Δευτέρα, 23 Απριλίου 2018

TAS2R38 Predisposition to Bitter Taste Associated with Differential Changes in Vegetable Intake in Response to a Community-Based Dietary Intervention

Although vegetable consumption associates with decreased risk for a variety of diseases, few Americans meet dietary recommendations for vegetable intake. TAS2R38 encodes a taste receptor that confers bitter taste sensing from chemicals found in some vegetables. Common polymorphisms in TAS2R38 lead to coding substitutions that alter receptor function and result in the loss of bitter taste perception. Our study examined whether bitter taste perception TAS2R38 diplotypes associated with vegetable consumption in participants enrolled in either an enhanced or a minimal nutrition counseling intervention. DNA was isolated from the peripheral blood cells of study participants (N = 497) and analyzed for polymorphisms. Vegetable consumption was determined using the Block Fruit and Vegetable screener. We tested for differences in the frequency of vegetable consumption between intervention and genotype groups over time using mixed effects models. Baseline vegetable consumption frequency did not associate with bitter taste diplotypes (p = 0.937), however after six months of the intervention, we observed an interaction between bitter taste diplotypes and time (p = 0.046). Participants in the enhanced intervention increased their vegetable consumption frequency (p = 0.020) and within this intervention group, the bitter non-tasters and intermediate-bitter tasters had the largest increase in vegetable consumption. In contrast, in the minimal intervention group, the bitter tasting participants reported a decrease in vegetable consumption. Bitter-non tasters and intermediate-bitter tasters increased vegetable consumption in either intervention more than those who perceive bitterness. Future precision medicine applications could consider genetic variation in bitter taste perception genes when designing dietary interventions.



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Regulation of Global Transcription in Escherichia coli by Rsd and 6S RNA

In Escherichia coli, the sigma factor 70 directs RNA polymerase to transcribe growth-related genes, while 38 directs transcription of stress response genes during stationary phase. Two molecules hypothesized to regulate RNA polymerase are the protein Rsd, which binds to 70, and the non-coding 6S RNA which binds to the RNA polymerase-70 holoenzyme. Despite multiple studies, the functions of Rsd and 6S RNA remain controversial. Here we use RNA-Seq in five phases of growth to elucidate their function on a genome-wide scale. We show for the first time that Rsd and 6S RNA facilitate 38 activity throughout bacterial growth, while 6S RNA also regulates widely different genes depending upon growth phase. We discover novel interactions between 6S RNA and Rsd and show widespread expression changes in a strain lacking both regulators. Finally, we present a mathematical model of transcription which highlights the crosstalk between Rsd and 6S RNA as a crucial factor in controlling sigma factor competition and global gene expression.



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{-}{-}RNA Polymerase II Transcription Attenuation at the Yeast DNA Repair Gene, DEF1, Involves Sen1-Dependent and Polyadenylation Site-Dependent Termination

Termination of RNA Polymerase II (Pol II) activity serves a vital cellular function by separating ubiquitous transcription units and influencing RNA fate and function. In the yeast Saccharomyces cerevisiae, Pol II termination is carried out by cleavage and polyadenylation factor (CPF-CF) and Nrd1-Nab3-Sen1 (NNS) complexes, which operate primarily at mRNA and non-coding RNA genes, respectively. Premature Pol II termination (attenuation) contributes to gene regulation, but there is limited knowledge of its prevalence and biological significance. In particular, it is unclear how much crosstalk occurs between CPF-CF and NNS complexes and how Pol II attenuation is modulated during stress adaptation. In this study, we have identified an attenuator in the DEF1 DNA repair gene, which includes a portion of the 5'-untranslated region (UTR) and upstream open reading frame (ORF). Using a plasmid-based reporter gene system, we conducted a genetic screen of 14 termination mutants and their ability to confer Pol II read-through defects. The DEF1 attenuator behaved as a hybrid terminator, relying heavily on CPF-CF and Sen1 but without Nrd1 and Nab3 involvement. Our genetic selection identified 22 cis-acting point mutations that clustered into four regions, including a polyadenylation site efficiency element that genetically interacts with its cognate binding-protein Hrp1. Outside of the reporter gene context, a DEF1 attenuator mutant increased mRNA and protein expression, exacerbating the toxicity of a constitutively active Def1 protein. Overall, our data support a biologically significant role for transcription attenuation in regulating DEF1 expression, which can be modulated during the DNA damage response.



