Gene expression differs in susceptible and resistant amphibians exposed to Batrachochytrium dendrobatidis.

Chytridiomycosis, the disease caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd), has devastated global amphibian biodiversity. Nevertheless, some hosts avoid disease after Bd exposure even as others experience near-complete extirpation. It remains unclear whether the amphibian adaptive immune system plays a role in Bd defence. Here, we describe gene expression in two host species-one susceptible to chytridiomycosis and one resistant-following exposure to two Bd isolates that differ in virulence. Susceptible wood frogs (Rana sylvatica) had high infection loads and mortality when exposed to the more virulent Bd isolate but lower infection loads and no fatal disease when exposed to the less virulent isolate. Resistant American bullfrogs (R. catesbeiana) had high survival across treatments and rapidly cleared Bd infection or avoided infection entirely. We found widespread upregulation of adaptive immune genes and downregulation of important metabolic and cellular maintenance components in wood frogs after Bd exposure, whereas American bullfrogs showed little gene expression change and no evidence of an adaptive immune response. Wood frog responses suggest that adaptive immune defences may be ineffective against virulent Bd isolates that can cause rapid physiological dysfunction. By contrast, American bullfrogs exhibited robust resistance to Bd that is likely attributable, at least in part, to their continued upkeep of metabolic and skin integrity pathways as well as greater antimicrobial peptide expression compared to wood frogs, regardless of exposure. Greater understanding of these defences will ultimately help conservationists manage chytridiomycosis

A novel low-voltage electron-bombarded CCD readout

We present proof-of-concept results for a novel ultraviolet-sensitive, photon counting, solar blind detector that has the potential for high QE in a compact low voltage, low power, unsealed design. We utilize a delta-doped back-illuminated CCD to read out low energy electrons from a photocathode. In parallel, a new generation of high-QE ultraviolet-sensitive GaN photocathodes is being developed with initial success using delta-doping technology rather than cesiation. In this paper we present results with the new readout using a CsI test cathode, which produces events at under 1000 V accelerating potential

Developing a Rodent Model of Adverse Menopausal Symptoms

poster abstractMenopause is a condition where severe depletion of estrogen levels leads to a cluster of adverse symptoms such as anxiety, cutaneous vasodilation/sudomotor "hot flashes", sleep disturbances, and appetite change (Freeman et al., 2005; Seritan et al., 2010). Previously, estrogen replacement therapy was the first line treatment for menopausal symptoms. However, it is no longer acceptable due to increased risk of cancer (Rossouw et al., 2002). Therefore there is a need for creating non-hormonal therapies to reduce the incidence of adverse menopausal-related symptoms. This is hindered by the limited understanding of menopausal symptoms and a lack of animal models of "hot flashes" (Nelson et al., 2006). Currently, the most accepted model of hot flashes is addicting female rats to morphine then inducing morphine withdrawal using naloxone (a ?-opioid receptor competitive antagonist) to provoke increases in tail temp (an indicator of cutaneous vasodilation). Yet, there is no evidence that the opioid system is disrupted in women with menopause [e.g., naloxone does not provoke "hot flashes" clinically (DeFazio et al., 1984)]. Here we induced a menopausal state by surgically removing the ovaries (OVEX) to deplete estrogen which induces a cluster of adverse menopause-like symptoms that include: 1) increased anxiety; 2) weight gain; and 3) disrupted diurnal skin and core body tempature changes. Additionally, we have developed an alternative model of "hot flashes" where administering yohimbine (an alpha2-adrenergic autoreceptor antagonist that provokes "hot flashes in menopausal women) resulted in "hot flash"-related increases in skin temp in OVEX, but not sham-OVEX, female rats

CYP2D6 drug-gene and drug-drug-gene interactions among patients prescribed pharmacogenetically actionable opioids

Purpose When codeine and tramadol are used for pain management, it is imperative that nurses are able to assess for potential drug-gene and drug-drug-gene interactions that could adversely impact drug metabolism and ultimately pain relief. Both drugs are metabolized through the CYP2D6 metabolic pathway which can be affected by medications as well the patient's own pharmacogenotype. The purpose of this brief report is to identify drug-gene and drug-drug-gene interactions in 30 adult patients prescribed codeine or tramadol for pain. Methods We used three data sources: (1) six months of electronic health record data on the number and types of medications prescribed to each patient; (2) each patient's CYP2D6 pharmacogenotype, and (3) published data on known CYP2D6 gene-drug and drug-drug-gene interactions. Results Ten patients (33%) had possible drug-gene or drug-drug-gene interactions. Five patients had CYP2D6 drug-gene interactions indicating they were not good candidates for codeine or tramadol. In addition, five patients had potential CYP2D6 drug-drug-gene interactions with either codeine or tramadol. Conclusion Our findings from this exploratory study underscores the importance of assessing and accounting for drug-gene and drug-drug-gene interactions in patients prescribed codeine or tramadol

