Physical exercise-induced adult neurogenesis: A good strategy to prevent cognitive decline in neurodegenerative diseases?

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Sustained running in rats administered corticosterone prevents the development of depressive behaviors and enhances hippocampal neurogenesis and synaptic plasticity without increasing neurotrophic factor levels

We have previously shown that voluntary running acts as an anxiolytic and ameliorates deficits in hippocampal neurogenesis and spatial learning. It also reduces depression-like behaviors that are normally observed in rats that were administered either low (30 mg/kg) or moderate (40 mg/kg) doses of corticosterone (CORT). However, the protective effects of running were absent in rats treated with a high (50 mg/kg) dose of CORT. We examined whether allowing animals to exercise for 2 weeks prior and/or concurrently with the administration of 50 mg/kg CORT treatment could have similar protective effects. We examined hippocampal neurogenesis using immunohistochemical staining of proliferative and survival cells with the thymidine analogs (BrdU, CIdU, and IdU). In addition, we monitored synaptic protein expression and quantified the levels of neurotrophic factors in these animals as well as performing behavioral analyses (forced swim test and sucrose preference test). Our results indicate that the depressive phenotype and reductions in neurogenesis that normally accompany high CORT administration could only be prevented by allowing animals to exercise both prior to and concurrently with the CORT administration period. These animals also showed increases in both synaptophysin and PSD-95 protein levels, but surprisingly, neither brain-derived neurotrophic factor (BDNF) nor insulin-like growth factor 1 (IGF-1) levels were increased in these animals. The results suggest that persistent exercise can strengthen resilience to stress by promoting hippocampal neurogenesis and increasing synaptic protein levels, thereby reducing the deleterious effects of stress.published_or_final_versio

The ACUTE (Ambulance CPAP: Use, Treatment effect and economics) feasibility study: a pilot randomised controlled trial of prehospital CPAP for acute respiratory failure

Background: Acute respiratory failure (ARF) is a common and life-threatening medical emergency. Standard prehospital management involves controlled oxygen therapy and disease-specific ancillary treatments. Continuous positive airway pressure (CPAP) is a potentially beneficial alternative treatment that could be delivered by emergency medical services. However, it is uncertain whether this treatment could work effectively in United Kingdom National Health Service (NHS) ambulance services and if it represents value for money. Methods: An individual patient randomised controlled external pilot trial will be conducted comparing prehospital CPAP to standard oxygen therapy for ARF. Adults presenting to ambulance service clinicians will be eligible if they have respiratory distress with peripheral oxygen saturation below British Thoracic Society (BTS) target levels, despite titrated supplemental oxygen. Enrolled patients will be allocated (1:1 simple randomisation) to prehospital CPAP (O_two system) or standard oxygen therapy using identical sealed boxes. Feasibility outcomes will include incidence of recruited eligible patients, number of erroneously recruited patients and proportion of cases adhering to allocation schedule and treatment, followed up at 30 days and with complete data collection. Effectiveness outcomes will comprise survival at 30 days (definitive trial primary end point), endotracheal intubation, admission to critical care, length of hospital stay, visual analogue scale (VAS) dyspnoea score, EQ-5D-5L and health care resource use at 30 days. The cost-effectiveness of CPAP, and of conducting a definitive trial, will be evaluated by updating an existing economic model. The trial aims to recruit 120 patients over 12 months from four regional ambulance hubs within the West Midlands Ambulance Service (WMAS). This sample size will allow estimation of feasibility outcomes with a precision of < 5%. Feasibility and effectiveness outcomes will be reported descriptively for the whole trial population, and each trial arm, together with their 95% confidence intervals. Discussion: This study will determine if it is feasible, acceptable and cost-effective to undertake a full-scale trial comparing CPAP and standard oxygen treatment, delivered by ambulance service clinicians for ARF. This will inform NHS practice and prevent inappropriate prehospital CPAP adoption on the basis of limited evidence and at a potentially substantial cost. Trial registration: ISRCTN12048261. Registered on 30 August 2017. http://www.isrctn.com/ISRCTN1204826

