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Sample records for increases adult susceptibility

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

    EPA Science Inventory

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

  2. Neonatal dexamethasone treatment increases susceptibility to experimental autoimmune disease in adult rats.

    PubMed

    Bakker, J M; Kavelaars, A; Kamphuis, P J; Cobelens, P M; van Vugt, H H; van Bel, F; Heijnen, C J

    2000-11-15

    Major concern has emerged about the possible long term adverse effects of glucocorticoid treatment, which is frequently used for the prevention of chronic lung disease in preterm infants. Here we show that neonatal glucocorticoid treatment of rats increases the severity (p< or = 0.01) and incidence (p< or =0.01) of the inflammatory autoimmune disease experimental autoimmune encephalomyelitis in adult life. In search of possible mechanisms responsible for the increased susceptibility to experimental autoimmune encephalomyelitis, we investigated the reactivity of the hypothalamo-pituitary-adrenal axis and of immune cells in adult rats after neonatal glucocorticoid treatment. We observed that neonatal glucocorticoid treatment reduces the corticosterone response after an LPS challenge in adult rats (p< or =0.001). Interestingly, LPS-stimulated macrophages of glucocorticoid-treated rats produce less TNF-alpha and IL-1beta in adult life than control rats (p<0.05). In addition, splenocytes obtained from adult rats express increased mRNA levels of the proinflammatory cytokines IFN-gamma (p<0.01) and TNF-beta (p<0.05) after neonatal glucocorticoid treatment. Apparently, neonatal glucocorticoid treatment has permanent programming effects on endocrine as well as immune functioning in adult life. In view of the frequent clinical application of glucocorticoids to preterm infants, our data demonstrate that neonatal glucocorticoid treatment may be a risk factor for the development of (auto)immune disease in man. PMID:11067955

  3. In utero and early life exposure to diesel exhaust air pollution increases adult susceptibility to heart failure in mice

    PubMed Central

    2013-01-01

    Background Fine particulate air pollution (PM2.5) is a global health concern, as exposure to PM2.5 has consistently been found to be associated with increased cardiovascular morbidity and mortality. Although adult exposure to traffic related PM2.5, which is largely derived from diesel exhaust (DE), has been associated with increased cardiac hypertrophy, there are limited investigations into the potential effect of in utero and early life exposure on adult susceptibility to heart disease. In this study, we investigate the effect of in utero and early life exposure to DE on adult susceptibility to heart failure. Methods Female C57BL/6 J mice were exposed to either filtered air (FA) or DE for 3 weeks (≈300 μg/m3 PM2.5 for 6 hours/day, 5 days/week) and then introduced to male breeders for timed matings. Female mice were exposed to either FA or DE throughout pregnancy and until offspring were 3 weeks of age. Offspring were then transferred to either FA or DE for an additional 8 weeks of exposure. At 12 weeks of age, male offspring underwent a baseline echocardiographic assessment, followed by a sham or transverse aortic constriction (TAC) surgery to induce pressure overload. Following sacrifice three weeks post surgery, ventricles were processed for histology to assess myocardial fibrosis and individual cardiomyocyte hypertrophy. mRNA from lung tissue was isolated to measure expression of inflammatory cytokines IL6 and TNFα. Results We observed that mice exposed to DE during in utero and early life development have significantly increased susceptibility to cardiac hypertrophy, systolic failure, myocardial fibrosis, and pulmonary congestion following TAC surgery compared to FA control, or adult DE exposed mice. In utero and early life DE exposure also strongly modified the inflammatory cytokine response in the adult lung. Conclusions We conclude that exposure to diesel exhaust air pollution during in utero and early life development in mice increases adult

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

    SciTech Connect

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

    2014-01-15

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

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

    PubMed 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

  6. Prenatal cocaine exposure increases heart susceptibility to ischaemia–reperfusion injury in adult male but not female rats

    PubMed Central

    Bae, Soochan; Gilbert, Raymond D; Ducsay, Charles A; Zhang, Lubo

    2005-01-01

    The present study tested the hypothesis that prenatal cocaine exposure differentially regulates heart susceptibility to ischaemia–reperfusion (I/R) injury in adult offspring male and female rats. Pregnant rats were administered intraperitoneally either saline or cocaine (15 mg kg−1) twice daily from day 15 to day 21 of gestational age. There were no differences in maternal weight gain and birth weight between the two groups. Hearts were isolated from 2-month-old male and female offspring and were subjected to I/R (25 min/60 min) in a Langendorff preparation. Preischaemic values of left ventricular (LV) function were the same between the saline control and cocaine-treated hearts for both male and female rats. Prenatal cocaine exposure significantly increased I/R-induced myocardial apoptosis and infarct size, and significantly attenuated the postischaemic recovery of LV function in adult male offspring. In contrast, cocaine did not affect I/R-induced injury and postischaemic recovery of LV function in the female hearts. There was a significant decrease in PKCɛ and phospho-PKCɛ levels in LV in the male, but not female, offspring exposed to cocaine before birth. These results suggest that prenatal cocaine exposure causes a sex-specific increase in heart susceptibility to I/R injury in adult male offspring, and the decreased PKCɛ gene expression in the male heart may play an important role. PMID:15677681

  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". PMID:24275070

  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. 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

    2015-01-01

    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

  11. The Aging Kidney: Increased Susceptibility to Nephrotoxicity

    PubMed Central

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

    2014-01-01

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

  12. Hyperglycemia Increases Susceptibility to Ischemic Necrosis

    PubMed Central

    Lévigne, D.; Tobalem, M.; Modarressi, A.; Pittet-Cuénod, B.

    2013-01-01

    Diabetic patients are at risk for spontaneous foot ulcers, chronic wounds, infections, and tissue necrosis. Current theories suggest that the development and progression of diabetic foot ulcers are mainly caused by arteriosclerosis and peripheral neuropathy. Tissue necrosis plays a primordial role in the progression of diabetic foot ulcers but the underlying mechanisms are poorly understood. The aim of the present study was to investigate the effects of hyperglycemia per se on the susceptibility of ischemic tissue to necrosis, using a critical ischemic hind limb animal model. We inflicted the same degree of ischemia in both euglycemic and streptozotocin-induced hyperglycemic rats by resecting the external iliac, the femoral, and the saphenous arteries. Postoperative laser Doppler flowmetry of the ischemic feet showed the same degree of reduction in skin perfusion in both hyperglycemic and euglycemic animals. Nevertheless, we found a significantly higher rate of limb necrosis in hyperglycemic rats compared to euglycemic rats (71% versus 29%, resp.). In this study, we revealed that hyperglycemia per se increases the susceptibility to limb necrosis in ischemic conditions. Our results may help to better understand the physiopathology of progressive diabetic wounds and underline the importance of strict glycemic control in patients with critical limb ischemia. PMID:23509730

  13. 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

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

    PubMed Central

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

    2015-01-01

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

  15. 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. PMID:24499279

  16. 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

  17. 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

  18. 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. PMID:24013632

  19. INCREASED SUSCEPTIBILITY TO PARATHION POISONING FOLLOWING MURINE CYTOMEGALOVIRUS INFECTION

    EPA Science Inventory

    Increased Susceptibility to Parathion Poisoning Following Murine Cytomegalovirus Infection. Fifty to 100 percent mortality occurred in mice treated with ordinarily sublethal doses of parathion 2 to 5 days post infection with murine cytomegalovirus (MCMV). These mortalities appear...

  20. Maternal immune activation increases seizure susceptibility in juvenile rat offspring.

    PubMed

    Yin, Ping; Zhang, Xin-Ting; Li, Jun; Yu, Lin; Wang, Ji-Wen; Lei, Ge-Fei; Sun, Ruo-Peng; Li, Bao-Min

    2015-06-01

    Epidemiological data suggest a relationship between maternal infection and a high incidence of childhood epilepsy in offspring. However, there is little experimental evidence that links maternal infection with later seizure susceptibility in juvenile offspring. Here, we asked whether maternal immune challenge during pregnancy can alter seizure susceptibility and seizure-associated brain damage in adolescence. Pregnant Sprague-Dawley rats were treated with lipopolysaccharide (LPS) or normal saline (NS) on gestational days 15 and 16. At postnatal day 21, seizure susceptibility to kainic acid (KA) was evaluated in male offspring. Four groups were studied, including normal control (NS-NS), prenatal infection (LPS-NS), juvenile seizure (NS-KA), and "two-hit" (LPS-KA) groups. Our results demonstrated that maternal LPS exposure caused long-term reactive astrogliosis and increased seizure susceptibility in juvenile rat offspring. Compared to the juvenile seizure group, animals in the "two-hit" group showed exaggerated astrogliosis, followed by worsened spatial learning ability in adulthood. In addition, prenatal immune challenge alone led to spatial learning impairment in offspring but had no effect on anxiety. These data suggest that prenatal immune challenge causes a long-term increase in juvenile seizure susceptibility and exacerbates seizure-induced brain injury, possibly by priming astroglia. PMID:25982885

  1. Placental ischemia increases seizure susceptibility and cerebrospinal fluid cytokines

    PubMed Central

    Warrington, Junie P

    2015-01-01

    Eclampsia is diagnosed in preeclamptic patients who develop unexplained seizures and/or coma during pregnancy or postpartum. Eclampsia is one of the leading causes of maternal and infant morbidity and mortality, accounting for ∼13% of maternal deaths worldwide. Little is known about the mechanisms contributing to the pathophysiology of eclampsia, partly due to the lack of suitable animal models. This study tested the hypothesis that placental ischemia, induced by reducing utero-placental perfusion, increases susceptibility to seizures, cerebrospinal fluid (CSF) inflammation, and neurokinin B (NKB) expression in brain and plasma. Pentylenetetrazol (PTZ), a pro-convulsive drug, was injected into pregnant and placental ischemic rats (40 mg/kg, i.p.) on gestational day 19 followed by video monitoring for 30 min. Seizure scoring was blindly conducted. Placental ischemia hastened the onset of seizures compared to pregnant controls but had no effect on seizure duration. Placental ischemia increased CSF levels of IL-2, IL-17, IL-18 and eotaxin (CCL11), had no effect on plasma NKB; however, PTZ increased plasma NKB in both pregnant and placental ischemic rats. NKB was strongly correlated with latency to seizure in normal pregnant rats (R2 = 0.88 vs. 0.02 in placental ischemic rats). Lastly, NKB decreased in the anterior cerebrum in response to placental ischemia and PTZ treatment but was unchanged in the posterior cerebrum. These data demonstrate that placental ischemia is associated with increased susceptibility to seizures and CSF inflammation; thus provides an excellent model for elucidating mechanisms of eclampsia-like symptoms. Further studies are required to determine the role of CSF cytokines/chemokines in mediating increased seizure susceptibility. PMID:26603461

  2. Placental ischemia increases seizure susceptibility and cerebrospinal fluid cytokines.

    PubMed

    Warrington, Junie P

    2015-11-01

    Eclampsia is diagnosed in preeclamptic patients who develop unexplained seizures and/or coma during pregnancy or postpartum. Eclampsia is one of the leading causes of maternal and infant morbidity and mortality, accounting for ~13% of maternal deaths worldwide. Little is known about the mechanisms contributing to the pathophysiology of eclampsia, partly due to the lack of suitable animal models. This study tested the hypothesis that placental ischemia, induced by reducing utero-placental perfusion, increases susceptibility to seizures, cerebrospinal fluid (CSF) inflammation, and neurokinin B (NKB) expression in brain and plasma. Pentylenetetrazol (PTZ), a pro-convulsive drug, was injected into pregnant and placental ischemic rats (40 mg/kg, i.p.) on gestational day 19 followed by video monitoring for 30 min. Seizure scoring was blindly conducted. Placental ischemia hastened the onset of seizures compared to pregnant controls but had no effect on seizure duration. Placental ischemia increased CSF levels of IL-2, IL-17, IL-18 and eotaxin (CCL11), had no effect on plasma NKB; however, PTZ increased plasma NKB in both pregnant and placental ischemic rats. NKB was strongly correlated with latency to seizure in normal pregnant rats (R(2) = 0.88 vs. 0.02 in placental ischemic rats). Lastly, NKB decreased in the anterior cerebrum in response to placental ischemia and PTZ treatment but was unchanged in the posterior cerebrum. These data demonstrate that placental ischemia is associated with increased susceptibility to seizures and CSF inflammation; thus provides an excellent model for elucidating mechanisms of eclampsia-like symptoms. Further studies are required to determine the role of CSF cytokines/chemokines in mediating increased seizure susceptibility. PMID:26603461

  3. The mechanism of increased renal susceptibility to toxic substances in the elderly. Part I. The role of increased vasoconstriction.

    PubMed

    Jerkić, M; Vojvodić, S; López-Novoa, J M

    2001-01-01

    The mechanisms of increased susceptibility to nephrotoxins in aging are complex and incompletely understood. It is very important to try to increase our knowledge of them because adults become increasingly vulnerable to nephrotoxic substances, as they grow older. In addition, the percentage of elderly people will increase markedly in the near future, at least in the developed countries. Drugs such as diuretics, laxatives, NSAIDs, aminoglycosides and other nephrotoxic antibiotics, and converting enzyme inhibitors are used a lot by aging people and can produce severe renal problems. Beside drugs, the clinical use of radiocontrast agents also rises in older patients. It seems that the main mechanism of the increased renal susceptibility to toxic substances in the elderly is a disbalance between vasoconstrictor and vasodilator factors (in favor of vasoconstrictor ones). Increased propensity to vasoconstriction (to Ang II, ET and PAF), as well as increased levels of oxidatively modified biomolecules in the elderly, may enhance susceptibility of old kidney to toxic substances. In addition, all mechanisms that influence both mesangial and fibroblast cell proliferation and over-production of extracellular matrix might also be involved in the processes that make the old kidney prone to drug-induced chronic toxic injury. PMID:11989542

  4. 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.

  5. 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

  6. Asthma Increases Susceptibility to Heterologous but Not Homologous Secondary Influenza

    PubMed Central

    Furuya, Yoichi; Roberts, Sean; Hurteau, Gregory J.; Sanfilippo, Alan M.; Racine, Rachael

    2014-01-01

    ABSTRACT Asthma was the most common comorbidity observed among patients hospitalized with influenza A virus during the 2009 pandemic. However, little remains known about how the asthmatic phenotype influences protective immune responses against respiratory viral pathogens. Using the ovalbumin-induced allergic lung inflammation model, we found that asthmatic mice, unlike nonasthmatic mice, were highly susceptible to secondary heterologous virus challenge. While primary virus infection generated protective memory immune responses against homologous secondary virus challenge in both asthmatic and nonasthmatic mice, full protection against heterologous A/California/04/2009 (CA04) viral infection was observed only in nonasthmatic mice. Significant reductions in CA04-specific IgA, IgG, and IgM levels and in CA04-neutralizing activity of bronchoalveolar lavage fluid (BALF) was observed following secondary CA04 challenge of PR8-immunized asthmatic mice. Furthermore, transfer of immune BALF obtained from nonasthmatic, but not asthmatic, donors following secondary viral infection generated protection against CA04 in naive recipients. Nonspecific B-cell activation by CpG inoculation restored protection in PR8-immunized, CA04-challenged asthmatic mice. These results demonstrate a causal link between defective mucosal antibody responses and the heightened susceptibility of asthmatic mice to influenza infection and provide a mechanistic explanation for the observation that asthma was a major risk factor during the 2009 influenza pandemic. IMPORTANCE The prevalence of asthma worldwide is increasing each year. Unfortunately, there is no cure for asthma. Asthmatic individuals not only suffer from consistent wheezing and coughing but are also believed to be more prone to serious lung infections that result in bronchitis and pneumonia. However, little is known about the influence of asthma on host mucosal immunity. Here we show that antibody responses during secondary heterologous

  7. Gender-related differences in susceptibility to oxidative stress in healthy middle-aged Serbian adults.

    PubMed

    Topic, Aleksandra; Malic, Zivka; Francuski, Djordje; Stankovic, Marija; Markovic, Bojan; Soskic, Blagoje; Tomic, Branko; Ilic, Stefan; Dobrivojevic, Snezana; Drca, Sanja; Radojkovic, Dragica

    2016-03-01

    Gender-related differences in the association between polymorphism of xenobiotic-metabolising enzymes or non-genetic biomarkers and susceptibility to oxidative stress was assessed in healthy middle-aged Serbian adults, by urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG/creatinine) and total antioxidant status in serum (TAOS). Females were more susceptible to oxidative stress. In both genders, positive predictor of the antioxidative protection was serum triglyceride, while BMI <25 kg/m(2) was associated with oxidative stress. Susceptibility to oxidative stress in males was associated with GSTT1*null allele and increased serum iron, but in females, it was decreased serum bilirubin. Early identification of the risk factors could be important in the prevention of oxidative stress-related diseases. PMID:26754535

  8. Dysferlin deficiency confers increased susceptibility to coxsackievirus-induced cardiomyopathy.

    PubMed

    Wang, Chen; Wong, Jerry; Fung, Gabriel; Shi, Junyan; Deng, Haoyu; Zhang, Jingchun; Bernatchez, Pascal; Luo, Honglin

    2015-10-01

    Coxsackievirus infection can lead to viral myocarditis and its sequela, dilated cardiomyopathy, which represent major causes of cardiovascular mortality worldwide in children. Yet, the host genetic susceptible factors and the underlying mechanisms by which viral infection damages cardiac function remain to be fully resolved. Dysferlin is a transmembrane protein highly expressed in skeletal and cardiac muscles. In humans, mutations in the dysferlin gene can cause limb-girdle muscular dystrophy type 2B and Miyoshi myopathy. Dysferlin deficiency has also been linked to cardiomyopathy. Defective muscle membrane repair has been suggested to be an important mechanism responsible for muscle degeneration in dysferlin-deficient patients and animals. Using both naturally occurring and genetically engineered dysferlin-deficient mice, we demonstrated that loss of dysferlin confers increased susceptibility to coxsackievirus infection and myocardial damage. More interestingly, we found that dysferlin is cleaved following coxsackieviral infection through the proteolytic activity of virally encoded proteinases, suggesting an important mechanism underlying virus-induced cardiac dysfunction. Our results in this study not only identify dysferlin deficiency as a novel host risk factor for viral myocarditis but also reveal a key mechanism by which coxsackievirus infection impairs cardiac function, leading to the development of dilated cardiomyopathy. PMID:26073173

  9. Ozone increases susceptibility to antigen inhalation in allergic dogs

    SciTech Connect

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

    1990-06-01

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

  10. 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

  11. 5-Lipoxygenase Activity Increases Susceptibility to Experimental Paracoccidioides brasiliensis Infection

    PubMed Central

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

    2013-01-01

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

  12. 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. PMID:23237369

  13. 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

  14. 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

  15. 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. PMID:25541383

  16. 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

  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. 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 ...

  19. Increased LDL susceptibility to oxidation accelerates future carotid artery atherosclerosis

    PubMed Central

    2012-01-01

    Background We analyzed the causal relationship between LDL susceptibility to oxidation and the development of new carotid artery atherosclerosis over a period of 5 years. We previously described the determinants related to a risk of cardiovascular changes determined in a Japanese population participating in the Niigata Study, which is an ongoing epidemiological investigation of the prevention of cardiovascular diseases. Methods We selected 394 individuals (169 males and 225 females) who underwent a second carotid artery ultrasonographic examination in 2001 - 2002 for the present study. The susceptibility of LDL to oxidation was determined as the photometric absorbance and electrophoretic mobility of samples that had been collected in 1996 - 1997. The measurements were compared with ultrasonographic findings obtained in 2001 - 2002. Results The multivariate-adjusted model showed that age (odds ratio (OR), 1.034; 95% confidence interval (95%CI), 1.010 - 1.059), HbA1c (OR, 1.477; 95%CI, 0.980 - 2.225), and photometric O/N (OR, 2.012; 95%CI, 1.000 - 4.051) were significant variables that could independently predict the risk of new carotid artery atherosclerosis. Conclusion The susceptibility of LDL to oxidation was a significant parameter that could predict new carotid artery atherosclerosis over a 5-year period, and higher susceptibility was associated with a higher incidence of new carotid artery atherosclerosis. PMID:22230558

  20. 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

  1. 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. PMID:24371444

  2. 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

  3. Quantitative susceptibility mapping of striatum in children and adults, and its association with working memory performance.

    PubMed

    Darki, Fahimeh; Nemmi, Federico; Möller, Annie; Sitnikov, Rouslan; Klingberg, Torkel

    2016-08-01

    Quantitative susceptibility mapping (QSM) is a magnetic resonance imaging (MRI) technique in which the magnetic susceptibility characteristic of molecular and cellular components, including iron and myelin, is quantified. Rapid iron accumulation in subcortical nuclei and myelination of the white matter tracts are two important developmental processes that contribute to cognitive functions. Both also contribute to the magnetic susceptibility of the brain tissues. Here, we used the QSM as indirect measures of iron in subcortical nuclei and myelin in caudo-frontal white matter pathways. We included two groups of participants; 21 children aged 6-7years and 25 adults aged 21-40years. All subjects also performed tests estimating their visuo-spatial working memory capacity. Adults had higher magnetic susceptibility in all subcortical nuclei, compared to children. The magnetic susceptibility of these nuclei highly correlated with their previously reported iron content. Moreover, working memory performance correlated significantly with the magnetic susceptibility in caudate nucleus in both children and adults, while the correlation was not significant for gray matter density. QSM of white matter in the caudo-frontal tract also differed between children and adults, but did not correlate with working memory scores. These results indicate that QSM is a feasible technique to measure developmental aspects of changes in the striatum, possibly related to iron content that is relevant to cognition. PMID:27132546

  4. 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. PMID:26341562

  5. 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

  6. Low maternal care exacerbates adult stress susceptibility in the chronic mild stress rat model of depression.

    PubMed

    Henningsen, Kim; Dyrvig, Mads; Bouzinova, Elena V; Christiansen, Sofie; Christensen, Trine; Andreasen, Jesper T; Palme, Rupert; Lichota, Jacek; Wiborg, Ove

    2012-12-01

    In the present study we report the finding that the quality of maternal care, in early life, increased the susceptibility to stress exposure in adulthood, when rats were exposed to the chronic mild stress paradigm. Our results indicate that high, as opposed to low maternal care, predisposed rats to a differential stress-coping ability. Thus rats fostered by low maternal care dams became more prone to adopt a stress-susceptible phenotype developing an anhedonic-like condition. Moreover, low maternal care offspring had lower weight gain and lower locomotion, with no additive effect of stress. Subchronic exposure to chronic mild stress induced an increase in faecal corticosterone metabolites, which was only significant in rats from low maternal care dams. Examination of glucocorticoid receptor exon 17 promoter methylation in unchallenged adult, maternally characterized rats, showed an insignificant tendency towards higher total cytosine methylation in rats from low maternal care dams. Assessment of methylation in the resilient versus anhedonic-like rat phenotypes, revealed only minor differences. Thus, maternal care status seems to be a strong predictor or trait marker for the behavioural phenotype. PMID:23075705

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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…

  12. Bipolar risk and mental imagery susceptibility in a representative sample of Chinese adults residing in the community

    PubMed Central

    Ng, Roger Man-kin; Heyes, Stephanie Burnett; McManus, Freda; Kennerley, Helen; Holmes, Emily A

    2016-01-01

    Background: We need to better understand the cognitive factors associated with risk for bipolar disorders. Recent research suggests that increased susceptibility to mental imagery may be one such factor. However, since this research was primarily conducted with Western students and at a single time-point, it is not known whether the relationship between imagery susceptibility and bipolar symptoms exists across cultures or within the general community, or whether this relationship remains stable over time. Aim: This study evaluated whether Chinese adults identified as being at high (HR) versus low (LR) risk of developing bipolar disorders showed greater mental imagery susceptibility. We aimed to test whether such a relationship was stable over time by measuring imagery characteristics at baseline and at the 7-week follow-up. Method: This prospective study recruited a community sample of N = 80 Chinese adults screened for the absence of neurotic and psychotic disorders. The sample was split into HR (n = 18) and LR (n = 62) groups at baseline based on a criterion cut-off score on a measure of hypomania, the Mood Disorder Questionnaire (MDQ). Participants completed measures of imagery susceptibility and its impact: the Spontaneous Use of Imagery Scale (SUIS) and the Impact of Future Events Scale (IFES), at baseline and 7 weeks later. Results: HR group reported greater tendency to use imagery in daily life (SUIS) and greater emotional impact of prospective imagery (IFES) than LR group at baseline. These results remained stable at follow-up. Conclusion: This study provides preliminary evidence for increased susceptibility to mental imagery in individuals at high risk of bipolar disorders recruited from a community sample of Chinese adults. This extends previous research in Western student samples suggesting that imagery (both levels of use and its emotional impact) may be a cognitive factor with cross-cultural relevance that is stable over time. PMID:26271252

  13. 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

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

    PubMed Central

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

    2016-01-01

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

  15. 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

  16. Deltamethrin Increases Candida albicans infection susceptibility in mice.

    PubMed

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

    2011-05-01

    Deltamethrin, an alpha-cyano type II synthetic pyrethroid insecticide, is used to control a wide range of insects on a variety of crops and vectors of diseases. Deltamethrin has been previously reported for its immunotoxic effects and therefore its exposure may affect the host resistance to infection and tumour challenge. Effect of exposure of deltamethrin on host resistance to Candida albicans infection was examined in Swiss albino mice. The objective of this study was to investigate the modulatory action of deltamethrin in C. albicans infected mice. The dose of deltamethrin was initially tested and selected from our previous study (18 mg/kg). Percentage of infection in deltamethrin treated animals increased faster when compared to that of the controls. Deltamethrin exposure along with C. albicans infection caused alteration of humoral immune response. The number of colony forming unit in liver and spleen were also found to be significantly increased in the treated group. The results from our present study suggest that deltamethrin exhibits an immunosuppressive effect and has a negative impact on host resistance to C. albicans infection. PMID:21272049

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

    PubMed

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

    2005-01-01

    We have previously shown that P11-20 treatment with d-methamphetamine (MA) induces impaired spatial navigation in the Morris water maze (MWM), whereas P1-10 treatment does not. Little is known about the long-term behavioral consequences of MA during juvenile, adolescent, and early adult brain development. In dose-response experiments, we tested successive 10-day intervals of exposure to MA in rats (P21-30, P31-40, P41-50, and P51-60; four doses per day). MA dosing prior to P21 produces little or no toxicity; however, we observed an increased toxicity with advancing age. Across-age comparisons revealed no MWM acquisition or Cincinnati water maze (CWM) effects after MA treatment on P21-30 (2.5-10 mg/kg/dose), P31-40 (1.25-7.5 mg/kg/dose), or P51-60 (1.25-5.0 mg/kg/dose); however, significantly impaired MWM acquisition was observed after P41-50 MA treatment at the highest dose (6.25 mg/kg/dose). Learning in the CWM was also impaired in this group. No effects were seen at 1.25, 2.5, or 5 mg/kg/dose following P41-50 MA treatment. MWM reversal learning trials after P41-50 treatment showed a trend towards longer latency in all MA dose groups, but no effect on double-reversal trials. Reversal and double-reversal also showed no effects at the other exposure ages. No differences in straight channel swimming or cued learning in the MWM were seen after MA treatment at any exposure age. P41-50 is the periadolescent stage of brain development in rodents. The effects observed at this age may suggest a previously unrecognized period of susceptibility for MA-induced cognitive deficits. PMID:15681126

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

    PubMed Central

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

    2010-01-01

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

  19. 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…

  20. 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. PMID:26100658

  1. PRENATAL TCDD IN MICE INCREASES ADULT AUTOIMMUNITY

    PubMed Central

    Holladay, Steven D.; Gogal, Robert M.

    2010-01-01

    Two immunologically-different mouse strains, C57BL/6 and SNF1, were exposed to a mid-gestation dose of TCDD. The C57BL/6 mouse has a high-affinity aryl hydrocarbon receptor (AhR) and is sensitive to TCDD. The SNF1 mouse has a low-affinity AhR but spontaneously develops autoimmune nephritis. Autoreactive Vβ+CD4+17a and Vβ+CD3+ T cells were increased at 24-weeks-of-age in offspring of C57BL/6 mice, more so in females than males. The cytokine IFN-γ was elevated in the females, while IL-10 was elevated in males. Phenotypic changes in B-lineage cells were present in bone marrow and spleen, and circulating autoantibodies were increased after prenatal TCDD. Kidneys of males showed significant anti-IgG and anti-C3 deposition, suggesting early-stage autoimmune disease. The SNF1 offspring similarly showed increased peripheral Vβ+ cells in the females, increased autoantibody production in both sexes, and increased IFN-γ production in females. Male SNF1 mice had increased anti-IgG and anti-C3 deposition in kidneys. Both mouse models therefore showed clear signatures of enhanced autoimmunity after prenatal TCDD. PMID:20728533

  2. Progesterone increases susceptibility and decreases immune responses to genital herpes infection.

    PubMed

    Kaushic, Charu; Ashkar, Ali A; Reid, Lesley A; Rosenthal, Kenneth L

    2003-04-01

    Depo-provera, a long-acting progestational formulation, is widely used to facilitate infection of sexually transmitted diseases in animal models. We have previously reported that hormone treatments change susceptibility and immune responses to genital tract infections. In this study we compared the changes in susceptibility of mice to genital herpes simplex virus type 2 (HSV-2) after Depo-provera or a saline suspension of progesterone (P-sal). We found that following Depo-provera-treatment, mice had prolonged diestrus that lasted more than 4 weeks. This coincided with a 100-fold increase in susceptibility to genital HSV-2 compared to that of untreated mice. Mice given P-sal were in diestrous stage for 4 to 6 days before returning to irregular reproductive cycles. When these mice were infected at diestrus they showed a 10-fold increase in susceptibility compared to that of normal, untreated mice. P-sal-treated mice infected at estrus were susceptible to HSV-2, depending on the infectious dose. Normal, untreated mice in estrus were not susceptible to HSV-2, even at a high infectious dose of 10(7) PFU. In addition to alterations in susceptibility, Depo-provera treatment had inhibitory effects on immune responses to HSV-2. Mice immunized with HSV-2 protein (gB) and treated with Depo-provera showed significant lowering of local HSV-2-specific immunoglobulin G (IgG) and IgA in their vaginal washes. Mice immunized with an attenuated strain of HSV-2 2 weeks after Depo-provera treatment failed to develop protection when challenged intravaginally with wild-type HSV-2. In contrast, mice given progesterone and immunized at diestrus or estrus were completely protected from intravaginal challenge. These studies show that Depo-provera treatment changes susceptibility and local immune responses to genital HSV-2 infection. Animal models and vaccine strategies for sexually transmitted diseases need to consider the effect of hormone treatments on susceptibility and immune responses

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

    PubMed

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

    2016-08-01

    The rising incidence of Clostridium difficile infections (CDIs) in adults is partly related to the global spread of fluoroquinolone-resistant strains, namely, BI/NAP1/027. Although CDIs are also increasingly diagnosed in children, BI/NAP1/027 is relatively uncommon in children. Little is known about the antibiotic susceptibility of pediatric CDI isolates. C. difficile was cultured from tcdB-positive stools collected from children diagnosed with CDI between December 2012 and December 2013 at an academic children's hospital. CDI isolates were grouped by restriction endonuclease analysis (REA). MICs were measured by agar dilution method for 7 antibiotics. Susceptibility breakpoints were based on guidelines from CLSI and/or the European Committee on Antimicrobial Susceptibility Testing (EUCAST). MICs and REA groupings of C. difficile isolates from 74 adult patients (29 isolates underwent REA) from a temporally and geographically similar adult cohort were compared to those of pediatric isolates. Among 122 pediatric and 74 adult isolates, respectively, the rates of resistance were as follows: metronidazole, 0% and 0%; vancomycin, 0% and 8% (P = 0.003); rifaximin, 1.6% and 6.7% (P = 0.11); clindamycin, 18.9% and 25.3% (P = 0.29); and moxifloxacin, 2.5% and 36% (P = <0.0001). Only 1 of 122 (0.8%) BI/NAP1/027 isolates was identified among the children, compared to 9 of 29 (31%) isolates identified among the adults (P = <0.0001). The 3 moxifloxacin-resistant pediatric isolates were of REA groups BI and CF and a nonspecific group. The 2 rifaximin-resistant pediatric isolates were of REA groups DH and Y. The 21 clindamycin-resistant pediatric isolates were distributed among 9 REA groups (groups A, CF, DH, G, L, M, and Y and 2 unique nonspecific REA groups). These data suggest that a diverse array of relatively antibiotic-susceptible C. difficile strains predominate in a cohort of children with CDI compared to adults. PMID:27270275

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

    PubMed Central

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

    2013-01-01

    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. PMID:24225328

  5. 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

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

    PubMed

    Clark, Sarah E; Filak, Holly C; Guthrie, Brandon S; Schmidt, Rebecca L; Jamieson, Amanda; Merkel, Patricia; Knight, Vijaya; Cole, Caroline M; Raulet, David H; Lenz, Laurel L

    2016-06-01

    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

  7. 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

  8. Staphylococcus aureus antimicrobial susceptibility of abscess samples from adults and children from the Kaleida Health System in western New York State, 2003 to 2006.

