Mmf1p, a novel yeast mitochondrial protein conserved throughout evolution and involved in maintenance of the mitochondrial genome

A novel protein family (p14.5, or YERO57c/YJGFc) highly conserved throughout evolution has recently been identified. The biological role of these proteins is not yet well characterized. Two members of the p14.5 family are present in the yeast Saccharomyces cerevisiae. In this study, we have characterized some of the biological functions of the two yeast proteins. Mmf1p is a mitochondrial matrix factor, and homologous Mmf1p factor (Hmf1p) copurifies with the soluble cytoplasmic fraction. Δmmf1 cells lose mitochondrial DNA (mtDNA) and have a decreased growth rate, while Δhmf1 cells do not display any visible phenotype. Furthermore, we demonstrate by genetic analysis that Mmf1p does not play a direct role in replication and segregation of the mtDNA. rho(+) Δmmf1 haploid cells can be obtained when tetrads are directly dissected on medium containing a nonfermentable carbon source. Our data also indicate that Mmf1p and Hmf1p have similar biological functions in different subcellular compartments. Hmf1p, when fused with the Mmf1p leader peptide, is transported into mitochondria and is able to functionally replace Mmf1p. Moreover, we show that homologous mammalian proteins are functionally related to Mmf1p. Human p14.5 localizes in yeast mitochondria and rescues the Δmmf1-associated phenotypes. In addition, fractionation of rat liver mitochondria showed that rat p14.5, like Mmf1p, is a soluble protein of the matrix. Our study identifies a biological function for Mmf1p and furthermore indicates that this function is conserved between members of the p14.5 family

The effects of thiopurine therapy on health-related quality of life in Inflammatory Bowel Disease patients

<p>Abstract</p> <p>Background</p> <p>The effect of thiopurine immunomodulators on health-related quality of life (HRQoL) in patients with inflammatory bowel disease (IBD) has been controversial. The aims were to evaluate the HRQoL in patients with IBD treated with thiopurines and assess the short- and long-term impacts of the treatment on HRQoL.</p> <p>Methods</p> <p>Ninety-two consecutive patients who started treatment with thiopurines were prospectively included. Evaluation of HRQoL was performed at months 0, 6, and 12 using two questionnaires, the Short-Form Health Survey (SF-36) and the Inflammatory Bowel Disease Questionnaire (IBDQ).</p> <p>Results</p> <p>Baseline score of IBDQ was 4,6, range (2,31-6,84), with an impairment of the five dimensions of HRQoL compared with inactive patients. Results obtained in 8 dimensions of SF-36 showed worse HRQoL than Spanish general population. At 6 months patients had a significant improvement in overall IBDQ score -5,8 (1,58 -6,97)- and also in all IBDQ dimensions. All the 8 dimensions of SF-36 obtained a significant improvement. At twelve months score of IBDQ was 6,1, range (2,7-6,98), with improvement in all dimensions compared with baseline and 6 months. SF-36 showed a similar significant improvement in all subscales.</p> <p>Conclusions</p> <p>Thiopurine immunomodulators alone or with other treatments have a positive and long lasting impact on HRQoL of IBD patients.</p

