Morphological and Genetic Activation of Microglia after Diffuse Traumatic Brain Injury in the Rat

Traumatic brain injury (TBI) survivors experience long, term post-traumatic morbidities. In diffuse brain injured rats, a chronic sensory sensitivity to whisker stimulation models agitation in brain injury survivors and provides anatomical landmarks across the whisker-barrel circuit to evaluate traumatic neuropathology. As a consequence of TBI, acute and chronic microglial activation can contribute to degenerative and reparative events underlying post-traumatic morbidity. Here, we hypothesize that delayed microglial activation is concomitant with neuroplastic change after diffuse brain injury in the rat, by examining differential microglial activation states and neuroplasticity through gene and protein expression. Adult male, Sprague-Dawley rats were subjected to a single moderate midline fluid percussion (FPI) or sham injury. Microglial activation was determined by immunohistochemistry, receptor autoradiography, and quantitative real-time PCR in the primary somatosensory barrel field (S1 BF) and ventral posteromedial nucleus of the thalamus (VPM) at seven and 28 days following FPI. At seven days post-injury in both relays of the whisker circuit, classical activation (CD45) and acquired deactivation (TGFl, TGF R2) gene expression were elevated significantly above uninjured sham levels. Evidence for alternative activation (arginase I) was not observed. Daily anti-inflammatory ibuprofen administration (20 mg/kg, i . p.) significantly reduced evidence of classical activation, but had no effect on neuroplastic (GAP-43, synaptophysin) compared to saline vehicle. These data confirm concomitant classical activation and de-activation phenotypes of microglia after diffuse TBI, which are unlikely to impact injury-induced neuroplasticity that is typically associated with alternative microglial activation

Traumatic Brain Injury and Firearm Use and Risk of Progressive Supranuclear Palsy Among Veterans

Background: Progressive supranuclear palsy (PSP) is a tauopathy that has a multifactorial etiology. Numerous studies that have investigated lead exposure and traumatic brain injury (TBI) as risk factors for other tauopathies, such as Alzheimer's disease, but not for PSP.Objective: We sought to investigate the role of firearm usage, as a possible indicator of lead exposure, and TBI as risk factors for PSP in a population of military veterans.Methods: We included participants from a larger case-control study who reported previous military service. Our sample included 67 PSP cases and 68 controls. Participants were administered a questionnaire to characterize firearm use in the military and occurrence of TBI.Results: Cases were significantly less educated than controls. In unadjusted analyses, the proportion of PSP cases (80.6%) and controls (64.7%) who reported use of firearms as part of their military job was positively associated with PSP, odds ratio (OR) 2.2 (95% CI: 1–5.0). There were no significant case-control differences in mean service duration. There was only a weak association with history of TBI, OR 1.6 (95% CI: 0.8–3.4). In multivariate models, firearm usage (OR 3.7, 95% CI: 1.5, 9.8) remained significantly associated with PSP.Conclusions: Our findings show a positive association between firearm usage and PSP and an inverse association between education and PSP. The former suggests a possible etiologic role of lead. Further studies are needed to confirm the potential etiologic effects of metals on PSP.The study was registered in clinicaltrials.gov. ClinicalTrials.gov Identifier: NCT00431301

Feasibility of Implementing a School Nutrition Intervention That Addresses Policies, Systems, and Environment

We conducted a process evaluation of the Shaping Healthy Choices Program, a multicomponent school-based nutrition program, when implemented in partnership with University of California (UC) CalFresh and UC Cooperative Extension (UCCE). There were positive impacts on participating students, but results varied across counties, possibly due to variation in fidelity to the curriculum and implementation of program components. Our evaluation identified the strength of UCCE in delivering nutrition education and a need for additional support and training for building capacity to effect change in school policies, systems, and environment. Because educators throughout Extension are working to integrate programs addressing policies, systems, and environment, our results may have applicability in other Extension programs

Two-Loop Renormalization Group Equations for Soft Supersymmetry-Breaking Couplings

We compute the two-loop renormalization group equations for all soft supersymmetry-breaking couplings in a general softly broken N=1 supersymmetric model. We also specialize these results to the Minimal Supersymmetric Standard Model.Comment: 26 pages. [v4: Signs of equations (4.2) and (4.3) are fixed.

Effects of Supersymmetric Threshold Corrections on High-Scale Flavor Textures

Integration of superpartners out of the spectrum induces potentially large contributions to Yukawa couplings. These corrections, the supersymmetric threshold corrections, therefore influence the CKM matrix prediction in a non-trivial way. We study effects of threshold corrections on high-scale flavor structures specified at the gauge coupling unification scale in supersymmetry. In our analysis, we first consider high-scale Yukawa textures which qualify phenomenologically viable at tree level, and find that they get completely disqualified after incorporating the threshold corrections. Next, we consider Yukawa couplings, such as those with five texture zeroes, which are incapable of explaining flavor-changing proceses. Incorporation of threshold corrections, however, makes them phenomenologically viable textures. Therefore, supersymmetric threshold corrections are found to leave observable impact on Yukawa couplings of quarks, and any confrontation of high-scale textures with experiments at the weak scale must take into account such corrections.Comment: 25 pages, submitted to JHE

Bottom-Tau Unification in SUSY SU(5) GUT and Constraints from b to s gamma and Muon g-2

