Attenuated total reflectance infrared spectroelectrochemistry at a carbon particle electrode; unmediated redox control of a [NiFe]-hydrogenase solution

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.We report a versatile infrared spectroscopic method for studying redox chemistry of metalloproteins, and demonstrate for the first time electrochemically-induced changes to the active site of the regulatory [NiFe]-hydrogenase from Ralstonia eutropha. A carbon particle network working electrode allows control over a wide potential window without the need for solution mediators.EC/FP7/258600/EU/Understanding and Exploiting Biological Catalysts for Energy Cycling: Development of Infrared Spectroelectrochemistry for Studying Intermediates in Metalloenzyme Catalysis/ENERGYBIOCATALYSISDFG, EXC 314, Unifying Concepts in Catalysi

The extent of violence inflicted on adolescent Aboriginal girls in the Northern Territory

Background: Australian Aboriginal and Torres Strait Islander women are at very high risk of violence but there is little evidence about the age at which their higher exposure to violence commences. The aim of this study was to investigate violence inflicted on Aboriginal girls during childhood and adolescence, relative to Aboriginal boys and non-Aboriginal girls. Methods: This was a retrospective cohort study using de-identified administrative data for NT residents aged 0-17 years. This study used linked hospital and child protection data to investigate hospitalization for injury caused by assault and substantiated child maltreatment involving violence (physical and sexual abuse). Results: The incidence of assault hospitalization and substantiated physical/sexual abuse was much higher for Aboriginal than non-Aboriginal adolescents but similar for girls and boys to about age ten, then increased much more for Aboriginal girls than boys. In the 14-17 age-group, assault hospitalization incidence was 125% higher for Aboriginal girls than boys but 56% lower for non-Aboriginal girls than boys. 4.6% of Aboriginal girls were hospitalized (30.9% more than once) for assault between twelfth and eighteenth birthdays, compared to 3.4% of Aboriginal boys and 0.3% of non-Aboriginal girls. The incidence of assault hospitalization during adolescence was over three times higher for Aboriginal children who had substantiated child maltreatment during childhood. Conclusion: The very high levels of violence suffered by Aboriginal women commence in the pre-teen years. Non-Aboriginal girls are ‘protected’ from the rising levels of violence that boys experience as they progress through adolescence, but Aboriginal girls are not afforded such protection

Comparison of carbon materials as electrodes for enzyme electrocatalysis:hydrogenase as a case study

We present a study of electrocatalysis by an enzyme adsorbed on a range of carbon materials, with different size, surface area, morphology and graphitic structure, which are either commercially available or prepared via simple, established protocols. We choose as our model enzyme the hydrogenase I from E. coli (Hyd-1), which is an active catalyst for H2 oxidation, is relatively robust and has been demonstrated in H2 fuel cells and H2-driven chemical synthesis. The carbon materials were characterised according to their surface area, surface morphology and graphitic character, and we use the electrocatalytic H2 oxidation current for Hyd-1 adsorbed on these materials to evaluate their effectiveness as enzyme electrodes. Here, we show that a variety of carbon materials are suitable for adsorbing hydrogenases in an electroactive configuration. This unified study provides insight into selection and design of carbon materials for study of redox enzymes and different applications of enzyme electrocatalysis

Electrochemical control of [FeFe]-hydrogenase single crystals reveals complex redox populations at the catalytic site

Elucidating the distribution of intermediates at the active site of redox metalloenzymes is vital to understanding their highly efficient catalysis. Here we demonstrate that it is possible to generate, and detect, the key catalytic redox states of an [FeFe]-hydrogenase in a protein crystal. Individual crystals of the prototypical [FeFe]-hydrogenase I from Clostridium pasteurianum (CpI) are maintained under electrochemical control, allowing for precise tuning of the redox potential, while the crystal is simultanaously probed via Fourier Transform Infrared (FTIR) microspectroscopy. The high signal/noise spectra reveal potential-dependent variation in the distribution of redox states at the active site (H-cluster) according to state-specific vibrational bands from the endogeneous CO and CN- ligands. CpI crystals are shown to populate the same H-cluster states as those detected in solution, including the oxidised species Hox, the reduced species Hred/HredH+, the super-reduced HsredH+ and the hydride species Hhyd. The high sensitivity and precise redox control offered by this approach also facilitates the detection and characterisation of low abundance species that only accumulate within a narrow window of conditions, revealing new redox intermediates

Papua New Guinean genomes reveal the complex settlement of north Sahul

The settlement of Sahul, the lost continent of Oceania, remains one of the most ancient and debated human migrations. Modern New Guineans inherited a unique genetic diversity tracing back 50,000 years, and yet there is currently no model reconstructing their past population dynamics. We generated 58 new whole-genome sequences from Papua New Guinea, filling geographical gaps in previous sampling, specifically to address alternative scenarios of the initial migration to Sahul and the settlement of New Guinea. Here, we present the first genomic models for the settlement of northeast Sahul considering one or two migrations from Wallacea. Both models fit our data set, reinforcing the idea that ancestral groups to New Guinean and Indigenous Australians split early, potentially during their migration in Wallacea where the northern route could have been favored. The earliest period of human presence in Sahul was an era of interactions and gene flow between related but already differentiated groups, from whom all modern New Guineans, Bismarck islanders, and Indigenous Australians descend. The settlement of New Guinea was probably initiated from its southeast region, where the oldest archaeological sites have been found. This was followed by two migrations into the south and north lowlands that ultimately reached the west and east highlands. We also identify ancient gene flows between populations in New Guinea, Australia, East Indonesia, and the Bismarck Archipelago, emphasizing the fact that the anthropological landscape during the early period of Sahul settlement was highly dynamic rather than the traditional view of extensive isolation

Profiling the landscape of transcription, chromatin accessibility and chromosome conformation of cattle, pig, chicken and goat genomes [FAANG pilot project]

Functional annotation of livestock genomes is a critical and obvious next step to derive maximum benefit for agriculture, animal science, animal welfare and human health. The aim of the Fr-AgENCODE project is to generate multi-species functional genome annotations by applying high-throughput molecular assays on three target tissues/cells relevant to the study of immune and metabolic traits. An extensive collection of stored samples from other tissues is available for further use (FAANG Biosamples ‘FR-AGENCODE’). From each of two males and two females per species (pig, cattle, goat, chicken), strand-oriented RNA-seq and chromatin accessibility ATAC-seq assays were performed on liver tissue and on two T-cell types (CD3+CD4+&CD3+CD8+) sorted from blood (mammals) or spleen (chicken). Chromosome Conformation Capture (in situ Hi-C) was also carried out on liver. Sequencing reads from the 3 assays were processed using standard processing pipelines. While most (50–70%) RNA-seq reads mapped to annotated exons, thousands of novel transcripts and genes were found, including extensions of annotated protein-coding genes and new lncRNAs (see abstract #69857). Consistency of ATAC-seq results was confirmed by the significant proportion of called peaks in promoter regions (36–66%) and by the specific accumulation pattern of peaks around gene starts (TSS) v. gene ends (TTS). Principal Component Analyses for RNA-seq (based on quantified gene expression) and ATAC-seq (based on quantified chromatin accessibility) highlighted clusters characterised by cell type and sex in all species. From Hi-C data, we generated 40kb-resolution interaction maps, profiled a genome-wide Directionality Index and identified from 4,100 (chicken) to 12,100 (pig) topologically-associating do- mains (TADs). Correlations were reported between RNA-seq and ATAC-seq results (see abstract #71581). In summary, we present here an overview of the first multi-species and -tissue annotations of chromatin accessibility and genome architecture related to gene expression for farm animals

Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations.

OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens