Naturalness and Fine Tuning in the NMSSM: Implications of Early LHC Results

We study the fine tuning in the parameter space of the semi-constrained NMSSM, where most soft Susy breaking parameters are universal at the GUT scale. We discuss the dependence of the fine tuning on the soft Susy breaking parameters M_1/2 and m0, and on the Higgs masses in NMSSM specific scenarios involving large singlet-doublet Higgs mixing or dominant Higgs-to-Higgs decays. Whereas these latter scenarios allow a priori for considerably less fine tuning than the constrained MSSM, the early LHC results rule out a large part of the parameter space of the semi-constrained NMSSM corresponding to low values of the fine tuning.Comment: 19 pages, 10 figures, bounds from Susy searches with ~1/fb include

Gene Expression Analysis in the Thalamus and Cerebrum of Horses Experimentally Infected with West Nile Virus

Gene expression associated with West Nile virus (WNV) infection was profiled in the central nervous system of horses. Pyrosequencing and library annotation was performed on pooled RNA from the CNS and lymphoid tissues on horses experimentally infected with WNV (vaccinated and naïve) and non-exposed controls. These sequences were used to create a custom microarray enriched for neurological and immunological sequences to quantitate gene expression in the thalamus and cerebrum of three experimentally infected groups of horses (naïve/WNV exposed, vaccinated/WNV exposed, and normal)

High Burden of Prevalent and Recently Acquired HIV among Female Sex Workers and Female HIV Voluntary Testing Center Clients in Kigali, Rwanda

Objectives: To estimate HIV prevalence and risk factors in population-based samples of female sex workers (FSW) and female voluntary counseling and testing (VCT) clients in Rwanda. Methods: We conducted a cross-sectional survey of 800 FSW and 1,250 female VCT clients in Rwanda, which included interviewing and testing for HIV-1/2, HSV-2 and pregnancy, and BED-CEIA and Avidity Index (AI) to identify recent infections among HIV-infected women. Results: Prevalence of HIV-1, HSV-2, and pregnancy were 24% (95% CI: 21.0-27.0), 59.8% (56.4-63.2), and 7.6% (5.8-9.5) among FSW, and 12.8% (10.9-14.6), 43.2% (40.4-46.0), and 11.4% (9.7-13.3) among VCT clients, respectively. Thirty-five percent of FSW and 25% of VCT clients had never been HIV tested. Per national guidelines, 33% of newly HIV-diagnosed FSW and 36% of VCT clients were already eligible for ART based on CD4,350 cells/ml. Condom use at last sex was higher among FSW (74%) than VCT clients (12%). In age and district of residence-adjusted models, HIV-1 seropositivity was associated with HSV-2 co-infection; recent treatment for sexually transmitted infection (STI); genital symptoms; forced sex; imprisonment; widowhood; and alcohol consumption. Eleven percent of FSW and 12% of VCT clients had recently acquired HIV-1 per BED-CEIA and AI. HSV-2 infection and recent STI treatment were associated with recent HIV infection in both groups, and being married and vaginal cleansing were associated with recent infection before last sex among VCT clients. Conclusions: This population-based survey reveals a high HIV prevalence and incidence among FSW and female VCT clients in Kigali, the scale of which is masked by the low general-population HIV prevalence in Rwanda. HIV/STI and family planning services should be strengthene

Yukawa-unified natural supersymmetry

Previous work on t-b-\tau Yukawa-unified supersymmetry, as expected from SUSY GUT theories based on the gauge group SO(10), tended to have exceedingly large electroweak fine-tuning (EWFT). Here, we examine supersymmetric models where we simultaneously require low EWFT ("natural SUSY") and a high degree of Yukawa coupling unification, along with a light Higgs scalar with m_h\sim125 GeV. As Yukawa unification requires large tan\beta\sim50, while EWFT requires rather light third generation squarks and low \mu\sim100-250 GeV, B-physics constraints from BR(B\to X_s\gamma) and BR(B_s\to \mu+\mu-) can be severe. We are able to find models with EWFT \Delta\lesssim 50-100 (better than 1-2% EWFT) and with Yukawa unification as low as R_yuk\sim1.3 (30% unification) if B-physics constraints are imposed. This may be improved to R_yuk\sim1.2 if additional small flavor violating terms conspire to improve accord with B-constraints. We present several Yukawa-unified natural SUSY (YUNS) benchmark points. LHC searches will be able to access gluinos in the lower 1-2 TeV portion of their predicted mass range although much of YUNS parameter space may lie beyond LHC14 reach. If heavy Higgs bosons can be accessed at a high rate, then the rare H, A\to \mu+\mu- decay might allow a determination of tan\beta\sim50 as predicted by YUNS models. Finally, the predicted light higgsinos should be accessible to a linear e+e- collider with \sqrt{s}\sim0.5 TeV.Comment: 18 pages, 7 figures, pdflatex; 3 references adde

