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Signaling by serine/threonine phosphorylation controls diverse processes in bacteria, and identification of the stimuli that activate protein kinases is an outstanding question in the field. Recently, we showed that nutrients stimulate phosphorylation of the protein kinase G substrate GarA in Mycobacterium smegmatis and Mycobacterium tuberculosis and that the action of GarA in regulating central metabolism depends upon whether it is phosphorylated. Here we present an investigation into the mechanism by which nutrients activate PknG. Two unknown genes were identified as co-conserved and co-expressed with PknG: their products were a putative lipoprotein, GlnH, and putative transmembrane protein, GlnX. Using a genetic approach, we showed that the membrane protein GlnX is functionally linked to PknG. Furthermore, we determined that the ligand specificity of GlnH matches the amino acids that stimulate GarA phosphorylation. We determined the structure of GlnH in complex with different amino acid ligands (aspartate, glutamate, and asparagine), revealing the structural basis of ligand specificity. We propose that the amino acid concentration in the periplasm is sensed by GlnH and that protein-protein interaction allows transmission of this information across the membrane via GlnX to activate PknG. This sensory system would allow regulation of nutrient utilization in response to changes in nutrient availability. The sensor, signaling, and effector proteins are conserved throughout the Actinobacteria , including the important human pathogen Mycobacterium tuberculosis , industrial amino acid producer Corynebacterium glutamicum , and antibiotic-producing Streptomyces species. IMPORTANCE Tuberculosis (TB) kills 5,000 people every day, and the prevalence of multidrug-resistant TB is increasing in every country. The processes by which the pathogen Mycobacterium tuberculosis senses and responds to changes in its environment are attractive targets for drug development. Bacterial metabolism differs dramatically between growing and dormant cells, and these changes are known to be important in pathogenesis of TB. Here, we used genetic and biochemical approaches to identify proteins that allow M. tuberculosis to detect amino acids in its surroundings so that it can regulate its metabolism. We have also shown how individual amino acids are recognized. The findings have broader significance for other actinobacterial pathogens, such as nontuberculous mycobacteria, as well as Actinobacteria used to produce billions of dollars of amino acids and antibiotics every year. Tuberculosis (TB) kills 5,000 people every day, and the prevalence of multidrug-resistant TB is increasing in every country. The processes by which the pathogen Mycobacterium tuberculosis senses and responds to changes in its environment are attractive targets for drug development. Bacterial metabolism differs dramatically between growing and dormant cells, and these changes are known to be important in pathogenesis of TB. Here, we used genetic and biochemical approaches to identify proteins that allow M. tuberculosis to detect amino acids in its surroundings so that it can regulate its metabolism. We have also shown how individual amino acids are recognized. The findings have broader significance for other actinobacterial pathogens, such as nontuberculous mycobacteria, as well as Actinobacteria used to produce billions of dollars of amino acids and antibiotics every year.

The meaning of language is represented in regions of the cerebral cortex collectively known as the ‘semantic system’. However, little of the semantic system has been mapped comprehensively, and the semantic selectivity of most regions is unknown. Here we systematically map semantic selectivity across the cortex using voxel-wise modelling of functional MRI (fMRI) data collected while subjects listened to hours of narrative stories. We show that the semantic system is organized into intricate patterns that seem to be consistent across individuals. We then use a novel generative model to create a detailed semantic atlas. Our results suggest that most areas within the semantic system represent information about specific semantic domains, or groups of related concepts, and our atlas shows which domains are represented in each area. This study demonstrates that data-driven methods—commonplace in studies of human neuroanatomy and functional connectivity—provide a powerful and efficient means for mapping functional representations in the brain. It has been proposed that language meaning is represented throughout the cerebral cortex in a distributed ‘semantic system’, but little is known about the details of this network; here, voxel-wise modelling of functional MRI data collected while subjects listened to natural stories is used to create a detailed atlas that maps representations of word meaning in the human brain. A semantic atlas of the cerebral cortex It is thought that the meanings of words and language are represented in a semantic system distributed across much of the cerebral cortex. However, little is known about the detailed functional and anatomical organization of this network. Alex Huth, Jack Gallant and colleagues set out to map the functional representations of semantic meaning in the human brain using voxel-based modelling of functional magnetic resonance imaging (fMRI) recordings made while subjects listened to natural narrative speech. They find that each semantic concept is represented in multiple semantic areas, and each semantic area represents multiple semantic concepts. The recovered semantic maps are largely consistent across subjects, however, providing the basis for a semantic atlas that can be used for future studies of language processing. An interactive version of the atlas can be explored at http://gallantlab.org/huth2016 .

