895 research outputs found

    Compressed representation of a partially defined integer function over multiple arguments

    Get PDF
    In OLAP (OnLine Analitical Processing) data are analysed in an n-dimensional cube. The cube may be represented as a partially defined function over n arguments. Considering that often the function is not defined everywhere, we ask: is there a known way of representing the function or the points in which it is defined, in a more compact manner than the trivial one

    A novel function of the mitochondrial transcription factor Mtf1 in fission yeast; Mtf1 regulates the nuclear transcription of srk1

    Get PDF
    In eukaryotic cells, Mtf1 and its homologues function as mitochondrial transcription factors for the mitochondrial RNA polymerase in the mitochondrion. Here we show that in fission yeast Mtf1 exerts a non-mitochondrial function as a nuclear factor that regulates transcription of srk1, which is a kinase involved in the stress response and cell cycle progression. We first found Mtf1 expression in the nucleus. A ChIP-chip approach identified srk1 as a putative Mtf1 target gene. Over expression of Mtf1 induced transcription of the srk1 gene and Mtf1 deletion led to a reduction in transcription of the srk1 gene in vivo. Mtf1 overexpression causes cell elongation in a srk1 dependent manner. Mtf1 overexpression can cause cytoplasmic accumulation of Cdc25. We also provide biochemical evidence that Mtf1 binds to the upstream sequence of srk1. This is the first evidence that a mitochondrial transcription factor Mtf1 can regulate a nuclear gene. Mtf1 may also have a role in cell cycle progression

    Identification and characterization of the mitochondrial RNA polymerase and transcription factor in the fission yeast Schizosaccharomyces pombe

    Get PDF
    We have characterized the mitochondrial transcription factor (Mtf1) and RNA polymerase (Rpo41) of Schizosaccharomyces pombe. Deletion mutants show Mtf1 or Rpo41 to be essential for cell growth, cell morphology and mitochondrial membrane potential. Overexpression of Mtf1 and Rpo41 can induce mitochondrial transcription. Mtf1 and Rpo41 can bind and transcribe mitochondrial promoters in vitro and the initiating nucleotides were the same in vivo and in vitro. Mtf1 is required for efficient transcription. We discuss the functional differences between Mtf1 and Rpo41 of S. pombe with Saccharomyces cerevisiae and higher organisms. In contrast to S. cerevisiae, the established model for mitochondrial transcription, S. pombe, a petite-negative yeast, resembles higher organisms that cannot tolerate the loss of mitochondrial function. The S. pombe and human mitochondrial genomes are similar in size and much smaller than that of S. cerevisiae. This is an important first step in the development of S. pombe as an alternative and complementary model system for molecular genetic and biochemical studies of mitochondrial transcription and mitochondrial–nuclear interactions. This is the first systematic study of the cellular function and biochemistry of Rpo41 and Mtf1 in S. pombe

    Application of a theoretical model to evaluate COPD disease management

    Get PDF
    Background: Disease management programmes are heterogeneous in nature and often lack a theoretical basis. An evaluation model has been developed in which theoretically driven inquiries link disease management interventions to outcomes. The aim of this study is to methodically evaluate the impact of a disease management programme for patients with chronic obstructive pulmonary disease (COPD) on process, intermediate and final outcomes of care in a general practice setting. Methods. A quasi-experimental research was performed with 12-months follow-up of 189 COPD patients in primary care in the Netherlands. The programme included patient education, protocolised a

    Blood pressure and body mass index in an ethnically diverse sample of adolescents in Paramaribo, Suriname

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>High blood pressure (BP) is now an important public health problem in non-industrialised countries. The limited evidence suggests ethnic inequalities in BP in adults in some non-industrialised countries. However, it is unclear whether these ethnic inequalities in BP patterns in adults reflect on adolescents. Hence, we assessed ethnic differences in BP, and the association of BP with body mass index (BMI) among adolescents aged 12–17 years in Paramaribo, Suriname.</p> <p>Methods</p> <p>Cross-sectional study with anthropometric and blood pressure measurements. A random sample of 855 adolescents (167 Hindustanis, 169 Creoles, 128 Javanese, 91 Maroons and 300 mixed-ethnicities) were studied. Ethnicity was based on self-reported ethnic origin.</p> <p>Results</p> <p>Among boys, Maroons had a lower age- and height-adjusted systolic BP than Creoles, and a lower diastolic BP than other ethnic groups. However, after further adjustment for BMI, only diastolic BP in Maroons was significantly lower than in Javanese (67.1 versus 70.9 mmHg). Creole boys had a lower diastolic BP than Hindustani (67.3 versus 70.2 mmHg) and Javanese boys after adjustment for age, height and BMI. Among girls, there were no significant differences in systolic BP between the ethnic groups. Maroon girls, however, had a lower diastolic BP (65.6 mmHg) than Hindustani (69.1 mmHg), Javanese (71.2 mmHg) and Mixed-ethnic (68.3 mmHg) girls, but only after differences in BMI had been adjusted for. Javanese had a higher diastolic BP than Creoles (71.2 versus 66.8 mmHg) and Mixed-ethnicity girls. BMI was positively associated with BP in all the ethnic groups, except for diastolic BP in Maroon girls.</p> <p>Conclusion</p> <p>The study findings indicate higher mean BP levels among Javanese and Hindustani adolescents compared with their African descent peers. These findings contrast the relatively low BP reported in Javanese and Hindustani adult populations in Suriname and underscore the need for public health measures early in life to prevent high BP and its sequelae in later life.</p

