Transcriptional signatures of synaptic vesicle genes define myotonic dystrophy type I neurodegeneration

Aim: To delineate the neurogenetic profiles of brain degeneration patterns in myotonic dystrophy type I (DM1). Methods: In two cohorts of DM1 patients, brain maps of volume loss (VL) and neuropsychological deficits (NDs) were intersected to large-scale transcriptome maps provided by the Allen Human Brain Atlas (AHBA). For validation, neuropathological and RNA analyses were performed in a small series of DM1 brain samples. Results: Twofold: (1) From a list of preselected hypothesis-driven genes, confirmatory analyses found that three genes play a major role in brain degeneration: dystrophin (DMD), alpha-synuclein (SNCA) and the microtubule-associated protein tau (MAPT). Neuropathological analyses confirmed a highly heterogeneous Tau-pathology in DM1, different to the one in Alzheimer's disease. (2) Exploratory analyses revealed gene clusters enriched for key biological processes in the central nervous system, such as synaptic vesicle recycling, localization, endocytosis and exocytosis, and the serotonin and dopamine neurotransmitter pathways. RNA analyses confirmed synaptic vesicle dysfunction. Conclusions: The combination of large-scale transcriptome interactions with brain imaging and cognitive function sheds light on the neurobiological mechanisms of brain degeneration in DM1 that might help define future therapeutic strategies and research into this condition

Performance of Screening Strategies for Latent Tuberculosis Infection in Patients with Inflammatory Bowel Disease: Results from the ENEIDA Registry of GETECCU

(1) Aims: Patients receiving antitumor necrosis factor (anti-TNF) therapy are at risk of developing tuberculosis (TB), usually due to the reactivation of a latent TB infection (LTBI). LTBI screening and treatment decreases the risk of TB. This study evaluated the diagnostic performance of different LTBI screening strategies in patients with inflammatory bowel disease (IBD). (2) Methods: Patients in the Spanish ENEIDA registry with IBD screened for LTBI between January 2003 and January 2018 were included. The diagnostic yield of different strategies (dual screening with tuberculin skin test [TST] and interferon-gamma-release assay [IGRA], two-step TST, and early screening performed at least 12 months before starting biological treatment) was analyzed. (3) Results: Out of 7594 screened patients, 1445 (19%; 95% CI 18-20%) had LTBI. Immunomodulator (IMM) treatment at screening decreased the probability of detecting LTBI (20% vs. 17%, p = 0.001). Regarding screening strategies, LTBI was more frequently diagnosed by dual screening than by a single screening strategy (IGRA, OR 0.60; 95% CI 0.50-0.73, p < 0.001; TST, OR 0.76; 95% CI 0.66-0.88, p < 0.001). Two-step TST increased the diagnostic yield of a single TST by 24%. More cases of LTBI were diagnosed by early screening than by routine screening before starting anti-TNF agents (21% [95% CI 20-22%] vs. 14% [95% CI 13-16%], p < 0.001). The highest diagnostic performance for LTBI (29%) was obtained by combining early and TST/IGRA dual screening strategies in patients without IMM. (4): Conclusions: Both early screening and TST/IGRA dual screening strategies significantly increased diagnostic performance for LTBI in patients with IBD, with optimal performance achieved when they are used together in the absence of IMM

isotracer: An R package for the analysis of tracer addition experiments

Tracer addition experiments, particularly using isotopic tracers, are becoming increasingly important in a variety of studies aiming at characterizing the flows of molecules or nutrients at different levels of biological organization, from the cellular and tissue levels, to the organismal and ecosystem levels. However, performing rigorous statistical analyses to gain reliable quantitative insights from these experiments often remains challenging. We present an approach based on Hidden Markov Models (HMM) to estimate nutrient flow parameters across a network, and its implementation in the R package isotracer. The isotracer package is capable of handling a variety of tracer study designs, including continuous tracer drips, pulse experiments, and pulse-chase experiments. It can also take into account tracer decay when radioactive isotopes are used. To illustrate its use, we present three case studies based on published data and spanning different levels of biological organization: a molecular-level study of protein synthesis and degradation in Arabidopsis thaliana, an organismal-level study of phosphorus incorporation in the eelgrass Zostera marina, and an ecosystem-level study of nitrogen dynamics in Trinidadian montane streams. With these case studies, we illustrate how isotracer can be used to estimate uptake rates, turnover rates, and total flows, as well as their uncertainty. We also show how to perform model selection to compare alternative hypotheses. The isotracer package allows researchers from a broad range of disciplines to fully take advantage of their datasets through rigorous statistical analyses. We conclude by discussing isotracer's further applications, limitations, and possible future improvements and expansions.peerReviewe

Consumer functional responses under intra- and inter-specific interference competition

International audienc

Data from: Evaluating the potential for evolutionary mismatch in Batesian mimics: a case study in the endangered Smooth Snake (Coronella austriaca).

Many harmless organisms gain a survival advantage by mimicking venomous species. This is the case of the endangered smooth snake (Coronella austriaca), which mimics venomous vipers. Although this may protect the smooth snake against most of its natural predators, it may render them at greater risk of mortality from humans, who are more inclined to kill species, such as vipers, that they consider dangerous. This may cause an evolutionary mismatch, whereby humans may counteract the natural advantage of mimicry. We explore this possibility evaluating the willingness of humans to kill smooth snakes versus the adder (Vipera berus), as well as their ability to discern them in the Åland Islands. Our results show that, even when respondents did not wish to kill the smooth snakes, they were often mistaken for adders, which they were willing to kill. Altogether, viper-mimicry brought about a 2.3-fold increase in the likelihood of smooth snakes being killed upon human encounter. These results open up the possibility that naturally selected mimicry can pose a threat to endangered snakes in human influenced habitats. We discuss the potential for this to be the case, and highlight the importance of protecting entire mimicry complexes, rather than single species, when the endangered species is a mimic

Data from: Predation-associated differences in sex-linkage of wild guppy coloration

Evolutionary theory predicts that the sex-linkage of sexually selected traits can influence the direction and rate of evolutionary change, and also itself be subject to selection. Theory abounds on how sex-specific selection, mate choice, or other phenomena should favor different types of sex-linked inheritance, yet evidence in nature remains limited. Here we use hormone assays in Trinidadian guppies to explore the extent to which linkage of male coloration differs among populations adapted to varying predation regimes. Results show there is consistently higher degree of X- and autosomal linkage in body coloration among populations adapted to low-predation environments. More strikingly, analyses of an introduced population of guppies from a high to a low predation environment suggest that this difference can change in 50 years or less

Evaluating the potential for evolutionary mismatch in Batesian mimics : a case study in the endangered Smooth Snake (Coronella austriaca)

Many harmless organisms gain a survival advantage by mimicking venomous species. This is the case of the endangered smooth snake (Coronella austriaca), which mimics venomous vipers. Although this may protect the smooth snake against most of its natural predators, it may render them at greater risk of mortality from humans, who are more inclined to kill species, such as vipers, that they consider dangerous. This may cause an evolutionary mismatch, whereby humans may counteract the natural advantage of mimicry. We explore this possibility of evaluating the willingness of humans to kill smooth snakes versus the adder (Vipera berus), as well as their ability to discern them in the Åland Islands. Our results show that, even when respondents did not wish to kill the smooth snakes, these were often mistaken for adders, which they were willing to kill. Altogether, viper mimicry brought about a 2.3‐fold increase in the likelihood of smooth snakes being killed upon human encounter. These results open up the possibility that naturally selected mimicry can pose a threat to endangered snakes in human‐influenced habitats. We discuss the potential for this to be the case, and highlight the importance of protecting entire mimicry complexes, rather than single species, when the endangered species is a mimic.peerReviewe