An analysis is made on bottom-tau Yukawa unification in supersymmetric (SUSY) SU(5) grand unified theory (GUT) in the framework of minimal supergravity, in which the parameter space is restricted by some experimental constraints including Br(b to s gamma) and muon g-2. The bottom-tau unification can be accommodated to the measured branching ratio Br(b to s gamma) if superparticle masses are relatively heavy and higgsino mass parameter \mu is negative. On the other hand, if we take the latest muon g-2 data to require positive SUSY contributions, then wrong-sign threshold corrections at SUSY scale upset the Yukawa unification with more than 20 percent discrepancy. It has to be compensated by superheavy threshold corrections around the GUT scale, which constrains models of flavor in SUSY GUT. A pattern of the superparticle masses preferred by the three requirements is also commented.Comment: 21pages, 6figure

A mathematical model of the human metabolic system and metabolic flexibility

In healthy subjects some tissues in the human body display metabolic flexibility, by this we mean the ability for the tissue to switch its fuel source between predominantly carbohydrates in the post prandial state and predominantly fats in the fasted state. Many of the pathways involved with human metabolism are controlled by insulin, and insulin- resistant states such as obesity and type-2 diabetes are characterised by a loss or impairment of metabolic flexibility. In this paper we derive a system of 12 first-order coupled differential equations that describe the transport between and storage in different tissues of the human body. We find steady state solutions to these equations and use these results to nondimensionalise the model. We then solve the model numerically to simulate a healthy balanced meal and a high fat meal and we discuss and compare these results. Our numerical results show good agreement with experimental data where we have data available to us and the results show behaviour that agrees with intuition where we currently have no data with which to compare

The Supersymmetric Particle Spectrum

We examine the spectrum of supersymmetric particles predicted by grand unified theoretical (GUT) models where the electroweak symmetry breaking is accomplished radiatively. We evolve the soft supersymmetry breaking parameters according to the renormalization group equations (RGE). The minimization of the Higgs potential is conveniently described by means of tadpole diagrams. We present complete one-loop expressions for these minimization conditions, including contributions from the matter and the gauge sectors. We concentrate on the low $\tan \beta$ fixed point region (that provides a natural explanation of a large top quark mass) for which we find solutions to the RGE satisfying both experimental bounds and fine-tuning criteria. We also find that the constraint from the consideration of the lightest supersymmetric particle as the dark matter of the universe is accommodated in much of parameter space where the lightest neutralino is predominantly gaugino. The supersymmetric mass spectrum displays correlations that are model-independent over much of the GUT parameter space.Comment: 62 pages + 10 PS figures included (uuencoded), MAD/PH/80

SIGNALS FOR MINIMAL SUPERGRAVITY AT THE CERN LARGE HADRON COLLIDER: MULTI-JET PLUS MISSING ENERGY CHANNEL,

We use ISAJET to perform a detailed study of the missing transverse energy \eslt plus multi-jet signal expected from superparticle production at the CERN LHC. Our analysis is performed within the framework of the minimal supergravity model with gauge coupling unification and radiative electroweak symmetry breaking. We delineate the region of parameter space where the \eslt supersymmetry signal should be observable at the LHC and compare it to the regions explorable via searches for sleptons and for chargino/neutralino production. We confirm that, given a data sample of 10~\fb^{-1}, $m_{\tg}\sim 1300$ GeV can be explored if m_{\tq}\gg m_{\tg}, while $m_{\tg}\sim 2000$ GeV can be probed if m_{\tq}\simeq m_{\tg}. We further examine what information can be gleaned from scrutinizing this event sample. For instance, the multi-jet multiplicity yields information on whether squark production makes a significant contribution to the observed \eslt sample. Furthermore, reconstructing hemispheric masses may yield a measure of $m_{\tg}$ to $\sim 15-25\%$. Finally, for favourable ranges of parameters, by reconstructing masses of tagged $b\bar{b}$ jet pairs, it may be possible to detect Higgs bosons produced via sparticle cascade decay chains.Comment: 22 pages (REVTEX); a PS text file (etmiss.ps) and 12 figures (etlhc.uu or etlhc.ps) can be obtained via anonymous ftp at ftp://hep.fsu.edu/anonymous.bae

Off-target piRNA gene silencing in Drosophila melanogaster rescued by a transposable element insertion

Transposable elements (TE) are selfish genetic elements that can cause harmful mutations. In Drosophila, it has been estimated that half of all spontaneous visible marker phenotypes are mutations caused by TE insertions. Several factors likely limit the accumulation of exponentially amplifying TEs within genomes. First, synergistic interactions between TEs that amplify their harm with increasing copy number are proposed to limit TE copy number. However, the nature of this synergy is poorly understood. Second, because of the harm posed by TEs, eukaryotes have evolved systems of small RNA-based genome defense to limit transposition. However, as in all immune systems, there is a cost of autoimmunity and small RNA-based systems that silence TEs can inadvertently silence genes flanking TE insertions. In a screen for essential meiotic genes in Drosophila melanogaster, a truncated Doc retrotransposon within a neighboring gene was found to trigger the germline silencing of ald, the Drosophila Mps1 homolog, a gene essential for proper chromosome segregation in meiosis. A subsequent screen for suppressors of this silencing identified a new insertion of a Hobo DNA transposon in the same neighboring gene. Here we describe how the original Doc insertion triggers flanking piRNA biogenesis and local gene silencing. We show that this local gene silencing occurs in cis and is dependent on deadlock, a component of the Rhino-Deadlock-Cutoff (RDC) complex, to trigger dual-strand piRNA biogenesis at TE insertions. We further show how the additional Hobo insertion leads to de-silencing by reducing flanking piRNA biogenesis triggered by the original Doc insertion. These results support a model of TE-mediated gene silencing by piRNA biogenesis in cis that depends on local determinants of transcription. This may explain complex patterns of off-target gene silencing triggered by TEs within populations and in the laboratory. It also provides a mechanism of sign epistasis among TE insertions, illuminates the complex nature of their interactions and supports a model in which off-target gene silencing shapes the evolution of the RDC complex