Mutational processes molding the genomes of 21 breast cancers

All cancers carry somatic mutations. The patterns of mutation in cancer genomes reflect the DNA damage and repair processes to which cancer cells and their precursors have been exposed. To explore these mechanisms further, we generated catalogs of somatic mutation from 21 breast cancers and applied mathematical methods to extract mutational signatures of the underlying processes. Multiple distinct single- and double-nucleotide substitution signatures were discernible. Cancers with BRCA1 or BRCA2 mutations exhibited a characteristic combination of substitution mutation signatures and a distinctive profile of deletions. Complex relationships between somatic mutation prevalence and transcription were detected. A remarkable phenomenon of localized hypermutation, termed "kataegis," was observed. Regions of kataegis differed between cancers but usually colocalized with somatic rearrangements. Base substitutions in these regions were almost exclusively of cytosine at TpC dinucleotides. The mechanisms underlying most of these mutational signatures are unknown. However, a role for the APOBEC family of cytidine deaminases is proposed

Prevalência de criptosporidiose em bezerros na região de Araçatuba, Estado de São Paulo, Brasil Prevalence of cryptosporidiosis in calves from Araçatuba region, São Paulo State, Brazil

Avaliou-se a prevalência de oocistos de Cryptosporidium parvum em amostras de fezes de 459 bezerros com até 30 dias de idade e em amostras de água e piso dos bezerreiros de 33 propriedades leiteiras na região de Araçatuba-Estado de São Paulo. A maior porcentagem de excreção de oocistos foi verificada em bezerros com faixa etária variando entre oito e 14 dias de idade (14,5%) sendo, a menor taxa (6,4%), detectada no grupo de animais mais velhos (22 a 30 dias de vida). Observaram-se, na amostragem total, valores positivos aproximados de 10,26% pelo ensaio de imunoadsorção enzimática e de 12,4% pelo teste de Sheather. As amostras de água foram negativas e duas de solo positivas.<br>The purpose of this study was to evaluete the prevalence of Criptosporidium parvum oocists in faeces samples from 459 calves up to 30 days old and from water and floor samples from 33 farmers from Araçatuba region - Sâo Paulo. The higher percentage of oocists excreted was observed in calves with 8 to 14 days old, and the lower was noted in the oldest animals group (22 to 30 days old). In total amostrage 10.26% were positive using enzyme-linked immunosorbent assay and 12.4% by the Sheather test. The water samples were negative and two of soil positive

Guidelines for the use and interpretation of assays for monitoring autophagy

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. 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 vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most 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 field 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. 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. 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