Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10−5. We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10−17; including ADGC data, meta P = 5.0 × 10−21) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10−14; including ADGC data, meta P = 1.2 × 10−16) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10−4; including ADGC data, meta P = 8.6 × 10−9), CD33 (GERAD+, P = 2.2 × 10−4; including ADGC data, meta P = 1.6 × 10−9) and EPHA1 (GERAD+, P = 3.4 × 10−4; including ADGC data, meta P = 6.0 × 10−10)

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Estratégias para ensino de hábitos posturais em crianças: história em quadrinhos versus experiência prática Strategies for teaching postural habits to children: comic strips vs. practical experience

Este estudo experimental verificou os efeitos de um programa de educação postural comparando duas estratégias de ensino, a utilização de uma história em quadrinhos (HQ) e a experiência prática de posturas corretas e incorretas (EP). O programa de educação postural foi aplicado em três encontros com escolares das 2ª e 3ª séries, com idades entre 7 e 11 anos; 40 meninas e 40 meninos foram divididos igualmente em dois grupos, cada um submetido a uma estratégia de ensino: GHQ e GEP. O conhecimento dos hábitos posturais foi verificado por meio de questionários aplicados antes e após 6 meses do término das sessões. Foram ensinadas as posturas corretas em pé, sentado, de transportar mochilas, de abaixar, de mudar objetos de lugar e jeito de dormir. Os resultados do estudo indicaram que, para todas as variáveis estudadas houve aumento significativo no aprendizado e memorização dos hábitos posturais corretos em ambos os grupos, e que não houve diferença significativa entre as duas estratégias educativas. Não foram detectadas diferenças no aprendizado e memorização dos hábitos posturais corretos em crianças de ambos os sexos submetidas às duas metodologias de ensino.<br>This experimental study assessed the effects of a posture education program comparing two teaching strategies: by means of a comic strip (CS) and through practical experience (PE), in which children experienced each correct and incorrect posture. The posture education program was applied to 2nd- and 3rd-grade students aged 7-to-11 in three teaching meetings. The sample consisted of 40 boys and 40 girls evenly distributed into two groups, each taught by one teaching strategy: CS group and PE group. Questionnaires were applied before program onset and six months after the end of the program, in order to assess participants' postural habits. Correct postures taught were standing, sitting, knapsack carrying, bending down, moving objects, and sleeping posture. Results showed significant improvement in learning and memorizing correct postures by all subjects; no significant differences were found between the groups in all variables assessed. Both comic strip and practical experience teaching strategies were thus efficient in teaching boys and girls healthy postural habits