J/psi production from proton-proton collisions at sqrt(s) = 200 GeV

J/psi production has been measured in proton-proton collisions at sqrt(s)= 200 GeV over a wide rapidity and transverse momentum range by the PHENIX experiment at RHIC. Distributions of the rapidity and transverse momentum, along with measurements of the mean transverse momentum and total production cross section are presented and compared to available theoretical calculations. The total J/psi cross section is 3.99 +/- 0.61(stat) +/- 0.58(sys) +/- 0.40(abs) micro barns. The mean transverse momentum is 1.80 +/- 0.23(stat) +/- 0.16(sys) GeV/c.Comment: 326 authors, 6 pages text, 4 figures, 1 table, RevTeX 4. To be submitted to PRL. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Centrality Dependence of Charm Production from Single Electrons in Au+Au Collisions at sqrt(s_NN) = 200 GeV

The PHENIX experiment has measured mid-rapidity transverse momentum spectra (0.4 < p_T < 4.0 GeV/c) of single electrons as a function of centrality in Au+Au collisions at sqrt(s_NN) = 200 GeV. Contributions to the raw spectra from photon conversions and Dalitz decays of light neutral mesons are measured by introducing a thin (1.7% X_0) converter into the PHENIX acceptance and are statistically removed. The subtracted ``non-photonic'' electron spectra are primarily due to the semi-leptonic decays of hadrons containing heavy quarks (charm and bottom). For all centralities, charm production is found to scale with the nuclear overlap function, T_AA. For minimum-bias collisions the charm cross section per binary collision is N_cc^bar/T_AA = 622 +/- 57 (stat.) +/- 160 (sys.) microbarns.Comment: 326 authors, 4 pages text, 3 figures, 1 table, RevTeX 4. To be submitted to Physical Review Letters. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Affinity purification of FH on the 5151 construct.

<p>(<b>A</b>) Schematic representation of the 5151 construct. See text. (<b>B</b>) FH has higher affinity for 5151 than for the M5-HVR. The 5151 and M5-HVR proteins were immobilized and analyzed for ability to bind pure FH. The data represent mean values with SD from three experiments. (<b>C</b> and <b>D</b>) Affinity purification of FH on the 5151 construct and FH-depletion of human serum. Whole serum containing the Y402 protein (C) or the H402 protein (D) was applied to a column containing immobilized 5151. Bound protein was analyzed by SDS-PAGE (left panels) and western blot (right panels). The control represents the eluate from a column without immobilized 5151. Ft, flow-through. Pure FH was included as a reference. The blots were probed with sheep anti-FH. Bound antibodies were detected with radiolabeled protein G and autoradiography. Protein G also bound to the heavy chain of IgG (γ), as indicated. (<b>E</b>) Cofactor activity of purified Y402 FH compared to that of commercial FH. The analysis measured the ability of FH to act as a cofactor for FI in the degradation of the C3b α’ chain to 68 kDa and 43 kDa fragments of iC3b. The two FH proteins had similar activity when diluted, showing that they had similar cofactor activity.</p

Differential binding of Y402 and H402 FH to different M proteins: enrichment of the Y402 protein on an M6 derived construct.

<p>(<b>A</b>) Binding of pure Y402 and H402 FH to <i>S. pyogenes</i> M5, M6 and M18 bacteria. The pure FH proteins were added at the concentrations indicated. Bound FH was detected with sheep anti-FH and radiolabeled protein G. The binding to M-negative control strains was low (not shown). (<b>B</b>) Differential binding of the Y402 and H402 proteins to pure M5, M6 and M18 immobilized in microtiter wells. The FH proteins were added at the concentrations indicated. Bound FH was detected with sheep anti-FH and radiolabeled protein G. The data in A and B represent mean values with SD from three experiments. Two-way ANOVA analysis was performed on the binding values corresponding to the highest concentrations of FH corrected for the difference between individual experiments (not set to 100 % as in the graph) (n=3). The differences in binding to Y402 and H402 FH were found to be significant with P<0.001 for M5, P<0.001 for M6 and P=0.004 for M18. (<b>C</b>) Schematic representation of the 6161 construct. See text. (<b>D</b>) Affinity purification of FH on the 6161 and 5151 constructs. Serum containing Y402 and H402 FH (from a heterozygote) was applied to columns with immobilized 6161 or 5151. Bound protein was eluted and analyzed by SDS-PAGE (left panel) and western blot (middle and right panels). The blots were probed with mAbs specific for Y402 or H402 FH, as indicated. Pure Y402 and H402 FH were included as controls.</p

Phagocytosis tests with M1 and M3 strains.

