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Sample records for increases adult susceptibility

  1. Increased susceptibility to proactive interference in adults with dyslexia?

    PubMed

    Bogaerts, Louisa; Szmalec, Arnaud; Hachmann, Wibke M; Page, Mike P A; Woumans, Evy; Duyck, Wouter

    2015-01-01

    Recent findings show that people with dyslexia have an impairment in serial-order memory. Based on these findings, the present study aimed to test the hypothesis that people with dyslexia have difficulties dealing with proactive interference (PI) in recognition memory. A group of 25 adults with dyslexia and a group of matched controls were subjected to a 2-back recognition task, which required participants to indicate whether an item (mis)matched the item that had been presented 2 trials before. PI was elicited using lure trials in which the item matched the item in the 3-back position instead of the targeted 2-back position. Our results demonstrate that the introduction of lure trials affected 2-back recognition performance more severely in the dyslexic group than in the control group, suggesting greater difficulty in resisting PI in dyslexia.

  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. Silencing of Dok-7 in Adult Rat Muscle Increases Susceptibility to Passive Transfer Myasthenia Gravis.

    PubMed

    Gomez, Alejandro M; Stevens, Jo A A; Mané-Damas, Marina; Molenaar, Peter; Duimel, Hans; Verheyen, Fons; Cossins, Judith; Beeson, David; De Baets, Marc H; Losen, Mario; Martinez-Martinez, Pilar

    2016-10-01

    Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies that target proteins at the neuromuscular junction, primarily the acetylcholine receptor (AChR) and the muscle-specific kinase. Because downstream of kinase 7 (Dok-7) is essential for the full activation of muscle-specific kinase and consequently for dense clustering of AChRs, we hypothesized that reduced levels of Dok-7 increase the susceptibility to passive transfer MG. To test this hypothesis, Dok-7 expression was reduced by transfecting shRNA-coding plasmids into the tibialis anterior muscle of adult rats by in vivo electroporation. Subclinical MG was subsequently induced with a low dose of anti-AChR monoclonal antibody 35. Neuromuscular transmission was significantly impaired in Dok-7-siRNA-electroporated legs compared with the contralateral control legs, which correlated with a reduction of AChR protein levels at the neuromuscular junction (approximately 25%) in Dok-7-siRNA-electroporated muscles, compared with contralateral control muscles. These results suggest that a reduced expression of Dok-7 may play a role in the susceptibility to passive transfer MG, by rendering AChR clusters less resistant to the autoantibody attack. PMID:27658713

  4. Young adults with head and neck cancer express increased susceptibility to mutagen-induced chromosome damage

    SciTech Connect

    Schantz, S.P.; Hsu, T.C.; Ainslie, N.; Moser, R.P. )

    1989-12-15

    Factors that contribute to an increased prevalence of squamous cell carcinoma of the upper aerodigestive tract among young adults in the United States remain unknown. A potential etiologic factor may relate to a genetically controlled sensitivity to environmental carcinogens. This study, therefore, examined 20 young adult patients who had squamous cell carcinoma for mutagen-induced chromosome sensitivity. Lymphocytes from respective patients were cultured, exposed to the clastogen bleomycin, arrested during metaphase, and examined quantitatively for chromosome breakage. The young adult population with squamous cell carcinoma expressed a significantly increased number of bleomycin-induced chromosome breaks per cell. Furthermore, among the study patients, chromosome sensitivity was most apparent in the non-tobacco users and in patients less than 30 years of age. The expression of such chromosome fragility following mutagen exposure should be considered in epidemiologic studies that intend to define risk factors for development of head and neck cancer.

  5. 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

  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. 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…

  10. 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

  11. 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.

  12. Sex-specific increase in susceptibility to metabolic syndrome in adult offspring after prenatal ethanol exposure with post-weaning high-fat diet.

    PubMed

    He, Zheng; Li, Jing; Luo, Hanwen; Zhang, Li; Ma, Lu; Chen, Liaobin; Wang, Hui

    2015-12-03

    Prenatal ethanol exposure (PEE) is an established risk factor for intrauterine growth retardation. The present study was designed to determine whether PEE can increase the susceptibility of high-fat diet (HFD)-induced metabolic syndrome (MS) in adult offspring in a sex-specific manner, based on a generalized linear model analysis. Pregnant Wistar rats were administered ethanol (4 g/kg.d) from gestational day 11 until term delivery. All offspring were fed either a normal diet or a HFD after weaning and were sacrificed at postnatal week 20, and blood samples were collected. Results showed that PEE reduced serum adrenocorticotropic hormone (ACTH) and corticosterone levels but enhanced serum glucose, insulin, insulin resistant index (IRI), triglyceride and total cholesterol (TC) concentrations. Moreover, the analysis showed interactions among PEE, HFD and sex. In the PEE offspring, HFD aggravated the decrease in ACTH and corticosterone levels and further increased serum glucose, insulin, triglyceride and TC levels. The changes of serum ACTH, glucose and IRI levels in the female HFD rats were greater than those in the male HFD rats. Our findings suggest that PEE enhances the susceptibility to MS induced by HFD in a sex-specific manner, which might be primarily associated with the neuroendocrine metabolic programming by PEE.

  13. Sex-specific increase in susceptibility to metabolic syndrome in adult offspring after prenatal ethanol exposure with post-weaning high-fat diet

    PubMed Central

    He, Zheng; Li, Jing; Luo, Hanwen; Zhang, Li; Ma, Lu; Chen, Liaobin; Wang, Hui

    2015-01-01

    Prenatal ethanol exposure (PEE) is an established risk factor for intrauterine growth retardation. The present study was designed to determine whether PEE can increase the susceptibility of high-fat diet (HFD)-induced metabolic syndrome (MS) in adult offspring in a sex-specific manner, based on a generalized linear model analysis. Pregnant Wistar rats were administered ethanol (4 g/kg.d) from gestational day 11 until term delivery. All offspring were fed either a normal diet or a HFD after weaning and were sacrificed at postnatal week 20, and blood samples were collected. Results showed that PEE reduced serum adrenocorticotropic hormone (ACTH) and corticosterone levels but enhanced serum glucose, insulin, insulin resistant index (IRI), triglyceride and total cholesterol (TC) concentrations. Moreover, the analysis showed interactions among PEE, HFD and sex. In the PEE offspring, HFD aggravated the decrease in ACTH and corticosterone levels and further increased serum glucose, insulin, triglyceride and TC levels. The changes of serum ACTH, glucose and IRI levels in the female HFD rats were greater than those in the male HFD rats. Our findings suggest that PEE enhances the susceptibility to MS induced by HFD in a sex-specific manner, which might be primarily associated with the neuroendocrine metabolic programming by PEE. PMID:26631430

  14. Leukotriene C4 increases the susceptibility of adult mice to Shiga toxin-producing Escherichia coli infection.

    PubMed

    Cabrera, Gabriel; Fernández-Brando, Romina J; Mejías, María Pilar; Ramos, María Victoria; Abrey-Recalde, María Jimena; Vanzulli, Silvia; Vermeulen, Mónica; Palermo, Marina S

    2015-12-01

    Shiga toxin-producing Escherichia coli (STEC) is a food-borne pathogen that causes hemorrhagic colitis. Under some circumstances, Shiga toxin (Stx) produced within the intestinal tract enters the bloodstream, leading to systemic complications that may cause the potentially fatal hemolytic-uremic syndrome (HUS). Despite STEC human infection is characterized by acute inflammation of the colonic mucosa, little is known regarding the role of proinflammatory mediators like cysteine leukotrienes (cysLTs) in this pathology. Thus, the aim of this work was to analyze whether leukotriene C4 (LTC4) influences STEC pathogenesis in mice. We report that exogenous LTC4 pretreatment severely affected the outcome of STEC gastrointestinal infection. LTC4-pretreated (LTC4+) and STEC-infected (STEC+) mice showed an increased intestinal damage by histological studies, and a decreased survival compared to LTC4-non-pretreated (LTC4-) and STEC+ mice. LTC4+/STEC+ mice that died after the infection displayed neutrophilia and high urea levels, indicating that the cause of death was related to Stx2-toxicity. Despite the differences observed in the survival between LTC4+ and LTC4- mice after STEC infection, both groups showed the same survival after Stx2-intravenous inoculation. In addition, LTC4 pretreatment increased the permeability of mucosal intestinal barrier, as assessed by FITC-dextran absorption experiments. Altogether these results suggest that LTC4 detrimental effect on STEC infection is related to the increased passage of pathogenic factors to the bloodstream. Finally, we showed that STEC infection per se increases the endogenous LTC4 levels in the gut, suggesting that this inflammatory mediator plays a role in the pathogenicity of STEC infection in mice, mainly by disrupting the mucosal epithelial barrier.

  15. 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. PMID:25595182

  16. Correlates of susceptibility to scams in older adults without dementia.

    PubMed

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

    2014-01-01

    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 a five-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.

  17. 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

  18. 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

  19. 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. PMID:23350303

  20. 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.

  1. Exposure to automotive pollution increases plasma susceptibility to oxidation.

    PubMed

    Sharman, James E; Coombes, Jeff S; Geraghty, Dominic P; Fraser, David I

    2002-01-01

    Low-density lipoprotein oxidation is implicated in the development of atherosclerosis. Plasma susceptibility to oxidation may be used as a marker of low-density lipoprotein oxidation and thus predict atherosclerotic risk. In this study the authors investigated the relationship between plasma susceptibility to oxidation and exposure to automotive pollution in a group of automobile mechanics (n = 16) exposed to high levels of automotive pollution, vs. matched controls (n = 13). The authors induced plasma oxidation by a free radical initiator and they determined susceptibility to oxidation by (1) change in absorbance at 234 nm, (2) lag time to conjugated diene formation, and (3) linear slope of the oxidation curve. Mechanics had significantly higher values (mean +/- standard error) for change in absorbance (1.60 +/- 0.05 vs. 1.36 +/- 0.05; p < .002), and slope (1.6 x 10(-3) +/- 0.1 x 10(-3) vs. 1.3 x 10(-3) +/- 0.1 x 10(-3); p < .001), compared with controls. These results indicate that regular exposure to automotive pollutants increases plasma susceptibility to oxidation and may, in the long-term, increase the risk of developing atherosclerosis.

  2. Paternal care paradoxically increases offspring seizure susceptibility in the El mouse model of epilepsy.

    PubMed

    Orefice, Lauren L; Heinrichs, Stephen C

    2008-02-01

    The El mouse is a model of idiopathic epilepsy in which seizures emerge on Postnatal Days (PNDs) 80-90, although time to first seizure can be modified by experiential factors including handling during development and history of past seizures. This study tested the hypothesis that a significant increase in the amount of parental investment would impact seizure susceptibility in adult El offspring. The study used a single dam control, in which the litter was reared by a female biological parent, and a biparental experimental group, in which both biological parents reared the litter. Components of parental care and pup body weights were quantified on PNDs 2-21, and adult offspring were examined using a handling-induced seizure susceptibility (HISS) test on PNDs 80-90 to assess the long-term impact of alterations in the perinatal environment. As expected, presence of both parents did increase parental/pup contact time by 350% relative to single-mother parenting and also reduced body weight, an index of perinatal stressor exposure, in already underweight El offspring. Accordingly, HISS testing of adult El offspring revealed a deleterious effect of biparental rearing, which increased seizure incidence to 30% relative to 0% for the single dam condition. These results suggest that the presence of a second care provider in addition to the dam constitutes a form of stressor exposure in El pups and, as a consequence, reduces the time to first seizure in genetically susceptible offspring.

  3. 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.

  4. Arginine depletion increases susceptibility to serious infections in preterm newborns

    PubMed Central

    Badurdeen, Shiraz; Mulongo, Musa; Berkley, James A.

    2015-01-01

    Preterm newborns are highly susceptible to bacterial infections. This susceptibility is regarded as being due to immaturity of multiple pathways of the immune system. However, it is unclear whether a mechanism that unifies these different, suppressed pathways exists. Here, we argue that the immune vulnerability of the preterm neonate is critically related to arginine depletion. Arginine, a “conditionally essential” amino acid, is depleted in acute catabolic states, including sepsis. Its metabolism is highly compartmentalized and regulated, including by arginase-mediated hydrolysis. Recent data suggest that arginase II-mediated arginine depletion is essential for the innate immune suppression that occurs in newborn models of bacterial challenge, impairing pathways critical for the immune response. Evidence that arginine depletion mediates protection from immune activation during first gut colonization suggests a regulatory role in controlling gut-derived pathogens. Clinical studies show that plasma arginine is depleted during sepsis. In keeping with animal studies, small clinical trials of L-arginine supplementation have shown benefit in reducing necrotizing enterocolitis in premature neonates. We propose a novel, broader hypothesis that arginine depletion during bacterial challenge is a key factor limiting the neonate's ability to mount an adequate immune response, contributing to the increased susceptibility to infections, particularly with respect to gut-derived sepsis. PMID:25360828

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

    PubMed

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

    2015-08-01

    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.

  6. Cadmium exposure increases susceptibility to testicular autoimmunity in mice.

    PubMed

    Ogawa, Yuki; Itoh, Masahiro; Hirai, Shuichi; Suna, Shigeru; Naito, Munekazu; Qu, Ning; Terayama, Hayato; Ikeda, Ayumi; Miyaso, Hidenobu; Matsuno, Yoshiharu; Komiyama, Masatoshi; Mori, Chisato

    2013-07-01

    Cadmium, one of various environmental toxicants, is known to suppress systemic immunity and to injure the testicular capillary endothelia with resultant necrosis of testicular tissues in mice and rats treated with high doses. Recently, it also became evident that cadmium can affect the integrity of the blood-testis barrier (BTB), the endocrine function of Leydig cells, apoptosis of germ cells and systemic immunity, even on treatment with a low dose that does not induce spermatogenic disturbance. Experimental autoimmune orchitis (EAO), i.e., an organ-specific autoimmunity of the testis, can be induced by repeated immunization with testicular antigens, and its pathology is characterized by lymphocytic inflammation and spermatogenic disturbance. In the present study, we investigated the morphological and functional changes of testes in mice treated with a low dose of cadmium chloride (CdCl2 ) and also examined its toxicity as to susceptibility to EAO. The results showed that exposure to 3 mg CdCl2 kg(-1) body weight did not affect the spermatogenic state. However, the BTB at the tubuli recti and the rete testis, but not the seminiferous tubules, was slightly weakened, and intra-testicular mRNA expression of interleukin (IL)-6, tumor necrosis factor-α and IL-1β was significantly increased by the CdCl2 treatment. Furthermore, immunization with testicular antigens after the CdCl2 exposure significantly augmented the EAO severity. Therefore, exposure to a low dose of CdCl2 induces no significant disturbance of spermatogenesis, however, it does change the immunological microcircumstances in the testis, resulting in increased susceptibility to testicular autoimmunity. PMID:22271428

  7. Inhibition or knockdown of ABC transporters enhances susceptibility of adult and juvenile schistosomes to Praziquantel.

    PubMed

    Kasinathan, Ravi S; Sharma, Lalit Kumar; Cunningham, Charles; Webb, Thomas R; Greenberg, Robert M

    2014-10-01

    Parasitic flatworms of the genus Schistosoma cause schistosomiasis, a neglected tropical disease that affects hundreds of millions. Treatment of schistosomiasis depends almost entirely on the drug praziquantel (PZQ). Though essential to treating and controlling schistosomiasis, a major limitation of PZQ is that it is not active against immature mammalian-stage schistosomes. Furthermore, there are reports of field isolates with heritable reductions in PZQ susceptibility, and researchers have selected for PZQ-resistant schistosomes in the laboratory. P-glycoprotein (Pgp; ABCB1) and other ATP binding cassette (ABC) transporters remove a wide variety of toxins and xenobiotics from cells, and have been implicated in multidrug resistance (MDR). Changes in ABC transporter structure or expression levels are also associated with reduced drug susceptibility in parasitic helminths, including schistosomes. Here, we show that the activity of PZQ against schistosome adults and juveniles ex vivo is potentiated by co-administration of either the highly potent Pgp inhibitor tariquidar or combinations of inhibitors targeting multiple ABC multidrug transporters. Adult worms exposed to sublethal PZQ concentrations remain active, but co-administration of ABC transporter inhibitors results in complete loss of motility and disruption of the tegument. Notably, juvenile schistosomes (3-4 weeks post infection), normally refractory to 2 µM PZQ, become paralyzed when transporter inhibitors are added in combination with the PZQ. Experiments using the fluorescent PZQ derivative (R)-PZQ-BODIPY are consistent with the transporter inhibitors increasing effective intraworm concentrations of PZQ. Adult worms in which expression of ABC transporters has been suppressed by RNA interference show increased responsiveness to PZQ and increased retention of (R)-PZQ-BODIPY consistent with an important role for these proteins in setting levels of PZQ susceptibility. These results indicate that parasite ABC

  8. 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

  9. 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.

  10. 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

  11. Alcohol exposure in utero increases susceptibility to prostate tumorigenesis in rat offspring

    PubMed Central

    Murugan, Sengottuvelan; Zhang, Changqing; Mojtahedzadeh, Sepideh; Sarkar, Dipak K.

    2013-01-01

    Background Prenatal alcohol exposure has been shown to increase offspring susceptibility to some chemical carcinogens. Whether prenatal exposure to alcohol makes the offspring more susceptible to the development of prostate cancer is not known. Therefore, we determined if any functional abnormalities and increased cancer susceptibility exist in the prostate of fetal alcohol exposed male rats during the adult period. Methods Pregnant rats were fed with a liquid diet containing alcohol (alcohol-fed), pair-fed with isocaloric liquid diet (pair-fed), or ad libitum fed with rat chow (ad lib-fed). Male offspring of these rats were given N-Nitroso-N-methylurea and testosterone to induce prostate neoplasia or left untreated. Around 6 to 8 months of age, the prostate of these animals were processed for determination of biochemical changes and histopathologies. Results Prostates of non-carcinogen treated animals which were alcohol exposed during the prenatal period demonstrated inflammatory cell infiltration and epithelial atypia and increased number of proliferative cells in the ventral lobe of this gland, but the prostate of control animal showed normal cytoarchitecture. In addition, prenatally alcohol-exposed rats showed decreased levels of cell-cell adhesion marker and increased estrogenic activity in the ventral prostate. Prenatally ethanol-exposed rats, when treated with carcinogen and testosterone, showed histological evidence for high-grade prostatic intraepithelial neoplasia primarily in the ventral prostate, whereas control animals showed only low-grade prostatic intraepithelial neoplasia. Prenatally ethanol-exposed rats treated with carcinogen and testosterone also showed increased number of proliferative cells and androgen receptor with concomitant decreased levels of tumor suppressor proteins in the ventral prostate. Conclusions These results suggest for the first time that prenatal ethanol exposures induces histophysiological changes in the prostate as well as

  12. 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.

  13. Caspase 9 promoter polymorphisms confer increased susceptibility to breast cancer.

    PubMed

    Theodoropoulos, George E; Michalopoulos, Nikolaos V; Pantou, Malena P; Kontogianni, Panagiota; Gazouli, Maria; Karantanos, Theodoros; Lymperi, Maria; Zografos, George C

    2012-10-01

    Caspases (CASPs), play a crucial role in the development and progression of cancer. We evaluated the association between two polymorphisms (rs4645978 and rs4645981) of the CASP9 gene and the risk of breast cancer (BC). Genotypes and allelic frequencies for the two polymorphisms were determined in 261 patients with breast cancer and 480 healthy controls. Polymerase chain reaction-restriction fragment length polymorphisms were used, and statistical significance was determined by the χ(2) test. Carriers of the rs4645978G allele (AG and GG genotypes) were at higher risk for BC than individuals with other genotypes (odds ratio (OR) 1.59, 95% confidence interval (CI) 1.07-2.37, P = 0.022). The rs4645978GG genotype, in particular, was associated with the highest risk for BC development (OR 2.25, 95% CI 1.45-3.49, P = 0.0003). Similarly, individuals with at least one rs4645981T allele were at a significantly increased risk of developing BC compared with those harboring the CC genotype (OR 2.75, 95% CI 1.99-3.78, P < 0.0001), and the risk of BC increased with increasing numbers of rs4645981T alleles (OR 2.66, 95% CI 1.91-3.69, P < 0.0001 for the CT genotype; OR 3.95, 95% CI 1.58-9.88, P = 0.004 for the TT genotype). The CASP9 promoter polymorphisms rs4645978 and rs4645981 are associated with BC susceptibility and suggest that CASP9 transcriptional regulation is an important factor during BC development.

  14. Nandrolone Plus Moderate Exercise Increases the Susceptibility to Lethal Arrhythmias

    PubMed Central

    Ghorbani Baravati, Hamideh; Joukar, Siyavash; Fathpour, Hossein; Kordestani, Zeinab

    2015-01-01

    Background: Until now, no experimental study has directly assessed the arrhythmogenesis of chronic consumption of anabolic androgenic steroids along with moderate-intensity endurance exercise. Objectives: We evaluated the influence of integration of anabolic androgenic steroids along with moderate-intensity endurance exercise on susceptibility to lethal ventricular arrhythmias in rat. Materials and Methods: The animal groups were as follows: control group (CTL); exercise group (EX) which were under 6 weeks of treadmill exercise; nandrolone group (Nan) which received 5 mg/kg of nandrolone decanoate twice a week; vehicle group (Arach) which received Arachis oil (solvent of nandrolone); trained vehicle group (Arach + Ex); and trained nandrolone group (Nan + Ex). One day after ending of the intervention period, arrhythmia was inducted by intravenous infusion of aconitine and ventricular arrhythmias were recorded. Then malondialdehyde (MDA) and glutathione peroxidase (GPX) of heart tissue were measured. Results: Nandrolone, exercise, and their combination were associated with heart hypertrophy. Exercise could prevent the incremental effect of nandrolone on MDA/GPX ratio. Chronic administration of nandrolone with moderate-intensity endurance exercise had no significant effect on blood pressure, heart rate, and basal electrocardiographic parameters. Combination of nandrolone and exercise significantly increased the incidence of ventricular fibrillation (VF) and reduced the VF latency (P < 0.05). Conclusions: The findings suggest that chronic coadministration of nandrolone with moderate-intensity endurance exercise facilitates the VF occurrence in rat. Complementary studies are needed to elucidate the involved mechanisms of this abnormality. PMID:26396972

  15. 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. PMID:27427119

  16. 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 ...

  17. 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 ...

  18. 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

  19. 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.

  20. 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

  1. Aging increases the susceptibility to develop anhedonia in male rats.

    PubMed

    Herrera-Pérez, J J; Martínez-Mota, L; Fernández-Guasti, A

    2008-12-12

    The objective of this study was to establish the effect of aging on the development of anhedonia, a core feature of depression. Young and old male Wistar rats (of around 3-5 and 12-15 months, respectively) were exposed to a chronic variable stress (CVS) schedule for 3 weeks. CVS produced anhedonia, indicated by a reduction in the intake of a sucrose solution (1%), in 8 out of 23 (35%) young rats and in 19 out of 26 (73%) old rats, implying that old animals are more susceptible to stress and develop anhedonia more readily than young animals. Young and old anhedonic rats showed a similar temporal course in the reduction of sucrose consumption, reaching the anhedonic state after 2 weeks of CVS exposure. Compared with young animals, old rats had lower basal serum testosterone and estradiol levels. The systemic levels of corticosterone did not vary between both age groups. No significant pathological condition was detected in old animals. It is suggested that the higher susceptibility to develop anhedonia in male rats could be associated to neuroendocrine changes consequent to aging.

  2. 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.

  3. Why aging leads to increased susceptibility to infection.

    PubMed

    Terpenning, M S; Bradley, S F

    1991-02-01

    The elderly are predisposed to various infections through a multitude of factors. Although intrinsic, unalterable defects occur in the aging immune system and nonspecific host defenses, there are factors that physician and patient can concentrate on to reduce the risk of infection. For example, meticulous attention to skin care can reduce the risk of soft tissue infection. Improvement in oral hygiene and relief of xerostomia might promote recolonization with normal oral flora. Correction of urinary tract obstruction where possible, relying on the use of indwelling urinary catheters only when necessary, can significantly reduce the risk of UTIs. Medications that impair cognitive function should be prescribed judiciously, since they can promote aspiration with subsequent pneumonia, xerostomia, and urinary retention. Correction of protein malnutrition may improve cell-mediated immunity and skin integrity, thereby reducing the risk of infection. The signs and symptoms of infection in the aged may be subtle. Therefore, the primary care physician should approach this susceptible population with a heightened clinical suspicion, thus expediting possibly life-saving early diagnosis and treatment. PMID:1991623

  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. 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

    2015-01-01

    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

  6. 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.

  7. 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

  8. 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. PMID:27033451

  9. Decline in Decreased Cephalosporin Susceptibility and Increase in Azithromycin Resistance in Neisseria gonorrhoeae, Canada

    PubMed Central

    Sawatzky, P.; Liu, G.; Allen, V; Lefebvre, B.; Hoang, L.; Drews, S.; Horsman, G.; Wylie, J.; Haldane, D.; Garceau, R.; Ratnam, S.; Wong, T.; Archibald, C.; Mulvey, M.R.

    2016-01-01

    Antimicrobial resistance profiles were determined for Neisseria gonorrhoeae strains isolated in Canada during 2010–2014. The proportion of isolates with decreased susceptibility to cephalosporins declined significantly between 2011 and 2014, whereas azithromycin resistance increased significantly during that period. Continued surveillance of antimicrobial drug susceptibilities is imperative to inform treatment guidelines. PMID:26689114

  10. Decline in Decreased Cephalosporin Susceptibility and Increase in Azithromycin Resistance in Neisseria gonorrhoeae, Canada.

    PubMed

    Martin, I; Sawatzky, P; Liu, G; Allen, V; Lefebvre, B; Hoang, L; Drews, S; Horsman, G; Wylie, J; Haldane, D; Garceau, R; Ratnam, S; Wong, T; Archibald, C; Mulvey, M R

    2016-01-01

    Antimicrobial resistance profiles were determined for Neisseria gonorrhoeae strains isolated in Canada during 2010-2014. The proportion of isolates with decreased susceptibility to cephalosporins declined significantly between 2011 and 2014, whereas azithromycin resistance increased significantly during that period. Continued surveillance of antimicrobial drug susceptibilities is imperative to inform treatment guidelines.

  11. Stem Cells as Hormone Targets That Lead to Increased Cancer Susceptibility

    PubMed Central

    Calderon-Gierszal, Esther L.; Hu, Wen-Yang

    2015-01-01

    Major advances during the past decade have permitted a clearer understanding of processes that regulate stem cell self-renewal and lineage commitment toward differentiated progeny that populate all tissues. Considerable evidence has also accumulated to indicate that aberrations in the stem and progenitor cell populations can lead to increased cancer risk in specific organs systems. It is long recognized that environmental factors play a major role in cancer etiology, and emerging data suggest that endocrine-disrupting chemicals (EDCs) may contribute to an increased cancer risk. Using the prostate gland as a model system, the present review highlights recent data that find that estrogens and EDCs can reprogram prostate stem and progenitor cell populations, leading to increased cancer susceptibility. We propose that stem cell programming during early development in hormone-regulated tissues may lead to heightened sensitivity to early-life EDC exposures and that aberrant stem cell reprogramming by EDCs may contribute to the developmental basis of adult cancer risk. PMID:26241068

  12. Stem Cells as Hormone Targets That Lead to Increased Cancer Susceptibility.

    PubMed

    Prins, Gail S; Calderon-Gierszal, Esther L; Hu, Wen-Yang

    2015-10-01

    Major advances during the past decade have permitted a clearer understanding of processes that regulate stem cell self-renewal and lineage commitment toward differentiated progeny that populate all tissues. Considerable evidence has also accumulated to indicate that aberrations in the stem and progenitor cell populations can lead to increased cancer risk in specific organs systems. It is long recognized that environmental factors play a major role in cancer etiology, and emerging data suggest that endocrine-disrupting chemicals (EDCs) may contribute to an increased cancer risk. Using the prostate gland as a model system, the present review highlights recent data that find that estrogens and EDCs can reprogram prostate stem and progenitor cell populations, leading to increased cancer susceptibility. We propose that stem cell programming during early development in hormone-regulated tissues may lead to heightened sensitivity to early-life EDC exposures and that aberrant stem cell reprogramming by EDCs may contribute to the developmental basis of adult cancer risk. PMID:26241068

  13. 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…

  14. 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

  15. 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.

  16. 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.

  17. Toll-Like Receptor Polymorphisms and Susceptibility to Urinary Tract Infections in Adult Women

    PubMed Central

    Hawn, Thomas R.; Scholes, Delia; Li, Shuying S.; Wang, Hongwei; Yang, Yin; Roberts, Pacita L.; Stapleton, Ann E.; Janer, Marta; Aderem, Alan; Stamm, Walter E.; Zhao, Lue Ping; Hooton, Thomas M.

    2009-01-01

    Background Although behavioral risk factors are strongly associated with urinary tract infection (UTI) risk, the role of genetics in acquiring this disease is poorly understood. Methodology/Principal Findings To test the hypothesis that polymorphisms in Toll-like receptor (TLR) pathway genes are associated with susceptibility to UTIs, we conducted a population-based case-control study of women ages 18–49 years. We examined DNA variants in 9 TLR pathway genes in 431 recurrent cystitis (rUTI) cases, 400 pyelonephritis cases, and 430 controls with no history of UTIs. In the Caucasian subgroup of 987 women, polymorphism TLR4_A896G was associated with protection from rUTI, but not pyelonephritis, with an odds ratio (OR) of 0.54 and a 95% confidence interval (CI) of 0.31 to 0.96. Polymorphism TLR5_C1174T, which encodes a variant that abrogates flagellin-induced signaling, was associated with an increased risk of rUTI (OR(95%CI): 1.81 (1.00–3.08)), but not pyelonephritis. Polymorphism TLR1_G1805T was associated with protection from pyelonephritis (OR(95%CI): 0.53 (0.29–0.96)). Conclusions These results provide the first evidence of associations of TLR5 and TLR1 variants with altered risks of acquiring rUTI and pyelonephritis, respectively. Although these data suggest that TLR polymorphisms are associated with adult susceptibility to UTIs, the statistical significance was modest and will require further study including validation with independent cohorts. PMID:19543401

  18. 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…

  19. 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.

  20. 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

  1. Increases in cerebrovascular impedance in older adults.

    PubMed

    Zhu, Yong-Sheng; Tseng, Benjamin Y; Shibata, Shigeki; Levine, Benjamin D; Zhang, Rong

    2011-08-01

    This study explored a novel method for measuring cerebrovascular impedance to quantify the relationship between pulsatile changes in cerebral blood flow (CBF) and arterial pressure. Arterial pressure in the internal or common carotid artery (applanation tonometry), CBF velocity in the middle cerebral artery (transcranial Doppler), and end-tidal CO(2) (capnography) were measured in six young (28 ± 4 yr) and nine elderly subjects (70 ± 6 yr). Transfer function method was used to estimate cerebrovascular impedance. Under supine resting conditions, CBF velocity was reduced in the elderly despite the fact that they had higher arterial pressure than young subjects. As expected, cerebrovascular resistance index was increased in the elderly. In both young and elderly subjects, impedance modulus was reduced gradually in the frequency range of 0.78-8 Hz. Phase was negative in the range of 0.78-4.3 Hz and fluctuated at high frequencies. Compared with the young, impedance modulus increased by 38% in the elderly in the range of 0.78-2 Hz and by 39% in the range of 2-4 Hz (P < 0.05). Moreover, increases in impedance were correlated with reductions in CBF velocity. Collectively, these findings demonstrate the feasibility of assessing cerebrovascular impedance using the noninvasive method developed in this study. The estimated impedance modulus and phase are similar to those observed in the systemic circulation and other vascular beds. Moreover, increases in impedance in the elderly suggest that arterial stiffening, besides changes in cerebrovascular resistance, contributes to reduction in CBF with age.

  2. 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

  3. Genetic Variants and Increased Expression of Parascaris equorum P-glycoprotein-11 in Populations with Decreased Ivermectin Susceptibility

    PubMed Central

    Janssen, I. Jana I.; Krücken, Jürgen; Demeler, Janina; Basiaga, Marta; Kornaś, Sławomir; von Samson-Himmelstjerna, Georg

    2013-01-01

    Macrocyclic lactones (MLs) represent the major drug class for control of parasitic infections in humans and animals. However, recently reports of treatment failures became more frequent. In addition to human and ruminant parasitic nematodes this also is the case for the horse-nematode Parascaris equorum. Nevertheless, to date the molecular basis of ML resistance is still not understood. Unspecific resistance mechanisms involving transporters such as P-glycoproteins (Pgps) are expected to contribute to ML resistance in nematodes. Here, complete sequences of two P. equorum Pgps were cloned and identified as orthologs of Caenorhabditis elegans Ppg-11 and an unnamed Caenorhabditis briggsae Pgp designated as Pgp-16 using phylogenetic analysis. Quantitative real-time PCR was used to compare expression between tissues. Significantly higher PeqPgp-11 expression was found in the gut for both genders, whereas for PeqPgp-16 the body wall was identified as predominant expression site. Furthermore, Pgps were analyzed regarding their participation in resistance development. Using SeqDoC analyses, Pgp-sequences of P. equorum populations with different ML susceptibility were compared. This approach revealed three single nucleotide polymorphisms (SNPs) causing missense mutations in the PeqPgp-11 sequence which correlated with decreased ML susceptibility. However, no resistance associated differences in mRNA expression levels were detected between embryonated eggs of these populations. In contrast, comparison of two pre-adult groups with different ivermectin (IVM) susceptibility revealed the presence of the three SNPs and in addition statistically significant PeqPgp-11 overexpression in the group of worms with reduced susceptibility. These results indicate that Pgp-11 might be involved in IVM resistance in P. equorum as it shows increased expression in an IVM exposed life-cycle stage of an IVM resistant population as well as occurrence of putatively resistance associated SNPs in

  4. Longitudinal Increase in Anisometropia in Older Adults

    PubMed Central

    Haegerstrom-Portnoy, Gunilla; Schneck, Marilyn E.; Lott, Lori A.; Hewlett, Susan E.; Brabyn, John A.

    2014-01-01

    Purpose Anisometropia shows an exponential increase in prevalence with increasing age based on cross-sectional studies. The purpose of this study was to evaluate longitudinal changes in anisometropia in all refractive components in older observers and to assess the influence of early cataract development. Methods Refractive error was assessed at two time points separated by ~12 years in 118 older observers (ages 67.1 and 79.3 years at the two test times). Anisometropia defined as ≥1.00 D was calculated for all refractive components. The subjects had intact ocular lenses in both eyes throughout the study. Lens evaluations were performed at the second test using LOCS III. Results All refractive components approximately doubled in prevalence of anisometropia. Spherical equivalent anisometropia changed from 16.1% to 32.2%. Similar changes were found for spherical error (17% to 38.1%), primary astigmatism (7.6% to 17.8%) and oblique astigmatism (14.4% to 29.7%). Many who did not have anisometropia at the first visit subsequently developed anisometropia (for ex. 26.3% for spherical error and 22.9% for oblique cylinder). The onset of anisometropia occurred at all ages within the studied age range with no particular preference for any one age. A small number lost anisometropia over time. Individual comparisons of refractive error changes in the two eyes in combination with nuclear lens changes showed that early changes in nuclear sclerosis in the two eyes could account for a large proportion of anisometropia (~40%) but unequal hyperopic shift in the spherical component in the two eyes was the primary cause of the anisometropia. Conclusions Anisometropia is at least 10 times more common in the elderly than in children and anisometropia develops in all refractive components in the oldest observers. Clinicians need to be aware of this common condition that could lead to binocular vision problems and potentially cause falls in the elderly. PMID:24276578

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

    PubMed

    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 postdrought, which was previously shown to be adaptive. Here, we report the novel finding that postdrought 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.

  6. 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.

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

    PubMed

    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 postdrought, which was previously shown to be adaptive. Here, we report the novel finding that postdrought 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

  8. 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.

  9. 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. PMID:12076006

  10. 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.

  11. Comparison of apoptosis between adult worms of Schistosoma japonicum from susceptible (BALB/c mice) and less-susceptible (Wistar rats) hosts.

    PubMed

    Wang, Tao; Guo, Xiaoyong; Hong, Yang; Han, Hongxiao; Cao, Xiaodan; Han, Yanhui; Zhang, Min; Wu, Miaoli; Fu, Zhiqiang; Lu, Ke; Li, Hao; Zhao, Zhixin; Lin, Jiaojiao

    2016-10-30

    Schistosomiasis remains a serious public health concern in China. BALB/c mice are susceptible to Schistosoma japonicum infection, whereas the Wistar rats are less susceptible. Apoptosis phenomenon was observed in 42d adult worms of S. japonicum from both rats and mice at the morphologic, DNA, cellular, and gene levels by transmission electron microscopy (TEM), fluorometric terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) analysis, fluorescein isothiocyanate-annexin-V/propidium iodide staining flow cytometry (FCM) analysis, and real-time PCR. The results showed that the apoptotic state in worms from two different susceptible hosts was diverse. Several classical hallmarks of apoptosis, including cell shrinkage, chromatin condensation and lunate marginalization, splitting of the nucleoli, nuclear shrinkage and apoptotic body formation were observed by TEM. TUNEL analysis showed that there were much more apoptosis spots in adult worms from rats than those from mice. Statistical analysis revealed that the degree of apoptosis and percentage of necrotic cells in adult worms from Wistar rats were significantly greater (P<0.01) than those from BALB/c mice by flow cytometry. A total of 15 apoptosis-associated genes including the major components of an intrinsic cell-death pathway were identified from S. japonicum in this study, suggested that a similar apoptosis pathway might occur in S. japonicum. Real-time PCR analyses revealed that the expression levels of most of the tested apoptosis-associated genes, except CASP7, were significantly higher or at the similar level in adult worms from Wistar rats, as compared to those from BALB/c mice. The results obtained in this study collectively demonstrated that differential development of adult S. japonicum in less-susceptible rats and susceptible mice was significantly associated with apoptosis in the worm, and provided valuable information to guide further investigations of the mechanisms governing

  12. Comparison of apoptosis between adult worms of Schistosoma japonicum from susceptible (BALB/c mice) and less-susceptible (Wistar rats) hosts.

    PubMed

    Wang, Tao; Guo, Xiaoyong; Hong, Yang; Han, Hongxiao; Cao, Xiaodan; Han, Yanhui; Zhang, Min; Wu, Miaoli; Fu, Zhiqiang; Lu, Ke; Li, Hao; Zhao, Zhixin; Lin, Jiaojiao

    2016-10-30

    Schistosomiasis remains a serious public health concern in China. BALB/c mice are susceptible to Schistosoma japonicum infection, whereas the Wistar rats are less susceptible. Apoptosis phenomenon was observed in 42d adult worms of S. japonicum from both rats and mice at the morphologic, DNA, cellular, and gene levels by transmission electron microscopy (TEM), fluorometric terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) analysis, fluorescein isothiocyanate-annexin-V/propidium iodide staining flow cytometry (FCM) analysis, and real-time PCR. The results showed that the apoptotic state in worms from two different susceptible hosts was diverse. Several classical hallmarks of apoptosis, including cell shrinkage, chromatin condensation and lunate marginalization, splitting of the nucleoli, nuclear shrinkage and apoptotic body formation were observed by TEM. TUNEL analysis showed that there were much more apoptosis spots in adult worms from rats than those from mice. Statistical analysis revealed that the degree of apoptosis and percentage of necrotic cells in adult worms from Wistar rats were significantly greater (P<0.01) than those from BALB/c mice by flow cytometry. A total of 15 apoptosis-associated genes including the major components of an intrinsic cell-death pathway were identified from S. japonicum in this study, suggested that a similar apoptosis pathway might occur in S. japonicum. Real-time PCR analyses revealed that the expression levels of most of the tested apoptosis-associated genes, except CASP7, were significantly higher or at the similar level in adult worms from Wistar rats, as compared to those from BALB/c mice. The results obtained in this study collectively demonstrated that differential development of adult S. japonicum in less-susceptible rats and susceptible mice was significantly associated with apoptosis in the worm, and provided valuable information to guide further investigations of the mechanisms governing

  13. 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.

  14. A small increase in UV-B increases the susceptibility of tadpoles to predation.

    PubMed

    Alton, Lesley A; Wilson, Robbie S; Franklin, Craig E

    2011-09-01

    Increased ultraviolet-B (UV-B) radiation as a consequence of ozone depletion is one of the many potential drivers of ongoing global amphibian declines. Both alone and in combination with other environmental stressors, UV-B is known to have detrimental effects on the early life stages of amphibians, but our understanding of the fitness consequences of these effects remains superficial. We examined the independent and interactive effects of UV-B and predatory chemical cues (PCC) on a suite of traits of Limnodynastes peronii embryos and tadpoles, and assessed tadpole survival time in a predator environment to evaluate the potential fitness consequences. Exposure to a 3 to 6 per cent increase in UV-B, which is comparable to changes in terrestrial UV-B associated with ozone depletion, had no effect on any of the traits measured, except survival time in a predator environment, which was reduced by 22 to 28 per cent. Exposure to PCC caused tadpoles to hatch earlier, have reduced hatching success, have improved locomotor performance and survive for longer in a predator environment, but had no effect on tadpole survival, behaviour or morphology. Simultaneous exposure to UV-B and PCC resulted in no interactive effects. These findings demonstrate that increased UV-B has the potential to reduce tadpole fitness, while exposure to PCCs improves their fitness. PMID:21270039

  15. A small increase in UV-B increases the susceptibility of tadpoles to predation

    PubMed Central

    Alton, Lesley A.; Wilson, Robbie S.; Franklin, Craig E.

    2011-01-01

    Increased ultraviolet-B (UV-B) radiation as a consequence of ozone depletion is one of the many potential drivers of ongoing global amphibian declines. Both alone and in combination with other environmental stressors, UV-B is known to have detrimental effects on the early life stages of amphibians, but our understanding of the fitness consequences of these effects remains superficial. We examined the independent and interactive effects of UV-B and predatory chemical cues (PCC) on a suite of traits of Limnodynastes peronii embryos and tadpoles, and assessed tadpole survival time in a predator environment to evaluate the potential fitness consequences. Exposure to a 3 to 6 per cent increase in UV-B, which is comparable to changes in terrestrial UV-B associated with ozone depletion, had no effect on any of the traits measured, except survival time in a predator environment, which was reduced by 22 to 28 per cent. Exposure to PCC caused tadpoles to hatch earlier, have reduced hatching success, have improved locomotor performance and survive for longer in a predator environment, but had no effect on tadpole survival, behaviour or morphology. Simultaneous exposure to UV-B and PCC resulted in no interactive effects. These findings demonstrate that increased UV-B has the potential to reduce tadpole fitness, while exposure to PCCs improves their fitness. PMID:21270039

  16. 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...

  17. Increased susceptibility to pentylenetetrazol following survival of cerebral malaria in mice.

    PubMed

    Grauncke, Ana C B; Souza, Thaíze L; Ribeiro, Leandro R; Brant, Fátima; Machado, Fabiana S; Oliveira, Mauro S

    2016-07-01

    Malaria is considered a neglected disease and public health problem, affecting >200 million people worldwide. In the present study we used the Plasmodium berghei ANKA (PbA) model of experimental cerebral malaria (CM) in C57BL/6 mice. After rescue from CM and parasite clearance, animals were submitted to a seizure susceptibility test (45 days after infection) using a low dose of pentylenetetrazol (PTZ, 30 mg/kg) and monitored with use of behavioral and electroencephalography (EEG) methods. Mice rescued from CM presented a reduced latency to myoclonic and tonic-clonic seizures and an increased duration of tonic-clonic seizures. In addition, quantitative analysis of EEG revealed a decrease in relative power at beta frequency band in PbA-infected animals after PTZ injection. Our results suggest that CM may lead to increased susceptibility to seizures in mice.

  18. 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

  19. Seizures following hippocampal kindling induce QT interval prolongation and increased susceptibility to arrhythmias in rats.

    PubMed

    Bealer, Steven L; Little, Jason G

    2013-07-01

    The prolonged seizures of status epilepticus produce chronic arrhythmogenic changes in cardiac function. This study was designed to determine if repeated, self-limiting seizures administered to kindled rats induce similar cardiac dysfunction. Multiple seizures administered to rats following hippocampal kindling resulted in cardiac QT interval prolongation and increased susceptibility to experimental arrhythmias. These data suggest that multiple, self-limiting seizures of intractable epilepsy may have cardiac effects that can contribute to sudden unexpected death in epilepsy (SUDEP).

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. Lyn deficiency leads to increased microbiota-dependent intestinal inflammation and susceptibility to enteric pathogens.

    PubMed

    Roberts, Morgan E; Bishop, Jennifer L; Fan, Xueling; Beer, Jennifer L; Kum, Winnie W S; Krebs, Danielle L; Huang, Morris; Gill, Navkiran; Priatel, John J; Finlay, B Brett; Harder, Kenneth W

    2014-11-15

    The Lyn tyrosine kinase governs the development and function of various immune cells, and its dysregulation has been linked to malignancy and autoimmunity. Using models of chemically induced colitis and enteric infection, we show that Lyn plays a critical role in regulating the intestinal microbiota and inflammatory responses as well as protection from enteric pathogens. Lyn(-/-) mice were highly susceptible to dextran sulfate sodium (DSS) colitis, characterized by significant wasting, rectal bleeding, colonic pathology, and enhanced barrier permeability. Increased DSS susceptibility in Lyn(-/-) mice required the presence of T but not B cells and correlated with dysbiosis and increased IFN-γ(+) and/or IL-17(+) colonic T cells. This dysbiosis was characterized by an expansion of segmented filamentous bacteria, associated with altered intestinal production of IL-22 and IgA, and was transmissible to wild-type mice, resulting in increased susceptibility to DSS. Lyn deficiency also resulted in an inability to control infection by the enteric pathogens Salmonella enterica serovar Typhimurium and Citrobacter rodentium. Lyn(-/-) mice exhibited profound cecal inflammation, bacterial dissemination, and morbidity following S. Typhimurium challenge and greater colonic inflammation throughout the course of C. rodentium infection. These results identify Lyn as a key regulator of the mucosal immune system, governing pathophysiology in multiple models of intestinal disease.

  8. Gold nanoparticles do not induce myotube cytotoxicity but increase the susceptibility to cell death.

    PubMed

    Leite, Paulo Emílio Corrêa; Pereira, Mariana Rodrigues; do Nascimento Santos, Carlos Antonio; Campos, Andrea Porto Carreiro; Esteves, Ticiana Mota; Granjeiro, José Mauro

    2015-08-01

    Gold nanoparticles (AuNP) have been widely used for many applications, including as biological carriers. A better understanding concerning AuNP safety on muscle cells is crucial, since it could be a potential tool in the nanomedicine field. Here, we describe the impact of polyethylene glycol-coated gold nanoparticles (PEG-AuNP) interaction with differentiated skeletal muscle C2C12 cells on cell viability, mitochondria function, cell signaling related to survival, cytokine levels and susceptibility to apoptosis. Intracellular localization of 4.5 nm PEG-AuNP diameter size was evidenced by STEM-in-SEM in myotube cells. Methods for cytotoxicity analysis showed that PEG-AuNP did not affect cell viability, but intracellular ATP levels and mitochondrial membrane potential increased. Phosphorylation of ERK was not altered but p-AKT levels reduced (p<0.01). Pre-treatment of cells with PEG-AuNP followed by staurosporine induction increased the caspases-3/7 activity. Indeed, cytokines analysis revealed a sharp increase of IFN-γ and TGF-β1 levels after PEG-AuNP treatment, suggesting that inflammatory and fibrotic phenotypes process were activated. These data demonstrate that PEG-AuNP affect the myotube physiology leading these cells to be more susceptible to death stimuli in the presence of staurosporine. Altogether, these results present evidence that PEG-AuNP affect the susceptibility to apoptosis of muscle cells, contributing to development of safer strategies for intramuscular delivery. PMID:25790728

  9. Common genetic variation associated with increased susceptibility to prostate cancer does not increase risk of radiotherapy toxicity

    PubMed Central

    Ahmed, Mahbubl; Dorling, Leila; Kerns, Sarah; Fachal, Laura; Elliott, Rebecca; Partliament, Matt; Rosenstein, Barry S; Vega, Ana; Gómez-Caamaño, Antonio; Barnett, Gill; Dearnaley, David P; Hall, Emma; Sydes, Matt; Burnet, Neil; Pharoah, Paul D P; Eeles, Ros; West, Catharine M L

    2016-01-01

    Background: Numerous germline single-nucleotide polymorphisms increase susceptibility to prostate cancer, some lying near genes involved in cellular radiation response. This study investigated whether prostate cancer patients with a high genetic risk have increased toxicity following radiotherapy. Methods: The study included 1560 prostate cancer patients from four radiotherapy cohorts: RAPPER (n=533), RADIOGEN (n=597), GenePARE (n=290) and CCI (n=150). Data from genome-wide association studies were imputed with the 1000 Genomes reference panel. Individuals were genetically similar with a European ancestry based on principal component analysis. Genetic risks were quantified using polygenic risk scores. Regression models tested associations between risk scores and 2-year toxicity (overall, urinary frequency, decreased stream, rectal bleeding). Results were combined across studies using standard inverse-variance fixed effects meta-analysis methods. Results: A total of 75 variants were genotyped/imputed successfully. Neither non-weighted nor weighted polygenic risk scores were associated with late radiation toxicity in individual studies (P>0.11) or after meta-analysis (P>0.24). No individual variant was associated with 2-year toxicity. Conclusion: Patients with a high polygenic susceptibility for prostate cancer have no increased risk for developing late radiotherapy toxicity. These findings suggest that patients with a genetic predisposition for prostate cancer, inferred by common variants, can be safely treated using current standard radiotherapy regimens. PMID:27070714

  10. Plasmids in antibiotic susceptible and antibiotic resistant commensal Escherichia coli from healthy Australian adults.

    PubMed

    Moran, Robert A; Anantham, Sashindran; Pinyon, Jeremy L; Hall, Ruth M

    2015-07-01

    A collection of 111 commensal Escherichia coli isolated from 84 faecal samples from healthy Australian adults were screened using PCR-based replicon typing. Each isolate represented a distinct strain found in a particular faecal sample. Fifty-one isolates were resistant to one or more of 12 antibiotics tested. FII and FIB replicons were most common and usually found together. The FII replicon was detected in 63 isolates (35 susceptible, 28 resistant), the FIB replicon was present in 65 (32 susceptible, 33 resistant) and 54 (30 susceptible, 24 resistant) included both. Other replicon types were found infrequently (A/C, I1, K, L/M, P, R, Y, FIA and FIC) or not at all (HI1, HI2, N, T, U, W, X). Only the B/O amplicon, found in 21 resistant but only 4 susceptible isolates, was associated with antibiotic resistance. Detailed analysis of this group revealed that the B/O PCR also detected Z plasmids of several distinguishable types. PCR assays were developed to detect the two repA genes (repABKI and repAZ) found in members of the I-complex (I, B/O, K and Z plasmids). These assays distinguished the B/O and Z plasmids detected by the original "B/O" PCR. One isolate carried repABKI and the remainder carried repAZ. These genes were also detected in further isolates in the collection. Conjugative transfer of resistance genes was detected for the B/O plasmid and two Z groups. Evidence for transfer of repAZ plasmids in the human colon in the absence of antibiotic selection was also obtained.

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

    PubMed Central

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

    2012-01-01

    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. PMID:22751298

  12. 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…

  13. 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

  14. 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.

  15. 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

  16. 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. PMID:27057552

  17. 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.

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

    PubMed

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

    2003-07-01

    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. PMID:12626488

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

    PubMed Central

    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. PMID:27057552

  20. 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.

  1. Helminthosporium maydis T toxin increased membrane permeability to Ca/sup 2 +/ in susceptible corn mitochondria

    SciTech Connect

    Holden, M.J.; Sze, H.

    1984-05-01

    Though Helminthosporium maydis race T (HmT) toxin decreased active Ca/sup 2 +/ uptake into mitochondria isolated from susceptible (T) but not resistant (N) corn. The mode of toxin action is not understood. This study shows that HmT toxin or A23187 (a Ca/sup 2 +/ ionophore) dissipated a Ca/sup 2 +/ gradient in T mitochondria. However, HmT toxin had no effect on Ca/sup 2 +/ gradients in N mitochondria or microsomal vesicles from T or N corn. The results suggest that HmT toxin increased membrane permeability to Ca/sup 2 +/ in mitochondria of T corn specifically.

  2. Organophosphate and pyrethroid susceptibilities of Culex salinarius adults from Texas and New Jersey.

    PubMed

    Sukontason, K; Olson, J K; Hartberg, W K; Duhrkopf, R E

    1998-12-01

    Susceptibilities of adults from newly established colonies of Culex salinarius from New Jersey and Texas to commonly used mosquito adulticides were assessed using the insecticide-coated vial bioassay technique. Females from both colonies were similar in their susceptibilities to naled, chlorpyrifos, resmethrin, and permethrin. However, females from the New Jersey colony (established from collections made in Cape May County, NJ) were found to be 9 times more tolerant to malathion than were those from the Texas colony (established from collections made in Chambers County, TX), with median lethal concentration values for malathion tested against these 2 colonies of 0.70 and 0.08 microgram malathion/vial, respectively. The differences between these 2 colonies with respect to their tolerances to malathion may be a product of the age of each colony at the time assessments were made and/or the degree to which the parent stock used to start each colony was previously exposed to malathion in the field. PMID:10084146

  3. 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

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

    PubMed

    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.

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

    PubMed

    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

  6. 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.

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

    PubMed

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

    2015-02-01

    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.

