The Mannose Receptor Mediates Dengue Virus Infection of Macrophages

Macrophages (MØ) and mononuclear phagocytes are major targets of infection by dengue virus (DV), a mosquito-borne flavivirus that can cause haemorrhagic fever in humans. To our knowledge, we show for the first time that the MØ mannose receptor (MR) binds to all four serotypes of DV and specifically to the envelope glycoprotein. Glycan analysis, ELISA, and blot overlay assays demonstrate that MR binds via its carbohydrate recognition domains to mosquito and human cell–produced DV antigen. This binding is abrogated by deglycosylation of the DV envelope glycoprotein. Surface expression of recombinant MR on NIH3T3 cells confers DV binding. Furthermore, DV infection of primary human MØ can be blocked by anti-MR antibodies. MR is a prototypic marker of alternatively activated MØ, and pre-treatment of human monocytes or MØ with type 2 cytokines (IL-4 or IL-13) enhances their susceptibility to productive DV infection. Our findings indicate a new functional role for the MR in DV infection

Run Generation Revisited: What Goes Up May or May Not Come Down

In this paper, we revisit the classic problem of run generation. Run generation is the first phase of external-memory sorting, where the objective is to scan through the data, reorder elements using a small buffer of size M , and output runs (contiguously sorted chunks of elements) that are as long as possible. We develop algorithms for minimizing the total number of runs (or equivalently, maximizing the average run length) when the runs are allowed to be sorted or reverse sorted. We study the problem in the online setting, both with and without resource augmentation, and in the offline setting. (1) We analyze alternating-up-down replacement selection (runs alternate between sorted and reverse sorted), which was studied by Knuth as far back as 1963. We show that this simple policy is asymptotically optimal. Specifically, we show that alternating-up-down replacement selection is 2-competitive and no deterministic online algorithm can perform better. (2) We give online algorithms having smaller competitive ratios with resource augmentation. Specifically, we exhibit a deterministic algorithm that, when given a buffer of size 4M , is able to match or beat any optimal algorithm having a buffer of size M . Furthermore, we present a randomized online algorithm which is 7/4-competitive when given a buffer twice that of the optimal. (3) We demonstrate that performance can also be improved with a small amount of foresight. We give an algorithm, which is 3/2-competitive, with foreknowledge of the next 3M elements of the input stream. For the extreme case where all future elements are known, we design a PTAS for computing the optimal strategy a run generation algorithm must follow. (4) Finally, we present algorithms tailored for nearly sorted inputs which are guaranteed to have optimal solutions with sufficiently long runs

Dioxin Toxicity In Vivo Results from an Increase in the Dioxin-Independent Transcriptional Activity of the Aryl Hydrocarbon Receptor

The Aryl hydrocarbon receptor (Ahr) is the nuclear receptor mediating the toxicity of dioxins -widespread and persistent pollutants whose toxic effects include tumor promotion, teratogenesis, wasting syndrome and chloracne. Elimination of Ahr in mice eliminates dioxin toxicity but also produces adverse effects, some seemingly unrelated to dioxin. Thus the relationship between the toxic and dioxin-independent functions of Ahr is not clear, which hampers understanding and treatment of dioxin toxicity. Here we develop a Drosophila model to show that dioxin actually increases the in vivo dioxin-independent activity of Ahr. This hyperactivation resembles the effects caused by an increase in the amount of its dimerisation partner Ahr nuclear translocator (Arnt) and entails an increased transcriptional potency of Ahr, in addition to the previously described effect on nuclear translocation. Thus the two apparently different functions of Ahr, dioxin-mediated and dioxin-independent, are in fact two different levels (hyperactivated and basal, respectively) of a single function

T helper cell subsets specific for pseudomonas aeruginosa in healthy individuals and patients with cystic fibrosis

Background: We set out to determine the magnitude of antigen-specific memory T helper cell responses to Pseudomonas aeruginosa in healthy humans and patients with cystic fibrosis. Methods: Peripheral blood human memory CD4+ T cells were co-cultured with dendritic cells that had been infected with different strains of Pseudomonas aeruginosa. The T helper response was determined by measuring proliferation, immunoassay of cytokine output, and immunostaining of intracellular cytokines. Results: Healthy individuals and patients with cystic fibrosis had robust antigen-specific memory CD4+ T cell responses to Pseudomonas aeruginosa that not only contained a Th1 and Th17 component but also Th22 cells. In contrast to previous descriptions of human Th22 cells, these Pseudomonal-specific Th22 cells lacked the skin homing markers CCR4 or CCR10, although were CCR6+. Healthy individuals and patients with cystic fibrosis had similar levels of Th22 cells, but the patient group had significantly fewer Th17 cells in peripheral blood. Conclusions: Th22 cells specific to Pseudomonas aeruginosa are induced in both healthy individuals and patients with cystic fibrosis. Along with Th17 cells, they may play an important role in the pulmonary response to this microbe in patients with cystic fibrosis and other conditions

