241 research outputs found

    Prevalence and predictors of video game addiction: a study based on a national representative sample of gamers

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    Video gaming has become a popular leisure activity in many parts of the world, and an increasing number of empirical studies examine the small minority that appears to develop problems as a result of excessive gaming. This study investigated prevalence rates and predictors of video game addiction in a sample of gamers, randomly selected from the National Population Registry of Norway (N =3389). Results showed there were 1.4 % addicted gamers, 7.3 % problem gamers, 3.9 % engaged gamers, and 87.4 % normal gamers. Gender (being male) and age group (being young) were positively associated with addicted-, problem-, and engaged gamers. Place of birth (Africa, Asia, South- and Middle America) were positively associated with addicted- and problem gamers. Video game addiction was negatively associated with conscientiousness and positively associated with neuroticism. Poor psychosomatic health was positively associated with problem- and engaged gaming. These factors provide insight into the field of video game addiction, and may help to provide guidance as to how individuals that are at risk of becoming addicted gamers can be identified

    Tailor-Made Zinc-Finger Transcription Factors Activate FLO11 Gene Expression with Phenotypic Consequences in the Yeast Saccharomyces cerevisiae

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    Cys2His2 zinc fingers are eukaryotic DNA-binding motifs, capable of distinguishing different DNA sequences, and are suitable for engineering artificial transcription factors. In this work, we used the budding yeast Saccharomyces cerevisiae to study the ability of tailor-made zinc finger proteins to activate the expression of the FLO11 gene, with phenotypic consequences. Two three-finger peptides were identified, recognizing sites from the 5′ UTR of the FLO11 gene with nanomolar DNA-binding affinity. The three-finger domains and their combined six-finger motif, recognizing an 18-bp site, were fused to the activation domain of VP16 or VP64. These transcription factor constructs retained their DNA-binding ability, with the six-finger ones being the highest in affinity. However, when expressed in haploid yeast cells, only one three-finger recombinant transcription factor was able to activate the expression of FLO11 efficiently. Unlike in the wild-type, cells with such transcriptional activation displayed invasive growth and biofilm formation, without any requirement for glucose depletion. The VP16 and VP64 domains appeared to act equally well in the activation of FLO11 expression, with comparable effects in phenotypic alteration. We conclude that the functional activity of tailor-made transcription factors in cells is not easily predicted by the in vitro DNA-binding activity

    The usefulness of arbekacin compared to vancomycin

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    The bacteriological efficacy response (improved, arbekacin vs. vancomycin; 71.2% vs. 79.5%) and clinical efficacy response (improved, arbekacin vs. vancomycin; 65.3% vs. 76.1%) were not statistically different between the two groups. The complication rate was significantly higher in the vancomycin group (32.9%) compared to the arbekacin group (15.1%) (p = 0.019). Arbekacin was not inferior to vancomycin, and it could be a good alternative drug for vancomycin in methicillin-resistant Staphylococcus aureus (MRSA) treatment

    Adaptive Evolution in Zinc Finger Transcription Factors

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    The majority of human genes are conserved among mammals, but some gene families have undergone extensive expansion in particular lineages. Here, we present an evolutionary analysis of one such gene family, the poly–zinc-finger (poly-ZF) genes. The human genome encodes approximately 700 members of the poly-ZF family of putative transcriptional repressors, many of which have associated KRAB, SCAN, or BTB domains. Analysis of the gene family across the tree of life indicates that the gene family arose from a small ancestral group of eukaryotic zinc-finger transcription factors through many repeated gene duplications accompanied by functional divergence. The ancestral gene family has probably expanded independently in several lineages, including mammals and some fishes. Investigation of adaptive evolution among recent paralogs using dN/dS analysis indicates that a major component of the selective pressure acting on these genes has been positive selection to change their DNA-binding specificity. These results suggest that the poly-ZF genes are a major source of new transcriptional repression activity in humans and other primates

    Functional cyclophilin D moderates platelet adhesion, but enhances the lytic resistance of fibrin

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    In the course of thrombosis, platelets are exposed to a variety of activating stimuli classified as ‘strong’ (e.g. thrombin and collagen) or ‘mild’ (e.g. ADP). In response, activated platelets adhere to injured vasculature, aggregate, and stabilise the three-dimensional fibrin scaffold of the expanding thrombus. Since ‘strong’ stimuli also induce opening of the mitochondrial permeability transition pore (MPTP) in platelets, the MPTP-enhancer Cyclophilin D (CypD) has been suggested as a critical pharmacological target to influence thrombosis. However, it is poorly understood what role CypD plays in the platelet response to ‘mild’ stimuli which act independently of MPTP. Furthermore, it is unknown how CypD influences platelet-driven clot stabilisation against enzymatic breakdown (fibrinolysis). Here we show that treatment of human platelets with Cyclosporine A (a cyclophilin-inhibitor) boosts ADP-induced adhesion and aggregation, while genetic ablation of CypD in murine platelets enhances adhesion but not aggregation. We also report that platelets lacking CypD preserve their integrity in a fibrin environment, and lose their ability to render clots resistant against fibrinolysis. Our results indicate that CypD has opposing haemostatic roles depending on the stimulus and stage of platelet activation, warranting a careful design of any antithrombotic strategy targeting CypD

    Critical pathways for the management of preeclampsia and severe preeclampsia in institutionalised health care settings

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    BACKGROUND: Preeclampsia is a complex disease in which several providers should interact continuously and in a coordinated manner to provide proper health care. However, standardizing criteria to treat patients with preeclampsia is problematical and severe flaws have been observed in the management of the disease. This paper describes a set of critical pathways (CPs) designed to provide uniform criteria for clinical decision-making at different levels of care of pregnant patients with preeclampsia or severe preeclampsia. METHODS: Clinicians and researchers from different countries participated in the construction of the CPs. The CPs were developed using the following steps: a) Definition of the conceptual framework; b) Identification of potential users: primary care physicians and maternal and child health nurses in ambulatory settings; ob/gyn and intensive care physicians in secondary and tertiary care levels. c) Structural development. RESULTS: The CPs address the following care processes: 1. Screening for preeclampsia, risk assessment and classification according to the level of risk. 2. Management of preeclampsia at primary care clinics. 3. Evaluation and management of preeclampsia at secondary and tertiary care hospitals: 4. Criteria for clinical decision-making between conservative management and expedited delivery of patients with severe preeclampsia. CONCLUSION: Since preeclampsia continues to be one of the primary causes of maternal deaths and morbidity worldwide, the expected impact of these CPs is the contribution to improving health care quality in both developed and developing countries. The CPs are designed to be applied in a complex health care system, where different physicians and health providers at different levels of care should interact continuously and in a coordinated manner to provide care to all preeclamptic women. Although the CPs were developed using evidence-based criteria, they could require careful evaluation and remodelling according to each system's demands. Additionally, the CPs need to be tested in large-scale, multi-level studies in order to thoroughly examine and evaluate their efficacy and effectiveness

    Local Gene Regulation Details a Recognition Code within the LacI Transcriptional Factor Family

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    The specific binding of regulatory proteins to DNA sequences exhibits no clear patterns of association between amino acids (AAs) and nucleotides (NTs). This complexity of protein-DNA interactions raises the question of whether a simple set of wide-coverage recognition rules can ever be identified. Here, we analyzed this issue using the extensive LacI family of transcriptional factors (TFs). We searched for recognition patterns by introducing a new approach to phylogenetic footprinting, based on the pervasive presence of local regulation in prokaryotic transcriptional networks. We identified a set of specificity correlations –determined by two AAs of the TFs and two NTs in the binding sites– that is conserved throughout a dominant subgroup within the family regardless of the evolutionary distance, and that act as a relatively consistent recognition code. The proposed rules are confirmed with data of previous experimental studies and by events of convergent evolution in the phylogenetic tree. The presence of a code emphasizes the stable structural context of the LacI family, while defining a precise blueprint to reprogram TF specificity with many practical applications.Ministerio de Ciencia e Innovación, Spain (Formación de Profesorado Universitario fellowship)Ministerio de Ciencia e Innovación, Spain (grant BFU2008-03632/BMC)Madrid (Spain : Region) (grant CCG08-CSIC/SAL-3651

    Characterisation of Human Embryonic Stem Cells Conditioning Media by 1H-Nuclear Magnetic Resonance Spectroscopy

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    BACKGROUND: Cell culture media conditioned by human foreskin fibroblasts (HFFs) provide a complex supplement of protein and metabolic factors that support in vitro proliferation of human embryonic stem cells (hESCs). However, the conditioning process is variable with different media batches often exhibiting differing capacities to maintain hESCs in culture. While recent studies have examined the protein complement of conditioned culture media, detailed information regarding the metabolic component of this media is lacking. METHODOLOGY/PRINCIPAL FINDINGS: Using a (1)H-Nuclear Magnetic Resonance ((1)H-NMR) metabonomics approach, 32 metabolites and small compounds were identified and quantified in media conditioned by passage 11 HFFs (CMp11). A number of metabolites were secreted by HFFs with significantly higher concentration of lactate, alanine, and formate detected in CMp11 compared to non-conditioned media. In contrast, levels of tryptophan, folate and niacinamide were depleted in CMp11 indicating the utilisation of these metabolites by HFFs. Multivariate statistical analysis of the (1)H-NMR data revealed marked age-related differences in the metabolic profile of CMp11 collected from HFFs every 24 h over 72 h. Additionally, the metabolic profile of CMp11 was altered following freezing at -20°C for 2 weeks. CM derived from passage 18 HFFs (CMp18) was found to be ineffective at supporting hESCs in an undifferentiated state beyond 5 days culture. Multivariate statistical comparison of CMp11 and CMp18 metabolic profiles enabled rapid and clear discrimination between the two media with CMp18 containing lower concentrations of lactate and alanine as well as higher concentrations of glucose and glutamine. CONCLUSIONS/SIGNIFICANCE: (1)H-NMR-based metabonomics offers a rapid and accurate method of characterising hESC conditioning media and is a valuable tool for monitoring, controlling and optimising hESC culture media preparation
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