The effects of catchment and riparian forest quality on stream environmental conditions across a tropical rainforest and oil palm landscape in Malaysian Borneo

Freshwaters provide valuable habitat and important ecosystem services, but are threatened worldwide by habitat loss and degradation. In Southeast Asia, rainforest streams are particularly threatened by logging and conversion to oil palm, but we lack information on the impacts of this on freshwater environmental conditions, and the relative importance of catchment versus riparian-scale disturbance. We studied sixteen streams in Sabah, Borneo, including old growth forest, logged forest, and oil palm sites. We assessed forest quality in riparian zones and across the whole catchment, and compared it with stream environmental conditions including water quality, structural complexity and organic inputs. We found that streams with the highest riparian forest quality were nearly 4 °C cooler, over 20 cm deeper, had over 40% less sand, greater canopy cover, more stored leaf litter and wider channels than oil palm streams with the lowest riparian forest quality. Other variables were significantly related to catchment-scale forest quality, with streams in the highest quality forest catchments having 40% more bedrock and 20 times more dead wood, along with higher phosphorus, and lower nitrate-N levels compared to streams with the lowest catchment-scale forest quality. Although riparian buffer strips went some way to protecting waterways, they did not maintain fully forest-like stream conditions. In addition, logged forest streams still showed signs of disturbance 10-15 years after selective logging. Our results suggest that maintenance and restoration of buffer strips can help to protect healthy freshwater ecosystems, but logging practices and catchment-scale forest management also need to be considered.During this work SHL was funded by a Natural Environment Research Council (NERC) studentship (number 1122589), Proforest, the Varley Gradwell Travelling Fellowship, Tim Whitmore Fund, Panton Trust and the Cambridge University Commonwealth Fund. MP and RME were supported by European Research Council Project number 281986. HB was funded by the S.T. Lee Fund

Human Female Genital Tract Infection by the Obligate Intracellular Bacterium Chlamydia trachomatis Elicits Robust Type 2 Immunity

While Chlamydia trachomatis infections are frequently asymptomatic, mechanisms that regulate host response to this intracellular Gram-negative bacterium remain undefined. This investigation thus used peripheral blood mononuclear cells and endometrial tissue from women with or without Chlamydia genital tract infection to better define this response. Initial genome-wide microarray analysis revealed highly elevated expression of matrix metalloproteinase 10 and other molecules characteristic of Type 2 immunity (e.g., fibrosis and wound repair) in Chlamydia-infected tissue. This result was corroborated in flow cytometry and immunohistochemistry studies that showed extant upper genital tract Chlamydia infection was associated with increased co-expression of CD200 receptor and CD206 (markers of alternative macrophage activation) by endometrial macrophages as well as increased expression of GATA-3 (the transcription factor regulating TH2 differentiation) by endometrial CD4+ T cells. Also among women with genital tract Chlamydia infection, peripheral CD3+ CD4+ and CD3+ CD4- cells that proliferated in response to ex vivo stimulation with inactivated chlamydial antigen secreted significantly more interleukin (IL)-4 than tumor necrosis factor, interferon-γ, or IL-17; findings that repeated in T cells isolated from these same women 1 and 4 months after infection had been eradicated. Our results thus newly reveal that genital infection by an obligate intracellular bacterium induces polarization towards Type 2 immunity, including Chlamydia-specific TH2 development. Based on these findings, we now speculate that Type 2 immunity was selected by evolution as the host response to C. trachomatis in the human female genital tract to control infection and minimize immunopathological damage to vital reproductive structures. © 2013 Vicetti Miguel et al

Holographic fermions in charged Gauss-Bonnet black hole

We study the properties of the Green's functions of the fermions in charged Gauss-Bonnet black hole. What we want to do is to investigate how the presence of Gauss-Bonnet coupling constant $\alpha$ affects the dispersion relation, which is a characteristic of Fermi or non-Fermi liquid, as well as what properties such a system has, for instance, the Particle-hole (a)symmetry. One important result of this research is that we find for $q=1$, the behavior of this system is different from that of the Landau Fermi liquid and so the system can be candidates for holographic dual of generalized non-Fermi liquids. More importantly, the behavior of this system increasingly similar to that of the Landau Fermi liquid when $\alpha$ is approaching its lower bound. Also we find that this system possesses the Particle-hole asymmetry when $q\neq 0$, another important characteristic of this system. In addition, we also investigate briefly the cases of the charge dependence.Comment: 22 pages, 6 figures; version published in JHE

Determinants of the voltage dependence of G protein modulation within calcium channel β subunits

