KRIT1 loss of function causes a ROS-dependent upregulation of c-Jun

Loss-of-function mutations in the KRIT1 gene (CCM1) have been associated with the pathogenesis of cerebral cavernous malformations (CCM), a major cerebrovascular disease. However, KRIT1 functions and CCM pathogenetic mechanisms remain incompletely understood. Indeed, recent experiments in animal models have clearly demonstrated that the homozygous loss of KRIT1 is not sufficient to induce CCM lesions, suggesting that additional factors are necessary to cause CCM disease. Previously, we found that KRIT1 is involved in the maintenance of the intracellular reactive oxygen species (ROS) homeostasis to prevent ROS-induced cellular dysfunctions, including a reduced ability to maintain a quiescent state. Here, we show that KRIT1 loss of function leads to enhanced expression and phosphorylation of the redox-sensitive transcription factor c-Jun, as well as induction of its downstream target COX-2, in both cellular models and human CCM tissues. Furthermore, we demonstrate that c-Jun upregulation can be reversed by either KRIT1 re-expression or ROS scavenging, whereas KRIT1 overexpression prevents forced upregulation of c-Jun induced by oxidative stimuli. Taken together with the reported role of c-Jun in vascular dysfunctions triggered by oxidative stress, our findings shed new light on the molecular mechanisms underlying KRIT1 function and CCM pathogenesis

Comparación morfológica y micrográfica de dos especies nativas de Hedeoma utilizadas en medicina tradicional.

PosterEn Argentina el género Hedeoma está representado por H.medium; H. multiflora; H. mandoniana y H. teyucuarensis, se destacan las dos primeras por ser las de más ampliadistribución. Hedeoma medium se utiliza como digestivo y H. multiflora para el dolor abdominal y estomacal, como así también para las úlceras y hemorroides. Ambas especies son muy parecidas morfológicamente con lo cual resulta muy difícil la distinción al momento de la recolección de su ambiente silvestre.Fil: Peralta, Patricia Angelica. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Recursos Biológicos; Argentina. Universidad de Morón. Escuela Superior de Ciencias Exactas y Naturales; ArgentinaFil: Vazquez, S. Universidad de Morón. Escuela Superior de Ciencias Exactas y Naturales; ArgentinaFil: Van Baren, Catalina Maria. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacognosia; ArgentinaFil: Retta, Daiana S. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacognosia; ArgentinaFil: Bach, Hernán Gerónimo. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Recursos Biológicos; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Museo Farmacobotanica; Argentin

Análisis de la fracción “no volátil” (flavonoides) y perfil de compuestos no polares de Achyrocline satureioides. Red marcela

Objetivo: Evaluar el contenido de flavonoides y determinar el perfil de compuestos no polares en inflorescencias cosechadas de plantas ex vitro provenientes de un genotipo selecto de marcela (Achyrocline satureioides) cultivado en tres ambientes: Río Cuarto, Merlo y Castelar.Instituto de GenéticaFil: Retta, Daiana S. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacognosia; Argentina. Universidad de Buenos Aires. Instituto de Química y Metabolismo del Fármaco; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Guariniello, Julian. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; ArgentinaFil: Suárez, S. A. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Físico-Químicas y Naturales; ArgentinaFil: Galli, Maria Carolina. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria San Luis. Agencia de Extensión Rural Concarán; ArgentinaFil: Van Baren, Catalina Maria. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacognosia; Argentina. Universidad de Buenos Aires. Instituto de Química y Metabolismo del Fármaco; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Acantholippia seriphioides : chemical biodiversity of wild populations from the Cuyo Region in Argentina = Acantholippia seriphioides: Biodiversidad química de poblaciones silvestres de la región de Cuyo de la Argentina

