Genetic background influences tumour development in heterozygous Men1 knockout mice

Multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disorder caused by MEN1 germline mutations, is characterised by parathyroid, pancreatic and pituitary tumours. MEN1 mutations also cause familial isolated primary hyperparathyroidism (FIHP), a milder condition causing hyperparathyroidism only. Identical mutations can cause either MEN1 or FIHP in different families, thereby implicating a role for genetic modifiers in altering phenotypic expression of tumours. We therefore investigated the effects of genetic background and potential for genetic modifiers on tumour development in adult Men1+/- mice, which develop tumours of the parathyroids, pancreatic islets, anterior pituitary, adrenal cortex and gonads, that had been backcrossed to generate C57BL/6 and 129S6/SvEv congenic strains. A total of 275 Men1+/- mice, aged 5–26 months were macroscopically studied, and this revealed that genetic background significantly influenced the development of pituitary, adrenal and ovarian tumours, which occurred in mice over 12 months of age and more frequently in C57BL/6 females, 129S6/SvEv males and 129S6/SvEv females, respectively. Moreover, pituitary and adrenal tumours developed earlier, in C57BL/6 males and 129S6/SvEv females, respectively, and pancreatic and testicular tumours developed earlier in 129S6/SvEv males. Furthermore, glucagon-positive staining pancreatic tumours occurred more frequently in 129S6/SvEv Men1+/- mice. Whole genome sequence analysis of 129S6/SvEv and C57BL/6 Men1+/- mice revealed >54,000 different variants in >300 genes. These included, Coq7, Dmpk, Ccne2, Kras, Wnt2b, Il3ra and Tnfrsf10a, and qRT-PCR analysis revealed that Kras was significantly higher in pituitaries of male 129S6/SvEv mice. Thus, our results demonstrate that Kras and other genes could represent possible genetic modifiers of Men1

Variability of the Spectral Energy Distribution of the Blazar S5 0716+714

The emission from blazars is known to be variable at all wavelengths. The flux variability is often accompanied by spectral changes. Spectral energy distribution (SED) changes must be associated with changes in the spectra of emitting electrons and/or the physical parameters of the jet. Meaningful modeling of blazar broadband spectra is required to understand the extreme conditions within the emission region. Not only is the broadband SED crucial, but also information about its variability is needed to understand how the highest states of emission occur and how they differ from the low states. This may help in discriminating between models. Here we present the results of our SED modeling of the blazar S5 0716+714 during various phases of its activity. The SEDs are classified into different bins depending on the optical brightness state of the source.Comment: 4 pages, 3 figures, contributed talk presented at the conference Multifrequency Variability of Blazars, Guangzhou, China, September 22-24, 2010. To appear in Journal of Astrophysics and Astronomy (JAA

Subclinical myocardial disease by cardiac magnetic resonance imaging and spectroscopy in healthy HIV/Hepatitis C virus-coinfected persons.

Objective The contribution of hepatitis C virus (HCV) infection to the risk of heart failure in human immunodeficiency virus (HIV)-coinfected persons is unknown. The objective was to characterize cardiac function and morphology in HIV-treated coinfected persons. Methods In a cross-sectional study, HIV-infected patients virologically suppressed on antiretroviral therapy without known cardiovascular disease or diabetes mellitus underwent cardiac magnetic resonance imaging and spectroscopy for measures of cardiac function, myocardial fibrosis, and steatosis. Results The study included 18 male patients with a median age of 44 years. Of these, 10 had untreated HCV coinfection and eight had HIV monoinfection. Global systolic and diastolic function in the cohort were normal, and median myocardial fat content was 0.48% (interquartile range 0.35-1.54). Left ventricular (LV) mass index and LV mass/volume ratio were significantly greater in the HIV/HCV-coinfected group compared with the HIV-monoinfected group. In the HIV-monoinfected group, there was more myocardial fibrosis as measured by extracellular volume fraction. Conclusions There were differences between HIV/HCV-coinfected and HIV-monoinfected patients in cardiac structure and morphology. Larger studies are needed to examine whether HIV and HCV independently contribute to mechanisms of heart failure

Body odor quality predicts behavioral attractiveness in humans

Growing effort is being made to understand how different attractive physical traits co-vary within individuals, partly because this might indicate an underlying index of genetic quality. In humans, attention has focused on potential markers of quality such as facial attractiveness, axillary odor quality, the second-to-fourth digit (2D:4D) ratio and body mass index (BMI). Here we extend this approach to include visually-assessed kinesic cues (nonverbal behavior linked to movement) which are statistically independent of structural physical traits. The utility of such kinesic cues in mate assessment is controversial, particularly during everyday conversational contexts, as they could be unreliable and susceptible to deception. However, we show here that the attractiveness of nonverbal behavior, in 20 male participants, is predicted by perceived quality of their axillary body odor. This finding indicates covariation between two desirable traits in different sensory modalities. Depending on two different rating contexts (either a simple attractiveness rating or a rating for long-term partners by 10 female raters not using hormonal contraception), we also found significant relationships between perceived attractiveness of nonverbal behavior and BMI, and between axillary odor ratings and 2D:4D ratio. Axillary odor pleasantness was the single attribute that consistently predicted attractiveness of nonverbal behavior. Our results demonstrate that nonverbal kinesic cues could reliably reveal mate quality, at least in males, and could corroborate and contribute to mate assessment based on other physical traits

