Filoviruses utilize glycosaminoglycans for their attachment to target cells

Filoviruses are the cause of severe hemorrhagic fever in human and nonhuman primates. The envelope glycoprotein (GP), responsible for both receptor binding and fusion of the virus envelope with the host cell membrane, has been demonstrated to interact with multiple molecules in order to enhance entry into host cells. Here we have demonstrated that filoviruses utilize glycosaminoglycans, and more specifically heparan sulfate proteoglycans, for their attachment to host cells. This interaction is mediated by GP and does not require the presence of the mucin domain. Both the degree of sulfation and the structure of the carbohydrate backbone play a role in the interaction with filovirus GPs. This new step of filovirus interaction with host cells can potentially be a new target for antiviral strategies. As such, we were able to inhibit filovirus GP-mediated infection using carrageenan, a broad-spectrum microbicide that mimics heparin, and also using the antiviral dendrimeric peptide SB105-A10, which interacts with heparan sulfate, antagonizing the binding of the virus to cells

Looking the Part: Social Status Cues Shape Race Perception

It is commonly believed that race is perceived through another's facial features, such as skin color. In the present research, we demonstrate that cues to social status that often surround a face systematically change the perception of its race. Participants categorized the race of faces that varied along White–Black morph continua and that were presented with high-status or low-status attire. Low-status attire increased the likelihood of categorization as Black, whereas high-status attire increased the likelihood of categorization as White; and this influence grew stronger as race became more ambiguous (Experiment 1). When faces with high-status attire were categorized as Black or faces with low-status attire were categorized as White, participants' hand movements nevertheless revealed a simultaneous attraction to select the other race-category response (stereotypically tied to the status cue) before arriving at a final categorization. Further, this attraction effect grew as race became more ambiguous (Experiment 2). Computational simulations then demonstrated that these effects may be accounted for by a neurally plausible person categorization system, in which contextual cues come to trigger stereotypes that in turn influence race perception. Together, the findings show how stereotypes interact with physical cues to shape person categorization, and suggest that social and contextual factors guide the perception of race

Timing of immune escape linked to success or failure of vaccination

Successful vaccination against HIV should limit viral replication sufficiently to prevent the emergence of viral immune escape mutations. Broadly directed immunity is likely to be required to limit opportunities for immune escape variants to flourish. We studied the emergence of an SIV Gag cytotoxic T cell immune escape variant in pigtail macaques expressing the Mane-A*10 MHC I allele using a quantitative RT-PCR to measure viral loads of escape and wild type variants. Animals receiving whole Gag expressing vaccines completely controlled an SIVmac251 challenge, had broader CTL responses and exhibited minimal CTL escape. In contrast, animals vaccinated with only a single CTL epitope and challenged with the same SIVmac251 stock had high levels of viral replication and rapid CTL escape. Unvaccinated na&iuml;ve animals exhibited a slower emergence of immune escape variants. Thus narrowly directed vaccination against a single epitope resulted in rapid immune escape and viral levels equivalent to that of na&iuml;ve unvaccinated animals. These results emphasize the importance of inducing broadly directed HIV-specific immunity that effectively quashes early viral replication and limits the generation of immune escape variants. This has important implications for the selection of HIV vaccines for expanded human trials.<br /

Do differences in understory light contribute to species distributions along a tropical rainfall gradient?

In tropical forests, regional differences in annual rainfall correlate with differences in plant species composition. Although water availability is clearly one factor determining species distribution, other environmental variables that covary with rainfall may contribute to distributions. One such variable is light availability in the understory, which decreases towards wetter forests due to differences in canopy density and phenology. We established common garden experiments in three sites along a rainfall gradient across the Isthmus of Panama in order to measure the differences in understory light availability, and to evaluate their influence on the performance of 24 shade-tolerant species with contrasting distributions. Within sites, the effect of understory light availability on species performance depended strongly on water availability. When water was not limiting, either naturally in the wetter site or through water supplementation in drier sites, seedling performance improved at higher light. In contrast, when water was limiting at the drier sites, seedling performance was reduced at higher light, presumably due to an increase in water stress that affected mostly wet-distribution species. Although wetter forest understories were on average darker, wet-distribution species were not more shade-tolerant than dry-distribution species. Instead, wet-distribution species had higher absolute growth rates and, when water was not limiting, were better able to take advantage of small increases in light than dry-distribution species. Our results suggest that in wet forests the ability to grow fast during temporary increases in light may be a key trait for successful recruitment. The slower growth rates of the dry-distribution species, possibly due to trade-offs associated with greater drought tolerance, may exclude these species from wetter forests

Evaluation of Wuchereria bancrofti GST as a Vaccine Candidate for Lymphatic Filariasis