<p>(<b>A</b>) Suspensions of the bacterial strains indicated were analyzed for ability to bind human FH. After incubation of a bacterial suspension with pure FH (50 µg/ml), the bacteria were washed twice and bound protein was eluted and analyzed by western blot, employing anti-FH for detection. The analysis included wild type M5, M1 and M3 strains and their M-negative mutants (ΔM5, ΔM1 and ΔM3, respectively). Pure FH was included as a control in the blot (right). (<b>B</b>) Phagocytosis assay in whole human blood with M1 and M3 strains, and M-negative mutants, as indicated. MF, multiplication factor.</p

Isolated HVRs derived from M5, M6 and M18 specifically bind FH.

<p>(<b>A</b>) Analysis by non-reducing SDS-PAGE of HVRs dimerized via a C-terminal cysteine residue. As previously observed <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003323#ppat.1003323-Morfeldt1" target="_blank">[26]</a>, dimerized HVRs move more slowly than expected in gels. (<b>B</b>) Binding of FH to isolated HVRs immobilized in microtiter wells. The wells were coated with 0.1 µg of the HVRs, as indicated, and tested for ability to bind added FH. (<b>C</b>) Immobilized HVRs, derived from FH-binding M proteins, specifically bind FH among all proteins in human serum. Whole human serum was applied to columns in which the HVRs indicated had been immobilized. After washings, bound protein was eluted and analyzed by SDS-PAGE. A column without HVR was used as control. Pure FH was included as a reference in the gel analysis (right). (<b>D</b>) Sequence alignment of the three FH-binding HVRs that were studied in isolated form. This alignment does not include a C-terminal Cys residue included to allow dimerization. The lengths of these HVR vary slightly from those previously reported <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003323#ppat.1003323-Lannergrd1" target="_blank">[79]</a>, because the position of the C-terminal end was chosen to allow optimal dimerization and FH-binding. Asterisks indicate residues identical in all three sequences. Pair-wise identities (based on regions present in both sequences) are indicated to the right.</p

Streptococcal M proteins vary in ability to bind human FH and C4BP.

<p>(<b>A</b>) Schematic representation of the human complement regulators FH and C4BP and of an M protein. For FH and C4BP, each circle represents an SCR domain. While FH is a single chain with 20 SCR domains, C4BP typically contains 7 α-chains with 8 SCR domains and one β-chain with 3 SCRs. An M protein has an N-terminal HVR and a more conserved C-terminal region that includes C repeats and the wall-anchoring region. The location of M protein binding sites in FH and C4BP are indicated. (<b>B</b>) SDS-PAGE analysis of the purified recombinant M proteins studied, five of which were of class I, and two of class II. The presence of doublet or triplet bands is typical for M proteins expressed in <i>E. coli</i> or <i>S. pyogenes </i><a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003323#ppat.1003323-Stenberg1" target="_blank">[32]</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003323#ppat.1003323-Scott1" target="_blank">[82]</a>. (<b>C</b>) Binding of human FH, C4BP or fibrinogen (Fg) to pure M proteins immobilized in microtiter wells. The wells were coated with 0.1 µg M protein and human ligands (50 µl) were added at the following concentrations: FH 2 µg/ml, C4BP 1 µg/ml, Fg 0.28 µg/ml. Bound ligands were detected with specific antibodies. Binding is given in percent of maximal binding for each ligand. (<b>D</b>) Binding of human FH analyzed for the M-positive M5, M6 and M18 <i>S. pyogenes</i> strains and their M-negative mutants (ΔM5, ΔM6, and ΔM18, respectively). Bacterial suspensions were incubated with pure FH (50 µg/ml). After two washes bound protein was eluted and analyzed by western blot, employing anti-FH for detection. Pure FH was included as a control in the blot (right).</p