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FXR Deletion in Hepatocytes does not Affect the Severity of Alcoholic Liver Disease in Mice

Emerging evidence has shown that FXR activation ameliorates the development of alcoholic liver diseases (ALD) while whole-body deficiency of FXR in mice leads to more severe ALD. However, it's unknown whether the enhanced susceptibility to ALD development in FXR−/− mice is due to deficiency of hepatic FXR or increased toxicity secondary to increased bile acid (BA) levels. Hepatocyte-specific FXR knockout mice (FXRhep−/−) present similar BA levels compared to wild-type mice, and are therefore a useful model to study a direct role of hepatic FXR in ALD development.

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☆EUS–guided reconstruction of the biliary system in a patient post right hemihepatectomy



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Webinar: How data is being used to improve patient care

NHTSA's Office of EMS will discuss how two EMS agencies are using data to not only improve performance, but demonstrate value

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Coagulase-Negative Staphylococci Isolated from Human Bloodstream Infections Showed Multidrug Resistance Profile

Microbial Drug Resistance, Ahead of Print.


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Significance of Coexisting Mutations on Determination of the Degree of Isoniazid Resistance in Mycobacterium tuberculosis Strains

Microbial Drug Resistance, Ahead of Print.


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Antibiotic Resistance in Food Animals in Africa: A Systematic Review and Meta-Analysis

Microbial Drug Resistance, Ahead of Print.


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Mom wins AED for school after son’s death at hockey practice

In addition to creating the 4AlecFoundation to raise awareness for undetected heart disease, Stephanie Kornet also won a national contest by sharing her son's story

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Webinar to be hosted on improving patient care with data

NHTSA's Office of EMS will discuss how two EMS agencies are using data to not only improve performance, but demonstrate value

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Post-stroke unilateral spatial neglect: virtual reality-based navigation and detection tasks reveal lateralized and non-lateralized deficits in tasks of varying perceptual and cognitive demands

Unilateral spatial neglect (USN), a highly prevalent and disabling post-stroke impairment, has been shown to affect the recovery of locomotor and navigation skills needed for community mobility. We recently fo...

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Evoked potentials predict psychomotor development in neonates with normal MRI after hypothermia for hypoxic-ischemic encephalopathy

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Publication date: June 2018
Source:Clinical Neurophysiology, Volume 129, Issue 6
Author(s): Elisa Cainelli, Daniele Trevisanuto, Francesco Cavallin, Renzo Manara, Agnese Suppiej
ObjectivesTo assess the prognostic role of evoked potentials (EP) in neonates with normal magnetic resonance imaging (MRI) after therapeutic hypothermia (TH) for hypoxic-ischemic encephalopathy (HIE).MethodsThirty-five neonates recruited for TH because of HIE, having normal neonatal MRI, performed neonatal somatosensory (SEP), visual (VEP) evoked potentials and electroencephalogram (EEG). The effect of SEP, VEP or EEG abnormalities on Griffith's developmental scales at 12 and 24 months was measured; positive (PPV) and negative (NPV) predictive value, sensitivity, specificity and accuracy were calculated.ResultsAt 24 months, 28% had global psychomotor impairment and 57% had isolated impairments. VEP abnormality was associated with impaired hearing-language score (p = 0.002) and performance score (p < 0.0001). VEP achieved best PPV (0.91, 95% C.I. 0.62–0.99) and specificity (0.93, 95% C.I. 0.70–0.99). The combination of neurophysiological tests achieved the best NPV (0.85, 95% C.I. 0.58–0.96), sensitivity (0.90, 95% C.I. 0.70–0.97), overall accuracy (0.83, 95% C.I. 0.67–0.92).ConclusionsPsychomotor sequelae may occur in survivors of neonatal HIE with normal MRI. VEP is the single best neurophysiological prognostic marker but the combination of neurophysiological tests has a better value.SignificanceWhen facing the challenge of neurodevelopmental prognosis in infants with normal MRI after TH, EPs are useful prognostic tools, complementary to EEG.



