RNAi technology and its use in studying the function of nuclear receptors and coregulators

Until just a few years ago, RNA interference (RNAi) technology was restricted to the research fields of plants, C. elegans or Drosophila. The discovery of gene silencing by in vitro synthesized double-stranded RNA (dsRNA) in mammalian cells has made the use of RNAi possible in nearly the entire life science kingdom. DNA vectors delivering small interfering RNA (siRNA) directed by polymerase III or polymerase II promoters to persistently inhibit target genes expression have extended this technology to study in vivo function of these genes. Recently, RNAi has been used as a powerful tool in the functional analysis of nuclear receptors and their coregulators. This short review will cover studies in this area

The influence of fines content and size-ratio on the micro-scale properties of dense bimodal materials

This paper considers factors influencing the fabric of bimodal or gap-graded soils. Discrete element method simulations were carried out in which the volumetric fines content and the size ratio between coarse and fine particles were systematically varied. Frictionless particles were used during isotropic compression to create dense samples; the coefficient of friction was then set to match that of spherical glass beads. The particle-scale data generated in the simulations revealed key size ratios and fines contents at which transitions in soil fabric occur. These transitions are identified from changes in the contact distributions and stress-transfer characteristics of the soils and by changes in the size of the void space between the coarse particles. The results are broadly in agreement with available experimental data on minimum void ratio and contact distributions. The results have implications for engineering applications including assessment of the internal stability of gap-graded soils in embankment dams and flood embankments

Up-Cycling Waste Glass to Minimal Water Adsorption/Absorption Lightweight Aggregate by Rapid Low Temperature Sintering: Optimization by Dual Process-Mixture Response Surface Methodology

Mixed color waste glass extracted from municipal solid waste is either not recycled, in which case it is an environmental and financial liability, or it is used in relatively low value applications such as normal weight aggregate. Here, we report on converting it into a novel glass-ceramic lightweight aggregate (LWA), potentially suitable for high added value applications in structural concrete (upcycling). The artificial LWA particles were formed by rapidly sintering (<10 min) waste glass powder with clay mixes using sodium silicate as binder and borate salt as flux. Composition and processing were optimized using response surface methodology (RSM) modeling, and specifically (i) a combined process-mixture dual RSM, and (ii) multiobjective optimization functions. The optimization considered raw materials and energy costs. Mineralogical and physical transformations occur during sintering and a cellular vesicular glass-ceramic composite microstructure is formed, with strong correlations existing between bloating/shrinkage during sintering, density and water adsorption/absorption. The diametrical expansion could be effectively modeled via the RSM and controlled to meet a wide range of specifications; here we optimized for LWA structural concrete. The optimally designed LWA is sintered in comparatively low temperatures (825-835 °C), thus potentially saving costs and lowering emissions; it had exceptionally low water adsorption/absorption (6.1-7.2% w/wd; optimization target: 1.5-7.5% w/wd); while remaining substantially lightweight (density: 1.24-1.28 g.cm-3; target: 0.9-1.3 g.cm-3). This is a considerable advancement for designing effective environmentally friendly lightweight concrete constructions, and boosting resource efficiency of waste glass flows

Identification of low oxygen-tolerating bacteria in prostate secretions of cancer patients and discussion of possible aetiological significance

MW was in receipt of Barts and The London Charity Equipment Grant for provision of MOLDI-TOF (Grant reference number 486/1193)

SRC-1 is involved in the control of the gene expression of myelin protein Po

Steroid receptor coactivator-1 (SRC-1) has a crucial role in many different biological effects mediated by nuclear receptors. However, in spite of its ubiquitous expression, there are no data regarding its possible involvement in nuclear receptor transcriptional activity at the level of the peripheral nervous system. We investigated whether this coactivator might have a role in the control of glycoprotein Po gene expression. This myelin protein is a specific product of Schwann cells, with a fundamental role in the maintenance and functionality of peripheral myelin. Po is known to be stimulated by progesterone and by its 5alpha-reduced metabolite, dihydroprogesterone (DHP), through the corresponding steroid receptor. To determine whether the effect exerted by DHP on Po mRNA levels could be affected by and therefore associated with altered levels of SRC-1, a mouse Schwann cell line was stably transfected to over- or underexpress this coactivator. We found that SRC-1 overexpressing cells are more responsive to Po mRNA induction by DHP, whereas the effect of the steroid is completely lost in SRC-1-deficient cells. Interestingly, SRC-1 levels are also positively correlated with Po gene expression independently of DHP exposure. Finally, DHP treatment increases not only Po but also SRC-1 mRNA levels. Altogether, these data indicate for the first time that in rat Schwann cells, SRC-1 plays a role in the regulation of one of the most typical proteins of peripheral myelin

