The rockefeller university

We present a measurement of the B-s(0) lifetime in fully and partially reconstructed B-s(0) -> D-s(-)(phi pi(-))X decays in 1.3 fb(-1) collected in p (p) over bar collisions at root s = 1.96 Tev by the CDF II detector at the Fermilab Tevatron. We measure tau(B-s(0)) = 1.518 +/- 0.041(stat) +/- 0.027(stat) ps. The ratio of this result and the world average B-0 lifetime tau(B-s(0))/tau(B-0) = 99 +/- 0.03, which is in agreement with recent theoretical predictions.

FUS, EWSR1 and TAF15, constituting the FET protein family, are abundant, highly conserved RNA-binding proteins with important roles in oncogenesis and neuronal disease, yet their RNA targets and recognition elements are unknown. Using PAR-CLIP, we defined global RNA targets for all human FET proteins and two ALS-causing human FUS mutants. FET members showed similar binding profiles, whereas FUS mutants showed a drastically altered binding pattern, consistent with changes in subcellular localization.

Innocuous touch of the skin is detected by distinct populations of neurons, the low-threshold mechano-receptors (LTMRs), which are classified as A beta-, A delta-, and C-LTMRs. Here, we report genetic labeling of LTMR subtypes and visualization of their relative patterns of axonal endings in hairy skin and the spinal cord. We found that each of the three major hair follicle types of trunk hairy skin (guard, awl/auchene, and zigzag hairs) is innervated by a unique and invariant combination of LTMRs; thus, each hair follicle type is a functionally distinct mechanosensory end organ. Moreover, the central projections of A beta-, A delta-, and C-LTMRs that innervate the same or adjacent hair follicles form narrow LTMR columns in the dorsal horn. These findings support a model of mechanosensation in which the activities of A beta-, A delta-, and C-LTMRs are integrated within dorsal horn LTMR columns and processed into outputs that underlie the perception of myriad touch sensations.

In this brief report, we provide a portrait of the CEM-NET initiative and review studies that highlight contributions of this molecular epidemiological network to the understanding of the molecular mechanisms of drug resistance in Staphylococcus aureus and Streptococcus pneumoniae clones as well as their routes and modes of geographic expansion. (C) 2011 Elsevier GmbH. All rights reserved.

Cocaine-induced plasticity of mesocorticolimbic dopamine (DA) neurons, originating in the ventral tegmental area (WA), persists in the absence of cocaine and may contribute to both drug-craving and relapse. Glutamate AMPA receptors (AMPARs) in these neurons are implicated in this plasticity. However, there is no ultrastructural evidence that the absence of cocaine following repeated administrations affects the critical surface/synaptic availability of AMPAR GluR1 subunits in either DA or non-DA, putative GABAergic neurons within the VIA. To assess this, we used electron microscopic immunolabeling in the VTA of adult male mice sacrificed at 30 min or 72 h after receiving the final of six (15 mg/kg) cocaine injections, a dosing paradigm that resulted in development of locomotor sensitization. At each time point, both cocaine- and saline-injected mice showed AMPAR GluR1 immunogold labeling in somatodendritic profiles, many of which contained immunoperoxidase labeling for the DA-synthesizing enzyme, tyrosine hydroxylase (TH). At 30 min after the last injection, when cocaine was systemically present, only the non-TH labeled dendrites showed a significant increase in the synaptic/plasmalemmal density of GluR1 immunogold particles. At 72 h, when systemic cocaine was depleted, synaptic GluR1 labeling was greatly enhanced in TH-containing dendrites throughout the VTA and in non-TH dendrites of the limbic-associated paranigral VTA. Our results demonstrate that systemic cocaine produces GluR1 trafficking specifically in non-DA neurons of the VFA, which may subsequently contribute to the abstinent-induced enhancement of AMPA receptor synaptic transmission in mesocorticolimbic DA neurons leading to heightened drug seeking behavior. This article is part of a Special Issue entitled 'Synaptic Plasticity and Addiction'. (C) 2011 Elsevier Ltd. All rights reserved.

