Corneodesmosin und die Genetik der Psoriasis vulgaris unter Betrachtung geschlechtsspezifischer Allel-Transmissionen im MHC

Diese Arbeit befasst sich mit dem wichtigen genetischen Suszeptibilitäts-Lokus der Psoriasis vulgaris PSORS1. Von Interesse ist das Corneodesmosin-Gen (CDSN). Im Transmissions/Disequilibrium-Test (TDT) wurde bei 199 Falk-Rubinstein-Trios der Mikrosatelliten-Marker TN62 und der CDSN-SNP *1243 analysiert. Im RC-TDT ergab CDSN*1243 (Allel2) ein signifikantes p von 0,0084 und TN62 (Allel4) ein hochsignifikantes p von 6,2x10-7. Im Hinblick auf den paternalen Effekt der Psoriasis zeigt die parent-of-origin-Analyse jeweils ein Überwiegen der paternalen Transmissionen bei CDSN*1243(2) (pmat=0,023; ppat=0,00055) bzw. der maternalen Transmissionen bei TN62(4) (pmat=0,96x10-5; pat=0,00159). Die Ergebnisse sprechen für ein Kopplungsungleichgewicht zwischen CDSN*1243 und PSORS1, aber für unterschiedliche MHC-Haplotypen mit je CDSN*1243(2) oder TN62(4). Potentielle Transmissionseffekte können bei einer signifikanten Bestätigung des Befundes im Sinne einer genomischen Prägung interpretiert werden

Thermoelectric Response of an Interacting Two-Dimensional Electron Gas in Quantizing Magnetic Field

We present a discussion of the linear thermoelectric response of an interacting electron gas in a quantizing magnetic field. Boundary currents can carry a significant fraction of the net current passing through the system. We derive general expressions for the bulk and boundary components of the number and energy currents. We show that the local current density may be described in terms of ``transport'' and ``internal magnetization'' contributions. The latter carry no net current and are not observable in standard transport experiments. We show that although Onsager relations cannot be applied to the local current, they are valid for the transport currents and hence for the currents observed in standard transport experiments. We relate three of the four thermoelectric response coefficients of a disorder-free interacting two-dimensional electron gas to equilibrium thermodynamic quantities. In particular, we show that the diffusion thermopower is proportional to the entropy per particle, and we compare this result with recent experimental observations.Comment: 18 pages, 2 postscript figures included. Revtex with epsf.tex and multicol.sty. In the revised version, the comparison with experimental observations at $\nu=1/2, 3/2$ is extended to include the possibility of corrections due to weak impurity scattering. The conclusions that we reach regarding the applicability of the composite fermion model at these filling fractions are not affecte

Diffusion Thermopower at Even Denominator Fractions

We compute the electron diffusion thermopower at compressible Quantum Hall states corresponding to even denominator fractions in the framework of the composite fermion approach. It is shown that the deviation from the linear low temperature behavior of the termopower is dominated by the logarithmic temperature corrections to the conductivity and not to the thermoelectric coefficient, although such terms are present in both quantities. The enhanced magnitude of this effect compared to the zero field case may allow its observation with the existing experimental techniques.Comment: Latex, 12 pages, Nordita repor

Thermohydrodynamics in Quantum Hall Systems

A theory of thermohydrodynamics in two-dimensional electron systems in quantizing magnetic fields is developed including a nonlinear transport regime. Spatio-temporal variations of the electron temperature and the chemical potential in the local equilibrium are described by the equations of conservation with the number and thermal-energy flux densities. A model of these flux densities due to hopping and drift processes is introduced for a random potential varying slowly compared to both the magnetic length and the phase coherence length. The flux measured in the standard transport experiment is derived and is used to define a transport component of the flux density. The equations of conservation can be written in terms of the transport component only. As an illustration, the theory is applied to the Ettingshausen effect, in which a one-dimensional spatial variation of the electron temperature is produced perpendicular to the current.Comment: 10 pages, 1 figur

Quality of life and clinical characteristics of self-improving congenital ichthyosis within the disease spectrum of autosomal recessive congenital ichthyosis

