The rockefeller university

We present a search for supersymmetric neutrino (nu) over tilde production using the Tevatron p (p) over bar collision data collected with the CDF II detector and corresponding to an integrated luminosity of 1 fb(-1). We focus on the scenarios predicted by the R-parity violating (RPV) supersymmetric models in which sneutrinos decay to two charged leptons of different flavor. With the data consistent with the standard model expectations, we set upper limits on sigma(p (p) over bar -> (nu) over tilde) BR((nu) over tilde -> e mu, mu tau, e tau) and use these results to constrain the RPV couplings as a function of the sneutrino mass.

Total internal reflection fluorescence (TIRF) microscopy can be used in a wide range of cell biological applications, and is particularly well suited to analysis of the localization and dynamics of molecules and events near the plasma membrane. The TIRF excitation field decreases exponentially with distance from the cover slip on which cells are grown. This means that fluorophores close to the cover slip (e.g. within similar to 100 nm) are selectively illuminated, highlighting events that occur within this region. The advantages of using TIRF include the ability to obtain high-contrast images of fluorophores near the plasma membrane, very low background from the bulk of the cell, reduced cellular photodamage and rapid exposure times. In this Commentary, we discuss the applications of TIRF to the study of cell biology, the physical basis of TIRF, experimental setup and troubleshooting.

We report on a search for the flavor-changing neutral-current decay D-0 -> mu(+)mu(-) in p (p) over bar collisions at root s = 1.96 TeV using 360 pb(-1) of integrated luminosity collected by the CDF II detector at the Fermilab Tevatron collider. A displaced vertex trigger selects long-lived D-0 candidates in the mu(+)mu(-), pi(+)pi(-), and K-pi(+) decay modes. We use the Cabibbo-favored D-0 -> K-pi(+) channel to optimize the selection criteria in an unbiased manner, and the kinematically similar D-0 -> pi(+)pi(-) channel for normalization. We set an upper limit on the branching fraction B(D-0 -> mu(+)mu(-)) < 2.1 X 10(-7) (3.0 X 10(-7)) at the 90% (95%) confidence level.

Autosomal recessive interleukin-1 receptor-associated kinase (IRAK)-4 and myeloid differentiation factor (MyD) 88 deficiencies impair Toll-like receptor (TLR)-and interleukin-1 receptor-mediated immunity. We documented the clinical features and outcome of 48 patients with IRAK-4 deficiency and 12 patients with MyD88 deficiency, from 37 kindreds in 15 countries. The clinical features of IRAK-4 and MyD88 deficiency were indistinguishable. There were no severe viral, parasitic, and fungal diseases, and the range of bacterial infections was narrow. Noninvasive bacterial infections occurred in 52 patients, with a high incidence of infections of the upper respiratory tract and the skin, mostly caused by Pseudomonas aeruginosa and Staphylococcus aureus, respectively. The leading threat was invasive pneumococcal disease, documented in 41 patients (68%) and causing 72 documented invasive infections (52.2%). P. aeruginosa and Staph. aureus documented invasive infections also occurred (16.7% and 16%, respectively, in 13 and 13 patients, respectively). Systemic signs of inflammation were usually weak or delayed. The first invasive infection occurred before the age of 2 years in 53 (88.3%) and in the neonatal period in 19 (32.7%) patients. Multiple or recurrent invasive infections were observed in most survivors (n = 36/50, 72%). Clinical outcome was poor, with 24 deaths, in 10 cases during the first invasive episode and in 16 cases of invasive pneumococcal disease. However, no death and invasive infectious disease were reported in patients after the age of 8 years and 14 years, respectively. Antibiotic prophylaxis (n = 34), antipneumococcal vaccination (n = 31), and/or IgG infusion (n = 19), when instituted, had a beneficial impact on patients until the teenage years, with no seemingly detectable impact thereafter. IRAK-4 and MyD88 deficiencies predispose patients to recurrent life-threatening bacterial diseases, such as invasive pneumococcal disease in particular, in infancy and early childhood, with weak signs of inflammation. Patients and families should be informed of the risk of developing life-threatening infections; empiric antibacterial treatment and immediate medical consultation are strongly recommended in cases of suspected infection or moderate fever. Prophylactic measures in childhood are beneficial, until spontaneous improvement occurs in adolescence.

HIV-1 Gag drives a number of events during the genesis of virions and is the only viral protein required for the assembly of virus-like particles in vitro and in cells. Although a reasonable understanding of the processes that accompany the later stages of HIV-1 assembly has accrued, events that occur at the initiation of assembly are less well defined. In this regard, important uncertainties include where in the cell Gag first multimerizes and interacts with the viral RNA, and whether Gag-RNA interaction requires or induces Gag multimerization in a living cell. To address these questions, we developed assays in which protein crosslinking and RNA/protein co-immunoprecipitation were coupled with membrane flotation analyses in transfected or infected cells. We found that interaction between Gag and viral RNA occurred in the cytoplasm and was independent of the ability of Gag to localize to the plasma membrane. However, Gag: RNA binding was stabilized by the C-terminal domain (CTD) of capsid (CA), which participates in Gag-Gag interactions. We also found that Gag was present as monomers and low-order multimers (e. g. dimers) but did not form higher-order multimers in the cytoplasm. Rather, high-order multimers formed only at the plasma membrane and required the presence of a membrane-binding signal, but not a Gag domain (the CA-CTD) that is essential for complete particle assembly. Finally, sequential RNA-immunoprecipitation assays indicated that at least a fraction of Gag molecules can form multimers on viral genomes in the cytoplasm. Taken together, our results suggest that HIV-1 particle assembly is initiated by the interaction between Gag and viral RNA in the cytoplasm and that this initial Gag-RNA encounter involves Gag monomers or low order multimers. These interactions per se do not induce or require high-order Gag multimerization in the cytoplasm. Instead, membrane interactions are necessary for higher order Gag multimerization and subsequent particle assembly in cells.

A search for narrow resonances in the dijet mass spectrum is performed using data corresponding to an integrated luminosity of 2.9 pb(-1) collected by the CMS experiment at the Large Hadron Collider. Upper limits at the 95% confidence level are presented on the product of the resonance cross section, branching fraction into dijets, and acceptance, separately for decays into quark-quark, quark-gluon, or gluon-gluon pairs. The data exclude new particles predicted in the following models at the 95% confidence level: string resonances, with mass less than 2.50 TeV, excited quarks, with mass less than 1.58 TeV, and axigluons, colorons, and E-6 diquarks, in specific mass intervals. This extends previously published limits on these models.

P>Repeated administration of cocaine induces heightened behavioral hyperactivity termed sensitization. Although NK-3 receptors have been shown to modulate acute cocaine-induced behaviors, their role in behavioral sensitization is unknown. The present study investigated whether NK-3 receptor blockade altered behavioral sensitization to cocaine. Additionally, glycogen synthase kinase-3 (GSK3) has been shown to be involved in dopamine receptor signaling and in development of sensitization; therefore regulation of GSK3 activity in the nucleus accumbens was also investigated. Administration of the NK-3 receptor antagonist SB 222200 (5 mg/kg, s.c.) prior to repeated cocaine (20 mg/kg, i.p.) prevented the development of sensitized responses after a cocaine challenge. Pre-treatment with SB 222200 before a cocaine challenge also blocked expression of sensitization. Decrease in GSK3 activity demonstrated by increased phosphorylation of GSK3 alpha and GSK3 beta was detected 20 mins after an acute cocaine injection. In contrast, a cocaine challenge failed to alter phosphorylation of GSK3 alpha and GSK3 beta in sensitized mice. SB 222200 prior to repeated cocaine resulted in increased phosphorylation of GSK3 alpha and GSK3 beta akin to changes following acute cocaine. Collectively, these findings demonstrate the involvement of NK-3 receptors in development and expression of behavioral sensitization and in regulation of GSK3 activity in the nucleus accumbens after repeated cocaine.

Protease inhibitor cocktails are routinely added to clinical samples used for proteomic studies to inactivate proteases. As these same samples are often used for microbial studies, we determined whether the addition of protease inhibitors could affect the quantitative or qualitative assessment of microbial profiles. Twenty-two saliva samples were collected and processed immediately with or without the addition of a protease inhibitor cocktail. Conventional cultivation methods were used to evaluate total bacterial growth. Total genomic DNA was isolated and a specific 16S rRNA gene-targeted region was PCR-amplified and separated by denaturing gradient gel electrophoresis. A combination of 1D sodium dodecyl sulfate polyacrylamide gel electrophoresis and LC-MS/MS methods was used to determine the effect of the protease inhibitors on the integrity of salivary proteins and peptides. Interestingly, no significant differences were observed in either the bacterial growth and composition or the integrity of salivary proteins between the two groups. Correlation coefficients between the paired samples for total cultivable microbiota (r2=0.847), total mutans streptococci (r2=0.898), total oral lactobacilli (r2=0.933), and total Streptococcus mutans (r2=0.870) also exceeded expected values. The results suggest that the addition of a protease inhibitor cocktail in saliva samples does not impact the growth of oral microbiota or compromise the ability to characterize its composition.

We have recently reported in male rats that medial prefrontal cortex (mPFC) neurons that project to the basolateral nucleus of the amygdala (BLA) are resilient to stress-induced dendritic remodeling. The present study investigated whether this also occurs in female rats. This pathway was identified using the retrograde tracer Fast Blue injected into the BLA of ovariectomized female rats with estrogen replacement (OVX + E) and without (OVX + veh). Animals were exposed for 10 days either to 2-h immobilization stress or to home cage rest, after which layer III mPFC neurons that were either retrogradely labeled by Fast Blue or unlabeled were filled with Lucifer Yellow and analyzed for apical dendritic length and spine density. No dendritic remodeling occurred in unlabeled neurons from OVX + veh or OVX + E animals. In BLA-projecting neurons, however, stress had no effect on length in OVX + veh animals, but stressed OVX + E females showed greater dendritic length than controls at intermediate branches. Stress also caused an increase in spine density in all neurons in OVX + veh animals and a spine density increase in BLA-projecting neurons in OVX + E females. Estrogen also increased spine density on BLA-projecting neurons in unstressed animals. These data demonstrate both independent effects of estrogen on pyramidal cell morphology and effects that are interactive with stress, with the BLA-projecting neurons being sensitive to both kinds of effects.