2,141 research outputs found

    Segregating the Distinct Effects of Sedentary Behavior and Physical Activity on Older Adults' Cardiovascular Profile: Part 2-Isotemporal Substitution Approach.

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    The aim of the study was to provide an isotemporal substitution model to predict how changes in physical behavior may affect the cardiovascular parameters (CVPs) of older adults. Methods: Participants wore a thigh-mounted accelerometer for 7 days. Phenotype of the carotid, brachial, and popliteal artery was conducted using ultrasound. Isotemporal substitution was used to simulate the degree to which replacing 1 hour of physical behavior with another would affect CVP. Results: Substitution of sedentary behavior with Standing and sporadic moderate- to vigorous-intensity physical activity (MVPA accumulated in bouts <10 min) would reduce resting heart rate [−6.20 beats per minute (−12.1 to −0.22) and −3.72 beats per minute (−7.01 to −0.44), respectively]. Substitution of sedentary behavior with light-intensity physical activity would reduce carotid artery diameter [−0.54 mm (−1.00 to −0.07)]. Substitution of Standing with sporadic MVPA would increase popliteal artery diameter [1.31 mm (0.11 to 2.51)]. Conclusions: Our modeling suggests that an accumulation of MVPA bouts that are shorter than the recommended 10-minute minimum may still improve CVP, with lower intensity physical activity also influencing CVP. Our findings are a promising avenue for lifestyle interventions in older adults to reduce the aging effects on CVP for those who cannot engage or sustain sufficient MVPA

    Influences of carbohydrate plus amino acid supplementation on differing exercise intensity adaptations in older persons: skeletal muscle and endocrine responses

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    Losses in physiological function in healthy ageing occur partly as a consequence of reduced protein intake and partly as a consequence of less than 30-min/day of moderate to vigorous physical activity. The current study aimed to compare the effects of two different intensities of resistance training in healthy older adults, whose habitual dietary intake was supplemented with carbohydrate and amino acid preparations. We hypothesised that although intensive exercise with appropriate carbohydrate and amino acid supplementation would result in the most profound impact on in vivo markers of healthy physiologic and endocrine functions in previously sedentary older individuals, the effectiveness of the less intense exercise prescription with supplementation would also result in beneficial adaptations over and above findings of previous studies on low intensity exercise alone. Twenty-nine older adults (out of 32) completed the study after being randomly assigned to low (SUP-LowR, i.e., ∼40% 1RM; n=16) versus high resistance training (SUP-HighR, i.e., ∼80% 1RM; n=13) for 12 weeks. A carbohydrate supplement was ingested immediately before and during every exercise session and an amino acid cocktail was ingested post-exercise. Neither intervention significantly impacted upon body composition assessed using: Body mass index, waist/hip ratio and bioelectric impedance. Muscle strength increased similarly in the two groups with the SUP-HighR protocol showing 46±8%, 10.8±4.4% and 26.9± 4.9% (P<0.01) improvements in 1-RM strength, unilateral and bilateral knee extension torque, respectively, compared with 39±2%, 9.4±3.7% and 29.5± 8.2% (P<0.01) increments in the same measures in the SUP-LowR group. Lean muscle thickness however, showed a greater benefit of the SUP-LowR protocol (8.7±3.9% increase, P<0.05) compared with the SUP-HighR protocol, which elicited no significant change. In terms of functional abilities, only the standing-from-lying (SFL) test exhibited an improvement in rate in the SUP-HighR group (-11.4%, P< 0.05). The SUP-LowR group, on the other hand, showed significant improvements in the get-up-andgo (-8.7±3.6%, P<0.05), the SFL (-4.7% change, P=0.05) and the 6-min walk (7.2±2.2% increase in distance covered, P<0.01) tests. Following overnight fasting, serum levels of glucose changed significantly (-13±4.7% decrease, P<0.01) in SUP-LowR. Serum levels of insulin (-25±5.3% decrease, P=0.05), neuropeptide Y (-24±15.3% decrease, P=0.02), and IGFBP-3 (-11±6.6% decrease, P=0.03), changed significantly in SUP-HighR. Circulating levels of interleukin-6, tumour necrosis factor-alpha and insulin- like growth factor 1 did not alter significantly in either intervention group. These data suggest that whilst both interventions were beneficial in older persons, the end targets as well as metabolic and hormonal adaptations are different. The supplementation plus low exercise regimen tended to impact on muscle hypertrophy combined with increased habitual function. Supplementation plus high-intensity exercise regimen improved markers of strength, but not to a significantly greater extent than supplementation plus low intensity exercise. © American Aging Association 2010