The Heartbleed bug : insecurity repackaged, rebranded and resold

The emergence of a post-industrial information economy shaped by and around networked communication technology has presented new opportunities for identity theft. In particular, the accidental leakage or deliberate harvesting of information, via either hacking or social engineering, is an omnipresent threat to a large number of commercial organisations and state agencies who manage digital databases and sociotechnical forms of data. Throughout the twenty-first century the global media have reported on a series of data breaches fuelling amongst the public an anxiety concerning the safety and security of their personal and financial data. With concern outpacing reliable information a reassurance gap has emerged between the public's expectations and the state's ability to provide safety and security online. This disparity presents a significant opportunity for a commercial computer crime control industry who has sought to position itself as being able to offer consumer citizens the antidotes for such ills. This paper considers how neoliberal discourses of cybercrime control are packaged, branded and sold, through an examination of the social construction of the Heartbleed bug. It demonstrates how security company Codenomicon masterfully communicated the vulnerability, the product of a simple coding error, through its name, a logo and an accompanying website, in turn, shaping news coverage across the mainstream media and beyond

The Extinction of Dengue through Natural Vulnerability of Its Vectors

Dengue transmission has not always been confined to tropical areas. In some cases, this has been due to a reduced geographic range of the mosquitoes that are able to carry dengue viruses. In Australia, Aedes aegypti mosquitoes once occurred throughout temperate, drier parts of the country but are now restricted to the wet tropics. We used a computer modelling approach to determine whether these mosquitoes could inhabit their former range. This was done by simulating dengue mosquito populations in virtual environments that experienced 10 years of actual daily weather conditions (1998–2007) obtained for 13 locations inside and outside the current tropical range. We discovered that in areas outside the Australian wet tropics, Ae. aegypti often becomes extinct, particularly when conditions are too cool for year-round egg-laying activity, and/or too dry for eggs to hatch. Thus, despite being a global pest and disease vector, Ae. aegypti mosquitoes are naturally vulnerable to extinction in certain conditions. Such vulnerability should be exploited in vector control programs

Do dividends signal future earnings in the Nordic stock markets?

We study the informational content of dividends on three Nordic civil law markets, where other simultaneous but blurring motives for dividends may be weaker. Using aggregate data on real earnings per share and payout ratios, long time series from 1969 to 2010, and methodologies which address problems of endogeneity, non-stationarity and autocorrelation (including a Vector Error Correction Model approach), we find evidence on dividend signaling in Nordic markets. However, we also find heterogeneity in the relationship between dividends and earnings on markets similar in many respects, suggesting that even small variations in the institutional surroundings may be important for the results

The p75 neurotrophin receptor is expressed by adult mouse dentate progenitor cells and regulates neuronal and non-neuronal cell genesis

<p>Abstract</p> <p>Background</p> <p>The ability to regulate neurogenesis in the adult dentate gyrus will require further identification and characterization of the receptors regulating this process. <it>In vitro </it>and <it>in vivo </it>studies have demonstrated that neurotrophins and the p75 neurotrophin receptor (p75^NTR) can promote neurogenesis; therefore we tested the hypothesis that p75^NTRis expressed by adult dentate gyrus progenitor cells and is required for their proliferation and differentiation.</p> <p>Results</p> <p>In a first series of studies focusing on proliferation, mice received a single BrdU injection and were sacrificed 2, 10 and 48 hours later. Proliferating, BrdU-positive cells were found to express p75^NTR. In a second series of studies, BrdU was administered by six daily injections and mice were sacrificed 1 day later. Dentate gyrus sections demonstrated a large proportion of BrdU/p75^NTRco-expressing cells expressing either the NeuN neuronal or GFAP glial marker, indicating that p75^NTRexpression persists at least until early stages of maturation. In p75^NTR(-/-) mice, there was a 59% decrease in the number of BrdU-positive cells, with decreases in the number of BrdU cells co-labeled with NeuN, GFAP or neither marker of 35%, 60% and 64%, respectively.</p> <p>Conclusions</p> <p>These findings demonstrate that p75^NTRis expressed by adult dentate progenitor cells and point to p75^NTRas an important receptor promoting the proliferation and/or early maturation of not only neural, but also glial and other cell types.</p

