During pregnancy, the maternal endocrine pancreas undergoes, as a consequence of placental lactogens and prolactin (PRL) action, functional changes that are characterized by increased glucose-induced ...insulin secretion. After delivery, the maternal endocrine pancreas rapidly returns to non-pregnant state, which is mainly attributed to the increased serum levels of glucocorticoids (GCs). Although GCs are known to decrease insulin secretion and counteract PRL action, the mechanisms for these effects are poorly understood. We have previously demonstrated that signal transducer and activator of transcription 3 (STAT3) is increased in islets treated with PRL. In the present study, we show that STAT3 expression and serine phosphorylation are increased in pancreatic islets at the end of pregnancy (P19). STAT3 serine phosphorylation rapidly returned to basal levels 3 days after delivery (L3). The expression of the sarcoendoplasmic reticulum Ca2+-ATPase 2 (SERCA2), a crucial protein involved in the regulation of calcium handling in β-cells, was also increased in P19, returning to basal levels at L3. PRL increased SERCA2 and STAT3 expressions and STAT3 serine phosphorylation in RINm5F cells. The upregulation of SERCA2 by PRL was abolished after STAT3 knockdown. Moreover, PRL-induced STAT3 serine phosphorylation and SERCA2 expression were inhibited by dexamethasone (DEX). Insulin secretion from islets of P19 rats pre-incubated with thapsigargin and L3 rats showed a dramatic suppression of first phase of insulin release. The present results indicate that PRL regulates SERCA2 expression by a STAT3-dependent mechanism. PRL effect is counteracted by DEX and might contribute to the adaptation of maternal endocrine pancreas during the peripartum period.
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•Methodology of cost analysis based on process conditions was presented and detailed.•The core expenses were related to medium and cooling.•Energy costs were mainly related to the ...extent of the cultivation.•Induction with IPTG and temperatures around 32 °C presented lower production costs.•The price of peptones had a strong influence on the cost of the complex media.
The impact of cultivation strategy on the cost of recombinant protein production is crucial for defining cost-effective bioreactor operation conditions. This paper presents a methodology to estimate and compare cost impacts related to utilities as well as medium composition, using simple design equations and accessible data. Data from batch bioreactor cultures were used as case study involving the production of pneumococcal surface protein A, a soluble recombinant protein, employing E. coli BL21(DE3). Cultivation strategies and corresponding process costs covered a wide range of operational conditions, including different media, inducers, and temperatures. The core expenses were related to the medium and cooling. When the price of peptone was above the threshold value of US$ 30/kg, defined medium became the best choice. IPTG and temperatures around 32 °C led to shorter cultures and lower PspA4Pro production costs. The procedure offers a simple, accessible theoretical tool to identify cost-effective production strategies using bioreactors.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Since respiratory insufficiency is the main cause of death in patients affected by Duchenne Muscular Dystrophy (DMD), the present study aims at establishing a new non-invasive method to ...evaluate the clinical parameters of respiratory conditions of experimental models affected by DMD. With this purpose in mind, we evaluated the cardiorespiratory clinical conditions, the changes in the intercostal muscles, the diaphragmatic mobility, and the respiratory cycles in Golden Retriever Muscular Dystrophy (GRMD) employing ultrasonography (US). A control group consisting of dogs of the same race, but not affected by muscular dystrophy, were used in this study. The results showed that inspiration, expiration and plateau movements (diaphragm mobility) were lower in the affected group. Plateau phase in the affected group was practically non-existent and showed that the diaphragm remained in constant motion. Respiratory rate reached 15.5 per minute for affected group and 26.93 per minute for the control group. Expiration and inspiration movements of intercostal muscles reached 8.99mm and 8.79mm, respectively, for control group and 7.42mm and 7.40mm, respectively, for affected group. Methodology used in the present analysis proved to be viable for the follow-up and evaluation of the respiratory model in GRMD and may be adapted to other muscular dystrophy experimental models.
Resumo Uma vez que, a insuficiência respiratória é a principal causa de morte em pacientes afetados pela Distrofia Muscular de Duchenne (DMD), o presente estudo avaliou as condições clínicas cardiorrespiratórias, o movimento dos músculos intercostais, a mobilidade diafragmática, os ciclos respiratórios e a expansão da cavidade torácica em cães Golden Retriever com Distrofia Muscular (GRMD) por ultrassonografia (US) a fim de estabelecer um novo método não invasivo para avaliar os parâmetros de avaliação clínica de doenças respiratórias de modelos experimentais afetados por DMD. Um grupo controle constituído por cães da mesma raça e espécie, mas não afetados pela distrofia muscular também foram utilizados neste estudo. Os resultados mostraram que os movimentos de inspiração, expiração e platô (mobilidade do diafragma) foram menores no grupo afetado. A fase de platô no grupo afetado foi praticamente inexistente e mostrou que o diafragma destes animais permaneceu em constante movimento. A frequência respiratória atingiu 15,5 por minuto para o grupo afetado e 26,93 para o controle. Movimento de expiração e inspiração dos músculos intercostais atingiu 8,99 milímetros e 8,79 milímetros, respectivamente para o grupo controle e 7,42 milímetros e 7,40 milímetros, respectivamente para o grupo afetado. A metodologia utilizada nesta análise foi viável para o acompanhamento e avaliação do modelo respiratória em modelo GRMD e pode ser adaptado para outros modelos experimentais de distrofia muscular.
Patients with end-stage chronic renal failure (CRF) (uremia) have a high prevalence of inflammation, malnutrition, and oxidative stress. All of these features seem to be associated with the increased ...cardiovascular mortality observed in these patients. Nitric oxide (NO) is involved in the pathogenesis of CRF. The present study investigates the effects of nutritional status on L-arginine transport (NO precursor), plasma amino acid profile, and concentration of tumor necrosis factor (TNF)-alpha in uremic patients on hemodialysis (HD).
A total of 32 uremic patients on regular HD and 16 healthy controls were included in this study. Kinetic studies of L-arginine transport, mediated by cationic transport systems y(+) and y(+)L into red blood cells, plasma concentrations of amino acids (measured by high-performance liquid chromatography), and plasma TNF-alpha level (evaluated by enzyme-linked immunosorbent assay), were analyzed in malnourished and well-nourished patients (isolated by body mass index).
L-arginine influx by system y(+) in red blood cells (micromol/L cells(-1)h(-1)) was increased in both malnourished (377 +/- 41) and well-nourished (461 +/- 63) patients with CRF compared with controls (287 +/- 28). Plasma levels of all cationic amino acids (L-arginine, L-ornithine, and L-lysine) were low in uremic patients compared with controls. Among the uremic population, the reduction in plasma cationic amino acids levels was greater in malnourished patients. L-cysteine and L-glutamate, precursors of glutathione, were dramatically increased in plasma from uremic patients, independently of nutritional status. In addition, TNF-alpha concentration in plasma was enhanced in malnourished uremic patients (3.4 +/- 0.7 pg/mL) compared with controls (1.2 +/- 0.1 pg/mL) and well-nourished patients (1.9 +/- 0.1 pg/mL).
Our results suggest an increased catabolism of cationic amino acids, inflammatory markers, and oxidative stress in CRF, especially in malnourished patients. The reduced plasma concentration of plasma L-arginine is counterbalanced by enhanced rates of transport, resulting in an activation of NO synthesis in uremia.
Although not a new technique, due to the advent of 3D-stacked technologies, the integration of large memories and logic circuitry able to compute large amount of data has revived the ...Processing-in-Memory (PIM) techniques. PIM is a technique to increase performance while reducing energy consumption when dealing with large amounts of data. Despite several designs of PIM are available in the literature, their effective implementation still burdens the programmer. Also, various PIM instances are required to take advantage of the internal 3D-stacked memories, which further increases the challenges faced by the programmers. In this way, this work presents the Processing-In-Memory cOmpiler (PRIMO). Our compiler is able to efficiently exploit large vector units on a PIM architecture, directly from the original code. PRIMO is able to automatically select suitable PIM operations, allowing its automatic offloading. Moreover, PRIMO concerns about several PIM instances, selecting the most suitable instance while reduces internal communication between different PIM units. The compilation results of different benchmarks depict how PRIMO is able to exploit large vectors, while achieving a near-optimal performance when compared to the ideal execution for the case study PIM. PRIMO allows a speedup of 38× for specific kernels, while on average achieves 11.8 × for a set of benchmarks from PolyBench Suite.
