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

The JAK/STAT3 Pathway Is a Common Inducer of Astrocyte Reactivity in Alzheimer's and Huntington's Diseases.

Astrocyte reactivity is a hallmark of neurodegenerative diseases (ND), but its effects on disease outcomes remain highly debated. Elucidation of the signaling cascades inducing reactivity in astrocytes during ND would help characterize the function of these cells and identify novel molecular targets to modulate disease progression. The Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway is associated with reactive astrocytes in models of acute injury, but it is unknown whether this pathway is directly responsible for astrocyte reactivity in progressive pathological conditions such as ND. In this study, we examined whether the JAK/STAT3 pathway promotes astrocyte reactivity in several animal models of ND. The JAK/STAT3 pathway was activated in reactive astrocytes in two transgenic mouse models of Alzheimer's disease and in a mouse and a nonhuman primate lentiviral vector-based model of Huntington's disease (HD). To determine whether this cascade was instrumental for astrocyte reactivity, we used a lentiviral vector that specifically targets astrocytes in vivo to overexpress the endogenous inhibitor of the JAK/STAT3 pathway [suppressor of cytokine signaling 3 (SOCS3)]. SOCS3 significantly inhibited this pathway in astrocytes, prevented astrocyte reactivity, and decreased microglial activation in models of both diseases. Inhibition of the JAK/STAT3 pathway within reactive astrocytes also increased the number of huntingtin aggregates, a neuropathological hallmark of HD, but did not influence neuronal death. Our data demonstrate that the JAK/STAT3 pathway is a common mediator of astrocyte reactivity that is highly conserved between disease states, species, and brain regions. This universal signaling cascade represents a potent target to study the role of reactive astrocytes in ND

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

A practical indicator for surface ocean heat and freshwater buoyancy fluxes and its application to the NCEP reanalysis data

The buoyancy flux at the air/sea interface plays a key role in water mass transformation and mixing as it modifies surface water density and in turn drives overturning and enhances stratification. It is the interplay of these two independent heat and freshwater buoyancy flux components that is of central importance when analysing mechanisms of the ocean/atmosphere interaction. Here, a diagnostic quantity (ΘB) is presented that allows to capture the relative contribution of both components on the buoyancy flux in one single quantity. Using NCEP reanalysis of heat and freshwater fluxes (1948–2009) demonstrates that ΘB is a convenient tool to analyse both the temporal and spatial variability of their corresponding buoyancy fluxes. For the global ocean the areal extent of buoyancy gain and loss regions changed by 10%, with the largest extent of buoyancy gain during the 1970–1990 period. In the subpolar North Atlantic, and likewise in the South Pacific, decadal variability in freshwater flux is pronounced and, for the latter region, takes control over the total buoyancy flux since the 1980s. Some of the areal extent time series show a significant correlation with large-scale climate indices

Altered Skeletal Muscle Lipase Expression and Activity Contribute to Insulin Resistance in Humans

International audienceOBJECTIVE: Insulin resistance is associated with elevated content of skeletal muscle lipids, including triacylglycerols (TAGs) and diacylglycerols (DAGs). DAGs are by-products of lipolysis consecutive to TAG hydrolysis by adipose triglyceride lipase (ATGL) and are subsequently hydrolyzed by hormone-sensitive lipase (HSL). We hypothesized that an imbalance of ATGL relative to HSL (expression or activity) may contribute to DAG accumulation and insulin resistance. RESEARCH DESIGN AND METHODS: We first measured lipase expression in vastus lateralis biopsies of young lean (n = 9), young obese (n = 9), and obese-matched type 2 diabetic (n = 8) subjects. We next investigated in vitro in human primary myotubes the impact of altered lipase expression/activity on lipid content and insulin signaling. RESULTS: Muscle ATGL protein was negatively associated with whole-body insulin sensitivity in our population (r = -0.55, P = 0.005), whereas muscle HSL protein was reduced in obese subjects. We next showed that adenovirus-mediated ATGL overexpression in human primary myotubes induced DAG and ceramide accumulation. ATGL overexpression reduced insulin-stimulated glycogen synthesis (-30%, P < 0.05) and disrupted insulin signaling at Ser1101 of the insulin receptor substrate-1 and downstream Akt activation at Ser473. These defects were fully rescued by nonselective protein kinase C inhibition or concomitant HSL overexpression to restore a proper lipolytic balance. We show that selective HSL inhibition induces DAG accumulation and insulin resistance. CONCLUSIONS: Altogether, the data indicate that altered ATGL and HSL expression in skeletal muscle could promote DAG accumulation and disrupt insulin signaling and action. Targeting skeletal muscle lipases may constitute an interesting strategy to improve insulin sensitivity in obesity and type 2 diabetes

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