Obestatin as a key regulator of metabolism and cardiovascular function with emerging therapeutic potential for diabetes

Obestatin is a 23-amino acid C-terminally amidated gastrointestinal peptide derived from preproghrelin and which forms an alpha helix. Although obestatin has a short biological half-life and is rapidly degraded, it is proposed to exert wide-ranging pathophysiological actions. Whilst the precise nature of many of its effects is unclear, accumulating evidence supports positive actions on both metabolism and cardiovascular function. For example, obestatin has been reported to inhibit food and water intake, body weight gain, and gastrointestinal motility, and to also mediate promotion of cell survival and prevention of apoptosis. Obestatin-induced increases in β-cell mass, enhanced adipogenesis and improved lipid metabolism have been noted along with upregulation of genes associated with β-cell regeneration, insulin production and adipogenesis. Furthermore, human circulating obestatin levels generally demonstrate an inverse association with obesity and diabetes, whilst the peptide has been shown to confer protective metabolic effects in experimental diabetes, suggesting that it may hold therapeutic potential in this setting. Obestatin also appears to be involved in blood pressure regulation and to exert beneficial effects on endothelial function, with experimental studies indicating that it may also promote cardioprotective actions against, for example, ischaemia-reperfusion injury. This review will present a critical appraisal of the expanding obestatin research area and discuss the emerging therapeutic potential of this peptide for both metabolic and cardiovascular complications of diabetes. 

Discovery of a New Retrograde Trans-Neptunian Object: Hint of a Common Orbital Plane for Low Semimajor Axis, High-inclination TNOs and Centaurs

Although the majority of Centaurs are thought to have originated in the scattered disk, with the high-inclination members coming from the Oort cloud, the origin of the high-inclination component of trans-Neptunian objects (TNOs) remains uncertain. We report the discovery of a retrograde TNO, which we nickname “Niku,” detected by the Pan-STARRS 1 Outer Solar System Survey. Our numerical integrations show that the orbital dynamics of Niku are very similar to that of 2008 KV42 (Drac), with a half-life of ˜500 Myr. Comparing similar high-inclination TNOs and Centaurs (q > 10 au, a <100 au, and i > 60°), we find that these objects exhibit a surprising clustering of ascending node, and occupy a common orbital plane. This orbital configuration has high statistical significance: 3.8-σ. An unknown mechanism is required to explain the observed clustering. This discovery may provide a pathway to investigating a possible reservoir of high-inclination objects.

Destino no ambiente e comportamento agronômico de atrazina em resposta a doses e níveis de palha de espécies de cobertura de solo

The use of cover crops is a fundamental strategy to the weed management in Southern Brazil. In highly infested areas, the herbicides use is increasing, which increases the costs of the crops production as well as the environmental contamination. Oat and velvet bean plants havecontrasting characteristics regarding to residues decomposition speed and the capacity to immobilize Nitrogen in the soil, providing distinct results of weeds suppression throughout the time, and therefore, requiring distinct management strategies before, during, and after the corn crop establishment. The general objective of the experiment was to evaluate the environmental dynamics of the herbicide atrazine, the corn grain yield, and the efficiency of the weed control, considering areas with distinct history regarding the use of mulching, levels of straw and rates of atrazine. For this, the experiment was carried out in two parts: in the first part, two trials with the corn crop were established, one using oat and the other using velvet bean as cover crops. The experimental design used for both field trials was randomized complete blocks arrangement with four replications. The factor A was constituted by four levels of straw (0; 0.75x; 1.5x; 3x) and the factor B was constituted by four rates of the herbicide atrazine (0; 2100; 4200; 8400 g a i. ha-1). Soil samples were collected for greenhouse trialsto determine the persistence. Atrazine leaching evaluation was performed by chromatography using samples collected over the soil profile.In the field, the weed density, the fresh and dry weight and the yield of the corn were evaluated. In the greenhouse trials, the main variables evaluated were plant height and injury caused by the herbicide toxicity. In the second part, soils with distinct covering history were sampled, and the mineralization and sorption studies, both with 14C-atrazine, were conducted in the laboratory. The experimental design was randomized complete blocks arrangement with four replications. The results from the field experiment show that the high levels of straw above ground, isolated, were not efficient to control completely the weeds, and that high levels of velvet bean`s straw decreased the corn potential yield. The greenhouse trials showed that high levels of oat straw prevent the scape of atrazine to soil, this effect of oat straw upon the herbicide availability on soil was detected up to 12 days after spraying. The half-life of atrazine sprayed over oat straw varied from 7 to 14 days after spraying, while the half-life of atrazine sprayed over velvet bean varied from 5 to 14 days after spraying. Increasing oat straw levels presents the capacity to reduce the lixiviation of atrazine in the soil profile, however, this effect was not verified when using velvet bean straw, because the herbicide was not detected in the soil profile, at 21 days after spraying. The chromatographic analysis indicate thatthe atrazine concentrates closer to the soil surface regardless of amount of straw, not being detected deeper than 8 cm in the soil. The accumulated mineralization of 14C-arazine sprayed over V. sativa is superior if compared to soils with S. cereale or non-covered soils. The sorption coefficient of atrazine is superior when sprayed over straw than over the soil.