  8. Toll-like receptors gene polymorphisms may confer increased susceptibility to breast cancer development.

    PubMed

    Theodoropoulos, George E; Saridakis, Vasilios; Karantanos, Theodoros; Michalopoulos, Nikolaos V; Zagouri, Flora; Kontogianni, Panagiota; Lymperi, Maria; Gazouli, Maria; Zografos, George C

    2012-08-01

    Toll-like receptor (TLR) activation may be an important event in tumor cell immune evasion. TLR2 and TLR4 gene polymorphisms have been related to increased susceptibility to cancer development in various organs. 261 patients and 480 health individuals were investigated for genotype and allelic frequencies of a 22-bp nucleotide deletion (-196 to -174del) in the promoter of TLR2 gene as well as two polymorphisms causing amino acid substitutions (Asp299Gly and Thr399Ile) in TLR4 gene. As far as (-196 to -174del) in TLR2 gene is concerned ins/del and del/del genotypes and del allele were significantly more frequent in breast cancer patients compared to healthy controls. Considering Asp299Gly replacement of TLR4 gene, Gly carriers (Asp/Gly & Gly/Gly genotype) and Gly allele were overrepresented among the breast cancer cases. The -174 to -196del of TLR2 gene and Asp299Gly of TLR4 gene polymorphisms may confer an increased susceptibility to breast cancer development.

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. Increased susceptibility to microdamage in Brtl/+ mouse model for osteogenesis imperfecta☆

    PubMed Central

    Davis, Mathieu S.; Kovacic, Bethany L.; Marini, Joan C.; Shih, Albert J.; Kozloff, Kenneth M.

    2012-01-01

    Osteogenesis imperfecta (OI) is a genetic disease of collagen or collagen-related proteins that adversely impacts bone mass and fracture resistance. Little is known regarding the role that microdamage plays in OI and whether or not OI bone is more prone to damage accumulation than bone with unaffected collagen. The Brtl/+ mouse is a heterozygous model for OI which contains a Gly349Cys substitution in one COL1A1 allele, and demonstrates a low ductility phenotype. At 8 weeks of age, Brtl/+ demonstrates an increase in osteoclast number, which mimics the upregulated bone turnover often found in OI patients. We hypothesize that upregulated osteoclast activity in Brtl/+ is due, in part, to increased remodeling associated with microdamage repair. In the present study, we used Brtl/+ to investigate the susceptibility of OI bone to microdamage. The mouse ulnar loading model was used to induce microdamage and to test the hypothesis that Brtl/+ is more susceptible to damage accumulation than age-matched wild type (WT) counterparts. Linear elastic fracture mechanics (LEFM) was used to investigate the fracture toughness properties of both Brtl/+ and WT bones to determine if there is any correlation with toughness and the degree of microdamage. Results show that Brtl/+ ulnae subject to normal cage activity demonstrate an inherently larger amount of microdamage than WT controls. Following axial compressive loading, Brtl/+ ulnae are more prone to damage than WT counterparts despite demonstrating a greater resistance to whole-bone deformation. Fracture toughness results demonstrate that Brtl/+ specimens, despite not exhibiting a significant difference, display a trend toward lower fracture toughness values than their WT counterparts. Correlations show that microdamage levels tend to increase as fracture toughness decreases. Together, these findings may have strong clinical implications for explaining increased fragility and remodeling activity in OI patients. PMID:22207275

  17. Increased post-operative haemorrhage seen in adult coblation tonsillectomy.

    PubMed

    Noon, A P; Hargreaves, S

    2003-09-01

    Coblation is a new soft tissue surgical technique that is being used for tonsillectomy. Published results show a significant decrease in the amount of post-operative pain experienced by patients undergoing coblation tonsillectomy. There has been no published work to date on the incidence of post-operative haemorrhage. From August 2001 to November 2002 one surgeon performed 36 coblation tonsillectomies on adults. On another list he performed 29 by his standard method of dissection and bipolar coagulation. Retrospective analysis found a significant increase in the secondary haemorrhage rate in adult patients undergoing coblation tonsillectomy (22.2 vs. 3.4 per cent). At our department coblation tonsillectomy has been abandoned until further work into its safety has been published.

  18. A mouse model of Alzheimer's disease displays increased susceptibility to kindling and seizure-associated death.

    PubMed

    Chan, Jianxiong; Jones, Nigel C; Bush, Ashley I; O'Brien, Terence J; Kwan, Patrick

    2015-06-01

    People with Alzheimer's disease (AD) are up to 10 times more likely to develop epilepsy than the age-matched general population. However, given that only a proportion of patients with AD develop epilepsy, it is likely that additional factors may be required for the epilepsy to emerge. This study aimed to better understand the relationship between AD pathology and seizure susceptibility. It also aimed to investigate a "two-hit" hypothesis for seizure susceptibility through amygdala kindling of rodent AD models. Aged AD mice (Tg2576 model) and wild-type (WT) mice underwent electrical amygdala kindling. Compared with WT mice, Tg2576 mice had significantly lower afterdischarge threshold. Significantly fewer stimulations were required for the Tg2576 mice to reach the first class V seizure. Higher death rate was observed with Tg2576 mice in the kindling group. Both sham and kindled Tg2576 animals had increased levels of sprouting in the supragranular layer of the dentate gyrus compared with the WT counterparts. These findings support the "two-hit" hypothesis and represent a potentially novel research model to help better understand the relationship between AD pathology and epilepsy.

  19. 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

  20. Transformation of adrenal medullary chromaffin cells increases asthmatic susceptibility in pups from allergen-sensitized rats

    PubMed Central

    2012-01-01

    Background Studies have shown that epinephrine release is impaired in patients with asthma. The pregnancy of female rats (dams) with asthma promotes in their pups the differentiation of adrenal medulla chromaffin cells (AMCCs) into sympathetic neurons, mediated by nerve growth factor, which leads to a reduction in epinephrine secretion. However, the relatedness between the alteration of AMCCs and increased asthma susceptibility in such offspring has not been established. Methods In this study, we observed the effects of allergization via ovalbumin on rat pups born of asthmatic dams. Results Compared to the offspring of untreated controls, bronchial hyperreactivity and airway inflammation were more severe in the pups from sensitized (asthmatic) dams. In pups exposed to nerve growth factor (NGF) in utero these effects were aggravated further, but the effects were blocked in pups whose dams had been treated with anti-NGF. Furthermore, alterations in AMCC phenotype corresponded to the degree of bronchial hyperreactivity and lung lesions of the different treatment groups. Such AMCC alterations included degranulation of chromaffin granules, reduction of epinephrine and phenylethanolamine-n-methyl transferase, and elevation of NGF and peripherin levels. Conclusions Our results present evidence that asthma during the pregnancy of rat dams promotes asthma susceptibility in their offspring, and that the transformation of AMCCs to neurons induced by NGF plays an important role in this process. PMID:23137120

  1. Red wine mitigates the postprandial increase of LDL susceptibility to oxidation.

    PubMed

    Natella, F; Ghiselli, A; Guidi, A; Ursini, F; Scaccini, C

    2001-05-01

    The aim of the present study was to verify the extent of oxidative stress induced by a meal at plasma and LDL level, and to investigate the capacity of red wine to counteract this action. In two different sessions, six healthy men ate the same test meal consisting of "Milanese" meat and fried potatoes. The meal was taken either with 400 ml red wine or with an isocaloric hydroalcoholic solution. Oxidative stress at plasma level was estimated through the measure of ascorbic acid, alpha-tocopherol, protein SH groups, uric acid, and antioxidant capacity, measured before and 1 and 3 h after the meal. The change in the resistance of LDL to oxidative modification was taken as an index of exposure to pro-oxidants. The susceptibility to Cu(II)-catalyzed oxidation of baseline and postprandial LDL was measured as conjugated dienes formation, tryptophan residues, and relative electrophoretic mobility. The experimental meal taken with wine provoked a significant increase in the total plasma antioxidant capacity and in the plasma concentration of alpha-tocopherol and SH groups. Postprandial LDL was more susceptible to metal-catalyzed oxidation than the homologous baseline LDL after the ethanol meal. On the contrary, postprandial LDL obtained after the wine meal was as resistant or more resistant to lipid peroxidation than fasting LDL.

  2. Prenatal Ethanol Exposure Increases Brain Cholesterol Content in Adult Rats

    PubMed Central

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

    2013-01-01

    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 is known to change 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 PUFA, in the n-3/n-6 ratio, and in the 22:6 n-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 post-natal ethanol consumption was not sufficient to reverse the large increase in cholesterol observed in the adult rats. PMID:23996454

  3. A Safe and Stable Neonatal Vaccine Targeting GAPDH Confers Protection against Group B Streptococcus Infections in Adult Susceptible Mice

    PubMed Central

    Alves, Joana; Madureira, Pedro; Baltazar, Maria Teresa; Barros, Leandro; Oliveira, Liliana; Dinis-Oliveira, Ricardo Jorge; Andrade, Elva Bonifácio; Ribeiro, Adília; Vieira, Luís Mira; Trieu-Cuot, Patrick; Duarte, José Alberto; Carvalho, Félix; Ferreira, Paula

    2015-01-01

    Group B Streptococcus (GBS), a commensal organism, can turn into a life-threatening pathogen in neonates and elderly, or in adults with severe underlying diseases such as diabetes. We developed a vaccine targeting the GBS glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a glycolytic enzyme detected at the bacterial surface, which was proven to be effective in a neonatal mouse model of infection. Since this bacterium has emerged as an important pathogen in non-pregnant adults, here we investigated whether this vaccine also confers protection in an adult susceptible and in a diabetic mouse model of infection. For immunoprotection studies, sham or immunized adult mice were infected with GBS serotype Ia and V strains, the two most prevalent serotypes isolated in adults. Sham and vaccinated mice were also rendered diabetic and infected with a serotype V GBS strain. For toxicological (pre-clinical) studies, adult mice were vaccinated three times, with three concentrations of recombinant GAPDH adjuvanted with Allydrogel, and the toxicity parameters were evaluated twenty-four hours after the last immunization. For the stability tests, the vaccine formulations were maintained at 4°C for 6 and 12 months prior immunization. The results showed that all tested doses of the vaccine, including the stability study formulations, were immunogenic and that the vaccine was innocuous. The organs (brain, blood, heart, and liver) of vaccinated susceptible or diabetic adult mice were significantly less colonized compared to those of control mice. Altogether, these results demonstrate that the GAPDH-based vaccine is safe and stable and protects susceptible and diabetic adult mice against GBS infections. It is therefore a promising candidate as a global vaccine to prevent GBS-induced neonatal and adult diseases. PMID:26673420

  4. A Safe and Stable Neonatal Vaccine Targeting GAPDH Confers Protection against Group B Streptococcus Infections in Adult Susceptible Mice.

    PubMed

    Alves, Joana; Madureira, Pedro; Baltazar, Maria Teresa; Barros, Leandro; Oliveira, Liliana; Dinis-Oliveira, Ricardo Jorge; Andrade, Elva Bonifácio; Ribeiro, Adília; Vieira, Luís Mira; Trieu-Cuot, Patrick; Duarte, José Alberto; Carvalho, Félix; Ferreira, Paula

    2015-01-01

    Group B Streptococcus (GBS), a commensal organism, can turn into a life-threatening pathogen in neonates and elderly, or in adults with severe underlying diseases such as diabetes. We developed a vaccine targeting the GBS glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a glycolytic enzyme detected at the bacterial surface, which was proven to be effective in a neonatal mouse model of infection. Since this bacterium has emerged as an important pathogen in non-pregnant adults, here we investigated whether this vaccine also confers protection in an adult susceptible and in a diabetic mouse model of infection. For immunoprotection studies, sham or immunized adult mice were infected with GBS serotype Ia and V strains, the two most prevalent serotypes isolated in adults. Sham and vaccinated mice were also rendered diabetic and infected with a serotype V GBS strain. For toxicological (pre-clinical) studies, adult mice were vaccinated three times, with three concentrations of recombinant GAPDH adjuvanted with Allydrogel, and the toxicity parameters were evaluated twenty-four hours after the last immunization. For the stability tests, the vaccine formulations were maintained at 4°C for 6 and 12 months prior immunization. The results showed that all tested doses of the vaccine, including the stability study formulations, were immunogenic and that the vaccine was innocuous. The organs (brain, blood, heart, and liver) of vaccinated susceptible or diabetic adult mice were significantly less colonized compared to those of control mice. Altogether, these results demonstrate that the GAPDH-based vaccine is safe and stable and protects susceptible and diabetic adult mice against GBS infections. It is therefore a promising candidate as a global vaccine to prevent GBS-induced neonatal and adult diseases. PMID:26673420

  5. Different KIRs confer susceptibility and protection to adults with latent autoimmune diabetes in Latvian and Asian Indian populations.

    PubMed

    Shastry, Arun; Sedimbi, Saikiran K; Rajalingam, Raja; Rumba, Ingrida; Kanungo, Alok; Sanjeevi, C B

    2008-12-01

    KIRs (killer Ig-like receptors) expressed on natural killer (NK) cells are an important component of innate (and adaptive) immunity. They are either activatory or inhibitory, and certain KIRs are known to interact with specific motifs of HLA Class I molecules, which is very crucial in determining whether a cell is targeted to lysis or otherwise. Latent autoimmune diabetes in adults (LADA) is a slowly progressive form of autoimmune diabetes, with an adult onset (>30 years). Because autoantibodies and autoimmunity involved are involved in the etiology of LADA, KIRs might play an important role in conferring susceptibility to or protection against the disease. The purpose of this study was to identify killer immunoglobulin-like receptor (KIR) genes, which are associated with susceptibility to and protection against type 1 diabetes in Latvian and Asian Indian patients with LADA. KIR and HLA-C ligand genotyping was performed using PCR-SSP in LADA patients from Latvia (n= 45) with age- and sex-matched controls (n= 92) and from India (n= 86) with controls (n= 98). Results showed that in Latvian patients with LADA, KIRs 2DL1, 2DS2, and 2DS4 were associated with susceptibility and KIR 2DS5 with protection. In Asian Indian LADA patients, KIRs 2DL5 and 3DL1 were associated with susceptibility and KIRs 2DS1 and 2DS3 with protection. Stratification analyses for KIRs that bind to HLA-C1 and C2 were performed. We concluded that KIRs are important in conferring susceptibility (or protection) to adult patients with LADA in both our study populations. However the KIR genes (and their HLA-C ligands) conferring susceptibility or protection in these two populations differ, showing a role of ethnicity in disease susceptibility.

  6. 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

  7. 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

  8. Testosterone Increases Susceptibility to Amebic Liver Abscess in Mice and Mediates Inhibition of IFNγ Secretion in Natural Killer T Cells

    PubMed Central

    Lotter, Hannelore; Helk, Elena; Bernin, Hannah; Jacobs, Thomas; Prehn, Cornelia; Adamski, Jerzy; González-Roldán, Nestor; Holst, Otto; Tannich, Egbert

    2013-01-01

    Amebic liver abscess (ALA), a parasitic disease due to infection with the protozoan Entamoeba histolytica, occurs age and gender dependent with strong preferences for adult males. Using a mouse model for ALA with a similar male bias for the disease, we have investigated the role of female and male sexual hormones and provide evidence for a strong contribution of testosterone. Removal of testosterone by orchiectomy significantly reduced sizes of abscesses in male mice, while substitution of testosterone increased development of ALA in female mice. Activation of natural killer T (NKT) cells, which are known to be important for the control of ALA, is influenced by testosterone. Specifically activated NKT cells isolated from female mice produce more IFNγ compared to NKT cells derived from male mice. This high level production of IFNγ in female derived NKT cells was inhibited by testosterone substitution, while the IFNγ production in male derived NKT cells was increased by orchiectomy. Gender dependent differences were not a result of differences in the total number of NKT cells, but a result of a higher activation potential for the CD4− NKT cell subpopulation in female mice. Taken together, we conclude that the hormone status of the host, in particular the testosterone level, determines susceptibility to ALA at least in a mouse model of the disease. PMID:23424637

  9. 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

  10. Working memory deficits, increased anxiety-like traits, and seizure susceptibility in BDNF overexpressing mice.

    PubMed

    Papaleo, Francesco; Silverman, Jill L; Aney, Jordan; Tian, Qingjun; Barkan, Charlotte L; Chadman, Kathryn K; Crawley, Jacqueline N

    2011-08-01

    BDNF regulates components of cognitive processes and has been implicated in psychiatric disorders. Here we report that genetic overexpression of the BDNF mature isoform (BDNF-tg) in female mice impaired working memory functions while sparing components of fear conditioning. BDNF-tg mice also displayed reduced breeding efficiency, higher anxiety-like scores, high self-grooming, impaired prepulse inhibition, and higher susceptibility to seizures when placed in a new empty cage, as compared with wild-type (WT) littermate controls. Control measures of general health, locomotor activity, motor coordination, depression-related behaviors, and sociability did not differ between genotypes. The present findings, indicating detrimental effects of life-long increased BDNF in mice, may inform human studies evaluating the role of BDNF functional genetic variations on cognitive abilities and vulnerability to psychiatric disorders. PMID:21791566

  11. 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

  12. Working memory deficits, increased anxiety-like traits, and seizure susceptibility in BDNF overexpressing mice

    PubMed Central

    Papaleo, Francesco; Silverman, Jill L.; Aney, Jordan; Tian, Qingjun; Barkan, Charlotte L.; Chadman, Kathryn K.; Crawley, Jacqueline N.

    2011-01-01

    BDNF regulates components of cognitive processes and has been implicated in psychiatric disorders. Here we report that genetic overexpression of the BDNF mature isoform (BDNF-tg) in female mice impaired working memory functions while sparing components of fear conditioning. BDNF-tg mice also displayed reduced breeding efficiency, higher anxiety-like scores, high self-grooming, impaired prepulse inhibition, and higher susceptibility to seizures when placed in a new empty cage, as compared with wild-type (WT) littermate controls. Control measures of general health, locomotor activity, motor coordination, depression-related behaviors, and sociability did not differ between genotypes. The present findings, indicating detrimental effects of life-long increased BDNF in mice, may inform human studies evaluating the role of BDNF functional genetic variations on cognitive abilities and vulnerability to psychiatric disorders. PMID:21791566

  13. 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.

  14. 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.

  15. 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.

  16. Increased Akt signaling in the mosquito fat body increases adult survivorship

    PubMed Central

    Arik, Anam J.; Hun, Lewis V.; Quicke, Kendra; Piatt, Michael; Ziegler, Rolf; Scaraffia, Patricia Y.; Badgandi, Hemant; Riehle, Michael A.

    2015-01-01

    Akt signaling regulates diverse physiologies in a wide range of organisms. We examine the impact of increased Akt signaling in the fat body of 2 mosquito species, the Asian malaria mosquito Anopheles stephensi and the yellow fever mosquito Aedes aegypti. Overexpression of a myristoylated and active form of A. stephensi and Ae. aegypti Akt in the fat body of transgenic mosquitoes led to activation of the downstream signaling molecules forkhead box O (FOXO) and p70 S6 kinase in a tissue and blood meal–specific manner. In both species, increased Akt signaling in the fat body after blood feeding significantly increased adult survivorship relative to nontransgenic sibling controls. In A. stephensi, survivorship was increased by 15% to 45%, while in Ae. aegypti, it increased 14% to 47%. Transgenic mosquitoes fed only sugar, and thus not expressing active Akt, had no significant difference in survivorship relative to nontransgenic siblings. Expression of active Akt also increased expression of fat body vitellogenin, but the number of viable eggs did not differ significantly between transgenic and nontransgenic controls. This work demonstrates a novel mechanism of enhanced survivorship through increased Akt signaling in the fat bodies of multiple mosquito genera and provides new tools to unlock the molecular underpinnings of aging in eukaryotic organisms.—Arik, A. J., Hun, L. V., Quicke, K., Piatt, M., Ziegler, R., Scaraffia, P. Y., Badgandi H., Riehle, M. A. Increased Akt signaling in the mosquito fat body increases adult survivorship. PMID:25550465

  17. 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

  18. Porcine malignant hyperthermia susceptibility: increased calcium-sequestering activity of skeletal muscle sarcoplasmic reticulum.

    PubMed Central

    O'Brien, P J

    1986-01-01

    This study tested the hypothesis that calcium-sequestration by isolated sarcoplasmic reticulum was abnormal in skeletal muscle of malignant hyperthermia-susceptible swine. A heavy sarcoplasmic reticulum fraction was isolated from malignant hyperthermia and control muscle using differential and density-gradient centrifugation. Prior to onset of malignant hyperthermia, calcium-sequestering activity (Vmax at 37 degrees C, mumol calcium/mg/min) was twofold increased in malignant hyperthermia sarcoplasmic reticulum compared to control sarcoplasmic reticulum (1.96 +/- 0.50 versus 4.00 +/- 0.87, P less than 0.01), although thermodynamic and kinetic properties of this activity were otherwise indistinguishable between groups. This increased activity of the malignant hyperthermia sarcoplasmic reticulum fraction was associated with twofold increased concentration of Ca-ATPase and calsequestrin protein. When a malignant hyperthermia-reaction developed, calcium-uptake was depressed to less than 5% of control values. These data indicate that malignant hyperthermia is not initiated due to a defect in the calcium-sequestration mechanism, however, loss of calcium-uptake activity occurring after the onset of malignant hyperthermia might result in the propagation and irreversibility of the malignant hyperthermia reaction. Images Fig. 1. PMID:3742368

  19. Diet-induced obesity promotes systemic inflammation and increased susceptibility to murine visceral leishmaniasis.

    PubMed

    Sarnáglia, Glênia Daros; Covre, Luciana Polaco; Pereira, Fausto Edmundo Lima; DE Matos Guedes, Herbert Leonel; Faria, Ana Maria Caetano; Dietze, Reynaldo; Rodrigues, Rodrigo Ribeiro; Maioli, Tatiani Uceli; Gomes, Daniel Cláudio Oliviera

    2016-10-01

    Obesity is the main causal factor for metabolic syndrome and chronic systemic inflammation, which impacts on immune function and increases susceptibility to pathogens. Here, we investigated the effect of obesity on the outcome of visceral leishmaniasis caused by Leishmaniasis infantum chagasi. C57BL/6 mice fed with high-sugar and butter diet (HSB) showed a significant increase in body weight, adiposity index and morphological changes in adipocyte. To investigate the consequences of obesity on the specific immunity against Leishmania, both control and HSB diet groups were infected with 107 L. infantum chagasi promastigotes in the eighth-week after diet started and euthanized 4 weeks later. HSB-diet fed mice exhibited a significantly higher parasite burden in both liver and spleen compared with control- diet group. Gonadal adipocyte tissue from HSB-diet mice showed increased TNF-α, IL-6 and leptin and diminished IL-10 production compared with control. Cytokines production analysis in the spleen and liver from these animals also demonstrated higher production of IFN-γ, TNF-α, IL-6 and nitric oxide and diminished production of IL-10 and TGF-β, which correlate with inflammatory foci and the cell hyperplasia observed. Taken together, obesity can interfere with responses to pathogen-derived signals and impair the development of protective anti-Leishmania immunity.

  20. Increased Susceptibility to Klebsiella Pneumonia and Mortality in GSNOR-Deficient Mice

    PubMed Central

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

    2013-01-01

    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 hours after intranasal infection with K. pneumoniae were increased over four folds in lung and spleen and strikingly, over a thousand 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 hours 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. PMID:24239886

  1. Diet-induced obesity promotes systemic inflammation and increased susceptibility to murine visceral leishmaniasis.

    PubMed

    Sarnáglia, Glênia Daros; Covre, Luciana Polaco; Pereira, Fausto Edmundo Lima; DE Matos Guedes, Herbert Leonel; Faria, Ana Maria Caetano; Dietze, Reynaldo; Rodrigues, Rodrigo Ribeiro; Maioli, Tatiani Uceli; Gomes, Daniel Cláudio Oliviera

    2016-10-01

    Obesity is the main causal factor for metabolic syndrome and chronic systemic inflammation, which impacts on immune function and increases susceptibility to pathogens. Here, we investigated the effect of obesity on the outcome of visceral leishmaniasis caused by Leishmaniasis infantum chagasi. C57BL/6 mice fed with high-sugar and butter diet (HSB) showed a significant increase in body weight, adiposity index and morphological changes in adipocyte. To investigate the consequences of obesity on the specific immunity against Leishmania, both control and HSB diet groups were infected with 107 L. infantum chagasi promastigotes in the eighth-week after diet started and euthanized 4 weeks later. HSB-diet fed mice exhibited a significantly higher parasite burden in both liver and spleen compared with control- diet group. Gonadal adipocyte tissue from HSB-diet mice showed increased TNF-α, IL-6 and leptin and diminished IL-10 production compared with control. Cytokines production analysis in the spleen and liver from these animals also demonstrated higher production of IFN-γ, TNF-α, IL-6 and nitric oxide and diminished production of IL-10 and TGF-β, which correlate with inflammatory foci and the cell hyperplasia observed. Taken together, obesity can interfere with responses to pathogen-derived signals and impair the development of protective anti-Leishmania immunity. PMID:27440305

  2. Increased susceptibility to pulmonary Pseudomonas infection in Splunc1 knockout mice.

    PubMed

    Liu, Yanyan; Di, Marissa E; Chu, Hong Wei; Liu, Xinyu; Wang, Ling; Wenzel, Sally; Di, Y Peter

    2013-10-15

    The airway epithelium is the first line of host defense against pathogens. The short palate, lung, and nasal epithelium clone (SPLUNC)1 protein is secreted in respiratory tracts and is a member of the bacterial/permeability increasing (BPI) fold-containing protein family, which shares structural similarities with BPI-like proteins. On the basis of its homology with BPIs and restricted expression of SPLUNC1 in serous cells of submucosal glands and surface epithelial cells of the upper respiratory tract, SPLUNC1 is thought to possess antimicrobial activity in host defense. SPLUNC1 is also reported to have surfactant properties, which may contribute to anti-biofilm defenses. The objective of this study was to determine the in vivo functions of SPLUNC1 following Pseudomonas aeruginosa infection and to elucidate the underlying mechanism by using a knockout (KO) mouse model with a genetic ablation of Splunc1. Splunc1 KO mice showed accelerated mortality and increased susceptibility to P. aeruginosa infection with significantly decreased survival rates, increased bacterial burdens, exaggerated tissue injuries, and elevated proinflammatory cytokine levels as compared with those of their wild-type littermates. Increased neutrophil infiltration in Splunc1 KO mice was accompanied by elevated chemokine levels, including Cxcl1, Cxcl2, and Ccl20. Furthermore, the expression of several epithelial secretory proteins and antimicrobial molecules was considerably suppressed in the lungs of Splunc1 KO mice. The deficiency of Splunc1 in mouse airway epithelium also results in increased biofilm formation of P. aeruginosa. Taken together, our results support that the ablation of Splunc1 in mouse airways affects the mucociliary clearance, resulting in decreased innate immune response during Pseudomonas-induced respiratory infection. PMID:24048904

  3. Meditation potentially capable of increasing susceptibility to epilepsy - a follow-up hypothesis.

    PubMed

    Jaseja, Harinder

    2006-01-01

    In an earlier article entitled "Meditation may predispose to epilepsy: an insight into the alteration in brain environment induced by meditation" published in Medical Hypotheses 2005:64(3):464-7, the author has hypothesized that meditation exerts predisposing influence on epileptogenesis. The hypothesis is based on certain EEG changes and electrographic features (namely hypersynchrony and coherence of EEG activity) and increase in chemical transmitters (namely glutamate and serotonin) in the brain during the course and attainment of meditation. This paper aims to further strengthen the hypothesized predisposing influence of meditation on epilepsy by providing stronger evidences and with more elaboration. Studies on meditators have reported various adverse outcomes and one such study has indeed revealed significantly higher incidence of complex partial epileptic-like signs and experiences in a large number (n = 221) of meditators compared to non-meditators (controls n = 860), the researcher claiming "cognitive kindling" by meditation to be the underlying basis. These studies thus do highlight and underscore the strong influence of meditation in increasing susceptibility to epilepsy.

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

    PubMed

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

    2015-05-01

    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

  5. Reduced thrombin generation increases host susceptibility to group A streptococcal infection

    PubMed Central

    Sun, Hongmin; Wang, Xixi; Degen, Jay L.

    2009-01-01

    Bacterial plasminogen activators are commonplace among microbial pathogens, implying a central role of host plasmin in supporting bacterial virulence. Group A streptococci (GAS) secrete streptokinase, a specific activator of human plasminogen (PLG). The critical contribution of the streptokinase-PLG interaction to GAS pathogenicity was recently demonstrated using mice expressing human PLG. To examine the importance of thrombin generation in antimicrobial host defense, we challenged mice with deficiency of factor V (FV) in either the plasma or platelet compartment. Reduction of FV in either pool resulted in markedly increased mortality after GAS infection, with comparison to heterozygous F5-deficient mice suggesting a previously unappreciated role for the platelet FV pool in host defense. Mice with complete deficiency of fibrinogen also demonstrated markedly increased mortality to GAS infection relative to controls. Although FV Leiden may be protective in the setting of severe sepsis in humans, no significant survival advantage was observed in GAS-infected mice carrying the FV Leiden mutation. Taken together, our data support the hypothesis that local thrombosis/fibrin deposition limits the survival and dissemination of at least a subset of microbial pathogens and suggest that common variation in hemostatic factors among humans could affect host susceptibility to a variety of infectious diseases. PMID:19056689

  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. Early Life Exposure to Chronic Intermittent Hypoxia Primes Increased Susceptibility to Hypoxia-Induced Weakness in Rat Sternohyoid Muscle during Adulthood.

    PubMed

    McDonald, Fiona B; Dempsey, Eugene M; O'Halloran, Ken D

    2016-01-01

    Intermittent hypoxia is a feature of apnea of prematurity (AOP), chronic lung disease, and sleep apnea. Despite the clinical relevance, the long-term effects of hypoxic exposure in early life on respiratory control are not well defined. We recently reported that exposure to chronic intermittent hypoxia (CIH) during postnatal development (pCIH) causes upper airway muscle weakness in both sexes, which persists for several weeks. We sought to examine if there are persistent sex-dependent effects of pCIH on respiratory muscle function into adulthood and/or increased susceptibility to re-exposure to CIH in adulthood in animals previously exposed to CIH during postnatal development. We hypothesized that pCIH would cause long-lasting muscle impairment and increased susceptibility to subsequent hypoxia. Within 24 h of delivery, pups and their respective dams were exposed to CIH: 90 s of hypoxia reaching 5% O2 at nadir; once every 5 min, 8 h per day for 3 weeks. Sham groups were exposed to normoxia in parallel. Three groups were studied: sham; pCIH; and pCIH combined with adult CIH (p+aCIH), where a subset of the pCIH-exposed pups were re-exposed to the same CIH paradigm beginning at 13 weeks. Following gas exposures, sternohyoid and diaphragm muscle isometric contractile and endurance properties were examined ex vivo. There was no apparent lasting effect of pCIH on respiratory muscle function in adults. However, in both males and females, re-exposure to CIH in adulthood in pCIH-exposed animals caused sternohyoid (but not diaphragm) weakness. Exposure to this paradigm of CIH in adulthood alone had no effect on muscle function. Persistent susceptibility in pCIH-exposed airway dilator muscle to subsequent hypoxic insult may have implications for the control of airway patency in adult humans exposed to intermittent hypoxic stress during early life.

  8. 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. PMID:26647170

  9. 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.

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

    PubMed

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

    2015-05-01

    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.

  11. 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

  12. Inactivation of the lipoxygenase ZmLOX3 increases susceptibility of maize to Aspergillus spp

    PubMed Central

    Gao, Xiquan; Brodhagen, Marion; Isakeit, Tom; Brown, Sigal Horowitz; Göbel, Cornelia; Betran, Javier; Feussner, Ivo; Keller, Nancy P.; Kolomiets, Michael V.

    2009-01-01

    Plant and fungal lipoxygenases catalyze the oxidation of polyunsaturated fatty acids, creating fatty acid hydroperoxides (oxylipins). Fungal oxylipins are required for normal fungal development and secondary metabolism, and plant host-derived oxylipins interfere with these processes in fungi, presumably by signal mimicry. The maize lipoxygenase gene ZmLOX3 has been implicated previously in seed-Aspergillus interactions, so we tested the interactions of a mutant maize line (lox3–4, in which ZmLOX3 is disrupted) with the mycotoxigenic seed-infecting fungi Aspergillus flavus and Aspergillus nidulans. The lox3–4 mutant was more susceptible than wild type maize to both Aspergillus species. All strains of A. flavus and A. nidulans produced more conidia and aflatoxin (or the precursor sterigmatocystin) on lox3–4 kernels than on wild type kernels, in vitro and under field conditions. Although oxylipins did not differ detectably between A. flavus-infected kernels of the lox3–4 and WT maize, oxylipin precursors (free fatty acids) and a downstream metabolite (jasmonic acid) accumulated to greater levels in lox3–4 than in WT kernels. The increased resistance of the lox3–4 mutant to other fungal pathogens (Fusarium, Colletotrichum, Cochliobolus, and Exserohilum) is in sharp contrast with results described herein for Aspergillus, suggesting that outcomes of lipoxygenase-governed host-pathogen interactions are pathogen-specific. PMID:19132874

  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. 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

  15. MTHFR polymorphisms and Opisthorchis viverrini infection: a relationship with increased susceptibility to cholangiocarcinoma in Thailand.

    PubMed

    Songserm, Nopparat; Promthet, Supannee; Sithithaworn, Paiboon; Pientong, Chamsai; Ekalaksananan, Tipaya; Chopjitt, Peechanika; Parkin, Donald Maxwell

    2011-01-01

    Opisthorchis viverrini (OV) infection is the major risk factor for cholangiocarcinoma (CCA). Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme in folate metabolism. Change in MTHFR activity may influence both DNA methylation and synthesis, crucial steps in carcinogenesis. This study aimed to investigate the association between MTHFR polymorphisms and OV infection with CCA risk in a high-incidence area of Thailand. A nested case-control study within cohort study was carried out: 219 subjects with primary CCA were matched with two non-cancer controls from the same cohort on sex, age at recruitment and presence/ absence of OV eggs in stool. At the time of recruitment information on consumption of foodstuffs potentially contaminated by OV was obtained by questionnaire. MTHFR polymorphisms were analyzed using PCR with high resolution melting analysis. Associations between variables and the risk of CCA were assessed using conditional logistic regression. Risk of CCA was related to consumption of a dish of raw freshwater fish (Koi- Pla) with clear dose-response effects, and there were joint effects on CCA risk between MTHFR polymorphisms and consumption of dishes containing raw- and/or semi-raw freshwater fish. This study provides evidence to support a relationship of increased susceptibility to CCA in individuals with MTHFR variants, especially for those individuals who have OV infection or consume semi-raw freshwater fish (acting either as a source of OV or of pre-formed nitrosamine). Folate may play an important role in OV-related cholangiocarcinogenesis by upsetting the balance between DNA methylation and synthesis in the folate pathway. PMID:21875294

  16. 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…

  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. 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

  19. 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…

  20. 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

  1. 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. PMID:24146848

  2. 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.

  3. Cu/Zn superoxide dismutase mRNA and enzyme activity, and susceptibility to lipid peroxidation, increases with aging in murine brains.

    PubMed

    de Haan, J B; Newman, J D; Kola, I

    1992-04-01

    To protect against reactive oxygen species, prokaryotic and eukaryotic cells have developed an antioxidant defence mechanism where O2- is converted to H2O2 by superoxide dismutase (Sod), and in a second step, H2O2 is converted to H2O by catalase (Cat) and/or glutathione peroxidase (Gpx). If Sod levels are increased without a concomitant Gpx increase, then the intermediate H2O2 accumulates. This intermediate could undergo the Fenton's reaction, generating hydroxyl radicals which may lead to lipid peroxidation in cells. In this study, we investigate the expression of Sod1, Gpx1 and susceptibility to lipid peroxidation during the aging process in mouse brains. We demonstrate that the mRNA levels and enzyme activity of Sod1 are higher in brains from adult mice compared to neonatal mice. Furthermore, we show that a linear increase in Sod1 mRNA and enzyme activity occurs with aging (1-100 weeks). On the contrary, we find that the mRNA and enzyme activity for Gpx1 does not increase with aging in mouse brains. In addition, our results demonstrate that the susceptibility of murine brains to lipid peroxidation increases with aging. The data in this study are consistent with the notion that reactive oxygen species may contribute to the aging process in mammalian brains. These results are discussed in relation to the normal aging process in mammals, and to the premature aging and mental retardation in Down syndrome.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  5. 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…

  6. [Increased susceptibility to non-beta-lactam antimicrobial agents of MRSA isolates: relationship between genotype and antibiotype].

    PubMed

    Bertrand, X; Muller, A; Thouverez, M; Talon, D

    2004-10-01

    The objective of our study was to investigate the relationship between molecular epidemiology and antibiotic susceptibility of MRSA during a four-year period. In this aim, we determined the antibiotype of all MRSA identified during a yearly period of 3 months and typed 50 consecutive non-replicate MRSA isolates of each year. We also recorded antibiotic use. Susceptibility rates to gentamicin, tobramycin and ofloxacin remained stable, respectively, 95, 16 and 4%. In contrast, the proportion of MRSA susceptible to erythromycin progressively increased from 7.0% to 32.5% (P < 0.001). PFGE analysis of genomic DNA from the 200 isolates revealed 15 different clones. We identified two epidemic clones, which contained 150 (clone A) and 28 isolates (clone C), respectively. The proportion of isolates belonging to clone A decreased during the study from 86% to 66%. Conversely, clone C increased from 4% to 22%. The increase of erythromycin-susceptibility within MRSA was caused by the emergence of clone C. Non-epidemic strains were more frequently susceptible to ofloxacin (31.8% vs. 1.1%) and tobramycin (45.4% vs. 16.8%) than epidemic strains. Antimicrobial use had not significantly varied during the study. The proportion of beta-lactams, fluoroquinolones, macrolides and aminosides was 71.8, 13.9, 5.0 and 3.8% of the total antibiotic use, respectively. In our hospital, MRSA isolates became more susceptible to antimicrobial of minor use. The selection pressure exerted by beta-lactams and fluoroquinolones was in favor of the spread of strains resistant to these both major antibiotic classes.

  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. PMID:26484605

  8. Intrauterine low-functional programming of IGF1 by prenatal nicotine exposure mediates the susceptibility to osteoarthritis in female adult rat offspring.

    PubMed

    Tie, Kai; Zhang, Xianrong; Tan, Yang; Deng, Yu; Li, Jing; Ni, Qubo; Wang, Hui; Chen, Liaobin

    2016-02-01

    This study aimed to evaluate whether female adult offspring born with intrauterine growth retardation induced by prenatal nicotine exposure (PNE) are susceptible to osteoarthritis (OA) and to explore the underlying programming mechanisms. Pregnant rats were treated with nicotine or saline at 2.0 mg/kg/d from gestational d 11 to 20. The female adult offspring with or without PNE were forced with a strenuous treadmill running for 6 wk to induce OA. Nicotine's effects on fetal articular chondrocytes were studied by exposing chondrocytes to nicotine for 10 d, and dihydro-β-erythroidine, a selective α4β2-nicotinic acetylcholine receptor (nAChR) inhibitor, was used to identify the change of nicotine's effect. For adult offspring, increased cartilage destruction and accelerated OA progression were observed in the PNE group with running; the expression of α1 chain of type II collagen (Col2A1), aggrecan, SRY-type high mobility group box 9 (Sox9), and IGF1 signaling molecules in the cartilage of PNE offspring were decreased. For fetuses, elevated serum corticosteroid and nicotine levels and suppressed IGF1 levels were observed; expression of Col2A1, aggrecan, Sox9, and IGF1 were reduced. The result of chondrocytes revealed that nicotine impeded the expression of Col2A1, aggrecan, and IGF1; blocking α4β2-nAChR rescued nicotine's suppression. In conclusion, PNE increases the susceptibility of adult offspring to OA; the potential mechanism involves IGF1 low-functional programming in articular cartilage caused directly by the action of nicotine on α4β2-nAChR.

  9. 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.

  10. 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.

  11. 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

  12. West Nile Virus in Eastern Screech Owls: susceptibility of adults and transmission of maternal antibodies to young

    USGS Publications Warehouse

    Hahn, D.C.; Bright, P.; Deem, S.; Bowen, R.A.; Nemeth, N.; Komar, N.

    2005-01-01

    We studied the susceptibility and transmission of West Nile Virus in screech owls (Megascaps asia) in three ways: (1) investigating natural infection in captive screech owls housed in outdoor cages in MD, (2) tracking maternal transmission of WNV antibodies to hatchling owls, and (3) experimentally infecting juveniles under laboratory conditions. Three-quarters of the adult owls housed at PWRC showed WNV antibodies, but there was no pattern of infection related to age or cage location. Maternal transmission of WNV antibodies occurred in all broods of females that were WNV positive, and young owls within a brood showed different levels of antibodies. Screech owls were susceptible to experimental infection with live virus both by subcutaneous injection and oral ingestion, but not by vertical transmission from cage-mates. Individuals differed in degree of sickness, and some became severely ill and required euthanasia

  13. 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

  14. Low Iron Diet Increases Susceptibility to Noise-Induced Hearing Loss in Young Rats.

    PubMed

    Yu, Fei; Hao, Shuai; Yang, Bo; Zhao, Yue; Yang, Jun

    2016-01-01

    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

  15. 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

  16. Neonatal glucocorticoid treatment increased depression-like behaviour in adult rats.

    PubMed

    Ko, Meng-Chang; Hung, Yu-Hui; Ho, Pei-Yin; Yang, Yi-Ling; Lu, Kwok-Tung

    2014-12-01

    Synthetic glucocorticoid dexamethasone (DEX) is frequently used as a therapeutic agent to lessen the morbidity of chronic lung disease in premature infants. Previous studies suggested that neonatal DEX treatment altered brain development and cognitive function. It has been recognized that the amygdala is involved in emotional processes and also a critical site of neuronal plasticity for fear conditioning. Little is known about the possible long-term adverse effect of neonatal DEX treatment on amygdala function. The present study was aimed to evaluate the possible effect of neonatal DEX treatment on the synaptic function of amygdala in adult rats. Newborn Wistar rats were subjected to subcutaneous tapering-dose injections of DEX (0.5, 0.3 and 0.1 mg/kg) from post-natal day one to three, PN1-PN3. Animals were then subjected to a forced swimming test (FST) and electrophysiological recording aged eight weeks. The results of the FST showed neonatal DEX treatment increased depression-like behaviour in adulthood. After acute stress evoking, the percentage of time spent free floating is significantly increased in the DEX treated group compared with the control animals. Furthermore, neonatal DEX treatment elevated long-term potentiation (LTP) response and the phosphorylation level of MAPK in the lateral nucleus of amygdala (LA). Intracerebroventricular infusion of the MAPK inhibitor, PD98059, showed significant rescue effects including reduced depression-like behaviour and restoration of LTP to within normal range. In conclusion, our results suggested that MAPK signalling cascade in the LA plays an important role in the adverse effect of neonatal DEX treatment on amygdala function, which may result in adverse consequences in adult age, such as the enhancement of susceptibility for a depressive disorder in later life. PMID:24945924

  17. 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

  18. 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

  19. 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.

  20. Exposure to the Paralytic Shellfish Toxin Producer Alexandrium catenella Increases the Susceptibility of the Oyster Crassostrea gigas to Pathogenic Vibrios.

    PubMed

    Abi-Khalil, Celina; Lopez-Joven, Carmen; Abadie, Eric; Savar, Veronique; Amzil, Zouher; Laabir, Mohamed; Rolland, Jean-Luc

    2016-01-15

    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.

  1. Exposure to the Paralytic Shellfish Toxin Producer Alexandrium catenella Increases the Susceptibility of the Oyster Crassostrea gigas to Pathogenic Vibrios.

    PubMed

    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

  2. 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

  3. 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.

  4. Antimicrobial susceptibility testing for Helicobacter pylori in times of increasing antibiotic resistance.

    PubMed

    Smith, Sinéad M; O'Morain, Colm; McNamara, Deirdre

    2014-08-01

    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.

  5. Apoplastic Nucleoside Accumulation in Arabidopsis Leads to Reduced Photosynthetic Performance and Increased Susceptibility Against Botrytis cinerea.

    PubMed

    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.

  6. Antimicrobial susceptibility testing for Helicobacter pylori in times of increasing antibiotic resistance

    PubMed Central

    Smith, Sinéad M; O’Morain, Colm; McNamara, Deirdre

    2014-01-01

    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. PMID:25110421

  7. 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

  8. Increased susceptibility to hippocampal and amygdala kindling following intrahippocampal kainic acid.

    PubMed

    Feldblum, S; Ackermann, R F

    1987-08-01

    The effects of unilateral intrahippocampal injection of kainic acid, a potent neuroexcitant and neurotoxin, on subsequent susceptibility to kindling of the contralateral hippocampus or contralateral amygdala were investigated in albino rats. At the chosen doses (0.20 to 1.25 micrograms dissolved in physiologic saline), the kainic acid-induced lesion was confined to the injected hippocampus and in two cases the ipsilateral entorhinal cortex; never were there contralateral lesions. Approximately 2 to 6 weeks post-injection, each animal received daily afterdischarge-producing electrical stimulations until stage 5 kindled limbic seizures occurred. Kindling in pretreated animals was significantly accelerated compared with controls; the hippocampal kindling rate decreased from 13.2 stimulations to 3.7, the amygdala kindling rate from 7.8 stimulations to 3.0. Many treated animals had first-stimulation stage 5 seizures, compared with none for controls. Importantly, this facilitation of kindling was not reversed by suppression of the acute, induced seizures with the anticonvulsants, diazepam and phenobarbital, which have repeatedly been demonstrated to effectively suppress limbic kindling. Such results, considered together with findings from the literature, suggest that partial kindling does not occur during kainic acid-induced seizures, and that the observed susceptibility to kindling and other epileptogenic agents subsequent to kainic acid treatment may in fact be related to neurophysiologic and neurochemical consequences of kainic acid-induced lesions.

  9. HSV-2-Driven Increase in the Expression of α4β7 Correlates with Increased Susceptibility to Vaginal SHIVSF162P3 Infection

    PubMed Central

    Goode, Diana; Truong, Rosaline; Villegas, Guillermo; Calenda, Giulia; Guerra-Perez, Natalia; Piatak, Michael; Lifson, Jeffrey D.; Blanchard, James; Gettie, Agegnehu; Robbiani, Melissa; Martinelli, Elena

    2014-01-01

    The availability of highly susceptible HIV target cells that can rapidly reach the mucosal lymphoid tissues may increase the chances of an otherwise rare transmission event to occur. Expression of α4β7 is required for trafficking of immune cells to gut inductive sites where HIV can expand and it is expressed at high level on cells particularly susceptible to HIV infection. We hypothesized that HSV-2 modulates the expression of α4β7 and other homing receptors in the vaginal tissue and that this correlates with the increased risk of HIV acquisition in HSV-2 positive individuals. To test this hypothesis we used an in vivo rhesus macaque (RM) model of HSV-2 vaginal infection and a new ex vivo model of macaque vaginal explants. In vivo we found that HSV-2 latently infected RMs appeared to be more susceptible to vaginal SHIVSF162P3 infection, had higher frequency of α4β7high CD4+ T cells in the vaginal tissue and higher expression of α4β7 and CD11c on vaginal DCs. Similarly, ex vivo HSV-2 infection increased the susceptibility of the vaginal tissue to SHIVSF162P3. HSV-2 infection increased the frequencies of α4β7high CD4+ T cells and this directly correlated with HSV-2 replication. A higher amount of inflammatory cytokines in vaginal fluids of the HSV-2 infected animals was similar to those found in the supernatants of the infected explants. Remarkably, the HSV-2-driven increase in the frequency of α4β7high CD4+ T cells directly correlated with SHIV replication in the HSV-2 infected tissues. Our results suggest that the HSV-2-driven increase in availability of CD4+ T cells and DCs that express high levels of α4β7 is associated with the increase in susceptibility to SHIV due to HSV-2. This may persists in absence of HSV-2 shedding. Hence, higher availability of α4β7 positive HIV target cells in the vaginal tissue may constitute a risk factor for HIV transmission. PMID:25521298

  10. Lingual Kinematic Strategies Used to Increase Speech Rate: Comparison between Younger and Older Adults

    ERIC Educational Resources Information Center

    Goozee, Justine V.; Stephenson, Dayna K.; Murdoch, Bruce E.; Darnell, Ross E.; Lapointe, Leonard L.

    2005-01-01

    The primary objective of this study was to assess the lingual kinematic strategies used by younger and older adults to increase rate of speech. It was hypothesised that the strategies used by the older adults would differ from the young adults either as a direct result of, or in response to a need to compensate for, age-related changes in the…

  11. 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:…

  12. 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

  13. 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.

  14. Increased susceptibility to beta-lactam antibiotics and decreased porin content caused by envB mutations of Salmonella typhimurium.

    PubMed Central

    Oppezzo, O J; Avanzati, B; Antón, D N

    1991-01-01

    Isogenic derivatives carrying envB6, envB9, or envB+ alleles were obtained from a strain of Salmonella typhimurium that was partially resistant to mecillinam, a beta-lactam antibiotic specific for penicillin-binding protein 2 (PBP 2). Testing of the isogenic strains with several antibacterial agents demonstrated that envB mutations either increased resistance (mecillinam) or did not affect the response (imipemen) to beta-lactams that act primarily on PBP 2, while susceptibilities to beta-lactams that act on PBP 1B, PBP 3, or both were increased. Furthermore, the susceptibilities of envB strains to hydrophobic compounds such as rifampin, novobiocin, or chloramphenicol were not modified, even though their susceptibilities to deoxycholate and crystal violet were enhanced. Outer cell membranes of envB mutants presented a 50% reduction in protein content compared with that of the isogenic envB+ strains, and OmpF and OmpD porins were particularly affected by the reduction. No alteration in the amount or pattern of periplasmic proteins was noticed, and lipopolysaccharides from envB mutants appeared to be normal by sodium dodecyl sulfate-urea-polyacrylamide gel electrophoresis. By using derivatives that produced a plasmid-encoded beta-lactamase, it was demonstrated that envB cells are slightly less permeable to cephalothin than envB+ bacteria are. It is concluded that the high susceptibility of envB mutants to beta-lactams is due to the increased effectiveness of the antibiotics on PBP 1B, PBP 3, or both. Images PMID:1656857

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. A diphtheria epidemic in Lesotho, 1989. Did vaccination increase the population's susceptibility?

    PubMed

    van Geldermalsen, A A; Wenning, U

    1993-01-01

    We report a diphtheria outbreak which occurred in the 1st 6 months of 1989 in the Quthing district of Lesotho in Southern Africa. Sixty-eight clinical cases were identified in patients with ages ranging from 14 months to 51 years. The 10-15-year age group represented 38% of the cases and the 15-20-year age group another 26%. Age-adjusted incidence rates were higher in patients aged between 15 and 35 than in those aged 0-15 years (p < 0.001). The overall case fatality rate was 23%. Most deaths occurred in the age range 10-14 years, but the case fatality rate tended to be higher in the younger age groups. The epidemic raises the question of the influence of the ongoing vaccination programme, established since 1977, and the importance of naturally acquired immunity. It is suggested that the number of throat carriers, who in the absence of skin diphtheria would provide most of the population's immunity, decreases as an indirect consequence of vaccination, and that certain groups not immediately reached by vaccination become more susceptible to diphtheria. This outbreak also illustrates that a sporadic case of diphtheria in a partially immunized community warrants serious efforts to curb the spread of the disease.

  1. 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

  2. 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

  3. Impaired sinoatrial node function and increased susceptibility to atrial fibrillation in mice lacking natriuretic peptide receptor C

    PubMed Central

    Egom, Emmanuel E; Vella, Kimberly; Hua, Rui; Jansen, Hailey J; Moghtadaei, Motahareh; Polina, Iuliia; Bogachev, Oleg; Hurnik, Rhea; Mackasey, Martin; Rafferty, Sara; Ray, Gibanananda; Rose, Robert A

    2015-01-01

    Natriuretic peptides (NPs) are critical regulators of the cardiovascular system that are currently viewed as possible therapeutic targets for the treatment of heart disease. Recent work demonstrates potent NP effects on cardiac electrophysiology, including in the sinoatrial node (SAN) and atria. NPs elicit their effects via three NP receptors (NPR-A, NPR-B and NPR-C). Among these receptors, NPR-C is poorly understood. Accordingly, the goal of this study was to determine the effects of NPR-C ablation on cardiac structure and arrhythmogenesis. Cardiac structure and function were assessed in wild-type (NPR-C+/+) and NPR-C knockout (NPR-C−/−) mice using echocardiography, intracardiac programmed stimulation, patch clamping, high-resolution optical mapping, quantitative polymerase chain reaction and histology. These studies demonstrate that NPR-C−/− mice display SAN dysfunction, as indicated by a prolongation (30%) of corrected SAN recovery time, as well as an increased susceptibility to atrial fibrillation (6% in NPR-C+/+ vs. 47% in NPR-C−/−). There were no differences in SAN or atrial action potential morphology in NPR-C−/− mice; however, increased atrial arrhythmogenesis in NPR-C−/− mice was associated with reductions in SAN (20%) and atrial (15%) conduction velocity, as well as increases in expression and deposition of collagen in the atrial myocardium. No differences were seen in ventricular arrhythmogenesis or fibrosis in NPR-C−/− mice. This study demonstrates that loss of NPR-C results in SAN dysfunction and increased susceptibility to atrial arrhythmias in association with structural remodelling and fibrosis in the atrial myocardium. These findings indicate a critical protective role for NPR-C in the heart. Key points Natriuretic peptides (NPs) elicit their effects via multiple NP receptors (including NPR-A, NPR-B and NPR-C, with NPR-C being relatively poorly understood). We have studied the effects of NPR-C ablation on cardiac structure

  4. 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.

