Developments in the tools and methodologies of synthetic biology.

Synthetic biology is principally concerned with the rational design and engineering of biologically based parts, devices, or systems. However, biological systems are generally complex and unpredictable, and are therefore, intrinsically difficult to engineer. In order to address these fundamental challenges, synthetic biology is aiming to unify a body of knowledge from several foundational scientific fields, within the context of a set of engineering principles. This shift in perspective is enabling synthetic biologists to address complexity, such that robust biological systems can be designed, assembled, and tested as part of a biological design cycle. The design cycle takes a forward-design approach in which a biological system is specified, modeled, analyzed, assembled, and its functionality tested. At each stage of the design cycle, an expanding repertoire of tools is being developed. In this review, we highlight several of these tools in terms of their applications and benefits to the synthetic biology community

Orientation of tabular mafic intrusions controls convective vigour and crystallization style

The microstructure in basaltic dykes is significantly different to that in sills and lava lakes of the same bulk composition. For a given width of intrusion (or depth of lava lake), vertical tabular bodies are coarser-grained than horizontal bodies, with an invariant plagioclase shape across the intrusion. When comparing samples from sills and dykes for which the average grain size is the same, the dyke samples contain fewer small grains and fewer large grains than the sill samples. In contrast, the variation of median clinopyroxene-plagioclase-plagioclase dihedral angles in dykes correlates precisely with that observed in sills and is a function of the rate of diffusive heat loss. These patterns can be accounted for if the early stages of crystallization in dykes primarily involve the growth of isolated grains suspended in a well-mixed convecting magma, with the final stage (during which dihedral angles form) occurring in a crystal-rich static magma during which heat loss is primarily diffusive. In contrast, crystallization in sills occurs predominantly in marginal solidification fronts, suggesting that any convective motions are insufficient to entrain crystals from the marginal mushy layers and to keep them suspended while they grow. An exception to this general pattern is provided by members of the Mull Solitary Dykes, which propagated 100-1000 km SE from the Mull Palaeogene Igneous Centre, Scotland, through the shallow crust. These dykes, where sampled > 100 km from Mull, have a microstructure indistinguishable from that of a sill of comparable thickness. We suggest that sufficient nucleation and crystallization occurred in these dykes to increase the viscosity sufficiently to damp convection once unidirectional flow had ceased

Astrocytes in neuroendocrine systems: An overview

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record A class of glial cell, astrocytes are highly abundant in the CNS. In addition to maintaining tissue homeostasis, astrocytes regulate neuronal communication and synaptic plasticity. There is an ever-increasing appreciation that astrocytes are involved in the regulation of physiology and behaviour in normal and pathological states, including within neuroendocrine systems. Indeed, astrocytes are direct targets of hormone action in the CNS, via receptors expressed on their surface, and are also a source of regulatory neuropeptides, neurotransmitters, and gliotransmitters. Furthermore, as part of the neurovascular unit, astrocytes can regulate hormone entry into the CNS. This review is intended to provide an overview of how astrocytes are impacted by and contribute to the regulation of a diverse range of neuroendocrine systems: energy homeostasis and metabolism, reproduction, fluid homeostasis, the stress response, and circadian rhythms. This article is protected by copyright. All rights reserved.Medical Research Council (MRC)Diabetes UKUniversity of Exete

Regulation of food intake by astrocytes in the brainstem dorsal vagal complex

This is the final version. Available on open access from Wiley via the DOI in this recordA role for glial cells in brain circuits controlling feeding has begun to be identified with hypothalamic astrocyte signaling implicated in regulating energy homeostasis. The nucleus of the solitary tract (NTS), within the brainstem dorsal vagal complex (DVC), integrates vagal afferent information from the viscera and plays a role in regulating food intake. We hypothesized that astrocytes in this nucleus respond to, and influence, food intake. Mice fed high‐fat chow for 12 hr during the dark phase showed NTS astrocyte activation, reflected in an increase in the number (65%) and morphological complexity of glial‐fibrillary acidic protein (GFAP)‐immunoreactive cells adjacent to the area postrema (AP), compared to control chow fed mice. To measure the impact of astrocyte activation on food intake, we delivered designer receptors exclusively activated by designer drugs (DREADDs) to DVC astrocytes (encompassing NTS, AP, and dorsal motor nucleus of the vagus) using an adeno‐associated viral (AAV) vector (AAV‐GFAP‐hM3Dq_mCherry). Chemogenetic activation with clozapine‐N‐oxide (0.3 mg/kg) produced in greater morphological complexity in astrocytes and reduced dark‐phase feeding by 84% at 4 hr postinjection compared with vehicle treatment. hM3Dq‐activation of DVC astrocytes also reduced refeeding after an overnight fast (71% lower, 4 hr postinjection) when compared to AAV‐GFAP‐mCherry expressing control mice. DREADD‐mediated astrocyte activation did not impact locomotion. hM3Dq activation of DVC astrocytes induced c‐FOS in neighboring neuronal feeding circuits (including in the parabrachial nucleus). This indicates that NTS astrocytes respond to acute nutritional excess, are involved in the integration of peripheral satiety signals, and can reduce food intake when activated.Diabetes UKMedical Research Council (MRC

Astrocytes in the nucleus of the solitary tract: Contributions to neural circuits controlling physiology

This is the final version. Available from Elsevier via the DOI in this record. The nucleus of the solitary tract (NTS) is the primary brainstem centre for the integration of physiological information from the periphery transmitted via the vagus nerve. In turn, the NTS feeds into downstream circuits regulating physiological parameters. Astrocytes are glial cells which have key roles in maintaining CNS tissue homeostasis and regulating neuronal communication. Recently an increasing number of studies have implicated astrocytes in the regulation of synaptic transmission and physiology. This review aims to highlight evidence for a role for astrocytes in the functions of the NTS. Astrocytes maintain and modulate NTS synaptic transmission contributing to the control of diverse physiological systems namely cardiovascular, respiratory, glucoregulatory, and gastrointestinal. In addition, it appears these cells may have a role in central control of feeding behaviour. As such these cells are a key component of signal processing and physiological control by the NTS.Medical Research Council (MRC)Diabetes U

Recent Advances in Ultralow-Pt-Loading Electrocatalysts for the Efficient Hydrogen Evolution.

Hydrogen production from water electrolysis provides a green and sustainable route. Platinum (Pt)-based materials have been regarded as efficient electrocatalysts for the hydrogen evolution reaction (HER). However, the large-scale commercialization of Pt-based catalysts suffers from the high cost. Therefore, ultralow-Pt-loading electrocatalysts, which can reach the balance of low cost and high HER performance, have attracted much attention. In this review, representative promising synthetic strategies, including wet chemistry, annealing, electrochemistry, photochemistry, and atomic layer deposition are summarized. Further, the interaction between different electrocatalyst components (transition metals and their derivatives) and Pt is discussed. Notably, this interaction can effectively accelerate the kinetics of the HER, enhancing the catalytic activity. At last, current challenges and future perspectives are briefly discussed

Revealing kleptoparasitic and predatory tendencies in an African mammal community using camera traps: a comparison of spatiotemporal approaches

Camera trap data are increasingly being used to characterise relationships between the spatiotemporal activity patterns of sympatric mammal species, often with a view to inferring inter-specific interactions. In this context, we attempted to characterise the kleptoparasitic and predatory tendencies of spotted hyaenas Crocuta crocuta and lions Panthera leo from photographic data collected across 54 camera trap stations and two dry seasons in Tanzania's Ruaha National Park. We applied four different methods of quantifying spatiotemporal associations, including one strictly temporal approach (activity pattern overlap), one strictly spatial approach (co-occupancy modelling), and two spatiotemporal approaches (co-detection modelling and temporal spacing at shared camera trap sites). We expected a kleptoparasitic relationship between spotted hyaenas and lions to result in a positive spatiotemporal association, and further hypothesised that the association between lions and their favourite prey in Ruaha, the giraffe Giraffa camelopardalis and the zebra Equus quagga, would be stronger than those observed with non-preferred prey species (the impala Aepyceros melampus and the dikdik Madoqua kirkii). Only approaches incorporating both the temporal and spatial components of camera trap data resulted in significant associative patterns. The latter were particularly sensitive to the temporal resolution chosen to define species detections (i.e. occasion length), and only revealed a significant positive association between lion on spotted hyaena detections, as well as a tendency for both species to follow each other at camera trap sites, during the dry season of 2013, but not that of 2014. In both seasons, observed spatiotemporal associations between lions and each of the four herbivore species considered provided no convincing or consistent indications of any predatory preferences. Our study suggests that, when making inferences on inter-specific interactions from camera trap data, due regards should be given to the potential behavioural and methodological processes underlying observed spatiotemporal patterns

Intergenerational change and familial aggregation of body mass index

The relationship between parental BMI and that of their adult offspring, when increased adiposity can become a clinical issue, is unknown. We investigated the intergenerational change in body mass index (BMI) distribution, and examined the sex-specific relationship between parental and adult offspring BMI. Intergenerational change in the distribution of adjusted BMI in 1,443 complete families (both parents and at least one offspring) with 2,286 offspring (1,263 daughters and 1,023 sons) from the west of Scotland, UK, was investigated using quantile regression. Familial correlations were estimated from linear mixed effects regression models. The distribution of BMI showed little intergenerational change in the normal range (\25 kg/m2), decreasing overweightness (25– \30 kg/m2) and increasing obesity (C30 kg/m2). Median BMI was static across generations in males and decreased in females by 0.4 (95% CI: 0.0, 0.7) kg/m2; the 95th percentileincreased by 2.2 (1.1, 3.2) kg/m2 in males and 2.7 (1.4, 3.9) kg/m2 in females. Mothers’ BMI was more strongly associated with daughters’ BMI than was fathers’ (correlation coefficient (95% CI): mothers 0.31 (0.27, 0.36), fathers 0.19 (0.14, 0.25); P = 0.001). Mothers’ and fathers’ BMI were equally correlated with sons’ BMI (correlation coefficient: mothers 0.28 (0.22, 0.33), fathers 0.27 (0.22, 0.33). The increase in BMI between generations was concentrated at the upper end of the distribution. This, alongside the strong parent-offspring correlation, suggests that the increase in BMI is disproportionally greater among offspring of heavier parents. Familial influences on BMI among middle-aged women appear significantly stronger from mothers than father