Neutralino dark matter in mSUGRA/CMSSM with a 125 GeV light Higgs scalar

The minimal supergravity (mSUGRA or CMSSM) model is an oft-used framework for exhibiting the properties of neutralino (WIMP) cold dark matter (CDM). However, the recent evidence from Atlas and CMS on a light Higgs scalar with mass m_h\simeq 125 GeV highly constrains the superparticle mass spectrum, which in turn constrains the neutralino annihilation mechanisms in the early universe. We find that stau and stop co-annihilation mechanisms -- already highly stressed by the latest Atlas/CMS results on SUSY searches -- are nearly eliminated if indeed the light Higgs scalar has mass m_h\simeq 125 GeV. Furthermore, neutralino annihilation via the A-resonance is essentially ruled out in mSUGRA so that it is exceedingly difficult to generate thermally-produced neutralino-only dark matter at the measured abundance. The remaining possibility lies in the focus-point region which now moves out to m_0\sim 10-20 TeV range due to the required large trilinear soft SUSY breaking term A_0. The remaining HB/FP region is more fine-tuned than before owing to the typically large top squark masses. We present updated direct and indirect detection rates for neutralino dark matter, and show that ton scale noble liquid detectors will either discover mixed higgsino CDM or essentially rule out thermally-produced neutralino-only CDM in the mSUGRA model.Comment: 17 pages including 9 .eps figure

Synaptic Proteins Linked to HIV-1 Infection and Immunoproteasome Induction: Proteomic Analysis of Human Synaptosomes

Infection of the central nervous system with human immunodeficiency virus type 1 (HIV-1) can produce morphological changes in the neocortical synaptodendritic arbor that are correlated with neurocognitive impairment. To determine whether HIV-1 infection influences the protein composition of human synapses, a proteomic study of isolated nerve endings was undertaken. Synaptosomes from frontal neocortex were isolated using isopyknic centrifugation from 19 human brain specimens. Purity and enrichment were assessed by measuring pre- and postsynaptic protein markers. Two-dimensional polyacrylamide gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry was used to screen for proteins differentially expressed in HIV/AIDS. The concentrations of 31 candidate protein spots were potentially abnormal in HIV-infected decedents with HIV encephalitis and/or increased expression of immunoproteasome subunits. Immunoblots showed that the concentration of some of them was related to HIV-1 infection of the brain and immunoproteasome (IPS) induction. Synapsin 1b and stathmin were inversely related to brain HIV-1 load; 14-3-3ζ and 14-4-4ε proteins were higher in subjects with HIV-1 loads. Perturbed synaptosome proteins were linked with IPS subunit composition, and 14-3-3ζ was histologically colocalized with IPS subunits in stained neocortical neurons. Proteomics illustrates that certain human proteins within the synaptic compartment are involved with changes in the synaptodendritic arbor and neurocognitive impairment in HIV-1-infected people

The Role of Fibrocytes in Sickle Cell Lung Disease

<div><h3>Background</h3><p>Interstitial lung disease is a frequent complication in sickle cell disease and is characterized by vascular remodeling and interstitial fibrosis. Bone marrow-derived fibrocytes have been shown to contribute to the pathogenesis of other interstitial lung diseases. The goal of this study was to define the contribution of fibrocytes to the pathogenesis of sickle cell lung disease.</p> <h3>Methodology/Principal Findings</h3><p>Fibrocytes were quantified and characterized in subjects with sickle cell disease or healthy controls, and in a model of sickle cell disease, the NY1DD mouse. The role of the chemokine ligand CXCL12 in trafficking of fibrocytes and phenotype of lung disease was examined in the animal model. We found elevated concentration of activated fibrocytes in the peripheral blood of subjects with sickle cell disease, which increased further during vaso-occlusive crises. There was a similar elevations in the numbers and activation phenotype of fibrocytes in the bone marrow, blood, and lungs of the NY1DD mouse, both at baseline and under conditions of hypoxia/re-oxygenation. In both subjects with sickle cell disease and the mouse model, fibrocytes expressed a hierarchy of chemokine receptors, with CXCR4 expressed on most fibrocytes, and CCR2 and CCR7 expressed on a smaller subset of cells. Depletion of the CXCR4 ligand, CXCL12, in the mouse model resulted in a marked reduction of fibrocyte trafficking into the lungs, reduced lung collagen content and improved lung compliance and histology.</p> <h3>Conclusions</h3><p>These data support the notion that activated fibrocytes play a significant role in the pathogenesis of sickle cell lung disease.</p> </div

