Hidrogéis preparados a partir da automontagem de desidrodipéptidos

Dissertação de mestrado em Medicinal ChemistrySelf-assembly of nanometric structures from molecular building blocks is an effective way to make new functional materials for biological and technological applications. In this work we synthesized new N-modified dehydrodipeptides based on phenylalanine and dehydroamino acid units attached to aromatic modifiers, namely trimesoyl, terephtaloyl, diphenylacetyl and 2,2´-(1,3-phenylene)diacetyl in a pattern that afforded mono or polysubstitued organic molecules. The potential use of these new compounds as hydrogelators was evaluated. The results showed that most of the prepared compounds behave as efficient molecular hydrogelators forming hydrogels at minimum gelation concentrations of 0.3-0.8 wt%. Two new compounds failed to form hydrogels probably due to unfavorable thermodynamic contribution of intermolecular interactions. The self-aggregation pattern of the hydrogelators was investigated by STEM microscopy technique, revealing different shapes depending on the N-aromatic moiety. A circular dichroism analysis was also performed in order to evaluate if the peptides aggregate into any characteristic secondary structure, usually found in protein folding. We found that the 5 hydrogelators had characteristic signals, demonstrating the presence of organized structures even below the minimum gelation concentration. At elevated pH or for the non-hydrogelating compounds, it was not observed signals indicative of the presence of such structures.A automontagem de estruturas manométricas, a partir de entes de dimensão molecular, consiste em uma alternativa eficiente para a síntese de novos materiais funcionais para aplicações biotecnológicas. Neste trabalho, foram sintetizados novos desidrodipéptidos modificados em sua porção N-terminal. Os dipéptidos continham fenilalanina e desidroaminoácidos e os grupos modificadores foram grupos aromáticos (trimesoil, tereftaloil, difenilacetil e o 2,2´-(1,3- phenileno)diacetil) os quais foram conjugados de forma a gerar compostos mono ou polissubstituídos. A capacidade de gelificar em meio aquoso, destes novos compostos, foi avaliada e os resultados mostraram que a maioria deles conseguiram gelificar em meio aquoso em concentrações mínimas na faixa 0.3-0.8 m%. Dois destes compostos não conseguiram originar hidrogéis, provavelmente devido a um balanço termodinamicamente desfavorável das interacções intermoleculares entre os constituintes do sistema. O padrão morfológico resultante da auto-agregação dos compostos que geraram os hidrogéis foi investigado pela técnica de microscopia electrónica de transmissão por scaneamento (STEM). Esta análise revelou que houve a ocorrência de diferentes tipos de estruturas nos hidrogéis, dependendo de qual modificador aromático foi utilizado. Também realizou-se uma análise de Dicroísmo Circular para avaliar se os péptidos agregavam-se em algum padrão de estrutura secundária característica de enovelamento proteico. Detectou-se que nos 5 agentes gelificates haviam sinais característicos da presença de estruturas organizadas mesmo abaixo da concentração de gelificação mínima. Em pH elevado e nas moléculas não gelificantes, não se observam sinais indicativos da presença deste tipo de estruturas.Fundação para a Ciência e a Tecnologia (FCT

Carbon storage in cacao (Theobroma cacao) plantations in Armero-Guayabal (Tolima, Colombia)

