UPR-mediated TRIB3 expression correlates with reduced AKT phosphorylation and inability of interleukin 6 to overcome palmitate-induced apoptosis in RINm5F cells

Unfolded protein response (UPR)-mediated pancreatic beta-cell death has been described as a common mechanism by which palmitate (PA) and pro-inflammatory cytokines contribute to the development of diabetes. There are evidences that interleukin 6 (IL6) has a protective action against beta-cell death induced by proinflammatory cytokines; the effects of IL6 on PA-induced apoptosis have not been investigated yet. In the present study, we have demonstrated that PA selectively disrupts IL6-induced RAC-alpha serine/threonine-protein kinase (AKT) activation without interfering with signal transducer and activator of transcription 3 phosphorylation in RINm5F cells. The inability of IL6 to activate AKT in the presence of PA correlated with an inefficient protection against PA-induced apoptosis. In contrast to PA, IL6 efficiently reduced apoptosis induced by pro-inflammatory cytokines. In addition, we have demonstrated that IL6 is unable to overcome PA-stimulated UPR, as assessed by activating transcription factor 4 (ATF4) andC/EBP homologous protein (CHOP) expression, X-box binding protein-1 gene mRNA splicing, and pancreatic eukaryotic initiation factor-2 alpha kinase phosphorylation, whereas no significant induction of UPR by pro-inflammatory cytokines was detected. This unconditional stimulation of UPR and apoptosis by PA was accompanied by the stimulation of CHOP and tribble3 (TRIB3) expression, irrespective of the presence of IL6. These findings suggest that IL6 is unable to protect pancreatic beta-cells from PA-induced apoptosis because it does not repress UPR activation. In this way, CHOP and ATF4 might mediate PA-induced TRIB3 expression and, by extension, the suppression of IL6 activation of pro-survival kinase AKT. Journal of Endocrinology (2010) 206, 183-193

Laterally transferred genomic islands in Xanthomonadales related to pathogenicity and primary metabolism

Lateral gene transfer (LGT) is considered as one of the drivers in bacterial genome evolution, usually associated with increased fitness and/or changes in behavior, especially if one considers pathogenic vs. non-pathogenic bacterial groups. The genomes of two phytopathogens, Xanthomonas campestris pv. campestris and Xanthomonas axonopodis pv. citri, were previously inspected for genome islands originating from LGT events, and, in this work, potentially early and late LGT events were identified according to their altered nucleotide composition. The biological role of the islands was also assessed, and pathogenicity, virulence and secondary metabolism pathways were functions highly represented, especially in islands that were found to be recently transferred. However, old islands are composed of a high proportion of genes related to cell primary metabolic functions. These old islands, normally undetected by traditional atypical composition analysis, but confirmed as product of LGT by atypical phylogenetic reconstruction, reveal the role of LGT events by replacing core metabolic genes normally inherited by vertical processes.

TLR2 and TLR4 expression after kidney ischemia and reperfusion injury in mice treated with FTY720

Ischemia and reperfusion injury (IR) is an antigen independent inflammatory process that causes tissue damage. After IR, kidneys up-regulate leukocyte adhesion molecules and toll-like receptors (TLRs). Moreover, injured kidneys can also secrete factors (i.e. heat shock protein) which bind to TLRs and trigger intracellular events culminating with the increase in the gene expression of inflammatory cytokines. FTY720 is an immunomodulatory compound and protects at least in part kidneys submitted to IR. The mechanisms associated with FTY720`s beneficial effects on kidneys after IR remain elusive. We investigated whether FTY720 administration in mice submitted to kidney IR is associated with modulation of TLR2 and TLR4 expression. C57BL/6 mice submitted to 30 min of renal pedicles clamp were evaluated for serum parameters (creatinine, urea and nitric oxide), kidney histology, spleen and kidney infiltrating cells expression of TLR2 and TLR4, resident kidney cells expression of TLR2 and TLR4 and IL-6 protein expression in kidney. FTY720-treated mice presented decrease in serum creatinine, urea and nitric oxide, diminished expression of TLR2 and TLR4 both in spleen and kidney infiltrating cells, and reduced kidney IL-6 protein expression in comparison with IR non-treated mice. However, acute tubular necrosis was present both in IR non-treated and IR + FTY720-treated groups. Also, FTY720 did not prevent TLR2 and TLR4 expression in kidney resident cells. In conclusion, FTY720 can promote kidney function recovery after IR by reducing the inflammatory process. Further studies are needed in order to establish whether TLR2 and TLR4 down regulation should be therapeutically addressed as protective targets of renal function and structure after IR. (C) 2011 Elsevier B.V. All rights reserved.

