Clove-Based Local Economic Development in Lede Sub-District, Taliabu Island District North Maluku Province

This study aimed to identify and describe the clove agribusiness system and its economic prospects in supporting local economic development in Lede District, Taliabu Island Regency, North Maluku Province. The research was conducted using descriptive qualitative method. The results of this study suggest that Lede sub-district is one of the sub-district areas that is the base of clove agricultural development in Taliabu Island district. The developed clove commodity involves most of the farmers in the Lede Sub-district area, with a large development area, coupled with a high level of productivity. The clove commodity has potential economic value and has contributed to household income and the quality of clove farmers' welfare. To realize local economic development efforts based on the clove commodity, it is necessary to have the intervention of various parties, especially the local government and the private sector, both on the intervention in the scale of on farm and off farm activities, especially on a number of interventions related to infrastructure and superstructure supporting agricultural production activities, capital, to marketing management aspects and efforts to increase the economic added value of the clove commodity developed

Synthèse et évaluation cinétique d'inhibiteurs de la Transglutaminase tissulaire

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal

Pengembangan Ekonomi Lokal Berbasis Cengkeh di Kecamatan Lede Kabupaten Pulau Taliabu Provinsi Maluku Utara

Perdesaan, kemiskinan dan pertanian merupakan tiga persoalan yang masih belum terselesaikan serta memiliki korelasi antara satu dengan lainnya. Melalui kerangka otonomi dan desentralisasi, cukup terbuka peluang bagi setiap daerah untuk merumuskan berbagai kebijakan yang relevan dengan kekhasan sosial dan ekonomi masing-masing. Salah satu solusi yang dapat diwujudkan sebagai alternatif kebijakan pembangunan wilayah dalam kerangka otonomi dan desentralisasi dimaksud adalah dengan penerapan konsep Pengembangan Ekonomi Lokal (PEL). Wilayah Kabupaten Pulau Taliabu di provinsi Maluku Utara merupakan salah satu daerah dengan tingginya angka prosentase kemiskinan serta dominasi kegiatan ekonomi dan serapan tenaga kerja tertinggi pada sektor pertanian. Kecamatan Lede di kabupaten Pulau Taliabu diantaranya merupakan kawasan pengembangan sektor pertanian dengan dominasi sub-sektor perkebunan cengkeh yang melibatkan sebagian besar petani lokal dan merupakan sumber pendapatan utama penduduk. Pengembangan areal perkebunan cengkeh pada setiap desa di Kecamatan Lede cukup luas dengan tingkat produksi tahunan tinggi. Pertanian cengkeh petani di Kecamatan Lede merupakan praktek pertanian komersial dengan sifat pengembangan yang masih konvesional, serta kegiatan agribisnis cengkeh yang cenderung bertumpu pada kemandirian petani lokal. Ekonomi cengkeh berkontribusi cukup tinggi pada pendapatan rumah tangga petani cengkeh, meskipun belum memberikan dampak secara luas dan berkesinambungan pada aktivitas perekonomian lokal yang disebabkan oleh berbagai faktor. Optimalisasi potensi ekonomi agribisnis cengkeh pada konteks lokal dapat dimulai dari intensitas pelibatan peran para pihak utamanya pemerintah daerah dan sektor swasta. Peran dimaksud dapat diimplementasikan pada tahap-tahap tertentu dari hulu hingga hilir dalam sistem pertanian cengkeh. Dengan upaya semacam ini, komoditi cengkeh dapat menjadi sektor basis potensial dalam pengembangan ekonomi lokal

O monólogo do zoo: nos caminhos de uma narrativa digital?

Resumo: : Os zoológicos são instituições científicas porque encerram coleções faunísticas com relevância biológica, além de repercutirem de formas distintas as características dos biomas de origem desses seres vivos. Disto provém sua potencialidade pedagógica, extensível para a Educação Básica com consequente aproveitamento desses lugares como ambientes não formais de ensino. Um ambiente não formal de ensino, mas com potencialidade para o ensino-aprendizagem e que vai ao encontro da proposição sempre vanguardista de turismo educativo feita por Célestin Freinet. Este trabalho é um relato de experiência sobre uma aula de campo que resultou na construção de uma narrativa digital, que se propõe como diálogo entre protagonistas escolares e institucionais, no sentido de modificar uma realidade no seio de um modelo de crise socioambiental.Palavras-chave: Ambiente não formal; Zoológico; Mídia; TDIC; Comunicação. The zoo monologue: on the ways of a digital narrative?Abstract: : Zoos are scientific institutions because they contain faunal collections with biological relevance, as well as having different repercussions on the characteristics of the biomes of origin of these living beings. From this comes their pedagogical potential, extendable to Basic Education with the consequent use of these places as non formal educational environments. A non-formal teaching environment, but with potential for teaching-learning and that meets the always avant-garde proposition of educational tourism made by Célestin Freinet. This work is an experience report about a field class that resulted in the construction of a digital narrative, which is proposed as a dialogue between school and institutional protagonists, in order to modify a reality within a socioenvironmental crisis model.Keywords: Non-formal environment; Zoo; Media; TDIC; Communication.