Lymphatic parasites survive for years in a complex immune environment by adopting various strategies of immune modulation, which includes counteracting the oxidative free radical damage caused by the host. We now know that the filarial parasites secrete antioxidant enzymes. Among these, the glutathione-S-transferases (GSTs) have the potent ability to effectively neutralize cytotoxic products arising from reactive oxygen species (ROS) that attack cell membranes. Thus, GSTs have the potential to protect the parasite against host oxidative stress. GSTs of several helminthes, including schistosomes, fasciola and the filarial parasite Seteria cervi, are also involved in inducing protective immunity in the host. The schistosome 28 kDa GST has been successfully developed into a vaccine and is currently in Phase II clinical trials. Thus, GST appears to be a potential target for vaccine development. Therefore, in the present study, we cloned W. bancrofti GST, and expressed and purified the recombinant protein. Immunization and challenge experiments showed that 61% of protection could be achieved against B. malayi infections in a jird model. In vitro studies confirm that the anti-WbGST antibodies participate in the killing of B. malayi L3 through an ADCC mechanism and enzymatic activity of WbGST appears to be critical for this larvicidal function

Role of voiding and storage symptoms for the quality of life before and after treatment in men with voiding dysfunction

Previous studies on associations between voiding dysfunction and quality of life (QoL) have largely been limited to baseline data. Therefore, we have explored associations between Q (max) and voiding and storage sub-scores of the International Prostate Symptom Score (IPSS) before and after treatment with QoL. Analysis of a single-center database of 2,316 men with voiding dysfunction attributed to benign prostatic hyperplasia undergoing various medical and surgical treatment forms. Q (max) exhibited little correlation with QoL before or after treatment. IPSS inversely correlated with QoL at baseline and after treatment, and IPSS improvements correlated with those of QoL. The associations applied to both the voiding and storage sub-score of the IPSS, with the latter consistently exhibiting somewhat tighter associations. Our post-treatment data support the idea of a cause-effect relationship between voiding symptoms and QoL irrespective of treatment form. While both voiding and storage symptoms contribute to this relationship, storage symptoms play a somewhat greater rol

Studying the Underlying Event in Drell-Yan and High Transverse Momentum Jet Production at the Tevatron

We study the underlying event in proton-antiproton collisions by examining the behavior of charged particles (transverse momentum pT > 0.5 GeV/c, pseudorapidity |\eta| < 1) produced in association with large transverse momentum jets (~2.2 fb-1) or with Drell-Yan lepton-pairs (~2.7 fb-1) in the Z-boson mass region (70 < M(pair) < 110 GeV/c2) as measured by CDF at 1.96 TeV center-of-mass energy. We use the direction of the lepton-pair (in Drell-Yan production) or the leading jet (in high-pT jet production) in each event to define three regions of \eta-\phi space; toward, away, and transverse, where \phi is the azimuthal scattering angle. For Drell-Yan production (excluding the leptons) both the toward and transverse regions are very sensitive to the underlying event. In high-pT jet production the transverse region is very sensitive to the underlying event and is separated into a MAX and MIN transverse region, which helps separate the hard component (initial and final-state radiation) from the beam-beam remnant and multiple parton interaction components of the scattering. The data are corrected to the particle level to remove detector effects and are then compared with several QCD Monte-Carlo models. The goal of this analysis is to provide data that can be used to test and improve the QCD Monte-Carlo models of the underlying event that are used to simulate hadron-hadron collisions.Comment: Submitted to Phys.Rev.

Precision measurement of the top quark mass from dilepton events at CDF II

We report a measurement of the top quark mass, M_t, in the dilepton decay channel of $t\bar{t}\to b\ell'^{+}\nu_{\ell'}\bar{b}\ell^{-}\bar{\nu}_{\ell}$ using an integrated luminosity of 1.0 fb^{-1} of p\bar{p} collisions collected with the CDF II detector. We apply a method that convolutes a leading-order matrix element with detector resolution functions to form event-by-event likelihoods; we have enhanced the leading-order description to describe the effects of initial-state radiation. The joint likelihood is the product of the likelihoods from 78 candidate events in this sample, which yields a measurement of M_{t} = 164.5 \pm 3.9(\textrm{stat.}) \pm 3.9(\textrm{syst.}) \mathrm{GeV}/c^2, the most precise measurement of M_t in the dilepton channel.Comment: 7 pages, 2 figures, version includes changes made prior to publication by journa

Measurement of the Ratios of Branching Fractions B(Bs -> Ds pi pi pi) / B(Bd -> Dd pi pi pi) and B(Bs -> Ds pi) / B(Bd -> Dd pi)

Using 355 pb^-1 of data collected by the CDF II detector in \ppbar collisions at sqrt{s} = 1.96 TeV at the Fermilab Tevatron, we study the fully reconstructed hadronic decays B -> D pi and B -> D pi pi pi. We present the first measurement of the ratio of branching fractions B(Bs -> Ds pi pi pi) / B(Bd -> Dd pi pi pi) = 1.05 pm 0.10 (stat) pm 0.22 (syst). We also update our measurement of B(Bs -> Ds pi) / B(Bd -> Dd pi) to 1.13 pm 0.08 (stat) pm 0.23 (syst) improving the statistical uncertainty by more than a factor of two. We find B(Bs -> Ds pi) = [3.8 pm 0.3 (stat) pm 1.3 (syst)] \times 10^{-3} and B(Bs -> Ds pi pi pi) = [8.4 pm 0.8 (stat) pm 3.2 (syst)] \times 10^{-3}.Comment: 7 pages, 2 figure