Correlation of Atrial Natriuretic Peptide and Cyclic Guanosine Monophosphate Plasma Concentrations in Patients with Heart Disorders During Rest and Exercise

Peer Reviewe

Drivers of Batrachochytrium dendrobatidis infection load, with evidence of infection tolerance in adult male toads (Bufo spinosus)

Chytridiomycosis is affecting hundreds of amphibian species worldwide, but while in tropical areas, adult individuals have been the focus of most investigations, the exact role played by infection intensity of breeding adults is not well understood in temperate areas. We conducted mark–recapture–capture surveys during spiny common toad breeding seasons from 2006 to 2018 at the site of the first recorded outbreak of chytridiomycosis in Europe, the Peñalara Massif (Sierra de Guadarrama National Park, central Spain), and collected infection samples and several variables related to the reproductive effort of male individuals. We used general linear mixed models to evaluate the contribution of study variables on the infection loads of adult male toads exhibited at their capturing date. We also analysed the differences on several male characteristics between the pond with the largest breeding population against the rest of the ponds. We found that the duration of time spent in the waterbody and the condition of the host predicted infection loads. Animals of good physical condition, that spent longer in water, have higher infection levels than individuals with the opposite set of traits. The pond supporting the largest breeding population housed smaller male toads and in poorer condition. Our results are consistent with a shift in reproductive strategy in response to infection and potentially a strategy of tolerance, rather than resistance to infection. These findings have applications for disease mitigation and theoretical implications related to the trade-offs made and the evolution of traits in response to the disease

Cryptic diversity and ranavirus infection of a critically endangered Neotropical frog before and after population collapse

Mesoamerican amphibian declines in apparently pristine and protected habitats have been severe, especially at elevations above 500 m sea level and have been linked to emerging diseases and a changing climate. The Craugastor punctariolus species series of direct developing frogs is endemic to the region and used to be comprised of 33 species, seven of which have known populations at present. One of these, Craugastor ranoides, endemic to southern Nicaragua and Costa Rica, was historically found in cloud forest sites of Área de Conservación Guanacaste (ACG) in north-west Costa Rica and extended into dry forest sites 20 km distant. Here C. ranoides declined and disappeared from high elevation sites between the late 1980s and early 1990s, but populations persisted in the lowland dry forest. We compared the genetic richness and ranavirus infection status of C. ranoides from extant dry forest populations to historic museum specimens of now extinct ACG cloud forest populations using DNA sequence diversity at two mitochondrial loci and molecular screening for ranavirus. Extant dry forest populations of C. ranoides formed a monophyletic group which included historic specimens sampled at cloud forest sites. However, the extirpated ACG cloud forest population contained additional diversity: samples formed a divergent clade with unknown spatial distribution. Ranavirus was detected in both current and museum samples of C. ranoides and sequences from a 267-nucleotide region of the major capsid protein gene shared 100% sequence identity with one another and with Frog virus 3. Our findings document cryptic diversity within an endangered species that has demonstrated no recovery in cloud forests and raises questions about Ranavirus as a potential driver of amphibian decline in this system. The presence of the same C. ranoides clade within present day and historical samples suggests a potential for effective translocation and repopulation of extirpated cloud forest populations

Examining the Evidence for Chytridiomycosis in Threatened Amphibian Species

Extinction risks are increasing for amphibians due to rising threats and minimal conservation efforts. Nearly one quarter of all threatened/extinct amphibians in the IUCN Red List is purportedly at risk from the disease chytridiomycosis. However, a closer look at the data reveals that Batrachochytrium dendrobatidis (the causal agent) has been identified and confirmed to cause clinical disease in only 14% of these species. Primary literature surveys confirm these findings; ruling out major discrepancies between Red List assessments and real-time science. Despite widespread interest in chytridiomycosis, little progress has been made between assessment years to acquire evidence for the role of chytridiomycosis in species-specific amphibian declines. Instead, assessment teams invoke the precautionary principle when listing chytridiomycosis as a threat. Precaution is valuable when dealing with the world's most threatened taxa, however scientific research is needed to distinguish between real and predicted threats in order to better prioritize conservation efforts. Fast paced, cost effective, in situ research to confirm or rule out chytridiomycosis in species currently hypothesized to be threatened by the disease would be a step in the right direction. Ultimately, determining the manner in which amphibian conservation resources are utilized is a conversation for the greater conservation community that we hope to stimulate here

Epigenetic Regulation of a Murine Retrotransposon by a Dual Histone Modification Mark

Large fractions of eukaryotic genomes contain repetitive sequences of which the vast majority is derived from transposable elements (TEs). In order to inactivate those potentially harmful elements, host organisms silence TEs via methylation of transposon DNA and packaging into chromatin associated with repressive histone marks. The contribution of individual histone modifications in this process is not completely resolved. Therefore, we aimed to define the role of reversible histone acetylation, a modification commonly associated with transcriptional activity, in transcriptional regulation of murine TEs. We surveyed histone acetylation patterns and expression levels of ten different murine TEs in mouse fibroblasts with altered histone acetylation levels, which was achieved via chemical HDAC inhibition with trichostatin A (TSA), or genetic inactivation of the major deacetylase HDAC1. We found that one LTR retrotransposon family encompassing virus-like 30S elements (VL30) showed significant histone H3 hyperacetylation and strong transcriptional activation in response to TSA treatment. Analysis of VL30 transcripts revealed that increased VL30 transcription is due to enhanced expression of a limited number of genomic elements, with one locus being particularly responsive to HDAC inhibition. Importantly, transcriptional induction of VL30 was entirely dependent on the activation of MAP kinase pathways, resulting in serine 10 phosphorylation at histone H3. Stimulation of MAP kinase cascades together with HDAC inhibition led to simultaneous phosphorylation and acetylation (phosphoacetylation) of histone H3 at the VL30 regulatory region. The presence of the phosphoacetylation mark at VL30 LTRs was linked with full transcriptional activation of the mobile element. Our data indicate that the activity of different TEs is controlled by distinct chromatin modifications. We show that activation of a specific mobile element is linked to a dual epigenetic mark and propose a model whereby phosphoacetylation of histone H3 is crucial for full transcriptional activation of VL30 elements

Chromatin Organization in Sperm May Be the Major Functional Consequence of Base Composition Variation in the Human Genome

Chromatin in sperm is different from that in other cells, with most of the genome packaged by protamines not nucleosomes. Nucleosomes are, however, retained at some genomic sites, where they have the potential to transmit paternal epigenetic information. It is not understood how this retention is specified. Here we show that base composition is the major determinant of nucleosome retention in human sperm, predicting retention very well in both genic and non-genic regions of the genome. The retention of nucleosomes at GC-rich sequences with high intrinsic nucleosome affinity accounts for the previously reported retention at transcription start sites and at genes that regulate development. It also means that nucleosomes are retained at the start sites of most housekeeping genes. We also report a striking link between the retention of nucleosomes in sperm and the establishment of DNA methylation-free regions in the early embryo. Taken together, this suggests that paternal nucleosome transmission may facilitate robust gene regulation in the early embryo. We propose that chromatin organization in the male germline, rather than in somatic cells, is the major functional consequence of fine-scale base composition variation in the human genome. The selective pressure driving base composition evolution in mammals could, therefore, be the need to transmit paternal epigenetic information to the zygote