Ein neuer Genort für eine autosomal-dominante, nichtsyndromale Schwerhörigkeit (DFNA33) liegt auf Chromosom 13q34-qte

Bei der Untersuchung einer deutschen Familie mit nichtsyndromalem Hörverlust mit frühem Beginn und autosomal-dominantem Erbgang konnten wir eine Kopplung zu bekannten DFNA-Loci ausschließen und die Existenz eines neuen Locus (DFNA33) bestätigen. Mit einem nachfolgenden Genom-Scan wurde der Phänotyp auf einem 6-cM-Intervall auf Chromosom 13q34-qter kartiert. Für den Marker D13S285 wurde ein maximaler 2-Punkt-Lodscore von 2,96 erreicht, der maximale Lodscore in der Multipoint-Analyse betrug 3,28 bei 124,56 cM. = By investigation of a German family pedigree with non-syndromic hearing impairment of early onset and autosomal-dominant mode of inheritance, linkage to known DFNA loci was excluded, and the existence of a new locus (DFNA33) was revealed. In a subsequent genomic scan the phenotype was mapped to a 6 cM interval on chromosome 13q34-qter. A maximum two-point lod score of 2.96 was obtained for the marker D13S285 with a maximum lod score in the multipoint analysis of 3.28 at 124.56 cM

Transient jets in V617 Sagittarii

Some of the luminous Compact Binary Supersoft X-Ray sources (CBSS) have shown indications of jets, also called satellites due to their appearance in the spectra. In V Sagittae (V Sge) stars, the galactic counterparts of the CBSS, such features have been reported only for WX Cen. If V Sge stars are indeed the analogs of CBSS, one may expect transient jet emission in other objects of this class. Spectroscopic observations of the V Sge star V617 Sgr have been made, both at high photometric state and at decline. We show that V617 Sgr presents Halpha satellites at high photometric state with velocities of +/-780 km/s. This feature confirms, once more, the CBSS nature of the V Sge stars, however the details of the spectral characteristics also suggest that the two groups of stars display some intrinsic spectroscopic differences, which are likely to be due to a selection effect related to chemical abundance.Comment: Four pages, accepted to be published as a Letter in A&

The Structure and Evolution of Circumbinary Disks in Cataclysmic Variable Systems

We investigate the structure and evolution of a geometrically thin viscous Keplerian circumbinary (CB) disk, using detailed models of their radiative/convective vertical structure. We use a simplified description for the evolution of the cataclysmic binary and focus on cases where the circumbinary disk causes accelerated mass transfer (> 1e-8 Msun/yr). The inner edge of the disk is assumed to be determined by the tidal truncation radius and the mass input rate into the disk is assumed to be a small fraction (1e-5-0.01) of the mass transfer rate. Under the action of the viscous stresses in the disk the matter drifts outward with the optically thick region extending to several AU. The inner part of the disk is cool with maximum effective temperatures < 3,000 K while the outermost parts of the disk are < 30 K and optically thin. We calculate the effects of thermal instability on a sufficiently massive CB disk. It leads to outbursts reminiscent of those in thermally unstable accretion disks, with the instability remaining confined to the inner regions of the CB disk. However, for most of the evolutionary sequences the surface densities required to trigger instability are not reached. The spectral energy distributions from circumbinary disks are calculated, and the prospects for the detection of such disks in the infrared and submm wavelength regions are discussed.Comment: 16 pages, 12 figures, accepted for publication by Ap

Circumbinary disks and cataclysmic variable evolution

The influence of a circumbinary (CB) disk on the evolution of cataclysmic variable (CV) binary systems is investigated. We show that CB mass surface densities sufficient to influence the evolution rate are plausibly provided by the outflows observed in CVs, if the net effect of these winds is to deliver $10^{-4}$--$10^{-3}$ of the mass transfer rate to the CB disk. The torque exerted by the CB disk provides a positive feedback between mass transfer rate and CB disk mass which can lead to mass transfer rates of \sim 10^{-8} -10^{-7} \mpy. This mechanism may be responsible for causing the range of variation of mass transfer rates in CV's. In particular, it may explain rates inferred for the novalike variables and the supersoft X-ray binary systems observed near the upper edge of the period gap ($P \sim 3 - 4$ hr), as well as the spread in mass transfer rates above and below the period gap. Consquences and the possible observability of such disks are discussed.Comment: submitted to Ap

Allele-specific differences in ryanodine receptor 1 mRNA expression levels may contribute to phenotypic variability in malignant hyperthermia

<p>Abstract</p> <p>Background</p> <p>Malignant hyperthermia (MH) is a dominantly inherited skeletal muscle disorder that can cause a fatal hypermetabolic reaction to general anaesthetics. The primary locus of MH (MHS1 locus) in humans is linked to chromosome 19q13.1, the position of the gene encoding the ryanodine receptor skeletal muscle calcium release channel (RyR1).</p> <p>Methods</p> <p>In this study, an inexpensive allele-specific PCR (AS-PCR) assay was designed that allowed the relative quantification of the two RyR1 transcripts in heterozygous samples found to be susceptible to MH (MHS). Allele-specific differences in RyR1 expression levels can provide insight into the observed variable penetrance and variations in MH phenotypes between individuals. The presence/absence of the H4833Y mutation in <it>RYR</it>1 transcripts was employed as a marker that allowed discrimination between the two alleles.</p> <p>Results</p> <p>In four skeletal muscle samples and two lymphoblastoid cell lines (LCLs) from different MHS patients, the wild type allele was found to be expressed at higher levels than the mutant RyR1 allele. For both LCLs, the ratios between the wild type and mutant <it>RYR</it>1 alleles did not change after different incubation times with actinomycin D. This suggests that there are no allele-specific differences in RyR1 mRNA stability, at least in these cells.</p> <p>Conclusion</p> <p>The data presented here revealed for the first time allele-specific differences in <it>RYR</it>1 mRNA expression levels in heterozygous MHS samples, and can at least in part contribute to the observed variable penetrance and variations in MH clinical phenotypes.</p