  5. Pre-existing diseases of patients increase susceptibility to hypoxemia during gastrointestinal endoscopy.

    PubMed

    Long, Yanhua; Liu, Hui-Hui; Yu, Changhong; Tian, Xia; Yang, Yi-Ran; Wang, Cheng; Pan, Yajuan

    2012-01-01

    Hypoxemia is the most common adverse event that happened during gastrointestinal endoscopy. To estimate risk of hypoxemia prior to endoscopy, American Society of Anesthesiology (ASA) classification scores were used as a major predictive factor. But the accuracy of ASA scores for predicting hypoxemia incidence was doubted here, considering that the classification system ignores much information about general health status and fitness of patient that may contribute to hypoxemia. In this retrospective review of clinical data collected prospectively, the data on 4904 procedures were analyzed. The Pearson's chi-square test or the Fisher exact test was employed to analyze variance of categorical factors. Continuous variables were statistically evaluated using t-tests or Analysis of variance (ANOVA). As a result, only 245 (5.0%) of the enrolled 4904 patients were found to present hypoxemia during endoscopy. Multivariable logistic regressions revealed that independent risk factors for hypoxemia include high BMI (BMI 30 versus 20, Odd ratio: 1.52, 95% CI: 1.13-2.05; P = 0.0098), hypertension (Odd ratio: 2.28, 95% CI: 1.44-3.60; P = 0.0004), diabetes (Odd ratio: 2.37, 95% CI: 1.30-4.34; P = 0.005), gastrointestinal diseases (Odd ratio: 1.77, 95% CI: 1.21-2.60; P = 0.0033), heart diseases (Odd ratio: 1.97, 95% CI: 1.06-3.68; P = 0.0325) and the procedures that combined esophagogastroduodenoscopy (EGD) and colonoscopy (Odd ratio: 4.84, 95% CI: 1.61-15.51; P = 0.0292; EGD as reference). It is noteworthy that ASA classification scores were not included as an independent predictive factor, and susceptibility of youth to hypoxemia during endoscopy was as high as old subjects. In conclusion, some certain pre-existing diseases of patients were newly identified as independent risk factors for hypoxemia during GI endoscopy. High ASA scores are a confounding predictive factor of pre-existing diseases. We thus recommend that youth (≤18 yrs), obese patients and

  6. C-Raf deficiency leads to hearing loss and increased noise susceptibility.

    PubMed

    de Iriarte Rodríguez, Rocío; Magariños, Marta; Pfeiffer, Verena; Rapp, Ulf R; Varela-Nieto, Isabel

    2015-10-01

    The family of RAF kinases transduces extracellular information to the nucleus, and their activation is crucial for cellular regulation on many levels, ranging from embryonic development to carcinogenesis. B-RAF and C-RAF modulate neurogenesis and neuritogenesis during chicken inner ear development. C-RAF deficiency in humans is associated with deafness in the rare genetic insulin-like growth factor 1 (IGF-1), Noonan and Leopard syndromes. In this study, we show that RAF kinases are expressed in the developing inner ear and in adult mouse cochlea. A homozygous C-Raf deletion in mice caused profound deafness with no evident cellular aberrations except for a remarkable reduction of the K(+) channel Kir4.1 expression, a trait that suffices as a cause of deafness. To explore the role of C-Raf in cellular protection and repair, heterozygous C-Raf (+/-) mice were exposed to noise. A reduced C-RAF level negatively affected hearing preservation in response to noise through mechanisms involving the activation of JNK and an exacerbated apoptotic response. Taken together, these results strongly support a role for C-RAF in hearing protection.

  7. Pseudomonas aeruginosa PAO1 adapted to 2-phenoxyethanol shows cross-resistance to dissimilar biocides and increased susceptibility to antibiotics.

    PubMed

    Abdel Malek, S M A; Badran, Y R

    2010-11-01

    The growth adaptability to increasing concentration of the biocide 2-phenoxyethanol (PE) was determined in Pseudomonas aeruginosa PAO1 (P.a.) as part of efforts to understand and control the biocide tolerance and its effect on cross-resistance to other biocides and resistance to antibiotics. After repeated subculturing in media containing increasing sub-minimum-inhibitory PE concentration, P.a. exhibited an adaptive resistance indicated by two-fold increase in MIC at the 10th passage. The resistance was stable and remained after passaging the strain in further 7 successive passages in PE-free growth media. The strain showed cross-resistance towards dissimilar biocides and displayed increased susceptibility to antibiotics, which was not influenced by the presence of the efflux inhibitor 'carbonyl cyanide m-chlorophenyl hydrazone'. Outer membranes of adapted strain showed altered protein profile when examined by SDS-PAGE.

  8. 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

  9. 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.

  10. 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.

  11. Longer genotypically-estimated leukocyte telomere length is associated with increased adult glioma risk

    PubMed Central

    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.

    2015-01-01

    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 = 7.82×10-8) and 27bp (5.0%) longer in glioma patients than controls in replication analyses (1.48×10-3). Glioma risk increased monotonically with each increasing septile of LTL (O.R.=1.12; P = 3.83×10-12). 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. PMID:26646793

  12. 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.

  13. 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:…

  14. 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

  15. Dysregulated autophagy in the RPE is associated with increased susceptibility to oxidative stress and AMD.

    PubMed

    Mitter, Sayak K; Song, Chunjuan; Qi, Xiaoping; Mao, Haoyu; Rao, Haripriya; Akin, Debra; Lewin, Alfred; Grant, Maria; Dunn, William; Ding, Jindong; Bowes Rickman, Catherine; Boulton, Michael

    2014-01-01

    Autophagic dysregulation has been suggested in a broad range of neurodegenerative diseases including age-related macular degeneration (AMD). To test whether the autophagy pathway plays a critical role to protect retinal pigmented epithelial (RPE) cells against oxidative stress, we exposed ARPE-19 and primary cultured human RPE cells to both acute (3 and 24 h) and chronic (14 d) oxidative stress and monitored autophagy by western blot, PCR, and autophagosome counts in the presence or absence of autophagy modulators. Acute oxidative stress led to a marked increase in autophagy in the RPE, whereas autophagy was reduced under chronic oxidative stress. Upregulation of autophagy by rapamycin decreased oxidative stress-induced generation of reactive oxygen species (ROS), whereas inhibition of autophagy by 3-methyladenine (3-MA) or by knockdown of ATG7 or BECN1 increased ROS generation, exacerbated oxidative stress-induced reduction of mitochondrial activity, reduced cell viability, and increased lipofuscin. Examination of control human donor specimens and mice demonstrated an age-related increase in autophagosome numbers and expression of autophagy proteins. However, autophagy proteins, autophagosomes, and autophagy flux were significantly reduced in tissue from human donor AMD eyes and 2 animal models of AMD. In conclusion, our data confirm that autophagy plays an important role in protection of the RPE against oxidative stress and lipofuscin accumulation and that impairment of autophagy is likely to exacerbate oxidative stress and contribute to the pathogenesis of AMD. PMID:25484094

  16. 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.

  17. 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. PMID:25353089

  18. Increasing Adult Hippocampal Neurogenesis is Sufficient to Reduce Anxiety and Depression-Like Behaviors.

    PubMed

    Hill, Alexis S; Sahay, Amar; Hen, René

    2015-09-01

    Adult hippocampal neurogenesis is increased by antidepressants, and is required for some of their behavioral effects. However, it remains unclear whether expanding the population of adult-born neurons is sufficient to affect anxiety and depression-related behavior. Here, we use an inducible transgenic mouse model in which the pro-apoptotic gene Bax is deleted from neural stem cells and their progeny in the adult brain, and thereby increases adult neurogenesis. We find no effects on baseline anxiety and depression-related behavior; however, we find that increasing adult neurogenesis is sufficient to reduce anxiety and depression-related behaviors in mice treated chronically with corticosterone (CORT), a mouse model of stress. Thus, neurogenesis differentially affects behavior under baseline conditions and in a model of chronic stress. Moreover, we find no effect of increased adult hippocampal neurogenesis on hypothalamic-pituitary-adrenal (HPA) axis regulation, either at baseline or following chronic CORT administration, suggesting that increasing adult hippocampal neurogenesis can affect anxiety and depression-related behavior through a mechanism independent of the HPA axis. The use of future techniques to specifically inhibit BAX in the hippocampus could be used to augment adult neurogenesis, and may therefore represent a novel strategy to promote antidepressant-like behavioral effects.

  19. Increasing Adult Hippocampal Neurogenesis is Sufficient to Reduce Anxiety and Depression-Like Behaviors.

    PubMed

    Hill, Alexis S; Sahay, Amar; Hen, René

    2015-09-01

    Adult hippocampal neurogenesis is increased by antidepressants, and is required for some of their behavioral effects. However, it remains unclear whether expanding the population of adult-born neurons is sufficient to affect anxiety and depression-related behavior. Here, we use an inducible transgenic mouse model in which the pro-apoptotic gene Bax is deleted from neural stem cells and their progeny in the adult brain, and thereby increases adult neurogenesis. We find no effects on baseline anxiety and depression-related behavior; however, we find that increasing adult neurogenesis is sufficient to reduce anxiety and depression-related behaviors in mice treated chronically with corticosterone (CORT), a mouse model of stress. Thus, neurogenesis differentially affects behavior under baseline conditions and in a model of chronic stress. Moreover, we find no effect of increased adult hippocampal neurogenesis on hypothalamic-pituitary-adrenal (HPA) axis regulation, either at baseline or following chronic CORT administration, suggesting that increasing adult hippocampal neurogenesis can affect anxiety and depression-related behavior through a mechanism independent of the HPA axis. The use of future techniques to specifically inhibit BAX in the hippocampus could be used to augment adult neurogenesis, and may therefore represent a novel strategy to promote antidepressant-like behavioral effects. PMID:25833129

  20. 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

  1. Calpain 2-mediated autophagy defect increases susceptibility of fatty livers to ischemia–reperfusion injury

    PubMed Central

    Zhao, Q; Guo, Z; Deng, W; Fu, S; Zhang, C; Chen, M; Ju, W; Wang, D; He, X

    2016-01-01

    Hepatic steatosis is associated with significant morbidity and mortality after liver resection and transplantation. This study focuses on the role of autophagy in regulating sensitivity of fatty livers to ischemia and reperfusion (I/R) injury. Quantitative immunohistochemistry conducted on human liver allograft biopsies showed that, the reduction of autophagy markers LC3 and Beclin-1 at 1 h after reperfusion, was correlated with hepatic steatosis and poor survival of liver transplant recipients. In animal studies, western blotting and confocal imaging analysis associated the increase in sensitivity to I/R injury with low autophagy activity in fatty livers. Screening of autophagy-related proteins showed that Atg3 and Atg7 expression levels were marked decreased, whereas calpain 2 expression was upregulated during I/R in fatty livers. Calpain 2 inhibition or knockdown enhanced autophagy and suppressed cell death. Further point mutation experiments revealed that calpain 2 cleaved Atg3 and Atg7 at Atg3Δ92–97 and Atg7Δ344–349, respectively. In vivo and in vitro overexpression of Atg3 or Atg7 enhanced autophagy and suppressed cell death after I/R in fatty livers. Collectively, calpain 2-mediated degradation of Atg3 and Atg7 in fatty livers increases their sensitivity to I/R injury. Increasing autophagy may ameliorate fatty liver damage and represent a valuable method to expand the liver donor pool. PMID:27077802

  2. 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

  3. Increased susceptibility to ethylmercury-induced mitochondrial dysfunction in a subset of autism lymphoblastoid cell lines.

    PubMed

    Rose, Shannon; Wynne, Rebecca; Frye, Richard E; Melnyk, Stepan; James, S Jill

    2015-01-01

    The association of autism spectrum disorders with oxidative stress, redox imbalance, and mitochondrial dysfunction has become increasingly recognized. In this study, extracellular flux analysis was used to compare mitochondrial respiration in lymphoblastoid cell lines (LCLs) from individuals with autism and unaffected controls exposed to ethylmercury, an environmental toxin known to deplete glutathione and induce oxidative stress and mitochondrial dysfunction. We also tested whether pretreating the autism LCLs with N-acetyl cysteine (NAC) to increase glutathione concentrations conferred protection from ethylmercury. Examination of 16 autism/control LCL pairs revealed that a subgroup (31%) of autism LCLs exhibited a greater reduction in ATP-linked respiration, maximal respiratory capacity, and reserve capacity when exposed to ethylmercury, compared to control LCLs. These respiratory parameters were significantly elevated at baseline in the ethylmercury-sensitive autism subgroup as compared to control LCLs. NAC pretreatment of the sensitive subgroup reduced (normalized) baseline respiratory parameters and blunted the exaggerated ethylmercury-induced reserve capacity depletion. These findings suggest that the epidemiological link between environmental mercury exposure and an increased risk of developing autism may be mediated through mitochondrial dysfunction and support the notion that a subset of individuals with autism may be vulnerable to environmental influences with detrimental effects on development through mitochondrial dysfunction.

  4. Increased Susceptibility to Ethylmercury-Induced Mitochondrial Dysfunction in a Subset of Autism Lymphoblastoid Cell Lines

    PubMed Central

    Wynne, Rebecca; Frye, Richard E.; Melnyk, Stepan; James, S. Jill

    2015-01-01

    The association of autism spectrum disorders with oxidative stress, redox imbalance, and mitochondrial dysfunction has become increasingly recognized. In this study, extracellular flux analysis was used to compare mitochondrial respiration in lymphoblastoid cell lines (LCLs) from individuals with autism and unaffected controls exposed to ethylmercury, an environmental toxin known to deplete glutathione and induce oxidative stress and mitochondrial dysfunction. We also tested whether pretreating the autism LCLs with N-acetyl cysteine (NAC) to increase glutathione concentrations conferred protection from ethylmercury. Examination of 16 autism/control LCL pairs revealed that a subgroup (31%) of autism LCLs exhibited a greater reduction in ATP-linked respiration, maximal respiratory capacity, and reserve capacity when exposed to ethylmercury, compared to control LCLs. These respiratory parameters were significantly elevated at baseline in the ethylmercury-sensitive autism subgroup as compared to control LCLs. NAC pretreatment of the sensitive subgroup reduced (normalized) baseline respiratory parameters and blunted the exaggerated ethylmercury-induced reserve capacity depletion. These findings suggest that the epidemiological link between environmental mercury exposure and an increased risk of developing autism may be mediated through mitochondrial dysfunction and support the notion that a subset of individuals with autism may be vulnerable to environmental influences with detrimental effects on development through mitochondrial dysfunction. PMID:25688267

  5. Complement component 6 deficiency increases susceptibility to dextran sulfate sodium-induced murine colitis.

    PubMed

    Ding, Peipei; Li, Ling; Huang, Tianbao; Yang, Chaoqun; Xu, Enjie; Wang, Na; Zhang, Long; Gu, Hongyu; Yao, Xudong; Zhou, Xuhui; Hu, Weiguo

    2016-11-01

    As a potent effector of innate immunity, the complement system has been shown to be involved in the pathogenesis of inflammatory bowel disease (IBD). However, the role of the membrane attack complex (MAC) in the development of IBD is still largely unknown. Here, we used C6-deficient mice in which MAC formation was blocked due to the absence of C6 to develop an acute colitis model by the administration of dextran sulfate sodium (DSS). The results showed that DSS-induced colitis was aggravated in C6-deficient mice compared with wild-type (WT) mice, as represented by the markedly greater weight loss, higher disease activity index (DAI), shortened colon length, more severe histological injury with increased epithelial ulcerations, and massively increased infiltration of leukocytes accompanied by much higher myeloperoxidase (MPO) levels in local inflammatory colonic sites. In addition, the DSS-induced colitis in C6-deficient mice could be significantly ameliorated by the exogenous C6 from WT sera. Furthermore, the significantly enhanced production of pro-inflammatory mediators, including IL-1β, IL-6, CXCL-1, CCL-3, TGF-β1 and IL-17F, was also observed in C6-deficient mice. Unexpectedly, the aggravated colitis in C6-deficient mice may be not due to the increase of lipopolysaccharide (LPS) levels in serum. Overall, we demonstrated that MAC exerts a protective role in acute colitis, strongly highlighting the host defense function of the complement system. PMID:27316715

  6. 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.

  7. 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.

  8. Safety margins in older adults increase with improved control of a dynamic object.

    PubMed

    Hasson, Christopher J; Sternad, Dagmar

    2014-01-01

    Older adults face decreasing motor capabilities due to pervasive neuromuscular degradations. As a consequence, errors in movement control increase. Thus, older individuals should maintain larger safety margins than younger adults. While this has been shown for object manipulation tasks, several reports on whole-body activities, such as posture and locomotion, demonstrate age-related reductions in safety margins. This is despite increased costs for control errors, such as a fall. We posit that this paradox could be explained by the dynamic challenge presented by the body or also an external object, and that age-related reductions in safety margins are in part due to a decreased ability to control dynamics. To test this conjecture we used a virtual ball-in-cup task that had challenging dynamics, yet afforded an explicit rendering of the physics and safety margin. The hypotheses were: (1) When manipulating an object with challenging dynamics, older adults have smaller safety margins than younger adults. (2) Older adults increase their safety margins with practice. Nine young and 10 healthy older adults practiced moving the virtual ball-in-cup to a target location in exactly 2 s. The accuracy and precision of the timing error quantified skill, and the ball energy relative to an escape threshold quantified the safety margin. Compared to the young adults, older adults had increased timing errors, greater variability, and decreased safety margins. With practice, both young and older adults improved their ability to control the object with decreased timing errors and variability, and increased their safety margins. These results suggest that safety margins are related to the ability to control dynamics, and may explain why in tasks with simple dynamics older adults use adequate safety margins, but in more complex tasks, safety margins may be inadequate. Further, the results indicate that task-specific training may improve safety margins in older adults.

  9. Safety margins in older adults increase with improved control of a dynamic object

    PubMed Central

    Hasson, Christopher J.; Sternad, Dagmar

    2014-01-01

    Older adults face decreasing motor capabilities due to pervasive neuromuscular degradations. As a consequence, errors in movement control increase. Thus, older individuals should maintain larger safety margins than younger adults. While this has been shown for object manipulation tasks, several reports on whole-body activities, such as posture and locomotion, demonstrate age-related reductions in safety margins. This is despite increased costs for control errors, such as a fall. We posit that this paradox could be explained by the dynamic challenge presented by the body or also an external object, and that age-related reductions in safety margins are in part due to a decreased ability to control dynamics. To test this conjecture we used a virtual ball-in-cup task that had challenging dynamics, yet afforded an explicit rendering of the physics and safety margin. The hypotheses were: (1) When manipulating an object with challenging dynamics, older adults have smaller safety margins than younger adults. (2) Older adults increase their safety margins with practice. Nine young and 10 healthy older adults practiced moving the virtual ball-in-cup to a target location in exactly 2 s. The accuracy and precision of the timing error quantified skill, and the ball energy relative to an escape threshold quantified the safety margin. Compared to the young adults, older adults had increased timing errors, greater variability, and decreased safety margins. With practice, both young and older adults improved their ability to control the object with decreased timing errors and variability, and increased their safety margins. These results suggest that safety margins are related to the ability to control dynamics, and may explain why in tasks with simple dynamics older adults use adequate safety margins, but in more complex tasks, safety margins may be inadequate. Further, the results indicate that task-specific training may improve safety margins in older adults. PMID:25071566

  10. Community-based exergaming program increases physical activity and perceived wellness in older adults.

    PubMed

    Strand, Kara A; Francis, Sarah L; Margrett, Jennifer A; Franke, Warren D; Peterson, Marc J

    2014-07-01

    Exergaming may be an effective strategy to increase physical activity participation among rural older adults. This pilot project examined the effects of a 24-wk exergaming and wellness program (8 wk onsite exergaming, 16-wk wellness newsletter intervention) on physical activity participation and subjective health in 46 rural older adults. Sociodemographic data and self-reported physical activity were analyzed using descriptive statistics and Cochran's Q, respectively. Qualitative data were reviewed, categorized on the basis of theme, and tabulated for frequency. Increased physical activity and perceived health were the most reported perceived positive changes. Significant increases in physical activity participation were maintained among participants who were physically inactive at baseline. Best-liked features were physical activity and socialization. Findings suggest that this pilot exergaming and wellness program is effective in increasing physical activity in sedentary rural older adults, increasing socialization, and increasing subjective physical health among rural older adults.

  11. Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers

    PubMed Central

    Plant, Darren; Flynn, Edward; Mbarek, Hamdi; Dieudé, Philippe; Cornelis, François; Ärlestig, Lisbeth; Dahlqvist, Solbritt Rantapää; Goulielmos, George; Boumpas, Dimitrios T; Sidiropoulos, Prodromos; Johansen, Julia S; Ørnbjerg, Lykke M; Hetland, Merete Lund; Klareskog, Lars; Filer, Andrew; Buckley, Christopher D; Raza, Karim; Witte, Torsten; Schmidt, Reinhold E; Worthington, Jane

    2010-01-01

    Background Genetic factors have a substantial role in determining development of rheumatoid arthritis (RA), and are likely to account for 50–60% of disease susceptibility. Genome-wide association studies have identified non-human leucocyte antigen RA susceptibility loci which associate with RA with low-to-moderate risk. Objectives To investigate recently identified RA susceptibility markers using cohorts from six European countries, and perform a meta-analysis including previously published results. Methods 3311 DNA samples were collected from patients from six countries (UK, Germany, France, Greece, Sweden and Denmark). Genotype data or DNA samples for 3709 controls were collected from four countries (not Sweden or Denmark). Eighteen single nucleotide polymorphisms (SNPs) were genotyped using Sequenom MassArray technology. Samples with a >95% success rate and only those SNPs with a genotype success rate of >95% were included in the analysis. Scandinavian patient data were pooled and previously published Swedish control data were accessed as a comparison group. Meta-analysis was used to combine results from this study with all previously published data. Results After quality control, 3209 patients and 3692 controls were included in the study. Eight markers (ie, rs1160542 (AFF3), rs1678542 (KIF5A), rs2476601 (PTPN22), rs3087243 (CTLA4), rs4810485 (CD40), rs5029937 (6q23), rs10760130 (TRAF1/C5) and rs7574865 (STAT4)) were significantly associated with RA by meta-analysis. All 18 markers were associated with RA when previously published studies were incorporated in the analysis. Data from this study increased the significance for association with RA and nine markers. Conclusions In a large European RA cohort further evidence for the association of 18 markers with RA development has been obtained. PMID:20498205

  12. Increased Risk Taking in Relation to Chronic Stress in Adults.

    PubMed

    Ceccato, Smarandita; Kudielka, Brigitte M; Schwieren, Christiane

    2015-01-01

    Chronic stress is a public health problem that affects a significant part of the population. While the physiological damage it causes is under ongoing scrutiny, its behavioral effects have been overlooked. This is one of the first studies to examine the relation between chronic stress and decision-making, using a standard lottery paradigm. We measured risk taking in the gain domain through binary choices between financially incentivized lotteries. We then measured self-reported chronic stress with the Trier Inventory for the Assessment of Chronic Stress (TICS). We additionally collected hair samples in a subsample of volunteers, in order to quantify accumulation of the stress hormone cortisol. We discovered a significant positive, though modest, correlation between self-reported chronic stress and risk taking that is stronger for women than for men. This confirms part of the findings in acute stress research that show a connection between higher stress and increased risk taking. However, unlike the biologically-based results from acute stress research, we did not identify a significant relation between hair cortisol and behavior. In line with previous literature, we found a clear gender difference in risk taking and self-reports: women generally take less risk and report slightly higher stress levels than men. We conclude that perceived chronic stress can impact behavior in risky situations. PMID:26858663

  13. Increased Risk Taking in Relation to Chronic Stress in Adults

    PubMed Central

    Ceccato, Smarandita; Kudielka, Brigitte M.; Schwieren, Christiane

    2016-01-01

    Chronic stress is a public health problem that affects a significant part of the population. While the physiological damage it causes is under ongoing scrutiny, its behavioral effects have been overlooked. This is one of the first studies to examine the relation between chronic stress and decision-making, using a standard lottery paradigm. We measured risk taking in the gain domain through binary choices between financially incentivized lotteries. We then measured self-reported chronic stress with the Trier Inventory for the Assessment of Chronic Stress (TICS). We additionally collected hair samples in a subsample of volunteers, in order to quantify accumulation of the stress hormone cortisol. We discovered a significant positive, though modest, correlation between self-reported chronic stress and risk taking that is stronger for women than for men. This confirms part of the findings in acute stress research that show a connection between higher stress and increased risk taking. However, unlike the biologically-based results from acute stress research, we did not identify a significant relation between hair cortisol and behavior. In line with previous literature, we found a clear gender difference in risk taking and self-reports: women generally take less risk and report slightly higher stress levels than men. We conclude that perceived chronic stress can impact behavior in risky situations. PMID:26858663

  14. ATOX1 gene silencing increases susceptibility to anticancer therapy based on copper ionophores or chelating drugs.

    PubMed

    Barresi, Vincenza; Spampinato, Giorgia; Musso, Nicolò; Trovato Salinaro, Angela; Rizzarelli, Enrico; Condorelli, Daniele Filippo

    2016-03-01

    Copper is a catalytic cofactor required for the normal function of many enzymes involved in fundamental biological processes but highly cytotoxic when in excess. Therefore its homeostasis and distribution is strictly regulated by a network of transporters and intracellular chaperones. ATOX1 (antioxidant protein 1) is a copper chaperone that plays a role in copper homeostasis by binding and transporting cytosolic copper to ATPase proteins in the trans-Golgi network. In the present study the Caco-2 cell line, a colon carcinoma cell line, was used as an in vitro model to evaluate if ATOX1 deficiency could affect sensitivity to experimentally induced copper dyshomeostasis. Silencing of ATOX1 increased toxicity of a short treatment with a high concentration of Cu(2+). Copper ionophores, such as 5-chloro-8-hydroxyquinoline, induced a copper-dependent cell toxicity which was significantly potentiated after ATOX1 silencing. The copper chelator TPEN (N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine) produced a form of cell toxicity that was reversed by the addition of Cu(2+). ATOX1 silencing increased Caco-2 cell sensitivity to TPEN toxicity. Our results suggest the possibility of a therapy with copper-chelating or ionophore drugs in subtypes of tumors showing specific alterations in ATOX1 expression. PMID:26784148

  15. Recombinant human DNase I decreases biofilm and increases antimicrobial susceptibility in staphylococci.

    PubMed

    Kaplan, Jeffrey B; LoVetri, Karen; Cardona, Silvia T; Madhyastha, Srinivasa; Sadovskaya, Irina; Jabbouri, Saïd; Izano, Era A

    2012-02-01

    Extracellular DNA is an adhesive component of staphylococcal biofilms. The aim of this study was to evaluate the antibiofilm activity of recombinant human DNase I (rhDNase) against Staphylococcus aureus and Staphylococcus epidermidis. Using a 96-well microtiter plate crystal-violet binding assay, we found that biofilm formation by S. aureus was efficiently inhibited by rhDNase at 1-4 μg l⁻¹, and preformed S. aureus biofilms were efficiently detached in 2 min by rhDNase at 1 mg l⁻¹. Pretreatment of S. aureus biofilms for 10 min with 10 mg l⁻¹ rhDNase increased their sensitivity to biocide killing by 4-5 log units. rhDNase at 10 mg l⁻¹ significantly inhibited biofilm formation by S. epidermidis in medium supplemented with sub-MICs of antibiotics. We also found that rhDNase significantly increased the survival of S. aureus-infected Caenorhabditis elegans nematodes treated with tobramycin compared with nematodes treated with tobramycin alone. We concluded that rhDNase exhibits potent antibiofilm and antimicrobial-sensitizing activities against S. aureus and S. epidermidis at clinically achievable concentrations. rhDNase, either alone or in combination with antimicrobial agents, may have applications in treating or preventing staphylococcal biofilm-related infections. PMID:22167157

  16. 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.

  17. 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

  18. Using the Natural Language Paradigm (NLP) to Increase Vocalizations of Older Adults with Cognitive Impairments

    ERIC Educational Resources Information Center

    LeBlanc, Linda A.; Geiger, Kaneen B.; Sautter, Rachael A.; Sidener, Tina M.

    2007-01-01

    The Natural Language Paradigm (NLP) has proven effective in increasing spontaneous verbalizations for children with autism. This study investigated the use of NLP with older adults with cognitive impairments served at a leisure-based adult day program for seniors. Three individuals with limited spontaneous use of functional language participated…

  19. Effects of Increased Mobility Skills on Meaningful Life Participation for an Adult with Severe Multiple Disabilities

    ERIC Educational Resources Information Center

    Whinnery, Stacie B.; Whinnery, Keith W.

    2012-01-01

    This article presents a case study of an adult with severe, multiple disabilities and discusses issues affecting meaningful life participation. Emphasis is placed on the role of functional mobility skills to increase active engagement in age-appropriate activities and opportunities to make informed choices. MOVE for Adults (Mobility Opportunities…

  20. Impaired regulation of NF-κB and increased susceptibility to colitis-associated tumorigenesis in CYLD-deficient mice

    PubMed Central

    Zhang, Jun; Stirling, Brigid; Temmerman, Stephane T.; Ma, Chi A.; Fuss, Ivan J.; Derry, Jonathan M.J.; Jain, Ashish

    2006-01-01

    Cylindromatosis (CYLD) is a deubiquitinating enzyme that is altered in patients with familial cylindromatosis, a condition characterized by numerous benign adnexal tumors. However, the regulatory function of CYLD remains unsettled. Here we show that the development of B cells, T cells, and myeloid cells was unaffected in CYLD-deficient mice, but that the activation of these cells with mediators of innate and adaptive immunity resulted in enhanced NF-κB and JNK activity associated with increased TNF receptor–associated factor 2 (TRAF2) and NF-κB essential modulator (NEMO) ubiquitination. CYLD-deficient mice were more susceptible to induced colonic inflammation and showed a dramatic increase in the incidence of tumors compared with controls in a colitis-associated cancer model. These results suggest that CYLD limits inflammation and tumorigenesis by regulating ubiquitination in vivo. PMID:17053834

  1. 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

  2. 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

  3. Increasing phonological complexity reveals heightened instability in inter-articulatory coordination in adults who stutter

    PubMed Central

    Smith, Anne; Sadagopan, Neeraja; Walsh, Bridget; Weber-Fox, Christine

    2010-01-01

    The potential role of phonological complexity in destabilizing the speech motor systems of adults who stutter was explored by assessing the performance of 17 adults who stutter and 17 matched control participants on a nonword repetition task. The nonwords varied in length and phonological complexity. Behavioral results revealed no differences between the stuttering and normally fluent groups on accuracy of nonword repetition. In contrast, dramatic differences between groups were observed in the kinematic data. Indices of the consistency of inter-articulator coordination revealed that adults who stutter were much less consistent in their coordinative patterns over repeated productions. With increasing length and complexity of the nonwords, between-group differences in coordinative consistency were more pronounced. Coordination consistency measures revealed that adults who stutter (but not normally fluent adults) showed within-session practice effects; their coordinative consistency improved in five later compared to five earlier productions. Adults who stutter produced the nonwords at a slower rate, but both groups showed increased rates of production on the later trials, indicating a practice effect for duration for both groups. We conclude that, though the adults who stutter performed behaviorally with the same accuracy as normally fluent adults, the nonword repetition task reveals remarkable differences in the speech motor dynamics underlying fluent speech production in adults who stutter compared to their normally fluent peers. These results support a multifactorial, dynamic model of stuttering in which linguistic complexity and utterance length are factors that contribute to the probability of breakdown of the speech motor system. PMID:20412979

  4. Polygenic mutations in the cytotoxicity pathway increase susceptibility to develop HLH immunopathology in mice.

    PubMed

    Sepulveda, Fernando E; Garrigue, Alexandrine; Maschalidi, Sophia; Garfa-Traore, Meriem; Ménasché, Gaël; Fischer, Alain; de Saint Basile, Geneviève

    2016-04-28

    Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory disease. Inherited forms of HLH are caused by biallelic mutations in several effectors of granule-dependent lymphocyte-mediated cytotoxicity. A small proportion of patients with a so-called "secondary" form of HLH, which develops in the aftermath of infection, autoimmunity, or cancer, carry a monoallelic mutation in one or more HLH-associated genes. Although this observation suggests that HLH may have a polygenic mode of inheritance, the latter is very difficult to prove in humans. In order to determine whether the accumulation of partial genetic defects in lymphocyte-mediated cytotoxicity can contribute to the development of HLH, we generated mice that were doubly or triply heterozygous for mutations in HLH-associated genes, those coding for perforin, Rab27a, and syntaxin-11. We found that the accumulation of monoallelic mutations did indeed increase the risk of developing HLH immunopathology after lymphocytic choriomeningitis virus infection. In mechanistic terms, the accumulation of heterozygous mutations in the two degranulation genes Rab27a and syntaxin-11, impaired the dynamics and secretion of cytotoxic granules at the immune synapse of T lymphocytes. In addition, the accumulation of heterozygous mutations within the three genes impaired natural killer lymphocyte cytotoxicity in vivo. The genetic defects can be ranked in terms of the severity of the resulting HLH manifestations. Our results form the basis of a polygenic model of the occurrence of secondary HLH. PMID:26864340

  5. 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.

  6. 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

  7. Lexical decisions in adults with low and high susceptibility to pattern-related visual stress: a preliminary investigation.

    PubMed

    Gilchrist, James M; Allen, Peter M

    2015-01-01

    Pattern-related visual stress (PRVS) is a form of sensory hypersensitivity that some people experience when viewing high contrast repeating patterns, notably alternating dark and light stripes. Those susceptible to PRVS typically have a strong aversion to such stimuli, and this is often accompanied by experiences of visual discomfort and disturbance. The patterns most likely to elicit symptoms of PRVS have a square-wave grating configuration of spatial frequency ~3 cycles/degree. Such stimuli are characteristic of printed text in which lines of words and the spaces between them present a high contrast grating-like stimulus. Consequently, much printed reading material has the potential to elicit PRVS that may impair reading performance, and this problem appears to be common in individuals with reading difficulties including dyslexia. However, the manner in which PRVS affects reading ability is unknown. One possibility is that the early sensory visual stress may interfere with the later cognitive word recognition stage of the reading process, resulting in reading performance that is slower and/or less accurate. To explore the association of PRVS with word recognition ability, lexical decision performance (speed and accuracy) to words and pronounceable non-words was measured in two groups of adults, having low and high susceptibility to PRVS. Results showed that lexical decisions were generally faster but less accurate in high-PRVS, and also that high-PRVS participants made decisions significantly faster for words than for non-words, revealing a strong lexicality effect that was not present in low-PRVS. These findings are novel and, as yet, unconfirmed by other studies.

  8. Lexical decisions in adults with low and high susceptibility to pattern-related visual stress: a preliminary investigation

    PubMed Central

    Gilchrist, James M.; Allen, Peter M.

    2015-01-01

    Pattern-related visual stress (PRVS) is a form of sensory hypersensitivity that some people experience when viewing high contrast repeating patterns, notably alternating dark and light stripes. Those susceptible to PRVS typically have a strong aversion to such stimuli, and this is often accompanied by experiences of visual discomfort and disturbance. The patterns most likely to elicit symptoms of PRVS have a square-wave grating configuration of spatial frequency ~3 cycles/degree. Such stimuli are characteristic of printed text in which lines of words and the spaces between them present a high contrast grating-like stimulus. Consequently, much printed reading material has the potential to elicit PRVS that may impair reading performance, and this problem appears to be common in individuals with reading difficulties including dyslexia. However, the manner in which PRVS affects reading ability is unknown. One possibility is that the early sensory visual stress may interfere with the later cognitive word recognition stage of the reading process, resulting in reading performance that is slower and/or less accurate. To explore the association of PRVS with word recognition ability, lexical decision performance (speed and accuracy) to words and pronounceable non-words was measured in two groups of adults, having low and high susceptibility to PRVS. Results showed that lexical decisions were generally faster but less accurate in high-PRVS, and also that high-PRVS participants made decisions significantly faster for words than for non-words, revealing a strong lexicality effect that was not present in low-PRVS. These findings are novel and, as yet, unconfirmed by other studies. PMID:25926810

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. Eliminating Medicaid adult dental coverage in California led to increased dental emergency visits and associated costs.

    PubMed

    Singhal, Astha; Caplan, Daniel J; Jones, Michael P; Momany, Elizabeth T; Kuthy, Raymond A; Buresh, Christopher T; Isman, Robert; Damiano, Peter C

    2015-05-01

    Dental coverage for adults is an elective benefit under Medicaid. As a result of budget constraints, California Medicaid eliminated its comprehensive adult dental coverage in July 2009. We examined the impact of this policy change on emergency department (ED) visits by Medicaid-enrolled adults for dental problems in the period 2006-11. We found that the policy change led to a significant and immediate increase in dental ED use, amounting to more than 1,800 additional dental ED visits per year. Young adults, members of racial/ethnic minority groups, and urban residents were disproportionately affected by the policy change. Average yearly costs associated with dental ED visits increased by 68 percent. The California experience provides evidence that eliminating Medicaid adult dental benefits shifts dental care to costly EDs that do not provide definitive dental care. The population affected by the Medicaid adult dental coverage policy is increasing as many states expand their Medicaid programs under the ACA. Hence, such evidence is critical to inform decisions regarding adult dental coverage for existing Medicaid enrollees and expansion populations. PMID:25941275

  15. Variation occurring in group A streptococci during human infection; progressive loss of M substance correlated with increasing susceptibility to bacteriostasis.

    PubMed

    ROTHBARD, S; WATSON, R F

    1948-06-01

    A study was made of the variation occurring in group A streptococci during the natural course of infection in man. From 54 patients with 56 different group A streptococcal infections of the upper respiratory tract, 251 strains of streptococci, isolated at weekly intervals following infection, were tested for their capacity to resist the bacteriostatic action of normal human blood. In 52 of the infections the streptococci were of recognized serological types and were also tested for variation in their ability to produce the type-specific M protein antigen. Strains isolated in the 1st week of infection were uniformly highly resistant to bacteriostasis and elaborated large amounts of M substance. In 42 per cent of the 52 infections, strains isolated in the convalescent and carrier stages showed an increasing susceptibility to bacteriostasis correlated with a progressive loss of M substance; whereas in the remaining 58 per cent resistance to bacteriostasis and the capacity to produce M protein were maintained throughout the observation period. In 3 different infections, the streptococci became so degraded that no M protein could be demonstrated in acid extracts of these variants. Concomitantly these strains became highly susceptible to bacteriostasis. Spontaneous reversion did not occur, but serial mouse passage reestablished these functions. These degraded variants had the same T antigen as their respective original strains. No evidence was obtained that variation of group A streptococci in resistance to bacteriostasis or in the ability to produce the type-specific M antigen was associated (a) with the appearance of type-specific bacteriostatic antibodies; (b) with any particular serological type of streptococcus; (c) with the production of streptococcal proteinase which digests the M protein; (d) with the therapeutic administration of sulfadiazine; or (e) with the development of complications. The possible relationship of these observations to the problem of the

  16. Loss of the transcription factor Meis1 prevents sympathetic neurons target-field innervation and increases susceptibility to sudden cardiac death.

    PubMed

    Bouilloux, Fabrice; Thireau, Jérôme; Ventéo, Stéphanie; Farah, Charlotte; Karam, Sarah; Dauvilliers, Yves; Valmier, Jean; Copeland, Neal G; Jenkins, Nancy A; Richard, Sylvain; Marmigère, Frédéric

    2016-01-01

    Although cardio-vascular incidents and sudden cardiac death (SCD) are among the leading causes of premature death in the general population, the origins remain unidentified in many cases. Genome-wide association studies have identified Meis1 as a risk factor for SCD. We report that Meis1 inactivation in the mouse neural crest leads to an altered sympatho-vagal regulation of cardiac rhythmicity in adults characterized by a chronotropic incompetence and cardiac conduction defects, thus increasing the susceptibility to SCD. We demonstrated that Meis1 is a major regulator of sympathetic target-field innervation and that Meis1 deficient sympathetic neurons die by apoptosis from early embryonic stages to perinatal stages. In addition, we showed that Meis1 regulates the transcription of key molecules necessary for the endosomal machinery. Accordingly, the traffic of Rab5(+) endosomes is severely altered in Meis1-inactivated sympathetic neurons. These results suggest that Meis1 interacts with various trophic factors signaling pathways during postmitotic neurons differentiation. PMID:26857994

  17. Loss of the transcription factor Meis1 prevents sympathetic neurons target-field innervation and increases susceptibility to sudden cardiac death

    PubMed Central

    Bouilloux, Fabrice; Thireau, Jérôme; Ventéo, Stéphanie; Farah, Charlotte; Karam, Sarah; Dauvilliers, Yves; Valmier, Jean; Copeland, Neal G; Jenkins, Nancy A; Richard, Sylvain; Marmigère, Frédéric

    2016-01-01

    Although cardio-vascular incidents and sudden cardiac death (SCD) are among the leading causes of premature death in the general population, the origins remain unidentified in many cases. Genome-wide association studies have identified Meis1 as a risk factor for SCD. We report that Meis1 inactivation in the mouse neural crest leads to an altered sympatho-vagal regulation of cardiac rhythmicity in adults characterized by a chronotropic incompetence and cardiac conduction defects, thus increasing the susceptibility to SCD. We demonstrated that Meis1 is a major regulator of sympathetic target-field innervation and that Meis1 deficient sympathetic neurons die by apoptosis from early embryonic stages to perinatal stages. In addition, we showed that Meis1 regulates the transcription of key molecules necessary for the endosomal machinery. Accordingly, the traffic of Rab5+ endosomes is severely altered in Meis1-inactivated sympathetic neurons. These results suggest that Meis1 interacts with various trophic factors signaling pathways during postmitotic neurons differentiation. DOI: http://dx.doi.org/10.7554/eLife.11627.001 PMID:26857994

  18. ABA Suppresses Botrytis cinerea Elicited NO Production in Tomato to Influence H2O2 Generation and Increase Host Susceptibility

    PubMed Central

    Sivakumaran, Anushen; Akinyemi, Aderemi; Mandon, Julian; Cristescu, Simona M.; Hall, Michael A.; Harren, Frans J. M.; Mur, Luis A. J.

    2016-01-01

    Abscisic acid (ABA) production has emerged a susceptibility factor in plant-pathogen interactions. This work examined the interaction of ABA with nitric oxide (NO) in tomato following challenge with the ABA-synthesizing pathogen, Botrytis cinerea. Trace gas detection using a quantum cascade laser detected NO production within minutes of challenge with B. cinerea whilst photoacoustic laser detection detected ethylene production – an established mediator of defense against this pathogen – occurring after 6 h. Application of the NO generation inhibitor N-Nitro-L-arginine methyl ester (L-NAME) suppressed both NO and ethylene production and resistance against B. cinerea. The tomato mutant sitiens fails to accumulate ABA, shows increased resistance to B. cinerea and we noted exhibited elevated NO and ethylene production. Exogenous application of L-NAME or ABA reduced NO production in sitiens and reduced resistance to B. cinerea. Increased resistance to B. cinerea in sitiens have previously been linked to increased reactive oxygen species (ROS) generation but this was reduced in both L-NAME and ABA-treated sitiens. Taken together, our data suggests that ABA can decreases resistance to B. cinerea via reduction of NO production which also suppresses both ROS and ethylene production. PMID:27252724

  19. ABA Suppresses Botrytis cinerea Elicited NO Production in Tomato to Influence H2O2 Generation and Increase Host Susceptibility.

    PubMed

    Sivakumaran, Anushen; Akinyemi, Aderemi; Mandon, Julian; Cristescu, Simona M; Hall, Michael A; Harren, Frans J M; Mur, Luis A J

    2016-01-01

    Abscisic acid (ABA) production has emerged a susceptibility factor in plant-pathogen interactions. This work examined the interaction of ABA with nitric oxide (NO) in tomato following challenge with the ABA-synthesizing pathogen, Botrytis cinerea. Trace gas detection using a quantum cascade laser detected NO production within minutes of challenge with B. cinerea whilst photoacoustic laser detection detected ethylene production - an established mediator of defense against this pathogen - occurring after 6 h. Application of the NO generation inhibitor N-Nitro-L-arginine methyl ester (L-NAME) suppressed both NO and ethylene production and resistance against B. cinerea. The tomato mutant sitiens fails to accumulate ABA, shows increased resistance to B. cinerea and we noted exhibited elevated NO and ethylene production. Exogenous application of L-NAME or ABA reduced NO production in sitiens and reduced resistance to B. cinerea. Increased resistance to B. cinerea in sitiens have previously been linked to increased reactive oxygen species (ROS) generation but this was reduced in both L-NAME and ABA-treated sitiens. Taken together, our data suggests that ABA can decreases resistance to B. cinerea via reduction of NO production which also suppresses both ROS and ethylene production. PMID:27252724

  20. Dietary vitamin D3 deficiency alters intestinal mucosal defense and increases susceptibility to Citrobacter rodentium-induced colitis.

    PubMed

    Ryz, Natasha R; Lochner, Arion; Bhullar, Kirandeep; Ma, Caixia; Huang, Tina; Bhinder, Ganive; Bosman, Else; Wu, Xiujuan; Innis, Sheila M; Jacobson, Kevan; Vallance, Bruce A

    2015-11-01

    Vitamin D deficiency affects more that 1 billion people worldwide. Although thought to increase risk of bacterial infections, the importance of vitamin D on host defense against intestinal bacterial pathogens is currently unclear since injection of the active form of vitamin D, 1,25(OH)2D3, increased susceptibility to the enteric bacterial pathogen Citrobacter rodentium by suppressing key immune/inflammatory factors. To further characterize the role of vitamin D during bacteria-induced colitis, we fed weanling mice either vitamin D3-deficient or vitamin D3-sufficient diets for 5 wk and then challenged them with C. rodentium. Vitamin D3-deficient mice lost significantly more body weight, carried higher C. rodentium burdens, and developed worsened histological damage. Vitamin D3-deficient mice also suffered greater bacterial translocation to extra-intestinal tissues, including mesenteric lymph nodes, spleen, and liver. Intestinal tissues of infected vitamin D3-deficient mice displayed increased inflammatory cell infiltrates as well as significantly higher gene transcript levels of inflammatory mediators TNF-α, IL-1β, IL-6, TGF-β, IL-17A, and IL-17F as well as the antimicrobial peptide REG3γ. Notably, these exaggerated inflammatory responses accelerated the loss of commensal microbes and were associated with an impaired ability to detoxify bacterial lipopolysaccharide. Overall, these studies show that dietary-induced vitamin D deficiency exacerbates intestinal inflammatory responses to infection, also impairing host defense.

  1. Increased dopaminergic innervation in the brain of conditional mutant mice overexpressing Otx2: effects on locomotor behavior and seizure susceptibility.

    PubMed

    Tripathi, P P; Di Giovannantonio, L G; Sanguinetti, E; Acampora, D; Allegra, M; Caleo, M; Wurst, W; Simeone, A; Bozzi, Y

    2014-03-01

    The homeobox-containing transcription factor Otx2 controls the identity, fate and proliferation of mesencephalic dopaminergic (mesDA) neurons. Transgenic mice, in which Otx2 was conditionally overexpressed by a Cre recombinase expressed under the transcriptional control of the Engrailed1 gene (En1(Cre/+); tOtx2(ov/+)), show an increased number of mesDA neurons during development. In adult mice, Otx2 is expressed in a subset of neurons in the ventral tegmental area (VTA) and its overexpression renders mesDA more resistant to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-HCl (MPTP) neurotoxin. Here we further investigated the neurological consequences of the increased number of mesDA neurons in En1(Cre/+); tOtx2(ov/+) adult mice. Immunohistochemistry for the active, glycosylated form of the dopamine transporter (glyco-Dat) showed that En1(Cre/+); tOtx2(ov/+) adult mice display an increased density of mesocortical DAergic fibers, as compared to control animals. Increased glyco-Dat staining was accompanied by a marked hypolocomotion in En1(Cre/+); tOtx2(ov/+) mice, as detected in the open field test. Since conditional knockout mice lacking Otx2 in mesDA precursors (En1(Cre/+); Otx2(floxv/flox) mice) show a marked resistance to kainic acid (KA)-induced seizures, we investigated the behavioral response to KA in En1(Cre/+); tOtx2(ov/+) and control mice. No difference was observed between mutant and control mice, but En1(Cre/+); tOtx2(ov/+) mice showed a markedly different c-fos mRNA induction profile in the cerebral cortex and hippocampus after KA seizures, as compared to controls. Accordingly, an increased density of parvalbumin (PV)-positive inhibitory interneurons was detected in the deep layers of the frontal cortex of naïve En1(Cre/+); tOtx2(ov/+) mice, as compared to controls. These data indicate that Otx2 overexpression results in increased DAergic innervation and PV cell density in the fronto-parietal cortex, with important consequences on spontaneous locomotor

  2. Resistance to Bacillus thuringiensis Mediated by an ABC Transporter Mutation Increases Susceptibility to Toxins from Other Bacteria in an Invasive Insect

    PubMed Central

    Zhang, Dandan; Gong, Lingling; He, Fei; Soberón, Mario; Bravo, Alejandra; Tabashnik, Bruce E.; Wu, Kongming

    2016-01-01

    Evolution of pest resistance reduces the efficacy of insecticidal proteins from the gram-positive bacterium Bacillus thuringiensis (Bt) used widely in sprays and transgenic crops. Recent efforts to delay pest adaptation to Bt crops focus primarily on combinations of two or more Bt toxins that kill the same pest, but this approach is often compromised because resistance to one Bt toxin causes cross-resistance to others. Thus, integration of Bt toxins with alternative controls that do not exhibit such cross-resistance is urgently needed. The ideal scenario of negative cross-resistance, where selection for resistance to a Bt toxin increases susceptibility to alternative controls, has been elusive. Here we discovered that selection of the global crop pest, Helicoverpa armigera, for >1000-fold resistance to Bt toxin Cry1Ac increased susceptibility to abamectin and spineotram, insecticides derived from the soil bacteria Streptomyces avermitilis and Saccharopolyspora spinosa, respectively. Resistance to Cry1Ac did not affect susceptibility to the cyclodiene, organophospate, or pyrethroid insecticides tested. Whereas previous work demonstrated that the resistance to Cry1Ac in the strain analyzed here is conferred by a mutation disrupting an ATP-binding cassette protein named ABCC2, the new results show that increased susceptibility to abamectin is genetically linked with the same mutation. Moreover, RNAi silencing of HaABCC2 not only decreased susceptibility to Cry1Ac, it also increased susceptibility to abamectin. The mutation disrupting ABCC2 reduced removal of abamectin in live larvae and in transfected Hi5 cells. The results imply that negative cross-resistance occurs because the wild type ABCC2 protein plays a key role in conferring susceptibility to Cry1Ac and in decreasing susceptibility to abamectin. The negative cross-resistance between a Bt toxin and other bacterial insecticides reported here may facilitate more sustainable pest control. PMID:26872031

  3. Hypoxia-Induced Intrauterine Growth Restriction Increases the Susceptibility of Rats to High-Fat Diet–Induced Metabolic Syndrome

    PubMed Central

    Rueda-Clausen, Christian F.; Dolinsky, Vernon W.; Morton, Jude S.; Proctor, Spencer D.; Dyck, Jason R.B.; Davidge, Sandra T.

    2011-01-01

    OBJECTIVE It is recognized that there is a remarkable variability in the systemic response to high-fat (HF) diets that cannot be completely explained by genetic factors. In addition, pregnancy complications leading to intrauterine growth restriction (IUGR) have been associated with an increased risk of developing metabolic syndrome (MetS) later in life. Thus, we hypothesized that offspring born with IUGR exhibit permanent metabolic changes that make them more susceptible to HF diet–induced MetS. RESEARCH DESIGN AND METHODS SD rats born normal (control) or with hypoxia-induced IUGR were randomized to low-fat (10% fat) or HF (45% fat) diets. After 9 weeks of feeding, physiological and molecular pathways involved in the MetS were evaluated. RESULTS IUGR offspring exhibited decreased energy intake and physical activity relative to controls. In offspring fed a HF diet, IUGR was associated with decreased total body fat content, a relative increase in intra-abdominal fat deposition and adipocyte size, an increase in fasting plasma concentrations of leptin, triglyceride and free fatty acids, and an increased concentration of triglycerides and ceramides in both liver and skeletal muscle. These changes in lipid homeostasis were accompanied by in vivo insulin resistance and impaired glucose tolerance and associated with increased phosphorylation of protein kinase C θ, inhibition of insulin receptor substrate 1, and a decreased activation of protein kinase B (PKB; also known as Akt) in liver and skeletal muscle in response to insulin. CONCLUSIONS IUGR enhances specific deleterious metabolic responses to a HF diet. Our results suggest that offspring born with IUGR may require special attention and follow-up to prevent the early onset of MetS. PMID:21270262

  4. Proanthocyanidins inhibit Ascaris suum glutathione-S-transferase activity and increase susceptibility of larvae to levamisole in vitro.

    PubMed

    Hansen, Tina V A; Fryganas, Christos; Acevedo, Nathalie; Caraballo, Luis; Thamsborg, Stig M; Mueller-Harvey, Irene; Williams, Andrew R

    2016-08-01

    Proanthocyanidins (PAC) are a class of plant secondary metabolites commonly found in the diet that have shown potential to control gastrointestinal nematode infections. The anti-parasitic mechanism(s) of PAC remain obscure, however the protein-binding properties of PAC suggest that disturbance of key enzyme functions may be a potential mode of action. Glutathione-S-transferases (GSTs) are essential for parasite detoxification and have been investigated as drug and vaccine targets. Here, we show that purified PAC strongly inhibit the activity of both recombinant and native GSTs from the parasitic nematode Ascaris suum. As GSTs are involved in detoxifying xenobiotic substances within the parasite, we hypothesised that this inhibition may render parasites hyper-susceptible to anthelmintic drugs. Migration inhibition assays with A. suum larvae demonstrated that the potency of levamisole (LEV) and ivermectin (IVM) were significantly increased in the presence of PAC purified from pine bark (4.6-fold and 3.2-fold reduction in IC50 value for LEV and IVM, respectively). Synergy analysis revealed that the relationship between PAC and LEV appeared to be synergistic in nature, suggesting a specific enhancement of LEV activity, whilst the relationship between PAC and IVM was additive rather than synergistic, suggesting independent actions. Our results demonstrate that these common dietary compounds may increase the efficacy of synthetic anthelmintic drugs in vitro, and also suggest one possible mechanism for their well-known anti-parasitic activity. PMID:27094225

  5. Ligand binding to an Allergenic Lipid Transfer Protein Enhances Conformational Flexibility resulting in an Increase in Susceptibility to Gastroduodenal Proteolysis.

