A peptide from the staphylococcal protein Efb binds P-selectin and inhibits the interaction of platelets with leukocytes

Aims: P-selectin is a key surface adhesion molecule for the interaction of platelets with leukocytes. We have shown previously that the N-terminal domain of Staphylococcus aureus extracellular fibrinogen-binding protein (Efb) binds to P-selectin and interferes with platelet-leukocyte aggregate formation. Here, we aimed to identify the minimal Efb motif required for binding platelets and to characterize its ability to interfering with the formation of platelet-leukocyte aggregates. Methods and Results: Using a library of synthetic peptides, we mapped the platelet-binding site to a continuous 20 amino acid stretch. The peptide Efb68-87 was able to bind to resting and, to a greater extent, thrombin-stimulated platelets in the absence of fibrinogen. Dot blots, pull-down assays and P-selectin glycoprotein ligand-1 (PSGL-1) competitive binding experiments identified P-selectin as the cellular docking site mediating Efb68-87 platelet binding. Accordingly, Efb68-87 did not bind to other blood cells and captured platelets from human whole blood under low shear stress conditions. Efb68-87 did not affect platelet activation as tested by aggregometry, flow cytometry and immunoblotting, but inhibited the formation of platelet-leukocyte aggregates (PLAs). Efb68-87 also interfered with the platelet-dependent stimulation of neutrophil extracellular traps (NETs) formation in vitro. Conclusions: We have identified Efb68-87 as a novel selective platelet-binding peptide. Efb68-87 binds directly to P-selectin and inhibits interactions of platelets with leukocytes that lead to PLA and NET formation. As PLAs and NETs play a key role in thromboinflammation, Efb68-87 is an exciting candidate for the development of novel selective inhibitors of the proinflammatory activity of platelets

How public can public goods be? Environmental context shapes the evolutionary ecology of partially private goods

The production of costly public goods (as distinct from metabolic byproducts) has largely been understood through the realization that spatial structure can minimize losses to non-producing “cheaters” by allowing for the positive assortment of producers. In well-mixed systems, where positive assortment is not possible, the stable production of public goods has been proposed to depend on lineages that become indispensable as the sole producers of those goods while their neighbors lose production capacity through genome streamlining (the Black Queen Hypothesis). Here, we develop consumer-resource models motivated by nitrogen-fixing, siderophore-producing bacteria that consider the role of colimitation in shaping eco-evolutionary dynamics. Our models demonstrate that in well-mixed environments, single “public goods” can only be ecologically and evolutionarily stable if they are partially privatized (i.e., if producers reserve a portion of the product pool for private use). Colimitation introduces the possibility of subsidy: strains producing a fully public good can exclude non-producing strains so long as the producing strain derives sufficient benefit from the production of a second partially private good. We derive a lower bound for the degree of privatization necessary for production to be advantageous, which depends on external resource concentrations. Highly privatized, low-investment goods, in environments where the good is limiting, are especially likely to be stably produced. Coexistence emerges more rarely in our mechanistic model of the external environment than in past phenomenological approaches. Broadly, we show that the viability of production depends critically on the environmental context (i.e., external resource concentrations), with production of shared resources favored in environments where a partially-privatized resource is scarce

Effect of Brachionus rubens on the growth characteristics of various species of microalgae

Background: Cultivation of algae for conversion to biofuels has gained global interest. Outdoor raceway cultivation is preferred because of its lower capital and operating costs. A major disadvantage of outdoor cultivation is susceptibility of algal crops to attack by predatory rotifers. In order to quantify the impact of rotifer attack on different species of algae, we evaluated the growth of eleven microalgal species over a 21-d period after being infected by the predatory rotifer Brachionus rubens. Results: Of the eleven species, Chlorella sorokiniana was the most susceptible with rapid decline in algal growth concomitant with increase in rotifer population growth (3.82/d). In contrast, Synechococcus elongatus and Scenedesmus dimorphus were both resistant to the rotifer and suppressed rotifer growth (-0.06/d). An index of algal species susceptibility to be consumed by the rotifer was generated with C. sorokiniana as the baseline (index = 1.000) indicating most susceptible among species tested. Other species' susceptibilities are indicated in parenthesis as follows: Monoraphidium spp. (0.997), Chlamydomonas globosa (0.827), Botryococcus braunii (0.740), Chlorella minutissima (0.570), Chlamydomonas augustae (0.530), Chlamydomonas yellowstonensis (0.500), Scenedesmus bijuga (0.420), and Haematococcus pluvialis (0.360). Two species, namely, S. dimorphus and S. elongatus were unique in that they exhibited an ability to suppress the growth of the rotifer as indicated by the decline in rotifer populations in their presence. Conclusions: Variations in susceptibility of algal species to rotifer predation could be a result of their individual morphology, cell walls structure, or the biochemical composition of individual species

5-Aza-2'-deoxycytidine causes replication lesions that require Fanconi anemia-dependent homologous recombination for repair

5-Aza-2′-deoxycytidine (5-azadC) is a DNA methyltransferase (DNMT) inhibitor increasingly used in treatments of hematological diseases and works by being incorporated into DNA and trapping DNMT. It is unclear what DNA lesions are caused by 5-azadC and if such are substrates for DNA repair. Here, we identify that 5-azadC induces DNA damage as measured by γ-H2AX and 53BP1 foci. Furthermore, 5-azadC induces radial chromosomes and chromatid breaks that depend on active replication, which altogether suggest that trapped DNMT collapses oncoming replication forks into double-strand breaks. We demonstrate that RAD51-mediated homologous recombination (HR) is activated to repair 5-azadC collapsed replication forks. Fanconi anemia (FA) is a rare autosomal recessive disorder, and deaths are often associated with leukemia. Here, we show that FANCG -deficient cells fail to trigger HR-mediated repair of 5-azadC-induced lesions, leading to accumulation of chromatid breaks and inter-chromosomal radial fusions as well as hypersensitivity to the cytotoxic effects of 5-azadC. These data demonstrate that the FA pathway is important to protect from 5-azadC-induced toxicity. Altogether, our data demonstrate that cytotoxicity of the epigenetic drug 5-azadC can, at least in part, be explained by collapsed replication forks requiring FA-mediated HR for repair

Criterion A of the AMPD in HiTOP

The categorical model of personality disorder classification in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (5th ed. [DSM-5]; American Psychiatric Association, 2013) is highly and fundamentally problematic. Proposed for DSM-5 and provided within Section III (for Emerging Measures and Models) was the Alternative Model of Personality Disorder (AMPD) classification, consisting of Criterion A (self-interpersonal deficits) and Criterion B (maladaptive personality traits). A proposed alternative to the DSM-5 more generally is an empirically based dimensional organization of psychopathology identified as the Hierarchical Taxonomy of Psychopathology (HiTOP; Kotov etal., 2017). HiTOP currently includes, at the highest level, a general factor of psychopathology. Further down are the five domains of detachment, antagonistic externalizing, disinhibited externalizing, thought disorder, and internalizing (along with a provisional sixth somatoform dimension) that align with Criterion B. The purpose of this article is to discuss the potential inclusion and placement of the self-interpersonal deficits of the DSM-5 Section III Criterion A within HiTOP

Search for B0→π0π0B^{0}\to \pi^{0}\pi^{0} Decay

We have searched for the charmless hadronic decay of B0 mesons into two neutral pions. Using 9.13fb^-1 taken at the Upsilon(4S) with the CLEO detector, we obtain an improved upper limit for the branching fraction BR(B0-->pi0pi0) < 5.7*10^-6 at the 90% confidence level.Comment: pages postscript, also available through http://w4.lns.cornell.edu/public/CLN

Search for the Higgs boson in lepton, tau and jets final states

We present a search for the standard model Higgs boson in final states with an electron or muon and a hadronically decaying tau lepton in association with two or more jets using 9.7 fb^{-1} of Run II Fermilab Tevatron Collider data collected with the D0 detector. The analysis is sensitive to Higgs boson production via gluon fusion, associated vector boson production, and vector boson fusion, followed by the Higgs boson decay to tau lepton pairs or to W boson pairs. The ratios of 95% C.L. upper limits on the cross section times branching ratio to those predicted by the standard model are obtained for orthogonal subsamples that are enriched in either H -> tau tau decays or H -> WW decays, and for the combination of these subsample limits. The observed and expected limit ratios for the combined subsamples at a Higgs boson mass of 125 GeV are 11.3 and 9.0 respectively

Measurement of Leptonic Asymmetries and Top Quark Polarization in ttbar Production

We present measurements of lepton (l) angular distributions in ttbar -> W+ b W- b -> l+ nu b l- nubar bbar decays produced in ppbar collisions at a center-of-mass energy of sqrt(s)=1.96TeV, where l is an electron or muon. Using data corresponding to an integrated luminosity of 5.4fb^-1, collected with the D0 detector at the Fermilab Collider, we find that the angular distributions of l- relative to anti-protons and l+ relative to protons are in agreement with each other. Combining the two distributions and correcting for detector acceptance we obtain the forward-backward asymmetry A^l_FB = (5.8 +- 5.1(stat) +- 1.3(syst))%, compared to the standard model prediction of A^l_FB (predicted) = (4.7 +- 0.1)%. This result is further combined with the measurement based on the analysis of the l+jets final state to obtain A^l_FB = (11.8 +- 3.2)%. Furthermore, we present a first study of the top-quark polarization.Comment: submitted versio

Search for WHWH associated production in ppˉp \bar{p} collisions at s=1.96 TeV\sqrt{s}=1.96\,{\rm TeV}

This report describes a search for associated production of $W$ and Higgs bosons based on data corresponding to an integrated luminosity of $\cal{L}$$\approx 5.3 \rm fb^{-1}$ collected with the D0 detector at the Fermilab Tevatron $p\bar{p}$ Collider. Events containing a $W\rightarrow \ell \nu$ candidate (with $\ell$ corresponding to $e$ or $\mu$) are selected in association with two or three reconstructed jets. One or two of the jets are required to be consistent with having evolved from a $b$ quark. A multivariate discriminant technique is used to improve the separation of signal and backgrounds. Expected and observed upper limits are obtained for the product of the $WH$ production cross section and branching ratios and reported in terms of ratios relative to the prediction of the standard model as a function of the mass of the Higgs boson ($M_{H}$). The observed and expected 95% C.L. upper limits obtained for an assumed $M_{H}=115 \rm GeV$ are, respectively, factors of 4.5 and 4.8 larger than the value predicted by the standard model.Comment: 25 pages, 14 figure

Search for first generation leptoquark pair production in the electron + missing energy + jets final state

We present a search for the pair production of first generation scalar leptoquarks (LQ) in data corresponding to an integrated luminosity of 5.4 fb$^{-1}$ collected with the D0 detector at the Fermilab Tevatron Collider in ppbar collisions at $\sqrt{s}=1.96$ TeV. In the channel $LQ \bar{LQ} \rightarrow e\nu_e qq'$, where q, q' are u or d quarks, no significant excess of data over background is observed, and we set a 95% C.L. lower limit of 326 GeV on the leptoquark mass, assuming equal probabilities of leptoquark decays to eq and $\nu_e q'$.Comment: 7 pages, 6 figures, submitted to PRD-R