    PubMed

    Hsiao, Chiu-Bin; Dryja, Diane; Abbatessa, Laurie; Patel, Pravin H

    2010-05-01

    Staphylococcus aureus is the most common etiologic agent of skin abscesses. The regional rate of methicillin-resistant S. aureus (MRSA) abscesses may reflect the prevalence of local community-acquired MRSA (CAMRSA). A retrospective study was conducted to compare the antimicrobial susceptibility patterns of S. aureus isolates recovered from abscesses from 2003 to 2006 from patients at hospitals of the Kaleida Health System in western New York. S. aureus susceptibility information was obtained from a Vitek Legacy system, and the location and source of each isolate were identified. EpiInfo software was used to analyze the antimicrobial susceptibilities of all isolates and the trends in the rates of MRSA. A total of 2,848 S. aureus abscesses were identified by the Kaleida Health Clinical Microbiology Laboratory. Of those, 978 S. aureus abscess events occurred in four hospitals, including three adult facilities (547 episodes with 62 cases of bacteremia) and one children's facility (431 episodes with 2 cases of bacteremia). The MRSA rates in adults increased from 56% (2003) to 71% (2006), and that in children increased from 26% (2003) to 64% (2006). Of the MRSA isolates in the children's samples, more than 92% were susceptible to clindamycin. Of the MRSA isolates in the adult samples, 50% were susceptible to clindamycin in 2003 and 2004, whereas greater than 75% were susceptible in 2005 and 2006. The increased rates of MRSA abscesses with susceptibility to clindamycin may reflect the high prevalence level of CAMRSA in the western New York community. The variations in S. aureus susceptibilities could serve as an indicator of the changing resistance patterns within a broad urban community. PMID:20181909

  9. 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

  10. Inhibition of LpxC Increases Antibiotic Susceptibility in Acinetobacter baumannii.

    PubMed

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

    2016-08-01

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

  11. Neurite formation by neurons derived from adult rat hippocampal progenitor cells is susceptible to myelin inhibition.

    PubMed

    Mellough, Carla B; Cho, Seongeun; Wood, Andrew; Przyborski, Stefan

    2011-09-01

    Myelin-associated inhibitors expressed following injury to the adult central nervous system (CNS) induce growth cone collapse and retraction of the axonal cytoskeleton. Myelin-associated glycoprotein (MAG) is a bi-functional molecule that promotes neuritogenesis in some immature neurons during development then becomes inhibitory to neurite outgrowth as neurons mature. Progress is being made towards the elucidation of the downstream events that regulate myelin inhibition of regeneration in neuronal populations. However it is not known how adult-derived neural stem cells or progenitors respond to myelin during neuronal differentiation and neuritogenesis. Here we examine the effect of MAG on neurons derived from an adult rat hippocampal progenitor cell line (AHPCs). We show that, unlike their developmental counterparts, AHPC-derived neurons are susceptible to MAG inhibition of neuritogenesis during differentiation and display a 57% reduction in neurite outgrowth when compared with controls. We demonstrate that this effect can be overcome (by up to 69%) by activation of the neurotrophin, cyclic AMP and protein kinase A pathways or by Rho-kinase suppression. We also demonstrate that combination of these factors enhanced neurite outgrowth from differentiating neurons in the presence of MAG. This work provides important information for the successful generation of new neurons from adult neural stem cell populations within compromised adult circuitry and is thus directly relevant to endogenous repair and regeneration of the adult CNS. PMID:21256909

  12. 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. PMID:26766792

  13. Schizophrenia susceptibility alleles are enriched for alleles that affect gene expression in adult human brain

    PubMed Central

    Richards, Alexander L; Jones, Lesley; Moskvina, Valentina; Kirov, George; Gejman, Pablo V; Levinson, Douglas F; Sanders, Alan R; Purcell, Shaun; Visscher, Peter M; Craddock, Nick; Owen, Michael J; Holmans, Peter; O’Donovan, Michael C

    2016-01-01

    It is widely thought that alleles that influence susceptibility to common diseases, including schizophrenia, will frequently do so through effects on gene expression. Since only a small proportion of the genetic variance for schizophrenia has been attributed to specific loci, this remains an unproven hypothesis. The International Schizophrenia Consortium (ISC) recently reported a substantial polygenic contribution to that disorder, and that schizophrenia risk alleles are enriched among SNPs selected for marginal evidence for association (p<0.5) from genome wide association studies (GWAS). It follows that if schizophrenia susceptibility alleles are enriched for those that affect gene expression, those marginally associated SNPs which are also eQTLs should carry more true association signals compared with SNPs which are not. To test this, we identified marginally associated (p<0.5) SNPs from two of the largest available schizophrenia GWAS datasets. We assigned eQTL status to those SNPs based upon an eQTL dataset derived from adult human brain. Using the polygenic score method of analysis reported by the ISC, we observed and replicated the observation that higher probability cis-eQTLs predicted schizophrenia better than those with a lower probability for being a cis-eQTL. Our data support the hypothesis that alleles conferring risk of schizophrenia are enriched among those that affect gene expression. Moreover, our data show that notwithstanding the likely developmental origin of schizophrenia, studies of adult brain tissue can in principle allow relevant susceptibility eQTLs to be identified. PMID:21339752

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  15. 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

  16. 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

  17. 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.

  18. 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

  19. 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...

  20. NLRP3 rs35829419 polymorphism is associated with increased susceptibility to multiple diseases in humans.

    PubMed

    Zhang, Q; Fan, H W; Zhang, J Z; Wang, Y M; Xing, H J

    2015-01-01

    Using a meta-analysis framework, we investigated the association between the NLRP3 rs35829419 polymorphism and increased susceptibility to diverse diseases in humans. Relevant published studies were identified through a comprehensive and systematic electronic search, using the following scientific literature databases: Science Citation Index, the Cochrane Library, PubMed, Embase, CINAHL, Current Contents Index, Chinese Biomedical, the Chinese Journal Full-Text, and the Weipu Journal. Statistical analysis of data extracted from the selected high quality studies was performed using the Version 12.0 STATA software. A total of 13 case-control studies met our stringent inclusion and exclusion criteria for the present meta-analysis. These 13 high quality studies contained relevant information on 7719 patients with various diseases and 7094 healthy controls. Our meta-analysis results showed that the NLRP3 gene rs35829419 C>A polymorphism was associated with a significantly increased risk of developing multiple diseases in humans under 5 genetic models (all P < 0.05). Data stratification and subgroup analysis based on the disease type revealed that rs35829419 C>A carriers displayed a markedly increase susceptibility to leprosy, colorectal cancer, HIV-1 infection, rheumatoid arthritis, abdominal aortic aneurysms, inflammatory bowel disease, ulcerative colitis, and atopic dermatitis. In summary, our meta-analysis results revealed the first identified strong correlation between the NLRP3 rs35829419 polymorphism and increased susceptibility to various diseases in humans. PMID:26535712

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

    PubMed

    Czarnecki, Douglas

    2014-09-01

    The number of melanomas removed from Australians is increasing. Despite this, it has been reported that the incidence of melanoma is decreasing in the young Australian population. However, the denominator for these estimates includes individuals at low risk of melanoma, and the proportion of such individuals has changed over recent decades due to immigration. In this study, the incidence was calculated for the susceptible young population. Data from the Australian Bureau of Statistics were analysed to determine the number of people younger than 30 years at low risk of developing melanoma in 1982 and 2009. Low risk people were defined as those born in Asia, the Pacific Islands, The Middle East, or Sub-Saharan Africa, or had parents born in these regions. There was a significant increase in the number of young Australians at low risk for melanoma. If these people are not included when calculating the crude rate of melanoma, the rate increased from 5.9 per 100,000 in 1982 to 6.3 in 2009. If the estimated number of young Maoris and young Aborigines is excluded from the susceptible population, the crude rate increased from 6.0 per 100,000 in 1982 to 6.8 in 2009. This is the first calculation of the rate of melanoma for the susceptible young Australian population. PMID:24889972

  2. 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

  3. 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. PMID:23431080

  4. 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.

  5. 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

  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. 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. PMID:26350705

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

    ERIC Educational Resources Information Center

    Sumner, Edward D.; Haight, Barbara K.

    1993-01-01

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

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

    PubMed Central

    Wilcox, Douglas R.; Folmsbee, Stephen S.; Muller, William J.

    2016-01-01

    ABSTRACT Newborns are significantly more susceptible to severe viral encephalitis than adults, with differences in the host response to infection implicated as a major factor. However, the specific host signaling pathways responsible for differences in susceptibility and neurologic morbidity have remained unknown. In a murine model of HSV encephalitis, we demonstrated that the choroid plexus (CP) is susceptible to herpes simplex virus 1 (HSV-1) early in infection of the newborn but not the adult brain. We confirmed susceptibility of the CP to HSV infection in a human case of newborn HSV encephalitis. We investigated components of the type I interferon (IFN) response in the murine brain that might account for differences in cell susceptibility and found that newborns have a dampened interferon response and significantly lower basal levels of the alpha/beta interferon (IFN-α/β) receptor (IFNAR) than do adults. To test the contribution of IFNAR to restricting infection from the CP, we infected IFNAR knockout (KO) adult mice, which showed restored CP susceptibility to HSV-1 infection in the adult. Furthermore, reduced IFNAR levels did not account for differences we found in the basal levels of several other innate signaling proteins in the wild-type newborn and the adult, including protein kinase R (PKR), that suggested specific regulation of innate immunity in the developing brain. Viral targeting of the CP, a region of the brain that plays a critical role in neurodevelopment, provides a link between newborn susceptibility to HSV and long-term neurologic morbidity among survivors of newborn HSV encephalitis. PMID:27073094

  12. 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

  13. 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.

  14. 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

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

    NASA Technical Reports Server (NTRS)

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

    2003-01-01

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

  16. 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. 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

  18. 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

  19. 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.

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

    PubMed

    MacKenzie, Georgina; Maguire, Jamie

    2015-01-01

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

  1. Alginate Microencapsulation of Human Islets Does Not Increase Susceptibility to Acute Hypoxia

    PubMed Central

    Hals, I. K.; Rokstad, A. M.; Strand, B. L.; Oberholzer, J.; Grill, V.

    2013-01-01

    Islet transplantation in diabetes is hampered by the need of life-long immunosuppression. Encapsulation provides partial immunoprotection but could possibly limit oxygen supply, a factor that may enhance hypoxia-induced beta cell death in the early posttransplantation period. Here we tested susceptibility of alginate microencapsulated human islets to experimental hypoxia (0.1–0.3% O2 for 8 h, followed by reoxygenation) on viability and functional parameters. Hypoxia reduced viability as measured by MTT by 33.8 ± 3.5% in encapsulated and 42.9 ± 5.2% in nonencapsulated islets (P < 0.2). Nonencapsulated islets released 37.7% (median) more HMGB1 compared to encapsulated islets after hypoxic culture conditions (P < 0.001). Glucose-induced insulin release was marginally affected by hypoxia. Basal oxygen consumption was equally reduced in encapsulated and nonencapsulated islets, by 22.0 ± 6.1% versus 24.8 ± 5.7%. Among 27 tested cytokines/chemokines, hypoxia increased the secretion of IL-6 and IL-8/CXCL8 in both groups of islets, whereas an increase of MCP-1/CCL2 was seen only with nonencapsulated islets. Conclusion. Alginate microencapsulation of human islets does not increase susceptibility to acute hypoxia. This is a positive finding in relation to potential use of encapsulation for islet transplantation. PMID:24364039

  2. 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

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

    PubMed Central

    MacKenzie, Georgina; Maguire, Jamie

    2014-01-01

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

  4. 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

  5. A cyst nematode effector binds to diverse plant proteins, increases nematode susceptibility and affects root morphology.

    PubMed

    Pogorelko, Gennady; Juvale, Parijat S; Rutter, William B; Hewezi, Tarek; Hussey, Richard; Davis, Eric L; Mitchum, Melissa G; Baum, Thomas J

    2016-08-01

    Cyst nematodes are plant-parasitic roundworms that are of significance in many cropping systems around the world. Cyst nematode infection is facilitated by effector proteins secreted from the nematode into the plant host. The cDNAs of the 25A01-like effector family are novel sequences that were isolated from the oesophageal gland cells of the soybean cyst nematode (Heterodera glycines). To aid functional characterization, we identified an orthologous member of this protein family (Hs25A01) from the closely related sugar beet cyst nematode H. schachtii, which infects Arabidopsis. Constitutive expression of the Hs25A01 CDS in Arabidopsis plants caused a small increase in root length, accompanied by up to a 22% increase in susceptibility to H. schachtii. A plant-expressed RNA interference (RNAi) construct targeting Hs25A01 transcripts in invading nematodes significantly reduced host susceptibility to H. schachtii. These data document that Hs25A01 has physiological functions in planta and a role in cyst nematode parasitism. In vivo and in vitro binding assays confirmed the specific interactions of Hs25A01 with an Arabidopsis F-box-containing protein, a chalcone synthase and the translation initiation factor eIF-2 β subunit (eIF-2bs), making these proteins probable candidates for involvement in the observed changes in plant growth and parasitism. A role of eIF-2bs in the mediation of Hs25A01 virulence function is further supported by the observation that two independent eIF-2bs Arabidopsis knock-out lines were significantly more susceptible to H. schachtii. PMID:26575318

  6. MicroRNA Gene Polymorphisms and Environmental Factors Increase Patient Susceptibility to Hepatocellular Carcinoma

    PubMed Central

    Chu, Yin-Hung; Hsieh, Ming-Ju; Chiou, Hui-Ling; Liou, Yi-Sheng; Yang, Chen-Chieh; Yang, Shun-Fa; Kuo, Wu-Hsien

    2014-01-01

    Background Micro RNAs (miRNAs) are small RNA fragments that naturally exist in the human body. Through various physiological mechanisms, miRNAs can generate different functions for regulating RNA protein levels and balancing abnormalities. Abnormal miRNA expression has been reported to be highly related to several diseases and cancers. Single-nucleotide polymorphisms (SNPs) in miRNAs have been reported to increase patient susceptibility and affect patient prognosis and survival. We adopted a case-control research design to verify the relationship between miRNAs and hepatocellular carcinoma. Methodology/Principal Findings A total of 525 subjects, including 377 controls and 188 hepatocellular carcinoma patients, were selected. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and real-time PCR were used to analyze miRNA146a (rs2910164), miRNA149 (rs2292832), miRNA196 (rs11614913), and miRNA499 (rs3746444) genetic polymorphisms between the control group and the case group. The results indicate that people who carry the rs3746444 CT or CC genotypes may have a significantly increased susceptibility to hepatocellular carcinoma (adjusted odds ratio [AOR] = 2.84, 95% confidence interval [CI] = 1.88–4.30). In addition, when combined with environmental risk factors, such as smoking and alcohol consumption, interaction effects were observed between gene polymorphisms and environmental factors (odds ratio [OR] = 4.69, 95% CI = 2.52–8.70; AOR = 3.38, 95% CI = 1.68–6.80). Conclusions These results suggest that a significant association exists between miRNA499 SNPs and hepatocellular carcinoma. Gene-environment interactions of miRNA499 polymorphisms, smoking, and alcohol consumption might alter hepatocellular carcinoma susceptibility. PMID:24587132

  7. 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. PMID:26313967

  8. 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. PMID:24643875

  9. Increased Susceptibility to DNA Virus Infection in Mice with a GCN2 Mutation

    PubMed Central

    Won, Sungyong; Eidenschenk, Celine; Arnold, Carrie N.; Siggs, Owen M.; Sun, Lei; Brandl, Katharina; Mullen, Tina-Marie; Nemerow, Glen R.; Moresco, Eva Marie Y.

    2012-01-01

    The downregulation of translation through eIF2α phosphorylation is a cellular response to diverse stresses, including viral infection, and is mediated by the GCN2 kinase, protein kinase R (PKR), protein kinase-like endoplasmic reticulum kinase (PERK), and heme-regulated inhibitor kinase (HRI). Although PKR plays a major role in defense against viruses, other eIF2α kinases also may respond to viral infection and contribute to the shutdown of protein synthesis. Here we describe the recessive, loss-of-function mutation atchoum (atc) in Eif2ak4, encoding GCN2, which increased susceptibility to infection by the double-stranded DNA viruses mouse cytomegalovirus (MCMV) and human adenovirus. This mutation was identified by screening macrophages isolated from mice carrying N-ethyl-N-nitrosourea (ENU)-induced mutations. Cells from Eif2ak4atc/atc mice failed to phosphorylate eIF2α in response to MCMV. Importantly, homozygous Eif2ak4atc mice showed a modest increase in susceptibility to MCMV infection, demonstrating that translational arrest dependent on GCN2 contributes to the antiviral response in vivo. PMID:22114338

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

    PubMed

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

    2015-06-01

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

  11. Chronic omeprazole treatment increases duodenal susceptibility to ethanol injury in rats.

    PubMed

    Erickson, R A; Bezabah, S; Jonas, G; Lifrak, E; Tarnawski, A S

    1991-07-01

    To test whether omeprazole would increase the susceptibility of the duodenum to damage, 200 to 250-g male Sprague-Dawley rats were given 10 mg/kg of omeprazole (Losec) by gavage every morning for 29 days. Control rats were given gavage buffer alone. After fasting overnight, half the rats received 10 mg/kg indomethacin intraperitoneally; then all rats were given 2 ml of 50% ethanol by gavage. Three hours later the rats were killed and the stomach and duodenum removed and histologic injury to the duodenal mucosal was quantitated. In omeprazole pretreated rats, gavage with ethanol resulted in a significant twofold worsening of duodenal injury. Pretreatment with indomethacin to decrease endogenous prostaglandin production resulted in more severe ethanol-induced duodenal injury in both groups; however, there were no longer statistically significant differences between the omeprazole and control groups. Measurement of duodenal mucosal synthesis of prostaglandin E2 showed no difference between the omeprazole and control groups. Thus chronic administration of omeprazole appears to increase the susceptibility of the duodenal mucosa to ethanol injury in rats. The mechanism of this effect is as yet unknown but does not appear to be prostaglandin-mediated. PMID:2070702

  12. 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

  13. 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.

  14. Clinical review: Immunodepression in the surgical patient and increased susceptibility to infection

    PubMed Central

    Angele, Martin K; Faist, Eugen

    2002-01-01

    Several studies indicate that organ failure is the leading cause of death in surgical patients. An excessive inflammatory response followed by a dramatic paralysis of cell-mediated immunity following major surgery appears to be responsible for the increased susceptibility to subsequent sepsis. In view of this, most of the scientific and medical research has been directed towards measuring the progression and inter-relationship of mediators following major surgery. Furthermore, the effect of those mediators on cell-mediated immune responses has been studied. This article will focus on the effect of blood loss and surgical injury on cell-mediated immune responses in experimental studies utilizing models of trauma and hemorrhagic shock, which have defined effects on the immunoinflammatory response. Subsequently these findings will be correlated with data generated from surgical patients. The results of these studies may generate new approaches for the treatment of immunodepression following major surgery, thus reducing the susceptibility to infection and increasing the survival rate of the critical ill surgical patient. PMID:12225603

  15. Maternal deprivation of rat pups increases clinical symptoms of experimental autoimmune encephalomyelitis at adult age.

    PubMed

    Teunis, Marc A T; Heijnen, Cobi J; Sluyter, Frans; Bakker, Joost M; Van Dam, Anne-Marie M W; Hof, Maleen; Cools, Alexander R; Kavelaars, Annemieke

    2002-12-01

    Maternal deprivation of neonatal animals has been shown to induce long-lasting changes in the reactivity of the neuroendocrine system. The aim of the present study was to investigate whether maternal deprivation also affects susceptibility to immune-mediated diseases such as experimental autoimmune encephalomyelitis (EAE) in adult life. To this end, 9-day-old rat pups were subjected to a short-lasting maternal deprivation for a period of 24 h. At the age of 8 weeks, we induced EAE in these rats by immunization with myelin basic protein (MBP) in complete Freund's adjuvant. Our data demonstrate that short-lasting maternal deprivation induces a marked increase in the severity of EAE in the animals in later life. The histopathological evaluation of spinal cord and cerebellum corresponded with the observed differences in clinical symptoms of EAE. Moreover, neonatal maternal deprivation affects macrophage functioning at adult age. In contrast, no differences were observed in in vitro mitogen- and MBP-induced cytokine production by splenocytes. LPS-induced corticosterone release did not differ either between maternally deprived and control animals. We conclude that short-lasting neonatal maternal deprivation of rat pups has long-lasting consequences for macrophage activity and for susceptibility to the inflammatory autoimmune disease EAE. PMID:12446005

  16. 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

  17. 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

  18. Optical increase of photo-integrated micro- and nano-periodic susceptibility lattices

    NASA Astrophysics Data System (ADS)

    Smirnov, Vitaly A.; Vostrikova, Liubov I.

    2015-03-01

    It is demonstrated that the nonlinear photo-integrated micro- and nano-periodic second-order susceptibility lattices with very small amplitudes which were preliminarily recorded using bi-chromatic powerful laser light in amorphous glass materials can be increased up to some orders of magnitude under the action of a simple coherent monochromatic radiation. The optical increase of the small lattices takes place independent of the polarization and direction of propagation of the optical amplifying radiation and is achieved at various wavelengths. The observed phenomenon is not be explained only by nonlinear wave interaction in medium and also may be related to the microscopic asymmetry processes of the optical transitions between local centers in an isotropic medium that leads to the appearance and growth of the all-optically induced small micro- and nano-periodic electrical charges separations inside the sample. Possible mechanisms that may be responsible for the observed effects in the studied phosphate glasses are discussed.

  19. 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.

  20. 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. PMID:26092986

  1. 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

  2. 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

  3. 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

  4. Selective pharmacologic inhibition of a PASTA kinase increases Listeria monocytogenes susceptibility to β-lactam antibiotics.

    PubMed

    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; Sauer, John-Demian

    2014-08-01

    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

  5. TOP2 gene disruption reduces drug susceptibility by increasing intracellular ergosterol biosynthesis in Candida albicans.

    PubMed

    Zheng, Hao; Jiang, Yuan-Ying; Wang, Yan; Jia, Xin-Ming; Yan, Tian-Hua; Gao, Ping-Hui; Yan, Lan; Jiang, Ling-Huo; Ji, Hui; Cao, Yong-Bing

    2010-07-01

    In this study the role of the TOP2 gene in fungal drug susceptibility was investigated by disrupting and overexpressing the gene in Candida albicans. MIC determination and a spot assay showed that a top2Delta/Delta null mutant (strain T2bc) was more resistant to the antifungals tested than the wild-type (strain CAI4). Real-time RT-PCR and rhodamine 6G efflux examination showed that TOP2 did not influence the activity of drug efflux pumps. Sterol analysis with GC/high-resolution MS indicated that the intracellular ergosterol composition of the top2Delta/Delta mutant was significantly increased. Subsequently, fluorescence polarization measurements also revealed that Top2-deprived cells displayed a decrease in membrane fluidity, resulting in enhanced passive diffusion of the drugs. Quantitative real-time RT-PCR analysis further confirmed that the ERG11 gene, an essential gene in ergosterol biosynthesis, was upregulated. These results demonstrate a close relationship between the TOP2 gene and drug susceptibility in C. albicans. PMID:20223895

  6. 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

  7. 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

  8. Testosterone increases susceptibility to amebic liver abscess in mice and mediates inhibition of IFNγ secretion in natural killer T cells.

    PubMed

    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. 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

  10. 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

  11. 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

  12. 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

  13. Multigenerational Undernutrition Increases Susceptibility to Obesity and Diabetes that Is Not Reversed after Dietary Recuperation.

    PubMed

    Hardikar, Anandwardhan A; Satoor, Sarang N; Karandikar, Mahesh S; Joglekar, Mugdha V; Puranik, Amrutesh S; Wong, Wilson; Kumar, Sandeep; Limaye, Amita; Bhat, Dattatray S; Januszewski, Andrzej S; Umrani, Malati R; Ranjan, Amaresh K; Apte, Kishori; Yajnik, Pranav; Bhonde, Ramesh R; Galande, Sanjeev; Keech, Anthony C; Jenkins, Alicia J; Yajnik, Chittaranjan S

    2015-08-01

    People in developing countries have faced multigenerational undernutrition and are currently undergoing major lifestyle changes, contributing to an epidemic of metabolic diseases, though the underlying mechanisms remain unclear. Using a Wistar rat model of undernutrition over 50 generations, we show that Undernourished rats exhibit low birth-weight, high visceral adiposity (DXA/MRI), and insulin resistance (hyperinsulinemic-euglycemic clamps), compared to age-/gender-matched control rats. Undernourished rats also have higher circulating insulin, homocysteine, endotoxin and leptin levels, lower adiponectin, vitamin B12 and folate levels, and an 8-fold increased susceptibility to Streptozotocin-induced diabetes compared to control rats. Importantly, these metabolic abnormalities are not reversed after two generations of unrestricted access to commercial chow (nutrient recuperation). Altered epigenetic signatures in insulin-2 gene promoter region of Undernourished rats are not reversed by nutrient recuperation, and may contribute to the persistent detrimental metabolic profiles in similar multigenerational undernourished human populations. PMID:26166746

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

    PubMed

    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

  15. 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

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

    PubMed

    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

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

    PubMed Central

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

    2014-01-01

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

  18. 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.

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

    PubMed Central

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

    2016-01-01

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

  20. 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.

  1. 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.

  2. The IL-33 gene is related to increased susceptibility to systemic sclerosis.

    PubMed

    Koca, Suleyman Serdar; Pehlivan, Yavuz; Kara, Murat; Alibaz-Oner, Fatma; Oztuzcu, Serdar; Yilmaz, Neslihan; Cetin, Gozde Yildirim; Kisacik, Bunyamin; Ozgen, Metin; Pamuk, Omer Nuri; Direskeneli, Haner; Sayarlioglu, Mehmet; Onat, Ahmet Mesut

    2016-04-01

    Systemic sclerosis (SSc) is a chronic inflammatory disease characterized by widespread fibrosis of the skin and several visceral organs. The pro-fibrotic potential of interleukin (IL)-33 has been demonstrated by in both in vitro and in vivo settings; moreover, increased level of IL-33 has also been reported in patients with SSc. Therefore, the aim of the present study was to detect the potential association of IL-33 gene polymorphisms on the susceptibility of SSc. A total of 300 SSc patients and 280 healthy controls (HC) were enrolled in this multicentric preliminary candidate gene study. DNA samples were harvested using an appropriate commercial DNA isolation kit. Four single nucleotide polymorphisms (SNPs) of IL-33 gene (rs7044343, rs1157505, rs11792633 and rs1929992) were genotyped using the appropriate commercial primer/probe sets on real-time PCR. There was no significant difference in terms of the allelic distributions and minor allele frequencies of evaluated four IL-33 polymorphisms between the SSc and HC groups (P > 0.05 for all). Moreover, the genotypic distributions of rs1157505, rs11792633 and rs1929992 polymorphisms were not significantly different (P > 0.05 for all). However, CC genotype of rs7044343 SNP was significantly higher in the SSc group compared to the HC group (P = 0.013, OR 1.75, 95 % CI 1.12-2.72). This preliminary candidate gene study demonstrates that rs7044343 polymorphism of IL-33 gene is associated with the susceptibility to the SSc in Turkish population. It may be suggested that IL-33 gene may be a candidate gene to research in SSc. PMID:26743213

  3. 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

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

    PubMed

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

    2014-02-15

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

  5. 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. PMID:26973537

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

    PubMed Central

    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. PMID:26973537

  7. 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

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

    PubMed

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

    2014-03-01

    Sweetpotato is a nutritional source worldwide. Soft rot caused by Rhizopus spp. is a major limiting factor in the storage of produce, rendering it potentially unsafe for human consumption. In this study, Rhizopus oryzae was used to develop a concept of postharvest disease control by weakening the pathogen through induction of spore germination under starvation conditions. We isolated the sweetpotato active fractions (SPAFs) that induce spore germination and used them at a low dose to enhance spore weakening caused by starvation. Germination in SPAF at 1 mg/ml weakened the pathogen spores by delaying their ability to form colonies on rich media and by increasing their sensitivity to heat stress. The weakening effect was also supported by reduced metabolic activity, as detected by Alarmar Blue fluorescent dye assays. Spores incubated with SPAF at 1 mg/ml showed DNA fragmentation in some of their nuclei, as observed by TUNEL assay. In addition, these spores exhibited changes in ultrastructural morphology (i.e., shrinkage of germ tubes, nucleus deformation, and vacuole formation) which are hallmarks of programmed cell death. We suggest that induction of spore germination under starvation conditions increases their susceptibility to stress and, therefore, might be considered a new strategy for pathogen control. PMID:24093921

  9. 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

  10. 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

  11. Autophagy deficiency in myeloid cells increases susceptibility to obesity-induced diabetes and experimental colitis.

    PubMed

    Lee, Hae-Youn; Kim, Jinyoung; Quan, Wenying; Lee, June-Chul; Kim, Min-Soo; Kim, Seok-Hyung; Bae, Jin-Woo; Hur, Kyu Yeon; Lee, Myung-Shik

    2016-08-01

    Autophagy, which is critical for the proper turnover of organelles such as endoplasmic reticulum and mitochondria, affects diverse aspects of metabolism, and its dysregulation has been incriminated in various metabolic disorders. However, the role of autophagy of myeloid cells in adipose tissue inflammation and type 2 diabetes has not been addressed. We produced mice with myeloid cell-specific deletion of Atg7 (autophagy-related 7), an essential autophagy gene (Atg7 conditional knockout [cKO] mice). While Atg7 cKO mice were metabolically indistinguishable from control mice, they developed diabetes when bred to ob/w mice (Atg7 cKO-ob/ob mice), accompanied by increases in the crown-like structure, inflammatory cytokine expression and inflammasome activation in adipose tissue. Mφs (macrophages) from Atg7 cKO mice showed significantly higher interleukin 1 β release and inflammasome activation in response to a palmitic acid plus lipopolysaccharide combination. Moreover, a decrease in the NAD(+):NADH ratio and increase in intracellular ROS content after treatment with palmitic acid in combination with lipopolysaccharide were more pronounced in Mφs from Atg7 cKO mice, suggesting that mitochondrial dysfunction in autophagy-deficient Mφs leads to an increase in lipid-induced inflammasome and metabolic deterioration in Atg7 cKO-ob/ob mice. Atg7 cKO mice were more susceptible to experimental colitis, accompanied by increased colonic cytokine expression, T helper 1 skewing and systemic bacterial invasion. These results suggest that autophagy of Mφs is important for the control of inflammasome activation in response to metabolic or extrinsic stress, and autophagy deficiency in Mφs may contribute to the progression of metabolic syndrome associated with lipid injury and colitis. PMID:27337687

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

    PubMed

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

    2015-05-01

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

  13. 8-Oxoguanine DNA Glycosylase (OGG1) Deficiency Increases Susceptibility to Obesity and Metabolic Dysfunction

    PubMed Central

    Sampath, Harini; Vartanian, Vladimir; Rollins, M. Rick; Sakumi, Kunihiko; Nakabeppu, Yusaku; Lloyd, R. Stephen

    2012-01-01

    Oxidative damage to DNA is mainly repaired via base excision repair, a pathway that is catalyzed by DNA glycosylases such as 8-oxoguanine DNA glycosylase (OGG1). While OGG1 has been implicated in maintaining genomic integrity and preventing tumorigenesis, we report a novel role for OGG1 in altering cellular and whole body energy homeostasis. OGG1-deficient (Ogg1−/−) mice have increased adiposity and hepatic steatosis following exposure to a high-fat diet (HFD), compared to wild-type (WT) animals. Ogg1−/− animals also have higher plasma insulin levels and impaired glucose tolerance upon HFD feeding, relative to WT counterparts. Analysis of energy expenditure revealed that HFD-fed Ogg1−/− mice have a higher resting VCO2 and consequently, an increased respiratory quotient during the resting phase, indicating a preference for carbohydrate metabolism over fat oxidation in these mice. Additionally, microarray and quantitative PCR analyses revealed that key genes of fatty acid oxidation, including carnitine palmitoyl transferase-1, and the integral transcriptional co-activator Pgc-1α were significantly downregulated in Ogg1−/− livers. Multiple genes involved in TCA cycle metabolism were also significantly reduced in livers of Ogg1−/− mice. Furthermore, hepatic glycogen stores were diminished, and fasting plasma ketones were significantly reduced in Ogg1−/− mice. Collectively, these data indicate that OGG1 deficiency alters cellular substrate metabolism, favoring a fat sparing phenotype, that results in increased susceptibility to obesity and related pathologies in Ogg1−/− mice. PMID:23284747

  14. 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

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

    PubMed Central

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

    2015-01-01

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

  16. Reduced Connexin26 in the Mature Cochlea Increases Susceptibility to Noise-Induced Hearing Lossin Mice.

    PubMed

    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

  17. Germ-free mice deficient of reactive oxygen species have increased arthritis susceptibility.

    PubMed

    Wing, Kajsa; Klocke, Katrin; Samuelsson, Annika; Holmdahl, Rikard

    2015-05-01

    The NADPH oxidase 2 (NOX2) complex is responsible for the production of ROS in phagocytic cells. Genetic defects in NOX2 lead to opportunistic infections and inflammatory manifestations such as granulomas in humans, also known as chronic granulomatous disease (CGD). This condition is mirrored in mice with defective ROS production and interestingly both species are predisposed to autoimmune diseases. An unresolved question is whether the hyper-inflammation and tendency to develop autoimmunity are secondary to the increased infections, or whether these are parallel phenomena. We generated germ-free ROS deficient Ncf1 mutant mice that when reared in specific pathogen-free condition, are highly susceptible to collagen-induced arthritis compared with wild-type mice. Strikingly, arthritis incidence and severity was almost identical in germ-free and specific pathogen-free ROS-deficient mice. In addition, partial reduction of the microbial flora by antibiotics treatment did not alter the disease course. Taken together, this shows that ROS has a clear immune regulatory function that is decoupled from its function in host defence. PMID:25689796

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

    PubMed

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

    2015-04-01

    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. PMID:25550465

  19. 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…

  20. 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

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

    PubMed Central

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

    2015-01-01

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

  2. 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…

  3. Chronic Fluoxetine Increases Extra-Hippocampal Neurogenesis in Adult Mice

    PubMed Central

    Sachs, Benjamin D.

