Frequency of extreme Sahelian storms tripled since 1982 in satellite observations

The hydrological cycle is expected to intensify under global warming, with studies reporting more frequent extreme rain events in many regions of the world, and predicting increases in future flood frequency. Such early, predominantly mid-latitude observations are essential because of shortcomings within climate models in their depiction of convective rainfall. A globally important group of intense storms—mesoscale convective systems (MCSs)—poses a particular challenge, because they organize dynamically on spatial scales that cannot be resolved by conventional climate models. Here, we use 35 years of satellite observations from the West African Sahel to reveal a persistent increase in the frequency of the most intense MCSs. Sahelian storms are some of the most powerful on the planet, and rain gauges in this region have recorded a rise in ‘extreme’ daily rainfall totals. We find that intense MCS frequency is only weakly related to the multidecadal recovery of Sahel annual rainfall, but is highly correlated with global land temperatures. Analysis of trends across Africa reveals that MCS intensification is limited to a narrow band south of the Sahara desert. During this period, wet-season Sahelian temperatures have not risen, ruling out the possibility that rainfall has intensified in response to locally warmer conditions. On the other hand, the meridional temperature gradient spanning the Sahel has increased in recent decades, consistent with anthropogenic forcing driving enhanced Saharan warming. We argue that Saharan warming intensifies convection within Sahelian MCSs through increased wind shear and changes to the Saharan air layer. The meridional gradient is projected to strengthen throughout the twenty-first century, suggesting that the Sahel will experience particularly marked increases in extreme rain. The remarkably rapid intensification of Sahelian MCSs since the 1980s sheds new light on the response of organized tropical convection to global warming, and challenges conventional projections made by general circulation models

Human pancreatic islet transplantation: an update and description of the establishment of a pancreatic islet isolation laboratory

Type 1 diabetes mellitus (T1DM) is associated with chronic complications that lead to high morbidity and mortality rates in young adults of productive age. Intensive insulin therapy has been able to reduce the likelihood of the development of chronic diabetes complications. However, this treatment is still associated with an increased incidence of hypoglycemia. In patients with "brittle T1DM", who have severe hypoglycemia without adrenergic symptoms (hypoglycemia unawareness), islet transplantation may be a therapeutic option to restore both insulin secretion and hypoglycemic perception. The Edmonton group demonstrated that most patients who received islet infusions from more than one donor and were treated with steroid-free immunosuppressive drugs displayed a considerable decline in the initial insulin independence rates at eight years following the transplantation, but showed permanent C-peptide secretion, which facilitated glycemic control and protected patients against hypoglycemic episodes. Recently, data published by the Collaborative Islet Transplant Registry (CITR) has revealed that approximately 50% of the patients who undergo islet transplantation are insulin independent after a 3-year follow-up. Therefore, islet transplantation is able to successfully decrease plasma glucose and HbA1c levels, the occurrence of severe hypoglycemia, and improve patient quality of life. The goal of this paper was to review the human islet isolation and transplantation processes, and to describe the establishment of a human islet isolation laboratory at the Endocrine Division of the Hospital de Clínicas de Porto Alegre - Rio Grande do Sul, Brazil

Very extreme seasonal precipitation in the NARCCAP ensemble: model performance and projections

Seasonal extreme daily precipitation is analyzed in the ensemble of NARCAPP regional climate models. Significant variation in these models' abilities to reproduce observed precipitation extremes over the contiguous United States is found. Model performance metrics are introduced to characterize overall biases, seasonality, spatial extent and the shape of the precipitation distribution. Comparison of the models to gridded observations that include an elevation correction is found to be better than to gridded observations without this correction. A complicated model weighting scheme based on model performance in simulating observations is found to cause significant improvements in ensemble mean skill only if some of the models are poorly performing outliers. The effect of lateral boundary conditions are explored by comparing the integrations driven by reanalysis to those driven by global climate models. Projected mid-century future changes in seasonal precipitation means and extremes are presented and discussions of the sources of uncertainty and the mechanisms causing these changes are presented. © 2012 The Author(s)

The role of horizontal resolution in simulating drivers of the global hydrological cycle

The role of atmospheric general circulation model (AGCM) horizontal resolution in representing the global energy budget and hydrological cycle is assessed, with the aim of improving the understanding of model uncertainties in simulating the hydrological cycle. We use two AGCMs from the UK Met Office Hadley Centre: HadGEM1-A at resolutions ranging from 270 to 60 km, and HadGEM3-A ranging from 135 to 25 km. The models exhibit a stable hydrological cycle, although too intense compared to reanalyses and observations. This over-intensity is explained by excess surface shortwave radiation, a common error in general circulation models (GCMs). This result is insensitive to resolution. However, as resolution is increased, precipitation decreases over the ocean and increases over the land. This is associated with an increase in atmospheric moisture transport from ocean to land, which changes the partitioning of moisture fluxes that contribute to precipitation over land from less local to more non-local moisture sources. The results start to converge at 60-km resolution, which underlines the excessive reliance of the mean hydrological cycle on physical parametrization (local unresolved processes) versus model dynamics (large-scale resolved processes) in coarser HadGEM1 and HadGEM3 GCMs. This finding may be valid for other GCMs, showing the necessity to analyze other chains of GCMs that may become available in the future with such a range of horizontal resolutions. Our finding supports the hypothesis that heterogeneity in model parametrization is one of the underlying causes of model disagreement in the Coupled Model Intercomparison Project (CMIP) exercises