Identification of Stage-Specific Breast Markers using Quantitative Proteomics

YesMatched healthy and diseased tissues from breast cancer patients were analyzed by quantitative proteomics. By comparing proteomic profiles of fibroadenoma (benign tumors, three patients), DCIS (noninvasive cancer, three patients), and invasive ductal carcinoma (four patients), we identified protein alterations that correlated with breast cancer progression. Three 8-plex iTRAQ experiments generated an average of 826 protein identifications, of which 402 were common. After excluding those originating from blood, 59 proteins were significantly changed in tumor compared with normal tissues, with the majority associated with invasive carcinomas. Bioinformatics analysis identified relationships between proteins in this subset including roles in redox regulation, lipid transport, protein folding, and proteasomal degradation, with a substantial number increased in expression due to Myc oncogene activation. Three target proteins, cofilin-1 and p23 (increased in invasive carcinoma) and membrane copper amine oxidase 3 (decreased in invasive carcinoma), were subjected to further validation. All three were observed in phenotype-specific breast cancer cell lines, normal (nontransformed) breast cell lines, and primary breast epithelial cells by Western blotting, but only cofilin-1 and p23 were detected by multiple reaction monitoring mass spectrometry analysis. All three proteins were detected by both analytical approaches in matched tissue biopsies emulating the response observed with proteomics analysis. Tissue microarray analysis (361 patients) indicated cofilin-1 staining positively correlating with tumor grade and p23 staining with ER positive status; both therefore merit further investigation as potential biomarkers.Cyprus Research Promotion Foundation, Yorkshire Cancer Researc

The Cochaperone p23 Differentially Regulates Estrogen Receptor Target Genes and Promotes Tumor Cell Adhesion and Invasion

The cochaperone p23 plays an important role in estrogen receptor alpha (ER) signal transduction. In this study, we investigated how p23 regulates ER target gene activation and affects tumor growth and progression. Remarkably, we found that changes in the expression of p23 differentially affected the activation of ER target genes in a manner dependent upon the type of DNA regulatory element. p23 overexpression enhanced the expression of the ER target genes cathepsin D and pS2, which are regulated by direct DNA binding of ER to estrogen response elements (ERE). In contrast, the expression of other target genes, including c-Myc, cyclin D1, and E2F1, to which ER is recruited indirectly through its interaction with other transcription factors remains unaffected by changes in p23 levels. The p23-induced expression of pS2 is associated with enhanced recruitment of ER to the ERE in the promoter, whereas ER recruitment to the ERE-less c-Myc promoter does not respond to p23. Intriguingly, p23-overexpressing MCF-7 cells exhibit increased adhesion and invasion in the presence of fibronectin. Our findings demonstrate that p23 differentially regulates ER target genes and is involved in the control of distinct cellular processes in breast tumor development, thus revealing novel functions of this cochaperone

Health-promoting factors in higher education for a sustainable working life - protocol for a multicenter longitudinal study.

BACKGROUND: The World Health Organization has highlighted the importance of health promotion for health service providers in order to ensure sustainable working life for individuals involved in providing health services. Such sustainability begins when students are preparing to manage their own future health and welfare in working life. It has been suggested that universities, employees and trainee health professionals should adopt or follow a salutogenic approach that not only complements the providing of information on known health risks but also favors health promotion strategies. This paper describes the study design and data collection methods in a planned study aiming to explore health-promoting factors for a sustainable working life among students in higher education within healthcare and social work. METHODS: This protocol describes a multicenter longitudinal study involving Swedish students on higher education programs in the healthcare and social work sectors. In 2018, the study invited students on seven education programs at six universities to participate. These programs were for qualification as: biomedical laboratory scientists (n = 121); dental hygienists (n = 87); nurses (n = 1411); occupational therapists (n = 111); physiotherapists (n = 48); radiographers (n = 60); and, social workers (n = 443). In total, 2283 students were invited to participate. Participants completed a baseline, a self-reported questionnaire including six validated instruments measuring health-promoting factors and processes. There are to be five follow-up questionnaires. Three while the students are studying, one a year after graduating, and one three years after graduating. Each questionnaire captures different health-promoting dimensions, namely: health-promoting resources (i.e. sense of coherence); occupational balance; emotional intelligence; health and welfare; social interaction; and work and workplace experiences/perceptions. DISCUSSION: This study focuses on the vastly important aspect of promoting a sustainable working life for healthcare and social work employees. In contrast to previous studies in this area, the present study uses different, validated instruments in health promotion, taking a salutogenic approach. It is hoped that, by stimulating the implementation of new strategies, the study's findings will lead to education programs that prepare students better for a sustainable working life in healthcare and social work