Kinetics and Thermodynamics of Membrane Protein Folding

Understanding protein folding has been one of the great challenges in biochemistry and molecular biophysics. Over the past 50 years, many thermodynamic and kinetic studies have been performed addressing the stability of globular proteins. In comparison, advances in the membrane protein folding field lag far behind. Although membrane proteins constitute about a third of the proteins encoded in known genomes, stability studies on membrane proteins have been impaired due to experimental limitations. Furthermore, no systematic experimental strategies are available for folding these biomolecules in vitro. Common denaturing agents such as chaotropes usually do not work on helical membrane proteins, and ionic detergents have been successful denaturants only in few cases. Refolding a membrane protein seems to be a craftsman work, which is relatively straightforward for transmembrane {\beta}-barrel proteins but challenging for {\alpha}-helical membrane proteins. Additional complexities emerge in multidomain membrane proteins, data interpretation being one of the most critical. In this review, we will describe some recent efforts in understanding the folding mechanism of membrane proteins that have been reversibly refolded allowing both thermodynamic and kinetic analysis. This information will be discussed in the context of current paradigms in the protein folding field

Participation and Organizational Commitment in the Mondragon Group

The scientific literature has shown Mondragon Corporation (MC), with 65 years of history, as a clear example that cooperativism can be highly competitive in the capitalist market while being highly egalitarian and democratic. This cooperative group has focused on its corporate values of cooperation, participation, social responsibility, and innovation. Previous scientific research reports its enormous transformative and emancipatory potential. However, studies on the effects of various types of worker participation on competitiveness and workers' psychological wellbeing in this cooperative group exist to a lesser extent. Specifically, one aspect that needs further empirical research and that represents a competitive advantage for Mondragon is the degree of commitment and emotional attachment that can be observed in the people who work there. For this reason, this article aims to identify key elements of the democratic participation of workers in these cooperatives that relate to the development of organizational commitment. Based on a communicative and qualitative approach, data collection included 29 interviews to different profiles of workers (senior and junior workers, members and non-members of the cooperative, and researchers involved in the cooperatives) from eight different cooperatives of the Corporation. Through this research methodology, the participants interpret their reality through egalitarian and intersubjective dialogue because their voices are considered essential to measure the social impact. This study found three different ways in which the democratic participation of worker-members in management and ownership contributes to developing affective organizational commitment among those working in Mondragon cooperatives, generating positive psychological and economic outcomes for both workers and cooperatives

Innovation as competitiveness driving force through the resources and capacities of SMEs in Costa Rica, Puerto Rico, and Dominican Republic

Literature reflects that Latin America and the Caribbean register more SMEs and produce more entrepreneurial activity than any other place in the world. Using the Theory of Resources and Capabilities, this research explored how SMEs in Costa Rica, Puerto Rico, and the Dominican Republic managed the heterogeneity of their entrepreneurial orientation, market orientation, social and human capital resources and their impact on innovation capacity and competitiveness. With a survey of 467 SMEs and the analysis of data with the use of PLS-SEM & PLS-MGA, this study contributed new information based on resources and capacities that showed the maximum set of possible variables analyzed for a theoretical understanding and practice of the heterogeneity of resources. The results reflected a positive impact on the proposed hypothesis through the structural model. The data highlight market orientation as the most valuable resource that facilitates innovation and competitiveness in SMEs analyzed. The results revealed and contributed to the new lines of research on how differences and the degree of importance in managing resources generated high competitiveness through their capacity for innovation

Qualitative Inquiry: A Key Element for Assessing the Social Impact of Research

The need to develop adequate methodologies to comprehensively assess the impact of research, especially the social impact of European Union (EU)-funded research, is one of the main concerns within the European Commission as well as for EU citizens, who are more active than ever. This article discusses the rationale behind using a qualitative approach to better address these concerns. Drawing on the FP7 IMPACT-EV research project, the present article discusses how to overcome a positivist approach that evaluates the social impact of research conducted only for its economic objectives and using only quantitative data. The focus on what is needed and what research is expected to bring to society are emphasized and made possible through qualitative inquiry of the social impact of the EU social sciences and the humanities (SSH) research. Thus, the development of qualitative-based analysis of the social impact of research is increasingly required to be conducted in dialogue with citizens

Rapid Increases in the Steady-state Concentration of Reactive Oxygen Species in the Lungs and Heart After Particulate Air Pollution Inhalation.

