Crucial role of CB(2) cannabinoid receptor in the regulation of central immune responses during neuropathic pain

Neuropathic pain is a clinical manifestation of nerve injury difficult to treat even with potent analgesic compounds. Here, we used different lines of genetically modified mice to clarify the role played by CB2 cannabinoid receptors in the regulation of the central immune responses leading to the development of neuropathic pain. CB2 knock-out mice and wild-type littermates were exposed to sciatic nerve injury, and both genotypes developed a similar hyperalgesia and allodynia in the ipsilateral paw. Most strikingly, knock-outs also developed a contralateral mirror image pain, associated with an enhanced microglial and astrocytic expression in the contralateral spinal horn. In agreement, hyperalgesia, allodynia, and microglial and astrocytic activation induced by sciatic nerve injury were attenuated in transgenic mice overexpressing CB2 receptors. These results demonstrate the crucial role of CB2 cannabinoid receptor in modulating glial activation in response to nerve injury. The enhanced manifestations of neuropathic pain were replicated in irradiated wild-type mice reconstituted with bone marrow cells from CB2 knock-outs, thus demonstrating the implication of the CB2 receptor expressed in hematopoietic cells in the development of neuropathic pain at the spinal cord.

Technology educational affordance: Bridging the gap between patterns of interaction and technology usage

Peer-reviewed

Open Educational Resources: an opportunity for virtual learning institutions

The Universitat Oberta de Catalunya (UOC, Open University of Catalonia) is involved inseveral research projects and educational activities related to the use of Open Educational Resources (OER). Some of the discussed issues in the concept of OER are research issues which are being tackled in two EC projects (OLCOS and SELF). Besides the research part, the UOC aims at developing a virtual centre for analysing and promoting the concept of OERin Europe in the sector of Higher and Further Education. The objectives are to makeinformation and learning services available to provide university management staff,eLearning support centres, faculty and learners with practical information required to create, share and re-use such interoperable digital content, tools and licensing schemes. In the realisation of these objectives, the main activities are the following: to provide organisationaland individual e-learning end-users with orientation; to develop perspectives and useful recommendations in the form of a medium-term Roadmap 2010 for OER in Higher and Further Education in Europe; to offer practical information and support services about how to create, share and re-use open educational content by means of tutorials, guidelines, best practices, and specimen of exemplary open e-learning content; to establish a larger group ofcommitted experts throughout Europe and other continents who not only share theirexpertise but also steer networking, workshops, and clustering efforts; and to foster and support a community of practice in open e-learning content know-how and experiences.

Analyzing hidden semantics in social bookmarking of open educational resources

Web 2.0 services such as social bookmarking allow users to manage and share the links they find interesting, adding their own tags for describingthem. This is especially interesting in the field of open educational resources, asdelicious is a simple way to bridge the institutional point of view (i.e. learningobject repositories) with the individual one (i.e. personal collections), thuspromoting the discovering and sharing of such resources by other users. In this paper we propose a methodology for analyzing such tags in order to discover hidden semantics (i.e. taxonomies and vocabularies) that can be used toimprove descriptions of learning objects and make learning object repositories more visible and discoverable. We propose the use of a simple statistical analysis tool such as principal component analysis to discover which tags createclusters that can be semantically interpreted. We will compare the obtained results with a collection of resources related to open educational resources, in order to better understand the real needs of people searching for open educational resources.

The effects of regional educational policies on school failure in Spain

This paper presents a regional analysis of the effects of educational policies implemented in Spain between 1992 and 2003, focusing specifically on school failure rates. We consider the impact of expenditure per pupil, class size, and pupil-teacher ratio on dropout rates at the end of compulsory education and on the proportion of early school-leavers in the 18-24 year age group. Our results indicate that higher levels of educational expenditure per pupil and lower class sizes and pupil-teacher ratios reduce rates of dropout and early school-leaving (although class-size is not always significant). However, the magnitude of the effects of these variables is small at the average level.

