A multidimensional systems biology analysis of cellular senescence in aging and disease.

BACKGROUND: Cellular senescence, a permanent state of replicative arrest in otherwise proliferating cells, is a hallmark of aging and has been linked to aging-related diseases. Many genes play a role in cellular senescence, yet a comprehensive understanding of its pathways is still lacking. RESULTS: We develop CellAge (http://genomics.senescence.info/cells), a manually curated database of 279 human genes driving cellular senescence, and perform various integrative analyses. Genes inducing cellular senescence tend to be overexpressed with age in human tissues and are significantly overrepresented in anti-longevity and tumor-suppressor genes, while genes inhibiting cellular senescence overlap with pro-longevity and oncogenes. Furthermore, cellular senescence genes are strongly conserved in mammals but not in invertebrates. We also build cellular senescence protein-protein interaction and co-expression networks. Clusters in the networks are enriched for cell cycle and immunological processes. Network topological parameters also reveal novel potential cellular senescence regulators. Using siRNAs, we observe that all 26 candidates tested induce at least one marker of senescence with 13 genes (C9orf40, CDC25A, CDCA4, CKAP2, GTF3C4, HAUS4, IMMT, MCM7, MTHFD2, MYBL2, NEK2, NIPA2, and TCEB3) decreasing cell number, activating p16/p21, and undergoing morphological changes that resemble cellular senescence. CONCLUSIONS: Overall, our work provides a benchmark resource for researchers to study cellular senescence, and our systems biology analyses reveal new insights and gene regulators of cellular senescence

Violência autoinfligida por intoxicação exógena em um serviço de urgência e emergência

RESUMO Objetivo Analisar as violências autoinfligidas por intoxicação exógena notificadas em um serviço de saúde. Métodos Estudo epidemiológico, retrospectivo e analítico realizado em um serviço de urgência e emergência do município de Teresina, Piauí. Procedeu-se nos meses de janeiro e fevereiro de 2015, mediante análise de todos os casos de violência autoinfligida por intoxicação exógena notificados no Sistema de Informação de Agravos de Notificação, no período de 2009 a 2014. O teste qui-quadrado de Pearson foi utilizado na análise. Resultados Foram notificadas 277 vítimas de violência autoinfligida por intoxicação exógena, sendo que 10,5% morreram por suicídio. Houve associação entre o óbito e as variáveis idade, escolaridade, zona de ocorrência e tipo de exposição, assim como entre o tipo de exposição e a quantidade de agentes utilizados. Conclusão Os resultados fornecem subsídios para a definição de estratégias de prevenção considerando os grupos vulneráveis e a complexidade dos fatores associados à violência autoinfligida

Is the Good Polity Attainable? Measuring the Quality of Democracy

This article introduces a discussion on defining, measuring, and assessing the quality of democracy. Providing a short overview of the papers of the Symposium, it places them within a broader context of current academic debate on various methodological, theoretical, and policy outreach dimensions of the topic

A Review of Supervised Machine Learning Applied to Ageing Research

Broadly speaking, supervised machine learning is the computational task of learning correlations between variables in annotated data (the training set), and using this information to create a predictive model capable of inferring annotations for new data, whose annotations are not known. Ageing is a complex process that affects nearly all animal species. This process can be studied at several levels of abstraction, in different organisms and with different objectives in mind. Not surprisingly, the diversity of the supervised machine learning algorithms applied to answer biological questions reflects the complexities of the underlying ageing processes being studied. Many works using supervised machine learning to study the ageing process have been recently published, so it is timely to review these works, to discuss their main findings and weaknesses. In summary, the main findings of the reviewed papers are: the link between specific types of DNA repair and ageing, ageing-related proteins tend to be highly connected and seem to play a central role in molecular pathways; ageing/longevity is linked with autophagy and apoptosis, nutrient receptor genes, and copper and iron ion transport. Additionally, several biomarkers of ageing were found by machine learning. Despite some interesting machine learning results, we also identified a weakness of current works on this topic: only one of the reviewed papers has corroborated the computational results of machine learning algorithms through wet-lab experiments. In conclusion, supervised machine learning has contributed to advance our knowledge and has provided novel insights on ageing, yet future work should have a greater emphasis in validating the predictions

Glycophenotypic Alterations Induced by Pteridium aquilinum in Mice Gastric Mucosa: Synergistic Effect with Helicobacter pylori Infection

The bracken fern Pteridium aquilinum is a plant known to be carcinogenic to animals. Epidemiological studies have shown an association between bracken fern exposure and gastric cancer development in humans. The biological effects of exposure to this plant within the gastric carcinogenesis process are not fully understood. In the present work, effects in the gastric mucosa of mice treated with Pteridium aquilinum were evaluated, as well as molecular mechanisms underlying the synergistic role with Helicobacter pylori infection. Our results showed that exposure to Pteridium aquilinum induces histomorphological modifications including increased expression of acidic glycoconjugates in the gastric mucosa. The transcriptome analysis of gastric mucosa showed that upon exposure to Pteridium aquilinum several glycosyltransferase genes were differently expressed, including Galntl4, C1galt1 and St3gal2, that are mainly involved in the biosynthesis of simple mucin-type carbohydrate antigens. Concomitant treatment with Pteridium aquilinum and infection with Helicobacter pylori also resulted in differently expressed glycosyltransferase genes underlying the biosynthesis of terminal sialylated Lewis antigens, including Sialyl-Lewisx. These results disclose the molecular basis for the altered pattern of glycan structures observed in the mice gastric mucosa. The gene transcription alterations and the induced glycophenotypic changes observed in the gastric mucosa contribute for the understanding of the molecular mechanisms underlying the role of Pteridium aquilinum in the gastric carcinogenesis process

Validity of Vegard’s rule for Al1−x_{1−x}Inx_xN (0.08 < xx < 0.28) thin films grown on GaN templates

In this work, comparative x-ray diffraction (XRD) and Rutherford backscattering spectrometry (RBS) measurements allow a comprehensive characterization of Al$_{1-x}$In$_x$N thin films grown on GaN. Within the limits of experimental accuracy, and in the compositional range 0.08 < $x$ < 0.28, the lattice parameters of the alloys generally obey Vegard's rule, varying linearly with the InN fraction. Results are also consistent with the small deviation from linear behaviour suggested by Darakchieva $\textit{et al}$ (2008 Appl. Phys. Lett. 93 261908). However, unintentional incorporation of Ga, revealed by atom probe tomography (APT) at levels below the detection limit for RBS, may also affect the lattice parameters. Furthermore, in certain samples the compositions determined by XRD and RBS differ significantly. This fact, which was interpreted in earlier publications as an indication of a deviation from Vegard's rule, may rather be ascribed to the influence of defects or impurities on the lattice parameters of the alloy. The wide-ranging set of Al$_{1-x}$In$_x$N films studied allowed furthermore a detailed investigation of the composition leading to lattice-matching of Al$_{1-x}$In$_x$N/GaN bilayers.Funding by FCT Portugal grants PTDC/FIS/65233/2006 and PTDC/FIS-NAN/0973/2012 is gratefully acknowledged. SM thanks FCT for his post-doc grant SFRH/BPD/98738/2013 and KL for her grant as ‘Investigador FCT’. RAO and FT acknowledge funding from the European Research Council under the European Community’s Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no 279361 (MACONS). The LEAP 5000 XR was funded by the EPSRC grant EP/M022803/1