McrD binds asymmetrically to methyl-coenzyme M reductase improving active-site accessibility during assembly

Methyl-coenzyme M reductase (MCR) catalyzes the formation of methane, and its activity accounts for nearly all biologically produced methane released into the atmosphere. The assembly of MCR is an intricate process involving the installation of a complex set of posttranslational modifications and the unique Ni-containing tetrapyrrole called coenzyme F430. Despite decades of research, details of MCR assembly remain largely unresolved. Here, we report the structural characterization of MCR in two intermediate states of assembly. These intermediate states lack one or both F430 cofactors and form complexes with the previously uncharacterized McrD protein. McrD is found to bind asymmetrically to MCR, displacing large regions of the alpha subunit and increasing active-site accessibility for the installation of F430-shedding light on the assembly of MCR and the role of McrD therein. This work offers crucial information for the expression of MCR in a heterologous host and provides targets for the design of MCR inhibitors

Flood realities, perceptions, and the depth of divisions on climate

Research has led to broad agreement among scientists that anthropogenic climate change is happening now and likely to worsen. In contrast to scientific agreement, US public views remain deeply divided, largely along ideological lines. Science communication has been neutralised in some arenas by intense counter-messaging, but as adverse climate impacts become manifest they might intervene more persuasively in local perceptions. We look for evidence of this occurring with regard to realities and perceptions of flooding in the northeastern US state of New Hampshire. Although precipitation and flood damage have increased, with ample news coverage, most residents do not see a trend. Nor do perceptions about past and future local flooding correlate with regional impacts or vulnerability. Instead, such perceptions follow ideological patterns resembling those of global climate change. That information about the physical world can be substantially filtered by ideology is a common finding from sociological environment/society research

A life cycle stakeholder management framework for enhanced collaboration between stakeholders with competing interests

This is a postprint version of the Book Chapter. Information regarding the official publication is available from the link below - Copyright @ 2011 SpringerImplementation of a Life Cycle Sustainability Management (LCSM) strategy can involve significant challenges because of competing or conflicting objectives between stakeholders. These differences may, if not identified and managed, hinder successful adoption of sustainability initiatives. This article proposes a conceptual framework for stakeholder management in a LCSM context. The framework identifies the key sustainability stakeholder groups and suggests strategic ambiguity as a management tool to harness dysfunctional conflict into constructive collaboration. The framework is of practical value as it can be used as a guideline by managers who wish to improve collaboration with stakeholders along the supply chain. The article also fills a gap in the academic literature where there is only limited research on sustainability stakeholder management through strategic ambiguity

Impact of growth matrix on pharmacodynamics of antimicrobial drugs for pig pneumonia pathogens

Abstract Background The most widely used measure of potency of antimicrobial drugs is Minimum Inhibitory Concentration (MIC). MIC is usually determined under standardised conditions in broths formulated to optimise bacterial growth on a species-by-species basis. This ensures comparability of data between laboratories. However, differences in values of MIC may arise between broths of differing chemical composition and for some drug classes major differences occur between broths and biological fluids such as serum and inflammatory exudate. Such differences must be taken into account, when breakpoint PK/PD indices are derived and used to predict dosages for clinical use. There is therefore interest in comparing MIC values in several broths and, in particular, in comparing broth values with those generated in serum. For the pig pneumonia pathogens, Actinobacillus pleuropneumoniae and Pasteurella multocida, MICs were determined for three drugs, florfenicol, oxytetracycline and marbofloxacin, in five broths [Mueller Hinton Broth (MHB), cation-adjusted Mueller Hinton Broth (CAMHB), Columbia Broth supplemented with NAD (CB), Brain Heart Infusion Broth (BHI) and Tryptic Soy Broth (TSB)] and in pig serum. Results For each drug, similar MIC values were obtained in all broths, with one exception, marbofloxacin having similar MICs for three broths and 4–5-fold higher MICs for two broths. In contrast, for both organisms, quantitative differences between broth and pig serum MICs were obtained after correction of MICs for drug binding to serum protein (fu serum MIC). Potency was greater (fu serum MIC lower) in serum than in broths for marbofloxacin and florfenicol for both organisms. For oxytetracycline fu serum:broth MIC ratios were 6.30:1 (P. multocida) and 0.35:1 (A. pleuropneumoniae), so that potency of this drug was reduced for the former species and increased for the latter species. The chemical composition of pig serum and broths was compared; major matrix differences in 14 constituents did not account for MIC differences. Bacterial growth rates were compared in broths and pig serum in the absence of drugs; it was concluded that broth/serum MIC differences might be due to differing growth rates in some but not all instances. Conclusions For all organisms and all drugs investigated in this study, it is suggested that broth MICs should be adjusted by an appropriate scaling factor when used to determine pharmacokinetic/pharmacodynamic breakpoints for dosage prediction

Pathological and ecological host consequences of infection by an introduced fish parasite

