Project description:An emerging argument is that since humans can readily adapt to changing climatic conditions, there is less need to pursue aggressive emissions mitigation strategies. As temperature adaptation is a function of repeated exposure over time, we need empirical approaches that can depict individuals' temperature history to rigorously examine this claim. Using a longitudinal dataset representative of China, we construct lifetime temperature exposure unique to each individual based on their birth-dates, birth-locations, and movement history. We show that a 1°C increase in individualized temperature anomalies cause a 2% decrease in 1 standard deviation (S.D.) of well-being, where most of the impacts are driven by "hotter-than-expected" weather. In turn, while the adverse impacts of future temperature changes wane after accommodating for adaptation, acclimatization is unlikely to keep pace with future temperature increases except in the net-zero emissions scenario, indicating that stringent greenhouse gas (GHG) emissions cuts are still needed even in this less-pessimistic scenario.
Project description:The persistence of species may depend upon their capacity to keep pace with climate change. However, dispersal has been ignored in the vast majority of studies that aimed at estimating and predicting range shifts as a response to climate change. Long distance dispersal (LDD) in particular might promote rapid range shifts and allow species to track suitable habitat. Many aquatic plant species are dispersed by birds and have the potential to be dispersed over hundreds of kilometers during the bird migration seasons. I argue that such dispersal potential might be critical to allow species to track climate change happening at unprecedented high rates. As a case study, I used dispersal data from three aquatic plant species dispersed by migratory birds to model range shifts in response to climate change projections. By comparing four dispersal scenarios - (1) no dispersal, (2) unlimited dispersal, (3) LDD < 100 km, and (4) LDD mediated by bird migratory movements -, it was shown that, for bird-mediated dispersal, the rate of colonization is sufficient to counterbalance the rate of habitat loss. The estimated rates of colonization (3.2-31.5 km⋅year-1) are higher than, for example, the rate of global warming (previously estimated at 0.42 km⋅year-1). Although further studies are needed, the results suggest that these aquatic plant species can adjust their ranges under a severe climate change scenario. Therefore, investigating the dispersal capacity of species, namely their LDD potential, may contribute to estimate the likelihood of species to keep pace with climate change.
Project description:This multi-center study will compare multi-target DNA and quantitative FIT stool-based testing to colonoscopy in individuals with Cystic Fibrosis (CF) undergoing colon cancer screening with colonoscopy. The primary endpoint is detection of any adenomas, including advanced adenomas and colorectal cancer (CRC).
Project description:Despite the known benefits of a healthy lifestyle, many individuals find it hard to maintain such a lifestyle in our modern world, which facilitates sedentary behavior and overeating. As a consequence, the prevalence of type 2 diabetes mellitus is predicted to increase dramatically over the coming years. Will developments in treatments be able to counteract the resulting impact on morbidity and mortality? The various lines of research can be grouped into three main categories: technological, biological, and pharmacological. Technological solutions are focused on the delivery of insulin and glucagon via an artificial pancreas, and components of the system are already in use, suggesting this option may well be available within the next 10 years. Of the biological solutions, pancreas transplants seem unlikely to be used widely, and islet cell transplants have also been hampered by a lack of appropriate donor tissue and graft survival after transplant. However, significant progress has been made in these areas, and additional research suggests manipulating other cell types to replace beta cells may be a viable option in the longer term. The last category, pharmacological research, appears the most promising for significantly reducing the burden of type 2 diabetes mellitus. In recent years, research has concentrated on reducing blood glucose, and the increasing pace of research has been reflected in a growing number of antidiabetic agents. In the past few years, studies of the complementary approach of protecting cells from the damaging effects of high blood glucose have also been reported, as has research into the control of energy intake and energy expenditure. Evidence from studies of dietary restriction and bariatric surgery suggests it may be possible to reset metabolism to effectively cure diabetes, and research into pharmacological agents that could selectively restore energy balance is currently the most exciting prospect for future treatments for people with type 2 diabetes mellitus.
Project description:Future climate change is predicted to advance faster than the postglacial warming. Migration may therefore become a key driver for future development of biodiversity and ecosystem functioning. For 140 European plant species we computed past range shifts since the last glacial maximum and future range shifts for a variety of Intergovernmental Panel on Climate Change (IPCC) scenarios and global circulation models (GCMs). Range shift rates were estimated by means of species distribution modelling (SDM). With process-based seed dispersal models we estimated species-specific migration rates for 27 dispersal modes addressing dispersal by wind (anemochory) for different wind conditions, as well as dispersal by mammals (dispersal on animal's coat - epizoochory and dispersal by animals after feeding and digestion - endozoochory) considering different animal species. Our process-based modelled migration rates generally exceeded the postglacial range shift rates indicating that the process-based models we used are capable of predicting migration rates that are in accordance with realized past migration. For most of the considered species, the modelled migration rates were considerably lower than the expected future climate change induced range shift rates. This implies that most plant species will not entirely be able to follow future climate-change-induced range shifts due to dispersal limitation. Animals with large day- and home-ranges are highly important for achieving high migration rates for many plant species, whereas anemochory is relevant for only few species.
Project description:This study utilizes morphological and mechanistic endpoints to characterize the onset of bilateral atresia of the vas deferens in a recently derived cystic fibrosis (CF) rat model. Embryonic reproductive structures, including Wolffian (mesonephric) duct, Mullerian (paramesonephric) duct, mesonephric tubules, and gonad, were shown to mature normally through late embryogenesis, with involution of the vas deferens and/or epididymis typically occurring between birth and postnatal day 4 (P4), although timing and degree of atresia varied. No evidence of mucus obstruction, which is associated with pathology in other CF-affected tissues, was observed at any embryological or postnatal time point. Reduced epididymal coiling was noted post-partum and appeared to coincide with, or predate, loss of more distal vas deferens structure. Remarkably, α smooth muscle actin expression in cells surrounding duct epithelia was markedly diminished in CF animals by P2.5 when compared to wild type counterparts, indicating reduced muscle development. RNA-seq and immunohistochemical analysis of affected tissues showed disruption of developmental signaling by Wnt and related pathways. The findings have relevance to vas deferens loss in humans with CF, where timing of ductular damage is not well characterized and underlying mechanisms are not understood. If vas deferens atresia in humans begins in late gestation and continues through early postnatal life, emerging modulator therapies given perinatally might preserve and enhance integrity of the reproductive tract, which is otherwise absent or deficient in 97% of males with cystic fibrosis.
Project description:Purpose of reviewDevelopment of cystic fibrosis transmembrane conductance regulator (CFTR) modulators, small molecule therapies that target the basic defect in cystic fibrosis (CF), represents a new era in CF treatment. This review highlights recent progress in CF therapeutics as an example of precision medicine and personalized approaches to test CFTR modulators using preclinical model systems.Recent findingsCFTR modulators are now clinically available for approximately 50% of the United States CF population. The CFTR potentiator, ivacaftor, is approved for people with CF ages 2 years and older with at least one gating mutation (G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R) or the R117H conductance mutation. The recent Food and Drug Administration approval of the corrector/potentiator combination, lumacaftor/ivacaftor, expands modulator therapy to people with CF homozygous for the F508del mutation, ages 12 years and older. Ivacaftor and lumacaftor, however, do not fully restore CFTR activity. Thus, next-generation correctors and potentiators are in development. Read-through agents targeting nonsense mutations and genotype agnostic treatments (gene-editing and gene therapy) are also in various phases of clinical development.SummaryCFTR modulators promise to transform the therapeutic landscape in CF in a precision based fashion. Areas of ongoing research include developing drugs for all mutation classes so that all persons with CF can benefit from these therapies, and refining preclinical assays that allow the selection of the most effective treatments on an individual basis.
Project description:The objective of this study was to create a 5-year survivorship model to identify key clinical features of cystic fibrosis. Such a model could help researchers and clinicians to evaluate therapies, improve the design of prospective studies, monitor practice patterns, counsel individual patients, and determine the best candidates for lung transplantation. The authors used information from the Cystic Fibrosis Foundation Patient Registry (CFFPR), which has collected longitudinal data on approximately 90% of cystic fibrosis patients diagnosed in the United States since 1986. They developed multivariate logistic regression models by using data on 5,820 patients randomly selected from 11,630 in the CFFPR in 1993. Models were tested for goodness of fit and were validated for the remaining 5,810 patients for 1993. The validated 5-year survivorship model included age, forced expiratory volume in 1 second as a percentage of predicted normal, gender, weight-for-age z score, pancreatic sufficiency, diabetes mellitus, Staphylococcus aureus infection, Burkerholderia cepacia infection, and annual number of acute pulmonary exacerbations. The model provides insights into the complex nature of cystic fibrosis and supplies a rigorous tool for clinical practice and research.
Project description:The cystic fibrosis (CF) field is the beneficiary of five species of animal models that lack functional cystic fibrosis transmembrane conductance regulator (CFTR) channel. These models are rapidly informing mechanisms of disease pathogenesis and CFTR function regardless of how faithfully a given organ reproduces the human CF phenotype. New approaches of genetic engineering with RNA-guided nucleases are rapidly expanding both the potential types of models available and the approaches to correct the CFTR defect. The application of new CRISPR/Cas9 genome editing techniques are similarly increasing capabilities for in vitro modeling of CFTR functions in cell lines and primary cells using air-liquid interface cultures and organoids. Gene editing of CFTR mutations in somatic stem cells and induced pluripotent stem cells is also transforming gene therapy approaches for CF. This short review evaluates several areas that are key to building animal and cell systems capable of modeling CF disease and testing potential treatments.