Vascular responses of the extremities to transdermal application of vasoactive agents in Caucasian and African descent individuals

This is an accepted manuscript of an article published by Springer in European Journal of Applied Physiology on 04/04/2015, available online: https://doi.org/10.1007/s00421-015-3164-2 The accepted version of the publication may differ from the final published version.© 2015, Springer-Verlag Berlin Heidelberg. Purpose: Individuals of African descent (AFD) are more susceptible to non-freezing cold injury than Caucasians (CAU) which may be due, in part, to differences in the control of skin blood flow. We investigated the skin blood flow responses to transdermal application of vasoactive agents. Methods: Twenty-four young males (12 CAU and 12 AFD) undertook three tests in which iontophoresis was used to apply acetylcholine (ACh 1 w/v %), sodium nitroprusside (SNP 0.01 w/v %) and noradrenaline (NA 0.5 mM) to the skin. The skin sites tested were: volar forearm, non-glabrous finger and toe, and glabrous finger (pad) and toe (pad). Results: In response to SNP on the forearm, AFD had less vasodilatation for a given current application than CAU (P = 0.027–0.004). ACh evoked less vasodilatation in AFD for a given application current in the non-glabrous finger and toe compared with CAU (P = 0.043–0.014) with a lower maximum vasodilatation in the non-glabrous finger (median [interquartile], AFD n = 11, 41[234] %, CAU n = 12, 351[451] %, P = 0.011) and non-glabrous toe (median [interquartile], AFD n = 9, 116[318] %, CAU n = 12, 484[720] %, P = 0.018). ACh and SNP did not elicit vasodilatation in the glabrous skin sites of either group. There were no ethnic differences in response to NA. Conclusion: AFD have an attenuated endothelium-dependent vasodilatation in non-glabrous sites of the fingers and toes compared with CAU. This may contribute to lower skin temperature following cold exposure and the increased risk of cold injuries experienced by AFD.Published versio

Road to evolution? Local adaptation to road adjacency in an amphibian (Ambystoma maculatum)

The network of roads on the landscape is vast, and contributes a suite of negative ecological effects on adjacent habitats, ranging from fragmentation to contamination by runoff. In addition to the immediate consequences faced by biota living in roaded landscapes, road effects may further function as novel agents of selection, setting the stage for contemporary evolutionary changes in local populations. Though the ecological consequences of roads are well described, evolutionary outcomes remain largely unevaluated. To address these potential responses in tandem, I conducted a reciprocal transplant experiment on early life history stages of a pool-breeding salamander. My data show that despite a strong, negative effect of roadside pools on salamander performance, populations adjacent to roads are locally adapted. This suggests that the response of species to human-altered environments varies across local populations, and that adaptive processes may mediate this response

An acceptor-substrate binding site determining glycosyl transfer emerges from mutant analysis of a plant vacuolar invertase and a fructosyltransferase

Glycoside hydrolase family 32 (GH32) harbors hydrolyzing and transglycosylating enzymes that are highly homologous in their primary structure. Eight amino acids dispersed along the sequence correlated with either hydrolase or glycosyltransferase activity. These were mutated in onion vacuolar invertase (acINV) according to the residue in festuca sucrose:sucrose 1-fructosyltransferase (saSST) and vice versa. acINV(W440Y) doubles transferase capacity. Reciprocally, saSST(C223N) and saSST(F362Y) double hydrolysis. SaSST(N425S) shows a hydrolyzing activity three to four times its transferase activity. Interestingly, modeling acINV and saSST according to the 3D structure of crystallized GH32 enzymes indicates that mutations saSST(N425S), acINV(W440Y), and the previously reported acINV(W161Y) reside very close together at the surface in the entrance of the active-site pocket. Residues in- and outside the sucrose-binding box determine hydrolase and transferase capabilities of GH32 enzymes. Modeling suggests that residues dispersed along the sequence identify a location for acceptor-substrate binding in the 3D structure of fructosyltransferases

Benchmarking of cell type deconvolution pipelines for transcriptomics data

Many computational methods have been developed to infer cell type proportions from bulk transcriptomics data. However, an evaluation of the impact of data transformation, pre-processing, marker selection, cell type composition and choice of methodology on the deconvolution results is still lacking. Using five single-cell RNA-sequencing (scRNA-seq) datasets, we generate pseudo-bulk mixtures to evaluate the combined impact of these factors. Both bulk deconvolution methodologies and those that use scRNA-seq data as reference perform best when applied to data in linear scale and the choice of normalization has a dramatic impact on some, but not all methods. Overall, methods that use scRNA-seq data have comparable performance to the best performing bulk methods whereas semi-supervised approaches show higher error values. Moreover, failure to include cell types in the reference that are present in a mixture leads to substantially worse results, regardless of the previous choices. Altogether, we evaluate the combined impact of factors affecting the deconvolution task across different datasets and propose general guidelines to maximize its performance. Inferring cell type proportions from transcriptomics data is affected by data transformation, normalization, choice of method and the markers used. Here, the authors use single-cell RNAseq datasets to evaluate the impact of these factors and propose guidelines to maximise deconvolution performance