The online distribution strategy of luxury products and their vertical extensions

Uma importante tendência do mercado de luxo é a extensão de marca em um novo segmento de mercado por meio da chamada extensão vertical, que pode ser para cima ou para baixo. Em outras palavras, significa que a organização passa a atuar em um novo segmento dentro de uma mesma categoria de produtos, mas com diferente público-alvo que sua marca original. Nesse processo, a empresa inicia atividade em um novo segmento com diferente nível de luxo. A distribuição é um aspecto fundamental do composto de Marketing e a importância da internet como canal de distribuição dessa indústria tem aumentado expressivamente nos últimos anos. Dessa forma, faz-se necessário compreender como as marcas de luxo gerenciam suas estratégias de distribuição online quando desenvolvem processos de extensão de marca e penetração em novos segmentos. Com o objetivo de analisar a estratégia de distribuição da indústria de luxo, um estudo exploratório foi desenvolvido focando bens de luxo pessoal (em categorias como costura, relógios & jóias, couro e sapatos). Uma amostra significativa constituída de marcas originais e suas extensões foi analisada para constituir um modelo comparativo entre duas variáveis: o nível de diferenciação entre os canais de distribuição da marca original e suas extensões; e a distância entre as próprias marcas no que concerne ao seus posicionamentos. Esse estudo contribui para o entendimento da dinâmica de distribuição do mercado e colabora com a compreensão do comportamento das empresas que atuam nele, dependendo do tipo de extensões que elas desenvolvem e da forma como elas são conduzidas.

Old-age benefits and retirement decisions of rural elderly in Brazil

I estimate the impact of social security benefits on retirement decisions of rural workers by studying changes in the roles governing social security in Brazil. I focus on a 1991 reform, which brought a reduction in the minimum eligibility age for males and females, a doubling of benefit values and the extension of benefits to non-heads of households. Because beneficiaries are not subject to means or retirement tests, I estimate apure income effect. I find that a reduction in the minimum eligibility age for old-age benefits was an important determinant in the reduction in labor supply of elderly rural workers in Brazil. Finally, I find that benefit take-up rates are larger among the better educated, but least-schooled workers show the largest labor supply responses to the reform.

Análise e quantificação da formação de suítes no jornalismo online brasileiro.

No jornalismo, são chamadas suítes as matérias que trazem a sequência de um fato já noticiado. Conforme a imprensa cresce na Internet, podemos ver frequentemente um mesmo fato sendo repetido em portais de notícias dia após dia. Este trabalho visa medir as quantidades de artigos a respeito de um mesmo assunto que tenha iniciado uma suíte, com esta medição acontecendo ao longo dos dias em que ele foi explorado. Os resultados permitiram que fossem encontrados padrões que identifiquem os dias em que os fatos mais relevantes foram noticiados, bem como o tempo em que o assunto foi desenvolvido. Para esta análise, foram escolhidos alguns dos mais importantes fatos que viraram suítes no Brasil ao longo dos últimos anos. As quantidades de artigos são provenientes do maior portal de notícias do país, o G1, e da base de dados do Media Cloud Brasil.

Selective Coupling between Theta Phase and Neocortical Fast Gamma Oscillations during REM-Sleep in Mice

TORT, A. B. L. ; SCHEFFER-TEIXEIRA, R ; Souza, B.C. ; DRAGUHN, A. ; BRANKACK, J. . Theta-associated high-frequency oscillations (110-160 Hz) in the hippocampus and neocortex. Progress in Neurobiology , v. 100, p. 1-14, 2013.

