An interleukin-33/ST2 signaling deficiency reduces overt pain-like behaviors in mice

Interleukin (IL)-33, the most recent member of the IL family of cytokines, signals through the ST2 receptor. IL-33/ST2 signaling mediates antigen challenge-induced mechanical hyperalgesia in the joints and cutaneous tissues of immunized mice. The present study asked whether IL-33/ST2 signaling is relevant to overt pain-like behaviors in mice. Acetic acid and phenyl-p-benzoquinone induced significant writhing responses in wild-type (WT) mice; this overt nociceptive behavior was reduced in ST2-deficient mice. In an antigen-challenge model, ST2-deficient immunized mice had reduced induced flinch and licking overt pain-like behaviors. In the formalin test, ST2-deficient mice also presented reduced flinch and licking responses, compared with WT mice. Naive WT and ST2-deficient mice presented similar responses in the rota-rod, hot plate, and electronic von Frey tests, indicating no impairment of motor function or alteration in basal nociceptive responses. The results demonstrate that IL-33/ST2 signaling is important in the development of overt pain-like behaviors

Preparation of biodegradable functionalized polyesters aimed to be used as surgical adhesives

The study and development of new biocompatible materials to be applied as UV-curable adhesives is extremely important to grant the preparation of matrices with suitable mechanical, biological and thermal properties with a fast curing rate. Herein, photocrosslinkable biodegradable copolymers composed of unsaturated polyesters (UP) and lactic acid oligomers functionalized with 2-isocyanatoethyl methacrylate (IEMA) were produced. Henceforth, three different stoichiometric proportions were tested, which, after the addition of a biocompatible photoinitiator (Irgacure® 2959), resulted in flexible, resistant and uniform matrices after 2 minutes and 30 seconds of crosslinking. The synthesized materials were then further characterized in terms of chemical composition and thermal/mechanical behaviour. The gel content, dynamic contact angles, water sorption capacity and hydrolytic degradation were also assessed. The biocompatibility and antibacterial activity of the produced materials was also evaluated. Taking into account all the data obtained, it may be concluded that the new synthesized biodegradable bioadhesives present promising properties to be used as surgical adhesives.info:eu-repo/semantics/acceptedVersio

Development of E-learning in higher education and future directions

The present paper is based on the work of the ‘Future of E-Learning Group’, a constituent of the EUNIS E-Learning task Force. The group has set up a number of tasks to fulfill its role, one of which, is seeking and disseminating information on the development of e-learning with a view to ensuring the right guide is provided for progress into the future. In our work to date, in this era of globalization, we question the ability of present university systems to respond adequately and appropriately to complex demands of an Information Economy. There’s increasing involvement of private sector in higher education. The effects on future learning on the use of varying tools as well as the design of competency-based performance in e-learning have been reported (Wolrery et al, 2000; Sluijsmans et al, 2006). Several multimedia learning systems are being developed for use as future interactive educational tools (Low et al, 2003). New thinking is required for the new relationships that are being developed between creative subjects and technology when we consider the nature of universities in their present state of existence as public sector institutions. The university of the future can be perceived as a setup, based on international trade in educational services, with universities fulfilling the functions of licensing, quality assurance and cultural custodianship. The pressent paper discusses some of these issues and reports on the future directions of e-learning as they relate to higher education

AAV-CRB2 protects against vision loss in an inducible CRB1 retinitis pigmentosa mouse model

Loss of Crumbs homolog 1 (CRB1) or CRB2 proteins in Muller cells or photoreceptors in the mouse retina results in a CRB dose-dependent retinal phenotype. In this study, we present a novel Muller cell-specific Crb1(KO)Crb2(LowMGC) retinitis pigmentosa mouse model (complete loss of CRB1 and reduced levels of CRB2 specifically in Muller cells). The Crb double mutant mice showed deficits in electroretinography, optokinetic head tracking, and retinal morphology. Exposure of retinas to low levels of DL-alpha-aminoadipate acid induced gliosis and retinal disorganization in Crb1(KO)Crb2(LowMGC) retinas but not in wild-type or Crb1-deficient retinas. Crb1(KO)Crb2(LowMGC) mice showed a substantial decrease in inner/outer photoreceptor segment length and optokinetic head-tracking response. Intravitreal application of rAAV vectors expressing human CRB2 (hCRB2) in Muller cells of Crb1(KO)Crb2(LowMGC) mice subsequently exposed to low levels of DL-alpha-aminoadipate acid prevented loss of vision, whereas recombinant adeno-associated viral (rAAV) vectors expressing human CRB1 (hCRB1) did not. Both rAAV vectors partially protected the morphology of the retina. The results suggest that hCRB expression in Muller cells is vital for control of retinal cell adhesion at the outer limiting membrane, and that the rAAV-cytomegalovirus (CMV)-hCRB2 vector is more potent than rAAV-minimal CMV (CMVmin)-hCRB1 in protection against loss of vision.Ophthalmic researc

tackling malaria

Malaria is an infectious disease that affects over 216 million people worldwide, killing over 445,000 patients annually. Due to the constant emergence of parasitic resistance to the current antimalarial drugs, the discovery of new drug candidates is a major global health priority. Aiming to make the drug discovery processes faster and less expensive, we developed binary and continuous Quantitative Structure-Activity Relationships (QSAR) models implementing deep learning for predicting antiplasmodial activity and cytotoxicity of untested compounds. Then, we applied the best models for a virtual screening of a large database of chemical compounds. The top computational predictions were evaluated experimentally against asexual blood stages of both sensitive and multi-drug-resistant Plasmodium falciparum strains. Among them, two compounds, LabMol-149 and LabMol-152, showed potent antiplasmodial activity at low nanomolar concentrations (EC50 <500 nM) and low cytotoxicity in mammalian cells. Therefore, the computational approach employing deep learning developed here allowed us to discover two new families of potential next generation antimalarial agents, which are in compliance with the guidelines and criteria for antimalarial target candidates.publishersversionpublishe

