Apical Neural Stem Cells and the Effect of Growth/Differentiation Factor 15 on their Primary Cilia and Proliferation

The ventricular-subventricular zone (V-SVZ) is one of the two main neurogenic niches in the mouse brain that maintains neurogenesis throughout adulthood. However, a closer characterisation of the different subtypes of the neural stem cells (NSCs) residing there, their contribution to neurogenesis and the specifics of their regulation is yet to be performed. In the first part of this thesis, using a mouse model to genetically tag NSCs, I could show the presence of apical and basal NSCs in the adult V-SVZ. The two groups of NSCs differ in terms of Nestin expression and presence of primary cilia, which are predominantly observed in apical NSCs. Moreover, in a collaborative effort, I determined that although they also are capable of quiescence, cycling basal NSCs divide more rapidly than the apical counterpart and contribute the most to olfactory bulb neurogenesis in the adult mouse. In the second part of this thesis, I investigated the effect of growth/differentiation factor 15 (GDF15) on NSCs in the V-SVZ. Here, I found for the first time that its only recently discovered receptor GDNF-family receptor alpha-like (GFRAL) is expressed in NSCs in the E18 lateral ganglionic eminence (GE) and adult V-SVZ, as well as in primary cilia. Using immunofluorescence on homozygous Gdf15 knock-out / LacZ knock-in (Gdf15-/-) mice, I found that ablation of GDF15 increased proliferation and cell cycle speed especially at the apical side of the niche, and that apical cells carried shorter primary cilia, a phenotype that could be rescued by application of exogenous GDF15 protein for 24 h. To determine the mechanisms behind these changes, I first analysed epidermal growth factor (EGF) receptor (EGFR) signalling. In the mutant germinal niche, surface EGFR protein levels were lower and EGFR signalling dynamics were altered. Although exposure to GDF15 rescued EGFR surface expression, manipulation of EGFR signalling did not rescue the defect in proliferation. Instead, I found that ciliary length regulators adenylate cyclase 3 and histone deacetylase 6 were overexpressed in the mutant mice, and that their inhibition using pharmacological blockers led to a rescue of both ciliary morphology and proliferation similar to GDF15 application. Lastly, I found that sonic hedgehog signalling, a vital ciliary signalling pathway during development, was impaired but still responsive in Gdf15-/- mice, suggesting an impact of the altered ciliary morphology on organelle signalling. All in all, in this thesis I show that apical NSCs represent a smaller subgroup of NSCs in the V-SVZ and I describe for the first time the effect of GDF15 on the development of the apical region of the V-SVZ. This effect encompasses cilia morphology and proliferation of apical progenitors affecting the generation of apical NSCs and ependymal cells in the V-SVZ

A Flow Cytometry-Based Approach for the Isolation and Characterization of Neural Stem Cell Primary Cilia

In the adult mammalian brain, the apical surface of the subependymal zone (SEZ) is covered by many motile ependymal cilia and a few primary cilia originating from rare intermingled neural stem cells (NSCs). In NSCs the primary cilia are key for the transduction of essential extracellular signals such as Sonic hedgehog (SHH) and platelet-derived growth factor (PDGF). Despite their importance, the analysis of NSC primary cilia is greatly hampered by the fact that they are overwhelmingly outnumbered by the motile cilia. We here take advantage of flow cytometry to purify the two cilia types and allow their molecular characterization. Primary cilia were identified based on immunoreactivity to the marker adenylate cyclase type III (AC3) and differential levels of prominin-1 whereas motile cilia displayed immunoreactivity only to the latter. Consistent with the morphological differences between the two classes of cilia, enrichment of motile cilia positively correlated with size. Moreover, we observed age-dependent variations in the abundance of the two groups of ciliary organelles reflecting the changes associated with their development. The two cilia groups also differed with respect to the expression of signaling molecules, since PDGF receptor (PDGFR)α, smoothened (Smo) and CXC chemokine receptor (CXCR)4 were only detected in isolated primary but not motile cilia. Thus, our novel method of cilia isolation and characterization by flow cytometry has the potential to be extended to the study of cilia from different tissues and organs, providing a powerful tool for the investigation of primary cilia in physiological and pathological conditions

Summary of Milestones 2030 : Elements and milestones for the development of a stable and sustainable bioenergy strategy

This publication is the English version of the summary of the German report „Meilensteine 2030“ (THRÄN et al. 2015) which is published in the series of the funding programme “Biomass energy use”. The report describes elements and milestones for the development of a stable and sustainable bioenergy strategy

HIV-Nef and ADAM17-Containing Plasma Extracellular Vesicles Induce and Correlate with Immune Pathogenesis in Chronic HIV Infection

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Meilensteine 2030: Elemente und Meilensteine für die Entwicklung einer tragfähigen und nachhaltigen Bioenergiestrategie : Endbericht zu FKZ 03KB065, FKZ 03MAP230

In einer weitgehend auf erneuerbaren Energien fußenden Energieversorgung in Deutschland muss Bioenergie künftig die Lücken füllen, die nicht aus anderen Quellen gespeist werden können – diese These hat die Diskussion um Bioenergie im beginnenden 21. Jahrhundert stark bestimmt (BARZANTNY et al., 2009; KIRCHNER & MATTHES, 2009; SaCHVERSTÄNDIGENRAT FÜR UMWELTFRAGEN, 2011; SCHLESINGER et al., 2010, 2011). Dabei gibt es sowohl starke Argumente für den flexiblen Einsatz im Strombereich als auch für ausgewählte Kraftstoffpfade (z. B. Schwerlastverkehr, Schifffahrt, Flugverkehr), während im Wärmebereich Bioenergie als gut durch alternative erneuerbare Versorgungskonzepte ersetzbar gilt. Jedoch hat sich auch gezeigt, dass Biomasse zwar regenerativ, jedoch für den konkreten Zeitraum und unter Nachhaltigkeitsaspekten nur begrenzt verfügbar ist. Künftig wird erwartet, dass der Bedarf an Nahrungs- und Futtermitteln wie auch für die stoffliche Nutzung steigt. Damit wird eine Priorisierung der Einsatzbereiche für den weiteren Ausbau zunehmend notwendig (BMVBS, 2010; THRÄN et al., 2011; KOALITIONSVERTRAG, 2013; MAJER et al., 2013). Es herrscht Einigkeit, dass Bioenergienutzung im Einklang mit den Zielen der nachhaltigen Entwicklung stehen muss und insbesondere gegenüber der Ernährungssicherung nachrangig ist, dass die Nutzung zunehmend an den Erfordernissen des Energiesystems ausgerichtet sein müssen und dass nur bei stetiger Weiterentwicklung der Technologien ein angemessener Beitrag der Bioenergie erreicht werden kann. Auch scheint es sinnvoll, dass man – vor dem Hintergrund der vielfältigen aktuellen Entwicklungen im Bereich der regenerativen, nicht-biogenen Energietechnologien und Energieträger – Bioenergiestrategien favorisiert, die geringe Pfadabhängigkeiten aufweisen und z. B. Technologiekonzepte berücksichtigen, die sowohl im Strom- / Wärme-Bereich als auch im Kraftstoffsektor genutzt werden können

Search for supersymmetry in events with b-quark jets and missing transverse energy in pp collisions at 7 TeV

Results are presented from a search for physics beyond the standard model based on events with large missing transverse energy, at least three jets, and at least one, two, or three b-quark jets. The study is performed using a sample of proton-proton collision data collected at sqrt(s) = 7 TeV with the CMS detector at the LHC in 2011. The integrated luminosity of the sample is 4.98 inverse femtobarns. The observed number of events is found to be consistent with the standard model expectation, which is evaluated using control samples in the data. The results are used to constrain cross sections for the production of supersymmetric particles decaying to b-quark-enriched final states in the context of simplified model spectra.Comment: Submitted to Physical Review

