Charged Scalar Particles and τ\tau Leptonic Decay

Charged scalar particles introduced in some extensions of the standard model can induce $\tau$ leptonic decay at tree level. We find that with some charged SU(2)-singlet scalar particles, like ones introduced in Zee-type models, $\tau$ leptonic decay width is always smaller than what is predicted by the standard model, therefore they may offer a natural solution to $\tau$ decay puzzle. To be more specific, we examine some Zee-type models in detail to see if at the same time they are acceptable in particle physics, cosmology and astrophysics. It is shown that $\tau$ decay data do put some constrains on these models.Comment: ICTP Report No. IC/93/31, 12 pages, Latex, one figure is not included, it is available upon deman

Mitochondrial targeting adaptation of the hominoid-specific glutamate dehydrogenase driven by positive Darwinian selection

Many new gene copies emerged by gene duplication in hominoids, but little is known with respect to their functional evolution. Glutamate dehydrogenase (GLUD) is an enzyme central to the glutamate and energy metabolism of the cell. In addition to the single, GLUD-encoding gene present in all mammals (GLUD1), humans and apes acquired a second GLUD gene (GLUD2) through retroduplication of GLUD1, which codes for an enzyme with unique, potentially brain-adapted properties. Here we show that whereas the GLUD1 parental protein localizes to mitochondria and the cytoplasm, GLUD2 is specifically targeted to mitochondria. Using evolutionary analysis and resurrected ancestral protein variants, we demonstrate that the enhanced mitochondrial targeting specificity of GLUD2 is due to a single positively selected glutamic acid-to-lysine substitution, which was fixed in the N-terminal mitochondrial targeting sequence (MTS) of GLUD2 soon after the duplication event in the hominoid ancestor ~18–25 million years ago. This MTS substitution arose in parallel with two crucial adaptive amino acid changes in the enzyme and likely contributed to the functional adaptation of GLUD2 to the glutamate metabolism of the hominoid brain and other tissues. We suggest that rapid, selectively driven subcellular adaptation, as exemplified by GLUD2, represents a common route underlying the emergence of new gene functions

How and When Socially Entrepreneurial Nonprofit Organizations Benefit From Adopting Social Alliance Management Routines to Manage Social Alliances?

Social alliance is defined as the collaboration between for-profit and nonprofit organizations. Building on the insights derived from the resource-based theory, we develop a conceptual framework to explain how socially entrepreneurial nonprofit organizations (SENPOs) can improve their social alliance performance by adopting strategic alliance management routines. We test our framework using the data collected from 203 UK-based SENPOs in the context of cause-related marketing campaign-derived social alliances. Our results confirm a positive relationship between social alliance management routines and social alliance performance. We also find that relational mechanisms, such as mutual trust, relational embeddedness, and relational commitment, mediate the relationship between social alliance management routines and social alliance performance. Moreover, our findings suggest that different types of social alliance motivation can influence the impact of social alliance management routines on different types of the relational mechanisms. In general, we demonstrate that SENPOs can benefit from adopting social alliance management routines and, in addition, highlight how and when the social alliance management routines–social alliance performance relationship might be shaped. Our study offers important academic and managerial implications, and points out future research directions

Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation

We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis

Cellulose acetate phthalate, a common pharmaceutical excipient, inactivates HIV-1 and blocks the coreceptor binding site on the virus envelope glycoprotein gp120

BACKGROUND: Cellulose acetate phthalate (CAP), a pharmaceutical excipient used for enteric film coating of capsules and tablets, was shown to inhibit infection by the human immunodeficiency virus type 1 (HIV-1) and several herpesviruses. CAP formulations inactivated HIV-1, herpesvirus types 1 (HSV-1) and 2 (HSV-2) and the major nonviral sexually transmitted disease (STD) pathogens and were effective in animal models for vaginal infection by HSV-2 and simian immunodeficiency virus. METHODS: Enzyme-linked immunoassays and flow cytometry were used to demonstrate CAP binding to HIV-1 and to define the binding site on the virus envelope. RESULTS: 1) CAP binds to HIV-1 virus particles and to the envelope glycoprotein gp120; 2) this leads to blockade of the gp120 V3 loop and other gp120 sites resulting in diminished reactivity with HIV-1 coreceptors CXCR4 and CCR5; 3) CAP binding to HIV-1 virions impairs their infectivity; 4) these findings apply to both HIV-1 IIIB, an X4 virus, and HIV-1 BaL, an R5 virus. CONCLUSIONS: These results provide support for consideration of CAP as a topical microbicide of choice for prevention of STDs, including HIV-1 infection

Probing the seesaw mechanism with neutrino data and leptogenesis

In the framework of the seesaw mechanism with three heavy right-handed Majorana neutrinos and no Higgs triplets we carry out a systematic study of the structure of the right-handed neutrino sector. Using the current low-energy neutrino data as an input and assuming hierarchical Dirac-type neutrino masses $m_{Di}$, we calculate the masses $M_i$ and the mixing of the heavy neutrinos. We confront the inferred properties of these neutrinos with the constraints coming from the requirement of a successful baryogenesis via leptogenesis. In the generic case the masses of the right-handed neutrinos are highly hierarchical: $M_i \propto m_{Di}^2$; the lightest mass is $M_1 \approx 10^3 - 10^6$ GeV and the generated baryon-to-photon ratio $\eta_B\lesssim 10^{-14}$ is much smaller than the observed value. We find the special cases which correspond to the level crossing points, with maximal mixing between two quasi-degenerate right-handed neutrinos. Two level crossing conditions are obtained: ${m}_{ee}\approx 0$ (1-2 crossing) and $d_{12}\approx 0$ (2-3 crossing), where ${m}_{ee}$ and $d_{12}$ are respectively the 11-entry and the 12-subdeterminant of the light neutrino mass matrix in the basis where the neutrino Yukawa couplings are diagonal. We show that sufficient lepton asymmetry can be produced only in the 1-2 crossing where $M_1 \approx M_2 \approx 10^{8}$ GeV, $M_3 \approx 10^{14}$ GeV and $(M_2 - M_1)/ M_2 \lesssim 10^{-5}$.Comment: 30 pages, 2 eps figures, JHEP3.cls, typos corrected, note (and references) added on non-thermal leptogenesi

Implications of mirror neutrinos for early universe cosmology

The Exact Parity Model (EPM) is, in part, a theory of neutrino mass and mixing that can solve the atmospheric, solar and LSND anomalies. The central feature of the neutrino sector is three pairs of maximally mixed ordinary and mirror neutrinos. It has been shown that ordinary-mirror neutrino oscillations can generate large neutrino asymmetries in the epoch of the early universe immediately prior to Big Bang Nucleosynthesis (BBN). The large neutrino asymmetries generically suppress the production of mirror neutrinos, and a sufficiently large $\nu_e$ asymmetry can directly affect light element synthesis through nuclear reaction rates. In this paper we present a detailed calculation of neutrino asymmetry evolution driven by the six-flavour EPM neutrino sector, focusing on implications for BBN.Comment: Latex, about 55 pages long with some figure

A Pair of Dopamine Neurons Target the D1-Like Dopamine Receptor DopR in the Central Complex to Promote Ethanol-Stimulated Locomotion in Drosophila

Dopamine is a mediator of the stimulant properties of drugs of abuse, including ethanol, in mammals and in the fruit fly Drosophila. The neural substrates for the stimulant actions of ethanol in flies are not known. We show that a subset of dopamine neurons and their targets, through the action of the D1-like dopamine receptor DopR, promote locomotor activation in response to acute ethanol exposure. A bilateral pair of dopaminergic neurons in the fly brain mediates the enhanced locomotor activity induced by ethanol exposure, and promotes locomotion when directly activated. These neurons project to the central complex ellipsoid body, a structure implicated in regulating motor behaviors. Ellipsoid body neurons are required for ethanol-induced locomotor activity and they express DopR. Elimination of DopR blunts the locomotor activating effects of ethanol, and this behavior can be restored by selective expression of DopR in the ellipsoid body. These data tie the activity of defined dopamine neurons to D1-like DopR-expressing neurons to form a neural circuit that governs acute responding to ethanol

Leptogenesis in Theories with Large Extra Dimensions

We study the scenario of baryogenesis through leptogenesis in higher-dimensional theories, in which the scale of quantum gravity is many orders of magnitude smaller than the usual Planck mass. The minimal realization of these theories includes an isosinglet neutrino which feels the presence of large compact dimensions, whereas all the SM particles are localized on a $(1+3)$-dimensional subspace. In the formulation of minimal leptogenesis models, we pay particular attention to the existence of Majorana spinors in higher dimensions. After compactification of the extra dimensions, we obtain a tower of Majorana Kaluza-Klein excitations which act as an infinite series of CP-violating resonators, and derive the necessary conditions for their constructive interference. Based on this CP-violating mechanism, we find that the decays of the heavy Majorana excitations can produce a leptonic asymmetry which is reprocessed into the observed baryonic asymmetry of the Universe by means of out-of-equilibrium sphaleron interactions, provided the reheat temperature is above 5 GeV.Comment: 34 pages, minor rewordings, to appear in Physical Review