50 research outputs found
Diophantine quintuples containing triples of the first kind
No full textWe consider Diophantine quintuples {a, b, c, d, e}, sets of integers with a < b < c < d < e the product of any two elements of which is one less than a perfect square. Triples of the first kind are sets {A, B,C} with C ≥ B5. We show that there are no Diophantine quintuples {a, b, c, d, e} such that {a, b, d} is a triple of the first kind
Cloud CPFP: A Shotgun Proteomics Data Analysis Pipeline Using Cloud and High Performance Computing
No full text
Cloud CPFP: A Shotgun Proteomics Data Analysis Pipeline Using Cloud and High Performance Computing
No full textWe have extended the functionality of the Central Proteomics
Facilities
Pipeline (CPFP) to allow use of remote cloud and high performance
computing (HPC) resources for shotgun proteomics data processing.
CPFP has been modified to include modular local and remote scheduling
for data processing jobs. The pipeline can now be run on a single
PC or server, a local cluster, a remote HPC cluster, and/or the Amazon
Web Services (AWS) cloud. We provide public images that allow easy
deployment of CPFP in its entirety in the AWS cloud. This significantly
reduces the effort necessary to use the software, and allows proteomics
laboratories to pay for compute time ad hoc, rather than obtaining
and maintaining expensive local server clusters. Alternatively the
Amazon cloud can be used to increase the throughput of a local installation
of CPFP as necessary. We demonstrate that cloud CPFP allows users
to process data at higher speed than local installations but with
similar cost and lower staff requirements. In addition to the computational
improvements, the web interface to CPFP is simplified, and other functionalities
are enhanced. The software is under active development at two leading
institutions and continues to be released under an open-source license
at http://cpfp.sourceforge.net
Protein Kinase C and NF-κB–Dependent CD4 Downregulation in Macrophages Induced by T Cell-Derived Soluble Factors: Consequences for HIV-1 Infection
No full textAbstract
Upon activation, CD4+ T cells release cytokines, chemokines, and other soluble factors that influence the kinetics of HIV-1 replication in macrophages (Mϕ). In this article, we show that activation of human primary T cells suppresses the early stages of HIV-1 replication in human primary Mϕ by downregulating the main cellular receptor for the virus CD4. The secreted factors responsible for this effect have a molecular mass greater than conventional cytokines, are independent of Th1 or Th2 polarization, and are not IFN-γ, IL-16, RANTES, or macrophage inhibitory factor, as revealed by cytokine array analysis and neutralization assays. CD4 downregulation is entirely posttranslational and involves serine phosphorylation of CD4 and its targeting to an intracellular compartment destined for acidification and degradation. CD4 downregulation is dependent on the activities of both protein kinase C and NF-κB as well as the proteasomes. Using high-resolution liquid chromatography-tandem mass spectrometry analysis in conjugation with label-free protein quantitation software, we found that proteins that promote Mϕ adherence and spreading, such as attractin, fibronectin, and galectin-3–binding protein, were significantly overrepresented in the activated T cell supernatant fractions. These results reveal the existence of previously unreported anti–HIV-1 proteins, released by activated T cells that downregulate CD4 expression, and are of fundamental importance to understand the kinetics of HIV infection in vivo.</jats:p
Author response
No full textCholera toxin (CT) enters and intoxicates host cells after binding cell surface receptors using its B subunit (CTB). The ganglioside (glycolipid) GM1 is thought to be the sole CT receptor; however, the mechanism by which CTB binding to GM1 mediates internalization of CT remains enigmatic. Here we report that CTB binds cell surface glycoproteins. Relative contributions of gangliosides and glycoproteins to CTB binding depend on cell type, and CTB binds primarily to glycoproteins in colonic epithelial cell lines. Using a metabolically incorporated photocrosslinking sugar, we identified one CTB-binding glycoprotein and demonstrated that the glycan portion of the molecule, not the protein, provides the CTB interaction motif. We further show that fucosylated structures promote CTB entry into a colonic epithelial cell line and subsequent host cell intoxication. CTB-binding fucosylated glycoproteins are present in normal human intestinal epithelia and could play a role in cholera.</p
Antibacterial activities of <i>V</i>. <i>alginolyticus</i> T6SSs are differentially regulated by salinity and temperature.
No full text<p>Viability of <i>E</i>. <i>coli</i> prey before (0h) and after (4h) co-culture with indicated <i>V</i>. <i>alginolyticus</i> attacker strains or alone. Co-cultures were incubated for 4 hours on (A) LB or (B) MLB agar plates at 30°C or 37°C. None = medium only. WT = wild-type.</p
Va16922/Va16927, Va18287/Va18282, and Va03175/Va03170/Va03180 are VaT6SS2 effector/immunity pairs.
No full text<p>(A) Schematic representation of the VaT6SS2 gene cluster and effector/immunity pairs. V12G01 locus numbers listed above. Effectors in red, Immunity in green, and tail tube components in orange. (B-D) Viability counts of prey strains containing an empty plasmid or a plasmid for the arabinose-inducible expression of the immunity protein before (0h) and after (4h) co-culture with the indicated attacker strains. Effector/immunity pairs tested were: (B) Va16922/Va16927, (C) Va18287/Va18282, and (D) Va03175/Va03170/Va03180. Asterisks mark statistical significance between sample groups at t = 4h by an unpaired, two tailed student’s t-test (p<0.05).</p
Location of phosphorylated residues in the polymerase.
No full text<p>The position of S472 in the C-terminal tail of PB2 when (A) unbound (PDB 2GMO <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002993#ppat.1002993-Tarendeau1" target="_blank">[91]</a>) and (B) bound (PDB 2JDQ <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002993#ppat.1002993-Tarendeau1" target="_blank">[91]</a>) to importin α5. PB2 is shown in light blue and the importin in gold. In the bound form residues 742–747 are not resolved in the structure, and are indicated by a dotted line; the position of S742 has been estimated. (C) Portions of the consensus sequences of PB2, PB1 and PA from influenza A, B and C viruses. Colours are as in <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002993#ppat-1002993-g002" target="_blank">Figure 2</a>; basic residues of the bipartite NLS of influenza A virus PB2, and orthologous residues in the influenza B and C virus sequences, are blue.</p