P?ginas 6-10El cambio clim?tico sigue siendo la principal amenaza de la humanidad hoy en d?a. Esta problem?tica se ha incrementado debido a las acciones humanas, como el uso de combustibles f?siles, la deforestaci?n y la degradaci?n. La comunidad mundial organizada ha establecido esquemas para mitigar este problema ambiental, por ejemplo el mecanismo de desarrollo limpio. Los sistemas agroforestales con cacao son considerados como mitigadores del cambio clim?tico por capturar carbono en biomasa, necromasa y suelos. Se estim? el almacenamiento y la fijaci?n de carbono en biomasa arriba del suelo y necromasa de cacaotales de 18 y 35 a?os de edad en el Centro Universitario Regional del Norte, en Armero-Guayabal (Tolima, Colombia) CURDN. Los cacaotales estudiados almacenaron 28.8 y 33.6 t C ha-1 en biomasa arriba del suelo a los 18 y 35 a?os, respectivamente, que arrojaron una tasa de fijaci?n promedio de 1.1 t C ha-1 a?o-1 . El carbono almacenado en necromasa ascendi? a 4.4 t ha-1 , con diferencias leves entre las edades de las plantaciones. Los sistemas agroforestales con cacao en Armero-Guayabal (Tolima, Colombia) tienen potencial para mitigar el cambio clim?tico al capturar carbono en biomasa y necromasa.ABSTRACT. Climate change holds as the current main threat of the humankind. This problem has being increasing by human actions such as the use of fossil fuels, deforestation and degradation. The organized world community has established schemes to mitigate this environmental problem, such as the Clean Development Mechanism. Agroforestry systems with cacao are considered as mitigating activities of climate change due to their capture of carbon in biomass and necromass. The carbon storage and fixation in aboveground biomass and necromass in cacao plantations of 18 and 35 years in the Centro Universitario Regional del Norte (CURDN), in ArmeroGuayabal (Tolima, Colombia) were estimated. The studied cacao plantations stored 28.8 and 33.6 t C ha-1 in aboveground biomass with an age of 18 and 35 years respectively, showing an average fixation rate of 1.1 t C ha-1 year-1 . The stored carbon in necromass was 4.4 t ha-1 , with slight differences between the ages of plantations. Agroforestry systems with cacao in Armero-Guayabal, Tolima, Colombia have the potential to mitigate climate change due its capture of atmospheric carbon in aboveground biomass and necromass

Development and evaluation of superabsorbent hydrogels based on natural polymers

Superabsorbent hydrogels (SAHs) are three dimensional networks formed by polymers that can absorb aqueous solution of over 100% of their initial weight. This work aimed to develop and characterize SAHs of Chitosan/Xanthan gum (CG), Chitosan/Alginate (CA) and controlled Chitosan (C), Xanthan gum (G), and Alginate (A) produced using “onion-like” methodology. The swelling performance, the morphological structure, the crystallinity, and the Fourier transformed infrared spectroscopy characteristics of SAH were used for the characterization of polyelectrolytes complex. Swelling analysis showed that chitosan has a strong influence on the maintenance of hydrogels structure after swelling, mainly in the acid environment (pH=2). The chitosan hydrogel presented around 3000% of acidic fluid absorption after 24 h. The chitosan:xanthan gum (1:1 and 2:1 named as C1G1 and C2G1, respectively) hydrogels were the best combination regarding swelling performance in an acid environment, reaching 1665% and 2024%, respectively, as well at pH 7.0, presenting 1005% (C1G1) and 667% (C2G1). Scanning electron microscopy analysis showed samples with pores, and with different shapes. The X-ray diffraction showed the presence of a characteristic peak at 2θ=20° in all developed composition because of the crystalline nature of chitosan. This work shows the possibility of developing eco-friendly biopolymer-based SAHs at a low cost with a good swelling capacity and stability.The research was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior(CAPES/Brazil), Fundação de Amparo a Pesquisa do Estado de Sergipe (FAPITEC, MS/CNPq/FAPITEC/SE/SESN◦06/2018) e do Conselho Nacional de Pesquisas (CNPq, Apoio a Projetos de Pesquisa/MCTI/CNPQ/Universal 14/2014) for supporting funds. EBS acknowledges the Portuguese Science and Technology Foundation (FCT) for the funded projects M-ERA-NET/0004/2015 (PAIRED) and UIDB/04469/2020 (strategic fund) financed from national funds, and cofinanced education (FCT/MEC) from national funds and FEDER, under the Partnership Agreement PT2020. J.J. acknowledges the Ministry of Science and Technical Development of the Republic of Serbia, through Contract Number 200051 172015 OI.info:eu-repo/semantics/publishedVersio

Comparação entre hipertensão autoreferida e pressão arterial casual e presença de fatores de risco em funcionários da saúde de Bauru e Jaú

