Response of Bats and Nocturnal Food Webs to Mountain Pine Beetle (Dendroctonous Ponderosae) Outbreaks

Climate change has led to increased severity and frequency of forest disturbances globally which would predictably alter species compositions in affected habitats. Bats, as important bioindicators of ecosystem health, are known to respond to changes in habitat structure and prey composition. This dissertation describes how a forest disturbance event and ensuing successional changes altered the structure of bat-associated food web components along the highly biodiverse Front Range of Colorado. Mountain pine beetles (MPB) are important drivers of forest regeneration when populations are at background levels, however, unprecedented outbreaks of MPB populations in recent decades have severely impacted over 1.3 million hectares of lodgepole pine forests in Colorado. This has resulted in widespread structural changes in these forest habitats that comprise approximately 7% of the land area in the Rocky Mountains, and there are unclear patterns in the short-term shifts occurring in vegetation community composition following the recent MPB outbreak. The first project reported here (Chapter II) examines the community structure of vegetation in lodgepole pine forests after MPB-kill and relates time-since-kill and other environmental factors to ensuing secondary successional changes using a non-metric multidimensional scaling ordination. The second project (Chapter III) investigates how these shifting baselines in vegetation community structure alter bat-associated food web interactions in lodgepole pine ecosystems. The third project (Chapter IV) investigates activity patterns of tri-colored bats in these novel MPB-killed habitats and quantifies what site and environmental factors are influencing these patterns. Tri-colored bats (Perimyotis subflavus) are extending their distributional range westward in the United States including into the Front Range of Colorado. In sum, these projects describe how secondary successional patterns in lodgepole pine forests after severe beetle-kill disturbance shapes a diverse assemblage of vegetation, bats, and insects. This knowledge will help resource managers and biologists to better understand and plan for community and assembly-level management

Shakespeare’s original will: a re-reading, and a reflection on interdisciplinary research within archives

Much academic ink has been spilled on the importance of William Shakespeare’s last will and testament, particularly as a source illuminating his life and character. Drawing upon recent archival research and technical analysis, this article details the processes by which interdisciplinary approaches to the will have resulted in a fundamental reinterpretation of what the contents of the will can tell us about Shakespeare’s final years

Standards for the care of people with cystic fibrosis; establishing and maintaining health

Cystic fibrosis; Health; StandardsFibrosis quística; Salud; EstándaresFibrosi quística; Salut; EstàndardsThis is the second in a series of four papers updating the European Cystic Fibrosis Society (ECFS) standards for the care of people with CF. This paper focuses on establishing and maintaining health. The guidance is produced using an evidence-based framework and with wide stakeholder engagement, including people from the CF community. Authors provided a narrative description of their topic and statements, which were more directive. These statements were reviewed by a Delphi exercise, achieving good levels of agreement from a wide group for all statements. This guidance reinforces the importance of a multi-disciplinary CF team, but also describes developing models of care including virtual consultations. The framework for health is reinforced, including the need for a physically active lifestyle and the strict avoidance of all recreational inhalations, including e-cigarettes. Progress with cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy is reviewed, including emerging adverse events and advice for dose reduction and interruption. This paper contains guidance that is pertinent to all people with CF regardless of age and eligibility for and access to modulator therapy

Ecological role of an offshore industry artificial structure

Decommissioning of oil and gas infrastructure globally has focused attention on its importance as hard substratum on continental shelf and slope habitats. Observational studies are needed to improve understanding of faunal assemblages supported by offshore infrastructure and better predict the effect of removal. Here, we present results from visual inspection and physical sampling of a small oil and gas industry structure decommissioned from an oil field in the North East Atlantic. This is supported by observations of similar structures nearby and by photographs of the surrounding seabed from environmental baseline surveys. The structure supported a reasonably high biomass and diversity of invertebrates (>10 kg and >39 macrofaunal and 17 megafaunal species) and fishes (>20 kg biomass and >4 species). The invertebrate megafaunal species present on the structure were a sub-set of the hard substratum fauna observed on surrounding seabed. Porifera were absent from the structure. Biological succession in the first 2 years occurred as follows. Sparse colonies of the hydroid Obelia sp. stet were early colonisers then subsequent development of thick hydroid turf (Obelia sp. stet. and Halecium sp. stet.) supported an invertebrate assemblage (2654 individuals kg wet mass–1) dominated by saddle oysters [Pododesmus squama (Gmelin, 1791) and Heteranomia sp. stet.)] and scale worms (Harmothoe spp.). Percentage cover of hydroid turf varied significantly over the structure, with most growth on sections exposed to strongest currents. Commercially important fish species present around the structure included Gadus morhua (Atlantic cod), Pollachius virens (saithe) and Lophius piscatorius (monkfish). Studies of artificial structures such as this provide much needed data to understand their role in the ecology of seafloor habitats and inform environmental decision making on all stages of industry from exploration to decommissioning. We show that the ecological role of the decommissioned three-dimensional structures was to enhance the biomass of a sub-set of epifaunal invertebrates found in the area. This supported diverse associated macrofaunal organisms, providing a food source for motile invertebrates and fishes in an area where background hard substratum can be lost through the impacts of drilling