    2015-01-01

    Background: Chronic treatment with antidepressants has been shown to enhance neurogenesis in the adult mammalian brain. Although this effect was initially reported to be restricted to the hippocampus, recent work has suggested that fluoxetine, a selective serotonin reuptake inhibitor, also promotes neurogenesis in the cortex. However, whether antidepressants target neural progenitor cells in other brain regions has not been examined. Methods: Here, we used BrdU labeling and immunohistochemistry with a transgenic mouse line in which nestin+ neural progenitor cells can be inducibly labeled with the fluorescent protein, Tomato, following tamoxifen administration. We investigated the effects of chronic fluoxetine on cell proliferation and nestin+ progenitor cells in periventricular areas in the medial hypothalamus and medial habenula, two brain areas involved in stress and anxiety responses. Results: Our data provide the first in vivo evidence that fluoxetine promotes cell proliferation and neurogenesis and increases the mRNA levels of BDNF in the hypothalamus and habenula. Conclusions: By identifying novel cellular targets of fluoxetine, our results may provide new insight into the mechanisms underlying antidepressant responses. PMID:25583694

  4. 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

  5. Risk factors for increased multiple sclerosis susceptibility in the Iranian population.

    PubMed

    Mansouri, Behnam; Asadollahi, Shadi; Heidari, Kamran; Fakhri, Mohammad; Assarzadegan, Farhad; Nazari, Maryam; Divani, Afshin

    2014-12-01

    Multiple sclerosis (MS) is a complex autoimmune disease with increasing prevalence. Many factors have been assessed in relation to its development and its worldwide geographical and racial distribution. Therefore, we decided to conduct a nationwide case-control matched study to estimate the possible influence of putative risk factors on MS status in an Iranian MS population. Between January 2008 and September 2013, 1403 patients diagnosed with MS according to the Poser or McDonald criteria and 883 controls were studied. Of all patients, there were 921 women and 296 men (ratio 3.1:1) with a mean age of 32.6 ± 8.7 years. In the multivariate model adjusted for sex and age (±2years), we found associated risk factors of MS to be: history of any allergic condition (Odds ratio (OR): 1.92, 95% Confidence interval (CI): 1.55-2.47, p<0.001), and smoking (OR: 1.93, 95% CI: 1.31-2.73, p<0.001). Sunlight exposure ⩾ 3 hours was found to be associated with a reduced risk of MS (OR: 0.23, 95% CI: 0.15-0.31, p<0.001). As expected, cases were more likely to have a positive family history of MS than controls (OR: 1.91, 95% CI: 1.33-2.75, p<0.001). A significant association was found between family history of other autoimmune diseases and MS risk (OR: 1.57, 95% CI: 1.18-2.09, p=0.002). These results support the hypothesis that sun exposure is associated with a decreased risk of MS while smoking, autoimmune family history, MS family history, and personal allergy history are risk factors for MS susceptibility. PMID:25082407

  6. 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

  7. Increasing Access to Postsecondary Education for Adults in Rural Appalachia.

    ERIC Educational Resources Information Center

    Sullins, W. Robert; And Others

    1987-01-01

    Reports on a study of the barriers to adult participation in postsecondary education in the Appalachian regions of six southern states. Discusses policy-related, dispositional, situational, and institutional barriers to enrollment, and offers recommendations for reducing the obstacles. (DMM)

  8. 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

  9. 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

  10. Adaptation to resistant hosts increases fitness on susceptible hosts in the plant parasitic nematode Globodera pallida.

    PubMed

    Fournet, Sylvain; Eoche-Bosy, Delphine; Renault, Lionel; Hamelin, Frédéric M; Montarry, Josselin

    2016-04-01

    Trade-offs between virulence (defined as the ability to infect a resistant host) and life-history traits are of particular interest in plant pathogens for durable management of plant resistances. Adaptation to plant resistances (i.e., virulence acquisition) is indeed expected to be associated with a fitness cost on susceptible hosts. Here, we investigated whether life-history traits involved in the fitness of the potato cyst nematode Globodera pallida are affected in a virulent lineage compared to an avirulent one. Both lineages were obtained from the same natural population through experimental evolution on resistant and susceptible hosts, respectively. Unexpectedly, we found that virulent lineages were more fit than avirulent lineages on susceptible hosts: they produced bigger cysts, containing more larvae and hatching faster. We thus discuss possible reasons explaining why virulence did not spread into natural G. pallida populations. PMID:27066239

  11. Food insecurity and increased BMI in young adult women

    PubMed Central

    Gooding, Holly C; Walls, Courtney E; Richmond, Tracy K

    2014-01-01

    Food insecurity has been associated with weight status in children and adults although results have been mixed. We aimed to identify whether food insecurity was associated with BMI in young adults and whether this association differed by gender and was modified by food stamp use and the presence of children in the home. Cross-sectional data from Wave 4 (2007–2008) of the National Longitudinal Study of Adolescent Health were analyzed. Multiple linear regression was used to investigate the association between food insecurity and BMI in gender stratified models of young adult women (n=7116) and men (n=6604) controlling for age, race/ethnicity, income, education, physical activity, smoking, alcohol use, the presence of children in the home, and food stamp use in young adulthood and/or adolescence. Food insecurity was more common in young adult women (14%) than young adult men (9%). After controlling for a variety of individual variables, food insecure women had a BMI that was on average 0.9kg/m2 units higher than women who were food secure. This difference in BMI persisted after controlling for recent or past food stamp use and was not different among women with or without children in the household. No relationship was found between food insecurity and BMI in young adult men. Providers should inquire about food insecurity, especially when treating obesity, and policy initiatives should address the role of access to healthy food in those facing food insecurity. PMID:21779092

  12. 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. PMID:26499267

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

    PubMed Central

    2010-01-01

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

  14. In Utero and Lactational TCDD Exposure Increases Susceptibility to Lower Urinary Tract Dysfunction in Adulthood.

    PubMed

    Ricke, William A; Lee, Calvin W; Clapper, Tyler R; Schneider, Andrew J; Moore, Robert W; Keil, Kimberly P; Abler, Lisa L; Wynder, Jalissa L; López Alvarado, Arnaldo; Beaubrun, Isaac; Vo, Jenny; Bauman, Tyler M; Ricke, Emily A; Peterson, Richard E; Vezina, Chad M

    2016-04-01

    Benign prostatic hyperplasia, prostate cancer, and changes in the ratio of circulating testosterone and estradiol often occur concurrently in aging men and can lead to lower urinary tract (LUT) dysfunction. To explore the possibility of a fetal basis for the development of LUT dysfunction in adulthood, Tg(CMV-cre);Nkx3-1(+/-);Pten(fl/+) mice, which are genetically predisposed to prostate neoplasia, were exposedin uteroand during lactation to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 1 μg/kg po) or corn oil vehicle (5 ml/kg) after a single maternal dose on 13 days post coitus, and subsequently were aged without further manipulation, or at 8 weeks of age were exposed to exogenous 17 β-estradiol (2.5 mg) and testosterone (25 mg) (T+E2) via slow release subcutaneous implants.In uteroand lactational (IUL) TCDD exposure in the absence of exogenous hormone treatment reduced voiding pressure in adult mice, but otherwise had little effect on mouse LUT anatomy or function. By comparison, IUL TCDD exposure followed by exogenous hormone treatment increased relative kidney, bladder, dorsolateral prostate, and seminal vesicle weights, hydronephrosis incidence, and prostate epithelial cell proliferation, thickened prostate periductal smooth muscle, and altered prostate and bladder collagen fiber distribution. We propose a 2-hit model whereby IUL TCDD exposure sensitizes mice to exogenous-hormone-induced urinary tract dysfunction later in life. PMID:26865671

  15. 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...

  16. Quantitative Trait Locus Mapping of Increased Fusarium Head Blight Susceptibility Associated with a Wild Emmer Wheat Chromosome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chromosome 2A of wild emmer (Triticum turgidum var. dicoccoides) line Israel A increases Fusarium head blight (FHB) severity when present in durum wheat (T. turgidum var. durum) cvc. Langdon (LDN), suggesting that FHB susceptibility genes are located on this chromosome. The goals of this study were ...

  17. 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.

  18. Increased Susceptibility to Cortical Spreading Depression in the Mouse Model of Familial Hemiplegic Migraine Type 2

    PubMed Central

    Barone, Virginia; De Fusco, Maurizio; Pietrobon, Daniela; Pizzorusso, Tommaso; Casari, Giorgio

    2011-01-01

    Familial hemiplegic migraine type 2 (FHM2) is an autosomal dominant form of migraine with aura that is caused by mutations of the α2-subunit of the Na,K-ATPase, an isoform almost exclusively expressed in astrocytes in the adult brain. We generated the first FHM2 knock-in mouse model carrying the human W887R mutation in the Atp1a2 orthologous gene. Homozygous Atp1a2R887/R887 mutants died just after birth, while heterozygous Atp1a2+/R887 mice showed no apparent clinical phenotype. The mutant α2 Na,K-ATPase protein was barely detectable in the brain of homozygous mutants and strongly reduced in the brain of heterozygous mutants, likely as a consequence of endoplasmic reticulum retention and subsequent proteasomal degradation, as we demonstrate in transfected cells. In vivo analysis of cortical spreading depression (CSD), the phenomenon underlying migraine aura, revealed a decreased induction threshold and an increased velocity of propagation in the heterozygous FHM2 mouse. Since several lines of evidence involve a specific role of the glial α2 Na,K pump in active reuptake of glutamate from the synaptic cleft, we hypothesize that CSD facilitation in the FHM2 mouse model is sustained by inefficient glutamate clearance by astrocytes and consequent increased cortical excitatory neurotransmission. The demonstration that FHM2 and FHM1 mutations share the ability to facilitate induction and propagation of CSD in mouse models further support the role of CSD as a key migraine trigger. PMID:21731499

  19. 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

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

    PubMed

    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

  1. Serotype Distribution and Antimicrobial Susceptibilities of Invasive Streptococcus pneumoniae Isolates from Adults in Korea from 1997 to 2012.

    PubMed

    Kim, Chung Jong; Song, Jin-Su; Choi, Su-Jin; Song, Kyoung Ho; Choe, Pyeong Gyun; Park, Wan Beom; Bang, Ji Hwan; Kim, Eu Suk; Park, Sang Won; Kim, Hong Bin; Kim, Nam-Joong; Kim, Eui-Chong; Oh, Myoung-Don

    2016-05-01

    In Republic of Korea, a 7-valent pneumococcal conjugated vaccine (PCV7) was licensed for use in infants in 2003, and 13-valent PCV (PCV13) replaced it since 2010. We investigated trends in serotype distribution and antibiotic susceptibility of pneumococcal isolates from adult patients with invasive pneumococcal diseases (IPD). Invasive pneumococcal isolates from adult patients of ≥ 16 years of age were collected from 1997 to 2012. Serotypes of the isolates were determined by the Quellung reaction. Distribution of serotypes was analyzed according to the vaccine types. Antibiotic susceptibility was tested by using E-test strips. A total of 272 invasive pneumococcal isolates were included. The most common serotypes were serotype 19F (8.5%, 23/272), and serotype 3 (8.1%, 22/272), and 24.6% (67/272) of the isolates were of non-vaccine serotypes. Of the 272 isolates, 2.6% (7/272) were penicillin MICs of ≥ 4 µg/mL. The proportion of the PCV13 serotypes decreased from 63.3% (50/79) in 1997-2003 to 48.6% (17/35) in 2011-2012, whereas that of non-vaccine serotypes was 26.6% (21/79) and 25.7% (9/35), respectively, for the same periods. The proportion of the PCV13 serotypes showed a decreasing trend among adult patients with IPD over the study period. PMID:27134492

  2. Serotype Distribution and Antimicrobial Susceptibilities of Invasive Streptococcus pneumoniae Isolates from Adults in Korea from 1997 to 2012

    PubMed Central

    Song, Jin-Su; Kim, Eui-Chong

    2016-01-01

    In Republic of Korea, a 7-valent pneumococcal conjugated vaccine (PCV7) was licensed for use in infants in 2003, and 13-valent PCV (PCV13) replaced it since 2010. We investigated trends in serotype distribution and antibiotic susceptibility of pneumococcal isolates from adult patients with invasive pneumococcal diseases (IPD). Invasive pneumococcal isolates from adult patients of ≥ 16 years of age were collected from 1997 to 2012. Serotypes of the isolates were determined by the Quellung reaction. Distribution of serotypes was analyzed according to the vaccine types. Antibiotic susceptibility was tested by using E-test strips. A total of 272 invasive pneumococcal isolates were included. The most common serotypes were serotype 19F (8.5%, 23/272), and serotype 3 (8.1%, 22/272), and 24.6% (67/272) of the isolates were of non-vaccine serotypes. Of the 272 isolates, 2.6% (7/272) were penicillin MICs of ≥ 4 µg/mL. The proportion of the PCV13 serotypes decreased from 63.3% (50/79) in 1997-2003 to 48.6% (17/35) in 2011-2012, whereas that of non-vaccine serotypes was 26.6% (21/79) and 25.7% (9/35), respectively, for the same periods. The proportion of the PCV13 serotypes showed a decreasing trend among adult patients with IPD over the study period. PMID:27134492

  3. Overexpression of Forebrain CRH During Early Life Increases Trauma Susceptibility in Adulthood.

    PubMed

    Toth, Mate; Flandreau, Elizabeth I; Deslauriers, Jessica; Geyer, Mark A; Mansuy, Isabelle M; Merlo Pich, Emilio; Risbrough, Victoria B

    2016-05-01

    findings indicate that forebrain CRH hyper-signaling in early-life is sufficient to increase enduring effects of adult trauma and attenuate Crhr2 expression changes in response to stress in males. These data support growing evidence for significant sex differences in response to trauma, and support further study of CRHR2 as a candidate mechanism for PTSD risk. PMID:26538448

  4. 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

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

    PubMed

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

    2016-03-01

    The seasonality of depressive symptoms is prevalent in children and adolescents. However, the mechanisms that underlie such susceptibility to seasonal influences on mood disorders are unclear. We examined the effects of a short photoperiod condition on the susceptibility to subchronic unpredictable mild stress (SCUS) and rhythmic alterations of plasma corticosterone (CORT), melatonin, and neuropeptide Y (NPY) in adolescent male rats. Compared with the 12h/12h light/dark photoperiod control (CON) rats, the 8h/16h photoperiod SCUS rats exhibited significant anhedonia, a core symptom of human depression, together with a blunted diurnal rhythm and elevation of 24h CORT, melatonin, and NPY levels. The 8h/16h photoperiod condition also blunted the rhythmicity of CORT, caused a phase inversion of melatonin, and caused a phase delay of NPY compared with 12h/12h CON rats. Such abnormalities of plasma CORT, NPY, and melatonin might cause adolescent individuals to present higher stress reactivity and greater vulnerability to stress over their lifetimes. The present study provides evidence of the susceptibility to the seasonality of stress-related disorders in adolescence. PMID:26655789

  6. Lack of a Functioning P2X7 Receptor Leads to Increased Susceptibility to Toxoplasmic Ileitis

    PubMed Central

    Robinson, Dionne P.; Fuller, Stephen J.; Walker, Robert A.; Ikin, Rowan J.; Bao, Shisan J.; Grigg, Michael E.; Wiley, James S.; Smith, Nicholas C.

    2015-01-01

    Background Oral infection of C57BL/6J mice with the protozoan parasite Toxoplasma gondii leads to a lethal inflammatory ileitis. Principal Findings Mice lacking the purinergic receptor P2X7R are acutely susceptible to toxoplasmic ileitis, losing significantly more weight than C57BL/6J mice and exhibiting much greater intestinal inflammatory pathology in response to infection with only 10 cysts of T. gondii. This susceptibility is not dependent on the ability of P2X7R-deficient mice to control the parasite, which they accomplish just as efficiently as C57BL/6J mice. Rather, susceptibility is associated with elevated ileal concentrations of pro-inflammatory cytokines, reactive nitrogen intermediates and altered regulation of elements of NFκB activation in P2X7R-deficient mice. Conclusions Our data support the thesis that P2X7R, a well-documented activator of pro-inflammatory cytokine production, also plays an important role in the regulation of intestinal inflammation. PMID:26053862

  7. 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

  8. 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…

  9. 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:…

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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.

  16. Saponins increase susceptibility of vancomycin-resistant enterococci to antibiotic compounds

    PubMed Central

    Heimesaat, Markus M.; Fischer, André; Bereswill, Stefan; Melzig, Matthias F.

    2014-01-01

    The resistance of commensal bacteria to first and second line antibiotics has reached an alarming level in many parts of the world and endangers the effective treatment of infectious diseases. In this study, the influence of the plant-derived natural saponins glycyrrhizic acid, β-aescin, α-hederin, hederacoside C, and primulic acid 1 on the susceptibility of vancomycin-resistant enterococci (VRE) against antibiotics of clinical relevance was investigated in 20 clinical isolates. Furthermore, the antibacterial properties of saponins under study against VRE were determined in vitro. Results reveal that the susceptibility of VRE against gentamicin, teicoplanin, and daptomycin was enhanced in the presence of the saponin glycyrrhizic acid. Most importantly, glycyrrhizic acid (1 mg/ml) diminished the minimal inhibitory concentration (MIC) of gentamicin in gentamicin low-level intrinsic resistant VRE from 2 – >8 mg/l to ≤ 0.125–1 mg/l. The adding of β-aescin, α-hederin, hederacoside C, and primulic acid 1 to the antibiotics under study showed, compared to glycyrrhizic acid, less influence on the antibiotic potency. Only glycyrrhizic acid (1 mg/ml) and α‑hederin (0.2 mg/ml) showed weak antibacterial properties against the clinical isolates. Our study points towards a therapeutic potential of saponins in the coapplication with antibiotics for bacterial infections. PMID:25544893

  17. Saponins increase susceptibility of vancomycin-resistant enterococci to antibiotic compounds.

    PubMed

    Schmidt, Sebastian; Heimesaat, Markus M; Fischer, André; Bereswill, Stefan; Melzig, Matthias F

    2014-12-01

    The resistance of commensal bacteria to first and second line antibiotics has reached an alarming level in many parts of the world and endangers the effective treatment of infectious diseases. In this study, the influence of the plant-derived natural saponins glycyrrhizic acid, β-aescin, α-hederin, hederacoside C, and primulic acid 1 on the susceptibility of vancomycin-resistant enterococci (VRE) against antibiotics of clinical relevance was investigated in 20 clinical isolates. Furthermore, the antibacterial properties of saponins under study against VRE were determined in vitro. Results reveal that the susceptibility of VRE against gentamicin, teicoplanin, and daptomycin was enhanced in the presence of the saponin glycyrrhizic acid. Most importantly, glycyrrhizic acid (1 mg/ml) diminished the minimal inhibitory concentration (MIC) of gentamicin in gentamicin low-level intrinsic resistant VRE from 2 - >8 mg/l to ≤ 0.125-1 mg/l. The adding of β-aescin, α-hederin, hederacoside C, and primulic acid 1 to the antibiotics under study showed, compared to glycyrrhizic acid, less influence on the antibiotic potency. Only glycyrrhizic acid (1 mg/ml) and α‑hederin (0.2 mg/ml) showed weak antibacterial properties against the clinical isolates. Our study points towards a therapeutic potential of saponins in the coapplication with antibiotics for bacterial infections. PMID:25544893

  18. Abrupt suspension of probiotics administration may increase host pathogen susceptibility by inducing gut dysbiosis.

    PubMed

    Liu, Zhi; Liu, Wenshu; Ran, Chao; Hu, Jun; Zhou, Zhigang

    2016-01-01

    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

  19. 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

  20. 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

  1. Androgen-inducible gene 1 increases the ER Ca(2+) content and cell death susceptibility against oxidative stress.

    PubMed

    Nickel, Nadine; Cleven, Astrid; Enders, Vitalij; Lisak, Dmitrij; Schneider, Lars; Methner, Axel

    2016-07-15

    Androgen-induced gene 1 (AIG1) is a transmembrane protein implicated with survival (its expression level was shown to correlate with the survival of patients suffering from hepatocellular carcinoma) and Ca(2+) signaling (over-expression of AIG1 increased transcription mediated by the Ca(2+)-dependent nuclear factor of activated T cells). We aimed to shed light on this less-studied protein and investigated its tissue expression, genomic organization, intracellular localization and membrane topology as well as its effects on cell death susceptibility and the Ca(2+) content of the endoplasmic reticulum. Immunoblotting of mouse tissues demonstrated highest expression of AIG1 in the liver, lung and heart. AIG1 has a complex genomic organization and expresses several splice variants in a tissue-dependent manner. Analyzing the topology of AIG1 in the ER membrane using a protease-protection assay suggested that AIG has five transmembrane domains with a luminal N- and cytosolic C-terminus and a hydrophobic stretch between the third and fourth membrane domain that does not cross the membrane. AIG1 over-expression slightly increased susceptibility to oxidative stress, which correlated with an increased ER Ca(2+) concentration in two different cell lines. Together, these results indicate that AIG1 plays a role in the control of the intracellular Ca(2+) concentration and cell death susceptibility. PMID:27040980

  2. 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

  3. Do young adults demand more dental services as their income increases?

    PubMed

    Grytten, Jostein; Holst, Dorthe

    2002-12-01

    Several studies from the USA have shown that there is a positive and strong relationship between income and demand for dental care. All these studies have been performed on populations where treatment needs were high. Today, young adults represent one group of the population where treatment needs are low. But young adults will not necessarily demand or utilize more dental services as their income increases. As we do not know the extent to which demand will increase when income increases among young adults, future needs for dental manpower could be less than predicted from previous studies. The aim of the present study was to examine the relationship between income and demand/utilization for dental services among young adults in Norway. The analyses were performed on two large sets of survey data, collected in 1985 and 1995, which were representative of the Norwegian population aged 20 years and above. The main finding was that the increase in demand with an increase in income was less for young adults than for older adults. In particular, there was a marked fall in the income elasticities among young adults from 1985 to 1995. The fall in the income elasticity corresponds to a marked decrease in the prevalence of dental diseases among young adults during that period. Our results imply that future policies for dental manpower should take into account the lower income elasticity for young adults compared to for older adults, and that future needs for dental personnel should be planned accordingly. PMID:12453118

  4. 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. PMID:23607678

  5. Application of artificial photoperiod in fish: a factor that increases susceptibility to infectious diseases?

    PubMed

    Valenzuela, Ariel; Campos, Victor; Yañez, Francisco; Alveal, Katherine; Gutiérrez, Pamela; Rivas, Meyling; Contreras, Nancy; Klempau, Alfredo; Fernandez, Italo; Oyarzun, Ciro

    2012-08-01

    This paper describes and evaluates the mortality associated with the potential stressor effect induced by application of artificial photoperiods in rainbow trout (Oncorhynchus mykiss). After application of artificial photoperiods, high mortalities of trout subjected to this management were recorded (36% in LD 14:10 and 25% in LD 24:0) as compared to controls (7%). The recorded signology related to diseased trout included darkening, lethargy and erratic swimming. Among the morphological changes, skin lesions and ulcerative-type necrosis could be observed. Blood tests, histopathology and isolation of pathogens identified as Flavobacterium psychrophilum, associated with Aeromonas, Pseudomonas and Saprolegnia sp., were performed. The application of artificial photoperiods suggests that fish may be more susceptible to opportunistic diseases; thus, it is advisable to emphasize preventive measures in fish subjected to this management. PMID:22160663

  6. 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

  7. 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

  8. Air pollution and lung function among susceptible adult subjects: a panel study

    PubMed Central

    Lagorio, Susanna; Forastiere, Francesco; Pistelli, Riccardo; Iavarone, Ivano; Michelozzi, Paola; Fano, Valeria; Marconi, Achille; Ziemacki, Giovanni; Ostro, Bart D

    2006-01-01

    Background Adverse health effects at relatively low levels of ambient air pollution have consistently been reported in the last years. We conducted a time-series panel study of subjects with chronic obstructive pulmonary disease (COPD), asthma, and ischemic heart disease (IHD) to evaluate whether daily levels of air pollutants have a measurable impact on the lung function of adult subjects with pre-existing lung or heart diseases. Methods Twenty-nine patients with COPD, asthma, or IHD underwent repeated lung function tests by supervised spirometry in two one-month surveys. Daily samples of coarse (PM10–2.5) and fine (PM2.5) particulate matter were collected by means of dichotomous samplers, and the dust was gravimetrically analyzed. The particulate content of selected metals (cadmium, chrome, iron, nickel, lead, platinum, vanadium, and zinc) was determined by atomic absorption spectrometry. Ambient concentrations of nitrogen dioxide (NO2), carbon monoxide (CO), ozone (O3), and sulphur dioxide (SO2) were obtained from the regional air-quality monitoring network. The relationships between concentrations of air pollutants and lung function parameters were analyzed by generalized estimating equations (GEE) for panel data. Results Decrements in lung function indices (FVC and/or FEV1) associated with increasing concentrations of PM2.5, NO2 and some metals (especially zinc and iron) were observed in COPD cases. Among the asthmatics, NO2 was associated with a decrease in FEV1. No association between average ambient concentrations of any air pollutant and lung function was observed among IHD cases. Conclusion This study suggests that the short-term negative impact of exposure to air pollutants on respiratory volume and flow is limited to individuals with already impaired respiratory function. The fine fraction of ambient PM seems responsible for the observed effects among COPD cases, with zinc and iron having a potential role via oxidative stress. The respiratory function

  9. 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

  10. Increasing Participation of Adults in Higher Education: Factors for Successful Policies

    ERIC Educational Resources Information Center

    Broek, Simon; Hake, Barry J.

    2012-01-01

    This article contains an analysis of policies aimed at increasing the participation of adults in higher education (HE) in seven countries (NL, DK, SE, UK, BE Flanders, DE and the state of California in the USA). In order to maintain their economic competitiveness, many countries have developed policies to increase the participation of adults in…

  11. 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

  12. Increased susceptibility of Cftr-/- mice to LPS-induced lung remodeling.

    PubMed

    Bruscia, Emanuela M; Zhang, Ping-Xia; Barone, Christina; Scholte, Bob J; Homer, Robert; Krause, Diane S; Egan, Marie E

    2016-04-15

    Cystic fibrosis (CF) is caused by homozygous mutations of the CF transmembrane conductance regulator (CFTR) Cl(-) channel, which result in chronic pulmonary infection and inflammation, the major cause of morbidity and mortality. Although these processes are clearly related to each other, each is likely to contribute to the pathology differently. Understanding the contribution of each of these processes to the overall pathology has been difficult, because they are usually so intimately connected. Various CF mouse models have demonstrated abnormal immune responses compared with wild-type (WT) littermates when challenged with live bacteria or bacterial products acutely. However, these studies have not investigated the consequences of persistent inflammation on lung tissue in CF mice, which may better model the lung pathology in patients. We characterized the lung pathology and immune response of Cftr(-/-) (CF) and Cftr(+/+) (WT) mice to chronic administration of Pseudomonas aeruginosa lipopolysaccharide (LPS). We show that, after long-term repeated LPS exposure, CF mice develop an abnormal and persistent immune response, which is associated with more robust structural changes in the lung than those observed in WT mice. Although CF mice and their WT littermates develop lung pathology after chronic exposure to LPS, the inflammation and damage resolve in WT mice. However, CF mice do not recover efficiently, and, as a consequence of their chronic inflammation, CF mice are more susceptible to morphological changes and lung remodeling. This study shows that chronic inflammation alone contributes significantly to aspects of CF lung pathology. PMID:26851259

  13. Prenatal bupropion exposure enhances the cocaine reward and stress susceptibility in adult mice.

    PubMed

    Hsiao, S Y; Cherng, C F G; Yang, Y K; Yeh, T L; Yu, L

    2005-12-31

    Although a growing body of evidence supports the notion that certain antidepressant treatments in pregnancy produce earlier delivery and minor behavioral teratogenesis in infants, the long-term effects of such treatments in adulthood remain ill-defined. Recently, postnatal exposure to psychotropic drugs was found to affect the emotional development and susceptibility to abused drugs. Thus, this study aimed to examine whether prenatal exposure of four frequently-used antidepressants, bupropion, fluvoxamine, citalopram, and trazodone, altered the responsiveness to stress and cocaine in the adulthood. Dams received daily injection of bupropion (25 or 12.5 mg/kg), citalopram (5 mg/kg), fluvoxamine (10 mg/kg), trazodone (20 mg/kg) or saline throughout their third trimester of gestation, and several birth outcome indices were then examined. Locomotor activity, naive anxiety levels, and the sensitivity to the cocaine reinforcing effects were observed in pups at their day 56-60 post partum. We found that trazodone treatment produced a high mortality rate in pups after weaning. Mice, prenatally treated with bupropion at 25 mg/kg, exhibited lower rearing numbers and ambulatory activity as compared to the saline-treated mice. More importantly, such treatment enhanced the mouse sensitivity to the reinforcing effects of cocaine. Taken together, these results suggest that use of bupropion in the late pregnancy may run a risk of enhancing the offspring's susceptibility to stress and cocaine reward in adulthood. PMID:16548425

  14. 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

  15. Adult sulfatide null mice maintain an increased number of oligodendrocytes

    PubMed Central

    Shroff, S; Pomicter, AD; Fox, MA; Henderson, SC; Dupree, JL

    2015-01-01

    The galactolipids galactocerebroside and sulfatide have been implicated in oligodendrocyte development and myelin formation. Much of the evidence for these galactolipid functions has been derived from antibody and chemical perturbation of cultured oligodendrocytes. Recently, we have observed abundant, unstable myelin and an increased number of oligodendrocytes in mice incapable of synthesizing the myelin galactolipids galactocerebroside and sulfatide. We have also reported that mice lacking sulfatide but that synthesize normal levels of galactocerebroside generate myelin with unstable paranodes while Hirahara et al. (2004) have shown an enhanced population of oligodendrocytes in the forebrain, medulla and cerebellum in immature sulfatide null mice. Here, we demonstrate that an increase in the number of oligodendrocytes in sulfatide null mice is not transient but is maintained through, at least, 7 months of age. Moreover, we demonstrate that the enhanced oligodendrocyte population results from, at least in part, increased cell survival. Finally, sulfatide null oligodendrocytes exhibit decreased morphological complexity, a feature which may relate to increased oligodendrocyte survival. PMID:19224580

  16. The Histone Deacetylase Inhibitor Vorinostat (SAHA) Increases the Susceptibility of Uninfected CD4+ T Cells to HIV by Increasing the Kinetics and Efficiency of Postentry Viral Events

    PubMed Central

    Lucera, Mark B.; Tilton, Carisa A.; Mao, Hongxia; Dobrowolski, Curtis; Tabler, Caroline O.; Haqqani, Aiman A.; Karn, Jonathan

    2014-01-01

    ABSTRACT Latently infected cells remain a primary barrier to eradication of HIV-1. Over the past decade, a better understanding of the molecular mechanisms by which latency is established and maintained has led to the discovery of a number of compounds that selectively reactivate latent proviruses without inducing polyclonal T cell activation. Recently, the histone deacetylase (HDAC) inhibitor vorinostat has been demonstrated to induce HIV transcription from latently infected cells when administered to patients. While vorinostat will be given in the context of antiretroviral therapy (ART), infection of new cells by induced virus remains a clinical concern. Here, we demonstrate that vorinostat significantly increases the susceptibility of CD4+ T cells to infection by HIV in a dose- and time-dependent manner that is independent of receptor and coreceptor usage. Vorinostat does not enhance viral fusion with cells but rather enhances the kinetics and efficiency of postentry viral events, including reverse transcription, nuclear import, and integration, and enhances viral production in a spreading-infection assay. Selective inhibition of the cytoplasmic class IIb HDAC6 with tubacin recapitulated the effect of vorinostat. These findings reveal a previously unknown cytoplasmic effect of HDAC inhibitors promoting productive infection of CD4+ T cells that is distinct from their well-characterized effects on nuclear histone acetylation and long-terminal-repeat (LTR) transcription. Our results indicate that careful monitoring of patients and ART intensification are warranted during vorinostat treatment and indicate that HDAC inhibitors that selectively target nuclear class I HDACs could reactivate latent HIV without increasing the susceptibility of uninfected cells to HIV. IMPORTANCE HDAC inhibitors, particularly vorinostat, are currently being investigated clinically as part of a “shock-and-kill” strategy to purge latent reservoirs of HIV. We demonstrate here that

  17. 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

  18. 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. PMID:26646793

  19. Susceptibility to interference by music and speech maskers in middle-aged adults.

    PubMed

    Başkent, Deniz; van Engelshoven, Suzanne; Galvin, John J

    2014-03-01

    Older listeners commonly complain about difficulty in understanding speech in noise. Previous studies have shown an age effect for both speech and steady noise maskers, and it is largest for speech maskers. In the present study, speech reception thresholds (SRTs) measured with competing speech, music, and steady noise maskers significantly differed between young (19 to 26 years) and middle-aged (51 to 63 years) adults. SRT differences ranged from 2.1 dB for competing speech, 0.4-1.6 dB for music maskers, and 0.8 dB for steady noise. The data suggest that aging effects are already evident in middle-aged adults without significant hearing impairment. PMID:24606308

  20. Susceptibility to interference by music and speech maskers in middle-aged adults

    PubMed Central

    Başkent, Deniz; van Engelshoven, Suzanne; Galvin, John J.

    2014-01-01

    Older listeners commonly complain about difficulty in understanding speech in noise. Previous studies have shown an age effect for both speech and steady noise maskers, and it is largest for speech maskers. In the present study, speech reception thresholds (SRTs) measured with competing speech, music, and steady noise maskers significantly differed between young (19 to 26 years) and middle-aged (51 to 63 years) adults. SRT differences ranged from 2.1 dB for competing speech, 0.4–1.6 dB for music maskers, and 0.8 dB for steady noise. The data suggest that aging effects are already evident in middle-aged adults without significant hearing impairment. PMID:24606308

  1. 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

  2. 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. PMID:23945726

  3. Medial-Lateral Postural Control in Older Adults Exhibits Increased Stiffness and Damping

    PubMed Central

    Cenciarini, Massimo; Loughlin, Patrick J.; Sparto, Patrick J.; Redfern, Mark S.

    2016-01-01

    Older adults often exhibit increased co-contraction in response to a balance perturbation. This response is generally thought to enhance stability by increasing joint stiffness. We investigated the issue of increased stiffness in postural control by exposing seven older (75 ±5 y) and ten young (24 ± 3 y) adults to pseudo-random medial-lateral (ML) floor tilts, and then fitting the measured ML body sway data to a previously-developed postural control model that includes stiffness and damping parameters. Significant increases were found in both parameters in the older adults compared to the young adults. This concurrent increase in stiffness and damping is more stabilizing than an increase in stiffness alone, which can lead to resonances. PMID:19964728

  4. Spiral-in/out BOLD fMRI for increased SNR and reduced susceptibility artifacts.

    PubMed

    Glover, G H; Law, C S

    2001-09-01

    BOLD fMRI is hampered by dropout of signal in the orbitofrontal and parietal brain regions due to magnetic field gradients near air-tissue interfaces. This work reports the use of spiral-in trajectories that begin at the edge of k-space and end at the origin, and spiral in/out trajectories in which a spiral-in readout is followed by a conventional spiral-out trajectory. The spiral-in trajectory reduces the dropout and increases the BOLD contrast. The spiral-in and spiral-out images can be combined in several ways to simultaneously achieve increased signal-to-noise ratio (SNR) and reduced dropout artifacts. Activation experiments employing an olfaction task demonstrate significantly increased activation volumes due to reduced dropout, and overall increased SNR in all regions. PMID:11550244

  5. 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…

  6. Effects of Increasing Task Load on Memory Impairment in Adults with Down Syndrome

    ERIC Educational Resources Information Center

    Oliver, Chris; Holland, Tony; Hall, Scott; Crayton, Lissa

    2005-01-01

    The effect of increasing the number of stimuli to be recalled was investigated to evaluate whether sensitivity for memory impairment was enhanced in adults with Down syndrome when using higher task load. Three levels of load were compared across three groups of adults: those with cognitive deterioration, no cognitive deterioration over age 40, and…

  7. 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…

  8. Genotypic Homogeneity of Multidrug Resistant S. Typhimurium Infecting Distinct Adult and Childhood Susceptibility Groups in Blantyre, Malawi

    PubMed Central

    Msefula, Chisomo L.; Kingsley, Robert A.; Gordon, Melita A.; Molyneux, Elizabeth; Molyneux, Malcolm E.; MacLennan, Calman A.; Dougan, Gordon; Heyderman, Robert S.

    2012-01-01

    Nontyphoidal Salmonella (NTS) serovars are a common cause of bacteraemia in young children and HIV-infected adults in Malawi and elsewhere in sub-Saharan Africa. These patient populations provide diverse host-immune environments that have the potential to drive bacterial adaptation and evolution. We therefore investigated the diversity of 27 multidrug resistant (MDR) Salmonella Typhimurium strains isolated over 6 years (2002–2008) from HIV-infected adults and children and HIV-uninfected children. Sequence reads from whole-genome sequencing of these isolates using the Illumina GA platform were mapped to the genome of the laboratory strain S. Typhimurium SL1344 excluding homoplastic regions that contained prophage and insertion elements. A phylogenetic tree generated from single nucleotide polymorphisms showed that all 27 strains clustered with the prototypical MDR strain D23580. There was no clustering of strains based on host HIV status or age, suggesting that these susceptible populations acquire S. Typhimurium from common sources or that isolates are transmitted freely between these populations. However, 7/14 of the most recent isolates (2006/2008) formed a distinct clade that branched off 22 SNPs away from the cluster containing earlier isolates. These data suggest that the MDR bacterial population is not static, but is undergoing microevolution which might result in further epidemiology change. PMID:22848711

  9. 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

  10. 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

  11. 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.

  12. Haemophilus influenzae increases the susceptibility and inflammatory response of airway epithelial cells to viral infections.

    PubMed

    Gulraiz, Fahad; Bellinghausen, Carla; Bruggeman, Cathrien A; Stassen, Frank R

    2015-03-01

    Nontypeable Haemophilus influenzae (NTHI), a common colonizer of lungs of patients with chronic obstructive pulmonary disease (COPD), can enhance expression of the cellular receptor intercellular adhesion molecule 1 (ICAM-1), which in turn can be used by major group human rhinoviruses (HRVs) for attachment. Here, we evaluated the effect of NTHI-induced up-regulation of ICAM-1 on viral replication and inflammatory responses toward different respiratory viruses. Therefore, human bronchial epithelial cells were pretreated with heat-inactivated NTHI (hi-NTHI) and subsequently infected with either HRV16 (major group), HRV1B (minor group), or respiratory syncytial virus (RSV). Pretreatment with hi-NTHI significantly up-regulated ICAM-1 in BEAS-2B cells and primary bronchial epithelial cells. Concomitantly, release of infectious HRV16 particles was increased in cells pretreated with hi-NTHI. Pretreatment with hi-NTHI also caused a significant increase in HRV16 RNA, whereas replication of HRV1B and RSV were increased to a far lesser extent and only at later time points. Interestingly, release of IL-6 and IL-8 after RSV, but not HRV, infection was synergistically increased in hi-NTHI-pretreated BEAS-2B cells. In summary, exposure to hi-NTHI significantly enhanced sensitivity toward HRV16 but not HRV1B or RSV, probably through ICAM-1 up-regulation. Furthermore, hi-NTHI pretreatment may enhance the inflammatory response to RSV infection, suggesting that preexisting bacterial infections might exaggerate inflammation during secondary viral infection. PMID:25411435

  13. Fetal programming by maternal obesity increases offspring’s susceptibility to obesity in later-life

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To examine whether exposure of the developing fetus to an obese mother during pregnancy increases the risk of obesity in the children in later-life, we have developed an overfeeding-based model of maternal obesity in rats by tube feeding of liquid diets directly into the stomach using total enteral ...

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

    PubMed Central

    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

  15. Changes in human dendritic cell number and function in severe obesity may contribute to increased susceptibility to viral infection.

    PubMed

    O'Shea, D; Corrigan, M; Dunne, M R; Jackson, R; Woods, C; Gaoatswe, G; Moynagh, P N; O'Connell, J; Hogan, A E

    2013-11-01

    Dendritic cells (DCs) are key immune sentinels linking the innate and adaptive immune systems. DCs recognise danger signals and initiate T-cell tolerance, memory and polarisation. They are critical cells in responding to a viral illness. Obese individuals have been shown to have an impaired response to vaccinations against virally mediated conditions and to have an increased susceptibility to multi-organ failure in response to viral illness. We investigated if DCs are altered in an obese cohort (mean body mass index 51.7±7.3 kg m(-2)), ultimately resulting in differential T-cell responses. Circulating DCs were found to be significantly decreased in the obese compared with the lean cohort (0.82% vs 2.53%). Following Toll-like receptor stimulation, compared with lean controls, DCs generated from the obese cohort upregulated significantly less CD83 (40% vs 17% mean fluorescence intensity), a molecule implicated in the elicitation of T-cell responses, particularly viral responses. Obese DCs produced twofold more of the immunosuppressive cytokine interleukin (IL)-10 than lean controls, and in turn stimulated fourfold more IL-4-production from allogenic naive T cells. We conclude that obesity negatively impacts the ability of DCs to mature and elicit appropriate T-cell responses to a general stimulus. This may contribute to the increased susceptibility to viral infection observed in severe obesity. PMID:23439322

  16. 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

  17. Increased atrial arrhythmia susceptibility induced by intense endurance exercise in mice requires TNFα.

    PubMed

    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

  18. 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

  19. 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

  20. Increasing spectrum in antimicrobial resistance of Shigella isolates in Bangladesh: resistance to azithromycin and ceftriaxone and decreased susceptibility to ciprofloxacin.

    PubMed

    Rahman, Mahbubur; Shoma, Shereen; Rashid, Harunur; El Arifeen, Shams; Baqui, A H; Siddique, A K; Nair, G B; Sack, D A

    2007-06-01

    Antimicrobial resistance of Shigella isolates in Bangladesh, during 2001-2002, was studied and compared with that of 1991-1992 to identify the changes in resistance patterns and trends. A significant increase in resistance to trimethoprim-sulphamethoxazole (from 52% to 72%, p < 0.01) and nalidixic acid (from 19% to 51%, p < 0.01) was detected. High, but unchanged, resistance to tetracycline, ampicillin, and chloramphenicol, low resistance to mecillinam (resistance 3%, intermediate 3%), and to emergence of resistance to azithromycin (resistance 16%, intermediate 62%) and ceftriaxone/cefixime (2%) were detected in 2001-2002. Of 266 recent isolates, 63% were resistant to > or =3 anti-Shigella drugs (multidrug-resistant [MDR]) compared to 52% of 369 strains (p < 0.007) in 1991-1992. Of 154 isolates tested by E-test in 2001-2002, 71% were nalidixic acid-resistant (minimum inhibitory concentration [MIC] > or =32 microg/mL) and had 10-fold higher MIC90 (0.25 microg/mL) to ciprofloxacin than that of nalidixic acid-susceptible strains exhibiting decreased ciprofloxacin susceptibility, which were detected as ciprofloxacin-susceptible and nalidixic acid-resistant by the disc-diffusion method. These strains were frequently associated with MDR traits. High modal MICs were observed to azithromycin (MIC 6 microg/mL) and nalidixic acid (MIC 128 micdrog/mL) and low to ceftriaxone (MIC 0.023 microg/mL). Conjugative R-plasmids-encoded extended-spectrum beta-lactamase was responsible for resistance to ceftriaxone/cefixime. The growing antimicrobial resistance of Shigella is worrying and mandates monitoring of resistance. Pivmecillinam or ciprofloxacin might be considered for treating shigellosis with caution. PMID:17985817

  1. Increasing Spectrum in Antimicrobial Resistance of Shigella Isolates in Bangladesh: Resistance to Azithromycin and Ceftriaxone and Decreased Susceptibility to Ciprofloxacin

    PubMed Central

    Mahbubur, Rahman; Shoma, Shereen; Rashid, Harunur; Arifeen, Shams El; Baqui, A.H.; Siddique, A.K.; Nair, G.B.; Sack, D.A.

    2007-01-01

    Antimicrobial resistance of Shigella isolates in Bangladesh, during 2001-2002, was studied and compared with that of 1991-1992 to identify the changes in resistance patterns and trends. A significant increase in resistance to trimethoprim-sulphamethoxazole (from 52% to 72%, p<0.01) and nalidixic acid (from 19% to 51%, p<0.01) was detected. High, but unchanged, resistance to tetracycline, ampicillin, and chloramphenicol, low resistance to mecillinam (resistance 3%, intermediate 3%), and to emergence of resistance to azithromycin (resistance 16%, intermediate 62%) and ceftriaxone/cefixime (2%) were detected in 2001-2002. Of 266 recent isolates, 63% were resistant to ≥3 anti-Shigella drugs (multidrug-resistant [MDR]) compared to 52% of 369 strains (p<0.007) in 1991-1992. Of 154 isolates tested by E-test in 2001-2002, 71% were nalidixic acid-resistant (minimum inhibitory concentration [MIC] ≥32 μg/mL) and had 10-fold higher MIC90 (0.25 μg/mL) to ciprofloxacin than that of nalidixic acid-susceptible strains exhibiting decreased ciprofloxacin susceptibility, which were detected as ciprofloxacin-susceptible and nalidixic acid-resistant by the disc-diffusion method. These strains were frequently associated with MDR traits. High modal MICs were observed to azithromycin (MIC 6 μg/mL) and nalidixic acid (MIC 128 μg/mL) and low to ceftriaxone (MIC 0.023 μg/mL). Conjugative R-plasmids-encoded extended-spectrum ß-lactamase was responsible for resistance to ceftriaxone/cefixime. The growing antimicrobial resistance of Shigella is worrying and mandates monitoring of resistance. Pivmecillinam or ciprofloxacin might be considered for treating shigellosis with caution. PMID:17985817

  2. Repetitive trigeminal nociceptive stimulation in rats increases their susceptibility to cortical spreading depression.

    PubMed

    Toriumi, Haruki; Shimizu, Toshihiko; Ebine, Taeko; Takizawa, Tsubasa; Kayama, Yohei; Koh, Anri; Shibata, Mamoru; Suzuki, Norihiro

    2016-05-01

    We examined the ability of trigeminal nerve activation to induce cortical spreading depression in rats. Capsaicin was injected into the bilateral plantar or whisker pad for either 4 or 6 days in rats. The number and duration of cortical spreading depressions induced by potassium were significantly increased in animals injected with capsaicin in the bilateral whisker pad compared with animals injected in the bilateral plantar or in controls, while administration of a GABAA receptor agonist decreased these effects. Repetitive nociceptive stimulation of the trigeminal nerve lowers the threshold for the induction of cortical spreading depression by altering GABAergic neuronal activity. PMID:26739227

  3. 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

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

    PubMed Central

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

    2011-01-01

    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 pre-formed S. aureus biofilms were efficiently detached in 2 min by rhDNase at 1 mg l−1. Pre-treatment 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 subminimal inhibitory concentrations of antibiotics. We also also found rhDNase significantly increased the survival of S. aureus-infected C. elegans nematodes treated with tobramycin compared to 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

  5. 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.

  6. 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

  7. Ethanol and Reactive Species Increase Basal Sequence Heterogeneity of Hepatitis C Virus and Produce Variants with Reduced Susceptibility to Antivirals

    PubMed Central

    Seronello, Scott; Montanez, Jessica; Presleigh, Kristen; Barlow, Miriam; Park, Seung Bum; Choi, Jinah

    2011-01-01

    Hepatitis C virus (HCV) exhibits a high level of genetic variability, and variants with reduced susceptibility to antivirals can occur even before treatment begins. In addition, alcohol decreases efficacy of antiviral therapy and increases sequence heterogeneity of HCV RNA but how ethanol affects HCV sequence is unknown. Ethanol metabolism and HCV infection increase the level of reactive species that can alter cell metabolism, modify signaling, and potentially act as mutagen to the viral RNA. Therefore, we investigated whether ethanol and reactive species affected the basal sequence variability of HCV RNA in hepatocytes. Human hepatoma cells supporting a continuous replication of genotype 1b HCV RNA (Con1, AJ242652) were exposed to ethanol, acetaldehyde, hydrogen peroxide, or L-buthionine-S,R-sulfoximine (BSO) that decreases intracellular glutathione as seen in patients. Then, NS5A region was sequenced and compared with genotype 1b HCV sequences in the database. Ethanol and BSO elevated nucleotide and amino acid substitution rates of HCV RNA by 4–18 folds within 48 hrs which were accompanied by oxidative RNA damage. Iron chelator and glutathione ester decreased both RNA damage and mutation rates. Furthermore, infectious HCV and HCV core gene were sufficient to induce oxidative RNA damage even in the absence of ethanol or BSO. Interestingly, the dn/ds ratio and percentage of sites undergoing positive selection increased with ethanol and BSO, resulting in an increased detection of NS5A variants with reduced susceptibility to interferon alpha, cyclosporine, and ribavirin and others implicated in immune tolerance and modulation of viral replication. Therefore, alcohol is likely to synergize with virus-induced oxidative/nitrosative stress to modulate the basal mutation rate of HCV. Positive selection induced by alcohol and reactive species may contribute to antiviral resistance. PMID:22087316

  8. Chemical Sympathectomy Increases Susceptibility to Ocular Herpes Simplex Virus Type 1 Infection

    PubMed Central

    Templeton, Amanda; Nguyen, Gabrielle; Ash, John D.; Straub, Rainer H.; Carr, Daniel J. J.

    2008-01-01

    The cornea is one of the most highly innervated tissues in the mammalian host. We hypothesized changes to cornea innervation through chemical sympathectomy would significantly alter the host response to the neurotropic viral pathogen, herpes simplex virus type 1 (HSV-1) following ocular infection. Mice treated with 6-hydroxydopamine hydrobromide displayed reduced tyrosine hydroxylase-positive fibers residing in the cornea. Sympathectomized mice were also found to show a transient rise in virus recovered in infected tissues and succumbed to infection in greater numbers. Whereas there were no differences in infiltrating leukocyte populations including HSV-1-specific cytotoxic T lymphocytes in the infected tissue, an increase in substance P and a decrease in IFN-γ levels in the trigeminal ganglion but not brain stem of sympathectomized mice were noted. Sympathectomized mice treated with the neurokinin-1 receptor antagonist L703,606 had delayed mortality implicating the involvement of substance P in HSV-1-mediated death. PMID:18495255

  9. 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

  10. 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

  11. Increased production of mitochondrial reactive oxygen species and reduced adult life span in an insecticide-resistant strain of Anopheles gambiae

    PubMed Central

    Otali, Dennis; Novak, Robert J.; Wan, Wen; Bu, Su; Moellering, Douglas R.; De Luca, Maria

    2014-01-01

    Control of the malaria vector An. gambiae is still largely obtained through chemical intervention using pyrethroids, such as permethrin. However, strains of An. gambiae that are resistant to the toxic effects of pyrethroids have become widespread in several endemic areas over the last decade. The objective of this study was to assess differences in five life-history traits (larval developmental time and the body weight, fecundity, hatch rate, and longevity of adult females) and energy metabolism between a strain of An. gambiae that is resistant to permethrin (RSP), due to knockdown resistance and enhanced metabolic detoxification, and a permethrin susceptible strain reared under laboratory conditions. We also quantified the expression levels of five antioxidant enzyme genes: GSTe3, CAT, GPXH1, SOD1, and SOD2. We found that the RSP strain had a longer developmental time than the susceptible strain. Additionally, RSP adult females had higher wet body weight and increased water and glycogen levels. Compared to permethrin susceptible females, RSP females displayed reduced metabolic rate and mitochondrial coupling efficiency and higher mitochondrial ROS production. Furthermore, despite higher levels of GSTe3 and CAT transcripts, RSP females had a shorter adult life span than susceptible females. Collectively, these results suggest that permethrin resistance alleles might affect energy metabolism, oxidative stress, and adult survival of An. gambiae. However, because the strains used in this study differ in their genetic backgrounds, the results need to be interpreted with caution and replicated in other strains in order to have significant implications for malaria transmission and vector control. PMID:24555527

  12. 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

  13. 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. PMID:26595392

  14. High levels of retinal membrane docosahexaenoic acid increase susceptibility to stress-induced degeneration.

    PubMed

    Tanito, Masaki; Brush, Richard S; Elliott, Michael H; Wicker, Lea D; Henry, Kimberly R; Anderson, Robert E

    2009-05-01

    The fat-1 gene cloned from C. elegans encodes an n-3 fatty acid desaturase that converts n-6 to n-3 PUFA. Mice carrying the fat-1 transgene and wild-type controls were fed an n-3-deficient/n-6-enriched diet [fat-1- safflower oil (SFO) and wt-SFO, respectively]. Fatty acid profiles of rod outer segments (ROS), cerebellum, plasma, and liver demonstrated significantly lower n-6/n-3 ratios and higher docosahexaenoic acid (DHA) levels in fat-1-SFO compared with wt-SFO. When mice were exposed to light stress: 1) the outer nuclear layer (ONL) thickness was reduced; 2) amplitudes of the electroretinogram (ERG) were lower; 3) the number of apoptotic photoreceptor cells was greater; and 4) modification of retinal proteins by 4-hydroxyhexenal (4-HHE), an end-product of n-3 PUFA oxidation was increased in both fat-1-SFO and wt mice fed a regular lab chow diet compared with wt-SFO. The results indicate a positive correlation between the level of DHA, the degree of n-3 PUFA lipid peroxidation, and the vulnerability of the retina to photooxidative stress. In mice not exposed to intense light, the reduction in DHA resulted in reduced efficacy in phototransduction gain steps, while no differences in the retinal morphology or retinal biochemistry. These results highlight the dual roles of DHA in cellular physiology and pathology. PMID:19023138

  15. Susceptibility of neonatal T cells and adult thymocytes to peripheral tolerance to allogeneic stimuli

    PubMed Central

    do Canto, Fábio B; Lima, Celso; Teixeira, Ivan A; Bellio, Maria; Nóbrega, Alberto; Fucs, Rita

    2008-01-01

    We studied the tolerization of neonatal thymocytes (NT), neonatal splenocytes (NS) and adult thymocytes (AT), transferred to syngeneic nude (nu/nu) hosts previously injected with semi-allogeneic splenocytes, without any supportive immunosuppressive treatment. This protocol allows the study of peripheral tolerance in the absence of the thymus. BALB/c neonatal T cells and ATs were able to expand in syngeneic BALB/c nu/nu mice and functionally reconstituted an allogeneic response, rejecting (BALB/c × B6.Ba) F1 splenocytes transferred 3–4 weeks after injection of BALB/c cells. However, if (BALB/c × B6.Ba) F1 cells were injected into BALB/c nude hosts 30 days before transfer of NT, NS or AT cells, the F1 population was preserved and specific tolerance to B6 allografts was established. Furthermore, transfer to lymphopenic F1 nu/nu showed that tolerance could be established only for neonatal populations, showing that unique properties of neonatal T cells allow their tolerization in both lymphopenic and non-lymphopenic conditions, in the absence of suppressive immunotherapy. These results bring empirical support to the possibility of T-cell engraftment in immunodeficient patients showing partial identity with donor major histocompatibility complex (MHC) genes; the manipulation of immunological maturity of donor T cells may be the key for successful reconstitution of immunocompetence without induction of graft-versus-host disease. PMID:18462348

  16. Antibiotic susceptibility and molecular mechanisms of macrolide resistance in streptococci isolated from adult cystic fibrosis patients.

    PubMed

    Thornton, Christina S; Grinwis, Margot E; Sibley, Christopher D; Parkins, Michael D; Rabin, Harvey R; Surette, Michael G

    2015-11-01

    The cystic fibrosis (CF) airways are colonized by polymicrobial communities with high bacterial load and are influenced by frequent antibiotic exposures. This community includes diverse streptococci, some of which have been directly or indirectly associated with pulmonary exacerbations. As many streptococci are naturally competent, horizontal transfer of antibiotic-resistant determinants coupled with frequent and/or chronic antibiotic exposure may contribute to high resistance rates. In this study, we assessed antibiotic resistance in 413 streptococcal isolates from adult CF patients against nine antibiotics relevant in CF treatment. We observed very low rates of cephalosporin resistance [cefepime and ceftriaxone ( < 2%)], and higher rates of resistance to tetracycline (∼34%) and sulfamethoxazole/trimethoprim (∼45%). The highest rate of antibiotic resistance was to the macrolides [azithromycin (56.4%) and erythromycin (51.6%)]. We also investigated the molecular mechanisms of macrolide resistance and found that only half of our macrolide-resistant streptococci isolates contained the mef (efflux pump) or erm (methylation of 23S ribosomal target site) genes. The majority of isolates were, however, found to have point mutations at position 2058 or 2059 of the 23S ribosomal subunit - a molecular mechanism of resistance not commonly reported in the non-pyogenic and non-pneumococcal streptococci, and unique in comparison with previous studies. The high rates of resistance observed here may result in poor outcomes where specific streptococci are contributing to CF airway disease and serve as a reservoir of resistance genes within the CF airway microbiome. PMID:26408040

  17. Renal human organic anion transporter 3 increases the susceptibility of lymphoma cells to bendamustine uptake.

    PubMed

    Hagos, Yohannes; Hundertmark, Philip; Shnitsar, Volodymyr; Marada, Venkata V V R; Wulf, Gerald; Burckhardt, Gerhard

    2015-02-15

    Chronic lymphatic leukemia (CLL) is often associated with nephritic syndrome. Effective treatment of CLL by chlorambucil and bendamustine leads to the restoration of renal function. In this contribution, we sought to elucidate the impact of organic anion transporters (OATs) on the uptake of bendamustine and chlorambucil as a probable reason for the superior efficacy of bendamustine over chlorambucil in the treatment of CLL. We examined the effects of structural analogs of p-aminohippurate (PAH), melphalan, chlorambucil, and bendamustine, on OAT1-mediated [(3)H]PAH uptake and OAT3- and OAT4-mediated [(3)H]estrone sulfate (ES) uptake in stably transfected human embryonic kidney-293 cells. Melphalan had no significant inhibitory effect on any OAT, whereas chlorambucil reduced OAT1-, OAT3-, and OAT4-mediated uptake of PAH or ES down to 14.6%, 16.3%, and 66.0% of control, respectively. Bendamustine inhibited only OAT3-mediated ES uptake, which was reduced down to 14.3% of control cells, suggesting that it interacts exclusively with OAT3. The IC50 value for OAT3 was calculated to be 0.8 μM. Real-time PCR experiments demonstrated a high expression of OAT3 in lymphoma cell lines as well as primary CLL cells. OAT3-mediated accumulation of bendamustine was associated with reduced cell proliferation and an increased rate of apoptosis. We conclude that the high efficacy of bendamustine in treating CLL might be partly contributed to the expression of OAT3 in lymphoma cells and the high affinity of bendamustine for this transporter. PMID:25477469

  18. Neuronal PPARγ Deficiency Increases Susceptibility to Brain Damage after Cerebral Ischemia

    PubMed Central

    Zhao, Xiurong; Strong, Roger; Zhang, Jie; Sun, Guanghua; Tsien, Joe Z; Cui, Zhenzhong; Grotta, James C.; Aronowski, Jaroslaw

    2009-01-01

    Peroxisome proliferator-activated receptor gamma (PPARγ) plays a role in regulating a myriad of biological processes in virtually all brain cell types, including neurons. We and others have reported recently that drugs which activate PPARγ are effective in reducing damage to brain in distinct models of brain disease, including ischemia. However, the cell type responsible for PPARγ-mediated protection has not been established. In response to ischemia, PPARγ gene is robustly upregulated in neurons, suggesting that neuronal PPARγ may be a primary target for PPARγ-agonist mediated neuroprotection. To understand the contribution of neuronal PPARγ to ischemic injury, we generated conditional neuron-specific PPARγ knockout mice (N-PPARγ-KO). These mice are viable and appeared to be normal with respect to their gross behavior and brain anatomy. However, neuronal PPARγ deficiency caused these mice to experience significantly more brain damage and oxidative stress in response to middle cerebral artery occlusion. The primary cortical neurons harvested from N-PPARγ-KO mice, but not astroglia, exposed to ischemia in vitro demonstrated more damage and a reduced expression of numerous key gene products that could explain increased vulnerability, including: SOD1, catalase, glutathione S-transferase (GST), uncoupling protein-1 or transcription factor liver X receptor-alpha (LXRα). Also, PPARγ agonist based neuroprotective effect was lost in neurons from N-PPARγ neurons. Therefore, we conclude that PPARγ in neurons play an essential protective function, and that PPARγ agonists may have utility in neuronal self-defense, in addition to their well-established anti-inflammatory effect. PMID:19439596

  19. 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

  20. Potassium permanganate elicits a shift of the external fish microbiome and increases host susceptibility to columnaris disease.

    PubMed

    Mohammed, Haitham H; Arias, Covadonga R

    2015-01-01

    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. PMID:26170019

  1. 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

  2. Conditional Expression of the Androgen Receptor Increases Susceptibility of Bladder Cancer in Mice.

    PubMed

    Johnson, Daniel T; Hooker, Erika; 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

  3. Increased susceptibility of ethanol-treated gastric mucosa to naproxen and its inhibition by DA-9601, an Artemisia asiatica extract

    PubMed Central

    Oh, Tae Young; Ahn, Gook Jun; Choi, Seul Min; Ahn, Byoung Ok; Kim, Won Bae

    2005-01-01

    AIM: To examine the effect of DA-9601, a new gastroprotective agent, on the vulnerability of ethanol-treated rat’s stomach to naproxen (NAP). METHODS: Male Sprague-Dawley rats were pretreated with 1 mL of 50% ethanol twice a day for 5 d and then NAP (50 mg/kg) was administered. DA-9601 was administered 1 h before NAP. Four hours after NAP, the rats were killed to examine gross injury index (mm2), histologic change and to determine mucosal levels of malondialdehyde (MDA), prostaglandin E2 (PGE2), glutathione (GSH) and myeloperoxidase (MPO). RESULTS: Pretreatment of ethanol significantly increased NAP-induced gastric lesions, as well as an increase in MDA and MPO. On the contrary, mucosal PGE2 and GSH contents were decreased dramatically by ethanol pretreatment, which were aggravated by NAP. DA-9601 significantly reduced NAP-induced gastric injury grossly and microscopically, regardless of pretreatment with ethanol. DA-9601 preserved, or rather, increased mucosal PGE2 and GSH in NAP-treated rats (P<0.05), with reduction in mucosal MDA and MPO levels. CONCLUSION: These results suggest that repeated alcohol consumption renders gastric mucosa more susceptible to NSAIDs though, at least in part, reduction of endogenous cytoprotectants including PGE2 and GSH, and increase in MPO activation, and that DA-9601, a new gastroprotectant, can reduce the increased vulnerability of ethanol consumers to NSAIDs-induced gastric damage via the mechanism in which PGE2 and GSH are involved. PMID:16437715

  4. Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection

    PubMed Central

    Theriot, Casey M.; Koenigsknecht, Mark J.; Carlson, Paul E.; Hatton, Gabrielle E.; Nelson, Adam M.; Li, Bo; Huffnagle, Gary B.; Li, Jun; Young, Vincent B.

    2014-01-01

    Antibiotics can have significant and long lasting effects on the gastrointestinal tract microbiota, reducing colonization resistance against pathogens including Clostridium difficile. Here we show that antibiotic treatment induces substantial changes in the gut microbial community and in the metabolome of mice susceptible to C. difficile infection. Levels of secondary bile acids, glucose, free fatty acids, and dipeptides decrease, whereas those of primary bile acids and sugar alcohols increase, reflecting the modified metabolic activity of the altered gut microbiome. In vitro and ex vivo analyses demonstrate that C. difficile can exploit specific metabolites that become more abundant in the mouse gut after antibiotics, including primary bile acid taurocholate for germination, and carbon sources mannitol, fructose, sorbitol, raffinose and stachyose for growth. Our results indicate that antibiotic-mediated alteration of the gut microbiome converts the global metabolic profile to one that favors C. difficile germination and growth. PMID:24445449

  5. AhrdCyp1a2(−/−) mice show increased susceptibility to PCB-induced developmental neurotoxicity

    PubMed Central

    Curran, Christine Perdan; Altenhofen, Emily; Ashworth, Amy; Brown, Austin; Kamau-Cheggeh, Cellestine; Curran, Melinda; Evans, Amber; Floyd, Rikki; Fowler, Jocelyn; Garber, Helen; Hays, Breann; Kraemer, Sarah; Lang, Anna; Mynhier, Andrea; Samuels, Ashton; Strohmaier, Carly

    2012-01-01

    Polychlorinated biphenyls (PCBs) are developmental neurotoxicants that produce cognitive and behavioral changes in children exposed during gestation and lactation. Coplanar PCBs bind the aryl hydrocarbon receptor (AHR) and can be sequestered in liver by cytochrome P450 1A2 (CYP1A2). The AHR is a ligand-activated transcription factor which increases expression of the CYP1 family, including CYP1A2. Our previous work examining genetic susceptibility to developmental PCB neurotoxicity showed that AhrbCyp1a2(−/−) mice with the high-affinity Ahrb allele and lacking CYP1A2 were most susceptible while AhrbCyp1a2(+/+) and poor-affinity AhrdCyp1a2(+/+) mice were resistant. To follow up, a fourth line of mice was generated with the AhrdCyp1a2(−/−) genotype and compared with the background strain AhrbCyp1a2(+/+). Dams received a PCB mixture or the corn oil vehicle at gestational day 10 (GD10) and postnatal day 5 (PND5). Offspring were tested at PND60 in open field locomotor, acoustic startle with pre-pulse inhibition (PPI), novel object recognition and Morris water maze. Locomotor activity was increased in PCB-treated AhrbCyp1a2(+/+) mice, but no differences were seen in control v. PCB-treated AhrdCyp1a2(−/−) mice. PCB-treated AhrdCyp1a2(−/−) mice had a higher baseline startle response and significantly reduced pre-pulse inhibition at the 74dB level compared with corn oil-treated controls (P<0.05). PCB-treated AhrdCyp1a2(−/−) mice had impairments in novel objective recognition (P<0.05) and during all three hidden platform phases of Morris water maze (P<0.01). Combined with our previous findings, these results indicate Cyp1a2 genotype is more important in susceptibility to PCB-induced deficits in learning and memory, but Ahr genotype appears more important when assessing acoustic startle-PPI and locomotor activity. PMID:22935098

  6. 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

  7. 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

  8. 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

  9. 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. PMID:26336925

  10. 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

  11. 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

  12. 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

  13. Helping Adult ESOL Students Increase Speaking and Listening Skills by Serving as Volunteers in Authentic Settings.

    ERIC Educational Resources Information Center

    Harrell, Edith Lynn

    This practicum paper documents a program that was developed and implemented to help adult, advanced English-as-a-Second-Language (ESL) students increase their speaking and listening skills and build self confidence with native English speakers. The objective was to increase group average exit test scores in speaking and listening by at least two…

  14. 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

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

    PubMed

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

    2015-10-01

    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

  16. 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

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

    PubMed

    Xiao, Yutao; Liu, Kaiyu; Zhang, Dandan; Gong, Lingling; He, Fei; Soberón, Mario; Bravo, Alejandra; Tabashnik, Bruce E; Wu, Kongming

    2016-02-01

    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

  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. 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

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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

  5. Inherited variant on chromosome 11q23 increases susceptibility to IDH-mutated but not IDH-normal gliomas regardless of grade or histology

    PubMed Central

    Rice, Terri; Zheng, Shichun; Decker, Paul A.; Walsh, Kyle M.; Bracci, Paige; Xiao, Yuanyuan; McCoy, Lucie S.; Smirnov, Ivan; Patoka, Joseph S.; Hansen, Helen M.; Hsuang, George; Wiemels, Joe L.; Tihan, Tarik; Pico, Alexander R.; Prados, Michael D.; Chang, Susan M.; Berger, Mitchel S.; Caron, Alissa; Fink, Stephanie; Kollmeyer, Thomas; Rynearson, Amanda; Voss, Jesse; Kosel, Matthew L.; Fridley, Brooke L.; Lachance, Daniel H.; Eckel-Passow, Jeanette E.; Sicotte, Hugues; O'Neill, Brian Patrick; Giannini, Caterina; Wiencke, John K.; Jenkins, Robert B.; Wrensch, Margaret R.