In vitro studies suggest that reactive oxygen species contribute to the cardiopulmonary toxicity of particulate air pollution. To evaluate the ability of particulate air pollution to promote oxidative stress and tissue damage in vivo, we studied a rat model of short-term exposure to concentrated ambient particles (CAPs). We exposed adult Sprague-Dawley rats to either CAPs aerosols (group 1; average CAPs mass concentration, 300 +/- 60 micro g/m3) or filtered air (sham controls) for periods of 1-5 hr. Rats breathing CAPs aerosols for 5 hr showed significant oxidative stress, determined as in situ chemiluminescence in the lung [group 1, 41 +/- 4; sham, 24 +/- 1 counts per second (cps)/cm2] and heart (group 1, 45 +/- 4; sham, 24 +/- 2 cps/cm2) but not liver (group 1, 10 +/- 3; sham, 13 +/- 3 cps/cm2). Increases in oxidant levels were also triggered by highly toxic residual oil fly ash particles (lung chemiluminescence, 90 +/- 10 cps/cm2; heart chemiluminescence, 50 +/- 3 cps/cm2) but not by particle-free air or by inert carbon black aerosols (control particles). Increases in chemiluminescence showed strong associations with the CAPs content of iron, manganese, copper, and zinc in the lung and with Fe, aluminum, silicon, and titanium in the heart. The oxidant stress imposed by 5-hr exposure to CAPs was associated with slight but significant increases in the lung and heart water content (approximately 5% in both tissues, p < 0.05) and with increased serum levels of lactate dehydrogenase (approximately 80%), indicating mild damage to both tissues. Strikingly, CAPs inhalation also led to tissue-specific increases in the activities of the antioxidant enzymes superoxide dismutase and catalase, suggesting that episodes of increased particulate air pollution not only have potential for oxidant injurious effects but may also trigger adaptive responses

CCR5 deficiency predisposes to fatal outcome in influenza virus infection

Influenza epidemics affect all age groups, although children, the elderly and those with underlying medical conditions are the most severely affected. Whereas co-morbidities are present in 50% of fatal cases, 25-50% of deaths are in apparently healthy individuals. This suggests underlying genetic determinants that govern infection severity. Although some viral factors that contribute to influenza disease are known, the role of host genetic factors remains undetermined. Data for small cohorts of influenza-infected patients are contradictory regarding the potential role of chemokine receptor 5 deficiency (CCR5-Δ32 mutation, a 32 bp deletion in the CCR5 gene) in the outcome of influenza virus infection. We tested 171 respiratory samples from influenza patients (2009 pandemic) for CCR5-Δ32 and evaluated its correlation with patient mortality. CCR5-Δ32 patients (17.4%) showed a higher mortality rate than WT individuals (4.7%; P = 0.021), which indicates that CCR5-Δ32 patients are at higher risk than the normal population of a fatal outcome in influenza infection.This work was supported by the Instituto de Salud Carlos III (Programa especial de investigación sobre la gripe pandémica GR09/0040 and GR09/0023), Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES) and the Spanish Ministry of Science and Innovation (BFU 2011-26175)S

Effects of Parvovirus B19 Infection in Renal Transplant Recipients: A Retrospective Review of Three Cases

Parvovirus B19 (PVB19) is a DNA virus which causes clinically relevant infection in renal transplant recipients (RTR) leading to significant morbidity. Manifestations include erythropoietin resistant anemia, proteinuria, and glomerulosclerosis in the allograft. Severe infection may require administration of intravenous immunoglobulin, reduction in immunosuppression and transfusions. The major challenge in managing and preventing the infection in RTR involves the act of balancing the decreased level of immunosuppression and the risk of rejection. The objective of this article is to understand the importance of PVB19 infection and its outcome in RTR. We reviewed the medical records of three RTR with confirmed PVB19 infection and recorded patient information including demographics, clinical and laboratory data, management, and outcome. The average time of occurrence of PVB19 infection as transplant was 8.6 weeks and they presented with symptomatic anemia. Elevated creatinine values were noted in two of them. Following treatment, anemia improved and creatinine values returned to baseline. One of them developed an early relapse and had to be treated once again similarly. We emphasize the importance of maintaining a high index of suspicion for PVB19 infection in patients with anemia in the posttransplant phase, especially in patients on higher doses of immunosuppressants. Early and proper treatment can prevent worsening clinical condition and possible effects on the allograft