Adrenocortical, autonomic, and inflammatory causes of the metabolic syndrome: nested case-control study.

BACKGROUND: The causes of metabolic syndrome (MS), which may be a precursor of coronary disease, are uncertain. We hypothesize that disturbances in neuroendocrine and cardiac autonomic activity (CAA) contribute to development of MS. We examine reversibility and the power of psychosocial and behavioral factors to explain the neuroendocrine adaptations that accompany MS. METHODS AND RESULTS: This was a double-blind case-control study of working men aged 45 to 63 years drawn from the Whitehall II cohort. MS cases (n=30) were compared with healthy controls (n=153). Cortisol secretion, sensitivity, and 24-hour cortisol metabolite and catecholamine output were measured over 2 days. CAA was obtained from power spectral analysis of heart rate variability (HRV) recordings. Twenty-four-hour cortisol metabolite and normetanephrine (3-methoxynorepinephrine) outputs were higher among cases than controls (+ 0.49, +0.45 SD, respectively). HRV and total power were lower among cases (both -0.72 SD). Serum interleukin-6, plasma C-reactive protein, and viscosity were higher among cases (+0.89, +0.51, and +0.72 SD). Lower HRV was associated with higher normetanephrine output (r=-0.19; P=0.03). Among former cases (MS 5 years previously, n=23), cortisol output, heart rate, and interleukin-6 were at the level of controls. Psychosocial factors accounted for 37% of the link between MS and normetanephrine output, and 7% to 19% for CAA. Health-related behaviors accounted for 5% to 18% of neuroendocrine differences. CONCLUSIONS: Neuroendocrine stress axes are activated in MS. There is relative cardiac sympathetic predominance. The neuroendocrine changes may be reversible. This case-control study provides the first evidence that chronic stress may be a cause of MS. Confirmatory prospective studies are required

Explicit de Sitter Flux Vacua for Global String Models with Chiral Matter

We address the open question of performing an explicit stabilisation of all closed string moduli (including dilaton, complex structure and Kaehler moduli) in fluxed type IIB Calabi-Yau compactifications with chiral matter. Using toric geometry we construct Calabi-Yau manifolds with del Pezzo singularities. D-branes located at such singularities can support the Standard Model gauge group and matter content. In order to control complex structure moduli stabilisation we consider Calabi-Yau manifolds which exhibit a discrete symmetry that reduces the effective number of complex structure moduli. We calculate the corresponding periods in the symplectic basis of invariant three-cycles and find explicit flux vacua for concrete examples. We compute the values of the flux superpotential and the string coupling at these vacua. Starting from these explicit complex structure solutions, we obtain AdS and dS minima where the Kaehler moduli are stabilised by a mixture of D-terms, non-perturbative and perturbative alpha'-corrections as in the LARGE Volume Scenario. In the considered example the visible sector lives at a dP_6 singularity which can be higgsed to the phenomenologically interesting class of models at the dP_3 singularity.Comment: 49 pages, 5 figures; v2: references adde

A comparison of the effects of physical and chemical mutagens in sesame (Sesamum indicum L.)

Three sesame genotypes (Rama, SI 1666 and IC 21706) were treated with physical (γ-rays: 200 Gy, 400 Gy or 600 Gy) or chemical (ethyl methane sulphonate, EMS: 0.5%, 1.0%, 1.5% or 2.0%) mutagens and their mutagenic effectiveness and efficiency were estimated in the M 2 generation. The M 3 generation was used to identify the most effective mutagen and dose for induction of mutations. The average effectiveness of EMS was much higher than γ-rays. The lowest dose of γ-rays (200 Gy) and the lowest concentration of EMS (0.5%) showed the highest mutagenic efficiency in all genotypes. Analysis of the M 3 generation data based on parameters such as the variance ratio and the difference in residual variances derived from the model of Montalván and Ando indicated that 0.5% concentration of EMS was the most effective treatment for inducing mutations

The Photodynamic Effect of Different Size ZnO Nanoparticles on Cancer Cell Proliferation In Vitro

Nanomaterials have widely been used in the field of biological and biomedicine, such as tissue imaging, diagnosis and cancer therapy. In this study, we explored the cytotoxicity and photodynamic effect of different-sized ZnO nanoparticles to target cells. Our observations demonstrated that ZnO nanoparticles exerted dose-dependent and time-dependent cytotoxicity for cancer cells like hepatocellular carcinoma SMMC-7721 cells in vitro. Meanwhile, it was observed that UV irradiation could enhance the suppression ability of ZnO nanoparticles on cancer cells proliferation, and these effects were in the size-dependent manner. Furthermore, when ZnO nanoparticles combined with daunorubicin, the related cytotoxicity of anticancer agents on cancer cells was evidently enhanced, suggesting that ZnO nanoparticles could play an important role in drug delivery. This may offer the possibility of the great potential and promising applications of the ZnO nanoparticles in clinical and biomedical areas like photodynamic cancer therapy and others

