Elevated Pressure Increases Ca2+ Influx Through AMPA Receptors in Select Populations of Retinal Ganglion Cells

The predominate type of AMPA receptor expressed in the CNS is impermeable to Ca2+ (CI-AMPAR). However, some AMPA receptors are permeable to Ca2+ (CP-AMPAR) and play important roles in development, plasticity and disease. In the retina, ganglion cells (RGCs) are targets of disease including glaucoma and diabetic retinopathy, but there are many types of RGCs and not all types are targeted equally. In the present study, we sought to determine if there are differences in expression of AMPARs amongst RGC subtypes, and if these differences might contribute to differential vulnerability in a model of stress. Using cultured RGCs we first show that acute exposure to elevated pressure increased expression of Ca2+-permeable AMPA receptors (CP-AMPARs) in some, but not all classes of RGCs. When RGCs were sampled without regard to subtype, AMPA currents, measured using patch clamp recording, were blocked by the CP-AMPAR blocker PhTX-74 to a greater extent in pressure-treated RGCs vs. control. Furthermore, imaging experiments revealed an increase in Ca2+ influx during AMPA application in pressure-treated RGCs. However, examination of specific RGC subtypes using reporter lines revealed striking differences in both baseline AMPAR composition and modulation of this baseline composition by stress. Notably, ON alpha RGCs identified using the Opn4 mouse line and immunohistochemistry, had low expression of CP-AMPARs. Conversely, an ON-OFF direction selective RGC and putative OFF alpha RGC each expressed high levels of CP-AMPARs. These differences between RGC subtypes were also observed in RGCs from whole retina. Elevated pressure further lowered expression of CP-AMPARs in ON alpha RGCs, but raised expression in ON-OFF and OFF RGCs. Changes in CP-AMPAR expression following challenge with elevated pressure were correlated with RGC survival: ON alpha RGCs were unaffected by application of pressure, while the number of putative OFF alpha RGCs declined by approximately 50% following challenge with pressure. Differences in expression of CP-AMPARs between RGC subtypes may form the underpinnings for subtype-specific synaptic plasticity. Furthermore, the differential responses of these RGC subtypes to elevated pressure may contribute to the reported resistance of ON alpha, and susceptibility of OFF and ON-OFF RGCs to injury in models of glaucoma

Atlanta Youth Count 2018 Community Report: The Prevalence of Sex and Labor Trafficking Among Homeless Youth in Metro Atlanta

The 2018 Atlanta Youth Count (AYC18) was a follow-up study to the 2015 Atlanta Youth Count and Needs Assessment (AYCNA), expanded in 2018 to specifically address sex and labor trafficking among youth experiencing homelessness in metro Atlanta. The goals of this project were to: 1) provide metro Atlanta service providers, policymakers, and youth advocates with practical information on the size, nature, and needs of the homeless, precariously housed, and runaway youth in our community who are involved in various forms of sex and labor trafficking; 2) collect information that can be used to develop and refine policies, programs, and interventions to help these youth in our community; and 3) encourage a community-wide dialogue about the needs and social determinants of youth homelessness and human trafficking. This study was funded by the National Institute of Justice and was conducted in partnership with local service providers, advocates, researchers, and students. This document is the official public Human Trafficking Report and provides an overview of the study methodology and key findings, including the research team’s official estimates of the prevalence of trafficking among homeless youth in metro Atlanta, as well as a description of key characteristics of the population derived from the survey data collected. Members of the research team are continuing to analyze and use the data to improve the public’s and policymakers’ understanding of youth homelessness and trafficking and to guide community - based efforts to improve services for these young people

Ca2+ Sensor Synaptotagmin-1 Mediates Exocytosis in Mammalian Photoreceptors

To encode light-dependent changes in membrane potential, rod and cone photoreceptors utilize synaptic ribbons to sustain continuous exocytosis while making rapid, fine adjustments to release rate. Release kinetics are shaped by vesicle delivery down ribbons and by properties of exocytotic Ca2+ sensors. We tested the role for synaptotagmin-1 (Syt1) in photoreceptor exocytosis by using novel mouse lines in which Syt1 was conditionally removed from rods or cones. Photoreceptors lacking Syt1 exhibited marked reductions in exocytosis as measured by electroretinography and single-cell recordings. Syt1 mediated all evoked release in cones, whereas rods appeared capable of some slow Syt1-independent release. Spontaneous release frequency was unchanged in cones but increased in rods lacking Syt1. Loss of Syt1 did not alter synaptic anatomy or reduce Ca2+ currents. These results suggest that Syt1 mediates both phasic and tonic release at photoreceptor synapses, revealing unexpected flexibility in the ability of Syt1 to regulate Ca2+-dependent synaptic transmission

Human development and climate affect hibernation in a large carnivore with implications for human–carnivore conflicts

