The phenotype and genotype of adult obstructive sleep apnoea/hypopnoea syndrome

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldObstructive sleep apnoea/hypopnoea syndrome (OSAHS) is a common condition affecting approximately 2-4% of the middle-aged population. A hereditary component to the condition has long been recognised but its genetic basis has been difficult to elucidate. Progress in determining the genotype of OSAHS is hampered by the lack of a consistent definition of phenotype and the large environmental influences on its expression. "Intermediate phenotypes", such as craniofacial structure, obesity and upper airway control, have been utilised. Multiple gene polymorphisms have been explored in association with the latter, as well as with the sequelae of OSAHS, such as hypertension and increased insulin resistance. To date, two genome-wide scans have identified potential regions that may be of interest in further defining the intermediate phenotypes. The present paper focuses on human studies with an update of the most recent work in the area, including a short discussion on methods of genetic studies

Estimación de la supervivencia anual de aves canoras migratorias bajo el efecto de una fidelidad incompleta al área de reproducción: diseños de estudios que pueden resultar de utilidad

Many species of bird exhibit varying degrees of site–fidelity to the previous year’s territory or breeding area, a phenomenon we refer to as incomplete breeding site–fidelity. If the territory they occupy is located beyond the bounds of the study area or search area (i.e., they have emigrated from the study area), the bird will go undetected and is therefore indistinguishable from dead individuals in capture–mark–recapture studies. Differential emigration rates confound inferences regarding differences in survival between sexes and among species if apparent survival rates are used as estimates of true survival. Moreover, the bias introduced by using apparent survival rates for true survival rates can have profound effects on the predictions of population persistence through time, source/sink dynamics, and other aspects of life–history theory. We investigated four study design and analysis approaches that result in apparent survival estimates that are closer to true survival estimates. Our motivation for this research stemmed from a multi–year capture–recapture study of Prothonotary Warblers (Protonotaria citrea) on multiple study plots within a larger landscape of suitable breeding habitat where substantial inter–annual movements of marked individuals among neighboring study plots was documented. We wished to quantify the effects of this type of movement on annual survival estimation. The first two study designs we investigated involved marking birds in a core area and resighting them in the core as well as an area surrounding the core. For the first of these two designs, we demonstrated that as the resighting area surrounding the core gets progressively larger, and more "emigrants" are resighted, apparent survival estimates begin to approximate true survival rates (bias < 0.01). However, given observed inter–annual movements of birds, it is likely to be logistically impractical to resight birds on sufficiently large surrounding areas to minimize bias. Therefore, as an alternative protocol, we analyzed the data with subsets of three progressively larger areas surrounding the core. The data subsets provided four estimates of apparent survival that asymptotically approached true survival. This study design and analytical approach is likely to be logistically feasible in field settings and yields estimates of true survival unbiased (bias < 0.03) by incomplete breeding site–fidelity over a range of inter–annual territory movement patterns. The third approach we investigated used a robust design data collection and analysis approach. This approach resulted in estimates of survival that were unbiased (bias < 0.02), but were very imprecise and likely would not yield reliable estimates in field situations. The fourth approach utilized a fixed study area size, but modeled detection probability as a function of bird proximity to the study plot boundary (e.g., those birds closest to the edge are more likely to emigrate). This approach also resulted in estimates of survival that were unbiased (bias < 0.02), but because the individual covariates were normalized, the average capture probability was 0.50, and thus did not provide an accurate estimate of the true capture probability. Our results show that the core–area with surrounding resight–only can provide estimates of survival that are not biased by the effects of incomplete breeding site–fidelity.Numerosas especies de aves presentan distintos grados de fidelidad al territorio o área de reproducción del año anterior, fenómeno que denominamos fidelidad incompleta al lugar de reproducción. Si el territorio que ocupan las aves está situado más allá del área de estudio