CaVβ subunits of voltage-gated calcium channels contain two conserved domains, a src-homology-3 (SH3) domain and a guanylate kinase-like (GK) domain with an intervening HOOK domain. We have shown in a previous study that, although Gβγ-mediated inhibitory modulation of CaV2.2 channels did not require the interaction of a CaVβ subunit with the CaVα1 subunit, when such interaction was prevented by a mutation in the α1 subunit, G protein modulation could not be removed by a large depolarization and showed voltage-independent properties (Leroy et al., J Neurosci 25:6984–6996, 2005). In this study, we have investigated the ability of mutant and truncated CaVβ subunits to support voltage-dependent G protein modulation in order to determine the minimal domain of the CaVβ subunit that is required for this process. We have coexpressed the CaVβ subunit constructs with CaV2.2 and α2δ-2, studied modulation by the activation of the dopamine D2 receptor, and also examined basal tonic modulation. Our main finding is that the CaVβ subunit GK domains, from either β1b or β2, are sufficient to restore voltage dependence to G protein modulation. We also found that the removal of the variable HOOK region from β2a promotes tonic voltage-dependent G protein modulation. We propose that the absence of the HOOK region enhances Gβγ binding affinity, leading to greater tonic modulation by basal levels of Gβγ. This tonic modulation requires the presence of an SH3 domain, as tonic modulation is not supported by any of the CaVβ subunit GK domains alone

Metabolic effects of diets differing in glycaemic index depend on age and endogenous GIP

Aims/hypothesis High- vs low-glycaemic index (GI) diets unfavourably affect body fat mass and metabolic markers in rodents. Different effects of these diets could be age-dependent, as well as mediated, in part, by carbohydrate-induced stimulation of glucose-dependent insulinotrophic polypeptide (GIP) signalling. Methods Young-adult (16 weeks) and aged (44 weeks) male wild-type (C57BL/6J) and GIP-receptor knockout (Gipr −/− ) mice were exposed to otherwise identical high-carbohydrate diets differing only in GI (20–26 weeks of intervention, n = 8–10 per group). Diet-induced changes in body fat distribution, liver fat, locomotor activity, markers of insulin sensitivity and substrate oxidation were investigated, as well as changes in the gene expression of anorexigenic and orexigenic hypothalamic factors related to food intake. Results Body weight significantly increased in young-adult high- vs low-GI fed mice (two-way ANOVA, p < 0.001), regardless of the Gipr genotype. The high-GI diet in young-adult mice also led to significantly increased fat mass and changes in metabolic markers that indicate reduced insulin sensitivity. Even though body fat mass also slightly increased in high- vs low-GI fed aged wild-type mice (p < 0.05), there were no significant changes in body weight and estimated insulin sensitivity in these animals. However, aged Gipr −/− vs wild-type mice on high-GI diet showed significantly lower cumulative net energy intake, increased locomotor activity and improved markers of insulin sensitivity. Conclusions/interpretation The metabolic benefits of a low-GI diet appear to be more pronounced in younger animals, regardless of the Gipr genotype. Inactivation of GIP signalling in aged animals on a high-GI diet, however, could be beneficial

The antiandrogen enzalutamide downregulates TMPRSS2 and reduces cellular entry of SARS-CoV-2 in human lung cells

SARS-CoV-2 attacks various organs, most destructively the lung, and cellular entry requires two host cell surface proteins: ACE2 and TMPRSS2. Downregulation of one or both of these is thus a potential therapeutic approach for COVID-19. TMPRSS2 is a known target of the androgen receptor, a ligand-activated transcription factor; androgen receptor activation increases TMPRSS2 levels in various tissues, most notably prostate. We show here that treatment with the antiandrogen enzalutamide—a well-tolerated drug widely used in advanced prostate cancer—reduces TMPRSS2 levels in human lung cells and in mouse lung. Importantly, antiandrogens significantly reduced SARS-CoV-2 entry and infection in lung cells. In support of this experimental data, analysis of existing datasets shows striking co-expression of AR and TMPRSS2, including in specific lung cell types targeted by SARS-CoV-2. Together, the data presented provides strong evidence to support clinical trials to assess the efficacy of antiandrogens as a treatment option for COVID-19

Comparison of contact patterns relevant for transmission of respiratory pathogens in Thailand and the Netherlands using respondent-driven sampling

Understanding infection dynamics of respiratory diseases requires the identification and quantification of behavioural, social and environmental factors that permit the transmission of these infections between humans. Little empirical information is available about contact patterns within real-world social networks, let alone on differences in these contact networks between populations that differ considerably on a socio-cultural level. Here we compared contact network data that were collected in the Netherlands and Thailand using a similar online respondent-driven method. By asking participants to recruit contact persons we studied network links relevant for the transmission of respiratory infections. We studied correlations between recruiter and recruited contacts to investigate mixing patterns in the observed social network components. In both countries, mixing patterns were assortative by demographic variables and random by total numbers of contacts. However, in Thailand participants reported overall more contacts which resulted in higher effective contact rates. Our findings provide new insights on numbers of contacts and mixing patterns in two different populations. These data could be used to improve parameterisation of mathematical models used to design control strategies. Although the spread of infections through populations depends on more factors, found similarities suggest that spread may be similar in the Netherlands and Thailand

The therapeutic potential of attentional bias modification training for insomnia: study protocol for a randomised controlled trial.

