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We report on a search for a spin-zero non-standard model particle in proton-antiproton collisions collected by the Collider Detector at Fermilab at a center-of-mass-energy of 1.96 TeV. This particle, the phi boson, is expected to decay into a bottom-antibottom quark pair and to be produced in association with at least one bottom quark. The data sample consists of events with three jets identified as initiated by bottom quarks and corresponds to 5.4 fb(-1) of integrated luminosity. In each event, the invariant mass of the two most energetic jets is studied by looking for deviations from the multijet background, which is modeled using data. No evidence is found for such a particle. Exclusion upper limits ranging from 20 to 2 pb are set for the product of production cross sections times branching fraction for the hypothetical phi boson with mass between 100 and 300 GeV/c(2). These are the most stringent constraints to date.

We previously synthetized molybdenum oxide (MoO3) nanoparticles (NP) and showed their antibacterial activity against a representative collection of the most relevant bacterial species responsible for hospital-acquired infections, including Staphylococcus aureus. The aim of the present study was to prepare and characterize a novel coating with these MoO3 NP, confirm its mechanical stability, and investigate its biocidal effect to reduce S. aureus contamination on inanimate surfaces. In addition, the novel MoO3 NP coating was compared to a silver (Ag) NP coating synthetized by the same procedure. The MoO3 and Ag NP coatings were characterized in terms of their chemical structure by FT-IR, surface morphology by scanning electron microscopy, and mechanical properties by tensile and adhesion tests. The antimicrobial activity of the coatings was tested by following the loss of viability of S. aureus after 6h, 24h, 48h, and 72h exposure. MoO3 and Ag coatings exhibited surfaces of comparable morphologies and both presented elastomeric properties (tensile strength of similar to 420 kPa, Youngs modulus of similar to 48 kPa, and maximum elongation of similar to 12%), and excellent (classification of 5B) adhesion to glass, steel and polystyrene surfaces. The two coatings exhibited a good antibacterial activity (R) against S. aureus over time (R-MoO3 = 0.20.81; R-Ag = 0.612.37), although the effect of the Ag NP coating was more pronounced, especially at 72h (R-MoO3 = 0.81 vs R-Ag = 2.37). Noteworthy, contrary to the Ag NP coating, the MoO3 NP coating was colourless and transparent, avoiding undesired unaesthetic effects. The synthetized coating with NP of MoO3, which has low toxicity to humans, capability of biodegradation, and rapid excretion, can be applied onto most standard materials and therefore is a promising tool to reduce S. aureus contamination on usual inanimate surfaces found in healthcare and community environments.

Real-time PCR targeting lytA (the major autolysin gene) and piaB (permease gene of the pia ABC transporter) are currently used as the gold-standard culture-independent assays for Streptococcus pneumoniae identification. We evaluated the performance of a new real-time PCR assay-targeting SP2020 (putative transcriptional regulator gene)-and compared its performance with the assays previously described. A collection of 150 pneumococci, 433 non-pneumococci and 240 polymicrobial samples (obtained from nasopharynx, oropharynx, and saliva; 80 from each site) was tested. SP2020 and lytA-CDC assays had the best performance (sensitivity of 100% for each compared to 95.3% for piaB). The specificity for lytA and piaB was 99.5% and for SP2020 was 99.8%. Misidentifications occurred for the three genes: lytA, piaB and SP2020 were found in non-pneumococcal strains; piaB was absent in some pneumococci including a serotype 6B strain. Combining lytA and SP2020 assays resulted in no misidentifications. Most polymicrobial samples (88.8%) yielded concordant results for the three molecular targets. The remaining samples seemed to contain non-typeable pneumococci (0.8%), and non-pneumococci positive for lytA (1.7%) or SP2020 (8.7%). We propose that combined detection of both lytA-CDC and SP2020 is a powerful strategy for the identification of pneumococcus either in pure cultures or in polymicrobial samples.

Interferon-induced transmembrane proteins (IFITMs 1, 2 and 3) have emerged as important innate immune effectors that prevent diverse virus infections in vertebrates. However, the cellular mechanisms and live-cell imaging of these small membrane proteins have been challenging to evaluate during viral entry of mammalian cells. Using CRISPR-Cas9-mediated IFITM-mutant cell lines, we demonstrate that human IFITM1, IFITM2 and IFITM3 act cooperatively and function in a dose-dependent fashion in interferon-stimulated cells. Through site-specific fluorophore tagging and live-cell imaging studies, we show that IFITM3 is on endocytic vesicles that fuse with incoming virus particles and enhances the trafficking of this pathogenic cargo to lysosomes. IFITM3 trafficking is specific to restricted viruses, requires S-palmitoylation and is abrogated with loss-of-function mutants. The site-specific protein labeling and live-cell imaging approaches described here should facilitate the functional analysis of host factors involved in pathogen restriction as well as their mechanisms of regulation.