Common variation in NCAN, a risk factor for bipolar disorder and schizophrenia, influences local cortical folding in schizophrenia

Background Recent studies have provided strong evidence that variation in the gene neurocan (NCAN, rs1064395) is a common risk factor for bipolar disorder (BD) and schizophrenia. However, the possible relevance of NCAN variation to disease mechanisms in the human brain has not yet been explored. Thus, to identify a putative pathomechanism, we tested whether the risk allele has an influence on cortical thickness and folding in a well-characterized sample of patients with schizophrenia and healthy controls. Method Sixty-three patients and 65 controls underwent T1-weighted magnetic resonance imaging (MRI) and were genotyped for the single nucleotide polymorphism (SNP) rs1064395. Folding and thickness were analysed on a node-by-node basis using a surface-based approach (FreeSurfer). Results In patients, NCAN risk status (defined by AA and AG carriers) was found to be associated with higher folding in the right lateral occipital region and at a trend level for the left dorsolateral prefrontal cortex. Controls did not show any association (p>0.05). For cortical thickness, there was no significant effect in either patients or controls. Conclusions This study is the first to describe an effect of the NCAN risk variant on brain structure. Our data show that the NCAN risk allele influences cortical folding in the occipital and prefrontal cortex, which may establish disease susceptibility during neurodevelopment. The findings suggest that NCAN is involved in visual processing and top-down cognitive functioning. Both major cognitive processes are known to be disturbed in schizophrenia. Moreover, our study reveals new evidence for a specific genetic influence on local cortical folding in schizophreni

Investigating the use of a hybrid plasmonic–photonic nanoresonator for optical trapping using finite-difference time-domain method

We investigate the use of a hybrid nanoresonator comprising a photonic crystal (PhC) cavity coupled to a plasmonic bowtie nanoantenna (BNA) for the optical trapping of nanoparticles in water. Using finite difference time-domain simulations, we show that this structure can confine light to an extremely small volume of ~30,000 nm3 (~30 zl) in the BNA gap whilst maintaining a high quality factor (5400–7700). The optical intensity inside the BNA gap is enhanced by a factor larger than 40 compared to when the BNA is not present above the PhC cavity. Such a device has potential applications in optical manipulation, creating high precision optical traps with an intensity gradient over a distance much smaller than the diffraction limit, potentially allowing objects to be confined to much smaller volumes and making it ideal for optical trapping of Rayleigh particles (particles much smaller than the wavelength of light)

Electrons, Photons, and Force: Quantitative Single-Molecule Measurements from Physics to Biology

Single-molecule measurement techniques have illuminated unprecedented details of chemical behavior, including observations of the motion of a single molecule on a surface, and even the vibration of a single bond within a molecule. Such measurements are critical to our understanding of entities ranging from single atoms to the most complex protein assemblies. We provide an overview of the strikingly diverse classes of measurements that can be used to quantify single-molecule properties, including those of single macromolecules and single molecular assemblies, and discuss the quantitative insights they provide. Examples are drawn from across the single-molecule literature, ranging from ultrahigh vacuum scanning tunneling microscopy studies of adsorbate diffusion on surfaces to fluorescence studies of protein conformational changes in solution

Malignant hyperthermia

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stresses such as vigorous exercise and heat. The incidence of MH reactions ranges from 1:5,000 to 1:50,000–100,000 anesthesias. However, the prevalence of the genetic abnormalities may be as great as one in 3,000 individuals. MH affects humans, certain pig breeds, dogs, horses, and probably other animals. The classic signs of MH include hyperthermia to marked degree, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, muscle rigidity, and rhabdomyolysis, all related to a hypermetabolic response. The syndrome is likely to be fatal if untreated. Early recognition of the signs of MH, specifically elevation of end-expired carbon dioxide, provides the clinical diagnostic clues. In humans the syndrome is inherited in autosomal dominant pattern, while in pigs in autosomal recessive. The pathophysiologic changes of MH are due to uncontrolled rise of myoplasmic calcium, which activates biochemical processes related to muscle activation. Due to ATP depletion, the muscle membrane integrity is compromised leading to hyperkalemia and rhabdomyolysis. In most cases, the syndrome is caused by a defect in the ryanodine receptor. Over 90 mutations have been identified in the RYR-1 gene located on chromosome 19q13.1, and at least 25 are causal for MH. Diagnostic testing relies on assessing the in vitro contracture response of biopsied muscle to halothane, caffeine, and other drugs. Elucidation of the genetic changes has led to the introduction, on a limited basis so far, of genetic testing for susceptibility to MH. As the sensitivity of genetic testing increases, molecular genetics will be used for identifying those at risk with greater frequency. Dantrolene sodium is a specific antagonist of the pathophysiologic changes of MH and should be available wherever general anesthesia is administered. Thanks to the dramatic progress in understanding the clinical manifestation and pathophysiology of the syndrome, the mortality from MH has dropped from over 80% thirty years ago to less than 5%