Effects of zerumbone on cisplatin-induced clastogenesis in Sprague-Dawley rats bone marrow cells

Zerumbone (ZER) is derived from Zingiber zerumbet smith from the Zingiberaceae family. It has been shown to have anti-cancer and apoptosis-inducing properties against various human tumour cells. The aim of our study was to assess the effect of ZER on cisplatin-induced clastogenesis in Sprague-Dawley rat bone marrow polychromatic erythrocytes (PCEs) using micronucleus test (MN). Animals treated with two ZER doses for 4 consecutive days plus a single dose of cisplatin following treatment, presented a non-significant effects of ZER on cisplatin-induced clastogenesis. The results also indicated that ZER has no clastogenic effects on rat bone marrow polychromatic erythrocytes after 4 days treatment with 250 and 500 mg/kg body weight when compared to one dose cisplatin of 45 mg/kg body weight. On the other hand, significant decrease in the number of PCE was observed in all treatment groups, indicating cytotoxicity of ZER and cisplatin. Under the present experimental conditions, ZER could not prevent cisplatin-induced clastogenesis in rat.Key words: Clastogenicity, micronucleus, micronuclei in polychromatic erythrocytes (MNPCEs), zerumbone

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Why education in public schools should include religious ideals

This article aims to open a new line of debate about religion in public schools by focusing on religious ideals. The article begins with an elucidation of the concept ‘religious ideals’ and an explanation of the notion of reasonable pluralism, in order to be able to explore the dangers and positive contributions of religious ideals and their pursuit on a liberal democratic society. We draw our examples of religious ideals from Christianity and Islam, because these religions have most adherents in Western liberal democracies that are the focus of this article. The fifth and most important section "Reasonable pluralism and the inclusion of religious ideals in public secondary schools" provides three arguments for our claim that public schools should include religious ideals, namely that they are important to religious people, that they are conducive for the development of pupils into citizens of a liberal democracy, and that the flourishing of pupils as adults is advanced by encountering religious ideals. We also offer a more practical reason: religious ideals can more easily be included within public education than religious dogmas and rules

Publisher Connection: Export-Led Growth in the UAE: Multivariate Causality Between Primary Exports, Manufactured Exports and Economic Growth

The principal question that this research addresses is the validity of the Export-Led Growth hypothesis (ELG) in the United Arab Emirates (UAE) over the period 1981–2012, focusing on the causality between primary exports, manufactured exports and economic growth. Unit root tests are applied to examine the time-series properties of the variables, while the Johansen cointegration test is performed to confirm or not the existence of a long-run relationship between the variables. Moreover, the multivariate Granger causality test and a modified version of Wald test are applied to examine the direction of the short-run and long-run causality respectively. The cointegration analysis reveals that manufactured exports contribute more to economic growth than primary exports in the long-run. In addition, this research provides evidence to support a bi-directional causality between manufactured exports and economic growth in the short-run, while the Growth-Led Exports (GLE) hypothesis is valid in the long-run for UAE

Impact of Age on the Cerebrovascular Proteomes of Wild-Type and Tg-SwDI Mice

The structural integrity of cerebral vessels is compromised during ageing. Abnormal amyloid (Aβ) deposition in the vasculature can accelerate age-related pathologies. The cerebrovascular response associated with ageing and microvascular Aβ deposition was defined using quantitative label-free shotgun proteomic analysis. Over 650 proteins were quantified in vessel-enriched fractions from the brains of 3 and 9 month-old wild-type (WT) and Tg-SwDI mice. Sixty-five proteins were significantly increased in older WT animals and included several basement membrane proteins (nidogen-1, basement membrane-specific heparan sulfate proteoglycan core protein, laminin subunit gamma-1 precursor and collagen alpha-2(IV) chain preproprotein). Twenty-four proteins were increased and twenty-one decreased in older Tg-SwDI mice. Of these, increases in Apolipoprotein E (APOE) and high temperature requirement serine protease-1 (HTRA1) and decreases in spliceosome and RNA-binding proteins were the most prominent. Only six shared proteins were altered in both 9-month old WT and Tg-SwDI animals. The age-related proteomic response in the cerebrovasculature was distinctly different in the presence of microvascular Aβ deposition. Proteins found differentially expressed within the WT and Tg-SwDI animals give greater insight to the mechanisms behind age-related cerebrovascular dysfunction and pathologies and may provide novel therapeutic targets

Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer