Charakterisierung von Hyperpolarisationsaktivierten und zyklisch Nukleotid-gesteuerten Ionenkanälen (HCN-Kanäle) in der Retina und im Gehirn der Ratte

Hyperpolarization-activated and cyclic nucleotide-gated channels (HCN-channels) have been characterized electrophysiologically in numerous tissues. They play a fundamental role in shaping the autonomous rhythmic activity of pacemaker-cells. In many neurons, HCN-channels co-determine resting potential and membrane conductance and thereby play an important role in the integrative behavior of neurons and the sensitivity to synaptic input. Recently, four different genes for HCN-channels have been identified in all mammalian species investigated. But little is known about the cellular expression pattem of HCN-channel subtypes, and their function in these cells. Moreover, it is not clear, whether or not the different subtypes form heteromeric channels. In the present study specific antibodies against all four HCN-channel subtypes were raised. Biochemical studies revealed, that all four HCN-channel subtypes are expressed in the rat retina, and in the rat and mouse brain in glycosylated form. The sizes of deglycosylated channel proteins are in good agreement with the estimated molecular weights of the HCN-channels. Other posttranscriptional or posttranslational modifications, that would change the sizes of the proteins in westemblot experiments, were not detected. Immunohistochemical stainings of the rat retina showed different expression patterns for the four HCN-channel subtypes: In most bipolar celltypes only one HCN-channel subtype was detected. Only in type 5 bipolar cells and some ganglion cells HCN1 and HCN4 are co-localized and might form heteromeric channels. Immunoprecipitation experiments were performed to detect heteromeric HCN1/HCN4-complexes in co-transfected HEK 293-cells and in the rat retina. But the results were not unequivocal. To reveal the function of HCN-channels in different brain neurons, first investigation an the cellular expression pattern of the HCN-channels in the rat brain were started. As in the retina the HCN-channel subtypes are differentially expressed. The electrophysiological properties of the HCN-channel subtypes, as well as their cellular and subcellular localization indicate some of the physiological functions of HCN-channels in different cell types. We can now search for other ion channels or receptors, that interact with the HCN-channels. This knowledge will help to elucidate the role of HCN-channels in signal cascades or other cellular processes

Conduction spectroscopy of a proximity induced superconducting topological insulator

The combination of superconductivity and the helical spin-momentum locking at the surface state of a topological insulator (TI) has been predicted to give rise to p-wave superconductivity and Majorana bound states. The superconductivity can be induced by the proximity effect of a an s-wave superconductor (S) into the TI. To probe the superconducting correlations inside the TI, dI/dV spectroscopy has been performed across such S-TI interfaces. Both the alloyed Bi$_{1.5}$Sb$_{0.5}$Te$_{1.7}$Se$_{1.3}$ and the stoichiometric BiSbTeSe$_2$ have been used as three dimensional TI. In the case of Bi$_{1.5}$Sb$_{0.5}$Te$_{1.7}$Se$_{1.3}$, the presence of disorder induced electron-electron interactions can give rise to an additional zero-bias resistance peak. For the stoichiometric BiSbTeSe$_2$ with less disorder, tunnel barriers were employed in order to enhance the signal from the interface. The general observations in the spectra of a large variety of samples are conductance dips at the induced gap voltage, combined with an increased sub-gap conductance, consistent with p-wave predictions. The induced gap voltage is typically smaller than the gap of the Nb superconducting electrode, especially in the presence of an intentional tunnel barrier. Additional uncovered spectroscopic features are oscillations that are linearly spaced in energy, as well as a possible second order parameter component.Comment: Semiconductor Science and Technology; Special Issue on Hybrid Quantum Materials and Device

The Explanatory Power of QUAL in Veteran-Centered RCTs

The prevalence of Veterans returning from deployment in Iraq and Afghanistan with neurologic disabilities has spurred numerous “gold standard” quantitative studies, RCTs, on community reintegration interventions. We describe a qualitative process to enhance the meaningfulness of quantitative evidence by incorporating the Veteran perspective from study design through execution and forward into program development and implementation

Exact Solutions in Log-Concave Maximum Likelihood Estimation

We study probability density functions that are log-concave. Despite the space of all such densities being infinite-dimensional, the maximum likelihood estimate is the exponential of a piecewise linear function determined by finitely many quantities, namely the function values, or heights, at the data points. We explore in what sense exact solutions to this problem are possible. First, we show that the heights given by the maximum likelihood estimate are generically transcendental. For a cell in one dimension, the maximum likelihood estimator is expressed in closed form using the generalized W-Lambert function. Even more, we show that finding the log-concave maximum likelihood estimate is equivalent to solving a collection of polynomial-exponential systems of a special form. Even in the case of two equations, very little is known about solutions to these systems. As an alternative, we use Smale's alpha-theory to refine approximate numerical solutions and to certify solutions to log-concave density estimation.Comment: 29 pages, 5 figure

