23 research outputs found

    Transport of proteins into the various subcompartments of mitochondria

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    The import of proteins into mitochondria is an intricate process comprised of multiple steps. The first step involves the sorting of cytosolically synthesized precursor proteins to the mitochondrial surface. There precursor proteins are recognized by specific receptors which deliver them to the general import site present in the outer membrane. The second stage of import involves a series of complex intraorganelle sorting events which results in the delivery of the proteins to one of the four possible submitochondrial destinations, namely the outer and inner membranes, the matrix and intermembrane space. Here in this review, we discuss the current knowledge on these intramitochondrial sorting events. We especially focus on targetting of proteins to the intermembrane space. Sorting to the intermembrane space represents a particularly interesting situation, as at least three separate targetting pathways to this subcompartment are known to exist

    Food security risk level assessment : a fuzzy logic-based approach

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    A fuzzy logic (FL)-based food security risk level assessment system is designed and is presented in this article. Three inputs—yield, production, and economic growth—are used to predict the level of risk associated with food supply. A number of previous studies have related food supply with risk assessment for particular types of food, but none of the work was specifically concerned with how the wider food chain might be affected. The system we describe here uses the Mamdani method. The resulting system can assess risk level against three grades: severe, acceptable, and good. The method is tested with UK (United Kingdom) cereal data for the period from 1988 to 2008. The approach is discussed on the basis that it could be used as a starting point in developing tools that may either assess current food security risk or predict periods or regions of impending pressure on food supply

    Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

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    Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

    25th annual computational neuroscience meeting: CNS-2016

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    The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

    Improving medication adherence in patients with cardiovascular disease: a systematic review.

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    OBJECTIVE: To evaluate and compare the effect of interventions for improving adherence to medications for atherosclerotic cardiovascular disease (ASCVD) secondary prevention. METHODS: We extracted eligible trials from a 2014 Cochrane systematic review on adherence for any condition. We updated the search from CENTRAL, Medline, Embase, PsycINFO, CINAHL, Sociological Abstracts and trial registers through November 2016. Study reports needed to be from a randomised controlled trial, incorporate participants identified as having ASCVD and interventions aimed at improving adherence to medicines for secondary prevention of ASCVD and measure both adherence and a clinical outcome. Two reviewers independently determined the eligibility of studies, extracted data and conducted a narrative synthesis. RESULTS: We identified 17 trials (n=17 448 participants). Most trials had high risk of bias in at least one domain. The intervention group adherence rates ranged from 44%to99% and the comparator group adherence rates ranged from 13% to 96%. Three distinct interventions reported improvements in both adherence and clinical outcomes: short message service (65% vs 13% of participants with high adherence in the intervention vs control group), a fixed-dose combination pill (86% vs 65% adherence, risk ratio of being adherent, 1.33; 95% CI 1.26 to 1.41) and a community health worker-based intervention (97% in the intervention group compared with 92% in the control group; OR=2.62, 95% CI 1.32 to 5.19). CONCLUSIONS: We identified three interventions that demonstrated improvements in adherence and clinical outcomes. Ongoing, longer-term trials will help determine whether short-term changes in adherence can be maintained and lead to differences in clinical events

    A multi-site collaborative study of the hostile priming effect

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    In a now-classic study by Srull and Wyer (1979), people who were exposed to phrases with hostile content subsequently judged a man as being more hostile. And this “hostile priming effect” has had a significant influence on the field of social cognition over the subsequent decades. However, a recent multi-lab collaborative study (McCarthy et al., 2018) that closely followed the methods described by Srull and Wyer (1979) found a hostile priming effect that was nearly zero, which casts doubt on whether these methods reliably produce an effect. To address some limitations with McCarthy et al. (2018), the current multi-site collaborative study included data collected from 29 labs. Each lab conducted a close replication (total N = 2,123) and a conceptual replication (total N = 2,579) of Srull and Wyer\u27s methods. The hostile priming effect for both the close replication (d = 0.09, 95% CI [-0.04, 0.22], z = 1.34, p =.16) and the conceptual replication (d = 0.05, 95% CI [-0.04, 0.15], z = 1.15, p =.58) were not significantly different from zero and, if the true effects are non-zero, were smaller than what most labs could feasibly and routinely detect. Despite our best efforts to produce favorable conditions for the effect to emerge, we did not detect a hostile priming effect. We suggest that researchers should not invest more resources into trying to detect a hostile priming effect using methods like those described in Srull and Wyer (1979)
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