Profiling Trait Anxiety: Transcriptome Analysis Reveals Cathepsin B (Ctsb) as a Novel Candidate Gene for Emotionality in Mice

Behavioral endophenotypes are determined by a multitude of counteracting but precisely balanced molecular and physiological mechanisms. In this study, we aim to identify potential novel molecular targets that contribute to the multigenic trait “anxiety”. We used microarrays to investigate the gene expression profiles of different brain regions within the limbic system of mice which were selectively bred for either high (HAB) or low (LAB) anxiety-related behavior, and also show signs of comorbid depression-like behavior

Qualitätsentwicklung an Ganztagsschulen

Durch die Verlagerung bzw. Stärkung von Entscheidungskompetenzen auf die bzw. der Ebene der Einzelschule wird es ermöglicht, Lösungs-/Gestaltungsansätze zu entwickeln, die auf die jeweiligen Bedürfnisse und Gegebenheiten vor Ort zugeschnitten werden können. Die kritische Auseinandersetzung mit den Erfahrungen anderer, die auf entsprechenden Fortbildungsveranstaltungen kommuniziert werden können, lässt Good-practice-Beispiele entstehen, aus denen sich Anregungen zur Realisierung eigener Vorhaben im Zuge der Ganztagsschulentwicklung ableiten lassen. Der dritte bayerische Ganztagsschulkongress "Qualitätsentwicklung an Ganztagsschulen" am 1. und 2. März 2012 in Forchheim bot den Teilnehmerinnen und Teilnehmern anhand diverser Vorträge, Workshops und Schulbesuchen die Möglichkeit zu Diskussion und Austausch. Der vorliegende Band dokumentiert die Veranstaltung

Measurement of the underlying event activity in pp collisions at √s = 0.9 and 7 TeV with the novel jet-area/median approach

Open Access: This article is distributed under the terms of the Creative Commons Attribution License.-- Chatrchyan, S. et al.The first measurement of the charged component of the underlying event using the novel >jet-area/median> approach is presented for proton-proton collisions at centre-of-mass energies of 0.9 and 7 TeV. The data were recorded in 2010 with the CMS experiment at the LHC. A new observable, sensitive to soft particle production, is introduced and investigated inclusively and as a function of the event scale defined by the transverse momentum of the leading jet. Various phenomenological models are compared to data, with and without corrections for detector effects. None of the examined models describe the data satisfactorily. © 2012 SISSA.Acknowledge support from BMWF and FWF (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); MoER, SF0690030s09 and ERDF (Estonia); Academy of Finland, MEC, and HIP (Finland); CEA and CNRS/IN2P3 (France);BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF and WCU (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); MSI (New Zealand); PAEC (Pakistan); MSHE and NSC (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MON, RosAtom, RAS and RFBR (Russia); MSTD (Serbia); SEIDI and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); ThEP, IPST and NECTEC (Thailand); TUBITAK and TAEK (Turkey); NASU (Ukraine); STFC (United Kingdom); DOE and NSF (USA). Individuals have received support from the Marie-Curie program and the European Research Council (European Union); the Leventis Foundation; the A. P. Sloan Foundation; the Alexander von Humboldt Foundation; the Austrian Science Fund (FWF); the Belgian Federal Science Policy Office; the Fonds pour la Formation à la Recherche dans l’Industrie et dans l’Agriculture (FRIA-Belgium); the Agentschap voor Innovatie door Wetenschap en Technologie (IWTBelgium); the Ministry of Education, Youth and Sports (MEYS) of Czech Republic; the Council of Science and Industrial Research, India; the Compagnia di San Paolo (Torino); and the HOMING PLUS program of Foundation for Polish Science, cofinanced from European Union, Regional Development Fund.Peer Reviewe