Hereditäre Nephropathien: Dünne Basalmembranen, Alport-Glomerulopathie, Alport-Konduktorinnen

Zusammenfassung: Das Syndrom der dünnen Basalmembranen und das Alport-Syndrom sind hereditäre Nephropathien, die die glomerulären Basalmembranen betreffen. Bei allen Patienten mit Alport-Syndrom und bei etwa 40% der Patienten mit dünnen Basalmembranen finden sich Mutationen der α3-, α4- oder α5-Kette des Kollagen TypIV. Obwohl beide Erkrankungen einen sehr unterschiedlichen Verlauf zeigen, manifestieren sie sich initial als glomeruläre Hämaturie und sind klinisch zunächst nicht auseinanderzuhalten. Beide Erkrankungen lassen sich durch eine Nierenbiopsie diagnostizieren, vorausgesetzt, es wird eine elektronenmikroskopische Untersuchung durchgeführt. Die zusätzliche immunhistologische Darstellung der α3(IV)- und α5(IV)-Kette hilft in bis zu 80% der Fälle, das Alport-Syndrom sicher zu diagnostizieren und ermöglicht darüber hinaus auch, Alport-Konduktorinnen zu identifiziere

Glomeruläre Läsionen bei Transplantatabstoßung

Zusammenfassung: Abstoßungsreaktionen sind die häufigste Ursache für ein Transplantatversagen nach Nierentransplantation. Glomeruläre Läsionen finden sich dabei relativ selten. Die thrombotische Mikroangiopathie und die Transplantatglomerulitis treten früh nach Transplantation auf, die Transplantatglomerulopathie bildet sich in der Regel erst nach längerer Zeit aus. Die morphologischen Befunde, in deren Zentrum ein Endothelschaden steht, und mögliche pathogenetische Mechanismen werden diskutier

Multiple spin-orbit excitons and the electronic structure of α−RuCl3

The honeycomb compound α-RuCl_{3} is widely discussed as a proximate Kitaev spin-liquid material. This scenario builds on spin-orbit entangled j = 1/2 moments arising for a t_{2g}^{5} electron configuration with strong spin-orbit coupling λ and a large cubic crystal field. The actual low-energy electronic structure of α-RuCl_{3}, however, is still puzzling. In particular, infrared absorption features at 0.30, 0.53, and 0.75 eV seem to be at odds with a j = 1/2 scenario. Also the energy of the spin-orbit exciton, the excitation from j = 1/2 to 3/2, and thus the value of λ, are controversial. Combining infrared and Raman data, we show that the infrared features can be attributed to single, double, and triple spin-orbit excitons. We find λ = 0.16 eV and Δ = 42(4) meV for the observed noncubic crystal-field splitting, supporting the validity of the j = 1/2 picture for α-RuCl_{3}. The unusual strength of the double excitation is related to the underlying hopping interactions, which form the basis for dominant Kitaev exchange

Deterministic polarization chaos from a laser diode

Fifty years after the invention of the laser diode and fourty years after the report of the butterfly effect - i.e. the unpredictability of deterministic chaos, it is said that a laser diode behaves like a damped nonlinear oscillator. Hence no chaos can be generated unless with additional forcing or parameter modulation. Here we report the first counter-example of a free-running laser diode generating chaos. The underlying physics is a nonlinear coupling between two elliptically polarized modes in a vertical-cavity surface-emitting laser. We identify chaos in experimental time-series and show theoretically the bifurcations leading to single- and double-scroll attractors with characteristics similar to Lorenz chaos. The reported polarization chaos resembles at first sight a noise-driven mode hopping but shows opposite statistical properties. Our findings open up new research areas that combine the high speed performances of microcavity lasers with controllable and integrated sources of optical chaos.Comment: 13 pages, 5 figure

RIXS observation of bond-directional nearest-neighbor excitations in the Kitaev material Na2_2IrO3_3

Spin-orbit coupling locks spin direction and spatial orientation and generates, in semi-classical magnets, a local spin easy-axis and associated ordering. Quantum spin-1/2's defy this fate: rather than spins becoming locally anisotropic, the spin-spin interactions do. Consequently interactions become dependent on the spatial orientation of bonds between spins, prime theoretical examples of which are Kitaev magnets. Bond-directional interactions imply the existence of bond-directional magnetic modes, predicted spin excitations that render crystallographically equivalent bonds magnetically inequivalent, which yet have remained elusive experimentally. Here we show that resonant inelastic x-ray scattering allows us to explicitly probe the bond-directional character of magnetic excitations. To do so, we use a scattering plane spanned by one bond and the corresponding spin component and scan a range of momentum transfer that encompasses multiple Brillouin zones. Applying this approach to Na$_2$IrO$_3$ we establish the different bond-directional characters of magnetic excitations at 10 meV and 45 meV. Combined with the observation of spin-spin correlations that are confined to a single bond, this experimentally validates the Kitaev character of exchange interactions long proposed for this material.Comment: 6 pages, 5 figures, plus 4 pages Supplementary Information (incl. 5 figures

