Design, synthesis and biological activity of selective hCAs inhibitors based on 2-(benzylsulfinyl)benzoic acid scaffold

A large library of derivatives based on the scaffold of 2-(benzylsulfinyl)benzoic acid were synthesised and tested as atypical inhibitors against four different isoforms of human carbonic anhydrase (hCA I, II, IX and XII, EC 4.2.1.1). The exploration of the chemical space around the main functional groups led to the discovery of selective hCA IX inhibitors in the micromolar/nanomolar range, thus establishing robust structure-activity relationships within this versatile scaffold. HPLC separation of some selected chiral compounds and biological evaluation of the corresponding enantiomers was performed along with molecular modelling studies on the most active derivatives

Nebulized Delivery of the MAPKAP Kinase 2 Peptide Inhibitor MMI-0100 Protects Against Ischemia-Induced Systolic Dysfunction

Acute myocardial infarction (AMI) results in systolic dysfunction, myocarditis and fibrotic remodeling, which causes irreversible pathological remodeling of the heart. Associated cell death and inflammation cause cytokine release, which activates the p38 MAPK signaling pathway to propagate damaging signals via MAPKAP kinase 2 (MK2). Previously we showed that intraperitoneal injection of a cell permeable peptide inhibitor of MK2, MMI-0100, protects against fibrosis, apoptosis and systolic dysfunction in a mouse model of AMI induced by left-anterior descending coronary artery (LAD) ligation. Here we tested a new route of administration of MMI-0100: inhalation of nebulized peptide. When given within 30 min of AMI and daily for 2 weeks thereafter, both inhaled and injected MMI-0100 improved cardiac function as measured by conscious echocardiography. Limited fibrosis was observed after 2 weeks by Massons trichrome staining, suggesting that MMI-0100 protects the heart prior to the formation of significant fibrosis. These results support a nebulized route of administration of MMI-0100 can protect the myocardium from ischemic damage

Learning from the italian experience during covid-19 pandemic waves: Be prepared and mind some crucial aspects

COVID-19 pandemic has rapidly spread worldwide causing a serious challenge to the global medical community. Italy was struck hard during the first wave earlier this year and several weaknesses as well as general unpreparedness of the national healthcare system were acknowledged. Learning essential lessons from the past, we realized how implementing contingency response measures, human resources and social dynamics could have changed the outcome if promptly adopted. This review translates the previous experience into strategic actions that has to be considered when developing appropriate national and regional operational plans to respond to a pandemic

Resistência extrema a duas estirpes do Potato virus Y (PVY) de batata transgênica, cv. Achat, expressando o gene da capa protéica do PVYO

The coat protein (CP) gene of the potato virus Y strain “o” (PVYO) was introduced into potato, cultivar Achat, via Agrobacterium tumefaciens-mediated transformation. Sixty three putative transgenic lines were challenged against the Brazilian strains PVY-OBR and PVY-NBR. An extremely resistant phenotype, against the two strains, was observed in one line, denominated 1P. No symptoms or positive ELISA results were observed in 16 challenged plants from this line. Another clone, named as 63P, showed a lower level of resistance. Southern blot analysis showed five copies of the CP gene in the extremely resistant line and at least three copies in the other resistant line. The stability of the integrated transgenes in the extreme resistant line was examined during several in vitro multiplications over a period of three years, with no modification in the Southern pattern was observed. The stability of the transgenes, the absence of primary infections and the relatively broad spectrum of resistance suggest that the extremely resistant line obtained in this work can be useful for agricultural purposes.O gene da capa protéica (CP) do Potato virus Y estirpe “o”, foi introduzido em batata cultivar Achat, via Agrobacterium tumefaciens. Sessenta e três linhas possivelmente transgênicas foram desafiadas com as estirpes brasileiras PVY-OBR e PVY-NBR. Uma linha apresentou extrema resistência às duas estirpes inoculadas, e foi denominado clone 1P. Não foram observados sintomas sistêmicos de infecção e as plantas foram negativas em Elisa. Outra linha, denominada clone 63P, mostrou algum nível de resistência. Análises por Southern blot indicaram a presença de pelo menos cinco cópias do gen CP no clone 1P e pelo menos três cópias no clone 63P. A estabilidade do gene introduzido no clone 1P foi avaliada durante três anos, após várias multiplicações in vitro. Não foram observadas mudanças no padrão do Southern blot. A estabilidade do transgene, na ausência de infecções primárias e relativo largo espectro de resistência sugerem que o clone 1P pode ser utilizado para fins comerciais.Fil: Romano, Eduardo. Embrapa Recursos Genéticos; BrasilFil: Ferreira, Adriana T.. Embrapa Hortaliças; BrasilFil: Dusi, André N.. Embrapa Hortaliças; BrasilFil: Proite, Karina. Embrapa Recursos Genéticos; BrasilFil: Buso, Jose A.. Embrapa Hortaliças; BrasilFil: Avila, Antonio C.. Embrapa Hortaliças; BrasilFil: Nishijima, Marta L.. Embrapa Hortaliças; BrasilFil: Nascimento, Adriana S.. Embrapa Hortaliças; BrasilFil: Bravo Almonacid, Fernando Felix. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Mentaberry, Alejandro Nestor. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Monte, Damares. Embrapa Recursos Genéticos; BrasilFil: Campos, Magnolia A.. Embrapa Recursos Genéticos; BrasilFil: Melo, Paulo Eduardo. Embrapa Hortaliças; BrasilFil: Cattony, Monica K.. No especifica;Fil: Torres, Antonio C.. Embrapa Hortaliças; Brasi

