Alteration of Cardiac Progenitor Cell Potency in GRMD Dogs

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PTPBR7 Binding Proteins in Myelinating Neurons of the Mouse Brain

Mouse protein tyrosine phosphatase PTPBR7 is a receptor-like, transmembrane protein that is localized on the surface of neuronal cells. Its protein phosphatase activity is reduced upon multimerization, and PTPBR7-deficient mice display motor coordination defects. Extracellular molecules that may influence PTPBR7 activity, however, remain to be determined. We here show that the PTPBR7 extracellular domain binds to highly myelinated regions in mouse brain, in particular the white matter tracks in cerebellum. PTPBR7 deficiency does not alter this binding pattern, as witnessed by RAP in situ staining of Ptprr-/- mouse brain sections. Additional in situ and in vitro experiments also suggest that sugar moieties of heparan sulphate and chondroitin sulphate glycosaminoglycans are not critical for PTPBR7 binding. Candidate binding proteins were affinity-purified exploiting the PTPBR7 extracellular domain and identified by mass spectrometric means. Results support the suggested link between PTPRR isoforms and cerebellar calcium ion homeostasis, and suggest an additional role in the process of cell-cell adhesion

Forecasting the Cumulative Effects of Multiple Stressors on Breeding Habitat for a Steeply Declining Aerial Insectivorous Songbird, the Olive-sided Flycatcher (Contopus cooperi)

To halt ongoing loss in biodiversity, there is a need for landscape-level management recommendations that address cumulative impacts of anthropogenic and natural disturbances on wildlife habitat. We examined the cumulative effects of logging, roads, land-use change, fire, and bark beetle outbreaks on future habitat for olive-sided flycatcher (Contopus cooperi), a steeply declining aerial insectivorous songbird, in Canada’s western boreal forest. To predict the occurrence of olive-sided flycatcher we developed a suite of habitat suitability models using point count surveys (1997–2011) spatially- and temporally-matched with forest inventory data. Flycatcher occurrence was positively associated with small (∼10 ha) 10- to 20-year-old clearcuts, and with 10–100% tree mortality due to mountain pine beetle (Dendroctonus ponderosae) outbreaks, but we found no association with roads or distance to water. We used the parameter estimates from the best-fit habitat suitability models to inform spatially explicit state-and-transition simulation models to project change in habitat availability from 2020 to 2050 under six alternative scenarios (three management × two fire alternatives). The simulation models projected that the cumulative effects of land use conversion, forest harvesting, and fire will reduce the area of olive-sided flycatcher habitat by 16–18% under Business As Usual management scenarios and by 11–13% under scenarios that include protection of 30% of the land base. Scenarios limiting the size of all clearcuts to ≤10 ha resulted in a median habitat loss of 4–6%, but projections were highly variable. Under all three management alternatives, a 50% increase in fire frequency (expected due to climate change) exacerbated habitat loss. The projected losses of habitat in western boreal forest, even with an increase in protected areas, imply that reversing the ongoing population declines of olive-sided flycatcher and other migratory birds will require attention to forest management beyond protected areas. Further work should examine the effects of multiple stressors on the demographic mechanisms driving change in aerial insectivore populations, including stressors on the wintering grounds in South America, and should aim to adapt the design of protected areas and forest management policies to projected climate-driven increases in the size and frequency of wildfires.Fil: Norris, Andrea R.. Environment and Climate Change; CanadáFil: Frid, Leonardo. No especifíca;Fil: Debyser, Chloé. No especifíca;Fil: De Groot, Krista L.. Environment and Climate Change; CanadáFil: Thomas, Jeffrey. Environment and Climate Change; CanadáFil: Lee, Adam. Environment and Climate Change; CanadáFil: Dohms, Kimberly M.. Environment and Climate Change; CanadáFil: Robinson, Andrew. Environment and Climate Change; CanadáFil: Easton, Wendy. Environment and Climate Change; CanadáFil: Martin, Kathy. University of British Columbia; CanadáFil: Cockle, Kristina Louise. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Puerto Iguazú | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Puerto Iguazú; Argentin

Differential viral accessibility (DIVA) identifies alterations in chromatin architecture through large-scale mapping of lentiviral integration sites.