Reaction profiling of a set of acrylamide-based human tissue transglutaminase inhibitors

The major function of the enzyme human tissue transglutaminase (TG2) is the crosslinking of proteins via a transamidation between the γ-carboxamide of a glutamine and the ε-amino group of a lysine. Overexpression of TG2 can lead to undesirable outcomes and has been linked to conditions such as fibrosis, celiac disease and neurodegenerative diseases. Accordingly, TG2 is a tempting drug target. The most effective TG2 inhibitors to date are small-molecule peptidomimetics featuring electrophilic warheads that irreversibly modify the active site catalytic cysteine (CYS277). In an effort to facilitate the design of such TG2 inhibitors, we undertook a quantum mechanical reaction profiling of the Michael reaction between a set of six acrylamide-based known TG2 inhibitors and the TG2 CYS277. The inhibitors were docked into the active site and the coordinates were refined by MD simulations prior to modelling the covalent modification of the CYS277 thiolate. The results of QM/MM MD umbrella sampling applied to reaction coordinates driving the Michael reaction are presented for two approximations of the Michael reaction: a concerted reaction (simultaneous thiolate attack onto the acrylamide warhead and pronation from the adjacent HIS335) and a two-stage reaction (consecutive thiolate attack and protonation). The two-stage approximation of the Michael reaction gave the better results for the evaluation of acrylamide-based potential TG2 inhibitors in silico. Good correlations were observed between the experimental TG2 IC50 data and the calculated activation energies over the range 0.0061 – 6.3 µM (three orders of magnitude) and we propose that this approach may be used to evaluate acrylamide-based potential TG2 inhibitors

Development of potent and selective tissue transglutaminase inhibitors:their effect on TG2 function and application in pathological conditions

Potent-selective peptidomimetic inhibitors of tissue transglutaminase (TG2) were developed through a combination of protein-ligand docking and molecular dynamic techniques. Derivatives of these inhibitors were made with the aim of specific TG2 targeting to the intra- and extracellular space. A cell-permeable fluorescently labeled derivative enabled detection of in situ cellular TG2 activity in human umbilical cord endothelial cells and TG2-transduced NIH3T3 cells, which could be enhanced by treatment of cells with ionomycin. Reaction of TG2 with this fluorescent inhibitor in NIH3T3 cells resulted in loss of binding of TG2 to cell surface syndecan-4 and inhibition of translocation of the enzyme into the extracellular matrix, with a parallel reduction in fibronectin deposition. In human umbilical cord endothelial cells, this same fluorescent inhibitor also demonstrated a reduction in fibronectin deposition, cell motility, and cord formation in Matrigel. Use of the same inhibitor in a mouse model of hypertensive nephrosclerosis showed over a 40% reduction in collagen deposition

Activation and Inhibition of Transglutaminase 2 in Mice

Transglutaminase 2 (TG2) is an allosterically regulated enzyme with transamidating, deamidating and cell signaling activities. It is thought to catalyze sequence-specific deamidation of dietary gluten peptides in the small intestines of celiac disease patients. Because this modification has profound consequences for disease pathogenesis, there is considerable interest in the design of small molecule TG2 inhibitors. Although many classes of TG2 inhibitors have been reported, thus far an animal model for screening them to identify promising celiac drug candidates has remained elusive. Using intraperitoneal administration of the toll-like receptor 3 (TLR3) ligand, polyinosinic-polycytidylic acid (poly(I∶C)), we induced rapid TG2 activation in the mouse small intestine. Dose dependence was observed in the activation of TG2 as well as the associated villous atrophy, gross clinical response, and rise in serum concentration of the IL-15/IL-15R complex. TG2 activity was most pronounced in the upper small intestine. No evidence of TG2 activation was observed in the lung mucosa, nor were TLR7/8 ligands able to elicit an analogous response. Introduction of ERW1041E, a small molecule TG2 inhibitor, in this mouse model resulted in TG2 inhibition in the small intestine. TG2 inhibition had no effect on villous atrophy, suggesting that activation of this enzyme is a consequence, rather than a cause, of poly(I∶C) induced enteropathy. Consistent with this finding, administration of poly(I∶C) to TG2 knockout mice also induced villous atrophy. Our findings pave the way for pharmacological evaluation of small molecule TG2 inhibitors as drug candidates for celiac disease

Pré-Natal como estratégia de prevenção à violência obstétrica.

