First-principles modeling of the polycyclic aromatic hydrocarbons reduction

Density functional theory modelling of the reduction of realistic nanographene molecules (C42H18, C48H18 and C60H24) by molecular hydrogen evidences for the presence of limits in the hydrogenation process. These limits caused the contentions between three-fold symmetry of polycyclic aromatic hydrocarbon molecules and two-fold symmetry of adsorbed hydrogen pairs. Increase of the binding energy between nanographenes during reduction is also discussed as possible cause of the experimentally observed limited hydrogenation of studied nanographenes.Comment: 18 pages, 7 figures, accepted to J. Phys. Chem.

Novel role for the innate immune receptor toll-like receptor 4 (TLR4) in the regulation of the wnt signaling pathway and photoreceptor apoptosis

Recent evidence has implicated innate immunity in regulating neuronal survival in the brain during stroke and other neurodegenerations. Photoreceptors are specialized light-detecting neurons in the retina that are essential for vision. In this study, we investigated the role of the innate immunity receptor TLR4 in photoreceptors. TLR4 activation by lipopolysaccharide (LPS) significantly reduced the survival of cultured mouse photoreceptors exposed to oxidative stress. With respect to mechanism, TLR4 suppressed Wnt signaling, decreased phosphorylation and activation of the Wnt receptor LRP6, and blocked the protective effect of the Wnt3a ligand. Paradoxically, TLR4 activation prior to oxidative injury protected photoreceptors, in a phenomenon known as preconditioning. Expression of TNFα and its receptors TNFR1 and TNFR2 decreased during preconditioning, and preconditioning was mimicked by TNFα antagonists, but was independent of Wnt signaling. Therefore, TLR4 is a novel regulator of photoreceptor survival that acts through the Wnt and TNFα pathways. © 2012 Yi et al

Prevalence and risk factors of major depressive disorder in HIV/AIDS as seen in semi-urban Entebbe district, Uganda

BACKGROUND: Not much is known about the risk factors of major depressive disorder (MDD) in HIV/AIDS in the African socio-cultural context. Therefore a study was undertaken to examine the prevalence and risk factors of MDD in HIV/AIDS in semi-urban Uganda. METHODS: A cross-sectional study was undertaken among 618 respondents attending two HIV clinics in Uganda. RESULTS: Prevalence of MDD was 8.1%. Factors associated with MDD at univariate analysis only were female gender, family history of mental illness, negative coping style, alcohol dependency disorder, food insecurity and stress; not associated with MDD were social support, neurocognitive impairment, CD4 counts and BMI. Factors independently associated with MDD were psychosocial impairment, adverse life events, post traumatic stress disorder, generalised anxiety disorder and life-time attempted suicide. CONCLUSION: Psychological and social factors were the main risk factors of MDD among ambulatory HIV positive persons with no evidence for the role of the neurotoxic effects of HIV. Treatment approaches for MDD in this patient group should be modeled on those used among non-HIV groups

The impact of point mutations in the human androgen receptor : classification of mutations on the basis of transcriptional activity

Peer reviewedPublisher PD

ALMA Long Baseline Observations of the Strongly Lensed Submillimeter Galaxy HATLAS J090311.6+003906 at z=3.042

We present initial results of very high resolution Atacama Large Millimeter/submillimeter Array (ALMA) observations of the $z$=3.042 gravitationally lensed galaxy HATLAS J090311.6+003906 (SDP.81). These observations were carried out using a very extended configuration as part of Science Verification for the 2014 ALMA Long Baseline Campaign, with baselines of up to 15 km. We present continuum imaging at 151, 236 and 290 GHz, at unprecedented angular resolutions as fine as 23 milliarcseconds (mas), corresponding to an un-magnified spatial scale of ~180 pc at z=3.042. The ALMA images clearly show two main gravitational arc components of an Einstein ring, with emission tracing a radius of ~1.5". We also present imaging of CO(10-9), CO(8-7), CO(5-4) and H2O line emission. The CO emission, at an angular resolution of ~170 mas, is found to broadly trace the gravitational arc structures but with differing morphologies between the CO transitions and compared to the dust continuum. Our detection of H2O line emission, using only the shortest baselines, provides the most resolved detection to date of thermal H2O emission in an extragalactic source. The ALMA continuum and spectral line fluxes are consistent with previous Plateau de Bure Interferometer and Submillimeter Array observations despite the impressive increase in angular resolution. Finally, we detect weak unresolved continuum emission from a position that is spatially coincident with the center of the lens, with a spectral index that is consistent with emission from the core of the foreground lensing galaxy.Comment: 9 pages, 5 figures and 3 tables, accepted for publication in the Astrophysical Journal Letter

Data for: "Immune activation in the female genital tract: Expression profiles of soluble proteins in women at high risk for HIV infection"

An anonymised dataset containing details of a sub-study of 100 HIV-negative women in 2009. This sub-study was part of a microbicide feasibility study in North-West Tanzania that was carried out between 2008-2010. It contains information on sexual behaviour, vaginal practices, current contraception, STI symptoms, as well as results of a clinical and colposcopic examinatio

