Differential expression of THOC1 and ALY mRNP biogenesis/export factors in human cancers

<p>Abstract</p> <p>Background</p> <p>One key step in gene expression is the biogenesis of mRNA ribonucleoparticle complexes (mRNPs). Formation of the mRNP requires the participation of a number of conserved factors such as the THO complex. THO interacts physically and functionally with the Sub2/UAP56 RNA-dependent ATPase, and the Yra1/REF1/ALY RNA-binding protein linking transcription, mRNA export and genome integrity. Given the link between genome instability and cancer, we have performed a comparative analysis of the expression patterns of THOC1, a THO complex subunit, and ALY in tumor samples.</p> <p>Methods</p> <p>The mRNA levels were measured by quantitative real-time PCR and hybridization of a tumor tissue cDNA array; and the protein levels and distribution by immunostaining of a custom tissue array containing a set of paraffin-embedded samples of different tumor and normal tissues followed by statistical analysis.</p> <p>Results</p> <p>We show that the expression of two mRNP factors, THOC1 and ALY are altered in several tumor tissues. THOC1 mRNA and protein levels are up-regulated in ovarian and lung tumors and down-regulated in those of testis and skin, whereas ALY is altered in a wide variety of tumors. In contrast to THOC1, ALY protein is highly detected in normal proliferative cells, but poorly in high-grade cancers.</p> <p>Conclusions</p> <p>These results suggest a differential connection between tumorogenesis and the expression levels of human THO and ALY. This study opens the possibility of defining mRNP biogenesis factors as putative players in cell proliferation that could contribute to tumor development.</p

Decreased expression of the mannose 6- phosphate/insulin-like growth factor-II receptor promotes growth of human breast cancer cells

BACKGROUND: Loss or mutation of the mannose 6-phosphate/insulin-like growth factor-II receptor (M6P/IGF2R) has been found in breast cancer. However, whether or not decreased levels of functional M6P/IGF2R directly contribute to the process of carcinogenesis needs to be further verified by functional studies. METHODS: In this study, using viral and ribozyme strategies we reduced the expression of M6P/IGF2R in human breast cancer cells and then examined the effect on growth and apoptosis of these cells. RESULTS: Our results showed that infection of MCF-7 cells with the adenovirus carrying a ribozyme targeted against the M6P/IGF2R mRNA dramatically reduced the level of transcripts and the functional activity of M6P/IGF2R in these cells. Accordingly, cells treated with the ribozyme exhibited a higher growth rate and a lower apoptotic index than control cells (infected with a control vector). Furthermore, decreased expression of M6P/IGF2R enhanced IGF-II-induced proliferation and reduced cell susceptibility to TNF-induced apoptosis. CONCLUSIONS: These results suggest that M6P/IGF2R functions as a growth suppressor and its loss or mutation may contribute to development and progression of cancer. This study also demonstrates that adenoviral delivery of the ribozyme provides a useful tool for investigating the role of M6P/IGF2R in regulation of cell growth

Stringent response of Escherichia coli: revisiting the bibliome using literature mining

Understanding the mechanisms responsible for cellular responses depends on the systematic collection and analysis of information on the main biological concepts involved. Indeed, the identification of biologically relevant concepts in free text, namely genes, tRNAs, mRNAs, gene products and small molecules, is crucial to capture the structure and functioning of different responses. Results In this work, we review literature reports on the study of the stringent response in Escherichia coli. Rather than undertaking the development of a highly specialised literature mining approach, we investigate the suitability of concept recognition and statistical analysis of concept occurrence as means to highlight the concepts that are most likely to be biologically engaged during this response. The co-occurrence analysis of core concepts in this stringent response, i.e. the (p)ppGpp nucleotides with gene products was also inspected and suggest that besides the enzymes RelA and SpoT that control the basal levels of (p)ppGpp nucleotides, many other proteins have a key role in this response. Functional enrichment analysis revealed that basic cellular processes such as metabolism, transcriptional and translational regulation are central, but other stress-associated responses might be elicited during the stringent response. In addition, the identification of less annotated concepts revealed that some (p)ppGpp-induced functional activities are still overlooked in most reviews. Conclusions In this paper we applied a literature mining approach that offers a more comprehensive analysis of the stringent response in E. coli. The compilation of relevant biological entities to this stress response and the assessment of their functional roles provided a more systematic understanding of this cellular response. Overlooked regulatory entities, such as transcriptional regulators, were found to play a role in this stress response. Moreover, the involvement of other stress-associated concepts demonstrates the complexity of this cellular response

The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

Fetal abdominal wall repair with a collagen biomatrix in an experimental sheep model for gastroschisis.

Contains fulltext : 70287.pdf (publisher's version ) (Open Access)We evaluated the regeneration of the abdominal wall using a dual-layer collagen biomatrix, and the protective effect on the bowel of fetal abdominal wall repair in a fetal sheep model for gastroschisis. In 14 fetal lambs, the abdominal wall was opened at 79 days' gestation, creating a gastroschisis. In group 1, the gastroschisis was left uncovered. In group 2, the bowel was repositioned, and the defect was closed by suturing a collagen biomatrix into the abdominal wall. A cesarean section was performed at 140 days' gestation, and macroscopic and histological evaluation was performed. In the five lambs with a gastroschisis, the eviscerated part of the bowel was coalescent, showed extensive adhesions, and was covered by fibrous peel. In group 2, the abdominal wall had closed, with a firm connection to the native abdominal wall. The biomatrix was largely degraded and replaced by connective tissue with collagen and fibroblasts, neovascularisation, and scattered muscle cells. Minor or no adhesions of the bowel and no peel formation were observed. Abdominal wall tissue replacement using a collagen biomatrix was feasible in fetal lambs, resulting in a closed abdominal wall at birth. Immediate closure of the gastroschisis strongly diminished or prevented bowel adhesions and peel formation

The Presence of Maltreatment Fatality-Related Content in Pre-service Child Welfare Training Curricula: A Brief Report of 20 States

The purpose of this study was to assess the presence of evidence-based information about child maltreatment fatalities (CMFs) and risk factors for CMFs in pre-service child welfare training curricula in the United States. In this first paper to examine the extent to which child welfare workers receive content on CMFs in their pre-service child welfare training, we reviewed curricula from 20 states. We searched for content related to risk assessment and fatality characteristics in the following areas: child risk factors, parent risk factors, and family/household risk factors. Our results suggest that workers’ receive very little content regarding CMFs. We discuss the findings with regard to child welfare training and practice