    2013-01-01

    Introduction Recent discoveries of inherited glioma risk loci and acquired IDH mutations are providing new insights into glioma etiology. IDH mutations are common in lower grade gliomas and secondary glioblastomas and uncommon in primary glioblastomas. Because the inherited variant in 11q23 has been associated with risk of lower grade glioma and not with glioblastomas, we hypothesized that this variant increases susceptibility to IDH-mutated gliomas, but not to IDH-wild-type gliomas. Methods We tested this hypothesis in patients with glioma and controls from the San Francisco Adult Glioma Study, the Mayo Clinic, and Illumina controls (1102 total patients, 5299 total controls). Case-control additive associations of 11q23 risk alleles (rs498872, T allele) were calculated using logistic regression, stratified by tumor IDH status (mutated or wild-type) and by histology and grade. We also adjusted for the recently discovered 8q24 glioma risk locus rs55705857 G allele. Results The 11q23 glioma risk locus was associated with increased risk of IDH-mutated gliomas of all histologies and grades (odds ratio [OR] = 1.50; 95% confidence interval [CI] = 1.29–1.74; P = 1.3X10−7) but not with IDH-wild-type gliomas of any histology or grade (OR = 0.91; 95% CI = 0.81–1.03; P = 0.14). The associations were independent of the rs55705857 G allele. Conclusion A variant at the 11q23 locus increases risk for IDH-mutated but not IDH-wild-type gliomas, regardless of grade or histology. PMID:23361564

  6. LPS-induced imbalanced expression of hepatic vascular stress genes in cirrhosis: possible mechanism of increased susceptibility to endotoxemia.

    PubMed

    Baveja, Rajiv; Keller, Steve; Yokoyama, Yukihiro; Sonin, Natalie; Clemens, Mark G; Zhang, Jian X

    2002-04-01

    dilatory forces to counterbalance the constrictive effect of ET-1 upon a secondary insult of endotoxemia. These results may partly explain the increased susceptibility of cirrhotic livers to injury as a result of endotoxemia. PMID:11954834

  7. Evolution of increased adult longevity in Drosophila melanogaster populations selected for adaptation to larval crowding.

    PubMed

    Shenoi, V N; Ali, S Z; Prasad, N G

    2016-02-01

    In holometabolous animals such as Drosophila melanogaster, larval crowding can affect a wide range of larval and adult traits. Adults emerging from high larval density cultures have smaller body size and increased mean life span compared to flies emerging from low larval density cultures. Therefore, adaptation to larval crowding could potentially affect adult longevity as a correlated response. We addressed this issue by studying a set of large, outbred populations of D. melanogaster, experimentally evolved for adaptation to larval crowding for 83 generations. We assayed longevity of adult flies from both selected (MCUs) and control populations (MBs) after growing them at different larval densities. We found that MCUs have evolved increased mean longevity compared to MBs at all larval densities. The interaction between selection regime and larval density was not significant, indicating that the density dependence of mean longevity had not evolved in the MCU populations. The increase in longevity in MCUs can be partially attributed to their lower rates of ageing. It is also noteworthy that reaction norm of dry body weight, a trait probably under direct selection in our populations, has indeed evolved in MCU populations. To the best of our knowledge, this is the first report of the evolution of adult longevity as a correlated response of adaptation to larval crowding. PMID:26575793

  8. 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

  9. Cigarette Smoke Disrupted Lung Endothelial Barrier Integrity and Increased Susceptibility to Acute Lung Injury via Histone Deacetylase 6.

    PubMed

    Borgas, Diana; Chambers, Eboni; Newton, Julie; Ko, Junsuk; Rivera, Stephanie; Rounds, Sharon; Lu, Qing

    2016-05-01

    Epidemiologic evidence indicates that cigarette smoke (CS) is associated with the development of acute lung injury (ALI). We have previously shown that brief CS exposure exacerbates lipopolysaccharide (LPS)-induced ALI in vivo and endothelial barrier dysfunction in vitro. In this study, we found that CS also exacerbated Pseudomonas-induced ALI in mice. We demonstrated that lung microvascular endothelial cells (ECs) isolated from mice exposed to CS had a greater permeability or incomplete recovery after challenges by LPS and thrombin. Histone deacetylase (HDAC) 6 deacetylates proteins essential for maintenance of endothelial barrier function. We found that HDAC6 phosphorylation at serine-22 was increased in lung tissues of mice exposed to CS and in lung ECs exposed to cigarette smoke extract (CSE). Inhibition of HDAC6 attenuated CSE-induced increases in EC permeability and CS priming of ALI. Similar barrier protection was provided by the microtubule stabilizer taxol, which preserved α-tubulin acetylation. CSE decreased α-tubulin acetylation and caused microtubule depolymerization. In coordination with increased HDAC6 phosphorylation, CSE inhibited Akt and activated glycogen synthase kinase (GSK)-3β; these effects were ameliorated by the antioxidant N-acetyl cysteine. Our results suggest that CS increases lung EC permeability, thereby enhancing susceptibility to ALI, likely through oxidative stress-induced Akt inactivation and subsequent GSK-3β activation. Activated GSK-3β may activate HDAC6 via phosphorylation of serine-22, leading to α-tubulin deacetylation and microtubule disassembly. Inhibition of HDAC6 may be a novel therapeutic option for ALI in cigarette smokers. PMID:26452072

  10. 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

  11. 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

  12. Cytochrome 4A11 Genetic Polymorphisms Increase Susceptibility to Ischemic Stroke and Associate with Atherothrombotic Events After Stroke in Chinese

    PubMed Central

    Zhang, Biao; Wang, Chun; Liao, Duanxiu; Lin, Jing; Chi, Lifen

    2015-01-01

    To evaluate the associations between four single-nucleotide polymorphisms (SNPs) in CYP4A11 and CYP4F2 and ischemic stroke (IS), and between these variants and atherothrombotic events after stroke. IS patients (n=396) and controls (n=378) were genotyped for two CYP4A11 SNPs (rs2269231 and rs9333025) and two CYP4F2 SNPs (rs2108622 and rs3093135). Patients were followed up for 12 months after the stroke for the atherothrombotic events. The frequency of the rs9333025 GG genotype was significantly higher in IS patients than in controls. Logistic regression analysis showed that the presence of rs9333025 GG in patients was associated with significantly higher risk of IS. Cox regression analysis revealed that the rs9333025 GG genotype was an independent risk factor for atherothrombotic events after stroke. The rs9333025 GG genotype increases patients' susceptibility to IS and is associated with high frequencies of atherothrombotic events in stroke patients. PMID:25734770

  13. 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

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

    PubMed Central

    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

    2014-01-01

    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

  15. 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

  16. 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

  17. The Use of Gap Analysis to Increase Student Completion Rates at Travelor Adult School

    ERIC Educational Resources Information Center

    Gil, Blanca Estela

    2013-01-01

    This project applied the gap analysis problem-solving framework (Clark & Estes, 2008) in order to help develop strategies to increase completion rates at Travelor Adult School. The purpose of the study was to identify whether the knowledge, motivation and organization barriers were contributing to the identified gap. A mixed method approached…

  18. 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…

  19. Adult Illiteracy: An Alarming Problem. A Position Paper on Increasing Literacy in Washington.

    ERIC Educational Resources Information Center

    Rosenwasser, Marie

    With declines in reading skills and increases in the standards for literacy, illiteracy has become a growing national problem. The task of dealing with illiteracy ranges from educating those adults whose basic skills are below the eighth grade level to teaching those who are struggling to learn English as their second language to serving those…

  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. 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

  2. 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

  3. Activated T cells exhibit increased uptake of silicon phthalocyanine Pc 4 and increased susceptibility to Pc 4-photodynamic therapy-mediated cell death.

    PubMed

    Soler, David C; Ohtola, Jennifer; Sugiyama, Hideaki; Rodriguez, Myriam E; Han, Ling; Oleinick, Nancy L; Lam, Minh; Baron, Elma D; Cooper, Kevin D; McCormick, Thomas S

    2016-06-01

    Photodynamic therapy (PDT) is an emerging treatment for malignant and inflammatory dermal disorders. Photoirradiation of the silicon phthalocyanine (Pc) 4 photosensitizer with red light generates singlet oxygen and other reactive oxygen species to induce cell death. We previously reported that Pc 4-PDT elicited cell death in lymphoid-derived (Jurkat) and epithelial-derived (A431) cell lines in vitro, and furthermore that Jurkat cells were more sensitive than A431 cells to treatment. In this study, we examined the effectiveness of Pc 4-PDT on primary human CD3(+) T cells in vitro. Fluorometric analyses of lysed T cells confirmed the dose-dependent uptake of Pc 4 in non-stimulated and stimulated T cells. Flow cytometric analyses measuring annexin V and propidium iodide (PI) demonstrated a dose-dependent increase of T cell apoptosis (6.6-59.9%) at Pc 4 doses ranging from 0-300 nM. Following T cell stimulation through the T cell receptor using a combination of anti-CD3 and anti-CD28 antibodies, activated T cells exhibited increased susceptibility to Pc 4-PDT-induced apoptosis (10.6-81.2%) as determined by Pc 4 fluorescence in each cell, in both non-stimulated and stimulated T cells, Pc 4 uptake increased with Pc 4 dose up to 300 nM as assessed by flow cytometry. The mean fluorescence intensity (MFI) of Pc 4 uptake measured in stimulated T cells was significantly increased over the uptake of resting T cells at each dose of Pc 4 tested (50, 100, 150 and 300 nM, p < 0.001 between 50 and 150 nM, n = 8). Treg uptake was diminished relative to other T cells. Cutaneous T cell lymphoma (CTCL) T cells appeared to take up somewhat more Pc 4 than normal resting T cells at 100 and 150 nm Pc 4. Confocal imaging revealed that Pc 4 localized in cytoplasmic organelles, with approximately half of the Pc 4 co-localized with mitochondria in T cells. Thus, Pc 4-PDT exerts an enhanced apoptotic effect on activated CD3(+) T cells that may be exploited in targeting T cell-mediated skin

  4. 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

  5. Adult neuroblastoma complicated by increased intracranial pressure: a case report and review of the literature.

    PubMed

    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, I(131) 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

  6. 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

  7. 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. PMID:24714816

  8. 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

  9. Young adult stimulant users' increased striatal activation during uncertainty is related to impulsivity

    PubMed Central

    Leland, David S.; Arce, Estibaliz; Feinstein, Justin S.; Paulus, Martin P.

    2006-01-01

    Background Young adults who use stimulants (e.g., cocaine, amphetamines) are at particular risk of transitioning to dependence. Previously, we demonstrated increased risk-taking in young adults who had used stimulants (Leland and Paulus, 2005). Since outcome uncertainty is a critical element of risk, we investigated whether such individuals have different neural responses to uncertainty than their stimulant-naïve peers. Method Eleven young adults (age 18–25) who had used stimulants were compared with 11 age- and education-matched stimulant-naïve controls using functional magnetic resonance imaging and a card prediction task with relatively certain/uncertain outcome conditions. Results The caudate, an area involved in processing salient events, was among those regions more active in users than controls in response to uncertainty. Personality measures revealed that users were more impulsive than controls, and that neural response to uncertainty in a number of areas including the thalamus/caudate was positively correlated with impulsivity. Conclusions These results are consistent with the idea that young adults who have used stimulant find uncertainty particularly salient, due in part to preexisting differences in impulsivity, and may be subject to more “action pressure” when making decisions under uncertainty. This neural and personality profile may constitute a marker for increased risk of stimulant use. PMID:16959497

  10. Increased marijuana use and gender predict poorer cognitive functioning in adolescents and emerging adults.

    PubMed

    Lisdahl, Krista M; Price, Jenessa S

    2012-07-01

    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

  11. Maternal Treatment with Agonistic Autoantibodies against Type-1 Angiotensin II Receptor in Late Pregnancy Increases Apoptosis of Myocardial Cells and Myocardial Susceptibility to Ischemia-Reperfusion Injury in Offspring Rats

    PubMed Central

    Wang, Xiaofang; Zheng, Yanqian; Zhang, Qiaoyan; Zhi, Jianming

    2013-01-01

    Epidemiological studies have demonstrated that offspring born to mothers preeclampsia (PE) are at increased risk for developing cardiovascular diseases after birth, but the underlying mechanism is unknown. Angiotensin II receptor type 1 autoantibody (AT1-AA), an agonist acting via activation of the AT1 receptor, is believed to be involved in the pathogenesis of both PE and fetal growth restriction. The aim of the present study was to confirm the hypothesis that prenatal AT1-AA exposure increases the heart susceptibility to ischemia/reperfusion injury (IRI) in the offspring in an AT1-AA-induced animal model of PE, and determine whether or not the increase of maternal AT1-AA level is a factor contributing to sustained abnormalities of the heart structure during infancy. The hearts of 45-day-old offspring rats were studied using Langendorff preparation to determine the susceptibility of the heart to IRI. The results showed that the body weight of the maternal rats was not significantly different between the study and control groups, but the body weight of their offspring in AT1-AA group was decreased slightly at day 21 of gestational age, and at day 3 after birth. Although the heart weight index was not significantly affected at all ages examined, AT1-AA significantly increased the size of myocardial cells of the left ventricle (LV) at the age of 45 days. AT1-AA gained access to fetal circulation via the placenta and induced apoptosis of fetal myocardial cells. AT1-AA also significantly delayed recovery from IRI and affected the LV function of 45-day-old offspring. This was associated with a significant increase in IRI-induced LV myocardial infarct size. These results suggest that AT1-AA induced abnormal apoptosis of fetal myocardial cells during the fetal period and increased the cardiac susceptibility to IRI in adult offspring. PMID:24278308

  12. Does selection on increased cold tolerance in the adult stage confer resistance throughout development?

    PubMed

    Dierks, A; Kölzow, N; Franke, K; Fischer, K

    2012-08-01

    Artificial selection is a powerful approach to unravel constraints on genetic adaptation. Although it has been frequently used to reveal genetic trade-offs among different fitness-related traits, only a few studies have targeted genetic correlations across developmental stages. Here, we test whether selection on increased cold tolerance in the adult stage increases cold resistance throughout ontogeny in the butterfly Bicyclus anynana. We used lines selected for decreased chill-coma recovery time and corresponding controls, which had originally been set up from three levels of inbreeding (outbred control, one or two full-sib matings). Four generations after having terminated selection, a response to selection was found in 1-day-old butterflies (the age at which selection took place). Older adults showed a very similar although weaker response. Nevertheless, cold resistance did not increase in either egg, larval or pupal stage in the selection lines but was even lower compared to control lines for eggs and young larvae. These findings suggest a cost of increased adult cold tolerance, presumably reducing resource availability for offspring provisioning and thereby stress tolerance during development, which may substantially affect evolutionary trajectories. PMID:22686583

  13. 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

  14. Skeletal muscle amino acid transporter expression is increased in young and older adults following resistance exercise

    PubMed Central

    Fry, Christopher S.; Glynn, Erin L.; Timmerman, Kyle L.; Dickinson, Jared M.; Walker, Dillon K.; Gundermann, David M.; Volpi, Elena; Rasmussen, Blake B.

    2011-01-01

    Amino acid transporters and mammalian target of rapamycin complex 1 (mTORC1) signaling are important contributors to muscle protein anabolism. Aging is associated with reduced mTORC1 signaling following resistance exercise, but the role of amino acid transporters is unknown. Young (n = 13; 28 ± 2 yr) and older (n = 13; 68 ± 2 yr) subjects performed a bout of resistance exercise. Skeletal muscle biopsies (vastus lateralis) were obtained at basal and 3, 6, and 24 h postexercise and were analyzed for amino acid transporter mRNA and protein expression and regulators of amino acid transporter transcription utilizing real-time PCR and Western blotting. We found that basal amino acid transporter expression was similar in young and older adults (P > 0.05). Exercise increased L-type amino acid transporter 1/solute-linked carrier (SLC) 7A5, CD98/SLC3A2, sodium-coupled neutral amino acid transporter 2/SLC38A2, proton-assisted amino acid transporter 1/SLC36A1, and cationic amino acid transporter 1/SLC7A1 mRNA expression in both young and older adults (P < 0.05). L-type amino acid transporter 1 and CD98 protein increased only in younger adults (P < 0.05). eukaryotic initiation factor 2 α-subunit (S52) increased similarly in young and older adults postexercise (P < 0.05). Ribosomal protein S6 (S240/244) and activating transcription factor 4 nuclear protein expression tended to be higher in the young, while nuclear signal transducer and activator of transcription 3 (STAT3) (Y705) was higher in the older subjects postexercise (P < 0.05). These results suggest that the rapid upregulation of amino acid transporter expression following resistance exercise may be regulated differently between the age groups, but involves a combination of mTORC1, activating transcription factor 4, eukaryotic initiation factor 2 α-subunit, and STAT3. We propose an increase in amino acid transporter expression may contribute to enhanced amino acid sensitivity following exercise in young and older

  15. Increased reprogramming of human fetal hepatocytes compared with adult hepatocytes in feeder-free conditions.

    PubMed

    Hansel, Marc C; Gramignoli, Roberto; Blake, William; Davila, Julio; Skvorak, Kristen; Dorko, Kenneth; Tahan, Veysel; Lee, Brian R; Tafaleng, Edgar; Guzman-Lepe, Jorge; Soto-Gutierrez, Alejandro; Fox, Ira J; Strom, Stephen C

    2014-01-01

    Hepatocyte transplantation has been used to treat liver disease. The availability of cells for these procedures is quite limited. Human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) may be a useful source of hepatocytes for basic research and transplantation if efficient and effective differentiation protocols were developed and problems with tumorigenicity could be overcome. Recent evidence suggests that the cell of origin may affect hiPSC differentiation. Thus, hiPSCs generated from hepatocytes may differentiate back to hepatocytes more efficiently than hiPSCs from other cell types. We examined the efficiency of reprogramming adult and fetal human hepatocytes. The present studies report the generation of 40 hiPSC lines from primary human hepatocytes under feeder-free conditions. Of these, 37 hiPSC lines were generated from fetal hepatocytes, 2 hiPSC lines from normal hepatocytes, and 1 hiPSC line from hepatocytes of a patient with Crigler-Najjar syndrome, type 1. All lines were confirmed reprogrammed and expressed markers of pluripotency by gene expression, flow cytometry, immunocytochemistry, and teratoma formation. Fetal hepatocytes were reprogrammed at a frequency over 50-fold higher than adult hepatocytes. Adult hepatocytes were only reprogrammed with six factors, while fetal hepatocytes could be reprogrammed with three (OCT4, SOX2, NANOG) or four factors (OCT4, SOX2, NANOG, LIN28 or OCT4, SOX2, KLF4, C-MYC). The increased reprogramming efficiency of fetal cells was not due to increased transduction efficiency or vector toxicity. These studies confirm that hiPSCs can be generated from adult and fetal hepatocytes including those with genetic diseases. Fetal hepatocytes reprogram much more efficiently than adult hepatocytes, although both could serve as useful sources of hiPSC-derived hepatocytes for basic research or transplantation. PMID:23394081

  16. Inequality in mortality decreased among the young while increasing for older adults, 1990-2010.

    PubMed

    Currie, J; Schwandt, H

    2016-05-01

    Many recent studies point to increasing inequality in mortality in the United States over the past 20 years. These studies often use mortality rates in middle and old age. We used poverty level rankings of groups of U.S. counties as a basis for analyzing inequality in mortality for all age groups in 1990, 2000, and 2010. Consistent with previous studies, we found increasing inequality in mortality at older ages. For children and young adults below age 20, however, we found strong mortality improvements that were most pronounced in poorer counties, implying a strong decrease in mortality inequality. These younger cohorts will form the future adult U.S. population, so this research suggests that inequality in old-age mortality is likely to decline. PMID:27103667

  17. Increase in primary and secondary syphilis cases in older adults in Louisiana.

    PubMed

    Holden, Julie; Trachtman, Louis

    2011-01-01

    Sexually active young adults and adolescents experience a majority of the burden of sexually transmitted diseases in the United States and public health resources are appropriately directed at these age groups. However, sexual health of older adults is often ignored. An analysis of sexually transmitted disease surveillance data from the Louisiana Office of Public Health show that both the numbers and rates of primary and secondary syphilis cases have increased in older age groups over the past 10 years. Clinicians must be aware of increased use of erectile dysfunction drugs in older persons as a possible risk factor for sexually transmitted diseases. Clinicians must also realize that a significant number of older persons display sexually risky behavior and safe sexual health counseling is often overlooked in this population. PMID:22324089

  18. 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

  19. Motor Variability during Sustained Contractions Increases with Cognitive Demand in Older Adults

    PubMed Central

    Vanden Noven, Marnie L.; Pereira, Hugo M.; Yoon, Tejin; Stevens, Alyssa A.; Nielson, Kristy A.; Hunter, Sandra K.

    2014-01-01

    To expose cortical involvement in age-related changes in motor performance, we compared steadiness (force fluctuations) and fatigability of submaximal isometric contractions with the ankle dorsiflexor muscles in older and young adults and with varying levels of cognitive demand imposed. Sixteen young (20.4 ± 2.1 year: 8 men, 9 women) and 17 older adults (68.8 ± 4.4 years: 9 men, 8 women) attended three sessions and performed a 40 s isometric contraction at 5% maximal voluntary contraction (MVC) force followed by an isometric contraction at 30% MVC until task failure. The cognitive demand required during the submaximal contractions in each session differed as follows: (1) high-cognitive demand session where difficult mental math was imposed (counting backward by 13 from a 4-digit number); (2) low-cognitive demand session which involved simple mental math (counting backward by 1); and (3) control session with no mental math. Anxiety was elevated during the high-cognitive demand session compared with other sessions for both age groups but more so for the older adults than young adults (p  < 0.05). Older adults had larger force fluctuations than young adults during: (1) the 5% MVC task as cognitive demand increased (p  = 0.007), and (2) the fatiguing contraction for all sessions (p  = 0.002). Time to task failure did not differ between sessions or age groups (p  > 0.05), but the variability between sessions (standard deviation of three sessions) was greater for older adults than young (2.02 ± 1.05 vs. 1.25 ± 0.51 min, p  < 0.05). Thus, variability in lower limb motor performance for low- and moderate-force isometric tasks increased with age and was exacerbated when cognitive demand was imposed, and may be related to modulation of synergist and antagonist muscles and an altered neural strategy with age originating from central sources. These data have significant implications for cognitively demanding low-force motor tasks

  20. 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.

  1. Increased severity of experimental autoimmune encephalomyelitis in rats tolerized as adults but not neonatally to a protective TCR V beta 8 CDR2 idiotope.

    PubMed

    Offner, H; Malotky, M K; Pope, L; Vainiene, M; Celnik, B; Miller, S D; Vandenbark, A A

    1995-01-15

    The ability of synthetic V region peptides to induce regulatory T cells and Abs in rodents and humans provides clear evidence that these idiotopes do not naturally induce tolerance. In this study, we investigated the ability of TCR V beta 8.2 peptides to experimentally induce specific T cell tolerance, as measured by loss of Ag-specific proliferation and delayed-type hypersensitivity responses, and by increased susceptibility to experimental autoimmune encephalomyelitis (EAE). We found that both neonatal and adult exposure to V beta 8.2-39-59 or V beta 8-44-54 peptides could induce efficient T cell tolerance, resulting in a significant inhibition of peptide-specific proliferative responses. In addition, neonatal tolerance resulted in a partial reduction in delayed-type hypersensitivity response and an inability to vaccinate against EAE after adult immunization with the tolerizing peptide. We further evaluated the contribution of naturally induced TCR-specific responses to EAE resistance induced by challenging neonatally or adult tolerized rats with myelin basic protein in adjuvant. The clinical course of EAE was not significantly altered in rats tolerized neonatally to V beta 8.2 peptides, but both the severity and incidence of mortality from EAE was increased in rats tolerized as adults with V beta 8.2 peptides conjugated to syngeneic splenocytes. These results demonstrate that V beta 8.2 peptides are tolerogenic as well as immunogenic. Moreover, the observation of different effects of neonatal vs adult tolerization on the course of EAE suggests either the emergence of additional protective idiotopes after neonatal tolerization and/or mechanistic differences in the two tolerance-inducing protocols. Most importantly, the enhancement of clinical EAE in rats tolerized as adults with V beta 8.2 peptides provides evidence for an innate regulatory role of the CDR2 idiotope in recovery from EAE. PMID:7529291

  2. 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

  3. Food restriction increases long-term memory persistence in adult or aged mice.

    PubMed

    Talhati, F; Patti, C L; Zanin, K A; Lopes-Silva, L B; Ceccon, L M B; Hollais, A W; Bizerra, C S; Santos, R; Tufik, S; Frussa-Filho, R

    2014-04-01

    Food restriction (FR) seems to be the unique experimental manipulation that leads to a remarkable increase in lifespan in rodents. Evidences have suggested that FR can enhance memory in distinct animal models mainly during aging. However, only few studies systemically evaluated the effects FR on memory formation in both adult (3-month-old) and aged (18-24-month-old) mice. Thus, the aim of the present study was to investigate the effects of acute (12h) or repeated (12h/day for 2days) FR protocols on learning and memory of adult and aged mice evaluated in the plus-maze discriminative avoidance task (PM-DAT), an animal model that concurrently (but independently) evaluates learning and memory, anxiety and locomotion. We also investigated the possible role of FR-induced stress by the corticosterone concentration in adult mice. Male mice were kept at home cage with food ad libitum (CTRL-control condition) or subjected to FR during the dark phase of the cycle for 12h/day or 12h/2days. The FR protocols were applied before training, immediately after it or before testing. Our results demonstrated that only FR for 2days enhanced memory persistence when applied before training in adults and before testing in aged mice. Conversely, FR for 2days impaired consolidation and exerted no effects on retrieval irrespective of age. These effects do not seem to be related to corticosterone concentration. Collectively, these results indicate that FR for 2days can promote promnestic effects not only in aged mice but also in adults. PMID:24361378

  4. 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

  5. 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.

  6. 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

  7. 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. PMID:24947605

  8. 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

  9. 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

  10. 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. PMID:25216299

  11. 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

  12. Preliminary efficacy of prize-based contingency management to increase activity levels in healthy adults.

    PubMed

    Washington, Wendy Donlin; Banna, Kelly M; Gibson, Amanda L

    2014-01-01

    An estimated 30% of Americans meet the criteria for obesity. Effective, low-cost interventions to increase physical activity are needed to prevent and treat obesity. In this study, 11 healthy adults wore Fitbit accelerometers for 3 weeks. During the initial baseline, subjects earned prize draws for wearing the Fitbit. During intervention, percentile schedules were used to calculate individual prize-draw criteria. The final week was a return to baseline. Four subjects increased step counts as a result of the intervention. A bout analysis of interresponse times revealed that subjects increased overall step counts by increasing daily minutes active and within-bout response rates and decreasing pauses between bouts of activity. Strategies to improve effectiveness are suggested, such as modification of reinforcement probability and amount and identification of the function of periods of inactivity. PMID:24740477

  13. Increasing hepatitis C knowledge among homeless adults: results of a community-based, interdisciplinary intervention.

    PubMed

    Tyler, Darlene; Nyamathi, Adeline; Stein, Judith A; Koniak-Griffin, Deborah; Hodge, Felicia; Gelberg, Lillian

    2014-01-01

    Homeless adults have high rates of hepatitis C virus infection (HCV) and low levels of HCV knowledge. This study reports results of an interdisciplinary, community-based intervention using stakeholder cooperation, case management, risk factor identification, and modification of dysfunctional psychosocial factors to increase HCV knowledge among homeless adults (N = 747). Data are from a randomized quasi-experimental study, with the major goal of evaluating the effectiveness of a Nurse Case Managed Intervention compared to a Standard Intervention, encouraging completion of a three-series hepatitis A/hepatitis B vaccination program. Increased HCV knowledge was measured with an 18-item questionnaire discerning risk factors for HCV and common misconceptions about individuals with HCV. A significant increase in HCV knowledge resulted regardless of intervention format. Receiving the Nurse Case Managed Intervention predicted greatest gain in HCV knowledge (p < 0.000). Successfully engaging key stakeholders, outreach workers, community organizations, and homeless people themselves proved most efficacious in increasing HCV knowledge. PMID:23616250

  14. 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

  15. 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

  16. 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

  17. 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

  18. Analysis of Triclosan-Selected Salmonella enterica Mutants of Eight Serovars Revealed Increased Aminoglycoside Susceptibility and Reduced Growth Rates

    PubMed Central

    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. 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

  20. 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

  1. Intravenous gestational nicotine exposure results in increased motivation for sucrose reward in adult rat offspring

    PubMed Central

    Lacy, Ryan T.; Hord, Lauren L.; Morgan, Amanda J.; Harrod, Steven B.

    2012-01-01

    Background Prenatal tobacco smoke exposure is associated with alterations in motivated behavior in offspring, such as increased consumption of highly palatable foods and abused drugs. Animal models show that gestational nicotine (GN) exposure mediates changes in responding for sucrose and drug reward. Methods A novel, intermittent low-dose intravenous (IV) exposure model was used to administer nicotine (0.05 mg/kg/injection) or saline 3×/day to rats on gestational days 8-21. Two experiments investigated the effect of IV GN on 1) the habituation of spontaneous locomotor activity and on 2) sucrose reinforced responding in offspring. For the operant experiments, animals acquired fixed-ratio (FR-3) responding for sucrose, 26% (w/v), and were tested on varying concentrations (0, 3, 10, 30, 56%; Latin-square) according to a FR-3, and then a progressive-ratio (PR) schedule. Male and female adult offspring were used. Results IV GN did not alter birth or growth weight, or the number of pups born. No between-group differences in habituation to spontaneous locomotor activity were observed. FR testing produced an inverted U-shaped response curve, and rats showed peak responding for 10% sucrose reinforcement. Neither gestation nor sex affected responding, suggesting equivalent sensitivity to varying sucrose concentrations. PR testing revealed that GN rats showed greater motivation for sucrose reinforcement relative to controls. Conclusions A low-dose, IV GN exposure model resulted in increased motivation to respond for sucrose reinforcement in adult offspring. This suggests that using a low number of cigarettes throughout pregnancy will result in increased motivation for highly palatable foods in adult, and perhaps, adolescent offspring. PMID:22377090

  2. Adult male mice conceived by in vitro fertilization exhibit increased glucocorticoid receptor expression in fat tissue.

    PubMed

    Simbulan, R K; Liu, X; Feuer, S K; Maltepe, E; Donjacour, A; Rinaudo, P

    2016-02-01

    Prenatal development is highly plastic and readily influenced by the environment. Adverse conditions have been shown to alter organ development and predispose offspring to chronic diseases, including diabetes and hypertension. Notably, it appears that the changes in glucocorticoid hormones or glucocorticoid receptor (GR) levels in peripheral tissues could play a role in the development of chronic diseases. We have previously demonstrated that in vitro fertilization (IVF) and preimplantation embryo culture is associated with growth alterations and glucose intolerance in mice. However, it is unknown if GR signaling is affected in adult IVF offspring. Here we show that GR expression is increased in inbred (C57Bl6/J) and outbred (CF-1× B6D2F1/J) blastocysts following in vitro culture and elevated levels are also present in the adipose tissue of adult male mice. Importantly, genes involved in lipolysis and triglyceride synthesis and responsive to GR were also increased in adipose tissue, indicating that increased GR activates downstream gene pathways. The promoter region of GR, previously reported to be epigenetically modified by perinatal manipulation, showed no changes in DNA methylation status. Our findings demonstrate that IVF results in a long-term change in GR gene expression in a sex- and tissue-specific manner. These changes in adipose tissues may well contribute to the metabolic phenotype in mice conceived by IVF. PMID:26511158

  3. 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

  4. Perinatal Nicotine Exposure Increases Angiotensin II Receptor-Mediated Vascular Contractility in Adult Offspring

    PubMed Central

    Xiao, DaLiao; Dasgupta, Chiranjib; Li, Yong; Huang, Xiaohui; Zhang, Lubo

    2014-01-01

    Previous studies have reported that perinatal nicotine exposure causes development of hypertensive phenotype in adult offspring. Aims The present study was to determine whether perinatal nicotine exposure causes an epigenetic programming of vascular Angiotensin II receptors (ATRs) and their-mediated signaling pathway leading to heightened vascular contraction in adult offspring. Main methods Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps from day 4 of gestation to day 10 after birth. The experiments were conducted at 5 months of age of male offspring. Key Findings Nicotine treatment enhanced Angitension II (Ang II)-induced vasoconstriction and 20-kDa myosin light chain phosphorylation (MLC20-P) levels. In addition, the ratio of Ang II-induced tension/MLC-P was also significantly increased in nicotine-treated group compared with the saline group. Nicotine-mediated enhanced constrictions were not directly dependent on the changes of [Ca2+]i concentrations but dependent on Ca2+ sensitivity. Perinatal nicotine treatment significantly enhanced vascular ATR type 1a (AT1aR) but not AT1bR mRNA levels in adult rat offspring, which was associated with selective decreases in DNA methylation at AT1aR promoter. Contrast to the effect on AT1aR, nicotine decreased the mRNA levels of vascular AT2R gene, which was associated with selective increases in DNA methylation at AT2R promoter. Significance Our results indicated that perinatal nicotine exposure caused an epigenetic programming of vascular ATRs and their-mediated signaling pathways, and suggested that differential regulation of AT1R/AT2R gene expression through DNA methylation mechanism may be involved in nicotine-induced heightened vasoconstriction and development of hypertensive phenotype in adulthood. PMID:25265052

  5. 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

  6. Increased bone density and decreased bone turnover, but no evident alteration of fracture susceptibility in elderly women with diabetes mellitus.