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Genetics of CRISPR arrays in Salmonella Typhimurium 14028 associated with foreign DNA decay

Abstract

Clustered regularly interspaced short palindromic repeats (CRISPRs) are a genetic locus of prokaryotes and contain highly conserved direct repeats, spacers, and CRISPR-associated genes. Spacers in CRISPRs are known as adaptive immune markers and reveal what types of phage or foreign DNA have been introduced in the past. The primary objective of this study was to analyze spacer sequences in CRISPR arrays of 15 Salmonella enterica subspecies and to determine if Salmonella CRISPRs are indeed involved in resistance to foreign DNAs. Using a bioinformatics algorithm, the CRISPR arrays of 15 subspecies of S. enterica were predicted. The transformation efficiencies of the wild-type and mutant strains lacking a space were determined using the plasmid harboring the same sequences with the space. Analysis of the CRISPR arrays indicated that S. Typhimurium encoded three possible CRISPR regions in the genome. Notably, 48 or 55 spacers were predicted in the genomes of S. Typhimurium 14028 and LT2 strains, respectively, and 39 were precisely identical. To confirm this prediction, the predicted CRISPR regions of S. Typhimurium 14028 were sequenced using the specific primers. Interestingly, a homology search of individual spacers found that the 2nd spacer of CRISPR 2 was nearly identical to a partial genome region of phage FSL SP-016. The mutant strain showed two to threefold increased transformation efficiency compared to that of the wild-type strain. These results demonstrate that the spacer sequence is dependent on genetic relations, especially for adaptive immunity against phage or foreign DNAs.



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Muscle quality characteristics of muscles in the thigh, upper arm and lower back in elderly men and women

Abstract

Purpose

The ratio of fat within skeletal muscle is an important parameter that is indicative of muscle quality, and can be assessed using ultrasonography to measure echo intensity (EI). Muscle EI indicates muscle strength and risk of physical dysfunction; however, this observation was determined following examinations of only selected muscle. The purpose of this study was to investigate the EI characteristics of muscles in several regions in elderly men and women, using physical function tests and serum cholesterol levels.

Methods

Twenty-two men and women (age 78 ± 8 years) participated in this study. The EIs were calculated from rectus femoris (RF), biceps femoris (BF) triceps brachii (TB) and multifidus (MF) using B-mode transverse ultrasound images. Seven functional tests (isometric knee-extension peak torque, functional reach, sit-to-stand, 5-m normal/maximal speed walking, handgrip strength and timed up-and-go) and blood lipid components including adipocytokines were measured in all participants.

Results

A statistically significant correlation between EI of the RF, TB and BF was observed (r = 0.46–0.50, P < 0.05), but not between EI of the MF and that of other muscles. EI of muscles of the limbs, which was averaged EI for RF, TB and BF, was negatively correlated with leptin levels (adjusted R2 = 0.27, P < 0.01), and EI of the MF was correlated with muscle mass and performance in the timed up-and-go test (adjusted R2 = 0.61, P < 0.01).

Conclusion

These results suggest that EI might be influenced by specific parameters depending on the location of the muscle.



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Taking aim at transcriptional regulator targets

Taking aim at transcriptional regulator targets

Taking aim at transcriptional regulator targets, Published online: 23 April 2018; doi:10.1038/s41576-018-0010-5

A paper in Science reports a strategy that combines rapid chemical-genetic perturbation with measurements of immediate gene expression changes to identify targets of transcriptional regulators.

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Linking tissues to disease

Linking tissues to disease

Linking tissues to disease, Published online: 23 April 2018; doi:10.1038/s41576-018-0009-y

A recent analysis in Nature Genetics combines genome-wide association study summary statistics with gene expression data to identify the contribution of different cell types and tissues to disease.