Proteomic Analysis of Human Osteoblastic Cells: Relevant Proteins and Functional Categories for Differentiation

Abstract Osteoblasts are the bone forming cells, capable of secreting an extracellular matrix with mineralization potential. The exact mechanism by which osteoblasts differentiate and form a mineralized extracellular matrix is presently not fully understood. To increase our knowledge about this process, we conducted proteomics analysis in human immortalized preosteoblasts (SV-HFO) able to differentiate and mineralize. We identified 381 proteins expressed during the time course of osteoblast differentiation. Gene ontology analysis revealed an overrepresentation of protein categories established as important players for osteoblast differentiation, bone formation, and mineralization such as pyrophosphatases. Proteins involved in antigen presentation, energy metabolism and cytoskeleton rearrangement constitute other overrepresented processes, whose function, albeit interesting, is not fully understood in the context of osteoblast differentiation and bone formation. Correlation analysis, based on quantitative data, revealed a biphasic osteoblast differentiation, encompassing a premineralization and a mineralization period. Identified differentially expressed proteins between mineralized and nonmineralized cells include cytoskeleton (e.g., CCT2, PLEC1, and FLNA) and extracellular matrix constituents (FN1, ANXA2, and LGALS1) among others. FT-ICR-MS data obtained for FN1, ANXA2, and LMNA shows a specific regulation of these proteins during the different phases of osteoblast differentiation. Taken together, this study increases our understanding of the proteomics changes that accompany osteoblast differentiation and may permit the discovery of novel modulators of bone formation

Hepatic Trauma: A 21-year Experience [trauma Hepático: Uma Experiência De 21 Anos]

Objective: To evaluate the epidemiological aspects, behavior, morbidity and treatment outcomes for liver trauma. Methods: We conducted a retrospective study of patients over 13 years of age admitted to a university hospital from 1990 to 2010, submitted to surgery or nonoperative management (NOM). Results: 748 patients were admitted with liver trauma. The most common mechanism of injury was penetrating trauma (461 cases, 61.6%), blunt trauma occurring in 287 patients (38.4%). According to the degree of liver injury (AAST-OIS) in blunt trauma we predominantly observed Grades I and II and in penetrating trauma, Grade III. NOM was performed in 25.7% of patients with blunt injury. As for surgical procedures, suturing was performed more frequently (41.2%). The liver-related morbidity was 16.7%. The survival rate for patients with liver trauma was 73.5% for blunt and 84.2% for penetrating trauma. Mortality in complex trauma was 45.9%. Conclusion: trauma remains more common in younger populations and in males. There was a reduction of penetrating liver trauma. NOM proved safe and effective, and often has been used to treat patients with penetrating liver trauma. 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Technology-enhanced learning on campus: insights from EUNIS e-Learning Task Force

In 2010 the EUNIS e-Learning Task Force (ELTF) members collaborated on a review of tools and technologies in use across our member institutions. One of the key features of that paper was the use of technology to give off-campus learners, such as distance learners, those undertaking field studies and learners in the workplace a richly supported learning experience. Building on the success of that collaboration, the ELTF members have turned their attention this year to the use of technology on campus. Whilst technology and distance learning go hand in hand, universities are often slower to take advantage of the possibilities offered by technology to enrich the learning that takes place in our lecture theatres and classrooms. The reasons for this are often cultural as much as financial or technical. Drawing on experience from across the EUNIS member nations we take a look at the types of tools, learning resources and learning activities that are being used to enhance the traditional curriculum, promote deeper learning and bridge the learning that takes place inside and outside the classroom. We look at a range of innovative projects and the benefits they have delivered, ways of overcoming the barriers to technology-enhanced learning on campus and we speculate about the role and function of the campus of the future

A concepção de um projeto de observatório de qualidade de vida: relato de uma experiência realizada em Campinas - SP

Given the assumption that the construction of a Healthy City demands a joint effort of all its inhabitants and that this is possible from a scientific basis the authors of the text present the experience of the Campinas Quality of Life Observatory Project that aims at the design of a quality of life index instrument. The phases described are the first intersectorial mobilization, conceptualization and localization of administrative and planning areas with special basis for the urbanistic project to be developed by future regional scope administrations. Second, the construction of the quality of life index itself from the 1991 demographic database and next discussions and recommendations. Such exercise has laid the bases for the consolidation of an efficient and feasible tool of continuous monitoring of an intersectorial process of quality of life betterment such as the one proposed by WHO for Healthy Cities.Partindo do pressuposto que a construção de uma Cidade Saudável exige esforços de todos seus moradores e que para que isto possa ser realizado a partir de bases científicas, os autores deste artigo apresentam a experiência do Projeto Observatório de Qualidade de Vida de Campinas com vistas à construção de um instrumento, indicador de qualidade de vida. As fases descritas foram as seguintes: mobilização intersetorial; conceituação e localização de áreas administrativas a áreas de planejametno com bases espaciais para o projeto urbanístico a ser realizado por futuras secretarias de ação regionais; construção do indicador de qualidade de vida propriamente dito a partir das bases de dados demográficos de 1991; discussões e recomendações. Tal exercício lançou bases para a consolidação de um instrumetal eficiente e factível de monitoramento contínuo de um processo intersetorial de melhoria de qualidade de vida, tal qual propõe a OMS para Cidades Saudáveis