OPA1 deficiency accelerates hippocampal synaptic remodelling and age-related deficits in learning and memory

A healthy mitochondrial network is essential for the maintenance of neuronal synaptic integrity. Mitochondrial and metabolic dysfunction contributes to the pathogenesis of many neurodegenerative diseases including dementia. OPA1 is the master regulator of mitochondrial fusion and fission and is likely to play an important role during neurodegenerative events. To explore this, we quantified hippocampal dendritic and synaptic integrity and the learning and memory performance of aged Opa1 haploinsufficient mice carrying the Opa1Q285X mutation (B6; C3-Opa1Q285STOP; Opa1+/−). We demonstrate that heterozygous loss of Opa1 results in premature age-related loss of spines in hippocampal pyramidal CA1 neurons and a reduction in synaptic density in the hippocampus. This loss is associated with subtle memory deficits in both spatial novelty and object recognition. We hypothesize that metabolic failure to maintain normal neuronal activity at the level of a single spine leads to premature age-related memory deficits. These results highlight the importance of mitochondrial homeostasis for maintenance of neuronal function during ageing

VEGF-A165b is an endogenous neuroprotective splice isoform of vascular endothelial growth factor A in vivo and in vitro

Vascular endothelial growth factor (VEGF) A is generated as two isoform families by alternative RNA splicing, represented by VEGF-A165a and VEGF-A165b. These isoforms have opposing actions on vascular permeability, angiogenesis, and vasodilatation. The proangiogenic VEGF-A165a isoform is neuroprotective in hippocampal, dorsal root ganglia, and retinal neurons, but its propermeability, vasodilatatory, and angiogenic properties limit its therapeutic usefulness. In contrast, a neuroprotective effect of endogenous VEGF-A165b on neurons would be advantageous for neurodegenerative pathologies. Endogenous expression of human and rat VEGF-A165b was detected in hippocampal and cortical neurons. VEGF-A165b formed a significant proportion of total VEGF-A in rat brain. Recombinant human VEGF-A165b exerted neuroprotective effects in response to multiple insults, including glutamatergic excitotoxicity in hippocampal neurons, chemotherapy-induced cytotoxicity of dorsal root ganglion neurons, and retinal ganglion cells (RGCs) in rat retinal ischemia-reperfusion injury in vivo. Neuroprotection was dependent on VEGFR2 and MEK1/2 activation but not on p38 or phosphatidylinositol 3-kinase activation. Recombinant human VEGF-A165b is a neuroprotective agent that effectively protects both peripheral and central neurons in vivo and in vitro through VEGFR2, MEK1/2, and inhibition of caspase-3 induction. VEGF-A165b may be therapeutically useful for pathologies that involve neuronal damage, including hippocampal neurodegeneration, glaucoma diabetic retinopathy, and peripheral neuropathy. The endogenous nature of VEGF-A165b expression suggests that non-isoform-specific inhibition of VEGF-A (for antiangiogenic reasons) may be damaging to retinal and sensory neurons

How Many Thymocytes Audition for Selection?

T cell maturation requires the rearrangement of clonotypic T cell receptors (TCR) capable of interacting with major histocompatibility complex (MHC) ligands to initiate positive and negative selection. Only 3–5% of thymocytes mature to join the peripheral T cell pool. To investigate the basis for this low success rate, we have measured the frequency of preselection thymocytes capable of responding to MHC. As many as one in five MHC-naive thymocytes show upregulation of activation markers on exposure to MHC-expressing thymic stroma in short-term reaggregate culture. The majority of these cells display physiological changes consistent with entry into the selection process within 24 h. By exposing TCR transgenic thymocytes to a range of MHC–peptide complexes, we show that CD69 induction is indicative of thymocyte selection, positive or negative. Our data provide evidence that the fraction of thymocytes that qualify to enter the thymic selection process far exceeds the fraction that successfully complete it, and suggest that most MHC-reactive thymocytes are actively eliminated in the course of selection

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year

Standards of care for CFTR variant-specific therapy (including modulators) for people with cystic fibrosis

Cystic fibrosis (CF) has entered the era of variant-specific therapy, tailored to the genetic variants in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. CFTR modulators, the first variant-specific therapy available, have transformed the management of CF.The latest standards of care from the European CF Society (2018) did not include guidance on variant-specific therapy, as CFTR modulators were becoming established as a novel therapy. We have produced interim standards to guide healthcare professionals in the provision of variant-specific therapy for people with CF.Here we provide evidence-based guidance covering the spectrum of care, established using evidence from systematic reviews and expert opinion. Statements were reviewed by key stakeholders using Delphi methodology, with agreement (≥80%) achieved for all statements after one round of consultation. Issues around accessibility are discussed and there is clear consensus that all eligible people with CF should have access to variant-specific therapy