    Identification of furfural resistant strains of Saccharomyces cerevisiae and Saccharomyces paradoxus from a collection of environmental and industrial isolates

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    Background Fermentation of bioethanol using lignocellulosic biomass as a raw material provides a sustainable alternative to current biofuel production methods by utilising waste food streams as raw material. Before lignocellulose can be fermented it requires physical, chemical and enzymatic treatment in order to release monosaccharides, a process that causes the chemical transformation of glucose and xylose into the cyclic aldehydes furfural and hydroxyfurfural. These furan compounds are potent inhibitors of Saccharomyces fermentation, and consequently furfural tolerant strains of Saccharomyces are required for lignocellulosic fermentation. Results This study investigated yeast tolerance to furfural and hydroxyfurfural using a collection of 71 environmental and industrial isolates of the baker’s yeast Saccharomyces cerevisiae and its closest relative Saccharomyces paradoxus. The Saccharomyces strains were initially screened for growth on media containing 100 mM glucose and 1.5 mg ml-1 furfural. Five strains were identified that showed a significant tolerance to growth in the presence of furfural and these were then screened for growth and ethanol production in the presence of increasing amounts (0.1-4 mg ml-1) of furfural. Conclusions Of the five furfural tolerant strains S. cerevisiae NCYC 3451 displayed the greatest furfural resistance, and was able to grow in the presence of up to 3.0 mg ml-1 furfural. Furthermore, ethanol production in this strain did not appear to be inhibited by furfural, with the highest ethanol yield observed at 3.0 mg ml-1 furfural. Although furfural resistance was not found to be a trait specific to any one particular lineage or population, three of the strains were isolated from environments where they might be continually exposed to low levels of furfural through the on-going natural degradation of lignocelluloses, and would therefore develop elevated levels of resistance to these furan compounds. Thus these strains represent good candidates for future studies of genetic variation relevant to understanding and manipulating furfural resistance and in the development of tolerant ethanologenic yeast strains for use in bioethanol production from lignocellulose processing

    Why Current Statistical Approaches to Ransomware Detection Fail

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    The frequent use of basic statistical techniques to detect ransomware is a popular and intuitive strategy; statistical tests can be used to identify randomness, which in turn can indicate the presence of encryption and, by extension, a ransomware attack. However, common file formats such as images and compressed data can look random from the perspective of some of these tests. In this work, we investigate the current frequent use of statistical tests in the context of ransomware detection, primarily focusing on false positive rates. The main aim of our work is to show that the current over-dependence on simple statistical tests within anti-ransomware tools can cause serious issues with the reliability and consistency of ransomware detection in the form of frequent false classifications. We determined thresholds for five key statistics frequently used in detecting randomness, namely Shannon entropy, chi-square, arithmetic mean, Monte Carlo estimation for Pi and serial correlation coefficient. We obtained a large data set of 84,327 files comprising of images, compressed data and encrypted data. We then tested these thresholds (taken from a variety of previous publications in the literature where possible) against our dataset, showing that the rate of false positives is far beyond what could be considered acceptable. False positive rates were often above 50% and even above 90% on several occasions. False negative rates were also generally between 5% and 20%, numbers which are also far too high. As a direct result of these experiments, we determine that relying on these simple statistical approaches is not good enough to detect ransomware attacks consistently. We instead recommend the exploration of higher-order statistics such as skewness and kurtosis for future ransomware detection techniques