o investigación (es decir, si las aves han emigrado del área de estudio), el ave no podrá ser detectada y, por consiguiente, en los estudios de captura–marcaje–recaptura, no podrá distinguirse de los individuos muertos. Si se emplean las tasas de supervivencia aparente como estimaciones de la supervivencia real, las tasas de emigración diferencial sesgan las distintas inferencias sobre variaciones en supervivencia entre sexos y entre especies. Además, el sesgo introducido por el empleo de tasas de supervivencia aparente en lugar de tasas de supervivencia real puede repercutir significativamente en las predicciones de la persistencia poblacional a través del tiempo, la dinámica de fuente/sumidero, y otros aspectos de la teoría sobre historias vitales. Investigamos cuatro enfoques de diseños de estudios y análisis que proporcionan estimaciones de supervivencia aparente más próximas a las estimaciones de supervivencia real. Esta investigación es fruto de un estudio multianual de captura–recaptura de reinitas cabecidoradas (Protonotaria citrea) en múltiples parcelas de estudio incluidas en un paisaje más amplio de hábitats de reproducción adecuados, en los que se documentaron los movimientos interanuales más importantes entre distintas parcelas de estudio adyacentes por parte de individuos marcados. Nuestro objetivo era cuantificar los efectos de este tipo de movimiento en la estimación de la supervivencia anual. Los dos primeros diseños de estudio que investigamos consistían en el marcaje de aves en un área central, para posteriormente volverlas a avistar, tanto en dicha área como en un área adyacente a la misma. Por lo que respecta al primero de estos dos diseños, demostramos que cuando el área de reavistaje que rodea al área central se va ampliando y el número de "emigrantes" reavistados aumenta, las estimaciones de supervivencia aparente empiezan a aproximarse a las tasas de supervivencia real (sesgo < 0,01). Sin embargo, teniendo en cuenta los movimientos interanuales de las aves observados, lo más probable es que, desde un punto de vista logístico, no resulte práctico reavistar aves en áreas adyacentes que sean lo suficientemente amplias como para minimizar el sesgo. Por consiguiente, como protocolo alternativo, analizamos los datos con subconjuntos de tres áreas adyacentes al área principal, que se iban ampliando de forma progresiva. Los subconjuntos de datos proporcionaron cuatro estimaciones de supervivencia aparente que abordaban asintóticamente la supervivencia real. Lo más probable es que, desde un punto de vista logístico, este diseño de estudio y enfoque analítico resulte viable en estudios de campo, además de producir estimaciones de supervivencia real no sesgadas (sesgo < 0,03) por fidelidad incompleta al área de reproducción en un rango de patrones de movimiento territorial interanual. El tercer enfoque que investigamos empleaba una serie de datos de un diseño robusto de toma de datos y un enfoque analítico. Este enfoque proporcionó estimaciones de supervivencia que, si bien no eran sesgadas (sesgo < 0,02), resultaban muy imprecisas, por lo que probablemente no proporcionarían estimaciones fiables en situaciones de campo. El cuarto enfoque utilizaba un tamaño de área de estudio fijo, pero modelaba la probabilidad de detección como una función de la proximidad de las aves al límite de la parcela de estudio (es decir, las aves situadas más cerca del borde presentan más probabilidades de emigrar). Este enfoque también produjo estimaciones de supervivencia no sesgadas (sesgo < 0,02), pero debido a que las covarianzas individuales se normalizaron, la probabilidad de captura media era de 0,50, por lo que no proporcionaba una estimación precisa de la probabilidad de captura real. Nuestros resultados demuestran que el hecho de combinar el área principal con áreas adyacentes dedicadas exclusivamente al reavistaje puede proporcionar estimaciones de supervivencia que no resulten sesgadas por los efectos de una fidelidad incompleta al área de reproducción

Realtime calibration of the A4 electromagnetic lead fluoride calorimeter

Sufficient energy resolution is the key issue for the calorimetry in particle and nuclear physics. The calorimeter of the A4 parity violation experiment at MAMI is a segmented calorimeter where the energy of an event is determined by summing the signals of neighbouring channels. In this case the precise matching of the individual modules is crucial to obtain a good energy resolution. We have developped a calibration procedure for our total absorbing electromagnetic calorimeter which consists of 1022 lead fluoride (PbF_2) crystals. This procedure reconstructs the the single-module contributions to the events by solving a linear system of equations, involving the inversion of a 1022 x 1022-matrix. The system has shown its functionality at beam energies between 300 and 1500 MeV and represents a new and fast method to keep the calorimeter permanently in a well-calibrated state

