguyen, Anh; Dooley, James; Aguilera-Lizarraga, Javier; Van Brabant, Winde; Garcia-Perez, Josselyn E; Van Oudenhove, Lukas; Van Ranst, Marc; Verhaegen, Jan; Liston, Adrian; Boeckxstaens, Guy

    2016-08-01

    Psychological factors increase the risk to develop postinfectious IBS (PI-IBS), but the mechanisms involved are unclear. As stress affects the immune system, we investigated the potential interaction between psychological factors, the immune response against infectious gastroenteritis (IGE) and the development of IGE and PI-IBS in a large cohort exposed to contaminated drinking water. 18 620 people exposed to contaminated drinking water (norovirus, Giardia lamblia, Campylobacter jejuni) were invited to participate in a prospective controlled cohort study. They were asked to complete questionnaires assessing demographic, psychological and clinical data during the outbreak and 1 year later. At both time points, in-depth immune function (peripheral blood and rectal biopsies) was studied in a subgroup of subjects. 1379 subjects completed the questionnaires during the outbreak, of which 271 developed IGE. Risk factors for IGE included younger age, pre-existing dyspepsia-like symptoms, anxiety and drinking contaminated tap water. Anxiety scores before the outbreak inversely correlated with interleukin-2-expressing CD4+ T cells (r=0.6, p=0.01, n=23). At follow-up, 34 of 172 (20%) IGE subjects developed IBS compared with 24/366 exposed participants (7%, p<0.0001, χ(2) test). A Th2 cytokine phenotype at time of infection was associated with increased risk for PI-IBS 1 year later. Except for increased B cell numbers, no evidence for systemic or rectal mucosal immune activation in PI-IBS was demonstrated at follow-up. Our study shows that the increased risk of patients with psychological comorbidity to develop PI-IBS may partly result from an increased susceptibility to develop IGE, possibly resulting from a Th2-immune bias. (ClinicalTrials.gov NCT01497847). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  4. Deficiency of the Angiotensinase Aminopeptidase A Increases Susceptibility to Glomerular Injury.

    PubMed

    Velez, Juan Carlos Q; Arif, Ehtesham; Rodgers, Jessalyn; Hicks, Megan P; Arthur, John M; Nihalani, Deepak; Bruner, Evelyn T; Budisavljevic, Milos N; Atkinson, Carl; Fitzgibbon, Wayne R; Janech, Michael G

    2017-07-01

    Aminopeptidase A (APA) is expressed in glomerular podocytes and tubular epithelia and metabolizes angiotensin II (AngII), a peptide known to promote glomerulosclerosis. In this study, we tested whether APA expression changes in response to progressive nephron loss or whether APA exerts a protective role against glomerular damage and during AngII-mediated hypertensive kidney injury. At advanced stages of FSGS, fawn-hooded hypertensive rat kidneys exhibited distinctly increased APA staining in areas of intact glomerular capillary loops. Moreover, BALB/c APA-knockout (KO) mice injected with a nephrotoxic serum showed persistent glomerular hyalinosis and albuminuria 96 hours after injection, whereas wild-type controls achieved virtually full recovery. We then tested the effect of 4-week infusion of AngII (400 ng/kg per minute) in APA-KO and wild-type mice. Although we observed no significant difference in achieved systolic BP, AngII-treated APA-KO mice developed a significant rise in albuminuria not observed in AngII-treated wild-type mice along with increased segmental and global sclerosis and/or collapse of juxtamedullary glomeruli, microcystic tubular dilation, and tubulointerstitial fibrosis. In parallel, AngII treatment significantly increased the kidney AngII content and attenuated the expression of podocyte nephrin in APA-KO mice but not in wild-type controls. These data show that deficiency of APA increases susceptibility to glomerular injury in BALB/c mice. The augmented AngII-mediated kidney injury observed in association with increased intrarenal AngII accumulation in the absence of APA suggests a protective metabolizing role of APA in AngII-mediated glomerular diseases. Copyright © 2017 by the American Society of Nephrology.

  5. Induction of Rhizopus oryzae germination under starvation using host metabolites increases spore susceptibility to heat stress.

    PubMed

    Turgeman, Tidhar; Kakongi, Nathan; Schneider, Avishai; Vinokur, Yakov; Teper-Bamnolker, Paula; Carmeli, Shmuel; Levy, Maggie; Skory, Christopher D; Lichter, Amnon; Eshel, Dani

    2014-03-01

    Sweetpotato is a nutritional source worldwide. Soft rot caused by Rhizopus spp. is a major limiting factor in the storage of produce, rendering it potentially unsafe for human consumption. In this study, Rhizopus oryzae was used to develop a concept of postharvest disease control by weakening the pathogen through induction of spore germination under starvation conditions. We isolated the sweetpotato active fractions (SPAFs) that induce spore germination and used them at a low dose to enhance spore weakening caused by starvation. Germination in SPAF at 1 mg/ml weakened the pathogen spores by delaying their ability to form colonies on rich media and by increasing their sensitivity to heat stress. The weakening effect was also supported by reduced metabolic activity, as detected by Alarmar Blue fluorescent dye assays. Spores incubated with SPAF at 1 mg/ml showed DNA fragmentation in some of their nuclei, as observed by TUNEL assay. In addition, these spores exhibited changes in ultrastructural morphology (i.e., shrinkage of germ tubes, nucleus deformation, and vacuole formation) which are hallmarks of programmed cell death. We suggest that induction of spore germination under starvation conditions increases their susceptibility to stress and, therefore, might be considered a new strategy for pathogen control.

  6. Manipulation of the Xanthophyll Cycle Increases Plant Susceptibility to Sclerotinia sclerotiorum

    PubMed Central

    Zhou, Jun; Zeng, Lizhang; Liu, Jian; Xing, Da

    2015-01-01

    The xanthophyll cycle is involved in dissipating excess light energy to protect the photosynthetic apparatus in a process commonly assessed from non-photochemical quenching (NPQ) of chlorophyll fluorescence. Here, it is shown that the xanthophyll cycle is modulated by the necrotrophic pathogen Sclerotinia sclerotiorum at the early stage of infection. Incubation of Sclerotinia led to a localized increase in NPQ even at low light intensity. Further studies showed that this abnormal change in NPQ was closely correlated with a decreased pH caused by Sclerotinia-secreted oxalate, which might decrease the ATP synthase activity and lead to a deepening of thylakoid lumen acidification under continuous illumination. Furthermore, suppression (with dithiothreitol) or a defect (in the npq1-2 mutant) of violaxanthin de-epoxidase (VDE) abolished the Sclerotinia-induced NPQ increase. HPLC analysis showed that the Sclerotinia-inoculated tissue accumulated substantial quantities of zeaxanthin at the expense of violaxanthin, with a corresponding decrease in neoxanthin content. Immunoassays revealed that the decrease in these xanthophyll precursors reduced de novo abscisic acid (ABA) biosynthesis and apparently weakened tissue defense responses, including ROS induction and callose deposition, resulting in enhanced plant susceptibility to Sclerotinia. We thus propose that Sclerotinia antagonizes ABA biosynthesis to suppress host defense by manipulating the xanthophyll cycle in early pathogenesis. These findings provide a model of how photoprotective metabolites integrate into the defense responses, and expand the current knowledge of early plant-Sclerotinia interactions at infection sites. PMID:25993128

  7. SIGLEC-G deficiency increases susceptibility to develop B-cell lymphoproliferative disorders

    PubMed Central

    Simonetti, Giorgia; Bertilaccio, Maria Teresa Sabrina; Rodriguez, Tania Veliz; Apollonio, Benedetta; Dagklis, Antonis; Rocchi, Martina; Innocenzi, Anna; Casola, Stefano; Winkler, Thomas H.; Nitschke, Lars; Ponzoni, Maurilio; Caligaris-Cappio, Federico; Ghia, Paolo

    2014-01-01

    The sialic-acid-binding immunoglobulin-like lectin SIGLEC-G is a negative regulator of B-cell receptor-mediated calcium signaling. Its deficiency leads to reduced turnover and increased proliferation and survival of murine B-1a cells. Siglecg−/− mice show a premature expansion of polyclonal CD5+ B cells in the spleen and the peritoneal cavity. Here we studied the fate of B lymphocytes in Siglecg−/− mice over time. We demonstrate that in aging animals SIGLEC-G deficiency promotes progressive accumulation of monoclonal B lymphocytes and increases the susceptibility to develop B-cell lymphoproliferative disorders. Lymphoid tumors arising in aged Siglecg−/− mice are monoclonal and histologically heterogeneous as they include diffuse large B-cell lymphoma, follicular lymphoma, and medium-to-large B-cell monomorphic lymphoma but surprisingly not chronic lymphocytic leukemia. The tumors express high levels of BCL-2 and are transplantable. In keeping with these findings we have also observed a remarkable down-regulation of the human ortholog SIGLEC10 in human B-cell lymphoma and leukemia cell lines. Taken together, these observations indicate that the down-regulation of negative B-cell receptor regulators such as SIGLEC-G/SIGLEC10 may represent another mechanism relevant to the pathogenesis of B-cell lymphomas. PMID:24859880

  8. Prenatal ethanol exposure increases brain cholesterol content in adult rats.

    PubMed

    Barceló-Coblijn, Gwendolyn; Wold, Loren E; Ren, Jun; Murphy, Eric J

    2013-11-01

    Fetal alcohol syndrome is the most severe expression of the fetal alcohol spectrum disorders (FASD). Although alterations in fetal and neonate brain fatty acid composition and cholesterol content are known to occur in animal models of FASD, the persistence of these alterations into adulthood is unknown. To address this question, we determined the effect of prenatal ethanol exposure on individual phospholipid class fatty acid composition, individual phospholipid class mass, and cholesterol mass in brains from 25-week-old rats that were exposed to ethanol during gestation beginning at gestational day 2. While total phospholipid mass was unaffected, phosphatidylinositol and cardiolipin mass was decreased 14 and 43 %, respectively. Exposure to prenatal ethanol modestly altered brain phospholipid fatty acid composition, and the most consistent change was a significant 1.1-fold increase in total polyunsaturated fatty acids (PUFA), in the n-3/n-6 ratio, and in the 22:6n-3 content in ethanolamine glycerophospholipids and in phosphatidylserine. In contrast, prenatal ethanol consumption significantly increased brain cholesterol mass 1.4-fold and the phospholipid to cholesterol ratio was significantly increased 1.3-fold. These results indicate that brain cholesterol mass was significantly increased in adult rats exposed prenatally to ethanol, but changes in phospholipid mass and phospholipid fatty acid composition were extremely limited. Importantly, suppression of postnatal ethanol consumption was not sufficient to reverse the large increase in cholesterol observed in the adult rats.

  9. Western High-Fat Diet Consumption during Adolescence Increases Susceptibility to Traumatic Stress while Selectively Disrupting Hippocampal and Ventricular Volumes

    PubMed Central

    Kalyan-Masih, Priya; Vega-Torres, Julio David; Haddad, Elizabeth; Rainsbury, Sabrina; Baghchechi, Mohsen

    2016-01-01

    Abstract Psychological trauma and obesity co-occur frequently and have been identified as major risk factors for psychiatric disorders. Surprisingly, preclinical studies examining how obesity disrupts the ability of the brain to cope with psychological trauma are lacking. The objective of this study was to determine whether an obesogenic Western-like high-fat diet (WD) predisposes rats to post-traumatic stress responsivity. Adolescent Lewis rats (postnatal day 28) were fed ad libitum for 8 weeks with either the experimental WD diet (41.4% kcal from fat) or the control diet (16.5% kcal from fat). We modeled psychological trauma by exposing young adult rats to a cat odor threat. The elevated plus maze and the open field test revealed increased psychological trauma-induced anxiety-like behaviors in the rats that consumed the WD when compared with control animals 1 week after undergoing traumatic stress (p < 0.05). Magnetic resonance imaging showed significant hippocampal atrophy (20% reduction) and lateral ventricular enlargement (50% increase) in the animals fed the WD when compared with controls. These volumetric abnormalities were associated with behavioral indices of anxiety, increased leptin and FK506-binding protein 51 (FKBP51) levels, and reduced hippocampal blood vessel density. We found asymmetric structural vulnerabilities to the WD, particularly the ventral and left hippocampus and lateral ventricle. This study highlights how WD consumption during adolescence impacts key substrates implicated in post-traumatic stress disorder. Understanding how consumption of a WD affects the developmental trajectories of the stress neurocircuitry is critical, as stress susceptibility imposes a marked vulnerability to neuropsychiatric disorders. PMID:27844058

  10. Increased susceptibility of estrogen-induced bladder outlet obstruction in a novel mouse model.

    PubMed

    Tam, Neville Ngai-Chung; Zhang, Xiang; Xiao, Hong; Song, Dan; Levin, Linda; Meller, Jarek; Ho, Shuk-Mei

    2015-05-01

    Disorders of the prostate and lower urinary tract are common in elderly men. We investigated the role of metallothionein-1 (MT1) in prostate carcinogenesis by generating a prostate-specific, MT1-expressing mouse. Unexpectedly, genomic analyses revealed that a 12.1-kb genomic region harboring several conserved noncoding elements was unintentionally deleted, upstream of the transgene integration site in the mouse, which we named it 12.1ΔMT1. Male 12.1ΔMT1 mice chronically treated with testosterone (T) plus 17β-estradiol (E2) to induce prostate cancer exhibited no evidence of precancerous or cancerous lesions. Instead, most of them exhibited a bladder outlet obstruction (BOO) phenotype not observed in treated wild-type (WT) mice. Thus, we hypothesized that 12.1ΔMT1 is a novel model for studying the hormonal requirement for BOO induction. Adult male 12.1ΔMT1 and WT mice were treated with T, E2, bisphenol A (BPA), T+E2, or T+BPA for up to 6 months. Histologic and immunohistochemical analysis of the prostate, bladder, and urethra were performed. No significant prostate pathologies were observed in WT or 12.1ΔMT1 mice treated with any of the hormone regimens. As expected, prostatic regression occurred in all E2-treated animals (WT and 12.1ΔMT1). Of great interest, despite a small prostate, 100% of E2-treated 12.1ΔMT1 mice, but only 40% of E2-treated WT mice, developed severe BOO (P<0.01). In contrast, T+E2 treatment was less effective than E2 treatment in inducing severe BOO in 12.1ΔMT1 mice (68%, P<0.05) and was completely ineffective in WT animals. Similarly, T, BPA, and T+BPA treatments did not induce BOO in either WT or 12.1ΔMT1 mice. The BOO pathology includes a thinner detrusor wall, narrowing of bladder neck and urethral lumen, and basal cell hyperplasia in the bladder body and urethra. These findings indicate that 12.1ΔMT1 mice exhibit enhanced susceptibility to E2-induced BOO that is independent of prostate enlargement but that is attenuated by the

  11. Reduced salinity increases susceptibility of zooxanthellate jellyfish to herbicide toxicity during a simulated rainfall event.

    PubMed

    Klein, Shannon G; Pitt, Kylie A; Carroll, Anthony R

    2016-02-01

    Accurately predicting how marine biota are likely to respond to changing ocean conditions requires accurate simulation of interacting stressors, exposure regimes and recovery periods. Jellyfish populations have increased in some parts of the world and, despite few direct empirical tests, are hypothesised to be increasing because they are robust to a range of environmental stressors. Here, we investigated the effects of contaminated runoff on a zooxanthellate jellyfish by exposing juvenile Cassiopea sp. medusae to a photosystem II (PSII) herbicide, atrazine and reduced salinity conditions that occur following rainfall. Four levels of atrazine (0ngL(-1), 10ngL(-1), 2μgL(-1), 20μgL(-1)) and three levels of salinity (35 ppt, 25 ppt, 17 ppt) were varied, mimicking the timeline of light, moderate and heavy rainfall events. Normal conditions were then slowly re-established over four days to mimic the recovery of the ecosystem post-rain and the experiment continued for a further 7 days to observe potential recovery of the medusae. Pulse-amplitude modulated (PAM) chlorophyll fluorescence, growth and bell contraction rates of medusae were measured. Medusae exposed to the combination of high atrazine and lowest salinity died. After 3 days of exposure, bell contraction rates were reduced by 88% and medusae were 16% smaller in the lowest salinity treatments. By Day 5 of the experiment, all medusae that survived the initial pulse event began to recover quickly. Although atrazine decreased YII under normal salinity conditions, YII was further reduced when medusae were exposed to both low salinity and atrazine simultaneously. Atrazine breakdown products were more concentrated in jellyfish tissues than atrazine at the end of the experiment, suggesting that although bioaccumulation occurred, atrazine was metabolised. Our results suggest that reduced salinity may increase the susceptibility of medusae to herbicide exposure during heavy rainfall events.

  12. Sleep disruption increases seizure susceptibility: Behavioral and EEG evaluation of an experimental model of sleep apnea.

    PubMed

    Hrnčić, Dragan; Grubač, Željko; Rašić-Marković, Aleksandra; Šutulović, Nikola; Šušić, Veselinka; Bjekić-Macut, Jelica; Stanojlović, Olivera

    2016-03-01

    Sleep disruption accompanies sleep apnea as one of its major symptoms. Obstructive sleep apnea is particularly common in patients with refractory epilepsy, but causing factors underlying this are far from being resolved. Therefore, translational studies regarding this issue are important. Our aim was to investigate the effects of sleep disruption on seizure susceptibility of rats using experimental model of lindane-induced refractory seizures. Sleep disruption in male Wistar rats with implanted EEG electrodes was achieved by treadmill method (belt speed set on 0.02 m/s for working and 0.00 m/s for stop mode, respectively). Animals were assigned to experimental conditions lasting 6h: 1) sleep disruption (sleep interrupted, SI; 30s working and 90 s stop mode every 2 min; 180 cycles in total); 2) activity control (AC, 10 min working and 30 min stop mode, 9 cycles in total); 3) treadmill chamber control (TC, only stop mode). Afterwards, the animals were intraperitoneally treated with lindane (L, 4 mg/kg, SI+L, AC+L and TC+L groups) or dimethylsulfoxide (DMSO, SIc, ACc and TCc groups). Convulsive behavior was assessed by seizure incidence, latency time to first seizure, and its severity during 30 min after drug administration. Number and duration of ictal periods were determined in recorded EEGs. Incidence and severity of lindane-induced seizures were significantly increased, latency time significantly decreased in animals undergoing sleep disruption (SI+L group) compared with the animals from TC+L. Seizure latency was also significantly decreased in SI+L compared to AC+L groups. Number of ictal periods were increased and duration of it presented tendency to increase in SI+L comparing to AC+L. No convulsive signs were observed in TCc, ACc and SIc groups, as well as no ictal periods in EEG. These results indicate sleep disruption facilitates induction of epileptic activity in rodent model of lindane-epilepsy enabling translational research of this phenomenon.

  13. Crude oil impairs immune function and increases susceptibility to pathogenic bacteria in southern flounder.

    PubMed

    Bayha, Keith M; Ortell, Natalie; Ryan, Caitlin N; Griffitt, Kimberly J; Krasnec, Michelle; Sena, Johnny; Ramaraj, Thiruvarangan; Takeshita, Ryan; Mayer, Gregory D; Schilkey, Faye; Griffitt, Robert J

    2017-01-01

    Exposure to crude oil or its individual constituents can have detrimental impacts on fish species, including impairment of the immune response. Increased observations of skin lesions in northern Gulf of Mexico fish during the 2010 Deepwater Horizon oil spill indicated the possibility of oil-induced immunocompromisation resulting in bacterial or viral infection. This study used a full factorial design of oil exposure and bacterial challenge to examine how oil exposure impairs southern flounder (Paralichthys lethostigma) immune function and increases susceptibility to the bacteria Vibrio anguillarum, a causative agent of vibriosis. Fish exposed to oil prior to bacterial challenge exhibited 94.4% mortality within 48 hours of bacterial exposure. Flounder challenged with V. anguillarum without prior oil exposure had <10% mortality. Exposure resulted in taxonomically distinct gill and intestine bacterial communities. Mortality strongly correlated with V. anguillarum levels, where it comprised a significantly higher percentage of the microbiome in Oil/Pathogen challenged fish and was nearly non-existent in the No Oil/Pathogen challenged fish bacterial community. Elevated V. anguillarum levels were a direct result of oil exposure-induced immunosuppression. Oil-exposure reduced expression of immunoglobulin M, the major systemic fish antibody, and resulted in an overall downregulation in transcriptome response, particularly in genes related to immune function, response to stimulus and hemostasis. Ultimately, sediment-borne oil exposure impairs immune function, leading to increased incidences of bacterial infections. This type of sediment-borne exposure may result in long-term marine ecosystem effects, as oil-bound sediment in the northern Gulf of Mexico will likely remain a contamination source for years to come.

  14. Crude oil impairs immune function and increases susceptibility to pathogenic bacteria in southern flounder

    PubMed Central

    Bayha, Keith M.; Ortell, Natalie; Ryan, Caitlin N.; Griffitt, Kimberly J.; Krasnec, Michelle; Sena, Johnny; Ramaraj, Thiruvarangan; Takeshita, Ryan; Mayer, Gregory D.; Schilkey, Faye; Griffitt, Robert J.

    2017-01-01

    Exposure to crude oil or its individual constituents can have detrimental impacts on fish species, including impairment of the immune response. Increased observations of skin lesions in northern Gulf of Mexico fish during the 2010 Deepwater Horizon oil spill indicated the possibility of oil-induced immunocompromisation resulting in bacterial or viral infection. This study used a full factorial design of oil exposure and bacterial challenge to examine how oil exposure impairs southern flounder (Paralichthys lethostigma) immune function and increases susceptibility to the bacteria Vibrio anguillarum, a causative agent of vibriosis. Fish exposed to oil prior to bacterial challenge exhibited 94.4% mortality within 48 hours of bacterial exposure. Flounder challenged with V. anguillarum without prior oil exposure had <10% mortality. Exposure resulted in taxonomically distinct gill and intestine bacterial communities. Mortality strongly correlated with V. anguillarum levels, where it comprised a significantly higher percentage of the microbiome in Oil/Pathogen challenged fish and was nearly non-existent in the No Oil/Pathogen challenged fish bacterial community. Elevated V. anguillarum levels were a direct result of oil exposure-induced immunosuppression. Oil-exposure reduced expression of immunoglobulin M, the major systemic fish antibody, and resulted in an overall downregulation in transcriptome response, particularly in genes related to immune function, response to stimulus and hemostasis. Ultimately, sediment-borne oil exposure impairs immune function, leading to increased incidences of bacterial infections. This type of sediment-borne exposure may result in long-term marine ecosystem effects, as oil-bound sediment in the northern Gulf of Mexico will likely remain a contamination source for years to come. PMID:28464028

  15. Increased susceptibility to otitis media in a Splunc1-deficient mouse model

    PubMed Central

    Bartlett, Jennifer A.; Meyerholz, David K.; Wohlford-Lenane, Christine L.; Naumann, Paul W.; Salzman, Nita H.; McCray, Paul B.

    2015-01-01

    ABSTRACT Otitis media (inflammation of the middle ear) is one of the most common diseases of early childhood. Susceptibility to otitis is influenced by a number of factors, including the actions of innate immune molecules secreted by the epithelia lining the nasopharynx, middle ear and Eustachian tube. The SPLUNC1 (short palate, lung, nasal epithelial clone 1) protein is a highly abundant secretory product of the mammalian nasal, oral and respiratory mucosa that is thought to play a multifunctional role in host defense. In this study we investigated Splunc1 expression in the ear of the mouse, and examined whether this protein contributes to overall host defense in the middle ear and/or Eustachian tube. We found that Splunc1 is highly expressed in both the surface epithelium and in submucosal glands in these regions in wild-type mice. In mice lacking Splunc1, we noted histologically an increased frequency of otitis media, characterized by the accumulation of leukocytes (neutrophils with scattered macrophages), proteinaceous fluid and mucus in the middle ear lumens. Furthermore, many of these mice had extensive remodeling of the middle ear wall, suggesting a chronic course of disease. From these observations, we conclude that loss of Splunc1 predisposes mice to the development of otitis media. The Splunc1−/− mouse model should help investigators to better understand both the biological role of Splunc1 as well as host defense mechanisms in the middle ear. PMID:25765466

  16. Increased susceptibility to retinoid-induced teratogenesis in TGF-beta2 knockout mice.

    PubMed

    Nugent, Paul; Pisano, Michele M; Weinrich, Martin C; Greene, Robert M

    2002-01-01

    Transforming growth factor-beta (TGF-beta) and retinoic acid (RA) have been implicated in normal and abnormal embryonic development. The aim of this study was to investigate the effect of TGF-beta2 gene deletion on susceptibility to RA-induced teratogenesis in a mouse model. TGF-beta2 heterozygous or wild-type mice were mated and the dams dosed with a teratogenic dose of RA, or with control vehicle. The incidence of RA-induced cleft palate (CP) was 48% in wild-type embryos from wild-type dams, increasing to 71% in TGF-beta2 heterozygous littermates. Wild-type and TGF-beta2 heterozygous embryos from heterozygous dams exhibited a CP incidence of 74 and 77% respectively, following treatment with RA. Ninety-one percent of littermates nullizygous for TGF-beta2 were dead when examined; the remainder exhibited a CP. We conclude that the genotype of the dam and embryo with respect to TGF-beta2 affects the incidence of RA-induced teratogenesis.

  17. Hyperbaric pressure and increased susceptibility to glutamate toxicity in retinal ganglion cells in vitro.

    PubMed

    Aihara, Makoto; Chen, Yi-Ning; Uchida, Saiko; Nakayama, Mao; Araie, Makoto

    2014-01-01

    To investigate the effect of hyperbaric pressure on purified retinal ganglion cells (RGCs) and the additive effect of hyperbaric pressure on glutamate-induced RGC death. An RGC primary culture from 8-day-old Wistar rats was prepared and cultured in a hyperbaric chamber. The RGC survival rate under various pressure conditions and with 5 or 25 µM of glutamate stimulation was determined and compared with that of RGCs under isobaric conditions. First, RGCs were cultured at atmospheric pressure (0 mmHg) and under hyperbaric pressure (+30 and +90 mmHg, with pressure fluctuations varying from 0 to +30 or +60 mmHg). Next, RGCs were cultured at +15, +30, and +90 mmHg with the addition of 5 or 25 µM of glutamate. The effects of N-Methyl-D-aspartic acid (NMDA) and 2-amino-3-(5-methyl-3-oxo-1,2- oxazol-4-yl)propanoic acid (AMPA)/kainate receptor antagonists, MK-801, and 6,7-dinitroquinoxaline-2,3-dione (DNQX), on cell survival were assessed. Additionally, types of cell death and the induction of Bcl-2-associated X protein (BAX) leading to apoptosis were studied under hyperbaric pressure conditions and/or with 5 µM of glutamate. RGC death was not induced under increasing or fluctuating pressure conditions. RGC death was induced by 25 µM of glutamate and increased as pressure increased. RGC death was not induced by 5 µM of glutamate but was induced by and increased with increasing pressure. MK-801 and DNQX significantly reduced glutamate-induced RGC death, and DNQX was more effective than MK-801. Under hyperbaric pressure conditions, the addition of 5 µM of glutamate resulted in the induction of apoptosis and BAX, which did not occur under hyperbaric pressure conditions or with the addition of glutamate alone. In a rat RGC culture, hyperbaric pressure alone did not induce RGC death but increased RGC susceptibility to glutamate toxicity, which may be of relevance to ocular diseases with pressure-induced RGC death.

  18. Hyperbaric pressure and increased susceptibility to glutamate toxicity in retinal ganglion cells in vitro

    PubMed Central

    Chen, Yi-Ning; Uchida, Saiko; Nakayama, Mao; Araie, Makoto

    2014-01-01

    Purpose To investigate the effect of hyperbaric pressure on purified retinal ganglion cells (RGCs) and the additive effect of hyperbaric pressure on glutamate-induced RGC death. Methods An RGC primary culture from 8-day-old Wistar rats was prepared and cultured in a hyperbaric chamber. The RGC survival rate under various pressure conditions and with 5 or 25 µM of glutamate stimulation was determined and compared with that of RGCs under isobaric conditions. First, RGCs were cultured at atmospheric pressure (0 mmHg) and under hyperbaric pressure (+30 and +90 mmHg, with pressure fluctuations varying from 0 to +30 or +60 mmHg). Next, RGCs were cultured at +15, +30, and +90 mmHg with the addition of 5 or 25 µM of glutamate. The effects of N-Methyl-D-aspartic acid (NMDA) and 2-amino-3-(5-methyl-3-oxo-1,2- oxazol-4-yl)propanoic acid (AMPA)/kainate receptor antagonists, MK-801, and 6,7-dinitroquinoxaline-2,3-dione (DNQX), on cell survival were assessed. Additionally, types of cell death and the induction of Bcl-2-associated X protein (BAX) leading to apoptosis were studied under hyperbaric pressure conditions and/or with 5 µM of glutamate. Results RGC death was not induced under increasing or fluctuating pressure conditions. RGC death was induced by 25 µM of glutamate and increased as pressure increased. RGC death was not induced by 5 µM of glutamate but was induced by and increased with increasing pressure. MK-801 and DNQX significantly reduced glutamate-induced RGC death, and DNQX was more effective than MK-801. Under hyperbaric pressure conditions, the addition of 5 µM of glutamate resulted in the induction of apoptosis and BAX, which did not occur under hyperbaric pressure conditions or with the addition of glutamate alone. Conclusion In a rat RGC culture, hyperbaric pressure alone did not induce RGC death but increased RGC susceptibility to glutamate toxicity, which may be of relevance to ocular diseases with pressure-induced RGC death. PMID:24826068

  19. Increased putamen volume in adults with autism spectrum disorder.

    PubMed

    Sato, Wataru; Kubota, Yasutaka; Kochiyama, Takanori; Uono, Shota; Yoshimura, Sayaka; Sawada, Reiko; Sakihama, Morimitsu; Toichi, Motomi

    2014-01-01

    Basal ganglia (BG) abnormalities are implicated in the pathophysiology of autism spectrum disorder (ASD). However, studies measuring the volume of the entire BG in individuals with ASD have reported discrepant findings, and no study conducted volume measurement of the entire substructures of the BG (the caudate, putamen, nucleus accumbens, and globus pallidus) in individuals with ASD. We delineated the BG substructures and measured their volumes in 29 adults with ASD without intellectual disabilities and 29 age- and gender-matched typically developed adult controls. We acquired T1-weighted anatomical images and performed semiautomated delineation and volume measurements of the above-mentioned subregions. Total cerebral volumes, sex, and ages were partialed out. Compared with controls, the putamen was significantly larger in the ASD group. The increased volume of the putamen found in high-functioning adults with ASD suggests that structural or histological abnormalities of the putamen may underlie the pathologies of ASD, such as repetitive and stereotyped behaviors and impaired social interactions.

  20. Is adult gait less susceptible than paediatric gait to hip joint centre regression equation error?

    PubMed

    Kiernan, D; Hosking, J; O'Brien, T

    2016-03-01

    Hip joint centre (HJC) regression equation error during paediatric gait has recently been shown to have clinical significance. In relation to adult gait, it has been inferred that comparable errors with children in absolute HJC position may in fact result in less significant kinematic and kinetic error. This study investigated the clinical agreement of three commonly used regression equation sets (Bell et al., Davis et al. and Orthotrak) for adult subjects against the equations of Harrington et al. The relationship between HJC position error and subject size was also investigated for the Davis et al. set. Full 3-dimensional gait analysis was performed on 12 healthy adult subjects with data for each set compared to Harrington et al. The Gait Profile Score, Gait Variable Score and GDI-kinetic were used to assess clinical significance while differences in HJC position between the Davis and Harrington sets were compared to leg length and subject height using regression analysis. A number of statistically significant differences were present in absolute HJC position. However, all sets fell below the clinically significant thresholds (GPS <1.6°, GDI-Kinetic <3.6 points). Linear regression revealed a statistically significant relationship for both increasing leg length and increasing subject height with decreasing error in anterior/posterior and superior/inferior directions. Results confirm a negligible clinical error for adult subjects suggesting that any of the examined sets could be used interchangeably. Decreasing error with both increasing leg length and increasing subject height suggests that the Davis set should be used cautiously on smaller subjects.

  1. Downregulation of FoxC2 Increased Susceptibility to Experimental Colitis: Influence of Lymphatic Drainage Function?

    PubMed Central

    Becker, Felix; Potepalov, Sergey; Shehzahdi, Romana; Bernas, Michael; Witte, Marlys; Abreo, Fleurette; Traylor, James; Orr, Wayne A.; Tsunoda, Ikuo

    2015-01-01

    Background: Although inflammation-induced expansion of the intestinal lymphatic vasculature (lymphangiogenesis) is known to be a crucial event in limiting inflammatory processes, through clearance of interstitial fluid and immune cells, considerably less is known about the impact of an impaired lymphatic clearance function (as seen in inflammatory bowel diseases) on this cascade. We aimed to investigate whether the impaired intestinal lymphatic drainage function observed in FoxC2(+/−) mice would influence the course of disease in a model of experimental colitis. Methods: Acute dextran sodium sulfate colitis was induced in wild-type and haploinsufficient FoxC2(+/−) mice, and survival, disease activity, colonic histopathological injury, neutrophil, T-cell, and macrophage infiltration were evaluated. Functional and structural changes in the intestinal lymphatic vessel network were analyzed, including submucosal edema, vessel morphology, and lymphatic vessel density. Results: We found that FoxC2 downregulation in FoxC2(+/−) mice significantly increased the severity and susceptibility to experimental colitis, as displayed by lower survival rates, increased disease activity, greater histopathological injury, and elevated colonic neutrophil, T-cell, and macrophage infiltration. These findings were accompanied by structural (dilated torturous lymphatic vessels) and functional (greater submucosal edema, higher immune cell burden) changes in the intestinal lymphatic vasculature. Conclusions: These results indicate that sufficient lymphatic clearance plays a crucial role in limiting the initiation and perpetuation of experimental colitis and those disturbances in the integrity of the intestinal lymphatic vessel network could intensify intestinal inflammation. Future therapies might be able to exploit these processes to restore and maintain adequate lymphatic clearance function in inflammatory bowel disease. PMID:25822012

  2. Genomic Variant in CAV1 Increases Susceptibility to Coronary Artery Disease and Myocardial Infarction

    PubMed Central

    Zhang, Rongfeng; Wang, Fan; Xu, Chaoping; Huang, Yufeng; Li, Sisi; Yin, Dan; Xiong, Xin; Li, Xiuchun; Chen, Qiuyun; Tu, Xin; Yang, Yanzong; Xia, Yonglong; Xu, Chengqi; Wang, Qing K.

    2016-01-01

    Background The CAV1 gene encodes caveolin-1 expressed in cell types relevant to atherosclerosis. Cav-1-null mice showed a protective effect on atherosclerosis under the ApoE−/− background. However, it is unknown whether CAV1 is linked to CAD and MI in humans. In this study we analyzed a tagSNP for CAV1 in intron 2, rs3807989, for potential association with CAD. Methods and Results We performed case-control association studies in three independent Chinese Han populations from GeneID, including 1,249 CAD cases and 841 controls in Population I, 1,260 cases and 833 controls in Population II and 790 cases and 1,212 controls in Population III (a total of 3,299 cases and 2,886 controls). We identified significant association between rs3807989 and CAD in three independent populations and in the combined population (Padj=2.18×10−5, OR=1.19 for minor allele A). We also detected significant association between rs3807989 and MI (Padj=5.43×10−5, OR=1.23 for allele A). Allele A of SNP rs3807989 was also associated with a decreased level of LDL cholesterol. Although rs3807989 is a tagSNP for both CAV1 and nearby CAV2, allele A of SNP rs3807989 was associated with an increased expression level of CAV1 (both mRNA and protein), but not CAV2. Conclusions The data in this study demonstrated that rs3807989 at the CAV1/CAV2 locus was associated with significant risk of CAD and MI by increasing expression CAV1 (but not CAV2). Thus, CAV1 becomes a strong candidate susceptibility gene for CAD/MI in humans. PMID:26775120

  3. Early handling increases susceptibility to experimental autoimmune encephalomyelitis (EAE) in C57BL/6 male mice.

    PubMed

    Columba-Cabezas, Sandra; Iaffaldano, Grazia; Chiarotti, Flavia; Alleva, Enrico; Cirulli, Francesca

    2009-07-25

    Brief maternal separations of neonatal animals can exert long-lasting effects on the reactivity of the neuroendocrine system. The aim of the present study was to investigate whether manipulations of the mother-infant interaction could affect susceptibility to immune-mediated diseases, such experimental autoimmune encephalomyelitis (EAE), and whether this effect would be mediated by changes in leptin which has been shown to regulate disease susceptibility and severity at adulthood. Given the different gender susceptibility to EAE previously described, we tested also whether early experiences could differentially affect the two genders. To this purpose, female and male C56BL/6 mice were subjected to handling (15 min daily) postnatally, from day 2 until day 14. All subjects were weaned at 21 days. At 7 weeks of age mice were immunized with MOG(35-55) to actively induce EAE. We thus determined the effect of neonatal handling on plasma concentrations of testosterone in male mice and leptin in both genders at different times post EAE induction. Our results show that early experiences influence susceptibility to EAE in a gender-specific manner, early manipulations resulting in an enhancement of sex-related differences in susceptibility. These effects were associated with changes in the testosterone profile of male subjects. Changes in leptin levels during the preclinical stage of EAE may predict a more severe disease course.