Background Autosomal-recessive congenital ichthyosis (ARCI) is a heterogeneous group of ichthyoses presenting at birth. Self-improving congenital ichthyosis (SICI) is a subtype of ARCI and is diagnosed when skin condition improves remarkably (within years) after birth. So far, there are sparse data on SICI and quality of life (QoL) in this ARCI subtype. This study aims to further delineate the clinical spectrum of SICI as a rather unique subtype of ARCI. Objectives This prospective study included 78 patients (median age: 15 years) with ARCI who were subdivided in SICI (n = 18) and non-SICI patients (nSICI, n = 60) by their ARCI phenotype. Methods Quality of life (QoL) was assessed using the (Children's) Dermatology Life Quality Index. Statistical analysis was performed with chi-squared and t-Tests. Results The genetically confirmed SICI patients presented causative mutations in the following genes: ALOXE3 (8/16; 50.0%), ALOX12B (6/16; 37.5%), PNPLA1 (1/16; 6.3%) and CYP4F22 (1/16; 6.3%). Hypo-/anhidrosis and insufficient vitamin D levels (<30 ng/mL) were often seen in SICI patients. Brachydactyly (a shortening of the 4th and 5th fingers) was statistically more frequent in SICI (P = 0.023) than in nSICI patients. A kink of the ear's helix was seen in half of the SICI patients and tends to occur more frequently in patients with ALOX12B mutations (P = 0.005). QoL was less impaired in patients under the age of 16, regardless of ARCI type. Conclusions SICI is an underestimated, milder clinical variant of ARCI including distinct features such as brachydactyly and kinking of the ears. Clinical experts should be aware of these features when seeing neonates with a collodion membrane. SICI patients should be regularly checked for clinical parameters such as hypo-/anhidrosis or vitamin D levels and monitored for changes in quality of life

The zinc finger domain of Wilms' tumor 1 suppressor gene (WT1) behaves as a dominant negative, leading to abrogation of WT1 oncogenic potential in breast cancer cells

Abstract Introduction There is growing evidence that the Wilms' tumor 1 suppressor gene (WT1) behaves as an oncogene in some forms of breast cancer. Previous studies have demonstrated that the N-terminal domain of WT1 can act as a dominant negative through self-association. In the studies presented here we have explored the potential for the zinc finger domain (ZF) of WT1 to also have dominant-negative effects, and thus further our understanding of this protein. Methods Using full-length and ZF-only forms of WT1 we assessed their effect on the WT1 and c-myc promoter using luciferase and chromatin immunoprecipitation assays. The gene expression levels were determined by quantitative real-time RT-PCR, northern blot and western blot. We also assessed the effect of the ZF-only form on the growth of breast cancer cell lines in culture. Results Transfection with WT1–ZF plasmids resulted in a stronger inhibition of WT1 promoter than full-length WT1 in breast cancer cells. The WT1–ZF form lacking the lysine–threonine–serine (KTS) insert (ZF - KTS) can bind to the majority of WT1 consensus sites throughout the WT1 promoter region, while the ZF containing the insert (ZF + KTS) form only binds to sites in the proximal promoter. The abundances of endogenous WT1 mRNA and protein were markedly decreased following the stable expression of ZF - KTS in breast cancer cells. The expressions of WT1 target genes, including c-myc, Bcl-2, amphiregulin and TERT, were similarly suppressed by ZF - KTS. Moreover, WT1–ZF - KTS abrogated the transcriptional activation of c-myc mediated by all four predominant isoforms of WT1 (including or lacking alternatively spliced exons 5 and 9). Finally, WT1–ZF - KTS inhibited colony formation and cell division, but induced apoptosis in MCF-7 cells. Conclusion Our observations strongly argue that the WT1–ZF plasmid behaves as a dominant-negative regulator of the endogenous WT1 in breast cancer cells. The inhibition on proliferation of breast cancer cells by WT1–ZF - KTS provides a potential candidate of gene therapy for breast cancer

In vivo characterization of connective tissue remodeling using infrared photoacoustic spectra

Premature cervical remodeling is a critical precursor of spontaneous preterm birth, and the remodeling process is characterized by an increase in tissue hydration. Nevertheless, current clinical measurements of cervical remodeling are subjective and detect only late events, such as cervical effacement and dilation. Here, we present a photoacoustic endoscope that can quantify tissue hydration by measuring near-infrared cervical spectra. We quantify the water contents of tissue-mimicking hydrogel phantoms as an analog of cervical connective tissue. Applying this method to pregnant women in vivo, we observed an increase in the water content of the cervix throughout pregnancy. The application of this technique in maternal healthcare may advance our understanding of cervical remodeling and provide a sensitive method for predicting preterm birth