Depression, Stressful Life Events, and the Impact of Variation in the Serotonin Transporter: Findings from the National Longitudinal Study of Adolescent to Adult Health (Add Health)

BackgroundThe low transcriptionally efficient short-allele of the 5HTTLPR serotonin transporter polymorphism has been implicated to moderate the relationship between the experience of stressful life events (SLEs) and depression. Despite numerous attempts at replicating this observation, results remain inconclusive.MethodsWe examined this relationship in young-adult Non-Hispanic white males and females between the ages of 22 and 26 (n = 4724) participating in the National Longitudinal Study of Adolescent to Adult Health (Add Health) with follow-up information every six years since 1995.ResultsLinear and logistic regression models, corrected for multiple testing, indicated that carriers of one or more of the S-alleles were more sensitive to stress than those with two L-alleles and at a higher risk for depression. This relationship behaved in a dose-response manner such that the risk for depression was greatest among those who reported experiencing higher numbers of SLEs. In post-hoc analyses we were not able to replicate an interaction effect for suicide ideation but did find suggestive evidence that the effects of SLEs and 5HTTLPR on suicide ideation differed for males and females. There were no effects of childhood maltreatment.DiscussionOur results provide partial support for the original hypothesis that 5-HTTLPR genotype interacts with the experience of stressful life events in the etiology of depression during young adulthood. However, even with this large sample, and a carefully constructed a priori analysis plan, the results were still not definitive. For the purposes of replication, characterizing the 5HTTLPR in other large data sets with extensive environmental and depression measures is needed

Submonolayer Quantum Dots for High Speed Surface Emitting Lasers

We report on progress in growth and applications of submonolayer (SML) quantum dots (QDs) in high-speed vertical-cavity surface-emitting lasers (VCSELs). SML deposition enables controlled formation of high density QD arrays with good size and shape uniformity. Further increase in excitonic absorption and gain is possible with vertical stacking of SML QDs using ultrathin spacer layers. Vertically correlated, tilted or anticorrelated arrangements of the SML islands are realized and allow QD strain and wavefunction engineering. Respectively, both TE and TM polarizations of the luminescence can be achieved in the edge-emission using the same constituting materials. SML QDs provide ultrahigh modal gain, reduced temperature depletion and gain saturation effects when used in active media in laser diodes. Temperature robustness up to 100 °C for 0.98 μm range vertical-cavity surface-emitting lasers (VCSELs) is realized in the continuous wave regime. An open eye 20 Gb/s operation with bit error rates better than 10−12has been achieved in a temperature range 25–85 °Cwithout current adjustment. Relaxation oscillations up to ∼30 GHz have been realized indicating feasibility of 40 Gb/s signal transmission

Similarities in drinking behavior of twin's friends: moderation of heritability of alcohol use

Previous research has indicated that friends' drinking may influence alcohol use in adolescents and young adults. We explored whether similarities in the drinking behavior of friends of twins influence the genetic architecture of alcohol use in adolescence and young adulthood. Survey data from The Netherlands Twin Register were available for 1,526 twin pairs aged 16-25 years. We categorized the twin pairs as concordant (both report similar alcohol use in their friends) or discordant for the alcohol use of their friends. Genetic moderator models were tested by carrying out multi-group analyzes in Mplus. Findings showed a significant moderation effect. Genetic factors were more and common environment less important in the explanation of variation in alcohol use in twins discordant for alcohol use of friends than in twins concordant for alcohol use of friend

Mechanisms of Resistance to Decitabine in the Myelodysplastic Syndrome

Purpose: The DNA methylation inhibitor 5-aza-29-deoxycytidine (DAC) is approved for the treatment of myelodysplastic syndromes (MDS), but resistance to DAC develops during treatment and mechanisms of resistance remain unknown. Therefore, we investigated mechanisms of primary and secondary resistance to DAC in MDS. Patients and Methods: We performed Quantitative Real-Time PCR to examine expression of genes related to DAC metabolism prior to therapy in 32 responders and non-responders with MDS as well as 14 patients who achieved a complete remission and subsequently relapsed while on therapy (secondary resistance). We then performed quantitative methylation analyses by bisulfite pyrosequencing of 10 genes as well as Methylated CpG Island Amplification Microarray (MCAM) analysis of global methylation in secondary resistance. Results: Most genes showed no differences by response, but the CDA/DCK ratio was 3 fold higher in non-responders than responders (P,.05), suggesting that this could be a mechanism of primary resistance. There were no significant differences at relapse in DAC metabolism genes, and no DCK mutations were detected. Global methylation measured by the LINE1 assay was lower at relapse than at diagnosis (P,.05). On average, the methylation of 10 genes was lower at relapse (16.1%) compared to diagnosis (18.1%) (P,.05).MCAM analysis showed decreased methylation of an average of 4.5 % (range 0.6%– 9.7%) of the genes at relapse. By contrast, new cytogenetic changes were found in 20 % of patients