Pathway aberrations of murine melanoma cells observed in Paired-End diTag transcriptomes

<p>Abstract</p> <p>Background</p> <p>Melanoma is the major cause of skin cancer deaths and melanoma incidence doubles every 10 to 20 years. However, little is known about melanoma pathway aberrations. Here we applied the robust Gene Identification Signature Paired End diTag (GIS-PET) approach to investigate the melanoma transcriptome and characterize the global pathway aberrations.</p> <p>Methods</p> <p>GIS-PET technology directly links 5' mRNA signatures with their corresponding 3' signatures to generate, and then concatenate, PETs for efficient sequencing. We annotated PETs to pathways of KEGG database and compared the murine B16F1 melanoma transcriptome with three non-melanoma murine transcriptomes (Melan-a2 melanocytes, E14 embryonic stem cells, and E17.5 embryo). Gene expression levels as represented by PET counts were compared across melanoma and melanocyte libraries to identify the most significantly altered pathways and investigate the expression levels of crucial cancer genes.</p> <p>Results</p> <p>Melanin biosynthesis genes were solely expressed in the cells of melanocytic origin, indicating the feasibility of using the PET approach for transcriptome comparison. The most significantly altered pathways were metabolic pathways, including upregulated pathways: purine metabolism, aminophosphonate metabolism, tyrosine metabolism, selenoamino acid metabolism, galactose utilization, nitrobenzene degradation, and bisphenol A degradation; and downregulated pathways: oxidative phosphorylation, ATPase synthesis, TCA cycle, pyruvate metabolism, and glutathione metabolism. The downregulated pathways concurrently indicated a slowdown of mitochondrial activities. Mitochondrial permeability was also significantly altered, as indicated by transcriptional activation of ATP/ADP, citrate/malate, Mg⁺⁺, fatty acid and amino acid transporters, and transcriptional repression of zinc and metal ion transporters. Upregulation of cell cycle progression, MAPK, and PI3K/Akt pathways were more limited to certain region(s) of the pathway. Expression levels of c-<it>Myc </it>and <it>Trp53 </it>were also higher in melanoma. Moreover, transcriptional variants resulted from alternative transcription start sites or alternative polyadenylation sites were found in <it>Ras </it>and genes encoding adhesion or cytoskeleton proteins such as integrin, β-catenin, α-catenin, and actin.</p> <p>Conclusion</p> <p>The highly correlated results unmistakably point to a systematic downregulation of mitochondrial activities, which we hypothesize aims to downgrade the mitochondria-mediated apoptosis and the dependency of cancer cells on angiogenesis. Our results also demonstrate the advantage of using the PET approach in conjunction with KEGG database for systematic pathway analysis.</p

A Major Determinant of Cyclophilin Dependence and Cyclosporine Susceptibility of Hepatitis C Virus Identified by a Genetic Approach

Since the advent of genome-wide small interfering RNA screening, large numbers of cellular cofactors important for viral infection have been discovered at a rapid pace, but the viral targets and the mechanism of action for many of these cofactors remain undefined. One such cofactor is cyclophilin A (CyPA), upon which hepatitis C virus (HCV) replication critically depends. Here we report a new genetic selection scheme that identified a major viral determinant of HCV's dependence on CyPA and susceptibility to cyclosporine A. We selected mutant viruses that were able to infect CyPA-knockdown cells which were refractory to infection by wild-type HCV produced in cell culture. Five independent selections revealed related mutations in a single dipeptide motif (D316 and Y317) located in a proline-rich region of NS5A domain II, which has been implicated in CyPA binding. Engineering the mutations into wild-type HCV fully recapitulated the CyPA-independent and CsA-resistant phenotype and four putative proline substrates of CyPA were mapped to the vicinity of the DY motif. Circular dichroism analysis of wild-type and mutant NS5A peptides indicated that the D316E/Y317N mutations (DEYN) induced a conformational change at a major CyPA-binding site. Furthermore, nuclear magnetic resonance experiments suggested that NS5A with DEYN mutations adopts a more extended, functional conformation in the putative CyPA substrate site in domain II. Finally, the importance of this major CsA-sensitivity determinant was confirmed in additional genotypes (GT) other than GT 2a. This study describes a new genetic approach to identifying viral targets of cellular cofactors and identifies a major regulator of HCV's susceptibility to CsA and its derivatives that are currently in clinical trials