Anharmonic Decay of Vibrational States in Amorphous Silicon

Anharmonic decay rates are calculated for a realistic atomic model of amorphous silicon. The results show that the vibrational states decay on picosecond timescales and follow the two-mode density of states, similar to crystalline silicon, but somewhat faster. Surprisingly little change occurs for localized states. These results disagree with a recent experiment.Comment: 10 pages, 4 Postscript figure

Dissecting grain yield pathways and their interactions with grain dry matter content by a two-step correlation approach with maize seedling transcriptome

<p>Abstract</p> <p>Background</p> <p>The importance of maize for human and animal nutrition, but also as a source for bio-energy is rapidly increasing. Maize yield is a quantitative trait controlled by many genes with small effects, spread throughout the genome. The precise location of the genes and the identity of the gene networks underlying maize grain yield is unknown. The objective of our study was to contribute to the knowledge of these genes and gene networks by transcription profiling with microarrays.</p> <p>Results</p> <p>We assessed the grain yield and grain dry matter content (an indicator for early maturity) of 98 maize hybrids in multi-environment field trials. The gene expression in seedlings of the parental inbred lines, which have four different genetic backgrounds, was assessed with genome-scale oligonucleotide arrays. We identified genes associated with grain yield and grain dry matter content using a newly developed two-step correlation approach and found overlapping gene networks for both traits. The underlying metabolic pathways and biological processes were elucidated. Genes involved in sucrose degradation and glycolysis, as well as genes involved in cell expansion and endocycle were found to be associated with grain yield.</p> <p>Conclusions</p> <p>Our results indicate that the capability of providing energy and substrates, as well as expanding the cell at the seedling stage, highly influences the grain yield of hybrids. Knowledge of these genes underlying grain yield in maize can contribute to the development of new high yielding varieties.</p

Zebrafish Recoverin Isoforms Display Differences in Calcium Switch Mechanisms

Primary steps in vertebrate vision occur in rod and cone cells of the retina and require precise molecular switches in excitation, recovery, and adaptation. In particular, recovery of the photoresponse and light adaptation processes are under control of neuronal Ca2+ sensor (NCS) proteins. Among them, the Ca2+ sensor recoverin undergoes a pronounced Ca2+-dependent conformational change, a prototypical so-called Ca2+-myristoyl switch, which allows selective targeting of G protein-coupled receptor kinase. Zebrafish (Danio rerio) has gained attention as a model organism in vision research. It expresses four different recoverin isoforms (zRec1a, zRec1b, zRec2a, and zRec2b) that are orthologs to the one known mammalian variant. The expression pattern of the four isoforms cover both rod and cone cells, but the differential distribution in cones points to versatile functions of recoverin in these cell types. Initial functional studies on zebrafish larvae indicate different Ca2+-sensitive working modes for zebrafish recoverins, but experimental evidence is lacking so far. The aims of the present study are (1) to measure specific Ca2+-sensing properties of the different recoverin isoforms, (2) to ask whether switch mechanisms triggered by Ca2+ resemble that one observed with mammalian recoverin, and (3) to investigate a possible impact of an attached myristoyl moiety. For addressing these questions, we employ fluorescence spectroscopy, surface plasmon resonance (SPR), dynamic light scattering, and equilibrium centrifugation. Exposure of hydrophobic amino acids, due to the myristoyl switch, differed among isoforms and depended also on the myristoylation state of the particular recoverin. Ca2+-induced rearrangement of the protein-water shell was for all variants less pronounced than for the bovine ortholog indicating either a modified Ca2+-myristoyl switch or no switch. Our results have implications for a step-by-step response of recoverin isoforms to changing intracellular Ca2+ during illumination

Re-annotation of the maize oligonucleotide array

The microarray technology has become an established approach for large-scale gene expression analysis with mature protocols for sample, microarray, and data processing. The maize oligonucleotide array (maizearray) is one of the few microarray platforms designed for genome-wide gene expression analysis in Zea mays L. Many datasets addressing various genetic, physiological and developmental topics generated with this platform are available. The original 57,452 microarray probes were compiled based on expressed sequence tags (ESTs). Meanwhile the maize genome sequence became available providing the possibility for an improved annotation of the microarray probe set. In this study we determined the genome positions of all maize array probes to obtain current gene annotations and generated current Gene Ontology (GO) annotations. These new data allow tracing redundancy of the probe set and interfering cross-hybridizations, and doubled the number of genes with functional GO data. Our re-annotation will largely improve the functional analysis of available and future datasets generated on this microarray platform

Validation, optimisation, and application data in support of the development of a targeted selected ion monitoring assay for degraded cardiac troponin T

AbstractCardiac troponin T (cTnT) fragmentation in human serum was investigated using a newly developed targeted selected ion monitoring assay, as described in the accompanying article: “Development of a targeted selected ion monitoring assay for the elucidation of protease induced structural changes in cardiac troponin T” [1]. This article presents data describing aspects of the validation and optimisation of this assay. The data consists of several figures, an excel file containing the results of a sequence identity search, and a description of the raw mass spectrometry (MS) data files, deposited in the ProteomeXchange repository with id PRIDE: PXD003187