Similar to other hepatotropic viruses, hepatitis E virus (HEV) has been notoriously difficult to propagate in cell culture, limiting studies to unravel its biology. Recently, major advances have been made by passaging primary HEV isolates and selecting variants that replicate efficiently in carcinoma cells. These adaptations, however, can alter HEV biology. We have explored human embryonic or induced pluripotent stem cell (hESUiPSC)-derived hepatocyte-like cells (HLCs) as an alternative to conventional hepatoma and hepatocyte cell culture systems for HEV studies. HLCs are permissive for nonadapted HEV isolate genotypes (gt)1-4 replication and can be readily genetically manipulated. HLCs, therefore, enable studies of pan-genotype HEV biology and will serve as a platform for testing anti-HEV treatments. Finally, we discuss how hepatocyte polarity is likely an important factor in the maturation and spread of infectious HEV particles.

Self-renewal of intestinal stem cells is controlled by Wingless/Wnt-beta catenin signaling in both Drosophila and mammals. As Axin is a rate-limiting factor in Wingless signaling, its regulation is essential. Iduna is an evolutionarily conserved ubiquitin E3 ligase that has been identified as a crucial regulator for degradation of ADP-ribosylated Axin and, thus, of Wnt/beta-catenin signaling. However, its physiological significance remains to be demonstrated. Here, we generated loss-offunction mutants of Idune to investigate its physiological role in Drosophila. Genetic depletion of Iduna causes the accumulation of both Tankyrase and Axin. Increase of Axin protein in enterocytes non-autonomously enhanced stem cell divisions in the Drosophila midgut. Enterocytes secreted Unpaired proteins and thereby stimulated the activity of the JAK-STAT pathway in intestinal stem cells. A decrease in Axin gene expression suppressed the over-proliferation of stem cells and restored their numbers to normal levels in !dune mutants. These findings suggest that Iduna-mediated regulation of Axin proteolysis is essential for tissue homeostasis in the Drosophila midgut.

Purpose: To assess the potential biologic significance of variations in

Nuclear size correlates with cell size, but the mechanism by which this scaling is achieved is not known. Here we screen fission yeast gene deletion mutants to identify essential factors involved in this process. Our screen has identified 25 essential factors that alter nuclear size, and our analysis has implicated RNA processing and LINC complexes in nuclear size control. This study has revealed lower and more extreme higher nuclear size phenotypes and has identified global cellular processes and specific structural nuclear components important for nuclear size control. Author summary As cells grow and divide, the size of the nucleus is generally maintained as a fixed proportion of cell size. The mechanism by which this nuclear/cytoplasmic ratio is maintained is unclear. Previous studies have suggested that essential gene products may be important for nuclear size control. Therefore, we have exploited the genetic tractability of fission yeast to carry out a systematic genetic screen of deleted essential genes to identify those with aberrant nuclear size phenotypes. Our study has revealed 25 novel genes that influence nuclear size and our bioinformatic analyses have implicated both RNA processing and protein complexes connecting nuclear chromatin to the cytoskeleton in nuclear size control. Our work sheds light on the biological processes that contribute to nuclear size control in fission yeast contributing to our mechanistic understanding of nuclear scaling, a biological phenomenon that is conserved through evolution.

The latter steps in this biosynthetic pathway for the antimalarial phosphonic acid FR-900098 include the installation of a hydroxamate onto 3-aminopropylphosphonate, which is catalyzed by the consecutive actions of an acetyltransferase and an amine hydroxylase. Here, we present the 1.6 A resolution co-crystal structure and accompanying biochemical characterization of FrbG, which catalyzes the hydroxylation of aminopropylphosphonate. We show that FrbG is a flavin-dependent N-hydroxylating monooxygenase (NMO), which shares a similar overall structure with flavin-containing monooxygenases (FMOs). Notably, we also show that the cytidine-5'-monophosphate moiety of the substrate is a critical determinant of specificity, distinguishing FrbG from other FMOs in that the nucleotide cofactor-binding domain also serves in conferring substrate recognition. In the FrbG-FAD+-NADPH co-crystal structure, the C4 of the NADPH nicotinamide is situated near the N5 of the FAD isoalloxazine, and is oriented with a distance and stereochemistry to facilitate hydride transfer.