Cardio-Protection Afforded by Β-Blockade Is Maintained During Resistance Exercise

Objectives Whether or not the cardio-protective effect of β-adrenergic blockade is retained during resistance exercise has not been systematically evaluated. Therefore the purpose of this study was to measure selected cardiorespiratory responses to isometric exercise involving hand-gripping, single-leg extension, or double-leg dead-lift, under placebo (control), β1-selective (atenolol), and non-selective (propranolol) adrenergic blockade conditions. Design Eleven young male adults were evaluated in a randomized, double-blinded, repeated measures study design and performed all three exercise modalities at 30% of maximal voluntary contraction under placebo, atenolol and propranolol conditions. Methods Heart rate, systolic and diastolic blood pressure, rate-pressure product, oxygen uptake, cardiac output, stroke volume and total peripheral resistance were directly measured or calculated at rest and during the third minute of each of the three exercise modes. Results Irrespective of drug condition, a graded pressor response was observed going from rest to exercise so that rest \u3c handgrip \u3c leg extension \u3c dead-lift for heart rate, systolic and diastolic blood pressures, rate-pressure product and oxygen uptake (p \u3c 0.05 for all). Cardiac output only increased with the dead-lift mode of exercise (p \u3c 0.01). Importantly β-adrenergic blockade with either atenolol or propranolol similarly attenuated the rise in heart rate, and systolic blood pressure; thus rate-pressure product demonstrated a mode-of-exercise by drug interaction effect (p \u3c 0.001) with the greatest reductions seen with the dead-lift procedure. Conclusions The findings indicate that cardio-protection afforded by selective or non-selective β-blockade at rest is preserved during isometric exercise and even enhanced once heart rate increases above 100 beats min−1

Beyond Tryptophan Synthase: Identification of Genes That Contribute to Chlamydia trachomatis Survival during Gamma Interferon-Induced Persistence and Reactivation

Chlamydia trachomatis can enter a viable but nonculturable state in vitro termed persistence. A common feature of C. trachomatis persistence models is that reticulate bodies fail to divide and make few infectious progeny until the persistence-inducing stressor is removed. One model of persistence that has relevance to human disease involves tryptophan limitation mediated by the host enzyme indoleamine 2,3-dioxygenase, which converts l-tryptophan to N-formylkynurenine. Genital C. trachomatis strains can counter tryptophan limitation because they encode a tryptophan-synthesizing enzyme. Tryptophan synthase is the only enzyme that has been confirmed to play a role in interferon gamma (IFN-γ)-induced persistence, although profound changes in chlamydial physiology and gene expression occur in the presence of persistence-inducing stressors. Thus, we screened a population of mutagenized C. trachomatis strains for mutants that failed to reactivate from IFN-γ-induced persistence. Six mutants were identified, and the mutations linked to the persistence phenotype in three of these were successfully mapped. One mutant had a missense mutation in tryptophan synthase; however, this mutant behaved differently from previously described synthase null mutants. Two hypothetical genes of unknown function, ctl0225 and ctl0694, were also identified and may be involved in amino acid transport and DNA damage repair, respectively. Our results indicate that C. trachomatis utilizes functionally diverse genes to mediate survival during and reactivation from persistence in HeLa cells

HYPOFIBRINOGENAEMIA

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Evaluation of concentrated space solar arrays using computer modeling

A general approach is developed for predicting the power output of a concentrator enhanced photovoltaic space array. A ray trace routine determines the concentrator intensity arriving at each solar cell. An iterative calculation determines the cell's operating temperature since cell temperature and cell efficiency are functions of one another. The end result of the iterative calculation is that the individual cell's power output is determined as a function of temperature and intensity. Circuit output is predicted by combining the individual cell outputs using the single diode model of a solar cell. Concentrated array characteristics such as uniformity of intensity and operating temperature at various points across the array are examined using computer modeling techniques. An illustrative example is given showing how the output of an array can be enhanced using solar concentration techniques

Interrogating Genes That Mediate Chlamydia trachomatis Survival in Cell Culture Using Conditional Mutants and Recombination