Development and Disease: How Susceptibility to an Emerging Pathogen Changes through Anuran Development

Ranaviruses have caused die-offs of amphibians across the globe. In North America, these pathogens cause more amphibian mortality events than any other pathogen. Field observations suggest that ranavirus epizootics in amphibian communities are common during metamorphosis, presumably due to changes in immune function. However, few controlled studies have compared the relative susceptibility of amphibians to ranaviruses across life stages. Our objectives were to measure differences in mortality and infection prevalence following exposure to ranavirus at four developmental stages and determine whether the differences were consistent among seven anuran species. Based on previous studies, we hypothesized that susceptibility to ranavirus would be greatest at metamorphosis. Our results did not support this hypothesis, as four of the species were most susceptible to ranavirus during the larval or hatchling stages. The embryo stage had the lowest susceptibility among species probably due to the protective membranous layers of the egg. Our results indicate that generalizations should be made cautiously about patterns of susceptibility to ranaviruses among amphibian developmental stages and species. Further, if early developmental stages of amphibians are susceptible to ranaviruses, the impact of ranavirus epizootic events may be greater than realized due to the greater difficulty of detecting morbid hatchlings and larvae compared to metamorphs

The eROSITA X-ray telescope on SRG

eROSITA (extended ROentgen Survey with an Imaging Telescope Array) is the primary instrument on the Spectrum-Roentgen-Gamma (SRG) mission, which was successfully launched on July 13, 2019, from the Baikonour cosmodrome. After the commissioning of the instrument and a subsequent calibration and performance verification phase, eROSITA started a survey of the entire sky on December 13, 2019. By the end of 2023, eight complete scans of the celestial sphere will have been performed, each lasting six months. At the end of this program, the eROSITA all-sky survey in the soft X-ray band (0.2-2.3 keV) will be about 25 times more sensitive than the ROSAT All-Sky Survey, while in the hard band (2.3-8 keV) it will provide the first ever true imaging survey of the sky. The eROSITA design driving science is the detection of large samples of galaxy clusters up to redshifts z > 1 in order to study the large-scale structure of the universe and test cosmological models including Dark Energy. In addition, eROSITA is expected to yield a sample of a few million AGNs, including obscured objects, revolutionizing our view of the evolution of supermassive black holes. The survey will also provide new insights into a wide range of astrophysical phenomena, including X-ray binaries, active stars, and diffuse emission within the Galaxy. Results from early observations, some of which are presented here, confirm that the performance of the instrument is able to fulfil its scientific promise. With this paper, we aim to give a concise description of the instrument, its performance as measured on ground, its operation in space, and also the first results from in-orbit measurements

Neuropeptidomic Components Generated by Proteomic Functions in Secretory Vesicles for Cell–Cell Communication

Diverse neuropeptides participate in cell–cell communication to coordinate neuronal and endocrine regulation of physiological processes in health and disease. Neuropeptides are short peptides ranging in length from ~3 to 40 amino acid residues that are involved in biological functions of pain, stress, obesity, hypertension, mental disorders, cancer, and numerous health conditions. The unique neuropeptide sequences define their specific biological actions. Significantly, this review article discusses how the neuropeptide field is at the crest of expanding knowledge gained from mass-spectrometry-based neuropeptidomic studies, combined with proteomic analyses for understanding the biosynthesis of neuropeptidomes. The ongoing expansion in neuropeptide diversity lies in the unbiased and global mass-spectrometry-based approaches for identification and quantitation of peptides. Current mass spectrometry technology allows definition of neuropeptide amino acid sequence structures, profiling of multiple neuropeptides in normal and disease conditions, and quantitative peptide measures in biomarker applications to monitor therapeutic drug efficacies. Complementary proteomic studies of neuropeptide secretory vesicles provide valuable insight into the protein processes utilized for neuropeptide production, storage, and secretion. Furthermore, ongoing research in developing new computational tools will facilitate advancements in mass-spectrometry-based identification of small peptides. Knowledge of the entire repertoire of neuropeptides that regulate physiological systems will provide novel insight into regulatory mechanisms in health, disease, and therapeutics