414 research outputs found
A regional analysis of CAP expenditure in Austria
This paper reflects the demand for taking account of the territorial dimension in the application of Common Agricultural Policy (CAP) more comprehensively. While this has been addressed in rural development discourse to a wide extent over the last two decades and consensus for regionalized strategies is emerging, programme evaluation is in general still limited to the analysis of policy interventions at the national level. This implies that conclusions on the territorial effects of CAP are largely missing. Therefore the intention of this paper is to provide a regional analysis of CAP expenditures for pillar 1 and pillar 2, and to demonstrate and assess their actual territorial impacts, represented on the basis of the NUTS 3 region ‘Obersteiermark West’: The territorial analysis presented is an example to reduce this gap (national vs territorial) in the evaluation of CAP.CAP expenditure, regional analysis, territorial effectiveness, Agricultural and Food Policy, Q18,
Yeast phosphatidylinositol 4-kinase, Pik1, has essential roles at the Golgi and in the nucleus
Phosphatidylinositol 4-kinase, Pik1, is essential for viability. GFP-Pik1 localized to cytoplasmic puncta and the nucleus. The puncta colocalized with Sec7-DsRed, a marker of trans-Golgi cisternae. Kap95 (importin-β) was necessary for nuclear entry, but not Kap60 (importin-α), and exportin Msn5 was required for nuclear exit. Frq1 (frequenin orthologue) also is essential for viability and binds near the NH(2) terminus of Pik1. Frq1-GFP localized to Golgi puncta, and Pik1 lacking its Frq1-binding site (or Pik1 overexpressed in frq1Δ cells) did not decorate the Golgi, but nuclear localization was unperturbed. Pik1(Δ10-192), which lacks its nuclear export sequence, displayed prominent nuclear accumulation and did not rescue inviability of pik1Δ cells. A Pik1-CCAAX chimera was excluded from the nucleus and also did not rescue inviability of pik1Δ cells. However, coexpression of Pik1(Δ10-192) and Pik1-CCAAX in pik1Δ cells restored viability. Catalytically inactive derivatives of these compartment-restricted Pik1 constructs indicated that PtdIns4P must be generated both in the nucleus and at the Golgi for normal cell function
Praxis durch Praxis – Das Braunschweiger Experimentierseminar für Lehramtsstudierende
In diesem Beitrag wird das an der TU Braunschweig erfolgreich erprobte und evaluierte Konzept eines Experimentierseminars für Lehramtsstudierende vorgestellt. Das Experimentierseminar ist ein bedeutender Teil des Studiums. Hier lernen die Studierenden das Experimentieren, indem sie Versuche selbst konzipieren, aufbauen, vorführen und beschreiben
Praxis durch Praxis – Das Braunschweiger Experimentierseminar für Lehramtsstudierende
In diesem Beitrag wird das an der TU Braunschweig erfolgreich erprobte und evaluierte Konzept eines Experimentierseminars für Lehramtsstudierende vorgestellt. Das Experimentierseminar ist ein bedeutender Teil des Studiums. Hier lernen die Studierenden das Experimentieren, indem sie Versuche selbst konzipieren, aufbauen, vorführen und beschreiben
Das neue milq - Quantenphysik in der Schule
Die seit 2001 im Internet existente Plattform milq zur Quantenphysik, deren Ziel es ist, das komplizierte Thema verständlicher zu machen, wird an der TU Braunschweig im Institut für FachÂdidaktik der Naturwissenschaften (IFdN), Abteilung Physik und Physikdidaktik überarbeitet und erweitert. Ein Beispiel für die inhaltliche Erweiterung ist die Neugestaltung einer Blended-E-Learning-Unterrichtseinheit zur Quantenphysik in der Sekundarstufe II. Das Konzept entspricht dabei einer Modulbauweise, die einen flexiblen Einsatz nach den Erfordernissen und Bedürfnissen der Lehrkräfte ermöglicht und sich in seiner Methodik nach den Kompetenzen des Kerncurriculums richtet. In diesem Beitrag wird zunächst kurz auf das Internetportal milq und seine Neuerungen einÂgegangen, um dann etwas ausführlicher die Unterrichtseinheit zu besprechen
Potent and Selective Peptide-based Inhibition of the G Protein Gαq
In contrast to G protein-coupled receptors, for which chemical and peptidic inhibitors have been extensively explored, few compounds are available that directly modulate heterotrimeric G proteins. Active Gα q binds its two major classes of effectors, the phospholipase C (PLC)-β isozymes and Rho guanine nucleotide exchange factors (RhoGEFs) related to Trio, in a strikingly similar fashion: a continuous helix-turn-helix of the effectors engages Gα q within its canonical binding site consisting of a groove formed between switch II and helix α3. This information was exploited to synthesize peptides that bound active Gα q in vitro with affinities similar to full-length effectors and directly competed with effectors for engagement of Gα q A representative peptide was specific for active Gα q because it did not bind inactive Gα q or other classes of active Gα subunits and did not inhibit the activation of PLC-β3 by Gβ 1 γ 2 In contrast, the peptide robustly prevented activation of PLC-β3 or p63RhoGEF by Gα q ; it also prevented G protein-coupled receptor-promoted neuronal depolarization downstream of Gα q in the mouse prefrontal cortex. Moreover, a genetically encoded form of this peptide flanked by fluorescent proteins inhibited Gα q -dependent activation of PLC-β3 at least as effectively as a dominant-negative form of full-length PLC-β3. These attributes suggest that related, cell-penetrating peptides should effectively inhibit active Gα q in cells and that these and genetically encoded sequences may find application as molecular probes, drug leads, and biosensors to monitor the spatiotemporal activation of Gα q in cells
Site of cochlear stimulation and its effect on electrically evoked compound action potentials using the MED-EL standard electrode array
<p>Abstract</p> <p>Background</p> <p>The standard electrode array for the MED-EL MAESTRO cochlear implant system is 31 mm in length which allows an insertion angle of approximately 720°. When fully inserted, this long electrode array is capable of stimulating the most apical region of the cochlea. No investigation has explored Electrically Evoked Compound Action Potential (ECAP) recordings in this region with a large number of subjects using a commercially available cochlear implant system. The aim of this study is to determine if certain properties of ECAP recordings vary, depending on the stimulation site in the cochlea.</p> <p>Methods</p> <p>Recordings of auditory nerve responses were conducted in 67 subjects to demonstrate the feasibility of ECAP recordings using the Auditory Nerve Response Telemetry (ART™) feature of the MED-EL MAESTRO system software. These recordings were then analyzed based on the site of cochlear stimulation defined as basal, middle and apical to determine if the amplitude, threshold and slope of the amplitude growth function and the refractory time differs depending on the region of stimulation.</p> <p>Results</p> <p>Findings show significant differences in the ECAP recordings depending on the stimulation site. Comparing the apical with the basal region, on average higher amplitudes, lower thresholds and steeper slopes of the amplitude growth function have been observed. The refractory time shows an overall dependence on cochlear region; however post-hoc tests showed no significant effect between individual regions.</p> <p>Conclusions</p> <p>Obtaining ECAP recordings is also possible in the most apical region of the cochlea. However, differences can be observed depending on the region of the cochlea stimulated. Specifically, significant higher ECAP amplitude, lower thresholds and steeper amplitude growth function slopes have been observed in the apical region. These differences could be explained by the location of the stimulating electrode with respect to the neural tissue in the cochlea, a higher density, or an increased neural survival rate of neural tissue in the apex.</p> <p>Trial registration</p> <p>The Clinical Investigation has the Competent Authority registration number DE/CA126/AP4/3332/18/05.</p
Regulation of transcriptional elongation in pluripotency and cell differentiation by the PHD-finger protein Phf5a
Pluripotent embryonic stem cells (ESCs) self-renew or differentiate into all tissues of the developing embryo and cell-specification factors are necessary to balance gene expression. Here we delineate the function of the PHD-finger protein 5a (Phf5a) in ESC self-renewal and ascribe its role in regulating pluripotency, cellular reprogramming, and myoblast specification. We demonstrate that Phf5a is essential for maintaining pluripotency, since depleted ESCs exhibit hallmarks of differentiation. Mechanistically, we attribute Phf5a function to the stabilization of the Paf1 transcriptional complex and control of RNA polymerase II elongation on pluripotency loci. Apart from an ESC-specific factor, we demonstrate that Phf5a controls differentiation of adult myoblasts. Our findings suggest a potent mode of regulation by the Phf5a in stem cells, which directs their transcriptional program ultimately regulating maintenance of pluripotency and cellular reprogramming
Identification of ELK1 interacting peptide segments in the androgen receptor
Prostate cancer (PCa) growth requires tethering of the androgen receptor (AR) to chromatin by the ETS domain transcription factor ELK1 to coactivate critical cell proliferation genes. Disruption of the ELK1–AR complex is a validated potential means of therapeutic intervention in PCa. AR associates with ELK1 by coopting its two ERK docking sites, through the amino-terminal domain (A/B domain) of AR. Using a mammalian two-hybrid assay, we have now functionally mapped amino acids within the peptide segments 358–457 and 514–557 in the A/B domain as required for association with ELK1. The mapping data were validated by GST (glutathione S-transferase)-pulldown and BRET (bioluminescence resonance energy transfer) assays. Comparison of the relative contributions of the interacting motifs/segments in ELK1 and AR to coactivation of ELK1 by AR suggested a parallel mode of binding of AR and ELK1 polypeptides. Growth of PCa cells was partially inhibited by deletion of the upstream segment in AR and nearly fully inhibited by deletion of the downstream segment. Our studies have identified two peptide segments in AR that mediate the functional association of AR with its two docking sites in ELK1. Identification of the ELK1 recognition sites in AR should enable further structural studies of the ELK1–AR interaction and rational design of small molecule drugs to disrupt this interaction
De-ubiquitination of ELK-1 by USP17 potentiates mitogenic gene expression and cell proliferation
ELK-1 is a transcription factor involved in ERK-induced cellular proliferation. Here we show that its transcriptional activity is modulated by ubiquitination at lysine 35 (K35). The level of ubiquitinated ELK-1 rises in mitogen-deprived cells and falls upon mitogen stimulation or oncogene expression. Ectopic expression of USP17, a cell cycle-dependent deubiquitinase, decreases ELK-1 ubiquitination and up-regulates ELK-1 target-genes with a concomitant increase in cyclin D1 expression. In contrast, USP17 depletion attenuates ELK-1-dependent gene expression and slows cell proliferation. The reduced rate of proliferation upon USP17 depletion appears to be a direct effect of ELK-1 ubiquitination because it is rescued by an ELK-1(K35R) mutant refractory to ubiquitination. Overall, our results show that ubiquitination of ELK-1 at K35, and its reversal by USP17, are important mechanisms in the regulation of nuclear ERK signalling and cellular proliferation. Our findings will be relevant for tumours that exhibit elevated USP17 expression and suggest a new target for intervention
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