Urinary Phthalate Metabolite Concentrations and Diabetes among Women in the National Health and Nutrition Examination Survey (NHANES) 2001–2008

Background: Previous studies have shown that women have higher urinary concentrations of several phthalate metabolites than do men, possibly because of a higher use of personal care products. Few studies have evaluated the association between phthalate metabolites, diabetes, and diabetes-related risk factors among women. Objective: We explored the association between urinary phthalate metabolite concentrations and diabetes among women who participated in a cross-sectional study. Methods: We used urinary concentrations of phthalate metabolites, analyzed by the Centers for Disease Control and Prevention, and self-reported diabetes of 2,350 women between 20 and 79 years of age who participated in the NHANES (2001–2008). We used multiple logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) and adjusted for urinary creatinine, sociodemographic characteristics, dietary factors, and body size. A secondary analysis was conducted for women who did not have diabetes to evaluate the association between phthalate metabolite concentrations and fasting blood glucose (FBG), homeostasis model assessment–estimated insulin resistance, and glycosylated hemoglobin A1c. Results: After adjusting for potential confounders, women with higher levels of mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono-(3-carboxypropyl) phthalate (MCPP), and three di-(2-ethylhexyl) phthalate metabolites (ΣDEHP) had an increased odds of diabetes compared with women with the lowest levels of these phthalates. Women in the highest quartile for MBzP and MiBP had almost twice the odds of diabetes [OR = 1.96 (95% CI: 1.11, 3.47) and OR = 1.95 (95% CI: 0.99, 3.85), respectively] compared with women in the lowest quartile. Nonmonotonic, positive associations were found for MnBP and ΣDEHP, whereas MCPP appeared to have a threshold effect. Certain phthalate metabolites were positively associated with FBG and insulin resistance. Discussion: Urinary levels of several phthalates were associated with prevalent diabetes. Future prospective studies are needed to further explore these associations to determine whether phthalate exposure can alter glucose metabolism and increase the risk of insulin resistance and diabetes

Adult life expectancy trends in the era of antiretroviral treatment in rural Uganda (1991-2012).

OBJECTIVE: To estimate the impact of antiretroviral therapy (ART) on population-wide adult life expectancy. STUDY DESIGN: A population-based open cohort study with repeated HIV status measurements and registration of vital events in Southwestern Uganda (1991-2012). METHODS: Nonparametric survival analysis techniques are used for estimating trends in the adult life expectancy of the general population (aged 15 and above), the adult life expectancy by HIV status, and the adult life expectancy deficit. The life expectancy deficit is estimated as the difference between overall life expectancy and life expectancy of the HIV-negative population. All estimates are disaggregated by sex. RESULTS: Between 1991-1993 and 2009-2012, population-wide adult life expectancy increased from 39.3 [95% confidence interval (CI): 35.9-42.8] to 56.1 years (95% CI: 54.0-58.5) in women, and from 38.6 (95% CI: 35.4-42.1) to 51.4 years (95% CI: 49.2-53.7) in men. Most of the adult life expectancy gains coincide with the introduction of ART in 2004; as evidenced by an increase in the adult life expectancy of people living with HIV between 2000-2002 and 2009-2012 of 22.9 and 20.0 years for women and men, respectively. Over the whole period of observation, the adult life expectancy deficit associated with HIV decreased from 16.1 (95% CI: 12.7-19.8) to 6.0 years (95% CI: 4.1-7.8) among women, and from 16.0 (95% CI: 12.1-19.9) to 2.8 years (95% CI: 1.2-4.6) among men. CONCLUSION: Population-wide life expectancy increased substantially, largely driven by reductions in HIV-related mortality. Women have gained more adult life years than men since the introduction of ART, but the burden of HIV in terms of the life years lost is still larger for women than it is for men

Structure and activity of DmmA, a marine haloalkane dehalogenase

DmmA is a haloalkane dehalogenase (HLD) identified and characterized from the metagenomic DNA of a marine microbial consortium. Dehalogenase activity was detected with 1,3‐dibromopropane as substrate, with steady‐state kinetic parameters typical of HLDs ( K m = 0.24 ± 0.05 mM, k cat = 2.4 ± 0.1 s −1 ). The 2.2‐Å crystal structure of DmmA revealed a fold and active site similar to other HLDs, but with a substantially larger active site binding pocket, suggestive of an ability to act on bulky substrates. This enhanced cavity was shown to accept a range of linear and cyclic substrates, suggesting that DmmA will contribute to the expanding industrial applications of HLDs. PDB Code(s): 3U1TPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90241/1/PRO_2009_sm_suppinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/90241/2/2009_ftp.pd