Dietary Manipulation and Social Isolation Alter Disease Progression in a Murine Model of Coronary Heart Disease

Background: Mice with a deficiency in the HDL receptor SR-BI and low expression of a modified apolipoprotein E gene (SR-BI KO/ApoeR61h/h) called ‘HypoE’ when fed an atherogenic, ‘Paigen’ diet develop occlusive, atherosclerotic coronary arterial disease (CHD), myocardial infarctions (MI), and heart dysfunction and die prematurely (50% mortality ~40 days after initiation of this diet). Because few murine models share with HypoE mice these cardinal, human-like, features of CHD, HypoE mice represent a novel, small animal, diet-inducible and genetically tractable model for CHD. To better describe the properties of this model, we have explored the effects of varying the composition and timing of administration of atherogenic diets, as well as social isolation vs. group housing, on these animals. Methodology/Principal Findings: HypoE mice were maintained on a standard lab chow diet (control) until two months of age. Subsequently they received one of three atherogenic diets (Paigen, Paigen without cholate, Western) or control diet for varying times and were housed in groups or singly, and we determined the plasma cholesterol levels, extent of cardiomegaly and/or survival. The rate of disease progression could be reduced by lowering the severity of the atherogenic diet and accelerated by social isolation. Disease could be induced by Paigen diets either containing or free of cholate. We also established conditions under which CHD could be initiated by an atherogenic diet and then subsequently, by replacing this diet with standard lab chow, hypercholesterolemia could be reduced and progression to early death prevented. Conclusions/Significance: HypoE mice provide a powerful, surgery-free, diet-‘titratable’ small animal model that can be used to study the onset of recovery from occlusive, atherosclerotic CHD and heart failure due to MI. HypoE mice can be used for the analysis of the effects of environment (diet, social isolation) on a variety of features of cardiovascular disease.National Institutes of Health (U.S.)National Heart, Lung, and Blood Institut

Quantification of HLA class I molecules on renal cell carcinoma using Edman degradation

<p>Abstract</p> <p>Background</p> <p>Unimpaired HLA class I antigen presentation is a prerequisite for the recognition of tumor cells by cytotoxic T lymphocytes and thus essential for the success of anticancer immunotherapeutic concepts. Several approaches have been taken in the immunotherapy of metastatic renal cell carcinoma (RCC), however of limited success. HLA loss or down-regulation have often been reported and might interfere with immunotherapeutic approaches aimed at the recognition of HLA-presented peptides.</p> <p>Methods</p> <p>We employed a quantitative method of molecular analysis for the comparison of HLA amounts on primary tumor, normal kidney and metastases of RCC, using Edman degradation. We analyzed a series of 47 RCC samples including corresponding renal parenchyma, local lymph node metastases and distant metastases.</p> <p>Results</p> <p>Results of quantitative Edman degradation revealed significantly higher HLA yields on primary tumor and metastases compared to normal kidney tissue. This effect was shown not to result from infiltrating immune cells, since tumor-infiltrating lymphocytes had no influence on the overall HLA recovery from tumor tissue. Unexpectedly, we found a higher amount of HLA class I molecules on distant metastases compared to local lymph node metastases.</p> <p>Conclusion</p> <p>Edman degradation allows the direct quantitative comparison of HLA class I protein expression by tumor or normal tissue and metastases of RCC patients. Our results raise hopes for improving the success and effectiveness of future immunotherapeutic concepts for metastatic RCC.</p

Gnotobiotic IL-10−/−; NF-κBEGFP Mice Develop Rapid and Severe Colitis Following Campylobacter jejuni Infection

Limited information is available on the molecular mechanisms associated with Campylobacter jejuni (C. jejuni) induced food-borne diarrheal illnesses. In this study, we investigated the function of TLR/NF-κB signaling in C. jejuni induced pathogenesis using gnotobiotic IL-10−/−; NF-κBEGFP mice. In vitro analysis showed that C. jejuni induced IκB phosphorylation, followed by enhanced NF-κB transcriptional activity and increased IL-6, MIP-2α and NOD2 mRNA accumulation in infected-mouse colonic epithelial cells CMT93. Importantly, these events were blocked by molecular delivery of an IκB inhibitor (Ad5IκBAA). NF-κB signalling was also important for C.jejuni-induced cytokine gene expression in bone marrow-derived dendritic cells. Importantly, C. jejuni associated IL-10−/−; NF-κBEGFP mice developed mild (day 5) and severe (day 14) ulcerating colonic inflammation and bloody diarrhea as assessed by colonoscopy and histological analysis. Macroscopic analysis showed elevated EGFP expression indicating NF-κB activation throughout the colon of C. jejuni associated IL-10−/−; NF-κBEGFP mice, while fluorescence microscopy revealed EGFP positive cells to be exclusively located in lamina propria mononuclear cells. Pharmacological NF-κB inhibition using Bay 11-7085 did not ameliorate C. jejuni induced colonic inflammation. Our findings indicate that C. jejuni induces rapid and severe intestinal inflammation in a susceptible host that correlates with enhanced NF-κB activity from lamina propria immune cells