1. Expanding human development and climate change are dramatically altering habitat conditions for wildlife. While the initial response of wildlife to changing environmental conditions is typically a shift in behavior, little is known about the effects of these stressors on hibernation behavior, an important life-history trait that can subsequently affect animal physiology, demography, interspecific interactions and human-wildlife interactions. Given future trajectories of land use and climate change, it is important that wildlife professionals understand how animals that hibernate are adapting to altered landscape conditions so that management activities can be appropriately tailored. 2. We investigated the influence of human development and weather on hibernation in black bears (Ursus americanus), a species of high management concern, whose behavior is strongly tied to natural food availability, anthropogenic foods around development and variation in annual weather conditions. Using GPS collar data from 131 den events of adult female bears (n = 51), we employed fine-scale, animal-specific habitat information to evaluate the relative and cumulative influence of natural food availability, anthropogenic food and weather on the start, duration and end of hibernation. 3. We found that weather and food availability (both natural and human) additively shaped black bear hibernation behavior. Of the habitat variables we examined, warmer temperatures were most strongly associated with denning chronology, reducing the duration of hibernation and expediting emergence in the spring. Bears appeared to respond to natural and anthropogenic foods similarly, as more natural foods, and greater use of human foods around development, both postponed hibernation in the fall and decreased its duration. 4. Synthesis and applications. Warmer temperatures and use of anthropogenic food subsides additively reduced black bear hibernation, suggesting that future changes in climate and land use may further alter bear behavior and increase the length of their active season. We speculate that longer active periods for bears will result in subsequent increases in human–bear conflicts and human-caused bear mortalities. These metrics are commonly used by wildlife agencies to index trends in bear populations, but have the potential to be misleading when bear behavior dynamically adapts to changing environmental conditions, and should be substituted with reliable demographic methods

Sediment, Nutrient, and Bacterial Runoff from Biosolids and Mineral Fertilizer Applied to a Mixed Cool- and Native Warm-Season Grassland in the Ozark Mountains

Rainfall simulations were conducted within mixed (cool- and native warm-season) grasslands in the sloping, rocky soils typical of the Ozark Mountains region to estimate nutrient and bacteria levels in runoff from biosolids and mineral fertilizer (MF). The ability of narrow (1 m) vegetated filter strips (VFS) to reduce losses was evaluated. Experiment 1 included an untreated control (C); 37 kg plant available nitrogen (PAN) ha−1 from biosolids applied to the upslope half of the plot with the downslope half serving as a VFS (LBF); 74 kg PAN ha−1 from biosolids, with VFS (HBF); and a uniform biosolids application at the lower rate and no VFS (LBU). Experiment 2 examined runoff from MF applied at 89 kg ammoniacal nitrogen (NH4-N) ha−1 and 147 kg phosphorous (P) ha−1 over the whole plot (MFW) or only on the upslope half (with VFS) (MFF). No significant differences were detected among mean fecal coliform levels despite large differences in magnitude. Losses of NH4-N and P were greater for LBU than for LBF. Although only marginally significant (P=0.058), total phosphorous contained in runoff was nearly three times higher in MFW than in MFF. Results of this study suggest that even a small VFS can potentially reduce nutrient levels in runoff

Modeling Progressive Fibrosis with Pluripotent Stem Cells Identifies an Anti-fibrotic Small Molecule.

Progressive organ fibrosis accounts for one-third of all deaths worldwide, yet preclinical models that mimic the complex, progressive nature of the disease are lacking, and hence, there are no curative therapies. Progressive fibrosis across organs shares common cellular and molecular pathways involving chronic injury, inflammation, and aberrant repair resulting in deposition of extracellular matrix, organ remodeling, and ultimately organ failure. We describe the generation and characterization of an in vitro progressive fibrosis model that uses cell types derived from induced pluripotent stem cells. Our model produces endogenous activated transforming growth factor β (TGF-β) and contains activated fibroblastic aggregates that progressively increase in size and stiffness with activation of known fibrotic molecular and cellular changes. We used this model as a phenotypic drug discovery platform for modulators of fibrosis. We validated this platform by identifying a compound that promotes resolution of fibrosis in in vivo and ex vivo models of ocular and lung fibrosis

Effectiveness and efficiency of methods of dialysis therapy for end-stage renal disease : a review

Peer reviewedPublisher PD

Conservative interventions for urinary incontinence in women: an overview of Cochrane systematic reviews

This is the protocol for a review and there is no abstract. The objectives are as follows:  To synthesise Cochrane reviews of conservative interventions, as described above, for the prevention or treatment of female urinary incontinence.Output Type: Protoco

Systematic review and economic modelling of the effectiveness and cost-effectiveness of non-surgical treatments for women with stress urinary incontinence

Peer reviewedPublisher PD