    PubMed

    Abdullah, Syed Umer; Alexeev, Yuri; Johnson, Philip E; Rigby, Neil M; Mackie, Alan R; Dhaliwal, Balvinder; Mills, E N Clare

    2016-01-01

    Non-specific lipid transfer proteins (LTPs) are a family of lipid-binding molecules that are widely distributed across flowering plant species, many of which have been identified as allergens. They are highly resistant to simulated gastroduodenal proteolysis, a property that may play a role in determining their allergenicity and it has been suggested that lipid binding may further increase stability to proteolysis. It is demonstrated that LTPs from wheat and peach bind a range of lipids in a variety of conditions, including those found in the gastroduodenal tract. Both LTPs are initially cleaved during gastroduodenal proteolysis at three major sites between residues 39-40, 56-57 and 79-80, with wheat LTP being more resistant to cleavage than its peach ortholog. The susceptibility of wheat LTP to proteolyic cleavage increases significantly upon lipid binding. This enhanced digestibility is likely to be due to the displacement of Tyr79 and surrounding residues from the internal hydrophobic cavity upon ligand binding to the solvent exposed exterior of the LTP, facilitating proteolysis. Such knowledge contributes to our understanding as to how resistance to digestion can be used in allergenicity risk assessment of novel food proteins, including GMOs. PMID:27458082

  6. Proanthocyanidins inhibit Ascaris suum glutathione-S-transferase activity and increase susceptibility of larvae to levamisole in vitro.

    PubMed

    Hansen, Tina V A; Fryganas, Christos; Acevedo, Nathalie; Caraballo, Luis; Thamsborg, Stig M; Mueller-Harvey, Irene; Williams, Andrew R

    2016-08-01

    Proanthocyanidins (PAC) are a class of plant secondary metabolites commonly found in the diet that have shown potential to control gastrointestinal nematode infections. The anti-parasitic mechanism(s) of PAC remain obscure, however the protein-binding properties of PAC suggest that disturbance of key enzyme functions may be a potential mode of action. Glutathione-S-transferases (GSTs) are essential for parasite detoxification and have been investigated as drug and vaccine targets. Here, we show that purified PAC strongly inhibit the activity of both recombinant and native GSTs from the parasitic nematode Ascaris suum. As GSTs are involved in detoxifying xenobiotic substances within the parasite, we hypothesised that this inhibition may render parasites hyper-susceptible to anthelmintic drugs. Migration inhibition assays with A. suum larvae demonstrated that the potency of levamisole (LEV) and ivermectin (IVM) were significantly increased in the presence of PAC purified from pine bark (4.6-fold and 3.2-fold reduction in IC50 value for LEV and IVM, respectively). Synergy analysis revealed that the relationship between PAC and LEV appeared to be synergistic in nature, suggesting a specific enhancement of LEV activity, whilst the relationship between PAC and IVM was additive rather than synergistic, suggesting independent actions. Our results demonstrate that these common dietary compounds may increase the efficacy of synthetic anthelmintic drugs in vitro, and also suggest one possible mechanism for their well-known anti-parasitic activity.

  7. Droughts may increase susceptibility of prairie dogs to fleas: Incongruity with hypothesized mechanisms of plague cycles in rodents

    USGS Publications Warehouse

    Eads, David; Biggins, Dean E.; Long, Dustin H.; Gage, Kenneth L.; Antolin, Michael F.

    2016-01-01

    Plague is a reemerging, rodent-associated zoonosis caused by the flea-borne bacterium Yersinia pestis. As a vector-borne disease, rates of plague transmission may increase when fleas are abundant. Fleas are highly susceptible to desiccation under hot-dry conditions; we posited that their densities decline during droughts. We evaluated this hypothesis with black-tailed prairie dogs (Cynomys ludovicianus) in New Mexico, June–August 2010–2012. Precipitation was relatively plentiful during 2010 and 2012 but scarce during 2011, the driest spring–summer on record for the northeastern grasslands of New Mexico. Unexpectedly, fleas were 200% more abundant in 2011 than in 2010 and 2012. Prairie dogs were in 27% better condition during 2010 and 2012, and they devoted 287% more time to grooming in 2012 than in 2011. During 2012, prairie dogs provided with supplemental food and water were in 23% better condition and carried 40% fewer fleas. Collectively, these results suggest that during dry years, prairie dogs are limited by food and water, and they exhibit weakened defenses against fleas. Long-term data are needed to evaluate the generality of whether droughts increase flea densities and how changes in flea abundance during sequences of dry and wet years might affect plague cycles in mammalian hosts.

  8. Impaired neutrophil activity and increased susceptibility to bacterial infection in mice lacking glucose-6-phosphatase–β

    PubMed Central

    Cheung, Yuk Yin; Kim, So Youn; Yiu, Wai Han; Pan, Chi-Jiunn; Jun, Hyun-Sik; Ruef, Robert A.; Lee, Eric J.; Westphal, Heiner; Mansfield, Brian C.; Chou, Janice Y.

    2007-01-01

    Neutropenia and neutrophil dysfunction are common in many diseases, although their etiology is often unclear. Previous views held that there was a single ER enzyme, glucose-6-phosphatase–α (G6Pase-α), whose activity — limited to the liver, kidney, and intestine — was solely responsible for the final stages of gluconeogenesis and glycogenolysis, in which glucose-6-phosphate (G6P) is hydrolyzed to glucose for release to the blood. Recently, we characterized a second G6Pase activity, that of G6Pase-β (also known as G6PC), which is also capable of hydrolyzing G6P to glucose but is ubiquitously expressed and not implicated in interprandial blood glucose homeostasis. We now report that the absence of G6Pase-β led to neutropenia; defects in neutrophil respiratory burst, chemotaxis, and calcium flux; and increased susceptibility to bacterial infection. Consistent with this, G6Pase-β–deficient (G6pc3–/–) mice with experimental peritonitis exhibited increased expression of the glucose-regulated proteins upregulated during ER stress in their neutrophils and bone marrow, and the G6pc3–/– neutrophils exhibited an enhanced rate of apoptosis. Our results define a molecular pathway to neutropenia and neutrophil dysfunction of previously unknown etiology, providing a potential model for the treatment of these conditions. PMID:17318259

  9. Ligand binding to an Allergenic Lipid Transfer Protein Enhances Conformational Flexibility resulting in an Increase in Susceptibility to Gastroduodenal Proteolysis

    PubMed Central

    Abdullah, Syed Umer; Alexeev, Yuri; Johnson, Philip E.; Rigby, Neil M.; Mackie, Alan R.; Dhaliwal, Balvinder; Mills, E. N. Clare

    2016-01-01

    Non-specific lipid transfer proteins (LTPs) are a family of lipid-binding molecules that are widely distributed across flowering plant species, many of which have been identified as allergens. They are highly resistant to simulated gastroduodenal proteolysis, a property that may play a role in determining their allergenicity and it has been suggested that lipid binding may further increase stability to proteolysis. It is demonstrated that LTPs from wheat and peach bind a range of lipids in a variety of conditions, including those found in the gastroduodenal tract. Both LTPs are initially cleaved during gastroduodenal proteolysis at three major sites between residues 39–40, 56–57 and 79–80, with wheat LTP being more resistant to cleavage than its peach ortholog. The susceptibility of wheat LTP to proteolyic cleavage increases significantly upon lipid binding. This enhanced digestibility is likely to be due to the displacement of Tyr79 and surrounding residues from the internal hydrophobic cavity upon ligand binding to the solvent exposed exterior of the LTP, facilitating proteolysis. Such knowledge contributes to our understanding as to how resistance to digestion can be used in allergenicity risk assessment of novel food proteins, including GMOs. PMID:27458082

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

    PubMed

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

    2013-03-01

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

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

    PubMed

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

    2013-03-01

    A chronic stress paradigm comprising exposure to predation, tail suspension and restraint induces a depressive syndrome in C57BL/6J mice that occurs in some, but not all, animals. Here, we sought to extend our behavioural studies to investigate how susceptibility (sucrose preference<65%) or resilience (sucrose preference>65%) to stress-induced anhedonia affects the 5HT system and the expression of inflammation-related genes. All chronically stressed animals, displayed increased level of anxiety, but susceptible mice exhibited an increased propensity to float in the forced swim test and demonstrate hyperactivity under stressful lighting conditions. These changes were not present in resilient or acutely stressed animals. Compared to resilient animals, susceptible mice showed elevated expression of tumour necrosis factor alpha (TNF) and the 5-HT transporter (SERT) in the pre-frontal area. Enhanced expression of 5HT(2A) and COX-1 in the pre-frontal area was observed in all stressed animals. In turn, indoleamine-2,3-dioxygenase (IDO) was significantly unregulated in the raphe of susceptible animals. At the cellular level, increased numbers of Iba-1-positive microglial cells were also present in the prefrontal area of susceptible animals compared to resilient animals. Consequently, the susceptible animals display a unique molecular profile when compared to resilient, but anxious, animals. Unexpectedly, this altered profile provides a rationale for exploring anti-inflammatory, and possibly, TNF-targeted therapy for major depression. PMID:23305936

  12. Low brain ascorbic acid increases susceptibility to seizures in mouse models of decreased brain ascorbic acid transport and Alzheimer's disease.

    PubMed

    Warner, Timothy A; Kang, Jing-Qiong; Kennard, John A; Harrison, Fiona E

    2015-02-01

    Seizures are a known co-occurring symptom of Alzheimer's disease, and they can accelerate cognitive and neuropathological dysfunction. Sub-optimal vitamin C (ascorbic acid) deficiency, that is low levels that do not lead the sufferer to present with clinical signs of scurvy (e.g. lethargy, hemorrhage, hyperkeratosis), are easily obtainable with insufficient dietary intake, and may contribute to the oxidative stress environment of both Alzheimer's disease and epilepsy. The purpose of this study was to test whether mice that have diminished brain ascorbic acid in addition to carrying human Alzheimer's disease mutations in the amyloid precursor protein (APP) and presenilin 1 (PSEN1) genes, had altered electrical activity in the brain (electroencephalography; EEG), and were more susceptible to pharmacologically induced seizures. Brain ascorbic acid was decreased in APP/PSEN1 mice by crossing them with sodium vitamin C transporter 2 (SVCT2) heterozygous knockout mice. These mice have an approximately 30% decrease in brain ascorbic acid due to lower levels of SVCT2 that supplies the brain with ASC. SVCT2+/-APP/PSEN1 mice had decreased ascorbic acid and increased oxidative stress in brain, increased mortality, faster seizure onset latency following treatment with kainic acid (10 mg/kg i.p.), and more ictal events following pentylenetetrazol (50 mg/kg i.p.) treatment. Furthermore, we report the entirely novel phenomenon that ascorbic acid deficiency alone increased the severity of kainic acid- and pentylenetetrazol-induced seizures. These data suggest that avoiding ascorbic acid deficiency may be particularly important in populations at increased risk for epilepsy and seizures, such as Alzheimer's disease.

  13. Low brain ascorbic acid increases susceptibility to seizures in mouse models of decreased brain ascorbic acid transport and Alzheimer's disease.

    PubMed

    Warner, Timothy A; Kang, Jing-Qiong; Kennard, John A; Harrison, Fiona E

    2015-02-01

    Seizures are a known co-occurring symptom of Alzheimer's disease, and they can accelerate cognitive and neuropathological dysfunction. Sub-optimal vitamin C (ascorbic acid) deficiency, that is low levels that do not lead the sufferer to present with clinical signs of scurvy (e.g. lethargy, hemorrhage, hyperkeratosis), are easily obtainable with insufficient dietary intake, and may contribute to the oxidative stress environment of both Alzheimer's disease and epilepsy. The purpose of this study was to test whether mice that have diminished brain ascorbic acid in addition to carrying human Alzheimer's disease mutations in the amyloid precursor protein (APP) and presenilin 1 (PSEN1) genes, had altered electrical activity in the brain (electroencephalography; EEG), and were more susceptible to pharmacologically induced seizures. Brain ascorbic acid was decreased in APP/PSEN1 mice by crossing them with sodium vitamin C transporter 2 (SVCT2) heterozygous knockout mice. These mice have an approximately 30% decrease in brain ascorbic acid due to lower levels of SVCT2 that supplies the brain with ASC. SVCT2+/-APP/PSEN1 mice had decreased ascorbic acid and increased oxidative stress in brain, increased mortality, faster seizure onset latency following treatment with kainic acid (10 mg/kg i.p.), and more ictal events following pentylenetetrazol (50 mg/kg i.p.) treatment. Furthermore, we report the entirely novel phenomenon that ascorbic acid deficiency alone increased the severity of kainic acid- and pentylenetetrazol-induced seizures. These data suggest that avoiding ascorbic acid deficiency may be particularly important in populations at increased risk for epilepsy and seizures, such as Alzheimer's disease. PMID:25616451

  14. The neurodevelopmental differences of increasing verbal working memory demand in children and adults.

    PubMed

    Vogan, V M; Morgan, B R; Powell, T L; Smith, M L; Taylor, M J

    2016-02-01

    Working memory (WM) - temporary storage and manipulation of information in the mind - is a key component of cognitive maturation, and structural brain changes throughout development are associated with refinements in WM. Recent functional neuroimaging studies have shown that there is greater activation in prefrontal and parietal brain regions with increasing age, with adults showing more refined, localized patterns of activations. However, few studies have investigated the neural basis of verbal WM development, as the majority of reports examine visuo-spatial WM. We used fMRI and a 1-back verbal WM task with six levels of difficulty to examine the neurodevelopmental changes in WM function in 40 participants, twenty-four children (ages 9-15 yr) and sixteen young adults (ages 20-25 yr). Children and adults both demonstrated an opposing system of cognitive processes with increasing cognitive demand, where areas related to WM (frontal and parietal regions) increased in activity, and areas associated with the default mode network decreased in activity. Although there were many similarities in the neural activation patterns associated with increasing verbal WM capacity in children and adults, significant changes in the fMRI responses were seen with age. Adults showed greater load-dependent changes than children in WM in the bilateral superior parietal gyri, inferior frontal and left middle frontal gyri and right cerebellum. Compared to children, adults also showed greater decreasing activation across WM load in the bilateral anterior cingulate, anterior medial prefrontal gyrus, right superior lateral temporal gyrus and left posterior cingulate. These results demonstrate that while children and adults activate similar neural networks in response to verbal WM tasks, the extent to which they rely on these areas in response to increasing cognitive load evolves between childhood and adulthood. PMID:26615571

  15. The neurodevelopmental differences of increasing verbal working memory demand in children and adults.

    PubMed

    Vogan, V M; Morgan, B R; Powell, T L; Smith, M L; Taylor, M J

    2016-02-01

    Working memory (WM) - temporary storage and manipulation of information in the mind - is a key component of cognitive maturation, and structural brain changes throughout development are associated with refinements in WM. Recent functional neuroimaging studies have shown that there is greater activation in prefrontal and parietal brain regions with increasing age, with adults showing more refined, localized patterns of activations. However, few studies have investigated the neural basis of verbal WM development, as the majority of reports examine visuo-spatial WM. We used fMRI and a 1-back verbal WM task with six levels of difficulty to examine the neurodevelopmental changes in WM function in 40 participants, twenty-four children (ages 9-15 yr) and sixteen young adults (ages 20-25 yr). Children and adults both demonstrated an opposing system of cognitive processes with increasing cognitive demand, where areas related to WM (frontal and parietal regions) increased in activity, and areas associated with the default mode network decreased in activity. Although there were many similarities in the neural activation patterns associated with increasing verbal WM capacity in children and adults, significant changes in the fMRI responses were seen with age. Adults showed greater load-dependent changes than children in WM in the bilateral superior parietal gyri, inferior frontal and left middle frontal gyri and right cerebellum. Compared to children, adults also showed greater decreasing activation across WM load in the bilateral anterior cingulate, anterior medial prefrontal gyrus, right superior lateral temporal gyrus and left posterior cingulate. These results demonstrate that while children and adults activate similar neural networks in response to verbal WM tasks, the extent to which they rely on these areas in response to increasing cognitive load evolves between childhood and adulthood.

  16. Convergent and Divergent fMRI Responses in Children and Adults to Increasing Language Production Demands

    PubMed Central

    Krishnan, Saloni; Leech, Robert; Mercure, Evelyne; Lloyd-Fox, Sarah; Dick, Frederic

    2015-01-01

    In adults, patterns of neural activation associated with perhaps the most basic language skill—overt object naming—are extensively modulated by the psycholinguistic and visual complexity of the stimuli. Do children's brains react similarly when confronted with increasing processing demands, or they solve this problem in a different way? Here we scanned 37 children aged 7–13 and 19 young adults who performed a well-normed picture-naming task with 3 levels of difficulty. While neural organization for naming was largely similar in childhood and adulthood, adults had greater activation in all naming conditions over inferior temporal gyri and superior temporal gyri/supramarginal gyri. Manipulating naming complexity affected adults and children quite differently: neural activation, especially over the dorsolateral prefrontal cortex, showed complexity-dependent increases in adults, but complexity-dependent decreases in children. These represent fundamentally different responses to the linguistic and conceptual challenges of a simple naming task that makes no demands on literacy or metalinguistics. We discuss how these neural differences might result from different cognitive strategies used by adults and children during lexical retrieval/production as well as developmental changes in brain structure and functional connectivity. PMID:24907249

  17. Using targeted messaging to increase physical activity in older adults: a review.

    PubMed

    Ostrander, Rachel E; Thompson, Hilaire J; Demiris, George

    2014-09-01

    Physical activity has many benefits for older adults; however, motivating older adults to engage in and maintain optimal levels of physical activity can be challenging for health care providers. A comprehensive literature review was performed to determine whether any evidence-based methods of delivery or particular content for targeted messaging exist that result in actual improvements in physical activity of older adults. Findings of the review demonstrate that messaging directed toward older adults to be physically active resulted in improvements in physical activity up to 1 year. Across studies many different modes of message delivery were shown to be effective. Message content, whether tailored or not, resulted in significant increases in physical activity. There is evidence to support the use of environmentally mediated messaging (i.e., local walking paths) for stronger results. Targeting the client's stage of change, having an activity partner if preferred, and scheduling physical activity also contribute to improved effects.

  18. Do adult Little Egrets respond to disturbance at their nest by increased breeding dispersal?

    USGS Publications Warehouse

    Henry, P.-Y.; Bennetts, R.E.; Kayser, Y.; Hafner, H.

    2004-01-01

    When studying breeding dispersal with marked individuals, manipulation-induced disturbance should not affect movement patterns. As part of a study on the Little Egret (Egretta garzetta), we tested whether the capture of breeding adults at their nest and handling (i.e., disturbance) increased their probability to move to a new colony in the subsequent breeding season (i.e., breeding dispersal). The proportion of adults disturbed in a given year that had changed colony in the subsequent breeding season was compared with the dispersal of adults observed during at least two consecutive years at colonies and not disturbed on the previous year: (1) birds marked as chicks and (2) birds marked as aduhs and observed ??? two years after capture at the nest. Disturbed birds were not found to have an increased propensity to disperse. We conclude that, for this species, capture did not increase the subsequent breeding dispersal.

  19. Are agricultural soils under a continental temperate climate susceptible to episodic reducing conditions and increased leaching of phosphorus?

    PubMed

    Scalenghe, Riccardo; Edwards, Anthony C; Barberis, Elisabetta; Ajmone-Marsan, Franco

    2012-04-30

    Soil science research has probably underestimated the significance that short-term, episodic cycles of reduction and oxidation has had on phosphorus (P) reactivity. Here, the effects of eleven pulsed reduction-oxidation (including wet-dry) cycles on soil P dynamics are compared for 12 soils having contrasting properties and all overfertilised with respect to P. The laboratory based incubation conditions attempted to simulate transient waterlogging of the soil profile and involved repeated sampling and analysis of both the solution and solid phase P forms. An initial increase in P concentration in solution that occurred up to and including the fourth full cycle was followed by a sharp decline in concentration for all but one soil. Accompanying changes in the main extractable forms of P, which appeared to be cumulative, could be summarised as a general decline in the organic P fraction and an overall increase in amorphous associated inorganic forms of P. The fact that up to 60% of the total soil P was demonstrated to change its sensitivity for a particular extractant suggests that these operationally defined P forms are susceptible to transformation as a consequence of changing environmental conditions. There was also a suggestion that certain of the changes in P forms were irreversible. While the laboratory conditions imposed do represent extreme conditions the soils only experienced cyclic changes in their moisture regime. If timing and frequency of intense precipitation events are likely to increase, as predicted in many climate change scenarios, then these results suggest that the effects of episodic redox pulses may have implications for P cycling in agricultural soils.

  20. Reduced Connexin26 in the Mature Cochlea Increases Susceptibility to Noise-Induced Hearing Loss in Mice

    PubMed Central

    Zhou, Xing-Xing; Chen, Sen; Xie, Le; Ji, Yu-Zi; Wu, Xia; Wang, Wen-Wen; Yang, Qi; Yu, Jin-Tao; Sun, Yu; Lin, Xi; Kong, Wei-Jia

    2016-01-01

    Connexin26 (Cx26, encoded by GJB2) mutations are the most common cause of non-syndromic deafness. GJB2 is thought to be involved in noise-induced hearing loss (NIHL). However, the role of Cx26 in NIHL is still obscure. To explore the association between Cx26 and NIHL, we established a Cx26 knockdown (KD) mouse model by conditional knockdown of Cx26 at postnatal day 18 (P18), and then we observed the auditory threshold and morphologic changes in these mice with or without noise exposure. The Cx26 KD mice did not exhibit substantial hearing loss and hair cell degeneration, while the Cx26 KD mice with acoustic trauma experienced higher hearing loss than simple noise exposure siblings and nearly had no recovery. Additionally, extensive outer hair cell loss and more severe destruction of the basal organ of Corti were observed in Cx26 KD mice after noise exposure. These data indicate that reduced Cx26 expression in the mature mouse cochlea may increase susceptibility to noise-induced hearing loss and facilitate the cell degeneration in the organ of Corti. PMID:26927086

  1. Diminished brain resilience syndrome: A modern day neurological pathology of increased susceptibility to mild brain trauma, concussion, and downstream neurodegeneration

    PubMed Central

    Morley, Wendy A.; Seneff, Stephanie

    2014-01-01

    The number of sports-related concussions has been steadily rising in recent years. Diminished brain resilience syndrome is a term coined by the lead author to describe a particular physiological state of nutrient functional deficiency and disrupted homeostatic mechanisms leading to increased susceptibility to previously considered innocuous concussion. We discuss how modern day environmental toxicant exposure, along with major changes in our food supply and lifestyle practices, profoundly reduce the bioavailability of neuro-critical nutrients such that the normal processes of homeostatic balance and resilience are no longer functional. Their diminished capacity triggers physiological and biochemical ‘work around’ processes that result in undesirable downstream consequences. Exposure to certain environmental chemicals, particularly glyphosate, the active ingredient in the herbicide, Roundup®, may disrupt the body's innate switching mechanism, which normally turns off the immune response to brain injury once danger has been removed. Deficiencies in serotonin, due to disruption of the shikimate pathway, may lead to impaired melatonin supply, which reduces the resiliency of the brain through reduced antioxidant capacity and alterations in the cerebrospinal fluid, reducing critical protective buffering mechanisms in impact trauma. Depletion of certain rare minerals, overuse of sunscreen and/or overprotection from sun exposure, as well as overindulgence in heavily processed, nutrient deficient foods, further compromise the brain's resilience. Modifications to lifestyle practices, if widely implemented, could significantly reduce this trend of neurological damage. PMID:25024897

  2. Vagotomy Affects the Development of Oral Tolerance and Increases Susceptibility to Develop Colitis Independently of α-7 Nicotinic Receptor

    PubMed Central

    Di Giovangiulio, Martina; Bosmans, Goele; Meroni, Elisa; Stakenborg, Nathalie; Florens, Morgane; Farro, Giovanna; Gomez-Pinilla, Pedro J; Matteoli, Gianluca; Boeckxstaens, Guy E

    2016-01-01

    Vagotomy (VGX) increases the susceptibility to develop colitis suggesting a crucial role for the cholinergic anti-inflammatory pathway in the regulation of the immune responses. Since oral tolerance and the generation of regulatory T cells (Tregs) are crucial to preserve mucosal immune homeostasis, we studied the effect of vagotomy and the involvement of α7 nicotinic receptors (α7nAChR) at the steady state and during colitis. Therefore, the development of both oral tolerance and colitis (induced by dextran sulfate sodium (DSS) or via T cell transfer) was studied in vagotomized mice and in α7nAChR-/- mice. VGX, but not α7nAChR deficiency, prevented oral tolerance establishment. This effect was associated with reduced Treg conversion in the lamina propria and mesenteric lymphnodes. To the same extent, vagotomized mice, but not α7nAChR-/- mice, developed a more severe DSS colitis compared with control mice treated with DSS, associated with a decreased number of colonic Tregs. However, neither VGX nor absence of α7nAChR in recipient mice affected colitis development in the T cell transfer model. In line, deficiency of α7nAChR exclusively in T cells did not influence the development of colitis induced by T cell transfer. Our results indicate a key role for the vagal intestinal innervation in the development of oral tolerance and colitis, most likely by modulating induction of Tregs independently of α7nAChR. PMID:27341335

  3. Decreased SIRT3 in aged human mesenchymal stromal/stem cells increases cellular susceptibility to oxidative stress.

    PubMed

    Wang, Xue-Qing; Shao, Yong; Ma, Chong-Yi; Chen, Wei; Sun, Lu; Liu, Wei; Zhang, Dong-Yang; Fu, Bi-Cheng; Liu, Kai-Yu; Jia, Zhi-Bo; Xie, Bao-Dong; Jiang, Shu-Lin; Li, Ren-Ke; Tian, Hai

    2014-11-01

    Sirtuin3 (SIRT3) is an important member of the sirtuin family of protein deacetylases that is localized to mitochondria and linked to lifespan extension in organisms ranging from yeast to humans. As aged cells have less regenerative capacity and are more susceptible to oxidative stress, we investigated the effect of ageing on SIRT3 levels and its correlation with antioxidant enzyme activities. Here, we show that severe oxidative stress reduces SIRT3 levels in young human mesenchymal stromal/stem cells (hMSCs). Overexpression of SIRT3 improved hMSCs resistance to the detrimental effects of oxidative stress. By activating manganese superoxide dismutase (MnSOD) and catalase (CAT), SIRT3 protects hMSCs from apoptosis under stress. SIRT3 expression, levels of MnSOD and CAT, as well as cell survival showed little difference in old versus young hMSCs under normal growth conditions, whereas older cells had a significantly reduced capacity to withstand oxidative stress compared to their younger counterparts. Expression of the short 28 kD SIRT3 isoform was higher, while the long 44 kD isoform expression was lower in young myocardial tissues compared with older ones. These results suggest that the active short isoform of SIRT3 protects hMSCs from oxidative injury by increasing the expression and activity of antioxidant enzymes. The expression of this short isoform decreases in cardiac tissue during ageing, leading to a reduced capacity for the heart to withstand oxidative stress. PMID:25210848

  4. Diminished brain resilience syndrome: A modern day neurological pathology of increased susceptibility to mild brain trauma, concussion, and downstream neurodegeneration.

    PubMed

    Morley, Wendy A; Seneff, Stephanie

    2014-01-01

    The number of sports-related concussions has been steadily rising in recent years. Diminished brain resilience syndrome is a term coined by the lead author to describe a particular physiological state of nutrient functional deficiency and disrupted homeostatic mechanisms leading to increased susceptibility to previously considered innocuous concussion. We discuss how modern day environmental toxicant exposure, along with major changes in our food supply and lifestyle practices, profoundly reduce the bioavailability of neuro-critical nutrients such that the normal processes of homeostatic balance and resilience are no longer functional. Their diminished capacity triggers physiological and biochemical 'work around' processes that result in undesirable downstream consequences. Exposure to certain environmental chemicals, particularly glyphosate, the active ingredient in the herbicide, Roundup(®), may disrupt the body's innate switching mechanism, which normally turns off the immune response to brain injury once danger has been removed. Deficiencies in serotonin, due to disruption of the shikimate pathway, may lead to impaired melatonin supply, which reduces the resiliency of the brain through reduced antioxidant capacity and alterations in the cerebrospinal fluid, reducing critical protective buffering mechanisms in impact trauma. Depletion of certain rare minerals, overuse of sunscreen and/or overprotection from sun exposure, as well as overindulgence in heavily processed, nutrient deficient foods, further compromise the brain's resilience. Modifications to lifestyle practices, if widely implemented, could significantly reduce this trend of neurological damage. PMID:25024897

  5. Using the Natural Language Paradigm (NLP) to increase vocalizations of older adults with cognitive impairments.

    PubMed

    Leblanc, Linda A; Geiger, Kaneen B; Sautter, Rachael A; Sidener, Tina M

    2007-01-01

    The Natural Language Paradigm (NLP) has proven effective in increasing spontaneous verbalizations for children with autism. This study investigated the use of NLP with older adults with cognitive impairments served at a leisure-based adult day program for seniors. Three individuals with limited spontaneous use of functional language participated in a multiple baseline design across participants. Data were collected on appropriate and inappropriate vocalizations with appropriate vocalizations coded as prompted or unprompted during baseline and treatment sessions. All participants experienced increases in appropriate speech during NLP with variable response patterns. Additionally, the two participants with substantial inappropriate vocalizations showed decreases in inappropriate speech. Implications for intervention in day programs are discussed.

  6. Adult immunization

    PubMed Central

    Mehta, Bharti; Chawla, Sumit; Kumar Dharma, Vijay; Jindal, Harashish; Bhatt, Bhumika

    2014-01-01

    Vaccination is recommended throughout life to prevent vaccine-preventable diseases and their sequel. The primary focus of vaccination programs has historically been directed to childhood immunizations. For adults, chronic diseases have been the primary focus of preventive and medical health care, though there has been increased emphasis on preventing infectious diseases. Adult vaccination coverage, however, remains low for most of the routinely recommended vaccines. Though adults are less susceptible to fall prey to traditional infectious agents, the probability of exposure to infectious agents has increased manifold owing to globalization and increasing travel opportunities both within and across the countries. Thus, there is an urgent need to address the problem of adult immunization. The adult immunization enterprise is more complex, encompassing a wide variety of vaccines and a very diverse target population. There is no coordinated public health infrastructure to support an adult immunization program as there is for children. Moreover, there is little coordination among adult healthcare providers in terms of vaccine provision. Substantial improvement in adult vaccination is needed to reduce the health consequences of vaccine-preventable diseases among adults. Routine assessment of adult patient vaccination needs, recommendation, and offer of needed vaccines for adults should be incorporated into routine clinical care of adults. PMID:24128707

  7. Evolution of Phenotypic Drug Susceptibility and Viral Replication Capacity during Long-Term Virologic Failure of Protease Inhibitor Therapy in Human Immunodeficiency Virus-Infected Adults

    PubMed Central

    Barbour, Jason D.; Wrin, Terri; Grant, Robert M.; Martin, Jeffrey N.; Segal, Mark R.; Petropoulos, Christos J.; Deeks, Steven G.

    2002-01-01

    Continued use of antiretroviral therapy despite the emergence of drug-resistant human immunodeficiency virus (HIV) has been associated with the durable maintenance of plasma HIV RNA levels below pretherapy levels. The factors that may account for this partial control of viral replication were assessed in a longitudinal observational study of 20 HIV-infected adults who remained on a stable protease inhibitor-based regimen despite ongoing viral replication (plasma HIV RNA levels consistently >500 copies/ml). Longitudinal plasma samples (n = 248) were assayed for drug susceptibility and viral replication capacity (measured by using a single-cycle recombinant-virus assay). The initial treatment-mediated decrease in plasma viremia was directly proportional to the reduction in replicative capacity (P = 0.01). Early virologic rebound was associated the emergence of a virus population exhibiting increased protease inhibitor phenotypic resistance, while replicative capacity remained low. During long-term virologic failure, plasma HIV RNA levels often remained stable or increased slowly, while phenotypic resistance continued to increase and replicative capacity decreased slowly. The emergence of primary genotypic mutations within protease (particularly V82A, I84V, and L90M) was temporally associated with increasing phenotypic resistance and decreasing replicative capacity, while the emergence of secondary mutations within protease was associated with more-gradual changes in both phenotypic resistance and replicative capacity. We conclude that HIV may be constrained in its ability to become both highly resistant and highly fit and that this may contribute to the continued partial suppression of plasma HIV RNA levels that is observed in some patients with drug-resistant viremia. PMID:12368352

  8. Genetic variants of MAOB affect serotonin level and specific behavioral attributes to increase autism spectrum disorder (ASD) susceptibility in males.

    PubMed

    Chakraborti, Barnali; Verma, Deepak; Karmakar, Arijit; Jaiswal, Preeti; Sanyal, Aritrika; Paul, Debarshi; Sinha, Swagata; Singh, Asem Surindro; Guhathakurta, Subhrangshu; Roychowdhury, Anirban; Panda, Chinmoy Kumar; Ghosh, Saurabh; Mohanakumar, Kochupurackal P; Mukhophadhyay, Kanchan; Rajamma, Usha

    2016-11-01

    Serotonergic system participates in various developmental processes and modulation of behaviour. Autism Spectrum Disorder (ASD) is characterized by a range of behavioral symptoms scaling from mild to severe. Abnormal 5-HT synthesis and signalling, platelet hyperserotonemia and amelioration of repetitive behaviours by SSRI are some of the key findings, which reinforced the hypothesis that serotonergic genes might act as ASD susceptible genes. Therefore, genes encoding monoamine oxidases A/B (MAOA/MAOB) received special attention as these genes are located on the X-chromosome and the gene products are responsible for 5-HT degradation. In the present study, we conducted population-based association analysis of eight markers of MAOB with ASD in a study cohort of 203 cases and 236 controls form India and examined its effect on platelet 5-HT content and behaviour. Gender-specific changes were observed for the contrasting LD between pair of markers among cases and controls. Case-control analysis demonstrated over-distribution of major C allele of rs2283728 and rs2283727 in male and female ASD cases respectively. Haplotypic distribution and interaction among markers showed more robust effect in male cases. Interestingly, male ASD cases displayed higher platelet 5-HT content in comparison to the respective controls. Quantitative trait analysis revealed significant correlation of genetic variants and haplotypes of MAOB markers, rs1799836 and rs6324 with increased platelet 5-HT level and CARS scores for specific behavioral symptoms respectively in males. This study suggests that MAOB increases ASD risk in males, possibly through its sex-specific regulatory effect on 5-HT metabolism and behavior.

  9. Genetic variants of MAOB affect serotonin level and specific behavioral attributes to increase autism spectrum disorder (ASD) susceptibility in males.

    PubMed

    Chakraborti, Barnali; Verma, Deepak; Karmakar, Arijit; Jaiswal, Preeti; Sanyal, Aritrika; Paul, Debarshi; Sinha, Swagata; Singh, Asem Surindro; Guhathakurta, Subhrangshu; Roychowdhury, Anirban; Panda, Chinmoy Kumar; Ghosh, Saurabh; Mohanakumar, Kochupurackal P; Mukhophadhyay, Kanchan; Rajamma, Usha

    2016-11-01

    Serotonergic system participates in various developmental processes and modulation of behaviour. Autism Spectrum Disorder (ASD) is characterized by a range of behavioral symptoms scaling from mild to severe. Abnormal 5-HT synthesis and signalling, platelet hyperserotonemia and amelioration of repetitive behaviours by SSRI are some of the key findings, which reinforced the hypothesis that serotonergic genes might act as ASD susceptible genes. Therefore, genes encoding monoamine oxidases A/B (MAOA/MAOB) received special attention as these genes are located on the X-chromosome and the gene products are responsible for 5-HT degradation. In the present study, we conducted population-based association analysis of eight markers of MAOB with ASD in a study cohort of 203 cases and 236 controls form India and examined its effect on platelet 5-HT content and behaviour. Gender-specific changes were observed for the contrasting LD between pair of markers among cases and controls. Case-control analysis demonstrated over-distribution of major C allele of rs2283728 and rs2283727 in male and female ASD cases respectively. Haplotypic distribution and interaction among markers showed more robust effect in male cases. Interestingly, male ASD cases displayed higher platelet 5-HT content in comparison to the respective controls. Quantitative trait analysis revealed significant correlation of genetic variants and haplotypes of MAOB markers, rs1799836 and rs6324 with increased platelet 5-HT level and CARS scores for specific behavioral symptoms respectively in males. This study suggests that MAOB increases ASD risk in males, possibly through its sex-specific regulatory effect on 5-HT metabolism and behavior. PMID:27381555

  10. CLIC5 mutant mice are resistant to diet-induced obesity and exhibit gastric hemorrhaging and increased susceptibility to torpor

    PubMed Central

    Bradford, Emily M.; Miller, Marian L.; Prasad, Vikram; Nieman, Michelle L.; Gawenis, Lara R.; Berryman, Mark; Lorenz, John N.; Tso, Patrick

    2010-01-01

    Chloride intracellular channel 5 (CLIC5) and other CLIC isoforms have been implicated in a number of biological processes, but their specific functions are poorly understood. The association of CLIC5 with ezrin and the actin cytoskeleton led us to test its possible involvement in gastric acid secretion. Clic5 mutant mice exhibited only a minor reduction in acid secretion, Clic5 mRNA was expressed at only low levels in stomach, and Clic5 mutant parietal cells were ultrastructurally normal, negating the hypothesis that CLIC5 plays a major role in acid secretion. However, the mutants exhibited gastric hemorrhaging in response to fasting, reduced monocytes and granulocytes suggestive of immune dysfunction, behavioral and social disorders suggestive of neurological dysfunction, and evidence of a previously unidentified metabolic defect. Wild-type and mutant mice were maintained on normal and high-fat diets; plasma levels of various hormones, glucose, and lipids were determined; and body composition was studied by quantitative magnetic resonance imaging. Clic5 mutants were lean, hyperphagic, and highly resistant to diet-induced obesity. Plasma insulin and glucose levels were reduced, and leptin levels were very low; however, plasma triglycerides, cholesterol, phospholipids, and fatty acids were normal. Indirect calorimetry revealed increased peripheral metabolism and greater reliance on carbohydrate metabolism. Because Clic5 mutants were unable to maintain energy reserves, they also exhibited increased susceptibility to fasting-induced torpor, as indicated by telemetric measurements showing episodes of reduced body temperature and heart rate. These data reveal a requirement for CLIC5 in the maintenance of normal systemic energy metabolism. PMID:20357015

  11. Interspecies and interstrain studies on the increased susceptibility to metrazol-induced convulsions in animals given aspartame.

    PubMed

    Diomede, L; Romano, M; Guiso, G; Caccia, S; Nava, S; Salmona, M

    1991-02-01

    The ability of aspartame (APM) to increase the susceptibility to metrazol-induced convulsions was studied in two strains of mice (CD1 and DBA/2J) and in guinea-pigs. Rats were included as known positive controls. Plasma and brain levels of phenylalanine (Phe) and tyrosine (Tyr) were measured in CD1 mice and guinea-pigs at various intervals after a dose of 1 g APM/kg body weight (administered orally to mice and ip to guinea-pigs). In mice, peak levels of Phe and Tyr were observed in plasma after 30 min and in brain after 60 min. In guinea-pigs peak plasma levels of Phe and Tyr occurred 30 min after treatment. Phe was at a maximum in guinea-pig brain after 30 min, while Tyr levels reached a peak at 120 min. In further experiments Phe and Tyr levels were measured 1 hr after APM doses of 0.5, 0.75 or 1 g/kg. In CD1 mice, plasma Phe and Tyr levels were increased significantly only at the highest dose, whereas in brain, Tyr concentrations were significantly increased by 0.75 or 1 g APM/kg and Phe was significantly increased by all three doses. In the guinea-pig, plasma Phe and Tyr were increased significantly only by 1 g APM/kg and in brain this dose significantly raised only the Phe levels. Monoamine and metabolite levels were determined in the brain striata of CD1 and DBA/2J mice 1 hr after the oral administration of 1 or 2 g APM/kg body weight; no differences from control values were found in either strain. The studies of potentiation of metrazol-induced convulsions showed that APM, at doses of up to 2 g/kg body weight, had no such effect in mice or guinea-pigs. In contrast, as expected, the potentiation was significant in the rat at 1 g/kg.

  12. Hunting Increases Phosphorylation of Calcium/Calmodulin-Dependent Protein Kinase Type II in Adult Barn Owls

    PubMed Central

    Nichols, Grant S.; DeBello, William M.

    2015-01-01

    Juvenile barn owls readily adapt to prismatic spectacles, whereas adult owls living under standard aviary conditions do not. We previously demonstrated that phosphorylation of the cyclic-AMP response element-binding protein (CREB) provides a readout of the instructive signals that guide plasticity in juveniles. Here we investigated phosphorylation of calcium/calmodulin-dependent protein kinase II (pCaMKII) in both juveniles and adults. In contrast to CREB, we found no differences in pCaMKII expression between prism-wearing and control juveniles within the external nucleus of the inferior colliculus (ICX), the major site of plasticity. For prism-wearing adults that hunted live mice and are capable of adaptation, expression of pCaMKII was increased relative to prism-wearing adults that fed passively on dead mice and are not capable of adaptation. This effect did not bear the hallmarks of instructive information: it was not localized to rostral ICX and did not exhibit a patchy distribution reflecting discrete bimodal stimuli. These data are consistent with a role for CaMKII as a permissive rather than an instructive factor. In addition, the paucity of pCaMKII expression in passively fed adults suggests that the permissive default setting is “off” in adults. PMID:25789177

  13. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus.

    PubMed

    van Praag, H; Kempermann, G; Gage, F H

    1999-03-01

    Exposure to an enriched environment increases neurogenesis in the dentate gyrus of adult rodents. Environmental enrichment, however, typically consists of many components, such as expanded learning opportunities, increased social interaction, more physical activity and larger housing. We attempted to separate components by assigning adult mice to various conditions: water-maze learning (learner), swim-time-yoked control (swimmer), voluntary wheel running (runner), and enriched (enriched) and standard housing (control) groups. Neither maze training nor yoked swimming had any effect on bromodeoxyuridine (BrdU)-positive cell number. However, running doubled the number of surviving newborn cells, in amounts similar to enrichment conditions. Our findings demonstrate that voluntary exercise is sufficient for enhanced neurogenesis in the adult mouse dentate gyrus.

  14. Calf exercise-induced vasodilation is blunted in healthy older adults with increased walking performance fatigue.

    PubMed

    Gonzales, Joaquin U; Defferari, Elizabeth; Fisher, Amy; Shephard, Jordan; Proctor, David N

    2014-09-01

    Vascular aging as measured by central arterial stiffness contributes to slow walking speed in older adults, but the impact of age-related changes in peripheral vascular function on walking performance is unclear. The aim of this study was to test the hypothesis that calf muscle-specific vasodilator responses are associated with walking performance fatigue in healthy older adults. Forty-five older (60-78yrs) adults performed a fast-paced 400m walk test. Twelve of these adults exhibited fatigue as defined by slowing of walking speed (≥0.02m/s) measured during the first and last 100m segments of the 400m test. Peak calf vascular conductance was measured following 10min of arterial occlusion using strain-gauge plethysmography. Superficial femoral artery (SFA) vascular conductance response to graded plantar-flexion exercise was measured using Doppler ultrasound. No difference was found for peak calf vascular conductance between adults that slowed walking speed and those that maintained walking speed (p>0.05); however, older adults that slowed walking speed had a lower SFA vascular conductance response to calf exercise (at highest workload: slowed group, 2.4±0.9 vs. maintained group, 3.6±0.9ml/kg/min/mmHg; p<0.01). Moreover, the initial increase in SFA vascular conductance from rest to exercise was positively correlated with the change in walking speed for all adults (rho=0.41, p=0.005). In conclusion, these results suggest that calf exercise hemodynamics are associated with walking performance fatigability in older adults. PMID:24786722

  15. Distractibility during retrieval of long-term memory: domain-general interference, neural networks and increased susceptibility in normal aging

    PubMed Central

    Wais, Peter E.; Gazzaley, Adam

    2014-01-01

    The mere presence of irrelevant external stimuli results in interference with the fidelity of details retrieved from long-term memory (LTM). Recent studies suggest that distractibility during LTM retrieval occurs when the focus of resource-limited, top-down mechanisms that guide the selection of relevant mnemonic details is disrupted by representations of external distractors. We review findings from four studies that reveal distractibility during episodic retrieval. The approach cued participants to recall previously studied visual details when their eyes were closed, or were open and irrelevant visual information was present. The results showed a negative impact of the distractors on the fidelity of details retrieved from LTM. An fMRI experiment using the same paradigm replicated the behavioral results and found that diminished episodic memory was associated with the disruption of functional connectivity in whole-brain networks. Specifically, network connectivity supported recollection of details based on visual imagery when eyes were closed, but connectivity declined in the presence of visual distractors. Another experiment using auditory distractors found equivalent effects for auditory and visual distraction during cued recall, suggesting that the negative impact of distractibility is a domain-general phenomenon in LTM. Comparisons between older and younger adults revealed an aging-related increase in the negative impact of distractibility on retrieval of LTM. Finally, a new study that compared categorization abilities between younger and older adults suggests a cause underlying age-related decline of visual details in LTM. The sum of our findings suggests that cognitive control resources, although limited, have the capability to resolve interference from distractors during tasks of moderate effort, but these resources are overwhelmed when additional processes associated with episodic retrieval, or categorization of complex prototypes, are required. PMID

  16. Processing speed training increases the efficiency of attentional resource allocation in young adults.

    PubMed

    Burge, Wesley K; Ross, Lesley A; Amthor, Franklin R; Mitchell, William G; Zotov, Alexander; Visscher, Kristina M

    2013-01-01

    Cognitive training has been shown to improve performance on a range of tasks. However, the mechanisms underlying these improvements are still unclear. Given the wide range of transfer effects, it is likely that these effects are due to a factor common to a wide range of tasks. One such factor is a participant's efficiency in allocating limited cognitive resources. The impact of a cognitive training program, Processing Speed Training (PST), on the allocation of resources to a set of visual tasks was measured using pupillometry in 10 young adults as compared to a control group of a 10 young adults (n = 20). PST is a well-studied computerized training program that involves identifying simultaneously presented central and peripheral stimuli. As training progresses, the task becomes increasingly more difficult, by including peripheral distracting stimuli and decreasing the duration of stimulus presentation. Analysis of baseline data confirmed that pupil diameter reflected cognitive effort. After training, participants randomized to PST used fewer attentional resources to perform complex visual tasks as compared to the control group. These pupil diameter data indicated that PST appears to increase the efficiency of attentional resource allocation. Increases in cognitive efficiency have been hypothesized to underlie improvements following experience with action video games, and improved cognitive efficiency has been hypothesized to underlie the benefits of PST in older adults. These data reveal that these training schemes may share a common underlying mechanism of increasing cognitive efficiency in younger adults. PMID:24151461

  17. Increasing Adult Learner Persistence and Completion Rates: A Guide for Student Affairs Leaders and Practitioners

    ERIC Educational Resources Information Center

    Culp, Marguerite McGann, Ed.; Dungy, Gwendolyn Jordan, Ed.

    2014-01-01

    More than a third of all undergraduate students are 25 or older, and their presence on college and university campuses is growing. However, institutions of higher learning are struggling to meet the needs of, and improve persistence and completion rates for, this significant student population. "Increasing Adult Learner Persistence and…

  18. Langerhans cells increase in the dermal lesions of adult T cell leukaemia in Japan

    PubMed Central

    Shamoto, M

    1983-01-01

    In cases of adult T cell leukaemia neoplastic T cell infiltration in the skin was accompanied by an increase in Langerhans cells. This is in keeping with the view that Langerhans cells may induce antigen-specific and allogenic T cell activation. Images PMID:6600750

  19. Pedometers and Brief E-Counseling: Increasing Physical Activity for Overweight Adults

    ERIC Educational Resources Information Center

    VanWormer, Jeffrey J.

    2004-01-01

    Physical inactivity has emerged as a public health epidemic and is associated with the rising obesity rate. A multiple-treatments reversal design was utilized to test whether pedometer-aided self-monitoring and brief e-counseling could help 3 overweight adults increase their physical activity. Dependent measures were taken for pedometer steps and…

  20. PREPUBERTAL EXPOSURES TO COMPOUNDS THAT INCREASE PROLACTIN SECRETION IN THE MALE RAT: EFFECTS ON ADULT PROSTATE

    EPA Science Inventory

    Prepubertal exposure to compounds that increase prolactin secretion in the male rat: effects on the adult prostate.

    Stoker TE, Robinette CL, Britt BH, Laws SC, Cooper RL.

    Endocrinology Branch, Reproductive Toxicology Division, National Health and Environmental Effec...

  1. Improving Oral Reading in Mentally Handicapped Adults through Increased Opportunity and Practice.

    ERIC Educational Resources Information Center

    Gillette, Tracy L.

    A project developed a plan to improve oral reading in 12 mentally handicapped adults by stressing observation of punctuation marks, reading in phrases, using proper volume, and increasing confidence levels. Identifying the parts of a book and identifying new words were also included. The 12 students were reading below their potential, as shown by…

  2. The relative susceptibilities of juvenile and adult Bulinus globosus and Bulinus truncatus to the molluscicidal activities in the fruit of Ghanaian Blighia sapida, Blighia unijugata and Balanites aegyptiaca.

    PubMed

    Anto, F; Aryeetey, M E; Anyorigiya, T; Asoala, V; Kpikpi, J

    2005-03-01

    The relative susceptibilities of juvenile (2- to 3-week-old) and adult (5- to 7-week-old) Bulinus globosus and Bu. truncatus to the molluscicidal activities of aqueous preparations of the powdered, dried fruits of Blighia sapida, Bl. unijugata and Balanites aegyptiaca were investigated under laboratory conditions. For the extract prepared from the freeze-dried, semi-ripe fruits of Bl. sapida, the concentrations killing 95% of the snails after an exposure for 24 h (LC95) were, respectively, 232.7 and 161.2 ppm for the juveniles and adults of Bu. globosus and 187.6 and 140.2 ppm for the juveniles and adults of Bu. truncatus. The corresponding values for Bl. unijugata were 136.9 and 98.7 ppm for Bu. globosus and 132.2 and 98.5 ppm for Bu. truncatus, respectively. Extracts of the freeze-dried, ripe fruit of Ba. aegyptiaca were much more active, however, giving LC95 of just 16.9 and 19.7 ppm for the juveniles and adults of Bu. globosus, and 14.2 and 12.0 ppm for the juveniles and adults of Bu. truncatus, respectively. In general, similar results were obtained when the fruit were oven-dried rather than freeze-dried but the potency of Balanites extracts produced from oven-dried fruit was relatively low. That the juvenile snails appeared less susceptible than the adults to the molluscicidal activity in each Blighia extract is interesting. This observation may have implications for snail control, in terms of the optimal frequency, timing and concentration of molluscicides applied in a particular habitat.

  3. Adult Neuroblastoma Complicated by Increased Intracranial Pressure: A Case Report and Review of the Literature

    PubMed Central

    Stevens, Patrick L.; Johnson, Douglas B.; Thompson, Mary Ann; Keedy, Vicki L.; Frangoul, Haydar A.; Snyder, Kristen M.

    2014-01-01

    Neuroblastoma is the third most commonly occurring malignancy of the pediatric population, although it is extremely rare in the adult population. In adults, neuroblastoma is often metastatic and portends an extremely poor overall survival. Our case report documents metastatic neuroblastoma occurring in a healthy 29-year-old woman whose course was complicated by an unusual presentation of elevated intracranial pressures. The patient was treated with systemic chemotherapy, I131 metaiodobenzylguanidine (MIBG) radiotherapy, and autologous stem cell transplant (SCT). Unfortunately the patient's response to therapy was limited and she subsequently died. We aim to review neuroblastoma in the context of increased intracranial pressure and the limited data of neuroblastoma occurring in the adult population, along with proposed treatment options. PMID:25328733

  4. Arterial stiffness is higher in older adults with increased perceived fatigue and fatigability during walking.

    PubMed

    Gonzales, Joaquin U; Wiberg, Matthew; Defferari, Elizabeth; Proctor, David N

    2015-01-01

    We investigated whether central and/or peripheral arterial stiffness contributes to increased perceived fatigue during walking in mobility-intact older adults. Arterial stiffness of the common carotid artery and superficial femoral artery (SFA) was measured using Doppler-ultrasound in 45 community-dwelling women and men (60-78yrs). The change in perceived fatigue was measured after a fast-pace 400meter walk test. Adults that rated feeling more tired after walking (n=10) had higher SFA stiffness (p<0.01), but not carotid artery stiffness, than adults that reported feeling more energetic after walking (n=22). The change in perceived fatigue rating was normalized to energy expenditure during walking to determine perceived fatigability. Adults were divided into lower and higher perceived fatigability groups (n=22 per group). Carotid artery stiffness was not different between perceived fatigability groups after adjusting for age, sex, body fat, systolic blood pressure, fasting blood glucose, daily physical activity levels, and resting diameter. However, SFA stiffness was significantly elevated in the higher as compared to lower perceived fatigability group (β-index: 20.7±1.3 vs. 15.3±1.4U; p=0.02) after adjusting for the abovementioned variables. Moreover, stepwise regression identified SFA β-index to be an independent predictor of perceived fatigability (r(2)=0.38, p<0.01). These results suggest that peripheral arterial stiffness is independently associated with perceived fatigue and fatigability in older adults. PMID:25482474

  5. Salivary testosterone and immunoglobulin A were increased by resistance training in adults with Down syndrome.

    PubMed

    Fornieles, G; Rosety, M A; Elosegui, S; Rosety, J M; Alvero-Cruz, J R; Garcia, N; Rosety, M; Rodriguez-Pareja, T; Toro, R; Rosety-Rodriguez, M; Ordonez, F J; Rosety, I

    2014-04-01

    This study was designed to assess the influence of resistance training on salivary immunoglobulin A (IgA) levels and hormone profile in sedentary adults with Down syndrome (DS). A total of 40 male adults with DS were recruited for the trial through different community support groups for people with intellectual disabilities. All participants had medical approval for participation in physical activity. Twenty-four adults were randomly assigned to perform resistance training in a circuit with six stations, 3 days per week for 12 weeks. Training intensity was based on functioning in the eight-repetition maximum (8RM) test for each exercise. The control group included 16 age-, gender-, and BMI-matched adults with DS. Salivary IgA, testosterone, and cortisol levels were measured by ELISA. Work task performance was assessed using the repetitive weighted-box-stacking test. Resistance training significantly increased salivary IgA concentration (P=0.0120; d=0.94) and testosterone levels (P=0.0088; d=1.57) in the exercising group. Furthermore, it also improved work task performance. No changes were seen in the controls who had not exercised. In conclusion, a short-term resistance training protocol improved mucosal immunity response as well as salivary testosterone levels in sedentary adults with DS.

