Genome-Wide Transcriptional Reorganization Associated with Senescence-to-Immortality Switch during Human Hepatocellular Carcinogenesis

Cataloged from PDF version of article.Senescence is a permanent proliferation arrest in response to cell stress such as DNA damage. It contributes strongly to tissue aging and serves as a major barrier against tumor development. Most tumor cells are believed to bypass the senescence barrier (become "immortal") by inactivating growth control genes such as TP53 and CDKN2A. They also reactivate telomerase reverse transcriptase. Senescence-to-immortality transition is accompanied by major phenotypic and biochemical changes mediated by genome-wide transcriptional modifications. This appears to happen during hepatocellular carcinoma (HCC) development in patients with liver cirrhosis, however, the accompanying transcriptional changes are virtually unknown. We investigated genome-wide transcriptional changes related to the senescence-to-immortality switch during hepatocellular carcinogenesis. Initially, we performed transcriptome analysis of senescent and immortal clones of Huh7 HCC cell line, and identified genes with significant differential expression to establish a senescence-related gene list. Through the analysis of senescence-related gene expression in different liver tissues we showed that cirrhosis and HCC display expression patterns compatible with senescent and immortal phenotypes, respectively; dysplasia being a transitional state. Gene set enrichment analysis revealed that cirrhosis/senescence-associated genes were preferentially expressed in non-tumor tissues, less malignant tumors, and differentiated or senescent cells. In contrast, HCC/immortality genes were up-regulated in tumor tissues, or more malignant tumors and progenitor cells. In HCC tumors and immortal cells genes involved in DNA repair, cell cycle, telomere extension and branched chain amino acid metabolism were up-regulated, whereas genes involved in cell signaling, as well as in drug, lipid, retinoid and glycolytic metabolism were down-regulated. Based on these distinctive gene expression features we developed a 15-gene hepatocellular immortality signature test that discriminated HCC from cirrhosis with high accuracy. Our findings demonstrate that senescence bypass plays a central role in hepatocellular carcinogenesis engendering systematic changes in the transcription of genes regulating DNA repair, proliferation, differentiation and metabolism

How has internet addiction research evolved since the advent of internet gaming disorder? An overview of cyberaddictions from a psychological perspective

During the past two decades, Internet addiction (IA) has been the most commonly used term in research into online activities and their influence on the development of behavioral addictions. The aim of this review is to assess the impact of the concept of Internet gaming disorder (IGD), proposed by the American Psychiatric Association, on the scientific literature regarding IA. It presents a bibliometric analysis of the IA literature starting from the time IGD was first proposed, with the objective of observing and comparing the topics that have arisen during this period among the different IA themes researched. The findings demonstrate a steady evolution, particularly regarding publications related to the general aspects of IA: its clinical component, its prevalence and psychometric measures, the growing interest in the contextual factors promoting this addictive behavior, scientific progress in its conceptualization based on existing theoretical models, and neuropsychological studies. Nevertheless, many of the studies (22 %) focus on specific IA behaviors and show heterogeneity among the cyberaddictions, with online gaming (related to IGD) most common, followed by cybersex and social networking. Although research on the general concept of IA continues, investigators have begun to pay attention to the diverse spectrum of specific cyberaddictions and their psychological components

GENOTYPIC IDENTIFICATION AND CHARACTERISATION OF PROBIOTIC PROPERTIES OF LACTIC ACID BACTERIA FROM NIGDE CHEESE

WOS: 000386104000021Probiotics are live microorganisms having profound health benefit on its host and among them lactic acid bacteria (LAB) are common group found in human food. As this is a very vast group of microorganisms having different strains, therefore genotypic identification has been performed by primers that are specific for 16s ribosomal DNA gene on a total of 24 exopolysaccharides (EPS) producing LAB: those are Lactobacillus, Enterococcus and Pediococcus isolated from Nigde cheese of Turkey. Subsequently, characterization of probiotic properties of LAB was studied by final pH, acidification, and amount of EPS concentration and aggregation properties. EPS productions by the strains were found between 54.1-93.6 mg/l. The highest EPS production was detected in the Pediococcus pentosaceus EC18 and the lowest EPS were estimated in the Enterococcus faecium EC26. All LAB strains showed auto- and coaggregation ability with Escherichia coli (E. coli) ATCC 25923 and Salmonella enterica serotype typhmurium (S. typhmurium) SL 1344. Results showed that the aggregation property is specific for each strain and dependent on EPS production. Our results indicate that the ability to autoaggregate, together with exopolysaccharide and final pH properties and coaggregation abilities with E. coli and S. typhmurium strains, can be used for preliminary screening in order to identify potentially probiotic bacteria suitable for human

