τ−μ−e\tau - \mu - e Universality in τ\tau Decays and Constraints on the Slepton Masses

The leptonic $\tau$ decays are calculated at the 1-loop level in the Minimal Supersymmetric Standard Model. The deviation from the $\tau - \mu - e$ universality is studied as a function of the supersymmetric parameters and discussed in the context of the expected improvement of the experimental accuracy.Comment: 10 pages, standard LaTeX, report DFPD 94/TH-27,MPI-Ph/94-24,DESY 94-077. 5 figures can be obtained via conventional mail from P. Chankowski upon reques

Complete On-Shell Renormalization Scheme for the Minimal Supersymmetric Higgs Sector

Systematic on-shell renormalization programme is carried out for the Higgs and gauge boson sectors of the Minimal Supersymmetric Standard Model. Complete 1-loop results for the 2- and 3-point Green's functions are explicitly given. The Higgs boson masses and the cross sections for the neutral scalar production in the $e^+e^-$ colliders are calculated.Comment: 64 pages, 10 figures (not included, availaible on request in PostScript format), LaTeX, preprint no MPI-Ph/92-117 and DFPD 93/TH/1

Identification of Autophagy as a Functional Target Suitable for the Pharmacological Treatment of Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN) In Vitro

Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a relentlessly progressive neurodegenerative disorder caused by mutations in the C19orf12 gene. C19orf12 has been implicated in playing a role in lipid metabolism, mitochondrial function, and autophagy, however, the precise functions remain unknown. To identify new robust cellular targets for small compound treatments, we evaluated reported mitochondrial function alterations, cellular signaling, and autophagy in a large cohort of MPAN patients and control fibroblasts. We found no consistent alteration of mitochondrial functions or cellular signaling messengers in MPAN fibroblasts. In contrast, we found that autophagy initiation is consistently impaired in MPAN fibroblasts and show that C19orf12 expression correlates with the amount of LC3 puncta, an autophagy marker. Finally, we screened 14 different autophagy modulators to test which can restore this autophagy defect. Amongst these compounds, carbamazepine, ABT-737, LY294002, oridonin, and paroxetine could restore LC3 puncta in the MPAN fibroblasts, identifying them as novel potential therapeutic compounds to treat MPAN. In summary, our study confirms a role for C19orf12 in autophagy, proposes LC3 puncta as a functionally robust and consistent readout for testing compounds, and pinpoints potential therapeutic compounds for MPAN.</p

Identification of Autophagy as a Functional Target Suitable for the Pharmacological Treatment of Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN) In Vitro

Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a relentlessly progressive neurodegenerative disorder caused by mutations in the C19orf12 gene. C19orf12 has been implicated in playing a role in lipid metabolism, mitochondrial function, and autophagy, however, the precise functions remain unknown. To identify new robust cellular targets for small compound treatments, we evaluated reported mitochondrial function alterations, cellular signaling, and autophagy in a large cohort of MPAN patients and control fibroblasts. We found no consistent alteration of mitochondrial functions or cellular signaling messengers in MPAN fibroblasts. In contrast, we found that autophagy initiation is consistently impaired in MPAN fibroblasts and show that C19orf12 expression correlates with the amount of LC3 puncta, an autophagy marker. Finally, we screened 14 different autophagy modulators to test which can restore this autophagy defect. Amongst these compounds, carbamazepine, ABT-737, LY294002, oridonin, and paroxetine could restore LC3 puncta in the MPAN fibroblasts, identifying them as novel potential therapeutic compounds to treat MPAN. In summary, our study confirms a role for C19orf12 in autophagy, proposes LC3 puncta as a functionally robust and consistent readout for testing compounds, and pinpoints potential therapeutic compounds for MPAN

Identification of Autophagy as a Functional Target Suitable for the Pharmacological Treatment of Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN) In Vitro

Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a relentlessly progressive neurodegenerative disorder caused by mutations in the C19orf12 gene. C19orf12 has been implicated in playing a role in lipid metabolism, mitochondrial function, and autophagy, however, the precise functions remain unknown. To identify new robust cellular targets for small compound treatments, we evaluated reported mitochondrial function alterations, cellular signaling, and autophagy in a large cohort of MPAN patients and control fibroblasts. We found no consistent alteration of mitochondrial functions or cellular signaling messengers in MPAN fibroblasts. In contrast, we found that autophagy initiation is consistently impaired in MPAN fibroblasts and show that C19orf12 expression correlates with the amount of LC3 puncta, an autophagy marker. Finally, we screened 14 different autophagy modulators to test which can restore this autophagy defect. Amongst these compounds, carbamazepine, ABT-737, LY294002, oridonin, and paroxetine could restore LC3 puncta in the MPAN fibroblasts, identifying them as novel potential therapeutic compounds to treat MPAN. In summary, our study confirms a role for C19orf12 in autophagy, proposes LC3 puncta as a functionally robust and consistent readout for testing compounds, and pinpoints potential therapeutic compounds for MPAN.</p

Viable tt-bb-τ\tau Yukawa Unification in SUSY SO(10)

The supersymmetric SO(10) GUT with $t$--$b$--$\tau$ Yukawa coupling unification has problems with correct electroweak symmetry breaking, experimental constraints (especially $b\rightarrow s\gamma$) and neutralino abundance, if the scalar masses are universal at the GUT scale. We point out that non-universality of the scalar masses at the GUT scale generated both by (1) renormalization group running from the Planck scale to the GUT scale and (2) $D$--term contribution induced by the reduction of the rank of the gauge group, has a desirable pattern to make the model phemenologically viable (in fact the only one which is consistent with experimental and cosmological constraints). At the same time the top quark mass has to be either close to its quasi IR--fixed point value or below $\sim$170 GeV. We also briefly discuss the spectrum of superpartners which is then obtained.Comment: 11 pages LaTeX, 2 PS figures as uuencoded tar-gzipped fil

From Flavour to SUSY Flavour Models

If supersymmetry (SUSY) will be discovered, successful models of flavour not only have to provide an explanation of the flavour structure of the Standard Model fermions, but also of the flavour structure of their scalar superpartners. We discuss aspects of such "SUSY flavour" models, towards predicting both flavour structures, in the context of supergravity (SUGRA). We point out the importance of carefully taking into account SUSY-specific effects, such as 1-loop SUSY threshold corrections and canonical normalization, when fitting the model to the data for fermion masses and mixings. This entangles the flavour model with the SUSY parameters and leads to interesting predictions for the sparticle spectrum. We demonstrate these effects by analyzing an example class of flavour models in the framework of an SU(5) Grand Unified Theory with a family symmetry with real triplet representations. For flavour violation through the SUSY soft breaking terms, the class of models realizes a scheme we refer to as "Trilinear Dominance", where flavour violation effects are dominantly induced by the trilinear terms.Comment: 44 pages, 10 figures, version published in Nuclear Physics

Finite Supersymmetric Threshold Corrections to CKM Matrix Elements in the Large tanβtan\beta Regime

We evaluate the finite 1-loop threshold corrections, proportional to $tan\beta$, to the down quark mass matrix. These result in corrections to down quark masses and to Cabibbo-Kobayashi-Maskawa [CKM] matrix elements. The corrections to CKM matrix elements are the novel feature of this paper. For grand unified theories with large $\tan\beta$ these corrections may significantly alter the low energy predictions of four of the CKM matrix elements and the Jarlskog parameter J, a measure of CP violation. The angles $\alpha,\: \beta$ and $\gamma$ of the unitarity triangle and the ratio $|{V_{ub} \over V_{cb}}|$, however, are not corrected to this order. We also discuss these corrections in the light of recent models for fermion masses. Here the corrections may be useful in selecting among the various models. Moreover, if one model fits the data, it will only do so for a particular range of SUSY parameters.Comment: 15 pages, 3 figures not included; hard copy of the figures may be obtained upon reques