  6. Mitochondrial DNA Subhaplogroups L0a2 and L2a Modify Susceptibility to Peripheral Neuropathy in Malawian Adults on Stavudine Containing Highly Active Antiretroviral Therapy

    PubMed Central

    Kampira, Elizabeth; Kumwenda, Johnstone; van Oosterhout, Joep J.

    2013-01-01

    Background: Peripheral neuropathy (PN) is one of the main toxicities associated with stavudine. Genetic variants in mitochondrial DNA (mtDNA) haplogroups have been associated with increased risk of developing PN in European non-Hispanic and black patients on stavudine containing antiretroviral therapy (ART). We investigated mtDNA haplogroups and their role in susceptibility to stavudine-induced peripheral in Malawian patients on ART. Method: Two hundred and fifteen adults on stavudine containing regimens were recruited from the ART clinic at Queen Elizabeth Central Hospital, Blantyre, into a cross-sectional study to investigate the effects of genetic variants in mtDNA of individuals in relation to response to treatment. Patients were categorized according to whether or not they had developed PN after a minimum of 6 months on stavudine containing ART. Whole mtDNA coding regions of each patient were sequenced, and CD4 count, viral load, and creatinine were determined. The mtDNA variation was correlated with clinical characteristics. Results: Fifty-three (25%) of the participants developed PN after starting stavudine containing ART. Mitochondrial DNA subhaplogroup L0a2 was independently associated with increased risk of PN in a multivariate model (odds ratio, 2.23; 95% confidence interval, 1.14 to 4.39; P = 0.019), and subhaplogroup L2a was independently associated with reduced risk of PN (odds ratio, 0.39; 95% confidence interval, 0.16 to 0.94; P = 0.036). Conclusions: Genetic variation in mtDNA confers differential risk of developing PN in patients on stavudine containing ART among Malawians. PMID:23614993

  7. Maternal obesity characterized by gestational diabetes increases the susceptibility of rat offspring to hepatic steatosis via a disrupted liver metabolome.

    PubMed

    Pereira, Troy J; Fonseca, Mario A; Campbell, Kristyn E; Moyce, Brittany L; Cole, Laura K; Hatch, Grant M; Doucette, Christine A; Klein, Julianne; Aliani, Michel; Dolinsky, Vernon W

    2015-07-15

    Maternal obesity is associated with a high risk for gestational diabetes mellitus (GDM), which is a common complication of pregnancy. The influence of maternal obesity and GDM on the metabolic health of the offspring is poorly understood. We hypothesize that GDM associated with maternal obesity will cause obesity, insulin resistance and hepatic steatosis in the offspring. Female Sprague-Dawley rats were fed a high-fat (45%) and sucrose (HFS) diet to cause maternal obesity and GDM. Lean control pregnant rats received low-fat (LF; 10%) diets. To investigate the interaction between the prenatal environment and postnatal diets, rat offspring were assigned to LF or HFS diets for 12 weeks, and insulin sensitivity and hepatic steatosis were evaluated. Pregnant GDM dams exhibited excessive gestational weight gain, hyperinsulinaemia and hyperglycaemia. Offspring of GDM dams gained more weight than the offspring of lean dams due to excess adiposity. The offspring of GDM dams also developed hepatic steatosis and insulin resistance. The postnatal consumption of a LF diet did not protect offspring of GDM dams against these metabolic disorders. Analysis of the hepatic metabolome revealed increased diacylglycerol and reduced phosphatidylethanolamine in the offspring of GDM dams compared to offspring of lean dams. Consistent with altered lipid metabolism, the expression of CTP:phosphoethanolamine cytidylyltransferase, and peroxisomal proliferator activated receptor-α mRNA was reduced in the livers of GDM offspring. GDM exposure programs gene expression and hepatic metabolite levels and drives the development of hepatic steatosis and insulin resistance in young adult rat offspring.

  8. Influence of stripe rust infection on the photosynthetic characteristics and antioxidant system of susceptible and resistant wheat cultivars at the adult plant stage.

    PubMed

    Chen, Yang-Er; Cui, Jun-Mei; Su, Yan-Qiu; Yuan, Shu; Yuan, Ming; Zhang, Huai-Yu

    2015-01-01

    Wheat stripe rust (Puccinia striiformis f. sp. tritici, Pst), is one of the most serious diseases of wheat (Triticum aestivum L.) worldwide. To gain a better understanding of the protective mechanism against stripe rust at the adult plant stage, the differences in photosystem II and antioxidant enzymatic systems between susceptible and resistant wheat in response to stripe rust disease (P. striiformis) were investigated. We found that chlorophyll fluorescence and the activities of the antioxidant enzymes were higher in resistant wheat than in susceptible wheat after stripe rust infection. Compared with the susceptible wheat, the resistant wheat accumulated a higher level of D1 protein and a lower level of reactive oxygen species after infection. Furthermore, our results demonstrate that D1 and light-harvesting complex II (LHCII) phosphorylation are involved in the resistance to stripe rust in wheat. The CP29 protein was phosphorylated under stripe rust infection, like its phosphorylation in other monocots under environmental stresses. More extensive damages occur on the thylakoid membranes in the susceptible wheat compared with the resistant wheat. The findings provide evidence that thylakoid protein phosphorylation and antioxidant enzyme systems play important roles in plant responses and defense to biotic stress.

  9. Influence of stripe rust infection on the photosynthetic characteristics and antioxidant system of susceptible and resistant wheat cultivars at the adult plant stage

    PubMed Central

    Chen, Yang-Er; Cui, Jun-Mei; Su, Yan-Qiu; Yuan, Shu; Yuan, Ming; Zhang, Huai-Yu

    2015-01-01

    Wheat stripe rust (Puccinia striiformis f. sp. tritici, Pst), is one of the most serious diseases of wheat (Triticum aestivum L.) worldwide. To gain a better understanding of the protective mechanism against stripe rust at the adult plant stage, the differences in photosystem II and antioxidant enzymatic systems between susceptible and resistant wheat in response to stripe rust disease (P. striiformis) were investigated. We found that chlorophyll fluorescence and the activities of the antioxidant enzymes were higher in resistant wheat than in susceptible wheat after stripe rust infection. Compared with the susceptible wheat, the resistant wheat accumulated a higher level of D1 protein and a lower level of reactive oxygen species after infection. Furthermore, our results demonstrate that D1 and light-harvesting complex II (LHCII) phosphorylation are involved in the resistance to stripe rust in wheat. The CP29 protein was phosphorylated under stripe rust infection, like its phosphorylation in other monocots under environmental stresses. More extensive damages occur on the thylakoid membranes in the susceptible wheat compared with the resistant wheat. The findings provide evidence that thylakoid protein phosphorylation and antioxidant enzyme systems play important roles in plant responses and defense to biotic stress. PMID:26442087

  10. The Quorum Sensing Inhibitor Hamamelitannin Increases Antibiotic Susceptibility of Staphylococcus aureus Biofilms by Affecting Peptidoglycan Biosynthesis and eDNA Release

    PubMed Central

    Brackman, Gilles; Breyne, Koen; De Rycke, Riet; Vermote, Arno; Van Nieuwerburgh, Filip; Meyer, Evelyne; Van Calenbergh, Serge; Coenye, Tom

    2016-01-01

    Treatment of Staphylococcus aureus infections has become increasingly challenging due to the rapid emergence and dissemination of methicillin-resistant strains. In addition, S. aureus reside within biofilms at the site of infection. Few novel antibacterial agents have been developed in recent years and their bacteriostatic or bactericidal activity results in selective pressure, inevitably inducing antimicrobial resistance. Consequently, innovative antimicrobials with other modes of action are urgently needed. One alternative approach is targeting the bacterial quorum sensing (QS) system. Hamamelitannin (2′,5-di-O-galloyl-d-hamamelose; HAM) was previously suggested to block QS through the TraP QS system and was shown to increase S. aureus biofilm susceptibility towards vancomycin (VAN) although mechanistic insights are still lacking. In the present study we provide evidence that HAM specifically affects S. aureus biofilm susceptibility through the TraP receptor by affecting cell wall synthesis and extracellular DNA release of S. aureus. We further provide evidence that HAM can increase the susceptibility of S. aureus biofilms towards different classes of antibiotics in vitro. Finally, we show that HAM increases the susceptibility of S. aureus to antibiotic treatment in in vivo Caenorhabditis elegans and mouse mammary gland infection models. PMID:26828772

  11. Flagellin treatment prevents increased susceptibility to systemic bacterial infection after injury by inhibiting anti-inflammatory IL-10+ IL-12- neutrophil polarization.

    PubMed

    Neely, Crystal J; Kartchner, Laurel B; Mendoza, April E; Linz, Brandon M; Frelinger, Jeffrey A; Wolfgang, Matthew C; Maile, Robert; Cairns, Bruce A

    2014-01-01

    Severe trauma renders patients susceptible to infection. In sepsis, defective bacterial clearance has been linked to specific deviations in the innate immune response. We hypothesized that innate immune modulations observed during sepsis also contribute to increased bacterial susceptibility after severe trauma. A well-established murine model of burn injury, used to replicate infection following trauma, showed that wound inoculation with P. aeruginosa quickly spreads systemically. The systemic IL-10/IL-12 axis was skewed after burn injury with infection as indicated by a significant elevation in serum IL-10 and polarization of neutrophils into an anti-inflammatory ("N2"; IL-10(+) IL-12(-)) phenotype. Infection with an attenuated P. aeruginosa strain (ΔCyaB) was cleared better than the wildtype strain and was associated with an increased pro-inflammatory neutrophil ("N1"; IL-10(-)IL-12(+)) response in burn mice. This suggests that neutrophil polarization influences bacterial clearance after burn injury. Administration of a TLR5 agonist, flagellin, after burn injury restored the neutrophil response towards a N1 phenotype resulting in an increased clearance of wildtype P. aeruginosa after wound inoculation. This study details specific alterations in innate cell populations after burn injury that contribute to increased susceptibility to bacterial infection. In addition, for the first time, it identifies neutrophil polarization as a therapeutic target for the reversal of bacterial susceptibility after injury.

  12. Flagellin Treatment Prevents Increased Susceptibility to Systemic Bacterial Infection after Injury by Inhibiting Anti-Inflammatory IL-10+ IL-12- Neutrophil Polarization

    PubMed Central

    Neely, Crystal J.; Kartchner, Laurel B.; Mendoza, April E.; Linz, Brandon M.; Frelinger, Jeffrey A.; Wolfgang, Matthew C.; Maile, Robert; Cairns, Bruce A.

    2014-01-01

    Severe trauma renders patients susceptible to infection. In sepsis, defective bacterial clearance has been linked to specific deviations in the innate immune response. We hypothesized that innate immune modulations observed during sepsis also contribute to increased bacterial susceptibility after severe trauma. A well-established murine model of burn injury, used to replicate infection following trauma, showed that wound inoculation with P. aeruginosa quickly spreads systemically. The systemic IL-10/IL-12 axis was skewed after burn injury with infection as indicated by a significant elevation in serum IL-10 and polarization of neutrophils into an anti-inflammatory (“N2”; IL-10+ IL-12−) phenotype. Infection with an attenuated P. aeruginosa strain (ΔCyaB) was cleared better than the wildtype strain and was associated with an increased pro-inflammatory neutrophil (“N1”; IL-10−IL-12+) response in burn mice. This suggests that neutrophil polarization influences bacterial clearance after burn injury. Administration of a TLR5 agonist, flagellin, after burn injury restored the neutrophil response towards a N1 phenotype resulting in an increased clearance of wildtype P. aeruginosa after wound inoculation. This study details specific alterations in innate cell populations after burn injury that contribute to increased susceptibility to bacterial infection. In addition, for the first time, it identifies neutrophil polarization as a therapeutic target for the reversal of bacterial susceptibility after injury. PMID:24454904

  13. Increased arterial stiffness in young adults with end-stage renal disease since childhood.

    PubMed

    Groothoff, Jaap W; Gruppen, Mariken P; Offringa, Martin; de Groot, Eric; Stok, Willem; Bos, Willem Jan; Davin, Jean Claude; Lilien, Marc R; Van de Kar, Nicole Caj; Wolff, Eric D; Heymans, Hugo S

    2002-12-01

    Increased arterial stiffness is a risk factor for mortality in adults over 40 yr of age with end-stage renal disease (ESRD). As no data exist on vascular changes in young adults with ESRD since childhood, a long-term outcome study was performed. All living Dutch adult patients with onset of ESRD between 1972 and 1992 at age 0 to 14 yr were invited for carotid artery and cardiac ultrasound and BP measurements. Data on clinical characteristics were collected by review of all medical charts. Carotid ultrasound data were compared with those of 48 age-matched and gender-matched healthy controls. Carotid artery and cardiac ultrasound was performed in 130 out of 187 eligible patients. Mean age was 29.0 (20.7 to 40.6) yr. Compared with controls, patients had a similar intima media thickness but a reduced mean arterial wall distensibility DC (40.0 versus 45.0 kPa(-1). 10(-3); 95% CI, -9.1 to -0.8; P < 0.001), an increased stiffness parameter beta (4.2 versus 3.8; 95% CI, 0.05 to 0.68; P = 0.02), an increased elastic incremental modulus E(inc) (0.35 versus 0.27 kPa. 10(3); 95% CI, 0.02 to 0.12; P < 0.001). Multiple regression analyses in all subjects revealed that ESRD was associated with an increase in beta and E(inc). Arterial wall properties of patients currently on dialysis and transplanted patients were comparable. In all patients, current systolic hypertension was associated with increased E(inc) and decreased DC. In conclusion, carotid arterial wall stiffness is increased in young adult patients with pediatric ESRD. Hypertension is a main determinant and might be a target for treatment of these potentially lethal arterial wall changes.

  14. Increased Marijuana Use and Gender Predict Poorer Cognitive Functioning in Adolescents and Emerging Adults

    PubMed Central

    Lisdahl, Krista M.; Price, Jenessa S.

    2014-01-01

    This study sought to characterize neuropsychological functioning in MJ-using adolescents and emerging adults (ages 18–26) and to investigate whether gender moderated these effects. Data were collected from 59 teens and emerging adults including MJ users (n = 23, 56% female) and controls (n = 35, 50% female) aged 18–26 (M = 21 years). Exclusionary criteria included independent Axis I disorders (besides SUD), and medical and neurologic disorders. After controlling for reading ability, gender, subclinical depressive symptoms, body mass index, and alcohol and other drug use, increased MJ use was associated with slower psychomotor speed/sequencing ability (p< .01), less efficient sustained attention (p< .05), and increased cognitive inhibition errors (p< .03). Gender significantly moderated the effects of MJ on psychomotor speed/sequencing ability (p< .003) in that males had a more robust negative relationship. The current study demonstrated that MJ exposure was associated with poorer psychomotor speed, sustained attention and cognitive inhibition in a dose-dependent manner in young adults, findings that are consistent with other samples of adolescent MJ users. Male MJ users demonstrated greater cognitive slowing than females. Future studies need to examine the neural substrates underlying with these cognitive deficits and whether cognitive rehabilitation or exercise interventions may serve as a viable treatments of cognitive deficits in emerging adult MJ users. PMID:22613255

  15. Methylphenidate treatment increases Na(+), K (+)-ATPase activity in the cerebrum of young and adult rats.

    PubMed

    Scherer, Emilene B S; Matté, Cristiane; Ferreira, Andréa G K; Gomes, Karin M; Comim, Clarissa M; Mattos, Cristiane; Quevedo, João; Streck, Emilio L; Wyse, Angela T S

    2009-12-01

    Methylphenidate is a central nervous system stimulant used for the treatment of attention-deficit hyperactivity disorder. Na(+), K(+)-ATPase is a membrane-bound enzyme necessary to maintain neuronal excitability. Considering that methylphenidate effects on central nervous system metabolism are poorly known and that Na(+), K(+)-ATPase is essential to normal brain function, the purpose of this study was to evaluate the effect of this drug on Na(+), K(+)-ATPase activity in the cerebrum of young and adult rats. For acute administration, a single injection of methylphenidate (1.0, 2.0, or 10.0 mg/Kg) or saline was given to rats on postnatal day 25 or postnatal day 60, in the young and adult groups, respectively. For chronic administration, methylphenidate (1.0, 2.0, or 10.0 mg/Kg) or saline injections were given to young rats starting at postnatal day 25 once daily for 28 days. In adult rats, the same regimen was performed starting at postnatal day 60. Our results showed that acute methylphenidate administration increased Na(+), K(+)-ATPase activity in hippocampus, prefrontal cortex, and striatum of young and adult rats. In young rats, chronic administration of methylphenidate also enhanced Na(+), K(+)-ATPase activity in hippocampus and prefrontal cortex, but not in striatum. When tested in adult rats, Na(+), K(+)-ATPase activity was increased in all cerebral structures studied. The present findings suggest that increased Na(+), K(+)-ATPase activity may be associated with neuronal excitability caused by methylphenidate.

  16. Environmentally Induced Epigenetic Transgenerational Inheritance of Disease Susceptibility

    PubMed Central

    Nilsson, Eric E.; Skinner, Michael K.

    2014-01-01

    Environmental insults, such as exposure to toxicants or nutritional abnormalities, can lead to epigenetic changes that are in turn related to increased susceptibility to disease. The focus of this review is on the transgenerational inheritance of such epigenetic abnormalities (epimutations), and how it is that these inherited epigenetic abnormalities can lead to increased disease susceptibility, even in the absence of continued environmental insult. Observations of environmental toxicant specificity and exposure specific disease susceptibility are discussed. How epimutations are transmitted across generations and how epigenetic changes in the germline are translated into an increased disease susceptibility in the adult is reviewed in regards to disease etiology. PMID:24657180

  17. Association Between Increased Vascular Nitric Oxide Bioavailability and Progression to Dengue Hemorrhagic Fever in Adults.

    PubMed

    Thein, Tun-Linn; Wong, Joshua; Leo, Yee-Sin; Ooi, Eng-Eong; Lye, David; Yeo, Tsin W

    2015-09-01

    In a prospective longitudinal adult study, vascular nitric oxide bioavailability measured as reactive hyperemia index was significantly higher at enrollment in patients who developed dengue hemorrhagic fever (DHF) (n = 11), compared with the non-DHF group (n = 63) and those with other febrile illnesses (n = 25) (P = .01). After adjustment for age, fever day, and body mass index, enrollment reactive hyperemia index was associated with a 4-fold increased risk for DHF, and predicted DHF with an area under the receiver operating curve of 0.86. Increased vascular nitric oxide in dengue is associated with increased vascular permeability and impaired homeostasis and may have utility as a predictor of DHF.

  18. Asymmetric otolith function and increased susceptibility to motion sickness during exposure to variations in gravitoinertial acceleration level

    NASA Technical Reports Server (NTRS)

    Lackner, James R.; Graybiel, Ashton; Johnson, Walter H.; Money, Kenneth E.

    1987-01-01

    Von Baumgarten and coworkers (1979, 1981) have suggested that asymmetries in otolith function between the left and right labyrinths may result from differences in otoconial mass and could play a role in space motion sickness. Such asymmetries would be centrally compensated for under terrestrial conditions, but on exposure to weightlessness the persisting central compensation would produce a central imbalance that could lead to motion sickness. In this work ocular counterrolling was used as a way of measuring the relative 'efficiency' of the left and right otoliths; the ocular counterrolling scores of individuals were compared with their susceptibility to motion sickness during passive exposure to variations in Gz in parabolic flight maneuvers. The experimental findings indicate that large asymmetries in counterrolling for leftward and rightward body tilts are associated with greater susceptibility to motion sickness in parabolic flight.

  19. The current age of youthful melancholia. Evidence for increase in depression among adolescents and young adults.

    PubMed

    Klerman, G L

    1988-01-01

    The possibility of a rise in rates of depression among adolescents and young adults was first reported in the 1970s. Particular note was taken of the emergence of childhood depression and the increase in suicide attempts and death among adolescents and young adults. Data from large-sample family studies and community epidemiological surveys have been reviewed and reanalysed, using life-table statistical methodology. Evidence for secular trends are presented, and the problems of disentangling period and cohort effect are discussed. It appears that the 'baby boomers' - those born in the years after World War II - have had increased rates of depression and other related illnesses, including drug abuse and alcoholism. The theoretical aspects of this are discussed, particularly for gene-environment interactions.

  20. Gender-specific increase in susceptibility to metabolic syndrome of offspring rats after prenatal caffeine exposure with post-weaning high-fat diet

    SciTech Connect

    Li, Jing; Luo, Hanwen; Wu, Yimeng; He, Zheng; Zhang, Li; Guo, Yu; Ma, Lu; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-05-01

    Prenatal caffeine exposure (PCE) alters the hypothalamic–pituitary–adrenocortical (HPA) axis-associated neuroendocrine metabolic programming and induces an increased susceptibility to metabolic syndrome (MS) in intrauterine growth retardation (IUGR) offspring rats. High-fat diet (HFD) is one of the main environmental factors accounting for the incidence of MS. In this study, we aimed to clarify the gender-specific increase in susceptibility to MS in offspring rats after PCE with post-weaning HFD. Maternal Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. The offspring rats with normal diet or HFD were euthanized at postnatal week 24, and blood samples were collected. Results showed that PCE not only reduced serum adrenocorticotropic hormone (ACTH) and corticosterone levels, but also enhanced serum glucose, triglyceride and total cholesterol (TCH) concentrations in the offspring rats. Moreover, several interactions among PCE, HFD and gender were observed by a three-way ANOVA analysis. In PCE offspring, HFD could aggravate the degree of increased serum triglyceride level. Meanwhile, serum corticosterone levels of females were decreased more obviously than those of males in PCE offspring. The results also revealed interactions between HFD and gender in the levels of serum ACTH, triglyceride and TCH, which were changed more evidently in female HFD offspring. These results indicate that HFD could exacerbate the dysfunction of lipid metabolism and the susceptibility to MS induced by PCE, and the female offspring are more sensitive to HFD-induced neuroendocrine metabolic dysfunction than their male counterparts. - Highlights: • Caffeine induced HPA axis dysfunction in offspring rats fed by high-fat diet (HFD). • Caffeine induced an increased susceptibility to metabolic syndrome. • HFD aggravated susceptibility to metabolic syndrome induced by caffeine. • Female was more sensitive to HFD-induced neuroendocrine

  1. PIRIN2 stabilizes cysteine protease XCP2 and increases susceptibility to the vascular pathogen Ralstonia solanacearum in Arabidopsis

    PubMed Central

    Zhang, Bo; Tremousaygue, Dominique; Denancé, Nicolas; van Esse, H Peter; Hörger, Anja C; Dabos, Patrick; Goffner, Deborah; Thomma, Bart P H J; van der Hoorn, Renier A L; Tuominen, Hannele

    2014-01-01

    PIRIN (PRN) is a member of the functionally diverse cupin protein superfamily. There are four members of the Arabidopsis thaliana PRN family, but the roles of these proteins are largely unknown. Here we describe a function of the Arabidopsis PIRIN2 (PRN2) that is related to susceptibility to the bacterial plant pathogen Ralstonia solanacearum. Two prn2 mutant alleles displayed decreased disease development and bacterial growth in response to R.  solanacearum infection. We elucidated the underlying molecular mechanism by analyzing PRN2 interactions with the papain-like cysteine proteases (PLCPs) XCP2, RD21A, and RD21B, all of which bound to PRN2 in yeast two-hybrid assays and in Arabidopsis protoplast co-immunoprecipitation assays. We show that XCP2 is stabilized by PRN2 through inhibition of its autolysis on the basis of PLCP activity profiling assays and enzymatic assays with recombinant protein. The stabilization of XCP2 by PRN2 was also confirmed in planta. Like prn2 mutants, an xcp2 single knockout mutant and xcp2 prn2 double knockout mutant displayed decreased susceptibility to R. solanacearum, suggesting that stabilization of XCP2 by PRN2 underlies susceptibility to R. solanacearum in Arabidopsis. PMID:24947605

  2. PIRIN2 stabilizes cysteine protease XCP2 and increases susceptibility to the vascular pathogen Ralstonia solanacearum in Arabidopsis.

    PubMed

    Zhang, Bo; Tremousaygue, Dominique; Denancé, Nicolas; van Esse, H Peter; Hörger, Anja C; Dabos, Patrick; Goffner, Deborah; Thomma, Bart P H J; van der Hoorn, Renier A L; Tuominen, Hannele

    2014-09-01

    PIRIN (PRN) is a member of the functionally diverse cupin protein superfamily. There are four members of the Arabidopsis thaliana PRN family, but the roles of these proteins are largely unknown. Here we describe a function of the Arabidopsis PIRIN2 (PRN2) that is related to susceptibility to the bacterial plant pathogen Ralstonia solanacearum. Two prn2 mutant alleles displayed decreased disease development and bacterial growth in response to R.  solanacearum infection. We elucidated the underlying molecular mechanism by analyzing PRN2 interactions with the papain-like cysteine proteases (PLCPs) XCP2, RD21A, and RD21B, all of which bound to PRN2 in yeast two-hybrid assays and in Arabidopsis protoplast co-immunoprecipitation assays. We show that XCP2 is stabilized by PRN2 through inhibition of its autolysis on the basis of PLCP activity profiling assays and enzymatic assays with recombinant protein. The stabilization of XCP2 by PRN2 was also confirmed in planta. Like prn2 mutants, an xcp2 single knockout mutant and xcp2 prn2 double knockout mutant displayed decreased susceptibility to R. solanacearum, suggesting that stabilization of XCP2 by PRN2 underlies susceptibility to R. solanacearum in Arabidopsis.

  3. Increased reports of measles in a low endemic region during a rubella outbreak in adult populations.

    PubMed

    Kurata, Takako; Kanbayashi, Daiki; Nishimura, Hiroshi; Komano, Jun; Kase, Tetsuo; Takahashi, Kazuo

    2015-06-01

    In 2013, a rubella outbreak was observed in Japan, Romania, and Poland. The outbreak in Japan was accompanied by an increase of measles reports, especially from a region where measles is highly controlled. This was attributed to the adult populations affected by this rubella outbreak, similarity of clinical signs between rubella and measles, sufficiently small impact of measles outbreaks from neighboring nations, and elimination levels of measles endemicity. Current and future concerns for measles control are discussed.

  4. Pedometers and brief e-counseling: increasing physical activity for overweight adults.

    PubMed Central

    VanWormer, Jeffrey J

    2004-01-01

    Physical inactivity has emerged as a public health epidemic and is associated with the rising obesity rate. A multiple-treatments reversal design was utilized to test whether pedometer-aided self-monitoring and brief e-counseling could help 3 overweight adults increase their physical activity. Dependent measures were taken for pedometer steps and weight. Two participants approximately doubled their daily step totals and lost a modest amount of weight by study end. PMID:15529901

  5. Exploration of risk taking behaviors and perceived susceptibility of colorectal cancer among Malaysian adults: a community based cross-sectional study

    PubMed Central

    2013-01-01

    Background Perceived susceptibility to an illness has been shown to affect Health-risk behavior. The objective of the present study was to determine the risk taking behaviors and the demographic predictors of perceived susceptibility to colorectal cancer in a population-based sample. Methods A cross-sectional study was carried out among 305 Malaysian adults in six major districts, selected from urban, semi-urban, and rural settings in one state in Malaysia. A self-administered questionnaire was used in this study. It was comprised of socio-demographics, risk-taking behaviors, and validated domains of the Health Belief Model (HBM). Results The mean (± SD) age of the respondents was 34.5 (± 9.6) and the majority (59.0%) of them were 30 years or older. Almost 20.7% of the respondents felt they were susceptible to colorectal cancer. Self-reported perceived susceptibility mirrored unsatisfactory screening behaviors owing to the lack of doctors’ recommendation, ignorance of screening modalities, procrastination, and the perception that screening was unnecessary. Factors significantly associated with perceived susceptibility to colorectal cancer were gender (OR = 1.8, 95% CI 1.0-3.3), age (OR = 2. 2, 95% CI 1.2-4.0), ethnicity (OR = 0. 3, 95% CI 0.2-0.6), family history of colorectal cancer (OR = 3. 2, 95% CI 1.4-7.4) and alcohol intake (OR = 3.9, 95% CI 2.1-7.5). Conclusion The present study revealed that screening behavior among respondents was unsatisfactory. Hence, awareness of the importance of screening to prevent colorectal cancers is imperative. PMID:24093502

  6. Effects of increasing physical activity on foot structure and ankle muscle strength in adults with obesity

    PubMed Central

    Zhao, Xiaoguang; Tsujimoto, Takehiko; Kim, Bokun; Katayama, Yasutomi; Wakaba, Kyousuke; Wang, Zhennan; Tanaka, Kiyoji

    2016-01-01

    [Purpose] The purpose of this study was to examine the effects of increasing physical activity on foot structure and ankle muscle strength in adults with obesity and to verify whether the rate of change in foot structure is related to that in ankle muscle strength. [Subjects and Methods] Twenty-seven adults with obesity completed a 12-week program in which the intensity of physical activity performed was gradually increased. Physical activity was monitored using a three-axis accelerometer. Foot structure was assessed using a three-dimensional foot scanner, while ankle muscle strength was measured using a dynamometry. [Results] With the increasing physical activity, the participants’ feet became thinner (the rearfoot width, instep height, and girth decreased) and the arch became higher (the arch height index increased) and stiffer (the arch stiffness index increased); the ankle muscle strength also increased after the intervention. Additionally, the changes in the arch height index and arch stiffness index were not associated with changes in ankle muscle strength. [Conclusion] Increasing physical activity may be one possible approach to improve foot structure and function in individuals with obesity.

  7. Effects of increasing physical activity on foot structure and ankle muscle strength in adults with obesity.

    PubMed

    Zhao, Xiaoguang; Tsujimoto, Takehiko; Kim, Bokun; Katayama, Yasutomi; Wakaba, Kyousuke; Wang, Zhennan; Tanaka, Kiyoji

    2016-08-01

    [Purpose] The purpose of this study was to examine the effects of increasing physical activity on foot structure and ankle muscle strength in adults with obesity and to verify whether the rate of change in foot structure is related to that in ankle muscle strength. [Subjects and Methods] Twenty-seven adults with obesity completed a 12-week program in which the intensity of physical activity performed was gradually increased. Physical activity was monitored using a three-axis accelerometer. Foot structure was assessed using a three-dimensional foot scanner, while ankle muscle strength was measured using a dynamometry. [Results] With the increasing physical activity, the participants' feet became thinner (the rearfoot width, instep height, and girth decreased) and the arch became higher (the arch height index increased) and stiffer (the arch stiffness index increased); the ankle muscle strength also increased after the intervention. Additionally, the changes in the arch height index and arch stiffness index were not associated with changes in ankle muscle strength. [Conclusion] Increasing physical activity may be one possible approach to improve foot structure and function in individuals with obesity. PMID:27630426

  8. Effects of increasing physical activity on foot structure and ankle muscle strength in adults with obesity

    PubMed Central

    Zhao, Xiaoguang; Tsujimoto, Takehiko; Kim, Bokun; Katayama, Yasutomi; Wakaba, Kyousuke; Wang, Zhennan; Tanaka, Kiyoji

    2016-01-01

    [Purpose] The purpose of this study was to examine the effects of increasing physical activity on foot structure and ankle muscle strength in adults with obesity and to verify whether the rate of change in foot structure is related to that in ankle muscle strength. [Subjects and Methods] Twenty-seven adults with obesity completed a 12-week program in which the intensity of physical activity performed was gradually increased. Physical activity was monitored using a three-axis accelerometer. Foot structure was assessed using a three-dimensional foot scanner, while ankle muscle strength was measured using a dynamometry. [Results] With the increasing physical activity, the participants’ feet became thinner (the rearfoot width, instep height, and girth decreased) and the arch became higher (the arch height index increased) and stiffer (the arch stiffness index increased); the ankle muscle strength also increased after the intervention. Additionally, the changes in the arch height index and arch stiffness index were not associated with changes in ankle muscle strength. [Conclusion] Increasing physical activity may be one possible approach to improve foot structure and function in individuals with obesity. PMID:27630426

  9. Maximal exercise does not increase ventilation heterogeneity in healthy trained adults.

    PubMed

    Wrobel, Jeremy P; Ellis, Matthew J; Kee, Kirk; Stuart-Andrews, Christopher R; Thompson, Bruce R

    2016-04-01

    The effect of exercise on ventilation heterogeneity has not been investigated. We hypothesized that a maximal exercise bout would increase ventilation heterogeneity. We also hypothesized that increased ventilation heterogeneity would be associated with exercise-induced arterial hypoxemia (EIAH). Healthy trained adult males were prospectively assessed for ventilation heterogeneity using lung clearance index (LCI), Scond, and Sacinat baseline, postexercise and at recovery, using the multiple breath nitrogen washout technique. The maximal exercise bout consisted of a maximal, incremental cardiopulmonary exercise test at 25 watt increments. Eighteen subjects were recruited with mean ± SDage of 35 ± 9 years. There were no significant changes inLCI, Scond, or Sacinfollowing exercise or at recovery. While there was an overall reduction in SpO2with exercise (99.3 ± 1 to 93.7 ± 3%,P < 0.0001), the reduction in SpO2was not associated with changes inLCI, Scondor Sacin Ventilation heterogeneity is not increased following a maximal exercise bout in healthy trained adults. Furthermore,EIAHis not associated with changes in ventilation heterogeneity in healthy trained adults.

  10. Increasing body size among adult cook islanders between 1966 and 1996.

    PubMed

    Ulijaszek, S J

    2001-01-01

    There is limited evidence of a secular trend toward increased body size among populations in the Pacific Region, although some populations have shown a clear rise in overweight and obesity across the past 30 years or so. Mean height, weight and body mass index (BMI) of adults surveyed in 1996 on Rarotonga, the Cook Islands, are reported by age group and compared with data collected in 1966 by Evans and Prior, to determine the extent to which a secular trend in increasing body size has taken place across this 30-year period. In addition, a comparison of these anthropometric variables between subjects born on the most modernized island of Rarotonga with those born on other less-modernized islands is made, to determine the extent to which adult body size differs according to place of origin. Comparing the sample of those born on Rarotonga, the most modernized island, with those born on other, less modernized islands shows those born on Rarotonga to be taller, but not relatively heavier than those born elsewhere in the Cook Islands. Both males and females of the 1996 sample of adults are significantly taller, heavier, with higher BMI compared with the 1966 sample, indicating a secular trend toward increased body size across this 30-year period. The mean BMIs of the younger age groups in 1996 are greater than those of the same age groups in 1966, indicating a secular trend toward greater body fatness. There has been a significant increase in obesity among both males and females. In 1966, 14% of males had a BMI greater than 30, while in 1996, the proportion was 52%. Among females, 44% of those measured in 1966 had a BMI greater than 30, while in 1996 the proportion was 57%. The higher mean stature of younger adult males relative to older ones suggests that the secular trend toward increasing height may have been underway prior to 1966. The mean statures and weights of adults aged 60 years and older in the 1996 sample are more similar to values given for most age groups

  11. Increased susceptibility to liver injury after hemorrhagic shock in rats chronically fed ethanol: role of nuclear factor-kappa B, interleukin-6, and granulocyte colony-stimulating factor.

    PubMed

    Ono, Masafumi; Yu, Bi; Hardison, Edith G; Mastrangelo, Mary-Ann A; Tweardy, David J

    2004-06-01

    Chronic ethanol use preceding severe trauma and hemorrhagic shock (HS) is associated with an increased incidence of multiorgan failure (MOF) and death; however, the molecular basis for this increased susceptibility is unknown. We previously demonstrated that production of interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF), mediated by nuclear factor-kappa B (NF-kappa B), each make essential contributions to organ injury and inflammation in a rodent model of controlled HS, and we proposed in this study to examine the hypothesis that the increased susceptibility to MOF after shock/trauma in the setting of chronic ethanol use is due to an exaggerated activation of NF-kappa B and production of these proinflammatory cytokines. We observed increased HS-induced liver injury 4 h after resuscitation in rats fed the ethanol-containing Lieber-DeCarli liquid diet for 8 weeks compared with rats fed the control liquid diet (3-fold increase in serum alanine aminotransferase [ALT], P = 0.008, and 2-fold increase in focal liver necrosis, P = 0.005). The increased liver injury in the ethanol-fed HS rats was accompanied by a 70% increase in liver NF-kappa B activation (P < 0.05), a 3- to 5-fold increase in hepatocyte and Kupffer cell production of IL-6 and G-CSF (P < 0.05 for each), and a 2-fold increase in neutrophil infiltration (P < 0.005) compared with the control diet-fed HS rats. Thus, increased susceptibility to HS-induced liver injury in the setting of chronic ethanol use may be mediated, at least in part, by increased NF-kappa B activation resulting in increased local production of IL-6 and G-CSF and increased infiltration of neutrophils, which can damage liver cells directly and contribute to impaired sinusoidal blood flow.

  12. Interaction between asthma and smoking increases the risk of adult airway obstruction.

    PubMed

    Aanerud, Marianne; Carsin, Anne-Elie; Sunyer, Jordi; Dratva, Julia; Gislason, Thorarinn; Jarvis, Deborah; deMarco, Roberto; Raherison, Chantal; Wjst, Matthias; Dharmage, Shyamali C; Svanes, Cecilie

    2015-03-01

    The aim of the present study was to analyse the interaction between asthma and smoking in the risk of adult airway obstruction, accounting for atopy. In the European Community Respiratory Health Survey, 15 668 persons aged 20-56 years underwent spirometry in 1991-1993 and 9 years later (n=8916). Risk of airway obstruction and lung function decline associated with smoking and early-onset (<10 years of age) and late-onset (>10 years of age) asthma were analysed with generalised estimating equation models and random-effect linear models, adjusting for covariates. Interaction of asthma with smoking was expressed as relative excess risk due to interaction (RERI). A 20-fold increase in adult airway obstruction was found among those with early-onset asthma independently of smoking status (never-smokers: OR 21.0, 95% CI 12.7-35; current smokers: OR 23.7, 95% CI 13.9-40.6). Late-onset asthma was associated with airway obstruction, with a stronger association among current smokers (OR 25.6, 95% CI 15.6-41.9) than among never-smokers (OR 11.2, 95% CI 6.8-18.6) (RERI 12.02, 95% CI 1.96-22.07). Stratifying by atopy, the association between smoking and asthma was most pronounced among nonatopics. Early- and late-onset asthma were associated with 10-20-fold increased risk of adult airway obstruction. Smoking increased the risk of adult airway obstruction in subjects with asthma onset after age 10 years. Investigation of measures potentially preventive of chronic obstructive pulmonary disease development following asthma is urgently needed.

  13. Increased GABA Levels in Medial Prefrontal Cortex of Young Adults with Narcolepsy

    PubMed Central

    Kim, Seog Ju; Lyoo, In Kyoon; Lee, Yujin S.; Sung, Young Hoon; Kim, Hengjun J.; Kim, Jihyun H.; Kim, Kye Hyun; Jeong, Do-Un

    2008-01-01

    Study Objectives: To explore absolute concentrations of brain metabolites including gamma amino-butyric acid (GABA) in the medial prefrontal cortex and basal ganglia of young adults with narcolepsy. Design: Proton magnetic resonance (MR) spectroscopy centered on the medial prefrontal cortex and the basal ganglia was acquired. The absolute concentrations of brain metabolites including GABA and glutamate were assessed and compared between narcoleptic patients and healthy comparison subjects. Setting: Sleep and Chronobiology Center at Seoul National University Hospital; A high strength 3.0 Tesla MR scanner in the Department of Radiology at Seoul National University Hospital. Patients or Participants: Seventeen young adults with a sole diagnosis of HLA DQB1 0602 positive narcolepsy with cataplexy (25.1 ± 4.6 years old) and 17 healthy comparison subjects (26.8 ± 4.8 years old). Interventions: N/A. Measurements and Results: Relative to comparison subjects, narcoleptic patients had higher GABA concentration in the medial prefrontal cortex (t = 4.10, P <0.001). Narcoleptic patients with nocturnal sleep disturbance had higher GABA concentration in the medial prefrontal cortex than those without nocturnal sleep disturbance (t = 2.45, P= 0.03), but had lower GABA concentration than comparison subjects (t = 2.30, P = 0.03). Conclusions: The current study reports that young adults with narcolepsy had a higher GABA concentration in the medial prefrontal cortex, which was more prominent in patients without nocturnal sleep disturbance. Our findings suggest that the medial prefrontal GABA level may be increased in narcolepsy, and the increased medial prefrontal GABA might be a compensatory mechanism to reduce nocturnal sleep disturbances in narcolepsy. Citation: Kim SJ; Lyoo IK; Lee YS; Sung YH; Kim HJ; Kim JH; Kim KH; Jeong DU. Increased GABA levels in medial prefrontal cortex of young adults with narcolepsy. SLEEP 2008;31(3):342-347. PMID:18363310

  14. Increased carboxyhemoglobin in adult falciparum malaria is associated with disease severity and mortality.

    PubMed

    Yeo, Tsin W; Lampah, Daniel A; Kenangalem, Enny; Tjitra, Emiliana; Price, Ric N; Anstey, Nicholas M

    2013-09-01

    Heme oxygenase 1 expression is increased in pediatric patients with malaria. The carboxyhemoglobin level (a measure of heme oxygenase 1 activity) has not been assessed in adult patients with malaria. Results of pulse co-oximetry revealed that the mean carboxyhemoglobin level was elevated in 29 Indonesian adults with severe falciparum malaria (10%; 95% confidence interval [CI], 8%-13%) and in 20 with severe sepsis (8%; 95% CI, 5%-12%), compared with the mean levels in 32 patients with moderately severe malaria (7%; 95% CI, 5%-8%) and 36 controls (3.6%; 95% CI, 3%-5%; P < .001). An increased carboxyhemoglobin level was associated with an increased odds of death among patients with severe malaria (odds ratio, 1.2 per percentage point increase; 95% CI, 1.02-1.5). While also associated with severity and fatality, methemoglobin was only modestly increased in patients with severe malaria. Increased carboxyhemoglobin levels during severe malaria and sepsis may exacerbate organ dysfunction by reducing oxygen carriage and cautions against the use of adjunctive CO therapy, which was proposed on the basis of mouse models.

  15. Modeling the Potential Impact of a Prescription Drug Copayment Increase on the Adult Asthmatic Medicaid Population

    PubMed Central

    Bae, Seung Jin; Paltiel, A. David; Fuhlbrigge, Anne L.; Weiss, Scott T.; Kuntz, Karen M.

    2012-01-01

    Objectives The Commonwealth of Massachusetts increased the copayment for prescription drugs by $1.50 for Medicaid (MassHealth) beneficiaries in 2003. We sought to determine the likely health outcomes and cost shifts attributable to this copayment increase using the example of inhaled corticosteroids (ICS) use among adult asthmatic Medicaid beneficiaries. Method We compared the predicted costs and health outcomes projected over a 1-year time horizon with and without the increase in copayment from the perspective of MassHealth, providers, pharmacies, and MassHealth beneficiaries by employing decision analysis simulation model. Results In a target population of 17,500 adult asthmatics, increased copayments from 50¢ to $2.00 would result in an additional 646 acute events per year, caused by increased drug nonadherence. Annual combined net savings for the state and federal governments would be $2.10 million. Projected MassHealth savings are attributable to both decreased drug utilization and lower pharmacy reimbursement rates; these more than offset the additional costs of more frequent acute exacerbations. Pharmacies would lose $1.98 million in net revenues, MassHealth beneficiaries would pay an additional $0.28 million, and providers would receive additional $0.16 million. Conclusion Over its first year of implementation, increase in the prescription drug copayment is expected to produce more frequent acute exacerbations among asthmatic MassHealth beneficiaries who use ICS and to shift the financial burden from government to other stakeholders. PMID:18237365

  16. Physical skill training increases the number of surviving new cells in the adult hippocampus.

    PubMed

    Curlik, Daniel M; Maeng, Lisa Y; Agarwal, Prateek R; Shors, Tracey J

    2013-01-01

    The dentate gyrus is a major site of plasticity in the adult brain, giving rise to thousands of new neurons every day, through the process of adult neurogenesis. Although the majority of these cells die within two weeks of their birth, they can be rescued from death by various forms of learning. Successful acquisition of select types of associative and spatial memories increases the number of these cells that survive. Here, we investigated the possibility that an entirely different form of learning, physical skill learning, could rescue new hippocampal cells from death. To test this possibility, rats were trained with a physically-demanding and technically-difficult version of a rotarod procedure. Acquisition of the physical skill greatly increased the number of new hippocampal cells that survived. The number of surviving cells positively correlated with performance on the task. Only animals that successfully mastered the task retained the cells that would have otherwise died. Animals that failed to learn, and those that did not learn well did not retain any more cells than those that were untrained. Importantly, acute voluntary exercise in activity wheels did not increase the number of surviving cells. These data suggest that acquisition of a physical skill can increase the number of surviving hippocampal cells. Moreover, learning an easier version of the task did not increase cell survival. These results are consistent with previous reports revealing that learning only rescues new neurons from death when acquisition is sufficiently difficult to achieve. Finally, complete hippocampal lesions did not disrupt acquisition of this physical skill. Therefore, physical skill training that does not depend on the hippocampus can effectively increase the number of surviving cells in the adult hippocampus, the vast majority of which become mature neurons.

  17. Increased excitability and molecular changes in adult rats after a febrile seizure.

    PubMed

    Reid, Aylin Y; Riazi, Kiarash; Campbell Teskey, G; Pittman, Quentin J

    2013-04-01

    Both early life inflammation and prolonged febrile seizures have been associated with increased excitation in the adult brain. We hypothesized this may be due in part to changes in the cation-chloride cotransporter system. Rat pups received saline or lipopolysaccharide/kainic acid (LPS/KA) resulting in inflammation, followed by a behavioral febrile seizure (FS) in approximately 50% of rats. Adult animals from the saline, inflammation, or inflammation + FS groups underwent the following: (1) in vitro electrophysiologic studies; (2) Western blotting or polymerase chain reaction; or (3) application of the Na-K-Cl cotransporter 1 (NKCC1) blocker bumetanide to determine its effect on reversing increased excitability in vitro. The inflammation and inflammation + FS groups demonstrated increased excitability in vitro and increased hippocampal protein expression of NR2B and GABAA α5 receptor subunits and mRNA expression of NKCC1. The inflammation + FS group also had decreased protein expression of GluR2 and GABAA α1 receptor subunits and mRNA and protein expression of KCC2. Bumetanide decreased in vitro 4-aminopyridine-induced inter-ictal activity in the inflammation and inflammation + FS groups. The results demonstrate early-life inflammation with or without a behavioral FS can lead to long-lasting molecular changes and increased excitability in the adult rat hippocampus, although some changes are more extensive when inflammation is accompanied by behavioral seizure activity. Bumetanide is effective in reversing increased excitability in vitro, providing evidence for a causal role for cation-chloride cotransporters and suggesting this drug may prove useful for treating epilepsy that develops after a FS. PMID:23293960

  18. Analysis of triclosan-selected Salmonella enterica mutants of eight serovars revealed increased aminoglycoside susceptibility and reduced growth rates.

    PubMed

    Rensch, Ulrike; Klein, Guenter; Kehrenberg, Corinna

    2013-01-01

    The biocide triclosan (TRC) is used in a wide range of household, personal care, veterinary, industrial and medical products to control microbial growth. This extended use raises concerns about a possible association between the application of triclosan and the development of antibiotic resistance. In the present study we determined triclosan mutant prevention concentrations (MPC) for Salmonella enterica isolates of eight serovars and investigated selected mutants for their mechanisms mediating decreased susceptibility to triclosan. MPCTRC values were 8-64-fold higher than MIC values and ranged between 1-16 µg/ml. The frequencies at which mutants were selected varied between 1.3 x 10(-10)-9.9 x 10(-11). Even if MIC values of mutants decreased by 3-7 dilution steps in the presence of the efflux pump inhibitor Phe-Arg-β-naphtylamide, only minor changes were observed in the expression of genes encoding efflux components or regulators, indicating that neither the major multidrug efflux pump AcrAB-TolC nor AcrEF are up-regulated in triclosan-selected mutants. Nucleotide sequence comparisons confirmed the absence of alterations in the regulatory regions acrRA, soxRS, marORAB, acrSE and ramRA of selected mutants. Single bp and deduced Gly93→Val amino acid exchanges were present in fabI, the target gene of triclosan, starting from a concentration of 1 µg/ml TRC used for MPC determinations. The fabI genes were up to 12.4-fold up-regulated. Complementation experiments confirmed the contribution of Gly93→Val exchanges and fabI overexpression to decreased triclosan susceptibility. MIC values of mutants compared to parent strains were even equal or resulted in a more susceptible phenotype (1-2 dilution steps) for the aminoglycoside antibiotics kanamycin and gentamicin as well as for the biocide chlorhexidine. Growth rates of selected mutants were significantly lower and hence, might partly explain the rare occurrence of Salmonella field isolates exhibiting decreased

  19. Maternal obesity characterized by gestational diabetes increases the susceptibility of rat offspring to hepatic steatosis via a disrupted liver metabolome

    PubMed Central

    Pereira, Troy J; Fonseca, Mario A; Campbell, Kristyn E; Moyce, Brittany L; Cole, Laura K; Hatch, Grant M; Doucette, Christine A; Klein, Julianne; Aliani, Michel; Dolinsky, Vernon W

    2015-01-01

    Maternal obesity is associated with a high risk for gestational diabetes mellitus (GDM), which is a common complication of pregnancy. The influence of maternal obesity and GDM on the metabolic health of the offspring is poorly understood. We hypothesize that GDM associated with maternal obesity will cause obesity, insulin resistance and hepatic steatosis in the offspring. Female Sprague-Dawley rats were fed a high-fat (45%) and sucrose (HFS) diet to cause maternal obesity and GDM. Lean control pregnant rats received low-fat (LF; 10%) diets. To investigate the interaction between the prenatal environment and postnatal diets, rat offspring were assigned to LF or HFS diets for 12 weeks, and insulin sensitivity and hepatic steatosis were evaluated. Pregnant GDM dams exhibited excessive gestational weight gain, hyperinsulinaemia and hyperglycaemia. Offspring of GDM dams gained more weight than the offspring of lean dams due to excess adiposity. The offspring of GDM dams also developed hepatic steatosis and insulin resistance. The postnatal consumption of a LF diet did not protect offspring of GDM dams against these metabolic disorders. Analysis of the hepatic metabolome revealed increased diacylglycerol and reduced phosphatidylethanolamine in the offspring of GDM dams compared to offspring of lean dams. Consistent with altered lipid metabolism, the expression of CTP:phosphoethanolamine cytidylyltransferase, and peroxisomal proliferator activated receptor-α mRNA was reduced in the livers of GDM offspring. GDM exposure programs gene expression and hepatic metabolite levels and drives the development of hepatic steatosis and insulin resistance in young adult rat offspring. Key points Gestational diabetes mellitus is a common complication of pregnancy, but its effects on the offspring are poorly understood. We developed a rat model of diet-induced gestational diabetes mellitus that recapitulates many of the clinical features of the disease, including excessive gestational

  20. Increased load computerized dynamic posturography in prefrail and nonfrail community-dwelling older adults.

    PubMed

    Biggan, John R; Melton, Forest; Horvat, Michael A; Ricard, Mark; Keller, David; Ray, Christopher T

    2014-01-01

    The understanding of prefrail and nonfrail older adults' postural control with and without increased environmental and cognitive stress is imperative to the development of targeted interventions to decrease fall risk within these populations. Thirty-eight individuals participated in this study. Postural control testing included the Sensory Organization Test (SOT) on a NeuroCom EquiTest. Cognitive and environmental load testing was performed during Condition 6 of the SOT. Though there were no group differences on composite equilibrium score (p = .06), the cognitive task (Stroop task) impaired equilibrium scores more than the auditory or visual distracter tasks (p < .05 and p < .01) for both groups. These results suggest that both prefrail and nonfrail older adults' postural control is reduced in demanding environments. Given these findings, the need for multimodal exercise interventions to target both physical and cognitive factors is apparent. PMID:23416307

  1. Exposure to dim light at night during early development increases adult anxiety-like responses.

    PubMed

    Borniger, Jeremy C; McHenry, Zachary D; Abi Salloum, Bachir A; Nelson, Randy J

    2014-06-22

    Early experiences produce effects that may persist throughout life. Therefore, to understand adult phenotype, it is important to investigate the role of early environmental stimuli in adult behavior and health. Artificial light at night (LAN) is an increasingly common phenomenon throughout the world. However, animals, including humans, evolved under dark night conditions. Many studies have revealed affective, immune, and metabolic alterations provoked by aberrant light exposure and subsequent circadian disruption. Pups are receptive to entraining cues from the mother and then light early during development, raising the possibility that the early life light environment may influence subsequent behavior. Thus, to investigate potential influences of early life exposure to LAN on adult phenotype, we exposed mice to dim (~5 lux; full spectrum white light) or dark (~0 lux) nights pre- and/or postnatally. After weaning at 3 weeks of age, all mice were maintained in dark nights until adulthood (9 weeks of age) when behavior was assessed. Mice exposed to dim light in early life increased anxiety-like behavior and fearful responses on the elevated plus maze and passive avoidance tests. These mice also displayed reduced growth rates, which ultimately normalized during adolescence. mRNA expression of brain derived neurotrophic factor (BDNF), a neurotrophin previously linked to early life environment and adult phenotype, was not altered in the prefrontal cortex or hippocampus by early life LAN exposure. Serum corticosterone concentrations were similar between groups at weaning, suggesting that early life LAN does not elicit a long-term physiologic stress response. Dim light exposure did not influence behavior on the open field, novel object, sucrose anhedonia, or forced swim tests. Our data highlight the potential deleterious consequences of low levels of light during early life to development and subsequent behavior. Whether these changes are due to altered maternal behavior

  2. Deletion of the β-acetoacetyl synthase FabY in Pseudomonas aeruginosa induces hypoacylation of lipopolysaccharide and increases antimicrobial susceptibility.