Intracellular bacterial pathogens in the family Chlamydiaceae are causes of human blindness, sexually transmitted disease, and pneumonia. Genetic dissection of the mechanisms of chlamydial pathogenicity has been hindered by multiple limitations, including the inability to inactivate genes that would prevent the production of elementary bodies. Many genes are also Chlamydia-specific genes, and chlamydial genomes have undergone extensive reductive evolution, so functions often cannot be inferred from homologs in other organisms. Conditional mutants have been used to study essential genes of many microorganisms, so we screened a library of 4,184 ethyl methanesulfonate-mutagenized Chlamydia trachomatis isolates for temperature-sensitive (TS) mutants that developed normally at physiological temperature (37°C) but not at nonphysiological temperatures. Heat-sensitive TS mutants were identified at a high frequency, while cold-sensitive mutants were less common. Twelve TS mutants were mapped using a novel markerless recombination approach, PCR, and genome sequencing. TS alleles of genes that play essential roles in other bacteria and chlamydia-specific open reading frames (ORFs) of unknown function were identified. Temperature-shift assays determined that phenotypes of the mutants manifested at distinct points in the developmental cycle. Genome sequencing of a larger population of TS mutants also revealed that the screen had not reached saturation. In summary, we describe the first approach for studying essential chlamydial genes and broadly applicable strategies for genetic mapping in Chlamydia spp. and mutants that both define checkpoints and provide insights into the biology of the chlamydial developmental cycle. IMPORTANCE: Study of the pathogenesis of Chlamydia spp. has historically been hampered by a lack of genetic tools. Although there has been recent progress in chlamydial genetics, the existing approaches have limitations for the study of the genes that mediate growth of these organisms in cell culture. We used a genetic screen to identify conditional Chlamydia mutants and then mapped these alleles using a broadly applicable recombination strategy. Phenotypes of the mutants provide fundamental insights into unexplored areas of chlamydial pathogenesis and intracellular biology. Finally, the reagents and approaches we describe are powerful resources for the investigation of these organisms

The Impact of Lateral Gene Transfer in Chlamydia

Lateral gene transfer (LGT) facilitates many processes in bacterial ecology and pathogenesis, especially regarding pathogen evolution and the spread of antibiotic resistance across species. The obligate intracellular chlamydiae, which cause a range of diseases in humans and animals, were historically thought to be highly deficient in this process. However, research over the past few decades has demonstrated that this was not the case. The first reports of homologous recombination in the Chlamydiaceae family were published in the early 1990s. Later, the advent of whole-genome sequencing uncovered clear evidence for LGT in the evolution of the Chlamydiaceae, although the acquisition of tetracycline resistance in Chlamydia (C.) suis is the only recent instance of interphylum LGT. In contrast, genome and in vitro studies have shown that intraspecies DNA exchange occurs frequently and can even cross species barriers between closely related chlamydiae, such as between C. trachomatis, C. muridarum, and C. suis. Additionally, whole-genome analysis led to the identification of various DNA repair and recombination systems in C. trachomatis, but the exact machinery of DNA uptake and homologous recombination in the chlamydiae has yet to be fully elucidated. Here, we reviewed the current state of knowledge concerning LGT in Chlamydia by focusing on the effect of homologous recombination on the chlamydial genome, the recombination machinery, and its potential as a genetic tool for Chlamydia

Pre-treatment of surface waters for ceramic microfiltration

The influence of pre-treatment on the suppression of irreversible (IR) fouling of ceramic membranes challenged with three UK surface waters has been studied at pilot scale. An initial scoping study compared the efficacy of suspended ion exchange (SIX) and clarification (coagulation followed by sludge blanket clarification) individually and in combination. Direct membrane filtration following in-line coagulation (ILCA) was also investigated with and without SIX. The impact on the various organic fractions, specifically high molecular weight (HMW) biopolymers (BPs) and humic substances (HSs), and lower molecular weight (LMW) building blocks (BBs) and neutrals, was studied using liquid chromatography-organic carbon detection (LC-OCD). Results revealed SIX and coagulation to preferentially remove the LMW and HMW organic fractions respectively. Residual HMW organic matter (primarily BPs) following SIX pre-treatment were retained by the membrane which led to rapid irreversible fouling. Coagulation pre-treatment provided stable membrane operation and the residual LMW organics were not significantly retained by the membrane. Combining clarification and SIX resulted in significantly increased removal of organics and lower membrane fouling rates. Tests performed using SIX and ILCA revealed high dissolved organic carbon (DOC) removal compared to SIX with clarification. However, unlike the case for clarification with SIX, the addition of SIX to optimised ILCA dosing offered no additional suppression of membrane fouling compared to ILCA alone. Optimised ILCA pretreatment led to very low IR fouling rates of <0.3 kPa/day trans-membrane pressure, despite highly challenging operating conditions of elevated fluxes (185 L m−2 h−1) and highly variable feedwater dissolved organic carbon concentrations