Effect of minor SNPs on enzymatic activity regulated by common human haplotypes of the catechol-O-methyltransferase gene

Three common haplotypes of the human catechol-O-methyltransferase (COMT) gene are associated with experimental pain sensitivity. Based on subjects' pain responsiveness, haplotypes were designated as low (LPS), average (APS), or high (HPS) pain sensitive; APS and HPS haplotypes exhibit lower COMT enzymatic activity. Minor frequency SNPs naturally occur within the APS and HPS haplotypes, but their functional impact is unknown. We hypothesized that these minor SNPs, one occurring in the APS construct (G/A, rs769224) and three in the HPS construct (G/T, rs6267; G/A, rs740602; C/T, rs8192488), may compensate for the observed reductions in enzymatic activity. Testing was carried out via transient transfection of rat adrenal (PC-12) cells with each of the four constructs. No difference exists between the haplotype mutants and their respective parent haplotype for RNA abundance, protein expression, or enzymatic activity (P > 0.05). Additionally, the minor allele of SNP re6267 is a likely marker of the HPS haplotype

Metal Abundances of KISS Galaxies III. Nebular Abundances for Fourteen Galaxies and the Luminosity-Metallicity Relationship for HII Galaxies

We report results from the third in a series of nebular abundance studies of emission-line galaxies from the KPNO International Spectroscopic Survey (KISS). Galaxies with coarse metallicity estimates of 12 + log(O/H) less than 8.2 dex were selected for observation. Spectra of 14 galaxies, which cover the full optical region from [OII]3727,3729 to beyond [SII]6717,6731, are presented, and abundance ratios of N, O, Ne, S, and Ar are computed. The auroral [OIII]4363 line is detected in all 14 galaxies. Oxygen abundances determined through the direct electron temperature T_e method confirm that the sample is metal-poor with 7.61 <= 12 + log(O/H) <= 8.32. By using these abundances in conjunction with other T_e-based measurements from the literature, we demonstrate that HII galaxies and more quiescent dwarf irregular galaxies follow similar metallicity-luminosity (L-Z) relationships. The primary difference is a zero-point shift between the correlations such that HII galaxies are brighter by an average of 0.8 B magnitudes at a given metallicity. This offset can be used as evidence to argue that low-luminosity HII galaxies typically undergo factor of two luminosity enhancements, and starbursts that elevate the luminosities of their host galaxies by 2 to 3 magnitudes are not as common. We also demonstrate that the inclusion of interacting galaxies can increase the scatter in the L-Z relation and may force the observed correlation towards lower metallicities and/or larger luminosities. This must be taken into account when attempting to infer metal abundance evolution by comparing local L-Z relations with ones based on higher redshift samples since the fraction of interacting galaxies should increase with look-back time.Comment: 36 pages, 5 figures. ApJ, in pres

Cross-validation of a Prediction Equation for Energy Expenditure of an Acute Resistance Exercise Bout

Previously, our laboratory introduced a regression equation for predicting net kcal consumption of a resistance exercise (RE) bout: Total net kcal = 0.874(height, cm) - 0.596(age, years) - 1.016(fat mass, kg) + 1.638(lean mass, kg) + 2.461(total volume x 10-3) - 110.742 (R2 = 0.773, SEE=28.5 kcal). PURPOSE: The purpose of this study was to validate this regression equation using the same variables as predictors. METHODS: Forty-seven healthy, active subjects (23 men, 24 women, 20-58 yrs, 173.5 ± 10.5 cm, 85.5 ± 19.0 kg, VO2max 36.0 ± 8.4 ml/kg/min) were randomly divided into validation and cross-validation groups (nv = 24, ncv = 23). The validation group’s data was used to develop an equation to predict net kcal consumption, which was applied to the cross-validation group’s data to estimate net kcal consumption. Similarly, a prediction equation was derived from the cross-validation group’s raw data and applied to that of the validation group. The strength of the relationship between each group’s measured and estimated net kcal consumption was assessed via correlational analysis. RESULTS: Multiple linear regression yielded the following estimates of net kcal consumption: validation net kcal = 1.125(height, cm) – 0.662(age, years) – 0.800(fat mass, kg) + 1.344(lean mass, kg) + 2.278(total volume x 10-3) – 144.846 (R2 = 0.751, p \u3c 0.0001, SEE=29.7 kcal); cross-validation net kcal = 0.515(height, cm) - 0.520(age, years) - 1.220(fat mass, kg) + 1.995(lean mass, kg) + 2.620(total volume x 10-3) – 59.988 (R2 = 0.823, p \u3c 0.0001, SEE=29.2 kcal). These equations had a cross-validation coefficient of 0.902 and a double cross-validation coefficient of 0.863. CONCLUSION: The strong relationship between the measured and estimated net kcal consumption of both the cross-validation and validation group lead us to conclude that the regression equation derived by this laboratory is valid for estimating net energy expenditure for a total RE bout

