Rfx6 Maintains the Functional Identity of Adult Pancreatic β Cells.

SummaryIncreasing evidence suggests that loss of β cell characteristics may cause insulin secretory deficiency in diabetes, but the underlying mechanisms remain unclear. Here, we show that Rfx6, whose mutation leads to neonatal diabetes in humans, is essential to maintain key features of functionally mature β cells in mice. Rfx6 loss in adult β cells leads to glucose intolerance, impaired β cell glucose sensing, and defective insulin secretion. This is associated with reduced expression of core components of the insulin secretion pathway, including glucokinase, the Abcc8/SUR1 subunit of KATP channels and voltage-gated Ca2+ channels, which are direct targets of Rfx6. Moreover, Rfx6 contributes to the silencing of the vast majority of “disallowed” genes, a group usually specifically repressed in adult β cells, and thus to the maintenance of β cell maturity. These findings raise the possibility that changes in Rfx6 expression or activity may contribute to β cell failure in humans

Valence band photoemission from the GaN(0001) surface

A detailed investigation by one-step photoemission calculations of the GaN(0001)-(1x1) surface in comparison with recent experiments is presented in order to clarify its structural properties and electronic structure. The discussion of normal and off-normal spectra reveals through the identified surface states clear fingerprints for the applicability of a surface model proposed by Smith et al. Especially the predicted metallic bonds are confirmed. In the context of direct transitions the calculated spectra allow to determine the valence band width and to argue in favor of one of two theoretical bulk band structures. Furthermore a commonly used experimental method to fix the valence band maximum is critically tested.Comment: 8 pages, 11 eps files, submitted to PR

Terahertz dynamics of a topologically protected state: quantum Hall effect plateaus near cyclotron resonance in a GaAs/AlGaAs heterojunction

We measure the Hall conductivity of a two-dimensional electron gas formed at a GaAs/AlGaAs heterojunction in the terahertz regime close to the cyclotron resonance frequency by employing a highly sensitive Faraday rotation method coupled with electrical gating of the sample to change the electron density. We observe clear plateau-and step-like features in the Faraday rotation angle vs. electron density and magnetic field (Landau-level filling factor), which are the high frequency manifestation of quantum Hall plateaus - a signature of topologically protected edge states. The results are compared to a recent dynamical scaling theory.Comment: 18 pages, 3 figure

Overexpression of Mcl-1 exacerbates lymphocyte accumulation and autoimmune kidney disease in lpr mice

Cell death by apoptosis has a critical role during embryonic development and in maintaining tissue homeostasis. In mammals, there are two converging apoptosis pathways: the ‘extrinsic’ pathway, which is triggered by engagement of cell surface ‘death receptors’ such as Fas/APO-1; and the ‘intrinsic’ pathway, which is triggered by diverse cellular stresses, and is regulated by prosurvival and pro-apoptotic members of the Bcl-2 family of proteins. Pro-survival Mcl-1, which can block activation of the proapoptotic proteins, Bax and Bak, appears critical for the survival and maintenance of multiple haemopoietic cell types. To investigate the impact on haemopoiesis of simultaneously inhibiting both apoptosis pathways, we introduced the vavP-Mcl-1 transgene, which causes overexpression of Mcl-1 protein in all haemopoietic lineages, into Faslpr/lpr mice, which lack functional Fas and are prone to autoimmunity. The combined mutations had a modest impact on myelopoiesis, primarily an increase in the macrophage/monocyte population in Mcl-1tg/lpr mice compared with lpr or Mcl-1tg mice. The impact on lymphopoiesis was striking, with a marked elevation in all major lymphoid subsets, including the non-conventional double-negative (DN) T cells (TCRβ+ CD4– CD8– B220+ ) characteristic of Faslpr/lpr mice. Of note, the onset of autoimmunity was markedly accelerated in Mcl-1tg/lpr mice compared with lpr mice, and this was preceded by an increase in immunoglobulin (Ig)-producing cells and circulating autoantibodies. This degree of impact was surprising, given the relatively mild phenotype conferred by the vavP-Mcl-1 transgene by itself: a two- to threefold elevation of peripheral B and T cells, no significant increase in the non-conventional DN T-cell population and no autoimmune disease. Comparison of the phenotype with that of other susceptible mice suggests that the development of autoimmune disease in Mcl-1tg/lpr mice may be influenced not only by Ig-producing cells but also other haemopoietic cell types

Identification of Ag-acceptors in 111 ⁣^{111}\!Ag 111 ⁣^{111}\!Cd doped ZnTe and CdTe