Accumulation, persistence and effects of indospicine residues in camels fed Indigofera plant

Indospicine (L-2-amino-6-amidinohexanoic acid) is a natural hepatotoxin found in all parts of some Indigofera plants such as I. linnaei and I. spicata. Several studies have documented a susceptibility to this hepatotoxin in different species of animals, including cattle, sheep, dogs and rats, which are associated with mild to severe liver disease after prolonged ingestion. However, there is little published data on the effects of this hepatotoxin in camels, even though Indigofera plants are known to be palatable to camels in central Australia. The secondary poisoning of dogs after prolonged dietary exposure to residual indospicine in camel muscle has raised additional food safety concerns. In this study, a feeding experiment was conducted to investigate the in vivo accumulation, excretion, distribution and histopathological effects of dietary indospicine on camels. Six young camels (2 – 4 year old), weighing 270 − 390 kg were fed daily a roughage diet consisting of Rhodes grass hay and lucerne chaff, supplemented with Indigofera and steam flaked barley. Indigofera (I. spicata) was offered at 597 mg DM/kg body weight (bw)/day designed to deliver 337 µg indospicine/kg bw/day, and fed for a period of 32 days. Blood and muscle biopsies were collected over the period of the study. Concentrations of indospicine in the plasma and muscle biopsy samples were quantitated by validated ultra-performance liquid chromatography−tandem mass spectrometry (UPLC−MS/MS). The highest concentrations in plasma (1.01 mg/L) and muscle (2.63 mg/kg fresh weight (fw)) were found at necropsy (day 33). Other tissues were also collected at necropsy and analysis showed ubiquitous distribution of indospicine, with the highest indospicine accumulation detected in the pancreas (4.86 ± 0.56 mg/kg fw) and liver (3.60 ± 1.34 mg/kg fw); followed by the muscle, heart and kidney. Histopathological examination of liver tissue showed multiple small foci of predominantly mononuclear inflammatory cells. After cessation of Indigofera intake, indospicine present in plasma in the remaining 3 camels had a longer terminal elimination half-life (18.6 days) than muscle (15.9 days), and both demonstrated mono-exponential decreases.