Dendritic cells exposed to MVA-based HIV-1 vaccine induce highly functional HIV-1-specific CD8+ T cell responses in HIV-1-infected individuals

Currently, MVA virus vectors carrying HIV-1 genes are being developed as HIV-1/AIDS prophylactic/therapeutic vaccines. Nevertheless, little is known about the impact of these vectors on human dendritic cells (DC) and their capacity to present HIV-1 antigens to human HIV-specific T cells. This study aimed to characterize the interaction of MVA and MVA expressing the HIV-1 genes Env-Gag-Pol-Nef of clade B (referred to as MVA-B) in human monocyte-derived dendritic cells (MDDC) and the subsequent processes of HIV-1 antigen presentation and activation of memory HIV-1-specific T lymphocytes. For these purposes, we performed ex vivo assays with MDDC and autologous lymphocytes from asymptomatic HIV-infected patients. Infection of MDDC with MVA-B or MVA, at the optimal dose of 0.3 PFU/MDDC, induced by itself a moderate degree of maturation of MDDC, involving secretion of cytokines and chemokines (IL1-ra, IL-7, TNF-α, IL-6, IL-12, IL-15, IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, IP-10, MIG, and IFN-α). MDDC infected with MVA or MVA-B and following a period of 48 h or 72 h of maturation were able to migrate toward CCL19 or CCL21 chemokine gradients. MVA-B infection induced apoptosis of the infected cells and the resulting apoptotic bodies were engulfed by the uninfected MDDC, which cross-presented HIV-1 antigens to autologous CD8+ T lymphocytes. MVA-B-infected MDDC co-cultured with autologous T lymphocytes induced a highly functional HIV-specific CD8+ T cell response including proliferation, secretion of IFN-γ, IL-2, TNF-α, MIP-1β, MIP-1α, RANTES and IL-6, and strong cytotoxic activity against autologous HIV-1-infected CD4+ T lymphocytes. These results evidence the adjuvant role of the vector itself (MVA) and support the clinical development of prophylactic and therapeutic anti-HIV vaccines based on MVA-B.

Dendritic cells exposed to MVA-based HIV-1 vaccine induce highly functional HIV-1-specific CD8+ T cell responses in HIV-1-infected individuals

Currently, MVA virus vectors carrying HIV-1 genes are being developed as HIV-1/AIDS prophylactic/therapeutic vaccines. Nevertheless, little is known about the impact of these vectors on human dendritic cells (DC) and their capacity to present HIV-1 antigens to human HIV-specific T cells. This study aimed to characterize the interaction of MVA and MVA expressing the HIV-1 genes Env-Gag-Pol-Nef of clade B (referred to as MVA-B) in human monocyte-derived dendritic cells (MDDC) and the subsequent processes of HIV-1 antigen presentation and activation of memory HIV-1-specific T lymphocytes. For these purposes, we performed ex vivo assays with MDDC and autologous lymphocytes from asymptomatic HIV-infected patients. Infection of MDDC with MVA-B or MVA, at the optimal dose of 0.3 PFU/MDDC, induced by itself a moderate degree of maturation of MDDC, involving secretion of cytokines and chemokines (IL1-ra, IL-7, TNF-α, IL-6, IL-12, IL-15, IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, IP-10, MIG, and IFN-α). MDDC infected with MVA or MVA-B and following a period of 48 h or 72 h of maturation were able to migrate toward CCL19 or CCL21 chemokine gradients. MVA-B infection induced apoptosis of the infected cells and the resulting apoptotic bodies were engulfed by the uninfected MDDC, which cross-presented HIV-1 antigens to autologous CD8+ T lymphocytes. MVA-B-infected MDDC co-cultured with autologous T lymphocytes induced a highly functional HIV-specific CD8+ T cell response including proliferation, secretion of IFN-γ, IL-2, TNF-α, MIP-1β, MIP-1α, RANTES and IL-6, and strong cytotoxic activity against autologous HIV-1-infected CD4+ T lymphocytes. These results evidence the adjuvant role of the vector itself (MVA) and support the clinical development of prophylactic and therapeutic anti-HIV vaccines based on MVA-B.

