The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

Mentored peer review of standardized manuscripts as a teaching tool for residents: a pilot randomized controlled multi-center study

Abstract Background There is increasing need for peer reviewers as the scientific literature grows. Formal education in biostatistics and research methodology during residency training is lacking. In this pilot study, we addressed these issues by evaluating a novel method of teaching residents about biostatistics and research methodology using peer review of standardized manuscripts. We hypothesized that mentored peer review would improve resident knowledge and perception of these concepts more than non-mentored peer review, while improving review quality. Methods A partially blinded, randomized, controlled multi-center study was performed. Seventy-eight neurology residents from nine US neurology programs were randomized to receive mentoring from a local faculty member or not. Within a year, residents reviewed a baseline manuscript and four subsequent manuscripts, all with introduced errors designed to teach fundamental review concepts. In the mentored group, mentors discussed completed reviews with residents. Primary outcome measure was change in knowledge score between pre- and post-tests, measuring epidemiology and biostatistics knowledge. Secondary outcome measures included level of confidence in the use and interpretation of statistical concepts before and after intervention, and RQI score for baseline and final manuscripts. Results Sixty-four residents (82%) completed initial review with gradual decline in completion on subsequent reviews. Change in primary outcome, the difference between pre- and post-test knowledge scores, did not differ between mentored (−8.5%) and non-mentored (−13.9%) residents (p = 0.48). Significant differences in secondary outcomes (using 5-point Likert scale, 5 = strongly agree) included mentored residents reporting enhanced understanding of research methodology (3.69 vs 2.61; p = 0.001), understanding of manuscripts (3.73 vs 2.87; p = 0.006), and application of study results to clinical practice (3.65 vs 2.78; p = 0.005) compared to non-mentored residents. There was no difference between groups in level of interest in peer review (3.00 vs 3.09; p = 0.72) or the quality of manuscript review assessed by the Review Quality Instrument (RQI) (3.25 vs 3.06; p = 0.50). Conclusions We used mentored peer review of standardized manuscripts to teach biostatistics and research methodology and introduce the peer review process to residents. Though knowledge level did not change, mentored residents had enhanced perception in their abilities to understand research methodology and manuscripts and apply study results to clinical practice.https://deepblue.lib.umich.edu/bitstream/2027.42/136916/1/41073_2017_Article_32.pd

Protected Areas: Mixed Success in Conserving East Africa’s Evergreen Forests

In East Africa, human population growth and demands for natural resources cause forest loss contributing to increased carbon emissions and reduced biodiversity. Protected Areas (PAs) are intended to conserve habitats and species. Variability in PA effectiveness and ‘leakage’ (here defined as displacement of deforestation) may lead to different trends in forest loss within, and adjacent to, existing PAs. Here, we quantify spatial variation in trends of evergreen forest coverage in East Africa between 2001 and 2009, and test for correlations with forest accessibility and environmental drivers. We investigate PA effectiveness at local, landscape and national scales, comparing rates of deforestation within park boundaries with those detected in park buffer zones and in unprotected land more generally. Background forest loss (BFL) was estimated at −9.3% (17,167 km2), but varied between countries (range: −0.9% to −85.7%; note: no BFL in South Sudan). We document high variability in PA effectiveness within and between PA categories. The most successful PAs were National Parks, although only 26 out of 48 parks increased or maintained their forest area (i.e. Effective parks). Forest Reserves (Ineffective parks, i.e. parks that lose forest from within boundaries: 204 out of 337), Nature Reserves (six out of 12) and Game Parks (24 out of 26) were more likely to lose forest cover. Forest loss in buffer zones around PAs exceeded background forest loss, in some areas indicating leakage driven by Effective National Parks. Human pressure, forest accessibility, protection status, distance to fires and long-term annual rainfall were highly significant drivers of forest loss in East Africa. Some of these factors can be addressed by adjusting park management. However, addressing close links between livelihoods, natural capital and poverty remains a fundamental challenge in East Africa’s forest conservation efforts