Unravelling main- and side-chain motions in polymers with NMR spectroscopy and relaxometry: The case of polyvinyl butyral

Polyvinyl butyral (PVB) is an amorphous polymer employed in many technological applications. In order to highlight the relationships between macroscopic properties and dynamics at a microscopic level, motions of the main-chain and of the propyl side-chains were investigated between Tg − 288◦ C and Tg + 55◦ C, with Tg indicating the glass transition temperature. To this aim, a combination of solid state Nuclear Magnetic Resonance (NMR) methods was applied to two purposely synthesized PVB isotopomers: one fully protonated and the other perdeuterated on the side-chains.1 H time domain NMR and1 H field cycling NMR relaxometry experiments, performed across and above Tg, revealed that the dynamics of the main-chain corresponds to the α-relaxation associated to the glass transition, which was previously characterized by dielectric spectroscopy. A faster secondary relaxation was observed for the first time and ascribed to side-chains. The geometry and rate of motions of the different groups in the side-chains were characterized below Tg by2 H NMR spectroscopy

Postharvest of acerola fruits grown in a semi-arid region: characteristics and levels of bioactive polyphenols.

O objetivo deste trabalho foi avaliar o desempenho de genótipos de acerola quanto à qualidade pós-colheita de frutos dos genótipos BRS 366 Jaburu, Clone 09, Clone 13, Clone 14, Junko e Sertaneja, cultivados no sudoeste piauiense, Nordeste do Brasil. Utilizou-se o delineamento em blocos casualizados (DBC), com tratamentos constituídos por seis genótipos, três repetições e três plantas por parcela. Foram avaliados a produtividade, massa do fruto, comprimento do fruto, diâmetro do fruto, cor, rendimento de suco, antocianinas e flavonóides, carotenóides, pH, acidez titulável e ácido ascórbico. Os resultados mostram um alto potencial produtivo do Clone 13. No entanto, o genótipo BRS 366 Jaburu destaca-se quanto às características físicas do fruto, proporcionando melhor equilíbrio na acidez titulável, bons teores de polifenóis totais e elevada quantidade de vitamina C aliada ao rendimento de suco, o que é exigido para frutos de acerola. Assim, a BRS 366 Jaburu mostra-se promissora para o cultivo nas condições edafoclimáticas da região Sudoeste Piauiense

Fulminant myocarditis parvovirus B19 related in a young woman

We present the case of a 18-year-old female with fulminant lymphocytic myocarditis caused by Parvovirus B19 (PVB19), successfully treated using temporary LVAD. In the literature there is no consensus on the surgical strategy. While some surgeons prefer to use a single device supporting only the LV, others prefer to start immediately with a biventricular supporting. At pre-procedural ultrasound evaluation, her anatomical features were not suitable for a percutaneous device such as the Impella. Thus, a temporary paracorporeal continuous flow LVAD was inserted. The heart recovery allowed LVAD removal 9 days after the implant

Integrating the Fermi Gamma-Ray Burst Monitor into the 3rd Interplanetary Network

We are integrating the Fermi Gamma-Ray Burst Monitor (GBM) into the Interplanetary Network (IPN) of Gamma-Ray Burst (GRB) detectors. With the GBM, the IPN will comprise 9 experiments. This will 1) assist the Fermi team in understanding and reducing their systematic localization uncertainties, 2) reduce the sizes of the GBM and Large Area Telescope (LAT) error circles by 1 to 4 orders of magnitude, 3) facilitate the identification of GRB sources with objects found by ground- and space-based observatories at other wavelengths, from the radio to very high energy gamma-rays, 4) reduce the uncertainties in associating some LAT detections of high energy photons with GBM bursts, and 5) facilitate searches for non-electromagnetic GRB counterparts, particularly neutrinos and gravitational radiation. We present examples and demonstrate the synergy between Fermi and the IPN. This is a Fermi Cycle 2 Guest Investigator project.Comment: 5 pages, 11 figures. 2009 Fermi Symposium. eConf Proceedings C09112

Perdas por volatilização de N-NH3 proveniente da mistura de uréia com zeolita natural aplicada no inverno na cultura da roseira.

Com objetivo de avaliar a mistura de zeolita natural (arenito zeolítico) com uréia quanto às perdas de NH3 por volatilização, realizou-se experimento em área de produção comercial de flores de corte em Nova Friburgo, RJ. No verão de 2007 foi realizada adubação de cobertura na cultura da roseira (Rosa spp.) com duas doses de uréia (60 e 120 kg N. ha-1) misturadas ou não com arenito zeolítico, na proporção de 20% p/p. As perdas de NH3 por volatilização foram avaliadas por período de seis dias consecutivos após aplicação dos fertilizantes. Utilizou-se câmara semi-aberta livre estática, confeccionada com frasco plástico transparente de 2 litros (PET). A mistura é eficiente na redução das perdas de NH3 por volatilização, sendo a mesma, em média 24%. O arenito zeolítico (CETEM) apresenta características favoráveis para uso em desenvolvimento de ?fertilizantes zeolíticos? de liberação lenta, principalmente com objetivo de proporcionar redução nas perdas de NH3 por volatilização