Leptogenesis parametrized by lepton mass matrices

The conventional seesaw-leptogenesis can simultaneously explain the suppression of neutrino masses and the generation of cosmic baryon asymmetry, but usually cannot predict an unambiguous relation between these two sectors. In this work we shall demonstrate a novel left-right symmetric scenario, motivated to solve the strong CP problem by parity symmetry, where the present baryon asymmetry is determined by three charged lepton masses and a seesaw-suppressed hermitian Dirac neutrino mass matrix up to an overall scale factor. To produce the observed baryon asymmetry, this scenario requires that the neutrinos must have a normal hierarchical mass spectrum and their mixing matrix must contain a sizable Dirac CP phase. Our model can be tested in neutrino oscillation and neutrinoless double beta decay experiments.Comment: 5 pages, 2 figures. Typos are correcte

Electrophilic dark matter with dark photon: from DAMPE to direct detection

The electron-positron excess reported by the DAMPE collaboration recently may be explained by an electrophilic dark matter (DM). A standard model singlet fermion may play the role of such a DM when it is stablized by some symmetries, such as a dark $U(1)_X^{}$ gauge symmetry, and dominantly annihilates into the electron-positron pairs through the exchange of a scalar mediator. The model, with appropriate Yukawa couplings, can well interpret the DAMPE excess. Naively one expects that in this type of models the DM-nucleon cross section should be small since there is no tree-level DM-quark interactions. We however find that at one-loop level, a testable DM-nucleon cross section can be induced for providing ways to test the electrophilic model. We also find that a $U(1)$ kinetic mixing can generate a sizable DM-nucleon cross section although the $U(1)_X^{}$ dark photon only has a negligible contribution to the DM annihilation. Depending on the signs of the mixing parameter, the dark photon can enhance/reduce the one-loop induced DM-nucleon cross section.Comment: 4 pages, typos are corrected, references are added as well as more discussions on direct detectio

Visualization of Alzheimer’s Disease Related α-/β-/γ-Secretase Ternary Complex by Bimolecular Fluorescence Complementation Based Fluorescence Resonance Energy Transfer

The competitive ectodomain shedding of amyloid-β precursor protein (APP) by α-secretase and β-secretase, and the subsequent regulated intramembrane proteolysis by γ-secretase are the key processes in amyloid-β peptides (Aβ) generation. Previous studies indicate that secretases form binary complex and the interactions between secretases take part in substrates processing. However, whether α-, β- and γ-secretase could form ternary complex remains to be explored. Here, we adopted bimolecular fluorescence complementation in combination with fluorescence resonance energy transfer (BiFC-FRET) to visualize the formation of triple secretase complex. We show that the interaction between α-secretase ADAM10 and β-secretase BACE1 could be monitored by BiFC assay and the binding of APP to α-/β-secretase binary complex was revealed by BiFC-FRET. Further, we observed that γ-secretase interacts with α-/β-secretase binary complex, providing evidence that α-, β- and γ-secretase might form a ternary complex. Thus our study extends the interplay among Alzheimer’s disease (AD) related α-/β-/γ-secretase

Die Rolle von Rab20 in der phagosomalen Reifung und der Einfluss von Rab20 in der Abtötung von Mykobakterien

Phagosome maturation is a progressive process, in which nascent phagosomes sequentially interact with early endosomes, late endosomes and lysosomes, leading to the formation of phagolysosomes. It is a critical part for innate immunity to eliminate intracellular pathogens and for adaptive immunity to process antigens. There is compelling evidence that IFN-g is able to regulate phagosome trafficking and consequently the immune function of this process. However, the molecular link by which IFN-g modulates phagosome trafficking and function is not known. Rab is a family of small GTPases, which function as central membrane organizers coordinating extracellular immune mediators and the intracellular trafficking. In this thesis, the role of Rab20 in phagosome maturation and its modulation by IFN-g was investigated. IFN-g enhanced Rab20 expression and Rab20 association to phagosomes in macrophages. Moreover, Rab20 association to phagosomes induced an early delay in phagosome maturation with the prolonged duration of Rab5 and PI3P association. Conversely, the expression of the dominant negative mutant of Rab20 and knockdown of Rab20 accelerated phagosome maturation decreasing the time that Rab5 and PI3P retained to phagosomes. Particularly, the killing of mycobacteria was not affected by the expression of Rab20 wild type. This work further demonstrated that Rab20 was required for the delay in phagosome maturation induced by IFN-g. Rabex-5, as an effector of Rab20, was recruited to phagosomes by Rab20 in an IFN-g dependent manner. Higher level of Rabex5 in phagosome results in a transient increase of active Rab5 in phagosomes. Altogether, this work uncovers Rab20 as a key player in the mechanism by which IFN-g induces a delay in phagosome maturation in macrophages.Die Reifung von Phagosomen ist ein progressiver Prozess in dem ein Phagosom nach und nach mit frühen Endosomen, späten Endosomen und letztendlich mit Lysosomen interagiert. Es entsteht ein Phagolysosom. Dieser Prozess spielt sowohl für das angeborene Immunsystem eine entscheidende Rolle indem es intrazellulare Pathogene eliminiert, als auch für das adaptive Immunsystem. Es konnte gezeigt werden, dass Interferon-g (IFN-g) generell regulierend auf den Reifungsprozess und dadurch verknüpfte Immunfunktionen wirken kann. Durch welche Akteure IFN-g die Phagosomenreifung moduliert ist jedoch weitestgehend unbekannt. Rab Proteine gehören zu der Familie der kleinen GTPasen. Als Membranproteine, die auf Vesikeln lokalisiert sind, koordinieren sie die intrazellulare Antwort auf extrazellulare Reize. IFN-g steigert nicht nur die Proteinexpression von Rab20 in der Zelle, sondern auch die Assoziation von Rab20 am Phagosom in Makrophagen. Befindet sich Rab20 am Phagosom so induziert es, in einem frühen Stadium, eine verlängerte Assoziation von Rab5 und PI3P mit dem Selbigen. Ein gegenteiliger Effekt ist zu erkennen, exprimiert man eine dominant negative Mutante von Rab20 oder generiert einen Rab20 knock-down in Makrophagen. In diesem Fall verkürzt sich der Zeitraum in dem Rab5 und PI3P mit dem Phagosom assoziiert sind. Auf das Überleben von Mykobakterien in Makrophagen hatte die Überexpression von Rab20 keinen Einfluss. Weiterhin wird gezeigt, dass Rabex5 ein Effektor von Rab20 ist und als solcher durch Rab20 zum Phagosom rekrutiert wird. Dieser Prozess ist IFN-g abhängig. In Folge dessen führt eine erhöhte Konzentration von Rabex5 am Phagosom zu einer vorrübergehend erhöhten Konzentration von aktivem Rab5 am Phagosom. Zusammenfassend kann gesagt werden, dass diese Dissertation Rab20 als einen der molekularen Hauptakteure beschreibt, der für die IFN-g induzierte Verzögerung der Phagosomenreifung in Makrophagen verantwortlich ist