An analysis of stomatal behavior reveals the importance of modeling slow stomatal responses and the impacts on photosynthesis under dynamic light environments.

To synthesise lessons learnt and determinants of success from human papillomavirus (HPV) vaccine demonstration projects and national programmes in low- and middle-income countries (LAMICs). Interviews were conducted with 56 key informants. A systematic literature review identified 2936 abstracts from five databases; after screening 61 full texts were included. Unpublished literature, including evaluation reports, was solicited from country representatives; 188 documents were received. A data extraction tool and interview topic guide outlining key areas of inquiry were informed by World Health Organization guidelines for new vaccine introduction. Results were synthesised thematically. Data were analysed from 12 national programmes and 66 demonstration projects in 46 countries. Among demonstration projects, 30 were supported by the GARDASIL® Access Program, 20 by Gavi, four by PATH and 12 by other means. School-based vaccine delivery supplemented with health facility-based delivery for out-of-school girls attained high coverage. There were limited data on facility-only strategies and little evaluation of strategies to reach out-of-school girls. Early engagement of teachers as partners in social mobilisation, consent, vaccination day coordination, follow-up of non-completers and adverse events was considered invaluable. Micro-planning using school/ facility registers most effectively enumerated target populations; other estimates proved inaccurate, leading to vaccine under- or over-estimation. Refresher training on adverse events and safe injection procedures was usually necessary. Considerable experience in HPV vaccine delivery in LAMICs is available. Lessons are generally consistent across countries and dissemination of these could improve HPV vaccine introduction.

Objective To identify the source (press releases or news) of distortions, exaggerations, or changes to the main conclusions drawn from research that could potentially influence a reader’s health related behaviour. Design Retrospective quantitative content analysis. Setting Journal articles, press releases, and related news, with accompanying simulations. Sample Press releases (n=462) on biomedical and health related science issued by 20 leading UK universities in 2011, alongside their associated peer reviewed research papers and news stories (n=668). Main outcome measures Advice to readers to change behaviour, causal statements drawn from correlational research, and inference to humans from animal research that went beyond those in the associated peer reviewed papers. Results 40% (95% confidence interval 33% to 46%) of the press releases contained exaggerated advice, 33% (26% to 40%) contained exaggerated causal claims, and 36% (28% to 46%) contained exaggerated inference to humans from animal research. When press releases contained such exaggeration, 58% (95% confidence interval 48% to 68%), 81% (70% to 93%), and 86% (77% to 95%) of news stories, respectively, contained similar exaggeration, compared with exaggeration rates of 17% (10% to 24%), 18% (9% to 27%), and 10% (0% to 19%) in news when the press releases were not exaggerated. Odds ratios for each category of analysis were 6.5 (95% confidence interval 3.5 to 12), 20 (7.6 to 51), and 56 (15 to 211). At the same time, there was little evidence that exaggeration in press releases increased the uptake of news. Conclusions Exaggeration in news is strongly associated with exaggeration in press releases. Improving the accuracy of academic press releases could represent a key opportunity for reducing misleading health related news.

Soil organisms have an important role in aboveground community dynamics and ecosystem functioning in terrestrial ecosystems. However, most studies have considered soil biota as a black box or focussed on specific groups, whereas little is known about entire soil networks. Here we show that during the course of nature restoration on abandoned arable land a compositional shift in soil biota, preceded by tightening of the belowground networks, corresponds with enhanced efficiency of carbon uptake. In mid- and long-term abandoned field soil, carbon uptake by fungi increases without an increase in fungal biomass or shift in bacterial-to-fungal ratio. The implication of our findings is that during nature restoration the efficiency of nutrient cycling and carbon uptake can increase by a shift in fungal composition and/or fungal activity. Therefore, we propose that relationships between soil food web structure and carbon cycling in soils need to be reconsidered. Effects of habitat restoration on belowground organisms and ecosystem processes are poorly understood. Morriën and colleagues show that changes in the composition and network interactions of soil biota lead to improved carbon uptake efficiency when formerly cultivated land is restored.

