Cholecystokinin, gastrin, cholecystokinin/gastrin receptors, and bitter taste receptor TAS2R14: trophoblast expression and signaling

We investigated expression of cholecystokinin (CCK) in humans and mice, and the bitter taste receptor TAS2R14 in the human placenta. Because CCK and gastrin activate the CCKBR receptor, we also explored placental gastrin expression. Finally, we investigated calcium signaling by CCK and TAS2R14. By RT-PCR, we found CCK/Cck and GAST/Gast mRNA expression in both normal human and mouse placentas, as well as in human trophoblast cell lines (TCL). Although both Cckar and -br mRNA were expressed in the mouse placenta, only CCKBR mRNA was detected in the human placenta and TCL. mRNA expression for TAS2R14 was also observed in the human placenta and TCL. Using immunohistochemistry, CCK protein was localized to the syncytiotrophoblast (ST) and extravillous trophoblast (EVT) in the human term placenta, and to trophoblast glycogen cells in mouse and human placentas. Gastrin and TAS2R14 proteins were also observed in ST and EVT of the human placenta. Both sulfated and nonsulfated CCK elicited a comparable rise in intracellular calcium in TCL, consistent with CCKBR expression. Three TAS2R14 agonists, flufenamic acid, chlorhexidine, and diphenhydramine, also evoked rises in intracellular calcium in TCL. These results establish CCK, gastrin, and their receptor(s) in both human and mouse placentas, and TAS2R14 in the human placenta. Both CCK and TAS2R14 agonists increased intracellular calcium in human TCL. Although the roles of these ligands and receptors, and their potential cross talk in normal and pathological placentas, are currently unknown, this study opens new avenues for placental research.Fil: Taher, Shèdy. University of Florida; Estados UnidosFil: Borja, Yamilette. University of Florida; Estados UnidosFil: Cabanela, Lucía. University of Florida; Estados UnidosFil: Costers, Vincent J.. University of Florida; Estados UnidosFil: Carson Marino, Morgan. University of Florida; Estados UnidosFil: Bailes, Julie C.. University of Florida; Estados UnidosFil: Dhar, Biswadeep. University of Florida; Estados UnidosFil: Beckworth, Mark T.. University of Florida; Estados UnidosFil: Rabaglino, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Post Uiterweer, Emiel D.. University Medical Center Utrecht; Países BajosFil: Conrad, Kirk P.. University of Florida; Estados Unido

The Upper Respiratory Tract as a Microbial Source for Pulmonary Infections in Cystic Fibrosis. Parallels from Island Biogeography

A continuously mixed series of microbial communities inhabits various points of the respiratory tract, with community composition determined by distance from colonization sources, colonization rates, and extinction rates. Ecology and evolution theory developed in the context of biogeography is relevant to clinical microbiology and could reframe the interpretation of recent studies comparing communities from lung explant samples, sputum samples, and oropharyngeal swabs. We propose an island biogeography model of the microbial communities inhabiting different niches in human airways. Island biogeography as applied to communities separated by time and space is a useful parallel for exploring microbial colonization of healthy and diseased lungs, with the potential to inform our understanding of microbial community dynamics and the relevance of microbes detected in different sample types. In this perspective, we focus on the intermixed microbial communities inhabiting different regions of the airways of patients with cystic fibrosis

Large impacts of small methane fluxes on carbon isotope values of soil respiration

Carbon dioxide isotope (δ13C of CO2) analysis is increasingly used to address a broad range of questions involving soil C dynamics and respiration sources. However, attaining δ13C mass balance is critical for robust interpretation. Many ecosystems exhibit methane (CH4) fluxes that are small in the context of total C budgets, yet may significantly impact δ13C values of CO2 due to large kinetic fractionations during CH4 production. Thus, the δ13C values of CO2 do not directly reflect respiration C sources when co-occurring with CH4, but few studies of terrestrial soils have considered this phenomenon. To assess how CH4 altered the interpretation of δ13C values of CO2, we incubated a Mollisol and Oxisol amended with C4-derived plant litter for 90 days under two headspace treatments: a fluctuating anaerobic/aerobic treatment (four days of anaerobic conditions alternating with four days of aerobic conditions), and a static aerobic treatment (control). We measured δ13C values of CO2 and CH4 with a tunable diode laser absorption spectrometer, using a novel in-line combustion method for CH4. Cumulative δ13C of CO2 differed significantly between treatments in both soils. The δ13C values of CO2 were affected by relatively small CH4 fluxes in the fluctuating anaerobic/aerobic treatment. Effects of CH4 on δ13C values of CO2 were greater in the Oxisol due to its higher percent contribution of CH4 to total C mineralization(18%) than in the Mollisol (3%) during periods of elevated CH4 production. When CH4accounted for just 2% of total C mineralization, the δ13C values of CO2 differed from total C mineralization by 0.3–1‰, and by 1.4–4.8‰ when CH4 was 10% of C mineralization. These differences are highly significant when interpreting natural abundance δ13C data. Small CH4fluxes may strongly alter the δ13C values of CO2 relative to total mineralized C. A broad range of mineral and peatland soils can experience temporary oxygen deficits. In these dynamic redox environments, the δ13C values of CO2 should be interpreted with caution and ideally combined with δ13C of CH4 when partitioning sources and mechanisms of soil respiration