  4. Increased levels of interleukin-8 in BAL fluid from smokers susceptible to pulmonary emphysema

    PubMed Central

    Tanino, M; Betsuyaku, T; Takeyabu, K; Tanino, Y; Yamaguchi, E; Miyamoto, K; Nishimura, M

    2002-01-01

    Background: It has previously been shown that smokers with computed tomographic (CT) evidence of subclinical emphysema have signs of neutrophil activation, despite having no appreciable increase in the number of neutrophils in their bronchoalveolar lavage (BAL) fluid. Methods: The levels of the following chemoattractants in BAL fluid from 61 community based older volunteers classified into four groups according to current smoking status and the presence or absence of emphysema were determined: interleukin 8 (IL-8), epithelial neutrophil activating protein 78 (ENA-78) and leukotriene B4 (LTB4) which are primarily chemotactic for neutrophils; monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α) which are predominantly chemotactic for mononuclear leucocytes. Results: Of the five chemoattractants studied, only the level of IL-8 in BAL fluid clearly distinguished between subjects with and without emphysema among current smokers (median values 34.7 and 12.2 pg/ml, respectively, p<0.01). In addition, the levels of IL-8 and neutrophil elastase-α1 protease inhibitor complex in BAL fluid were significantly correlated (r=0.65, p<0.01). There was no difference in either the release of IL-8 from cultured alveolar macrophages at 24 hours or the expression of IL-8 messenger RNA of alveolar macrophages in the two groups of current smokers with and without emphysema. Conclusion: An accelerated response of IL-8 to chronic smoking is a factor that characterises those smokers who are susceptible to pulmonary emphysema, although the cellular source of IL-8 remains to be determined. PMID:11978916

  5. Washing increases the susceptibility to exogenous oxidative stress in red deer spermatozoa.

    PubMed

    Domínguez-Rebolledo, A E; Fernández-Santos, M R; García-Alvarez, O; Maroto-Morales, A; Garde, J J; Martínez-Pastor, F

    2009-11-01

    The effects of routine sperm work are often overlooked. We assessed the effect of washing cryopreserved epididymal spermatozoa from red deer (Cervus elaphus hispanicus, Helzheimer 1909). After thawing, epididymal samples (four stags) were diluted in TALP-HEPES. A split was left untouched, another was centrifuged (300 x g, 5 min) and resuspended, and a third was centrifuged and the supernatant substituted by fresh TALP-HEPES (washing). Each split was supplemented either with nothing, 1mM of the antioxidant Trolox, 100 microM of the oxidant Fe (with ascorbate), or both. The 3x4 treatments were incubated at 37 degrees C and assessed each hour up to 3h for motility (computer-aided sperm assessment) and viability/apoptosis plus mitochondrial status (YO-PRO-1, propidium iodide, Mitotracker Deep Red; flow cytometry). DNA damage at 4h was assessed using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay. Centrifugation alone affected neither sperm quality nor DNA, and the oxidant had no effect in control or centrifuged samples. Washed samples were not different than control, but oxidant decreased motility, mitochondrial status and viability, and altered the motility subpopulation pattern, being partially suppressed by Trolox. Spermatozoa with damaged DNA dramatically increased in the washed-oxidized sample (from 22.30+/-3.52% to 67.94+/-5.07%), but not when antioxidant was present. Although samples from different males behaved similarly, male-to-male variability was detected regarding susceptibility to oxidative damage after washing. We concluded that, although red deer thawed spermatozoa seemed resilient to centrifugation, the vulnerability to oxidative stress after washing makes it advisable to supplement manipulation media with antioxidants, especially taking into account male-to-male variability.

  6. 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.

  7. Life expectancy without depression increases among Brazilian older adults

    PubMed Central

    Andrade, Flávia Cristina Drumond; Wu, Fan; Lebrão, Maria Lúcia; Duarte, Yeda Aparecida de Oliveira

    2016-01-01

    ABSTRACT OBJECTIVE To estimate life expectancy with and without depressive symptoms in older adults for the years 2000 and 2010. METHODS We evaluated individuals aged 60 years or older (n = 1,862 in 2000 and n = 1,280 in 2010), participants of the Saúde, Bem-Estar e Envelhecimento (SABE – Health, Wellbeing and Aging) study in in Sao Paulo, Southeastern Brazil. Depression was measured using the shorter version of the Geriatric Depression Scale (GDS-15); respondents scoring ≥ 6 were classified as having depression. Estimates of life expectancy with and without depression were obtained using the Sullivan method. RESULTS Data from 2000 indicate that 60-year-old men could expect to live, on average, 14.7 years without depression and 60-year-old women could expect to live 16.5 years without depression. By 2010, life expectancy without depression had increased to 16.7 years for men and 17.8 years for women. Expected length of life with depression differed by sex, with women expected to live more years with depression than men. CONCLUSIONS Between 2000 and 2010, life expectancy without depression in Sao Paulo increased. However, older adults in Brazil, especially older women, still face a serious burden of mental illness. PMID:27143612

  8. Life expectancy without depression increases among Brazilian older adults.

    PubMed

    Andrade, Flávia Cristina Drumond; Wu, Fan; Lebrão, Maria Lúcia; Duarte, Yeda Aparecida de Oliveira

    2016-01-01

    To estimate life expectancy with and without depressive symptoms in older adults for the years 2000 and 2010. We evaluated individuals aged 60 years or older (n = 1,862 in 2000 and n = 1,280 in 2010), participants of the Saúde, Bem-Estar e Envelhecimento (SABE - Health, Wellbeing and Aging) study in in Sao Paulo, Southeastern Brazil. Depression was measured using the shorter version of the Geriatric Depression Scale (GDS-15); respondents scoring ≥ 6 were classified as having depression. Estimates of life expectancy with and without depression were obtained using the Sullivan method. Data from 2000 indicate that 60-year-old men could expect to live, on average, 14.7 years without depression and 60-year-old women could expect to live 16.5 years without depression. By 2010, life expectancy without depression had increased to 16.7 years for men and 17.8 years for women. Expected length of life with depression differed by sex, with women expected to live more years with depression than men. Between 2000 and 2010, life expectancy without depression in Sao Paulo increased. However, older adults in Brazil, especially older women, still face a serious burden of mental illness.

  9. Increase of Fungal Pathogenicity and Role of Plant Glutamine in Nitrogen-Induced Susceptibility (NIS) To Rice Blast

    PubMed Central

    Huang, Huichuan; Nguyen Thi Thu, Thuy; He, Xiahong; Gravot, Antoine; Bernillon, Stéphane; Ballini, Elsa; Morel, Jean-Benoit

    2017-01-01

    Highlight  Modifications in glutamine synthetase OsGS1-2 expression and fungal pathogenicity underlie nitrogen-induced susceptibility to rice blast. Understanding why nitrogen fertilization increase the impact of many plant diseases is of major importance. The interaction between Magnaporthe oryzae and rice was used as a model for analyzing the molecular mechanisms underlying Nitrogen-Induced Susceptibility (NIS). We show that our experimental system in which nitrogen supply strongly affects rice blast susceptibility only slightly affects plant growth. In order to get insights into the mechanisms of NIS, we conducted a dual RNA-seq experiment on rice infected tissues under two nitrogen fertilization regimes. On the one hand, we show that enhanced susceptibility was visible despite an over-induction of defense gene expression by infection under high nitrogen regime. On the other hand, the fungus expressed to high levels effectors and pathogenicity-related genes in plants under high nitrogen regime. We propose that in plants supplied with elevated nitrogen fertilization, the observed enhanced induction of plant defense is over-passed by an increase in the expression of the fungal pathogenicity program, thus leading to enhanced susceptibility. Moreover, some rice genes implicated in nitrogen recycling were highly induced during NIS. We further demonstrate that the OsGS1-2 glutamine synthetase gene enhances plant resistance to M. oryzae and abolishes NIS and pinpoint glutamine as a potential key nutrient during NIS. PMID:28293247

  10. Increase of Fungal Pathogenicity and Role of Plant Glutamine in Nitrogen-Induced Susceptibility (NIS) To Rice Blast.

    PubMed

    Huang, Huichuan; Nguyen Thi Thu, Thuy; He, Xiahong; Gravot, Antoine; Bernillon, Stéphane; Ballini, Elsa; Morel, Jean-Benoit

    2017-01-01

    Highlight  Modifications in glutamine synthetase OsGS1-2 expression and fungal pathogenicity underlie nitrogen-induced susceptibility to rice blast. Understanding why nitrogen fertilization increase the impact of many plant diseases is of major importance. The interaction between Magnaporthe oryzae and rice was used as a model for analyzing the molecular mechanisms underlying Nitrogen-Induced Susceptibility (NIS). We show that our experimental system in which nitrogen supply strongly affects rice blast susceptibility only slightly affects plant growth. In order to get insights into the mechanisms of NIS, we conducted a dual RNA-seq experiment on rice infected tissues under two nitrogen fertilization regimes. On the one hand, we show that enhanced susceptibility was visible despite an over-induction of defense gene expression by infection under high nitrogen regime. On the other hand, the fungus expressed to high levels effectors and pathogenicity-related genes in plants under high nitrogen regime. We propose that in plants supplied with elevated nitrogen fertilization, the observed enhanced induction of plant defense is over-passed by an increase in the expression of the fungal pathogenicity program, thus leading to enhanced susceptibility. Moreover, some rice genes implicated in nitrogen recycling were highly induced during NIS. We further demonstrate that the OsGS1-2 glutamine synthetase gene enhances plant resistance to M. oryzae and abolishes NIS and pinpoint glutamine as a potential key nutrient during NIS.

  11. Bacteraemic pneumonia caused by Neisseria lactamica with reduced susceptibility to penicillin and ciprofloxacin in an adult with liver cirrhosis.

    PubMed

    Wang, Cheng-Yi; Chuang, Yu-Min; Teng, Lee-Jene; Lee, Li-Na; Yang, Pan-Chyr; Kuo, Sow-Hsong; Hsueh, Po-Ren

    2006-08-01

    This report presents a case of bacteraemic pneumonia caused by Neisseria lactamica in an adult patient with liver cirrhosis who was successfully treated with ceftriaxone. The isolate was confirmed as N. lactamica by analysis of a partial sequence of the 16S rRNA gene; it had reduced susceptibilities to penicillin (MIC 0.75 microg ml(-1)) and ciprofloxacin (MIC > or =0.5 mg l(-1)).

  12. Increased susceptibility to structural acute kidney injury in a mouse model of presymptomatic cardiomyopathy.

    PubMed

    Pleasant, LaTawnya; Ma, Qing; Devarajan, Mahima; Parameswaran, Priyanka; Drake, Keri; Siroky, Brian; Shay-Winkler, Kritton; Robbins, Jeffrey; Devarajan, Prasad

    2017-09-01

    The early events that signal renal dysfunction in presymptomatic heart failure are unclear. We tested the hypothesis that functional and mechanistic changes occur in the kidney that precede the development of symptomatic heart failure. We employed a transgenic mouse model with cardiomyocyte-specific overexpression of mutant α-B-crystallin that develops slowly progressive cardiomyopathy. Presymptomatic transgenic mice displayed an increase in serum creatinine (1.17 ± 0.34 vs. wild type 0.65 ± 0.16 mg/dl, P < 0.05) and in urinary neutrophil gelatinase-associated lipocalin (NGAL; 278.92 ± 176.24 vs. wild type 49.11 ± 22.79 ng/ml, P < 0.05) but no renal fibrosis. Presymptomatic transgenic mouse kidneys exhibited a twofold upregulation of the Ren1 gene, marked overexpression of renin protein in the tubules, and a worsened response to ischemia-reperfusion injury based on serum creatinine (2.77 ± 0.66 in transgenic mice vs. 2.01 ± 0.58 mg/dl in wild type, P < 0.05), urine NGAL (9,198.79 ± 3,799.52 in transgenic mice vs. 3,252.94 ± 2,420.36 ng/ml in wild type, P < 0.05), tubule dilation score (3.4 ± 0.5 in transgenic mice vs. 2.6 ± 0.5 in wild type, P < 0.05), tubule cast score (3.2 ± 0.4 in transgenic mice vs. 2.5 ± 0.5 in wild type, P < 0.05), and TdT-mediated dUTP nick-end labeling (TUNEL)-positive nuclei (10.1 ± 2.1 in the transgenic group vs. 5.7 ± 1.6 per 100 cells counted in wild type, P < 0.01). Our findings indicate functional renal impairment, urinary biomarker elevations, and induction of renin gene and protein expression in the kidney that occur in early presymptomatic heart failure, which increase the susceptibility to subsequent acute kidney injury. Copyright © 2017 the American Physiological Society.

  13. Burn Injury Leads to Increased Long-Term Susceptibility to Respiratory Infection in both Mouse Models and Population Studies.

    PubMed

    Fear, Vanessa S; Boyd, James H; Rea, Suzanne; Wood, Fiona M; Duke, Janine M; Fear, Mark W

    2017-01-01

    Burn injury initiates an acute inflammatory response that subsequently drives wound repair. However, acute disruption to the immune response is also common, leading to susceptibility to sepsis and increased morbidity and mortality. Despite increased understanding of the impact of burn injury on the immune system in the acute phase, little is known about long-term consequences of burn injury on immune function. This study was established to determine whether burn injury has long-term clinical impacts on patients' immune responses. Using a population-based retrospective longitudinal study and linked hospital morbidity and death data from Western Australia, comparative rates of hospitalisation for respiratory infections in burn patients and a non-injured comparator cohort were assessed. In addition, a mouse model of non-severe burn injury was also used in which viral respiratory infection was induced at 4 weeks post-injury using a mouse modified version of the Influenza A virus (H3NN; A/mem/71-a). The burn injured cohort contained 14893 adult patients from 1980-2012 after removal of those patients with evidence of smoke inhalation or injury to the respiratory tract. During the study follow-up study a total of 2,884 and 2,625 respiratory infection hospital admissions for the burn and uninjured cohorts, respectively, were identified. After adjusting for covariates, the burn cohort experienced significantly elevated admission rates for influenza and viral pneumonia (IRR, 95%CI: 1.73, 1.27-2.36), bacterial pneumonia (IRR, 95%CI: 2.05, 1.85-2.27) and for other types of upper and lower respiratory infections (IRR, 95% CI: 2.38, 2.09-2.71). In the mouse study an increased viral titre was observed after burn injury, accompanied by a reduced CD8 response and increased NK and NKT cells in the draining lymph nodes. This data suggests burn patients are at long-term increased risk of infection due to sustained modulation of the immune response.

  14. Burn Injury Leads to Increased Long-Term Susceptibility to Respiratory Infection in both Mouse Models and Population Studies

    PubMed Central

    Fear, Vanessa S.; Boyd, James H.; Rea, Suzanne; Wood, Fiona M.

    2017-01-01

    Background Burn injury initiates an acute inflammatory response that subsequently drives wound repair. However, acute disruption to the immune response is also common, leading to susceptibility to sepsis and increased morbidity and mortality. Despite increased understanding of the impact of burn injury on the immune system in the acute phase, little is known about long-term consequences of burn injury on immune function. This study was established to determine whether burn injury has long-term clinical impacts on patients’ immune responses. Methods Using a population-based retrospective longitudinal study and linked hospital morbidity and death data from Western Australia, comparative rates of hospitalisation for respiratory infections in burn patients and a non-injured comparator cohort were assessed. In addition, a mouse model of non-severe burn injury was also used in which viral respiratory infection was induced at 4 weeks post-injury using a mouse modified version of the Influenza A virus (H3NN; A/mem/71-a). Results and conclusions The burn injured cohort contained 14893 adult patients from 1980–2012 after removal of those patients with evidence of smoke inhalation or injury to the respiratory tract. During the study follow-up study a total of 2,884 and 2,625 respiratory infection hospital admissions for the burn and uninjured cohorts, respectively, were identified. After adjusting for covariates, the burn cohort experienced significantly elevated admission rates for influenza and viral pneumonia (IRR, 95%CI: 1.73, 1.27–2.36), bacterial pneumonia (IRR, 95%CI: 2.05, 1.85–2.27) and for other types of upper and lower respiratory infections (IRR, 95% CI: 2.38, 2.09–2.71). In the mouse study an increased viral titre was observed after burn injury, accompanied by a reduced CD8 response and increased NK and NKT cells in the draining lymph nodes. This data suggests burn patients are at long-term increased risk of infection due to sustained modulation of the

  15. Does obesity increase susceptibility to ozone? Respiratory, behavioral, and metabolic assessments in Brown Norway rats

    EPA Science Inventory

    There may be a link between obesity and susceptibility to the respiratory, cardiovascular, and other health effects of air pollutants. Furthermore, it has been proposed that some air pollutants are obesogenic and may contribute to obesity. In view of the epidemic growth of obesit...

  16. Does Reactivating a Witnessed Memory Increase Its Susceptibility to Impairment by Subsequent Misinformation?

    ERIC Educational Resources Information Center

    Rindal, Eric J.; DeFranco, Rachel M.; Rich, Patrick R.; Zaragoza, Maria S.

    2016-01-01

    In a recent PNAS article, Chan and LaPaglia (2013) provided arguments and evidence to support the claim that reactivating a witnessed memory (by taking a test) renders the memory labile and susceptible to impairment by subsequent misinformation. In the current article, we argue that Chan and LaPaglia's (2013) findings are open to alternative…

  17. Increased susceptibility to infectious salmon anemia virus (ISAv) in Lepeophtheirus salmonis – infected Atlantic salmon

    USDA-ARS?s Scientific Manuscript database

    The salmon louse and infectious salmon anemia virus (ISAv) are the two most significant pathogens of concern to the Atlantic salmon (Salmo salar) aquaculture industry. However, the interactions between sea lice and ISAv, as well as the impact of a prior sea lice infection on the susceptibility of th...

  18. Does Reactivating a Witnessed Memory Increase Its Susceptibility to Impairment by Subsequent Misinformation?

    ERIC Educational Resources Information Center

    Rindal, Eric J.; DeFranco, Rachel M.; Rich, Patrick R.; Zaragoza, Maria S.

    2016-01-01

    In a recent PNAS article, Chan and LaPaglia (2013) provided arguments and evidence to support the claim that reactivating a witnessed memory (by taking a test) renders the memory labile and susceptible to impairment by subsequent misinformation. In the current article, we argue that Chan and LaPaglia's (2013) findings are open to alternative…

  19. Does obesity increase susceptibility to ozone? Respiratory, behavioral, and metabolic assessments in Brown Norway rats

    EPA Science Inventory

    There may be a link between obesity and susceptibility to the respiratory, cardiovascular, and other health effects of air pollutants. Furthermore, it has been proposed that some air pollutants are obesogenic and may contribute to obesity. In view of the epidemic growth of obesit...

  20. Susceptibility of lesser mealworm (Coleoptera: Tenebrionidae) adults and larvae exposed to two commercial insecticides on unpainted plywood panels.

    PubMed

    Kaufman, Phillip E; Strong, Colleen; Rutz, Donald A

    2008-02-01

    The susceptibilities of adult and larval lesser mealworms, Alphitobius diaperinus (Panzer), to two commercially formulated insecticides, cyfluthrin and tetrachlorvinphos, were examined through exposure on treated plywood panels. Lesser mealworms were collected from four caged-layer poultry farms, three in New York and one in Maine. An additional strain was obtained from an infestation occurring in a cricket colony. In all poultry farm derived strains, a portion of the population (1.8-16.2%) survived cyfluthrin exposure. The Maine and cricket colony strains were tolerant of tetrachlorvinphos exposure as both larvae and adults, with 55-74% mortality, whereas nearly 100% mortality was observed with New York strains. The cricket colony adult beetles were highly susceptible to cyfluthrin, with 100% mortality following exposure, but larvae were considerably less susceptible (87.7%). Pesticide use histories for the poultry farms and their impact on the results are discussed. The results document that tetrachlorvinphos, an active ingredient with a long use history, may be losing its effectiveness against lesser mealworms in some poultry operations; however, it is still effective in many others.

  1. Antimicrobial susceptibility of Streptococcus pneumoniae in adult patients with pneumococcal pneumonia in an urban hospital in Mozambique.

    PubMed

    Bos, Jeannet C; Beishuizen, Sara J; Madeira, Geoffrey C; Gomonda, Elmano dos Santos; Cossa, Esmeralda O; Macome, Augusto C; van Steenwijk, Reindert P; Schultsz, Constance; Prins, Jan M

    2014-02-25

    Streptococcus pneumoniae is the leading cause of community-acquired pneumonia in Africa. Antimicrobial resistance of S. pneumoniae to penicillin and other commonly used antibiotics has increased worldwide. However, prevalence data from the African region are sparse, especially with regard to adults. In this study, adult patients presenting at an urban referral hospital in central Mozambique were screened for pneumococcal pneumonia during an 8-week period in 2010: Patients with a respiratory syndrome underwent chest radiography and a sputum sample was collected for pneumococcal culture and antimicrobial susceptibility testing. A urine sample was tested for the presence of pneumococcal antigen.177 patients with a respiratory syndrome were included. Overall, 41/177 (23%) patients fulfilled criteria for definite or probable pneumococcal pneumonia and in the group of patients with a positive chest x-ray this concerned 35/86 (41%) patients. 166 sputum cultures yielded 16 pneumococcal strains. One mg oxacillin disc testing identified potential penicillin resistance in 7/16 (44%) strains. Penicillin minimal inhibitory concentrations (MICs) were measured for 15 of these strains and ranged from <0.016-0.75 mg/L. No MICs >2 mg/L were found, but 3/15 (20%) pneumococcal strains had MICs >0.5 mg/L. All pneumococci were sensitive to erythromycin as measured by disc diffusion testing, whereas 44% was resistant to trimethoprim-sulfametoxazole. The proportion of pneumonia cases attributable to pneumococcus appeared to be high. Whilst none of the S. pneumoniae strains tested were penicillin resistant, standard penicillin dosing for pneumonia may be insufficient given the observed range of pneumococcal penicillin MICs.

  2. Pyrethroid resistance in Anopheles gambiae leads to increased susceptibility to the entomopathogenic fungi Metarhizium anisopliae and Beauveria bassiana

    PubMed Central

    2010-01-01

    Background Entomopathogenic fungi are being investigated as a new mosquito control tool because insecticide resistance is preventing successful mosquito control in many countries, and new methods are required that can target insecticide-resistant malaria vectors. Although laboratory studies have previously examined the effects of entomopathogenic fungi against adult mosquitoes, most application methods used cannot be readily deployed in the field. Because the fungi are biological organisms it is important to test potential field application methods that will not adversely affect them. The two objectives of this study were to investigate any differences in fungal susceptibility between an insecticide-resistant and insecticide-susceptible strain of Anopheles gambiae sensu stricto, and to test a potential field application method with respect to the viability and virulence of two fungal species Methods Pieces of white polyester netting were dipped in Metarhizium anisopliae ICIPE-30 or Beauveria bassiana IMI391510 mineral oil suspensions. These were kept at 27 ± 1°C, 80 ± 10% RH and the viability of the fungal conidia was recorded at different time points. Tube bioassays were used to infect insecticide-resistant (VKPER) and insecticide-susceptible (SKK) strains of An. gambiae s.s., and survival analysis was used to determine effects of mosquito strain, fungus species or time since fungal treatment of the net. Results The resistant VKPER strain was significantly more susceptible to fungal infection than the insecticide-susceptible SKK strain. Furthermore, B. bassiana was significantly more virulent than M. anisopliae for both mosquito strains, although this may be linked to the different viabilities of these fungal species. The viability of both fungal species decreased significantly one day after application onto polyester netting when compared to the viability of conidia remaining in suspension. Conclusions The insecticide-resistant mosquito strain was susceptible

  3. Chimpanzees Show a Developmental Increase in Susceptibility to Contagious Yawning: A Test of the Effect of Ontogeny and Emotional Closeness on Yawn Contagion

    PubMed Central

    Madsen, Elainie Alenkær; Persson, Tomas; Sayehli, Susan; Lenninger, Sara; Sonesson, Göran

    2013-01-01

    Contagious yawning has been reported for humans, dogs and several non-human primate species, and associated with empathy in humans and other primates. Still, the function, development and underlying mechanisms of contagious yawning remain unclear. Humans and dogs show a developmental increase in susceptibility to yawn contagion, with children showing an increase around the age of four, when also empathy-related behaviours and accurate identification of others’ emotions begin to clearly evince. Explicit tests of yawn contagion in non-human apes have only involved adult individuals and examined the existence of conspecific yawn contagion. Here we report the first study of heterospecific contagious yawning in primates, and the ontogeny of susceptibility thereto in chimpanzees, Pan troglodytes verus. We examined whether emotional closeness, defined as attachment history with the yawning model, affected the strength of contagion, and compared the contagiousness of yawning to nose-wiping. Thirty-three orphaned chimpanzees observed an unfamiliar and familiar human (their surrogate human mother) yawn, gape and nose-wipe. Yawning, but not nose-wiping, was contagious for juvenile chimpanzees, while infants were immune to contagion. Like humans and dogs, chimpanzees are subject to a developmental trend in susceptibility to contagious yawning, and respond to heterospecific yawn stimuli. Emotional closeness with the model did not affect contagion. The familiarity-biased social modulatory effect on yawn contagion previously found among some adult primates, seem to only emerge later in development, or be limited to interactions with conspecifics. The influence of the ‘chameleon effect’, targeted vs. generalised empathy, perspective-taking and visual attention on contagious yawning is discussed. PMID:24146848

  4. Chimpanzees show a developmental increase in susceptibility to contagious yawning: a test of the effect of ontogeny and emotional closeness on yawn contagion.

    PubMed

    Madsen, Elainie Alenkær; Persson, Tomas; Sayehli, Susan; Lenninger, Sara; Sonesson, Göran

    2013-01-01

    Contagious yawning has been reported for humans, dogs and several non-human primate species, and associated with empathy in humans and other primates. Still, the function, development and underlying mechanisms of contagious yawning remain unclear. Humans and dogs show a developmental increase in susceptibility to yawn contagion, with children showing an increase around the age of four, when also empathy-related behaviours and accurate identification of others' emotions begin to clearly evince. Explicit tests of yawn contagion in non-human apes have only involved adult individuals and examined the existence of conspecific yawn contagion. Here we report the first study of heterospecific contagious yawning in primates, and the ontogeny of susceptibility thereto in chimpanzees, Pan troglodytes verus. We examined whether emotional closeness, defined as attachment history with the yawning model, affected the strength of contagion, and compared the contagiousness of yawning to nose-wiping. Thirty-three orphaned chimpanzees observed an unfamiliar and familiar human (their surrogate human mother) yawn, gape and nose-wipe. Yawning, but not nose-wiping, was contagious for juvenile chimpanzees, while infants were immune to contagion. Like humans and dogs, chimpanzees are subject to a developmental trend in susceptibility to contagious yawning, and respond to heterospecific yawn stimuli. Emotional closeness with the model did not affect contagion. The familiarity-biased social modulatory effect on yawn contagion previously found among some adult primates, seem to only emerge later in development, or be limited to interactions with conspecifics. The influence of the 'chameleon effect', targeted vs. generalised empathy, perspective-taking and visual attention on contagious yawning is discussed.

  5. Increased nitrite reductase activity of fetal versus adult ovine hemoglobin

    PubMed Central

    Blood, Arlin B.; Tiso, Mauro; Verma, Shilpa T.; Lo, Jennifer; Joshi, Mahesh S.; Azarov, Ivan; Longo, Lawrence D.; Gladwin, Mark T.; Kim-Shapiro, Daniel B.; Power, Gordon G.

    2009-01-01

    Growing evidence indicates that nitrite, NO2−, serves as a circulating reservoir of nitric oxide (NO) bioactivity that is activated during physiological and pathological hypoxia. One of the intravascular mechanisms for nitrite conversion to NO is a chemical nitrite reductase activity of deoxyhemoglobin. The rate of NO production from this reaction is increased when hemoglobin is in the R conformation. Because the mammalian fetus exists in a low-oxygen environment compared with the adult and is exposed to episodes of severe ischemia during the normal birthing process, and because fetal hemoglobin assumes the R conformation more readily than adult hemoglobin, we hypothesized that nitrite reduction to NO may be enhanced in the fetal circulation. We found that the reaction was faster for fetal than maternal hemoglobin or blood and that the reactions were fastest at 50–80% oxygen saturation, consistent with an R-state catalysis that is predominant for fetal hemoglobin. Nitrite concentrations were similar in blood taken from chronically instrumented normoxic ewes and their fetuses but were elevated in response to chronic hypoxia. The findings suggest an augmented nitrite reductase activity of fetal hemoglobin and that the production of nitrite may participate in the regulation of vascular NO homeostasis in the fetus. PMID:19028797

  6. SU-E-I-62: Reduction of Susceptibility Artifacts by Increasing the Bandwidth (BW) and Echo Train Length (ETL)

    SciTech Connect

    Mavroidis, P; Boci, N; Kostopoulos, S; Ninos, C; Glotsos, D; Oikonomou, G; Bakas, A; Roka, V; Cavouras, D; Lavdas, E; Sakkas, G; Tsagkalis, A; Chatzivasileiou, V; Batsikas, G; Papanikolaou, N; Stathakis, S

    2015-06-15

    Purpose: The aim of this present study is to increase bandwidth (BW) and echo train length (ETL) in Proton Density Turbo Spin Echo (PD TSE) sequences with and without fat saturation (FS) as well as in Turbo Inversion Recovery Magnitude sequences (TIRM) in order to assess whether these sequences are capable of reducing susceptibility artifacts. Methods: We compared 1) TIRM coronal (COR) with the same sequence with increased both BW and ETL 2) Conventional PD TSE sagittal (SAG) with FS with an increased BW 3) Conventional PD TSE SAG without FS with an increased BW 4) Conventional PD TSE SAG without FS with increased both BW and ETL. A quantitative analysis was performed to measure the extent of the susceptibility artifacts. Furthermore, a qualitative analysis was performed by two radiologists in order to evaluate the susceptibility artifacts, image distortion and fat suppression. The depiction of cartilage, menisci, muscles, tendons and bone marrow were also qualitatively analyzed. Results: The quantitative analysis found that the modified TIRM sequence is significantly superior to the conventional one regarding the extent of the susceptibility artifacts. In the qualitative analysis, the modified TIRM sequence was superior to the corresponding conventional one in eight characteristics out of ten that were analyzed. The modified PD TSE with FS was superior to the corresponding conventional one regarding the susceptibility artifacts, image distortion and depiction of bone marrow and cartilage while achieving effective fat saturation. The modified PD TSE sequence without FS with a high (H) BW was found to be superior corresponding to the conventional one in the case of cartilage. Conclusion: Consequently, TIRM sequence with an increased BW and ETL is proposed for producing images of high quality and modified PD TSE with H BW for smaller metals, especially when FS is used.

  7. Defective DNA repair increases susceptibility to senescence through extension of Chk1-mediated G2 checkpoint activation

    PubMed Central

    Johmura, Yoshikazu; Yamashita, Emiri; Shimada, Midori; Nakanishi, Keiko; Nakanishi, Makoto

    2016-01-01

    Susceptibility to senescence caused by defective DNA repair is a major hallmark of progeroid syndrome patients, but molecular mechanisms of how defective DNA repair predisposes to senescence are largely unknown. We demonstrate here that suppression of DNA repair pathways extends the duration of Chk1-dependent G2 checkpoint activation and sensitizes cells to senescence through enhancement of mitosis skipping. Extension of G2 checkpoint activation by introduction of the TopBP1 activation domain and the nondegradable mutant of Claspin sensitizes cells to senescence. In contrast, a shortening of G2 checkpoint activation by expression of SIRT6 or depletion of OTUB2 reduces susceptibility to senescence. Fibroblasts from progeroid syndromes tested shows a correlation between an extension of G2 checkpoint activation and an increase in the susceptibility to senescence. These results suggest that extension of G2 checkpoint activation caused by defective DNA repair is critical for senescence predisposition in progeroid syndrome patients. PMID:27507734

  8. Molecular basis for increased susceptibility of Indigenous North Americans to seropositive rheumatoid arthritis.

    PubMed

    Scally, Stephen W; Law, Soi-Cheng; Ting, Yi Tian; Heemst, Jurgen van; Sokolove, Jeremy; Deutsch, Aaron J; Bridie Clemens, E; Moustakas, Antonis K; Papadopoulos, George K; Woude, Diane van der; Smolik, Irene; Hitchon, Carol A; Robinson, David B; Ferucci, Elizabeth D; Bernstein, Charles N; Meng, Xiaobo; Anaparti, Vidyanand; Huizinga, Tom; Kedzierska, Katherine; Reid, Hugh H; Raychaudhuri, Soumya; Toes, René E; Rossjohn, Jamie; El-Gabalawy, Hani; Thomas, Ranjeny

    2017-08-11

    The pathogenetic mechanisms by which HLA-DRB1 alleles are associated with anticitrullinated peptide antibody (ACPA)-positive rheumatoid arthritis (RA) are incompletely understood. RA high-risk HLA-DRB1 alleles are known to share a common motif, the 'shared susceptibility epitope (SE)'. Here, the electropositive P4 pocket of HLA-DRB1 accommodates self-peptide residues containing citrulline but not arginine. HLA-DRB1 His/Phe13β stratifies with ACPA-positive RA, while His13βSer polymorphisms stratify with ACPA-negative RA and RA protection. Indigenous North American (INA) populations have high risk of early-onset ACPA-positive RA, whereby HLA-DRB1*04:04 and HLA-DRB1*14:02 are implicated as risk factors for RA in INA. However, HLA-DRB1*14:02 has a His13βSer polymorphism. Therefore, we aimed to verify this association and determine its molecular mechanism. HLA genotype was compared in 344 INA patients with RA and 352 controls. Structures of HLA-DRB1*1402-class II loaded with vimentin-64Arg59-71, vimentin-64Cit59-71 and fibrinogen β-74Cit69-81 were solved using X-ray crystallography. Vimentin-64Cit59-71-specific and vimentin59-71-specific CD4+ T cells were characterised by flow cytometry using peptide-histocompatibility leukocyte antigen (pHLA) tetramers. After sorting of antigen-specific T cells, TCRα and β-chains were analysed using multiplex, nested PCR and sequencing. ACPA(+) RA in INA was independently associated with HLA-DRB1*14:02. Consequent to the His13βSer polymorphism and altered P4 pocket of HLA-DRB1*14:02, both citrulline and arginine were accommodated in opposite orientations. Oligoclonal autoreactive CD4+ effector T cells reactive with both citrulline and arginine forms of vimentin59-71 were observed in patients with HLA-DRB1*14:02(+) RA and at-risk ACPA(-) first-degree relatives. HLA-DRB1*14:02-vimentin59-71-specific and HLA-DRB1*14:02-vimentin-64Cit59-71-specific CD4+ memory T cells were phenotypically distinct populations. HLA-DRB1*14:02 broadens

  9. SerpinB1 deficiency is not associated with increased susceptibility to pulmonary emphysema in mice.

    PubMed

    Cremona, Tiziana P; Tschanz, Stefan A; von Garnier, Christophe; Benarafa, Charaf

    2013-12-01

    Chronic obstructive pulmonary disease (COPD) is characterized by emphysema and chronic bronchitis and is a leading cause of morbidity and mortality worldwide. Tobacco smoke and deficiency in α1-antitrypsin (AAT) are the most prominent environmental and genetic risk factors, respectively. Yet the pathogenesis of COPD is not completely elucidated. Disease progression appears to include a vicious circle driven by self-perpetuating lung inflammation, endothelial and epithelial cell death, and proteolytic degradation of extracellular matrix proteins. Like AAT, serpinB1 is a potent inhibitor of serine proteases including neutrophil elastase and cathepsin G. Because serpinB1 is expressed in myeloid and lung epithelial cells and is protective during lung infections, we investigated the role of serpinB1 in preventing age-related and cigarette smoke-induced emphysema in mice. Fifteen-month-old mice showed increased lung volume and decreased pulmonary function compared with young adult mice (3 mo old), but no differences were observed between serpinB1-deficient (KO) and wild-type (WT) mice. Chronic exposure to secondhand cigarette smoke resulted in structural emphysematous changes compared with respective control mice, but no difference in lung morphometry was observed between genotypes. Of note, the different pattern of stereological changes induced by age and cigarette smoke suggest distinct mechanisms leading to increased airway volume. Finally, expression of intracellular and extracellular protease inhibitors were differently regulated in lungs of WT and KO mice following smoke exposure; however, activity of proteases was not significantly altered. In conclusion, we showed that, although AAT and serpinB1 are similarly potent inhibitors of neutrophil proteases, serpinB1 deficiency is not associated with more severe emphysema.

  10. Epigallocatechin-3-gallate increases maximal oxygen uptake in adult humans.

    PubMed

    Richards, Jennifer C; Lonac, Mark C; Johnson, Tyler K; Schweder, Melani M; Bell, Christopher

    2010-04-01

    Epigallocatechin-3-gallate (EGCG), a component of green tea, increases endurance performance in animals and promotes fat oxidation during cycle ergometer exercise in adult humans. We have investigated the hypothesis that short-term consumption of EGCG delays the onset of the ventilatory threshold (VT) and increases maximal oxygen uptake (VO2max). In this randomized, repeated-measures, double-blind study, 19 healthy adults (11 males and 8 females, age = 26 ± 2 yr (mean ± SE)) received seven placebo or seven EGCG (135-mg) pills. Forty-eight hours before data collection, participants began consuming three pills per day; the last pill was taken 2 h before exercise testing. VT and VO2max were determined from breath-by-breath indirect calorimetry data collected during continuous incremental stationary cycle ergometer exercise (20-35 W·min(-1)), from rest until volitional fatigue. Each condition/exercise test was separated by a minimum of 14 d. Compared with placebo, short-term EGCG consumption increased VO2max (3.123 ± 0.187 vs 3.259 ± 0.196 L·min(-1), P = 0.04). Maximal work rate (301 ± 15 vs 301 ± 16 W, P = 0.98), maximal RER (1.21 ± 0.01 vs 1.22 ± 0.02, P = 0.27), and maximal HR were unaffected (180 ± 3 vs 180 ± 3 beats·min(-1), P = 0.87). In a subset of subjects (n = 11), maximal cardiac output (determined via open-circuit acetylene breathing) was also unaffected by EGCG (29.6 ± 2.2 vs 30.2 ± 1.4 L·min(-1), P = 0.70). Contrary to our hypothesis, EGCG decreased VO2 at VT (1.57 ± 0.11 vs 1.48 ± 0.10 L·min(-1)), but this change was not significant (P = 0.06). Short-term consumption of EGCG increased VO2max without affecting maximal cardiac output, suggesting that EGCG may increase arterial-venous oxygen difference.

  11. Collateral damage: rapid exposure-induced evolution of pesticide resistance leads to increased susceptibility to parasites.

    PubMed

    Jansen, Mieke; Stoks, Robby; Coors, Anja; van Doorslaer, Wendy; de Meester, Luc

    2011-09-01

    Although natural populations may evolve resistance to anthropogenic stressors such as pollutants, this evolved resistance may carry costs. Using an experimental evolution approach, we exposed different Daphnia magna populations in outdoor containers to the carbamate pesticide carbaryl and control conditions, and assessed the resulting populations for both their resistance to carbaryl as well as their susceptibility to infection by the widespread bacterial microparasite Pasteuria ramosa. Our results show that carbaryl selection led to rapid evolution of carbaryl resistance with seemingly no cost when assessed in a benign environment. However, carbaryl-resistant populations were more susceptible to parasite infection than control populations. Exposure to both stressors reveals a synergistic effect on sterilization rate by P. ramosa, but this synergism did not evolve under pesticide selection. Assessing costs of rapid adaptive evolution to anthropogenic stress in a semi-natural context may be crucial to avoid too optimistic predictions for the fitness of the evolving populations. © 2011 The Author(s).

  12. Short photoperiod condition increases susceptibility to stress in adolescent male rats.

    PubMed

    Xu, Ling-Zhi; Liu, Li-Jing; Yuan, Ming; Li, Su-Xia; Yue, Xiao-Dong; Lai, Ju-Lian; Lu, Lin

    2016-03-01

    The seasonality of depressive symptoms is prevalent in children and adolescents. However, the mechanisms that underlie such susceptibility to seasonal influences on mood disorders are unclear. We examined the effects of a short photoperiod condition on the susceptibility to subchronic unpredictable mild stress (SCUS) and rhythmic alterations of plasma corticosterone (CORT), melatonin, and neuropeptide Y (NPY) in adolescent male rats. Compared with the 12h/12h light/dark photoperiod control (CON) rats, the 8h/16h photoperiod SCUS rats exhibited significant anhedonia, a core symptom of human depression, together with a blunted diurnal rhythm and elevation of 24h CORT, melatonin, and NPY levels. The 8h/16h photoperiod condition also blunted the rhythmicity of CORT, caused a phase inversion of melatonin, and caused a phase delay of NPY compared with 12h/12h CON rats. Such abnormalities of plasma CORT, NPY, and melatonin might cause adolescent individuals to present higher stress reactivity and greater vulnerability to stress over their lifetimes. The present study provides evidence of the susceptibility to the seasonality of stress-related disorders in adolescence.

  13. Serum Sclerostin Increases in Healthy Adult Men during Bed Rest

    PubMed Central

    Fields, E. E.; Yu, E. W.; Pajevic, P. Divieti; Bouxsein, M. L.; Sibonga, J. D.; Zwart, S. R.; Smith, S. M.

    2012-01-01

    Context: Animal models and human studies suggest that osteocytes regulate the skeleton's response to mechanical unloading in part by an increase in sclerostin. However, few studies have reported changes in serum sclerostin in humans exposed to reduced mechanical loading. Objective: We determined changes in serum sclerostin and bone turnover markers in healthy adult men undergoing controlled bed rest. Design, Setting, and Participants: Seven healthy adult men (31 ± 3 yr old) underwent 90 d of 6° head down tilt bed rest at the University of Texas Medical Branch Institute for Translational Sciences-Clinical Research Center. Outcomes: Serum sclerostin, PTH, vitamin D, bone resorption and formation markers, urinary calcium and phosphorus excretion, and 24-h pooled urinary markers of bone resorption were evaluated before bed rest [baseline (BL)] and at bed rest d 28 (BR-28), d 60 (BR-60), and d 90 (BR-90). Bone mineral density was measured at BL, BR-60, and 5 d after the end of the study (BR+5). Data are reported as mean ± sd. Results: Consistent with prior reports, bone mineral density declined significantly (1–2% per month) at weight-bearing skeletal sites. Serum sclerostin was elevated above BL at BR-28 (+29 ± 20%; P = 0.003) and BR-60 (+42 ± 31%; P < 0.001), with a lesser increase at BR-90 (+22 ± 21%; P = 0.07). Serum PTH levels were reduced at BR-28 (−17 ± 16%; P = 0.02) and BR-60 (−24 ± 14%; P = 0.03) and remained lower than BL at BR-90 (−21 ± 21%; P = 0.14), but did not reach statistical significance. Serum bone turnover markers were unchanged; however, urinary bone resorption markers and calcium were significantly elevated at all time points after bed rest (P < 0.01). Conclusions: In healthy men subjected to controlled bed rest for 90 d, serum sclerostin increased, with a peak at 60, whereas serum PTH declined, and urinary calcium and bone resorption markers increased. PMID:22767636

  14. Overexpression of Forebrain CRH During Early Life Increases Trauma Susceptibility in Adulthood

    PubMed Central

    Toth, Mate; Flandreau, Elizabeth I; Deslauriers, Jessica; Geyer, Mark A; Mansuy, Isabelle M; Merlo Pich, Emilio; Risbrough, Victoria B

    2016-01-01

    findings indicate that forebrain CRH hyper-signaling in early-life is sufficient to increase enduring effects of adult trauma and attenuate Crhr2 expression changes in response to stress in males. These data support growing evidence for significant sex differences in response to trauma, and support further study of CRHR2 as a candidate mechanism for PTSD risk. PMID:26538448

  15. Enhanced cocaine-induced locomotor sensitization and intrinsic excitability of NAc medium spiny neurons in adult but not adolescent rats susceptible to diet-induced obesity

    PubMed Central

    Oginsky, Max F.; Maust, Joel D.; Corthell, John T.; Ferrario, Carrie R.

    2015-01-01

    Rationale Basal and diet-induced differences in mesolimbic function, particularly within the nucleus accumbens (NAc), may contribute to human obesity; these differences may be more pronounced in susceptible populations. Objectives We determined whether there are differences in cocaine-induced behavioral plasticity in rats that are susceptible vs. resistant to diet-induced obesity, and basal differences in the striatal neuron function in adult and adolescent obesity-prone and obesity-resistant rats. Methods Susceptible and resistant outbred rats were identified based on “junk-food” diet-induced obesity. Then, the induction and expression of cocaine-induced locomotor sensitization, which is mediated by enhanced striatal function and is associated with increased motivation for rewards and reward-paired cues, were evaluated. Basal differences in mesolimbic function were examined in selectively bred obesity-prone and obesity-resistant rats (P70-80 and P30-40) using both cocaine induced locomotion and whole-cell patch clamping approaches in NAc core medium spiny neurons (MSNs). Results In rats that became obese after eating “junk-food”, the expression of locomotor sensitization was enhanced compared to non-obese rats, with similarly strong responses to 7.5 and 15 mg/kg cocaine. Without diet manipulation, obesity-prone rats were hyper-responsive to the acute locomotor-activating effects of cocaine, and the intrinsic excitability of NAc core MSNs was enhanced by ~60% at positive and negative potentials. These differences were present in adult, but not adolescent rats. Post-synaptic glutamatergic transmission was similar between groups. Conclusions Mesolimbic systems, particularly NAc MSNs, are hyper-responsive in obesity-prone individuals; and interactions between predisposition and experience influence neurobehavioral plasticity in ways that may promote weight gain and hamper weight loss in susceptible rats. PMID:26612617

  16. Enhanced cocaine-induced locomotor sensitization and intrinsic excitability of NAc medium spiny neurons in adult but not in adolescent rats susceptible to diet-induced obesity.

    PubMed

    Oginsky, Max F; Maust, Joel D; Corthell, John T; Ferrario, Carrie R

    2016-03-01

    Basal and diet-induced differences in mesolimbic function, particularly within the nucleus accumbens (NAc), may contribute to human obesity; these differences may be more pronounced in susceptible populations. We examined differences in cocaine-induced behavioral plasticity in rats that are susceptible vs. resistant to diet-induced obesity and basal differences in striatal neuron function in adult and in adolescent obesity-prone and obesity-resistant rats. Susceptible and resistant outbred rats were identified based on "junk-food" diet-induced obesity. Then, the induction and expression of cocaine-induced locomotor sensitization, which is mediated by enhanced striatal function and is associated with increased motivation for rewards and reward-paired cues, were evaluated. Basal differences in mesolimbic function were examined in selectively bred obesity-prone and obesity-resistant rats (P70-80 and P30-40) using both cocaine-induced locomotion and whole-cell patch clamping approaches in NAc core medium spiny neurons (MSNs). In rats that became obese after eating junk-food, the expression of locomotor sensitization was enhanced compared to non-obese rats, with similarly strong responses to 7.5 and 15 mg/kg cocaine. Without diet manipulation, obesity-prone rats were hyper-responsive to the acute locomotor-activating effects of cocaine, and the intrinsic excitability of NAc core MSNs was enhanced by ∼60 % at positive and negative potentials. These differences were present in adult, but not adolescent rats. Post-synaptic glutamatergic transmission was similar between groups. Mesolimbic systems, particularly NAc MSNs, are hyper-responsive in obesity-prone individuals, and interactions between predisposition and experience influence neurobehavioral plasticity in ways that may promote weight gain and hamper weight loss in susceptible rats.

  17. The Intrauterine and Nursing Period Is a Window of Susceptibility for Development of Obesity and Intestinal Tumorigenesis by a High Fat Diet in Min/+ Mice as Adults

    PubMed Central

    Ngo, Ha Thi; Hetland, Ragna Bogen; Steffensen, Inger-Lise

    2015-01-01

    We studied how obesogenic conditions during various life periods affected obesity and intestinal tumorigenesis in adult C57BL/6J-Min (multiple intestinal neoplasia)/+ mice. The mice were given a 10% fat diet throughout life (negative control) or a 45% fat diet in utero, during nursing, during both in utero and nursing, during adult life, or during their whole life-span, and terminated at 11 weeks for tumorigenesis (Min/+) or 23 weeks for obesogenic effect (wild-type). Body weight at 11 weeks was increased after a 45% fat diet during nursing, during both in utero and nursing, and throughout life, but had normalized at 23 weeks. In the glucose tolerance test, the early exposure to a 45% fat diet in utero, during nursing, or during both in utero and nursing, did not affect blood glucose, whereas a 45% fat diet given to adults or throughout life did. However, a 45% fat diet during nursing or during in utero and nursing increased the number of small intestinal tumors. So did exposures to a 45% fat diet in adult life or throughout life, but without increasing the tumor numbers further. The intrauterine and nursing period is a window of susceptibility for dietary fat-induced obesity and intestinal tumor development. PMID:25874125

  18. Polymorphisms in the matrix metalloproteinase-1, 3, and 9 promoters and susceptibility to adult astrocytoma in northern China.

    PubMed

    Lu, Zhongqiang; Cao, Yanyan; Wang, Yimin; Zhang, Qingjun; Zhang, Xianghong; Wang, Shuheng; Li, Yuehong; Xie, Huiling; Jiao, Baohua; Zhang, Jianhui

    2007-10-01

    The single nucleotide polymorphisms (SNPs) in the promoter region of matrix metalloproteinase (MMP) genes may influence tumor occurrence and progression via modifying mRNA transcription and protein expression. The study aims to explore the association of the SNPs in MMP-1, 3 and MMP-9 promoters with susceptibility to adult brain astrocytoma in northern China. Genotyping for the MMP-1 -1607 2G/1G, MMP-3 -1171 5A/6A, and MMP-9 -1562 C/T SNPs were performed by PCR-RFLP methods among 236 adult astrocytoma patients and 366 healthy controls. The results showed that the overall distribution of the MMP-1 allelotype and genotype among astrocytoma patients and healthy controls was significantly different (P = 0.002 and P < 0.001, respectively). Compared with the 2G/2G genotype, the 1G/1G genotype significantly decreased the risk of astrocytoma development (adjusted OR = 0.58, 95% CI = 0.42-0.79). The similar results were obtained when stratified by gender and age at tumor diagnosis (< or =45 or >45 years). The association between MMP-3 -1171 5A/6A or MMP-9 -1562 C/T SNPs and susceptibility to astrocytoma was not observed in this study. However, MMP-1 1G-MMP-3 6A haplotype significantly reduced the risk of astrocytoma development when using MMP-1 2G-MMP-3 6A haplotype as a reference (OR = 0.45, 95% CI = 0.29-0.67). The present study suggested that, the MMP-1 -1607 1G/1G genotype and MMP-1 1G-MMP-3 6A haplotype may play protective role in the development of adult astrocytoma in northern Chinese, whereas the MMP-3 -1171 5A/6A and MMP-9 -1562 C/T polymorphisms may not be independent factors to influence susceptibility to adult astrocytoma in this population.

  19. Low Iron Diet Increases Susceptibility to Noise-Induced Hearing Loss in Young Rats

    PubMed Central

    Yu, Fei; Hao, Shuai; Yang, Bo; Zhao, Yue; Yang, Jun

    2016-01-01

    noise exposure compared to control (p < 0.05). The average number of young rat SGCs from the ID group were significantly decreased in the basal turn of the cochlea compared to the control (p < 0.05). Therefore, ID without anemia delayed the recovery from noise-induced hearing loss and ribbon synapses damage, increased SGCs loss, and upregulated prestin after noise exposure. Thus, the cochleae in rat pups with ID without anemia were potentially susceptible to loud noise exposure, and this deficit may be attributed to the reduction of ribbon synapses and SGCs. PMID:27483303

  20. Low Iron Diet Increases Susceptibility to Noise-Induced Hearing Loss in Young Rats.

    PubMed

    Yu, Fei; Hao, Shuai; Yang, Bo; Zhao, Yue; Yang, Jun

    2016-07-28

    noise exposure compared to control (p < 0.05). The average number of young rat SGCs from the ID group were significantly decreased in the basal turn of the cochlea compared to the control (p < 0.05). Therefore, ID without anemia delayed the recovery from noise-induced hearing loss and ribbon synapses damage, increased SGCs loss, and upregulated prestin after noise exposure. Thus, the cochleae in rat pups with ID without anemia were potentially susceptible to loud noise exposure, and this deficit may be attributed to the reduction of ribbon synapses and SGCs.

  1. Estimating the effects of novel on-pack warnings on young adult smokers and susceptible non-smokers.

    PubMed

    Gendall, Philip; Eckert, Christine; Hoek, Janet; Louviere, Jordan

    2017-08-19

    On-pack tobacco warnings can deter smoking initiation and provide powerful cessation cues. However, these warnings typically feature graphic health images, which many young adults dismiss as irrelevant. We estimated responses to more diverse warnings and examined how these performed relative to each other. We conducted a behavioural likelihood experiment and a choice modelling experiment in which 474 smokers and 476 susceptible non-smokers aged between 16 and 30 years evaluated 12 warnings featuring health, social, financial and cosmetic themes. The choice data were analysed by estimating Sequential-Best-Worst Choice and Scale-Adjusted Latent Class Models. Smokers found all test warnings aversive, particularly warnings featuring the effect of smoking on vulnerable third parties, including babies and animals, and showing a dying smoker. Susceptible non-smokers found graphic health warnings and a warning that combined graphic health with loss of physical attractiveness, significantly more aversive than other images tested. Illustrating the harms smoking causes to vulnerable groups may reduce the temporal distance and perceived control over smoking that young adults use to rationalise health warnings. Introducing more diverse warnings could recognise heterogeneity within smoker and susceptible non-smoker populations, and complement warnings featuring long-term health harms. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  2. Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer

    PubMed Central

    Bernardes de Jesus, Bruno; Vera, Elsa; Schneeberger, Kerstin; Tejera, Agueda M; Ayuso, Eduard; Bosch, Fatima; Blasco, Maria A

    2012-01-01

    A major goal in aging research is to improve health during aging. In the case of mice, genetic manipulations that shorten or lengthen telomeres result, respectively, in decreased or increased longevity. Based on this, we have tested the effects of a telomerase gene therapy in adult (1 year of age) and old (2 years of age) mice. Treatment of 1- and 2-year old mice with an adeno associated virus (AAV) of wide tropism expressing mouse TERT had remarkable beneficial effects on health and fitness, including insulin sensitivity, osteoporosis, neuromuscular coordination and several molecular biomarkers of aging. Importantly, telomerase-treated mice did not develop more cancer than their control littermates, suggesting that the known tumorigenic activity of telomerase is severely decreased when expressed in adult or old organisms using AAV vectors. Finally, telomerase-treated mice, both at 1-year and at 2-year of age, had an increase in median lifespan of 24 and 13%, respectively. These beneficial effects were not observed with a catalytically inactive TERT, demonstrating that they require telomerase activity. Together, these results constitute a proof-of-principle of a role of TERT in delaying physiological aging and extending longevity in normal mice through a telomerase-based treatment, and demonstrate the feasibility of anti-aging gene therapy. PMID:22585399

  3. A trade off between mlo resistance to powdery mildew and increased susceptibility of barley to a newly important disease, Ramularia leaf spot

    PubMed Central

    McGrann, Graham R. D.; Brown, James K. M.

    2014-01-01

    Ramularia leaf spot (RLS), caused by the fungus Ramularia collo-cygni, is a serious, recently emerged disease of barley in Europe and other temperate regions. This study investigated the trade off between strong resistance to powdery mildew conferred by mlo mutant alleles and increased susceptibility to RLS. In field trials and seedling tests, the presence of mlo alleles increased severity of RLS. Genetic analysis of a doubled-haploid population identified one quantitative trait locus for susceptibility to RLS, colocalizing with the mlo-11 allele for mildew resistance. The effect of mlo-11 on RLS severity was environmentally sensitive. Analysis of near-isogenic lines of different mlo mutations in various genetic backgrounds confirmed that mlo alleles increased RLS severity in seedlings and adult plants. For mlo resistance to mildew to be fully effective, the genes ROR1 and ROR2 are required. RLS symptoms were significantly reduced on mlo-5 ror double mutants but fungal DNA levels remained as high as in mlo-5 single mutants, implying that ror alleles modify the transition of the fungus from endophytism to necrotrophy. These results indicate that the widespread use of mlo resistance to control mildew may have inadvertently stimulated the emergence of RLS as a major disease of barley. PMID:24399175

  4. A genome-wide association study of susceptibility to acute lymphoblastic leukemia in adolescents and young adults.

    PubMed

    Perez-Andreu, Virginia; Roberts, Kathryn G; Xu, Heng; Smith, Colton; Zhang, Hui; Yang, Wenjian; Harvey, Richard C; Payne-Turner, Debbie; Devidas, Meenakshi; Cheng, I-Ming; Carroll, William L; Heerema, Nyla A; Carroll, Andrew J; Raetz, Elizabeth A; Gastier-Foster, Julie M; Marcucci, Guido; Bloomfield, Clara D; Mrózek, Krzysztof; Kohlschmidt, Jessica; Stock, Wendy; Kornblau, Steven M; Konopleva, Marina; Paietta, Elisabeth; Rowe, Jacob M; Luger, Selina M; Tallman, Martin S; Dean, Michael; Burchard, Esteban G; Torgerson, Dara G; Yue, Feng; Wang, Yanli; Pui, Ching-Hon; Jeha, Sima; Relling, Mary V; Evans, William E; Gerhard, Daniela S; Loh, Mignon L; Willman, Cheryl L; Hunger, Stephen P; Mullighan, Charles G; Yang, Jun J

    2015-01-22

    Acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYA) is characterized by distinct presenting features and inferior prognosis compared with pediatric ALL. We performed a genome-wide association study (GWAS) to comprehensively identify inherited genetic variants associated with susceptibility to AYA ALL. In the discovery GWAS, we compared genotype frequency at 635 297 single nucleotide polymorphisms (SNPs) in 308 AYA ALL cases and 6,661 non-ALL controls by using a logistic regression model with genetic ancestry as a covariate. SNPs that reached P ≤ 5 × 10(-8) in GWAS were tested in an independent cohort of 162 AYA ALL cases and 5,755 non-ALL controls. We identified a single genome-wide significant susceptibility locus in GATA3: rs3824662, odds ratio (OR), 1.77 (P = 2.8 × 10(-10)) and rs3781093, OR, 1.73 (P = 3.2 × 10(-9)). These findings were validated in the replication cohort. The risk allele at rs3824662 was most frequent in Philadelphia chromosome (Ph)-like ALL but also conferred susceptibility to non-Ph-like ALL in AYAs. In 1,827 non-selected ALL cases, the risk allele frequency at this SNP was positively correlated with age at diagnosis (P = 6.29 × 10(-11)). Our results from this first GWAS of AYA ALL susceptibility point to unique biology underlying leukemogenesis and potentially distinct disease etiology by age group.

  5. Adaptive Memory: Survival Processing Increases Both True and False Memory in Adults and Children

    ERIC Educational Resources Information Center

    Otgaar, Henry; Smeets, Tom

    2010-01-01

    Research has shown that processing information in a survival context can enhance the information's memorability. The current study examined whether survival processing can also decrease the susceptibility to false memories and whether the survival advantage can be found in children. In Experiment 1, adults rated semantically related words in a…

  6. Adaptive Memory: Survival Processing Increases Both True and False Memory in Adults and Children

    ERIC Educational Resources Information Center

    Otgaar, Henry; Smeets, Tom

    2010-01-01

    Research has shown that processing information in a survival context can enhance the information's memorability. The current study examined whether survival processing can also decrease the susceptibility to false memories and whether the survival advantage can be found in children. In Experiment 1, adults rated semantically related words in a…

  7. Chronic social defeat stress increases dopamine D2 receptor dimerization in the prefrontal cortex of adult mice.

    PubMed

    Bagalkot, T R; Jin, H-M; Prabhu, V V; Muna, S S; Cui, Y; Yadav, B K; Chae, H-J; Chung, Y-C

    2015-12-17

    The present study aimed to examine the effects of chronic social defeat stress on the dopamine receptors and proteins involved in post-endocytic trafficking pathways. Adult mice were divided into susceptible and unsusceptible groups after 10 days of social defeat stress. Western blot analysis was used to measure the protein expression levels of dopamine D2 receptors (D2Rs), a short (D2S) and a long form (D2L) and, D2R monomers and dimers, dopamine D1 receptors (D1Rs), neuronal calcium sensor-1 (NCS-1) and G protein-coupled receptor-associated sorting protein-1 (GASP-1), and reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the mRNA expression levels of D2S, D2L, D2R monomers and dimers, and D1Rs in different brain areas. We observed increased expression of D2S, D2L and D2Rs dimers in the prefrontal cortex (PFC) of susceptible and/or unsusceptible mice compared with controls. The only significant findings with regard to mRNA expression levels were lower expression of D2S mRNA in the amygdala (AMYG) of susceptible and unsusceptible mice compared with controls. The present study demonstrated that chronic social defeat stress induced increased expression of D2S, D2L, and D2R dimers in the PFC of susceptible and/or unsusceptible mice.

  8. The increase of diabetes mortality burden among Brazilian adults.

    PubMed

    Barreto, Sandhi Maria; Passos, Valeria Maria Azeredo; Almeida, Suzanne Kelly Ferreira; Assis, Tiago Duarte

    2007-10-01

    To estimate diabetes-related deaths among Brazilian adults between 1999 and 2003 and to investigate demographic factors associated with reporting diabetes as an associated cause of death. All deaths with diabetes as the underlying or associated cause were identified using the Brazilian Mortality Data System. Analysis was performed by sex, age, year, state of residence, and place of death. Mortality rates were age standardized by the 2000 Brazilian population. A total of 237 946 deaths (8.8%) were related to diabetes; in 4.2% of deaths it was the underlying cause and in 4.6% it was an associated cause. Between 1999 and 2003, age-standardized mortality rates for diabetes as the underlying cause increased 14% among males and 9% among females, while mortality with diabetes as an associated cause increased 22% and 28%, respectively. Diabetes appeared more often as an associated cause in death certificates among older individuals and in those residing in São Paulo State; it appeared less often as an associated cause among women, brown- and black-skinned populations, and in deaths occurring outside hospitals. Cardiovascular diseases accounted for 54.5% of the underlying causes of death when diabetes was an associated cause. Diabetes was related to almost 9% of the deaths in the South and Southeast regions of Brazil. Mortality from diabetes is increasing, especially deaths with diabetes as an associated cause. The probability of having diabetes as the underlying cause of death is greater among women and nonwhite individuals. Our results reinforce the importance of using multiple causes of death to monitor diabetes, because half the individuals with the disease will die of another cause, especially cardiovascular diseases.

  9. Dividing Attention Lowers Children's but Increases Adults' False Memories

    ERIC Educational Resources Information Center

    Otgaar, Henry; Peters, Maarten; Howe, Mark L.

    2012-01-01

    The present study examined the impact of divided attention on children's and adults' neutral and negative true and false memories in a standard Deese/Roediger-McDermott paradigm. Children (7- and 11-year-olds; n = 126) and adults (n = 52) received 5 neutral and 5 negative Deese/Roediger-McDermott word lists; half of each group also received a…

  10. Educating Older Adults about Their Increased Cancer Risk.

    ERIC Educational Resources Information Center

    Keintz, Martha K.; And Others

    1988-01-01

    The Cancer Program for Older Citizens is a program to improve the outcome of a possible cancer diagnosis for older adults by encouraging early detection of cancer. Program has achieved positive, though modest, changes in the cancer-related knowledge and beliefs of older adult participants, with these impacts sustained for months after the program.…

  11. Dividing Attention Lowers Children's but Increases Adults' False Memories

    ERIC Educational Resources Information Center

    Otgaar, Henry; Peters, Maarten; Howe, Mark L.

    2012-01-01

    The present study examined the impact of divided attention on children's and adults' neutral and negative true and false memories in a standard Deese/Roediger-McDermott paradigm. Children (7- and 11-year-olds; n = 126) and adults (n = 52) received 5 neutral and 5 negative Deese/Roediger-McDermott word lists; half of each group also received a…

  12. Bombay phenotype is associated with reduced plasma-VWF levels and an increased susceptibility to ADAMTS13 proteolysis.

    PubMed

    O'Donnell, James S; McKinnon, Thomas A J; Crawley, James T B; Lane, David A; Laffan, Michael A

    2005-09-15

    ABO blood group is an important determinant of plasma von Willebrand factor antigen (VWF:Ag) levels, with lower levels in group O. Previous reports have suggested that ABO(H) sugars affect the susceptibility of VWF to ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type-1 repeats-13) cleavage. To further test this hypothesis, we collected plasma from individuals with the rare Bombay blood group. VWF:Ag levels were significantly lower in Bombay patients (median, 0.69 IU/mL) than in groups AB, A, or B (P < .05) and lower than in group O individuals (median, 0.82 IU/mL). Susceptibility of purified VWF fractions to recombinant ADAMTS13 cleavage, assessed using VWF collagen-binding assay (VWF:CB), was increased in Bombays compared with either group O or AB. Increasing urea concentration (0.5 to 2 M) increased the cleavage rate for each blood group but eliminated the differences between groups. We conclude that reduction in the number of terminal sugars on N-linked glycan increases susceptibility of globular VWF to ADAMTS13 proteolysis and is associated with reduced plasma VWF:Ag and VWF:CB levels.

  13. Mitochondrial DNA common deletion increases susceptibility to noise-induced hearing loss in a mimetic aging rat model.

    PubMed

    Yu, Jintao; Wang, Yanjun; Liu, Peng; Li, Qingyu; Sun, Yu; Kong, Weijia

    2014-10-24

    Noise-induced hearing loss (NIHL) is an important occupational health hazard. However, susceptibility to NIHL remains poorly understood. The present study was designed to investigate whether mitochondrial DNA common deletion (CD) increases the susceptibility of individuals to NIHL. A mimetic aging rat model harboring increased CD in the inner ear was established by chronic d-galactose administration, and the synergic effect of CD and noise on hearing sensitivity was assessed. We determined that although developed the same magnitude of temporary threshold shifts and hair cell loss, the d-galactose treated rats with increased CD in the inner ear exhibited a longer hearing recovery process and experienced higher permanent hearing threshold shifts at high frequencies than the saline-treated control rats. Greater supporting cell damage and stria vascularis ultrastructural changes were observed in d-galactose treated rats three weeks after recovery. The results suggested that the elevated CD in the inner ear could increase an individual's susceptibility to NIHL, which likely through a reduction in the self-repairing capability within the cochlea after acoustic injury.

  14. Exposure to the Paralytic Shellfish Toxin Producer Alexandrium catenella Increases the Susceptibility of the Oyster Crassostrea gigas to Pathogenic Vibrios

    PubMed Central

    Abi-Khalil, Celina; Lopez-Joven, Carmen; Abadie, Eric; Savar, Veronique; Amzil, Zouher; Laabir, Mohamed; Rolland, Jean-Luc

    2016-01-01

    The multifactorial etiology of massive Crassostrea gigas summer mortalities results from complex interactions between oysters, opportunistic pathogens and environmental factors. In a field survey conducted in 2014 in the Mediterranean Thau Lagoon (France), we evidenced that the development of the toxic dinoflagellate Alexandrium catenella, which produces paralytic shellfish toxins (PSTs), was concomitant with the accumulation of PSTs in oyster flesh and the occurrence of C. gigas mortalities. In order to investigate the possible role of toxic algae in this complex disease, we experimentally infected C. gigas oyster juveniles with Vibrio tasmaniensis strain LGP32, a strain associated with oyster summer mortalities, after oysters were exposed to Alexandrium catenella. Exposure of oysters to A. catenella significantly increased the susceptibility of oysters to V. tasmaniensis LGP32. On the contrary, exposure to the non-toxic dinoflagellate Alexandrium tamarense or to the haptophyte Tisochrysis lutea used as a foraging alga did not increase susceptibility to V. tasmaniensis LGP32. This study shows for the first time that A. catenella increases the susceptibility of Crassostrea gigas to pathogenic vibrios. Therefore, in addition to complex environmental factors explaining the mass mortalities of bivalve mollusks, feeding on neurotoxic dinoflagellates should now be considered as an environmental factor that potentially increases the severity of oyster mortality events. PMID:26784228

  15. Apoplastic Nucleoside Accumulation in Arabidopsis Leads to Reduced Photosynthetic Performance and Increased Susceptibility Against Botrytis cinerea

    PubMed Central

    Daumann, Manuel; Fischer, Marietta; Niopek-Witz, Sandra; Girke, Christopher; Möhlmann, Torsten

    2015-01-01

    Interactions between plant and pathogen often occur in the extracellular space and especially nucleotides like ATP and NAD have been identified as key players in this scenario. Arabidopsis mutants accumulating nucleosides in the extracellular space were generated and studied with respect to susceptibility against Botrytis cinerea infection and general plant fitness determined as photosynthetic performance. The mutants used are deficient in the main nucleoside uptake system ENT3 and the extracellular nucleoside hydrolase NSH3. When grown on soil but not in hydroponic culture, these plants markedly accumulate adenosine and uridine in leaves. This nucleoside accumulation was accompanied by reduced photosystem II efficiency and altered expression of photosynthesis related genes. Moreover, a higher susceptibility toward Botrytis cinerea infection and a reduced induction of pathogen related genes PR1 and WRKY33 was observed. All these effects did not occur in hydroponically grown plants substantiating a contribution of extracellular nucleosides to these effects. Whether reduced general plant fitness, altered pathogen response capability or more direct interactions with the pathogen are responsible for these observations is discussed. PMID:26779190

  16. Abrupt suspension of probiotics administration may increase host pathogen susceptibility by inducing gut dysbiosis

    PubMed Central

    Liu, Zhi; Liu, Wenshu; Ran, Chao; Hu, Jun; Zhou, Zhigang

    2016-01-01

    In this study, we investigated the risk associated with suspension of probiotics administration in tilapia, an animal model that may mimic immune-compromised conditions in humans. Tilapias were fed for 14 days using a probiotics-supplemented diet, followed by a three-day suspension of probiotics treatment and a subsequent challenge by Aeromonas hydrophila. Unexpectedly, the suspension of a probiotic strain Lactobacillus plantarum JCM1149 significantly triggered susceptibility of the host to A. hydrophila. We further observed that suspension of JCM1149 resulted in host gut microbiota dysbiosis and the subsequent disorder in the intestinal metabolites (bile acids, amino acids, and glucose) and damage in the intestinal epithelium, giving rise to a condition similar to antibiotics-induced gut dysbiosis, which collectively impaired tilapia’s gut health and resistance to pathogenic challenges. Additionally, we determined that JCM1149 adhered relatively poorly to tilapia intestinal mucosa and was rapidly released from the gastrointestinal tract (GIT) after suspension, with the rapid loss of probiotic strain probably being the direct cause of gut dysbiosis. Finally, three other probiotic Lactobacillus strains with low intestinal mucosa binding activity showed similar rapid loss phenotype following administration suspension, and induced higher host susceptibility to infection, indicating that the risk is a generic phenomenon in Lactobacillus. PMID:26983596

  17. Antimicrobial susceptibility testing for Helicobacter pylori in times of increasing antibiotic resistance.

    PubMed

    Smith, Sinéad M; O'Morain, Colm; McNamara, Deirdre

    2014-08-07

    The gram-negative bacterium Helicobacter pylori (H. pylori) causes chronic gastritis, gastric and duodenal ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma. Treatment is recommended in all symptomatic patients. The current treatment options for H. pylori infection are outlined in this review in light of the recent challenges in eradication success, largely due to the rapid emergence of antibiotic resistant strains of H. pylori. Antibiotic resistance is a constantly evolving process and numerous studies have shown that the prevalence of H. pylori antibiotic resistance varies significantly from country to country, and even between regions within the same country. In addition, recent data has shown that previous antibiotic use is associated with harbouring antibiotic resistant H. pylori. Local surveillance of antibiotic resistance is warranted to guide clinicians in their choice of therapy. Antimicrobial resistance is assessed by H. pylori culture and antimicrobial susceptibility testing. Recently developed molecular tests offer an attractive alternative to culture and allow for the rapid molecular genetic identification of H. pylori and resistance-associated mutations directly from biopsy samples or bacterial culture material. Accumulating evidence indicates that surveillance of antimicrobial resistance by susceptibility testing is feasible and necessary to inform clinicians in their choice of therapy for management of H. pylori infection.

