Gap junction reduction in cardiomyocytes following transforming growth factor- beta treatment and Trypanosoma cruzi infection

Gap junction connexin-43 (Cx43) molecules are responsible for electrical impulse conduction in the heart and are affected by transforming growth factor-beta (TGF-beta). This cytokine increases during Trypanosoma cruzi infection, modulating fibrosis and the parasite cell cycle. We studied Cx43 expression in cardiomyocytes exposed or not to TGF-beta T. cruzi, or SB-431542, an inhibitor of TGF-beta receptor type I (ALK-5). Cx43 expression was also examined in hearts with dilated cardiopathy from chronic Chagas disease patients, in which TGF-beta signalling had been shown previously to be highly activated. We demonstrated that TGF-beta treatment induced disorganised gap junctions in non-infected cardiomyocytes, leading to a punctate, diffuse and non-uniform Cx43 staining. A similar pattern was detected in T. cruzi-infected cardiomyocytes concomitant with high TGF-beta secretion. Both results were reversed if the cells were incubated with SB-431542. Similar tests were performed using human chronic chagasic patients and we confirmed a down-regulation of Cx43 expression, an altered distribution of plaques in the heart and a significant reduction in the number and length of Cx43 plaques, which correlated negatively with cardiomegaly. We conclude that elevated TGF-beta levels during T. cruzi infection promote heart fibrosis and disorganise gap junctions, possibly contributing to abnormal impulse conduction and arrhythmia that characterise severe cardiopathy in Chagas disease

Monte Carlo simulation of the transmission of measles: Beyond the mass action principle

We present a Monte Carlo simulation of the transmission of measles within a population sample during its growing and equilibrium states by introducing two different vaccination schedules of one and two doses. We study the effects of the contact rate per unit time $\xi$ as well as the initial conditions on the persistence of the disease. We found a weak effect of the initial conditions while the disease persists when $\xi$ lies in the range 1/L-10/L ($L$ being the latent period). Further comparison with existing data, prediction of future epidemics and other estimations of the vaccination efficiency are provided. Finally, we compare our approach to the models using the mass action principle in the first and another epidemic region and found the incidence independent of the number of susceptibles after the epidemic peak while it strongly fluctuates in its growing region. This method can be easily applied to other human, animals and vegetable diseases and includes more complicated parameters.Comment: 15 pages, 4 figures, 1 table, Submitted to Phys.Rev.

Oncogenic and incidental HPV types associated with histologically confirmed cervical intraepithelial neoplasia in HIV-positive and HIV-negative South African women

Background. In Africa, data on the relationship between oncogenic human papillomavirus (HPV) types, immune status and cervical preinvasive lesions are lacking.Methods. We investigated low-risk (lrHPV) and high-risk (hrHPV) HPV types in a cohort of women with cervical intraepithelial neoplasia (CIN) II/III confirmed on histological examination, in an urban setting with a high prevalence of HIV infection.Results. Of 270 women with confirmed CIN II/III, 45 were HIV-negative and 225 HIV-positive. HIV-infected women had significantly more HPV type infections, including all HPV (p<0.001) and hrHPV (p=0.014) types. The prevalences of one or more hrHPV type/s were 93.3% and 92.9% in HIV-negative and positive patients, respectively. The most prevalent hrHPV type among HIV-negative women was HPV 16, followed by HPV 52, 31, 35 and 58. Among HIV-positive women, HPV 16 was followed by HPV 58, 35, 51 and 52. Not yet qualifying for highly active antiretroviral therapy (HAART) (CD4 count >350 cells/μL) or having received HAART for ≥12 months were negatively associated with HPV 18, 33, 45, 51, 52, 59 and 82.Conclusions. In South Africa, burdened by the HIV pandemic, high numbers of high- and low-risk HPV type infections are present in women with cervical preneoplasia. HPV type distribution differs among varying levels of HIV-induced immune depletion

Heterotic domain wall solutions and SU(3) structure manifolds

We examine compactifications of heterotic string theory on manifolds with SU(3) structure. In particular, we study N = 1/2 domain wall solutions which correspond to the perturbative vacua of the 4D, N =1 supersymmetric theories associated to these compactifications. We extend work which has appeared previously in the literature in two important regards. Firstly, we include two additional fluxes which have been, heretofore, omitted in the general analysis of this situation. This allows for solutions with more general torsion classes than have previously been found. Secondly, we provide explicit solutions for the fluxes as a function of the torsion classes. These solutions are particularly useful in deciding whether equations such as the Bianchi identities can be solved, in addition to the Killing spinor equations themselves. Our work can be used to straightforwardly decide whether any given SU(3) structure on a six-dimensional manifold is associated with a solution to heterotic string theory. To illustrate how to use these results, we discuss a number of examples taken from the literature.Comment: 34 pages, minor corrections in second versio

Mobile Communication Signatures of Unemployment

The mapping of populations socio-economic well-being is highly constrained by the logistics of censuses and surveys. Consequently, spatially detailed changes across scales of days, weeks, or months, or even year to year, are difficult to assess; thus the speed of which policies can be designed and evaluated is limited. However, recent studies have shown the value of mobile phone data as an enabling methodology for demographic modeling and measurement. In this work, we investigate whether indicators extracted from mobile phone usage can reveal information about the socio-economical status of microregions such as districts (i.e., average spatial resolution < 2.7km). For this we examine anonymized mobile phone metadata combined with beneficiaries records from unemployment benefit program. We find that aggregated activity, social, and mobility patterns strongly correlate with unemployment. Furthermore, we construct a simple model to produce accurate reconstruction of district level unemployment from their mobile communication patterns alone. Our results suggest that reliable and cost-effective economical indicators could be built based on passively collected and anonymized mobile phone data. With similar data being collected every day by telecommunication services across the world, survey-based methods of measuring community socioeconomic status could potentially be augmented or replaced by such passive sensing methods in the future