Further Evidence for Chemical Fractionation from Ultraviolet Observations of Carbon Monoxide

Ultraviolet absorption from interstellar 12CO and 13CO was detected toward rho Oph A and chi Oph. The measurements were obtained at medium resolution with the Goddard High Resolution Spectrograph on the Hubble Space Telescope. Column density ratios, N(12CO)/N(13CO), of 125 \pm 23 and 117 \pm 35 were derived for the sight lines toward rho Oph A and chi Oph, respectively. A value of 1100 \pm 600 for the ratio N(12C16O)/N(12C18O) toward rho Oph A was also obtained. Absorption from vibrationally excited H_2 (v" = 3) was clearly seen toward this star as well. The ratios are larger than the isotopic ratios for carbon and oxygen appropriate for ambient interstellar material. Since for both carbon and oxygen the more abundant isotopomer is enhanced, selective isotopic photodissociation plays the key role in the fractionation process for these directions. The enhancement arises because the more abundant isotopomer has lines that are more optically thick, resulting in more self shielding from dissociating radiation. A simple argument involving the amount of self shielding [from N(12CO)] and the strength of the ultraviolet radiation field premeating the gas (from the amount of vibrationally excited H_2) shows that selective isotopic photodissociation controls the fractionation seen in these two sight lines, as well as the sight line to zeta Oph.Comment: 40 pages, 8 figures, to appear in 10 July 2003 issue of Ap

The ABCD of obesity: An EASO position statement on a diagnostic term with clinical and scientific implications

Obesity is a frequent, serious, complex, relapsing, and chronic disease process that represents a major public health problem. The coining of obesity as an adiposity-based chronic disease (ABCD) is of particular relevance being in line with EASO’s proposal to improve the International Classification of Diseases ICD-11 diagnostic criteria for obesity based on three dimensions, namely etiology, degree of adiposity, and health risks. The body mass index as a unique measurement of obesity does not reflect the whole complexity of the disease. Obesity complications are mainly determined by 2 pathological processes, i.e., physical forces (fat mass disease) as well as endocrine and immune responses (sick fat disease), which are embedded in a cultural and physical context leading to a specific ABCD stage

European association for the study of obesity position statement on the global COVID-19 pandemic

COVID-19, the infectious disease caused by the coronavirus SARS-CoV-2, was declared a pandemic by the World Health Organization on March 12, 2020. The European Association for the Study of Obesity (EASO), as a scientific and medical society dedicated to the promotion of health and well-being, is greatly concerned about this global health challenge and its significant impacts on individuals, families, communities, health systems, nations, and wider society

Incorporating New Technologies Into Toxicity Testing and Risk Assessment: Moving From 21st Century Vision to a Data-Driven Framework

Based on existing data and previous work, a series of studies is proposed as a basis toward a pragmatic early step in transforming toxicity testing. These studies were assembled into a data-driven framework that invokes successive tiers of testing with margin of exposure (MOE) as the primary metric. The first tier of the framework integrates data from high-throughput in vitro assays, in vitro-to-in vivo extrapolation (IVIVE) pharmacokinetic modeling, and exposure modeling. The in vitro assays are used to separate chemicals based on their relative selectivity in interacting with biological targets and identify the concentration at which these interactions occur. The IVIVE modeling converts in vitro concentrations into external dose for calculation of the point of departure (POD) and comparisons to human exposure estimates to yield a MOE. The second tier involves short-term in vivo studies, expanded pharmacokinetic evaluations, and refined human exposure estimates. The results from the second tier studies provide more accurate estimates of the POD and the MOE. The third tier contains the traditional animal studies currently used to assess chemical safety. In each tier, the POD for selective chemicals is based primarily on endpoints associated with a proposed mode of action, whereas the POD for nonselective chemicals is based on potential biological perturbation. Based on the MOE, a significant percentage of chemicals evaluated in the first 2 tiers could be eliminated from further testing. The framework provides a risk-based and animal-sparing approach to evaluate chemical safety, drawing broadly from previous experience but incorporating technological advances to increase efficiency