Designing attractive models via automated identification of chaotic and oscillatory dynamical regimes

Chaos and oscillations continue to capture the interest of both the scientific and public domains. Yet despite the importance of these qualitative features, most attempts at constructing mathematical models of such phenomena have taken an indirect, quantitative approach, for example, by fitting models to a finite number of data points. Here we develop a qualitative inference framework that allows us to both reverse-engineer and design systems exhibiting these and other dynamical behaviours by directly specifying the desired characteristics of the underlying dynamical attractor. This change in perspective from quantitative to qualitative dynamics, provides fundamental and new insights into the properties of dynamical systems

Relaxin, a pleiotropic vasodilator for the treatment of heart failure

Relaxin is a naturally occurring peptide hormone that plays a central role in the hemodynamic and renovascular adaptive changes that occur during pregnancy. Triggering similar changes could potentially be beneficial in the treatment of patients with heart failure. The effects of relaxin include the production of nitric oxide, inhibition of endothelin, inhibition of angiotensin II, production of VEGF, and production of matrix metalloproteinases. These effects lead to systemic and renal vasodilation, increased arterial compliance, and other vascular changes. The recognition of this has led to the study of relaxin for the treatment of heart failure. An initial pilot study has shown favorable hemodynamic effects in patients with heart failure, including reduction in ventricular filling pressures and increased cardiac output. The ongoing RELAX-AHF clinical program is designed to evaluate the effects of relaxin on the symptoms and outcomes in a large group of patients admitted to hospital for acute heart failure. This review will summarize both the biology of relaxin and the data supporting its potential efficacy in human heart failure

Shadowing in Inelastic Scattering of Muons on Carbon, Calcium and Lead at Low XBj

Nuclear shadowing is observed in the per-nucleon cross-sections of positive muons on carbon, calcium and lead as compared to deuterium. The data were taken by Fermilab experiment E665 using inelastically scattered muons of mean incident momentum 470 GeV/c. Cross-section ratios are presented in the kinematic region 0.0001 < XBj <0.56 and 0.1 < Q**2 < 80 GeVc. The data are consistent with no significant nu or Q**2 dependence at fixed XBj. As XBj decreases, the size of the shadowing effect, as well as its A dependence, are found to approach the corresponding measurements in photoproduction.Comment: 22 pages, incl. 6 figures, to be published in Z. Phys.

Are self-report of disability pension and long-term sickness absence accurate? Comparisons of self-reported interview data with national register data in a Swedish twin cohort

<p>Abstract</p> <p>Background</p> <p>Self-reported disability pension (DP) and sickness absence are commonly used in epidemiological and other studies as a measure of exposure or even as an outcome. The aims were (1) to compare such self-reports with national register information in order to evaluate the validity of self-reported DP and sickness absence, and (2) to estimate the concordance of reporting behaviour in different twin zygosity groups, also by sex.</p> <p>Methods</p> <p>All Swedish twins born 1933-1958 who participated in the Screening Across the Lifespan Twin study (SALT) 1998-2003, were included (31,122 individuals). The self-reported DP and long-term sickness absence (LTSA) at the time of interview was compared to the corresponding register information retrieved from the National Social Insurance Agency by calculating the proportions of agreements, kappa, sensitivity, specificity, concordance rates, and chi-square test, to evaluate construct validity.</p> <p>Results</p> <p>The proportions of overall agreement were 96% and specificity 99% for both DP and LTSA, while the sensitivity was 70% for DP and 45% for LTSA. Kappa estimates were 0.76 for DP, and 0.58 for LTSA. The proportions of positive agreement were 64% for DP and 42% for LTSA. No difference in response style was found between zygosity groups among complete twin pairs for DP and LTSA. Results were similar for women and men and across age. Kappa estimates for DP differed somewhat depending on years of education, 0.68 (college/university) vs. 0.77 (less than 13 years in school) but not for LTSA.</p> <p>Conclusions</p> <p>Self-reported DP data may be very useful in studies when register information is not available, however, register data is preferred especially for LTSA. The same degree of twin similarity was found for truthful self-report of DP and LTSA in both monozygotic and dizygotic twin pairs. Thus, the response style was not influenced by genetic factors. One consequence of this would be that when estimating the relative importance of genetic and environmental effects from twin models, heritability estimates would not be biased.</p