Educational data mining and learning analytics : Clasificación de las matriculaciones de A.D.E. en la UOC

Trabajo de investigación que realiza un estudio clasificatorio de las asignaturas matriculadas en la carrera de Administración y Dirección de Empresas de la UOC en relación a su resultado. Se proponen diferentes métodos y modelos de comprensión del entorno en el que se realiza el estudio.

Identifying quantitative operation principles in metabolic pathways: a systematic method for searching feasible enzyme activity patterns leading to cellular adaptive responses

Background: Optimization methods allow designing changes in a system so that specific goals are attained. These techniques are fundamental for metabolic engineering. However, they are not directly applicable for investigating the evolution of metabolic adaptation to environmental changes. Although biological systems have evolved by natural selection and result in well-adapted systems, we can hardly expect that actual metabolic processes are at the theoretical optimum that could result from an optimization analysis. More likely, natural systems are to be found in a feasible region compatible with global physiological requirements. Results: We first present a new method for globally optimizing nonlinear models of metabolic pathways that are based on the Generalized Mass Action (GMA) representation. The optimization task is posed as a nonconvex nonlinear programming (NLP) problem that is solved by an outer- approximation algorithm. This method relies on solving iteratively reduced NLP slave subproblems and mixed-integer linear programming (MILP) master problems that provide valid upper and lower bounds, respectively, on the global solution to the original NLP. The capabilities of this method are illustrated through its application to the anaerobic fermentation pathway in Saccharomyces cerevisiae. We next introduce a method to identify the feasibility parametric regions that allow a system to meet a set of physiological constraints that can be represented in mathematical terms through algebraic equations. This technique is based on applying the outer-approximation based algorithm iteratively over a reduced search space in order to identify regions that contain feasible solutions to the problem and discard others in which no feasible solution exists. As an example, we characterize the feasible enzyme activity changes that are compatible with an appropriate adaptive response of yeast Saccharomyces cerevisiae to heat shock Conclusion: Our results show the utility of the suggested approach for investigating the evolution of adaptive responses to environmental changes. The proposed method can be used in other important applications such as the evaluation of parameter changes that are compatible with health and disease states.

Minimization of biosynthetic costs in adaptive gene expression responses of yeast to environmental changes

Yeast successfully adapts to an environmental stress by altering physiology and fine-tuning metabolism. This fine-tuning is achieved through regulation of both gene expression and protein activity, and it is shaped by various physiological requirements. Such requirements impose a sustained evolutionary pressure that ultimately selects a specific gene expression profile, generating a suitable adaptive response to each environmental change. Although some of the requirements are stress specific, it is likely that others are common to various situations. We hypothesize that an evolutionary pressure for minimizing biosynthetic costs might have left signatures in the physicochemical properties of proteins whose gene expression is fine-tuned during adaptive responses. To test this hypothesis we analyze existing yeast transcriptomic data for such responses and investigate how several properties of proteins correlate to changes in gene expression. Our results reveal signatures that are consistent with a selective pressure for economy in protein synthesis during adaptive response of yeast to various types of stress. These signatures differentiate two groups of adaptive responses with respect to how cells manage expenditure in protein biosynthesis. In one group, significant trends towards downregulation of large proteins and upregulation of small ones are observed. In the other group we find no such trends. These results are consistent with resource limitation being important in the evolution of the first group of stress responses.