INTRODUCTION: Research shows that in Brazil, one in four women suffer violence during childbirth. Studies carried out in Venezuela, Brazil and Mexico show that pregnant women are subjected to invasive practices without their consent. OBJECTIVE: To present, according to the scientific literature, the contribution of prenatal care to the prevention of obstetric violence. METHODOLOGY: This is a qualitative study, it refers to an integrative literature review, presenting a synthesis of the studies analyzed in full, organizing them for the elaboration of the results regarding the established theme, being carried out in the month of August 2023. RESULTS: the health education developed during the prenatal consultations not only provides the pregnant woman with information about pregnancy, delivery and postpartum, but also encourages and stimulates the woman's autonomy, strengthening her self-confidence and showing her protagonism during pregnancy and strengthening the power of choice regarding the procedures performed on her body. FINAL CONSIDERATIONS: Therefore, it is understood that prenatal care becomes an important part in the care of women during the gestational period, since it allows clarifying doubts and providing guidance and new information regarding childbirth and postpartum, the in order to let the pregnant woman inside the whole process, bringing autonomy to her, making her the protagonist of the active voice of the moment.INTRODUÇÃO: Pesquisas mostram que no Brasil, uma a cada quatro mulheres sofre violência no parto. Estudos realizados na Venezuela, no Brasil e no México mostram que as parturientes são submetidas a práticas invasivas sem o seu consentimento. OBJETIVO: Apresentar, de acordo com a literatura científica, a contribuição do pré-natal para a prevenção da violência obstétrica. METODOLOGIA: Trata-se de um estudo qualitativo, refere-se a uma revisão integrativa da literatura, apresentando uma síntese dos estudos analisados na íntegra, organizando-os para a elaboração dos resultados a respeito da temática estabelecida, sendo realizada no mês de agosto de 2023. RESULTADOS: a educação em saúde desenvolvida durante  as consultas do pré-natal,  não  só  favorecem  a  gestante  com informações sobre a gravidez, parto e pós-parto, como também incentiva e estimula a autonomia da mulher, fortalecendo sua autoconfiança e evidenciando seu protagonismo durante a gravidez e fortalecendo o poder de escolha frente aos procedimentos realizados em seu corpo. CONSIDERAÇÕES FINAIS: Portanto, entende-se que o pré-natal se torna peça importante no atendimento à mulher no período gestacional, visto que possibilita o esclarecimento de dúvidas e o fornecimento de orientações e novas informações a respeito do parto e pós-parto, a fim de deixar a gestante por dentro de todo o processo, trazendo autonomia para a mesma, tornando-a protagonista de voz ativa do momento

Cytosolic Guanine Nucledotide Binding Deficient Form of Transglutaminase 2 (R580a) Potentiates Cell Death in Oxygen Glucose Deprivation

Transglutaminase 2 (TG2) is a hypoxia-responsive protein that is a calcium-activated transamidating enzyme, a GTPase and a scaffolding/linker protein. Upon activation TG2 undergoes a large conformational change, which likely affects not only its enzymatic activities but its non-catalytic functions as well. The focus of this study was on the role of transamidating activity, conformation and localization of TG2 in ischemic cell death. Cells expressing a GTP binding deficient form of TG2 (TG2-R580A) with high basal transamidation activity and a more extended conformation showed significantly increased cell death in response to oxygen-glucose deprivation; however, targeting TG2-R580A to the nucleus abrogated its detrimental role in oxygen-glucose deprivation. Treatment of cells expressing wild type TG2, TG2-C277S (a transamidating inactive mutant) and TG2-R580A with Cp4d, a reversible TG2 inhibitor, did not affect cell death in response to oxygen-glucose deprivation. These findings indicate that the pro-cell death effects of TG2 are dependent on its localization to the cytosol and independent of its transamidation activity. Further, the conformational state of TG2 is likely an important determinant in cell survival and the prominent function of TG2 in ischemic cell death is as a scaffold to modulate cellular processes

Serotonylation of Vascular Proteins Important to Contraction

BACKGROUND:Serotonin (5-hydroxytryptamine, 5-HT) was named for its source (sero-) and ability to modify smooth muscle tone (tonin). The biological effects of 5-HT are believed to be carried out by stimulation of serotonin receptors at the plasma membrane. Serotonin has recently been shown to be synthesized in vascular smooth muscle and taken up from external sources, placing 5-HT inside the cell. The enzyme transglutaminase uses primary amines such as 5-HT to covalently modify proteins on glutamine residues. We tested the hypothesis that 5-HT is a substrate for transglutaminase in arterial vascular smooth muscle, with protein serotonylation having physiological function. METHODOLOGY/PRINCIPAL FINDINGS:The model was the rat aorta and cultured aortic smooth muscle cells. Western analysis demonstrated that transglutaminase II was present in vascular tissue, and transglutaminase activity was observed as a cystamine-inhibitable incorporation of the free amine pentylamine-biotin into arterial proteins. Serotonin-biotin was incorporated into alpha-actin, beta-actin, gamma-actin, myosin heavy chain and filamin A as shown through tandem mass spectrometry. Using antibodies directed against biotin or 5-HT, immunoprecipitation and immunocytochemistry confirmed serotonylation of smooth muscle alpha-actin. Importantly, the alpha-actin-dependent process of arterial isometric contraction to 5-HT was reduced by cystamine. CONCLUSIONS:5-HT covalently modifies proteins integral to contractility and the cytoskeleton. These findings suggest new mechanisms of action for 5-HT in vascular smooth muscle and consideration for intracellular effects of primary amines