Nominally undoped ZnTe and CdTe crystals were implanted with radioactive $^{111}\!$Ag, which decays to $^{111}\!$Cd, and investigated by photoluminescence spectroscopy (PL). In ZnTe, the PL lines caused by an acceptor level at 121 meV are observed: the principal bound exciton (PBE) line, the donor-acceptor pair (DAP) band, and the two-hole transition lines. In CdTe, the PBE line and the DAP band that correspond to an acceptor level at 108 meV appear. Since the intensities of all these PL lines decrease in good agreement with the half-life of $^{111}\!$Ag of 178.8 h, both acceptor levels are concluded to be associated with defects containing a single Ag atom. Therefore, the earlier assignments to substitutional Ag on Zn- and Cd-lattice sites in the respective II-VI semiconductors are confirmed. The assignments in the literature of the S$_1$, S$_2$, and S$_3$ lines in ZnTe and the X$\scriptstyle^\textrm{Ag}_{1}\,\,,$ X$\scriptstyle^\textrm{Ag}_{2}$/ C$\scriptstyle^\textrm{Ag}_{1}\,$ and C$\scriptstyle^\textrm{Ag}_{2}\,$ lines in CdTe to Ag-related defect complexes are not confirmed

Differential cross sections for muonic atom scattering in solid hydrogenic targets

The differential cross sections for low-energy muonic hydrogen atom scattering in solid molecular H$_2$, D$_2$ and T$_2$ targets under low pressure have been calculated for various temperatures. The polycrystalline fcc and hcp structure of the solid hydrogenic targets are considered. The Bragg and phonon scattering processes are described using the Debye model of a solid. The calculated cross sections are used for Monte Carlo simulations of the muonic atom slowing down in these targets. They have been successfully applied for a description of the production of the muonic atom beams in the multilayer hydrogenic crystals.Comment: 23 pages, 19 figures, 2 table

An interdisciplinary investigation of a recent submarine mass transport deposit at the continental margin off Uruguay

Assessing frequency and extent of mass movement at continental margins is crucial to evaluate risks for offshore constructions and coastal areas. A multidisciplinary approach including geophysical, sedimentological, geotechnical, and geochemical methods was applied to investigate multistage mass transport deposits (MTDs) off Uruguay, on top of which no surficial hemipelagic drape was detected based on echosounder data. Nonsteady state pore water conditions are evidenced by a distinct gradient change in the sulfate (SO42−) profile at 2.8 m depth. A sharp sedimentological contact at 2.43 m coincides with an abrupt downward increase in shear strength from ∼10 to >20 kPa. This boundary is interpreted as a paleosurface (and top of an older MTD) that has recently been covered by a sediment package during a younger landslide event. This youngest MTD supposedly originated from an upslope position and carried its initial pore water signature downward. The kink in the SO42− profile ∼35 cm below the sedimentological and geotechnical contact indicates that bioirrigation affected the paleosurface before deposition of the youngest MTD. Based on modeling of the diffusive re‐equilibration of SO42− the age of the most recent MTD is estimated to be <30 years. The mass movement was possibly related to an earthquake in 1988 (∼70 km southwest of the core location). Probabilistic slope stability back analysis of general landslide structures in the study area reveals that slope failure initiation requires additional ground accelerations. Therefore, we consider the earthquake as a reasonable trigger if additional weakening processes (e.g., erosion by previous retrogressive failure events or excess pore pressures) preconditioned the slope for failure. Our study reveals the necessity of multidisciplinary approaches to accurately recognize and date recent slope failures in complex settings such as the investigated area

ESCIMO.spread (v2) : parameterization of a spreadsheet-based energy balance snow model for inside-canopy conditions

This article describes the extension of the ESCIMO.spread spreadsheet-based point energy balance snow model by (i) an advanced approach for precipitation phase detection, (ii) a method for cold content and liquid water storage consideration and (iii) a canopy sub-model that allows the quantification of canopy effects on the meteorological conditions inside the forest as well as the simulation of snow accumulation and ablation inside a forest stand. To provide the data for model application and evaluation, innovative low-cost snow monitoring systems (SnoMoS) have been utilized that allow the collection of important meteorological and snow information inside and outside the canopy. The model performance with respect to both, the modification of meteorological conditions as well as the subsequent calculation of the snow cover evolution, are evaluated using inside- and outside-canopy observations of meteorological variables and snow cover evolution as provided by a pair of SnoMoS for a site in the Black Forest mountain range (southwestern Germany). The validation results for the simulated snow water equivalent with Nash–Sutcliffe model efficiency values of 0.81 and 0.71 and root mean square errors of 8.26 and 18.07 mm indicate a good overall model performance inside and outside the forest canopy, respectively. The newly developed version of the model referred to as ESCIMO.spread (v2) is provided free of charge together with 1 year of sample data including the meteorological data and snow observations used in this study