Saccadic facilitation by modulation of microsaccades in natural backgrounds

Saccades move objects of interest into the center of the visual field for high-acuity visual analysis. White, Stritzke, and Gegenfurtner (Current Biology, 18, 124–128, 2008) have shown that saccadic latencies in the context of a structured background are much shorter than those with an unstructured background at equal levels of visibility. This effect has been explained by possible preactivation of the saccadic circuitry whenever a structured background acts as a mask for potential saccade targets. Here, we show that background textures modulate rates of microsaccades during visual fixation. First, after a display change, structured backgrounds induce a stronger decrease of microsaccade rates than do uniform backgrounds. Second, we demonstrate that the occurrence of a microsaccade in a critical time window can delay a subsequent saccadic response. Taken together, our findings suggest that microsaccades contribute to the saccadic facilitation effect, due to a modulation of microsaccade rates by properties of the background

Following wrong suggestions: self-blame in human and computer scenarios

This paper investigates the specific experience of following a suggestion by an intelligent machine that has a wrong outcome and the emotions people feel. By adopting a typical task employed in studies on decision-making, we presented participants with two scenarios in which they follow a suggestion and have a wrong outcome by either an expert human being or an intelligent machine. We found a significant decrease in the perceived responsibility on the wrong choice when the machine offers the suggestion. At present, few studies have investigated the negative emotions that could arise from a bad outcome after following the suggestion given by an intelligent system, and how to cope with the potential distrust that could affect the long-term use of the system and the cooperation. This preliminary research has implications in the study of cooperation and decision making with intelligent machines. Further research may address how to offer the suggestion in order to better cope with user's self-blame.Comment: To be published in the Proceedings of IFIP Conference on Human-Computer Interaction (INTERACT)201

Identification of Colletotrichum species associated with anthracnose disease of coffee in Vietnam

Colletotrichum gloeosporioides, C. acutatum, C. capsici and C. boninense associated with anthracnose disease on coffee (Coffea spp.) in Vietnam were identified based on morphology and DNA analysis. Phylogenetic analysis of DNA sequences from the internal transcribed spacer region of nuclear rDNA and a portion of mitochondrial small subunit rRNA were concordant and allowed good separation of the taxa. We found several Colletotrichum isolates of unknown species and their taxonomic position remains unresolved. The majority of Vietnamese isolates belonged to C. gloeosporioides and they grouped together with the coffee berry disease (CBD) fungus, C. kahawae. However, C. kahawae could be distinguished from the Vietnamese C. gloeosporioides isolates based on ammonium tartrate utilization, growth rate and pathogenictity. C. gloeosporioides isolates were more pathogenic on detached green berries than isolates of the other species, i.e. C. acutatum, C capsici and C. boninense. Some of the C. gloeosporioides isolates produced slightly sunken lesion on green berries resembling CBD symptoms but it did not destroy the bean. We did not find any evidence of the presence of C. kahawae in Vietnam

Human Female Genital Tract Infection by the Obligate Intracellular Bacterium Chlamydia trachomatis Elicits Robust Type 2 Immunity

While Chlamydia trachomatis infections are frequently asymptomatic, mechanisms that regulate host response to this intracellular Gram-negative bacterium remain undefined. This investigation thus used peripheral blood mononuclear cells and endometrial tissue from women with or without Chlamydia genital tract infection to better define this response. Initial genome-wide microarray analysis revealed highly elevated expression of matrix metalloproteinase 10 and other molecules characteristic of Type 2 immunity (e.g., fibrosis and wound repair) in Chlamydia-infected tissue. This result was corroborated in flow cytometry and immunohistochemistry studies that showed extant upper genital tract Chlamydia infection was associated with increased co-expression of CD200 receptor and CD206 (markers of alternative macrophage activation) by endometrial macrophages as well as increased expression of GATA-3 (the transcription factor regulating TH2 differentiation) by endometrial CD4+ T cells. Also among women with genital tract Chlamydia infection, peripheral CD3+ CD4+ and CD3+ CD4- cells that proliferated in response to ex vivo stimulation with inactivated chlamydial antigen secreted significantly more interleukin (IL)-4 than tumor necrosis factor, interferon-γ, or IL-17; findings that repeated in T cells isolated from these same women 1 and 4 months after infection had been eradicated. Our results thus newly reveal that genital infection by an obligate intracellular bacterium induces polarization towards Type 2 immunity, including Chlamydia-specific TH2 development. Based on these findings, we now speculate that Type 2 immunity was selected by evolution as the host response to C. trachomatis in the human female genital tract to control infection and minimize immunopathological damage to vital reproductive structures. © 2013 Vicetti Miguel et al