    PubMed

    Gerdhem, P; Isaksson, A; Akesson, K; Obrant, Karl J

    2005-12-01

    Bone density, bone turnover and fracture susceptibility were evaluated in 1,132 randomly recruited women, all 75 years old. Seventy-four of the women had diabetes, while 1,058 women did not. Areal bone mineral density (aBMD) of the hip and lumbar spine was investigated by dual energy X-ray absorptiometry (DXA), and bone mass of the calcaneus was measured by ultrasound. Urinary deoxypyridinoline/creatinine (U-DPD/Crea) and serum C-terminal cross-linked telopeptide of type 1 collagen (S-CTX) were assessed as markers of bone resorption. Serum bone-specific alkaline phosphatase (S-bone ALP) and serum osteocalcin (S-OC) were assessed as markers of bone formation. Also, serum 25(OH) vitamin D and serum parathyroid hormone (S-PTH) were assessed. Fracture susceptibility was evaluated retrospectively and prospectively for up to 6.5 years. In diabetic women, the aBMD of the femoral neck was 11% higher (p<0.001), and BMD of the lumbar spine was 8% higher (p=0.002) than in non-diabetic women. There was no difference in bone mass by ultrasound of the calcaneus. Women with diabetes had higher BMD of the femoral neck (p<0.001) and lumbar spine (p=0.03) also after correction for differences in body weight. In diabetic women, U-DPD/Crea, S-CTX, and S-OC were decreased when compared with non-diabetic women (p=0.001 or less). After correction for covariance of body weight and plasma creatinine, S-CTX (p<0.001) and S-OC (p<0.001) were still lower in the diabetic women. Diabetic patients had hypovitaminosis D (p=0.008), a difference explained by differences in time spent outdoors and body weight. S-PTH did not differ between the groups. Women with diabetes had no more lifetime fractures (52%) than women without diabetic disease (57%), (p=0.31). This study shows that elderly women with diabetes and without severe renal insufficiency have high bone mass and low bone turnover. The high bone mass and low bone turnover is not likely to have a strong influence on fracture susceptibility

  7. Gut microbiota richness promotes its stability upon increased dietary fibre intake in healthy adults.

    PubMed

    Tap, Julien; Furet, Jean-Pierre; Bensaada, Martine; Philippe, Catherine; Roth, Hubert; Rabot, Sylvie; Lakhdari, Omar; Lombard, Vincent; Henrissat, Bernard; Corthier, Gérard; Fontaine, Eric; Doré, Joël; Leclerc, Marion

    2015-12-01

    Gut microbiota richness and stability are important parameters in host-microbe symbiosis. Diet modification, notably using dietary fibres, might be a way to restore a high richness and stability in the gut microbiota. In this work, during a 6-week nutritional trial, 19 healthy adults consumed a basal diet supplemented with 10 or 40 g dietary fibre per day for 5 days, followed by 15-day washout periods. Fecal samples were analysed by a combination of 16S rRNA gene pyrosequencing, intestinal cell genotoxicity assay, metatranscriptomics sequencing approach and short-chain fatty analysis. This short-term change in the dietary fibre level did not have the same impact for all individuals but remained significant within each individual gut microbiota at genus level. Higher microbiota richness was associated with higher microbiota stability upon increased dietary fibre intake. Increasing fibre modulated the expression of numerous microbiota metabolic pathways such as glycan metabolism, with genes encoding carbohydrate-active enzymes active on fibre or host glycans. High microbial richness was also associated with high proportions of Prevotella and Coprococcus species and high levels of caproate and valerate. This study provides new insights on the role of gut microbial richness in healthy adults upon dietary changes and host microbes' interaction. PMID:26235304

  8. 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. PMID:22118754

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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. PMID:25803605

  17. Deficiency of the Planar Cell Polarity Protein Vangl2 in Podocytes Affects Glomerular Morphogenesis and Increases Susceptibility to Injury

    PubMed Central

    Rocque, Brittany L.; Babayeva, Sima; Li, Jane; Leung, Vicki; Nezvitsky, Lisa; Cybulsky, Andrey V.; Gros, Philippe

    2015-01-01

    The planar cell polarity (PCP) signaling pathway is crucial for tissue morphogenesis. Van Gogh-like protein 2 (Vangl2) is central in the PCP pathway; in mice, Vangl2 loss is embryonically lethal because of neural tube defects, and mutations in Vangl2 are associated with human neural tube defects. In the kidney, PCP signaling may be important for tubular morphogenesis and organization of glomerular epithelial cells (podocytes) along the glomerular basement membrane. Podocyte cell protrusions (foot processes) are critical for glomerular permselectivity; loss of foot process architecture results in proteinuria and FSGS. Previously, we showed a profound effect of PCP signaling on podocyte shape, actin rearrangement, cell motility, and nephrin endocytosis. To test our hypothesis that the PCP pathway is involved in glomerular development and function and circumvent lethality of the ubiquitous Vangl2 mutation in the Looptail mouse, we generated a mouse model with a podocyte-specific ablation of the Vangl2 gene. We report here that podocyte-specific deletion of Vangl2 leads to glomerular maturation defects in fetal kidneys. In adult mice, we detected significantly smaller glomeruli, but it did not affect glomerular permselectivity in aging animals. However, in the context of glomerular injury induced by injection of antiglomerular basement membrane antibody, deletion of Vangl2 resulted in exacerbation of injury and accelerated progression to chronic segmental and global glomerular sclerosis. Our results indicate that Vangl2 function in podocytes is important for glomerular development and protects against glomerular injury in adult animals. PMID:25145929

  18. 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/...

  19. Fetal exposure to HIV-1 alters chemokine receptor expression by CD4+T cells and increases susceptibility to HIV-1.

    PubMed

    Bunders, Madeleine J; van Hamme, John L; Jansen, Machiel H; Boer, Kees; Kootstra, Neeltje A; Kuijpers, Taco W

    2014-01-01

    Absolute numbers of lymphocytes are decreased in uninfected infants born to HIV-1-infected women (HIV-1-exposed). Although the exact mechanism is unknown, fetal exposure to maternal HIV-1-infection could prime the immune system and affect T cell trafficking. We compared the expression of chemokine receptors on cord blood CD4(+) T cells from HIV-1-exposed children and healthy controls. At baseline CD4(+) T cells had a largely naïve phenotype. However, stimulation with cytokines resulted in an upregulation of inflammatory response-related chemokine receptors on CD4(+) T cells, with HIV-1-exposed infants having a significantly higher frequency of CD4(+) T cells expressing, in particularly Th2 associated chemokine receptors (CCR3 p < 0.01, CCR8 p = 0.03). Numbers of naive CCR7(+) CD4(+) T cells were reduced (p = 0.01) in HIV-1-exposed infants. We further assessed whether the inflammatory phenotype was associated with susceptibility to HIV-1 and detected higher levels of p24 upon in in vitro infection of stimulated CD4(+) T cells of HIV-1-exposed infants. In summary, fetal exposure to HIV-1 primes the immune system in the infant leading to an enhanced immune activation and altered T cell homing, with potential ramifications regarding T cell responses and the acquisition of HIV-1 as an infant. PMID:25341640

  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. 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

  2. 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

  3. Increased incidence of cancer in adult Gaucher disease in Western Europe.

    PubMed

    de Fost, M; Vom Dahl, S; Weverling, G J; Brill, N; Brett, S; Häussinger, D; Hollak, C E M

    2006-01-01

    The adult form of Gaucher disease (type I GD) is associated with a high prevalence of hypergammaglobulinemia and monoclonal gammopathy of undetermined significance (MGUS). A significantly increased risk of cancer, especially of hematological types, has been found in Ashkenazi-Jewish GD type 1 patients. In this study, incidence and mortality of cancer were assessed in a total of 131 GD patients of mixed ancestry in a population from Western Europe, i.e. 2 Gaucher referral centers in Germany (Düsseldorf) and the Netherlands (Amsterdam). Standardized rate ratios were determined by indirect standardization, using age- and sex-specific incidence and mortality rates of the Dutch population. A total of 14 GD patients of non-Ashkenazi-Jewish descent were identified of whom 5 had a hematologic malignancy. These numbers correspond to an increased risk of cancer of 2.5 (95% CI 1.1-4.7) and an increased risk of hematologic cancer of 12.7 (95% CI 2.6-37.0) among GD patients compared to the general population. In particular, the incidences of multiple myeloma and hepatocellular carcinoma in absence of preexisting cirrhosis were highly elevated, with standardized rate ratios of 51.1 (95% CI 6.2-184) and 141.3 (95% CI 17.1-510.5), respectively. These strongly increased risks on developing cancer suggest that measures for early detection and prevention of hematological and hepatic malignancies in patients with Gaucher type I disease are mandatory. PMID:16246599

  4. Prenatal nicotine exposure increases anxiety and modifies sensorimotor integration behaviors in adult female mice.

    PubMed

    Santiago, Sarah E; Huffman, Kelly J

    2014-02-01

    Prenatal exposure to nicotine (PNE) has been associated with a myriad of physiological, cognitive, and behavioral effects in the developing offspring. In this study, CD-1 dams were given injections of nicotine or control vehicle throughout gestation and their offspring were raised to 6 months of age. Adult mice were administered a battery of behavioral tests (the Suok test, the elevated platform test, and the elevated plus maze test) to assess anxiety and sensorimotor integration. PNE resulted in a decreased likelihood of jumping during the elevated platform test and decreased directed exploration in the Suok test, both indicative of increased anxiety. Also, PNE mice showed increased numbers of missteps while traversing an elevated rod in the Suok test, demonstrating altered sensorimotor integration. No significant differences were found in falls, segments traveled, latency to leave the central zone, vegetative responses, risk assessment behaviors, or autogroom behaviors. The elevated plus maze test revealed no significant differences between groups. No significant differences in body and brain weights, or cortical thickness within motor, somatosensory, and visual cortices were observed between PNE and control mice. Although neuroanatomical effects of PNE may be rescued as development progresses, defects in sensorimotor integration and increased anxiety persist into adulthood. PMID:24157430

  5. Physical Activity and Brain Function in Older Adults at Increased Risk for Alzheimer’s Disease

    PubMed Central

    Smith, J. Carson; Nielson, Kristy A.; Woodard, John L.; Seidenberg, Michael; Rao, Stephen M.

    2013-01-01

    Leisure-time physical activity (PA) and exercise training are known to help maintain cognitive function in healthy older adults. However, relatively little is known about the effects of PA on cognitive function or brain function in those at increased risk for Alzheimer’s disease through the presence of the apolipoproteinE epsilon4 (APOE-ε4) allele, diagnosis of mild cognitive impairment (MCI), or the presence of metabolic disease. Here, we examine the question of whether PA and exercise interventions may differentially impact cognitive trajectory, clinical outcomes, and brain structure and function among individuals at the greatest risk for AD. The literature suggests that the protective effects of PA on risk for future dementia appear to be larger in those at increased genetic risk for AD. Exercise training is also effective at helping to promote stable cognitive function in MCI patients, and greater cardiorespiratory fitness is associated with greater brain volume in early-stage AD patients. In APOE-ε4 allele carriers compared to non-carriers, greater levels of PA may be more effective in reducing amyloid burden and are associated with greater activation of semantic memory-related neural circuits. A greater research emphasis should be placed on randomized clinical trials for exercise, with clinical, behavioral, and neuroimaging outcomes in people at increased risk for AD. PMID:24961307

  6. Fear and C-reactive protein cosynergize annual pulse increases in healthy adults

    PubMed Central

    Shenhar-Tsarfaty, Shani; Yayon, Nadav; Waiskopf, Nir; Shapira, Itzhak; Toker, Sharon; Zaltser, David; Berliner, Shlomo; Ritov, Ya'acov; Soreq, Hermona

    2015-01-01

    Recent international terror outbreaks notably involve long-term mental health risks to the exposed population, but whether physical health risks are also anticipated has remained unknown. Here, we report fear of terror-induced annual increases in resting heart rate (pulse), a notable risk factor of all-cause mortality. Partial least squares analysis based on 325 measured parameters successfully predicted annual pulse increases, inverse to the expected age-related pulse decline, in approximately 4.1% of a cohort of 17,380 apparently healthy active Israeli adults. Nonbiased hierarchical regression analysis among 27 of those parameters identified pertinent fear of terror combined with the inflammatory biomarker C-reactive protein as prominent coregulators of the observed annual pulse increases. In comparison, basal pulse primarily depended on general physiological parameters and reduced cholinergic control over anxiety and inflammation, together indicating that consistent exposure to terror threats ignites fear-induced exacerbation of preexisting neuro-immune risks of all-cause mortality. PMID:25535364

  7. 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. PMID:25771125

  8. 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

  9. Increasing trends in central obesity among Chinese adults with normal body mass index, 1993–2009

    PubMed Central

    2013-01-01

    Background Central obesity is thought to be more pathogenic than overall obesity and studies have shown that the association between waist circumference (WC) and mortality was strongest in those with a normal body mass index (BMI). The objective of our study was to determine secular trends in the prevalence of central obesity (WC ≥ 90 cm for men and ≥ 80 cm for women) among Chinese adults with normal BMI from 1993 to 2009 and to examine the impact of performance of combined BMI and WC on the prevalence of obesity in Chinese adults. Methods We used data from the China Health and Nutrition Survey (CHNS) conducted from 1993 to 2009. From which we included a total of 52023 participants aged ≥ 18 years. Results The age-standardized prevalence of central obesity among Chinese adults with BMI < 25 kg/m2 increased from 11.9% in 1993 to 21.1% in 2009 (P for linear trend <0.001). The upward trends were noted in both genders, all ages, rural/urban settings, and education groups (all P for linear trend <0.001), with greater increments in men, participants aged 18–64 years, and rural residents (P for interaction terms survey × sex, survey × age, and survey × rural/urban settings were 0.042, 0.003, and < 0.001, respectively). Trends in the prevalence of central obesity were similar when a more stringent BMI < 23 kg/m2 cut point (Asian cut point) was applied. Central obesity is associated with a higher risk of incident hypertension within normal BMI category. More than 65% individuals with obesity would be missed if solely BMI was measured. Conclusions We observed an upward trend in the prevalence of central obesity among participants with normal BMI irrespective of sex, age, rural/urban settings, and education level. Central obesity is associated with a higher risk of incident hypertension within normal BMI category. Approximately two thirds of the individuals with obesity would be missed if WC was not measured. It is, therefore, urgent to emphasize the importance of

  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. PMID:26621120

  11. 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...

  12. Maternal complement C1q and increased odds for psychosis in adult offspring

    PubMed Central

    Severance, Emily G.; Gressitt, Kristin L.; Buka, Stephen L.; Cannon, Tyrone D.; Yolken, Robert H.

    2014-01-01

    The presence of maternal antibodies to food and infectious antigens may confer an increased risk of developing schizophrenia and psychosis in adult offspring. Complement factor C1q is an immune molecule with multiple functions including clearance of antigen-antibody complexes from circulation and mediation of synaptic pruning during fetal brain development. To determine if maternal C1q was associated with offspring schizophrenia and psychosis, we evaluated 55 matched case-control maternal serum pairs from the National Collaborative Perinatal Project. Sample pairs were composed of mothers whose offspring developed psychoses as adults and those whose offspring were free from psychiatric disease. Matching criteria for offspring included birth date, delivery hospital, race and gender, with further matching based on mother’s age. IgG markers of C1q, bovine milk casein, egg ovalbumin and wheat gluten were measured with enzyme-linked immunosorbent assays. C1q levels were compared to food antigen IgG and to previously generated data for C-reactive protein, adenovirus, herpes simplex viruses, influenza viruses, measles virus and Toxoplasma gondii. C1q was significantly elevated in case mothers with odds ratios of 2.66–6.31 (conditional logistic regressions, p≤0.008–0.05). In case mothers only, C1q was significantly correlated with antibodies to both food and infectious antigens: gluten (R2=0.26, p≤0.004), herpes simplex virus type 2 (R2=0.21, p≤0.02), adenovirus (R2=0.25, p≤0.006). In conclusion, exposure to maternal C1q activity during pregnancy may be a risk factor for the development of schizophrenia and psychosis in offspring. Prenatal measurement of maternal C1q may be an important and convergent screening tool to identify potentially deleterious immune activation from multiple sources. PMID:25195065

  13. Prenatal cocaine exposure increases apoptosis of neonatal rat heart and heart susceptibility to ischemia–reperfusion injury in 1-month-old rat

    PubMed Central

    Bae, Soochan; Zhang, Lubo

    2005-01-01

    Maternal cocaine administration during pregnancy increased apoptosis in near-term fetal rat heart. The present study tested the hypothesis that prenatal cocaine exposure increases the heart susceptibility to ischemia/reperfusion injury in the offspring. Pregnant Sprague–Dawley rats received cocaine (30 mg kg−1 day−1) or saline from days 15 to 21 of gestational age. Maternal body weights were not significantly different at the end of cocaine treatment, but body weights of offspring were decreased slightly at ages of 1, 3, and 7 days. Although heart-to-body weight ratio was not affected at all ages examined, prenatal cocaine significantly increased left ventricular myocyte size at an age of 30 days. Additionally, prenatal cocaine increased DNA fragmentation measured in the hearts isolated from offspring of 1, 3, 7, and 21 days, but not of 30 days, with the peak at 3-day neonates. Antiapoptotic (Bcl-2 and Bcl-XL) and proapoptotic (Bax and Bad) proteins were expressed in neonatal rat hearts of both groups. Prenatal cocaine exposure decreased levels of Bcl-2 in 21-day and increased Bax in 21- and 30-day rat hearts. In addition, hearts of 30-day-old male progeny were studied using the Langendorff preparation, and were subjected to 25 min of ischemia and 60 min of reperfusion. Preischemic baseline values of left ventricular (LV) function were the same between the two groups. However, prenatal cocaine exposure significantly attenuated postischemic recovery of LV function, and significantly increased elevated LV end diastolic pressure during reperfusion. This was associated with a significant increase in ischemia/reperfusion-induced LV myocardial infarct size. The results suggest that prenatal cocaine exposure induces abnormal apoptosis and myocyte hypertrophy in postnatal heart, leading to an increased heart susceptibility to ischemic insults in postnatal life. PMID:15685203

  14. 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 ; ...

  15. Urine sodium excretion increased slightly among U.S. adults between 1988 and 2010.

    PubMed

    Pfeiffer, Christine M; Hughes, Jeffery P; Cogswell, Mary E; Burt, Vicki L; Lacher, David A; Lavoie, Donna J; Rabinowitz, Daniel J; Johnson, Clifford L; Pirkle, James L

    2014-05-01

    Little information is available on temporal trends in sodium intake in the U.S. population using urine sodium excretion as a biomarker. Our aim was to assess 1988-2010 trends in estimated 24-h urine sodium (24hUNa) excretion among U.S. adults (age 20-59 y) participating in the cross-sectional NHANES. We used subsamples from a 1988-1994 convenience sample, a 2003-2006 one-third random sample, and a 2010 one-third random sample to comply with resource constraints. We estimated 24hUNa excretion from measured sodium concentrations in spot urine samples by use of calibration equations (for men and women) derived from the International Cooperative Study on Salt, Other Factors, and Blood Pressure study. Estimated 24hUNa excretion increased over the 20-y period [1988-1994, 2003-2006, and 2010; means ± SEMs (n): 3160 ± 38.4 mg/d (1249), 3290 ± 29.4 mg/d (1235), and 3290 ± 44.4 mg/d (525), respectively; P-trend = 0.022]. We observed significantly higher mean estimated 24hUNa excretion in each survey period (P < 0.001) for men compared with women (31-33%) and for persons with a higher body mass index (BMI; 32-35% for obese vs. normal weight) or blood pressure (17-26% for hypertensive vs. normal blood pressure). After adjusting for age, sex, and race-ethnicity, temporal trends in mean estimated 24hUNa excretion remained significant (P-trend = 0.004). We observed no temporal trends in mean estimated 24hUNa excretion among BMI subgroups, nor after adjusting for BMI. Although several limitations apply to this analysis (the use of a convenience sample in 1988-1994 and using estimated 24hUNa excretion as a biomarker of sodium intake), these first NHANES data suggest that mean estimated 24hUNa excretion increased slightly in U.S. adults over the past 2 decades, and this increase may be explained by a shift in the distribution of BMI. PMID:24623847

  16. 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

  17. Stress during first pregnancy increases seizure threshold in adult male offspring

    PubMed Central

    Pajand, Peyman; Elahdadi Salmani, Mahmoud; Shajiee, Hooman; Abiri, Hasan; Goudarzi, Iran; Abrari, Kataneh

    2014-01-01

    Objective(s): Stress induces many homeostatic aberrations which are followed by lifelong allostatic responses. Epilepsy is developed or influenced by different environmental factors, i.e. prenatal stress which makes many contradictory developmental changes in seizure threshold and intensity. We investigated the potential seizure response of the rat offspring to prenatal stress; the stress which was applied to their mothers. Materials and Methods: Nine day heterogeneous sequential stress (HSS) model was used before and during the first and before the second pregnancy. The kindling was induced using 13 IP injections of pentylenetetrazol (PTZ) every 48 hr to adult male Wistar rat's offspring. Results: The results of the present study demonstrated that, before pregnancy stress decreased the rate of kindling (P<0.05) in the offspring, while stress which was applied during pregnancy completely prevented kindling (P <0.001). Further, their convulsive latency was increased and tonic clonic seizure duration was decreased. In contrast, previous pregnancy and between pregnancies stress could not change kindling process. Although maternal separation stress did not change kindling development, it could increase convulsive intensities by elongating the duration of seizures (P<0.05) and reducing convulsion latency (P <0.05). Conclusion: It is concluded that stress detrimental effects could be prevented by stress which was applied around first pregnancy; however this beneficial effect is weakened by before second pregnancy stress. PMID:24592305

  18. Anxiety Sensitivity Uniquely Predicts Exercise Behaviors in Young Adults Seeking to Increase Physical Activity.

    PubMed

    Moshier, Samantha J; Szuhany, Kristin L; Hearon, Bridget A; Smits, Jasper A J; Otto, Michael W

    2016-01-01

    Individuals with elevated levels of anxiety sensitivity (AS) may be motivated to avoid aversive emotional or physical states, and therefore may have greater difficulty achieving healthy behavioral change. This may be particularly true for exercise, which produces many of the somatic sensations within the domain of AS concerns. Cross-sectional studies show a negative association between AS and exercise. However, little is known about how AS may prospectively affect attempts at behavior change in individuals who are motivated to increase their exercise. We recruited 145 young adults who self-identified as having a desire to increase their exercise behavior. Participants completed a web survey assessing AS and additional variables identified as important for behavior change-impulsivity, grit, perceived behavioral control, and action planning-and set a specific goal for exercising in the next week. One week later, a second survey assessed participants' success in meeting their exercise goals. We hypothesized that individuals with higher AS would choose lower exercise goals and would complete less exercise at the second survey. AS was not significantly associated with exercise goal level, but significantly and negatively predicted exercise at Time 2 and was the only variable to offer significant prediction beyond consideration of baseline exercise levels. These results underscore the importance of considering AS in relation to health behavior intentions. This is particularly apt given the absence of prediction offered by other traditional predictors of behavior change. PMID:26342011

  19. Meta-Analysis of Patient Education Interventions to Increase Physical Activity among Chronically Ill Adults

    PubMed Central

    Conn, Vicki S.; Hafdahl, Adam R.; Brown, Sharon A.; Brown, Lori M.

    2008-01-01

    Objective This meta-analysis integrates primary research testing the effect of patient education to increase physical activity (PA) on behavior outcomes among adults with diverse chronic illnesses. Methods Extensive literature searching strategies located published and unpublished intervention studies that measured PA behavior outcomes. Primary study results were coded. Fixed- and random-effects meta-analytic procedures included moderator analyses. Results Data were synthesized across 22,527 subjects from 213 samples in 163 reports. The overall mean weighted effect size for two-group comparisons was 0.45 (higher mean for treatment than control). This effect size is consistent with a difference of 48 minutes of PA per week or 945 steps per day. Preliminary moderator analyses suggest interventions were most effective when they targeted only PA behavior, used behavioral strategies (vs. cognitive strategies), and encouraged PA self-monitoring. Differences among chronic illnesses were documented. Individual strategies unrelated to PA outcomes included supervised exercise sessions, exercise prescription, fitness testing, goal setting, contracting, problem solving, barriers management, and stimulus/cues. PA outcomes were unrelated to gender, age, ethnicity, or socioeconomic distribution among samples. Conclusion These findings suggest that some patient education interventions to increase PA are effective, despite considerable heterogeneity in the magnitude of intervention effect. Practice Implications Moderator analyses are preliminary and provide suggestive evidence for further testing of interventions to inform practice. PMID:18023128

  20. Sertraline inhibits increases in body fat and carbohydrate dysregulation in adult female cynomolgus monkeys.

    PubMed

    Silverstein-Metzler, Marnie G; Shively, Carol A; Clarkson, Thomas B; Appt, Susan E; Carr, J Jeffrey; Kritchevsky, Stephen B; Jones, Sara R; Register, Thomas C

    2016-06-01

    Selective serotonin reuptake inhibitor (SSRI) antidepressants are widely prescribed for depression and other disorders. SSRIs have become one of the most commonly used drugs in the United States, particularly by women. Acute effects on body composition and carbohydrate metabolism have been reported, but little is known regarding the effects of chronic SSRI use. We evaluated the effects of chronic administration of a commonly prescribed SSRI, sertraline HCl, on body weight and composition, fat distribution, carbohydrate metabolism, as well as activity, in adult female depressed and nondepressed cynomolgus monkeys (Macaca fascicularis; n=42) using a placebo-controlled, longitudinal, randomized study design. Phenotypes were evaluated prior to and after 18 months of oral sertraline (20mg/kg) or placebo. Over the 18 month treatment period, the placebo group experienced increases in body weight, body fat (visceral and subcutaneous) fasting insulin concentrations, and homeostasis model assessment of insulin resistance scores (HOMA-IR). Sertraline treatment prevented increases in body weight, fat, insulin, and HOMA-IR (all p<0.05), without significantly altering activity levels. Sertraline treatment altered adiponectin in an unusual way - reducing circulating adiponectin in depressed monkeys without affecting fat mass or body weight. Deleterious effects on adiponectin, a potentially insulin-sensitizing and atheroprotective protein, may result in adverse effects on cardiovascular health despite otherwise beneficial effects on body composition and carbohydrate metabolism. PMID:26939086

  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. PMID:27063068

  2. 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

  3. Increasing wrist fracture rates in children may have major implications for future adult fracture burden

    PubMed Central

    Jerrhag, Daniel; Englund, Martin; Petersson, Ingmar; Lempesis, Vasileios; Landin, Lennart; Karlsson, Magnus K; Rosengren, Bjorn E

    2016-01-01

    Background and purpose Childhood fractures are associated with lower peak bone mass (a determinant of osteoporosis in old age) and higher adult fracture risk. By examining time trends in childhood fracture epidemiology, it may be possible to estimate the vector of fragility fracture risk in the future. Patients and methods By using official inpatient and outpatient data from the county of Skåne in Sweden, 1999–2010, we ascertained distal forearm fractures in children aged ≤ 16 years and estimated overall and age- and sex-specific rates and time trends (over 2.8 million patient years) and compared the results to earlier estimations in the same region from 1950 onwards. Results During the period 1999–2010, the distal forearm fracture rate was 634 per 105 patient years (750 in boys and 512 in girls). This was 50% higher than in the 1950s with a different age-rate distribution (p < 0.001) that was most evident during puberty. Also, within the period 1999–2010, there were increasing fracture rates per 105 and year (boys +2.0% (95% CI: 1.5–2.6), girls +2.4% (95% CI: 1.7–3.1)). Interpretation The distal forearm fracture rate in children is currently 50% higher than in the 1950s, and it still appears to be increasing. If this higher fracture risk follows the children into old age, numbers of fragility fractures may increase sharply—as an upturn in life expectancy has also been predicted. The origin of the increase remains unknown, but it may be associated with a more sedentary lifestyle or with changes in risk behavior. PMID:26905618

  4. Increasing wrist fracture rates in children may have major implications for future adult fracture burden.

    PubMed

    Jerrhag, Daniel; Englund, Martin; Petersson, Ingmar; Lempesis, Vasileios; Landin, Lennart; Karlsson, Magnus K; Rosengren, Bjorn E

    2016-06-01

    Background and purpose - Childhood fractures are associated with lower peak bone mass (a determinant of osteoporosis in old age) and higher adult fracture risk. By examining time trends in childhood fracture epidemiology, it may be possible to estimate the vector of fragility fracture risk in the future. Patients and methods - By using official inpatient and outpatient data from the county of Skåne in Sweden, 1999-2010, we ascertained distal forearm fractures in children aged ≤ 16 years and estimated overall and age- and sex-specific rates and time trends (over 2.8 million patient years) and compared the results to earlier estimations in the same region from 1950 onwards. Results - During the period 1999-2010, the distal forearm fracture rate was 634 per 10(5) patient years (750 in boys and 512 in girls). This was 50% higher than in the 1950s with a different age-rate distribution (p < 0.001) that was most evident during puberty. Also, within the period 1999-2010, there were increasing fracture rates per 10(5) and year (boys +2.0% (95% CI: 1.5-2.6), girls +2.4% (95% CI: 1.7-3.1)). Interpretation - The distal forearm fracture rate in children is currently 50% higher than in the 1950s, and it still appears to be increasing. If this higher fracture risk follows the children into old age, numbers of fragility fractures may increase sharply-as an upturn in life expectancy has also been predicted. The origin of the increase remains unknown, but it may be associated with a more sedentary lifestyle or with changes in risk behavior. PMID:26905618

  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. PMID:23746561

  6. Earlier Menarche Is Associated with Lower Insulin Sensitivity and Increased Adiposity in Young Adult Women

    PubMed Central

    Wilson, Dyanne A.; Derraik, José G. B.; Rowe, Deborah L.; Hofman, Paul L.; Cutfield, Wayne S.

    2015-01-01

    Objective We aimed to assess whether age at menarche was associated with insulin sensitivity in young adult women. Methods We studied 54 healthy young women aged 20–30 years. Participants were grouped according to age at menarche: Early (≤11.0 years; n=13), Average (>12.0 and ≤13.0 years; n=28), and Late (≥14.0 years, n=13). Primary outcome was insulin sensitivity measured using intravenous glucose tolerance tests and Bergman’s minimal model. Body composition was assessed using whole-body dual-energy X-ray absorptiometry. Results Earlier menarche was associated with lower insulin sensitivity (p=0.015). There was also a continuous increase in adiposity with younger age at menarche, which was associated with increased weight (p=0.001), BMI (p=0.002), total body fat (p=0.049), and truncal fat (p=0.020). Stratified analyses showed that insulin sensitivity in Early women (5.5 x10-4·min-1(mU/l)) was lower than in Average (8.0 x10-4·min-1(mU/l), p=0.021) and Late (8.6 x10-4·min-1(mU/l), p=0.033) groups. Early women (weight=66.1 kg; BMI=24.1 kg/m2) were considerably heavier and fatter than Average (59.0 kg, p=0.004; 21.4 kg/m2, p=0.002) and Late (57.0 kg, p=0.001; 20.8 kg/m2, p=0.0009) women. Conclusions Early menarche is associated with lower insulin sensitivity and increased adiposity in young adulthood, potentially increasing the risk of type 2 diabetes and the metabolic syndrome later in life. PMID:26061526

  7. 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

  8. 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

  9. 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

  10. Brain activation deficit in increased-load working memory tasks among adults with ADHD using fMRI.

    PubMed

    Ko, Chih-Hung; Yen, Ju-Yu; Yen, Cheng-Fang; Chen, Cheng-Sheng; Lin, Wei-Chen; Wang, Peng-Wei; Liu, Gin-Chung

    2013-10-01

    Working memory (WM) is impaired among adults with attention-deficit hyperactivity disorder (ADHD). This study aimed to investigate the brain activation deficit for low-level or increased-load WM among adults with ADHD. A total of 20 adults with ADHD and controls were recruited according to diagnostic interviewing by a psychiatrist. Phonological and visual-spatial 2-back and 3-back tasks were performed under functional magnetic resonance scanning. The results demonstrated that both the adults with ADHD and the controls exhibited activation of the fronto-parietal network for WM, and the intensity was greater in the adult ADHD group. The ADHD group had higher brain activation over the bilateral anterior cingulate, left inferior frontal lobe, hippocampus, and supplementary motor area (SMA) for phonological WM than the control group. When the task loading increased from 2-back to 3-back tasks, the adults with ADHD perceived greater difficulty. The control group exhibited increased brain activation over the frontal-parietal network in response to increased phonological WM load. However, the ADHD group showed decreased brain activation over the left precuneus, insula, and SMA. Further analysis demonstrated that the ADHD group exhibited a greater decrease in brain activation over the left fronto-parietal network, including the precuneus, SMA, insula/inferior frontal lobe, and dorsolateral prefrontal cortex, than the control group. These results suggest that adults with ADHD pay more effort to low demanding phonological WM. On the other hand, brain activation of the left fronto-parietal network is impaired when the demands of WM exceed the capacity of adults with ADHD. PMID:23645101

  11. Adults' Use of ICTs for Learning: Reducing or Increasing Educational Inequalities?

    ERIC Educational Resources Information Center

    Selwyn, Neil; Gorard, Stephen; Furlong, John

    2004-01-01

    Within the hyperbole surrounding information and communications technologies (ICTs) and lifelong learning, our understanding of what learning activities ICTs are actually being used for throughout the adult population remains under-developed. Based on a household survey of 1001 adults in the west of England and South Wales, this article considers…

  12. 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…

  13. Scaling Completion College Services as a Model for Increasing Adult Degree Completion. Lumina Issue Papers

    ERIC Educational Resources Information Center

    Johnson, Nate; Bell, Alli

    2014-01-01

    An estimated 46 million adults have some college education but have not completed their degrees. For many, especially those who have accumulated several years' worth of credits, the inability to finish college remains a frustration. If the United States is to achieve its ambitious education attainment goals, many more adults with such experience…

  14. 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…

  15. Who is missing the message? Targeting strategies to increase food label use among US adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: To evaluate the associations between sociodemographic and psychosocial characteristics and food label (FL) use in US adults. Design: The 1994-1996 Continuing Survey of Food Intakes by Individuals and the Diet and Health Knowledge Survey for 2,797 US adults were used. High socioeconomic st...

