Cholesterol impairment contributes to neuroserpin aggregation

Intraneural accumulation of misfolded proteins is a common feature of several neurodegenerative pathologies including Alzheimer's and Parkinson's diseases, and Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB). FENIB is a rare disease due to a point mutation in neuroserpin which accelerates protein aggregation in the endoplasmic reticulum (ER). Here we show that cholesterol depletion induced either by prolonged exposure to statins or by inhibiting the sterol regulatory binding-element protein (SREBP) pathway also enhances aggregation of neuroserpin proteins. These findings can be explained considering a computational model of protein aggregation under non-equilibrium conditions, where a decrease in the rate of protein clearance improves aggregation. Decreasing cholesterol in cell membranes affects their biophysical properties, including their ability to form the vesicles needed for protein clearance, as we illustrate by a simple mathematical model. Taken together, these results suggest that cholesterol reduction induces neuroserpin aggregation, even in absence of specific neuroserpin mutations. The new mechanism we uncover could be relevant also for other neurodegenerative diseases associated with protein aggregation.Comment: 7 figure

Energy Gap Contributes to Adolescent Obesity

Summarizes findings on the gap between the calories American children and adolescents consume and the calories needed for normal growth, physical activity, and body function. Compares the overall gap with that of overweight adolescents over ten years

Stigmergic hyperlink's contributes to web search

Stigmergic hyperlinks are hyperlinks with a "heart beat": if used they stay healthy and online; if neglected, they fade, eventually getting replaced. Their life attribute is a relative usage measure that regular hyperlinks do not provide, hence PageRank-like measures have historically been well informed about the structure of webs of documents, but unaware of what users effectively do with the links. This paper elaborates on how to input the users’ perspective into Google’s original, structure centric, PageRank metric. The discussion then bridges to the Deep Web, some search challenges, and how stigmergic hyperlinks could help decentralize the search experience, facilitating user generated search solutions and supporting new related business models.info:eu-repo/semantics/publishedVersio

How organic agriculture contributes to sustainable development

Organic agriculture can contribute to meaningful socio-economic and ecologically sustainable development, especially in poorer countries. This is due on the one hand to the application of organic principles, which means efficient management of local resources (e.g. local seed varieties, manure, etc.) and therefore costeffectiveness. On the other hand, the market for organic products – at local and international level – has tremendous growth prospects and offers creative producers and exporters in the South excellent opportunities to improve their income and living conditions. Establishing whether organic agriculture is a viable alternative for a particular holding needs to be carried out on a case-by-case basis. What potential does organic agriculture have for solving the problems of hunger and poverty? What can organic agriculture contribute to achieving socially and ecologically sustainable development in poor countries? Central to organic agriculture are promotion of soil fertility, biodiversity conservation (e.g. native flora and fauna), production methods adapted to the locality and avoidance of chemical inputs. These methods, together with cultivation of a diverse range of crops, stabilize the delicate ecosystems in the tropics and reduce drought sensitivity and pest infestation. Organic agriculture reduces the risk of yield failure, stabilizes returns and improves the quality of life of small farmers’ families. To date, no systematic attempt has been made to evaluate the benefits and effects of each system. In 2006, FiBL therefore launched a network of long-term system comparisons in the tropics that aims at examining the contribution of organic agriculture to food security, poverty alleviation and environmental conservation. The article presents this discussion based on experience gained in practice and encompasses the following hypotheses: 1. Organic agriculture is sustainable and diverse; 2. Organic farmers conserve resources; 3. Organic farmers produce more, better-quality products and achieve higher incomes; 4. Organic products provide market access and create added value; 5. Organic agriculture increases self-confidence and mobilizes new partnerships

Who Contributes to the Knowledge Sharing Economy?

Information sharing dynamics of social networks rely on a small set of influencers to effectively reach a large audience. Our recent results and observations demonstrate that the shape and identity of this elite, especially those contributing \emph{original} content, is difficult to predict. Information acquisition is often cited as an example of a public good. However, this emerging and powerful theory has yet to provably offer qualitative insights on how specialization of users into active and passive participants occurs. This paper bridges, for the first time, the theory of public goods and the analysis of diffusion in social media. We introduce a non-linear model of \emph{perishable} public goods, leveraging new observations about sharing of media sources. The primary contribution of this work is to show that \emph{shelf time}, which characterizes the rate at which content get renewed, is a critical factor in audience participation. Our model proves a fundamental \emph{dichotomy} in information diffusion: While short-lived content has simple and predictable diffusion, long-lived content has complex specialization. This occurs even when all information seekers are \emph{ex ante} identical and could be a contributing factor to the difficulty of predicting social network participation and evolution.Comment: 15 pages in ACM Conference on Online Social Networks 201

Haemogenic endocardium contributes to transient definitive haematopoiesis.