Genome-Wide Transcriptional Reorganization Associated with Senescence-to-Immortality Switch during Human Hepatocellular Carcinogenesis

Senescence is a permanent proliferation arrest in response to cell stress such as DNA damage. It contributes strongly to tissue aging and serves as a major barrier against tumor development. Most tumor cells are believed to bypass the senescence barrier (become "immortal") by inactivating growth control genes such as TP53 and CDKN2A. They also reactivate telomerase reverse transcriptase. Senescence-to-immortality transition is accompanied by major phenotypic and biochemical changes mediated by genome-wide transcriptional modifications. This appears to happen during hepatocellular carcinoma (HCC) development in patients with liver cirrhosis, however, the accompanying transcriptional changes are virtually unknown. We investigated genome-wide transcriptional changes related to the senescence-to-immortality switch during hepatocellular carcinogenesis. Initially, we performed transcriptome analysis of senescent and immortal clones of Huh7 HCC cell line, and identified genes with significant differential expression to establish a senescence-related gene list. Through the analysis of senescence-related gene expression in different liver tissues we showed that cirrhosis and HCC display expression patterns compatible with senescent and immortal phenotypes, respectively; dysplasia being a transitional state. Gene set enrichment analysis revealed that cirrhosis/senescence-associated genes were preferentially expressed in non-tumor tissues, less malignant tumors, and differentiated or senescent cells. In contrast, HCC/immortality genes were up-regulated in tumor tissues, or more malignant tumors and progenitor cells. In HCC tumors and immortal cells genes involved in DNA repair, cell cycle, telomere extension and branched chain amino acid metabolism were up-regulated, whereas genes involved in cell signaling, as well as in drug, lipid, retinoid and glycolytic metabolism were down-regulated. Based on these distinctive gene expression features we developed a 15-gene hepatocellular immortality signature test that discriminated HCC from cirrhosis with high accuracy. Our findings demonstrate that senescence bypass plays a central role in hepatocellular carcinogenesis engendering systematic changes in the transcription of genes regulating DNA repair, proliferation, differentiation and metabolism. © 2013 Yildiz et al

A strong effect of growth medium and organ type on the identification of QTLs for phytate and mineral concentrations in three Arabidopsis thaliana RIL populations

The regulation of mineral accumulation in plants is genetically complex, with several genetic loci involved in the control of one mineral and loci affecting the accumulation of different minerals. To investigate the role of growth medium and organ type on the genetics of mineral accumulation, two existing (LerxKond, LerxAn-1) and one new (LerxEri-1) Arabidopsis thaliana Recombinant Inbred Line populations were raised on soil and hydroponics as substrates. Seeds, roots, and/or rosettes were sampled for the determination of their Ca, Fe, K, Mg, Mn, P or Zn concentrations. For seeds only, the concentration of phytate (IP6), a strong chelator of seed minerals, was determined. Correlations between minerals/IP6, populations, growth conditions, and organs were determined and mineral/IP6 concentration data were used to identify quantitative trait loci (QTLs) for these traits. A striking difference was found between QTLs identified for soil-grown versus hydroponics-grown populations and between QTLs identified for different plant organs. Three common QTLs were identified for several populations, growth conditions, and organs, one of which corresponded to the ERECTA locus, variation of which has a strong effect on plant morpholog

A novel approach for small sample size family-based association studies: sequential tests

In this paper, we propose a sequential probability ratio test (SPRT) to overcome the problem of limited samples in studies related to complex genetic diseases. The results of this novel approach are compared with the ones obtained from the traditional transmission disequilibrium test (TDT) on simulated data. Although TDT classifies single-nucleotide polymorphisms (SNPs) to only two groups (SNPs associated with the disease and the others), SPRT has the flexibility of assigning SNPs to a third group, that is, those for which we do not have enough evidence and should keep sampling. It is shown that SPRT results in smaller ratios of false positives and negatives, as well as better accuracy and sensitivity values for classifying SNPs when compared with TDT. By using SPRT, data with small sample size become usable for an accurate association analysis