Nineteen samples from the aerial parts in bloom of Acantholippia seriphioides (Verbenaceae) were collected in three provinces belonging to the Cuyo region of Argentina. The essential oils were obtained by hydrodistillation, yielding between 0.57 and 2.46% (v/w). On the basis of the 13 main compounds determined by GC-FID-MS, representing the 87.2 and 95.3% of the total identified, four chemotypes were determined: carvacrol, thymol, cis and trans-dihydrocarvone and linalool-geraniol. The co-occurrence of different chemotypes in a same population indicates that the sample collection must be carefully done with the aid of an in situ olfactory testing of the plants, since no morphological differences at first sight were observed among them. The results showed in this study suggest that the pattern of variations for this species exists throughout its natural distribution area.Se colectaron 19 muestras de partes aéreas en floración de Acantholippia seriphioides (Verbenaceae) de tres provincias de la región de Cuyo de la Argentina. Los aceites esenciales fueron obtenidos por hidrodestilación, arrojando rendimientos entre 0.57 y 2.46% (v/p). A partir de la determinación por GC-FID-MS de los 13 compuestos principales, que representaban entre el 87.2 y 95.3% del total de los identificados, fueron determinados cuatro quimiotipos: carvacrol, timol, cis y trans-dihidrocarvona, y linalol-geraniol. La co-ocurrencia de diferentes quimiotipos en una misma población indica que la colecta debe ser realizada con la ayuda de un examen olfatorio in situ de la planta, ya que, a primera vista no se observan diferencias morfológicas entre ellas. Los resultados sugieren que el patrón de variación para esta especie existe en toda su área de distribución natural.Fil: Van Baren, Catalina Maria. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacognosia; ArgentinaFil: Elechosa, Miguel Angel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Recursos Biológicos; ArgentinaFil: Di Leo Lira, Paola. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacognosia; ArgentinaFil: Retta, Daiana S. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacognosia; ArgentinaFil: Juarez, Miguel Angel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Recursos Biológicos; ArgentinaFil: Martinez, Alejandro. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Recursos Biológicos; ArgentinaFil: Molina, Ana Maria. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Recursos Biológicos; ArgentinaFil: Bandoni, Arnaldo L. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacognosia; Argentin

Liberating Political Commitment Based on Democracy in General Election

The implementation of the General Election, including its implications for governance, has so far been full of various deviations from the principles of democracy. Therefore, with a theological perspective, democracy needs to be rebuilt to free society from democratic shifts in the Election and governance that have an impact on discomfort in living together. This article aims to construct a liberating political commitment of Christian society based on a dialogue between the ideas of democracy according to Karsadi and Franz Magnis-Suseno with the idea of the prophetic role of the church according to John Chr. Ruhulessin. The result of this study shows that a liberating political commitment can be built through the internalization of church teachings, so that the church is responsible for providing Christian political ethics education

Helicobacter pylori Type IV Secretion Apparatus Exploits β1 Integrin in a Novel RGD-Independent Manner

Translocation of the Helicobacter pylori (Hp) cytotoxin-associated gene A (CagA) effector protein via the cag-Type IV Secretion System (T4SS) into host cells is a major risk factor for severe gastric diseases, including gastric cancer. However, the mechanism of translocation and the requirements from the host cell for that event are not well understood. The T4SS consists of inner- and outer membrane-spanning Cag protein complexes and a surface-located pilus. Previously an arginine-glycine-aspartate (RGD)-dependent typical integrin/ligand type interaction of CagL with α5β1 integrin was reported to be essential for CagA translocation. Here we report a specific binding of the T4SS-pilus-associated components CagY and the effector protein CagA to the host cell β1 Integrin receptor. Surface plasmon resonance measurements revealed that CagA binding to α5β1 integrin is rather strong (dissociation constant, KD of 0.15 nM), in comparison to the reported RGD-dependent integrin/fibronectin interaction (KD of 15 nM). For CagA translocation the extracellular part of the β1 integrin subunit is necessary, but not its cytoplasmic domain, nor downstream signalling via integrin-linked kinase. A set of β1 integrin-specific monoclonal antibodies directed against various defined β1 integrin epitopes, such as the PSI, the I-like, the EGF or the β-tail domain, were unable to interfere with CagA translocation. However, a specific antibody (9EG7), which stabilises the open active conformation of β1 integrin heterodimers, efficiently blocked CagA translocation. Our data support a novel model in which the cag-T4SS exploits the β1 integrin receptor by an RGD-independent interaction that involves a conformational switch from the open (extended) to the closed (bent) conformation, to initiate effector protein translocation