Multi-lepton Signatures of a Hidden Sector in Rare B Decays

We explore the sensitivity of flavour changing b -> s transitions to a (sub-)GeV hidden sector with generic couplings to the Standard Model through the Higgs, vector and axion portals. The underlying two-body decays of B mesons, B -> X_s S and B0 -> SS, where S denotes a generic new GeV-scale particle, may significantly enhance the yield of monochromatic lepton pairs in the final state via prompt decays of S to a dilepton pair. Existing measurements of the charged lepton spectrum in neutral-current semileptonic B decays provide bounds on the parameters of the light sector that are significantly more stringent than the requirements of naturalness. New search modes, such as B -> X_s + n(l+l-) and B0 -> n(l+l-) with n > 1 can provide additional sensitivity to scenarios in which both the Higgs and vector portals are active, and are accessible to (super-)B factories and hadron colliders.Comment: 12 pages, 2 figures; v2: reference added, minor correction

Measuring a Light Neutralino Mass at the ILC: Testing the MSSM Neutralino Cold Dark Matter Model

The LEP experiments give a lower bound on the neutralino mass of about 46 GeV which, however, relies on a supersymmetric grand unification relation. Dropping this assumption, the experimental lower bound on the neutralino mass vanishes completely. Recent analyses suggest, however, that in the minimal supersymmetric standard model (MSSM), a light neutralino dark matter candidate has a lower bound on its mass of about 7 GeV. In light of this, we investigate the mass sensitivity at the ILC for very light neutralinos. We study slepton pair production, followed by the decay of the sleptons to a lepton and the lightest neutralino. We find that the mass measurement accuracy for a few-GeV neutralino is around 2 GeV, or even less if the relevant slepton is sufficiently light. We thus conclude that the ILC can help verify or falsify the MSSM neutralino cold dark matter model even for very light neutralinos.Comment: 7 pages, 1 figure; references adde

Posttransplant lymphoproliferative disorders in neuronal xenotransplanted macaques

Posttransplant lymphoproliferative disorders (PTLDs) are a heterogeneous group of lymphoid proliferations that occur in the setting of depressed T-cell function due to immunosuppressive therapy used following solid organ transplantation, hematopoietic stem cell transplantation, and also xenotransplantation. In the present study, 28 immunosuppressed parkinsonian Macaca fascicularis were intracerebrally injected with wild-type or CTLA4-Ig transgenic porcine xenografts to identify a suitable strategy to enable long-term cell survival, maturation, and differentiation. Nine of 28 (32%) immunosuppressed primates developed masses compatible with PTLD, located mainly in the gastrointestinal tract and/or nasal cavity. The masses were classified as monomorphic PTLD according to the World Health Organization classification. Immunohistochemistry and polymerase chain reaction (PCR) analyses revealed that the PTLDs were associated with macaca lymphocryptovirus as confirmed by double-labeling immunohistochemistry for CD20 and Epstein-Barr nuclear antigen 2 (EBNA-2), where the viral protein was located within the CD20+ neoplastic B cells. In sera from 3 distinct phases of the experimental life of the primates, testing by quantitative PCR revealed a progression of the viral load that paralleled the PTLD progression and no evidence of zoonotic transmission of porcine lymphotropic herpesvirus through xenoneuronal grafts. These data suggest that monitoring the variation of macaca lymphocryptovirus DNA in primates could be used as a possible early diagnostic tool for PTLD progression, allowing preemptive treatment such as immunosuppression therapy reduction

MHC matching fails to prevent long-term rejection of iPSC-derived neurons in non-human primates

open12siopenAron Badin R.; Bugi A.; Williams S.; Vadori M.; Michael M.; Jan C.; Nassi A.; Lecourtois S.; Blancher A.; Cozzi E.; Hantraye P.; Perrier A.L.Aron Badin, R.; Bugi, A.; Williams, S.; Vadori, M.; Michael, M.; Jan, C.; Nassi, A.; Lecourtois, S.; Blancher, A.; Cozzi, E.; Hantraye, P.; Perrier, A. L

New Physics in Bs -> J/psi phi: a General Analysis

Recently, the CDF and D0 collaborations measured indirect CP violation in Bs -> J/psi phi and found a hint of a signal. If taken at face value, this can be interpreted as a nonzero phase of Bs-Bsbar mixing (beta_s), in disagreement with the standard model, which predicts that beta_s ~= 0. In this paper, we argue that this analysis may be incomplete. In particular, there can be new physics (NP) in the bbar -> sbar c cbar decay. If so, the value of beta_s is different than for the case in which NP is assumed to be present only in the mixing. We have examined several models of NP and found that, indeed, there can be significant contributions to the decay. These effects are consistent with measurements in B -> J/psi K* and Bd -> J/psi Ks. Due to the NP in the decay, polarization-dependent indirect CP asymmetries and triple-product asymmetries are predicted in Bs -> J/psi phi.Comment: 28 pages, JHEP, no figures. Considerable changes made. Abstract and main text of paper modified to alter presentation. Appendix added. References added. Conclusions unchanged

Cap-Gly Proteins at Microtubule Plus Ends: Is EB1 Detyrosination Involved?

