Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Epidemiology of neurodegenerative diseases in sub-Saharan Africa: a systematic review

BACKGROUND:Sub-Saharan African (SSA) countries are experiencing rapid transitions with increased life expectancy. As a result the burden of age-related conditions such as neurodegenerative diseases might be increasing. We conducted a systematic review of published studies on common neurodegenerative diseases, and HIV-related neurocognitive impairment in SSA, in order to identify research gaps and inform prevention and control solutions. METHODS: We searched MEDLINE via PubMed, 'Banque de Donnees de Sante Publique' and the database of the 'Institut d'Epidemiologie Neurologique et de Neurologie Tropicale' from inception to February 2013 for published original studies from SSA on neurodegenerative diseases and HIV-related neurocognitive impairment. Screening and data extraction were conducted by two investigators. Bibliographies and citations of eligible studies were investigated. RESULTS: In all 144 publications reporting on dementia (n=49 publications, mainly Alzheimer disease), Parkinsonism (PD, n=20), HIV-related neurocognitive impairment (n=47), Huntington disease (HD, n=19), amyotrophic lateral sclerosis (ALS, n=15), cerebellar degeneration (n=4) and Lewy body dementia (n=1). Of these studies, largely based on prevalent cases from retrospective data on urban populations, half originated from Nigeria and South Africa. The prevalence of dementia (Alzheimer disease) varied between <1% and 10.1% (0.7% and 5.6%) in population-based studies and from <1% to 47.8% in hospital-based studies. Incidence of dementia (Alzheimer disease) ranged from 8.7 to 21.8/1000/year (9.5 to 11.1), and major risk factors were advanced age and female sex. HIV-related neurocognitive impairment's prevalence (all from hospital-based studies) ranged from <1% to 80%. Population-based prevalence of PD and ALS varied from 10 to 235/100,000, and from 5 to 15/100,000 respectively while that for Huntington disease was 3.5/100,000. Equivalent figures for hospital based studies were the following: PD (0.41 to 7.2%), ALS (0.2 to 8.0/1000), and HD (0.2/100,000 to 46.0/100,000). CONCLUSIONS: The body of literature on neurodegenerative disorders in SSA is large with regard to dementia and HIV-related neurocognitive disorders but limited for other neurodegenerative disorders. Shortcomings include few population-based studies, heterogeneous diagnostic criteria and uneven representation of countries on the continent. There are important knowledge gaps that need urgent action, in order to prepare the sub-continent for the anticipated local surge in neurodegenerative diseases

Rapid compensation of visual search strategy in patients with chronic visual field defects

INTRODUCTION: The aim of this study was to test the effect and specificity of a novel, compensatory eye movement training therapy designed to improve visual search performance in patients with homonymous visual field defects. METHODS: Seven patients with chronic homonymous visual field defects and six healthy control subjects were tested. All subjects completed the single training period (300 trials). Subjects were assessed on three different saccadic tasks (a visual search task, a rapid scanning task and a reading task) which were evaluated at three time points on the same day: two before and one after the training period. The computer-based training consisted of a novel ramp-step search paradigm that required subjects to pursue a stimulus (ramp phase) and then saccade to find its location when it suddenly jumped (step phase). RESULTS: Pre-therapy we confirmed that patients differed from controls on the visual search task. Post-training we demonstrated a clear improvement in terms of reaction time required to complete the visual search. This effect was confined to: (1) the patient group only; (2) targets presented to the blind visual field of the patients only; (3) the visual search task only and not the rapid scanning or reading task. CONCLUSION: These results demonstrate that rapid, compensatory changes can occur in patients with visual field defects that impact on their ability to carry out efficient visual search. We plan to translate this therapy, along with appropriate testing materials, in a free-to-use, internet-based application based on this intervention

Stress response varies with plumage colour and local habitat in feral pigeons

International audienceBird populations exposed to different extrinsic conditions often differ in the responsiveness of the hypothalamo–pituitary–adrenal (HPA) axis and thus in corticosterone response that individuals mount when facing stressful events. However, the contribution of genetic variation to among-individual variability in HPA axis responsiveness across different environmental conditions is poorly understood. Melanin-based coloured types provide reliable phenotypic markers of alternative genotypes underlying stress coping styles. Large variations in melanin-based colouration are heritable in feral pigeons. We tested whether melanin-based colouration is associated with variation in corticosterone stress response in feral pigeons. To this end, we examined how corticosterone response varies both within and between differently coloured individuals across different environmental conditions. Differently coloured individuals produced different stress-induced corticosterone levels in relation to their environmental conditions: dark pigeons exhibited a higher corticosterone when originating from rural habitats, while this was not observed in pale pigeons. This suggests that among-population variation in stress response is higher in dark pigeons, this variation possibly reflecting adjustment and/or (epi)genetic adaptation to environmental conditions. In addition, corticosterone response increased with the degree of melanin-based colouration in pigeons originating from rural habitats but not in pigeons originating from more urbanized populations, resulting in the coexistence of alternative stress responses in some populations, but not in others. Our results suggest that species with melanin-based variation in differently urbanized populations along rural–urban gradients are potentially good candidate systems for studying stress coping styles under alternative selective regimes