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Taking aim at transcriptional regulator targets



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Linking tissues to disease



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Exploring the Relationship Between Fundamental Motor Skill Interventions and Physical Activity Levels in Children: A Systematic Review and Meta-analysis

Abstract

Background

Physical activity provides many health benefits, yet few children meet the physical activity recommendations. In school-age children, low proficiency in fundamental movement skills (FMS) is associated with low physical activity (PA). It is unknown if the same relationship exists in pre-schoolers (aged 3–5 years).

Objectives

The aims of this review were to firstly evaluate interventions for improving FMS and PA levels in children aged 3–5 years and 5–12 years, and secondly to determine, where possible, if there is a similar relationship between change in FMS and change in PA across both age groups.

Methods

A systematic search of electronic databases was conducted up until 20 July 2017. Controlled trials that implemented an FMS/PA intervention and measured PA levels (objective/subjective) and FMS (objective) in healthy children between the ages of 3 and 12 years were included. Sub-analysis was conducted based on the type of intervention (teacher-led [TL] or teacher educated), sessions per week (< 3 or ≥ 3) and age group.

Results

Search terms yielded 17,553 articles, of which 18 met the inclusion criteria. There was significant improvement in FMS with TL interventions of three or more sessions per week (standardised mean difference = 0.23 [0.11–0.36]; p = 0.0002). In TL interventions, there was a strong negative correlation between moderate–vigorous physical activity (MVPA) and sedentary behaviour (SB) (r = − 0.969; p = 0.031).

Conclusions

There are limited studies measuring both FMS and PA following an FMS intervention, especially in school-aged children. Results indicate that training pre-schoolers at least three times a week in FMS can improve proficiency, increase intensity of PA, and reduce SB, possibly helping to reduce the burden of childhood obesity and its associated health risks.



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Physiological and psychological determinants of whole-body endurance exercise following short-term sustained operations with partial sleep deprivation

Abstract

Purpose

The study examined the effects of short-term field-based military training with partial sleep deprivation on whole-body endurance performance in well-trained individuals.

Methods

Before and after a 2-day sustained operations (SUSOPS), 14 cadets performed a 15-min constant-load cycling at 65% of peak power output (PPO; CLT65), followed by an exhaustive constant-load trial at 85% of PPO (CLT85). Physiological [oxygen uptake ( \(\dot {V}\) O2), heart rate (HR), mean arterial pressure (MAP), cardiac output (CO), and regional oxygenation (TOI) in the frontal cerebral cortex and vastus lateralis muscle] and psychological [effort perception (RPE), affective valence (FS), and perceived activation (FAS)] variables were monitored during exercise.

Results

SUSOPS reduced time to exhaustion in CLT85 by 29.1% (p = 0.01). During the CLT65 trial, SUSOPS potentiated the exercise-induced elevations in \(\dot {V}\) O2 and HR (p < 0.05), and blunted MAP (p = 0.001). CO did not differ between trials. Yet, towards the end of both CLT85 trials, CO tended to decline (p ≤ 0.08); a response that occurred at an earlier stage in the SUSOPS trial. During CLT65, SUSOPS altered neither cerebral nor muscle TOI. The SUSOPS CLT85 trial, however, was terminated at similar leg-muscle deoxygenation (p > 0.05) and lower prefrontal cortex deoxygenation (p < 0.01). SUSOPS increased RPE at submaximal intensities (p = 0.05), and suppressed FAS and FS throughout (p < 0.01).

Conclusions

The present findings indicate, therefore, that a brief period of military sustained operations with partial sleep deprivation augment cardiorespiratory and psychological strain, limiting high-intensity endurance capacity.



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Early milestones in the understanding of echolocation in bats

Abstract

Almost 80 years ago, Griffin and Galambos discovered the phenomenon of echolocation in bats. Since then, the field has grown exponentially as new generations of investigators have joined the chase and technological advances have revolutionized working with ultrasound in the laboratory and in the field. Today our understanding of the diversity of behavioral and neural adaptations for echolocation constitutes one of the paramount triumphs of neuroethology. At the invitation of the editor in chief, I here review some of the important milestones in the discovery and early understanding of echolocation in bats through about the mid-1980s.



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