    PubMed

    Six, David A; Yuan, Yanqiu; Leeds, Jennifer A; Meredith, Timothy C

    2014-01-01

    The β-acetoacetyl-acyl carrier protein synthase FabY is a key enzyme in the initiation of fatty acid biosynthesis in Pseudomonas aeruginosa. Deletion of fabY results in an increased susceptibility of P. aeruginosa in vitro to a number of antibiotics, including vancomycin and cephalosporins. Because antibiotic susceptibility can be influenced by changes in membrane lipid composition, we determined the total fatty acid profile of the ΔfabY mutant, which suggested alterations in the lipid A region of the lipopolysaccharide. The majority of lipid A species in the ΔfabY mutant lacked a single secondary lauroyl group, resulting in hypoacylated lipid A. Adding exogenous fatty acids to the growth media restored the wild-type antibiotic susceptibility profile and the wild-type lipid A fatty acid profile. We suggest that incorporation of hypoacylated lipid A species into the outer membrane contributes to the shift in the antibiotic susceptibility profile of the ΔfabY mutant.

  3. Targeted complement inhibition by C3d recognition ameliorates tissue injury without apparent increase in susceptibility to infection.

    PubMed

    Atkinson, Carl; Song, Hongbin; Lu, Bo; Qiao, Fei; Burns, Tara A; Holers, V Michael; Tsokos, George C; Tomlinson, Stephen

    2005-09-01

    Previous studies indicate a pivotal role for complement in mediating both local and remote injury following ischemia and reperfusion of the intestine. Here, we report on the use of a mouse model of intestinal ischemia/reperfusion injury to investigate the strategy of targeting complement inhibition to sites of complement activation by linking an iC3b/C3dg-binding fragment of mouse complement receptor 2 (CR2) to a mouse complement-inhibitory protein, Crry. We show that the novel CR2-Crry fusion protein targets sites of local and remote (lung) complement activation following intestinal ischemia and reperfusion injury and that CR2-Crry requires a 10-fold lower dose than its systemic counterpart, Crry-Ig, to provide equivalent protection from both local and remote injury. CR2-Crry has a significantly shorter serum half-life than Crry-Ig and, unlike Crry-Ig, had no significant effect on serum complement activity at minimum effective therapeutic doses. Furthermore, the minimum effective dose of Crry-Ig significantly enhanced susceptibility to infection in a mouse model of acute septic peritonitis, whereas the effect of CR2-Crry on susceptibility to infection was indistinguishable from that of PBS control. Thus, compared with systemic inhibition, CR2-mediated targeting of a complement inhibitor of activation improved bioavailability, significantly enhanced efficacy, and maintained host resistance to infection.

  4. Targeted complement inhibition by C3d recognition ameliorates tissue injury without apparent increase in susceptibility to infection.

    PubMed

    Atkinson, Carl; Song, Hongbin; Lu, Bo; Qiao, Fei; Burns, Tara A; Holers, V Michael; Tsokos, George C; Tomlinson, Stephen

    2005-09-01

    Previous studies indicate a pivotal role for complement in mediating both local and remote injury following ischemia and reperfusion of the intestine. Here, we report on the use of a mouse model of intestinal ischemia/reperfusion injury to investigate the strategy of targeting complement inhibition to sites of complement activation by linking an iC3b/C3dg-binding fragment of mouse complement receptor 2 (CR2) to a mouse complement-inhibitory protein, Crry. We show that the novel CR2-Crry fusion protein targets sites of local and remote (lung) complement activation following intestinal ischemia and reperfusion injury and that CR2-Crry requires a 10-fold lower dose than its systemic counterpart, Crry-Ig, to provide equivalent protection from both local and remote injury. CR2-Crry has a significantly shorter serum half-life than Crry-Ig and, unlike Crry-Ig, had no significant effect on serum complement activity at minimum effective therapeutic doses. Furthermore, the minimum effective dose of Crry-Ig significantly enhanced susceptibility to infection in a mouse model of acute septic peritonitis, whereas the effect of CR2-Crry on susceptibility to infection was indistinguishable from that of PBS control. Thus, compared with systemic inhibition, CR2-mediated targeting of a complement inhibitor of activation improved bioavailability, significantly enhanced efficacy, and maintained host resistance to infection. PMID:16127466

  5. Loci on chromosomes 2 (NIDDM1) and 15 interact to increase susceptibility to diabetes in Mexican Americans.

    PubMed

    Cox, N J; Frigge, M; Nicolae, D L; Concannon, P; Hanis, C L; Bell, G I; Kong, A

    1999-02-01

    Complex disorders such as diabetes, cardiovascular disease, asthma, hypertension and psychiatric illnesses account for a large and disproportionate share of health care costs, but remain poorly characterized with respect to aetiology. The transmission of such disorders is complex, reflecting the actions and interactions of multiple genetic and environmental factors. Genetic analyses that allow for the simultaneous consideration of susceptibility from multiple regions may improve the ability to map genes for complex disorders, but such analyses are currently computationally intensive and narrowly focused. We describe here an approach to assessing the evidence for statistical interactions between unlinked regions that allows multipoint allele-sharing analysis to take the evidence for linkage at one region into account in assessing the evidence for linkage over the rest of the genome. Using this method, we show that the interaction of genes on chromosomes 2 (NIDDM1) and 15 (near CYP19) makes a contribution to susceptibility to type 2 diabetes in Mexican Americans from Starr County, Texas. PMID:9988276

  6. Odour enrichment increases adult-born dopaminergic neurons in the mouse olfactory bulb.

    PubMed

    Bonzano, Sara; Bovetti, Serena; Fasolo, Aldo; Peretto, Paolo; De Marchis, Silvia

    2014-11-01

    The olfactory bulb (OB) is the first brain region involved in the processing of olfactory information. In adult mice, the OB is highly plastic, undergoing cellular/molecular dynamic changes that are modulated by sensory experience. Odour deprivation induces down-regulation of tyrosine hydroxylase (TH) expression in OB dopaminergic interneurons located in the glomerular layer (GL), resulting in decreased dopamine in the OB. Although the effect of sensory deprivation is well established, little is known about the influence of odour enrichment on dopaminergic cells. Here we report that prolonged odour enrichment on C57BL/6J strain mice selectively increases TH-immunopositive cells in the GL by nearly 20%. Following odour enrichment on TH-green fluorescent protein (GFP) transgenic mice, in which GFP identified both mature TH-positive cells and putative immature dopaminergic cells expressing TH mRNA but not TH protein, we found a similar 20% increase in GFP-expressing cells, with no changes in the ratio between TH-positive and TH-negative cells. These data suggest that enriched conditions induce an expansion in the whole dopaminergic lineage. Accordingly, by using 5-bromo-2-deoxyuridine injections to label adult-generated cells in the GL of TH-GFP mice, we found an increase in the percentage of 5-bromo-2-deoxyuridine-positive dopaminergic cells in enriched compared with control conditions, whereas no differences were found for calretinin- and calbindin-positive subtypes. Strikingly, the fraction of newborn cells among the dopaminergic population doubled in enriched conditions. On the whole, our results demonstrate that odour enrichment drives increased integration of adult-generated dopaminergic cells that could be critical to adapt the OB circuits to the environmental incoming information.

  7. Increased expression of estrogen-related receptor β during adaptation of adult cardiomyocytes to sustained hypoxia

    PubMed Central

    Cunningham, Kathryn F; Beeson, Gyda C; Beeson, Craig C; McDermott, Paul J

    2016-01-01

    Estrogen-related Receptors (ERR) are members of the steroid hormone receptor superfamily of transcription factors that regulate expression of genes required for energy metabolism including mitochondrial biogenesis, fatty acid oxidation and oxidative phosphorylation. While ERRα and EPPγ isoforms are known to share a wide array of target genes in the adult myocardium, the function of ERRβ has not been characterized in cardiomyocytes. The purpose of this study was to determine the role of ERRβ in regulating energy metabolism in adult cardiomyocytes in primary culture. Adult feline cardiomyocytes were electrically stimulated to contract in either hypoxia (0.5% O2) or normoxia (21% O2). As compared to baseline values measured in normoxia, ERRβ mRNA levels increased significantly after 8 hours of hypoxia and remained elevated over 24 h. Conversely, ERRβ mRNA decreased to normoxic levels after 4 hours of reoxygenation. Hypoxia increased expression of the α and β isoforms of Peroxisome Proliferator-Activated Receptor γ Coactivator-1 (PGC-1) mRNA by 6-fold and 3-fold, respectively. Knockdown of ERRβ expression via adenoviral-mediated delivery of ERRβ shRNA blocked hypoxia-induced increases in PGC-1β mRNA, but not PGC-1α mRNA. Loss of ERRβ had no effect on mtDNA content as measured after 24 h of hypoxia. To determine whether loss of ERRβ affected mitochondrial function, oxygen consumption rates (OCR) were measured in contracting versus quiescent cardiomyocytes in normoxia. OCR was significantly lower in contracting cardiomyocytes expressing ERRβ shRNA than scrambled shRNA controls. Maximal OCR also was reduced by ERRβ knockdown. In conclusion: 1) hypoxia increases in ERRβ mRNA expression in contracting cardiomyocytes; 2) ERRβ is required for induction of the PGC-1β isoform in response to hypoxia; 3) ERRβ expression is required to sustain OCR in normoxic conditions. PMID:27335690

  8. Cost-Effectiveness of Increasing Influenza Vaccination Coverage in Adults with Type 2 Diabetes in Turkey

    PubMed Central

    Akın, Levent; Macabéo, Bérengère; Caliskan, Zafer; Altinel, Serdar; Satman, Ilhan

    2016-01-01

    Objective In Turkey, the prevalence of diabetes is high but the influenza vaccination coverage rate (VCR) is low (9.1% in 2014), despite vaccination being recommended and reimbursed. This study evaluated the cost-effectiveness of increasing the influenza VCR of adults with type 2 diabetes in Turkey to 20%. Methods A decision-analytic model was adapted to Turkey using data derived from published sources. Direct medical costs and indirect costs due to productivity loss were included in the societal perspective. The time horizon was set at 1 year to reflect the seasonality of influenza. Results Increasing the VCR for adults with type 2 diabetes to 20% is predicted to avert an additional 19,777 influenza cases, 2376 hospitalizations, and 236 deaths. Associated influenza costs avoided were estimated at more than 8.3 million Turkish Lira (TRY), while the cost of vaccination would be more than TRY 8.4 million. The incremental cost-effectiveness ratio was estimated at TRY 64/quality-adjusted life years, which is below the per capita gross domestic product of TRY 21,511 and therefore very cost-effective according to World Health Organization guidelines. Factors most influencing the incremental cost-effectiveness ratio were the excess hospitalization rate, inpatient cost, vaccine effectiveness against hospitalization, and influenza attack rate. Increasing the VCR to >20% was also estimated to be very cost-effective. Conclusions Increasing the VCR for adults with type 2 diabetes in Turkey to ≥20% would be very cost-effective. PMID:27322384

  9. Evaluation of a Fotonovela to Increase Depression Knowledge and Reduce Stigma Among Hispanic Adults

    PubMed Central

    Cabassa, Leopoldo J.; Molina, Gregory B.; Contreras, Sandra; Baron, Melvin

    2013-01-01

    Fotonovelas—small booklets that portray a dramatic story using photographs and captions—represent a powerful health education tool for low-literacy and ethnic minority audiences. This study evaluated the effectiveness of a depression fotonovela in increasing depression knowledge, decreasing stigma, increasing self-efficacy to recognize depression, and increasing intentions to seek treatment, relative to a text pamphlet. Hispanic adults attending a community adult school (N = 157, 47.5 % female, mean age = 35.8 years, 84 % immigrants, 63 % with less than high school education) were randomly assigned to read the fotonovela or a low-literacy text pamphlet about depression. They completed surveys before reading the material, immediately after reading the material, and 1 month later. The fotonovela and text pamphlet both produced significant improvements in depression knowledge and self-efficacy to identify depression, but the fotonovela produced significantly larger reductions in antidepressant stigma and mental health care stigma. The fotonovela also was more likely to be passed on to family or friends after the study, potentially increasing its reach throughout the community. Results indicate that fotonovelas can be useful for improving health literacy among underserved populations, which could reduce health disparities. PMID:22485012

  10. Using function-focused care to increase physical activity among older adults.

    PubMed

    Resnick, Barbara; Galik, Elizabeth

    2013-01-01

    Despite the known benefits of physical activity for older adults, adherence to regular physical activity recommendations is poor. Less than half of adults in this country meet physical activity recommendations with reasons for lack of adherence including such things as access, motivation, pain, fear, comorbidities, among others. To overcome these challenges, function-focused care was developed. Function-focused care is a philosophy of care that focuses on evaluating the older adult's underlying capability with regard to function and physical activity and helping him or her optimize and maintain physical function and ability and continually increase time spent in physical activity. Examples of function-focused care include such things as using verbal cues during bathing, so the older individual performs the tasks rather than the caregiver bathing the individual; walking a resident or patient to the bathroom rather than using a urinal, or taking a resident to an exercise class. There are now over 20 studies supporting the benefits of function-focused care approaches across all settings and different types of patient groups (i.e, those with mild versus moderate-to-severe cognitive impairment). The approaches for implementation of function-focused care have also been well supported and have moved beyond establishing effectiveness to considering dissemination and implementation of this approach into real world clinical settings. The process of dissemination and implementation has likewise been articulated and supported, and ongoing work needs to continue in this venue across all care settings. PMID:24894140

  11. Tooth hardness increases with zinc-content in mandibles of young adult leaf-cutter ants.

    PubMed

    Schofield, Robert M S; Nesson, Michael H; Richardson, Kathleen A

    2002-12-01

    A wide variety of arthropods and members of other phyla have elevated concentrations of Zn, Mn, other heavy metals and halogens in their jaws, leg claws, and other "tools" for interacting with the environment. While measured Zn concentrations reach 25% of dry mass in scorpion stings, concentrations are often lower than this and the enriched structures are not heavily biomineralized like vertebrate teeth and the radula of mollusks. For this reason, the degree to which the inorganic components of these structures modify their mechanical properties is in question. Here we address this problem by measuring hardness during the development of Zn accumulations in ant mandibles. We found that Zn is incorporated into the mandibular teeth of leaf-cutter ants during early adult life, reaching concentrations of about 16% of dry mass. We show that the hardness of the mandibular teeth increases nearly three-fold as the adults age and that hardness correlates with Zn content ( r=0.91). We suggest that young adults rarely cut leaves partly because their mandibles are not yet rich in Zn. Zinc enrichment (along with enrichment by other heavy metals and halogens) may play an unrecognized role in the behavioral ecology and evolution of a wide variety of invertebrates.

  12. Tooth hardness increases with zinc-content in mandibles of young adult leaf-cutter ants.

    PubMed

    Schofield, Robert M S; Nesson, Michael H; Richardson, Kathleen A

    2002-12-01

    A wide variety of arthropods and members of other phyla have elevated concentrations of Zn, Mn, other heavy metals and halogens in their jaws, leg claws, and other "tools" for interacting with the environment. While measured Zn concentrations reach 25% of dry mass in scorpion stings, concentrations are often lower than this and the enriched structures are not heavily biomineralized like vertebrate teeth and the radula of mollusks. For this reason, the degree to which the inorganic components of these structures modify their mechanical properties is in question. Here we address this problem by measuring hardness during the development of Zn accumulations in ant mandibles. We found that Zn is incorporated into the mandibular teeth of leaf-cutter ants during early adult life, reaching concentrations of about 16% of dry mass. We show that the hardness of the mandibular teeth increases nearly three-fold as the adults age and that hardness correlates with Zn content ( r=0.91). We suggest that young adults rarely cut leaves partly because their mandibles are not yet rich in Zn. Zinc enrichment (along with enrichment by other heavy metals and halogens) may play an unrecognized role in the behavioral ecology and evolution of a wide variety of invertebrates. PMID:12536282

  13. Gender-specific increase in susceptibility to metabolic syndrome of offspring rats after prenatal caffeine exposure with post-weaning high-fat diet.

    PubMed

    Li, Jing; Luo, Hanwen; Wu, Yimeng; He, Zheng; Zhang, Li; Guo, Yu; Ma, Lu; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-05-01

    Prenatal caffeine exposure (PCE) alters the hypothalamic-pituitary-adrenocortical (HPA) axis-associated neuroendocrine metabolic programming and induces an increased susceptibility to metabolic syndrome (MS) in intrauterine growth retardation (IUGR) offspring rats. High-fat diet (HFD) is one of the main environmental factors accounting for the incidence of MS. In this study, we aimed to clarify the gender-specific increase in susceptibility to MS in offspring rats after PCE with post-weaning HFD. Maternal Wistar rats were administered with caffeine (120mg/kg·d) from gestational day 11 until delivery. The offspring rats with normal diet or HFD were euthanized at postnatal week 24, and blood samples were collected. Results showed that PCE not only reduced serum adrenocorticotropic hormone (ACTH) and corticosterone levels, but also enhanced serum glucose, triglyceride and total cholesterol (TCH) concentrations in the offspring rats. Moreover, several interactions among PCE, HFD and gender were observed by a three-way ANOVA analysis. In PCE offspring, HFD could aggravate the degree of increased serum triglyceride level. Meanwhile, serum corticosterone levels of females were decreased more obviously than those of males in PCE offspring. The results also revealed interactions between HFD and gender in the levels of serum ACTH, triglyceride and TCH, which were changed more evidently in female HFD offspring. These results indicate that HFD could exacerbate the dysfunction of lipid metabolism and the susceptibility to MS induced by PCE, and the female offspring are more sensitive to HFD-induced neuroendocrine metabolic dysfunction than their male counterparts.

  14. Juvenile ethanol exposure increases rewarding properties of cocaine and morphine in adult DBA/2J mice.

    PubMed

    Molet, Jenny; Hervé, Denis; Thiébot, Marie-Hélène; Hamon, Michel; Lanfumey, Laurence

    2013-12-01

    Convergent data showed that ethanol exposure during adolescence can alter durably ethanol-related behaviour at adulthood. However, the consequences of juvenile ethanol exposure on the reinforcing effects of other drugs of abuse remain unclear. In the present work, we evaluated in adult male DBA/2J mice the effects of early ethanol exposure on the sensitivity to the incentive effects of cocaine and morphine, and on extracellular signal-regulated kinase (ERK) activation in response to cocaine. Juvenile male mice received intragastric administration of ethanol (2×2.5g/kg/day) or water for 5 days starting on postnatal day 28. When reaching adult age (10 week-old), animals were subjected to an unbiased procedure to assess conditioned place preference (CPP) to cocaine or morphine. In addition, activation of ERK in response to an acute injection of cocaine was investigated using immunoblotting in the striatum and the nucleus accumbens. Mice that have been subjected to early ethanol exposure developed CPP to doses of cocaine (5mg/kg) or morphine (10mg/kg) below the threshold doses to induce CPP in water pre-exposed mice. In addition, early ethanol administration significantly increased striatal ERK phosphorylation normally induced by acute cocaine (10 and 20mg/kg) in adult mice. These results show that, in DBA/2J mice, early exposure to ethanol enhanced the perception of the incentive effects of cocaine and morphine. Ethanol pre-exposure also induced a positive modulation of striatal ERK signalling, in line with the inference that juvenile ethanol intake may contribute to the development of addictive behaviour at adult age. PMID:23619165

  15. Increased susceptibility to ultraviolet-B and carcinogens of mice lacking the DNA excision repair gene XPA.

    PubMed

    de Vries, A; van Oostrom, C T; Hofhuis, F M; Dortant, P M; Berg, R J; de Gruijl, F R; Wester, P W; van Kreijl, C F; Capel, P J; van Steeg, H; Verbeek, S J

    1995-09-14

    Xeroderma pigmentosum patients with a defect in the nucleotide-excision repair gene XPA are characterized by, for example, a > 1,000-fold higher risk of developing sunlight-induced skin cancer. Nucleotide-excision repair (NER) is involved in the removal of a wide spectrum of DNA lesions. The XPA protein functions in a pre-incision step, the recognition of DNA damage. To permit the functional analysis of the XPA gene in vivo, we have generated XPA-deficient mice by gene targeting in embryonic stem cells. The XPA-/-mice appear normal, at least until the age of 13 months. XPA-/-mice are highly susceptible to ultraviolet (UV)-B-induced skin and eye tumours and to 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin tumours. We conclude that the XPA-deficient mice strongly mimic the phenotype of humans with xeroderma pigmentosum. PMID:7675086

  16. Stroke Increases Neural Stem Cells and Angiogenesis in the Neurogenic Niche of the Adult Mouse

    PubMed Central

    Zhang, Rui Lan; Chopp, Michael; Roberts, Cynthia; Liu, Xianshuang; Wei, Min; Nejad-Davarani, Siamak P.; Wang, Xinli; Zhang, Zheng Gang

    2014-01-01

    The unique cellular and vascular architecture of the adult ventricular-subventricular zone (V/SVZ) neurogenic niche plays an important role in regulating neural stem cell function. However, the in vivo identification of neural stem cells and their relationship to blood vessels within this niche in response to stroke remain largely unknown. Using whole-mount preparation of the lateral ventricle wall, we examined the architecture of neural stem cells and blood vessels in the V/SVZ of adult mouse over the course of 3 months after onset of focal cerebral ischemia. Stroke substantially increased the number of glial fibrillary acidic protein (GFAP) positive neural stem cells that are in contact with the cerebrospinal fluid (CSF) via their apical processes at the center of pinwheel structures formed by ependymal cells residing in the lateral ventricle. Long basal processes of these cells extended to blood vessels beneath the ependymal layer. Moreover, stroke increased V/SVZ endothelial cell proliferation from 2% in non-ischemic mice to 12 and 15% at 7 and 14 days after stroke, respectively. Vascular volume in the V/SVZ was augmented from 3% of the total volume prior to stroke to 6% at 90 days after stroke. Stroke-increased angiogenesis was closely associated with neuroblasts that expanded to nearly encompass the entire lateral ventricular wall in the V/SVZ. These data indicate that stroke induces long-term alterations of the neural stem cell and vascular architecture of the adult V/SVZ neurogenic niche. These post-stroke structural changes may provide insight into neural stem cell mediation of stroke-induced neurogenesis through the interaction of neural stem cells with proteins in the CSF and their sub-ependymal neurovascular interaction. PMID:25437857

  17. A mutation in negative regulator of basal resistance WRKY17 of Arabidopsis increases susceptibility to Agrobacterium-mediated genetic transformation.

    PubMed

    Lacroix, Benoît; Citovsky, Vitaly

    2013-01-01

    Agrobacterium is a phytopathogenic bacterium that induces crown gall disease in many plant species by transferring and integrating a segment of its own DNA (T-DNA) into its host genome. Whereas Agrobacterium usually does not trigger an extensive defense response in its host plants, it induces the expression of several defense-related genes and activates plant stress reactions. In the complex interplay between Agrobacterium and its host plant, Agrobacterium has evolved to take advantage of these plant defense pathways for its own purpose of advancement of the infection process. For example, Agrobacterium utilizes the host stress response transcriptional regulator VIP1 to facilitate nuclear import and proteasomal uncoating of its T-DNA during genetic transformation of the host cell. In Arabidopsis, the VIP1 gene expression is repressed by WRKY17, a negative regulator of basal resistance to Pseudomonas. Thus, we examined whether WRKY17 is also involved in plant susceptibility to genetic transformation by Agrobacterium. Using reverse genetics, we showed that a wrky17 mutant displays higher expression of the VIP1 gene in roots, but not in shoots. In a root infection assay, the wrky17 mutant plants were hyper-susceptible to Agrobacterium compared to wild type plants. WRKY17, therefore, may act as a positive regulator of Arabidopsis resistance to Agrobacterium. This notion is important for understanding the complex regulation of Agrobacterium-mediated genetic transformation; thus, although this paper reports a relatively small set of data that we do not plan to pursue further in our lab, we believe it might be useful for the broad community of plant pathologists and plant biotechnologists. PMID:24358874

  18. A mutation in negative regulator of basal resistance WRKY17 of Arabidopsis increases susceptibility to Agrobacterium-mediated genetic transformation

    PubMed Central

    Lacroix, Benoît; Citovsky, Vitaly

    2013-01-01

    Agrobacterium is a phytopathogenic bacterium that induces crown gall disease in many plant species by transferring and integrating a segment of its own DNA (T-DNA) into its host genome. Whereas Agrobacterium usually does not trigger an extensive defense response in its host plants, it induces the expression of several defense-related genes and activates plant stress reactions. In the complex interplay between Agrobacterium and its host plant, Agrobacterium has evolved to take advantage of these plant defense pathways for its own purpose of advancement of the infection process. For example, Agrobacterium utilizes the host stress response transcriptional regulator VIP1 to facilitate nuclear import and proteasomal uncoating of its T-DNA during genetic transformation of the host cell. In Arabidopsis, the VIP1 gene expression is repressed by WRKY17, a negative regulator of basal resistance to Pseudomonas. Thus, we examined whether WRKY17 is also involved in plant susceptibility to genetic transformation by Agrobacterium. Using reverse genetics, we showed that a wrky17 mutant displays higher expression of the VIP1 gene in roots, but not in shoots. In a root infection assay, the wrky17 mutant plants were hyper-susceptible to Agrobacterium compared to wild type plants. WRKY17, therefore, may act as a positive regulator of Arabidopsis resistance to Agrobacterium. This notion is important for understanding the complex regulation of Agrobacterium-mediated genetic transformation; thus, although this paper reports a relatively small set of data that we do not plan to pursue further in our lab, we believe it might be useful for the broad community of plant pathologists and plant biotechnologists. PMID:24358874

  19. TNF-α/IL-10 Ratio Correlates with Burn Severity and May Serve as a Risk Predictor of Increased Susceptibility to Infections

    PubMed Central

    Tsurumi, Amy; Que, Yok-Ai; Ryan, Colleen M.; Tompkins, Ronald G.; Rahme, Laurence G.

    2016-01-01

    Severe burn injury renders patients susceptible to multiple infection episodes; however, identifying specific patient groups at high risk remains challenging. Burn-induced inflammatory response dramatically modifies the levels of various cytokines. Whether these changes could predict susceptibility to infections remains unknown. The aim of this study was to determine the early changes in the pro- to anti-inflammatory cytokine ratio and investigate its ability to predict susceptibility to repeated infections after severe burn trauma. The patient population consisted of 34 adult patients having early (≤48 h since injury) blood draws following severe (≥20% total burn surface area (TBSA)) burn injury and suffering from a first infection episode at least 1 day after blood collection. Plasma TNF-α and IL-10 levels were measured to explore the association between the TNF-α/IL-10 ratio, hypersusceptibility to infections, burn size (TBSA), and common severity scores (Acute Physiology and Chronic Health Evaluation II (APACHEII), Baux, modified Baux (R-Baux), Ryan Score, and Abbreviated Burn Severity Index (ABSI)). TNF-α/IL10 plasma ratio measured shortly after burn trauma was inversely correlated with burn size and the injury severity scores investigated, and was predictive of repeated infections (≥3 infection episodes) outcome (AUROC [95%CI] of 0.80 [0.63–0.93]). Early measures of circulating TNF-α/IL10 ratio may be a previously unidentified biomarker associated with burn injury severity and predictive of the risk of hypersusceptibility to repeated infections. PMID:27761434

  20. Juvenile Galápagos Pelicans Increase Their Foraging Success by Copying Adult Behaviour

    PubMed Central

    Brumm, Henrik; Teschke, Irmgard

    2012-01-01

    Social learning is the building block of culture and traditions in humans and nonhuman animals, and its study has a long history. Most investigations have addressed either the causation or the function of social learning. Though much is known about the underlying mechanisms of social learning, demonstrations of its adaptive value in a natural setting are lacking. Here we show that juvenile brown pelicans (Pelecanus occidentalis) can increase their foraging efficiency by copying adult diving behaviour, suggesting that social learning helps juveniles to find profitable food patches. Our findings demonstrate the potential fitness consequences of behavioural copying and thus highlight the possible adaptive importance of social learning. PMID:23251646

  1. Drinking to Distraction: Does Alcohol Increase Attentional Bias in Adults with ADHD?

    PubMed Central

    Roberts, Walter; Fillmore, Mark T.; Milich, Richard

    2012-01-01

    Previous research has shown that social drinkers continue to show attentional bias towards alcohol-related stimuli even after consuming a moderate dose of alcohol. In contrast, little is known about how alcohol acutely affects attentional bias in groups at risk to develop alcohol-related problems, such as adults with attention-deficit/hyperactivity disorder (ADHD). Such individuals may show increased attentional bias following alcohol relative to nonclinical controls. The present study tested this hypothesis by examining acute alcohol effects on attentional bias in 20 social drinkers with ADHD and 20 social drinkers with no history of ADHD. Participants performed a visual-probe task after receiving the following doses of alcohol: 0.64 g/kg, 0.32 g/kg, and 0.0 g/kg (placebo). Those in the ADHD group showed increased attentional bias under active alcohol doses, whereas attentional bias was similar across doses in the control group. Attentional bias predicted ad libitum alcohol consumption during a taste-rating session. This relation was observed only in the ADHD group. These findings indicate that an acute alcohol dose increases attentional bias in adults with ADHD. Further, attentional bias appears to be a predictor of ad libitum consumption in this group. PMID:22121850

  2. Drinking to distraction: does alcohol increase attentional bias in adults with ADHD?

    PubMed

    Roberts, Walter; Fillmore, Mark T; Milich, Richard

    2012-04-01

    Previous research has shown that social drinkers continue to show attentional bias toward alcohol-related stimuli even after consuming a moderate dose of alcohol. In contrast, little is known about how alcohol acutely affects attentional bias in groups at risk to develop alcohol-related problems, such as adults with attention-deficit/hyperactivity disorder (ADHD). Such individuals may show increased attentional bias following alcohol relative to nonclinical controls. The present study tested this hypothesis by examining acute alcohol effects on attentional bias in 20 social drinkers with ADHD and 20 social drinkers with no history of ADHD. Participants performed a visual-probe task after receiving the following doses of alcohol: 0.64 g/kg, 0.32 g/kg, and 0.0 g/kg (placebo). Those in the ADHD group showed increased attentional bias under active alcohol doses, whereas attentional bias was similar across doses in the control group. Attentional bias predicted ad libitum alcohol consumption during a taste-rating session. This relation was observed only in the ADHD group. These findings indicate that an acute alcohol dose increases attentional bias in adults with ADHD. Further, attentional bias appears to be a predictor of ad libitum consumption in this group.

  3. Adaptive peripheral immune response increases proliferation of neural precursor cells in the adult hippocampus.

    PubMed

    Wolf, Susanne A; Steiner, Barbara; Wengner, Antje; Lipp, Martin; Kammertoens, Thomas; Kempermann, Gerd

    2009-09-01

    To understand the link between peripheral immune activation and neuronal precursor biology, we investigated the effect of T-cell activation on adult hippocampal neurogenesis in female C57Bl/6 mice. A peripheral adaptive immune response triggered by adjuvant-induced rheumatoid arthritis (2 microg/microl methylated BSA) or staphylococcus enterotoxin B (EC(50) of 0.25 microg/ml per 20 g body weight) was associated with a transient increase in hippocampal precursor cell proliferation and neurogenesis as assessed by immunohistochemistry and confocal microscopy. Both treatments were paralleled by an increase in corticosterone levels in the hippocampus 1- to 2-fold over the physiological amount measured by quantitative radioimmunoassay. In contrast, intraperitoneal administration of the innate immune response activator lipopolysaccaride (EC(50) of 0.5 microg/ml per 20 g body weight) led to a chronic 5-fold increase of hippocampal glucocorticoid levels and a decrease of adult neurogenesis. In vitro exposure of murine neuronal progenitor cells to corticosterone triggered either cell death at high (1.5 nM) or proliferation at low (0.25 nM) concentrations. This effect could be blocked using a viral vector system expressing a transdomain of the glucocorticoid receptor. We suggest an evolutionary relevant communication route for the brain to respond to environmental stressors like inflammation mediated by glucocorticoid levels in the hippocampus.

  4. Chronic prenatal ethanol exposure increases disinhibition and perseverative responding in the adult guinea pig.

    PubMed

    Olmstead, Mary C; Martin, Amanda; Brien, James F; Reynolds, James N

    2009-09-01

    Cognitive and behavioural deficits, including increased impulsivity and perseveration, are associated with chronic prenatal ethanol exposure (CPEE) in humans. We tested whether these same deficits occur in the guinea pig after CPEE treatment. Pregnant guinea pigs received oral administration of ethanol (4 g/kg maternal body weight/day), or isocaloric-sucrose/pair-feeding throughout gestation. Young adult offspring were trained in lever-pressing paradigms to work for a sucrose-pellet food reward. CPEE increased No-Go, but not Go, responses in the Go/No-Go paradigm, indicative of a disinhibition deficit in these animals. Perseverative responses in the Cued Alternation task were also increased in CPEE offspring. These data show that CPEE induces behavioural deficits in the guinea pig that are remarkably similar to the executive function deficits that follow prenatal ethanol exposure in humans.

  5. Increased Lung and Bladder Cancer Incidence In Adults After In Utero and Early-Life Arsenic Exposure

    PubMed Central

    Steinmaus, Craig; Ferreccio, Catterina; Acevedo, Johanna; Yuan, Yan; Liaw, Jane; Durán, Viviana; Cuevas, Susana; García, José; Meza, Rodrigo; Valdés, Rodrigo; Valdés, Gustavo; Benítez, Hugo; VanderLinde, Vania; Villagra, Vania; Cantor, Kenneth P; Moore, Lee E; Perez, Saida G; Steinmaus, Scott; Smith, Allan H

    2014-01-01

    Background From 1958–70, >100,000 people in northern Chile were exposed to a well-documented, distinct period of high drinking water arsenic concentrations. We previously reported ecological evidence suggesting that early-life exposure in this population resulted in increased mortality in adults from several outcomes including lung and bladder cancer. Methods We have now completed the first study ever assessing incident cancer cases after early-life arsenic exposure, and the first study on this topic with individual participant exposure and confounding factor data. Subjects included 221 lung and 160 bladder cancer cases diagnosed in northern Chile from 2007–2010, and 508 age and gender-matched controls. Results Odds ratios (ORs) adjusted for age, sex, and smoking in those only exposed in early-life to arsenic water concentrations of ≤110, 110–800, and >800 μg/L were 1.00, 1.88 (95% confidence interval (CI), 0.96–3.71), and 5.24 (3.05–9.00) (p-trend<0.001) for lung cancer, and 1.00, 2.94 (1.29–6.70), and 8.11 (4.31–15.25) (p-trend<0.001) for bladder cancer. ORs were lower in those not exposed until adulthood. The highest category (>800 μg/L) involved exposures which started 49–52 years before, and ended 37–40 years before the cancer cases were diagnosed. Conclusion Lung and bladder cancer incidence in adults was markedly increased following exposure to arsenic in early-life, even up to 40 years after high exposures ceased. Findings like these have not been identified before for any environmental exposure, and suggest that humans are extraordinarily susceptible to early-life arsenic exposure. Impact Policies aimed at reducing early-life exposure may help reduce the long-term risks of arsenic-related disease. PMID:24859871

  6. Resistance training increases total energy expenditure and free-living physical activity in older adults.

    PubMed

    Hunter, G R; Wetzstein, C J; Fields, D A; Brown, A; Bamman, M M

    2000-09-01

    The purpose of this study was to determine what effects 26 wk of resistance training have on resting energy expenditure (REE), total free-living energy expenditure (TEE), activity-related energy expenditure (AEE), engagement in free-living physical activity as measured by the activity-related time equivalent (ARTE) index, and respiratory exchange ratio (RER) in 61- to 77-yr-old men (n = 8) and women (n = 7). Before and after training, body composition (four-compartment model), strength, REE, TEE (doubly labeled water), AEE (TEE - REE + thermic response to meals), and ARTE (AEE adjusted for energy cost of standard activities) were evaluated. Strength (36%) and fat-free mass (2 kg) significantly increased, but body weight did not change. REE increased 6.8%, whereas resting RER decreased from 0.86 to 0.83. TEE (12%) and ARTE (38%) increased significantly, and AEE (30%) approached significance (P = 0.06). The TEE increase remained significant even after adjustment for the energy expenditure of the resistance training. In response to resistance training, TEE increased and RER decreased. The increase in TEE occurred as a result of increases in both REE and physical activity. These results suggest that resistance training may have value in increasing energy expenditure and lipid oxidation rates in older adults, thereby improving their metabolic profiles.

  7. Psychological stress in adolescent and adult mice increases neuroinflammation and attenuates the response to LPS challenge

    PubMed Central

    2012-01-01

    Background There is ample evidence that psychological stress adversely affects many diseases. Recent evidence has shown that intense stressors can increase inflammation within the brain, a known mediator of many diseases. However, long-term outcomes of chronic psychological stressors that elicit a neuroinflammatory response remain unknown. Methods To address this, we have modified previously described models of rat/mouse predatory stress (PS) to increase the intensity of the interaction. We postulated that these modifications would enhance the predator-prey experience and increase neuroinflammation and behavioral dysfunction in prey animals. In addition, another group of mice were subjected to a modified version of chronic unpredictable stress (CUS), an often-used model of chronic stress that utilizes a combination of stressors that include physical, psychological, chemical, and other. The CUS model has been shown to exacerbate a number of inflammatory-related diseases via an unknown mechanism. Using these two models we sought to determine: 1) whether chronic PS or CUS modulated the inflammatory response as a proposed mechanism by which behavioral deficits might be mediated, and 2) whether chronic exposure to a pure psychological stressor (PS) leads to deficits similar to those produced by a CUS model containing psychological and physical stressors. Finally, to determine whether acute PS has neuroinflammatory consequences, adult mice were examined at various time-points after PS for changes in inflammation. Results Adolescent mice subjected to chronic PS had increased basal expression of inflammation within the midbrain. CUS and chronic PS mice also had an impaired inflammatory response to a subsequent lipopolysaccharide challenge and PS mice displayed increased anxiety- and depressive-like behaviors following chronic stress. Finally, adult mice subjected to acute predatory stress had increased gene expression of inflammatory factors. Conclusion Our results

  8. Impact of Maspin Polymorphism rs2289520 G/C and Its Interaction with Gene to Gene, Alcohol Consumption Increase Susceptibility to Oral Cancer Occurrence

    PubMed Central

    Yang, Po-Yu; Miao, Nae-Fang; Lin, Chiao-Wen; Chou, Ying-Erh; Yang, Shun-Fa; Huang, Hui-Chuan; Chang, Hsiu-Ju; Tsai, Hsiu-Ting

    2016-01-01

    Background The purpose of this study was to identify gene polymorphisms of mammary serine protease inhibitor (Maspin) specific to patients with oral cancer susceptibility and clinicopathological status. Methodology/Principal Findings Three single-nucleotide polymorphisms (SNPs) of the Maspin gene from 741 patients with oral cancer and 601 non-cancer controls were analyzed by real-time PCR. The participants with G/G homozygotes or with G/C heterozygotes of Maspin rs2289520 polymorphism had a 2.07-fold (p = 0.01) and a 2.01-fold (p = 0.02) risk of developing oral cancer compared to those with C/C homozygotes. Moreover, gene-gene interaction increased the risk of oral cancer susceptibility among subjects expose to oral cancer related risk factors, including areca, alcohol, and tobacco consumption. Conclusion G allele of Maspin rs2289520 polymorphism may be a factor that increases the susceptibility to oral cancer. The interactions of gene to oral cancer-related environmental risk factors have a synergetic effect that can further enhance oral cancer development. PMID:27525723

  9. Infrasound increases intracellular calcium concentration and induces apoptosis in hippocampi of adult rats.

    PubMed

    Liu, Zhaohui; Gong, Li; Li, Xiaofang; Ye, Lin; Wang, Bin; Liu, Jing; Qiu, Jianyong; Jiao, Huiduo; Zhang, Wendong; Chen, Jingzao; Wang, Jiuping

    2012-01-01

    In the present study, we determined the effect of infrasonic exposure on apoptosis and intracellular free Ca²⁺ ([Ca²⁺]i) levels in the hippocampus of adult rats. Adult rats were randomly divided into the control and infrasound exposure groups. For infrasound treatment, animals received infrasonic exposure at 90 (8 Hz) or 130 dB (8 Hz) for 2 h per day. Hippocampi were dissected, and isolated hippocampal neurons were cultured. The [Ca²⁺]i levels in hippocampal neurons from adult rat brains were determined by Fluo-3/AM staining with a confocal microscope system on days 1, 7, 14, 21 and 28 following infrasonic exposure. Apoptosis was evaluated by Annexin V-FITC and propidium iodide double staining. Positive cells were sorted and analyzed by flow cytometry. Elevated [Ca²⁺]i levels were observed on days 14 and 21 after rats received daily treatment with 90 or 130 dB sound pressure level (SPL) infrasonic exposure (p<0.01 vs. control). The highest levels of [Ca²⁺]i were detected in the 130 dB SPL infrasonic exposure group. Meanwhile, apoptosis in hippocampal neurons was found to increase on day 7 following 90 dB SPL infrasound exposure, and significantly increased on day 14. Upon 130 dB infrasound treatment, apoptosis was first observed on day 14, whereas the number of apoptotic cells gradually decreased thereafter. Additionally, a marked correlation between cell apoptosis and [Ca²⁺]i levels was found on day 14 and 21 following daily treatment with 90 and 130 dB SPL, respectively. These results demonstrate that a period of infrasonic exposure induced apoptosis and upregulated [Ca²⁺]i levels in hippocampal neurons, suggesting that infrasound may cause damage to the central nervous system (CNS) through the Ca²⁺‑mediated apoptotic pathway in hippocampal neurons. PMID:21946944

  10. Inverse Susceptibility to Oxidative Death of Lymphocytes Obtained From Alzheimer's Patients and Skin Cancer Survivors: Increased Apoptosis in Alzheimer's and Reduced Necrosis in Cancer

    PubMed Central

    Silva, Monica; Salech, Felipe; Ponce, Daniela P.; Merino, Daniela; Sinning, Mariana; Xiong, Chengjie; Roe, Catherine M.; Quest, Andrew F. G.

    2012-01-01

    A paucity of cancer in individuals with Alzheimer's disease (AD) and low rates of AD in cancer survivors has been reported in epidemiological studies. Deregulation in opposite directions of biological mechanisms, such as susceptibility to cell death, might be shared in the two disorders. We analyzed lymphocytes from AD and skin cancer patients as well as healthy controls and found significantly increased vulnerability of AD lymphocytes to H2O2-induced apoptotic death and higher resistance to death of skin cancer lymphocytes, due to reduced necrosis, as compared with healthy controls by pairwise comparisons adjusted for age and sex. H2O2-induced death in lymphocytes was caspase independent and significantly reduced by PARP-1 inhibition in all three groups. These differences in the susceptibility to cell death observed for lymphocytes from AD and skin cancer patients may be one of the mechanisms that help explain the inverse correlation detected between these diseases in epidemiological studies. PMID:22367434

  11. Salicylate decreases production of AmpC type beta-lactamases and increases susceptibility to beta-lactams in a Morganella morganii clinical isolate.

    PubMed

    Tavío, María M; Perilli, Mariagrazia; Vila, Jordi; Becerro, Pino; Casañas, Lucía; Amicosante, Gianfranco; Jiménez de Anta, María Teresa

    2004-09-01

    The effect of salicylate, a marRAB inducer, on the resistance to beta-lactams was characterized in an AmpC beta-lactamase hyperproducer Morganella morganii clinical isolate (the M1 strain). Results were compared with those of the effect of salicylate in a wild-type M. morganii strain. Salicylate induced a decreased susceptibility to nalidixic acid, norfloxacin and tetracycline and simultaneously increased the susceptibility to beta-lactams apparently due to the repression of AmpC beta-lactamase synthesis in the M1 strain. Likewise, salicylate only repressed 46 kDa outer membrane protein expression in the wild-type strain, since the clinical isolate M1 did not express it.

  12. Biologic effects of microwave exposure. II. Studies on the mechanisms controlling susceptibility to microwave-induced increases in complement receptor-positive spleen cells

    SciTech Connect

    Schlagel, C.J.; Sulek, K.; Ho, H.S.; Leach, W.M.; Ahmed, A.; Woody, J.N.

    1980-01-01

    In attempting to evaluate the mechanisms responsible for susceptibility to the inductive increase in splenic complement receptor-positive (CR+) cells following exposure to 2450-MHz microwaves, it was found that sensitivity to microwave-induced CR+ cell increases was under genetic control. In particular, evidence was accumulated suggesting that regulation was under the control of a gene or genes closely associated with but outside of the mouse major histocompatibility complex (H-2). All responsive strains of mice tested were of the H-2k haplotype, while mice of the H-2a, H-2b, H-2d and H-1i5 haplotypes were refractory to the microwave-induced increases in CR+ cells. By utilizing certain H-2k strains of mice that were genetically unable to respond to endotoxin, we were able to show that these strains of mice responded to microwaves, but not to endotoxin, by increasing CR+ cells. Microwave-induced increases in CR+ cells were not mimicked by the intraperitoneal injection of hydrocortisone. Athymic mice responded to microwave exposure, indicating that this event was not regulated by the T-cell population. Mice less than eight weeks old were found not to be susceptible to exposure to 2450-MHz microwaves. These studies indicate that microwaves do induce changes in the population of cells with specific cell-surface receptors, that susceptibility to these changes is under genetic control, and that it is unlikely that endotoxin, corticosteroids, or regulatory T cells play a significant role in the mechanisms regulating these increases.

  13. Electromyographically assessed empathic concern and empathic happiness predict increased prosocial behavior in adults.

    PubMed

    Light, Sharee N; Moran, Zachary D; Swander, Lena; Le, Van; Cage, Brandi; Burghy, Cory; Westbrook, Cecilia; Greishar, Larry; Davidson, Richard J

    2015-01-01

    The relation between empathy subtypes and prosocial behavior was investigated in a sample of healthy adults. "Empathic concern" and "empathic happiness", defined as negative and positive vicarious emotion (respectively) combined with an other-oriented feeling of "goodwill" (i.e. a thought to do good to others/see others happy), were elicited in 68 adult participants who watched video clips extracted from the television show Extreme Makeover: Home Edition. Prosocial behavior was quantified via performance on a non-monetary altruistic decision-making task involving book selection and donation. Empathic concern and empathic happiness were measured via self-report (immediately following each video clip) and via facial electromyography recorded from corrugator (active during frowning) and zygomatic (active during smiling) facial regions. Facial electromyographic signs of (a) empathic concern (i.e. frowning) during sad video clips, and (b) empathic happiness (i.e. smiling) during happy video clips, predicted increased prosocial behavior in the form of increased goodwill-themed book selection/donation.

  14. Neurotoxic Methamphetamine Doses Increase LINE-1 Expression in the Neurogenic Zones of the Adult Rat Brain

    PubMed Central

    Moszczynska, Anna; Flack, Amanda; Qiu, Ping; Muotri, Alysson R.; Killinger, Bryan A.

    2015-01-01

    Methamphetamine (METH) is a widely abused psychostimulant with the potential to cause neurotoxicity in the striatum and hippocampus. Several epigenetic changes have been described after administration of METH; however, there are no data regarding the effects of METH on the activity of transposable elements in the adult brain. The present study demonstrates that systemic administration of neurotoxic METH doses increases the activity of Long INterspersed Element (LINE-1) in two neurogenic niches in the adult rat brain in a promoter hypomethylation-independent manner. Our study also demonstrates that neurotoxic METH triggers persistent decreases in LINE-1 expression and increases the LINE-1 levels within genomic DNA in the striatum and dentate gyrus of the hippocampus, and that METH triggers LINE-1 retrotransposition in vitro. We also present indirect evidence for the involvement of glutamate (GLU) in LINE-1 activation. The results suggest that LINE-1 activation might occur in neurogenic areas in human METH users and might contribute to METH abuse-induced hippocampus-dependent memory deficits and impaired performance on several cognitive tasks mediated by the striatum. PMID:26463126

  15. Neurotoxic Methamphetamine Doses Increase LINE-1 Expression in the Neurogenic Zones of the Adult Rat Brain.

    PubMed

    Moszczynska, Anna; Flack, Amanda; Qiu, Ping; Muotri, Alysson R; Killinger, Bryan A

    2015-10-14

    Methamphetamine (METH) is a widely abused psychostimulant with the potential to cause neurotoxicity in the striatum and hippocampus. Several epigenetic changes have been described after administration of METH; however, there are no data regarding the effects of METH on the activity of transposable elements in the adult brain. The present study demonstrates that systemic administration of neurotoxic METH doses increases the activity of Long INterspersed Element (LINE-1) in two neurogenic niches in the adult rat brain in a promoter hypomethylation-independent manner. Our study also demonstrates that neurotoxic METH triggers persistent decreases in LINE-1 expression and increases the LINE-1 levels within genomic DNA in the striatum and dentate gyrus of the hippocampus, and that METH triggers LINE-1 retrotransposition in vitro. We also present indirect evidence for the involvement of glutamate (GLU) in LINE-1 activation. The results suggest that LINE-1 activation might occur in neurogenic areas in human METH users and might contribute to METH abuse-induced hippocampus-dependent memory deficits and impaired performance on several cognitive tasks mediated by the striatum.

  16. Combination of erythritol and fructose increases gastrointestinal symptoms in healthy adults.

    PubMed

    Kim, Yeonsoo; Park, Sonhee C; Wolf, Bryan W; Hertzler, Steven R

    2011-11-01

    Consumption of a large amount of dietary fructose induces gastrointestinal intolerance, and glucose has been known as an enhancer of fructose absorption. Erythritol is a nonglycemic sugar alcohol, and it has been suggested that erythritol is absorbed paracellularly. It was hypothesized that paracellular absorption of erythritol could also enhance paracellular absorption of fructose in healthy adults. This is one of the proposed pathways for how additional glucose enhances the absorption of fructose. Thirty-seven nondiabetic, healthy adults participated in a randomized, double-masked, controlled crossover study. After an overnight fast, participants consumed beverages containing either 50 g fructose and 50 g glucose, 50 g fructose and 33.3 g erythritol (an equimolar concentration of fructose), or 50 g fructose alone. Breath hydrogen response was determined for 8 hours postprandially. Gastrointestinal intolerance symptoms and the number and consistency of bowel movements were recorded for 24 hours postprandially. The breath hydrogen area under the curve (AUC) of the fructose and erythritol beverage was 2 times the AUC of the fructose beverage and 8.75 times the AUC of the fructose and glucose beverage (P < .001, respectively). Compared with fructose and glucose beverage and fructose alone, frequency of watery stools increased (P < .05) and gastrointestinal tolerance worsened (P < .05) when participants consumed fructose and erythritol. These data suggest that coingestion of equimolar concentrations of fructose and erythritol increased carbohydrate malabsorption.

  17. Reduced Metabolic Capacity in Aged Primary Retinal Pigment Epithelium (RPE) is Correlated with Increased Susceptibility to Oxidative Stress.

    PubMed

    Rohrer, Bärbel; Bandyopadhyay, Mausumi; Beeson, Craig

    2016-01-01

    One of the affected tissues in age-related macular degeneration (AMD) is the retinal pigment epithelium (RPE), a tissue that consists of terminally differentiated cells and that accumulates damage over time. In all tissues, mitochondria (mt), which play an essential role in both cell health (energy) and death (initiator of apoptosis), undergo an aging process through the accumulation of mtDNA damage, changes in mitochondrial dynamics, a reduction in biogenesis, and mitophagy, leading to an overall reduction in mitochondrial energy production and other non-energy-related functions. Here we have compared energy metabolism in primary human RPE cells isolated from aborted fetus or aged donor eyes and grown as stable monolayers. H2O2 treatment resulted in the generation of reactive oxygen species and superoxide, an effect that was significantly augmented by age. Mitochondrial metabolism, as analyzed by Seahorse respirometry, revealed reduced mitochondrial oxygen consumption (ATP production) at baseline and a complete loss of reserve capacity in aged cells. Likewise, glycolysis was blunted in aged cells. Taken together, these studies showed that RPE cells derived from aged donor eyes are more susceptible to oxidative stress, and exhibit a loss in mitochondrial respiratory reserve capacity and a reduction in glycolysis. These data suggest that while old cells may have sufficient energy at rest, they cannot mount a stress response requiring additional ATP and reducing agents. In summary, these data support the hypothesis that mitochondria or energy metabolism is a valid target for therapy in AMD. PMID:26427491

  18. Infection of host plants by Cucumber mosaic virus increases the susceptibility of Myzus persicae aphids to the parasitoid Aphidius colemani.

    PubMed

    Mauck, Kerry E; De Moraes, Consuelo M; Mescher, Mark C

    2015-06-04

    Plant viruses can profoundly alter the phenotypes of their host plants, with potentially far-reaching implications for ecology. Yet few studies have explored the indirect, host-mediated, effects of plant viruses on non-vector insects. We examined how infection of Cucurbita pepo plants by Cucumber mosaic virus (CMV) impacted the susceptibility of aphids (Myzus persicae) to attack by the parasitoid wasp Aphidius colemani. In semi-natural foraging assays, we observed higher rates of aphid parasitism on infected plants compared to healthy plants. Subsequent experiments revealed that this difference is not explained by different attack rates on plants differing in infection status, but rather by the fact that parasitoid larvae successfully complete their development more often when aphid hosts feed on infected plants. This suggests that the reduced nutritional quality of infected plants as host for aphids--documented in previous studies--compromises their ability to mount effective defenses against parasitism. Furthermore, our current findings indicate that the aphid diet during parasitoid development (rather than prior to wasp oviposition) is a key factor influencing resistance. These findings complement our previous work showing that CMV-induced changes in host plant chemistry alter patterns of aphid recruitment and dispersal in ways conducive to virus transmission.

  19. Lipid blood profile in captive Brahminy kite (Haliastur indus) as a possible indication of increased susceptibility to atherosclerosis.

