Altered Capicua expression drives regional Purkinje neuron vulnerability through ion channel gene dysregulation in spinocerebellar ataxia type 1

Selective neuronal vulnerability in neurodegenerative disease is poorly understood. Using the ATXN1[82Q] model of spinocerebellar ataxia type 1 (SCA1), we explored the hypothesis that regional differences in Purkinje neuron degeneration could provide novel insights into selective vulnerability. ATXN1[82Q] Purkinje neurons from the anterior cerebellum were found to degenerate earlier than those from the nodular zone, and this early degeneration was associated with selective dysregulation of ion channel transcripts and altered Purkinje neuron spiking. Efforts to understand the basis for selective dysregulation of channel transcripts revealed modestly increased expression of the ATXN1 co-repressor Capicua (Cic) in anterior cerebellar Purkinje neurons. Importantly, disrupting the association between ATXN1 and Cic rescued the levels of these ion channel transcripts, and lentiviral overexpression of Cic in the nodular zone accelerated both aberrant Purkinje neuron spiking and neurodegeneration. These findings reinforce the central role for Cic in SCA1 cerebellar pathophysiology and suggest that only modest reductions in Cic are needed to have profound therapeutic impact in SCA1

Assessment of Initial Vancomycin Dosing in Pediatric Oncology Patients

This was a retrospective audit assessing vancomycin dosing of 60 mg/kg/day in the attainment of therapeutic concentrations between 10–20 mcg/mL among 56 pediatric oncology patients. Twelve patients (21%) achieved therapeutic concentrations of 10–20 mcg/mL, while 44 patients (79%) obtained trough levels below 10 mcg/mL despite the addition of nephrotoxic agents

Assessment of Initial Vancomycin Dosing in Pediatric Oncology Patients

This was a retrospective audit assessing vancomycin dosing of 60 mg/kg/day in the attainment of therapeutic concentrations between 10–20 mcg/mL among 56 pediatric oncology patients. Twelve patients (21%) achieved therapeutic concentrations of 10–20 mcg/mL, while 44 patients (79%) obtained trough levels below 10 mcg/mL despite the addition of nephrotoxic agents

Context-dependent effects of shifting large herbivore assemblages on plant structure and diversity

Despite wide recognition of the importance of anthropogenically driven changes in large herbivore communities—including both declines in wildlife and increases in livestock—there remain large gaps in our knowledge about the impacts of these changes on plant communities, particularly when combined with concurrent changes in climate. Considering these prominent forms of global change in tandem enables us to better understand controls on savanna vegetation structure and diversity under real-world conditions.We conducted a field experiment using complete and semi-permeable herbivore exclosures to explore the difference in plant communities among sites with wild herbivores only, with cattle in addition to wild herbivores, and with no large herbivores. To understand variation in effects across climatic contexts, the experiment was replicated at three locations along a topoclimatic gradient in California. Critically, this is the first such experiment to compare cattle and wildlife impacts along an environmental gradient within a single controlled experiment.Vegetation structure responded strongly to herbivore treatment regardless of climate. Relative to the isolated effects of wildlife, exclusion of all large herbivores generally increased structural components related to cover and above-ground biomass while the addition of cattle led to reductions in vegetation cover, litter, shading and standing biomass. Furthermore, wildlife had a consistent neutral or positive effect on plant diversity, while the effect of livestock addition was context dependent. Cattle had a neutral to strongly negative effect at low aridity, but a positive effect at high aridity. These results suggest that (a) herbivore effects can override climate effects on vegetation structure, (b) cattle addition can drive different effects on diversity and (c) herbivore effects on diversity are modulated by climate.Synthesis. Our results illustrate very distinctive shifts in plant communities between two realistic forms of change in ungulate herbivore assemblages—livestock addition and large herbivore losses—particularly for plant diversity responses, and that these responses vary across climatic contexts. This finding has important implications for the management and protection of plant biodiversity given that over a quarter of the Earth’s land area is managed for livestock and climate regimes are changing globally.Our results illustrate very distinctive shifts in plant communities between two realistic forms of change in ungulate herbivore assemblages—livestock addition and large herbivore losses—particularly for plant diversity responses, and that these responses vary across climatic contexts. This finding has important implications for the management and protection of plant biodiversity given that over a quarter of the Earth’s land area is managed for livestock and climate regimes are changing globally.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/173033/1/jec13871.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/173033/2/jec13871-sup-0001-Supinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/173033/3/jec13871_am.pd

Table S7 - Geographic range codings from Migration in the Anthropocene: how collective navigation, environmental system and taxonomy shape the vulnerability of migratory species

Table with all species, literature, and geographic range information used to create Figure 3