INTERCELLULAR AND INTRACELLULAR TRAFFICKING OF NAD+ AND NAD+ PRECURSORS, INTERMEDIATE METABOLITES AND SIGNAL METABOLITES

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Spatio-temporal propagation of Ca2+ signals by cyclic ADP-ribose in 3T3 cells stimulated via purinergic P2Y receptors

The role of cyclic ADP-ribose in the amplification of subcellular and global Ca2+ signaling upon stimulation of P2Y purinergic receptors was studied in 3T3 fibroblasts. Either (1) 3T3 fibroblasts (CD38− cells), (2) 3T3 fibroblasts preloaded by incubation with extracellular cyclic ADP-ribose (cADPR), (3) 3T3 fibroblasts microinjected with ryanodine, or (4) 3T3 fibroblasts transfected to express the ADP-ribosyl cyclase CD38 (CD38+ cells) were used. Both preincubation with cADPR and CD38 expression resulted in comparable intracellular amounts of cyclic ADP-ribose (42.3 ± 5.2 and 50.5 ± 8.0 pmol/mg protein). P2Y receptor stimulation of CD38− cells yielded a small increase of intracellular Ca2+ concentration and a much higher Ca2+ signal in CD38-transfected cells, in cADPR-preloaded cells, or in cells microinjected with ryanodine. Confocal Ca2+ imaging revealed that stimulation of ryanodine receptors by cADPR or ryanodine amplified localized pacemaker Ca2+ signals with properties resembling Ca2+ quarks and triggered the propagation of such localized signals from the plasma membrane toward the internal environment, thereby initiating a global Ca2+ wave

Abscisic acid transport in human erythrocytes

Abscisic acid (ABA) is a plant hormone involved in the response to environmental stress. Recently, ABA has been shown to be present and active also in mammals, where it stimulates the functional activity of innate immune cells, of mesenchymal and hemopoietic stem cells, and insulin-releasing pancreatic \u3b2-cells. LANCL2, the ABA receptor in mammalian cells, is a peripheral membrane protein that localizes at the intracellular side of the plasma membrane. Here we investigated the mechanism enabling ABA transport across the plasmamembrane of human red blood cells (RBC). Both influx and efflux of [3H]ABA occur across intact RBC, as detected by radiometric and chromatographic methods. ABA binds specifically to Band 3 (the RBC anion transporter), as determined by labeling of RBC membranes with biotinylated ABA. Proteoliposomes reconstituted with human purified Band 3 transport [3H]ABA and [35S]sulfate, and ABA transport is sensitive to the specific Band 3 inhibitor 4,4\u2032-diisothiocyanostilbene-2,2\u2032-disulfonic acid. Once inside RBC, ABA stimulates ATP release through the LANCL2-mediated activation of adenylate cyclase. As ATP released from RBC is known to exert a vasodilator response, these results suggest a role for plasma ABA in the regulation of vascular ton

Suplementação prolongada com creatina melhora a capacidade aeróbica de eqüinos

O objetivo do presente estudo foi investigar os efeitos da suplementação oral com creatina sobre respostas fisiológicas ao treinamento aeróbico. Doze cavalos da raça Puro Sangue Árabe foram submetidos a treinamento aeróbico por 90 dias, com ou sem suplementação com creatina, que consistia da administração diária de 75g de monoidrato de creatina misturada à ração durante os 90 dias de treinamento. O treinamento físico foi conduzido exclusivamente em esteira rolante de alto desempenho sendo a intensidade do treinamento estabelecida em 80% da velocidade obtida através da V4 (velocidade na qual a concentração sangüínea de lactato atinge 4mmol L-1) determinada mensalmente para cada animal. Para o estabelecimento da V4 individual foi empregado um teste físico de esforço crescente em que, após um período de aquecimento de 4min a 4m s-1, a velocidade era aumentada à cada intervalo de dois minutos, para 6, 8 e 10m s-1. As amostras sangüíneas foram coletadas 15s antes do témino de cada intervalo para a determinação do lactato, hematócrito, hemoglobina e eritrócitos. Os resultados demonstraram um aumento significativo (P<0,05) da V4 dos animais que receberam creatina por 60 e 90 dias quando comparados, no mesmo período, com os animais que não receberam a suplementação. As outras variáveis hematológicas não apresentaram alterações. É possível sugerir que a suplementação prolongada com creatina pode promover efeitos benéficos no desempenho atlético de eqüinos. _________________________________________________________________________________________________________ ABSTRACTThe aim of the present study was to investigate the effect of long-term oral supplementation of creatine on the physiological responses to aerobic training. Twelve purebred Arabian horses were submitted to aerobic training for 90 days, with and without creatine supplementation which consisted of the daily administration of 75g of creatine monohydrate mixed into the ration for 90 days of training. Physical conditioning was conducted on a high performance treadmill and training intensity was stipulated by calculating the V4 (velocity at which blood lactate reaches 4mmol L-1) determined monthly for each animal. The individual intensity of physical force at 80% of aerobic threshold was established. An incremental exercise test was used to set the individual V4. After a warm up period of 4 min at 4m s-1, the speed was increased at 2min intervals to 6, 8 and 10m s-1. The blood samples were collected 15s before the end of each step to determine the concentration of lactate, packed cell volume, hemoglobin and red cell values. The results demonstrated a significant increase (P<0.05) in V4 in the groups that received creatine supplementation for 60 days or more when compared to the animals without creatine supplememntation. The other hematological variables were similar to all groups. The results showed that the prolonged creatine supplementation may have a beneficial al effect on the equine athletic performance