Haematopoietic cells arise from spatiotemporally restricted domains in the developing embryo. Although studies of non-mammalian animal and in vitro embryonic stem cell models suggest a close relationship among cardiac, endocardial and haematopoietic lineages, it remains unknown whether the mammalian heart tube serves as a haemogenic organ akin to the dorsal aorta. Here we examine the haemogenic activity of the developing endocardium. Mouse heart explants generate myeloid and erythroid colonies in the absence of circulation. Haemogenic activity arises from a subset of endocardial cells in the outflow cushion and atria earlier than in the aorta-gonad-mesonephros region, and is transient and definitive in nature. Interestingly, key cardiac transcription factors, Nkx2-5 and Isl1, are expressed in and required for the haemogenic population of the endocardium. Together, these data suggest that a subset of endocardial/endothelial cells serve as a de novo source for transient definitive haematopoietic progenitors

What contributes to depression in Parkinson's disease?

Background: Depression is a common problem in patients with Parkinson's disease, but its mechanism is poorly understood. It is thought that neurochemical changes contribute to its occurrence, but it is unclear why some patients develop depression and others do not. Using a community-based sample of patients with Parkinson's disease, we investigated the contributions of impairment, disability and handicap to depression in Parkinson's disease. Methods: Ninety-seven patients seen in a population-based study on the prevalence of Parkinson's disease completed the Beck Depression Inventory (BDI). Clinical and historical information on symptoms and complications of Parkinson's disease were obtained from the patients by a neurologist. In addition, clinician and patient ratings of disability on the Schwab and England scale were obtained and a quality of life questionnaire was completed. Results: Moderate to severe depression (BDI [gt-or-equal, slanted] 18) was reported by 19·6% of the patients. Higher depression scores were associated with advancing disease severity, recent self-reported deterioration, higher akinesia scores, a mini-mental score of 50% of the variance of depression scores. Conclusions: Depression in patients with Parkinson's disease is associated with advancing disease severity, recent disease deterioration and occurrence of falls. Regression analysis suggests that depression in Parkinson's disease is more strongly influenced by the patients' perceptions of handicap than by actual disability. The treatment of depression should therefore be targeted independently of treatment of the motor symptoms of Parkinson's disease, and consider the patients' own perception of their disease

What contributes to individual differences in brain structure?

Individual differences in adult human brain structure have been found to reveal a great deal of information about variability in behaviors, cognitive abilities and mental and physical health. Driven by such evidence, what contributes to individual variation in brain structure has gained accelerated attention as a research question. Findings thus far appear to support the notion that an individual’s brain architecture is determined largely by genetic and environmental influences. This review aims to evaluate the empirical literature on whether and how genes and the environment contribute to individual differences in brain structure. It first considers how genetic and environmental effects may separately contribute to brain morphology, by examining evidence from twin, genome-wide association, cross-sectional and longitudinal studies. Next, evidence for the influence of the complex interplay between genetic and environmental factors, characterized as gene-environment interactions and correlations, is reviewed. In evaluating the extant literature, this review will conclude that both genetic and environmental factors play critical roles in contributing to individual variability in brain structure

Sea surface temperature contributes to marine crocodylomorph evolution

During the Mesozoic and Cenozoic, four distinct crocodylomorph lineages colonized the marine environment. They were conspicuously absent from high latitudes, which in the Mesozoic were occupied by warm-blooded ichthyosaurs and plesiosaurs. Despite a relatively well-constrained stratigraphic distribution, the varying diversities of marine crocodylomorphs are poorly understood, because their extinctions neither coincided with any major biological crises nor with the advent of potential competitors. Here we test the potential link between their evolutionary history in terms of taxic diversity and two abiotic factors, sea level variations and sea surface temperatures (SST). Excluding Metriorhynchoidea, which may have had a peculiar ecology, significant correlations obtained between generic diversity and estimated Tethyan SST suggest that water temperature was a driver of marine crocodylomorph diversity. Being most probably ectothermic reptiles, these lineages colonized the marine realm and diversified during warm periods, then declined or became extinct during cold intervals