  18. Growth in microgravity increases susceptibility of soybean to a fungal pathogen

    NASA Technical Reports Server (NTRS)

    Ryba-White, M.; Nedukha, O.; Hilaire, E.; Guikema, J. A.; Kordyum, E.; Leach, J. E.; Spooner, B. S. (Principal Investigator)

    2001-01-01

    The influence of microgravity on the susceptibility of soybean roots to Phytophthora sojae was studied during the Space Shuttle Mission STS-87. Seedlings of soybean cultivar Williams 82 grown in spaceflight or at unit gravity were untreated or inoculated with the soybean root rot pathogen P. sojae. At 3, 6 and 7 d after launch while still in microgravity, seedlings were photographed and then fixed for subsequent microscopic analysis. Post-landing analysis of the seedlings revealed that at harvest day 7 the length of untreated roots did not differ between flight and ground samples. However, the flight-grown roots infected with P. sojae showed more disease symptoms (percentage of brown and macerated areas) and the root tissues were more extensively colonized relative to the ground controls exposed to the fungus. Ethylene levels were higher in spaceflight when compared to ground samples. These data suggest that soybean seedlings grown in microgravity are more susceptible to colonization by a fungal pathogen relative to ground controls.

  19. Abrupt suspension of probiotics administration may increase host pathogen susceptibility by inducing gut dysbiosis.

    PubMed

    Liu, Zhi; Liu, Wenshu; Ran, Chao; Hu, Jun; Zhou, Zhigang

    2016-03-17

    In this study, we investigated the risk associated with suspension of probiotics administration in tilapia, an animal model that may mimic immune-compromised conditions in humans. Tilapias were fed for 14 days using a probiotics-supplemented diet, followed by a three-day suspension of probiotics treatment and a subsequent challenge by Aeromonas hydrophila. Unexpectedly, the suspension of a probiotic strain Lactobacillus plantarum JCM1149 significantly triggered susceptibility of the host to A. hydrophila. We further observed that suspension of JCM1149 resulted in host gut microbiota dysbiosis and the subsequent disorder in the intestinal metabolites (bile acids, amino acids, and glucose) and damage in the intestinal epithelium, giving rise to a condition similar to antibiotics-induced gut dysbiosis, which collectively impaired tilapia's gut health and resistance to pathogenic challenges. Additionally, we determined that JCM1149 adhered relatively poorly to tilapia intestinal mucosa and was rapidly released from the gastrointestinal tract (GIT) after suspension, with the rapid loss of probiotic strain probably being the direct cause of gut dysbiosis. Finally, three other probiotic Lactobacillus strains with low intestinal mucosa binding activity showed similar rapid loss phenotype following administration suspension, and induced higher host susceptibility to infection, indicating that the risk is a generic phenomenon in Lactobacillus.

  20. Growth in microgravity increases susceptibility of soybean to a fungal pathogen

    NASA Technical Reports Server (NTRS)

    Ryba-White, M.; Nedukha, O.; Hilaire, E.; Guikema, J. A.; Kordyum, E.; Leach, J. E.; Spooner, B. S. (Principal Investigator)

    2001-01-01

    The influence of microgravity on the susceptibility of soybean roots to Phytophthora sojae was studied during the Space Shuttle Mission STS-87. Seedlings of soybean cultivar Williams 82 grown in spaceflight or at unit gravity were untreated or inoculated with the soybean root rot pathogen P. sojae. At 3, 6 and 7 d after launch while still in microgravity, seedlings were photographed and then fixed for subsequent microscopic analysis. Post-landing analysis of the seedlings revealed that at harvest day 7 the length of untreated roots did not differ between flight and ground samples. However, the flight-grown roots infected with P. sojae showed more disease symptoms (percentage of brown and macerated areas) and the root tissues were more extensively colonized relative to the ground controls exposed to the fungus. Ethylene levels were higher in spaceflight when compared to ground samples. These data suggest that soybean seedlings grown in microgravity are more susceptible to colonization by a fungal pathogen relative to ground controls.

  1. Adaptive memory: Survival processing increases both true and false memory in adults and children.

    PubMed

    Otgaar, Henry; Smeets, Tom

    2010-07-01

    Research has shown that processing information in a survival context can enhance the information's memorability. The current study examined whether survival processing can also decrease the susceptibility to false memories and whether the survival advantage can be found in children. In Experiment 1, adults rated semantically related words in a survival, moving, or pleasantness scenario. Even though the survival advantage was demonstrated for true recall, there also was an unexpected increase in false memories in the survival condition. Similarly, younger and older children in Experiment 2 displayed superior true recall but also higher rates of false memories in a survival condition. Experiment 3 showed that in adults false memories were also more likely to occur in the survival condition when categorized lists instead of Deese-Roediger-McDermott (DRM)-like word lists were used. In all three experiments, no survival recall advantage was found when net accuracy scores that take the total output into account were used. These findings question whether survival processing is an adaptive memory strategy per se, as such processing not only enriches true recall but simultaneously amplifies the vulnerability to false memories.

  2. Baseline Susceptibility and Cross-Resistance in Adult and Larval Alphitobius diaperinus (Coleoptera: Tenebrionidae) Collected from Poultry Farms in Arkansas.

    PubMed

    Singh, Narinderpal; Johnson, Donn

    2015-08-01

    Insecticide resistance in the lesser mealworm, Alphitobius diaperinus (Panzer) (Coleoptera: Tenebrionidae), can pose a serious threat to their successful management in broiler chicken farms in Arkansas. Resistance and cross-resistance were determined in lesser mealworm populations collected from two broiler farms in Arkansas, with different insecticide application histories. Farm M was treated with insecticides over the past 10 yr, whereas Farm S had no insecticidal usage history. Concentration-mortality bioassays using selected insecticides were conducted on adults and seventh-instar larval beetles. A probit analysis suggested the M population to be resistant to cyfluthrin and tetrachlorvinphos, while the S population was susceptible to both compounds. The M population showed no cross-resistance to imidacloprid, spinosad, or chlorfenapyr. The M and S populations were similar in their susceptibility to imidacloprid, spinosad, and chlorfenapyr. The suitability of imidacloprid and spinosad, and further testing of chlorfenapyr as a potential candidate for lesser mealworm control is discussed.

  3. Serotype Distribution and Antimicrobial Susceptibilities of Invasive Streptococcus pneumoniae Isolates from Adults in Korea from 1997 to 2012.

    PubMed

    Kim, Chung Jong; Song, Jin-Su; Choi, Su-Jin; Song, Kyoung Ho; Choe, Pyeong Gyun; Park, Wan Beom; Bang, Ji Hwan; Kim, Eu Suk; Park, Sang Won; Kim, Hong Bin; Kim, Nam-Joong; Kim, Eui-Chong; Oh, Myoung-don

    2016-05-01

    In Republic of Korea, a 7-valent pneumococcal conjugated vaccine (PCV7) was licensed for use in infants in 2003, and 13-valent PCV (PCV13) replaced it since 2010. We investigated trends in serotype distribution and antibiotic susceptibility of pneumococcal isolates from adult patients with invasive pneumococcal diseases (IPD). Invasive pneumococcal isolates from adult patients of ≥ 16 years of age were collected from 1997 to 2012. Serotypes of the isolates were determined by the Quellung reaction. Distribution of serotypes was analyzed according to the vaccine types. Antibiotic susceptibility was tested by using E-test strips. A total of 272 invasive pneumococcal isolates were included. The most common serotypes were serotype 19F (8.5%, 23/272), and serotype 3 (8.1%, 22/272), and 24.6% (67/272) of the isolates were of non-vaccine serotypes. Of the 272 isolates, 2.6% (7/272) were penicillin MICs of ≥ 4 µg/mL. The proportion of the PCV13 serotypes decreased from 63.3% (50/79) in 1997-2003 to 48.6% (17/35) in 2011-2012, whereas that of non-vaccine serotypes was 26.6% (21/79) and 25.7% (9/35), respectively, for the same periods. The proportion of the PCV13 serotypes showed a decreasing trend among adult patients with IPD over the study period.

  4. INCREASED LEVELS OF SUPEROXIDE AND HYDROGEN PEROXIDE MEDIATE THE DIFFERENTIAL SUSCEPTIBILITY OF CANCER CELLS VS. NORMAL CELLS TO GLUCOSE DEPRIVATION

    PubMed Central

    Aykin-Burns, Nùkhet; Ahmad, Iman M.; Zhu, Yueming; Oberley, Larry W.; Spitz, Douglas R.

    2009-01-01

    Cancer cells, relative to normal cells, demonstrate increased sensitivity to glucose deprivation-induced cytotoxicity. To determine if oxidative stress mediated by O2•− and hydroperoxides contributed to the differential susceptibility of human epithelial cancer cells to glucose deprivation, oxidation of dihydroethidine (DHE; for O2•−) and 5-(and-6)-carboxy-2', 7'-dichlorodihydrofluorescein diacetate (CDCFH2; for hydroperoxides) were measured in human colon and breast cancer cells (HT29, HCT116, SW480, MB231) and compared to normal human cells (FHC, 33Co, HMEC). Cancer cells showed significant increases in DHE (2–20 fold) and CDCFH2 (1.8–10 fold) oxidation, relative to normal cells that were more pronounced in the presence of the mitochondrial electron transport chain blocker, antimycin A. Furthermore, HCT116 and MB231 cells were more susceptible to glucose deprivation-induced cytotoxicity and oxidative stress, relative to 33Co and HMEC. HT-29 cells were also more susceptible to 2-deoxyglucose-(2DG)-induced cytotoxicity, relative to FHC. Over expression of manganese superoxide dismutase and mitochondrially targeted catalase significantly protected HCT116 and MB231 cells from glucose deprivation-induced cytotoxicity and oxidative stress, as well as protecting HT-29 cells from 2DG-induced cytotoxicity. These results show cancer cells (relative to normal cells) demonstrate increased steady-state levels of reactive oxygen species (ROS, i.e. O2•− and H2O2) that contribute to differential susceptibility to glucose deprivation-induced cytotoxicity and oxidative stress. These studies support the hypotheses that cancer cells increase glucose metabolism to compensate for excess metabolic production of ROS as well as that inhibition of glucose and hydroperoxide metabolism may provide a biochemical target for selectively enhancing cytotoxicity and oxidative stress in human cancer cells. PMID:18937644

  5. Increased Prevalence of Sleep-Disordered Breathing in Adults

    PubMed Central

    Peppard, Paul E.; Young, Terry; Barnet, Jodi H.; Palta, Mari; Hagen, Erika W.; Hla, Khin Mae

    2013-01-01

    Sleep-disordered breathing is a common disorder with a range of harmful sequelae. Obesity is a strong causal factor for sleep-disordered breathing, and because of the ongoing obesity epidemic, previous estimates of sleep-disordered breathing prevalence require updating. We estimated the prevalence of sleep-disordered breathing in the United States for the periods of 1988–1994 and 2007–2010 using data from the Wisconsin Sleep Cohort Study, an ongoing community-based study that was established in 1988 with participants randomly selected from an employed population of Wisconsin adults. A total of 1,520 participants who were 30–70 years of age had baseline polysomnography studies to assess the presence of sleep-disordered breathing. Participants were invited for repeat studies at 4-year intervals. The prevalence of sleep-disordered breathing was modeled as a function of age, sex, and body mass index, and estimates were extrapolated to US body mass index distributions estimated using data from the National Health and Nutrition Examination Survey. The current prevalence estimates of moderate to severe sleep-disordered breathing (apnea-hypopnea index, measured as events/hour, ≥15) are 10% (95% confidence interval (CI): 7, 12) among 30–49-year-old men; 17% (95% CI: 15, 21) among 50–70-year-old men; 3% (95% CI: 2, 4) among 30–49-year-old women; and 9% (95% CI: 7, 11) among 50–70 year-old women. These estimated prevalence rates represent substantial increases over the last 2 decades (relative increases of between 14% and 55% depending on the subgroup). PMID:23589584

  6. Atorvastatin Increases Exercise Leg Blood Flow in Healthy Adults

    PubMed Central

    Parker, Beth A.; Capizzi, Jeffrey A.; Augeri, Amanda L.; Grimaldi, Adam S.; White, C. Michael; Thompson, Paul D.

    2011-01-01

    OBJECTIVES We sought to examine the effect of atorvastatin therapy on exercise leg blood flow in healthy middle-aged and older, men and women. BACKGROUND The vasodilatory response to exercise decreases in humans with aging and disease and this reduction may contribute to reduced exercise capacity. METHODS We used a double-blind, randomly assigned, placebo-controlled protocol to assess the effect of atorvastatin treatment on exercising leg hemodynamics. We measured femoral artery blood flow (FBF) using Doppler ultrasound and calculated femoral vascular conductance (FVC) from brachial mean arterial pressure (MAP) before and during single knee-extensor exercise in healthy adults (ages 40–71) before (PRE) and after (POST) 6 months of 80 mg atorvastatin (A: 14 men, 16 women) or placebo (P: 14 men, 22 women) treatment. FBF and FVC were normalized to exercise power output and estimated quadriceps muscle mass. RESULTS Atorvastatin reduced LDL cholesterol by approximately 50%, but not in the placebo group (p < 0.01). Atorvastatin also increased exercise FBF from 44.2 ± 19.0 to 51.4 ± 22.0 mL/min/W/kg muscle whereas FBF in the placebo group was unchanged (40.1 ± 16.0 vs 39.5 ± 16.1) (p <0.01). FVC also increased with atorvastatin from 0.5 ± 0.2 to. 0.6 ± 0.2 mL/min/mmHg/W/kg muscle, but not in the placebo subjects (P: 0.4 ± 0.2 vs 0.4 ± 0.2) ( p < 0.01). CONCLUSIONS High-dose atorvastatin augments exercising leg hyperemia. Statins may mitigate reductions in the exercise vasodilatory response in humans that are associated with aging and disease. PMID:22018642

  7. Paraplegia increased cardiac NGF content, sympathetic tonus, and the susceptibility to ischemia-induced ventricular tachycardia in conscious rats

    PubMed Central

    Lujan, Heidi L.; Chen, Ying; DiCarlo, Stephen E.

    2009-01-01

    Midthoracic spinal cord injury is associated with ventricular arrhythmias that are mediated, in part, by enhanced cardiac sympathetic activity. Furthermore, it is well known that sympathetic neurons have a lifelong requirement for nerve growth factor (NGF). NGF is a neurotrophin that supports the survival and differentiation of sympathetic neurons and enhances target innervation. Therefore, we tested the hypothesis that paraplegia is associated with an increased cardiac NGF content, sympathetic tonus, and susceptibility to ischemia-induced ventricular tachyarrhythmias. Intact and paraplegic (6–9 wk posttransection, T5 spinal cord transection) rats were instrumented with a radiotelemetry device for recording arterial pressure, temperature, and ECG, and a snare was placed around the left main coronary artery. Following recovery, the susceptibility to ventricular arrhythmias (coronary artery occlusion) was determined in intact and paraplegic rats. In additional groups of matched intact and paraplegic rats, cardiac nerve growth factor content (ELISA) and cardiac sympathetic tonus were determined. Paraplegia, compared with intact, increased cardiac nerve growth factor content (2,146 ± 286 vs. 180 ± 36 pg/ml, P < 0.05) and cardiac sympathetic tonus (154 ± 4 vs. 68 ± 4 beats/min, P < 0.05) and decreased the ventricular arrhythmia threshold (3.6 ± 0.2 vs. 4.9 ± 0.2 min, P < 0.05). Thus altered autonomic behavior increases the susceptibility to ventricular arrhythmias in paraplegic rats. PMID:19286942

  8. Propofol Increases Host Susceptibility to Microbial Infection by Reducing Subpopulations of Mature Immune Effector Cells at Sites of Infection

    PubMed Central

    Visvabharathy, Lavanya; Xayarath, Bobbi; Weinberg, Guy; Shilling, Rebecca A.; Freitag, Nancy E.

    2015-01-01

    Anesthetics are known to modulate host immune responses, but separating the variables of surgery from anesthesia when analyzing hospital acquired infections is often difficult. Here, the bacterial pathogen Listeria monocytogenes (Lm) was used to assess the impact of the common anesthetic propofol on host susceptibility to infection. Brief sedation of mice with physiologically relevant concentrations of propofol increased bacterial burdens in target organs by more than 10,000-fold relative to infected control animals. The adverse effects of propofol sedation on immune clearance of Lm persisted after recovery from sedation, as animals given the drug remained susceptible to infection for days following anesthesia. In contrast to propofol, sedation with alternative anesthetics such as ketamine/xylazine or pentobarbital did not increase susceptibility to systemic Lm infection. Propofol altered systemic cytokine and chemokine expression during infection, and prevented effective bacterial clearance by inhibiting the recruitment and/or activity of immune effector cells at sites of infection. Propofol exposure induced a marked reduction in marginal zone macrophages in the spleens of Lm infected mice, resulting in bacterial dissemination into deep tissue. Propofol also significantly increased mouse kidney abscess formation following infection with the common nosocomial pathogen Staphylococcus aureus. Taken together, these data indicate that even brief exposure to propofol severely compromises host resistance to microbial infection for days after recovery from sedation. PMID:26381144

  9. Enhanced cardiac perception is associated with increased susceptibility to framing effects.

    PubMed

    Sütterlin, Stefan; Schulz, Stefan M; Stumpf, Theresa; Pauli, Paul; Vögele, Claus

    2013-07-01

    Previous studies suggest in line with dual process models that interoceptive skills affect controlled decisions via automatic or implicit processing. The "framing effect" is considered to capture implicit effects of task-irrelevant emotional stimuli on decision-making. We hypothesized that cardiac awareness, as a measure of interoceptive skills, is positively associated with susceptibility to the framing effect. Forty volunteers performed a risky-choice framing task in which the effect of loss versus gain frames on decisions based on identical information was assessed. The results show a positive association between cardiac awareness and the framing effect, accounting for 24% of the variance in the framing effect. These findings demonstrate that good interoceptive skills are linked to poorer performance in risky choices based on ambivalent information when implicit bias is induced by task-irrelevant emotional information. These findings support a dual process perspective on decision-making and suggest that interoceptive skills mediate effects of implicit bias on decisions.

  10. The interaction of BDNF and NTRK2 gene increases the susceptibility of paranoid schizophrenia.

    PubMed

    Lin, Zheng; Su, Yousong; Zhang, Chengfang; Xing, Mengjuan; Ding, Wenhua; Liao, Liwei; Guan, Yangtai; Li, Zezhi; Cui, Donghong

    2013-01-01

    The association between BDNF gene functional Val66Met polymorphism rs6265 and the schizophrenia is far from being consistent. In addition to the heterogeneous in schizophrenia per se leading to the inconsistent results, the interaction among multi-genes is probably playing the main role in the pathogenesis of schizophrenia, but not a single gene. Neurotrophic tyrosine kinase receptor 2 (NTRK2) is the high-affinity receptor of BDNF, and was reported to be associated with mood disorders, though no literature reported the association with schizophrenia. Thus, in the present study, total 402 patients with paranoid schizophrenia (the most common subtype of schizophrenia) and matched 406 healthy controls were recruited to investigate the role of rs6265 in BDNF, three polymorphisms in NTRK2 gene (rs1387923, rs2769605 and rs1565445) and their interaction in the susceptibility to paranoid schizophrenia in a Chinese Han population. We did not observe significant differences in allele and genotype frequencies between patients and healthy controls for all four polymorphisms separately. The haplotype analysis also showed no association between haplotype of NTRK2 genes (rs1387923, rs2769605, and rs1565445) and paranoid schizophrenia. However, we found the association between the interaction of BDNF and NTRK2 with paranoid schizophrenia by using the MDR method followed by conventional statistical analysis. The best gene-gene interaction model was a three-locus model (BDNF rs6265, NTRK2 rs1387923 and NTRK2 rs2769605), in which one low-risk and three high-risk four-locus genotype combinations were identified. Our findings implied that single polymorphism of rs6265 rs1387923, rs2769605, and rs1565445 in BDNF and NTRK2 were not associated with the development of paranoid schizophrenia in a Han population, however, the interaction of BDNF and NTRK2 genes polymorphisms (BDNF-rs6265, NTRK2-rs1387923 and NTRK2-rs2769605) may be involved in the susceptibility to paranoid schizophrenia.

  11. Increasing Access to Postsecondary Education for Adults in Rural Appalachia.

    ERIC Educational Resources Information Center

    Sullins, W. Robert; And Others

    1987-01-01

    Reports on a study of the barriers to adult participation in postsecondary education in the Appalachian regions of six southern states. Discusses policy-related, dispositional, situational, and institutional barriers to enrollment, and offers recommendations for reducing the obstacles. (DMM)

  12. Increasing Access to Postsecondary Education for Adults in Rural Appalachia.

    ERIC Educational Resources Information Center

    Sullins, W. Robert; And Others

    1987-01-01

    Reports on a study of the barriers to adult participation in postsecondary education in the Appalachian regions of six southern states. Discusses policy-related, dispositional, situational, and institutional barriers to enrollment, and offers recommendations for reducing the obstacles. (DMM)

  13. Susceptibility of adult and senescent Brown Norway rats to repeated ozone exposure: an assessment of behavior, serum biochemistry and cardiopulmonary function.

    PubMed

    Gordon, C J; Jarema, K A; Lehmann, J R; Ledbetter, A D; Schladweiler, M C; Schmid, J E; Ward, W O; Kodavanti, U P; Nyska, A; MacPhail, R C

    2013-02-01

    Ozone (O₃) is a pervasive air pollutant that produces pulmonary and cardiovascular dysfunction and possible neurological dysfunction. Young and old individuals are recognized as being susceptible to O₃; however, remarkably little is known about susceptibility with senescence. This study explored the pulmonary, cardiovascular and neurological effects of O₃ exposure in adult (4 m) and senescent (20 m) Brown Norway rats exposed to 0 or 0.8 ppm O₃ for 6 h, 1 d/week, for 17 weeks. Ventilatory function was assessed 1 and 7 d after each exposure (Buxco). Heart rate, blood pressure (tail cuff) and motor activity were measured biweekly. Blood, aorta and bronchoalveolar lavage fluid (BALF) were analyzed 24 h after the last exposure for pulmonary inflammation, serum biomarkers and aorta mRNA markers of vascular disease. Measures of normal ventilatory function declined following each O₃ exposure in both adult and senescent rats, however, senescent rats took weeks to exhibit a decline. Evidence for residual respiratory effects of O₃ 7 d after exposure in both age groups was observed. O₃ had no effect on either heart rate or blood pressure, but decreased motor activity in both age groups. BALF indicated mild neutrophilic inflammation and protein leakage in adults. Age affected 17/58 serum analytes, O₃ affected 6/58; 2/58 showed an age-O₃ interaction. Leptin, adiponectin, lipocalin and insulin were increased in senescent rats. Overall, adult rats exhibited more immediate effects of episodic O₃ than senescent rats. Residual effects were, however, obtained in both ages of rat, especially for ventilatory endpoints.

  14. Susceptibility of adult female Aedes aegypti (Diptera: Culicidae) to the entomopathogenic fungus Metarhizium anisopliae is modified following blood feeding.

    PubMed

    Paula, Adriano R; Carolino, Aline T; Silva, Carlos P; Samuels, Richard I

    2011-05-26

    The mosquito Aedes aegypti, vector of dengue fever, is a target for control by entomopathogenic fungi. Recent studies by our group have shown the susceptibility of adult A. aegypti to fungal infection by Metarhizium anisopliae. This fungus is currently being tested under field conditions. However, it is unknown whether blood-fed A. aegypti females are equally susceptible to infection by entomopathogenic fungi as sucrose fed females. Insect populations will be composed of females in a range of nutritional states. The fungus should be equally efficient at reducing survival of insects that rest on fungus impregnated surfaces following a blood meal as those coming into contact with fungi before host feeding. This could be an important factor when considering the behavior of A. aegypti females that can blood feed on multiple hosts over a short time period. Female A. aegypti of the Rockefeller strain and a wild strain were infected with two isolates of the entomopathogenic fungus M. anisopliae (LPP 133 and ESALQ 818) using an indirect contact bioassay at different times following blood feeding. Survival rates were monitored on a daily basis and one-way analysis of variance combined with Duncan's post-hoc test or Log-rank survival curve analysis were used for statistical comparisons of susceptibility to infection. Blood feeding rapidly reduced susceptibility to infection, determined by the difference in survival rates and survival curves, when females were exposed to either of the two M. anisopliae isolates. Following a time lag which probably coincided with digestion of the blood meal (96-120 h post-feeding), host susceptibility to infection returned to pre-blood fed (sucrose fed) levels. Reduced susceptibility of A. aegypti to fungi following a blood meal is of concern. Furthermore, engorged females seeking out intra-domicile resting places post-blood feeding, would be predicted to rest for prolonged periods on fungus impregnated black cloths, thus optimizing infection

  15. GSTT1 Null Genotype Significantly Increases the Susceptibility to Urinary System Cancer: Evidences from 63,876 Subjects.

    PubMed

    Wang, Ying; He, Jing; Ma, Tian-Jiao; Lei, Wei; Li, Feng; Shen, Han; Shen, Zhen-Ya

    2016-01-01

    GSTT1 gene plays an important role in detoxification and clearance of reactive oxygen species(ROS). A null variant in this gene has been demonstrated to confer cancer susceptibility. Although many studies have demonstrated the association between GSTT1 null polymorphism and urinary system cancer susceptibility, several publications reported opposite conclusions. For better understanding the effects of this polymorphism on the risk of urinary system cancer, a updated meta-analysis was performed with a total of 26,666 cases and 37,210 controls extracted from 117 studies, by following the latest meta-analysis guidelines (PRISMA). The results suggested that the GSTT1 null genotype was significantly associated with an increased risk of urinary system cancer (OR=1.13, 95%CI=1.05-1.22). Furthermore, stratified analyses by the type of cancer, ethnicity, source of control and quality score presented a significantly increased risk associated with GSTT1 null genotype in bladder and prostate cancer subgroup, Caucasians and Indians subgroup, population-based(PB) subgroup, medium quality and low quality subgroup. Overall, our meta-analysis suggested that GSTT1 null genotype is a potential cancer susceptibility variant. Well-designed and large-cohort studies are needed to confirm the association between GSTT1 null genotype and urinary system cancer risk.

  16. Intrauterine growth retardation increases the susceptibility of pigs to high-fat diet-induced mitochondrial dysfunction in skeletal muscle.

    PubMed

    Liu, Jingbo; Chen, Daiwen; Yao, Ying; Yu, Bing; Mao, Xiangbing; He, Jun; Huang, Zhiqing; Zheng, Ping

    2012-01-01

    It has been recognized that there is a relationship between prenatal growth restriction and the development of metabolic-related diseases in later life, a process involved in mitochondrial dysfunction. In addition, intrauterine growth retardation (IUGR) increases the susceptibility of offspring to high-fat (HF) diet-induced metabolic syndrome. Recent findings suggested that HF feeding decreased mitochondrial oxidative capacity and impaired mitochondrial function in skeletal muscle. Therefore, we hypothesized that the long-term consequences of IUGR on mitochondrial biogenesis and function make the offspring more susceptible to HF diet-induced mitochondrial dysfunction. Normal birth weight (NBW), and IUGR pigs were allotted to control or HF diet in a completely randomized design, individually. After 4 weeks of feeding, growth performance and molecular pathways related to mitochondrial function were determined. The results showed that IUGR decreased growth performance and plasma insulin concentrations. In offspring fed a HF diet, IUGR was associated with enhanced plasma leptin levels, increased concentrations of triglyceride and malondialdehyde (MDA), and reduced glycogen and ATP contents in skeletal muscle. High fat diet-fed IUGR offspring exhibited decreased activities of lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G6PD). These alterations in metabolic traits of IUGR pigs were accompanied by impaired mitochondrial respiration function, reduced mitochondrial DNA (mtDNA) contents, and down-regulated mRNA expression levels of genes responsible for mitochondrial biogenesis and function. In conclusion, our results suggest that IUGR make the offspring more susceptible to HF diet-induced mitochondrial dysfunction.

  17. Characterization of a JAZ7 activation-tagged Arabidopsis mutant with increased susceptibility to the fungal pathogen Fusarium oxysporum

    PubMed Central

    Thatcher, Louise F.; Cevik, Volkan; Grant, Murray; Zhai, Bing; Jones, Jonathan D.G.; Manners, John M.; Kazan, Kemal

    2016-01-01

    In Arabidopsis, jasmonate (JA)-signaling plays a key role in mediating Fusarium oxysporum disease outcome. However, the roles of JASMONATE ZIM-domain (JAZ) proteins that repress JA-signaling have not been characterized in host resistance or susceptibility to this pathogen. Here, we found most JAZ genes are induced following F. oxysporum challenge, and screening T-DNA insertion lines in Arabidopsis JAZ family members identified a highly disease-susceptible JAZ7 mutant (jaz7-1D). This mutant exhibited constitutive JAZ7 expression and conferred increased JA-sensitivity, suggesting activation of JA-signaling. Unlike jaz7 loss-of-function alleles, jaz7-1D also had enhanced JA-responsive gene expression, altered development and increased susceptibility to the bacterial pathogen Pst DC3000 that also disrupts host JA-responses. We also demonstrate that JAZ7 interacts with transcription factors functioning as activators (MYC3, MYC4) or repressors (JAM1) of JA-signaling and contains a functional EAR repressor motif mediating transcriptional repression via the co-repressor TOPLESS (TPL). We propose through direct TPL recruitment, in wild-type plants JAZ7 functions as a repressor within the JA-response network and that in jaz7-1D plants, misregulated ectopic JAZ7 expression hyper-activates JA-signaling in part by disturbing finely-tuned COI1-JAZ-TPL-TF complexes. PMID:26896849

  18. GSTT1 Null Genotype Significantly Increases the Susceptibility to Urinary System Cancer: Evidences from 63,876 Subjects

    PubMed Central

    Wang, Ying; He, Jing; Ma, Tian-Jiao; Lei, Wei; Li, Feng; Shen, Han; Shen, Zhen-Ya

    2016-01-01

    GSTT1 gene plays an important role in detoxification and clearance of reactive oxygen species(ROS). A null variant in this gene has been demonstrated to confer cancer susceptibility. Although many studies have demonstrated the association between GSTT1 null polymorphism and urinary system cancer susceptibility, several publications reported opposite conclusions. For better understanding the effects of this polymorphism on the risk of urinary system cancer, a updated meta-analysis was performed with a total of 26,666 cases and 37,210 controls extracted from 117 studies, by following the latest meta-analysis guidelines (PRISMA). The results suggested that the GSTT1 null genotype was significantly associated with an increased risk of urinary system cancer (OR=1.13, 95%CI=1.05-1.22). Furthermore, stratified analyses by the type of cancer, ethnicity, source of control and quality score presented a significantly increased risk associated with GSTT1 null genotype in bladder and prostate cancer subgroup, Caucasians and Indians subgroup, population-based(PB) subgroup, medium quality and low quality subgroup. Overall, our meta-analysis suggested that GSTT1 null genotype is a potential cancer susceptibility variant. Well-designed and large-cohort studies are needed to confirm the association between GSTT1 null genotype and urinary system cancer risk. PMID:27698905

  19. Characterization of a JAZ7 activation-tagged Arabidopsis mutant with increased susceptibility to the fungal pathogen Fusarium oxysporum.

    PubMed

    Thatcher, Louise F; Cevik, Volkan; Grant, Murray; Zhai, Bing; Jones, Jonathan D G; Manners, John M; Kazan, Kemal

    2016-04-01

    In Arabidopsis, jasmonate (JA)-signaling plays a key role in mediating Fusarium oxysporum disease outcome. However, the roles of JASMONATE ZIM-domain (JAZ) proteins that repress JA-signaling have not been characterized in host resistance or susceptibility to this pathogen. Here, we found most JAZ genes are induced following F. oxysporum challenge, and screening T-DNA insertion lines in Arabidopsis JAZ family members identified a highly disease-susceptible JAZ7 mutant (jaz7-1D). This mutant exhibited constitutive JAZ7 expression and conferred increased JA-sensitivity, suggesting activation of JA-signaling. Unlike jaz7 loss-of-function alleles, jaz7-1D also had enhanced JA-responsive gene expression, altered development and increased susceptibility to the bacterial pathogen PstDC3000 that also disrupts host JA-responses. We also demonstrate that JAZ7 interacts with transcription factors functioning as activators (MYC3, MYC4) or repressors (JAM1) of JA-signaling and contains a functional EAR repressor motif mediating transcriptional repression via the co-repressor TOPLESS (TPL). We propose through direct TPL recruitment, in wild-type plants JAZ7 functions as a repressor within the JA-response network and that in jaz7-1D plants, misregulated ectopic JAZ7 expression hyper-activates JA-signaling in part by disturbing finely-tuned COI1-JAZ-TPL-TF complexes.

  20. MDMA decreases glutamic acid decarboxylase (GAD) 67-immunoreactive neurons in the hippocampus and increases seizure susceptibility: Role for glutamate.

    PubMed

    Huff, Courtney L; Morano, Rachel L; Herman, James P; Yamamoto, Bryan K; Gudelsky, Gary A

    2016-12-01

    3,4-Methylenedioxy-methamphetamine (MDMA) is a unique psychostimulant that continues to be a popular drug of abuse. It has been well documented that MDMA reduces markers of 5-HT axon terminals in rodents, as well as humans. A loss of parvalbumin-immunoreactive (IR) interneurons in the hippocampus following MDMA treatment has only been documented recently. In the present study, we tested the hypothesis that MDMA reduces glutamic acid decarboxylase (GAD) 67-IR, another biochemical marker of GABA neurons, in the hippocampus and that this reduction in GAD67-IR neurons and an accompanying increase in seizure susceptibility involve glutamate receptor activation. Repeated exposure to MDMA (3×10mg/kg, ip) resulted in a reduction of 37-58% of GAD67-IR cells in the dentate gyrus (DG), CA1, and CA3 regions, as well as an increased susceptibility to kainic acid-induced seizures, both of which persisted for at least 30days following MDMA treatment. Administration of the NMDA antagonist MK-801 or the glutamate transporter type 1 (GLT-1) inducer ceftriaxone prevented both the MDMA-induced loss of GAD67-IR neurons and the increased vulnerability to kainic acid-induced seizures. The MDMA-induced increase in the extracellular concentration of glutamate in the hippocampus was significantly diminished in rats treated with ceftriaxone, thereby implicating a glutamatergic mechanism in the neuroprotective effects of ceftriaxone. In summary, the present findings support a role for increased extracellular glutamate and NMDA receptor activation in the MDMA-induced loss of hippocampal GAD67-IR neurons and the subsequent increased susceptibility to evoked seizures.