SemTree: An index for supporting semantic retrieval of documents

In this paper, we propose SemTree, a novel semantic index for supporting retrieval of information from huge amount of document collections, assuming that semantics of a document can be effectively expressed by a set of (subject, predicate, object) statements as in the RDF model. A distributed version of KD-Tree has been then adopted for providing a scalable solution to the document indexing, leveraging the mapping of triples in a vectorial space. We investigate the feasibility of our approach in a real case study, considering the problem of finding inconsistencies in documents related to software requirements and report some preliminary experimental results

Implantação dos serviços de vagão-biblioteca na Rede Ferroviária Federal S.A. : SR-6 (Rio Grande do Sul)

A difusão do uso do livro e a formação do hábito da leitura tem sido feita em locais carentes e onde inexistem bibliotecas, através de bibliotecas ambulantes, especialmente “carro-biblioteca”. Apresenta-se aqui o projeto de implantação de biblioteca-ambulante em “vagão-biblioteca”, que circulará por via férrea, acoplado a trens

Contribuciones del Arte y la Literatura en la construcción del conocimiento geográfico en la educación fundamental

O presente estudo tem por objetivo propor uma atividade interdisciplinar entre Geografia, Literatura e a Arte nos anos iniciais do ensino fundamental e, para isto, utilizamos uma obra da literatura infantil intitulada O Maluco do céu (2009), de Anna Gobel, a qual se inspira em uma lenda caribenha sobre a formação dos continentes. Considerando que a história possui elementos geográficos implícitos na arte do livro e no diálogo dos personagens, destacamos as potencialidades de instrumentalizar os alunos sobre esses conceitos e de estimular a sua capacidade de leitura e de apreciação e representação artística. As idealizações e as sugestões das atividades foram concebidas considerando as habilidades a serem desenvolvidas que são requeridas pela Base Nacional Comum Curricular (2017), nas disciplinas de Geografia, Artes e Língua Portuguesa para os 2° e 3° anos do ensino fundamental.El presente estudio tiene como objetivo proponer una actividad interdisciplinar entre Geografía, Literatura y Arte en los primeros años de la escuela primaria y, para ello, utilizamos una obra de literatura infantil titulada El loco del cielo (2009), de Anna Gobel, que está inspirado en una leyenda caribeña sobre la formación de continentes. Teniendo en cuenta que la historia tiene elementos geográficos implícitos en el arte del libro y en el diálogo de los personajes, destacamos el potencial de instruir a los estudiantes sobre estos conceptos y de estimular su capacidad para leer y apreciar y representar el arte. Las idealizaciones y sugerencias de las actividades fueron concebidas considerando las habilidades a desarrollar que son requeridas por la Base Curricular Común Nacional (2017), en las disciplinas de Geografía, Artes y Lengua Portuguesa para el 2º y 3º año de la escuela primaria.This study aims to propose an interdisciplinary activity between Geography, Literature and Art in the early years of elementary school and, for this, we use a work of children's literature entitled The crazy of heaven (2009), by Anna Gobel, which is inspired by a Caribbean legend about the formation of continents. Considering that history has geographic elements implicit in the art of the book and in the dialogue of the characters, we highlight the potential to instrumentalize students on these concepts and also to stimulate their capacity for reading and artistic appreciation and representation. The idealizations and suggestions of the activities were conceived considering the skills to be developed that are required by the Common National Curriculum Base (2017), in the subjects of Geography, Arts and Portuguese Language for the 2nd and 3rd years of elementary school.                                 

Low levels of granulocytic myeloid-derived suppressor cells may be a good marker of survival in the follow-up of patients with severe COVID-19

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a disease (coronavirus disease 2019, COVID-19) that may develop into a systemic disease with immunosuppression and death in its severe form. Myeloid-derived suppressive cells (MDSCs) are inhibitory cells that contribute to immunosuppression in patients with cancer and infection. Increased levels of MDSCs have been found in COVID-19 patients, although their role in the pathogenesis of severe COVID-19 has not been clarified. For this reason, we raised the question whether MDSCs could be useful in the follow-up of patients with severe COVID-19 in the intensive care unit (ICU). Thus, we monitored the immunological cells, including MDSCs, in 80 patients admitted into the ICU. After 1, 2, and 3 weeks, we examined for a possible association with mortality (40 patients). Although the basal levels of circulating MDSCs did not discriminate between the two groups of patients, the last measurement before the endpoint (death or ICU discharge) showed that patients discharged alive from the ICU had lower levels of granulocytic MDSCs (G-MDSCs), higher levels of activated lymphocytes, and lower levels of exhausted lymphocytes compared with patients who had a bad evolution (death). In conclusion, a steady increase of G-MDSCs during the follow-up of patients with severe COVID-19 was found in those who eventually died

G-protein coupling and nuclear translocation of the human abscisic acid receptor LANCL2

Abscisic acid (ABA), a long known phytohormone, has been recently demonstrated to be present also in humans, where it targets cells of the innate immune response, mesenchymal and hemopoietic stem cells and cells involved in the regulation of systemic glucose homeostasis. LANCL2, a peripheral membrane protein, is the mammalian ABA receptor. We show that N-terminal glycine myristoylation causes LANCL2 localization to the plasmamembrane and to cytoplasmic membrane vesicles, where it interacts with the \u3b1 subunit of a Gi protein and starts the ABA signaling pathway via activation of adenylate cyclase. Demyristoylation of LANCL2 by chemical or genetic means triggers its nuclear translocation. Nuclear enrichment of native LANCL2 is also induced by ABA treatment. Therefore human LANCL2 is a non-transmembrane G protein-coupled receptor susceptible to hormone-induced nuclear translocation