    FRA2A is a CGG repeat expansion associated with silencing of AFF3

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    Folate-sensitive fragile sites (FSFS) are a rare cytogenetically visible subset of dynamic mutations. Of the eight molecularly characterized FSFS, four are associated with intellectual disability (ID). Cytogenetic expression results from CGG tri-nucleotide-repeat expansion mutation associated with local CpG hypermethylation and transcriptional silencing. The best studied is the FRAXA site in the FMR1 gene, where large expansions cause fragile X syndrome, the most common inherited ID syndrome. Here we studied three families with FRA2A expression at 2q11 associated with a wide spectrum of neurodevelopmental phenotypes. We identified a polymorphic CGG repeat in a conserved, brain-active alternative promoter of the AFF3 gene, an autosomal homolog of the X-linked AFF2/FMR2 gene: Expansion of the AFF2 CGG repeat causes FRAXE ID. We found that FRA2A-expressing individuals have mosaic expansions of the AFF3 CGG repeat in the range of several hundred repeat units. Moreover, bisulfite sequencing and pyrosequencing both suggest AFF3 promoter hypermethylation. cSNP-analysis demonstrates monoallelic expression of the AFF3 gene in FRA2A carriers thus predicting that FRA2A expression results in functional haploinsufficiency for AFF3 at least in a subset of tissues. By whole-mount in situ hybridization the mouse AFF3 ortholog shows strong regional expression in the developing brain, somites and limb buds in 9.5-12.5dpc mouse embryos. Our data suggest that there may be an association between FRA2A and a delay in the acquisition of motor and language skills in the families studied here. However, additional cases are required to firmly establish a causal relationship

    Segregating the Distinct Effects of Sedentary Behavior and Physical Activity on Older Adults' Cardiovascular Structure and Function: Part 1-Linear Regression Analysis Approach

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    Background: Physical behavior [PB, physical activity (PA), and sedentary behavior (SB)] can adjust cardiovascular mortality risk in older adults. The aim of this study was to predict cardiovascular parameters (CVPs) using 21 parameters of PB. Methods: Participants [n = 93, 73.8 (6.23) y] wore a thigh-mounted accelerometer for 7 days. Phenotype of the carotid, brachial, and popliteal arteries was conducted using ultrasound. Results: Sedentary behavior was associated with one of the 19 CVPs. Standing and light-intensity PA was associated with 3 and 1 CVP, respectively. Our prediction model suggested that an hourly increase in light-intensity PA would be negatively associated with popliteal intima-media thickness [0.09 mm (95% confidence interval, 0.15 to 0.03)]. sMVPA [moderate–vigorous PA (MVPA), accumulated in bouts <10 min] was associated with 1 CVP. 10MVPA (MVPA accumulated in bouts ≥10 min) had no associations. W50% had associations with 3 CVP. SB%, alpha, true mean PA bout, daily sum of PA bout time, and total week 10MVPA each were associated with 2 CVP. Conclusions: Patterns of PB are more robust predictors of CVP than PB (hours per day). The prediction that popliteal intima-media thickness would be negatively associated with increased standing and light-intensity PA engagement suggests that older adults could obtain health benefits without MVPA engagement

    Modifiers of (CAG)(n) instability in Machado-Joseph disease (MJD/SCA3) transmissions: an association study with DNA replication, repair and recombination genes.

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    Twelve neurological disorders are caused by gene-specific CAG/CTG repeat expansions that are highly unstable upon transmission to offspring. This intergenerational repeat instability is clinically relevant since disease onset, progression and severity are associated with repeat size. Studies of model organisms revealed the involvement of some DNA replication and repair genes in the process of repeat instability, however, little is known about their role in patients. Here, we used an association study to search for genetic modifiers of (CAG)n instability in 137 parent-child transmissions in Machado-Joseph disease (MJD/SCA3). With the hypothesis that variants in genes involved in DNA replication, repair or recombination might alter the MJD CAG instability patterns, we screened 768 SNPs from 93 of these genes. We found a variant in ERCC6 (rs2228528) associated with an expansion bias of MJD alleles. When using a gene-gene interaction model, the allele combination G-A (rs4140804-rs2972388) of RPA3-CDK7 is also associated with MJD instability in a direction-dependent manner. Interestingly, the transcription-coupled repair factor ERCC6 (aka CSB), the single-strand binding protein RPA, and the CDK7 kinase part of the TFIIH transcription repair complex, have all been linked to transcription-coupled repair. This is the first study performed in patient samples to implicate specific modifiers of CAG instability in humans. In summary, we found variants in three transcription-coupled repair genes associated with the MJD mutation that points to distinct mechanisms of (CAG)n instability.This work was supported by the Canadian Institutes of Health Research; and the Levesque Chair for research in Neurogenetics [to G. A. R.]; and the Portuguese Foundation for Science and Technology [SFRH/BPD/77969/2011 to S.M]
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