  1. Low dose chronic Schistosoma mansoni infection increases susceptibility to Mycobacterium bovis BCG infection in mice

    PubMed Central

    Elias, D; Akuffo, H; Thors, C; Pawlowski, A; Britton, S

    2005-01-01

    The incidence of mycobacterial diseases is high and the efficacy of Bacillus Calmette Guérin (BCG) is low in most areas of the world where chronic worm infections are common. However, if and how concurrent worm infections could affect immunity to mycobacterial infections has not been elucidated. In this study we investigated whether infection of mice with Schistosoma mansoni could affect the ability of the animals to control Mycobacterium bovis BCG infection and the immune response to mycobacterial antigens. BALB/c mice subclinically infected with S. mansoni were challenged with M. bovis BCG via the intravenous route. The ability of the animals to contain the replication of M. bovis BCG in their organs, lung pathology as well as the in vitro mycobacterial and worm antigen induced immune responses were evaluated. The results showed that S. mansoni coinfected mice had significantly higher levels of BCG bacilli in their organs and sustained greater lung pathology compared to Schistosoma uninfected controls. Moreover, Schistosoma infected mice show depressed mycobacterial antigen specific Th1 type responses. This is an indication that chronic worm infection could affect resistance/susceptibility to mycobacterial infections by impairing mycobacteria antigen specific Th1 type responses. This finding is potentially important in the control of TB in helminth endemic parts of the world. PMID:15730384

  2. Increased susceptibility to Kuru of carriers of the PRNP 129 methionine/methionine genotype.

    PubMed

    Lee, H S; Brown, P; Cervenáková, L; Garruto, R M; Alpers, M P; Gajdusek, D C; Goldfarb, L G

    2001-01-15

    Kuru reached epidemic proportions by the mid-twentieth century among the Fore people of New Guinea and disappeared after the abolition of cannibalistic rituals. To determine susceptibility to kuru and its role in the spread and elimination of the epidemic, we analyzed the PRNP gene coding sequences in 5 kuru patients; no germline mutations were found. Analysis of the PRNP 129 methionine (M)/valine (V) polymorphism in 80 patients and 95 unaffected controls demonstrated that the kuru epidemic preferentially affected individuals with the M/M genotype. A higher representation of M/M carriers was observed among the affected young Fore males entering the age of risk, whereas a lower frequency of M/M homozygotes was found among the survivors. M/V and V/V genotypes predisposed to a lower risk of disease development and longer incubation times. These findings are relevant to the current outbreak of variant Creutzfeldt-Jakob disease (vCJD) in the United Kingdom, because all vCJD patients tested thus far have been M/M carriers.

  3. Increased Inner Ear Susceptibility to Noise Injury in Mice With Streptozotocin-Induced Diabetes

    PubMed Central

    Fujita, Takeshi; Yamashita, Daisuke; Katsunuma, Sayaka; Hasegawa, Shingo; Tanimoto, Hitoshi; Nibu, Ken-ichi

    2012-01-01

    We aimed to investigate the pathophysiology of diabetes-associated hearing impairment in type 1 diabetes using mice with streptozotocin-induced diabetes (C57BL/6J; male). Hearing function was evaluated 1, 3, and 5 months after induction of diabetes (five diabetic and five control animals per time point) using auditory-evoked brain stem responses (ABRs). Mice (four diabetic and four control) were exposed to loud noise (105 dB) 5 months after induction of diabetes. ABRs were measured before and after noise exposure. Cochlear blood flows were measured by laser-Doppler flowmeter. Spiral ganglion cells (SGCs) were counted. Vessel endothelial cells were observed by CD31 immunostaining. Chronologic changes in the ABR threshold shift were not significantly different between the diabetic and control groups. However, vessel walls in the modiolus of the cochleae were significantly thicker in the diabetic group than the control group. Additionally, recovery from noise-induced injury was significantly impaired in diabetic mice. Reduced cochlea blood flows and SGC loss were observed in diabetic mice cochleae after noise exposure. Our data suggest that diabetic cochleae are more susceptible than controls to loud noise exposure, and decreased cochlear blood flow due to sclerosis of the vessels and consequent loss of SGCs are possible mechanisms of hearing impairment in diabetic patients. PMID:22851574

  4. Serotonin depletion increases seizure susceptibility and worsens neuropathological outcomes in kainate model of epilepsy.

    PubMed

    Maia, Gisela H; Brazete, Cátia S; Soares, Joana I; Luz, Liliana L; Lukoyanov, Nikolai V

    2017-09-01

    Serotonin is implicated in the regulation of seizures, but whether or not it can potentiate the effects of epileptogenic factors is not fully established. Using the kainic acid model of epilepsy in rats, we tested the effects of serotonin depletion on (1) susceptibility to acute seizures, (2) development of spontaneous recurrent seizures and (3) behavioral and neuroanatomical sequelae of kainic acid treatment. Serotonin was depleted by pretreating rats with p-chlorophenylalanine. In different groups, kainic acid was injected at 3 different doses: 6.5mg/kg, 9.0mg/kg or 12.5mg/kg. A single dose of 6.5mg/kg of kainic acid reliably induced status epilepticus in p-chlorophenylalanine-pretreated rats, but not in saline-pretreated rats. The neuroexcitatory effects of kainic acid in the p-chlorophenylalanine-pretreated rats, but not in saline-pretreated rats, were associated with the presence of tonic-clonic convulsions and high lethality. Compared to controls, a greater portion of serotonin-depleted rats showed spontaneous recurrent seizures after kainic acid injections. Loss of hippocampal neurons and spatial memory deficits associated with kainic acid treatment were exacerbated by prior depletion of serotonin. The present findings are of particular importance because they suggest that low serotonin activity may represent one of the major risk factors for epilepsy and, thus, offer potentially relevant targets for prevention of epileptogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. PSCA gene variants (rs2294008 and rs2978974) confer increased susceptibility of gallbladder carcinoma in females.

    PubMed

    Rai, Rajani; Sharma, Kiran L; Misra, Sanjeev; Kumar, Ashok; Mittal, Balraj

    2013-11-10

    PSCA is a tissue specific tumor suppressor or oncogene which has been found to be associated with several human tumors including gallbladder cancer. It is considered to be involved in the cell-proliferation inhibition and/or cell-death induction activity. Therefore, we aimed to investigate the role of PSCA gene polymorphisms in gallbladder cancer risk in North Indian population. A total of 405 gallbladder cancer patients and 247 healthy controls were included in the case-control study for risk prediction. We examined the association of two functional SNPs, rs2294008 and rs2978974 in PSCA gene by genotyping using Taqman allelic discrimination assays. Statistical analysis was done using SPSS software, version 17. Linkage disequilibrium and haplotype analysis was done with the help of SNPstats software. FDR test was used to correct for multiple comparisons. No significant associations of rs2294008 and rs2978974 genetic variants of the PSCA gene were found with GBC risk at allele, genotype or haplotype levels. Stratifying the subjects on the basis of gallstone also did not show any significant result. However, on gender stratification, we found a significant association of Trs2294008-Grs2978974 haplotype with higher risk of GBC in females (FDR Pcorr=0.021, OR=1.6). In contrary, Trs2294008-A rs2978974 haplotype conferred significant lower risk in males (FDR Pcorr=0.013; OR=0.25). These findings suggest that PSCA genetic variants may have a significant effect on GBC susceptibility in a gender specific manner. © 2013.

  6. Increased susceptibility of aged hearts to ventricular fibrillation during oxidative stress

    PubMed Central

    Morita, Norishige; Sovari, Ali A.; Xie, Yuanfang; Fishbein, Michael C.; Mandel, William J.; Garfinkel, Alan; Lin, Shien-Fong; Chen, Peng-Sheng; Xie, Lai-Hua; Chen, Fuhua; Qu, Zhilin; Weiss, James N.

    2009-01-01

    Oxidative stress with hydrogen peroxide (H2O2) readily promotes early afterdepolarizations (EADs) and triggered activity (TA) in isolated rat and rabbit ventricular myocytes. Here we examined the effects of H2O2 on arrhythmias in intact Langendorff rat and rabbit hearts using dual-membrane voltage and intracellular calcium optical mapping and glass microelectrode recordings. Young adult rat (3–5 mo, N = 25) and rabbit (3–5 mo, N = 6) hearts exhibited no arrhythmias when perfused with H2O2 (0.1–2 mM) for up to 3 h. However, in 33 out of 35 (94%) aged (24–26 mo) rat hearts, 0.1 mM H2O2 caused EAD-mediated TA, leading to ventricular tachycardia (VT) and fibrillation (VF). Aged rabbits (life span, 8–12 yr) were not available, but 4 of 10 middle-aged rabbits (3–5 yr) developed EADs, TA, VT, and VF. These arrhythmias were suppressed by the reducing agent N-acetylcysteine (2 mM) and CaMKII inhibitor KN-93 (1 μM) but not by its inactive form (KN-92, 1 μM). There were no significant differences between action potential duration (APD) or APD restitution slope before or after H2O2 in aged or young adult rat hearts. In histological sections, however, trichrome staining revealed that aged rat hearts exhibited extensive fibrosis, ranging from 10–90%; middle-aged rabbit hearts had less fibrosis (5–35%), whereas young adult rat and rabbit hearts had <4% fibrosis. In aged rat hearts, EADs and TA arose most frequently (70%) from the left ventricular base where fibrosis was intermediate (∼30%). Computer simulations in two-dimensional tissue incorporating variable degrees of fibrosis showed that intermediate (but not mild or severe) fibrosis promoted EADs and TA. We conclude that in aged ventricles exposed to oxidative stress, fibrosis facilitates the ability of cellular EADs to emerge and generate TA, VT, and VF at the tissue level. PMID:19767530

  7. Knockout of a P-glycoprotein gene increases susceptibility to abamectin and emamectin benzoate in Spodoptera exigua.

    PubMed

    Zuo, Y-Y; Huang, J-L; Wang, J; Feng, Y; Han, T-T; Wu, Y-D; Yang, Y-H

    2017-07-28

    P-glycoprotein [P-gp or the ATP-binding cassette transporter B1 (ABCB1)] is an important participant in multidrug resistance of cancer cells, yet the precise function of this arthropod transporter is unknown. The aim of this study was to determine the importance of P-gp for susceptibility to insecticides in the beet armyworm (Spodoptera exigua) using clustered regularly interspaced short palindromic repeats/CRISPR-associated 9 (CRISPR/Cas9) gene-editing technology. We cloned an open reading frame (ORF) encoding the S. exigua P-gp protein (SeP-gp) predicted to display structural characteristics common to P-gp and other insect ABCB1 transporters. A knockout line with a frame shift deletion of four nucleotides in the SeP-gp ORF was established using the CRISPR/Cas9 gene-editing system to test its potential role in determining susceptibility to chemical insecticides or insecticidal proteins from the bacterium Bacillus thuringiensis (Bt). Results from comparative bioassays demonstrate that knockout of SeP-gp significantly increases susceptibility of S. exigua by around threefold to abamectin and emamectin benzoate (EB), but not to spinosad, chlorfenapyr, beta-cypermethrin, carbosulfan indoxacarb, chlorpyrifos, phoxim, diafenthiuron, chlorfluazuron, chlorantraniliprole or two Bt toxins (Cry1Ca and Cry1Fa). Our data support an important role for SeP-gp in susceptibility of S. exigua to abamectin and EB and imply that overexpression of SeP-gp may contribute to abamectin and EB resistance in S. exigua. © 2017 The Royal Entomological Society.

  8. Use of natural antimicrobials to increase antibiotic susceptibility of drug resistant bacteria.

    PubMed

    Palaniappan, Kavitha; Holley, Richard A

    2010-06-15

    Plant-derived antibacterial compounds may be of value as a novel means for controlling antibiotic resistant zoonotic pathogens which contaminate food animals and their products. Individual activity of natural antimicrobials (eugenol, thymol, carvacrol, cinnamaldehyde, allyl isothiocyanate (AIT)) and activity when paired with an antibiotic was studied using broth microdilution and checkerboard methods. In the latter assays, fractional inhibitory concentration (FIC) values were calculated to characterize interactions between the inhibitors. Bacteria tested were chosen because of their resistance to at least one antibiotic which had a known genetic basis. Substantial susceptibility of these bacteria toward the natural antimicrobials and a considerable reduction in the minimum inhibitory concentrations (MIC's) of the antibiotics were noted when paired combinations of antimicrobial and antibiotic were used. In the interaction study, thymol and carvacrol were found to be highly effective in reducing the resistance of Salmonella Typhimurium SGI 1 (tet A) to ampicillin, tetracycline, penicillin, bacitracin, erythromycin and novobiocin (FIC<0.4) and resistance of Streptococcus pyogenes ermB to erythromycin (FIC<0.5). With Escherichia coli N00 666, thymol and cinnamaldehyde were found to have a similar effect (FIC<0.4) in reducing the MIC's of ampicillin, tetracycline, penicillin, erythromycin and novobiocin. Carvacrol, thymol (FIC<0.3) and cinnamaldehyde (FIC<0.4) were effective against Staphylococcus aureus blaZ and in reducing the MIC's of ampicillin, penicillin and bacitracin. Allyl isothiocyanate (AIT) was effective in reducing the MIC of erythromycin (FIC<0.3) when tested against S. pyogenes. Fewer combinations were found to be synergistic when the decrease in viable population (log DP) was calculated. Together, fractional inhibitory concentrations < or = 0.5 and log DP<-1 indicated synergistic action between four natural antimicrobials and as many as three antibiotics

  9. The stay green mutations d1 and d2 increase water stress susceptibility in soybeans.

    PubMed

    Luquez, Virginia M; Guiamét, Juan J

    2002-06-01

    The stay green mutant genotype d1d1d2d2 inhibits the breakdown of chloroplast components in senescing leaves of soybean (Glycine max L. Merr.). Together with G (a gene that preserves chlorophyll in the seed coat) they may extend photosynthetic activity in some conditions. While wild-type soybeans maintain high leaf water potentials right up to abscission, leaves of (GG)d1d1d2d2 dehydrate late in senescence, which suggests that water relations may be altered in the mutant. Three-week-old plants were subjected to a moderate water deficit (soil water potential=-0.7 MPa) for 7-10 d. Leaf water potential and relative water content decreased significantly more in response to water deficit in unifoliate leaves of GGd1d1d2d2 than in a near-isogenic wild-type line. Down-regulation of stomatal conductance in response to drought was similar in mutant and wild-type leaves. Likewise, exogenously applied ABA reduced stomatal conductance to a similar extent in the mutant and the wild type, and applied ABA failed to restore water deficit tolerance in GGd1d1d2d2. Experiments with explants lacking roots indicate that the accelerated dehydration of GGd1d1d2d2 is probably not due to alterations in the roots. In a comparison of near-isogenic lines carrying different combinations of d1, d2 and G, only d1d1d2d2 and GGd1d1d2d2 (i.e. the genotypes that cause the stay green phenotype) were more susceptible to water deficit than the wild type. These data suggest that pathways involved in chloroplast disassembly and in the regulation of stress responses may be intertwined and controlled by the same factors.

  10. Increased susceptibility for white spot lesions by surplus orthodontic etching exceeding bracket base area.

    PubMed

    Knösel, Michael; Bojes, Mariana; Jung, Klaus; Ziebolz, Dirk

    2012-05-01

    There is a paucity of information with regard to the susceptibility of iatrogenic white spot lesion formation after inattentive, surplus orthodontic etching with 30% phosphoric acid and the subsequent provision or absence of adequate oral hygiene. Ninety sound enamel specimens were randomly allocated to 6 trial groups (n = 15 each) for etching with 30% phosphoric acid for either 15 seconds and standardized daily enamel brushing or no brushing, etching for 30 seconds with daily brushing or no brushing, or nonetched controls with brushing or no brushing. Nutritive acidic assaults were simulated by demineralization cycles 3 times per day for 1 hour with interim storage in artificial saliva. Lesion depths in terms of percentage of fluorescence loss (delta F, delta Q) and lesion extension compared with the baseline were assessed by using quantitative light-induced fluorescence after 2, 7, 14, 21, and 42 days. Etching duration, trial time elapse, and oral hygiene, as well as the significance of factor interactions, were analyzed with 3-way analysis of variance (α = 5%). The impact of the factors of enamel brushing, trial time elapse, and etching each had a comparably significant effect on lesion progression. The effect of surplus etching on white spot lesion formation was significantly enhanced by the simultaneous absence of enamel brushing and also the progression of trial time. The combination of 30 seconds of surplus etching with inadequate oral hygiene was especially detrimental. Excessive surplus orthodontic etching of the complete labial enamel surface, instead of the bracket bases only, must be avoided to prevent iatrogenic white spot lesions. Etching times not exceeding 15 seconds are favorable. Copyright © 2012 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  11. [Increased susceptibility for white spot lesions by surplus orthodontic etching exceeding bracket base area].

    PubMed

    Knösel, Michael; Bojes, Mariana; Jung, Klaus; Ziebolz, Dirk; Renger, Stéphane

    2015-09-01

    There is a paucity of information with regard to the susceptibility of iatrogenic white spot lesion formation after inattentive, surplus orthodontic etching with 30% phosphoric acid and the subsequent provision or absence of adequate oral hygiene. Ninety sound enamel specimens were randomly allocated to 6 trial groups (N = 15 each) for etching with 30% phosphoric acid for either 15 seconds and standardized daily enamel brushing or no brushing, etching for 30 seconds with daily brushing or no brushing, or nonetched controls with brushing or no brushing. Nutritive acidic assaults were simulated by demineralization cycles 3 times per day for 1 hour with interim storage in artificial saliva. Lesion depths in terms of percentage of fluorescence loss (delta F, delta Q) and lesion extension compared with the baseline were assessed by using quantitative light-induced fluorescence after 2, 7, 14, 21, and 42 days. Etching duration, trial time elapse, and oral hygiene, as well as the significance of factor interactions, were analyzed with 3-way analysis of variance (α=5%). The impact of the factors of enamel brushing, trial time elapse, and etching each had a comparably significant effect on lesion progression. The effect of surplus etching on white spot lesion formation was significantly enhanced by the simultaneous absence of enamel brushing and also the progression of trial time. The combination of 30 seconds of surplus etching with inadequate oral hygiene was especially detrimental. Excessive surplus orthodontic etching of the complete labial enamel surface, instead of the bracket bases only, must be avoided to prevent iatrogenic white spot lesions. Etching times not exceeding 15 seconds are favorable. © EDP Sciences, SFODF, 2015.

  12. Gestational Hypothyroidism Increases the Severity of Experimental Autoimmune Encephalomyelitis in Adult Offspring

    PubMed Central

    Albornoz, Eduardo A.; Carreño, Leandro J.; Cortes, Claudia M.; Gonzalez, Pablo A.; Cisternas, Pablo A.; Cautivo, Kelly M.; Catalán, Tamara P.; Opazo, M. Cecilia; Eugenin, Eliseo A.; Berman, Joan W.; Bueno, Susan M.; Kalergis, Alexis M.

    2013-01-01

    Background: Maternal thyroid hormones play a fundamental role in appropriate fetal development during gestation. Offspring that have been gestated under maternal hypothyroidism suffer cognitive impairment. Thyroid hormone deficiency during gestation can significantly impact the central nervous system by altering the migration, differentiation, and function of neurons, oligodendrocytes, and astrocytes. Given that gestational hypothyroidism alters the immune cell ratio in offspring, it is possible that this condition could result in higher sensitivity for the development of autoimmune diseases. Methods: Adult mice gestated under hypothyroidism were induced with experimental autoimmune encephalomyelitis (EAE). Twenty-one days after EAE induction, the disease score, myelin content, immune cell infiltration, and oligodendrocyte death were evaluated. Results: We observed that mice gestated under hypothyroidism showed higher EAE scores after disease induction during adulthood compared to mice gestated in euthyroidism. In addition, spinal cord sections of mice gestated under hypothyroidism that suffered EAE in adulthood showed higher demyelination, CD4+ and CD8+ infiltration, and increased oligodendrocyte death. Conclusions: These results show for the first time that a deficiency in maternal thyroid hormones during gestation can influence the outcome of a central nervous system inflammatory disease, such as EAE, in their offspring. These data strongly support evaluating thyroid hormones in pregnant women and treating hypothyroidism during pregnancy to prevent increased susceptibility to inflammatory diseases in the central nervous system of offspring. PMID:23777566

  13. Gestational hypothyroidism increases the severity of experimental autoimmune encephalomyelitis in adult offspring.

    PubMed

    Albornoz, Eduardo A; Carreño, Leandro J; Cortes, Claudia M; Gonzalez, Pablo A; Cisternas, Pablo A; Cautivo, Kelly M; Catalán, Tamara P; Opazo, M Cecilia; Eugenin, Eliseo A; Berman, Joan W; Bueno, Susan M; Kalergis, Alexis M; Riedel, Claudia A

    2013-12-01

    Maternal thyroid hormones play a fundamental role in appropriate fetal development during gestation. Offspring that have been gestated under maternal hypothyroidism suffer cognitive impairment. Thyroid hormone deficiency during gestation can significantly impact the central nervous system by altering the migration, differentiation, and function of neurons, oligodendrocytes, and astrocytes. Given that gestational hypothyroidism alters the immune cell ratio in offspring, it is possible that this condition could result in higher sensitivity for the development of autoimmune diseases. Adult mice gestated under hypothyroidism were induced with experimental autoimmune encephalomyelitis (EAE). Twenty-one days after EAE induction, the disease score, myelin content, immune cell infiltration, and oligodendrocyte death were evaluated. We observed that mice gestated under hypothyroidism showed higher EAE scores after disease induction during adulthood compared to mice gestated in euthyroidism. In addition, spinal cord sections of mice gestated under hypothyroidism that suffered EAE in adulthood showed higher demyelination, CD4(+) and CD8(+) infiltration, and increased oligodendrocyte death. These results show for the first time that a deficiency in maternal thyroid hormones during gestation can influence the outcome of a central nervous system inflammatory disease, such as EAE, in their offspring. These data strongly support evaluating thyroid hormones in pregnant women and treating hypothyroidism during pregnancy to prevent increased susceptibility to inflammatory diseases in the central nervous system of offspring.

  14. Schistosoma mansoni P-glycoprotein levels increase in response to praziquantel exposure and correlate with reduced praziquantel susceptibility.

    PubMed

    Messerli, Shanta M; Kasinathan, Ravi S; Morgan, William; Spranger, Stefani; Greenberg, Robert M

    2009-09-01

    One potential physiological target for new antischistosomals is the parasite's system for excretion of wastes and xenobiotics. P-glycoprotein (Pgp), a member of the ATP-binding-cassette superfamily of proteins, is an ATP-dependent efflux pump involved in transport of toxins and xenobiotics from cells. In vertebrates, increased expression of Pgp is associated with multidrug resistance in tumor cells. Pgp may also play a role in drug resistance in helminths. In this report, we examine the relationship between praziquantel (PZQ), the current drug of choice against schistosomiasis, and Pgp expression in Schistosoma mansoni. We show that levels of RNA for SMDR2, a Pgp homolog from S. mansoni, increase transiently in adult male worms following exposure to sub-lethal concentrations (100-500 nM) of PZQ. A corresponding, though delayed, increase in anti-Pgp immunoreactive protein expression occurs in adult males following exposure to PZQ. The level of anti-Pgp immunoreactivity in particular regions of adult worms also increases in response to PZQ. Adult worms from an Egyptian S. mansoni isolate with reduced sensitivity to PZQ express increased levels of SMDR2 RNA and anti-Pgp-immunoreactive protein, perhaps indicating a role for multidrug resistance proteins in development or maintenance of PZQ resistance.

  15. Schistosoma mansoni P-glycoprotein levels increase in response to praziquantel exposure and correlate with reduced praziquantel susceptibility

    PubMed Central

    Messerli, Shanta M.; Kasinathan, Ravi S.; Morgan, William; Spranger, Stefani; Greenberg, Robert M.

    2009-01-01

    One potential physiological target for new antischistosomals is the parasite’s system for excretion of wastes and xenobiotics. P-glycoprotein (Pgp), a member of the ATP-binding cassette superfamily of proteins, is an ATP-dependent efflux pump involved in transport of toxins and xenobiotics from cells. In vertebrates, increased expression of Pgp is associated with multidrug resistance in tumor cells. Pgp may also play a role in drug resistance in helminths. In this report, we examine the relationship between praziquantel (PZQ), the current drug of choice against schistosomiasis, and Pgp expression in Schistosoma mansoni. We show that levels of RNA for SMDR2, a Pgp homolog from S. mansoni, increase transiently in adult male worms following exposure to sublethal concentrations (100 – 500 nM) of PZQ. A corresponding, though delayed, increase in anti-Pgp immunoreactive protein expression occurs in adult males following exposure to PZQ. The level of anti-Pgp immunoreactivity in particular regions of adult worms also increases in response to PZQ. Adult worms from an Egyptian S. mansoni isolate with reduced sensitivity to PZQ express increased levels of SMDR2 RNA and anti-Pgp-immunoreactive protein, perhaps indicating a role for multidrug resistance proteins in development or maintenance of PZQ resistance. PMID:19406169

  16. Increased production of mitochondrial reactive oxygen species and reduced adult life span in an insecticide-resistant strain of Anopheles gambiae.

    PubMed

    Otali, D; Novak, R J; Wan, W; Bu, S; Moellering, D R; De Luca, M

    2014-06-01

    Control of the malaria vector An. gambiae is still largely obtained through chemical intervention using pyrethroids, such as permethrin. However, strains of An. gambiae that are resistant to the toxic effects of pyrethroids have become widespread in several endemic areas over the last decade. The objective of this study was to assess differences in five life-history traits (larval developmental time and the body weight, fecundity, hatch rate, and longevity of adult females) and energy metabolism between a strain of An. gambiae that is resistant to permethrin (RSP), due to knockdown resistance and enhanced metabolic detoxification, and a permethrin susceptible strain reared under laboratory conditions. We also quantified the expression levels of five antioxidant enzyme genes: GSTe3, CAT, GPXH1, SOD1, and SOD2. We found that the RSP strain had a longer developmental time than the susceptible strain. Additionally, RSP adult females had higher wet body weight and increased water and glycogen levels. Compared to permethrin susceptible females, RSP females displayed reduced metabolic rate and mitochondrial coupling efficiency and higher mitochondrial ROS production. Furthermore, despite higher levels of GSTe3 and CAT transcripts, RSP females had a shorter adult life span than susceptible females. Collectively, these results suggest that permethrin resistance alleles might affect energy metabolism, oxidative stress, and adult survival of An. gambiae. However, because the strains used in this study differ in their genetic backgrounds, the results need to be interpreted with caution and replicated in other strains to have significant implications for malaria transmission and vector control.

  17. Increased incidence of adult pneumococcal pneumonia during school holiday periods

    PubMed Central

    Rodrigo, Chamira; Bewick, Thomas; Sheppard, Carmen; Greenwood, Sonia; McKeever, Tricia M.; Slack, Mary; Lim, Wei Shen

    2017-01-01

    Child contact is a recognised risk factor for adult pneumococcal disease. Peaks in invasive pneumococcal disease incidence observed during winter holidays may be related to changes in social dynamics. This analysis was conducted to examine adult pneumococcal community-acquired pneumonia (CAP) incidence during school holiday periods. Between September 2008 and 2013, consecutive adults admitted to hospitals covering the Greater Nottingham area with a diagnosis of CAP were studied. Pneumococcal pneumonia was detected using culture and antigen detection methods. Of 2221 adults studied, 575 (25.9%) were admitted during school holidays and 643 (29.0%) had pneumococcal CAP. CAP of pneumococcal aetiology was significantly more likely in adults admitted during school holidays compared to term time (35.3% versus 26.7%; adjusted OR 1.38, 95% CI 1.11–1.72, p=0.004). Over the 5-year period, the age-adjusted incidence of hospitalised pneumococcal CAP was higher during school holidays compared to term time (incident rate ratio 1.35, 95% CI 1.14–1.60, p<0.001); there was no difference in rates of all-cause CAP or non-pneumococcal CAP. Reported child contact was higher in individuals with pneumococcal CAP admitted during school holidays compared to term time (42.0% versus 33.7%, OR 1.43, 95% CI 1.00–2.03, p=0.046). Further study of transmission dynamics in relation to these findings and to identify appropriate intervention strategies is warranted. PMID:28326311

  18. Experimentally increasing sedentary behavior results in increased anxiety in an active young adult population.

    PubMed

    Edwards, Meghan K; Loprinzi, Paul D

    2016-11-01

    Knowledge regarding the effects of sedentary behavior on anxiety has resulted mainly from observational studies. The purpose of this study was to examine the effects of a free-living, sedentary behavior-inducing randomized controlled intervention on anxiety symptoms. Participants confirmed to be active (i.e., acquiring 150min/week of physical activity) via self-report and accelerometry were randomly assigned into a sedentary behavior intervention group (n=26) or a control group (n=13). For one week, the intervention group eliminated exercise and minimized steps to ≤5000 steps/day whereas the control group continued their normal physical activity levels. Both groups completed the Overall Anxiety Severity Impairment Scale (OASIS) pre- and post-intervention, with higher OASIS scores indicating worse overall anxiety. The intervention group resumed normal physical activity levels for one week post-intervention and then completed the survey once more. A significant group x time interaction effect was observed (F(1,37)=11.13; P=.002), with post-hoc contrast tests indicating increased OASIS scores in the intervention group in Visit 2 compared with Visit 1. That is, we observed an increase in anxiety levels when participants increased their sedentary behavior. OASIS scores significantly decreased from Visit 2 to Visit 3 (P=.001) in the intervention group. A one-week sedentary behavior-inducing intervention has deleterious effects on anxiety in an active, young adult population. To prevent elevated anxiety levels among active individuals, consistent regular physical activity may be necessary. Clinicians treating inactive patients who have anxiety may recommend a physical activity program in addition to any other prescribed treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Low-dose exposure to di-(2-ethylhexyl) phthalate (DEHP) increases susceptibility to testicular autoimmunity in mice.

    PubMed

    Hirai, Shuichi; Naito, Munekazu; Kuramasu, Miyuki; Ogawa, Yuki; Terayama, Hayato; Qu, Ning; Hatayama, Naoyuki; Hayashi, Shogo; Itoh, Masahiro

    2015-09-01

    Exposure to di-(2-ethylhexyl) phthalate (DEHP) induces spermatogenic disturbance (SD) through oxidative stress, and affects the immune system by acting as an adjuvant. Recently, we reported that in mice, a low dose of DEHP, which did not affect spermatogenesis, was able to alter the testicular immune microenvironment. Experimental autoimmune orchitis (EAO) can be induced by repeated immunization with testicular antigens, and its pathology is characterized by production of autoantibodies and SD. In the present study, we investigated the effect of a low-dose DEHP on the susceptibility of mice to EAO. The exposure to DEHP-containing feed (0.01%) caused a modest functional damage to the blood-testis barrier (BTB) with an increase in testicular number of interferon gamma (IFN-γ)-positive cells and resulted in the production of autoantibodies targeting haploid cells, but did not affect spermatogenesis. While only single immunization with testicular antigens caused very mild EAO, the concurrent DEHP exposure induced severe EAO with significant increases in number of interferon gamma-positive cells and macrophages, as well as lymphocytic infiltration and serum autoantibody titer accompanied by severe SD. To summarize, the exposure of mice to the low-dose DEHP does not induce significant SD, but it may cause an increase in IFN-γ positive cells and modest functional damage to the BTB in the testis. These changes lead to an autoimmune response against haploid cell autoantigens, resulting in increased susceptibility to EAO.

  20. Medroxyprogesterone acetate and levonorgestrel increase genital mucosal permeability and enhance susceptibility to genital herpes simplex virus type 2 infection

    PubMed Central

    Calla, Nirk E Quispe; Miguel, Rodolfo D Vicetti; Boyaka, Prosper N; Hall-Stoodley, Luanne; Kaur, Balveen; Trout, Wayne; Pavelko, Stephen D; Cherpes, Thomas L

    2016-01-01

    Depot-medroxyprogesterone acetate (DMPA) is a hormonal contraceptive especially popular in areas with high prevalence of HIV and other sexually transmitted infections (STI). While observational studies identify DMPA as an important STI risk factor, mechanisms underlying this connection are undefined. Levonorgestrel (LNG) is another progestin used for hormonal contraception, but its effect on STI susceptibility is much less explored. Using a mouse model of genital HSV-2 infection, we herein found DMPA and LNG similarly reduced genital expression of the desmosomal cadherin desmoglein-1α (DSG1α), enhanced access of inflammatory cells to genital tissue by increasing mucosal epithelial permeability, and increased susceptibility to viral infection. Additional studies with uninfected mice revealed DMPA-mediated increases in mucosal permeability promoted tissue inflammation by facilitating endogenous vaginal microbiota invasion. Conversely, concomitant treatment of mice with DMPA and intravaginal estrogen restored mucosal barrier function and prevented HSV-2 infection. Evaluating ectocervical biopsy tissue from women before and 1 month after initiating DMPA remarkably revealed inflammation and barrier protection were altered by treatment identically to changes seen in progestin-treated mice. Together, our work reveals DMPA and LNG diminish the genital mucosal barrier; a first-line defense against all STI, but may offer foundation for new contraceptive strategies less compromising of barrier protection. PMID:27007679

  1. Medroxyprogesterone acetate and levonorgestrel increase genital mucosal permeability and enhance susceptibility to genital herpes simplex virus type 2 infection.

    PubMed

    Quispe Calla, N E; Vicetti Miguel, R D; Boyaka, P N; Hall-Stoodley, L; Kaur, B; Trout, W; Pavelko, S D; Cherpes, T L

    2016-11-01

    Depot-medroxyprogesterone acetate (DMPA) is a hormonal contraceptive especially popular in areas with high prevalence of HIV and other sexually transmitted infections (STI). Although observational studies identify DMPA as an important STI risk factor, mechanisms underlying this connection are undefined. Levonorgestrel (LNG) is another progestin used for hormonal contraception, but its effect on STI susceptibility is much less explored. Using a mouse model of genital herpes simplex virus type 2 (HSV-2) infection, we herein found that DMPA and LNG similarly reduced genital expression of the desmosomal cadherin desmoglein-1α (DSG1α), enhanced access of inflammatory cells to genital tissue by increasing mucosal epithelial permeability, and increased susceptibility to viral infection. Additional studies with uninfected mice revealed that DMPA-mediated increases in mucosal permeability promoted tissue inflammation by facilitating endogenous vaginal microbiota invasion. Conversely, concomitant treatment of mice with DMPA and intravaginal estrogen restored mucosal barrier function and prevented HSV-2 infection. Evaluating ectocervical biopsy tissue from women before and 1 month after initiating DMPA remarkably revealed that inflammation and barrier protection were altered by treatment identically to changes seen in progestin-treated mice. Together, our work reveals DMPA and LNG diminish the genital mucosal barrier; a first-line defense against all STI, but may offer foundation for new contraceptive strategies less compromising of barrier protection.