Using “Omics” and Integrated Multi-Omics Approaches to Guide Probiotic Selection to Mitigate Chytridiomycosis and Other Emerging Infectious Diseases

Emerging infectious diseases in wildlife are responsible for massive population declines. In amphibians, chytridiomycosis caused by Batrachochytrium dendrobatidis, Bd, has severely affected many amphibian populations and species around the world. One promising management strategy is probiotic bioaugmentation of antifungal bacteria on amphibian skin. In vivo experimental trials using bioaugmentation strategies have had mixed results, and therefore a more informed strategy is needed to select successful probiotic candidates. Metagenomic, transcriptomic, and metabolomic methods, colloquially called “omics,” are approaches that can better inform probiotic selection and optimize selection protocols. The integration of multiple omic data using bioinformatic and statistical tools and in silico models that link bacterial community structure with bacterial defensive function can allow the identification of species involved in pathogen inhibition. We recommend using 16S rRNA gene amplicon sequencing and methods such as indicator species analysis, the Kolmogorov–Smirnov Measure, and co-occurrence networks to identify bacteria that are associated with pathogen resistance in field surveys and experimental trials. In addition to 16S amplicon sequencing, we recommend approaches that give insight into symbiont function such as shotgun metagenomics, metatranscriptomics, or metabolomics to maximize the probability of finding effective probiotic candidates, which can then be isolated in culture and tested in persistence and clinical trials. An effective mitigation strategy to ameliorate chytridiomycosis and other emerging infectious diseases is necessary; the advancement of omic methods and the integration of multiple omic data provide a promising avenue toward conservation of imperiled species

Anesthesia of Epinephelus marginatus with essential oil of Aloysia polystachya: an approach on blood parameters

This study investigated the anesthetic potential of the essential oil (EO) of Aloysia polystachya in juveniles of dusky grouper (Epinephelus marginatus). Fish were exposed to different concentrations of EO of A. polystachya to evaluate time of induction and recovery from anesthesia. In the second experiment, fish were divided into four groups: control, ethanol and 50 or 300 mu L L-1 EO of A. polystachya, and each group was submitted to induction for 3.5 min and recovery for 5 or 10 min. The blood gases and glucose levels showed alterations as a function of the recovery times, but Na+ and K+ levels did not show any alteration. In conclusion, the EO from leaves of A. polystachya is an effective anesthetic for dusky grouper, because anesthesia was reached within the recommended time at EO concentrations of 300 and 400 mu L L-1. However, most evaluated blood parameters showed compensatory responses due to EO exposure.Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul/Programa de Apoio a Nucleos de Excelencia (FAPERGS/PRONEX) [10/0016-8]; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [470964/2009-0]; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brazil (CAPES)info:eu-repo/semantics/publishedVersio

Effects of systematic asymmetric discounting on physician-patient interactions: a theoretical framework to explain poor compliance with lifestyle counseling

BACKGROUND: This study advances the use of a utility model to model physician-patient interactions from the perspectives of physicians and patients. PRESENTATION OF THE HYPOTHESIS: In cases involving acute care, patient counseling involves a relatively straightforward transfer of information from the physician to a patient. The patient has less information than the physician on the impact the condition and its treatment have on utility. In decisions involving lifestyle changes, the patient may have more information than the physician on his/her utility of consumption; moreover, differences in discounting future health may contribute significantly to differences between patients' preferences and physicians' recommendations. TESTING THE HYPOTHESIS: The expectation of differences in internal discount rate between patients and their physicians is discussed. IMPLICATIONS OF THE HYPOTHESIS: This utility model provides a conceptual basis for the finding that educational approaches alone may not effect changes in patient behavior and suggests other economic variables that could be targeted in the attempt to produce healthier behavior

Supersymmetric 3-branes on smooth ALE manifolds with flux

We construct a new family of classical BPS solutions of type IIB supergravity describing 3-branes transverse to a 6-dimensional space with topology R^2*ALE. They are characterized by a non-trivial flux of the supergravity 2-forms through the homology 2-cycles of a generic smooth ALE manifold. Our solutions have two Killing spinors and thus preserve N=2 supersymmetry. They are expressed in terms of a quasi harmonic function H (the ``warp factor''), whose properties we study in the case of the simplest ALE, namely the Eguchi-Hanson manifold. The equation for H is identified as an instance of the confluent Heun equation. We write explicit power series solutions and solve the recurrence relation for the coefficients, discussing also the relevant asymptotic expansions. While, as in all such N=2 solutions, supergravity breaks down near the brane, the smoothing out of the vacuum geometry has the effect that the warp factor is regular in a region near the cycle. We interpret the behavior of the warp factor as describing a three-brane charge ``smeared'' over the cycle and consider the asymptotic form of the geometry in that region, showing that conformal invariance is broken even when the complex type IIB 3-form field strength is assumed to vanish. We conclude with a discussion of the basic features of the gauge theory dual.Comment: latex, 36 pages (26 + appendix). Some statements on the gauge dual made more precise. Final version to appear on NP