    PubMed

    Potier, Romain

    2013-09-01

    After reviewing several cases of atherosclerosis in young Brahminy kites (Haliastur indus), a genetic predisposition to atherosclerosis in this species was hypothesized. A direct relationship between plasma cholesterol levels and atherosclerosis has already been formerly demonstrated in various bird species. Therefore, to test this hypothesis, 62 blood samples were collected from hand-raised birds of prey species, including five Brahminy kites, fed with whole day-old chicks, in order to compare cholesterol, phospholipids, and triglycerids concentrations in serum. All birds included in the study came from the same collection. Cholesterol serum concentration in Brahminy kites was significantly higher (P < 0.001) compared to other bird of prey species. Results showed that, under study conditions, the Brahminy kite is likely to be an atherosclerosis-susceptible species. However, the diet offered in this study greatly differs from the diet of wild Brahminy kites, which includes shellfish and fish. The effect of diet in captivity, especially the polyunsaturated fatty acid/saturated fatty acid ratio, still needs to be evaluated in this species. PMID:24063081

  20. Infection of host plants by Cucumber mosaic virus increases the susceptibility of Myzus persicae aphids to the parasitoid Aphidius colemani

    PubMed Central

    Mauck, Kerry E.; De Moraes, Consuelo M.; Mescher, Mark C.

    2015-01-01

    Plant viruses can profoundly alter the phenotypes of their host plants, with potentially far-reaching implications for ecology. Yet few studies have explored the indirect, host-mediated, effects of plant viruses on non-vector insects. We examined how infection of Cucurbita pepo plants by Cucumber mosaic virus (CMV) impacted the susceptibility of aphids (Myzus persicae) to attack by the parasitoid wasp Aphidius colemani. In semi-natural foraging assays, we observed higher rates of aphid parasitism on infected plants compared to healthy plants. Subsequent experiments revealed that this difference is not explained by different attack rates on plants differing in infection status, but rather by the fact that parasitoid larvae successfully complete their development more often when aphid hosts feed on infected plants. This suggests that the reduced nutritional quality of infected plants as host for aphids—documented in previous studies—compromises their ability to mount effective defenses against parasitism. Furthermore, our current findings indicate that the aphid diet during parasitoid development (rather than prior to wasp oviposition) is a key factor influencing resistance. These findings complement our previous work showing that CMV-induced changes in host plant chemistry alter patterns of aphid recruitment and dispersal in ways conducive to virus transmission. PMID:26043237

  1. Food source provisioning and susceptibility of immature and adult Tribolium castaneum on concrete partially treated with chlorfenapyr (Phantom®)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A series of experiments were conducted in which adults, pupae, and 4-week-old larvae of Tribolium castaneum (Herbst), the red flour beetle, were exposed separately on concrete arenas partially treated (14.4 % of the total area) with the insecticide chlorfenapyr (Phantom®) at 1.1 g active ingredient/...

  2. A low α-linolenic intake during early life increases adiposity in the adult guinea pig

    PubMed Central

    2010-01-01

    Background The composition of dietary fatty acids (FA) during early life may impact adult adipose tissue (AT) development. We investigated the effects of α-linolenic acid (ALA) intake during the suckling/weaning period on AT development and metabolic markers in the guinea pig (GP). Methods Newborn GP were fed a 27%-fat diet (w/w %) with high (10%-ALA group), moderate (2.4%-ALA group) or low (0.8%-ALA group) ALA content (w/w % as total FA) until they were 21 days old (d21). Then all animals were switched to a 15%-fat diet containing 2% ALA (as total FA) until 136 days of age (d136). Results ALA and docosapentaenoic acid measured in plasma triglycerides (TG) at d21 decreased with decreasing ALA intake. Total body fat mass was not different between groups at d21. Adipose tissue TG synthesis rates and proliferation rate of total adipose cells, as assessed by 2H2O labelling, were unchanged between groups at d21, while hepatic de novo lipogenesis was significantly 2-fold increased in the 0.8%-ALA group. In older GP, the 0.8%-ALA group showed a significant 15-%-increased total fat mass (d79 and d107, p < 0.01) and epididymal AT weight (d136) and tended to show higher insulinemia compared to the 10%-ALA group. In addition, proliferation rate of cells in the subcutaneous AT was higher in the 0.8%-ALA (15.2 ± 1.3% new cells/5d) than in the 10%-ALA group (8.6 ± 1.7% new cells/5d, p = 0.021) at d136. AT eicosanoid profiles were not associated with the increase of AT cell proliferation. Conclusion A low ALA intake during early postnatal life promotes an increased adiposity in the adult GP. PMID:20205840

  3. Growth maintenance of the maize primary root at low water potentials involves increases in cell-wall extension properties, expansin activity, and wall susceptibility to expansins.

    PubMed Central

    Wu, Y; Sharp, R E; Durachko, D M; Cosgrove, D J

    1996-01-01

    Previous work on the growth biophysics of maize (Zea mays L.) primary roots suggested that cell walls in the apical 5 mm of the elongation zone increased their yielding ability as an adaptive response to low turgor and water potential (psi w). To test this hypothesis more directly, we measured the acid-induced extension of isolated walls from roots grown at high (-0.03 MPa) or low (-1.6 MPa) psi w using an extensometer. Acid-induced extension was greatly increased in the apical 5 mm and was largely eliminated in the 5- to 10-mm region of roots grown at low psi w. This pattern is consistent with the maintenance of elongation toward the apex and the shortening of the elongation zone in these roots. Wall proteins extracted from the elongation zone possessed expansin activity, which increased substantially in roots grown at low psi w. Western blots likewise indicated higher expansin abundance in the roots at low psi w. Additionally, the susceptibility of walls to expansin action was higher in the apical 5 mm of roots at low psi w than in roots at high psi w. The basal region of the elongation zone (5-10 mm) did not extend in response to expansins, indicating that loss of susceptibility to expansins was associated with growth cessation in this region. Our results indicate that both the increase in expansin activity and the increase in cell-wall susceptibility to expansins play a role in enhancing cell-wall yielding and, therefore, in maintaining elongation in the apical region of maize primary roots at low psi w. PMID:11536740

  4. Viewing Our Aged Selves: Age Progression Simulations Increase Young Adults' Aging Anxiety and Negative Stereotypes of Older Adults.

    PubMed

    Rittenour, Christine E; Cohen, Elizabeth L

    2016-04-01

    This experiment tests the effect of an old-age progression simulation on young adults' (N = 139) reported aging anxiety and perceptions about older adults as a social group. College students were randomly assigned to one of three conditions: self-aged simulation, stranger-aged simulation, or a control group. Compared with the control group, groups exposed to an age progression experienced more negative affect, and individuals in the self-aged condition reported greater aging anxiety. In accordance with stereotype activation theorizing, the self-age simulation group also perceived older adults as less competent and expressed more pity and less envy for older adults. Compared to the stranger-aged group, participants who observed their own age progression were also the more likely to deny the authenticity of their transformed image.These findings highlight potential negative social and psychological consequences of using age simulations to affect positive health outcomes, and they shed light on how virtual experiences can affect stereotyping of older adults. PMID:27076488

  5. Increased susceptibility to acute kidney injury due to endoplasmic reticulum stress in mice lacking tumor necrosis factor-α and its receptor 1.

    PubMed

    Huang, Lianghu; Zhang, Ruihua; Wu, Jin; Chen, Jian; Grosjean, Fabrizio; Satlin, Lisa H; Klein, Janet D; Sands, Jeffrey M; Striker, Gary E; Tan, Jianming; Zheng, Feng

    2011-03-01

    Endoplasmic reticulum (ER) stress is actively involved in acute organ injury. Since tumor necrosis factor α (TNFα) plays a role in acute kidney injury, and induces ER stress and cell death in vitro, we examined the contribution of TNFα to acute kidney ER stress induced by tunicamycin. Contrary to expectation, tunicamycin caused much more severe kidney injury in TNFα-/- than in wild-type mice. The major site of kidney injury in TNFα-/- mice was proximal tubules, which showed extensive cell vacuolation, lipid accumulation, and apoptosis. Reconstitution of TNFα-/- mice with TNFα 24 h before tunicamycin injection reversed the susceptibility. When TNFα-receptor-deficient mice were treated with tunicamycin, severe renal injury developed in TNFR1-/- but not TNFR2-/- mice, suggesting this aspect of TNFα action was through TNF receptor-1 (TNFR1). In response to tunicamycin-induced acute ER stress, kidneys from neither TNFα-/- nor TNFR1-/- mice showed a significant increase in phosphorylated eukaryotic translation initiation factor 2α (eIF2α), a key step in ER stress regulation. Moreover, proximal tubular cells from TNFR1-/- mice did not show increased eIF2α phosphorylation in response to tunicamycin and were susceptible to ER stress-induced cell death. Finally, treatment of proximal tubule cells isolated from TNFR1-/- mice with an inhibitor of eIF2α phosphatase increased the levels of phosphorylated eIF2α and substantially reduced tunicamycin-induced cell death. Thus, disruption of TNFR1 signaling leads to dysregulation of eIF2α and increased susceptibility to acute ER stress injury in the kidney.

  6. Impact of Increasing Age on Outcomes of Spinal Fusion in Adult Idiopathic Scoliosis

    PubMed Central

    Verla, Terence; Adogwa, Owoicho; Toche, Ulysses; Farber, S. Harrison; Petraglia, Frank; Murphy, Kelly R.; Thomas, Steven; Fatemi, Parastou; Gottfried, Oren; Bagley, Carlos A.; Lad, Shivanand P.

    2016-01-01

    Objective To investigate the role of advancing age on postoperative complications and revision surgery after fusion for scoliosis. Methods A retrospective, cohort study was performed using the Thomson Reuters MarketScan database, examining patients with adult scoliosis who underwent spinal fusion from 2000 to 2009. Primary outcomes included infection, hemorrhage and pulmonary embolism (PE) within 90 days of surgery, and refusion. The effect of increasing age was estimated using the odds ratio (OR) of complications in a multivariate logistic regression analysis, and a Cox proportional hazard model estimated the hazard ratio of refusion. Results A total of 8432 patients were included in this study. Overall, the average age was 53.3 years, with 26.90% males and 39% with a Charlson Comorbidity Score of ≥1. Most patients had commercial insurance (66.81%), with 26.03% and 7.16% covered by Medicare and Medicaid, respectively. Increasing age (per 5-year increment) was a significant predictor of hemorrhagic complication (OR, 1.06; confidence interval [CI], 1.01–1.11; P = 0.0196), PE (OR, 1.09; CI, 1.03–1.16; P = 0.0031), infection (OR, 1.04; CI, 1.01–1.07; P = 0.0053), and refusion (hazard ratio, 1.07; CI, 1.02–1.13; P = 0.0103). Conclusions In this study, age was associated with increased risk of hemorrhage, PE, infection, and refusion. With the aging population, the role of patient age on postoperative healing and outcomes deserves deeper investigation after repair of adult idiopathic scoliosis. PMID:26546999

  7. Obesity in older adults is associated with an increased prevalence and incidence of pain.

    PubMed

    Heim, Noor; Snijder, Marieke B; Deeg, Dorly J H; Seidell, Jaap C; Visser, Marjolein

    2008-11-01

    Cross-sectional studies suggest an association between BMI and pain. This prospective study investigated the associations of measured BMI and waist circumference with prevalent and incident pain in older adults. The study included participants of the Longitudinal Aging Study Amsterdam, aged 55-85 years at baseline (1992-1993). Pain was assessed using a subscale of the Nottingham Health Profile at baseline (N = 2,000), after 3 years (N = 1,478) and 6 years (N = 1,271) of follow-up. The overall prevalence of pain was 32.7% at baseline and increased significantly with higher quartiles of BMI or waist circumference. After adjustment for age, education, depression, smoking, physical activity, and chronic diseases, multiple logistic regression analyses showed odds ratios (ORs (95% confidence interval)) for prevalent pain of 2.16 (1.32-3.54) in men and 1.93 (1.26-2.95) in women comparing the highest with the lowest quartile of BMI. Of the participants without pain at baseline, those in the highest quartile of BMI had a twofold increased odds for incident pain after 3 years of follow-up. After 6 years of follow-up, ORs for incident pain were 2.34 (1.17-4.72) in men and 2.78 (1.36-5.70) in women. Additional adjustment for weight change did not change these associations. Similar results were found for the associations between waist circumference and pain. Exploring the reversed causal relation, analyses showed no significant associations between prevalent pain and weight gain. In conclusion, the prevalence of pain is higher among obese older men and women compared to their normal-weight peers. Furthermore, obese older adults are at increased odds to develop pain. PMID:18787527

  8. Learning new color names produces rapid increase in gray matter in the intact adult human cortex

    PubMed Central

    Kwok, Veronica; Niu, Zhendong; Kay, Paul; Zhou, Ke; Mo, Lei; Jin, Zhen; So, Kwok-Fai; Tan, Li Hai

    2011-01-01

    The human brain has been shown to exhibit changes in the volume and density of gray matter as a result of training over periods of several weeks or longer. We show that these changes can be induced much faster by using a training method that is claimed to simulate the rapid learning of word meanings by children. Using whole-brain magnetic resonance imaging (MRI) we show that learning newly defined and named subcategories of the universal categories green and blue in a period of 2 h increases the volume of gray matter in V2/3 of the left visual cortex, a region known to mediate color vision. This pattern of findings demonstrates that the anatomical structure of the adult human brain can change very quickly, specifically during the acquisition of new, named categories. Also, prior behavioral and neuroimaging research has shown that differences between languages in the boundaries of named color categories influence the categorical perception of color, as assessed by judgments of relative similarity, by response time in alternative forced-choice tasks, and by visual search. Moreover, further behavioral studies (visual search) and brain imaging studies have suggested strongly that the categorical effect of language on color processing is left-lateralized, i.e., mediated by activity in the left cerebral hemisphere in adults (hence “lateralized Whorfian” effects). The present results appear to provide a structural basis in the brain for the behavioral and neurophysiologically observed indices of these Whorfian effects on color processing. PMID:21464316

  9. Eat Smart, Live Strong intervention increases fruit and vegetable consumption among low-income older adults.

    PubMed

    Hersey, James C; Cates, Sheryl C; Blitstein, Jonathan L; Kosa, Katherine M; Santiago Rivera, Olga J; Contreras, Dawn A; Long, Valerie A; Singh, Anita; Berman, Danielle A

    2015-01-01

    This study evaluated the impact of a four-session interactive nutrition education program-Eat Smart, Live Strong (ESLS)-on the consumption of fruit and vegetables by low-income older adults. A pre-post quasi-experimental design study was conducted with a longitudinal sample of 614 low-income Supplemental Nutrition Assistance Program (SNAP) participants and those eligible for SNAP, aged 60 to 80 years, in 17 intervention and 16 comparison senior centers in Michigan. The study compared participants' self-reports of their consumption of fruit and vegetables using a modified version of the University of California Cooperative Extension Food Behavior Checklist. ESLS increased participants' average daily consumption of fruit by 0.2 cups (P < 0.05) and vegetables by 0.31 cups (P < 0.01). ESLS, a four-session, cognitive-behavioral nutrition education program is an effective curriculum for helping low-income older adults eat more fruit and vegetables.

  10. EFFECTS OF A DIETARY SUPPLEMENT ON THE INCIDENCE OF ACUTE RESPIRATORY INFECTIONS IN SUSCEPTIBLE ADULTS: A RANDOMIZED CONTROLLED TRIAL.

    PubMed

    Bernal-Orozco, María Fernanda; Posada-Falomir, Margarita; Ortega-Orozco, Rafael; Silva-Villanueva, Elvia Elaonor; Macedo-Ojeda, Gabriela; Márquez-Sandoval, Yolanda Fabiola; Vizmanos-Lamotte, Barbara

    2015-08-01

    Introducción: aunque la suplementación de micronutrientes específicos puede mejorar determinados factores inmunológicos, han sido publicados pocos estudios sobre la combinación de micronutrientes con extractos herbales y la incidencia de infecciones respiratorias agudas (ARI) . Objetivos: evaluar el efecto de un suplemento alimenticio con micronutrientes y extractos herbales en la incidencia de ARI en adultos susceptibles, en enero-abril de 2012. Métodos: se realizó un ensayo clínico paralelo, aleatorizado, doble ciego, controlado con placebo. Se incluyeron adultos susceptibles a ARI, sanos en el momento de la evaluación, que firmaron un consentimiento informado y que no tomaban medicamentos. Completaron una historia clínica y se evaluó: peso, talla, signos vitales y de laboratorio. Se asignaron aleatoriamente para consumir durante 90 días el suplemento o un placebo. Los sujetos registraron diariamente si presentaban o no síntomas de ARI en un diario. En caso de enfermedad, se lo notificaron a los investigadores y el médico responsable confirmó la presencia de infección. Se utilizó la prueba exacta de Fisher para comparar la proporción de enfermos entre los grupos y se calculó el riesgo relativo y la diferencia de riesgos (p < 0,05 significativa). Resultados: de 59 sujetos incluidos, 45 (25 mujeres) completaron el estudio (21 del grupo suplementado y 24 del placebo). No hubo diferencias significativas al inicio entre grupos. Al finalizar la intervención, el grupo suplementado tuvo una menor incidencia de ARI en comparación con el placebo (57,1% vs 91,7%, p = 0,013, RR = 0,62, IC95% 0,42, 0,92). Discusión: en conclusión, el consumo de un suplemento a base de micronutrientes y extractos herbales puede disminuir la incidencia de ARI en adultos susceptibles.

  11. Vegetable variety: an effective strategy to increase vegetable intake in adults.

    PubMed

    Meengs, Jennifer S; Roe, Liane S; Rolls, Barbara J

    2012-08-01

    Effective strategies are needed to increase vegetable intake in accordance with health recommendations. Previous research has shown that increasing the variety of foods leads to increased consumption, yet this strategy has not been investigated for promoting vegetable intake. This crossover study, conducted in 2008 and 2009, tested whether filling half the plate with a variety of vegetables influences vegetable consumption and meal energy intake. Once a week for 4 weeks, a meal of pasta and cooked vegetables was consumed ad libitum by 66 adults (34 women, 32 men). The meals were varied in the type of vegetables offered: at three meals 600 g of a single vegetable was served (broccoli, carrots, or snap peas) and at one meal 200 g of each of the three vegetables was served side by side. Data were analyzed using a mixed linear model with repeated measures. In this study, serving a variety of vegetables increased vegetable intake at the meal (P<0.0001). Subjects ate more vegetables when served the variety than when served any single type; the mean increase was 48±6 g, or more than one-half serving. This increase remained significant when intake of the variety of vegetables was compared with the preferred vegetable of each participant (mean 25±8 g; P=0.002). Vegetable intake was not significantly related to energy intake at the meal. The results of this study demonstrate that increasing the variety of low-energy-dense vegetables served at a meal can be used as a strategy to increase vegetable intake.

  12. Susceptibility Testing

    MedlinePlus

    ... page helpful? Also known as: Sensitivity Testing; Drug Resistance Testing; Culture and Sensitivity; C & S; Antimicrobial Susceptibility Formal name: Bacterial and Fungal Susceptibility Testing Related tests: Urine Culture ; ...

  13. Aberrant Neural Stem Cell Proliferation and Increased Adult Neurogenesis in Mice Lacking Chromatin Protein HMGB2

    PubMed Central

    Reddy, Avanish S.; Maletic-Savatic, Mirjana; Aguirre, Adan; Tsirka, Stella E.

    2013-01-01

    Neural stem and progenitor cells (NSCs/NPCs) are distinct groups of cells found in the mammalian central nervous system (CNS). Previously we determined that members of the High Mobility Group (HMG) B family of chromatin structural proteins modulate NSC proliferation and self-renewal. Among them HMGB2 was found to be dynamically expressed in proliferating and differentiating NSCs, suggesting that it may regulate NSC maintenance. We report now that Hmgb2−/− mice exhibit SVZ hyperproliferation, increased numbers of SVZ NSCs, and a trend towards aberrant increases in newly born neurons in the olfactory bulb (OB) granule cell layer. Increases in the levels of the transcription factor p21 and the Neural cell adhesion molecule (NCAM), along with down-regulation of the transcription/pluripotency factor Oct4 in the Hmgb2−/− SVZ point to a possible pathway for this increased proliferation/differentiation. Our findings suggest that HMGB2 functions as a modulator of neurogenesis in young adult mice through regulation of NSC proliferation, and identify a potential target via which CNS repair could be amplified following trauma or disease-based neuronal degeneration. PMID:24391977

  14. Experiencing neonatal maternal separation increased the seizure threshold in adult male mice: Involvement of the opioid system.

    PubMed

    Amini-Khoei, Hossein; Amiri, Shayan; Shirzadian, Armin; Haj-Mirzaian, Arya; Alijanpour, Sakineh; Rahimi-Balaei, Maryam; Mohammadi-Asl, Ali; Hassanipour, Mahsa; Mehr, Shahram Ejtemaie; Dehpour, Ahmad Reza

    2015-11-01

    Experiencing early-life stress has been considered as a potent risk factor for the development of many of brain disorders, including seizures. Intervening mechanisms through which neonatal maternal separation (MS) alters the seizure susceptibility in adulthood have not been well studied. In the current study, by applying 180 min of MS stress (PND 2-14), we determined the seizure susceptibility and considered the role of the opioid system. Maternal separation increased the seizure threshold, and administration of anticonvulsant/proconvulsant doses of morphine (1 and 30 mg/kg, respectively) reversed the impact of MS. Using tail flick and hot plate tests, we exposed animals to 30 min Restraint stress (RS) and found that MS decreased the pain threshold, suggesting the hyporesponsiveness of the opioid system. These results supported the abnormal seizure activity observed in the MS mice and suggested that abnormalities in the opioid system following MS alter seizure susceptibility in later life. PMID:26409126

  15. Increased Susceptibility to Chemical Toxicity with Pre-existing Diseases: Case Studies with Particulate Matter, Cadmium, Mercury, Trichloroethylene and Dioxin

    EPA Science Inventory

    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 increase...

  16. The Evidence for Increased L1 Activity in the Site of Human Adult Brain Neurogenesis

    PubMed Central

    Kurnosov, Alexey A.; Ustyugova, Svetlana V.; Nazarov, Vadim I.; Minervina, Anastasia A.; Komkov, Alexander Yu.; Shugay, Mikhail; Pogorelyy, Mikhail V.; Khodosevich, Konstantin V.; Mamedov, Ilgar Z.; Lebedev, Yuri B.

    2015-01-01

    Retroelement activity is a common source of polymorphisms in human genome. The mechanism whereby retroelements contribute to the intraindividual genetic heterogeneity by inserting into the DNA of somatic cells is gaining increasing attention. Brain tissues are suspected to accumulate genetic heterogeneity as a result of the retroelements somatic activity. This study aims to expand our understanding of the role retroelements play in generating somatic mosaicism of neural tissues. Whole-genome Alu and L1 profiling of genomic DNA extracted from the cerebellum, frontal cortex, subventricular zone, dentate gyrus, and the myocardium revealed hundreds of somatic insertions in each of the analyzed tissues. Interestingly, the highest concentration of such insertions was detected in the dentate gyrus—the hotspot of adult neurogenesis. Insertions of retroelements and their activity could produce genetically diverse neuronal subsets, which can be involved in hippocampal-dependent learning and memory. PMID:25689626

  17. Increasing the Availability of Physical Activity Programs for Older Adults: Lessons Learned From Texercise Stakeholders.

    PubMed

    Stevens, Alan B; Thiel, Shannon B; Thorud, Jennifer L; Smith, Matthew Lee; Howell, Doris; Cargill, Jessica; Swierc, Suzanne M; Ory, Marcia G

    2016-01-01

    Many initiatives have been developed to facilitate older adults' engagement in physical activity (PA) and document its benefits. One example is Texercise, a 12-week program with a focus on increasing participants' self-efficacy. The goal of this paper is to augment the knowledgebase of PA program implementation and dissemination by elucidating the experience of Texercise implementation as perceived by multiple stakeholders. We conducted 28 semistructured stakeholder interviews and categorized the responses into four preset themes: (1) program delivery and advocacy; (2) value/merit of the program; (3) successes/challenges of offering and sustaining the program; and (4) recommendations for enhancing implementation and delivery. We identified emergent subthemes through further analysis. Many perceptions that are broadly applicable to community organizations emerged. Our findings highlight the importance of stakeholder support when embedding PA programs in communities. Furthermore, the findings are crucial to understanding underlying processes that support widespread program dissemination and sustainability.

  18. Changes in satiety hormones and expression of genes involved in glucose and lipid metabolism in rats weaned onto diets high in fibre or protein reflect susceptibility to increased fat mass in adulthood

    PubMed Central

    Maurer, Alannah D; Chen, Qixuan; McPherson, Christine; Reimer, Raylene A

    2009-01-01

    Risk of developing obesity and diabetes may be influenced by the nutritional environment early in life. We examined the effects of high fibre or protein diets on satiety hormones and genes involved in glucose and lipid metabolism during postnatal development and on adult fat mass. At 21 days of age, Wistar rat pups were weaned onto control (C), high fibre (HF) or high protein (HP) diet. Tissue and blood were collected at 7, 14, 21, 28 and 35 days after birth. A second group of rats consumed the weaning diets until 4 months when they were switched to a high fat–high sugar diet for 6 weeks, after which body and fat mass and plasma glucose were determined. In young rats, HF diet increased plasma glucagon-like peptide (GLP-1) compared to C and HP and decreased leptin compared to C at postnatal days 28 and 35. Hepatic fatty acid synthase mRNA was down-regulated by HF and HP compared to C at days 28 and 35. In brown adipose tissue, HF increased uncoupling protein-3 mRNA whereas HP increased mRNA of the inflammatory cytokine interleukin-6. Body weight, fat mass and glycaemia in adult males and fat mass in females were greater after the high fat challenge in rats that consumed the HP diet from weaning. Increasing fibre or protein in postnatal diets causes rapid change in satiety hormone secretion and genes involved in glucose and lipid metabolism which appear to influence fat mass and glycaemia in adulthood, high protein being associated with increased susceptibility to obesity. PMID:19064620

  19. Selection for tameness, a key behavioral trait of domestication, increases adult hippocampal neurogenesis in foxes.

    PubMed

    Huang, Shihhui; Slomianka, Lutz; Farmer, Andrew J; Kharlamova, Anastasiya V; Gulevich, Rimma G; Herbeck, Yury E; Trut, Lyudmila N; Wolfer, David P; Amrein, Irmgard

    2015-08-01

    Work on laboratory and wild rodents suggests that domestication may impact on the extent of adult hippocampal neurogenesis and its responsiveness to regulatory factors. There is, however, no model of laboratory rodents and their nondomesticated conspecifics that would allow a controlled comparison of the effect of domestication. Here, we present a controlled within-species comparison of adult hippocampal neurogenesis in farm-bred foxes (Vulpes vulpes) that differ in their genetically determined degree of tameness. Quantitative comparisons of cell proliferation (Ki67) and differentiating cells of neuronal lineage (doublecortin, DCX) in the hippocampus of foxes were performed as a proxy for neurogenesis. Higher neurogenesis was observed in tameness-selected foxes, notably in an extended subgranular zone of the middle and temporal compartments of the hippocampus. Increased neurogenesis is negatively associated with aggressive behavior. Across all animals, strong septotemporal gradients were found, with higher numbers of proliferating cells and young neurons relative to resident granule cells in the temporal than in the septal hippocampus. The opposite gradient was found for the ratio of DCX/Ki67- positive cells. When tameness-selected and unselected foxes are compared with rodents and primates, proliferation is similar, while the number of young neurons is higher. The difference may be mediated by an extended period of differentiation or higher rate of survival. On the background of this species-specific neurogenic pattern, selection of foxes for a single behavioral trait key to domestication, i.e., genetic tameness, is accompanied by global and region-specific increases in neurogenesis.

  20. MicroRNA-146a constrains multiple parameters of intestinal immunity and increases susceptibility to DSS colitis.

    PubMed

    Runtsch, Marah C; Hu, Ruozhen; Alexander, Margaret; Wallace, Jared; Kagele, Dominique; Petersen, Charisse; Valentine, John F; Welker, Noah C; Bronner, Mary P; Chen, Xinjian; Smith, Daniel P; Ajami, Nadim J; Petrosino, Joseph F; Round, June L; O'Connell, Ryan M

    2015-10-01

    Host-microbial interactions within the mammalian intestines must be properly regulated in order to promote host health and limit disease. Because the microbiota provide constant immunological signals to intestinal tissues, a variety of regulatory mechanisms have evolved to ensure proper immune responses to maintain homeostasis. However, many of the genes that comprise these regulatory pathways, including immune-modulating microRNAs (miRNAs), have not yet been identified or studied in the context of intestinal homeostasis. Here, we investigated the role of microRNA-146a (miR-146a) in regulating intestinal immunity and barrier function and found that this miRNA is expressed in a variety of gut tissues in adult mice. By comparing intestinal gene expression in WT and miR-146a-/- mice, we demonstrate that miR-146a represses a subset of gut barrier and inflammatory genes all within a network of immune-related signaling pathways. We also found that miR-146a restricts the expansion of intestinal T cell populations, including Th17, Tregs, and Tfh cells. GC B cells, Tfh ICOS expression, and the production of luminal IgA were also reduced by miR-146a in the gut. Consistent with an enhanced intestinal barrier, we found that miR-146a-/- mice are resistant to DSS-induced colitis, a model of Ulcerative Colitis (UC), and this correlated with elevated colonic miR-146a expression in human UC patients. Taken together, our data describe a role for miR-146a in constraining intestinal barrier function, a process that alters gut homeostasis and enhances at least some forms of intestinal disease in mice.

  1. MicroRNA-146a constrains multiple parameters of intestinal immunity and increases susceptibility to DSS colitis

    PubMed Central

    Runtsch, Marah C.; Hu, Ruozhen; Alexander, Margaret; Wallace, Jared; Kagele, Dominique; Petersen, Charisse; Valentine, John F.; Welker, Noah C.; Bronner, Mary P.; Chen, Xinjian; Smith, Daniel P.; Ajami, Nadim J.; Petrosino, Joseph F.; Round, June L.; O'Connell, Ryan M.

    2015-01-01

    Host-microbial interactions within the mammalian intestines must be properly regulated in order to promote host health and limit disease. Because the microbiota provide constant immunological signals to intestinal tissues, a variety of regulatory mechanisms have evolved to ensure proper immune responses to maintain homeostasis. However, many of the genes that comprise these regulatory pathways, including immune-modulating microRNAs (miRNAs), have not yet been identified or studied in the context of intestinal homeostasis. Here, we investigated the role of microRNA-146a (miR-146a) in regulating intestinal immunity and barrier function and found that this miRNA is expressed in a variety of gut tissues in adult mice. By comparing intestinal gene expression in WT and miR-146a−/− mice, we demonstrate that miR-146a represses a subset of gut barrier and inflammatory genes all within a network of immune-related signaling pathways. We also found that miR-146a restricts the expansion of intestinal T cell populations, including Th17, Tregs, and Tfh cells. GC B cells, Tfh ICOS expression, and the production of luminal IgA were also reduced by miR-146a in the gut. Consistent with an enhanced intestinal barrier, we found that miR-146a−/− mice are resistant to DSS-induced colitis, a model of Ulcerative Colitis (UC), and this correlated with elevated colonic miR-146a expression in human UC patients. Taken together, our data describe a role for miR-146a in constraining intestinal barrier function, a process that alters gut homeostasis and enhances at least some forms of intestinal disease in mice. PMID:26456940

  2. Electrical and Pharmacological Stimuli Reveal a Greater Susceptibility for CA3 Network Excitability in Hippocampal Slices from Aged vs. Adult Fischer 344 Rats

    PubMed Central

    Kanak, Daniel J.; Jones, Ryan T.; Tokhi, Ashish; Willingham, Amy L.; Zaveri, Hitten P.; Rose, Gregory M.; Patrylo, Peter R.

    2011-01-01

    Clinical data and experimental studies in rats have shown that the aged CNS is more susceptible to the proconvulsive effects of the excitotoxic glutamate analogues kainate (KA) and domoate (DA), which bind high-affinity receptors localized at mossy fiber (MF) synapses in the CA3 subregion of the hippocampus. Although decreased renal clearance appears to play a role in the hypersensitivity of the aged hippocampus to systemically-administered DA, it is unclear if the excitability of the CA3 network is also altered with age. Therefore, this study monitored CA3 field potential activity in hippocampal slices from aged and adult male Fischer 344 rats in response to electrical and pharmacological network stimulation targeted to the MF-CA3 circuit. Network challenges with repetitive hilar stimulation or bath application of nanomolar concentrations of KA more readily elicited excitable network activity (e.g. population spike facilitation, multiple population spikes, and epileptiform bursts) in slices from aged vs. adult rats, although basal network excitability was comparable between age groups. Additionally, exposure to 200 nM KA often abolished epileptiform activity and revealed theta or gamma oscillations instead. However, slices from aged rats were less sensitive to the rhythmogenic effects of 200 nM KA. Taken together, these findings suggest that aging decreases the capacity of the CA3 network to constrain the spread of excitability during focal excitatory network challenges. PMID:22396884

  3. Susceptibility of Adults of the Cerambycid Beetle Hedypathes betulinus to the Entomopathogenic Fungi Beauveria bassiana, Metarhizium anisopliae, and Purpureocillium Lilacinum

    PubMed Central

    Schapovaloff, M. E.; Alves, L. F. A.; Fanti, A. L.; Alzogaray, R. A.; Lastra, C. C. López

    2014-01-01

    The cerambycid beetle Hedypathes betulinus (Klug) (Coleoptera: Cerambycidae) causes severe damage to yerba mate plants (Ilex paraguariensis (St. Hilaire) (Aquifoliales: Aquifoliaceae)), which results in large losses of production. In this study, the pathogenicity of entomopathogenic fungi of the species Beauveria bassiana (Balsamo-Crivelli) Vuillemin (Hypocreales: Cordycipitaceae), Metarhizium anisopliae sensu lato (Metschnikoff) Sorokin (Hypocreales: Clavicipitaceae), and Purpureocillium lilacinum (Thom) Luangsa-ard, Hywel-Jones, Houbraken and Samson (Hypocreales: Ophiocordycipitaceae) on yerba mate were evaluated. Fifteen isolates of B. bassiana, two of M. anisopliae, and seven of P. lilacinum on H. betulinus adults were analyzed under laboratory conditions. The raw mortality rate caused by B. bassiana isolates varied from 51.1 to 86.3%, and their LT50 values varied between 8.7 and 13.6 d. The isolates of M. anisopliae caused 69.6–81.8% mortality, and their LT50 values varied between 7.4 and 7.9 d. In contrast, isolates of P. lilacinum were not pathogenic. M. anisopliae and B. bassiana isolates were pathogenic against H. betulinus adults, suggesting that they may be useful in biological control programs for insect pests of yerba mate. PMID:25368071

  4. Increasing metabolic rate despite declining body weight in an adult parasitoid wasp.

    PubMed

    Casas, Jérôme; Body, Mélanie; Gutzwiller, Florence; Giron, David; Lazzari, Claudio R; Pincebourde, Sylvain; Richard, Romain; Llandres, Ana L

    2015-08-01

    Metabolic rate is a positive function of body weight, a rule valid for most organisms and the basis of several theories of metabolic ecology. For adult insects, however, the diversity of relationships between body mass and respiration remains unexplained. The aim of this study is to relate the respiratory metabolism of a parasitoid with body weight and foraging activity. We compared the metabolic rate of groups of starving and host-fed females of the parasitoid Eupelmus vuilleti recorded with respirometry for 7days, corresponding to the mean lifetime of starving females and over half of the lifetime of foraging females. The dynamics of carbohydrate, lipid and protein in the body of foraging females were quantified with biochemical techniques. Body mass and all body nutrients declined sharply from the first day onwards. By contrast, the CO2 produced and the O2 consumed increased steadily. Starving females showed the opposite trend, identifying foraging as the reason for the respiration increase of feeding females. Two complementary physiological processes explain the unexpected relationship between increasing metabolic rate and declining body weight. First, host hemolymph is a highly unbalanced food, and the excess nutrients (protein and carbohydrate) need to be voided, partially through excretion and partially through respiration. Second, a foraging young female produces eggs at an increasing rate during the first half of its lifetime, a process that also increases respiration. We posit that the time-varying metabolic rate contributions of the feeding and reproductive processes supplements the contribution of the structural mass and lead to the observed trend. We extend our explanations to other insect groups and discuss the potential for unification using Dynamic Energy Budget theory.

  5. Increased Difficulties in Managing Stairs in Visually Impaired Older Adults: A Community-Based Survey

    PubMed Central

    Sun, Hong-Peng; Xu, Yong

    2015-01-01

    Purpose Managing stairs is a challenging aspect of daily activities of living for older people. We assessed whether older adults with visual impairment (VI) have greater difficulties of managing stairs in daily lives. Methods The study was designed as a community-based cross-sectional study based on a Chinese cohort aged 60 years and older in rural China. Visual acuity (VA) was measured in both eyes using a retro-illuminated Snellen chart with tumbling-E optotypes. VI (including blindness) was defined as presenting VA of worse than 20/60 in either eye. Having any difficulties in managing stairs was self-reported based on a question drawn from the Barthel Index. Information on participants’ socioeconomic status, lifestyle-related factors, diseases histories and medication intake was collected using a questionnaire. Results The Barthel Index, Activities of Daily Living questionnaire was completed by 4597 (99.7%) participants including 2218 men and 2379 women. The age of the participants ranged from 60 to 93 years with a mean of 67.6 ± 6.3 years. In age and gender adjusted models, adults with VI had a higher likelihood of having difficulties in managing stairs (odds ratio [OR] = 2.7; 95% confidence interval [CI] 2.0, 3.7) compared with those without. The association of VI with the likelihood of having difficulties in managing stairs was stronger in older adults who lived alone (OR = 3.2; 95%CI 1.8, 4.5) compared with those who lived with other family members (OR = 2.0; 95%CI 1.3, 4.3). Compared with hypertension, diabetes, obesity and cognitive dysfunction, VI had the greatest impact on people's abilities of managing stairs. Conclusion VI was associated with an increased likelihood of having difficulties in managing stairs, especially in those who lived alone. However, whether the finding could be extrapolated to other populations warrants further studies as different environmental exposures such as illumination and types of stairs may alter the association

  6. Increased Susceptibility to Chemical Toxicity with (Pre-existing) Diseases: Case Studies with Particulate Matter, Cadmium, Mercury, Trichloroethylene and Dioxin

    EPA Science Inventory

    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 increas...

  7. Early adolescent Depo-Provera exposure increases stillbirths in adult sooty mangabeys.

    PubMed

    Cappelletti, Maurand; Ethun, Kelly; Meeker, Tracy; Von Scherr, Gretchen; Wallen, Kim

    2015-12-01

    The 3-month injectable contraceptive medroxyprogesterone acetate (MPA; Depo-Provera) is a synthetic progestin that protects against pregnancy by suppressing ovulation. Studies have focused on the resumption of ovulation after MPA-treatment cessation but neglected potential long-term effects of MPA exposure on future successful reproduction. MPA is frequently administered to adolescent girls; however, long-term fertility effects of adolescent MPA exposure have not been explored. We investigated fertility after extended MPA exposure in a species of old world primate, the sooty mangabey (Cercocebus atys). Female sooty mangabeys (n=31) received chronic MPA-treatment for 4-8 years. At MPA-treatment onset, subjects were either parous adults (n=14) or nulliparous adolescents (n=17), with adolescent-treated subjects being further divided into those who had reached first ovulation (n=10) and those who had not (n=7). After MPA-treatment cessation, adolescent-treated females had a significantly higher incidence of stillbirth than did age-matched and parity-matched controls, whereas adult-treated females did not differ from their matched controls. Females placed on MPA-treatment prior to first ovulation had a significantly higher incidence of stillbirth post-treatment than did females placed on MPA-treatment after first ovulation. Diabetic females had an increased incidence of stillbirth as compared to nondiabetic females; however, when controlling for diabetes, MPA exposure prior to first ovulation was still a significant positive predictor of stillbirth. These findings suggest that the post-treatment fertility effects of chronic MPA exposure vary with the developmental timing of treatment onset and raise concern about the use of MPA as a contraceptive for adolescent girls.

  8. High-fat/fructose feeding during prenatal and postnatal development in female rats increases susceptibility to renal and metabolic injury later in life.

    PubMed

    Flynn, Elizabeth R; Alexander, Barbara T; Lee, Jonathan; Hutchens, Zachary M; Maric-Bilkan, Christine

    2013-02-15

    Accumulating evidence suggests that both an adverse prenatal and early postnatal environment increase susceptibility to renal and metabolic dysfunction later in life; however, whether exposure to adverse conditions during both prenatal and postnatal development act synergistically to potentiate the severity of renal and metabolic injury remains unknown. Sprague-Dawley rats were fed either a standard diet or a diet high in fat/fructose throughout pregnancy and lactation. After being weaned, female offspring were randomized to either standard diet or the high-fat/high-fructose diet, resulting in the following treatment groups: NF-NF, offspring of mothers fed a standard diet and fed a standard diet postnatally; NF-HF, offspring of mothers fed a standard diet and fed a high-fat/fructose diet postnatally; HF-NF, offspring of mothers fed a high-fat/fructose diet and fed a standard diet postnatally; HF-HF, offspring of mothers fed a high-fat/fructose diet and fed a high-fat/fructose diet postnatally. At the time of euthanasia (17 wk of age), HF-HF offspring weighed 30% more and had 110% more visceral fat than NF-NF offspring. The HF-HF offspring also had elevated blood glucose levels, glucose intolerance, 286% increase in urine albumin excretion, and 60% increase in glomerulosclerosis compared with NF-NF. In addition, HF-HF offspring exhibited a 100% increase in transforming growth factor-β protein expression and 116% increase in the abundance of infiltrated macrophages compared with the NF-NF offspring. These observations suggest that high-fat/fructose feeding during prenatal and throughout postnatal life increases the susceptibility to renal and metabolic injury later in life.

  9. Adolescent exposure to cocaine increases anxiety-like behavior and induces morphologic and neurochemical changes in the hippocampus of adult rats.

    PubMed

    Zhu, W; Mao, Z; Zhu, C; Li, M; Cao, C; Guan, Y; Yuan, J; Xie, G; Guan, X

    2016-01-28

    Repeated exposure to cocaine during adolescence may affect both physical and psychological conditions in the brain, and increase the risk of psychiatric disorders and addiction behaviors in adulthood. Adolescence represents a critical development period for the hippocampus. Moreover, different regions of the hippocampus are involved in different functions. Dorsal hippocampus (dHP) has been implicated in learning and memory, whereas ventral hippocampus (vHP) plays an important role in emotional processing. In this study, the rats that were exposed to cocaine during adolescence (postnatal days, P28-P42) showed higher anxiety-like behavior in the elevated plus maze test in adulthood (P80), but displayed normal spatial learning and memory in the Morris water maze test. Furthermore, repeated exposure to cocaine during adolescence lead to alterations in morphology of pyramidal neurons, activities of astrocytes, and levels of proteins that involved in synaptic transmission, apoptosis, inflammation and addiction in both dHP and vHP of adult rats. These findings suggest that repeated exposure to cocaine during adolescence in rats may elicit morphologic and neurochemical changes in the hippocampus when the animals reach adulthood. These changes may contribute to the increased susceptibility for psychiatric disorders and addiction seen in adults. PMID:26621120

  10. Adolescent exposure to cocaine increases anxiety-like behavior and induces morphologic and neurochemical changes in the hippocampus of adult rats.

    PubMed

    Zhu, W; Mao, Z; Zhu, C; Li, M; Cao, C; Guan, Y; Yuan, J; Xie, G; Guan, X

    2016-01-28

    Repeated exposure to cocaine during adolescence may affect both physical and psychological conditions in the brain, and increase the risk of psychiatric disorders and addiction behaviors in adulthood. Adolescence represents a critical development period for the hippocampus. Moreover, different regions of the hippocampus are involved in different functions. Dorsal hippocampus (dHP) has been implicated in learning and memory, whereas ventral hippocampus (vHP) plays an important role in emotional processing. In this study, the rats that were exposed to cocaine during adolescence (postnatal days, P28-P42) showed higher anxiety-like behavior in the elevated plus maze test in adulthood (P80), but displayed normal spatial learning and memory in the Morris water maze test. Furthermore, repeated exposure to cocaine during adolescence lead to alterations in morphology of pyramidal neurons, activities of astrocytes, and levels of proteins that involved in synaptic transmission, apoptosis, inflammation and addiction in both dHP and vHP of adult rats. These findings suggest that repeated exposure to cocaine during adolescence in rats may elicit morphologic and neurochemical changes in the hippocampus when the animals reach adulthood. These changes may contribute to the increased susceptibility for psychiatric disorders and addiction seen in adults.

  11. Genetic Variation in miR-146a Is Not Associated with Susceptibility to IgA Nephropathy in Adults from a Chinese Han Population

    PubMed Central

    Yang, Bin; Wei, Wei; Shi, Yunying; Huang, Zhuochun; Cai, Bei; Zhang, Junlong; Ying, Binwu; Wang, Lanlan

    2015-01-01

    Background MicroRNA 146a (miR-146a) is a 19 to 23 nucleotide long, small non-coding RNA with gene regulatory functions that has influence on the pathogenesis of many diseases. A single nucleotide polymorphism (rs2910164 C>G) in pre-miR-146a is correlated with the expression of miR-146a. The aim of this study was to perform an association analysis of rs2910164 with IgA nephropathy in adult patients from a Chinese Han population. Methods A total of 145 patients with renal biopsy-proved IgA nephropathy (IgAN) and 179 healthy controls were recruited to the current study. rs2910164 was genotyped by the polymerase chain reaction (PCR) and high-resolution melting methods (HRM). Clinical characteristics and pathology grading of patients with IgAN were recorded at the time of kidney biopsy. Result There were significant differences among the population of patients grouped by different age of onset in a co-dominant model (CG vs. CC vs. GG) (p = 0.033) and a recessive model (CG+CC vs. GG) (p = 0.001). However, no significant difference was observed in the distribution of genotypes between cases and controls (p = 0.144). There was also no significant difference between rs2910164 and patient quantitative traits (all p > 0.003) or different pathology grading (Lee’s grading system and tubular atrophy/interstitial fibrosis in the Oxford classification) (all p > 0.05). Conclusions There was no association of rs2910164 with susceptibility to IgAN in adults from a Chinese Han population. However, rs2910164 was correlated with the age of onset of IgAN in adult patients. PMID:26426696

  12. Analysis of plasma microRNA expression profiles revealed different cancer susceptibility in healthy young adult smokers and middle-aged smokers

    PubMed Central

    Shi, Bing; Gao, Hongmin; Zhang, Tianyang; Cui, Qinghua

    2016-01-01

    Cigarette smoking is a world-wide habit and an important risk factor for cancer. It was known that cigarette smoking can change the expression of circulating microRNAs (miRNAs) in healthy middle-aged adults. However, it remains unclear whether cigarette smoking can change the levels of circulating miRNAs in young healthy smokers and whether there are differences in cancer susceptibility for the two cases. In this study, the miRNA expression profiles of 28 smokers and 12 non-smokers were determined by Agilent human MicroRNA array. We further performed bioinformatics analysis for the differentially expressed miRNAs. The result showed that 35 miRNAs were differentially expressed. Among them, 24 miRNAs were up-regulated and 11 miRNAs were down-regulated in smokers. Functional enrichment analysis showed that the deregulated miRNAs are related to immune system and hormones regulation. Strikingly, the up-regulated miRNAs are mostly associated with hematologic cancers, such as lymphoma, leukemia. As a comparison, the up-regulated plasma miRNAs in middle-aged smokers are mostly associated with solid cancers, such as hepatocellular carcinoma and lung cancer, suggesting that smoking could have different influences on young adults and middle-aged adults. In a conclusion, we identified the circulating miRNAs deregulated by cigarette smoking and revealed that the age-dependent deregulated miRNAs tend to be mainly involved in different types of human cancers. PMID:26943588

  13. High vancomycin MICs within the susceptible range in Staphylococcus aureus bacteraemia isolates are associated with increased cell wall thickness and reduced intracellular killing by human phagocytes.

    PubMed

    Falcón, Rocío; Martínez, Alba; Albert, Eliseo; Madrid, Silvia; Oltra, Rosa; Giménez, Estela; Soriano, Mario; Vinuesa, Víctor; Gozalbo, Daniel; Gil, María Luisa; Navarro, David

    2016-05-01

    Vancomycin minimum inhibitory concentrations (MICs) at the upper end of the susceptible range for Staphylococcus aureus have been associated with poor clinical outcomes of bloodstream infections. We tested the hypothesis that high vancomycin MICs in S. aureus bacteraemia isolates are associated with increased cell wall thickness and suboptimal bacterial internalisation or lysis by human phagocytes. In total, 95 isolates were evaluated. Original vancomycin MICs were determined by Etest. The susceptibility of S. aureus isolates to killing by phagocytes was assessed in a human whole blood assay. Internalisation of bacterial cells by phagocytes was investigated by flow cytometry. Cell wall thickness was evaluated by transmission electron microscopy. Genotypic analysis of S. aureus isolates was performed using a DNA microarray system. Vancomycin MICs were significantly higher (P=0.006) in isolates that were killed suboptimally (killing index <60%) compared with those killed efficiently (killing index >70%) and tended to correlate inversely (P=0.08) with the killing indices. Isolates in both killing groups were internalised by human neutrophils and monocytes with comparable efficiency. The cell wall was significantly thicker (P=0.03) in isolates in the low killing group. No genotypic differences were found between the isolates in both killing groups. In summary, high vancomycin MICs in S. aureus bacteraemia isolates were associated with increased cell wall thickness and reduced intracellular killing by phagocytes. PMID:27056298

  14. Nanomolar concentrations of zinc pyrithione increase cell susceptibility to oxidative stress induced by hydrogen peroxide in rat thymocytes.

    PubMed

    Oyama, Tomohiro M; Saito, Minoru; Yonezawa, Takayasu; Okano, Yoshiro; Oyama, Yasuo

    2012-06-01

    Zinc pyrithione is used as an antifouling agent. However, the environmental impacts of zinc pyrithione have recently been of concern. Zinc induces diverse actions during oxidative stress; therefore, we examined the effect of zinc pyrithione on rat thymocytes suffering from oxidative stress using appropriate fluorescent probes. The cytotoxicity of zinc pyrithione was not observed when the cells were incubated with 3 μM zinc pyrithione for 3 h. However, zinc pyrithione at nanomolar concentrations (10 nM or more) significantly increased the lethality of cells suffering from oxidative stress induced by 3 mM H(2)O(2). The application of zinc pyrithione alone at nanomolar concentrations increased intracellular Zn(2+) level and the cellular content of superoxide anions, and decreased the cellular content of nonprotein thiols. The simultaneous application of nanomolar zinc pyrithione and micromolar H(2)O(2) synergistically increased the intracellular Zn(2+) level. Therefore, zinc pyrithione at nanomolar concentrations may exert severe cytotoxic action on cells simultaneously exposed to chemicals that induce oxidative stress. If so, zinc pyrithione leaked from antifouling materials into surrounding environments would be a risk factor for aquatic ecosystems. Alternatively, zinc pyrithione under conditions of oxidative stress may become more potent antifouling ingredient. PMID:22356860

  15. Increased Bacterial Load and Expression of Antimicrobial Peptides in Skin of Barrier-Deficient Mice with Reduced Cancer Susceptibility.

    PubMed

    Natsuga, Ken; Cipolat, Sara; Watt, Fiona M

    2016-01-01

    Mice lacking three epidermal barrier proteins-envoplakin, periplakin, and involucrin (EPI-/- mice)-have a defective cornified layer, reduced epidermal γδ T cells, and increased dermal CD4(+) T cells. They are also resistant to developing skin tumors. The tumor-protective mechanism involves signaling between Rae-1 expressing keratinocytes and the natural killer group 2D receptor on immune cells, which also plays a role in host defenses against infection. Given the emerging link between bacteria and cancer, we investigated whether EPI-/- mice have an altered skin microbiota. The bacterial phyla were similar in wild-type and EPI-/- skin. However, bacteria were threefold more abundant in EPI-/- skin and penetrated deeper into the epidermis. The major epithelial defense mechanism against bacteria is production of antimicrobial proteins (AMPs). EPI-/- skin exhibited enhanced expression of antimicrobial peptides. However, reducing the bacterial load by antibiotic treatment or breeding mice under specific pathogen-free conditions did not reduce AMP expression or alleviate the abnormalities in T-cell populations. We conclude that the atopic characteristics of EPI-/- skin are a consequence of the defective barrier rather than a response to the increased bacterial load. It is therefore unlikely that the increase in skin microbiota contributes directly to the observed cancer resistance.

  16. Increased Bacterial Load and Expression of Antimicrobial Peptides in Skin of Barrier-Deficient Mice with Reduced Cancer Susceptibility

    PubMed Central

    Natsuga, Ken; Cipolat, Sara; Watt, Fiona M.

    2016-01-01

    Mice lacking three epidermal barrier proteins—envoplakin, periplakin, and involucrin (EPI-/- mice)—have a defective cornified layer, reduced epidermal γδ T cells, and increased dermal CD4+ T cells. They are also resistant to developing skin tumors. The tumor-protective mechanism involves signaling between Rae-1 expressing keratinocytes and the natural killer group 2D receptor on immune cells, which also plays a role in host defenses against infection. Given the emerging link between bacteria and cancer, we investigated whether EPI-/- mice have an altered skin microbiota. The bacterial phyla were similar in wild-type and EPI-/- skin. However, bacteria were threefold more abundant in EPI-/- skin and penetrated deeper into the epidermis. The major epithelial defense mechanism against bacteria is production of antimicrobial proteins (AMPs). EPI-/- skin exhibited enhanced expression of antimicrobial peptides. However, reducing the bacterial load by antibiotic treatment or breeding mice under specific pathogen-free conditions did not reduce AMP expression or alleviate the abnormalities in T-cell populations. We conclude that the atopic characteristics of EPI-/- skin are a consequence of the defective barrier rather than a response to the increased bacterial load. It is therefore unlikely that the increase in skin microbiota contributes directly to the observed cancer resistance. PMID:26763429

  17. Media multitasking is associated with distractibility and increased prefrontal activity in adolescents and young adults.