Zircon fission track and U-Th-Pb in situ dating of Rio Parana Formation, Parana Basin, Brazil

Ages of zircon from sedimentary samples of Rio Parana Formation, belonging of Bauru Group, north of Parana Basin, Brazil, has been determined by zircon Fission Track and U-Th-Pb in situ dating methods. The obtained ages are from same zircon grain that provided information on the source areas for the sediments and the morphotectonic events.

Perioperative cardiac arrest and its mortality in children. A 9-year survey in a Brazilian tertiary teaching hospital

Background: the incidence of perioperative cardiac arrest and mortality in children is higher than in adults. This survey evaluated the incidence, causes, and outcome of perioperative cardiac arrests in a pediatric surgical population in a tertiary teaching hospital between 1996 and 2004.Methods: the incidence of cardiac arrest during anesthesia was identified from an anesthesia database. During the study period, 15 253 anesthetics were performed in children. Data collected included patient demographics, surgical procedures (elective, urgent, or emergency), ASA physical status classification, anesthesia provider information, type of surgery, surgical areas, and outcome. All cardiac arrests were reviewed and grouped by the cause of arrest and death into one of four groups: totally anesthesia-related, partially anesthesia-related, totally surgery-related, or totally child disease or condition-related.Results: There were 35 cardiac arrests (22.9 : 10 000) and 15 deaths (9.8 : 10 000). Major risk factors for cardiac arrest were neonates and children under 1 year of age (P < 0.05) with ASA III or poorer physical status (P < 0.05), in emergency surgery (P < 0.05), and general anesthesia (P < 0.05). Child disease/condition was the major cause of cardiac arrest or death (P < 0.05). There were seven cardiac arrests because of anesthesia (4.58 : 10 000) - four totally (2.62 : 10 000) and three partially related to anesthesia (1.96 : 10 000). There were no anesthesia attributable deaths reported. The main causes of anesthesia attributable cardiac arrest were respiratory events (71.5%) and medication-related events (28.5%).Conclusions: Perioperative cardiac arrests were relatively higher in neonates and infants than in older children with severe underlying disease and during emergency surgery. The fact that all anesthesia attributable cardiac arrests were related to airway management and medication administration is important in prevention strategies.

Prognostic factors for perioperative pulmonary events among patients undergoing upper abdominal surgery

CONTEXTO E OBJETIVO: Associações significativas entre cirurgia do abdome superior e eventos pulmonares do período perioperatório foram investigadas em pacientes com condições pulmonares pré-operatórias submetidos a anestesia geral. TIPO DE ESTUDO E LOCAL: Estudo retrospectivo cujos dados foram retirados de banco de dados obtidos prospectivamente de forma protocolada, de 1 de janeiro de 1999 a 31 de dezembro de 2004, em hospital universitário terciário. MÉTODOS: Estudados 3107 pacientes com mais de 11 anos, American Society of Anesthesiologists (ASA) I, II, III, com cirurgia de abdome superior sob anestesia geral, enviados à sala de recuperação. Condições pré-operatórias analisadas por regressão logística foram: idade, sexo, estado físico ASA, insuficiência cardíaca congestiva, asma, doença pulmonar obstrutiva crônica, insuficiência respiratória e hábito de fumar. Os resultados estudados, ou variáveis dependentes, incluíram eventos intra- e pós-operatórios: broncoespasmo, hipoxemia, hipercapnia, intubação prolongada e secreção de vias aéreas. RESULTADOS: Dos 3.107 pacientes: 1.540 eram homens, 1.649 mulheres, tinham média de 48 anos, 1088 ASA I, 1402 ASA II, 617 ASA III, com insuficiência cardíaca havia 80, asma, 82, doença pulmonar obstrutiva, 122, insuficiência respiratória, 21, hábito de fumar, 428. Pela regressão logística, sexo feminino (p < 0.001), idade maior que 70 anos (p < 0.01), hábito de fumar (p < 0.001) e doença pulmonar obstrutiva crônica (p < 0.02) influenciaram significativamente o desenvolvimento de eventos pulmonares, principalmente hipoxemia e broncospasmo, em ambos os períodos, mas não nos mesmos pacientes. Asma e insuficiência cardíaca não se associaram com eventos pulmonares na sala de recuperação. CONCLUSÃO: em cirurgia do abdome superior sob anestesia geral, sexo feminino, idade maior que 70 anos, hábito de fumar e doença pulmonar obstrutiva crônica foram fatores de risco independentes para a ocorrência de eventos pulmonares intra- e pós-operatórios.