Barcoding life to conserve biological diversity: Beyond the taxonomic imperative

Barcoding scientists aspire to adhere to the objectives of the Convention on Biological Diversity by promoting conservation, sustainability, and the equitable sharing of benefits arising from use of genetic resources. (Image: Juan Manuel Escalante, wwww.realitat.com

Elevated CO₂ does not increase eucalypt forest productivity on a low-phosphorus soil

Rising atmospheric CO2 stimulates photosynthesis and productivity of forests, offsetting CO2 emissions. Elevated CO2 experiments in temperate planted forests yielded ~23% increases in productivity over the initial years. Whether similar CO2 stimulation occurs in mature evergreen broadleaved forests on low-phosphorus (P) soils is unknown, largely due to lack of experimental evidence. This knowledge gap creates major uncertainties in future climate projections as a large part of the tropics is P-limited. Here,we increased atmospheric CO2 concentration in a mature broadleaved evergreen eucalypt forest for three years, in the first large-scale experiment on a P-limited site. We show that tree growth and other aboveground productivity components did not significantly increase in response to elevated CO2 in three years, despite a sustained 19% increase in leaf photosynthesis. Moreover, tree growth in ambient CO2 was strongly P-limited and increased by ~35% with added phosphorus. The findings suggest that P availability may potentially constrain CO2-enhanced productivity in P-limited forests; hence, future atmospheric CO2 trajectories may be higher than predicted by some models. As a result, coupled climate-carbon models should incorporate both nitrogen and phosphorus limitations to vegetation productivity in estimating future carbon sinks

Diagnosis of childhood tuberculosis and host RNA expression in Africa

Improved diagnostic tests for tuberculosis in children are needed. We hypothesized that transcriptional signatures of host blood could be used to distinguish tuberculosis from other diseases in African children who either were or were not infected with the human immunodeficiency virus (HIV

Evidence-based practice educational intervention studies: A systematic review of what is taught and how it is measured

Abstract Background Despite the established interest in evidence-based practice (EBP) as a core competence for clinicians, evidence for how best to teach and evaluate EBP remains weak. We sought to systematically assess coverage of the five EBP steps, review the outcome domains measured, and assess the properties of the instruments used in studies evaluating EBP educational interventions. Methods We conducted a systematic review of controlled studies (i.e. studies with a separate control group) which had investigated the effect of EBP educational interventions. We used citation analysis technique and tracked the forward and backward citations of the index articles (i.e. the systematic reviews and primary studies included in an overview of the effect of EBP teaching) using Web of Science until May 2017. We extracted information on intervention content (grouped into the five EBP steps), and the outcome domains assessed. We also searched the literature for published reliability and validity data of the EBP instruments used. Results Of 1831 records identified, 302 full-text articles were screened, and 85 included. Of these, 46 (54%) studies were randomised trials, 51 (60%) included postgraduate level participants, and 63 (75%) taught medical professionals. EBP Step 3 (critical appraisal) was the most frequently taught step (63 studies; 74%). Only 10 (12%) of the studies taught content which addressed all five EBP steps. Of the 85 studies, 52 (61%) evaluated EBP skills, 39 (46%) knowledge, 35 (41%) attitudes, 19 (22%) behaviours, 15 (18%) self-efficacy, and 7 (8%) measured reactions to EBP teaching delivery. Of the 24 instruments used in the included studies, 6 were high-quality (achieved ≥3 types of established validity evidence) and these were used in 14 (29%) of the 52 studies that measured EBP skills; 14 (41%) of the 39 studies that measured EBP knowledge; and 8 (26%) of the 35 studies that measured EBP attitude. Conclusions Most EBP educational interventions which have been evaluated in controlled studies focus on teaching only some of the EBP steps (predominantly critically appraisal of evidence) and did not use high-quality instruments to measure outcomes. Educational packages and instruments which address all EBP steps are needed to improve EBP teaching

Adverse prognostic and predictive significance of low DNA-dependent protein kinase catalytic subunit (DNA-PKcs) expression in early-stage breast cancers

Background: DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a serine threonine kinase belonging to the PIKK family (phosphoinositide 3-kinase-like-family of protein kinase), is a critical component of the non-homologous end joining (NHEJ) pathway required for the repair of DNA double strand breaks. DNA-PKcs may be involved in breast cancer pathogenesis. Methods: We evaluated clinicopathological significance of DNA-PKcs protein expression in 1161 tumours and DNA-PKcs mRNA expression in 1950 tumours. We correlated DNA-PKcs to other markers of aggressive phenotypes, DNA repair, apoptosis and cell cycle regulation. Results: Low DNA-PKcs protein expression was associated with higher tumour grade, higher mitotic index, tumour de-differentiation and tumour type (ps<0.05). Absence of BRCA1, low XRCC1/SMUG1/APE1/Polβ were also more likely in low DNA-PKcs expressing tumours (ps<0.05). Low DNA-PKcs protein expression was significantly associated with worse breast cancer specific survival (BCCS) in univariate and multivariate analysis (ps<0.01). At the mRNA level, low DNA-PKcs was associated with PAM50.Her2 and PAM50.LumA molecular phenotypes (ps<0.01) and poor BCSS. In patients with ER positive tumours who received endocrine therapy, low DNA-PKcs (protein and mRNA) was associated with poor survival. In ER negative patients, low DNA-PKcs mRNA remains significantly associated with adverse outcome. Conclusions: Our study suggests that low DNA-PKcs expression may have prognostic and predictive significance in breast cancers