Self-generated stimuli have been found to elicit a reduced sensory response compared with externally-generated stimuli. However, much of the literature has not adequately controlled for differences in the temporal predictability and temporal control of stimuli. In two experiments, we compared the N1 (and P2) components of the auditory-evoked potential to self- and externally-generated tones that differed with respect to these two factors. In Experiment 1 (n = 42), we found that increasing temporal predictability reduced N1 amplitude in a manner that may often account for the observed reduction in sensory response to self-generated sounds. We also observed that reducing temporal control over the tones resulted in a reduction in N1 amplitude. The contrasting effects of temporal predictability and temporal control on N1 amplitude meant that sensory attenuation prevailed when controlling for each. Experiment 2 (n = 38) explored the potential effect of selective attention on the results of Experiment 1 by modifying task requirements such that similar levels of attention were allocated to the visual stimuli across conditions. The results of Experiment 2 replicated those of Experiment 1, and suggested that the observed effects of temporal control and sensory attenuation were not driven by differences in attention. Given that self- and externally-generated sensations commonly differ with respect to both temporal predictability and temporal control, findings of the present study may necessitate a re-evaluation of the experimental paradigms used to study sensory attenuation.

Background The WHO health systems Building Blocks framework has become ubiquitous in health systems research. However, it was not developed as a research instrument, but rather to facilitate investments of resources in health systems. In this paper, we reflect on the advantages and limitations of using the framework in applied research, as experienced in three empirical vaccine studies we have undertaken. Discussion We argue that while the Building Blocks framework is valuable because of its simplicity and ability to provide a common language for researchers, it is not suitable for analysing dynamic, complex and inter-linked systems impacts. In our three studies, we found that the mechanical segmentation of effects by the WHO building blocks, without recognition of their interactions, hindered the understanding of impacts on systems as a whole. Other important limitations were the artificial equal weight given to each building block and the challenge in capturing longer term effects and opportunity costs. Another criticism is not of the framework per se, but rather how it is typically used, with a focus on the six building blocks to the neglect of the dynamic process and outcome aspects of health systems. We believe the framework would be improved by making three amendments: integrating the missing “demand” component; incorporating an overarching, holistic health systems viewpoint and including scope for interactions between components. If researchers choose to use the Building Blocks framework, we recommend that it be adapted to the specific study question and context, with formative research and piloting conducted in order to inform this adaptation. Summary As with frameworks in general, the WHO Building Blocks framework is valuable because it creates a common language and shared understanding. However, for applied research, it falls short of what is needed to holistically evaluate the impact of specific interventions on health systems. We propose that if researchers use the framework, it should be adapted and made context-specific.

The sustainable management of land for agricultural production has at its core a healthy soil, because this reduces the quantity of external inputs, reduces losses of nutrients to the environment, maximises the number of days when the soil can be worked, and has a pore structure that maximises both the retention of water in dry weather and drainage of water in wet weather. Soil health encompasses the physical, chemical, and biological features, but the use of biological indicators is the least well advanced. Sustainability also implies the balanced provision of ecosystem services, which can be more difficult to measure than single indicators. We describe how the key components of the soil food web contribute to a healthy soil and give an overview of the increasing number of scientific studies that have examined the use of biological indicators. A case study is made of the ecosystem service of water infiltration, which is quite an undertaking to measure directly, but which can be inferred from earthworm abundance and biodiversity which is relatively easy to measure. This highlights the difficulty of putting any monitoring scheme into practice and we finish by providing the considerations in starting a new soil health monitoring service in the UK and in maintaining biological monitoring in The Netherlands.

The present study investigated the phenomenon of buying ‘virtual assets’ for game avatars. Virtual Assets are items that are bought with real-world money for an avatar in-game; weapons, items, pets, mounts and skin customisations the most popular examples. Using Interpretative phenomenological analysis (IPA) six gamers that regularly bought in-game assets were interviewed. IPA was chosen because of its emphasis on lived experience, and each participant had subjective experiences of gaming and purchase behaviour. Of particular focus in this study were the superordinate themes of motivations for purchase behaviour, the resulting psychological impact on the gamer, the social benefits of gaming and virtual asset purchasing, emotional attachment, self-expression through the avatar, impulsivity versus thoughtfulness in purchase intention, and the impact of a transaction machinery on the ‘game experience’. motivations that were found to be of particular importance were item exclusivity, function, social appeal, and collectability. It was found that virtual items enable the gamer to express themselves, feel real satisfaction, and build lasting friendships. Essentially, virtual assets and gaming mostly had a very positive impact on the participant’s psychological wellbeing. Implications for gamers and games production companies are considered