The genetic legacy of extreme exploitation in a polar vertebrate

Understanding the effects of human exploitation on the genetic composition of wild populations is important for predicting species persistence and adaptive potential. We therefore investigated the genetic legacy of large-scale commercial harvesting by reconstructing, on a global scale, the recent demographic history of the Antarctic fur seal (Arctocephalus gazella), a species that was hunted to the brink of extinction by 18th and 19th century sealers. Molecular genetic data from over 2,000 individuals sampled from all eight major breeding locations across the species’ circumpolar geographic distribution, show that at least four relict populations around Antarctica survived commercial hunting. Coalescent simulations suggest that all of these populations experienced severe bottlenecks down to effective population sizes of around 150–200. Nevertheless, comparably high levels of neutral genetic variability were retained as these declines are unlikely to have been strong enough to deplete allelic richness by more than around 15%. These findings suggest that even dramatic short-term declines need not necessarily result in major losses of diversity, and explain the apparent contradiction between the high genetic diversity of this species and its extreme exploitation history

Modeling rare gene variation to gain insight into the oldest biomarker in autism: construction of the serotonin transporter Gly56Ala knock-in mouse

Alterations in peripheral and central indices of serotonin (5-hydroxytryptamine, 5-HT) production, storage and signaling have long been associated with autism. The 5-HT transporter gene (HTT, SERT, SLC6A4) has received considerable attention as a potential risk locus for autism-spectrum disorders, as well as disorders with overlapping symptoms, including obsessive-compulsive disorder (OCD). Here, we review our efforts to characterize rare, nonsynonymous polymorphisms in SERT derived from multiplex pedigrees carrying diagnoses of autism and OCD and present the initial stages of our effort to model one of these variants, Gly56Ala, in vivo. We generated a targeting vector to produce the Gly56Ala substitution in the Slc6a4 locus by homologous recombination. Following removal of a neomycin resistance selection cassette, animals exhibiting germline transmission of the Ala56 variant were bred to establish a breeding colony on a 129S6 background, suitable for initial evaluation of biochemical, physiological and behavioral alterations relative to SERT Gly56 (wildtype) animals. SERT Ala56 mice were achieved and exhibit a normal pattern of transmission. The initial growth and gross morphology of these animals is comparable to wildtype littermate controls. The SERT Ala56 variant can be propagated in 129S6 mice without apparent disruption of fertility and growth. We discuss both the opportunities and challenges that await the physiological/behavioral analysis of Gly56Ala transgenic mice, with particular reference to modeling autism-associated traits

The importance of the cellular stress response in the pathogenesis and treatment of type 2 diabetes

Organisms have evolved to survive rigorous environments and are not prepared to thrive in a world of caloric excess and sedentary behavior. A realization that physical exercise (or lack of it) plays a pivotal role in both the pathogenesis and therapy of type 2 diabetes mellitus (t2DM) has led to the provocative concept of therapeutic exercise mimetics. A decade ago, we attempted to simulate the beneficial effects of exercise by treating t2DM patients with 3 weeks of daily hyperthermia, induced by hot tub immersion. The short-term intervention had remarkable success, with a 1 % drop in HbA1, a trend toward weight loss, and improvement in diabetic neuropathic symptoms. An explanation for the beneficial effects of exercise and hyperthermia centers upon their ability to induce the cellular stress response (the heat shock response) and restore cellular homeostasis. Impaired stress response precedes major metabolic defects associated with t2DM and may be a near seminal event in the pathogenesis of the disease, tipping the balance from health into disease. Heat shock protein inducers share metabolic pathways associated with exercise with activation of AMPK, PGC1-a, and sirtuins. Diabetic therapies that induce the stress response, whether via heat, bioactive compounds, or genetic manipulation, improve or prevent all of the morbidities and comorbidities associated with the disease. The agents reduce insulin resistance, inflammatory cytokines, visceral adiposity, and body weight while increasing mitochondrial activity, normalizing membrane structure and lipid composition, and preserving organ function. Therapies restoring the stress response can re-tip the balance from disease into health and address the multifaceted defects associated with the disease

Parkinson’s disease mouse models in translational research

Animal models with high predictive power are a prerequisite for translational research. The closer the similarity of a model to Parkinson’s disease (PD), the higher is the predictive value for clinical trials. An ideal PD model should present behavioral signs and pathology that resemble the human disease. The increasing understanding of PD stratification and etiology, however, complicates the choice of adequate animal models for preclinical studies. An ultimate mouse model, relevant to address all PD-related questions, is yet to be developed. However, many of the existing models are useful in answering specific questions. An appropriate model should be chosen after considering both the context of the research and the model properties. This review addresses the validity, strengths, and limitations of current PD mouse models for translational research