Differences in phasic development rate amongst wheat cultivars independent of responses to photoperiod and vernalization. A viewpoint of the intrinsic earliness hypothesis

Differences amongst wheat cultivars in the rate of reproductive development are largely dependent on differences in their sensitivity to photoperiod and vernalization. However, when these responses are accounted for, by growing vernalized seedlings under long photoperiods, cultivars can still differ markedly in time to ear emergence. Control of rate of development by this ‘third factor’ has been poorly understood and is variously referred to as intrinsic earliness, earliness in the narrow sense, basic vegetative period, earliness per se, and basic development rate. Certain assumptions are made in the concept of intrinsic earliness. They are that differences in intrinsic earliness (i) are independent of the responses of the cultivars to photoperiod and vernalization, (ii) apply only to the length of the vegetative period up to floral initiation (as suggested by several authors), (iii) are maintained under different temperatures, measured either in days or degree days. As a consequence of this, the ranking of cultivars (from intrinsically early to intrinsically late) must be maintained at different temperatures. This paper, by the re-analysis of published data, examines the extent to which these assumptions can be supported. Although it is shown that intrinsic earliness operates independently of photoperiod and vernalization responses, the other assumptions were not supported. The differences amongst genotypes in time to ear emergence, grown under above-optimum vernalization and photoperiod (that is when the response to these factors is saturated), were not exclusively due to parallel differences in the length of the vegetative phase, and the length of the reproductive phase was independent of that of the vegetative phase. Thus, it would be possible to change the relative allocation of time to vegetative and reproductive periods with no change in the full period to ear emergence. The differences in intrinsic earliness between cultivars were modified by the temperature regime under which they were grown, i.e. the difference between cultivars (both considering the full phase to ear emergence or some sub-phases) was not a constant amount of time or thermal time at different temperatures. In addition, in some instances genotypes changed their ranking for ‘intrinsic earliness’ depending on the temperature regime. This was interpreted to mean that while all genotypes are sensitive to temperature they differ amongst themselves in the extent of that sensitivity. Therefore, ‘intrinsic earliness’ should not be considered as a static genotypic characteristic, but the result of the interaction between the genotype and temperature. Intrinsic earliness is therefore likely to be related to temperature sensitivity. Some implications of these conclusions for plant breeding and crop simulation modelling are discussed.

Using narratives to study the impact of social networks on the educational paths of immigrant students

This paper presents the qualitative data collection process aimed at the study of the impactsocial relations and networks have on educational paths of immigrant students. In theframework of a R & D longitudinal study funded by the Ministry of Science and Innovation(2012-2014), the research team tracked the path of 87 immigrant students, from whom only 17successfully achieved the transition through the first and second year of Post-16 Education.A vast range of literature notes that relationships are an important part of migration process andsocial integration analysis, as well as school history in terms of success or failure. Through thefieldwork researchers collect the personal networks of all immigrant students from 3 highschools who were at that time attending last course of compulsory school. The network structureinfluences their social capital and therefore determines the resources, goods and types of supportindividuals can access. All these aspects are influential elements in the configuration anddevelopment of academic trajectories of immigrant students.At the end of the second year of Post-16 Education (two years later), the study captures personalnetworks of these students again, analyses and discusses their evolution and influence on theirpaths through qualitative interviews. Such interviews facilitated the discussion of theirrelationships while providing interesting narratives that are presented in the text. In order to do so, the biographical interpretive narrative method of interviewing is implemented.

Using narratives to study the impact of social networks on the educational paths of immigrant students

This paper presents the qualitative data collection process aimed at the study of the impactsocial relations and networks have on educational paths of immigrant students. In theframework of a R & D longitudinal study funded by the Ministry of Science and Innovation(2012-2014), the research team tracked the path of 87 immigrant students, from whom only 17successfully achieved the transition through the first and second year of Post-16 Education.A vast range of literature notes that relationships are an important part of migration process andsocial integration analysis, as well as school history in terms of success or failure. Through thefieldwork researchers collect the personal networks of all immigrant students from 3 highschools who were at that time attending last course of compulsory school. The network structureinfluences their social capital and therefore determines the resources, goods and types of supportindividuals can access. All these aspects are influential elements in the configuration anddevelopment of academic trajectories of immigrant students.At the end of the second year of Post-16 Education (two years later), the study captures personalnetworks of these students again, analyses and discusses their evolution and influence on theirpaths through qualitative interviews. Such interviews facilitated the discussion of theirrelationships while providing interesting narratives that are presented in the text. In order to do so, the biographical interpretive narrative method of interviewing is implemented.