Comparison of Cytokine Responses in Ecuadorian Children Infected with Giardia, Ascaris, or Both Parasites.

More than 2 billion people are infected with parasites globally, and the majority have coinfections. Intestinal protozoa and helminths induce polarizing CD4(+) T-helper cell 1 (Th1) mediated cytokine responses within the host. Such immune polarization may inhibit the ability of the host to mount an adequate immune response for pathogen clearance to concurrent pathogens. The current study evaluated the plasma cytokine profile in Ascaris and Giardia coinfected children compared with Giardia- and Ascaris-only infected children. Fecal samples and blood samples were collected from asymptomatic 3-year-old children living in the district of Quininde, Ecuador. Stool samples that tested positive for Giardia lamblia-only, Ascaris lumbricoides-only, or G. lamblia and A. lumbricoides coinfections were confirmed by quantitative real-time polymerase chain reaction. Plasma samples from the study subjects were used to quantitate cytokines. A total of 39 patients were evaluated. Children with coinfection had a significant decrease in Th1 cytokine production, interleukin 2 (IL-2) (P < 0.05), IL-12 (P < 0.05), and tumor necrosis factor alpha (P < 0.05) compared with Giardia-only infected children. Coinfected children had an increase in IL-10/interferon gamma (IFN-γ) ratio compared with uninfected (P < 0.05) and Ascaris alone (P < 0.05). The increased IL-10/IFN-γ ratio in the setting of decreased Th1 cytokine response indicates Th2 polarization in the coinfected group. Reduced Th1 cytokines in children coinfected with Ascaris and Giardia may impair the host's ability to eradicate Giardia infection leading to chronic giardiasis

Supergravity Black Holes and Billiards and Liouville integrable structure of dual Borel algebras

In this paper we show that the supergravity equations describing both cosmic billiards and a large class of black-holes are, generically, both Liouville integrable as a consequence of the same universal mechanism. This latter is provided by the Liouville integrable Poissonian structure existing on the dual Borel algebra B_N of the simple Lie algebra A_{N-1}. As a by product we derive the explicit integration algorithm associated with all symmetric spaces U/H^{*} relevant to the description of time-like and space-like p-branes. The most important consequence of our approach is the explicit construction of a complete set of conserved involutive hamiltonians h_{\alpha} that are responsible for integrability and provide a new tool to classify flows and orbits. We believe that these will prove a very important new tool in the analysis of supergravity black holes and billiards.Comment: 48 pages, 7 figures, LaTex; V1: misprints corrected, two references adde

Automatic Detection of Malignant Masses in Digital Mammograms Based on a MCET-HHO Approach

Digital image processing techniques have become an important process within medical images. These techniques allow the improvement of the images in order to facilitate their interpretation for specialists. Within these are the segmentation methods, which help to divide the images by regions based on different approaches, in order to identify details that may be complex to distinguish initially. In this work, it is proposed the implementation of a multilevel threshold segmentation technique applied to mammography images, based on the Harris Hawks Optimization (HHO) algorithm, in order to identify regions of interest (ROIs) that contain malignant masses. The method of minimum cross entropy thresholding (MCET) is used to select the optimal threshold values for the segmentation. For the development of this work, four mammography images were used (all with presence of a malignant tumor), in their two views, craniocaudal (CC) and mediolateral oblique (MLO), obtained from the Digital Database for Screening Mammography (DDSM). Finally, the ROIs calculated were compared with the original ROIs of the database through a series of metrics, to evaluate the behavior of the algorithm. According to the results obtained, where it is shown that the agreement between the original ROIs and the calculated ROIs is significantly high, it is possible to conclude that the proposal of the MCET-HHO algorithm allows the automatic identification of ROIs containing malignant tumors in mammography images with significant accuracy.Digital image processing techniques have become an important process within medical images. These techniques allow the improvement of the images in order to facilitate their interpretation for specialists. Within these are the segmentation methods, which help to divide the images by regions based on different approaches, in order to identify details that may be complex to distinguish initially. In this work, it is proposed the implementation of a multilevel threshold segmentation technique applied to mammography images, based on the Harris Hawks Optimization (HHO) algorithm, in order to identify regions of interest (ROIs) that contain malignant masses. The method of minimum cross entropy thresholding (MCET) is used to select the optimal threshold values for the segmentation. For the development of this work, four mammography images were used (all with presence of a malignant tumor), in their two views, craniocaudal (CC) and mediolateral oblique (MLO), obtained from the Digital Database for Screening Mammography (DDSM). Finally, the ROIs calculated were compared with the original ROIs of the database through a series of metrics, to evaluate the behavior of the algorithm. According to the results obtained, where it is shown that the agreement between the original ROIs and the calculated ROIs is significantly high, it is possible to conclude that the proposal of the MCET-HHO algorithm allows the automatic identification of ROIs containing malignant tumors in mammography images with significant accuracy

Can inorganic elements affect herpesvirus infections in European eels?