Long-term effects of insulin therapy, islet transplantation, and pancreas transplantation in the prevention of glomerular changes in kidneys of alloxan-induced diabetic rats

Groups of inbred alloxan-induced diabetic rats were treated with insulin (I), islets (IT), or pancreas transplantation (PT). Nondiabetic (N) and untreated diabetic (D) control groups were concurrently included. Each group was divided into five subgroups of 10 rats and killed after follow-up of 1, 3, 6, 9, and 12 months. Clinical and laboratory parameters were recorded, and kidney ultrastructural and morphometric analyses performed in each 12-month subgroup, namely glomerular basement membrane (GM) thickening, podocyte number, and number/extension of slit diaphragms (S). Rats from the I group showed poor metabolic control of diabetes compared with N group control rats. However, successfully transplanted rats (IT and PT) had complete restoration to normal levels for all metabolic parameters. GM thickening was significantly higher in diabetic compared with control rats. In contrast, the numbers of podocytes and slits as well as slit extensions were significantly decreased. Insulin therapy did not prevent any alterations upon comparison of diabetic vs control rats. Despite good metabolic control in IT rats, the degree of kidney lesion control never compared with that achieved in PT rats. In this group all glomerular changes were similar to the age-dependent lesions observed in control rats. We conclude that either IT or PT may be a good option for diabetes treatment, although pancreas transplantation seems to be the most effective treatment to control chronic complications.

Edge effect and phenology in Erythroxylum tortuosum (Erythroxylaceae), a typical plant of the Brazilian Cerrado

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Multiple events of horizontal transfer of the Minos transposable element between Drosophila species

In this study the Minos element was analyzed in 26 species of the repleta group and seven species of the saltans group of the genus Drosophila. The PCR and Southern blot analysis showed a wide occurrence of the Minos transposable element among species of the repleta and the saltans groups and also a low number of insertions in both genomes. Three different analyses, nucleotide divergence, historical associations, and comparisons between substitution rates (d(N) and d(S)) of Minos and Adh host gene sequences, suggest the occurrence of horizontal transfer between repleta and saltans species. These data reinforce and extend the Arca and Savakis [Genetica 108 (2000) 263] results and suggest five events of horizontal transfer to explain the present Minos distribution: between D. saltans and the ancestor of the mulleri and the mojavensis clusters; between D. hydei and the ancestor of the mulleri and the mojavensis clusters; between D. mojavensis and D. aldrichi; between D. buzzatii and D. serido; and between D. spenceri and D. emarginata. An alternative explanation would be that repeated events of horizontal transfer involving D. hydei, which is a cosmopolitan species that diverged from the others repleta species as long as 14 Mya, could have spread Minos within the repleta group and to D. saltans. The data presented in this article support a model in which distribution of Minos transposon among Drosophila species is determined by horizontal transmission balanced by vertical inactivation and extinction. (c) 2004 Elsevier B.V. All rights reserved.