The infection consequences of the introduced cestode fish parasite Bothriocephalus acheilognathi were studied in a cohort of wild, young-of-the-year common carp Cyprinus carpio that lacked co-evolution with the parasite. Within the cohort, parasite prevalence was 42% and parasite burdens were up to 12% body weight. Pathological changes within the intestinal tract of parasitized carp included distension of the gut wall, epithelial compression and degeneration, pressure necrosis and varied inflammatory changes. These were most pronounced in regions containing the largest proportion of mature proglottids. Although the body lengths of parasitized and non-parasitized fish were not significantly different, parasitized fish were of lower body condition and reduced weight compared to non-parasitized conspecifics. Stable isotope analysis (δ15N and δ13C) revealed trophic impacts associated with infection, particularly for δ15N where values for parasitized fish were significantly reduced as their parasite burden increased. In a controlled aquarium environment where the fish were fed ad libitum on an identical food source, there was no significant difference in values of δ15N and δ13C between parasitized and non-parasitized fish. The growth consequences remained, however, with parasitized fish growing significantly slower than non-parasitized fish, with their feeding rate (items s−1) also significantly lower. Thus, infection by an introduced parasite had multiple pathological, ecological and trophic impacts on a host with no experience of the parasite

Perioperative interventions to improve early mobilisation and physical function after hip fracture: a systematic review and meta-analysis.

BACKGROUND: Perioperative interventions could enhance early mobilisation and physical function after hip fracture surgery. OBJECTIVE: Determine the effectiveness of perioperative interventions on early mobilisation and physical function after hip fracture. METHODS: Ovid MEDLINE, CINAHL, Embase, Scopus and Web of Science were searched from January 2000 to March 2022. English language experimental and quasi-experimental studies were included if patients were hospitalised for a fractured proximal femur with a mean age 65 years or older and reported measures of early mobilisation and physical function during the acute hospital admission. Data were pooled using a random effect meta-analysis. RESULTS: Twenty-eight studies were included from 1,327 citations. Studies were conducted in 26 countries on 8,192 participants with a mean age of 80 years. Pathways and models of care may provide a small increase in early mobilisation (standardised mean difference [SMD]: 0.20, 95% confidence interval [CI]: 0.01-0.39, I2 = 73%) and physical function (SMD: 0.07, 95% CI 0.00 to 0.15, I2 = 0%) and transcutaneous electrical nerve stimulation analgesia may provide a moderate improvement in function (SMD: 0.65, 95% CI: 0.24-1.05, I2 = 96%). The benefit of pre-operative mobilisation, multidisciplinary rehabilitation, recumbent cycling and clinical supervision on mobilisation and function remains uncertain. Evidence of no effect on mobilisation or function was identified for pre-emptive analgesia, intraoperative periarticular injections, continuous postoperative epidural infusion analgesia, occupational therapy training or nutritional supplements. CONCLUSIONS: Perioperative interventions may improve early mobilisation and physical function after hip fracture surgery. Future studies are needed to model the causal mechanisms of perioperative interventions on mobilisation and function after hip fracture

Pollutant Emissions from Improved Cookstoves of the type used in Sub-Saharan Africa

Emissions from traditional cookstoves are a major health concern in developing world households. Improved cookstoves can reduce fuel use and pollutant emissions and here we compare three types of improved cookstoves widely used in Sub-Saharan Africa. These are a raised-bed charcoal stove, a rocket-type stove using wood and straw, and a gasifier stove. Laboratory measurements were made of the main gaseous pollutants, particle size distribution and composition. The genotoxicity of the particles was assessed using a comet assay. The rocket-type stove using dry wood had the highest emission factors for particulate matter and NOX. Emissions of CO and CH4 were a factor of 6-7 higher from the charcoal stove compared with the other stoves tested in this work, and also higher for burning high moisture wood. Fuel properties were critical for emitted particle size, and for the emissions of NOX, black carbon and organic matter

Neural Network Mechanisms Underlying Stimulus Driven Variability Reduction

It is well established that the variability of the neural activity across trials, as measured by the Fano factor, is elevated. This fact poses limits on information encoding by the neural activity. However, a series of recent neurophysiological experiments have changed this traditional view. Single cell recordings across a variety of species, brain areas, brain states and stimulus conditions demonstrate a remarkable reduction of the neural variability when an external stimulation is applied and when attention is allocated towards a stimulus within a neuron's receptive field, suggesting an enhancement of information encoding. Using an heterogeneously connected neural network model whose dynamics exhibits multiple attractors, we demonstrate here how this variability reduction can arise from a network effect. In the spontaneous state, we show that the high degree of neural variability is mainly due to fluctuation-driven excursions from attractor to attractor. This occurs when, in the parameter space, the network working point is around the bifurcation allowing multistable attractors. The application of an external excitatory drive by stimulation or attention stabilizes one specific attractor, eliminating in this way the transitions between the different attractors and resulting in a net decrease in neural variability over trials. Importantly, non-responsive neurons also exhibit a reduction of variability. Finally, this reduced variability is found to arise from an increased regularity of the neural spike trains. In conclusion, these results suggest that the variability reduction under stimulation and attention is a property of neural circuits