Spatial Sorting Drives Morphological Variation in the Invasive Bird, Acridotheris tristis

The speed of range expansion in many invasive species is often accelerating because individuals with stronger dispersal abilities are more likely to be found at the range front. This ‘spatial sorting’ of strong dispersers will drive the acceleration of range expansion. In this study, we test whether the process of spatial sorting is at work in an invasive bird population (Common myna, Acridotheris tristis) in South Africa. Specifically, we sampled individuals across its invasive range and compared morphometric measurements relevant and non-relevant to the dispersal ability. Besides testing for signals of spatial sorting, we further examined the effect of environmental factors on morphological variations. Our results showed that dispersal-relevant traits are significantly correlated with distance from the range core, with strong sexual dimorphism, indicative of sex-biased dispersal. Morphological variations were significant in wing and head traits of females, suggesting females as the primary dispersing sex. In contrast, traits not related to dispersal such as those associated with foraging showed no signs of spatial sorting but were significantly affected by environmental variables such as the vegetation and the intensity of urbanisation. When taken together, our results support the role of spatial sorting in facilitating the expansion of Common myna in South Africa despite its low propensity to disperse in the native range

Novel animal models for studying complex brain disorders: BAC-driven miRNA-mediated in vivo silencing of gene expression

In schizophrenia, glutamic acid decarboxylase 1 (GAD1) disturbances are robust, consistently observed, cell-type specific and represent a core feature of the disease. In addition, neuropeptide Y (NPY), which is a phenotypic marker of a sub-population of GAD1-containing interneurons, has shown reduced expression in the prefrontal cortex in subjects with schizophrenia, suggesting that dysfunction of the NPY+ cortical interneuronal sub-population might be a core feature of this devastating disorder. However, modeling gene expression disturbances in schizophrenia in a cell type-specific manner has been extremely challenging. To more closely mimic these molecular and cellular human post-mortem findings, we generated a transgenic mouse in which we downregulated GAD1 mRNA expression specifically in NPY+ neurons. This novel, cell type-specific in vivo system for reducing gene expression uses a bacterial artificial chromosome (BAC) containing the NPY promoter-enhancer elements, the reporter molecule (eGFP) and a modified intron containing a synthetic microRNA (miRNA) targeted to GAD1. The animals of isogenic strains are generated rapidly, providing a new tool for better understanding the molecular disturbances in the GABAergic system observed in complex neuropsychiatric disorders such as schizophrenia. In the future, because of the small size of the silencing miRNAs combined with our BAC strategy, this method may be modified to allow generation of mice with simultaneous silencing of multiple genes in the same cells with a single construct, and production of splice-variant-specific knockdown animals

The heritability of mating behaviour in a fly and its plasticity in response to the threat of sperm competition.

Phenotypic plasticity is a key mechanism by which animals can cope with rapidly changeable environments, but the evolutionary lability of such plasticity remains unclear. The socio-sexual environment can fluctuate very rapidly, affecting both the frequency of mating opportunities and the level of competition males may face. Males of many species show plastic behavioural responses to changes in social environment, in particular the presence of rival males. For example, Drosophila pseudoobscura males respond to rivals by extending mating duration and increasing ejaculate size. Whilst such responses are predicted to be adaptive, the extent to which the magnitude of response is heritable, and hence selectable, is unknown. We investigated this using isofemale lines of the fruit fly D. pseudoobscura, estimating heritability of mating duration in males exposed or not to a rival, and any genetic basis to the change in this trait between these environments (i.e. degree of plasticity). The two populations differed in population sex ratio, and the presence of a sex ratio distorting selfish chromosome. We find that mating duration is heritable, but no evidence of population differences. We find no significant heritability of plasticity in mating duration in one population, but borderline significant heritability of plasticity in the second. This difference between populations might be related to the presence of the sex ratio distorting selfish gene in the latter population, but this will require investigation in additional populations to draw any conclusions. We suggest that there is scope for selection to produce an evolutionary response in the plasticity of mating duration in response to rivals in D. pseudoobscura, at least in some populations

Erratum to: Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5).

[This corrects the article DOI: 10.1186/s13601-016-0116-9.]

Erratum to: Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5).

[This corrects the article DOI: 10.1186/s13601-016-0116-9.]