    CLIP-Seq analysis enables the design of protective ribosomal RNA bait oligonucleotides against C9ORF72 ALS/FTD poly-GR pathophysiology

    Get PDF
    Amyotrophic lateral sclerosis and frontotemporal dementia patients with a hexanucleotide repeat expansion in C9ORF72 (C9-HRE) accumulate poly-GR and poly-PR aggregates. The pathogenicity of these arginine-rich dipeptide repeats (R-DPRs) is thought to be driven by their propensity to bind low-complexity domains of multivalent proteins. However, the ability of R-DPRs to bind native RNA and the significance of this interaction remain unclear. Here, we used computational and experimental approaches to characterize the physicochemical properties of R-DPRs and their interaction with RNA. We find that poly-GR predominantly binds ribosomal RNA (rRNA) in cells and exhibits an interaction that is predicted to be energetically stronger than that for associated ribosomal proteins. Critically, modified rRNA “bait” oligonucleotides restore poly-GR–associated ribosomal deficits and ameliorate poly-GR toxicity in patient neurons and Drosophila models. Our work strengthens the hypothesis that ribosomal function is impaired by R-DPRs, highlights a role for direct rRNA binding in mediating ribosomal dysfunction, and presents a strategy for protecting against C9-HRE pathophysiological mechanisms.This work was supported by the U.S. National Institutes of Health (NIH) National Institute of Neurological Disorders and Stroke (NINDS) and National Institute of Aging (NIA) grant R01NS104219 (E.K.); NIH/NINDS grant R21NS107761 (E.K.); AFM-Telethon French Muscular Dystrophy Association Trampoline Grant #23648 (J.A.O.); AFM-Telethon postdoctoral fellowship (J.A.O.); Ramon y Cajal fellowships RYC2019-026980-I (J.A.O.) and RYC2021-033294-I (I.R.S.); Gipuzkoa Foru Aldundia 2019-FELL-000017-01 (I.R.S.); Maria de Maeztu Units of Excellence CEX2021-001159-M (J.A.O.) and MDM-2017-0720 (I.R.S.); NINDS grants R01NS097850 and R01NS131409 (J.K.I.); Department of Defense grants PR211919 and W81XWH2110131 (J.K.I.); John Douglas French Alzheimer’s Foundation (J.K.I.); Center for Regenerative Nanomedicine at the Simpson Querrey Institute (S.I.S. and T.D.C.); Intramural Research Program, NIH, National Cancer Institute (NCI), Center for Cancer Research (M.B. and S.L.W.); Les Turner ALS Foundation (E.K.); and New York Stem Cell Foundation (J.K.I. and E.K.).With funding from the Spanish government through the "Severo Ochoa Centre of Excellence" accreditation (CEX2021-001159-M (J.A.O.)).Peer reviewe

    The Impact of Personality Traits Towards the Intention to Adopt Mobile Learning

    Get PDF
    Mobile devices have become increasingly more common in the digitally connected world. Mobile learning as a model of e-learning refers to the acquisition of knowledge & skills utilizing mobile technologies. The aim of this study is to identify the extrinsic influential factors for the adoption of mobile learning. This study proposes the use of an extended technology acceptance model (TAM) theory that includes variables of personality traits such as perceived enjoyment and computer self-efficiency. The participants of this study were 351 students at University Technology Malaysia who had experiences in e-learning. The study found that perceived usefulness as an extrinsic factor has the highest influence on students’ intention to adopt mobile learning through an investigation of technology acceptance toward mobile learning. Personality traits such as perceived enjoyment and self-efficacy have impact on behavior intention to adopt mobile learning
    corecore