Environmental and occupational exposure to benzene from fuels is a major cause for concern for national and international authorities, as benzene is a known carcinogen in humans and there is no safe ...limit for exposure to carcinogens. The objective of this study was to evaluate the genotoxic effects of chronic occupational exposure to benzene among two groups of workers: filling station workers (Group I) and security guards working at vehicles entrances (Group II), both on the same busy highway in Rio de Janeiro, Brazil. Sociodemographic data on the workers were evaluated; the concentration of benzene/toluene (B/T) in atmospheric air and individual
,
-muconic acid (
MA) and
-phenylmercapturic acid (
-PMA) were measured; oxidative stress was analyzed by catalase (CAT), glutathione
-transferase (GST), superoxide dismutase (SOD), thiol groups (THIOL) and malondialdehyde (MDA); genotoxicity was measured by metaphases with chromosomal abnormalities (MCA) and nuclear abnormalities, comet assay using the enzyme formamidopyrimidine DNA glycosylase (C-FPG), and methylation of repetitive element LINE-1,
and
genes. Eighty-six workers participated: 51 from Group I and 35 from Group II. The B/T ratio was similar for both groups, but Group I had greater oscillation of benzene concentrations because of their work activities. No differences in
MA and
-PMA, and no clinical changes were found between both groups, but linearity was observed between leukocyte count and
MA; and 15% of workers had leukocyte counts less than 4.5 × 10
cells L
, demanding close worker's attention. No differences were observed between the two groups for THIOL, MDA, MCA, or nuclear abnormalities. A multiple linear relationship was obtained for the biomarkers MCA and C-FPG. A significant correlation was found between length of time in current job and the biomarkers C-FPG, MCA, GST, and MDA. Although both populations had chronic exposure to benzene, the filling station workers were exposed to higher concentrations of benzene during their work activities, indicating an increased risk of DNA damage.
The genetically modified maize TC1507 event with the cry1F gene (Cry1F maize) has been used to control Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) in Brazil since the 2009-2010 ...cropping season. As part of the insect resistance management program, we conducted studies to determine the baseline susceptibility to Cry1F before the widespread planting of Cry1F maize. Subsequently, we evaluated the geographical and temporal variability of susceptibility to this toxin in populations of S. frugiperda collected from major maize-growing regions in Brazil.Thebaseline susceptibility to Cry1F was determined using a diet-overlay bioassay for a susceptible reference population and four field populations of S. frugiperda.We then monitored the susceptibility to Cry1F in 43 populations of S. frugiperda sampled in nine States of Brazil between 2011 and 2013. In the baseline study, the MIC50 (the concentration that inhibits molting to second instars in 50% of individuals) ranged from 3.59 to 72.47 ng Cry1F toxin per centimeter square. Based on the upper limit of the MIC99 value of the joint analysis from the baseline susceptibility data, the concentrations of 200 and 2,000 ng of Cry1F toxin per centimeter square were defined as diagnostic concentrations for potentially resistant individuals, and these were used to monitor the susceptibility of S. frugiperda to Cry1F. Survival at 2,000 ng Cry1F toxin per centimeter square increased significantly throughout the cropping seasons in S. frugiperda populations from Sao Paulo, Santa Catarina, Rio Grande do Sul, Bahia, Mato Grosso, Goia s, Mato Grosso do Sul, and Parana. The highest survival (>50%) was reached in populations collected from Bahia, Mato Grosso, Goias, Mato Grosso do Sul, and Parana during the 2012-2013 cropping season. Therefore, a significant decrease in susceptibility to Cry1F was detected in S. frugiperda throughout cropping seasons, especially in regions with intensive maize production in Brazil, according to field-evolved resistance that has been demonstrated in Brazilian populations.
This paper investigates the behavior of paper strips containing iron-gall inks prepared with tannins from different sources, subjected to natural and thermally-induced aging. Results indicate that ...inks containing initial concentrations of ferrous sulphate ranging from 0.2 to 10.0 g are amenable to treatment with calcium phytate, and thata good correlation exists between the recovery of excess iron and the initial concentration. Infrared spectra showed an absorption band at 1,750 cm
−1
, typical of esther, solely in the samples prepared with a condensed tannin. The condensed nature of this tannin produced a different oxidation pattern, with iron removal inferior to those observed from inks produced with hydrolisable tannins. When tannic acid was used ferrous iron removals ranged from 0.050 to 1.800 g, decreasing to 0.5 g in the presence of copper; the same behavior was observed for the remaining hydrolisable tannins, with a lower recovery from the condensed tannin. The adopted natural aging procedure released a higher amount of ferrous iron compared to ASTM thermal aging. This was probably due to the marked effect of humidity, not considered in the thermal procedure. A series of archaeometric possibilities were used to help elucidate the degradation of cellulose strips impregnated with iron-gall inks.
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