  16. Increasing Hepatitis B Screening for Hmong adults: Results from a randomized controlled community-based study

    PubMed Central

    Chen, Moon S.; Fang, Dao M.; Stewart, Susan L.; Ly, May Ying; Lee, Serge; Dang, Julie H.T.; Nguyen, Tram T.; Maxwell, Annette E.; Bowlus, Christopher L.; Bastani, Roshan; Nguyen, Tung T.

    2013-01-01

    Background Hepatitis B-linked liver cancer disproportionately affects Hmong Americans. With an incidence rate of 18.9/100,000, Hmong Americans experience liver cancer at a rate that is 6–7 times greater than that of non-Hispanic Whites. Serological testing for the hepatitis B virus (HBV) is a principal means to prevent liver cancer deaths through earlier identification of those at risk. Methods Academic researchers and Hmong leaders collaborated in the design, conduct, and evaluation of a 5-year randomized controlled trial testing a lay health worker (LHW) intervention to promote HBV testing among 260 Hmong adults through in-home education and patient navigation. Results Intervention group participants were more likely to report receiving serological testing for HBV (24% vs. 10%, p=0.0056) and showed a greater mean increase in knowledge score (1.3 vs. 0.3 points, p=0.0003) than control group participants. Multivariable modeling indicated that self-reported test receipt was associated with intervention group assignment (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.3–9.2), improvement in knowledge score (OR 1.3 per point, 95% CI 1.02–1.7), female gender (OR 5.3, 95% CI 1.7–16.6), and having seen a doctor in the past year at baseline (OR 4.8, 95% CI 1.3–17.6). The most often cited reason for testing was a doctor’s recommendation. Conclusions LHWs were effective in bringing about HBV screening. Doctor visits and adherence to doctors’ recommendations were pivotal. Participation of health care providers is essential to increase HBV testing. Impact LHWs can significantly increase HBV screening rates for Hmong, but their doctors’ recommendation is highly influential and should be pursued. PMID:23613027

  17. Transportation and mixing with unfamiliar pigs increase the susceptibility of market-weight pigs to Salmonella enterica

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There is increasing evidence that stress can have a significant deleterious effect on food safety through a variety of potential mechanisms. However, there is very little research conducted to determine the potential effects of specific pre-slaughter stressors on Salmonella infection and carriage in...

  18. 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...

  19. 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

  20. 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. PMID:26763429

  1. 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

  2. Increased hepatic CD36 expression with age is associated with enhanced susceptibility to nonalcoholic fatty liver disease.

    PubMed

    Sheedfar, Fareeba; Sung, Miranda My; Aparicio-Vergara, Marcela; Kloosterhuis, Niels J; Miquilena-Colina, Maria Eugenia; Vargas-Castrillón, Javier; Febbraio, Maria; Jacobs, René L; de Bruin, Alain; Vinciguerra, Manlio; García-Monzón, Carmelo; Hofker, Marten H; Dyck, Jason Rb; Koonen, Debby P Y

    2014-04-01

    CD36 has been associated with obesity and diabetes in human liver diseases, however, its role in age-associated nonalcoholic fatty liver disease (NAFLD) is unknown. Therefore, liver biopsies were collected from individuals with histologically normal livers (n=30), and from patients diagnosed with simple steatosis (NAS; n=26). Patients were divided into two groups according to age and liver biopsy samples were immunostained for CD36. NAFLD parameters were examined in young (12-week) and middle-aged (52-week) C57BL/6J mice, some fed with chow-diet and some fed with low-fat (LFD; 10% kcal fat) or high-fat diet (HFD; 60% kcal fat) for 12-weeks. CD36 expression was positively associated with age in individuals with normal livers but not in NAS patients. However, CD36 was predominantly located at the plasma membrane of hepatocytes in aged NAS patients as compared to young. In chow-fed mice, aging, despite an increase in hepatic CD36 expression, was not associated with the development of NAFLD. However, middle-aged mice did exhibit the development of HFD-induced NAFLD, mediated by an increase of CD36 on the membrane. Enhanced CD36-mediated hepatic fat uptake may contribute to an accelerated progression of NAFLD in mice and humans. Therapies to prevent the increase in CD36 expression and/or CD36 from anchoring at the membrane may prevent the development of NAFLD. PMID:24751397

  3. Increased Susceptibility to Skin Carcinogenesis Associated with a Spontaneous Mouse Mutation in the Palmitoyl Transferase Zdhhc13 Gene.

    PubMed

    Perez, Carlos J; Mecklenburg, Lars; Jaubert, Jean; Martinez-Santamaria, Lucia; Iritani, Brian M; Espejo, Alexsandra; Napoli, Eleonora; Song, Gyu; del Río, Marcela; DiGiovanni, John; Giulivi, Cecilia; Bedford, Mark T; Dent, Sharon Y R; Wood, Richard D; Kusewitt, Donna F; Guénet, Jean-Louis; Conti, Claudio J; Benavides, Fernando

    2015-12-01

    Here we describe a spontaneous mutation in the Zdhhc13 (zinc finger, DHHC domain containing 13) gene (also called Hip14l), one of 24 genes encoding palmitoyl acyltransferase (PAT) enzymes in the mouse. This mutation (Zdhhc13luc) was identified as a nonsense base substitution, which results in a premature stop codon that generates a truncated form of the ZDHHC13 protein, representing a potential loss-of-function allele. Homozygous Zdhhc13luc/Zdhhc13luc mice developed generalized hypotrichosis, associated with abnormal hair cycle, epidermal and sebaceous gland hyperplasia, hyperkeratosis, and increased epidermal thickness. Increased keratinocyte proliferation and accelerated transit from basal to more differentiated layers were observed in mutant compared with wild-type (WT) epidermis in untreated skin and after short-term 12-O-tetradecanoyl-phorbol-13-acetate treatment and acute UVB exposure. Interestingly, this epidermal phenotype was associated with constitutive activation of NF-κB (RelA) and increased neutrophil recruitment and elastase activity. Furthermore, tumor multiplicity and malignant progression of papillomas after chemical skin carcinogenesis were significantly higher in mutant mice than WT littermates. To our knowledge, this is the first report of a protective role for PAT in skin carcinogenesis. PMID:26288350

  4. Increased Susceptibility to Skin Carcinogenesis Associated with a Spontaneous Mouse Mutation in the Palmitoyl Transferase Zdhhc13 gene

    PubMed Central

    Perez, Carlos J.; Mecklenburg, Lars; Jaubert, Jean; Santamaria, Lucia Martinez; Iritani, Brian M.; Espejo, Alexsandra; Napoli, Eleonora; Song, Gyu; del Río, Marcela; DiGiovanni, John; Giulivi, Cecilia; Bedford, Mark T.; Dent, Sharon Y.R.; Wood, Richard D.; Kusewitt, Donna F.; Guénet, Jean Louis; Conti, Claudio J.; Benavides, Fernando

    2016-01-01

    Here we describe a spontaneous mutation in the Zdhhc13 (zinc finger, DHHC domain containing 13) gene (also called Hip14l), one of 24 genes encoding palmitoyl acyltransferase (PAT) enzymes in the mouse. This mutation (Zdhhc13luc) was identified as a nonsense base substitution, which results in a premature stop codon that generates a truncated form of the ZDHHC13 protein, representing a potential loss-of-function allele. Homozygous Zdhhc13luc/Zdhhc13luc mice developed generalized hypotrichosis, associated with abnormal hair cycle, epidermal and sebaceous gland hyperplasia, hyperkeratosis and increased epidermal thickness. Increased keratinocyte proliferation and accelerated transit from basal to more differentiated layers were observed in mutant compared to wild-type epidermis, in untreated skin and after short-term 12-O-tetradecanoyl-phorbol-13-acetate (TPA) treatment and acute UVB exposure. Interestingly, this epidermal phenotype was associated with constitutive activation of NF-κB (RelA) and increased neutrophil recruitment and elastase activity. Furthermore, tumor multiplicity and malignant progression of papillomas after chemical skin carcinogenesis were significantly higher in mutant mice than wild-type littermates. To our knowledge, this is the first report of a protective role for a PAT in skin carcinogenesis. PMID:26288350

  5. 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

  6. 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

  7. Fast Eating Speed Increases the Risk of Endoscopic Erosive Gastritis in Korean Adults

    PubMed Central

    Kim, Min-Kyung; Kim, E-Yeon; Han, Byoung-Duck; Cho, Kyung-Hwan

    2015-01-01

    Background Fast eating or overeating can induce gastrointestinal diseases such as gastritis. However, the association between gastritis and speed of eating is unclear. The aim of this study was to determine whether eating speed is associated with increased risk of endoscopic erosive gastritis (EEG). Methods We carried out a cross-sectional study involving 10,893 adults who underwent a general health checkup between 2007 and 2009. Two groups, EEG patients and EEG-free patients, were compared by using the t-test and the chi-square test. Multiple logistic regression analyses were performed to investigate the association between eating speed and EEG. Results The group with EEG had a higher proportion of males, average age, body mass index, and percentages of current smokers and risky drinkers than those without EEG. After adjusting for anthropometric, social, and endoscopic parameters, the group with the highest eating speed (<5 min/meal) had 1.7 times higher risk for EEG than the group with the lowest eating speed (≥15 min/meal) (odds ratio, 1.71; 95% confidence interval, 1.20-2.45). Conclusion High eating speed is an independent risk factor for EEG. Our results indicate the need for further studies to clarify the role of eating speed in gastritis. PMID:26634096

  8. 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

  9. Perinatal Lead Exposure Alters Gut Microbiota Composition and Results in Sex-specific Bodyweight Increases in Adult Mice.

    PubMed

    Wu, Jianfeng; Wen, Xiaoquan William; Faulk, Christopher; Boehnke, Kevin; Zhang, Huapeng; Dolinoy, Dana C; Xi, Chuanwu

    2016-06-01

    Heavy metal pollution is a principle source of environmental contamination. Epidemiological and animal data suggest that early life lead (Pb) exposure results in critical effects on epigenetic gene regulation and child and adult weight trajectories. Using a mouse model of human-relevant exposure, we investigated the effects of perinatal Pb exposure on gut microbiota in adult mice, and the link between gut microbiota and bodyweight changes. Following Pb exposure during gestation and lactation via maternal drinking water, bodyweight in A(vy) strain wild-type non-agouti (a/a) offspring was tracked through adulthood. Gut microbiota of adult mice were characterized by deep DNA sequencing of bacterial 16S ribosomal RNA genes. Data analyses were stratified by sex and adjusted for litter effects. A Bayesian variable selection algorithm was used to analyze associations between bacterial operational taxonomic units and offspring adult bodyweight. Perinatal Pb exposure was associated with increased adult bodyweight in male (P < .05) but not in female offspring (P = .24). Cultivable aerobes decreased and anaerobes increased in Pb-exposed offspring (P < .005 and P < .05, respectively). Proportions of the 2 predominant phyla (Bacteroidetes and Firmicutes) shifted inversely with Pb exposure, and whole bacterial compositions were significantly different (analysis of molecular variance, P < .05) by Pb exposure without sex bias. In males, changes in gut microbiota were highly associated with adult bodyweight (P = .028; effect size = 2.59). Thus, perinatal Pb exposure results in altered adult gut microbiota regardless of sex, and these changes are highly correlated with increased bodyweight in males. Adult gut microbiota can be shaped by early exposures and may contribute to disease risks in a sex-specific manner. PMID:26962054

  10. Mannose-Binding Lectin Gene, MBL2, Polymorphisms Do Not Increase Susceptibility to Invasive Meningococcal Disease in a Population of Danish Children

    PubMed Central

    Lundbo, Lene F.; Sørensen, Henrik T.; Clausen, Louise N.; Hollegaard, Mads V.; Hougaard, David M.; Konradsen, Helle B.; Harboe, Zitta Barrella; Nørgaard, Mette; Benfield, Thomas

    2015-01-01

    Background. Neisseria meningitidis is the cause of meningococcal bacteremia and meningitis, and nasopharyngeal colonization with this pathogen is common. The incidence of invasive disease is highest in infants, whereas adolescents more often are carriers. Altered regulation or dysfunction of the innate immune system may predispose to invasive meningococcal disease (IMD). In this study, we investigated the effect of genetic variation in the mannose-binding lectin gene, MBL2, and its promoter on susceptibility to IMD and IMD-associated mortality among children. Methods. Children (<5 years) diagnosed during 1982–2007 with IMD and controls were identified through Danish national registries. DNA was obtained from the Danish Neonatal Screening Biobank. The associations between MBL2 diplotypes and IMD susceptibility and 30- and 90-day mortality were investigated using logistic regression analysis. Results. We included 1351 children: 406 with meningitis, 272 with bacteremia, and 673 age- and sex-matched controls. Of the children studied, 1292 (96%) were successfully genotyped and assigned MBL2 diplotypes. The median age in IMD cases was 19.1 months (interquartile range [IQR], 8.8–32.2 months). Children with defective MBL2 diplotypes were not at higher risk for meningococcal meningitis than children with intermediate and normal diplotypes (odds ratio [OR] = 0.69; 95% confidence interval [CI], .47–1.02). Similar results were found for children with bacteremia and defective diplotypes (OR = 0.84; 95% CI, .53–1.32) as well as for all cases (OR = 0.75; 95% CI, .56–1.01). There was no association between MBL2 diplotypes and mortality. Conclusions. Defective MBL2 diplotypes did not predict either an increased IMD susceptibility or mortality in a Danish population of children. PMID:26464842

  11. 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…

  12. Disruption of the Murine Glp2r Impairs Paneth Cell Function and Increases Susceptibility to Small Bowel Enteritis

    PubMed Central

    Lee, Seung-Jun; Lee, Jennifer; Li, Karen K.; Holland, Dianne; Maughan, Heather; Guttman, David S.; Yusta, Bernardo; Drucker, Daniel J.

    2013-01-01

    Exogenous glucagon-like peptide-2 receptor (GLP-2R) activation elicits proliferative and cytoprotective responses in the gastrointestinal mucosa and ameliorates experimental small and large bowel gut injury. Nevertheless, the essential physiological role(s) of the endogenous GLP-2R remain poorly understood. We studied the importance of the GLP-2R for gut growth, epithelial cell lineage allocation, the response to mucosal injury, and host-bacterial interactions in Glp2r−/− and littermate control Glp2r+/+ mice. Glp2r−/− mice exhibit normal somatic growth and preserved small and large bowel responses to IGF-I and keratinocyte growth factor. However, Glp2r−/− mice failed to up-regulate intestinal epithelial c-fos expression in response to acute GLP-2 administration and do not exhibit changes in small bowel conductance or small or large bowel growth after administration of GLP-2R agonists. The crypt and villus compartment and the numbers and localization of Paneth, enteroendocrine, and goblet cells were comparable in Glp2r+/+ vs. Glp2r−/− mice. Although the severity and extent of colonic mucosal injury in response to 3% oral dextran sulfate was similar across Glp2r genotypes, Glp2r−/− mice exhibited significantly increased morbidity and mortality and increased bacterial translocation after induction of enteritis with indomethacin and enhanced mucosal injury in response to irinotecan. Moreover, bacterial colonization of the small bowel was significantly increased, expression of Paneth cell antimicrobial gene products was reduced, and mucosal bactericidal activity was impaired in Glp2r−/− mice. Although the Glp2r is dispensable for gut development and the response to colonic injury, Glp2r−/− mice exhibit enhanced sensitivity to small bowel injury, and abnormal host-bacterial interactions in the small bowel. PMID:22253424

  13. 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.

  14. Increased Coronary Vessel Wall Thickness in HIV-Infected Young Adults

    PubMed Central

    Abd-Elmoniem, Khaled Z.; Unsal, Aylin B.; Eshera, Sarah; Matta, Jatin R.; Muldoon, Nancy; McAreavey, Dorothea; Purdy, Julia B.; Hazra, Rohan; Hadigan, Colleen; Gharib, Ahmed M.

    2014-01-01

    Background. Individuals with long-term human immunodeficiency virus (HIV) infection are at risk for premature vasculopathy and cardiovascular disease (CVD). We evaluated coronary vessel wall thickening, coronary plaque, and epicardial fat in patients infected with HIV early in life compared with healthy controls. Methods. This is a prospective cross-sectional study of 35 young adults who acquired HIV in early life and 11 healthy controls, free of CVD. Time resolved phase-sensitive dual inversion recovery black-blood vessel wall magnetic resonance imaging (TRAPD) was used to measure proximal right coronary artery (RCA) wall thickness, and multidetector computed tomography (CT) angiography was used to quantify coronary plaque and epicardial fat. Results. RCA vessel wall thickness was significantly increased in HIV-infected patients compared with sex- and race-matched controls (1.32 ± 0.21 mm vs 1.09 ± 0.14 mm, P = .002). No subject had discrete plaque on CT sufficient to cause luminal narrowing, and plaque was not related to RCA wall thickness. In multivariate regression analyses, smoking pack-years (P = .004) and HIV infection (P = .007) were independently associated with thicker RCA vessel walls. Epicardial fat did not differ between groups. Among the HIV-infected group, duration of antiretroviral therapy (ART) (P = .02), duration of stavudine exposure (P < .01), low-density lipoprotein cholesterol (P = .04), and smoking pack-years (P < .01) were positively correlated with RCA wall thickness. Conclusions. This investigation provides evidence of subclinical coronary vascular disease among individuals infected with HIV in early life. Increased duration of ART, hyperlipidemia, and smoking contributed to proximal RCA thickening, independent of atherosclerotic plaque quantified by CT. These modifiable risk factors appear to influence early atherogenesis as measured by coronary wall thickness and may be important targets for CVD risk reduction. PMID:25159580

  15. 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.

  16. Spermine synthase overexpression in vivo does not increase susceptibility to DMBA/TPA skin carcinogenesis or Min-Apc intestinal tumorigenesis.

    PubMed

    Welsh, Patricia A; Sass-Kuhn, Suzanne; Prakashagowda, Chethana; McCloskey, Diane; Feith, David

    2012-04-01

    Numerous studies have demonstrated a link between elevated polyamine biosynthesis and neoplastic growth, but the specific contribution of spermine synthase to epithelial tumor development has never been explored in vivo. Mice with widespread overexpression of spermine synthase (CAG-SpmS) exhibit decreased spermidine levels, increased spermine and a significant rise in tissue spermine:spermidine ratio. We characterized the response of CAG-SpmS mice to two-stage skin chemical carcinogenesis as well as spontaneous intestinal carcinogenesis induced by loss of the Apc tumor suppressor in Apc (Min) (/+) (Min) mice. CAG-SpmS mice maintained the canonical increases in ornithine decarboxylase (ODC) activity, polyamine content and epidermal thickness in response to tumor promoter treatment of the skin. The induction of S-adenosylmethionine decarboxylase (AdoMetDC) activity and its product decarboxylated AdoMet were impaired in CAG-SpmS mice, and the spermine:spermidine ratio was increased 3-fold in both untreated and 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated skin. The susceptibility to 7,12-dimethylbenz[a]anthracene (DMBA)/TPA skin carcinogenesis was not altered in CAG-SpmS mice, and SpmS overexpression did not modify the previously described tumor resistance of mice with targeted antizyme expression or the enhanced tumor response in mice with targeted spermidine/spermine-N ( 1) -acetyltransferase expression. CAG-SpmS/Min mice also exhibited elevated spermine:spermidine ratios in the small intestine and colon, yet their tumor multiplicity and size was similar to Min mice. Therefore, studies in two of the most widely used tumorigenesis models demonstrate that increased spermine synthase activity and the resulting elevation of the spermine:spermidine ratio does not alter susceptibility to tumor development initiated by c-Ha-Ras mutation or Apc loss. PMID:22258329

  17. 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

  18. Disruption of Cytochrome P4501A2 in mice leads to increased susceptibility to hyperoxic lung injury

    PubMed Central

    Wang, Lihua; Lingappan, Krithika; Jiang, Weiwu; Couroucli, Xanthi I.; Welty, Stephen E.; Shivanna, Binoy; Barrios, Roberto; Wang, Gangduo; Khan, M. Firoze; Gonzalez, Frank J.; Roberts, L Jackson; Moorthy, Bhagavatula

    2015-01-01

    Hyperoxia contributes to acute lung injury (ALI) in diseases such as acute respiratory distress syndrome (ARDS). Cytochrome P450 (CYP)1A enzymes have been implicated in hyperoxic lung injury, but the mechanistic role(s) of CYP1A2 in pulmonary injury is not known. We hypothesized that mice lacking the gene for Cyp1a2 (which is predominantly expressed in the liver) will be more sensitive to lung injury and inflammation mediated by hyperoxia, and that CYP1A2 will play a protective role by attenuating lipid peroxidation and oxidative stress in the lung. Eight to ten week old WT (C57BL/6) or Cyp1a2(−/−) mice were exposed to hyperoxia (>95% O2) or maintained in room air for 24–72 h. Lung injury was assessed by determining the ratios of lung weight/body weight (LW/BW), and by histology. Extent of inflammation was determined by measuring the number of neutrophils in the lung as well as cytokine expression. The Cyp1a2(−/−) mice under hyperoxic conditions showed increased LW/BW ratios, lung injury, neutrophil infiltration, IL-6 and TNF-α levels, and augmented lipid peroxidation, as evidenced by increased formation of malondialdehyde (MDA)- and 4-hydroxynonenal (4-HNE)-protein adducts, and pulmonary isofurans compared to those of WT mice. In vitro experiments showed that the F2-isoprostane PGF2-α is metabolized by CYP1A2 to a dinor metabolite, providing evidence for a catalytic role for CYP1A2 in the metabolism of F2-isoprostanes. In summary, our results support the hypothesis that hepatic CYP1A2 plays a critical role in the attenuation against hyperoxic lung injury by decreasing lipid peroxidation and oxidative stress in vivo. PMID:25680282

  19. Neonatal Pulmonary Macrophage Depletion Coupled to Defective Mucus Clearance Increases Susceptibility to Pneumonia and Alters Pulmonary Immune Responses.

    PubMed

    Saini, Yogesh; Wilkinson, Kristen J; Terrell, Kristy A; Burns, Kimberlie A; Livraghi-Butrico, Alessandra; Doerschuk, Claire M; O'Neal, Wanda K; Boucher, Richard C

    2016-02-01

    Resident immune cells (e.g., macrophages [MΦs]) and airway mucus clearance both contribute to a healthy lung environment. To investigate interactions between pulmonary MΦ function and defective mucus clearance, a genetic model of lysozyme M (LysM) promoter-mediated MΦ depletion was generated, characterized, and crossed with the sodium channel β subunit transgenic (Scnn1b-Tg) mouse model of defective mucus clearance. Diphtheria toxin A-mediated depletion of LysM(+) pulmonary MΦs in wild-type mice with normal mucus clearance resulted in lethal pneumonia in 24% of neonates. The pneumonias were dominated by Pasteurella pneumotropica and accompanied by emaciation, neutrophilic inflammation, and elevated Th1 cytokines. The incidence of emaciation and pneumonia reached 51% when LysM(+) MΦ depletion was superimposed on the airway mucus clearance defect of Scnn1b-Tg mice. In LysM(+) MΦ-depleted Scnn1b-Tg mice, pneumonias were associated with a broader spectrum of bacterial species and a significant reduction in airway mucus plugging. Bacterial burden (CFUs) was comparable between Scnn1b-Tg and nonpneumonic LysM(+) MΦ-depleted Scnn1b-Tg mice. However, the nonpneumonic LysM(+) MΦ-depleted Scnn1b-Tg mice exhibited increased airway inflammation, the presence of neutrophilic infiltration, and increased levels of inflammatory cytokines in bronchoalveolar lavage fluid compared with Scnn1b-Tg mice. Collectively, these data identify key MΦ-mucus clearance interactions with respect to both infectious and inflammatory components of muco-obstructive lung disease. PMID:26121027

  20. Peri-conceptional obesogenic exposure induces sex-specific programming of disease susceptibilities in adult mouse offspring.

    PubMed

    Dahlhoff, M; Pfister, S; Blutke, A; Rozman, J; Klingenspor, M; Deutsch, M J; Rathkolb, B; Fink, B; Gimpfl, M; Hrabě de Angelis, M; Roscher, A A; Wolf, E; Ensenauer, R

    2014-02-01

    Vulnerability of the fetus upon maternal obesity can potentially occur during all developmental phases. We aimed at elaborating longer-term health outcomes of fetal overnutrition during the earliest stages of development. We utilized Naval Medical Research Institute (NMRI) mice to induce pre-conceptional and gestational obesity and followed offspring outcomes in the absence of any postnatal obesogenic influences. Male adult offspring developed overweight, insulin resistance, hyperleptinemia, hyperuricemia and hepatic steatosis; all these features were not observed in females. Instead, they showed impaired fasting glucose and a reduced fat mass and adipocyte size. Influences of the interaction of maternal diet∗sex concerned offspring genes involved in fatty liver disease, lipid droplet size regulation and fat mass expansion. These data suggest that a peri-conceptional obesogenic exposure is sufficient to shape offspring gene expression patterns and health outcomes in a sex- and organ-specific manner, indicating varying developmental vulnerabilities between sexes towards metabolic disease in response to maternal overnutrition. PMID:24275555

  1. 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

  2. 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

  3. 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...

  4. 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

  5. Testosterone depletion increases the susceptibility of brain tissue to oxidative damage in a restraint stress mouse model.

    PubMed

    Son, Seung-Wan; Lee, Jin-Seok; Kim, Hyeong-Geug; Kim, Dong-Woon; Ahn, Yo-Chan; Son, Chang-Gue

    2016-01-01

    Among sex hormones, estrogen is particularly well known to act as neuroprotective agent. Unlike estrogen, testosterone has not been well investigated in regard to its effects on the brain, especially under psychological stress. To investigate the role of testosterone in oxidative brain injuries under psychological stress, we adapted an orchiectomy and restraint stress model. BALB/c mice were subjected to either an orchiectomy or sham operation. After allowing 15 days for recovery, mice were re-divided into four groups according to exposure of restraint stress: sham, sham plus stress, orchiectomy, and orchiectomy plus stress. Serum testosterone was undetectable in orchiectomized groups and restraint-induced stress significantly reduced testosterone levels in sham plus stress group. The serum levels of corticosterone and adrenaline were notably elevated by restraint stress, and these elevated hormones were markedly augmented by orchiectomy. Two oxidative stressors and biomarkers for lipid and protein peroxidation were significantly increased in the cerebral cortex and hippocampus by restraint stress, while the reverse pattern was observed in antioxidant enzymes. These results were supported by histopathological findings, with 4-hydroxynonenal staining for oxidative injury and Fluoro-Jade B staining showing the degenerating neurons. The aforementioned patterns of oxidative injury were accelerated by orchiectomy. These findings strongly suggest the conclusion that testosterone exerts a protective effect against oxidative brain damage, especially under stressed conditions. Unlike estrogen, the effects of testosterone on the brain have not been thoroughly investigated. In order to investigate the role of testosterone in oxidative brain injuries under psychological stress, we adapted an orchiectomy and restraint stress model. Orchiectomy markedly augmented the restraint stress-induced elevation of serum corticosterone and adrenaline levels as well as oxidative alterations

  6. An increased incidence of Hodgkin's lymphoma in patients with adult-onset sarcoma

    PubMed Central

    2012-01-01

    Background Sarcomas are rare, often fatal malignancies of connective tissues that can occur in genetic predisposition syndromes or result from carcinogen exposure. Hodgkin's lymphoma (HL) is not known to contribute to any recognised familial cancer syndrome comprising sarcomas, but is known to be associated with a variety of second cancers, including sarcomas. This study describes the prevalence of HL in families affected by sarcoma. Methods The International Sarcoma Kindred Study (ISKS) is a prospective cohort of 561 families ascertained via a proband with adult-onset sarcoma. Cancer-specific standardised incidence ratios (SIR) for multiple primary malignancies in probands were estimated. Clinical characteristics of individuals reporting both sarcoma and HL were described. Standardised incidence ratios for the occurrence of cancer in ISKS families were also estimated. Results Multiple primary cancers were reported in 16% of probands, significantly higher than in the general population. The risk of HL in probands was increased 15.8-fold (95%CI 7.9-31.6) and increased risks were also seen for breast cancer (SIR 2.9, 95%CI 1.9-4.4) and thyroid cancer (SIR 8.4, 95%CI 4.2-16.8). In 8 probands with both HL and sarcoma, the diagnosis of HL preceded that of sarcoma in 7 cases, and occurred synchronously in one case. Only 3 cases of sarcoma occurred in or close to prior radiotherapy fields. The overall incidence of HL in the ISKS cohort was not significantly increased by comparison with age- and gender-specific population estimates (SIR 1.63, 95%CI 1.05-2.43), suggesting that the association between HL and sarcomas did not extend to other family members. The age of onset of non-sarcoma, non-HL cancers in families affected by both HL and sarcoma was younger than the general population (56.2 y vs 65.6 y, P < 0.0001). Conclusions The basis for the association between HL and sarcomas may include the carcinogenic effects of therapy combined with excellent survival rates for HL

  7. HTLV-1-associated adult T cell leukemia is highly susceptible to Navitoclax due to enhanced Bax expression.

    PubMed

    Witzens-Harig, Mathias; Giaisi, Marco; Köhler, Rebecca; Krammer, Peter H; Li-Weber, Min

    2016-01-15

    Over-expression of Bcl-2, Bcl-xL and Bcl-w is frequently associated with cancer resistance to chemotherapy. Navitoclax (ABT-263), an orally bio-available small-molecule mimetic of the Bcl-2 homology domain 3, specifically inhibits Bcl-2, Bcl-xL and Bcl-w. Despite promising results obtained from the clinical trials, the use of Navitoclax in patients is dose-limited due to induction of death of platelets via inhibition of Bcl-xL and subsequent thrombocytopenia. This side effect limits the use of Navitoclax in low doses and to very sensitive tumors. In this study, we show that HTLV-1-associated adult T-cell leukemia/lymphoma (ATL) cells, which over-express Bcl-2, Bcl-xL and Bcl-w, show a 10- to 20-fold higher sensitivity (EC50 = ∼ 25-50 nM) to Navitoclax compared to non-HTLV-1-associated leukemic cells (EC50 = ∼ 1 μM). Investigation of the molecular mechanisms revealed that the HTLV-1 oncogenic protein Tax up-regulates expression of the pro-apoptotic protein Bax which enhances the therapeutic efficacy of Navitoclax. In addition, we show that agents that inhibit the transcription elongation or translation initiation such as Wogonin and Roc-A can further decrease the effective dose of Navitoclax. Our study suggests that HTLV-1 ATL may be a good candidate disease for low dose Navitoclax therapy and probably with less risk of thrombocytopenia. PMID:26260669

  8. Getting Grandma Online: Are Tablets the Answer for Increasing Digital Inclusion for Older Adults in the U.S.?

    PubMed Central

    Tsai, Hsin-yi Sandy; Shillair, Ruth; Cotten, Shelia R.; Winstead, Vicki; Yost, Elizabeth

    2015-01-01

    Using information and communication technologies (ICTs) can improve older adults’ quality of life. ICT use is associated with decreased feelings of loneliness and depression, along with increased feelings of independence and personal growth. However, limited access and low technological self-efficacy are key reasons why some groups, especially older adults, are excluded from being fully engaged in the digital world. In this study, we focus on older adults’ technological self-efficacy, which is related to their actual use of technology and the second level digital divide. Specifically, we examine: 1) how older adults decide to use a new technology, tablet computers; 2) how they conquer the barrier of technological self-efficacy through using tablets; and 3) the impacts of using this new technology in their lives. Twenty-one in-depth interviews were conducted with older adults residing in independent living communities in a medium-sized city in the Deep South region of the United States. Observational and enactive learning played important roles for older adults in using tablets. Seeing others use tablets, getting recommendations from family members, or having tablets given to them were the primary reasons they started to use tablet computers. The ease of use feature of tablets helped solve the problem of lacking technological self-efficacy. Using tablets helped increase a sense of connectedness. Tablet computers may be one way to increase digital inclusion among older adults. PMID:26877583

  9. Green tea supplementation increases glutathione and plasma antioxidant capacity in adults with the metabolic syndrome.