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

OBEDIS Core Variables Project : European Expert Guidelines on a Minimal Core Set of Variables to Include in Randomized, Controlled Clinical Trials of Obesity Interventions

Heterogeneity of interindividual and intraindividual responses to interventions is often observed in randomized, controlled trials for obesity. To address the global epidemic of obesity and move toward more personalized treatment regimens, the global research community must come together to identify factors that may drive these heterogeneous responses to interventions. This project, called OBEDIS (OBEsity Diverse Interventions Sharing - focusing on dietary and other interventions), provides a set of European guidelines for a minimal set of variables to include in future clinical trials on obesity, regardless of the specific endpoints. Broad adoption of these guidelines will enable researchers to harmonize and merge data from multiple intervention studies, allowing stratification of patients according to precise phenotyping criteria which are measured using standardized methods. In this way, studies across Europe may be pooled for better prediction of individuals' responses to an intervention for obesity - ultimately leading to better patient care and improved obesity outcomes.Peer reviewe

Distribution and seasonality of rhinovirus and other respiratory viruses in a cross-section of asthmatic children in Trinidad, West Indies

<p>Abstract</p> <p>Background</p> <p>Childhood asthma in the Caribbean is advancing in prevalence and morbidity. Though viral respiratory tract infections are reported triggers for exacerbations, information on these infections with asthma is sparse in Caribbean territories. We examined the distribution of respiratory viruses and their association with seasons in acute and stable asthmatic children in Trinidad.</p> <p>Methods</p> <p>In a cross-sectional study of 70 wheezing children attending the emergency department for nebulisation and 80 stable control subjects (2 to 16 yr of age) in the asthma clinic, nasal specimens were collected during the dry (<it>n </it>= 38, January to May) and rainy (<it>n </it>= 112, June to December) seasons. A multitarget, sensitive, specific high-throughput Respiratory MultiCode assay tested for respiratory-virus sequences for eight distinct groups: human rhinovirus, respiratory syncytial virus, parainfluenza virus, influenza virus, metapneumovirus, adenovirus, coronavirus, and enterovirus.</p> <p>Results</p> <p>Wheezing children had a higher [χ²= 5.561, <it>p </it>= 0.018] prevalence of respiratory viruses compared with stabilized asthmatics (34.3% (24) versus (vs.) 17.5% (14)). Acute asthmatics were thrice as likely to be infected with a respiratory virus (OR = 2.5, 95% CI = 1.2 – 5.3). The predominant pathogens detected in acute versus stable asthmatics were the rhinovirus (RV) (<it>n </it>= 18, 25.7% vs. <it>n </it>= 7, 8.8%; <it>p </it>= 0.005), respiratory syncytial virus B (RSV B) (<it>n </it>= 2, 2.9% vs. <it>n </it>= 4, 5.0%), and enterovirus (<it>n </it>= 1, 1.4% vs. <it>n </it>= 2, 2.5%). Strong odds for rhinoviral infection were observed among nebulised children compared with stable asthmatics (<it>p </it>= 0.005, OR = 3.6, 95% CI = 1.4 – 9.3,). RV was prevalent throughout the year (Dry, <it>n </it>= 6, 15.8%; Rainy, <it>n </it>= 19, 17.0%) and without seasonal association [χ²= 0.028, <it>p </it>= 0.867]. However it was the most frequently detected virus [Dry = 6/10, (60.0%); Rainy = 19/28, (67.9%)] in both seasons.</p> <p>Conclusion</p> <p>Emergent wheezing illnesses during childhood can be linked to infection with rhinovirus in Trinidad's tropical environment. Viral-induced exacerbations of asthma are independent of seasons in this tropical climate. Further clinical and virology investigations are recommended on the role of infections with the rhinovirus in Caribbean childhood wheeze.</p