Elevated expression of endogenous glial cell line-derived neurotrophic factor impairs spatial memory performance and raises inhibitory tone in the hippocampus

Parvalbumin-positive interneurons (PV+) are a key component of inhibitory networks in the brain and are known to modulate memory and learning by shaping network activity. The mechanisms of PV+ neuron generation and maintenance are not fully understood, yet current evidence suggests that signalling via the glial cell line-derived neurotrophic factor (GDNF) receptor GFR alpha 1 positively modulates the migration and differentiation of PV+ interneurons in the cortex. Whether GDNF also regulates PV+ cells in the hippocampus is currently unknown. In this study, we utilized a Gdnf "hypermorph" mouse model where GDNF is overexpressed from the native gene locus, providing greatly increased spatial and temporal specificity of protein expression over established models of ectopic expression. Gdnf(wt/hyper) mice demonstrated impairments in long-term memory performance in the Morris water maze test and an increase in inhibitory tone in the hippocampus measured electrophysiologically in acute brain slice preparations. Increased PV+ cell number was confirmed immunohistochemically in the hippocampus and in discrete cortical areas and an increase in epileptic seizure threshold was observed in vivo. The data consolidate prior evidence for the actions of GDNF as a regulator of PV+ cell development in the cortex and demonstrate functional effects upon network excitability via modulation of functional GABAergic signalling and under epileptic challenge.Peer reviewe

Compliance with Positive Airway Pressure Treatment for Obstructive Sleep Apnea

ObjectivesPositive airway pressure (PAP) is considered a standard treatment for moderate-to-severe obstructive sleep apnea (OSA) patients. However, compliance with PAP treatment is suboptimal because of several types of discomfort experienced by patients. This study investigated compliance with PAP therapy, and affecting factors for such compliance, in OSA patients.MethodsWe performed a survey on 69 patients who engaged in PAP therapy between December 2006 and November 2007. After diagnostic polysomnography and manual titration, patients trialed PAP using the ResMed instrument and explored autoadjusting PAP (APAP), continuous PAP (CPAP), and flexible PAP (using expiratory pressure relief [EPR]) at least once every week for 1 month. Compliance measures were mean daily use (hr), percentage of days on which PAP was used, and percentage of days on which PAP was used for >4 hr. Data were obtained at night using the software Autoscan version 5.7® of the ResMed Inc. We obtained data on anthropometric (age, BMI, neck circumflex, Epworth sleepiness scale, Pittsburgh Sleep Quality Index, hypertension, alcohol intake), polysomnographic data (severity of apnea-hypopnea index [AHI], proportion of nonsupine sleep time, position dependence of sleep), PAP mode and AHI during PAP use for affecting factors.ResultsAfter 1 month, 41 of the 69 patients (59.4%) were pleased with PAP therapy and purchased instruments. Twenty-four patients (34.7%) used PAP for more than 3 months. The percentage of days on which PAP was used was statistically higher in patients with hypertension than in normotensive patients (P=0.003). There were negative correlations 1) between nonsupine position sleep time and percentage of days on which PAP was used (r=-0.424, P=0.039), and 2) between the AHI during PAP use and the percentage of days on which PAP was used for >4 hr (r=-0.443, P=0.030). There were no statistical differences between AHI, BMI, PAP pressure, or other measured parameters, on the one hand, and compliance, on the other.ConclusionThe affecting factors for PAP use were hypertension history, sleep posture (shorter nonsupine sleep time), and lower AHI during PAP use

Temperature Influences Herbivory and Algal Biomass in the Galápagos Islands

Temperature can influence trophic interactions via predictable effects on the metabolism of ecothermic consumers. Under some conditions, warming should increase top–down control, and trophic transfer rates, leading to declines in prey populations. We tested this prediction in the Galápagos Islands, an equatorial upwelling region, where water temperatures are highly variable and nutrient availability is thought to control primary production and standing algal biomass. We used grazing assays, field surveys, and a herbivore exclusion experiment to test the hypothesis that grazing rate and algal biomass are, in part, regulated by temperature via the temperature–dependence of herbivory. Grazing rates were greater during the warm season for urchins and other consumers (including fishes, turtles, and iguanas). Field surveys at 10 sites over 5 years found that temperature was strongly negatively related to macroalgal cover. The results of the exclusion experiment indicate that herbivores had a large effect on macroalgal biomass, even during intense upwelling. Our results suggest that in shallow subtidal habitats across the Galápagos archipelago, grazing pressure increases with temperature, potentially resulting in reduced algal biomass when upwelling is weak and greater algal biomass when upwelling is strong and water is cold; an alternative explanation for widely observed association between upwelling intensity and algal biomass

Social research on neglected diseases of poverty: Continuing and emerging themes

Copyright: © 2009 Manderson et al.Neglected tropical diseases (NTDs) exist and persist for social and economic reasons that enable the vectors and pathogens to take advantage of changes in the behavioral and physical environment. Persistent poverty at household, community, and national levels, and inequalities within and between sectors, contribute to the perpetuation and re-emergence of NTDs. Changes in production and habitat affect the physical environment, so that agricultural development, mining and forestry, rapid industrialization, and urbanization all result in changes in human uses of the environment, exposure to vectors, and vulnerability to infection. Concurrently, political instability and lack of resources limit the capacity of governments to manage environments, control disease transmission, and ensure an effective health system. Social, cultural, economic, and political factors interact and influence government capacity and individual willingness to reduce the risks of infection and transmission, and to recognize and treat disease. Understanding the dynamic interaction of diverse factors in varying contexts is a complex task, yet critical for successful health promotion, disease prevention, and disease control. Many of the research techniques and tools needed for this purpose are available in the applied social sciences. In this article we use this term broadly, and so include behavioral, population and economic social sciences, social and cultural epidemiology, and the multiple disciplines of public health, health services, and health policy and planning. These latter fields, informed by foundational social science theory and methods, include health promotion, health communication, and heath education