We present the results of a search for pair production of a heavy toplike (t') quark decaying to Wq final states using data corresponding to an integrated luminosity of 5.6 fb(-1) collected by the CDF II detector in p (p) over bar collisions at root s = 1.96 TeV. We perform parallel searches for t' -> Wb and t' -> Wq (where q is a generic down-type quark) in events containing a lepton and four or more jets. By performing a fit to the two-dimensional distribution of total transverse energy versus reconstructed t' quark mass, we set upper limits on the t'(t) over bar' production cross section and exclude a standard model fourth-generation t' quark decaying to Wb (Wq) with mass below 358 (340) GeV/c(2) at 95% C. L.

Currently there is no general approach for achieving specific optogenetic control of genetically defined cell types in rats, which provide a powerful experimental system for numerous established neurophysiological and behavioral paradigms. To overcome this challenge we have generated genetically restricted recombinase-driver rat lines suitable for driving gene expression in specific cell types, expressing Cre recombinase under the control of large genomic regulatory regions (200-300 kb). Multiple tyrosine hydroxylase (Th)::Cre and choline acetyltransferase (Chat)::Cre lines were produced that exhibited specific opsin expression in targeted cell types. We additionally developed methods for utilizing optogenetic tools in freely moving rats and leveraged these technologies to clarify the causal relationship between dopamine (DA) neuron firing and positive reinforcement, observing that optical stimulation of DA neurons in the ventral tegmental area (VTA) of Th::Cre rats is sufficient to support vigorous intracranial self-stimulation (ICSS). These studies complement existing targeting approaches by extending the generalizability of optogenetics to traditionally non-genetically-tractable but vital animal models.

Processive chromosomal replication relies on sliding DNA clamps, which are loaded onto DNA by pentameric clamp loader complexes belonging to the AAA+ family of adenosine triphosphatases (ATPases). We present structures for the ATP-bound state of the clamp loader complex from bacteriophage T4, bound to an open clamp and primer-template DNA. The clamp loader traps a spiral conformation of the open clamp so that both the loader and the clamp match the helical symmetry of DNA. One structure reveals that ATP has been hydrolyzed in one subunit and suggests that clamp closure and ejection of the loader involves disruption of the ATP-dependent match in symmetry. The structures explain how synergy among the loader, the clamp, and DNA can trigger ATP hydrolysis and release of the closed clamp on DNA.

Eukaryotic DNA is packaged in nucleosomes. How does this sequestration affect the ability of transcription regulators to access their sites? We cite evidence against the idea that nucleosome positioning is determined primarily by the intrinsic propensities of DNA sequences to form nucleosomes - such that, for example, regulatory sites would be 'nucleosome-free'. Instead, studies in yeast show that nucleosome positioning is primarily determined by specific DNA-binding proteins. Where nucleosomes would otherwise compete with regulatory protein binding (a modest but potentially biologically important effect), this obstacle can be relieved by at least two strategies for exposing regulatory sites. In contrast to their lack of effect on nucleosome positioning, DNA sequence differences do directly affect both the efficiencies with which nucleosomes form in regions flanking regulatory sites before induction, and the extent of their removal upon induction. These nucleosomes, evidently, inhibit basal transcription but are poised to be removed quickly upon command.

We report on the comparative genomics and characterization of the virulence phenotypes of four S. pneumoniae strains that belong to the multidrug resistant clone PMEN1 (Spain(23F) ST81). Strains SV35-T23 and SV36-T3 were recovered in 1996 from the nasopharynx of patients at an AIDS hospice in New York. Strain SV36-T3 expressed capsule type 3 which is unusual for this clone and represents the product of an in vivo capsular switch event. A third PMEN1 isolate - PN4595-T23 - was recovered in 1996 from the nasopharynx of a child attending day care in Portugal, and a fourth strain - ATCC700669 - was originally isolated from a patient with pneumococcal disease in Spain in 1984. We compared the genomes among four PMEN1 strains and 47 previously sequenced pneumococcal isolates for gene possession differences and allelic variations within core genes. In contrast to the 47 strains - representing a variety of clonal types - the four PMEN1 strains grouped closely together, demonstrating high genomic conservation within this lineage relative to the rest of the species. In the four PMEN1 strains allelic and gene possession differences were clustered into 18 genomic regions including the capsule, the blp bacteriocins, erythromycin resistance, the MM1-2008 prophage and multiple cell wall anchored proteins. In spite of their genomic similarity, the high resolution chinchilla model was able to detect variations in virulence properties of the PMEN1 strains highlighting how small genic or allelic variation can lead to significant changes in pathogenicity and making this set of strains ideal for the identification of novel virulence determinants.