Model: Prevalence study. Objectives: To evaluate the presence of self-reported hypertension to compare with blood pressure measurements. Besides, this work investigated health information level of workers and if the job position has any influence on blood pressure (BP). Methods: This study evaluated 349 health workers (44±10 years old) from Bauru and Jau cities, who answered some questions about history of health condition, use of medicines, past surgeries as well as social, scholar and physical conditions and had their blood pressure measured. Each subject selfreported as normotensive or hypertensive. Values of systolic >≥ 140 mmHg and/or diastolic PA >-90 mmHg were considered elevated. Among the health workers evaluated, 198 were submitted to thropometric and biochemical evaluations. Values are presented as means ± SD and frequency of distribution. It was used T-student test (p<0.05). Results: From all workers evaluated only 16% self-reported as hypertensive, which 56% presented high BP, however 91% used to take antihypertensive medicines. Among the 84% who self-reported as normotensive, 24% presented high BP and 8% used to take medicines. Although most of the employees of each section self-reported as normotensive, more than a half presented high BP and which was more common in the health’s section (76.3%). Conclusion: These results suggest that besides the majority of the employees self-reported as normotensive, an elevated number of health workers presented high blood pressure and used to take medicines appropriately,which indicates that they did not have enough knowledge about their health. Furthermore, it was observed that Health Section presented the higher blood pressure values.Modelo : Estudo de prevalência. Objetivos:  Avaliar a presença de hipertensão arterial auto-referida e comparar com os níveis de pressão arterial aferidos. Além sso, o trabalho se propôs a avaliar o grau de informação dos funcionários da saúde e determinar se o setor onde trabalha o funcionário influencia a Pressão Arterial (PA). Métodos: Foram avaliados 349 funcionários (46±10 anos) das cidades de Bauru e Jaú, que responderam uma anamnese (dados pessoais, condição socioeconômica, presença de doenças, prática de exercícios físicos e setor ocupacional) e foram submetidos a uma avaliação da PA. Os avaliados se auto-referiram normotensos ou hipertensos. Valores de PA Sistólica >140 mmHg e/ou PA diastólica >90 mmHg foram considerados elevados. Dentre os avaliados, 198 foram submetidos à avaliações antropométricas e bioquímicas. Os resultados são apresentados como média ± desvio padrão e distribuição de frequência. Utilizou-se teste “T- student”  (p<0,05). Resultados: Dentre os servidores, 16% se auto-referiram hipertensos, dos quais 56% apresentaram PA elevada e, destes, 91% utilizavam medicação antihipertensiva. Dentre os 84% que se auto-referiram normotensos, 24% apresentaram PA elevada e 8% tomavam medicamentos. A maioria dos funcionários de cada setor se autoreferiu normotenso, entretanto, grande parcela apresentou PA elevada, sendo esta mais frequente no setor “Saúde” (76,3%). Conclusão: Os resultados sugerem que apesar da maioria dos funcionários se classificar como normotensos, uma parcela expressiva apresentou PA elevada e fazia uso de medicamentos inadequadamente, indicando que não tinham conhecimento do seu estado de saúde. Além disso, observou-se que o setor “Saúde” foi aquele que apresentou os maiores valores de PA.

Integrative multi-kinase approach for the identification of potent antiplasmodial hits

Malaria is a tropical infectious disease that affects over 219 million people worldwide. Due to the constant emergence of parasitic resistance to the current antimalarial drugs, the discovery of new antimalarial drugs is a global health priority. Multi-target drug discovery is a promising and innovative strategy for drug discovery and it is currently regarded as one of the best strategies to face drug resistance. Aiming to identify new multi-target antimalarial drug candidates, we developed an integrative computational approach to select multi-kinase inhibitors for Plasmodium falciparum calcium-dependent protein kinases 1 and 4 (CDPK1 and CDPK4) and protein kinase 6 (PK6). For this purpose, we developed and validated shape-based and machine learning models to prioritize compounds for experimental evaluation. Then, we applied the best models for virtual screening of a large commercial database of drug-like molecules. Ten computational hits were experimentally evaluated against asexual blood stages of both sensitive and multi-drug resistant P. falciparum strains. Among them, LabMol-171, LabMol-172, and LabMol-181 showed potent antiplasmodial activity at nanomolar concentrations (EC50 15 folds. In addition, LabMol-171 and LabMol-181 showed good in vitro inhibition of P. berghei ookinete formation and therefore represent promising transmission-blocking scaffolds. Finally, docking studies with protein kinases CDPK1, CDPK4, and PK6 showed structural insights for further hit-to-lead optimization studies.7CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP405996/2016-0; 400760/2014-2Sem informação2018/05926-2; 2017/02353-9; 2012/16525-2; 2017/18611-7; 2018/07007-4; 2013/13119-6; 2018/24878-9; 2015/20774-

Rarity of monodominance in hyperdiverse Amazonian forests.