A rare missense mutation in <i>GJB3</i> (Cx31G45E) is associated with a unique cellular phenotype resulting in necrotic cell death

Erythrokeratodermia variabilis et progressiva (EKV-P) is caused by mutations in either the GJB3 (Cx31) or GJB4 genes (Cx30.3). We identified a rare GJB3 missense mutation, c.134G>A (p.G45E), in two unrelated patients and investigated its cellular characteristics. Expression of Cx31G45E-GFP caused previously undescribed changes within HeLa cells and HaCaT cells, a model human keratinocyte cell line. Cx31WT-GFP localised to the plasma membrane, but expression of Cx31G45E-GFP caused vacuolar expansion of the endoplasmic reticulum (ER), the mutant protein accumulated within the ER membrane and disassembly of the microtubular network occurred. No ER stress responses were evoked. Cx31WT-myc-myc-6xHis and Cx31G45E-GFP co-immunoprecipitated, indicative of heteromeric interaction, but co-expression with Cx31WT-mCherry, Cx26 or Cx30.3 did not mitigate the phenotype. Cx31 and Cx31G45E both co-immunoprecipitated with Cx43, indicating the ability to form heteromeric connexons. WT-Cx31 and Cx43 assembled into large gap junction plaques at points of cell-to-cell contact; Cx31G45E restricted the ability of Cx43 to reach the plasma membrane in both HaCaT cells and HeLa cells stably expressing Cx43 where the proteins strongly co-localised with the vacolourised ER. Cell viability assays identified an increase in cell death in cells expressing Cx31G45E-GFP, which FACS analysis determined was necrotic. Blocking connexin channel function with 18α-glycyrrhetinic acid did not completely rescue necrosis or prevent propidium iodide uptake, suggesting that expression of Cx31G45E-GFP damages the cellular membrane independent of its channel function. Our data suggest that entrapment of Cx43 and necrotic cell death in the epidermis could underlie the EKV skin phenotype

FATP4 missense and nonsense mutations cause similar features in Ichthyosis Prematurity Syndrome

<p>Abstract</p> <p>Background</p> <p>Ichthyosis Prematurity Syndrome (IPS) is an autosomal recessive disorder characterized by premature birth, non-scaly ichthyosis and atopic manifestations. The disease was recently shown to be caused by mutations in the gene encoding the fatty acid transport protein 4 (FATP4) and a specific reduction in the incorporation of very long chain fatty acids (VLCFA) into cellular lipids.</p> <p>Findings</p> <p>We screened probands from five families segregating IPS for mutations in the <it>FATP4 </it>gene. Four probands were compound heterozygous for four different mutations of which three are novel. Four patients were heterozygous and one patient homozygous for the previously reported non-sense mutation p.C168X (c.504c > a). All patients had clinical characteristics of IPS and a similar clinical course.</p> <p>Conclusions</p> <p>Missense mutations and non-sense mutations in <it>FATP4 </it>are associated with similar clinical features suggesting that missense mutations have a severe impact on FATP4 function. The results broaden the mutational spectrum in <it>FATP4 </it>associated with IPS for molecular diagnosis of and further functional analysis of FATP4.</p

Quasiparticle Hall Transport of d-wave Superconductors in Vortex State

We present a theory of quasiparticle Hall transport in strongly type-II superconductors within their vortex state. We establish the existence of integer quantum spin Hall effect in clean unconventional $d_{x^2-y^2}$ superconductors in the vortex state from a general analysis of the Bogoliubov-de Gennes equation. The spin Hall conductivity $\sigma^s_{xy}$ is shown to be quantized in units of $\frac{\hbar}{8\pi}$. This result does not rest on linearization of the BdG equations around Dirac nodes and therefore includes inter-nodal physics in its entirety. In addition, this result holds for a generic inversion-symmetric lattice of vortices as long as the magnetic field $B$ satisfies $H_{c1} \ll B \ll H_{c2}$. We then derive the Wiedemann-Franz law for the spin and thermal Hall conductivity in the vortex state. In the limit of $T \to 0$, the thermal Hall conductivity satisfies $\kappa_{x y}=\frac{4\pi^2}{3}(\frac{k_B}{\hbar})^2 T \sigma^s_{xy}$. The transitions between different quantized values of $\sigma^s_{xy}$ as well as relation to conventional superconductors are discussed.Comment: 18 pages REVTex, 3 figures, references adde