Alterations in chromatin structure play a major role in the epigenetic regulation of gene expression. Here, we describe a step-by-step protocol for differential viral accessibility (DIVA), a method for identifying changes in chromatin accessibility genome-wide. Commonly used methods for mapping accessible genomic loci have strong preferences toward detecting 'open' chromatin found at regulatory regions but are not well suited to studying chromatin accessibility in gene bodies and intergenic regions. DIVA overcomes this limitation, enabling a broader range of sites to be interrogated. Conceptually, DIVA is similar to ATAC-seq in that it relies on the integration of exogenous DNA into the genome to map accessible chromatin, except that chromatin architecture is probed through mapping integration sites of exogenous lentiviruses. An isogenic pair of cell lines are transduced with a lentiviral vector, followed by PCR amplification and Illumina sequencing of virus-genome junctions; the resulting sequences define a set of unique lentiviral integration sites, which are compared to determine whether genomic loci exhibit significantly altered accessibility between experimental and control cells. Experienced researchers will take 6 d to generate lentiviral stocks and transduce the target cells, a further 5 d to prepare the Illumina sequencing libraries and a few hours to perform the bioinformatic analysis

FAHN/SPG35 : a narrow phenotypic spectrum across disease classifications

The endoplasmic reticulum enzyme fatty acid 2-hydroxylase (FA2H) plays a major role in the formation of 2-hydroxy glycosphingolipids, main components of myelin. FA2H deficiency in mice leads to severe central demyelination and axon loss. In humans it has been associated with phenotypes from the neurodegeneration with brain iron accumulation (fatty acid hydroxylase-associated neurodegeneration, FAHN), hereditary spastic paraplegia (HSP type SPG35) and leukodystrophy (leukodystrophy with spasticity and dystonia) spectrum. We performed an in-depth clinical and retrospective neurophysiological and imaging study in a cohort of 19 cases with biallelic FA2H mutations. FAHN/SPG35 manifests with early childhood onset predominantly lower limb spastic tetraparesis and truncal instability, dysarthria, dysphagia, cerebellar ataxia, and cognitive deficits, often accompanied by exotropia and movement disorders. The disease is rapidly progressive with loss of ambulation after a median of 7 years after disease onset and demonstrates little interindividual variability. The hair of FAHN/SPG35 patients shows a bristle-like appearance; scanning electron microscopy of patient hair shafts reveals deformities (longitudinal grooves) as well as plaque-like adhesions to the hair, likely caused by an abnormal sebum composition also described in a mouse model of FA2H deficiency. Characteristic imaging features of FAHN/SPG35 can be summarized by the WHAT' acronym: white matter changes, hypointensity of the globus pallidus, ponto-cerebellar atrophy, and thin corpus callosum. At least three of four imaging features are present in 85% of FA2H mutation carriers. Here, we report the first systematic, large cohort study in FAHN/SPG35 and determine the phenotypic spectrum, define the disease course and identify clinical and imaging biomarkers

Interventions to prevent pandemic-driven diversity loss

The pandemic has badly affected the most diverse career stage in UK Earth sciences: early career researchers. Disrupted careers must be rescued with contingency plans, remote networks, a focus on mental health and mentor support if we are to retain diversity and talent

Nutrient pathways and their susceptibility to past and future change in the Eurasian Arctic Ocean

Climate change is altering nutrient cycling within the Arctic Ocean, having knock-on effects to Arctic ecosystems. Primary production in the Arctic is principally nitrogen-limited, particularly in the western Pacific-dominated regions where denitrification exacerbates nitrogen loss. The nutrient status of the eastern Eurasian Arctic remains under debate. In the Barents Sea, primary production has increased by 88% since 1998. To support this rapid increase in productivity, either the standing stock of nutrients has been depleted, or the external nutrient supply has increased. Atlantic water inflow, enhanced mixing, benthic nitrogen cycling, and land–ocean interaction have the potential to alter the nutrient supply through addition, dilution or removal. Here we use new datasets from the Changing Arctic Ocean program alongside historical datasets to assess how nitrate and phosphate concentrations may be changing in response to these processes. We highlight how nutrient dynamics may continue to change, why this is important for regional and international policy-making and suggest relevant research priorities for the future

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

PTPBR7 Binding Proteins in Myelinating Neurons of the Mouse Brain

Abstract Mouse protein tyrosine phosphatase PTPBR7 is a receptor-like, transmembrane protein that is localized on the surface of neuronal cells. Its protein phosphatase activity is reduced upon multimerization, and PTPBR7-deficient mice display motor coordination defects. Extracellular molecules that may influence PTPBR7 activity, however, remain to be determined. We here show that the PTPBR7 extracellular domain binds to highly myelinated regions in mouse brain, in particular the white matter tracks in cerebellum. PTPBR7 deficiency does not alter this binding pattern, as witnessed by RAP in situ staining of Ptprr -/-mouse brain sections. Additional in situ and in vitro experiments also suggest that sugar moieties of heparan sulphate and chondroitin sulphate glycosaminoglycans are not critical for PTPBR7 binding. Candidate binding proteins were affinity-purified exploiting the PTPBR7 extracellular domain and identified by mass spectrometric means. Results support the suggested link between PTPRR isoforms and cerebellar calcium ion homeostasis, and suggest an additional role in the process of cell-cell adhesion