  2. Air pollution and lung function among susceptible adult subjects: a panel study

    PubMed Central

    Lagorio, Susanna; Forastiere, Francesco; Pistelli, Riccardo; Iavarone, Ivano; Michelozzi, Paola; Fano, Valeria; Marconi, Achille; Ziemacki, Giovanni; Ostro, Bart D

    2006-01-01

    Background Adverse health effects at relatively low levels of ambient air pollution have consistently been reported in the last years. We conducted a time-series panel study of subjects with chronic obstructive pulmonary disease (COPD), asthma, and ischemic heart disease (IHD) to evaluate whether daily levels of air pollutants have a measurable impact on the lung function of adult subjects with pre-existing lung or heart diseases. Methods Twenty-nine patients with COPD, asthma, or IHD underwent repeated lung function tests by supervised spirometry in two one-month surveys. Daily samples of coarse (PM10–2.5) and fine (PM2.5) particulate matter were collected by means of dichotomous samplers, and the dust was gravimetrically analyzed. The particulate content of selected metals (cadmium, chrome, iron, nickel, lead, platinum, vanadium, and zinc) was determined by atomic absorption spectrometry. Ambient concentrations of nitrogen dioxide (NO2), carbon monoxide (CO), ozone (O3), and sulphur dioxide (SO2) were obtained from the regional air-quality monitoring network. The relationships between concentrations of air pollutants and lung function parameters were analyzed by generalized estimating equations (GEE) for panel data. Results Decrements in lung function indices (FVC and/or FEV1) associated with increasing concentrations of PM2.5, NO2 and some metals (especially zinc and iron) were observed in COPD cases. Among the asthmatics, NO2 was associated with a decrease in FEV1. No association between average ambient concentrations of any air pollutant and lung function was observed among IHD cases. Conclusion This study suggests that the short-term negative impact of exposure to air pollutants on respiratory volume and flow is limited to individuals with already impaired respiratory function. The fine fraction of ambient PM seems responsible for the observed effects among COPD cases, with zinc and iron having a potential role via oxidative stress. The respiratory function

  3. Neonatal Progesterone Programs Adult Uterine Responses to Progesterone and Susceptibility to Uterine Dysfunction

    PubMed Central

    Rumi, M. A. Karim; Kubota, Kaiyu; Chakraborty, Damayanti; Chien, Jeremy; Roby, Katherine F.

    2015-01-01

    In this report, we investigated the consequences of neonatal progesterone exposure on adult rat uterine function. Female pups were subcutaneously injected with vehicle or progesterone from postnatal days 3 to 9. Early progesterone exposure affected endometrial gland biogenesis, puberty, decidualization, and fertility. Because decidualization and pregnancy success are directly linked to progesterone action on the uterus, we investigated the responsiveness of the adult uterus to progesterone. We first identified progesterone-dependent uterine gene expression using RNA sequencing and quantitative RT-PCR in Holtzman Sprague-Dawley rats and progesterone-resistant Brown Norway rats. The impact of neonatal progesterone treatment on adult uterine progesterone responsiveness was next investigated using quantitative RT-PCR. Progesterone resistance affected the spectrum and total number of progesterone-responsive genes and the magnitude of uterine responses for a subset of progesterone targets. Several progesterone-responsive genes in adult uterus exhibited significantly dampened responses in neonatally progesterone-treated females compared with those of vehicle-treated controls, whereas other progesterone-responsive transcripts did not differ between female rats exposed to vehicle or progesterone as neonates. The organizational actions of progesterone on the uterus were dependent on signaling through the progesterone receptor but not estrogen receptor 1. To summarize, neonatal progesterone exposure leads to disturbances in endometrial gland biogenesis, progesterone resistance, and uterine dysfunction. Neonatal progesterone effectively programs adult uterine responsiveness to progesterone. PMID:26204463

  4. CCR5 deficiency increased susceptibility to lipopolysaccharide-induced acute renal injury.

    PubMed

    Lee, Dong Hun; Park, Mi Hee; Hwang, Chul Ju; Hwang, Jae Yeon; Yoon, Hae Suk; Yoon, Do Young; Hong, Jin Tae

    2016-05-01

    C-C chemokine receptor 5 (CCR5) regulates leukocyte chemotaxis and activation, and its deficiency exacerbates development of nephritis. Therefore, we investigated the role of CCR5 during lipopolysaccharide (LPS)-induced acute kidney injury. CCR5-deficient (CCR5-/-) and wild-type (CCR5+/+) mice, both aged about 10 months, had acute renal injury induced by intraperitoneal injection of LPS (10 mg/kg). Compared with CCR5+/+ mice, CCR5-/- mice showed increased mortality and renal injury, including elevated creatinine and blood urea nitrogen levels, following LPS challenge. Compared to CCR5+/+ mice, CCR5-/- mice also exhibited greater increases in the serum concentrations of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β following LPS challenge. Furthermore, infiltration of macrophages and neutrophils, expression of intracellular adhesion molecule (ICAM)-1, and the number of apoptotic cells were more greatly increased by LPS treatment in CCR5-/- mice than in CCR5+/+ mice. The concentrations of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β were also significantly increased in the kidney of CCR5-/- mice after LPS challenge. Moreover, primary kidney cells from CCR5-/- mice showed greater increases in TNF-α production and p38 MAP kinase activation following treatment with LPS compared with that observed in the cells from CCR5+/+ mice. LPS-induced TNF-α production and apoptosis in the primary kidney cells from CCR5-/- mice were inhibited by treatment with p38 MAP kinase inhibitor. These results suggest that CCR5 deficiency increased the production of TNF-α following LPS treatment through increased activation of the p38 pathway in the kidney, resulting in renal apoptosis and leukocyte infiltration and led to exacerbation of LPS-induced acute kidney injury.

  5. Reduced erythrocyte susceptibility and increased host clearance of young parasites slows Plasmodium growth in a murine model of severe malaria

    NASA Astrophysics Data System (ADS)

    Khoury, David S.; Cromer, Deborah; Best, Shannon E.; James, Kylie R.; Sebina, Ismail; Haque, Ashraful; Davenport, Miles P.

    2015-05-01

    The best correlate of malaria severity in human Plasmodium falciparum (Pf) infection is the total parasite load. Pf-infected humans could control parasite loads by two mechanisms, either decreasing parasite multiplication, or increasing parasite clearance. However, few studies have directly measured these two mechanisms in vivo. Here, we have directly quantified host clearance of parasites during Plasmodium infection in mice. We transferred labelled red blood cells (RBCs) from Plasmodium infected donors into uninfected and infected recipients, and tracked the fate of donor parasites by frequent blood sampling. We then applied age-based mathematical models to characterise parasite clearance in the recipient mice. Our analyses revealed an increased clearance of parasites in infected animals, particularly parasites of a younger developmental stage. However, the major decrease in parasite multiplication in infected mice was not mediated by increased clearance alone, but was accompanied by a significant reduction in the susceptibility of RBCs to parasitisation.

  6. Evaluation of the olivocochlear efferent reflex strength in the susceptibility to temporary hearing deterioration after music exposure in young adults.

    PubMed

    Hannah, Keppler; Ingeborg, Dhooge; Leen, Maes; Annelies, Bockstael; Birgit, Philips; Freya, Swinnen; Bart, Vinck

    2014-01-01

    The objective of the current study was to evaluate the predictive role of the olivocochlear efferent reflex strength in temporary hearing deterioration in young adults exposed to music. This was based on the fact that a noise-protective role of the medial olivocochlear (MOC) system was observed in animals and that efferent suppression (ES) measured using contralateral acoustic stimulation (CAS) of otoacoustic emissions (OAEs) is capable of exploring the MOC system. Knowing an individual's susceptibility to cochlear damage after noise exposure would enhance preventive strategies for noise-induced hearing loss. The hearing status of 28 young adults was evaluated using pure-tone audiometry, transient evoked OAEs (TEOAEs) and distortion product OAEs (DPOAEs) before and after listening to music using an MP3 player during 1 h at an individually determined loud listening level. CAS of TEOAEs was measured before music exposure to determine the amount of ES. Regression analysis showed a distinctive positive correlation between temporary hearing deterioration and the preferred gain setting of the MP3 player. However, no clear relationship between temporary hearing deterioration and the amount of ES was found. In conclusion, clinical measurement of ES, using CAS of TEOAEs, is not correlated with the amount of temporary hearing deterioration after 1 h music exposure in young adults. However, it is possible that the temporary hearing deterioration in the current study was insufficient to activate the MOC system. More research regarding ES might provide more insight in the olivocochlear efferent pathways and their role in auditory functioning.

  7. California Adults Increase Fruit and Vegetable Consumption from 1997-2007

    ERIC Educational Resources Information Center

    Sugerman, Sharon; Foerster, Susan B.; Gregson, Jennifer; Linares, Amanda; Hudes, Mark

    2011-01-01

    Objective: To determine whether fruit and vegetable consumption among California adults significantly increased from 1997-2007. Design: Biennial telephone surveillance surveys of California adults' dietary practices. Participants: California adults (n = 9,105 total all 6 surveys). Intervention: Surveillance data reporting. Main Outcome Measures:…

  8. California Adults Increase Fruit and Vegetable Consumption from 1997-2007

    ERIC Educational Resources Information Center

    Sugerman, Sharon; Foerster, Susan B.; Gregson, Jennifer; Linares, Amanda; Hudes, Mark

    2011-01-01

    Objective: To determine whether fruit and vegetable consumption among California adults significantly increased from 1997-2007. Design: Biennial telephone surveillance surveys of California adults' dietary practices. Participants: California adults (n = 9,105 total all 6 surveys). Intervention: Surveillance data reporting. Main Outcome Measures:…

  9. Drought increases cowpea (Vigna unguiculata [L.] Walp.) susceptibility to cowpea severe mosaic virus (CPSMV) at early stage of infection.

    PubMed

    Silva, Rodolpho G G; Vasconcelos, Ilka M; Martins, Thiago F; Varela, Anna L N; Souza, Pedro F N; Lobo, Ana K M; Silva, Fredy D A; Silveira, Joaquim A G; Oliveira, Jose T A

    2016-12-01

    The physiological and biochemical responses of a drought tolerant, virus-susceptible cowpea genotype exposed to drought stress (D), infected by Cowpea severe mosaic virus (CPSMV) (V), and to these two combined stresses (DV), at 2 and 6 days post viral inoculation (DPI), were evaluated. Gas exchange parameters (net photosynthesis, transpiration rate, stomatal conductance, and internal CO2 partial pressure) were reduced in D and DV at 2 and 6 DPI compared to control plants (C). Photosynthesis was reduced by stomatal and biochemical limitations. Water use efficiency increased at 2 DPI in D, DV, and V, but at 6 DPI only in D and DV compared to C. Photochemical parameters (effective quantum efficiency of photosystem II and electron transport rate) decreased in D and DV compared to C, especially at 6 DPI. The potential quantum efficiency of photosystem II did not change, indicating reversible photoinhibition of photosystem II. In DV, catalase decreased at 2 and 6 DPI, ascorbate peroxidase increased at 2 DPI, but decreased at 6 DPI. Hydrogen peroxide increased at 2 and 6 DPI. Peroxidase increased at 6 DPI and chitinase at 2 and 6 DPI. β-1,3-glucanase decreased in DV at 6 DPI compared to V. Drought increased cowpea susceptibility to CPSMV at 2 DPI, as verified by RT-PCR. However, at 6 DPI, the cowpea plants overcome this effect. Likewise, CPSMV increased the negative effects of drought at 2 DPI, but not at 6 DPI. It was concluded that the responses to combined stresses are not additive and cannot be extrapolated from the study of individual stresses. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  10. The Difficulty with Experience: Does Practice Increase Susceptibility to Premature Closure?

    ERIC Educational Resources Information Center

    Eva, Kevin W.; Cunnington, John P. W.

    2006-01-01

    Introduction: A recent review of the physician performance literature concluded that the risk of prematurely closing one's diagnostic search increases with years of experience. To minimize confounding variables and gain insight into cognitive issues relevant to continuing education, the current study was performed to test this conclusion. Methods:…

  11. xCT increases tuberculosis susceptibility by regulating antimicrobial function and inflammation

    PubMed Central

    Zhang, Chi; Nambi, Subhalaxmi; Wang, Wenfei; Zhang, Mingxia; Wu, Junying; Deng, Guofang; Deng, Qunyi; Liu, Haiying; Zhou, Boping; Jin, Qi; Feng, Carl G; Sassetti, Christopher M; Wang, Fudi; Chen, Xinchun

    2016-01-01

    The physiological functions of macrophage, which plays a central role in the pathogenesis of tuberculosis, depend on its redox state. System xc-, a cystine-glutamate transporter, which consists of xCT and CD98, influences many ROS-dependent pathways by regulating the production of the antioxidant glutathione. xCT's ability to alter this critical host redox balance by increasing the glutathione synthesis aspect of phagocyte physiology suggested that it might influence tuberculosis pathogenesis. In this study, we found that the xCT expression was increased in peripheral blood monocyte of active tuberculosis. xCT expression in macrophage was induced by Mycobacterium tuberculosis (Mtb) through TLR2/Akt- and p38-dependent signaling pathway. Importantly, xCT deficiency conferred protection against tuberculosis, as xCT knock out mice displayed increased Mtb load and reduced pulmonary pathology in lung compared to wild type mice. xCT disruption enhanced the mycobateriacidal activity of macrophage through increasing the mycothiol oxidation. Importantly, chemical inhibition of xCT with sulfasalazine, a specific xCT inhibitor that is already approved by the FDA for treatment of inflammatory bowel disease, produces similar protective effects in vivo and in vitro, indicating xCT might be a novel and useful target for host-directed TB treatment strategy. PMID:27129162

  12. Silicone antitranspirant increases susceptibility of eastern white pine to the white pine weevil

    Treesearch

    Ronald C. Wilkinson

    1975-01-01

    Spraying 16-year-old eastern white pine (Pinus strobus L.) growing in a geographic seed-source test plantation with 10-percent silicone antitranspirant emulsion effectively increased internal water balance during the growing season when compared to control trees of the same seed sources that received no treatment. Extreme silicone toxicity was...

  13. Deficiency in macrophage-stimulating protein results in spontaneous intestinal inflammation and increased susceptibility toward epithelial damage in zebrafish.

    PubMed

    Witte, Merlijn; Huitema, Leonie F A; Nieuwenhuis, Edward E S; Brugman, Sylvia

    2014-12-01

    Several genome-wide association studies have identified the genes encoding for macrophage-stimulating protein (MSP) and its receptor RON (Recepteur d'Origine Nantais) as possible susceptibility factors in inflammatory bowel disease. While it has been shown that the MSP-RON signaling pathway is involved in tissue injury responses, current mouse models for MSP and RON deficiency have not clearly demonstrated a role of MSP-RON signaling in the context of intestinal inflammation. In this study, we report that the recently identified zebrafish Msp mutant (msp(t34230)) develops spontaneous intestinal inflammation over time. From 14 to 28 weeks postfertilization Msp-deficient zebrafish show intestinal eosinophilia, increased intestinal expression of inflammatory marker mmp9, and activation of intestinal goblet cells. Moreover, these Msp mutant zebrafish are more susceptible toward ethanol-induced epithelial damage, which resulted in increased infiltration and proliferation of immune cells within the lamina propria and prolonged intestinal proinflammatory cytokine responses in some mutant fish. In light of the recent development of many tools to visualize, monitor, and genetically modify zebrafish, these Msp-deficient zebrafish will enable in-depth in vivo analysis of epithelial and macrophage-specific MSP-RON signaling in the context of intestinal inflammation.

  14. Increased atrial arrhythmia susceptibility induced by intense endurance exercise in mice requires TNFα

    PubMed Central

    Aschar-Sobbi, Roozbeh; Izaddoustdar, Farzad; Korogyi, Adam S.; Wang, Qiongling; Farman, Gerrie P.; Yang, FengHua; Yang, Wallace; Dorian, David; Simpson, Jeremy A.; Tuomi, Jari M.; Jones, Douglas L.; Nanthakumar, Kumaraswamy; Cox, Brian; Wehrens, Xander H.T.; Dorian, Paul; Backx, Peter H.

    2015-01-01

    Atrial fibrillation (AF) is the most common supraventricular arrhythmia that, for unknown reasons, is linked to intense endurance exercise. Our studies reveal that 6 weeks of swimming or treadmill exercise improves heart pump function and reduces heart-rates. Exercise also increases vulnerability to AF in association with inflammation, fibrosis, increased vagal tone, slowed conduction velocity, prolonged cardiomyocyte action potentials and RyR2 phosphorylation (CamKII-dependent S2814) in the atria, without corresponding alterations in the ventricles. Microarray results suggest the involvement of the inflammatory cytokine, TNFα, in exercised-induced atrial remodelling. Accordingly, exercise induces TNFα-dependent activation of both NFκB and p38MAPK, while TNFα inhibition (with etanercept), TNFα gene ablation, or p38 inhibition, prevents atrial structural remodelling and AF vulnerability in response to exercise, without affecting the beneficial physiological changes. Our results identify TNFα as a key factor in the pathology of intense exercise-induced AF. PMID:25598495

  15. Increased Susceptibility to Staphylococcal Enterotoxin B Intoxication in Mice Primed with Actinomycin D

    DTIC Science & Technology

    1994-10-01

    blood congestion, inflammation, epithelial cell flattening, and villous blunting were seen in the small intestine. In lymphoid tissues, such as the spleen...pavementing and widen- flattening with villous and macrophage phagocytosis; ing of alveolar septa, with blunting; lymphocyte ne- PMN increase in the red pulp...point. Mice primed with ACT-D flattening with villous blunting (Fig. IB). and lymphocyte and injected with normal saline served as controls. Anatomical

  16. Bladder catheterization increases susceptibility to infection that can be prevented by prophylactic antibiotic treatment

    PubMed Central

    Rousseau, Matthieu; Goh, H.M. Sharon; Holec, Sarah; Albert, Matthew L.; Williams, Rohan B.H.; Ingersoll, Molly A.; Kline, Kimberly A.

    2016-01-01

    Catheter-associated urinary tract infections (CAUTI) are the most common hospital-associated infections. Here, we report that bladder catheterization initiated a persistent sterile inflammatory reaction within minutes of catheter implantation. Catheterization resulted in increased expression of genes associated with defense responses and cellular migration, with ensuing rapid and sustained innate immune cell infiltration into the bladder. Catheterization also resulted in hypersensitivity to Enterococcus faecalis and uropathogenic Escherichia coli (UPEC) infection, in which colonization was achieved using an inoculum 100-fold lower than the ID90 for infection of an undamaged urothelium with the same uropathogens. As the time of catheterization increased, however, colonization by the Gram-positive uropathogen E. faecalis was reduced, whereas catheterization created a sustained window of vulnerability to infection for Gram-negative UPEC over time. As CAUTI contributes to poorer patient outcomes and increased health care expenditures, we tested whether a single prophylactic antibiotic treatment, concurrent with catheterization, would prevent infection. We observed that antibiotic treatment protected against UPEC and E. faecalis bladder and catheter colonization as late as 6 hours after implantation. Thus, our study has revealed a simple, safe, and immediately employable intervention, with the potential to decrease one of the most costly hospital-incurred infections, thereby improving patient and health care economic outcome. PMID:27699248

  17. Lymnaea glabra: progressive increase in susceptibility to Fasciola hepatica through successive generations of experimentally infected snails.

    PubMed

    Rondelaud, D; Teukeng, F F Djuikwo; Vignoles, P; Dreyfuss, G

    2015-07-01

    Experimental infections of Lymnaea glabra (two populations) with Fasciola hepatica were carried out during seven successive snail generations, to determine if prevalence and intensity of snail infection increased over time through descendants of snails already infected with F. hepatica. Controls were descendants coming from uninfected parents and infected according to the same protocol. No larval forms were found in the bodies of control snails coming from uninfected parents. In contrast, prevalence and intensity of F. hepatica infection in snails originating from infected parents progressively increased from the F2 or F3 to the F6 generation of L. glabra. In another experiment carried out with the F7 generations of L. glabra and a single generation of Galba truncatula (as controls), the prevalence of F. hepatica infection and the total number of cercariae were lower in L. glabra (without significant differences between both populations). If the number of cercariae shed by infected snails was compared to overall cercarial production noted in snails containing cercariae but dying without emission, the percentage was greater in G. truncatula (69% instead of 52-54% in L. glabra). Even if most characteristics of F. hepatica infection were lower in L. glabra, prevalence and intensity of parasite infection increased with snail generation when tested snails came from infected parents. This mode of snail infection with F. hepatica suggests an explanation for cases of fasciolosis occurring in cattle-breeding farms where paramphistomosis is lacking and G. truncatula is absent.

  18. Aging per se Increases the Susceptibility to Free Fatty Acid–Induced Insulin Resistance

    PubMed Central

    Huffman, Derek M.; Fishman, Sigal; Jerschow, Elina; Heo, Hye J.; Atzmon, Gil; Schechter, Clyde; Muzumdar, Radhika H.

    2010-01-01

    Elevations in systemic free fatty acids (FFA) contribute to insulin resistance. To determine the effects of an acute elevation in FFA on insulin action with aging, we infused saline or intralipid (IL) during a hyperinsulinemic–euglycemic clamp in three groups of rats: young ad libitum–fed (YAL), old ad libitum–fed (OAL), and old on lifelong calorie restriction (OCR). The OCR group was included to distinguish between aging per se and age-related changes in body fat distribution. IL induced marked insulin resistance in both YAL and OCR, but the onset of insulin resistance was approximately two to three times more rapid in OCR as compared with YAL. In response to IL infusion, plasminogen-activating inhibitor-1 (PAI-1) expression was increased in subcutaneous fat from OAL animals. In visceral fat, a marked increase in PAI-1 and interleukin-6 expression was observed in OAL and OCR rats, but not YAL, in response to IL treatment. Thus, aging per se increases the inflammatory response to excess nutrients and vulnerability to FFA-induced insulin resistance with aging. PMID:20504893

  19. Increasing Spectrum in Antimicrobial Resistance of Shigella Isolates in Bangladesh: Resistance to Azithromycin and Ceftriaxone and Decreased Susceptibility to Ciprofloxacin

    PubMed Central

    Mahbubur, Rahman; Shoma, Shereen; Rashid, Harunur; Arifeen, Shams El; Baqui, A.H.; Siddique, A.K.; Nair, G.B.; Sack, D.A.

    2007-01-01

    Antimicrobial resistance of Shigella isolates in Bangladesh, during 2001-2002, was studied and compared with that of 1991-1992 to identify the changes in resistance patterns and trends. A significant increase in resistance to trimethoprim-sulphamethoxazole (from 52% to 72%, p<0.01) and nalidixic acid (from 19% to 51%, p<0.01) was detected. High, but unchanged, resistance to tetracycline, ampicillin, and chloramphenicol, low resistance to mecillinam (resistance 3%, intermediate 3%), and to emergence of resistance to azithromycin (resistance 16%, intermediate 62%) and ceftriaxone/cefixime (2%) were detected in 2001-2002. Of 266 recent isolates, 63% were resistant to ≥3 anti-Shigella drugs (multidrug-resistant [MDR]) compared to 52% of 369 strains (p<0.007) in 1991-1992. Of 154 isolates tested by E-test in 2001-2002, 71% were nalidixic acid-resistant (minimum inhibitory concentration [MIC] ≥32 μg/mL) and had 10-fold higher MIC90 (0.25 μg/mL) to ciprofloxacin than that of nalidixic acid-susceptible strains exhibiting decreased ciprofloxacin susceptibility, which were detected as ciprofloxacin-susceptible and nalidixic acid-resistant by the disc-diffusion method. These strains were frequently associated with MDR traits. High modal MICs were observed to azithromycin (MIC 6 μg/mL) and nalidixic acid (MIC 128 μg/mL) and low to ceftriaxone (MIC 0.023 μg/mL). Conjugative R-plasmids-encoded extended-spectrum ß-lactamase was responsible for resistance to ceftriaxone/cefixime. The growing antimicrobial resistance of Shigella is worrying and mandates monitoring of resistance. Pivmecillinam or ciprofloxacin might be considered for treating shigellosis with caution. PMID:17985817

  20. Increased susceptibility to amyloid-β-induced neurotoxicity in mice lacking the low-density lipoprotein receptor.

    PubMed

    de Oliveira, Jade; Moreira, Eduardo Luiz Gasnhar; dos Santos, Danúbia Bonfanti; Piermartiri, Tetsadê Camboim; Dutra, Rafael Cypriano; Pinton, Simone; Tasca, Carla Inês; Farina, Marcelo; Prediger, Rui Daniel Schröder; de Bem, Andreza Fabro

    2014-01-01

    Familial hypercholesterolemia is caused by inherited genetic abnormalities that directly or indirectly affect the function of the low-density lipoprotein (LDL) receptor. This condition is characterized by defective catabolism of LDL which results in increased plasma cholesterol concentrations and premature coronary artery disease. Nevertheless, there is increasing preclinical and clinical evidence indicating that familial hypercholesterolemia subjects show a particularly high incidence of mild cognitive impairment. Moreover, the LDL receptor (LDLr) has been implicated as the main central nervous system apolipoprotein E receptor that regulates amyloid deposition in distinct mouse models of β-amyloidosis. In this regard, herein we hypothesized that the lack of LDLr would enhance the susceptibility to amyloid-β-(Aβ)-induced neurotoxicity in mice. Using the acute intracerebroventricular injection of aggregated Aβ(1-40) peptide (400 pmol/mouse), a useful approach for the investigation of molecular mechanisms involved in Aβ toxicity, we observed oxidative stress, neuroinflammation, and neuronal membrane damage within the hippocampus of C57BL/6 wild-type mice, which were associated with spatial reference memory and working memory impairments. In addition, our data show that LDLr knockout (LDLr(-/-)) mice, regardless of Aβ treatment, displayed memory deficits and increased blood-brain barrier permeability. Nonetheless, LDLr(-/-) mice treated with Aβ(1-40) peptide presented increased acetylcholinesterase activity, astrogliosis, oxidative imbalance, and cell permeability within the hippocampus in comparison with Aβ(1-40)-treated C57BL/6 wild-type mice. Overall, the present study shows that the lack of LDLr increases the susceptibility to Aβ-induced neurotoxicity in mice providing new evidence about the crosslink between familial hypercholesterolemia and cognitive impairment.

  1. Minimal oxidation and storage of low density lipoproteins result in an increased susceptibility to phospholipid hydrolysis by phospholipase A2.

    PubMed

    Eckey, R; Menschikowski, M; Lattke, P; Jaross, W

    1997-07-25

    In vitro-studies have shown that phospholipid hydrolysis of low density lipoproteins (LDL) by bee venom or porcine pancreatic phospholipase A2 (PLA2) leads to an increased uptake of these lipoproteins by macrophages transforming them into foam cells. Recently, a secretory phospholipase A2, group II, was detected in human atherosclerotic plaques. In order to investigate the role of this enzyme in the pathogenesis of atherosclerosis, a structurally identical human secretory PLA2 was purified from the medium of HepG2 cells stimulated with interleukin-6 and tumor necrosis factor-alpha. The activity of the purified enzyme towards the phospholipids of native and modified low density lipoproteins was compared with the activity towards Escherichia coli-membranes and other phospholipid substrates. Compared to E. coli-membranes, native LDL proved to be a poor substrate for group II PLA2. After mild oxidation induced by copper ions or by 2,2-azobis(2-amidinopropane) (AAPH), the susceptibility of LDL to phospholipid hydrolysis was found to be increased by 25 and 23%, respectively, whereas extensive copper-mediated oxidation caused a decreased hydrolysis. Aging of LDL at 6 degrees C for weeks or at 37 degrees C for hours resulted in an increase in PLA2-catalyzed phospholipid hydrolysis of up to 26-fold. LDL protected from oxidation by probucol during aging showed a lesser increase in susceptibility to phospholipid hydrolysis. Our results suggest that PLA2, group II, can increase the atherogenicity of LDL by its ability to hydrolyze the phospholipids of these lipoproteins, especially after modifications that are likely to occur in vivo.

  2. Inhibition of Angiotensin-II Production Increases Susceptibility to Acute Ischemia/Reperfusion Arrhythmia

    PubMed Central

    Taskin, Eylem; Tuncer, Kadir Ali; Guven, Celal; Kaya, Salih Tunc; Dursun, Nurcan

    2016-01-01

    Background Myocardial ischemia and reperfusion lead to impairment of electrolyte balance and, eventually, lethal arrhythmias. The aim of this study was to investigate the effects of pharmacological inhibition of angiotensin-II (Ang-II) production on heart tissue with ischemia-reperfusion damage, arrhythmia, and oxidative stress. Material/Methods Rats were divided into 4 groups: only ischemia/reperfusion (MI/R), captopril (CAP), aliskiren (AL), and CAP+AL. The drugs were given by gavage 30 min before anesthesia. Blood pressure and electrocardiography (ECG) were recorded during MI/R procedures. The heart tissue and plasma was kept so as to evaluate the total oxidant (TOS), antioxidant status (TAS), and creatine kinase-MB (CK-MB). Results Creatine kinase-MB was not different among the groups. Although TAS was not affected by inhibition of Ang-II production, TOS was significantly lower in the CAP and/or AL groups than in the MI/R group. Furthermore, oxidative stress index was significantly attenuated in the CAP and/or AL groups. Captopril significantly increased the duration of VT during ischemia; however, it did not have any effect on the incidence of arrhythmias. During reperfusion periods, aliskiren and its combinations with captopril significantly reduced the incidence of other types of arrhythmias. Captopril alone had no effect on the incidence of arrhythmias, but significantly increased arrhythmias score and durations of arrhythmias during reperfusion. MAP and heart rate did not show changes in any groups during ischemic and reperfusion periods. Conclusions Angiotensin-II production appears to be associated with elevated levels of reactive oxygen species, but Ang-II inhibitions increases arrhythmia, mainly by initiating ventricular ectopic beats. PMID:27889788

  3. Effects of HLA-DRB1 alleles on susceptibility and clinical manifestations in Japanese patients with adult onset Still's disease.

    PubMed

    Asano, Tomoyuki; Furukawa, Hiroshi; Sato, Shuzo; Yashiro, Makiko; Kobayashi, Hiroko; Watanabe, Hiroshi; Suzuki, Eiji; Ito, Tomoyuki; Ubara, Yoshifumi; Kobayashi, Daisuke; Iwanaga, Nozomi; Izumi, Yasumori; Fujikawa, Keita; Yamasaki, Satoshi; Nakamura, Tadashi; Koga, Tomohiro; Shimizu, Toshimasa; Umeda, Masataka; Nonaka, Fumiaki; Yasunami, Michio; Ueki, Yukitaka; Eguchi, Katsumi; Tsuchiya, Naoyuki; Tohma, Shigeto; Yoshiura, Koh-Ichiro; Ohira, Hiromasa; Kawakami, Atsushi; Migita, Kiyoshi

    2017-09-12

    HLA-DRB1 alleles are major determinants of genetic predisposition to rheumatic diseases. We assessed whether DRB1 alleles are associated with susceptibility to particular clinical features of adult onset Still's disease (AOSD) in a Japanese population by determining the DRB1 allele distributions. DRB1 genotyping of 96 patients with AOSD and 1,026 healthy controls was performed. Genomic DNA samples from the AOSD patients were also genotyped for MEFV exons 1, 2, 3, and 10 by direct sequencing. In Japanese patients with AOSD, we observed a predisposing association of DRB1*15:01 (p = 8.60 × 10(-6), corrected p (Pc) = 0.0002, odds ratio (OR) = 3.04, 95% confidence interval (95% CI) = 1.91-4.84) and DR5 serological group (p = 0.0006, OR = 2.39, 95% CI = 1.49-3.83) and a protective association of DRB1*09:01 (p = 0.0004, Pc = 0.0110, OR = 0.34, 95% CI = 0.18-0.66) with AOSD, and amino acid residues 86 and 98 of the DRβ chain were protectively associated with AOSD. MEFV variants were identified in 49 patients with AOSD (56.3%). The predisposing effect of DR5 was confirmed only in patients with AOSD who had MEFV variants and not in those without MEFV variants. Additionally, DR5 in patients with AOSD are associated with macrophage activation syndrome (MAS) and steroid pulse therapy. The DRB1*15:01 and DR5 are both associated with AOSD susceptibility in Japanese subjects. A protective association between the DRB1*09:01 allele and AOSD was also observed in these patients. Our data also highlight the effects of DRB1 alleles in susceptibility to AOSD.

  4. Nitric oxide increases susceptibility of toll-like receptor-activated macrophages to spreading Listeria monocytogenes

    PubMed Central

    Cole, Caroline; Thomas, Stacey; Filak, Holly; Henson, Peter M.; Lenz, Laurel L.

    2012-01-01

    SUMMARY Toll-like receptor (TLR) stimulation activates macrophages to resist intracellular pathogens. Yet, the intracellular bacterium Listeria monocytogenes (Lm) causes lethal infections in spite of innate immune cell activation. Lm uses direct cell-cell spread to disseminate within its host. Here, we have shown that TLR-activated macrophages killed cell-free Lm but failed to prevent infection by spreading Lm. Instead, TLR signals increased the efficiency of Lm spread from “donor” to “recipient” macrophages. This enhancement required nitric oxide (NO) production by nitric oxide synthase-2 (NOS2). NO increased Lm escape from secondary vacuoles in recipient cells and delayed maturation of phagosomes containing membrane-like particles that mimic Lm-containing pseudopods. NO also promoted Lm spread during systemic in vivo infection, as inhibition of NOS2 with 1400W reduced spread-dependent Lm burdens in mouse livers. These findings reveal a mechanism by which pathogens capable of cell-cell spread can avoid the consequences of innate immune cell activation by TLR stimuli. PMID:22542147

  5. Prenatal exposure to testosterone increases ectoparasite susceptibility in the common lizard (Lacerta vivipara).

    PubMed Central

    Uller, Tobias; Olsson, Mats

    2003-01-01

    High levels of testosterone can benefit individual fitness, for example by increasing growth rate or ornament size, which may result in increased reproductive success. However, testosterone induces costs, such as a suppressed immune system, thereby generating trade-offs between growth or mate acquisition, and immunity. In birds and reptiles, females allocate steroids to their eggs, which may be a mechanism whereby females can influence the phenotype of their offspring. To our knowledge, only the benefits of early androgen exposure have been experimentally investigated to date. However, to understand this phenomenon, the costs also need to be evaluated. We manipulated testosterone levels in eggs of the viviparous common lizard and monitored growth, endurance and post-parturient responses to ectoparasites of the offspring. Testosterone-treated individuals had significantly higher growth rates than controls, but suffered a significant decrease in growth rate when exposed to ticks, whereas the corresponding difference for controls was non-significant. There was no difference in observed parasite load or leucocyte count between manipulated and control offspring. Thus, our results suggest that high testosterone levels during embryonic development have detrimental effects on immune function resulting in reduced growth rate, and that this must be taken into consideration when evaluating the potential adaptive value of maternal androgen allocation to eggs. PMID:12964990

  6. Claudin 4 knockout mice: normal physiological phenotype with increased susceptibility to lung injury

    PubMed Central

    Kage, Hidenori; Flodby, Per; Gao, Danping; Kim, Yong Ho; Marconett, Crystal N.; DeMaio, Lucas; Kim, Kwang-Jin; Crandall, Edward D.

    2014-01-01

    Claudins are tight junction proteins that regulate paracellular ion permeability of epithelium and endothelium. Claudin 4 has been reported to function as a paracellular sodium barrier and is one of three major claudins expressed in lung alveolar epithelial cells (AEC). To directly assess the role of claudin 4 in regulation of alveolar epithelial barrier function and fluid homeostasis in vivo, we generated claudin 4 knockout (Cldn4 KO) mice. Unexpectedly, Cldn4 KO mice exhibited normal physiological phenotype although increased permeability to 5-carboxyfluorescein and decreased alveolar fluid clearance were noted. Cldn4 KO AEC monolayers exhibited unchanged ion permeability, higher solute permeability, and lower short-circuit current compared with monolayers from wild-type mice. Claudin 3 and 18 expression was similar between wild-type and Cldn4 KO alveolar epithelial type II cells. In response to either ventilator-induced lung injury or hyperoxia, claudin 4 expression was markedly upregulated in wild-type mice, whereas Cldn4 KO mice showed greater degrees of lung injury. RNA sequencing, in conjunction with differential expression and upstream analysis after ventilator-induced lung injury, suggested Egr1, Tnf, and Il1b as potential mediators of increased lung injury in Cldn4 KO mice. These results demonstrate that claudin 4 has little effect on normal lung physiology but may function to protect against acute lung injury. PMID:25106430

  7. Cadmium-induced bone loss: Increased susceptibility in female beagles after ovariectomy

    SciTech Connect

    Bhattacharyya, M.H.; Sacco-Gibson, N.A.; Peterson, D.P.

