Changing environments and genetic variation: natural variation in inbreeding does not compromise short-term physiological responses

Selfing plant lineages are surprisingly widespread and successful in a broad range of environments, despite showing reduced genetic diversity, which is predicted to reduce their long-term evolutionary potential. However, appropriate short-term plastic responses to new environmental conditions might not require high levels of standing genetic variation. In this study, we tested whether mating system variation among populations, and associated changes in genetic variability, affected short-term responses to environmental challenges. We compared relative fitness and metabolome profiles of naturally outbreeding (genetically diverse) and inbreeding (genetically depauperate) populations of a perennial plant, Arabidopsis lyrata, under constant growth chamber conditions and an outdoor common garden environment outside its native range. We found no effect of inbreeding on survival, flowering phenology or short-term physiological responses. Specifically, naturally occurring inbreeding had no significant effects on the plasticity of metabolome profiles, using either multivariate approaches or analysis of variation in individual metabolites, with inbreeding populations showing similar physiological responses to outbreeding populations over time in both growing environments. We conclude that low genetic diversity in naturally inbred populations may not always compromise fitness or short-term physiological capacity to respond to environmental change, which could help to explain the global success of selfing mating strategies

Functional colour genes and signals of selection in colour polymorphic salamanders

Coloration has been associated with multiple biologically relevant traits that drive adaptation and diversification in many taxa. However, despite the great diversity of colour patterns present in amphibians the underlying molecular basis is largely unknown. Here, we use insight from a highly colour-variable lineage of the European fire salamander (Salamandra salamandra bernardezi) to identify functional associations with striking variation in colour morph and pattern. The three focal colour morphs—ancestral black-yellow striped, fully yellow and fully brown—differed in pattern, visible coloration and cellular composition. From population genomic analyses of up to 4,702 loci, we found no correlations of neutral population genetic structure with colour morph. However, we identified 21 loci with genotype–phenotype associations, several of which relate to known colour genes. Furthermore, we inferred response to selection at up to 142 loci between the colour morphs, again including several that relate to coloration genes. By transcriptomic analysis across all different combinations, we found 196 differentially expressed genes between yellow, brown and black skin, 63 of which are candidate genes involved in animal coloration. The concordance across different statistical approaches and ‘omic data sets provide several lines of evidence for loci linked to functional differences between colour morphs, including TYR, CAMK1 and PMEL. We found little association between colour morph and the metabolomic profile of its toxic compounds from the skin secretions. Our research suggests that current ecological and evolutionary hypotheses for the origins and maintenance of these striking colour morphs may need to be revisited.This research was supported by a Natural Environment Research Council; a Royal Society Research Grant; a Glasgow Natural History Society grant; a Wellcome Trust ISSF Catalyst Grant and a Spanish Ministry of Science Grant

The FeMoco-deficient MoFe Protein Produced by a nifH Deletion Strain of Azotobacter vinelandii Shows Unusual P-cluster Features

The His-tag MoFe protein expressed by the nifH deletion strain Azotobacter vinelandii DJ1165 (Delta nifH MoFe protein) was purified in large quantity. The alpha 2beta 2 tetrameric Delta nifH MoFe protein is FeMoco-deficient based on metal analysis and the absence of the S = 3/2 EPR signal, which arises from the FeMo cofactor center in wild-type MoFe protein. The Delta nifH MoFe protein contains 18.6 mol Fe/mol and, upon reduction with dithionite, exhibits an unusually strong S = 1/2 EPR signal in the g approx 2 region. The indigo disulfonate-oxidized Delta nifH MoFe protein does not show features of the P2+ state of the P-cluster of the Delta nifB MoFe protein. The oxidized Delta nifH MoFe protein is able to form a specific complex with the Fe protein containing the [4Fe-4S]1+ cluster and facilitates the hydrolysis of MgATP within this complex. However, it is not able to accept electrons from the [4Fe-4S]1+ cluster of the Fe protein. Furthermore, the dithionite-reduced Delta nifH MoFe can be further reduced by Ti(III) citrate, which is quite unexpected. These unusual catalytic and spectroscopic properties might indicate the presence of a P-cluster precursor or a P-cluster trapped in an unusual conformation or oxidation state

Potential effects of oilseed rape expressing oryzacystatin-1 (OC-1) and of purified insecticidal proteins on larvae of the solitary bee Osmia bicornis

Despite their importance as pollinators in crops and wild plants, solitary bees have not previously been included in non-target testing of insect-resistant transgenic crop plants. Larvae of many solitary bees feed almost exclusively on pollen and thus could be highly exposed to transgene products expressed in the pollen. The potential effects of pollen from oilseed rape expressing the cysteine protease inhibitor oryzacystatin-1 (OC-1) were investigated on larvae of the solitary bee Osmia bicornis (= O. rufa). Furthermore, recombinant OC-1 (rOC-1), the Bt toxin Cry1Ab and the snowdrop lectin Galanthus nivalis agglutinin (GNA) were evaluated for effects on the life history parameters of this important pollinator. Pollen provisions from transgenic OC-1 oilseed rape did not affect overall development. Similarly, high doses of rOC-1 and Cry1Ab as well as a low dose of GNA failed to cause any significant effects. However, a high dose of GNA (0.1%) in the larval diet resulted in significantly increased development time and reduced efficiency in conversion of pollen food into larval body weight. Our results suggest that OC-1 and Cry1Ab expressing transgenic crops would pose a negligible risk for O. bicornis larvae, whereas GNA expressing plants could cause detrimental effects, but only if bees were exposed to high levels of the protein. The described bioassay with bee brood is not only suitable for early tier non-target tests of transgenic plants, but also has broader applicability to other crop protection products

The assessment and rehabilitation of prospective memory problems in people with neurological disorders: A review

People with neurological disorders often report difficulty with prospective memory (PM), that is, remembering to do things they had intended to do. This paper briefly reviews the literature regarding the neuropsychology of PM function, concluding that from the clinical perspective, PM is best considered in terms of its separable but interacting mnemonic and executive components. Next, the strengths and limitations in the current clinical assessment of PM, including the assessment of component processes, desktop analogues of PM tasks, and naturalistic PM tasks, are outlined. The evidence base for the rehabilitation of PM is then considered, focusing on retraining PM, using retrospective memory strategies, problem-solving training, and finally, electronic memory aids. It is proposed that further research should focus on establishing the predictive validity of PM assessment, and refining promising rehabilitation techniques

IL-13 is a driver of COVID-19 severity

Immune dysregulation is characteristic of the more severe stages of SARS-CoV-2 infection. Understanding the mechanisms by which the immune system contributes to COVID-19 severity may open new avenues to treatment. Here, we report that elevated IL-13 was associated with the need for mechanical ventilation in 2 independent patient cohorts. In addition, patients who acquired COVID-19 while prescribed Dupilumab, a mAb that blocks IL-13 and IL-4 signaling, had less severe disease. In SARS-CoV-2–infected mice, IL-13 neutralization reduced death and disease severity without affecting viral load, demonstrating an immunopathogenic role for this cytokine. Following anti–IL-13 treatment in infected mice, hyaluronan synthase 1 (Has1) was the most downregulated gene, and accumulation of the hyaluronan (HA) polysaccharide was decreased in the lung. In patients with COVID-19, HA was increased in the lungs and plasma. Blockade of the HA receptor, CD44, reduced mortality in infected mice, supporting the importance of HA as a pathogenic mediator. Finally, HA was directly induced in the lungs of mice by administration of IL-13, indicating a new role for IL-13 in lung disease. Understanding the role of IL-13 and HA has important implications for therapy of COVID-19 and, potentially, other pulmonary diseases. IL-13 levels were elevated in patients with severe COVID-19. In a mouse model of the disease, IL-13 neutralization reduced the disease and decreased lung HA deposition. Administration of IL-13–induced HA in the lung. Blockade of the HA receptor CD44 prevented mortality, highlighting a potentially novel mechanism for IL-13–mediated HA synthesis in pulmonary pathology

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Genetically predicted cortisol levels and risk of venous thromboembolism

Introduction - In observational studies, venous thromboembolism (VTE) has been associated with Cushing’s syndrome and with persistent mental stress, two conditions associated with higher cortisol levels. However, it remains unknown whether high cortisol levels within the usual range are causally associated with VTE risk. We aimed to assess the association between plasma cortisol levels and VTE risk using Mendelian randomization. Methods - Three genetic variants in the SERPINA1/SERPINA6 locus (rs12589136, rs11621961 and rs2749527) were used to proxy plasma cortisol. The associations of the cortisol-associated genetic variants with VTE were acquired from the INVENT (28 907 cases and 157 243 non-cases) and FinnGen (6913 cases and 169 986 non-cases) consortia. Corresponding data for VTE subtypes were available from the FinnGen consortium and UK Biobank. Two-sample Mendelian randomization analyses (inverse-variance weighted method) were performed. Results - Genetic predisposition to higher plasma cortisol levels was associated with a reduced risk of VTE (odds ratio [OR] per one standard deviation increment 0.73, 95% confidence interval [CI] 0.62–0.87, p Conclusions - This study provides evidence that genetically predicted plasma cortisol levels in the high end of the normal range are associated with a decreased risk of VTE and that this association may be mediated by blood pressure. This study has implications for the planning of observational studies of cortisol and VTE, suggesting that blood pressure traits should be measured and accounted for