Localization of CAP-Gly proteins such as CLIP170 at microtubule+ends results from their dual interaction with α-tubulin and EB1 through their C-terminal amino acids −EEY. Detyrosination (cleavage of the terminal tyrosine) of α-tubulin by tubulin-carboxypeptidase abolishes CLIP170 binding. Can detyrosination affect EB1 and thus regulate the presence of CLIP170 at microtubule+ends as well? We developed specific antibodies to discriminate tyrosinated vs detyrosinated forms of EB1 and detected only tyrosinated EB1 in fibroblasts, astrocytes, and total brain tissue. Over-expressed EB1 was not detyrosinated in cells and chimeric EB1 with the eight C-terminal amino acids of α-tubulin was only barely detyrosinated. Our results indicate that detyrosination regulates CLIPs interaction with α-tubulin, but not with EB1. They highlight the specificity of carboxypeptidase toward tubulin

Influences of tongue biomechanics on speech movements during the production of velar stop consonants: a modeling study

This study explores the following hypothesis: forward looping movements of the tongue that are observed in VCV sequences are due partly to the anatomical arrangement of the tongue muscles and how they are used to produce a velar closure. The study uses an anatomically based 2D biomechanical tongue model. Tissue elastic properties are accounted for in finite-element modeling, and movement is controlled by constant-rate control parameter shifts. Tongue raising and lowering movements are produced by the model with the combined actions of the genioglossus, styloglossus and hyoglossus. Simulations of V1CV2 movements were made, where C is a velar consonant and V is [a], [i] or [u]. If V1 is one of the vowels [a] and [u], the resulting trajectories describe movements that begin to loop forward before consonant closure and continue to slide along the palate during the closure. This prediction is in agreement with classical data published in the literature. If V1 is vowel [i], we observe a small backward movement. This is also in agreement with some measurements on human speakers, but it is also in contradiction with the original data published by Houde (1967). These observations support the idea that the biomechanical properties of the tongue could be the main factor responsible for the forward loops when V1 is a back vowel. In the left [i] context, it seems that additional factors have to be taken into considerations, in order to explain the observations made on some speaker

Mutation of Ser172 in Yeast β Tubulin Induces Defects in Microtubule Dynamics and Cell Division

Ser172 of β tubulin is an important residue that is mutated in a human brain disease and phosphorylated by the cyclin-dependent kinase Cdk1 in mammalian cells. To examine the role of this residue, we used the yeast S. cerevisiae as a model and produced two different mutations (S172A and S172E) of the conserved Ser172 in the yeast β tubulin Tub2p. The two mutants showed impaired cell growth on benomyl-containing medium and at cold temperatures, altered microtubule (MT) dynamics, and altered nucleus positioning and segregation. When cytoplasmic MT effectors Dyn1p or Kar9p were deleted in S172A and S172E mutants, cells were viable but presented increased ploidy. Furthermore, the two β tubulin mutations exhibited synthetic lethal interactions with Bik1p, Bim1p or Kar3p, which are effectors of cytoplasmic and spindle MTs. In the absence of Mad2p-dependent spindle checkpoint, both mutations are deleterious. These findings show the importance of Ser172 for the correct function of both cytoplasmic and spindle MTs and for normal cell division

Translating cell therapies for neurodegenerative diseases: Huntington's disease as a model disorder

There has been substantial progress in the development of regenerative medicine strategies for central nervous system disorders over the last decade, with progression to early clinical studies for some conditions. However, there are multiple challenges along the translational pipeline, many of which are common across diseases and pertinent to multiple donor cell types. These include defining the point at which the preclinical data are sufficiently compelling to permit progression to the first clinical studies; scaling-up, characterization, quality control and validation of the cell product; design, validation and approval of the surgical device; and operative procedures for safe and effective delivery of cell product to the brain. Furthermore, clinical trials that incorporate principles of efficient design and disease specific outcomes are urgently needed (particularly for those undertaken in rare diseases, where relatively small cohorts are an additional limiting factor), and all processes must be adaptable in a dynamic regulatory environment. Here we set out the challenges associated with the clinical translation of cell therapy, using Huntington’s disease as a specific example, and suggest potential strategies to address these challenges. Huntington’s disease presents a clear unmet need, but, importantly, it is an autosomal dominant condition with a readily available gene test, full genetic penetrance and a wide range of associated animal models, which together mean that it is a powerful condition in which to develop principles and test experimental therapeutics. We propose that solving these challenges in Huntington’s disease would provide a road map for many other neurological conditions. This white paper represents a consensus opinion emerging from a series of meetings of the international translational platforms Stem Cells For Huntington’s Disease and the European Huntington’s Disease Network Advanced Therapies Working Group, established to identify the challenges of cell therapy, share experience, develop guidance, and highlight future directions, with the aim to expedite progress towards therapies for clinical benefit in Huntington’s disease