Tropical forests are known for their high diversity. Yet, forest patches do occur in the tropics where a single tree species is dominant. Such "monodominant" forests are known from all of the main tropical regions. For Amazonia, we sampled the occurrence of monodominance in a massive, basin-wide database of forest-inventory plots from the Amazon Tree Diversity Network (ATDN). Utilizing a simple defining metric of at least half of the trees ≥ 10 cm diameter belonging to one species, we found only a few occurrences of monodominance in Amazonia, and the phenomenon was not significantly linked to previously hypothesized life history traits such wood density, seed mass, ectomycorrhizal associations, or Rhizobium nodulation. In our analysis, coppicing (the formation of sprouts at the base of the tree or on roots) was the only trait significantly linked to monodominance. While at specific locales coppicing or ectomycorrhizal associations may confer a considerable advantage to a tree species and lead to its monodominance, very few species have these traits. Mining of the ATDN dataset suggests that monodominance is quite rare in Amazonia, and may be linked primarily to edaphic factors

Adherence to Antiretroviral Treatment and Correlation with Risk of Hospitalization among Commercially Insured HIV Patients in the United States

Purpose: A lower daily pill burden may improve adherence to antiretroviral treatment (ART) and clinical outcomes in patients with human immunodeficiency virus (HIV). This study assessed differences in adherence using the number of pills taken per day, and evaluated how adherence correlated with hospitalization. Methodology: Commercially insured patients in the LifeLink database with an HIV diagnosis (International Classification of Diseases, 9th Revision, Clinical Modification code 042.xx) between 6/1/2006 and 12/31/2008 and receipt of a complete ART regimen were selected for inclusion. Patients were grouped according to their daily pill count and remained on ART for at least 60 days. Outcomes included adherence and rates of hospitalization. Adherence was measured as the proportion of days between the start and end of the regimen in which the patient maintained supply of all initiated ART components. Logistic regressions assessed the relationship between pills per day, adherence, and hospitalization, controlling for demographics, comorbidities, and ART-naïve (vs. experienced) status. Results: 7,073 patients met the study inclusion criteria, and 33.4%, 5.8%, and 60.8 % received an ART regimen comprising one, two, or three or more pills per day, respectively. Regression analysis showed patients receiving a single pill per day were significantly more likely to reach a 95 % adherence threshold versus patients receiving three or more pills per day (odds ratio [OR] = 1.59; P,0.001). Regardless of the number of pills received per day, patients were over 40 % less likely to have

Analogues of Marine Guanidine Alkaloids Are in Vitro Effective against Trypanosoma cruzi and Selectively Eliminate Leishmania (L.) infantum Intracellular Amastigotes

Synthetic analogues of marine sponge guanidine alkaloids showed in vitro antiparasitic activity against Leishmania (L.) infantum and Trypanosoma cruzi. Guanidines 10 and 11 presented the highest selectivity index when tested against Leishmania. The antiparasitic activity of 10 and 11 was investigated in host cells and in parasites. Both compounds induced depolarization of mitochondrial membrane potential, upregulation of reactive oxygen species levels, and increased plasma membrane permeability in Leishmania parasites. Immunomodulatory assays suggested an NO-independent effect of guanidines 10 and 11 on macrophages. The same compounds also promoted anti-inflammatory activity in L. (L.) infantum-infected macrophages cocultived with splenocytes, reducing the production of cytokines MCP-1 and IFN-γ. Guanidines 10 and 11 affect the bioenergetic metabolism of Leishmania, with selective elimination of parasites via a host-independent mechanism