Identification of a Mutated Fibronectin As a Tumor Antigen Recognized by CD4+T Cells: Its Role in Extracellular Matrix Formation and Tumor Metastasis

CD4+ T cells play an important role in orchestrating host immune responses against cancer, particularly by providing critical help for priming and extending the survival of CD8+ T cells. However, relatively little is known about major histocompatibility complex class II–restricted human tumor antigens capable of activating CD4+ T cells. Here, we describe the identification of a mutated fibronectin (FN) as a tumor antigen recognized by human histocompatibility leukocyte antigen-DR2–restricted CD4+ T cells. Deoxyribonucleic acid (DNA) sequencing analysis indicated that this gene contains a mutation that results in the substitution of lysine for glutamic acid and gives rise to a new T cell epitope recognized by CD4+ T cells. Tumor cells harboring the mutant FN resulted in the loss of FN matrix formation and the gain of metastatic potential based on the migration pattern compared with that of tumor cells that express wild-type FN. Additional experiments using cell lines stably expressing the mutated FN cDNA demonstrated that the point mutation in FN was responsible for the loss of FN staining in extracellular matrices and the enhancement of tumor cell migration. These findings represent the first demonstration that a mutated gene product recognized by CD4+ T cells is directly involved in tumor metastasis, which indicates the importance of CD4+ T cells in controlling the spread of tumor cells to distant anatomic sites

Surgical removal of endometriotic lesions alters local and systemic proinflammatory cytokines in endometriosis patients

To determine the impact of endometriotic lesion removal on local and systemic inflammation

Reconversión laboral del sector agropecuario hacia el turismo. Desafíos para la Patagonia chilena

[EN] The development of tourism can help to diversify the productive matrix and reduce rural depopulation. This study analyzes the possibility of agricultural worker participation in the tourism sector in rural areas of Chilean Patagonia. Based on the 2017 CASEN survey, data matching and estimation of logit model are conducted to evaluate the probability of agricultural worker reconversion. The results indicate that the proportion of agricultural workers who can move to tourism is low. However, women and individuals with post-secondary education are more likely to be reconverted.[ES] La actividad turística puede ayudar a diversificar la matriz productiva y reducir el despoblamiento rural. Este estudio analiza la posibilidad de participación de trabajadores agropecuarios en el sector turismo en las zonas rurales de la Patagonia Chilena. Usando la encuesta CASEN del año 2017, se realiza un proceso de emparejamiento de datos (matching) y la estimación de un modelo logit para evaluar la probabilidad de reconversión laboral. Los resultados indican que hay una baja proporción de trabajadores que puedan transitar hacia el sector turismo. Sin embargo, las mujeres y los individuos con estudios postsecundarios tienen mayores probabilidades de reconversión.Este trabajo está enmarcado dentro del proyecto de investigación “La Vocación Productiva, el Nivel Educativo y la Funcionalidad del Centro Emisor y Receptor como Factores Explicativos de la Conmutación Inter e Intrarregional en la Región de los Andes Australes de la Patagonia Chilena”, financiado por CONICYT (Proyecto Fondecyt Número 1160196), por lo que los autores agradecen dichos aportes.Mancilla, C.; Ferrada, LM.; Soza-Amigo, S. (2019). Labour reconversion of the agricultural sector towards tourism. Challenges for Chilean Patagonia. Economía Agraria y Recursos Naturales - Agricultural and Resource Economics. 19(1):175-194. https://doi.org/10.7201/earn.2019.01.0917519419

Omega-6 Fatty Acid Biomarkers and Incident Type 2 Diabetes: Pooled Analysis of Individual-Level Data for 39 740 Adults from 20 Prospective Cohort Studies

Background: The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs) remain contentious, and little evidence is available regarding their potential role in primary prevention of type 2 diabetes. We aimed to assess the associations of linoleic acid and arachidonic acid biomarkers with incident type 2 diabetes. Methods: We did a pooled analysis of new, harmonised, individual-level analyses for the biomarkers linoleic acid and its metabolite arachidonic acid and incident type 2 diabetes. We analysed data from 20 prospective cohort studies from ten countries (Iceland, the Netherlands, the USA, Taiwan, the UK, Germany, Finland, Australia, Sweden, and France), with biomarkers sampled between 1970 and 2010. Participants included in the analyses were aged 18 years or older and had data available for linoleic acid and arachidonic acid biomarkers at baseline. We excluded participants with type 2 diabetes at baseline. The main outcome was the association between omega-6 PUFA biomarkers and incident type 2 diabetes. We assessed the relative risk of type 2 diabetes prospectively for each cohort and lipid compartment separately using a prespecified analytic plan for exposures, covariates, effect modifiers, and analysis, and the findings were then pooled using inverse-variance weighted meta-analysis. Findings: Participants were 39 740 adults, aged (range of cohort means) 49-76 years with a BMI (range of cohort means) of 23·3-28·4 kg/m(2), who did not have type 2 diabetes at baseline. During a follow-up of 366 073 person-years, we identified 4347 cases of incident type 2 diabetes. In multivariable-adjusted pooled analyses, higher proportions of linoleic acid biomarkers as percentages of total fatty acid were associated with a lower risk of type 2 diabetes overall (risk ratio [RR] per interquintile range 0·65, 95% CI 0·60-0·72,

Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality: An Individual-Level Pooled Analysis of 30 Cohort Studies

BACKGROUND: Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies. METHODS: We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance–weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available). RESULTS: In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15 198 incident cardiovascular events occurred among 68 659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88–0.99), 0.78 (0.70–0.85), and 0.88 (0.79–0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88–1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86–0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships. CONCLUSIONS: In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention