Respuesta celular diferencial a ΔK107, una mutante natural de apolipoproteina A-I humana

El objetivo de este trabajo es valuar si las respuestas celulares a ΔK107 están modificadas, y probar el papel funcional del dominio helicoidal central tipo Y, comparando el comportamiento de ΔK107 con apoAI tipo salvaje y una mutante donde el residuo equivalente del segmento helicoidal tipo Y de la región C terminal fue eliminado (ΔK226).Facultad de Ciencias Médica

Respuesta celular diferencial a ΔK107, una mutante natural de apolipoproteina A-I humana

El objetivo de este trabajo es valuar si las respuestas celulares a ΔK107 están modificadas, y probar el papel funcional del dominio helicoidal central tipo Y, comparando el comportamiento de ΔK107 con apoAI tipo salvaje y una mutante donde el residuo equivalente del segmento helicoidal tipo Y de la región C terminal fue eliminado (ΔK226).Facultad de Ciencias Médica

Respuesta celular diferencial a ΔK107, una mutante natural de apolipoproteina A-I humana

El objetivo de este trabajo es valuar si las respuestas celulares a ΔK107 están modificadas, y probar el papel funcional del dominio helicoidal central tipo Y, comparando el comportamiento de ΔK107 con apoAI tipo salvaje y una mutante donde el residuo equivalente del segmento helicoidal tipo Y de la región C terminal fue eliminado (ΔK226).Facultad de Ciencias Médica

Validation of the neuroconnective endophenotype questionnaire (NEQ): a new clinical tool for medicine and psychiatry resulting from the contribution of Ehlers–Danlos syndrome

IntroductionThe link between anxiety disorders and joint hypermobility syndrome (now under hypermobility spectrum disorders, which include hypermobile Ehlers–Danlos syndrome) has been widely replicated over the past 30 years and has grown beyond the initial nosological limits. To integrate clinical and research progress in this field, a new neuroconnective endophenotype (NE) and its corresponding instrument, the Neuroconnective Endophenotype Questionnaire (NEQ), have been developed. This new clinical construct, created with the active participation of patients, includes both somatic and psychological dimensions and symptoms and resilience items.MethodsThe NE includes five dimensions: (1) sensorial sensitivity, (2) body signs and symptoms, (3) somatic conditions, (4) polar behavioral strategies, and (5) psychological and psychopathological dimensions. The NEQ information is collected through four self-administered questionnaires (sensorial sensitivity, body signs and symptoms, polar behavioral strategies, and psychological characteristics) and a structured diagnostic part that should be completed by a trained observer. This hetero-administered part incorporates (a) psychiatric diagnoses (using structured criteria, e.g., MINI), (b) somatic disorders diagnosis, using structured criteria, and (c) assessment of joint hypermobility criteria.ResultsIn a sample of 36 anxiety cases with 36 matched controls, the NEQ obtained high scores for test–retest, inter-rater reliability, and internal consistency. As for predictive validity, cases and controls significantly differed in all five dimensions and hypermobility measurements.DiscussionWe can conclude that the NEQ has achieved acceptable reliability and validity values and, therefore, is ready to be used and tested in different samples. This original and consistent construct including somatic and mental items may improve clinical specificity, the search for more comprehensive therapies, and their genetic and neuroimaging bases

Apolipoproteína A-I Helsinki: su relación con acil-coa colesterol aciltransferasa (ACAT)

Apolipoproteína A-I (apoA-I), es la proteína mayoritaria de las lipoproteínas de alta densidad (HDL) la misma juega un rol clave en la respuesta antiaterogénica y en el transporte de colesterol reverso (TCR). Esta proteína está mayoritariamente compuesta por repeticiones de a-hélices anfipáticas de tipo A. Existen también dos regiones conformadas por hélices de tipo Y con una distribución particular de cargas; las mismas han sido propuestas que juegan un rol central en el eflujo lipídico mediado por apoA-I. Pacientes portadores de una variante de apoA-I con una deleción en una hélice de tipo Y en la región central (DK107) tienen el metabolismo de las HDL alterado y un incrementado riesgo aterogénico.Facultad de Ciencias Médica

Policy challenges for agroforestry implementation in Europe

Agroforestry (AF) is a sustainable land use practice and system that increases the ecosystem services delivery from agricultural lands compared with treeless systems. Agroforestry can be considered a practice when linked to plot scale (silvoarable, silvopasture, homegarden, woody linear landscape strips, and forest farming), and a system when associated with the global farm scale. The enhancement of the ecosystem services is associated with the use and promotion of the biodiversity caused by the presence of trees that optimizes the use of the resources if adequate species are mixed. Agroforestry can be implemented at temporal and spatial scales. At the temporal scale, the use of woody perennials to increase soil fertility is a traditional technique that improves soil health and reduces the need of using herbicides (e.g., the legume Ulex sown for 10 years in between crop cultivation). Five agroforestry practices can be implemented at the plot level: silvopasture, silvoarable/alley cropping, homegardens/kitchengardens, woody linear landscape strips, and forest farming. A farm including these practices is considered an agroforestry system working at the landscape level when several farms are mixed. In spite of the acknowledgment that AF has at the European level for being included as part of Pillars I and II, the spread of AF is limited across Europe. Four challenges, linked with technical, economic, educational, and policy development, have been identified by the AFINET thematic network that, if addressed, may foster policy adoption across the EU. This article proposes 15 different policy recommendations to overcome them and the need of developing an AF strategy for the EU.We acknowledge funding through Grant 101086563 from the European Commission (Project AF4EU, HEUROPE). This study was supported by National Funds by the FCT—Portuguese Foundation for Science and Technology, under the project UIDB/04033/2020. NF-D was funded by the Pilot Program of the University of Santiago de Compostela (USC) for the hiring of distinguished research staff—call 2021, funded under the collaboration agreement between USC and Banco Santander, for the years 2021–2024. JJS-F was supported by the USC and the Spanish Ministry of Universities through the “Convocatoria de Recualificación del Sistema Universitario Español” on its modality “Margarita Salas”; Ministry of Universities - Recovery Transformation and Resilience Plan (funded by the European Union through the NextGenerationEUS

Policy challenges for agroforestry implementation in Europe

Agroforestry (AF) is a sustainable land use practice and system that increases the ecosystem services delivery from agricultural lands compared with treeless systems. Agroforestry can be considered a practice when linked to plot scale (silvoarable, silvopasture, homegarden, woody linear landscape strips, and forest farming), and a system when associated with the global farm scale. The enhancement of the ecosystem services is associated with the use and promotion of the biodiversity caused by the presence of trees that optimizes the use of the resources if adequate species are mixed. Agroforestry can be implemented at temporal and spatial scales. At the temporal scale, the use of woody perennials to increase soil fertility is a traditional technique that improves soil health and reduces the need of using herbicides (e.g., the legume Ulex sown for 10 years in between crop cultivation). Five agroforestry practices can be implemented at the plot level: silvopasture, silvoarable/alley cropping, homegardens/kitchengardens, woody linear landscape strips, and forest farming. A farm including these practices is considered an agroforestry system working at the landscape level when several farms are mixed. In spite of the acknowledgment that AF has at the European level for being included as part of Pillars I and II, the spread of AF is limited across Europe. Four challenges, linked with technical, economic, educational, and policy development, have been identified by the AFINET thematic network that, if addressed, may foster policy adoption across the EU. This article proposes 15 different policy recommendations to overcome them and the need of developing an AF strategy for the EU.We acknowledge funding through Grant 101086563 from the European Commission (Project AF4EU, HEUROPE). This study was supported by National Funds by the FCT—Portuguese Foundation for Science and Technology, under the project UIDB/04033/2020. NF-D was funded by the Pilot Program of the University of Santiago de Compostela (USC) for the hiring of distinguished research staff—call 2021, funded under the collaboration agreement between USC and Banco Santander, for the years 2021–2024. JJS-F was supported by the USC and the Spanish Ministry of Universities through the “Convocatoria de Recualificación del Sistema Universitario Español” on its modality “Margarita Salas”; Ministry of Universities - Recovery Transformation and Resilience Plan (funded by the European Union through the NextGenerationEU).info:eu-repo/semantics/publishedVersio

Breast cancer cutaneous metastases are associated to uMUC1 and sialyl Lewis x and to highly malignant primary tumors

Breast cancer spreading to different organs have been related to different molecules and mechanisms, but cutaneous metastasis remains unexplored. Increasing evidence showed that MUC1 and some of its carbohydrate associated antigens may be implicated in breast cancer metastasis. In this study we analyzed these tumor markers in order to identify breast cancer cutaneous metastatic profiles. A cohort of 26 primary tumors from breast cancer patients with cutaneous metastases were included; also, cutaneous and lymphatic node metastatic samples and primary tumors from breast cancer patients without metastases were analysed. Immunohistochemical (IHC) studies demonstrated that both underglycosylated MUC1 (uMUC1) and sialyl Lewis x (sLex) to be positively associated with cutaneous metastatic primary tumors (p < 0.05). Notably, a high percentage of tumors with cutaneous metastases were characterized as triple negative and Her2+ tumors (37.5 % and 29 %, respectively). Some discordant results were found between primary tumors and their matched cutaneous metastases. To determine if MUC1 variants may be carriers of carbohydrate antigens, subcellular fractions from a cutaneous metastatic lesion were obtained, immunoprecipitated and analyzed by Western blot. We found that the isolated uMUC1 with a molecular weight of>200 kDa was also the site for binding of antisLex MAb; in coincidence, a high correlation of positive IHC expression of both markers was observed. Our findings confirm that breast cancer cutaneous metastases were associated to highly malignant primary tumors and sustain the hypothesis that u-MUC1 and sLe x may drive breast cancer cutaneous metastases.Centro de Investigaciones Inmunológicas Básicas y Aplicada

Apolipoproteína A-I e lipoproteínas de alta densidade: estrutura e papel na homeostase do colesterol celular

La apolipoproteína A-I (apoAI) es el componente proteico mayoritario de las lipoproteínas de alta densidad (HDL), cuyo nivel sérico se correlaciona inversamente con el riesgo aterogénico. Las propiedades antiaterogénicas son atribuidas en gran parte al rol protagónico que tiene en el transporte reverso de colesterol (RCT), proceso que remueve el exceso de colesterol de los tejidos periféricos. La apoAI es una proteína anfitrópica formada casi en exclusividad por α-hélices anfipáticas, y presenta una gran flexibilidad conformacional que es crucial para su ciclo funcional, en el que se interconvierte entre diferentes estados: libre, unida a membranas, o a una gran variedad de complejos lipoproteicos de diferente tamaño, morfología y composición. En este reporte se revisa el conocimiento actual sobre la estructura y propiedades de interacción con lípidos de apoAI, en relación a la biogénesis de HDL y su función en el RCT. Se trata en particular la configuración de apoAI en HDL discoidales, así como la interacción con lípidos y la importancia para la remoción celular de colesterol de un par de α-hélices anfipáticas que presentan una distribución particular de los residuos cargados y se localizan en el centro de la molécula de apoAI.Apolipoprotein A-I (apoAI) is the major protein component of high density lipoprotein (HDL), whose serum level is inversely correlated with atherogenic risk. Antiatherogenic properties are largely attributed to its key role in reverse cholesterol transport (RCT), a process that removes cholesterol excess from peripheral tissues. ApoAI is an amphitropic protein that almost exclusively contains amphipathic α-helices, and presents a large conformational flexibility that is crucial for its functional cycle, in which it inter-converts into different states: free or bound to membranes, or into a lipoprotein complex variety of different sizes, compositions and morphologies. This report reviews the current knowledge of the structure and lipid interaction properties of apoAI, in relation with HDL biogenesis and function in RCT. In particular, focus is made on the apoAI configuration in discoidal HDL; as well as on the interaction with lipids, and the importance for cellular cholesterol efflux, of an amphipathic α-helix pair having a particular distribution of the charged residues and that locate at the center of the apoAI molecule.Apolipoproteína A-I (apoAI) é o principal componente proteico das lipoproteínas de alta densidade (HDL), cujo nível sérico se correlaciona inversamente com o risco aterogênico. As propriedades antiaterogênicas são atribuídas, em grande parte, a seu papel principal no transporte reverso de colesterol (RCT), um processo que remove o excesso de colesterol dos tecidos periféricos. A ApoAI é uma proteína anfitrópica constituída quase exclusivamente por α-hélices anfipáticas, e apresenta uma grande flexibilidade conformacional que é essencial para seu ciclo funcional, no qual se interconverte entre diferentes estados: livre, ligada a membranas ou a uma grande variedade de complexos lipoproteicos de diferente tamanho, morfologia e composição. Este relatório analisa o conhecimento atual sobre a estrutura e propriedades de interação com lipídios de apoAI, com relação à biogênese de HDL e sua função no RCT. Em particular, trata-se a configuração de apoAI em HDL discoidais; bem como a interação com lipídios e a importância para a remoção celular de colesterol de um par de α-hélices anfipáticas que apresentam uma distribuição específica dos resíduos carregados e se localizam no centro da milécula de apoAI.Facultad de Ciencias MédicasInstituto de Investigaciones Bioquímicas de La PlataFacultad de Ciencias Exacta

Metástasis cutáneas de cáncer de mama

El objetivo de este estudio es identificar perfiles correspondientes a la metástasis cutánea en el cáncer de mama mediante el análisis de marcadores tumorales tales como MUC1 y antígenos carbohidratos asociados.Facultad de Ciencias Médica