UPR induces transient burst of apoptosis in islets of early lactating rats through reduced AKT phosphorylation via ATF4/CHOP stimulation of TRB3 expression

Bromati CR, Lellis-Santos C, Yamanaka TS, Nogueira TC, Leonelli M, Caperuto LC, Gorjao R, Leite AR, Anhe GF, Bordin S. UPR induces transient burst of apoptosis in islets of early lactating rats through reduced AKT phosphorylation via ATF4/CHOP stimulation of TRB3 expression. Am J Physiol Regul Integr Comp Physiol 300: R92-R100, 2011. First published November 10, 2010; doi:10.1152/ajpregu.00169.2010.-Endocrine pancreas from pregnant rats undergoes several adaptations that comprise increase in beta-cell number, mass and insulin secretion, and reduction of apoptosis. Lactogens are the main hormones that account for these changes. Maternal pancreas, however, returns to a nonpregnant state just after the delivery. The precise mechanism by which this reversal occurs is not settled but, in spite of high lactogen levels, a transient increase in apoptosis was already reported as early as the 3rd day of lactation (L3). Our results revealed that maternal islets displayed a transient increase in DNA fragmentation at L3, in parallel with decreased RAC-alpha serine/threonine-protein kinase (AKT) phosphorylation (pAKT), a known prosurvival kinase. Wortmannin completely abolished the prosurvival action of prolactin (PRL) in cultured islets. Decreased pAKT in L3-islets correlated with increased Tribble 3 (TRB3) expression, a pseudokinase inhibitor of AKT. PERK and eIF2 alpha phosphorylation transiently increased in islets from rats at the first day after delivery, followed by an increase in immunoglobulin heavy chain-binding protein (BiP), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP) in islets from L3 rats. Chromatin immunoprecipitation (ChIP) and Re-ChIP experiments further confirmed increased binding of the heterodimer ATF4/CHOP to the TRB3 promoter in L3 islets. Treatment with PBA, a chemical chaperone that inhibits UPR, restored pAKT levels and inhibited the increase in apoptosis found in L3. Moreover, PBA reduced CHOP and TRB3 levels in beta-cell from L3 rats. Altogether, our study collects compelling evidence that UPR underlies the physiological and transient increase in beta-cell apoptosis after delivery. The UPR is likely to counteract prosurvival actions of PRL by reducing pAKT through ATF4/CHOP-induced TRB3 expression.

Homocysteine induces oxidative stress, inflammatory infiltration, fibrosis and reduces glycogen/glycoprotein content in liver of rats

Hyperhomocysteinemia has been related to various diseases, including homocystinuria, neurodegenerative and hepatic diseases. In the present study we initially investigated the effect of chronic homocysteine administration on some parameters of oxidative stress, named total radical-trapping antioxidant potential, total antioxidant reactivity, catalase activity, chemiluminescence, thiobarbituric acid-reactive substances, and total thiol content in liver of rats. We also performed histological analysis, evaluating steatosis, inflammatory infiltration, fibrosis, and glycogen/glycoprotein content in liver tissue sections from hyperhomocysteinemic rats. Finally, we evaluated the activities of aminotransferases in liver and plasma of hyperhomocysteinemic rats. Wistar rats received daily subcutaneous injection of Hcy from their 6th to their 28th day of life. Twelve hours after the last injection the rats were sacrificed, liver and plasma were collected. Hyperhomocysteinemia decreased antioxidant defenses and total thiol content, and increased lipid peroxidation in liver of rats, characterizing a reliable oxidative stress. Histological analysis indicated the presence of inflammatory infiltrate, fibrosis and reduced content of glycogen/glycoprotein in liver tissue sections from hyperhomocysteinemic rats. Aminotransferases activities were not altered by homocysteine. Our data showed a consistent profile of liver injury elicited by homocysteine, which could contribute to explain, at least in part, the mechanisms involved in human liver diseases associated to hyperhomocysteinemia. (C) 2009 ISDN. Published by Elsevier Ltd. All rights reserved.

Chronic action of association of zidovudine, lamivudine and ritonavir on pregnant rats. A biologic assay

Purpose: To evaluate at term the effects of a highly active antiretroviral (HAAR) drug association administered during the entire period of rat pregnancy. Methods: Three groups (n = 10 each) of adult pregnant rats were treated with an oral solution of HAAR (Exp 1 = 10/5/20 mg/kg b.w.; Exp 2 = 30/15/60 mg/kg b.w.; Exp 3 = 90/45/180 mg/kg b.w.) from day ""0"" up to the 20th day of pregnancy. A fourth group served as a control. At term (20th day) the rats were killed under deep anesthesia and the number of implantations, resorptions, living fetuses, placentae and intrauterine deaths were recorded. Results: The highest HAAR doses caused lower maternal weight gain, lower litter weights, and lower placental weights compared to the control group. Conclusions: HAAR during the entire period of rat pregnancy can reduce maternal body weight gain and lower term placental weight.

In Vitro and In Vivo Antiplasmodial Activities of Risedronate and Its Interference with Protein Prenylation in Plasmodium falciparum

The increasing resistance of malarial parasites to almost all available drugs calls for the identification of new compounds and the detection of novel targets. Here, we establish the antimalarial activities of risedronate, one of the most potent bisphosphonates clinically used to treat bone resorption diseases, against blood stages of Plasmodium falciparum (50% inhibitory concentration [IC(50)] of 20.3 +/- 1.0 mu M). We also suggest a mechanism of action for risedronate against the intraerythrocytic stage of P. falciparum and show that protein prenylation seems to be modulated directly by this drug. Risedronate inhibits the transfer of the farnesyl pyrophosphate group to parasite proteins, an effect not observed for the transfer of geranylgeranyl pyrophosphate. Our in vivo experiments further demonstrate that risedronate leads to an 88.9% inhibition of the rodent parasite Plasmodium berghei in mice on the seventh day of treatment; however, risedronate treatment did not result in a general increase of survival rates.

Morphometric analysis of the urethra of castrated female rats treated with tamoxifen

Objectives: The aim of this study was to evaluate the effects of tamoxifen on the weight and thickness of the urethral epithelium of castrated female rats. Methods: Forty castrated adult female Wistar-Hannover rats were randomly divided into two groups: Group I (n = 20) in which the animals received only the vehicle (propylene glycol) and Group 11 (n = 20) in which the rats received tamoxifen 250 mu g/day by gavage. After 30 days of treatment, all animals were sacrificed and the urethra was immediately removed for weighing. Next, the urethra was divided into the proximal and distal segments, which were fixed in 10% formaldehyde and submitted to routine histological techniques for morphometric study. The data were analyzed using the weighted minimum mean-square error method and Student`s t-test for two independent samples (p < 0.05). Results: There was a significant increase in the mean weight of the urethra in the rats of Group 11 compared to the control group, 32.0 +/- 2.0 mg and 22.0 +/- 1.6 mg, respectively (p < 0.001). The mean thickness of the distal urethral epithelium of the animals treated with tamoxifen was significantly greater than that of the control group, 42.8 +/- 2.0 mu m and 36.6 +/- 1.5 mu m, respectively (p < 0.001). There was no statistically significant difference between the two groups with respect to the epithelial thickness of the proximal urethra (p = 0.514). Conclusion: Treating castrated adult rats with 250 mu g/day of tamoxifen for 30 days may increase the weight of the urethra and the thickness of the distal urethral epithelium. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

Household survey of hepatitis B vaccine coverage among Brazilian children

We conducted a multi-stage household cluster survey to calculate hepatitis B vaccine coverage among children 18-30 months of age in 27 Brazilian cities. Hepatitis B vaccine is administered at birth, 1 month and 6 months of age by Brazil`s national immunization program. Among 17,749 children surveyed, 40.2% received a birth dose within one day of birth, 94.8% received at least one dose of hepatitis B vaccine, and 86.7% completed the three-dose series by 12 months of age. Increased coverage with the birth dose and administration of hepatitis B in combination with diphtheria-tetanus-pertussis-Haemophilus influenzae type b antigens could improve protection against hepatitis B. (C) 2009 Elsevier Ltd. All rights reserved.

Alpha7 Nicotinic Acetylcholine Receptor Expression and Activity During Neuronal Differentiation of PC12 Pheochromocytoma Cells

Nicotinic acetylcholine receptors (nAChR) exert pivotal roles in synaptic transmission, neuroprotection and differentiation. Particularly, homomeric alpha 7 receptors participate in neurite outgrowth, presynaptic control of neurotransmitter release and Ca(2+) influx. However, the study of recombinant alpha 7 nAChRs in transfected cell lines is difficult due to low expression of functional receptor channels. We show that PC12 pheochromocytoma cells induced to differentiation into neurons are an adequate model for studying differential nAChR gene expression and receptor activity. Whole-cell current recording indicated that receptor responses increased during the course of differentiation. Transcription of mRNAs coding for alpha 3, alpha 5, alpha 7, beta 2 and beta 4 subunits was present during the course of differentiation, while mRNAs coding for alpha 2, alpha 4 and beta 3 subunits were not expressed in PC12 cells. alpha 7 subunit expression was highest following 1 day of induction to differentiation. Activity of alpha 7 nAChRs, however, was most elevated on day 2 as revealed by inhibition experiments in the presence of 10 nM methyllycaconitine, rapid current decay and receptor responsiveness to the alpha 7 agonist choline. Increased alpha 7 receptor activity was noted when PC12 were induced to differentiation in the presence of choline, confirming that chronic agonist treatment augments nAChR activity. In summary, PC12 cells are an adequate model to study the role and pharmacological properties of this receptor during neuronal differentiation.

Modelling Recreation Demand Using Choice Experiments : Using Swedish Snowmobilers Demand for Groomed trails

This paper is concerned with the use of the choice experiment method for modeling the demand for snowmobiling . The Choice Experiment includes five attributes, standard, composition, length, price day card and experience along trail. The paper estimates the snowmobile owners’ preferences and the most preferred attributes, including their will-ingness to pay for a daytrip on groomed snowmobile trail. The data consists of the an-swers from 479 registered snowmobile owners, who answered two hypothetical choice questions each. Estimating using the multinominal logit model, it is found that snow-mobilers on average are willing to pay 22.5 SEK for one day of snowmobiling on a trail with quality described as skidded every 14th day. Furthermore, it is found that the WTP increases with the quality of trail grooming. The result of this paper can be used as a yardstick for snowmobile clubs wanting to develop their trail net worth, organizations and companies developing snowmobiling as a recreational activities and marketers in-terested in marketing snowmobiling as recreational activities.

A computer study of the improvement of PV panel monthly outputs when the panel azimuth is changed thrice daily

The purpose of the calculations was to estimate the most suitable slopes and azimuths for three different positions per day of a solar panel in order to obtain the most possible energy from the PV panel compared with a stationary PV panel. The calculations were made in the computer program PV F-CHART.

New Meanings to Old Rituals : The Emergence of Mourning Rituals in Shiʿite Islam

This paper will discuss the emergence of Shiʿite mourning rituals around the grave of Husayn b. ʿAli. After the killing of Husayn at Karbala’ in 61/680, a number of men in Kufa feel deep regret for their neglect to come to the help of the grand­son of the Prophet. They gather and discuss how they can best make penitence for this crime. Eventually, they decide to take to arms and go against the Umayyad army – to kill those that killed Husayn, or be killed them­selves in the attempt to find revenge for him. Thus, they are called the Penitents (Ar. Tawwābūn). On their way to the battlefield they stop at Husayn’s tomb at Karbala’, dedicat­ing themselves to remorseful prayer, crying and wailing over the fate of Husayn and their own sin. When the Penitents perform certain ritual acts, such as weeping and wailing over the death of Husayn, visiting his grave, asking for God’s mercy upon him on the Day of Judgment, demand blood revenge for him etc., they enter into already existing rituals in the pre-Islamic Arab and early Muslim context. That is, they enter into rituals that were traditionally performed at the death of a person. What is new is that the rituals that the Penitents perform have partially received a new content. As described, the rituals are performed out of loyalty towards Husayn and the family of the Prophet. The lack of loyalty in connection with the death of Husayn is conceived of as a sin that has to be atoned. Blood revenge thus be­comes not only a pure action of revenge to restore honor, but equally an expression for true religious conversion and penitence. Humphrey and Laidlaw argue that ritual actions in themselves are not bearers of meaning, but that they are filled with mean­ing by the performer. Accord­ing to them, ritual actions are apprehensible, i.e. they can be, and should be filled with meaning, and the people who perform them try to do so within the context where the ritual is performed. The story of the Penitents is a clear example of mourning rituals as actions that survive from earlier times, but that are now filled with new meaning when they are performed in a new and developing move­ment with a different ideology. In later Shiʿism, these rituals are elaborated and become a main tenet of this form of Islam.

Provenance-based Validation of E-Science Experiments

E-Science experiments typically involve many distributed services maintained by different organisations. After an experiment has been executed, it is useful for a scientist to verify that the execution was performed correctly or is compatible with some existing experimental criteria or standards, not necessarily anticipated prior to execution. Scientists may also want to review and verify experiments performed by their colleagues. There are no existing frameworks for validating such experiments in today's e-Science systems. Users therefore have to rely on error checking performed by the services, or adopt other ad hoc methods. This paper introduces a platform-independent framework for validating workflow executions. The validation relies on reasoning over the documented provenance of experiment results and semantic descriptions of services advertised in a registry. This validation process ensures experiments are performed correctly, and thus results generated are meaningful. The framework is tested in a bioinformatics application that performs protein compressibility analysis.

OMG!: characterizing the role of emotions in the sharing of online commercial videos

"Se tornar viral" é visto pelos comerciantes como o novo Graal para alcançar grandes comunidades online. Neste contexto viral, vídeos têm um papel especial dada a forte capacidade deles de se espalhar exponencialmente pela internet através do compartilhamento social. Cada ano se vê a quebra de novos recordes através deste tipo de viralidade. Em março de 2012, o vídeo "Kony 2012" envolvendo a ação unida contra o líder de milícia Africano epônimo, atingiu mais de 34 milhões de visualizações em seu primeiro dia de lançamento. Em dezembro de 2012, o vídeo-clipe da música "Gangnam Style" tornou-se o primeiro vídeo do YouTube a alcançar mais de um bilhão de visualizações, totalizando mais de 1,4 bilhões de visualizações em março de 2013. Tais ilustrações mostram claramente a nova escala que a internet deu ao fenômeno do boca-a-boca. Os comerciantes entenderam o potencial fantástico dos vídeos virais e tentaram aproveitar o fenômeno de modo a reproduzi-lo para fins comerciais. Esta pesquisa oferece para os acadêmicos e os profissionais de marketing uma análise dos determinantes do compartilhamento de vídeos comerciais online. Mais especificamente, o foco da dissertação foi definido sobre o papel das emoções no compartilhamento, para identificar quais delas levam e como levam à partilha de vídeos comerciais online. A pesquisa foi realizada a partir de dois métodos científicos: uma pesquisa e uma análise de texto sobre a atribuição de emoções para comentários dos vídeos mais compartilhados do YouTube. A pesquisa confirma, com novos métodos, hipóteses previamente testadas e validadas por acadêmicos. Ela mostra que a positividade e a força das emoções são determinantes de compartilhamento maiores do que a negatividade e a fraqueza (Lindgreen and Vanhamme, 2005; Dobele et al., 2007). A dissertação também argumenta que o conteúdo do vídeo, bem como o contexto são determinantes significativos de compartilhamento de vídeo (Laskey et al., 1989; Taylor, 1999). Além de validar teorias existentes, a pesquisa trouxe novos conceitos para a discussão, especialmente o papel da dimensão força / fraqueza de emoções para analisar o fenômeno viral, e a importância de uma clara "chamada à ação" incluída no vídeo para aumentar a sua partilha. Estes novos conceitos enriquecem a literatura do tema – que evolui muito rapidamente – e preparam o caminho para futuras pesquisas.

Digestive enzymes during development of Ceratitis capitata (Diptera:Tephritidae) and effects of SBTI on its digestive serine proteinase targets

SILVA, Fatima C. B. L. et al. Digestive enzymes during development of Ceratitis capitata (Diptera:Tephritidae) and effects of SBTI on its digestive serine proteinase targets. Insect Biochemistry and Molecular Biology, v. 36, p. 561-569, 2006.ISSN: 0965-1748.DOI: 10.1016/j.ibmb.2006.04.004.

Influência da profundidade e dos parâmetros ambientais sobre o desenvolvimento de Gracilaria birdiae (Rhodophyta, Gracilariales) em viveiro de camarão

This study evaluates the influence of depth and environmental parameters on the development of Gracilaria birdiae Plastino & Oliveira (Gracilariaceae Rhodophyta) in an organic shrimp pound (Litopenaeus vannamei) under euthrophical conditions. PVC structures (module) witch four ropes laden with 150 g of macroalgae each, were kept during 35 days at three different depths (surface, 10 and 20 cm depth). Wet biomass weighing and environmental parameters (temperature, salinity, turbidity, pH, transparence, precipitation, evaporation, insolation, accumulated solar radiation, nitrite, nitrate, ammonium and orthophosphate) were measured weekly. At all three proposed depths, the macroalgae displayed a higher biomass at the end of experiment than at the initial inoculations. The module kept at a 10 cm depth presented the greatest average biomass (186,3), followed by that kept at 20 cm (180,4 g) and the surface module (169,9 g). Biomass variations showed algae to suffer the direct effects of depths. Biomass loss was associated with the factors that influence light penetration, such as sediment deposits above the thallus, rate of evaporation and precipitation. The smallest loses occurred in the algae kept on surface (0,16%), followed by the algae kept at 20 cm (0,20%) and 10 cm (0,22%). The specific growth rate (SGR) of G. birdiae showed no significant difference between the three depths nor the sample periods. Nevertheless, the modules kept at 10 and 20 cm depths presented similar growth evolution, both growing 0,38%·per day-1, while the module kept on surface had an average SGR of 0,36%·day-1. The models related to growth rate demonstrated temperature, salinity, pH, orthophosphate, ammonium, precipitation and turbidity as the principal environmental parameters influencing the development of G. birdiae

Efeitos da dieta hipoprotéica na formação e composição de estruturas dentárias. Estudo Experimental em ratos wistar

Protein and caloric malnutrition has been considered one of the most concerned endemic diseases in Brazil and in the world. It has been known that depletion or reduction of proteins as far as meals are concerned can steer irreversible damages upon several organic systems. This study had as aim evaluate the effects the low-protein diet had over the formation and composition of the teeth components. 18 females and 6 males were used for the experiment. 12 from the 18 females had undertaken the low-protein diet (DH) for 03 weeks and the other 6, which remained, and those males had undertaken a controlled diet (DC) for the same period. All animals had the diets during their mating, pregnancy and lactation cycle. As soon as the offsprings had been born, 10 young males and females of each group faced a disease hood analysis to check the teeth germs of their lower fore teeth. The rest of the group had their lactation cycle normally 60 days. Then they were put to death and had their lower fore teeth removed both to be analyzed through a scanning electronic microscopy (SEM) of the structure alterations and to have their calcium checked by an atomic absorption of the phosphorus vanadate-molibdate method and by other minerals EDX method. The animals livers were removed to have their hepatic proteins analyzed as well. The histopatologic study showed that at first day of birth, all animals had their lower fore teeth come out. It was verified that 90% of the animals teeth were in an apposition and calcification period and it was possible to observe the dentin formation from 60% of the 90% already mentioned. Through the SEM method it could be realized that 90% of the animals of the DH group had their lower fore teeth easily broken and no definite shape. In this same group itself, it was also observed long micro fissures 369,66 nm ± 3,45 while the DC group had fissures of 174 nm ± 5,72. Now regarding the calcium and phosphorus concentration, it could be noticed that there was a great reduction of these components and other minerals in the DH group. Almost all minerals, except for the Cl and K, presented higher levels in the DC group enamel.The reduction of the protein input greatly influenced the offsprings´ weight and height. However the hepatic proteins had no important difference between the groups what can make one believe that those animals suffered from protein malnutrition of marasmic kind