A36-dependent actin filament nucleation promotes release of vaccinia virus

Cell-to-cell transmission of vaccinia virus can be mediated by enveloped virions that remain attached to the outer surface of the cell or those released into the medium. During egress, the outer membrane of the double-enveloped virus fuses with the plasma membrane leaving extracellular virus attached to the cell surface via viral envelope proteins. Here we report that F-actin nucleation by the viral protein A36 promotes the disengagement of virus attachment and release of enveloped virus. Cells infected with the A36YdF virus, which has mutations at two critical tyrosine residues abrogating localised actin nucleation, displayed a 10-fold reduction in virus release. We examined A36YdF infected cells by transmission electron microscopy and observed that during release, virus appeared trapped in small invaginations at the plasma membrane. To further characterise the mechanism by which actin nucleation drives the dissociation of enveloped virus from the cell surface, we examined recombinant viruses by super-resolution microscopy. Fluorescently-tagged A36 was visualised at sub-viral resolution to image cell-virus attachment in mutant and parental backgrounds. We confirmed that A36YdF extracellular virus remained closely associated to the plasma membrane in small membrane pits. Virus-induced actin nucleation reduced the extent of association, thereby promoting the untethering of virus from the cell surface. Virus release can be enhanced via a point mutation in the luminal region of B5 (P189S), another virus envelope protein. We found that the B5P189S mutation led to reduced contact between extracellular virus and the host membrane during release, even in the absence of virus-induced actin nucleation. Our results posit that during release virus is tightly tethered to the host cell through interactions mediated by viral envelope proteins. Untethering of virus into the surrounding extracellular space requires these interactions be relieved, either through the force of actin nucleation or by mutations in luminal proteins that weaken these interactions. © 2013 Horsington et al

Measurement of the Transverse Beam Spin Asymmetry in Elastic Electron Proton Scattering and the Inelastic Contribution to the Imaginary Part of the Two-Photon Exchange Amplitude

We report on a measurement of the asymmetry in the scattering of transversely polarized electrons off unpolarized protons, A$_\perp$, at two Q$^2$ values of \qsquaredaveragedlow (GeV/c)$^2$ and \qsquaredaveragedhighII (GeV/c)$^2$ and a scattering angle of $30^\circ < \theta_e < 40^\circ$. The measured transverse asymmetries are A$_{\perp}$(Q$^2$ = \qsquaredaveragedlow (GeV/c)$^2$) = (\experimentalasymmetry alulowcorr $\pm$ \statisticalerrorlow$_{\rm stat}$ $\pm$ \combinedsyspolerrorlowalucor$_{\rm sys}$) $\times$ 10$^{-6}$ and A$_{\perp}$(Q$^2$ = \qsquaredaveragedhighII (GeV/c)$^2$) = (\experimentalasymme tryaluhighcorr $\pm$ \statisticalerrorhigh$_{\rm stat}$ $\pm$ \combinedsyspolerrorhighalucor$_{\rm sys}$) $\times$ 10$^{-6}$. The first errors denotes the statistical error and the second the systematic uncertainties. A$_\perp$ arises from the imaginary part of the two-photon exchange amplitude and is zero in the one-photon exchange approximation. From comparison with theoretical estimates of A$_\perp$ we conclude that $\pi$N-intermediate states give a substantial contribution to the imaginary part of the two-photon amplitude. The contribution from the ground state proton to the imaginary part of the two-photon exchange can be neglected. There is no obvious reason why this should be different for the real part of the two-photon amplitude, which enters into the radiative corrections for the Rosenbluth separation measurements of the electric form factor of the proton.Comment: 4 figures, submitted to PRL on Oct.