    1991-01-01

    Bone resorption, as measured by release of bone {sup 45}Ca, was significantly increased in elderly female beagles within 96 h of exposure to 15 mg/L Cd in drinking water. The {sup 45}Ca response was greater in ovariecotomized (OV) animals than in sham-operated (SO) controls and was not mediated by changes in calciotropic hormone concentrations. Mean blood Cd concentrations were 3--8 {mu}g/L during the earliest bone resorption response and 13--15 {mu}g/L at the end of the study. During 7 mo of Cd exposure, bone mineral densities decreased most in the OV animals exposed to Cd: {minus}15.4 {plus minus} 4.3% for the tibia distal end and {minus}7.2 {plus minus} 1.2% for the lumbar vertebrae (L2-L4) (mean {plus minus} SE, n=4). Results indicate that Cd may act directly on bone and that postmenopausal women exposed to Cd in industry or via cigarette smoke may be at increased risk of Cd-induced bone loss. 21 refs., 4 figs.

  8. Chemical sympathectomy increases susceptibility to ocular herpes simplex virus type 1 infection.

    PubMed

    Templeton, Amanda; Nguyen, Gabrielle; Ash, John D; Straub, Rainer H; Carr, Daniel J J

    2008-06-15

    The cornea is one of the most highly innervated tissues in the mammalian host. We hypothesized changes to cornea innervation through chemical sympathectomy would significantly alter the host response to the neurotropic viral pathogen, herpes simplex virus type 1 (HSV-1) following ocular infection. Mice treated with 6-hydroxydopamine hydrobromide displayed reduced tyrosine hydroxylase-positive fibers residing in the cornea. Sympathectomized mice were also found to show a transient rise in virus recovered in infected tissues and succumbed to infection in greater numbers. Whereas there were no differences in infiltrating leukocyte populations including HSV-1-specific cytotoxic T lymphocytes in the infected tissue, an increase in substance P and a decrease in IFN-gamma levels in the trigeminal ganglion but not brain stem of sympathectomized mice were noted. Sympathectomized mice treated with the neurokinin-1 receptor antagonist L703,606 had delayed mortality implicating the involvement of substance P in HSV-1-mediated death.

  9. Chemical Sympathectomy Increases Susceptibility to Ocular Herpes Simplex Virus Type 1 Infection

    PubMed Central

    Templeton, Amanda; Nguyen, Gabrielle; Ash, John D.; Straub, Rainer H.; Carr, Daniel J. J.

    2008-01-01

    The cornea is one of the most highly innervated tissues in the mammalian host. We hypothesized changes to cornea innervation through chemical sympathectomy would significantly alter the host response to the neurotropic viral pathogen, herpes simplex virus type 1 (HSV-1) following ocular infection. Mice treated with 6-hydroxydopamine hydrobromide displayed reduced tyrosine hydroxylase-positive fibers residing in the cornea. Sympathectomized mice were also found to show a transient rise in virus recovered in infected tissues and succumbed to infection in greater numbers. Whereas there were no differences in infiltrating leukocyte populations including HSV-1-specific cytotoxic T lymphocytes in the infected tissue, an increase in substance P and a decrease in IFN-γ levels in the trigeminal ganglion but not brain stem of sympathectomized mice were noted. Sympathectomized mice treated with the neurokinin-1 receptor antagonist L703,606 had delayed mortality implicating the involvement of substance P in HSV-1-mediated death. PMID:18495255

  10. Neonicotinoid Insecticides Alter Induced Defenses and Increase Susceptibility to Spider Mites in Distantly Related Crop Plants

    PubMed Central

    Szczepaniec, Adrianna; Raupp, Michael J.; Parker, Roy D.; Kerns, David; Eubanks, Micky D.

    2013-01-01

    Background Chemical suppression of arthropod herbivores is the most common approach to plant protection. Insecticides, however, can cause unintended, adverse consequences for non-target organisms. Previous studies focused on the effects of pesticides on target and non-target pests, predatory arthropods, and concomitant ecological disruptions. Little research, however, has focused on the direct effects of insecticides on plants. Here we demonstrate that applications of neonicotinoid insecticides, one of the most important insecticide classes worldwide, suppress expression of important plant defense genes, alter levels of phytohormones involved in plant defense, and decrease plant resistance to unsusceptible herbivores, spider mites Tetranychus urticae (Acari: Tetranychidae), in multiple, distantly related crop plants. Methodology/Principal Findings Using cotton (Gossypium hirsutum), corn (Zea mays) and tomato (Solanum lycopersicum) plants, we show that transcription of phenylalanine amonia lyase, coenzyme A ligase, trypsin protease inhibitor and chitinase are suppressed and concentrations of the phytohormone OPDA and salicylic acid were altered by neonicotinoid insecticides. Consequently, the population growth of spider mites increased from 30% to over 100% on neonicotinoid-treated plants in the greenhouse and by nearly 200% in the field experiment. Conclusions/Significance Our findings are important because applications of neonicotinoid insecticides have been associated with outbreaks of spider mites in several unrelated plant species. More importantly, this is the first study to document insecticide-mediated disruption of plant defenses and link it to increased population growth of a non-target herbivore. This study adds to growing evidence that bioactive agrochemicals can have unanticipated ecological effects and suggests that the direct effects of insecticides on plant defenses should be considered when the ecological costs of insecticides are evaluated. PMID

  11. Neonicotinoid insecticides alter induced defenses and increase susceptibility to spider mites in distantly related crop plants.

    PubMed

    Szczepaniec, Adrianna; Raupp, Michael J; Parker, Roy D; Kerns, David; Eubanks, Micky D

    2013-01-01

    Chemical suppression of arthropod herbivores is the most common approach to plant protection. Insecticides, however, can cause unintended, adverse consequences for non-target organisms. Previous studies focused on the effects of pesticides on target and non-target pests, predatory arthropods, and concomitant ecological disruptions. Little research, however, has focused on the direct effects of insecticides on plants. Here we demonstrate that applications of neonicotinoid insecticides, one of the most important insecticide classes worldwide, suppress expression of important plant defense genes, alter levels of phytohormones involved in plant defense, and decrease plant resistance to unsusceptible herbivores, spider mites Tetranychus urticae (Acari: Tetranychidae), in multiple, distantly related crop plants. Using cotton (Gossypium hirsutum), corn (Zea mays) and tomato (Solanum lycopersicum) plants, we show that transcription of phenylalanine ammonia lyase, coenzyme A ligase, trypsin protease inhibitor and chitinase are suppressed and concentrations of the phytohormone OPDA and salicylic acid were altered by neonicotinoid insecticides. Consequently, the population growth of spider mites increased from 30% to over 100% on neonicotinoid-treated plants in the greenhouse and by nearly 200% in the field experiment. Our findings are important because applications of neonicotinoid insecticides have been associated with outbreaks of spider mites in several unrelated plant species. More importantly, this is the first study to document insecticide-mediated disruption of plant defenses and link it to increased population growth of a non-target herbivore. This study adds to growing evidence that bioactive agrochemicals can have unanticipated ecological effects and suggests that the direct effects of insecticides on plant defenses should be considered when the ecological costs of insecticides are evaluated.

  12. Increased susceptibility to hyperoxic lung injury and alveolar simplification in newborn rats by prenatal administration of benzo[a]pyrene

    PubMed Central

    Thakur, Vijay S.; Liang, Yanhong W.; Lingappan, Krithika; Jiang, Weiwu; Wang, Lihua; Barrios, Roberto; Zhou, Guodong; Guntupalli, Bharath; Shivanna, Binoy; Maturu, Paramahamsa; Welty, Stephen E.; Moorthy, Bhagavatula; Couroucli, Xanthi I.

    2014-01-01

    Maternal smoking is one of the risk factors for preterm birth and for the development of bronchopulmonary dysplasia (BPD). In this study, we tested the hypothesis that prenatal exposure of rats to benzo[a]pyrene (BP), a component of cigarette smoke, will result in increased susceptibility of newborns to oxygen-mediated lung injury and alveolar simplification, and that cytochrome P450 (CYP)1A and 1B1 enzymes and oxidative stress mechanistically contribute to this phenomenon. Timed pregnant Fisher 344 rats were administered BP (25 mg/Kg) or the vehicle corn oil (CO) on gestational days 18, 19 and 20, and newborn were either maintained in room air or exposed to hyperoxia (85% O2) for 7 or 14 days. Hyperoxic newborn rats prenatally exposed to the vehicle CO showed lung injury and alveolar simplification, and inflammation, and these effects were potentiated in rats that were prenatally exposed to BP. Prenatal exposure to BP, followed by hyperoxia, also resulted in significant modulation of hepatic and pulmonary cytochrome P450 (CYP)1A and 1B1 enzymes at PND 7-14. These rats displayed significant oxidative stress in lungs at postnatal day (PND) 14, as evidenced by increased levels of the F2-isoprostane 8-iso-PGF2α. Furthermore, these animals showed BP-derived DNA adducts and oxidative DNA adducts in the lung. In conclusion, our results show increased susceptibility of newborns to oxygen-mediated lung injury and alveolar simplification following maternal exposure to BP, and our results suggest that modulation of CYP1A/1B1 enzymes, increases in oxidative stress, and BP-DNA adducts contributed to this phenomenon. PMID:24657529

  13. The Association of Neighborhood Gene-Environment Susceptibility with Cortisol and Blood Pressure in African-American Adults.

    PubMed

    Coulon, Sandra M; Wilson, Dawn K; Van Horn, M L; Hand, Gregory A; Kresovich, Stephen

    2016-02-01

    African-American adults are disproportionately affected by stress-related chronic conditions like high blood pressure (BP), and both environmental stress and genetic risk may play a role in its development. This study tested whether the dual risk of low neighborhood socioeconomic status (SES) and glucocorticoid genetic sensitivity interacted to predict waking cortisol and BP. Cross-sectional waking cortisol and BP were collected from 208 African-American adults who were participating in a follow-up visit as part of the Positive Action for Today's Health trial. Three single-nucleotide polymorphisms were genotyped, salivary cortisol samples were collected, and neighborhood SES was calculated using 2010 Census data. The sample was mostly female (65 %), with weight classified as overweight or obese (M BMI = 32.74, SD = 8.88) and a mean age of 55.64 (SD = 15.21). The gene-by-neighborhood SES interaction predicted cortisol (B = 0.235, p = .001, r (2) = .036), but not BP. For adults with high genetic sensitivity, waking cortisol was lower with lower SES but higher with higher SES (B = 0.87). Lower neighborhood SES was also related to higher systolic BP (B = -0.794, p = .028). Findings demonstrated an interaction whereby African-American adults with high genetic sensitivity had high levels of waking cortisol with higher neighborhood SES, and low levels with lower neighborhood SES. This moderation effect is consistent with a differential susceptibility gene-environment pattern, rather than a dual-risk pattern. These findings contribute to a growing body of evidence that demonstrates the importance of investigating complex gene-environment relations in order to better understand stress-related health disparities.

  14. Susceptibility to interference by music and speech maskers in middle-aged adults.

    PubMed

    Başkent, Deniz; van Engelshoven, Suzanne; Galvin, John J

    2014-03-01

    Older listeners commonly complain about difficulty in understanding speech in noise. Previous studies have shown an age effect for both speech and steady noise maskers, and it is largest for speech maskers. In the present study, speech reception thresholds (SRTs) measured with competing speech, music, and steady noise maskers significantly differed between young (19 to 26 years) and middle-aged (51 to 63 years) adults. SRT differences ranged from 2.1 dB for competing speech, 0.4-1.6 dB for music maskers, and 0.8 dB for steady noise. The data suggest that aging effects are already evident in middle-aged adults without significant hearing impairment.

  15. Impaired calcineurin signaling in myeloid cells results in downregulation of pentraxin-3 and increased susceptibility to aspergillosis.

    PubMed

    Zelante, T; Wong, A Y W; Mencarelli, A; Foo, S; Zolezzi, F; Lee, B; Poidinger, M; Ricciardi-Castagnoli, P; Fric, J

    2017-03-01

    Treatment of post-transplant patients with immunosuppressive drugs targeting the calcineurin-nuclear factor of activated T cells (NFAT) pathway, including cyclosporine A or tacrolimus, is commonly associated with a higher incidence of opportunistic infections, such as Aspergillus fumigatus, which can lead to severe life-threatening conditions. A component of the A. fumigatus cell wall, β-glucan, is recognized by dendritic cells (DCs) via the Dectin-1 receptor, triggering downstream signaling that leads to calcineurin-NFAT binding, NFAT translocation, and transcription of NFAT-regulated genes. Here, we address the question of whether calcineurin signaling in CD11c-expressing cells, such as DCs, has a specific role in the innate control of A. fumigatus. Impairment of calcineurin in CD11c-expressing cells (CD11c(cre)cnb1(loxP)) significantly increased susceptibility to systemic A. fumigatus infection and to intranasal infection in irradiated mice undergoing bone marrow transplant. Global expression profiling of bone marrow-derived DCs identified calcineurin-regulated processes in the immune response to infection, including expression of pentraxin-3, an important antifungal defense protein. These results suggest that calcineurin inhibition directly impairs important immunoprotective functions of myeloid cells, as shown by the higher susceptibility of CD11c(cre)cnb(loxP) mice in models of systemic and invasive pulmonary aspergillosis, including after allogeneic bone marrow transplantation. These findings are relevant to the clinical management of transplant patients with severe Aspergillus infections.

  16. Increased seizure susceptibility and other toxicity symptoms following acute sulforaphane treatment in mice.

    PubMed

    Socała, Katarzyna; Nieoczym, Dorota; Kowalczuk-Vasilev, Edyta; Wyska, Elżbieta; Wlaź, Piotr

    2017-07-01

    Activation of Nrf2 with sulforaphane has recently gained attention as a new therapeutic approach in the treatment of many diseases, including epilepsy. As a plant-derived compound, sulforaphane is considered to be safe and well-tolerated. It is widely consumed, also by patients suffering from seizure and taking antiepileptic drugs, but no toxicity profile of sulforaphane exists. Since many natural remedies and dietary supplements may increase seizure risk and potentially interact with antiepileptic drugs, the aim of our study was to investigate the acute effects of sulforaphane on seizure thresholds and activity of some first- and second-generation antiepileptic drugs in mice. In addition, some preliminary toxicity profile of sulforaphane in mice after intraperitoneal injection was evaluated. The LD50 value of sulforaphane in mice was estimated at 212.67mg/kg, while the TD50 value - at 191.58mg/kg. In seizure tests, sulforaphane at the highest dose tested (200mg/kg) significantly decreased the thresholds for the onset of the first myoclonic twitch and generalized clonic seizure in the iv PTZ test as well as the threshold for the 6Hz-induced psychomotor seizure. At doses of 10-200mg/kg, sulforaphane did not affect the threshold for the iv PTZ-induced forelimb tonus or the threshold for maximal electroshock-induced hindlimb tonus. Interestingly, sulforaphane (at 100mg/kg) potentiated the anticonvulsant efficacy of carbamazepine in the maximal electroshock seizure test. This interaction could have been pharmacokinetic in nature, as sulforaphane increased concentrations of carbamazepine in both serum and brain tissue. The toxicity study showed that high doses of sulforaphane produced marked sedation (at 150-300mg/kg), hypothermia (at 150-300mg/kg), impairment of motor coordination (at 200-300mg/kg), decrease in skeletal muscle strength (at 250-300mg/kg), and deaths (at 200-300mg/kg). Moreover, blood analysis showed leucopenia in mice injected with sulforaphane at 200mg

  17. Epigallocatechin Gallate Remodels Overexpressed Functional Amyloids in Pseudomonas aeruginosa and Increases Biofilm Susceptibility to Antibiotic Treatment.

    PubMed

    Stenvang, Marcel; Dueholm, Morten S; Vad, Brian S; Seviour, Thomas; Zeng, Guanghong; Geifman-Shochat, Susana; Søndergaard, Mads T; Christiansen, Gunna; Meyer, Rikke Louise; Kjelleberg, Staffan; Nielsen, Per Halkjær; Otzen, Daniel E

    2016-12-16

    Epigallocatechin-3-gallate (EGCG) is the major polyphenol in green tea. It has antimicrobial properties and disrupts the ordered structure of amyloid fibrils involved in human disease. The antimicrobial effect of EGCG against the opportunistic pathogen Pseudomonas aeruginosa has been shown to involve disruption of quorum sensing (QS). Functional amyloid fibrils in P. aeruginosa (Fap) are able to bind and retain quorum-sensing molecules, suggesting that EGCG interferes with QS through structural remodeling of amyloid fibrils. Here we show that EGCG inhibits the ability of Fap to form fibrils; instead, EGCG stabilizes protein oligomers. Existing fibrils are remodeled by EGCG into non-amyloid aggregates. This fibril remodeling increases the binding of pyocyanin, demonstrating a mechanism by which EGCG can affect the QS function of functional amyloid. EGCG reduced the amyloid-specific fluorescent thioflavin T signal in P. aeruginosa biofilms at concentrations known to exert an antimicrobial effect. Nanoindentation studies showed that EGCG reduced the stiffness of biofilm containing Fap fibrils but not in biofilm with little Fap. In a combination treatment with EGCG and tobramycin, EGCG had a moderate effect on the minimum bactericidal eradication concentration against wild-type P. aeruginosa biofilms, whereas EGCG had a more pronounced effect when Fap was overexpressed. Our results provide a direct molecular explanation for the ability of EGCG to disrupt P. aeruginosa QS and modify its biofilm and strengthens the case for EGCG as a candidate in multidrug treatment of persistent biofilm infections.

  18. Del1 Knockout Mice Developed More Severe Osteoarthritis Associated with Increased Susceptibility of Chondrocytes to Apoptosis

    PubMed Central

    Wang, Zhen; Tran, Misha C.; Bhatia, Namrata J.; Hsing, Alexander W.; Chen, Carol; LaRussa, Marie F.; Fattakhov, Ernst; Rashidi, Vania; Jang, Kyu Yun; Choo, Kevin J.; Nie, Xingju; Mathy, Jonathan A.; Longaker, Michael T.; Dauskardt, Reinhold H.; Helms, Jill A.; Yang, George P.

    2016-01-01

    Objective We identified significant expression of the matricellular protein, DEL1, in hypertrophic and mature cartilage during development. We hypothesized that this tissue-specific expression indicated a biological role for DEL1 in cartilage biology. Methods Del1 KO and WT mice had cartilage thickness evaluated by histomorphometry. Additional mice underwent medial meniscectomy to induce osteoarthritis, and were assayed at 1 week for apoptosis by TUNEL staining and at 8 weeks for histology and OA scoring. In vitro proliferation and apoptosis assays were performed on primary chondrocytes. Results Deletion of the Del1 gene led to decreased amounts of cartilage in the ears and knee joints in mice with otherwise normal skeletal morphology. Destabilization of the knee led to more severe OA compared to controls. In vitro, DEL1 blocked apoptosis in chondrocytes. Conclusion Osteoarthritis is among the most prevalent diseases worldwide and increasing in incidence as our population ages. Initiation begins with an injury resulting in the release of inflammatory mediators. Excessive production of inflammatory mediators results in apoptosis of chondrocytes. Because of the limited ability of chondrocytes to regenerate, articular cartilage deteriorates leading to the clinical symptoms including severe pain and decreased mobility. No treatments effectively block the progression of OA. We propose that direct modulation of chondrocyte apoptosis is a key variable in the etiology of OA, and therapies aimed at preventing this important step represent a new class of regenerative medicine targets. PMID:27505251

  19. Biogenic acidification reduces sea urchin gonad growth and increases susceptibility of aquaculture to ocean acidification.

    PubMed

    Mos, Benjamin; Byrne, Maria; Dworjanyn, Symon A

    2016-02-01

    Decreasing oceanic pH (ocean acidification) has emphasised the influence of carbonate chemistry on growth of calcifying marine organisms. However, calcifiers can also change carbonate chemistry of surrounding seawater through respiration and calcification, a potential limitation for aquaculture. This study examined how seawater exchange rate and stocking density of the sea urchin Tripneustes gratilla that were reproductively mature affected carbonate system parameters of their culture water, which in turn influenced growth, gonad production and gonad condition. Growth, relative spine length, gonad production and consumption rates were reduced by up to 67% by increased density (9-43 individuals.m(-2)) and reduced exchange rates (3.0-0.3 exchanges.hr(-1)), but survival and food conversion efficiency were unaffected. Analysis of the influence of seawater parameters indicated that reduced pH and calcite saturation state (ΩCa) were the primary factors limiting gonad production and growth. Uptake of bicarbonate and release of respiratory CO2 by T. gratilla changed the carbonate chemistry of surrounding water. Importantly total alkalinity (AT) was reduced, likely due to calcification by the urchins. Low AT limits the capacity of culture water to buffer against acidification. Direct management to counter biogenic acidification will be required to maintain productivity and reproductive output of marine calcifiers, especially as the ocean carbonate system is altered by climate driven ocean acidification. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Cerebral amyloid angiopathy increases susceptibility to infarction after focal cerebral ischemia in Tg2576 mice.

    PubMed

    Milner, Eric; Zhou, Meng-Liang; Johnson, Andrew W; Vellimana, Ananth K; Greenberg, Jacob K; Holtzman, David M; Han, Byung Hee; Zipfel, Gregory J

    2014-10-01

    We and others have shown that soluble amyloid β-peptide (Aβ) and cerebral amyloid angiopathy (CAA) cause significant cerebrovascular dysfunction in mutant amyloid precursor protein (APP) mice, and that these deficits are greater in aged APP mice having CAA compared with young APP mice lacking CAA. Amyloid β-peptide in young APP mice also increases infarction after focal cerebral ischemia, but the impact of CAA on ischemic brain injury is unknown. To determine this, we assessed cerebrovascular reactivity, cerebral blood flow (CBF), and extent of infarction and neurological deficits after transient middle cerebral artery occlusion in aged APP mice having extensive CAA versus young APP mice lacking CAA (and aged-matched littermate controls). We found that aged APP mice have more severe cerebrovascular dysfunction that is CAA dependent, have greater CBF compromise during and immediately after middle cerebral artery occlusion, and develop larger infarctions after middle cerebral artery occlusion. These data indicate CAA induces a more severe form of cerebrovascular dysfunction than amyloid β-peptide alone, leading to intra- and postischemic CBF deficits that ultimately exacerbate cerebral infarction. Our results shed mechanistic light on human studies identifying CAA as an independent risk factor for ischemic brain injury. © 2014 American Heart Association, Inc.

  1. Rapid growth results in increased susceptibility to predation in Menidia menidia.

    PubMed

    Munch, Stephan B; Conover, David O

    2003-09-01

    Several recent studies have demonstrated that rapid growth early in life leads to decreased physiological performance. Nearly all involved experiments over short time periods (<1 day) to control for potentially confounding effects of size. This approach, however, neglects the benefits an individual accrues by growing. The net effect of growth can only be evaluated over a longer interval in which rapidly growing individuals are allowed the time required to attain the expected benefits of large size. We used two populations of Menidia menidia with disparate intrinsic growth rates to address this issue. We compared growth and survivorship among populations subject to predation in mesocosms under ambient light and temperature conditions for a period of up to 30 days to address two questions: Do the growth rates of fish in these populations respond differently to the presence of predators? Is the previously demonstrated survival cost of growth counterbalanced by the benefits of increased size? We found that growth was insensitive to predation risk: neither population appeared to modify growth rates in response to predation levels. Moreover, the fast-growing population suffered significantly higher mortality throughout the trials despite being 40% larger than the slow-growing population at the experiment's end. These results confirm that the costs of rapid growth extend over prolonged intervals and are not ameliorated merely by the attainment of large size.

  2. Antisense-mediated depletion of tomato GDP-L-galactose phosphorylase increases susceptibility to chilling stress.

    PubMed

    Wang, Li-Yan; Li, Dong; Deng, Yong-Sheng; Lv, Wei; Meng, Qing-Wei

    2013-02-15

    The GDP-L-galactose phosphorylase (GGP), which converts GDP-l-galactose to l-Gal-1-phosphate, is generally considered to be a key enzyme of the major ascorbate biosynthesis pathways in higher plants, but experimental evidence for its role in tomato is lacking. In the present study, the GGP gene was isolated from tomato (Solanum lycopersicum) and transient expression of SlGGP-GFP (green fluorescent protein) fusion protein in onion cells revealed the cytoplasmic and nucleus localization of the protein. Antisense transgenic tomato lines with only 50-75% ascorbate level of the wild type (WT) were obtained. Chilling treatment induced lower increase in AsA levels and redox ratio of ascorbate in antisense transgenic plants compared with WT plants. Under chilling stress, transgenic plants accumulated more malendialdehyde (MDA) and more O(2)(·-), leaked more electrolytes and showed lower maximal photochemical efficiency of PSII (Fv/Fm), net photosynthetic rate (Pn), and oxidizable P700 compared with WT plants. Furthermore, the antisense transgenic plants exhibited significantly higher H(2)O(2) level and lower ascorbate peroxidase (APX) activity. Our results suggested that GGP plays an important role in protecting plants against chilling stress by maintaining ascorbate pool and ascorbate redox state.

  3. Indomethacin increases susceptibility to injury in human gastric cells independent of PG synthesis inhibition.

    PubMed

    Kokoska, E R; Smith, G S; Deshpande, Y; Wolff, A B; Miller, T A

    1998-10-01

    Indomethacin and other nonsteroidal anti-inflammatory drugs are commonly used to indirectly deduce the possible role of PGs in a process being studied. The objective of this study was to determine if indomethacin, at concentrations comparable to plasma and tissue levels obtained in humans taking therapeutic doses, predisposes human gastric cells to injury through inhibition of PGs or acts through an alternate mechanism. The role of intracellular Ca2+ in this damaging process was also assessed. Indomethacin pretreatment, although by itself nondamaging, was associated with elevated intracellular Ca2+ concentrations and an increased cellular permeability, an effect that was dependent on extracellular Ca2+. Furthermore, indomethacin pretreatment significantly predisposed AGS cells to injury induced by two dissimilar agents (deoxycholate and A-23187), both of which are associated with intracellular Ca2+ accumulation. The addition of exogenous PGs did not reverse the predisposition to injury induced by indomethacin. The observed effects of indomethacin were dependent on concentration and not on ability to inhibit PG synthesis. Similar effects were not observed with equipotent concentrations of ibuprofen or aspirin. Finally, the exacerbation of deoxycholate-induced injury induced by indomethacin was not observed when extracellular Ca2+ was removed. Indomethacin, by disturbing intracellular Ca2+ homeostasis, predisposes human gastric cells to injury through mechanisms independent of PG synthesis. The current study suggests that data resulting from studies employing only indomethacin as a PG synthesis inhibitor should be interpreted with caution.

  4. Standardization of a bottle assay--an indigenous method for laboratory and field monitoring of insecticide resistance and comparison with WHO adult susceptibility test.

    PubMed

    Elamathi, N; Barik, Tapan Kumar; Verma, Vaishali; Velamuri, Poonam Sharma; Bhatt, R M; Sharma, S K; Raghavendra, Kamaraju

    2014-10-01

    The WHO adult susceptibility test is in use for insecticide resistance monitoring. Presently, materials are being imported from the Universiti Sains Malaysia, Malaysia and sometimes it is cost prohibitive. As an alternative, we present here a method of bottle bioassay using indigenous material. Different aspects related to the assay were studied and validated in the field. Bottle assay was standardized in the laboratory by using locally sourced material and laboratory-maintained insecticide-susceptible Anopheles stephensi and Aedes aegypti strains against technical grade deltamethrin and cyfluthrin insecticides dissolved in ethanol in a range of different concentrations. The frequency of use of the deltamethrin-coated bottles and shelf-life were determined. Discriminating dose for deltamethrin and cyfluthrin was 10 μg against An. stephensi and 2 μg against Ae. aegypti females. Insecticide-coated bottles stored at 25 to 35 °C can be used for three exposures within 7 days of coating. The study carried out in the laboratory was validated on wild caught An. culicifacies in the states of Odisha and Chhattisgarh against deltamethrin-coated bottles in comparison to WHO adult susceptibility test. Results of the study indicated that deltamethrin-coated bottles were effective up to three exposures within 7 days of coating for field population and 100% mortality was recorded within 35 min as observed in laboratory studies for field collected susceptible population. Also in the WHO adult susceptibility test, 100% knock-down within 35 min and 100% mortality after 24 h holding period were observed in susceptible population, while in it was 50% knock-down in 1 h and 64% mortality after 24 h holding period for resistant population (50% mortality in bottle assay in 60 min). The bottle assay can be used as an alternative to the WHO adult susceptibility test both in the laboratory and field for monitoring insecticide resistance in mosquito vectors using locally sourced material.

  5. Blunted dynamics of adenosine A2A receptors is associated with increased susceptibility to Candida albicans infection in the elderly

    PubMed Central

    Rodrigues, Lisa; Miranda, Isabel M.; Andrade, Geanne M.; Mota, Marta; Cortes, Luísa; Rodrigues, Acácio G.; Cunha, Rodrigo A.; Gonçalves, Teresa

    2016-01-01

    Opportunistic gut infections and chronic inflammation, in particular due to overgrowth of Candida albicans present in the gut microbiota, are increasingly reported in the elder population. In aged, adult and young mice, we now compared the relative intestinal over-colonization by ingested C. albicans and their translocation to other organs, focusing on the role of adenosine A2A receptors that are a main stop signal of inflammation. We report that elderly mice are more prone to over-colonization by C. albicans than adult and young mice. This fungal over-growth seems to be related with higher growth rate in intestinal lumen, independent of gut tissues invasion, but resulting in higher GI tract inflammation. We observed a particularly high colonization of the stomach, with increased rate of yeast-to-hypha transition in aged mice. We found a correlation between A2A receptor density and tissue damage due to yeast infection: comparing with young and adults, aged mice have a lower gut A2A receptor density and C. albicans infection failed to increase it. In conclusion, this study shows that aged mice have a lower ability to cope with inflammation due to C. albicans over-colonization, associated with an inability to adaptively adjust adenosine A2A receptors density. PMID:27590517

  6. GSTM1 Gene Polymorphism is Implicated in Increased Susceptibility to Prostate Cancer in Caucasians and Asians.

    PubMed

    Wang, Zhong-Yang; Li, Hong-Yan; Jiang, Zongpei; Zhou, Tian-Biao; Drummen, Gregor P C

    2016-12-01

    Published reports on the relationship between GSTM1 gene polymorphisms and prostate cancer risk are heterogeneous in their conclusions, and the significance of these polymorphisms is still debated. This meta-analysis was performed to attempt to combine comparable studies, thereby increasing sample size and statistical significance in order to obtain a better evaluation of the association between GSTM1 polymorphisms and prostate cancer risk. The association investigations were identified from PubMed, Cochrane Library, and China Biological Medicine Database on March 1, 2014. Forty-three reports were recruited into this meta-analysis that contained data from 6741 patients and 9053 controls. There was a marked association between the GSTM1 null genotype and prostate cancer risk in the overall population (odds ratio = 1.39, 95% confidence interval: 1.21-1.60, P <00001), caucasians (odds ratio = 1.48, 95% confidence interval: 1.23-1.79, P <0001) and Asians (odds ratio = 1.62, 95% confidence interval: 1.16-2.27, P = .005). However, the GSTM1 null genotype was not associated with prostate cancer risk in Africans (odds ratio = 0.77, 95% confidence interval: 0.53-1.13, P = 0.19) and African Americans (odds ratio = 1.00, 95% confidence interval: 0.69-1.45, P = 0.99). In conclusion, GSTM1 null genotype was a risk factor to predict the prostate cancer risk in the overall population, Caucasians, and Asians. Although compelling, limitations inherent to meta-analysis, study design of the individual studies, and most importantly, possible gene-gene and gene-environment interactions, as well as the potential involvement of glutathione S-transferases in multiple cellular processes make drawing definite conclusions difficult. © The Author(s) 2015.

  7. Nontraditional Student Engagement: Increasing Adult Student Success and Retention

    ERIC Educational Resources Information Center

    Wyatt, Linda G.

    2011-01-01

    Today, more than any other time in history, student demographics of college and university students in the United States are experiencing rapid and profound changes. Along with these increases in nontraditional student enrollment comes an increasing percentage of working nontraditional college students with a multitude of commitments that serve to…

  8. Chronic administration of nandrolone increases susceptibility to morphine dependence without correlation with LVV-hemorphin 7 in rats.

    PubMed

    Huang, Eagle Yi-Kung; Chen, Yuan-Hao; Huang, Tzu-Ying; Chen, Ying-Jie; Chow, Lok-Hi

    2016-10-01

    LVV-hemorphin 7 (LVVYPWTQRF; LVV-H7), an N-terminal fragment of the β-chain of hemoglobin cleaved by cathepsin D/pepsin, is an atypical endogenous opioid peptide that is found in high concentration in blood. LVV-H7 acts as a μ-opioid agonist and an inhibitor of insulin-regulated aminopeptidase. Subchronic administration of anabolic androgenic steroids (AAS) has been clinically proven to induce the synthesis of erythrocytes and increase hemoglobin concentrations. Patients with a history of AAS abuse are more susceptible to opioid abuse. We hypothesized that this association could be at least partially attributed to the sensitization of the mesocorticolimbic dopaminergic pathway by LVV-H7. Using the conditioned place preference test and neurochemical analysis, we investigated the possible mechanism underlying the effect of chronic nandrolone administration on morphine-induced reward and its correlation with LVV-H7 in rats. Either LVV-H7 may not sensitize the rewarding neural circuits or its inhibition on locomotor activity could mask reward-related behaviors. Chronic nandrolone pretreatment indeed caused a significant reward by low dose morphine, which did not cause any reward in control rats. However, coadministration of anti-LVV-H7 antiserum with nandrolone did not block this effect. This may rule out the possibility of the involvement of LVV-H7 in the action of nandrolone to intensify morphine-induced reward. Moreover, the serum level of LVV-H7 was mildly increased in response to chronic nandrolone administration in our animal model. According to the current clinical observations, we may conclude that the chronic administration of nandrolone can increase susceptibility to morphine dependence, but that this effect is not related to elevated LVV-H7. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Aging increases the susceptivity of MSCs to reactive oxygen species and impairs their therapeutic potency for myocardial infarction.

    PubMed

    Li, Liang; Guo, Yingfei; Zhai, Hongxia; Yin, Yaxin; Zhang, Jinjin; Chen, Haiwei; Wang, Lei; Li, Na; Liu, Runmei; Xia, Yunfeng

    2014-01-01

    Myocardial infarction (MI) is one of the leading causes of death worldwide and Mesenchymal Stem Cells (MSCs) transplantation has been considered a promising therapy. Recently, it was reported that the therapeutic effectiveness of MSCs is dependent on the age of the donor, yet the underlying mechanism has not been thoroughly investigated. This study was designed to investigate whether this impaired therapeutic potency is caused by an increased susceptivity of MSCs from old donors to reactive oxygen species (ROS). The MSCs were isolated from the subcutaneous inguinal region of young (8-10 weeks) and old (18 months) Sprague-Dawley (SD) rats. By exposing these MSCs to H2O2, we found that the adhesion of MSCs from old donors was damaged more severely. Specifically, decreased expression of integrin and reduced phosphorylation of focal adhesion kinase Src and FAK were observed. Furthemore, H2O2 triggered an increased apoptosis of MSCs from old donors. To study the viability and therapeutic potency of MSCs from young and old donors in vivo, these MSCs were transplanted into acute MI model rats. We observed a more rapidly decreased survival rate of the old MSCs in the infarct region, which may be caused by their increased susceptivity to the micro-environmental ROS, as transplantation of the old MSCs with N-acetyl-L-cysteine (NAC), a ROS scavenger, protected them. The low viability of engrafted old MSCs consequently impaired their therapeutic effectiveness, judging by the histology and function of heart. Our study may help to understand the mechanism of MSCs-host interaction during MI, as well as shed light on the design of therapeutic strategy in clinic.

  10. Voluntary wheel running attenuates ethanol withdrawal-induced increases in seizure susceptibility in male and female rats.