    PubMed

    Moisala, M; Salmela, V; Hietajärvi, L; Salo, E; Carlson, S; Salonen, O; Lonka, K; Hakkarainen, K; Salmela-Aro, K; Alho, K

    2016-07-01

    The current generation of young people indulges in more media multitasking behavior (e.g., instant messaging while watching videos) in their everyday lives than older generations. Concerns have been raised about how this might affect their attentional functioning, as previous studies have indicated that extensive media multitasking in everyday life may be associated with decreased attentional control. In the current study, 149 adolescents and young adults (aged 13-24years) performed speech-listening and reading tasks that required maintaining attention in the presence of distractor stimuli in the other modality or dividing attention between two concurrent tasks. Brain activity during task performance was measured using functional magnetic resonance imaging (fMRI). We studied the relationship between self-reported daily media multitasking (MMT), task performance and brain activity during task performance. The results showed that in the presence of distractor stimuli, a higher MMT score was associated with worse performance and increased brain activity in right prefrontal regions. The level of performance during divided attention did not depend on MMT. This suggests that daily media multitasking is associated with behavioral distractibility and increased recruitment of brain areas involved in attentional and inhibitory control, and that media multitasking in everyday life does not translate to performance benefits in multitasking in laboratory settings. PMID:27063068

  18. Fruits and stir-fried vegetables increase plasma carotenoids in young adults.

    PubMed

    Lin, Yu-Ju; Chien, Yi-Wen; Yang, Shwu-Huey; Cheng, Hsing-Hsien

    2007-01-01

    We examined the plasma levels of carotenoids in young adults after a dietary intervention composed of increased intakes of fruits and stir-fried vegetables from a Taiwanese mixed diet. Thirty-four apparently healthy, non-smoking subjects who normally ingested less than two and a half servings of fruits and vegetables daily were selected for the study. Meals changed were lunch and dinner on weekdays for a period of 4 weeks. The test meal consisted of three servings of stir-fried vegetables and two servings of fresh fruits. Plasma carotenoid levels in subjects significantly increased from 19%-32% for beta-carotene, 15%-47% for lycopene and 59%-88% for beta-crytoxanthin (p < 0.05) from week 1 to 4. However, these concentrations of beta-carotene and lycopene significantly decreased after stopping the consumption of the test meals. This study reveals the importance of a continuous consumption of carotenoid rich foods in order to maintain high levels of plasma carotenoids for the potential prevention of chronic diseases in individuals. PMID:18042520

  19. Nicotine-Cadmium Interaction Alters Exploratory Motor Function and Increased Anxiety in Adult Male Mice

    PubMed Central

    Chris Ajonijebu, Duyilemi; Adeyemi Adeniyi, Philip; Oloruntoba Adekeye, Adeshina; Peter Olatunji, Babawale; Olakunle Ishola, Azeez; Michael Ogundele, Olalekan

    2014-01-01

    In this study we evaluated the time dependence in cadmium-nicotine interaction and its effect on motor function, anxiety linked behavioural changes, serum electrolytes, and weight after acute and chronic treatment in adult male mice. Animals were separated randomly into four groups of n = 6 animals each. Treatment was done with nicotine, cadmium, or nicotine-cadmium for 21 days. A fourth group received normal saline for the same duration (control). Average weight was determined at 7-day interval for the acute (D1-D7) and chronic (D7-D21) treatment phases. Similarly, the behavioural tests for exploratory motor function (open field test) and anxiety were evaluated. Serum electrolytes were measured after the chronic phase. Nicotine, cadmium, and nicotine-cadmium treatments caused no significant change in body weight after the acute phase while cadmium-nicotine and cadmium caused a decline in weight after the chronic phase. This suggests the role of cadmium in the weight loss observed in tobacco smoke users. Both nicotine and cadmium raised serum Ca2+ concentration and had no significant effect on K+ ion when compared with the control. In addition, nicotine-cadmium treatment increased bioaccumulation of Cd2+ in the serum which corresponded to a decrease in body weight, motor function, and an increase in anxiety. PMID:26317007

  20. Drinking orange juice increases total antioxidant status and decreases lipid peroxidation in adults.

    PubMed

    Foroudi, Shahrzad; Potter, Andrew S; Stamatikos, Alexis; Patil, Bhimanagouda S; Deyhim, Farzad

    2014-05-01

    Cardiovascular disease (CVD) is the leading cause of death in the world and is the primary cause of mortality among Americans. One of the many reasons for the pathogenesis of CVD is attributed to eating diets high in saturated fat and refined carbohydrates and low in fruits and vegetables. Epidemiological evidence has supported a strong association between eating diets rich in fruits and vegetables and cardiovascular health. An experiment was conducted utilizing 24 adults with hypercholesterolemia and hypertriglyceridemia to evaluate the impact of drinking 20 fl oz of freshly squeezed orange juice daily for 90 days on blood pressure, lipid panels, plasma antioxidant capacity, metabolic hormones, lipid peroxidation, and inflammatory markers. Except for addition of drinking orange juice, subjects did not modify their eating habits. The findings suggested that drinking orange juice does not affect (P>.1) blood pressure, lipid panels, metabolic hormones, body fat percentage, or inflammatory markers. However, total plasma antioxidant capacity was significantly increased (P<.05) and lipid peroxidation was significantly decreased (P<.05) after orange juice consumption. Drinking orange juice may protect the cardiovascular system by increasing total plasma antioxidant status and by lowering lipid peroxidation independent of other cardiovascular risk markers evaluated in this study.

  1. Media multitasking is associated with distractibility and increased prefrontal activity in adolescents and young adults.

    PubMed

    Moisala, M; Salmela, V; Hietajärvi, L; Salo, E; Carlson, S; Salonen, O; Lonka, K; Hakkarainen, K; Salmela-Aro, K; Alho, K

    2016-07-01

    The current generation of young people indulges in more media multitasking behavior (e.g., instant messaging while watching videos) in their everyday lives than older generations. Concerns have been raised about how this might affect their attentional functioning, as previous studies have indicated that extensive media multitasking in everyday life may be associated with decreased attentional control. In the current study, 149 adolescents and young adults (aged 13-24years) performed speech-listening and reading tasks that required maintaining attention in the presence of distractor stimuli in the other modality or dividing attention between two concurrent tasks. Brain activity during task performance was measured using functional magnetic resonance imaging (fMRI). We studied the relationship between self-reported daily media multitasking (MMT), task performance and brain activity during task performance. The results showed that in the presence of distractor stimuli, a higher MMT score was associated with worse performance and increased brain activity in right prefrontal regions. The level of performance during divided attention did not depend on MMT. This suggests that daily media multitasking is associated with behavioral distractibility and increased recruitment of brain areas involved in attentional and inhibitory control, and that media multitasking in everyday life does not translate to performance benefits in multitasking in laboratory settings.

  2. Sleep Disruption is Associated with Increased Ventricular Ectopy and Cardiac Arrest in Hospitalized Adults

    PubMed Central

    Miner, Steven Edward Stuart; Pahal, Dev; Nichols, Laurel; Darwood, Amanda; Nield, Lynne Elizabeth; Wulffhart, Zaev

    2016-01-01

    Study Objectives: To determine whether sleep disruption increases ventricular ectopy and the risk of cardiac arrest in hospitalized patients. Methods: Hospital emergency codes (HEC) trigger multiple hospital-wide overhead announcements. In 2014 an electronic “code white” program was instituted to protect staff from violent patients. This resulted in an increase in nocturnal HEC. Telemetry data was examined between September 14 and October 2, 2014. The frequency of nocturnal announcements was correlated with changes in frequency of premature ventricular complexes per hour (PVC/h). Cardiac arrest data were examined over a 3-y period. All HEC were assumed to have triggered announcements. The relationship between nocturnal HEC and the incidence of subsequent cardiac arrest was examined. Results: 2,603 hours of telemetry were analyzed in 87 patients. During nights with two or fewer announcements, PVC/h decreased 33% and remained 30% lower the next day. On nights with four or more announcements, PVC/h increased 23% (P < 0.001) and further increased 85% the next day (P = 0.001). In 2014, following the introduction of the code white program, the frequency of all HEC increased from 1.1/day to 6.2/day (P < 0.05). The frequency of cardiac arrest/24 h rose from 0.46/day in 2012–2013 to 0.62/day in 2014 (P = 0.001). During daytime hours (06:00–22:00), from 2012 through 2014, the frequency of cardiac arrest following zero, one or at least two nocturnal HEC were 0.331 ± 0.03, 0.396 ± 0.04 and 0.471 ± 0.09 respectively (R2 = 0.99, P = 0.03). Conclusions: Sleep disruption is associated with increased ventricular ectopy and increased frequency of cardiac arrest. Citation: Miner SE, Pahal D, Nichols L, Darwood A, Nield LE, Wulffart Z. Sleep disruption is associated with increased ventricular ectopy and cardiac arrest in hospitalized adults. SLEEP 2016;39(4):927–935. PMID:26715226

  3. Communal nesting increases pup growth but has limited effects on adult behavior and neurophysiology in inbred mice.

    PubMed

    Heiderstadt, Kathleen M; Vandenbergh, David J; Gyekis, Joseph P; Blizard, David A

    2014-03-01

    Laboratory mice preferentially rear their offspring in communal nests (CN), with all mothers contributing to maternal care and feeding of all the pups. Previous studies using primarily outbred mice have shown that offspring reared under CN conditions may display increased preweaning growth rates and differences in adult behavior and neurobiology compared with mice reared under single-nesting (SN; one dam with her litter) conditions. Here we compared pup mortality; weaning and adult body weights; adult behavior; and gene expression in the hippocampus and frontal cortex between C57BL/6J, DBA/2J and 129x1/SvJ mice reared by using CN (3 dams and their litters sharing a single nest) or SN. Male and female pups of all 3 strains reared in CN cages showed higher body weight at weaning than did SN pups of the same strain, with no significant difference in pup mortality between groups. Adult male offspring reared in CN showed no differences in any behavioral test when compared with SN offspring. Combining CN dams and litters after parturition revealed greater cortical brain-derived neurotropic factor expression in adult male C57BL/6J offspring and cortical glucocorticoid receptor expression in adult male C57BL/6J and 129x1/SvJ offspring as compared with SN offspring of the same strain. Communal rearing can enhance juvenile growth rates but does not change adult behavior in inbred mouse strains, although potential effects on adult neurophysiology are possible.

  4. Perinatal exposure to bisphenol a increases adult mammary gland progesterone response and cell number.

    PubMed

    Ayyanan, Ayyakkannu; Laribi, Ouahiba; Schuepbach-Mallepell, Sonia; Schrick, Christina; Gutierrez, Maria; Tanos, Tamara; Lefebvre, Gregory; Rougemont, Jacques; Yalcin-Ozuysal, Ozden; Brisken, Cathrin

    2011-11-01

    Bisphenol A [BPA, 2,2,-bis (hydroxyphenyl) propane] is one of the highest-volume chemicals produced worldwide. It is detected in body fluids of more than 90% of the human population. Originally synthesized as an estrogenic compound, it is currently utilized to manufacture food and beverage containers resulting in uptake with food and drinks. There is concern that exposure to low doses of BPA, defined as less than or equal to 5 mg/kg body weight /d, may have developmental effects on various hormone-responsive organs including the mammary gland. Here, we asked whether perinatal exposure to a range of low doses of BPA is sufficient to alter mammary gland hormone response later on in life, with a possible impact on breast cancer risk. To mimic human exposure, we added BPA to the drinking water of C57/Bl6 breeding pairs. Analysis of the mammary glands of their daughters at puberty showed that estrogen-dependent transcriptional events were perturbed and the number of terminal end buds, estrogen-induced proliferative structures, was altered in a dose-dependent fashion. Importantly, adult females showed an increase in mammary epithelial cell numbers comparable to that seen in females exposed to diethylbestrol, a compound exposure to which was previously linked to increased breast cancer risk. Molecularly, the mRNAs encoding Wnt-4 and receptor activator of nuclear factor κB ligand, two key mediators of hormone function implicated in control of mammary stem cell proliferation and carcinogenesis, showed increased induction by progesterone in the mammary tissue of exposed mice. Thus, perinatal exposure to environmentally relevant doses of BPA alters long-term hormone response that may increase the propensity to develop breast cancer.

  5. Acute and chronic caffeine administration increases physical activity in sedentary adults.

    PubMed

    Schrader, Patrick; Panek, Leah M; Temple, Jennifer L

    2013-06-01

    Caffeine is a commonly used stimulant thought to have ergogenic properties. Most studies on the ergogenic effects of caffeine have been conducted in athletes. The purpose of this study was to test the hypothesis that caffeine reduces ratings of perceived exertion and increases liking of physical activity in sedentary adults. Participants completed treadmill walking at 60% to 70% of their maximal heart rate at baseline and for 6 subsequent visits, during which half of the participants were given caffeine (3 mg/kg) and half given placebo in a sports drink vehicle. To investigate the potential synergistic effects of acute and chronic caffeine on self-determined exercise duration, participants were rerandomized to either the same or different condition for the last visit, creating 4 chronic/acute treatment groups (placebo/placebo, placebo/caffeine, caffeine/placebo, caffeine/caffeine). Participants rated how much they liked the activity and perceived exertion at each visit. There was a main effect of time on liking of physical activity, with liking increasing over time and an interaction of sex and caffeine treatment on liking, with liking of activity increasing in female participants treated with caffeine, but not with placebo. There was no effect of caffeine on ratings of perceived exertion. Individuals who received caffeine on the final test day exercised for significantly longer than those who received placebo. These data suggest that repeated exposure to physical activity significantly increases liking of exercise and reduces ratings of perceived exertion and that caffeine does little to further modify these effects.

  6. Class I-deficient resistant mice intracerebrally inoculated with Theiler's virus show an increased T cell response to viral antigens and susceptibility to demyelination.

    PubMed

    Pullen, L C; Miller, S D; Dal Canto, M C; Kim, B S

    1993-09-01

    Intracerebral inoculation of Theiler's murine encephalomyelitis virus (TMEV) results in immune-mediated demyelination in susceptible mouse strains. The histology of TMEV-induced demyelination is similar to that seen in patients suffering from multiple sclerosis. It was previously shown that the susceptibility of mice to TMEV-induced demyelination in certain strain combinations is closely associated with the major histocompatibility complex (MHC) class I locus. Here we examine disease susceptibility of beta 2-microglobulin (beta 2M)-deficient transgenic mice lacking class I expression and functional CD8+ T cells. In contrast to TMEV-infected parental C57BL/6 mice, the transgenics develop high levels of virus-specific DTH and T cell proliferation accompanied by an increased frequency of central nervous system (CNS) demyelinating lesions. However, clinical signs of demyelination were not noted. Neither antibody titer nor viral persistence were significantly affected in the beta 2M-deficient mice. These results suggest that in the absence of functional class I/CD8+ cells, the class II-restricted T cell response to TMEV is enhanced and CNS pathogenesis is heightened, although the level is not severe enough to result in clinical disease. When the TMEV-infected mice were subcutaneously immunized with virus, however, the beta 2M-deficient mice displayed clinical symptoms. Therefore, our results strongly suggest that CD8+ T cells do not directly contribute to CNS demyelination. In contrast, such T cells appear to be primarily involved in down-regulation of a potentially damaging CD4+ T cell response in resistant animals, although some of the T cells may play a role in clearing viral persistence in the CNS, resulting in the protection of the host from viral demyelination.

  7. Increased susceptibility to in vitro ultraviolet B radiation in fibroblasts and lymphocytes cultured from systemic lupus erythematosus patients

    SciTech Connect

    Golan, T.D.; Foltyn, V.; Roueff, A. )

    1991-02-01

    Sunlight is known to induce exacerbations of systemic lupus erythematosus (SLE) but its mechanism remains unclear. We have previously reported that ultraviolet A (UVA) exposure induces an increase in total DNA synthesis (DS) in vitro but a decrease in unscheduled DNA repair synthesis (UDRS) of splenocytes of murine SLE strains. In order to investigate whether similar observations are characteristic of human SLE, peripheral blood lymphocytes (PBL) and dermal fibroblast (DF) cultures of 20 patients and 15 matched controls were exposed in vitro to UVA or UVB at different doses. Thirteen (65%) SLE DF cultures exposed to UVB light (12-24 J/m2) showed an increase in DS compared to paired unirradiated cultures. In contrast, UVB-irradiated DF from normal individuals had no significant increase in DS following UVB irradiation. When SLE DF were exposed to higher doses of UVB (48-96 J/m2), 90% of cultures showed a decrease in DS compared to only 20% in the control group. All of the SLE DF cultures showed a decrease of their unscheduled DNA repair capacity following UVB (24-48 J/m2) irradiation whereas no UDRS was apparent in 74% of controls under the same conditions. Similar findings regarding UDRS were observed in SLE PBL cultures and were also confirmed by autoradiography. UVA exposure (0-3840 J/m2) had no effect on DS nor on UDRS in DF or PBL cultured from SLE and controls. The relevance of these in vitro findings to the in vivo pathogenesis of the disease is discussed.

  8. Increased susceptibility of Trpv4-Deficient Mice to Obesity and Obesity-Induced Osteoarthritis with Very High-Fat Diet

    PubMed Central

    O’Conor, Christopher J.; Griffin, Timothy M.; Liedtke, Wolfgang; Guilak, Farshid

    2013-01-01

    Objective To test the hypotheses that: 1) the transient receptor potential vanilloid 4 (TRPV4) ion channel is protective in the obesity-model of osteoarthritis (OA), resulting in more severe obesity-induced OA in Trpv4 knockout (Trpv4−/−) mice; and 2) loss of TRPV4 alters mesodermal stem cell differentiation. Methods Male Trpv4−/− and wild-type (Trpv4+/+)mice were fed a control or high-fat diet (10% kcal and 60% kcal from fat, respectively) for 22 weeks, at which time spontaneous cage activity and severity of knee OA were evaluated. In addition, the adipogenic, osteogenic, and chondrogenic potential of bone marrow-derived (MSC) and adipose-derived (ASC) stem cells from Trpv4−/− and Trpv4+/+ mice were compared. Results A high-fat diet significantly increased knee OA scores and reduced spontaneous cage activity in Trpv4−/− mice, while also increasing weight gain and adiposity. MSCs from Trpv4−/− mice had decreased adipogenic and osteogenic differentiation potential versus Trpv4+/+ MSCs. ASCs from Trpv4−/− mice had increased adipogenic and osteogenic and reduced chondrogenic differentiation potential versus Trpv4+/+ ASCs. Conclusion Pan-Trpv4−/− mice develop more severe OA with high-fat feeding, potentially due to more severe diet-induced obesity. The altered differentiation potential of Trpv4−/− progenitor cells may reflect the importance of this ion channel in the maintenance and turnover of mesodermally-derived tissues. PMID:23178209

  9. Placental-mediated increased cytokine response to lipopolysaccharides: a potential mechanism for enhanced inflammation susceptibility of the preterm fetus

    PubMed Central

    Boles, Julie L; Ross, Michael G; Beloosesky, Ron; Desai, Mina; Belkacemi, Louiza

    2012-01-01

    Background: Cerebral palsy is a nonprogressive motor impairment syndrome that has no effective cure. The etiology of most cases of cerebral palsy remains unknown; however, recent epidemiologic data have demonstrated an association between fetal neurologic injury and infection/inflammation. Maternal infection/inflammation may be associated with the induction of placental cytokines that could result in increased fetal proinflammatory cytokine exposure, and development of neonatal neurologic injury. Therefore, we sought to explore the mechanism by which maternal infection may produce a placental inflammatory response. We specifically examined rat placental cytokine production and activation of the Toll-like receptor 4 (TLR4) pathway in response to lipopolysaccharide exposure at preterm and near-term gestational ages. Methods: Preterm (e16) or near-term (e20) placental explants from pregnant rats were treated with 0, 1, or 10 μg/mL lipopolysaccharide. Explant integrity was assessed by lactate dehydrogenase assay. Interleukin-6 and tumor necrosis alpha levels were determined using enzyme-linked immunosorbent assay kits. TLR4 and phosphorylated nuclear factor kappa light chain enhancer of activated B cells (NFκB) protein expression levels were determined by Western blot analysis. Results: At both e16 and e20, lactate dehydrogenase levels were unchanged by treatment with lipopolysaccharide. After exposure to lipopolysaccharide, the release of interleukin-6 and tumor necrosis alpha from e16 placental explants increased by 4-fold and 8–9-fold, respectively (P < 0.05 versus vehicle). Conversely, interleukin-6 release from e20 explants was not significantly different compared with vehicle, and tumor necrosis alpha release was only 2-fold higher (P < 0.05 versus vehicle) following exposure to lipopolysaccharide. Phosphorylated NFκB protein expression was significantly increased in the nuclear fraction from placental explants exposed to lipopolysaccharide at both e16 and e

  10. Macrophage ABCA5 deficiency influences cellular cholesterol efflux and increases susceptibility to atherosclerosis in female LDLr knockout mice

    SciTech Connect

    Ye, Dan; Meurs, Illiana; Ohigashi, Megumi; Calpe-Berdiel, Laura; Habets, Kim L.L.; Zhao, Ying; Kubo, Yoshiyuki; Yamaguchi, Akihito; Van Berkel, Theo J.C.; Nishi, Tsuyoshi; Van Eck, Miranda

    2010-05-07

    Objectives: To determine the role of macrophage ATP-binding cassette transporter A5 (ABCA5) in cellular cholesterol homeostasis and atherosclerotic lesion development. Methods and results: Chimeras with dysfunctional macrophage ABCA5 (ABCA5{sup -M/-M}) were generated by transplantation of bone marrow from ABCA5 knockout (ABCA5{sup -/-}) mice into irradiated LDLr{sup -/-} mice. In vitro, bone marrow-derived macrophages from ABCA5{sup -M/-M} chimeras exhibited a 29% (P < 0.001) decrease in cholesterol efflux to HDL, whereas a 21% (P = 0.07) increase in cholesterol efflux to apoA-I was observed. Interestingly, expression of ABCA1, but not ABCG1, was up-regulated in absence of functional ABCA5 in macrophages. To induce atherosclerosis, the transplanted LDLr{sup -/-} mice were fed a high-cholesterol Western-type diet (WTD) for 6, 10, or 18 weeks, allowing analysis of effects on initial as well as advanced lesion development. Atherosclerosis development was not affected in male ABCA5{sup -M/-M} chimeras after 6, 10, and 18 weeks WTD feeding. However, female ABCA5{sup -M/-M} chimeras did develop significantly (P < 0.05) larger aortic root lesions as compared with female controls after 6 and 10 weeks WTD feeding. Conclusions: ABCA5 influences macrophage cholesterol efflux, and selective disruption of ABCA5 in macrophages leads to increased atherosclerotic lesion development in female LDLr{sup -/-} mice.

  11. Molecular basis for increased susceptibility of isolates with atazanavir resistance-conferring substitution I50L to other protease inhibitors.

    PubMed

    Yanchunas, Joseph; Langley, David R; Tao, Li; Rose, Ronald E; Friborg, Jacques; Colonno, Richard J; Doyle, Michael L

    2005-09-01

    Protease inhibitors (PIs) are highly effective drugs against the human immunodeficiency virus (HIV), yet long-term therapeutic use is limited by emergence of HIV type 1 (HIV-1) protease substitutions that confer cross-resistance to multiple protease inhibitor drugs. Atazanavir is a highly potent HIV protease inhibitor with a distinct resistance profile that includes effectiveness against most HIV-1 isolates resistant to one or two PIs. The signature resistance substitution for atazanavir is I50L, and it is frequently (53%) accompanied by a compensatory A71V substitution that helps restore viability and increases atazanavir resistance levels. We measured the binding affinities of wild-type (WT) and I50L/A71V HIV-1 proteases to atazanavir and other currently approved PIs (ritonavir, lopinavir, saquinavir, nelfinavir, indinavir, and amprenavir) by isothermal titration calorimetry. Remarkably, we find that all of the PIs have 2- to 10-fold increased affinities for I50L/A71V protease, except for atazanavir. The results are also manifested by thermal stability measures of affinity for WT and I50L/A71V proteases. Additional biophysical and enzyme kinetics experiments show I50L/A71V protease is a stable enzyme with catalytic activity that is slightly reduced (34%) relative to the WT. Computational modeling reveals that the unique resistance phenotype of I50L/A71V protease likely originates from bulky tert-butyl groups at P2 and P2' (specific to atazanavir) that sterically clash with methyl groups on residue L50. The results of this study provide a molecular understanding of the novel hypersusceptibility of atazanavir-resistant I50L/A71V-containing clinical isolates to other currently approved PIs.

  12. Older Adults with Intellectual Disabilities: Targets for Increasing Victimization, a Call for a Preemptive Screening Policy

    ERIC Educational Resources Information Center

    Strasser, Sheryl; O'Quin, Karen; Price, Thomas; Leyda, Elizabeth

    2012-01-01

    The aging population is a rapidly growing demographic in the United States. Isolation, limited autonomy, and declining physical and mental health render many older adults vulnerable to abuse, neglect, and exploitation. As the population grows, so does the need for Adult Protective Services (APS). This article highlights an ultrasensitive subgroup…

  13. Violent Crime Victimization Increases the Risk of Nursing Home Placement in Older Adults

    ERIC Educational Resources Information Center

    Lachs, Mark; Bachman, Ronet; Williams, Christianna S.; Kossack, Alice; Bove, Carolyn; O'Leary, John R.

    2006-01-01

    Purpose: We estimate the independent contribution of crime victimization to nursing home placement in a cohort of older adults who were community dwelling at baseline. Design and Methods: The data come from an observational cohort study of 2,321 community-residing older adults who were members of the New Haven Established Populations for…

  14. Running increases neurogenesis without retinoic acid receptor activation in the adult mouse dentate gyrus.

    PubMed

    Aberg, Elin; Perlmann, Thomas; Olson, Lars; Brené, Stefan

    2008-01-01

    Both vitamin A deficiency and high doses of retinoids can result in learning and memory impairments, depression as well as decreases in cell proliferation, neurogenesis and cell survival. Physical activity enhances hippocampal neurogenesis and can also exert an antidepressant effect. Here we elucidate a putative link between running, retinoid signaling, and neurogenesis in hippocampus. Adult transgenic reporter mice designed to detect ligand-activated retinoic acid receptors (RAR) or retinoid X receptors (RXR) were used to localize the distribution of activated RAR or RXR at the single-cell level in the brain. Two months of voluntary wheel-running induced an increase in hippocampal neurogenesis as indicated by an almost two-fold increase in doublecortin-immunoreactive cells. Running activity was correlated with neurogenesis. Under basal conditions a distinct pattern of RAR-activated cells was detected in the granule cell layer of the dentate gyrus (DG), thalamus, and cerebral cortex layers 3-4 and to a lesser extent in hippocampal pyramidal cell layers CA1-CA3. Running did not change the number of RAR-activated cells in the DG. There was no correlation between running and RAR activation or between RAR activation and neurogenesis in the DG of hippocampus. Only a few scattered activated retinoid X receptors were found in the DG under basal conditions and after wheel-running, but RXR was detected in other areas such as in the hilus region of hippocampus and in layer VI of cortex cerebri. RAR agonists affect mood in humans and reduce neurogenesis, learning and memory in animal models. In our study, long-term running increased neurogenesis but did not alter RAR ligand activation in the DG in individually housed mice. Thus, our data suggest that the effects of exercise on neurogenesis and other plasticity changes in the hippocampal formation are mediated by mechanisms that do not involve retinoid receptor activation.

  15. 10′(Z),13′(E)-Heptadecadienylhydroquinone Inhibits Swarming and Virulence Factors and Increases Polymyxin B Susceptibility in Proteus mirabilis

    PubMed Central

    Wang, Won-Bo; Yuan, Yu-Han; Hsueh, Po-Ren; Liaw, Shwu-Jen

    2012-01-01

    In this study, we demonstrated that 10′(Z), 13′(E)-heptadecadienylhydroquinone (HQ17-2), isolated from the lacquer tree, could decrease swarming motility and hemolysin activity but increase polymyxin B (PB) susceptibilityof Proteus mirabilis which is intrinsically highly-resistant to PB. The increased PB susceptibility induced by HQ17-2 was also observed in clinical isolates and biofilm-grown cells. HQ17-2 could inhibit swarming in the wild-type and rppA mutant but not in the rcsB mutant, indicating that HQ17-2 inhibits swarming through the RcsB-dependent pathway, a two-component signaling pathway negatively regulating swarming and virulence factor expression. The inhibition of hemolysin activity by HQ17-2 is also mediated through the RcsB-dependent pathway, because HQ17-2 could not inhibit hemolysin activity in the rcsB mutant. Moreover, the finding that HQ17-2 inhibits the expression of flhDC gene in the wild-type and rcsB-complemented strain but not in the rcsB mutant supports the notion. By contrast, HQ17-2 could increase PB susceptibility in the wild-type and rcsB mutant but not in the rppA mutant, indicating that HQ17-2 increases PB susceptibility through the RppA-dependent pathway, a signaling pathway positively regulating PB resistance. In addition, HQ17-2 could inhibit the promoter activities of rppA and pmrI, a gene positively regulated by RppA and involved in PB resistance, in the wild-type but not in the rppA mutant. The inhibition of rppA and pmrI expression caused lipopolysaccharide purified from HQ17-2-treated cells to have higher affinity for PB. Altogether, this study uncovers new biological effects of HQ17-2 and provides evidence for the potential of HQ17-2 in clinical applications. PMID:23029100

  16. Epithelial-to-Mesenchymal Transition of RPE Cells In Vitro Confers Increased β1,6-N-Glycosylation and Increased Susceptibility to Galectin-3 Binding

    PubMed Central

    Priglinger, Claudia S.; Obermann, Jara; Szober, Christoph M.; Merl-Pham, Juliane; Ohmayer, Uli; Behler, Jennifer; Gruhn, Fabian; Kreutzer, Thomas C.; Wertheimer, Christian; Geerlof, Arie; Priglinger, Siegfried G.; Hauck, Stefanie M.

    2016-01-01

    Epithelial-to-mesenchymal transition (EMT) of retinal pigment epithelial cells is a crucial event in the onset of proliferative vitreoretinopathy (PVR), the most common reason for treatment failure in retinal detachment surgery. We studied alterations in the cell surface glycan expression profile upon EMT of RPE cells and focused on its relevance for the interaction with galectin-3 (Gal-3), a carbohydrate binding protein, which can inhibit attachment and spreading of human RPE cells in a dose- and carbohydrate-dependent manner, and thus bares the potential to counteract PVR-associated cellular events. Lectin blot analysis revealed that EMT of RPE cells in vitro confers a glycomic shift towards an abundance of Thomsen-Friedenreich antigen, poly-N-acetyllactosamine chains, and complex-type branched N-glycans. Using inhibitors of glycosylation we found that both, binding of Gal-3 to the RPE cell surface and Gal-3-mediated inhibition of RPE attachment and spreading, strongly depend on the interaction of Gal-3 with tri- or tetra-antennary complex type N-glycans and sialylation of glycans but not on complex-type O-glycans. Importantly, we found that β1,6 N-acetylglucosaminyltransferase V (Mgat5), the key enzyme catalyzing the synthesis of tetra- or tri-antennary complex type N-glycans, is increased upon EMT of RPE cells. Silencing of Mgat5 by siRNA and CRISPR-Cas9 genome editing resulted in reduced Gal-3 binding. We conclude from these data that binding of recombinant Gal-3 to the RPE cell surface and inhibitory effects on RPE attachment and spreading largely dependent on interaction with Mgat5 modified N-glycans, which are more abundant on dedifferentiated than on the healthy, native RPE cells. Based on these findings we hypothesize that EMT of RPE cells in vitro confers glycomic changes, which account for high affinity binding of recombinant Gal-3, particularly to the cell surface of myofibroblastic RPE. From a future perspective recombinant Gal-3 may disclose a

  17. Tick-susceptible Bos taurus cattle display an increased cellular response at the site of larval Rhipicephalus (Boophilus) microplus attachment, compared with tick-resistant Bos indicus cattle.

    PubMed

    Piper, Emily K; Jackson, Louise A; Bielefeldt-Ohmann, Helle; Gondro, Cedric; Lew-Tabor, Ala E; Jonsson, Nicholas N

    2010-03-15

    Cattle demonstrate divergent and heritable phenotypes of resistance and susceptibility to infestation with the cattle tick Rhipicephalus (Boophilus) microplus. Bos indicus cattle are generally more resistant to tick infestation than Bos taurus breeds although large variations in resistance can occur within subspecies and within breed. Increased tick resistance has been previously associated with an intense hypersensitivity response in B. taurus breeds; however, the mechanism by which highly resistant B. indicus cattle acquire and sustain high levels of tick resistance remains to be elucidated. Using the commercially available Affymetrix microarray gene expression platform, together with histological examination of the larval attachment site, this study aimed to describe those processes responsible for high levels of tick resistance in Brahman (B. indicus) cattle that differ from those in low-resistance Holstein-Friesian (B. taurus) cattle. We found that genes involved in inflammatory processes and immune responsiveness to infestation by ticks, although up-regulated in tick-infested Holstein-Friesian cattle, were not up-regulated in Brahman cattle. In contrast, genes encoding constituents of the extracellular matrix were up-regulated in Brahmans. Furthermore, the susceptible Holstein-Friesian animals displayed a much greater cellular inflammatory response at the site of larval R. microplus attachment compared with the tick-resistant Brahman cattle. PMID:19852965

  18. Overlap of genetic susceptibility to type 1 diabetes, type 2 diabetes, and latent autoimmune diabetes in adults.

    PubMed

    Basile, Kevin J; Guy, Vanessa C; Schwartz, Stanley; Grant, Struan F A

    2014-01-01

    Despite the notion that there is a degree of commonality to the biological etiology of type 1 diabetes (T1D) and type 2 diabetes (T2D), the lack of overlap in the genetic factors underpinning each of them suggests very distinct mechanisms. A disorder considered to be at the "intersection" of these two diseases is "latent autoimmune diabetes in adults" (LADA). Interestingly, genetic signals from both T1D and T2D are also seen in LADA, including the key HLA and transcription factor 7-like 2 (TCF7L2) loci, but the magnitudes of these effects are more complex than just pointing to LADA as being a simple admixture of T1D and T2D. We review the current status of the understanding of the genetics of LADA and place it in the context of what is known about the genetics of its better-studied "cousins," T1D and T2D, especially with respect to the myriad of discoveries made over the last decade through genome-wide association studies.

  19. Piezotolerant Small-Colony Variants with Increased Thermotolerance, Antibiotic Susceptibility, and Low Invasiveness in a Clonal Staphylococcus aureus Population▿

    PubMed Central

    Karatzas, Kimon A. G.; Zervos, Angelos; Tassou, Chrysoula C.; Mallidis, Costas G.; Humphrey, Tom J.

    2007-01-01

    Following a pressure treatment of a clonal Staphylococcus aureus culture with 400 MPa for 30 min, piezotolerant variants were isolated. Among 21 randomly selected survivors, 9 were piezotolerant and all formed small colonies on several agar media. The majority of the isolates showed increased thermotolerance, impaired growth, and reduced antibiotic resistance compared to the wild type. However, several nonpiezotolerant isolates also demonstrated impaired growth and the small-colony phenotype. In agglutination tests for the detection of protein A and fibrinogen, the piezotolerant variants showed weaker agglutination reactions than the wild type and the other isolates. All variants also showed defective production of the typical S. aureus golden color, a characteristic which has previously been linked with virulence. They were also less able to invade intestinal epithelial cells than the wild type. These S. aureus variants showed phenotypic similarities to previously isolated Listeria monocytogenes piezotolerant mutants that contained mutations in ctsR. Because of these similarities, possible alterations in the ctsR hypermutable regions of the S. aureus variants were investigated through amplified fragment length polymorphism analysis. No mutations were identified, and subsequently we sequenced the ctsR and hrcA genes of three representative variants, finding no mutations. This work demonstrates that S. aureus probably possesses a strategy resulting in an abundance of multiple-stress-resistant variants within clonal populations. This strategy, however, seems to involve genes and regulatory mechanisms different from those previously reported for L. monocytogenes. We are in the process of identifying these mechanisms. PMID:17259364

  20. Corticospinal Motor Neurons Are Susceptible to Increased ER Stress and Display Profound Degeneration in the Absence of UCHL1 Function

    PubMed Central

    Jara, Javier H.; Genç, Barış; Cox, Gregory A.; Bohn, Martha C.; Roos, Raymond P.; Macklis, Jeffrey D.; Ulupınar, Emel; Özdinler, P. Hande

    2015-01-01

    Corticospinal motor neurons (CSMN) receive, integrate, and relay cerebral cortex's input toward spinal targets to initiate and modulate voluntary movement. CSMN degeneration is central for numerous motor neuron disorders and neurodegenerative diseases. Previously, 5 patients with mutations in the ubiquitin carboxy-terminal hydrolase-L1 (UCHL1) gene were reported to have neurodegeneration and motor neuron dysfunction with upper motor neuron involvement. To investigate the role of UCHL1 on CSMN health and stability, we used both in vivo and in vitro approaches, and took advantage of the Uchl1nm3419 (UCHL1−/−) mice, which lack all UCHL1 function. We report a unique role of UCHL1 in maintaining CSMN viability and cellular integrity. CSMN show early, selective, progressive, and profound cell loss in the absence of UCHL1. CSMN degeneration, evident even at pre-symptomatic stages by disintegration of the apical dendrite and spine loss, is mediated via increased ER stress. These findings bring a novel understanding to the basis of CSMN vulnerability, and suggest UCHL1−/− mice as a tool to study CSMN pathology. PMID:25596590

  1. Neuroinflammation mediated by IL-1β increases susceptibility of dopamine neurons to degeneration in an animal model of Parkinson's disease

    PubMed Central

    Koprich, James B; Reske-Nielsen, Casper; Mithal, Prabhakar; Isacson, Ole

    2008-01-01

    Background The etiology of Parkinson's disease (PD) remains elusive despite identification of several genetic mutations. It is more likely that multiple factors converge to give rise to PD than any single cause. Here we report that inflammation can trigger degeneration of dopamine (DA) neurons in an animal model of Parkinson's disease. Methods We examined the effects of inflammation on the progressive 6-OHDA rat model of Parkinson's disease using immunohistochemistry, multiplex ELISA, and cell counting stereology. Results We show that a non-toxic dose of lipopolysaccharide (LPS) induced secretion of cytokines and predisposed DA neurons to be more vulnerable to a subsequent low dose of 6-hydroxydopamine. Alterations in cytokines, prominently an increase in interleukin-1beta (IL-1β), were identified as being potential mediators of this effect that was associated with activation of microglia. Administration of an interleukin-1 receptor antagonist resulted in significant reductions in tumor necrosis factor-α and interferon-γ and attenuated the augmented loss of DA neurons caused by the LPS-induced sensitization to dopaminergic degeneration. Conclusion These data provide insight into the etiology of PD and support a role for inflammation as a risk factor for the development of neurodegenerative disease. PMID:18304357

  2. The ironic effect of guessing: increased false memory for mediated lists in younger and older adults

    PubMed Central

    Coane, Jennifer H.; Huff, Mark J.; Hutchison, Keith A.

    2016-01-01

    Younger and older adults studied lists of words directly (e.g., creek, water) or indirectly (e.g., beaver, faucet) related to a nonpresented critical lure (CL; e.g., river). Indirect (i.e., mediated) lists presented items that were only related to CLs through nonpresented mediators (i.e., directly related items). Following study, participants completed a condition-specific task, math, a recall test with or without a warning about the CL, or tried to guess the CL. On a final recognition test, warnings (vs. math and recall without warning) decreased false recognition for direct lists, and guessing increased mediated false recognition (an ironic effect of guessing) in both age groups. The observed age-invariance of the ironic effect of guessing suggests that processes involved in mediated false memory are preserved in aging and confirms the effect is largely due to activation in semantic networks during encoding and to the strengthening of these networks during the interpolated tasks. PMID:26393390

  3. How does increasingly plainer cigarette packaging influence adult smokers’ perceptions about brand image? An experimental study

    PubMed Central

    Wakefield, M A; Germain, D; Durkin, S J

    2008-01-01

    Background: Cigarette packaging is a key marketing strategy for promoting brand image. Plain packaging has been proposed to limit brand image, but tobacco companies would resist removal of branding design elements. Method: A 3 (brand types) × 4 (degree of plain packaging) between-subject experimental design was used, using an internet online method, to expose 813 adult Australian smokers to one randomly selected cigarette pack, after which respondents completed ratings of the pack. Results: Compared with current cigarette packs with full branding, cigarette packs that displayed progressively fewer branding design elements were perceived increasingly unfavourably in terms of smokers’ appraisals of the packs, the smokers who might smoke such packs, and the inferred experience of smoking a cigarette from these packs. For example, cardboard brown packs with the number of enclosed cigarettes displayed on the front of the pack and featuring only the brand name in small standard font at the bottom of the pack face were rated as significantly less attractive and popular than original branded packs. Smokers of these plain packs were rated as significantly less trendy/stylish, less sociable/outgoing and less mature than smokers of the original pack. Compared with original packs, smokers inferred that cigarettes from these plain packs would be less rich in tobacco, less satisfying and of lower quality tobacco. Conclusion: Plain packaging policies that remove most brand design elements are likely to be most successful in removing cigarette brand image associations. PMID:18827035

  4. Low birth weight may increase body fat mass in adult women with polycystic ovarian syndrome

    PubMed Central

    Minooee, Sonia; Ramezani Tehrani, Fahimeh; Mirmiran, Parvin; Azizi, Fereidoun

    2016-01-01

    Background: Women engaged with polycystic ovarian syndrome (PCOS), as the commonest endocrine disorder, are known to have a specific type of adiposity. Birth weight is among different contributors reported to be responsible for this diversity. Objective: We aimed to compare the relation between birth weight and body fat mass (BFM)/ body lean mass (BLM) in PCOS and their age and body mass index (BMI) matched normal controls. Materials and Methods: In this case-control study, a total number of 70 reproductive aged women, diagnosed with PCOS and 70 age- BMI matched healthy women without hirsutism and/or ovulatory dysfunction were recruited., control group had no polycystic ovaries in ultrasonographic scans. A detailed history of birth weight was taken and was divided into the following categories: <2,500 (low birth weight, LBW) and 2,500-4,000 (normal birth weight; NBW). Results: Results showed that LBW prevalence was higher in women with PCOS than in controls (19.3% (27) vs. 15.7% (22)). Also body fat and lean mass (BFM, BLM) have increased in adult women with PCOS who were born underweight compared to their normal (19.8±9.05 vs. 12.9±4.5, p=0.001 and 48.9±6.9 vs. 43.2±5.8, p=0.004 respectively). Conclusion: Fetal birth weight influences on the adulthood obesity, BFM and BLM. This impact is different among women with and without PCOS. PMID:27326419

  5. Myocardial infarction induces cognitive impairment by increasing the production of hydrogen peroxide in adult rat hippocampus.

    PubMed

    Liu, Chunhua; Liu, Ye; Yang, Zhuo

    2014-02-01

    Accumulating clinical evidence has shown a causal relationship between heart diseases and cognitive impairment in clinical, but the underlying mechanism remains unclear. In this study, rats with myocardial infarction (MI) were used to investigate cognition-related synaptic function and proteins. Adult male Wistar rats were subjected to MI by ligating of left anterior descending artery (LAD) and the infarct size of rat heart was measured by 2,3,5-triphenyltetrazoium chloride (TTC) staining. In this study, results showed that compared with control group, long-term potentiation was suppressed in dentate gyrus area, the contents of hydrogen peroxide (H2O2) and malondialdehyde were significantly increased, whereas the Cu/Zn-superoxide dismutase activity and N-methyl-d-aspartate receptor subunit 2B were attenuated in hippocampus of MI rats. Interestingly, it was observed that the PI3K/Akt pathway was activated in MI rats. Therefore, this study suggests that H2O2 plays an important role in cognitive dysfunction induced by MI.

  6. Comparison of Outcomes among Adult Patients with Nosocomial Bacteremia Caused by Methicillin-Susceptible and Methicillin-Resistant Staphylococcus aureus: A Retrospective Cohort Study

    PubMed Central

    Wang, Jann-Tay; Hsu, Le-Yin; Lauderdale, Tsai-Ling; Fan, Wen-Chien; Wang, Fu-Der

    2015-01-01

    Several studies have shown that patients with bacteremia caused by methicillin-resistant Staphylococcus aureus (MRSA) have worse outcomes than those with bacteremia caused by methicillin-susceptible S. aureus (MSSA). However, only a limited number of studies have stratified the MRSA isolates into healthcare-associated (HA-) and community-associated (CA-) MRSA strains in such a comparison. This three-year retrospective cohort study, enrolling adult patients with nosocomial S. aureus bacteremia (SAB), was designed to investigate whether CA-MRSA and/or HA-MRSA strains were associated with different outcomes in comparison to MSSA in such a setting. The drug susceptibilities and staphylococcal cassette chromosome mec (SCCmec) types were determined for all of the causative isolates available. The MRSA bacteremia was further categorized into those caused by CA-MRSA strains (CA-MRSA-S bacteremia) when the causative isolates carried the type IV or V SCCmec element, those caused by HA-MRSA strains (HA-MRSA-S bacteremia) when the isolates carried the type I, II, or III SCCmec element, or unclassified MRSA bacteremia when the isolates were not available. The relevant demographic, clinical, and laboratory data were collected by reviewing the patients’ charts. The primary outcome was all-cause in-hospital mortality. A total of 353 patients were studied. The overall in-hospital mortality rate was 32.6%, with 23.3% in MSSA, 30.5% in CA-MRSA-S, 47.5% in HA-MRSA-S, and 35.3% in unclassified MRSA bacteremia, respectively. The multivariate analysis showed that HA-MRSA-S, but not CA-MRSA-S, bacteremia was associated with a significantly worse outcome compared with MSSA. The other risk factors independently associated with all-cause in-hospital mortality included the Charlson co-morbidity index, septic shock, thrombocytopenia, and persistent bacteremia. Resistance to linezolid and daptomycin was found among the MRSA isolates. The present study showed that bacteremia caused by HA

  7. Augmented oxygen-mediated transcriptional activation of cytochrome P450 (CYP)1A expression and increased susceptibilities to hyperoxic lung injury in transgenic mice carrying the human CYP1A1 or mouse 1A2 promoter in vivo.

    PubMed

    Jiang, Weiwu; Couroucli, Xanthi I; Wang, Lihua; Barrios, Roberto; Moorthy, Bhagavatula

    2011-04-01

    Supplemental oxygen administration is frequently administered to pre-term and term infants having pulmonary insufficiency. However, hyperoxia contributes to the development of bronchopulmonary dysplasia (BPD) in premature infants. Cytochrome P450 (CYP)A enzymes have been implicated in hyperoxic lung injury. In this study, we tested the hypothesis that hyperoxia induces CYP1A1 and 1A2 enzymes by transcriptional activation of the corresponding promoters in vivo, and transgenic mice expressing the human CYP1A1 or the mouse 1A2 promoter would be more susceptible to hyperoxic lung injury than wild type (WT) mice. Adult WT (CD-1) (12week-old) mice, transgenic mice carrying a 10kb human CYP1A1 promoter and the luciferase (luc) reporter gene (CYP1A1-luc), or mice expressing the mouse CYP1A2 promoter (CYP1A2-luc) were maintained in room air or exposed to hyperoxia for 24-72h. Hyperoxia exposure of CYP1A1-luc mice for 24 and 48h resulted in 2.5- and 1.25-fold increases, respectively, in signal intensities, compared to room air controls. By 72h, the induction had declined to control levels. CYP1A2-luc mice also showed enhanced luc expression after 24-48h, albeit to a lesser extent than those expressing the CYP1A1 promoter. Also, these mice showed decreased levels of endogenous CYP1A1 and 1A2 expression after prolonged hyperoxia, and were also more susceptible to lung injury than similarly exposed WT mice, with CYP1A2-luc mice showing the greatest injury. Our results support the hypothesis that hyperoxia induces CYP1A enzymes by transcriptional activation of its corresponding promoters, and that decreased endogenous expression of these enzymes contribute to the increased susceptibilities to hyperoxic lung injury in the transgenic animals. In summary, this is the first report providing direct evidence of hyperoxia-mediated induction of CYP1A1 and CYP1A2 expression in vivo by mechanisms entailing transcriptional activation of the corresponding promoters, a phenomenon that has

  8. Susceptibility of juvenile and adult blood–brain barrier to endothelin-1: regulation of P-glycoprotein and breast cancer resistance protein expression and transport activity

    PubMed Central

    2012-01-01

    significant increase of the activity of both transporters was evidenced at the BBB in the adult brain. Moreover, juvenile and adult brain showed differences in their expression profiles of cytokines and chemokines mediated by ET-1. Conclusions BBB transporter activity during neuroinflammation differs between the juvenile and adult brains. These findings emphasize the importance of considering differential P-gp and BCRP transport regulation mechanisms between adult and juvenile BBB in the context of neuroinflammation. PMID:23253775

  9. Increased presence of capillaries next to remodeling sites in adult human cancellous bone.

    PubMed

    Kristensen, Helene Bjoerg; Andersen, Thomas Levin; Marcussen, Niels; Rolighed, Lars; Delaisse, Jean-Marie

    2013-03-01

    Vascularization is a prerequisite for osteogenesis in a number of situations, including bone development, fracture healing, and cortical bone remodeling. It is unknown whether a similar link exists between cancellous bone remodeling and vascularization. Here, we show an association between remodeling sites, capillaries, proliferative cells, and putative osteoblast progenitors. Iliac crest biopsies from normal human individuals were subjected to histomorphometry and immunohistochemistry to identify the respective positions of bone remodeling sites, CD34-positive capillaries, smooth muscle actin (SMA)-positive putative osteoblast progenitors, including pericytes, Ki67-positive proliferative cells, and bone remodeling compartment (BRC) canopies. The BRC canopy is a recently described structure separating remodeling sites from the bone marrow, consisting of CD56-positive osteoblasts at an early differentiation stage. We found that bone remodeling sites were associated with a significantly increased presence of capillaries, putative osteoblast progenitors, and proliferative cells in a region within 50 µm of the bone or the canopy surface. The increases were the highest above eroded surfaces and at the level of the light-microscopically assessed contact of these three entities with the bone or canopy surfaces. Between 51 and 100 µm, their densities leveled to that found above quiescent surfaces. Electron microscopy asserted the close proximity between BRC canopies and capillaries lined by pericytes. Furthermore, the BRC canopy cells were found to express SMA. These ordered distributions support the existence of an osteogenic-vascular interface in adult human cancellous bone. The organization of this interface fits the current knowledge on the mode of action of vasculature on osteogenesis, and points to the BRC canopy as a central player in this mechanism. We propose a model where initiation of bone remodeling coincides with the induction of proximity of the

  10. The Utilization of an iPad for Increasing Work-Related Behaviors in Adults with Disabilities

    ERIC Educational Resources Information Center

    Jones, Sarah; Bucholz, Jessica L.

    2014-01-01

    The purpose of this study was to investigate the effectiveness of an iPad to increase work related behaviors for one adult with disabilities in a vocational setting. A multiple baseline across behaviors single subject research design was used to determine if an iPad helped to increase independence in three identified behaviors, which included…

  11. AGING AND SUSCEPTIBILITY TO TOLUENE IN RATS: A PHARMACOKINETIC, BIOMARKER, AND PHYSIOLOGICAL APPROACH.

    EPA Science Inventory

    Aging adults are a growing segment of the U.S. population and are likely to exhibit increased susceptibility to many environmental toxicants. However, there is little information on the susceptibility of the aged to toxicants. The toxicity of toluene has been well characterized i...

  12. Increased cellular apoptosis susceptibility (CSE1L/CAS) protein expression promotes protrusion extension and enhances migration of MCF-7 breast cancer cells

    SciTech Connect

    Tai, Cheng-Jeng; Shen, Shing-Chuan; Lee, Woan-Ruoh; Liao, Ching-Fong; Deng, Win-Ping; Chiou, Hung-Yi; Hsieh, Cheng-I; Tung, Jai-Nien; Chen, Ching-Shyang; Chiou, Jeng-Fong; Li, Li-Tzu; Lin, Chuang-Yu; Hsu, Chung-Huei; Jiang, Ming-Chung

    2010-10-15

    Microtubules are part of cell structures that play a role in regulating the migration of cancer cells. The cellular apoptosis susceptibility (CSE1L/CAS) protein is a microtubule-associated protein that is highly expressed in cancer. We report here that CSE1L regulates the association of {alpha}-tubulin with {beta}-tubulin and promotes the migration of MCF-7 breast cancer cells. CSE1L was associated with {alpha}-tubulin and {beta}-tubulin in GST (glutathione S-transferase) pull-down and immunoprecipitation assays. CSE1L-GFP (green fluorescence protein) fusion protein experiments showed that the N-terminal of CSE1L interacted with microtubules. Increased CSE1L expression resulted in decreased tyrosine phosphorylation of {alpha}-tubulin and {beta}-tubulin, increased {alpha}-tubulin and {beta}-tubulin association, and enhanced assembly of microtubules. Cell protrusions or pseudopodia are temporary extensions of the plasma membrane and are implicated in cancer cell migration and invasion. Increased CSE1L expression increased the extension of MCF-7 cell protrusions. In vitro migration assay showed that enhanced CSE1L expression increased the migration of MCF-7 cells. Our results indicate that CSE1L plays a role in regulating the extension of cell protrusions and promotes the migration of cancer cells.

  13. Honey bees (Apis mellifera) reared in brood combs containing high levels of pesticide residues exhibit increased susceptibility to Nosema (Microsporidia) infection.

    PubMed

    Wu, Judy Y; Smart, Matthew D; Anelli, Carol M; Sheppard, Walter S

    2012-03-01

    Nosema ceranae and pesticide exposure can contribute to honey bee health decline. Bees reared from brood comb containing high or low levels of pesticide residues were placed in two common colony environments. One colony was inoculated weekly with N. ceranae spores in sugar syrup and the other colony received sugar syrup only. Worker honey bees were sampled weekly from the treatment and control colonies and analyzed for Nosema spore levels. Regardless of the colony environment (spores+syrup added or syrup only added), a higher proportion of bees reared from the hig