    PubMed

    Basu, Arpita; Betts, Nancy M; Mulugeta, Afework; Tong, Capella; Newman, Emily; Lyons, Timothy J

    2013-03-01

    Green tea, a popular polyphenol-containing beverage, has been shown to alleviate clinical features of the metabolic syndrome. However, its effects in endogenous antioxidant biomarkers are not clearly understood. Thus, we tested the hypothesis that green tea supplementation will upregulate antioxidant parameters (enzymatic and nonenzymatic) in adults with the metabolic syndrome. Thirty-five obese participants with the metabolic syndrome were randomly assigned to receive one of the following for 8 weeks: green tea (4 cups per day), control (4 cups water per day), or green tea extract (2 capsules and 4 cups water per day). Blood samples and dietary information were collected at baseline (0 week) and 8 weeks of the study. Circulating carotenoids (α-carotene, β-carotene, lycopene) and tocopherols (α-tocopherol, γ-tocopherol) and trace elements were measured using high-performance liquid chromatography and inductively coupled plasma mass spectroscopy, respectively. Serum antioxidant enzymes (glutathione peroxidase, glutathione, catalase) and plasma antioxidant capacity were measured spectrophotometrically. Green tea beverage and green tea extract significantly increased plasma antioxidant capacity (1.5 to 2.3 μmol/L and 1.2 to 2.5 μmol/L, respectively; P < .05) and whole blood glutathione (1783 to 2395 μg/g hemoglobin and 1905 to 2751 μg/g hemoglobin, respectively; P < .05) vs controls at 8 weeks. No effects were noted in serum levels of carotenoids and tocopherols and glutathione peroxidase and catalase activities. Green tea extract significantly reduced plasma iron vs baseline (128 to 92 μg/dL, P < .02), whereas copper, zinc, and selenium were not affected. These results support the hypothesis that green tea may provide antioxidant protection in the metabolic syndrome. PMID:23507223

  10. Conventional hemofiltration during cardiopulmonary bypass increases the serum lactate level in adult cardiac surgery

    PubMed Central

    Soliman, Rabie; Fouad, Eman; Belghith, Makhlouf; Abdelmageed, Tarek

    2016-01-01

    Objective: To evaluate the effect of hemofiltration during cardiopulmonary bypass on lactate level in adult patients who underwent cardiac surgery. Design: An observational study. Setting: Prince Sultan cardiac center, Riyadh, Saudi Arabia. Participants: The study included 283 patients classified into two groups: Hemofiltration group (n=138), hemofiltration was done during CPB. Control group (n = 145), patients without hemofiltration. Interventions: Hemofiltration during cardiopulmonary bypass. Measurements and Main Results: Monitors included hematocrit, lactate levels, mixed venous oxygen saturation, amount of fluid removal during hemofiltration and urine output. The lactate elevated in group H than group C (P < 0.05), and the PH showed metabolic acidosis in group H (P < 0.05). The mixed venous oxygen saturation decreased in group H than group C (P < 0.05). The number of transfused packed red blood cells was lower in group H than group C (P < 0.05). The hematocrit was higher in group H than group C (P < 0.05). The urine output was lower in group H than group C (P < 0.05). Conclusions: Hemofiltration during cardiopulmonary bypass leads to hemoconcentration, elevated lactate level and increased inotropic support. There are some recommendations for hemofiltration: First; Hemofiltration should be limited for patients with impaired renal function, positive fluid balance, reduced response to diuretics or prolonged bypass time more than 2 hours. Second; Minimal amount of fluids should be administered to maintain adequate cardiac output and reduction of priming volumes is preferable to maintain controlled hemodilution. Third; it should be done before weaning of or after cardiopulmonary bypass and not during the whole time of cardiopulmonary bypass. PMID:26750673

  11. Increasing Steps/Day Predicts Improvement in Physical Function and Pain Interference in Adults with Fibromyalgia

    PubMed Central

    Kaleth, Anthony S.; Slaven, James E.; Ang, Dennis C.

    2014-01-01

    Objective To examine the concurrent and predictive associations between the number of steps taken per day (steps/day) and clinical outcomes in patients with fibromyalgia (FM). Methods 199 adults with FM [mean age = 46.1 yr; 95% females] enrolled in a randomized clinical trial wore a hip-mounted accelerometer for 1 week and completed self-report measures of physical function [Fibromyalgia Impact Questionnaire-Physical Impairment (FIQ-PI), SF-36 physical component score (SF-36 PCS)], pain intensity and interference (Brief Pain Inventory; BPI), and depressive symptoms (Patient Health Questionnaire-8; PHQ-8) as part of their baseline and follow-up assessments. Associations of steps/day with self-report clinical measures were evaluated from baseline to week 12 using multivariate regression models adjusted for demographic and baseline covariates. Results Study participants were primarily sedentary, averaging 4,019 ± 1,530 steps/day. Our findings demonstrate a linear relationship between the change in steps/day and improvement in health outcomes for FM. Incremental increases on the order of 1,000 steps/day were significantly associated with (and predictive of) improvements in FIQ-PI, SF-36 PCS, BPI pain interference, and PHQ-8 (all p<0.05). Although higher step counts were associated with lower FIQ and BPI pain intensity scores, these were not statistically significant. Conclusion Step counts is an easily obtained and understood objective measure of daily physical activity. An exercise prescription that includes recommendations to gradually accumulate at least 5,000 additional steps/day may result in clinically significant improvements in outcomes relevant to patients with FM. Future studies are needed to elucidate the dose-response relationship between steps/day and patient outcomes in FM. PMID:25049001

  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. Occupations with an increased prevalence of self-reported asthma in Indian adults

    PubMed Central

    Pearce, Neil; Millett, Christopher; Subramanian, S.V.; Ebrahim, Shah

    2014-01-01

    Objectives Occupational asthma remains relatively under-recognized in India with little or no information regarding preventable causes. We studied occupations with an increased prevalence of self-reported asthma among adult men and women in India. Methods Analysis is based on 64 725 men aged 15–54 years and 52 994 women aged 15–49 years who participated in India’s third National Family Health Survey, 2005–2006, and reported their current occupation. Prevalence odds ratios (ORs) for specific occupations and asthma were estimated using multivariate logistic regression, separately for men and women, adjusting for age, education, household wealth index, current tobacco smoking, cooking fuel use, rural/urban residence and access to healthcare. Results The prevalence of asthma among the working population was 1.9%. The highest odds ratios for asthma were found among men in the plant and machine operators and assemblers major occupation category (OR: 1.67; 95% CI: 1.14–2.45; p = 0.009). Men working in occupation subcategories of machine operators and assemblers (OR: 1.85; 95% CI: 1.24–2.76; p = 0.002) and mining, construction, manufacturing and transport (OR: 1.33; 95% CI: 1.00–1.77; p = 0.051) were at the highest risk of asthma. Reduced odds of asthma prevalence in men was observed among extraction and building trades workers (OR: 0.72; 95% CI: 0.53–0.97; p = 0.029). Among women none of the occupation categories or subcategories was found significant for asthma risk. Men and women employed in high-risk occupations were not at a higher risk of asthma when compared with those in low-risk occupations. Conclusions This large population-based, nationally representative cross-sectional study has confirmed findings from high income countries showing high prevalence of asthma in men in a number of occupational categories and subcategories; however, with no evidence of increased risks for women in the same occupations. PMID:24712498

  14. Self-Reports of Increased Prospective and Retrospective Memory Problems in Adults with Developmental Dyslexia.

    PubMed

    Smith-Spark, James H; Zięcik, Adam P; Sterling, Christopher

    2016-08-01

    Short-term and working memory problems in dyslexia are well-documented, but other memory domains have received little empirical scrutiny, despite some evidence to suggest that they might be impaired. Prospective memory is memory for delayed intentions, whilst retrospective memory relates to memory for personally experienced past events. To gain an understanding of subjective everyday memory experience, a self-report measure designed to tap prospective and retrospective memory was administered to 28 adults with dyslexia and 26 IQ-matched adults without dyslexia. Adults with dyslexia reported experiencing significantly more frequent problems with memory than the adults without dyslexia. Group differences were found across seven out of the eight questionnaire scales. Further to these analyses, the participants' own ratings were compared with proxy ratings provided by close associates. The perception of poorer memory abilities in the participants did not differ between respondent types. The self-reported difficulties are, thus, unlikely to be the result of lowered self-esteem or metacognitive awareness. More frequent difficulties with both types of memory would seem, therefore, to be experienced by adults with dyslexia in everyday life. Further laboratory-based research is recommended to explore both memory domains in dyslexia and to identify the cognitive mechanisms by which these problems occur. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27121331

  15. Natural history of beta-cell autoimmunity in young children with increased genetic susceptibility to type 1 diabetes recruited from the general population.

    PubMed

    Kimpimäki, T; Kulmala, P; Savola, K; Kupila, A; Korhonen, S; Simell, T; Ilonen, J; Simell, O; Knip, M

    2002-10-01

    The aim of this study was to evaluate the frequency and predictive value of diabetes-associated autoantibodies, such as islet cell antibodies (ICA) and autoantibodies to insulin (IAA), GAD65 (GADA), and the IA-2 molecule (IA-2A) in genetically susceptible children from the general population during the first 2 yr of life. Of 12,170 newborn infants, 1,005 with increased genetic risk of type 1 diabetes (high risk, human leukocyte antigen DQB1*02/*0302; moderate risk, DQB1*0302/x, where x = other than *02, *0301, or *0602) were monitored for ICA, IAA, GADA, and IA-2A at 3- to 6-month intervals from birth up to a minimum age of 2 yr. In addition, all 15 genetically susceptible children from the general population who had participated in regular immunological follow-up and developed clinical type 1 diabetes by the end of April 2000 were analyzed for the development of autoantibodies. Among 1,005 children, 63 (6.3%) tested positive for at least one autoantibody, 31 for ICA (3.1%), 48 for IAA (4.8%), 23 for GADA (2.3%), and 13 for IA-2A (1.3%) at least once by the age of 2 yr. Both ICA and IAA identified 95% [95% confidence interval (CI), 77.2-99.9%] of those who tested persistently positive for multiple (> or = 2) antibodies at the age of 2 yr, GADA identified 86% (CI, 65.1-97.1%), and IA-2A identified 55% (CI, 32.2-75.6%). Close to half of the antibody-positive children (29 of 63) reverted back to antibody negativity. Autoantibodies disappeared more often among those who tested positive for IAA than among those who tested positive for other autoantibodies (P < or = 0.021). Among the 15 children who developed type 1 diabetes, the disease sensitivity of ICA was 80% (CI, 51.9-95.7%), that of IAA was 93% (CI, 68.0-99.8%), that of GADA was 60% (CI, 32.3-83.7%), and that of IA-2A was 40% (CI, 16.3-67.7%). These results suggest that IAA are characterized by high sensitivity, early appearance, and high frequency of transient antibody positivity, whereas ICA detected with a

  16. Short-term bed rest increases TLR4 and IL-6 expression in skeletal muscle of older adults.

    PubMed

    Drummond, Micah J; Timmerman, Kyle L; Markofski, Melissa M; Walker, Dillon K; Dickinson, Jared M; Jamaluddin, Mohammad; Brasier, Allan R; Rasmussen, Blake B; Volpi, Elena

    2013-08-01

    Bed rest induces significant loss of leg lean mass in older adults. Systemic and tissue inflammation also accelerates skeletal muscle loss, but it is unknown whether inflammation is associated to inactivity-induced muscle atrophy in healthy older adults. We determined if short-term bed rest increases toll-like receptor 4 (TLR4) signaling and pro-inflammatory markers in older adult skeletal muscle biopsy samples. Six healthy, older adults underwent seven consecutive days of bed rest. Muscle biopsies (vastus lateralis) were taken after an overnight fast before and at the end of bed rest. Serum cytokine expression was measured before and during bed rest. TLR4 signaling and cytokine mRNAs associated with pro- and anti-inflammation and anabolism were measured in muscle biopsy samples using Western blot analysis and qPCR. Participants lost ∼4% leg lean mass with bed rest. We found that after bed rest, muscle levels of TLR4 protein expression and interleukin-6 (IL-6), nuclear factor-κB1, interleukin-10, and 15 mRNA expression were increased after bed rest (P < 0.05). Additionally, the cytokines interferon-γ, and macrophage inflammatory protein-1β, were elevated in serum samples following bed rest (P < 0.05). We conclude that short-term bed rest in older adults modestly increased some pro- and anti-inflammatory cytokines in muscle samples while systemic changes in pro-inflammatory cytokines were mostly absent. Upregulation of TLR4 protein content suggests that bed rest in older adults increases the capacity to mount an exaggerated, and perhaps unnecessary, inflammatory response in the presence of specific TLR4 ligands, e.g., during acute illness. PMID:23761639

  17. Short-term bed rest increases TLR4 and IL-6 expression in skeletal muscle of older adults

    PubMed Central

    Timmerman, Kyle L.; Markofski, Melissa M.; Walker, Dillon K.; Dickinson, Jared M.; Jamaluddin, Mohammad; Brasier, Allan R.; Rasmussen, Blake B.; Volpi, Elena

    2013-01-01

    Bed rest induces significant loss of leg lean mass in older adults. Systemic and tissue inflammation also accelerates skeletal muscle loss, but it is unknown whether inflammation is associated to inactivity-induced muscle atrophy in healthy older adults. We determined if short-term bed rest increases toll-like receptor 4 (TLR4) signaling and pro-inflammatory markers in older adult skeletal muscle biopsy samples. Six healthy, older adults underwent seven consecutive days of bed rest. Muscle biopsies (vastus lateralis) were taken after an overnight fast before and at the end of bed rest. Serum cytokine expression was measured before and during bed rest. TLR4 signaling and cytokine mRNAs associated with pro- and anti-inflammation and anabolism were measured in muscle biopsy samples using Western blot analysis and qPCR. Participants lost ∼4% leg lean mass with bed rest. We found that after bed rest, muscle levels of TLR4 protein expression and interleukin-6 (IL-6), nuclear factor-κB1, interleukin-10, and 15 mRNA expression were increased after bed rest (P < 0.05). Additionally, the cytokines interferon-γ, and macrophage inflammatory protein-1β, were elevated in serum samples following bed rest (P < 0.05). We conclude that short-term bed rest in older adults modestly increased some pro- and anti-inflammatory cytokines in muscle samples while systemic changes in pro-inflammatory cytokines were mostly absent. Upregulation of TLR4 protein content suggests that bed rest in older adults increases the capacity to mount an exaggerated, and perhaps unnecessary, inflammatory response in the presence of specific TLR4 ligands, e.g., during acute illness. PMID:23761639

  18. Reduced glycosylation of human cell lines increases susceptibility to CD4-independent infection by human immunodeficiency virus type 2 (LAV-2/B).

    PubMed Central

    Talbot, S J; Weiss, R A; Schulz, T F

    1995-01-01

    The human immunodeficiency virus type 2 (HIV-2) strain LAV-2/B is able to infect a variety of human cell lines via a CD4-independent pathway. We have used the glycosylation inhibitors tunicamycin, swainsonine, and deoxymannojirimycin to further characterize this putative alternative receptor for HIV-2 (LAV-2/B). These antibiotics resulted in an increase (5- to 30-fold) in the susceptibility of a variety of CD4- human cell lines to infection by LAV-2/B (RD, HeLa, HT29, Rsb, Heb7a, Hos, and Daudi). Several nonprimate cell lines (mink Mv-1-lu, rabbit SIRC, hamster a23, mouse NIH 3T3, cat CCC, and rat HSN) remained resistant to infection by LAV-2/B after treatment with glycosylation inhibitors, suggesting that they do not express the HIV-2 CD4-independent receptor. Two of these nonprimate cell lines are readily infected by HIV-2 when they express CD4 (Mv-1-lu and CCC). Treatment of human cells with neuraminidase had no effect on subsequent infection by LAV-2/B, suggesting that the increase in susceptibility to infection of deglycosylated cells is not due to a change in the electrostatic charge of the cell surface. Treatment of RD CD4- cells and HeLa CD4+ cells with a variety of proteases resulted in a 75 to 90% decrease in infection by LAV-2/B when compared with untreated cells. Taken together, all these data suggest that HIV-2 can utilize a membrane glycoprotein other than CD4 to attach and fuse with a variety of human cells. PMID:7745686

  19. Suppression of Adult Neurogenesis Leads to an Increased HPA Axis Response

    PubMed Central

    Schloesser, Robert J.; Manji, Husseini K.; Martinowich, Keri

    2009-01-01

    Stress and glucocorticoids are among the strongest inhibitors of adult hippocampal neurogenesis. Despite the known role of the hippocampus in negative feedback regulation of the hypothalamo-pituitary adrenal axis, whether loss of hippocampal neurogenesis affects this inhibition has not been examined. Here we tested whether suppression of adult neurogenesis affected the hypothalamo-pituitary-adrenal axis response. Our results show that suppression of neurogenesis leads to a potentiated hypothalamo-pituitary-adrenal axis response following exposure to a mild stressor. This study suggests that suppressed neurogenesis directly regulates the hypothalamo-pituitary-adrenal axis response. PMID:19322118

  20. Monitoring of resistance or susceptibility of adults and larvae of Amblyomma cajennense (Acari: Ixodidae) to synthetic acaricides in Goiás, Brazil.

    PubMed

    Freitas, Edméia de Paula e Souza; Zapata, Marco Túlio Antônio Garcia; Fernandes, Fernando de Freitas

    2011-02-01

    Amblyomma cajennense or the Cayenne tick is a three-host ixodid tick species of low parasitic specificity that is the principal vector of Brazilian spotted fever. The primary objective of this study was to evaluate the possible development of resistance by adult specimens of A. cajennense to deltamethrin, a synthetic pyrethroid insecticide and the principal miticide/acaricide commercially available in the region. The second objective was to monitor the susceptibility and/or resistance of larvae of this species to 12 synthetic acaricide formulations selected from the principal pesticides available in Goiás for the control of ticks. Unfed male and female adult specimens of A. cajennense were collected from leaves of bushes along a nature trail in the municipality of Caldas Novas, Goiás, Brazil. They were submitted to immersion in the highest recommended dose of deltamethrin and subsequently, were placed in contact with filter paper impregnated with the substance. The toxicological effects caused by the insecticide were observed every 6 h over a 36 h period. To obtain larvae, engorged females of A. cajennense were collected from naturally infested horses that had been free of acaricidal residue for at least 45 days, in farms situated in five different municipalities in the state (Caldas Novas, Hidrolândia, Goiás, Terezópolis and Goiânia). The larvae were exposed to different concentrations of 12 commercially available acaricidal formulations using the larval packet test (LPT) method. The control groups were treated with distilled water alone. The bioassays were performed in quadruplicate at a temperature of 27 °C, relative air humidity > 80% and 12 h light/dark cycles. The mean percentage of mortality MX was 72.6% in the adult specimens after 24 h of exposure to the dose of deltamethrin recommended by the manufacturer, characterizing a status of resistance. MX of 82, 89, 89.6 and 90% of the larvae were obtained, respectively, for deltamethrin, cypermethrin

  1. Methods To Increase the Number of Successful Transfers between Programs by Students in Adult Literacy Programming. A Research Report.

    ERIC Educational Resources Information Center

    Challis, Stephen

    A study examined ways of increasing the number of successful transfers by students between community- and institution-based literacy programs in Manitoba. A literature review was conducted, and 18 adult literacy programs or related offices throughout Manitoba were visited. During the visits, classroom settings and curriculum materials were…

  2. Social behaviors increase more when children with ASD are imitated by their mother vs. an unfamiliar adult.

    PubMed

    Slaughter, Virginia; Ong, Su Sen

    2014-10-01

    Previous research suggests that being imitated by an adult increases the social behaviors of children with an autism spectrum disorder (ASD). In the current study, we examined whether familiarity with the imitating social partner modulates this effect. Ten children with ASD and their mothers participated. The children's social behaviors were observed prior to and following a 3-min period in which an adult social partner imitated everything they did. In one condition the partner was the child's mother, and in the other condition the partner was an unfamiliar experimenter. The results revealed significant increases in distal social behaviors (gazes toward the adult, vocalizing) following imitation by both partners. There was a significantly greater increase in proximal social behaviors (including approach, being physically close, and touching) and a greater decrease in playing alone when the imitator was the child's mother as opposed to the experimenter. The findings suggest that the experience of being imitated creates an atmosphere of mutuality and rapport between children with ASD and their social partners, which increases their sociability even in interactions with already familiar adults. PMID:24903832

  3. Getting Grandma Online: Are Tablets the Answer for Increasing Digital Inclusion for Older Adults in the U.S.?

    ERIC Educational Resources Information Center

    Tsai, Hsin-yi Sandy; Shillair, Ruth; Cotten, Shelia R.; Winstead, Vicki; Yost, Elizabeth

    2015-01-01

    Using information and communication technologies (ICTs) can improve older adults' quality of life. ICT use is associated with decreased feelings of loneliness and depression, along with increased feelings of independence and personal growth. However, limited access and low technological self-efficacy are key reasons why some groups, especially…

  4. A microenvironment approach to reducing sedentary time and increasing physical activity of children and adults at a playground

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective. Test whether a micro-environment park intervention in Grand Forks, ND, movement of seating away from a playground, would increase the physical activity and length of stay of park users. Method. STUDY 1, summer 2012: physical activity of children and adults was assessed during baseline (...

  5. Mindfulness Training Increases Momentary Positive Emotions and Reward Experience in Adults Vulnerable to Depression: A Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Geschwind, Nicole; Peeters, Frenk; Drukker, Marjan; van Os, Jim; Wichers, Marieke

    2011-01-01

    Objective: To examine whether mindfulness-based cognitive therapy (MBCT) increases momentary positive emotions and the ability to make use of natural rewards in daily life. Method: Adults with a life-time history of depression and current residual depressive symptoms (mean age = 43.9 years, SD = 9.6; 75% female; all Caucasian) were randomized to…

  6. Maternal allergy increases susceptibility to offspring allergy in association with Th2 biased epigenetic alterations in a mouse model of peanut allergy

    PubMed Central

    Song, Ying; Liu, Changda; Hui, Yiqun; Srivastava, Kamal; Zhou, Zhenwen; Chen, Jia; Miller, Rachel L.; Finkelman, Fred D.; Li, Xiu-Min

    2014-01-01

    Background Although maternal atopy is a risk factor for development of peanut allergy, this phenomenon has not been well-characterized experimentally, and the mechanisms underlying offspring risk are unclear. Objective To determine if offspring of peanut allergic mothers (O-PAM) are more susceptible to peanut allergy than offspring of naive mothers (O-NM) in a murine model; and if so whether the susceptibility is linked to Th2 biased epigenetic alterations. Methods Five-week-old O-PAM and O-NM were intragastrically (i.g.) sensitized to and challenged with peanut. Serum peanut-specific IgE, plasma histamine, anaphylactic reactions, and splenocyte (SPC) and mesenteric lymph node (MLN) cell cytokine production were measured. DNA methylation levels of the IL-4 gene promoter from sensitized offspring SPC and MLN cells and un-sensitized neonatal offspring SPCs were determined by pyrosequencing. Results O-PAM exhibited 3-fold higher peanut-specific IgE levels following peanut sensitization as well as 5-fold higher histamine levels and significantly higher anaphylactic symptom scores following challenge than O-NM (p<0.05-0.01). Cultured O-PAM SPCs and MLN produced significantly more Th2 cytokines than O-NM cells (p<0.05-0.01). O-PAM cells exhibited significantly reduced DNA methylation at CpG sites of the IL-4 gene promoter than O-NM cells. DNA methylation levels were inversely correlated with IL-4 and IgE production. O-PAM neonatal splenocyte hypomethylation of the IL-4 gene promoter was also present. Conclusion This study is the first to demonstrate that increased susceptibility to peanut allergy in offspring of peanut allergic mothers is associated with epigenetic alternation of the IL-4 gene promoter. This finding may provide an insight into preventing the development of early life allergy. Clinical Implications This study is the first to demonstrate that offspring of peanut allergic mothers are predisposed to develop peanut allergy, which is associated with epigenetic

  7. A Case Study: Increase Enrollment by Reducing Dropout Rates in Adult Distance Education.

    ERIC Educational Resources Information Center

    Chyung, Yonnie; Winiecki, Donald J.; Fenner, Jo Ann

    The Instructional and Performance Technology Department at Boise State University (Idaho) offers a master's degree program via distance education to prepare adult students for careers in the areas of instructional design, job performance improvement, human resources, organizational redesign, training, and training management. Most students attend…

  8. Increased levels of hyper-stable protein aggregates in plasma of older adults.

    PubMed

    Xia, Ke; Trasatti, Hannah; Wymer, James P; Colón, Wilfredo

    2016-06-01

    Proteins that misfold into hyper-stable/degradation-resistant species during aging may accumulate and disrupt protein homeostasis (i.e., proteostasis), thereby posing a survival risk to any organism. Using the method diagonal two-dimensional (D2D) SDS-PAGE, which separates hyper-stable SDS-resistant proteins at a proteomics level, we analyzed the plasma of healthy young (<30 years) and older (60-80 years) adults. We discovered the presence of soluble SDS-resistant protein aggregates in the plasma of older adults, but found significantly lower levels in the plasma of young adults. We identified the inflammation-related chaperone protein haptoglobin as the main component of the hyper-stable aggregates. This observation is consistent with the growing link between accumulations of protein aggregates and aging across many organisms. It is plausible higher amounts of SDS-resistant protein aggregates in the plasma of older adults may reflect a compromise in proteostasis that may potentially indicate cellular aging and/or disease risk. The results of this study have implications for further understanding the link between aging and the accumulation of protein aggregates, as well as potential for the development of aging-related biomarkers. More broadly, this novel application of D2D SDS-PAGE may be used to identify, quantify, and characterize the degradation-resistant protein aggregates in human plasma or any biological system. PMID:27179971

  9. Evaluation of Two Instruction Methods to Increase Employment Options for Young Adults with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Burke, Raymond V.; Andersen, Melissa N.; Bowen, Scott L.; Howard, Monica R.; Allen, Keith D.

    2010-01-01

    We evaluated the efficacy of a vocational training program including behavioral skills training, and a "performance cue system" (i.e., a proprietary iPhone application adapted for the study) to teach targeted social-vocational skills to six young adults with an Autism Spectrum Disorder. In two separate studies, participants were employed to assist…

  10. Basil oil fumigation increases radiation sensitivity in adult Sitophilus oryzae (Coleoptera: Curculionidae).

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The biological activity of basil (Ocimum basilicum L.) oil was tested against the stored product pest rice weevil, Sitophilus oryzae(L.). Adult weevils were exposed to seven different concentrations of basil oil ranging from 0.12 µl/ml-0.60 µl/ml in Petri dishes and mortality was assessed at 3,4 and...

  11. 5,7-DIHYDROXYTRYPTAMINE INJECTIONS INCREASE GLIAL FIBRILLARY ACIDIC PROTEIN IN THE HYPOTHALAMUS OF ADULT RATS

    EPA Science Inventory

    The distribution and level of glial fibrillary acidic protein (GFAP) were determined in the adult rat hypothalamus following axotomy of serotonin (5-HT) neurons. even days after unilateral intrahypothalamic injection of the 5-HT neurotoxic, 5,7- dihydroxytryptamine, there gas a m...

  12. Evaluation of Two Instruction Methods to Increase Employment Options for Young Adults with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Burke, Raymond V.; Andersen, Melissa N.; Bowen, Scott L.; Howard, Monica R.; Allen, Keith D.

    2010-01-01

    We evaluated the efficacy of a vocational training program including behavioral skills training, and a "performance cue system" (i.e., a proprietary iPhone application adapted for the study) to teach targeted social-vocational skills to six young adults with an Autism Spectrum Disorder. In two separate studies, participants were employed…

  13. Increased susceptibility to Strongyloides venezuelensis in mice due to Mycobacterium bovis co-infection which modulates production of Th2 cytokines.

    PubMed

    Carmo, A M; Vicentini, M A; Dias, A T; Alves, L L; Alves, C C S; Brandi, J S; De Paula, M L; Fernandes, A; Barsante, M M; Souza, M A; Teixeira, H C; Negrão-Corrêa, D; Ferreira, A P

    2009-09-01

    An estimated quarter of the world's population possesses an infection caused by gastrointestinal nematodes, which induce a Th2 type immune response. Concomitant infection of nematodes with Mycobacterium tuberculosis, which induces a predominantly Th1 type response, is very frequent in tropical and subtropical regions. This study examined immune responses of BALB/c mice infected with Strongyloides venezuelensis and then co-infected with Mycobacterium bovis. The number of worms in the intestine, eggs in feces, cytokine production in lungs and intestine and the expression of CD80, CD86, CTLA-4 and CD28 cell markers on pulmonary cells were analysed. Our results indicate that co-infected mice had an increased parasite burden, which correlates with elevated IFN-gamma and IL-10 cytokine production and decreased IL-4 and IL-13. Moreover, decreased expression of CD80 and increased expression of CTLA-4 were observed in co-infected mice. Our data point out that susceptibility to Strongyloides venezuelensis infection is increased by Mycobacterium bovis co-infection, resulting in higher parasite survival. PMID:19660155

  14. The association between advanced maternal and paternal ages and increased adult mortality is explained by early parental loss

    PubMed Central

    Elo, Irma T.; Kohler, Iliana; Martikainen, Pekka

    2015-01-01

    The association between advanced maternal and paternal ages at birth and increased mortality among adult offspring is often attributed to parental reproductive ageing, e.g., declining oocyte or sperm quality. Less attention has been paid to alternative mechanisms, including parental socio-demographic characteristics or the timing of parental death. Moreover, it is not known if the parental age-adult mortality association is mediated by socioeconomic attainment of the children, or if it varies over the lifecourse of the adult children. We used register-based data drawn from the Finnish 1950 census (sample size 89,737; mortality follow-up 1971–2008) and discrete-time survival regression with logit link to analyze these alternative mechanisms in the parental age-offspring mortality association when the children were aged 35–49 and 50–72. Consistent with prior literature, we found that adult children of older parents had increased mortality relative to adults whose parents were aged 25–29 at the time of birth. For example, maternal and paternal ages 40–49 were associated with mortality odds ratios (ORs)of 1.31 (p<.001) and 1.22 (p<.01), respectively, for offspring mortality at ages 35–49. At ages 50–72 advanced parental age also predicted higher mortality, though not as strongly. Adjustment for parental socio-demographic characteristics (education, occupation, family size, household crowding, language) weakened the associations only slightly. Adjustment for parental survival, measured by whether the parents were alive when the child reached age 35, reduced the advanced parental age coefficients substantially and to statistically insignificant levels. These results indicate that the mechanism behind the advanced parental age-adult offspring mortality association is mainly social, reflecting early parental loss and parental characteristics, rather than physiological mechanisms reflecting reproductive ageing. PMID:24997641

  15. The association between advanced maternal and paternal ages and increased adult mortality is explained by early parental loss.

    PubMed

    Myrskylä, Mikko; Elo, Irma T; Kohler, Iliana V; Martikainen, Pekka

    2014-10-01

    The association between advanced maternal and paternal ages at birth and increased mortality among adult offspring is often attributed to parental reproductive aging, e.g., declining oocyte or sperm quality. Less attention has been paid to alternative mechanisms, including parental socio-demographic characteristics or the timing of parental death. Moreover, it is not known if the parental age-adult mortality association is mediated by socioeconomic attainment of the children, or if it varies over the lifecourse of the adult children. We used register-based data drawn from the Finnish 1950 census (sample size 89,737; mortality follow-up 1971-2008) and discrete-time survival regression with logit link to analyze these alternative mechanisms in the parental age-offspring mortality association when the children were aged 35-49 and 50-72. Consistent with prior literature, we found that adult children of older parents had increased mortality relative to adults whose parents were aged 25-29 at the time of birth. For example, maternal and paternal ages 40-49 were associated with mortality odds ratios (ORs) of 1.31 (p<.001) and 1.22 (p<.01), respectively, for offspring mortality at ages 35-49. At ages 50-72 advanced parental age also predicted higher mortality, though not as strongly. Adjustment for parental socio-demographic characteristics (education, occupation, family size, household crowding, language) weakened the associations only slightly. Adjustment for parental survival, measured by whether the parents were alive when the child reached age 35, reduced the advanced parental age coefficients substantially and to statistically insignificant levels. These results indicate that the mechanism behind the advanced parental age-adult offspring mortality association is mainly social, reflecting early parental loss and parental characteristics, rather than physiological mechanisms reflecting reproductive aging. PMID:24997641

  16. A low vitamin A status increases the susceptibility to cigarette smoke-induced lung emphysema in C57BL/6J mice.

    PubMed

    van Eijl, S; Mortaz, E; Versluis, C; Nijkamp, F P; Folkerts, G; Bloksma, N

    2011-04-01

    Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation. Cigarette smoke has been considered a major player in the pathogenesis of COPD. The inflamed airways of COPD patients contain several inflammatory cells. Vitamin A metabolites have been implicated in the repair of lung damage. Exposure to cigarette smoke has been shown to depress levels of retinol in lungs of rats. The purpose of this study was to investigate if a low, but not deficient, vitamin A status potentiated susceptibility to the development of cigarette smoke-induced lung emphysema in mice. Mice were bred that were the offspring's of 3 generations of mice that were fed a purified diet containing low levels of vitamin A and exposed to cigarette smoke for 3 months, every weekday. Then, levels of 9-cis, 13-cis, and all-trans retinoic acid, retinol and retinyl palmitate were measured in plasma, liver and right lung lobe. The left lung lobe was used to assess mean linear intercept (Lm), as a measure of smoke-induced lung damage. Average feed intakes were not different between treatment groups. We show that both retinol and retinyl palmitate levels were dramatically decreased in the storage organs of mice on the low vitamin A diet (retinol 2-fold in both lung and liver, and retinyl palmitate 5- fold in lung) which shows that the depletion was successful