Role of catestatin as such as slowly released by fibronectin-coated pharmacologically active microcarriers (Fn-Pam) in limiting hypoxicinduced cell death

International audience

137Cs in the meat of wild boars: a comparison of the impacts of Chernobyl and Fukushima

The impact of Chernobyl on the 137Cs activities found in wild boars in Europe, even in remote locations from the NPP, has been much greater than the impact of Fukushima on boars in Japan. Although there is great variability within the 137Cs concentrations throughout the wild boar populations, some boars in southern Germany in recent years exhibit higher activity concentrations (up to 10,000 Bq/kg and higher) than the highest 137Cs levels found in boars in the governmental food monitoring campaign (7900 Bq/kg) in Fukushima prefecture in Japan. The levels of radiocesium in boar appear to be more persistent than would be indicated by the constantly decreasing 137Cs inventory observed in the soil which points to a food source that is highly retentive to 137Cs contamination or to other radioecological anomalies that are not yet fully understood.

Obtenção e caracterização de queratinase de bacillus sp. P45 a partir de coprodutos e aplicação na produção de queijos cremosos enriquecidos com chia e quinoa

As proteases constituem 60-65% do mercado global das enzimas industriais e são utilizadas na indústria de alimentos no processo de amaciamento de carne, na síntese de peptídeos, preparo de fórmulas infantis, panificação, cervejarias, produtos farmacêuticos, diagnósticos médicos, como aditivos na indústria de detergentes e na indústria têxtil no processo de depilação e transformação do couro. Proteases específicas produzidas por micro-organismos queratinolíticos são chamadas de queratinases e distinguem-se de outras proteases pela maior capacidade de degradação de substratos compactos e insolúveis como a queratina. Atualmente, processos que apontem o uso total das matérias-primas e que não resultem em impactos negativos ao meio ambiente tem ganhado destaque. Dentro desta temática, destacam-se a reutilização da farinha de penas residual durante o cultivo do Bacillus sp. P45 para produção de proteases e a biomassa residual de levedura, ambas com elevados teores de proteínas, podendo ser utilizadas no cultivo do Bacillus sp. P45 para obtenção de proteases. O objetivo deste trabalho foi obter a enzima queratinase purificada em grandes quantidades, sua caracterização, bem como a sua aplicação em processos de coagulação enzimática do leite para o desenvolvimento de um queijo cremoso enriquecido com farinha de chia e quinoa. Além disso, aplicar diferentes coprodutos para produção de enzimas proteolíticas e queratinolíticas. A presente tese foi dividida em quatro artigos: no primeiro foi realizado a obtenção da queratinase purificada em maiores quantidades e a determinação dos parâmetros de estabilidade térmica e a influência de componentes químicos na atividade enzimática. A obtenção da enzima em maiores quantidades alcançou fatores de purificação de 2,6, 6,7 e 4,0 vezes, paras 1º SAB, 2º SAB e diafiltração, respectivamente. A recuperação enzimática alcançou valores de 75,3% para o 1º SAB, 75,1% no 2º sistema e 84,3% na diafiltração. A temperatura de 55ºC e o pH 7,5 foram determinados como ótimos para atividade da enzima queratinase. O valor da energia de desativação (Ed) médio foi de 118,0 kJ/mol e os valores de z e D variaram de 13,6 a 18,8ºC, e 6,9 a 237,3 min, respectivamente. Além disso a adição de sais (CaCl2, CaO, C8H5KO4 e MgSO4) elevou a atividade da enzima na presença destes compostos. O segundo artigo apresenta a aplicação da queratinase como coagulante de leite bovino e sua aplicação na obtenção de queijo cremoso enriquecido com chia e quinoa. A enzima mostrou atividade de coagulação semelhante ao coagulante comercial, na concentração de 30mg/mL. A enzima purificada foi empregada de forma eficiente na fabricação do queijo cremoso, que apresentou valores de pH de 5,3 e acidez de 0,06 a 0,1 mol/L, com elevação durante os 25 dias de armazenamento. O terceiro artigo apresenta o perfil do queijo cremoso enriquecido com farinha de chia e quinoa, o qual apresentou alto índice de retenção de água (>99,0%) e baixos valores de sinérese (<0,72%). Elevados teores de fibras foi verificado (3,0 a 5,0%), sugerindo seu consumo como fonte de fibras. As análises microbiológicas foram de acordo com a legislação vigente. Na análise sensorial foi verificado altos valores de suavidade ao paladar e verificado maiores valores de consistência e untabilidade nas amostras com maiores concentrações de nata e quinoa. O quarto artigo traz a extração de β-galactosidase por ultrassom e o uso da biomassa residual da levedura, bem como o uso de farinha de penas residuais como substrato para obtenção de proteases. O ultrassom foi eficiente para ruptura celular e extração de β-galactosidase, apresentando alta atividade (35,0 U/mL) e rendimento (876,0 U/g de biomassa). A maior atividade proteolítica (1300 U/mL em 32 h) e queratinolítica (89,2 U/mL) verificadas ocorreram utilizando-se a biomassa e a farinha de penas residuais, respectivamente. Maior produtividade proteolítica (40,8 U/mL/h) foi verificado no meio utilizando biomassa residual como substrato. Já a maior produtividade queratinolítica (2,8 U/mL/h) foi alcançada utilizando farinha de penas reutilizada.

