Effect of Exercise Training on Lipoprotein Subclass Particle Concentrations and Sizes in Older Women: Results From a Randomized Controlled Trial

Background: Evidence suggests that lipoprotein subclass particles are critical markers of cardiovascular disease (CVD) risk. Older women have increased CVD risk related to age. The purpose of this study was to determine whether low and moderate doses of exercise influence lipoprotein subclasses. Methods: Women (60–75 years) were randomized into groups for 16 weeks of moderate-intensity exercise training at a low or moderate dose (33.6 and 58.8 kJ/kg body weight weekly, respectively). Lipoprotein subclasses were determined by nuclear magnetic resonance spectroscopy before and after the training. RESULTS: The average weekly exercise duration was 109 and 164 min, for low- and moderate-dose groups, respectively. In the low-dose group, highdensity lipoprotein particle (HDL-P) concentration decreased (∆ = −1.9 ± 3.1 µmol/L, mean ± SD, p = 0.002) and mean HDL-P size increased (∆ = 0.1 ± 0.3 nm, p = 0.028). In the moderate-dose group, mean HDL-P size (∆ = 0.1 ± 0.2 nm; p = 0.024) and low-density lipoprotein particle size increased (∆ = 0.4 ± 3.9 nm; p = 0.007). Baseline body mass index, peak oxygen consumption and age were associated with changes in a few lipoprotein subclasses. Conclusions: In this sample of inactive older women, moderate-intensity exercise training at a dose equivalent to or even lower than the minimally recommended level by public health agencies induced changes in lipoprotein subclasses in line with reduced CVD risk. However, higher doses are encouraged for greater health benefits

A Chemical Genetic Screen for Modulators of Asymmetrical 2,2′-Dimeric Naphthoquinones Cytotoxicity in Yeast

BACKGROUND: Dimeric naphthoquinones (BiQ) were originally synthesized as a new class of HIV integrase inhibitors but have shown integrase-independent cytotoxicity in acute lymphoblastic leukemia cell lines suggesting their use as potential anti-neoplastic agents. The mechanism of this cytotoxicity is unknown. In order to gain insight into the mode of action of binaphthoquinones we performed a systematic high-throughput screen in a yeast isogenic deletion mutant array for enhanced or suppressed growth in the presence of binaphthoquinones. METHODOLOGY/PRINCIPAL FINDINGS: Exposure of wild type yeast strains to various BiQs demonstrated inhibition of yeast growth with IC(50)s in the microM range. Drug sensitivity and resistance screens were performed by exposing arrays of a haploid yeast deletion mutant library to BiQs at concentrations near their IC(50). Sensitivity screens identified yeast with deletions affecting mitochondrial function and cellular respiration as having increased sensitivity to BiQs. Corresponding to this, wild type yeast grown in the absence of a fermentable carbon source were particularly sensitive to BiQs, and treatment with BiQs was shown to disrupt the mitochondrial membrane potential and lead to the generation of reactive oxygen species (ROS). Furthermore, baseline ROS production in BiQ sensitive mutant strains was increased compared to wild type and could be further augmented by the presence of BiQ. Screens for resistance to BiQ action identified the mitochondrial external NAD(P)H dehydrogenase, NDE1, as critical to BiQ toxicity and over-expression of this gene resulted in increased ROS production and increased sensitivity of wild type yeast to BiQ. CONCLUSIONS/SIGNIFICANCE: In yeast, binaphthoquinone cytotoxicity is likely mediated through NAD(P)H:quonine oxidoreductases leading to ROS production and dysfunctional mitochondria. Further studies are required to validate this mechanism in mammalian cells

A Novel 5-Enolpyruvylshikimate-3-Phosphate Synthase Shows High Glyphosate Tolerance in Escherichia coli and Tobacco Plants

A key enzyme in the shikimate pathway, 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) is the primary target of the broad-spectrum herbicide glyphosate. Identification of new aroA genes coding for EPSPS with a high level of glyphosate tolerance is essential for the development of glyphosate-tolerant crops. In the present study, the glyphosate tolerance of five bacterial aroA genes was evaluated in the E. coli aroA-defective strain ER2799 and in transgenic tobacco plants. All five aroA genes could complement the aroA-defective strain ER2799, and AM79 aroA showed the highest glyphosate tolerance. Although glyphosate treatment inhibited the growth of both WT and transgenic tobacco plants, transgenic plants expressing AM79 aroA tolerated higher concentration of glyphosate and had a higher fresh weight and survival rate than plants expressing other aroA genes. When treated with high concentration of glyphosate, lower shikimate content was detected in the leaves of transgenic plants expressing AM79 aroA than transgenic plants expressing other aroA genes. These results suggest that AM79 aroA could be a good candidate for the development of transgenic glyphosate-tolerant crops

A Microarray-Based Genetic Screen for Yeast Chronological Aging Factors

Model organisms have played an important role in the elucidation of multiple genes and cellular processes that regulate aging. In this study we utilized the budding yeast, Saccharomyces cerevisiae, in a large-scale screen for genes that function in the regulation of chronological lifespan, which is defined by the number of days that non-dividing cells remain viable. A pooled collection of viable haploid gene deletion mutants, each tagged with unique identifying DNA “bar-code” sequences was chronologically aged in liquid culture. Viable mutants in the aging population were selected at several time points and then detected using a microarray DNA hybridization technique that quantifies abundance of the barcode tags. Multiple short- and long-lived mutants were identified using this approach. Among the confirmed short-lived mutants were those defective for autophagy, indicating a key requirement for the recycling of cellular organelles in longevity. Defects in autophagy also prevented lifespan extension induced by limitation of amino acids in the growth media. Among the confirmed long-lived mutants were those defective in the highly conserved de novo purine biosynthesis pathway (the ADE genes), which ultimately produces IMP and AMP. Blocking this pathway extended lifespan to the same degree as calorie (glucose) restriction. A recently discovered cell-extrinsic mechanism of chronological aging involving acetic acid secretion and toxicity was suppressed in a long-lived ade4Δ mutant and exacerbated by a short-lived atg16Δ autophagy mutant. The identification of multiple novel effectors of yeast chronological lifespan will greatly aid in the elucidation of mechanisms that cells and organisms utilize in slowing down the aging process

Molecular Communications: Model-Based and Data-Driven Receiver Design and Optimization

International audienceIn this paper, we consider a molecular communication system that is made of a 3D unboundeddiffusion channel model without flow, a point transmitter, and a spherical absorbing receiver. In particular,we study the impact of inter-symbol interference and analyze the performance of different threshold-basedreceiver schemes. The aim of this paper is to analyze and optimize the receivers by using the conventionalmodel-based approach, which relies on an accurate model of the system, and the emerging data-drivenapproach, which, on the other hand, does not need any apriori information about the system model andexploits deep learning tools. We develop a general analytical framework for analyzing the performanceof threshold-based receiver schemes, which are suitable to optimize the detection threshold. In addition,we show that data-driven receiver designs yield the same performance as receivers that have perfectknowledge of the underlaying channel model