Influence of Landscape Structure and Human Modifications on Insect Biomass and Bat Foraging Activity in an Urban Landscape

Urban landscapes are often located in biologically diverse, productive regions. As such, urbanization may have dramatic consequences for this diversity, largely due to changes in the structure and function of urban communities. We examined the influence of landscape productivity (indexed by geology), housing density and vegetation clearing on the spatial distribution of nocturnal insect biomass and the foraging activity of insectivorous bats in the urban landscape of Sydney, Australia. Nocturnal insect biomass (g) and bat foraging activity were sampled from 113 sites representing backyard, open space, bushland and riparian landscape elements, across urban, suburban and vegetated landscapes within 60 km of Sydney's Central Business District. We found that insect biomass was at least an order of magnitude greater within suburban landscapes in bushland and backyard elements located on the most fertile shale influenced geologies (both p<0.001) compared to nutrient poor sandstone landscapes. Similarly, the feeding activity of bats was greatest in bushland, and riparian elements within suburbs on fertile geologies (p = 0.039). Regression tree analysis indicated that the same three variables explained the major proportion of the variation in insect biomass and bat foraging activity. These were ambient temperature (positive), housing density (negative) and the percent of fertile shale geologies (positive) in the landscape; however variation in insect biomass did not directly explain bat foraging activity. We suggest that prey may be unavailable to bats in highly urbanized areas if these areas are avoided by many species, suggesting that reduced feeding activity may reflect under-use of urban habitats by bats. Restoration activities to improve ecological function and maintain the activity of a diversity of bat species should focus on maintaining and restoring bushland and riparian habitat, particularly in areas with fertile geology as these were key bat foraging habitats

Behavioral genomics of honeybee foraging and nest defense

The honeybee has been the most important insect species for study of social behavior. The recently released draft genomic sequence for the bee will accelerate honeybee behavioral genetics. Although we lack sufficient tools to manipulate this genome easily, quantitative trait loci (QTLs) that influence natural variation in behavior have been identified and tested for their effects on correlated behavioral traits. We review what is known about the genetics and physiology of two behavioral traits in honeybees, foraging specialization (pollen versus nectar), and defensive behavior, and present evidence that map-based cloning of genes is more feasible in the bee than in other metazoans. We also present bioinformatic analyses of candidate genes within QTL confidence intervals (CIs). The high recombination rate of the bee made it possible to narrow the search to regions containing only 17–61 predicted peptides for each QTL, although CIs covered large genetic distances. Knowledge of correlated behavioral traits, comparative bioinformatics, and expression assays facilitated evaluation of candidate genes. An overrepresentation of genes involved in ovarian development and insulin-like signaling components within pollen foraging QTL regions suggests that an ancestral reproductive gene network was co-opted during the evolution of foraging specialization. The major QTL influencing defensive/aggressive behavior contains orthologs of genes involved in central nervous system activity and neurogenesis. Candidates at the other two defensive-behavior QTLs include modulators of sensory signaling (Am5HT(7) serotonin receptor, AmArr4 arrestin, and GABA-B-R1 receptor). These studies are the first step in linking natural variation in honeybee social behavior to the identification of underlying genes

mTOR: from growth signal integration to cancer, diabetes and ageing

In all eukaryotes, the target of rapamycin (TOR) signalling pathway couples energy and nutrient abundance to the execution of cell growth and division, owing to the ability of TOR protein kinase to simultaneously sense energy, nutrients and stress and, in metazoans, growth factors. Mammalian TOR complex 1 (mTORC1) and mTORC2 exert their actions by regulating other important kinases, such as S6 kinase (S6K) and Akt. In the past few years, a significant advance in our understanding of the regulation and functions of mTOR has revealed the crucial involvement of this signalling pathway in the onset and progression of diabetes, cancer and ageing.National Institutes of Health (U.S.)Howard Hughes Medical InstituteWhitehead Institute for Biomedical ResearchJane Coffin Childs Memorial Fund for Medical Research (Postdoctoral Fellowship)Human Frontier Science Program (Strasbourg, France