The efficacy of attentional bias modification (ABM) as a treatment for anxiety and depression has been extensively studied with promising results. Despite some evidence of sleep-related attentional biases in insomnia, only a small number of studies, yielding mixed results, have examined the application of ABM in insomnia. This study specifically aims to determine whether ABM can reduce (i) the presence of an attentional bias for sleep-related threatening words; (ii) insomnia symptom severity; (iii) sleep onset latency; and (iv) pre-sleep cognitive arousal amongst individuals with insomnia compared to a non-treatment control group of individuals with insomnia. We propose a randomised controlled trial of 90 individuals from the general population who meet the criteria for Insomnia Disorder. Following an initial examination for the presence of a sleep-related attentional bias using the dot-probe paradigm, participants will be randomised to an online attentional bias modification training condition, or to a standard attentional bias task (non-treatment) control condition. Both conditions will be delivered online by a web platform. All participants allocated to the non-treatment control group will be offered ABM training once the study is complete. The primary outcome will be the attentional bias indices of vigilance and disengagement and self-reported insomnia symptoms, sleep onset latency and pre-sleep cognitive arousal. Attentional bias and insomnia symptoms will be assessed at baseline (day 1) and post-treatment (2 days after the final training session: day 9). Insomnia symptoms will be again assessed at follow-up (day 16). Secondary outcomes include examining whether sleep associated monitoring and worry are related to a sleep-related attentional bias in insomnia, and whether such reports reduce following ABM. All main analyses will be carried out on completion of follow-up assessments. The trial is supported by the Department of Psychology, Sociology and Politics at Sheffield Hallam University. This study will extend the research base examining the efficacy of attentional bias modification for insomnia. ISRCTN ( ISRCTN11643569 , registered on 5 June 2018)

Velocity vector imaging to quantify left atrial function

The aim of our study was to assess the feasibility of a new image analysis, velocity vector imaging (VVI), in the assessment of left atrial volumes (LAV) and left atrial ejection fraction (LAEF). We retrospectively analysed 100 transthoracic echocardiographic findings in 71 men, and 29 women (mean age 57 ± 19.8 years). Two subgroups of patients were defined: (1) with left ventricular (LV) EF > 50%, and (2) LV EF < 50%. For the VVI method of indexed LAV assessment we used the apical four-chamber view. From the displacement of LA endocardial pixels time–volume curves were extracted which provided automatically data regarding indexed maximum LAV (LAVImax), indexed minimum LAV (LAVImin), and LAEF. LAVs and LAEF by 2-dimensional echocardiograhy (2DE) were measured by Simpson’s biplane disc summation method. Comparing LAVImax, LAVImin, and LAEF by VVI versus 2DE in the total study population, we found significant correlations: r = 0.94, P < 0.0001, r = 0.94, P < 0.0001, r = 0.79, P < 0.0001, respectively. In addition, LAVImax ≥ 40 ml/m2 was 94% sensitive and 72% specific, LAVImin ≥ 27 ml/m2 was 90% sensitive and 86% specific, and LAEF < 30% was 80% sensitive and 96% specific for the detection of LV systolic dysfunction. There were highly significant inverse associations of LAVImax and LAVImin to LVEF. LAEF was also significantly related to LV systolic function. When comparing the time required for VVI and 2DE measurements, VVI led to 62% reduction in the measurement time. In conclusion, VVI is a feasible method for the assessment of LAVs and LAEF. It provides close agreement with that measured by conventional 2DE Simpson’s biplane method with significant time saved

Structure-Function Study of Mammalian Munc18-1 and C. elegans UNC-18 Implicates Domain 3b in the Regulation of Exocytosis

Munc18-1 is an essential synaptic protein functioning during multiple stages of the exocytotic process including vesicle recruitment, docking and fusion. These functions require a number of distinct syntaxin-dependent interactions; however, Munc18-1 also regulates vesicle fusion via syntaxin-independent interactions with other exocytotic proteins. Although the structural regions of the Munc18-1 protein involved in closed-conformation syntaxin binding have been thoroughly examined, regions of the protein involved in other interactions are poorly characterised. To investigate this we performed a random transposon mutagenesis, identifying domain 3b of Munc18-1 as a functionally important region of the protein. Transposon insertion in an exposed loop within this domain specifically disrupted Mint1 binding despite leaving affinity for closed conformation syntaxin and binding to the SNARE complex unaffected. The insertion mutation significantly reduced total amounts of exocytosis as measured by carbon fiber amperometry in chromaffin cells. Introduction of the equivalent mutation in UNC-18 in Caenorhabditis elegans also reduced neurotransmitter release as assessed by aldicarb sensitivity. Correlation between the two experimental methods for recording changes in the number of exocytotic events was verified using a previously identified gain of function Munc18-1 mutation E466K (increased exocytosis in chromaffin cells and aldicarb hypersensitivity of C. elegans). These data implicate a novel role for an exposed loop in domain 3b of Munc18-1 in transducing regulation of vesicle fusion independent of closed-conformation syntaxin binding