Atherosclerotic cardiovascular risk in paralympic athletes with a locomotor Impairment: beneficial effects of high aerobic fitness and practiced sport.

INTRODUCTION: Atherosclerotic cardiovascular disease (ACVD), the leading cause of morbidity and mortality in individuals (I) with a locomotor impairment (LI), occurs at earlier ages in I-LI than in ambulatory individuals because I-LI, in particular those with a spinal cord injury (SCI), display a higher prevalence of ACVD risk factors (RF) mainly due to their increased sedentary habit. However even in Paralympic Athletes (PA) with a LI (PA-LI) the prevalence of ACVD-RF is very high. We tested the hypotheses that both a high oxygen uptake peak (VO2peak) and different types of practiced sport (skilled sport – SS; power sports – PS; intermittent, aerobic and anaerobic mixed metabolisms, sports – IS; endurance sports – ES) affect ACVD-RF prevalence, which is supposed to be low in PA-LI competing in ES and having high VO2peak. METHODS: Data from a total of 118 male PA (62 PA-SCI and 56 PA with other health conidiations (HC) determining a LI – PA-OHC) were retrospectively evaluated. Thirty-six PA competed in SS, 20 in PS, 42 in IS and 20 in ES. They had been screened through anthropometric and blood pressure (BP) measurements and laboratory blood tests to estimate an ACVD-RF score summing 1 point for each of the following RF: central obesity –OB- (waist circumference ≥102 cm), hypertension –HT- (rest systolic BP ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg), dyslipidemia -DL- (total Cholesterol -TC ≥200 mg·dl-1 or LDL-C ≥130 mg·dl-1 or HDL-C &lt;40mg·dl-1), impaired fasting glucose -IFG (glycemia≥100 mg·dl-1) and subtracting 1 point when serum HDL-C was higher than 60 mg·dl-1. All PA underwent to an incremental cardiopulmonary maximal exercise test to assess VO2peak. RESULTS: Prevalence of HT, TC, LDL-C, low-HDL-C, IFG and OB were equal to 8.1% and 8.9%, 39.3% and 41.2%, 45.2% and 41.1%, 27.9% and 24.3%, 33.9% and 32.1%, 19.4% and 7.1% in PA-SCI and PA-OHC, respectively, being significantly different only the OB prevalence (p=0.046). Based on the ACVD-RF score, 3 ACVD-RF groups were formed: group 1 (RF≤0, N=43, 13 PA competing in ES, 15 in IS, 8 in PS and 7 in SS), group 2 (RF=1, N=43, 6 PA competing in ES, 16 in IS, 8 in PS and 13 in SS), group 3 (RF≥2, N=32, 1 PA competing in ES, 11 in IS, 4 in PS and 16 in SS). Grouping the PA depending on sports and ACVD-RF determined a significant difference (χ2), indeed 65% of PA competing in ES had no ACVD-RF while 30% and 5% were in Group 2 and group 3, respectively, while 6.3% of PA competing in SS were in group 1 and 50% in group 3. VO2peak equal to 36±8.3 ml/kg/min in PA of group 1 was significantly higher than the VO2peak of PA included in group 2, equal to 31±8.9, which was significantly higher than that of the PA of group 3 (25±7.5). CONCLUSION: Prevalence of RF was similar in the 2 groups of HC, with the exception of OB which was more prevalent in PA-SCI. DL had a relevant and dangerous prevalence in PA regardless the HC. Competing in ES and having high levels of VO2peak seems to provide a protective effect against the risk of developing ACVD