Microleakage and nanoleakage: Influence of laser in cavity preparation and dentin pretreatment

Objective: the purpose of this study was to verify if the application of the Nd:YAG laser following pretreatment of dentin with adhesive systems that were not light cured in class V cavities and were prepared with Er:YAG laser would promote better sealing of the gingival margins when compared to cavities prepared the conventional way. Background Data: Previous studies had shown that the pretreatment of dentin with laser irradiation after the application of an adhesive system is efficient in achieving higher shear bond and tensile bond strength. Materials and Methods: Er:YAG laser (Kavo-Key, Germany) with 350 mJ, 4 Hz, and 116.7 J/cm(2) was used for cavity preparation. The conventional preparation was made with diamond bur mounted in high-speed turbine. Dentin treatment was accomplished using an Nd:YAG laser (Pulse Master 1000, ADT. USA) at 60 mJ, 10 Hz, and 74.65/cm(2) following application of the adhesive system. The cavities were stored with Single Bond/Z100 and Prime & Bond NT/TPH. Eighty bovine incisors were used, and class V preparations were done at buccal and lingual surfaces divided into eight groups: (1) Er:YAG preparation + Prime & Bond NT + TPH; (2) Er:YAG preparation + Single Bond + Z100; (3) Er:YAG preparation + Single Bond + Nd:YAG + Z100; (4) Er:YAG preparation + Prime & Bond NT + Nd:YAG + TPH; (5) conventional preparation + Prime & Bond NT + TPH; (6) conventional preparation + Single Bond + Z100; (7) conventional preparation + Single Bond + Nd:YAG + Z100; (8) conventional preparation + Prime & Bond NT + Nd:YAG + TPH. All specimens were thermocycled for 300 full cycles between 5 degreesC +/- 2 degreesC and 55 degreesC +/- 2 degreesC (dwell time of 30 sec), and stored in 50% silver nitrate solution for 24 h soaked in photodeveloping solution and exposed to fluorescent light for 6 h. After this procedure, the specimens were sectioned longitudinally in 3 portions and the extension of microleakage at the gingival wall was determined following a criteria ranging from 0 to 4 using scanning electron microscopy (SEM). The medium portion sectioned of each specimen was polished and prepared for nanoleakage avaliation by SEM. Results: Kruskall-Wallis and Miller statistical tests determined that group 3 presented less microleakage and nanoleakage. Conclusion: Application of the Nd:YAG laser following pretreatment of dentin with adhesive Single Bond non-photocured Single Bond adhesive in cavities prepared with Er:YAG promote better sealing of the gingival margins.

An open-label, comparative study of the efficacy and safety of once-daily dose of enoxaparin versus unfractionated heparin in the treatment of proximal lower limb deep-vein thrombosis

Background: Treatment of deep-vein thrombosis (DVT) with a once-daily regimen of enoxaparin, rather than a continuous infusion of unfractionated heparin (UFH) is more convenient and allows for home care in some patients. This study was designed to compare the efficacy and safety of these two regimens for the treatment of patients with proximal lower limb DVT. Methods: 201 patients with proximal lower limb DVT from 13 centers in Brazil were randomized in an open manner to receive either enoxaparin [1.5 mg/kg subcutaneous (s.c.) OD] or intravenous (i.v.) UFH (adjusted to aPTT 1.5-2.5 times control) for 5-10 days. All patients also received warfarin (INR 2-3) for at least 3 months. The primary efficacy endpoint Was recurrent DVT (confirmed by venography or ultrasonography), and safety endpoints included bleeding and serious adverse events. The rate of pulmonary embolism (PE) was also collected. Hospitalization was at the physician's discretion. Results: Baseline patient characteristics were comparable between groups. The duration of hospital stay was significantly shorter with enoxaparin than with UFH (3 versus 7 days). In addition, 36% of patients receiving enoxaparin did not need to be hospitalized, whereas all of the patients receiving UFH were! hospitalized. The treatment duration was slightly longer with enoxaparin (8 versus 7 days). There was a nonsignificant trend toward a reduction in the rate of recurrent DVT with enoxaparin versus UFH, and similar safety. Conclusions: A once-daily regimen of enoxaparin 1.5 mg/kg subcutaneous is at least as effective and safe as conventional treatment with a continuous intravenous infusion of UFH. However, the once daily enoxaparin regimen is easier to administer (subcutaneous versus intravenous), does not require aPTT monitoring, and leads to both a reduced number of hospital admissions and an average 4-day-shorter hospital stay. (C) 2004 Elsevier Ltd. All rights reserved.