    PubMed

    Devaud, Leslie L; Walls, Shawn A; McCulley, Walter D; Rosenwasser, Alan M

    2012-11-01

    We recently found that voluntary wheel running attenuated ethanol withdrawal-induced increased susceptibility to chemoconvulsant-induced seizures in male rats. Since female rats recover from ethanol withdrawal (EW) more quickly than male rats across several behavioral measures, this study was designed to determine whether the effects of exercise on EW seizures also exhibited sex differences. Animals were maintained under no-wheel, locked-wheel or free-wheel conditions and ethanol was administered by liquid diet for 14 days with control animals pair-fed an isocaloric diet, after which seizure thresholds were determined at 1 day or 3 days of EW. Consistent with previous reports, females ran significantly more than males, regardless of diet condition. Introduction of the ethanol-containing liquid diet dramatically increased running for females during the day (rest) phase, with little impact on night phase activity. Consistent with previous reports, EW increased seizure susceptibility at 1 day in non-exercising males and females and at 3 days in males. These effects were attenuated by access to running wheels in both sexes. We also assessed the effects of sex, ethanol diet and exercise on ethanol clearance following an acute ethanol administration at 1 day EW in a separate set of animals. Blood ethanol concentrations at 30 min post-injection were lower in males, ethanol-exposed animals, and runners, but no interactions among these factors were detected. Interestingly, females displayed more rapid ethanol clearance than males and there were no effects of either diet or wheel access on clearance rates. Taken together, these data suggest that voluntary wheel running during ethanol administration provides protective effects against EW seizures in both males and females. This effect may be mediated, in part, in male, but not in female rat, by effects of exercise on early pharmacokinetic contributions. This supports the idea that encouraging alcoholics to exercise may

  11. Potassium permanganate elicits a shift of the external fish microbiome and increases host susceptibility to columnaris disease.

    PubMed

    Mohammed, Haitham H; Arias, Covadonga R

    2015-07-15

    The external microbiome of fish is thought to benefit the host by hindering the invasion of opportunistic pathogens and/or stimulating the immune system. Disruption of those microbial communities could increase susceptibility to diseases. Traditional aquaculture practices include the use of potent surface-acting disinfectants such as potassium permanganate (PP, KMnO4) to treat external infections. This study evaluated the effect of PP on the external microbiome of channel catfish and investigated if dysbiosis leads to an increase in disease susceptibility. Columnaris disease, caused by Flavobacterium columnare, was used as disease model. Four treatments were compared in the study: (I) negative control (not treated with PP nor challenged with F. columnare), (II) treated but not challenged, (III) not treated but challenged, and (IV) treated and challenged. Ribosomal intergenic spacer analysis (RISA) and pyrosequencing were used to analyze changes in the external microbiome during the experiment. Exposure to PP significantly disturbed the external microbiomes and increased catfish mortality following the experimental challenge. Analysis of similarities of RISA profiles showed statistically significant changes in the skin and gill microbiomes based on treatment and sampling time. Characterization of the microbiomes using 16S rRNA gene pyrosequencing confirmed the disruption of the skin microbiome by PP at different phylogenetic levels. Loss of diversity occurred during the study, even in the control group, but was more noticeable in fish subjected to PP than in those challenged with F. columnare. Fish treated with PP and challenged with the pathogen exhibited the least diverse microbiome at the end of the study.

  12. Brain pericytes from stress-susceptible pigs increase blood-brain barrier permeability in vitro

    PubMed Central

    2012-01-01

    Background The function of pericytes remains questionable but with improved cultured technique and the use of genetically modified animals, it has become increasingly clear that pericytes are an integral part of blood–brain barrier (BBB) function, and the involvement of pericyte dysfunction in certain cerebrovascular diseases is now emerging. The porcine stress syndrome (PSS) is the only confirmed, homologous model of malignant hyperthermia (MH) in veterinary medicine. Affected animals can experience upon slaughter a range of symptoms, including skeletal muscle rigidity, metabolic acidosis, tachycardia and fever, similar to the human syndrome. Symptoms are due to an enhanced calcium release from intracellular stores. These conditions are associated with a point mutation in ryr1/hal gene, encoding the ryanodine receptor, a calcium channel. Important blood vessel wall muscle modifications have been described in PSS, but potential brain vessel changes have never been documented in this syndrome. Methods In the present work, histological and ultrastructural analyses of brain capillaries from wild type and ryr1 mutated pigs were conducted to investigate the potential impairment of pericytes, in this pathology. In addition, brain pericytes were isolated from the three porcine genotypes (wild-type NN pigs; Nn and nn pigs, bearing one or two (n) mutant ryr1/hal alleles, respectively), and tested in vitro for their influence on the permeability of BBB endothelial monolayers. Results Enlarged perivascular spaces were observed in ryr1-mutant samples, corresponding to a partial or total detachment of the astrocytic endfeet. These spaces were electron lucent and sometimes filled with lipid deposits and swollen astrocytic feet. At the ultrastructural level, brain pericytes did not seem to be affected because they showed regular morphology and characteristics, so we aimed to check their ability to maintain BBB properties in vitro. Our results indicated that pericytes from the

  13. Conditional Expression of the Androgen Receptor Increases Susceptibility of Bladder Cancer in Mice

    PubMed Central

    Luong, Richard; Yu, Eun-Jeong; He, Yongfeng; Gonzalgo, Mark L.; Sun, Zijie

    2016-01-01

    Bladder cancer represents a significant human tumor burden, accounting for about 7.7% and 2.4% of all cancer cases in males and females, respectively. While men have a higher risk of developing bladder cancer, women tend to present at a later stage of disease and with more aggressive tumors. Previous studies have suggested a promotional role of androgen signaling in enhancing bladder cancer development. To directly assess the role of androgens in bladder tumorigenesis, we have developed a novel transgenic mouse strain, R26hARLoxP/+:Upk3aGCE/+, in which the human AR transgene is conditionally expressed in bladder urothelium. Intriguingly, both male and female R26hARLoxP/+:Upk3aGCE/+ mice display a higher incidence of urothelial cell carcinoma (UCC) than the age and sex matched control littermates in response to the carcinogen, N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). We detect expression of the human AR transgene in CK5-positive and p63-positive basal cells in bladder urothelium. Further analyses of UCC tissues from R26hARLoxP/+:Upk3aGCE/+ mice showed that the majority of tumor cells are of urothelial basal cell origin. Positive immunostaining of transgenic AR protein was observed in the majority of tumor cells of the transgenic mice, providing a link between transgenic AR expression and oncogenic transformation. We observed an increase in Ki67 positive cells within the UCC lesions of transgenic AR mice. Manipulating endogenous androgen levels by castration and androgen supplementation directly affected bladder tumor development in male and female R26hARLoxP/+:Upk3aGCE/+ mice, respectively. Taken together, our data demonstrate for the first time that conditional activation of transgenic AR expression in bladder urothelium enhances carciongen-induced bladder tumor formation in mice. This new AR transgenic mouse line mimics certain features of human bladder cancer and can be used to study bladder tumorigenesis and for drug development. PMID:26862755

  14. Increased activity in frontal motor cortex compensates impaired speech perception in older adults

    PubMed Central

    Du, Yi; Buchsbaum, Bradley R.; Grady, Cheryl L.; Alain, Claude

    2016-01-01

    Understanding speech in noisy environments is challenging, especially for seniors. Although evidence suggests that older adults increasingly recruit prefrontal cortices to offset reduced periphery and central auditory processing, the brain mechanisms underlying such compensation remain elusive. Here we show that relative to young adults, older adults show higher activation of frontal speech motor areas as measured by functional MRI during a syllable identification task at varying signal-to-noise ratios. This increased activity correlates with improved speech discrimination performance in older adults. Multivoxel pattern classification reveals that despite an overall phoneme dedifferentiation, older adults show greater specificity of phoneme representations in frontal articulatory regions than auditory regions. Moreover, older adults with stronger frontal activity have higher phoneme specificity in frontal and auditory regions. Thus, preserved phoneme specificity and upregulation of activity in speech motor regions provide a means of compensation in older adults for decoding impoverished speech representations in adverse listening conditions. PMID:27483187

  15. Increased seizure susceptibility and up-regulation of nNOS expression in hippocampus following recurrent early-life seizures in rats.

    PubMed

    Kim, Doo-Kwun

    2010-06-01

    This study aimed to determine the long-term change of seizure susceptibility and the role of nNOS on brain development following recurrent early-life seizures in rats. Video-EEG recordings were conducted between postnatal days 50 and 60. Alterations in seizure susceptibility were assayed on day 22 or 50 using the flurothyl method. Changes in nNOS expression were determined by quantitative immunoblotting on day 50. On average, rats had 8.4+/-2.7 seizures during 10 daily 1 hr behavioral monitoring sessions. As adults (days 50-60), all rats displayed interictal spikes in the hippocampus and/or overlying cortex. Brief electrographic seizures were recorded in only one of five animals. Rats appeared to progress from a period of marked seizure susceptibility (day 22) to one of lessened seizure susceptibility (day 50). Up-regulation of nNOS expression following early-life recurrent seizures was observed on day 50. In conclusion, these data suggested that recurrent early-life seizures had the long-term effects on seizure susceptibility late in life and up-regulatory nNOS expression on the hippocampus during brain development, and nNOS appeared to contribute to the persistent changes in seizure susceptibility, and epileptogenesis.

  16. Increased susceptibility of transgenic mice expressing human PrP to experimental sheep bovine spongiform encephalopathy is not due to increased agent titre in sheep brain tissue

    PubMed Central

    Plinston, Chris; Hart, Patricia; Hunter, Nora; Manson, Jean C.

    2014-01-01

    Bovine spongiform encephalopathy (BSE) in cattle and variant Creutzfeldt–Jakob disease in humans have previously been shown to be caused by the same strain of transmissible spongiform encephalopathy agent. It is hypothesized that the agent spread to humans following consumption of food products prepared from infected cattle. Despite evidence supporting zoonotic transmission, mouse models expressing human prion protein (HuTg) have consistently shown poor transmission rates when inoculated with cattle BSE. Higher rates of transmission have however been observed when these mice are exposed to BSE that has been experimentally transmitted through sheep or goats, indicating that humans may potentially be more susceptible to BSE from small ruminants. Here we demonstrate that increased transmissibility of small ruminant BSE to HuTg mice was not due to replication of higher levels of infectivity in sheep brain tissue, and is instead due to other specific changes in the infectious agent. PMID:24828334

  17. Increased susceptibility of transgenic mice expressing human PrP to experimental sheep bovine spongiform encephalopathy is not due to increased agent titre in sheep brain tissue.

    PubMed

    Plinston, Chris; Hart, Patricia; Hunter, Nora; Manson, Jean C; Barron, Rona M

    2014-08-01

    Bovine spongiform encephalopathy (BSE) in cattle and variant Creutzfeldt-Jakob disease in humans have previously been shown to be caused by the same strain of transmissible spongiform encephalopathy agent. It is hypothesized that the agent spread to humans following consumption of food products prepared from infected cattle. Despite evidence supporting zoonotic transmission, mouse models expressing human prion protein (HuTg) have consistently shown poor transmission rates when inoculated with cattle BSE. Higher rates of transmission have however been observed when these mice are exposed to BSE that has been experimentally transmitted through sheep or goats, indicating that humans may potentially be more susceptible to BSE from small ruminants. Here we demonstrate that increased transmissibility of small ruminant BSE to HuTg mice was not due to replication of higher levels of infectivity in sheep brain tissue, and is instead due to other specific changes in the infectious agent. © 2014 The Authors.

  18. Susceptibility of Ceraeochrysa cubana larvae and adults to six insect growth-regulator insecticides.

    PubMed

    Ono, Éric Kodi; Zanardi, Odimar Zanuzo; Aguiar Santos, Kenia Fernanda; Yamamoto, Pedro Takao

    2017-02-01

    The impacts of six insect growth-regulators were assessed on the predator Ceraeochrysa cubana (Hagen) larvae and adults. Our results showed that diflubenzuron, lufenuron and pyriproxyfen caused 100% larva mortality, whereas buprofezin, methoxyfenozide and tebufenozide were similar to control treatment. In comparison to the control, buprofezin prolonged the duration of larval stage, while methoxyfenozide and tebufenozide reduced the predator larva development time. Buprofezin, methoxyfenozide and tebufenozide did not affect the C. cubana duration and survival of pupal stage, fecundity and fertility. However, methoxyfenozide and tebufenozide reduced predator female and male longevities. Based on a reduction coefficient, diflubenzuron, lufenuron and pyriproxyfen were highly harmful to first instar larvae, while buprofezin, methoxyfenozide and tebufenozide were considered slightly harmful to the predator. Estimating the life table parameters, our results showed that buprofezin, methoxyfenozide and tebufenozide reduced the C. cubana Ro, r and λ. In comparison to the control, buprofezin prolonged the T and methoxyfenozide and tebufenozide shortened the predator T. In adults, our results showed that the insecticides did not cause significant mortality, but diflubenzuron, lufenuron and pyriproxyfen reduced the C. cubana fecundity and longevity. Diflubenzuron and lufenuron also reduced the C. cubana fertility. Based on a reduction coefficient, diflubenzuron and lufenuron were highly harmful to C. cubana adults, while pyriproxyfen was slightly harmful and buprofezin, methoxyfenozide and tebufenozide were considered harmless to the predator. Therefore, insect growth-regulators affect the C. cubana biological or populational parameters, and they can harm the integrated pest management programs that aim the predator conservation and/or augmentation in agroecosystems.

  19. Progressive resistance strength training and the related injuries in older adults: the susceptibility of the shoulder.

    PubMed

    Sousa, Nelson; Mendes, Romeu; Monteiro, Graça; Abrantes, Catarina

    2014-06-01

    The benefits of progressive resistance training (PRT) among the older adults are evident, especially in the prevention of sarcopenia and improving muscle strength, which reverse the age-related loss of functional ability. However, PRT carries some risk, particularly when participants are older adults with a certain degree of muscle weakness. The purpose of this article is to discuss the PRT-related injuries, and present an overview of documented shoulder injuries among the elderly, discerning possible mechanisms of injury and risk factors. A literature search was conducted in the PUBMED database to identify the relevant literature using combinations of keywords: strength-training injuries, resistance-training injuries, sports injuries in the elderly, shoulder complex, shoulder injury, and shoulder disorder. Acute and chronic injuries attributed to PRT have been cited in the epidemiological literature. The shoulder complex, has been alluded to as one of the most prevalent regions of injury, particularly in exercises that place the arm extended above the head and posterior to the trunk. However, the risk for injuries appears to be higher for testing than for training itself. One-repetition maximum strength testing may result in a greater injury risk. This technique, though acceptable, needs additional precautions in inexperience older adults to prevent injury. Thus, the best treatment for PRT age-related injuries is prevention. Appropriate and individualized training programs, the use of safe equipment, careful warming up and cooling down, correct range of motion, progressive intensity training, cardiovascular and musculoskeletal fitness are essential aspects of injury prevention among the elderly.

  20. Increased susceptibility of ethanol-treated gastric mucosa to naproxen and its inhibition by DA-9601, an Artemisia asiatica extract

    PubMed Central

    Oh, Tae Young; Ahn, Gook Jun; Choi, Seul Min; Ahn, Byoung Ok; Kim, Won Bae

    2005-01-01

    AIM: To examine the effect of DA-9601, a new gastroprotective agent, on the vulnerability of ethanol-treated rat’s stomach to naproxen (NAP). METHODS: Male Sprague-Dawley rats were pretreated with 1 mL of 50% ethanol twice a day for 5 d and then NAP (50 mg/kg) was administered. DA-9601 was administered 1 h before NAP. Four hours after NAP, the rats were killed to examine gross injury index (mm2), histologic change and to determine mucosal levels of malondialdehyde (MDA), prostaglandin E2 (PGE2), glutathione (GSH) and myeloperoxidase (MPO). RESULTS: Pretreatment of ethanol significantly increased NAP-induced gastric lesions, as well as an increase in MDA and MPO. On the contrary, mucosal PGE2 and GSH contents were decreased dramatically by ethanol pretreatment, which were aggravated by NAP. DA-9601 significantly reduced NAP-induced gastric injury grossly and microscopically, regardless of pretreatment with ethanol. DA-9601 preserved, or rather, increased mucosal PGE2 and GSH in NAP-treated rats (P<0.05), with reduction in mucosal MDA and MPO levels. CONCLUSION: These results suggest that repeated alcohol consumption renders gastric mucosa more susceptible to NSAIDs though, at least in part, reduction of endogenous cytoprotectants including PGE2 and GSH, and increase in MPO activation, and that DA-9601, a new gastroprotectant, can reduce the increased vulnerability of ethanol consumers to NSAIDs-induced gastric damage via the mechanism in which PGE2 and GSH are involved. PMID:16437715

  1. Overexpression of Transcription Factor Sp2 Inhibits Epidermal Differentiation and Increases Susceptibility to Wound and Carcinogen-Induced Tumorigenesis

    PubMed Central

    Kim, Tae-Hyung; Chiera, Shannon L.; Linder, Keith E.; Trempus, Carol S.; Smart, Robert C.; Horowitz, Jonathan M.

    2010-01-01

    Sp proteins are evolutionarily-conserved transcription factors required for the expression of a wide variety of genes that are critical for development and cell-cycle progression. De-regulated expression of certain Sp proteins is associated with the formation of a variety of human tumors, however direct evidence that any given Sp protein is oncogenic has been lacking. Here we report that Sp2 protein abundance in mice increases in concert with the progression of carcinogen-induced murine squamous cell carcinomas. Transgenic mice specifically overexpressing murine Sp2 in epidermal basal keratinocytes were highly susceptible to wound- and carcinogen-induced papillomagenesis. Transgenic animals that were homozygous rather than hemizygous for the Sp2 transgene exhibited a striking arrest in the epidermal differentiation program, perishing within two weeks of birth. Our results directly support the likelihood that Sp2 overexpression occurring in various human cancers has significant functional impact. PMID:20959487

  2. Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection.

    PubMed

    Theriot, Casey M; Koenigsknecht, Mark J; Carlson, Paul E; Hatton, Gabrielle E; Nelson, Adam M; Li, Bo; Huffnagle, Gary B; Z Li, Jun; Young, Vincent B

    2014-01-01

    Antibiotics can have significant and long-lasting effects on the gastrointestinal tract microbiota, reducing colonization resistance against pathogens including Clostridium difficile. Here we show that antibiotic treatment induces substantial changes in the gut microbial community and in the metabolome of mice susceptible to C. difficile infection. Levels of secondary bile acids, glucose, free fatty acids and dipeptides decrease, whereas those of primary bile acids and sugar alcohols increase, reflecting the modified metabolic activity of the altered gut microbiome. In vitro and ex vivo analyses demonstrate that C. difficile can exploit specific metabolites that become more abundant in the mouse gut after antibiotics, including the primary bile acid taurocholate for germination, and carbon sources such as mannitol, fructose, sorbitol, raffinose and stachyose for growth. Our results indicate that antibiotic-mediated alteration of the gut microbiome converts the global metabolic profile to one that favours C. difficile germination and growth.

  3. Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection

    PubMed Central

    Theriot, Casey M.; Koenigsknecht, Mark J.; Carlson, Paul E.; Hatton, Gabrielle E.; Nelson, Adam M.; Li, Bo; Huffnagle, Gary B.; Li, Jun; Young, Vincent B.

    2014-01-01

    Antibiotics can have significant and long lasting effects on the gastrointestinal tract microbiota, reducing colonization resistance against pathogens including Clostridium difficile. Here we show that antibiotic treatment induces substantial changes in the gut microbial community and in the metabolome of mice susceptible to C. difficile infection. Levels of secondary bile acids, glucose, free fatty acids, and dipeptides decrease, whereas those of primary bile acids and sugar alcohols increase, reflecting the modified metabolic activity of the altered gut microbiome. In vitro and ex vivo analyses demonstrate that C. difficile can exploit specific metabolites that become more abundant in the mouse gut after antibiotics, including primary bile acid taurocholate for germination, and carbon sources mannitol, fructose, sorbitol, raffinose and stachyose for growth. Our results indicate that antibiotic-mediated alteration of the gut microbiome converts the global metabolic profile to one that favors C. difficile germination and growth. PMID:24445449

  4. Aging increases the susceptibility of hepatic inflammation, liver fibrosis and aging in response to high-fat diet in mice.

    PubMed

    Kim, In Hee; Xu, Jun; Liu, Xiao; Koyama, Yukinori; Ma, Hsiao-Yen; Diggle, Karin; You, Young-Hyun; Schilling, Jan M; Jeste, Dilip; Sharma, Kumar; Brenner, David A; Kisseleva, Tatiana

    2016-08-01

    We aimed to investigate whether aging increases the susceptibility of hepatic and renal inflammation or fibrosis in response to high-fat diet (HFD) and explore the underlying genetic alterations. Middle (10 months old) and old (20 months old) aged, male C57BL/6N mice were fed either a low-fat diet (4 % fat) or HFD (60 % fat) for 4 months. Young (3 months old) aged mice were included as control group. HFD-induced liver and kidney injuries were analyzed by serum and urine assay, histologic staining, immunohistochemistry, and reverse-transcription real-time quantitative polymerase chain reaction. Total RNA sequencing with next-generation technology was done with RNA extracted from liver tissues. With HFD feeding, aged was associated with higher serum alanine aminotransferase levels, marked infiltration of hepatic macrophages, and increased expression of inflammatory cytokines (MCP1, TNF-α, IL-1β, IL-6, IL-12, IL-17A). Importantly, aged mice showed more advanced hepatic fibrosis and increased expression of fibrogenic markers (Col-I-α1, αSMA, TGF-β1, TGF-β2, TGFβRII, PDGF, PDGFRβII, TIMP1) in response to HFD. Aged mice fed on HFD also showed increased oxidative stress and TLR4 expression. In the total RNA seq and gene ontology analysis of liver, old-aged HFD group showed significant up-regulation of genes linked to innate immune response, immune response, defense response, inflammatory response compared to middle-aged HFD group. Meanwhile, aging and HFD feeding showed significant increase in glomerular size and mesangial area, higher urine albumin/creatinine ratio, and advanced renal inflammation or fibrosis. However, the difference of HFD-induced renal injury between old-aged group and middle-aged group was not significant. The susceptibility of hepatic fibrosis as well as hepatic inflammation in response to HFD was significantly increased with aging. In addition, aging was associated with glomerular alterations and increased renal inflammation or

  5. Increasing Participation of Adults in Higher Education: Factors for Successful Policies

    ERIC Educational Resources Information Center

    Broek, Simon; Hake, Barry J.

    2012-01-01

    This article contains an analysis of policies aimed at increasing the participation of adults in higher education (HE) in seven countries (NL, DK, SE, UK, BE Flanders, DE and the state of California in the USA). In order to maintain their economic competitiveness, many countries have developed policies to increase the participation of adults in…

  6. Low vagally-mediated heart rate variability and increased susceptibility to ventricular arrhythmias in rats bred for high anxiety.

    PubMed

    Carnevali, Luca; Trombini, Mimosa; Graiani, Gallia; Madeddu, Denise; Quaini, Federico; Landgraf, Rainer; Neumann, Inga D; Nalivaiko, Eugene; Sgoifo, Andrea

    2014-04-10

    In humans, there is a documented association between anxiety disorders and cardiovascular disease. Putative underlying mechanisms may include an impairment of the autonomic nervous system control of cardiac function. The primary objective of the present study was to characterize cardiac autonomic modulation and susceptibility to arrhythmias in genetic lines of rats that differ largely in their anxiety level. To reach this goal, electrocardiographic recordings were performed in high-anxiety behavior (HAB, n=10) and low-anxiety behavior (LAB, n=10) rats at rest, during stressful stimuli and under autonomic pharmacological manipulations, and analyzed by means of time- and frequency-domain indexes of heart rate variability. During resting conditions, HAB rats displayed a reduced heart rate variability, mostly in terms of lower parasympathetic (vagal) modulation compared to LAB rats. In HAB rats, this relatively low cardiac vagal control was associated with smaller heart rate responsiveness to acute stressors compared to LAB counterparts. In addition, beta-adrenergic pharmacological stimulation induced a larger incidence of ventricular tachyarrhythmias in HABs compared to LABs. At sacrifice, a moderate increase in heart-body weight ratio was observed in HAB rats. We conclude that high levels of anxiety-related behavior in rats are associated with signs of i) impaired autonomic modulation of heart rate (low vagally-mediated heart rate variability), ii) poor adaptive heart rate responsiveness to stressful stimuli, iii) increased arrhythmia susceptibility, and iv) cardiac hypertrophy. These results highlight the utility of the HAB/LAB model for investigating the mechanistic basis of the comorbidity between anxiety disorders and cardiovascular disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Mitochondrial Vulnerability and Increased Susceptibility to Nutrient-Induced Cytotoxicity in Fibroblasts from Leigh Syndrome French Canadian Patients

    PubMed Central

    Burelle, Yan; Thompson Legault, Julie; Boucher, Gabrielle; Morin, Charles; Coderre, Lise; Des Rosiers, Christine

    2015-01-01

    Mutations in LRPPRC are responsible for the French Canadian variant of Leigh Syndrome (LSFC), a severe disorder characterized biochemically by a tissue-specific deficiency of cytochrome c oxidase (COX) and clinically by the occurrence of severe and deadly acidotic crises. Factors that precipitate these crises remain unclear. To better understand the physiopathology and identify potential treatments, we performed a comprehensive analysis of mitochondrial function in LSFC and control fibroblasts. Furthermore, we have used this cell-based model to screen for conditions that promote premature cell death in LSFC cells and test the protective effect of ten interventions targeting well-defined aspects of mitochondrial function. We show that, despite maintaining normal ATP levels, LSFC fibroblasts present several mitochondrial functional abnormalities under normal baseline conditions, which likely impair their capacity to respond to stress. This includes mitochondrial network fragmentation, impaired oxidative phosphorylation capacity, lower membrane potential, increased sensitivity to Ca2+-induced permeability transition, but no changes in reactive oxygen species production. We also show that LSFC fibroblasts display enhanced susceptibility to cell death when exposed to palmitate, an effect that is potentiated by high lactate, while high glucose or acidosis alone or in combination were neutral. Furthermore, we demonstrate that compounds that are known to promote flux through the electron transport chain independent of phosphorylation (methylene blue, dinitrophenol), or modulate fatty acid (L-carnitine) or Krebs cycle metabolism (propionate) are protective, while antioxidants (idebenone, N-acetyl cysteine, resveratrol) exacerbate palmitate plus lactate-induced cell death. Collectively, beyond highlighting multiple alterations in mitochondrial function and increased susceptibility to nutrient-induced cytotoxicity in LSFC fibroblasts, these results raise questions about the

  8. Increased Tumor Necrosis Factor (TNF)-α and Its Promoter Polymorphisms Correlate with Disease Progression and Higher Susceptibility towards Vitiligo

    PubMed Central

    Laddha, Naresh C.; Dwivedi, Mitesh; Begum, Rasheedunnisa

    2012-01-01

    Abstract Tumor Necrosis Factor (TNF)-α, is a paracrine inhibitor of melanocytes, which plays a critical role in the pathogenesis of several autoimmune diseases including vitiligo, as abnormal immune responses have frequently been observed in vitiligo patients. Moreover, vitiligo patients show higher lesion levels of TNF-α. Genetic polymorphisms in the promoter region of TNF-α are involved in the regulation of its expression. The present study explores TNF-α promoter polymorphisms and correlates them with TNF-α transcript and protein levels in vitiligo patients and controls of Gujarat along with its effect on disease onset and progression. PCR-RFLP technique was used for genotyping of these polymorphisms in 977 vitiligo patients and 990 controls. TNF-α transcript and protein levels were measured by Real time PCR and ELISA respectively. The genotype and allele frequencies for the investigated polymorphisms were significantly associated with vitiligo patients. The study revealed significant increase in TNF-α transcript and protein levels in vitiligo patients compared to controls. In particular, haplotypes: AATCC, AACCT, AGTCT, GATCT, GATCC and AGCCT were found to increase the TNF-α levels in vitiligo patients. Analysis of TNF-α levels based on the gender and disease progression suggests that female patients and patients with active vitiligo had higher levels of TNF-α. Also, the TNF-α levels were high in patients with generalized vitiligo as compared to localized vitiligo. Age of onset analysis of the disease suggests that the haplotypes: AACAT, AACCT, AATCC and AATCT had a profound effect in the early onset of the disease. Moreover, the analysis suggests that female patients had an early onset of vitiligo. Overall, our results suggest that TNF-α promoter polymorphisms may be genetic risk factors for susceptibility and progression of the disease. The up-regulation of TNF-α transcript and protein levels in individuals with susceptible haplotypes advocates

  9. Altered T cell surface glycosylation in HIV-1 infection results in increased susceptibility to galectin-1-induced cell death.

    PubMed

    Lantéri, Marion; Giordanengo, Valérie; Hiraoka, Nobuyoshi; Fuzibet, Jean-Gabriel; Auberger, Patrick; Fukuda, Minoru; Baum, Linda G; Lefebvre, Jean-Claude

    2003-12-01

    The massive T cell death that occurs in HIV type 1 (HIV-1) infection contributes profoundly to the pathophysiology associated with AIDS. The mechanisms controlling cell death of both infected and uninfected T cells ("bystander" death) are not completely understood. We have shown that HIV-1 infection of T cells results in altered glycosylation of cell surface glycoproteins; specifically, it decreased sialylation and increased expression of core 2 O-glycans. Galectin-1 is an endogenous human lectin that recognizes these types of glycosylation changes and induces cell death of activated lymphocytes. Therefore we studied the possible contribution of galectin-1 in the pathophysiology of AIDS. O-glycan modifications were investigated on peripheral lymphocytes from AIDS patients. Oligosaccharides from CD43 and CD45 of CEM cells latently infected with HIV-1 were chemically analyzed. Consistent with our previous results, we show that HIV-1 infection results in accumulation of exposed lactosamine residues, oligosaccharides recognized by galectin-1 on cell surface glycoproteins. Both latently HIV-1-infected T cell lines and peripheral CD4 and CD8 T cells from AIDS patients exhibited exposed lactosamine residues and demonstrated marked susceptibility to galectin-1-induced cell death, in contrast to control cultures or cells from uninfected donors. The fraction of cells that died in response to galectin-1 exceeded the fraction of infected cells, indicating that death of uninfected cells occurred. Altered cell surface glycosylation of T cells during HIV-1 infection increases the susceptibility to galectin-1-induced cell death, and this death pathway can contribute to loss of both infected and uninfected T cells in AIDS.

  10. Prevalence of diphtheria and tetanus antibodies among adults in Singapore: a national serological study to identify most susceptible population groups.

    PubMed

    Ang, L W; James, L; Goh, K T

    2016-03-01

    In view of waning antitoxin titres over time after the last vaccine dose against diphtheria and tetanus, we determined the immunity levels in adults to identify most susceptible groups for protection in Singapore. Our study involved residual sera from 3293 adults aged 18-79 who had participated in a national health survey in 2010. IgG antibody levels were determined using commercial enzyme-linked immunosorbent assay. Overall, 92.0% (95% confidence interval [CI]: 91.1-92.9%) had at least basic protection against diphtheria (antibody levels ≥0.01 IU/ml), while 71.4% (95% CI: 69.8-72.9%) had at least short-term protection against tetanus (antibody levels >0.1 IU/ml). The seroprevalence declined significantly with age for both diseases; the drop was most marked in the 50- to 59-year age group for diphtheria and 60- to 69-year age group for tetanus. There was a significant difference in seroprevalence by residency for diphtheria (92.8% among Singapore citizens versus 87.1% among permanent residents; P = 0.001). The seroprevalence for tetanus was significantly higher among males (83.2%) than females (62.4%) (P < 0.0005). It may be of value to consider additional vaccination efforts to protect older adults at higher risk for exposure against diphtheria and tetanus, particularly those travelling to areas where diphtheria is endemic or epidemic. © The Author 2015. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. Irradiation of juvenile, but not adult, mammary gland increases stem cell self-renewal and estrogen receptor negative tumors.

    PubMed

    Tang, Jonathan; Fernandez-Garcia, Ignacio; Vijayakumar, Sangeetha; Martinez-Ruis, Haydeliz; Illa-Bochaca, Irineu; Nguyen, David H; Mao, Jian-Hua; Costes, Sylvain V; Barcellos-Hoff, Mary Helen

    2014-03-01

    Children exposed to ionizing radiation have a substantially greater breast cancer risk than adults; the mechanism for this strong age dependence is not known. Here we show that pubertal murine mammary glands exposed to sparsely or densely ionizing radiation exhibit enrichment of mammary stem cell and Notch pathways, increased mammary repopulating activity indicative of more stem cells, and propensity to develop estrogen receptor (ER) negative tumors thought to arise from stem cells. We developed a mammary lineage agent-based model (ABM) to evaluate cell inactivation, self-renewal, or dedifferentiation via epithelial-mesenchymal transition (EMT) as mechanisms by which radiation could increase stem cells. ABM rejected cell inactivation and predicted increased self-renewal would only affect juveniles while dedifferentiation could act in both juveniles and adults. To further test self-renewal versus dedifferentiation, we used the MCF10A human mammary epithelial cell line, which recapitulates ductal morphogenesis in humanized fat pads, undergoes EMT in response to radiation and transforming growth factor β (TGFβ) and contains rare stem-like cells that are Let-7c negative or express both basal and luminal cytokeratins. ABM simulation of population dynamics of double cytokeratin cells supported increased self-renewal in irradiated MCF10A treated with TGFβ. Radiation-induced Notch concomitant with TGFβ was necessary for increased self-renewal of Let-7c negative MCF10A cells but not for EMT, indicating that these are independent processes. Consistent with these data, irradiating adult mice did not increase mammary repopulating activity or ER-negative tumors. These studies suggest that irradiation during puberty transiently increases stem cell self-renewal, which increases susceptibility to developing ER-negative breast cancer.

  12. Longer genotypically-estimated leukocyte telomere length is associated with increased adult glioma risk.

    PubMed

    Walsh, Kyle M; Codd, Veryan; Rice, Terri; Nelson, Christopher P; Smirnov, Ivan V; McCoy, Lucie S; Hansen, Helen M; Elhauge, Edward; Ojha, Juhi; Francis, Stephen S; Madsen, Nils R; Bracci, Paige M; Pico, Alexander R; Molinaro, Annette M; Tihan, Tarik; Berger, Mitchel S; Chang, Susan M; Prados, Michael D; Jenkins, Robert B; Wiemels, Joseph L; Samani, Nilesh J; Wiencke, John K; Wrensch, Margaret R

    2015-12-15

    Telomere maintenance has emerged as an important molecular feature with impacts on adult glioma susceptibility and prognosis. Whether longer or shorter leukocyte telomere length (LTL) is associated with glioma risk remains elusive and is often confounded by the effects of age and patient treatment. We sought to determine if genotypically-estimated LTL is associated with glioma risk and if inherited single nucleotide polymorphisms (SNPs) that are associated with LTL are glioma risk factors. Using a Mendelian randomization approach, we assessed differences in genotypically-estimated relative LTL in two independent glioma case-control datasets from the UCSF Adult Glioma Study (652 patients and 3735 controls) and The Cancer Genome Atlas (478 non-overlapping patients and 2559 controls). LTL estimates were based on a weighted linear combination of subject genotype at eight SNPs, previously associated with LTL in the ENGAGE Consortium Telomere Project. Mean estimated LTL was 31bp (5.7%) longer in glioma patients than controls in discovery analyses (P = 7.82x10-8) and 27bp (5.0%) longer in glioma patients than controls in replication analyses (1.48x10-3). Glioma risk increased monotonically with each increasing septile of LTL (O.R.=1.12; P = 3.83x10-12). Four LTL-associated SNPs were significantly associated with glioma risk in pooled analyses, including those in the telomerase component genes TERC (O.R.=1.14; 95% C.I.=1.03-1.28) and TERT (O.R.=1.39; 95% C.I.=1.27-1.52), and those in the CST complex genes OBFC1 (O.R.=1.18; 95% C.I.=1.05-1.33) and CTC1 (O.R.=1.14; 95% C.I.=1.02-1.28). Future work is needed to characterize the role of the CST complex in gliomagenesis and further elucidate the complex balance between ageing, telomere length, and molecular carcinogenesis.