Range dynamics of small mammals along an elevational gradient over an 80-year interval

One expected response to observed global warming is an upslope shift of species elevational ranges. Here, we document changes in the elevational distributions of the small mammals within the Ruby Mountains in northeastern Nevada over an 80-year interval. We quantified range shifts by comparing distributional records from recent comprehensive field surveys (2006–2008) to earlier surveys (1927–1929) conducted at identical and nearby locations. Collector field notes from the historical surveys provided detailed trapping records and locality information, and museum specimens enabled confirmation of species' identifications. To ensure that observed shifts in range did not result from sampling bias, we employed a binomial likelihood model (introduced here) using likelihood ratios to calculate confidence intervals around observed range limits. Climate data indicate increases in both precipitation and summer maximum temperature between sampling periods. Increases in winter minimum temperatures were only evident at mid to high elevations. Consistent with predictions of change associated with climate warming, we document upslope range shifts for only two mesic-adapted species. In contrast, no xeric-adapted species expanded their ranges upslope. Rather, they showed either static distributions over time or downslope contraction or expansion. We attribute these unexpected findings to widespread land-use driven habitat change at lower elevations. Failure to account for land-use induced changes in both baseline assessments and in predicting shifts in species distributions may provide misleading objectives for conservation policies and management practices.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78655/1/j.1365-2486.2009.02150.x.pd

Oceanography and life history predict contrasting genetic population structure in two Antarctic fish species

Understanding the key drivers of population connectivity in the marine environment is essential for the effective management of natural resources. Although several different approaches to evaluating connectivity have been used, they are rarely integrated quantitatively. Here, we use a ‘seascape genetics’ approach, by combining oceanographic modelling and microsatellite analyses, to understand the dominant influences on the population genetic structure of two Antarctic fishes with contrasting life histories, Champsocephalus gunnari and Notothenia rossii. The close accord between the model projections and empirical genetic structure demonstrated that passive dispersal during the planktonic early life stages is the dominant influence on patterns and extent of genetic structuring in both species. The shorter planktonic phase of C. gunnari restricts direct transport of larvae between distant populations, leading to stronger regional differentiation. By contrast, geographic distance did not affect differentiation in N. rossii, whose longer larval period promotes long-distance dispersal. Interannual variability in oceanographic flows strongly influenced the projected genetic structure, suggesting that shifts in circulation patterns due to climate change are likely to impact future genetic connectivity and opportunities for local adaptation, resilience and recovery from perturbations. Further development of realistic climate models is required to fully assess such potential impacts

Genetic correlations between adults and larvae in a marine fish: potential effects of fishery selection on population replenishment

Correlated genetic responses have been hypothesized as important components of fishery-induced evolution, although predictive data from wild populations have been difficult to obtain. Here, we demonstrate substantial genetic correlations between a trait often subjected to fishery selection (adult body length) and traits that affect survival of larvae (length and swimming performance) in a wild population of a marine fish (bicolor damselfish, Stegastes partitus). Through both genetic covariance and size-dependent maternal effects, selection on adult size may cause a considerable, correlated response in larval traits. To quantify how variation in larval traits may affect survival, we introduce a flexible method that uses information from selection measurements to account for frequency dependence and estimate the relationship between phenotype and relative survival across a broad range of phenotypic values. Using this method, we synthesize studies of selective mortality on larval size for eight species of fish and show that variation in larval size may result in considerable variation in larval survival. We predict that observed rates of fishery selection on adult marine fishes may substantially reduce larval size and survival. The evolution of smaller larvae in response to fishery selection may therefore have substantial consequences for the viability of fished populations

Inhibition of Myostatin Signaling through Notch Activation following Acute Resistance Exercise

Myostatin is a TGFb family member and negative regulator of muscle size. Due to the complexity of the molecular pathway between myostatin mRNA/protein and changes in transcription, it has been difficult to understand whether myostatin plays a role in resistance exercise-induced skeletal muscle hypertrophy. To circumvent this problem, we determined the expression of a unique myostatin target gene, Mighty, following resistance exercise. Mighty mRNA increased by 6 h (82.9624.21%) and remained high out to 48 h (56.5619.67%) after resistance exercise. Further examination of the soleus, plantaris and tibialis anterior muscles showed that the change in Mighty mRNA at 6 h correlated with the increase in muscle size associated with this protocol (R2 = 0.9996). The increase in Mighty mRNA occurred both independent of Smad2 phosphorylation and in spite of an increase in myostatin mRNA (341.86147.14% at 3 h). The myostatin inhibitor SKI remained unchanged. However, activated Notch, another potential inhibitor of TGFb signaling, increased immediately following resistance exercise (83611.2%) and stayed elevated out to 6 h (78616.6%). Electroportion of the Notch intracellular domain into the tibialis anterior resulted in an increase in Mighty mRNA (63613.4%) that was equivalent to the canonical Notch target HES-1 (94.467.32%). These data suggest that acute resistance exercise decreases myostatin signaling through the activation of the TGFb inhibitor Notch resulting in a decrease in myostatin transcriptional activity that correlates well with muscle hypertrophy

Development and psychometric properties the Barriers to Access to Care Evaluation scale (BACE) related to people with mental ill health

Many people with mental illness do not seek or delay seeking care. This study aimed to develop, and provide an initial validation of, a comprehensive measure for assessing barriers to access to mental health care including a 'treatment stigma' subscale, and to present preliminary evidence about the prevalence of barriers experienced by adults currently or recently using secondary mental health services in the UK