A doorway to Borromean halo nuclei: the Samba configuration

We exploit the possibility of new configurations in three-body halo nuclei, Samba type (the neutron-core form a bound system) as a doorway to Borromean systems. The nuclei Be-12, B-15, N-23 and F-27 are of such nature, in particular N-23 with a half-life of 37.7 s and a halo radius of 6.07 fm is an excellent example of Samba-halo configuration. The fusion below the barrier of the Samba halo nuclei with heavy targets could reveal the so far elusive enhancement and a dominance of one-neutron over two-neutron transfers, in contrast to what was found recently for the Borromean halo nucleus He-6 + U-238.

Pharmacokinetic Profile of Liposome-Encapsulated Ropivacaine after Maxillary Infiltration Anaesthesia

The aim of this study was to determine the pharmacokinetic parameters of liposomal ropivacaine after dental anesthesia in 14 healthy volunteers. In this randomized, double-blind and crossover study, the volunteers received maxillary infiltration of liposome-encapsulated 0.5% ropivacaine and, 0.5% ropivacaine with 1:200,000 epinephrine in two different sessions. Blood samples were collected before and after (from 15 to 1440 min) the administration of either ropivacaine formulation. HPLC with UV detection was used to quantify plasma ropivacaine concentrations. The pharmacokinetic parameters AUC(0-24) (area under the plasma concentration x time curve from baseline to 24 h), AUC(0-infinity) (area under the plasma concentration-time curve from baseline to infinity), C-max (maximum drug concentration), CL (renal clearance), T-max (maximum drug concentration time), t(1/2) (elimination half-life) and Vd (volume of distribution) were analyzed using the Wilcoxon signed-rank test. No differences (p > 0.05) were observed between both formulations for any of the pharmacokinetic parameters evaluated and plasma ropivacaine concentrations, considering each period of time. Both formulations showed similar pharmacokinetic profiles, indicating that the liposomal formulation could be a safer option for use of this local anesthetic, due to the absence of a vasoconstrictor.

Epigenetics and alternative splicing

Dissertação de Mestrado, Oncobiologia: Mecanismos Moleculares do Cancro, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2015

Comportamento do herbicida hexazinone em área de recarga do Aqüífero Guarani cultivada com cana-de-açúcar.

THE BEHAVIOR OF HEXAZINONE HERBICIDE IN RECHARGE ZONE OF GUARANI AQUIFER WITH SUGARCANE CULTIVATED AREA. São Paulo state (Brazil) has an important area of sugarcane production, mainly for obtaining alcohol and sugar, where there is an intensive use of pesticides. An important recharge zone of Guarani aquifer, with supplies water for the local population, is located at Ribeirão Preto city, so the local behavior of pesticides must be investigated. The GUS index was obtained by using the paramenters Koc and half-life for hezazinone herbicide, determinated in representative soil of this region. This study has demonstrated that there is potential risks of hexazinone leaching to ground water, indicating that this herbicide must be monitored in ground water.