SHORT RESEARCH AND DISCUSSION ARTICLEIn combination, pollution and pathogens represent a serious threat to the health of European eels that has been increasingly recognized. Thus, the impact of contaminants, cadmium, lead,mercury, and selenium, on anguillid herpesvirus 1 infection inwild European eels has been evaluated. Despite the small sample size, results indicate that selenium and mercury concentrations may compromise the European eel immune system as herpesvirus infection was more prevalent in specimens with higher Hg and Se hepatic concentrations.Versión del editor2,65

CDK targets Sae2 to control DNA-end resection and homologous recombination

DNA double-strand breaks (DSBs) are repaired by two principal mechanisms: non-homologous end-joining (NHEJ) and homologous recombination (HR)1. HR is the most accurate DSB repair mechanism but is generally restricted to the S and G2 phases of the cell cycle, when DNA has been replicated and a sister chromatid is available as a repair template2-5. By contrast, NHEJ operates throughout the cell cycle but assumes most importance in G1 (refs 4​, ​6). The choice between repair pathways is governed by cyclin-dependent protein kinases (CDKs)2,3,5,7, with a major site of control being at the level of DSB resection, an event that is necessary for HR but not NHEJ, and which takes place most effectively in S and G2 (refs 2​, ​5). Here we establish that cell-cycle control of DSB resection in Saccharomyces cerevisiae results from the phosphorylation by CDK of an evolutionarily conserved motif in the Sae2 protein. We show that mutating Ser 267 of Sae2 to a non-phosphorylatable residue causes phenotypes comparable to those of a sae2Δ null mutant, including hypersensitivity to camptothecin, defective sporulation, reduced hairpin-induced recombination, severely impaired DNA-end processing and faulty assembly and disassembly of HR factors. Furthermore, a Sae2 mutation that mimics constitutive Ser 267 phosphorylation complements these phenotypes and overcomes the necessity of CDK activity for DSB resection. The Sae2 mutations also cause cell-cycle-stage specific hypersensitivity to DNA damage and affect the balance between HR and NHEJ. These findings therefore provide a mechanistic basis for cell-cycle control of DSB repair and highlight the importance of regulating DSB resection

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

SIMS: A Hybrid Method for Rapid Conformational Analysis

Proteins are at the root of many biological functions, often performing complex tasks as the result of large changes in their structure. Describing the exact details of these conformational changes, however, remains a central challenge for computational biology due the enormous computational requirements of the problem. This has engendered the development of a rich variety of useful methods designed to answer specific questions at different levels of spatial, temporal, and energetic resolution. These methods fall largely into two classes: physically accurate, but computationally demanding methods and fast, approximate methods. We introduce here a new hybrid modeling tool, the Structured Intuitive Move Selector (SIMS), designed to bridge the divide between these two classes, while allowing the benefits of both to be seamlessly integrated into a single framework. This is achieved by applying a modern motion planning algorithm, borrowed from the field of robotics, in tandem with a well-established protein modeling library. SIMS can combine precise energy calculations with approximate or specialized conformational sampling routines to produce rapid, yet accurate, analysis of the large-scale conformational variability of protein systems. Several key advancements are shown, including the abstract use of generically defined moves (conformational sampling methods) and an expansive probabilistic conformational exploration. We present three example problems that SIMS is applied to and demonstrate a rapid solution for each. These include the automatic determination of ﾑﾑactiveﾒﾒ residues for the hinge-based system Cyanovirin-N, exploring conformational changes involving long-range coordinated motion between non-sequential residues in Ribose- Binding Protein, and the rapid discovery of a transient conformational state of Maltose-Binding Protein, previously only determined by Molecular Dynamics. For all cases we provide energetic validations using well-established energy fields, demonstrating this framework as a fast and accurate tool for the analysis of a wide range of protein flexibility problems