Rough virulent strain of Brucella ovis induces pro- and anti-inflammatory cytokines in reproductive tissues in experimentally infected rams

The ovine brucellosis caused by Brucella ovis has tropism for reproductive tissues but until now the mechanism of bacterial persistence is not understood. Cytokine expression profiles were studied for 8 months in rams after being experimentally infected with the rough virulent strain of B. ovis (R- B. ovis) to study the pathogenesis of B. ovis and immune mechanism possibly associated to bacteria tropism and persistence. The messenger RNA (mRNA) expression levels of interleukin-1α (IL-1α), IL-1β, IL-6, IL-10, IL-12, interferon-γ (INF-γ) and tumour necrosis factor-α (TNF-α) cytokines were quantified by real-time quantitative RT-PCR (qRT-PCR) in reproductive tissues (epididymus, testicles, ampolae, vesicular glands and bulbourethral glands), and non-reproductive (liver, spleen and kidneys) tissues at 30, 60, 120 and 240 days post infection (dpi). During the acute phase of infection at 30. dpi, the host immune response was most notable demonstrating an up-regulation of several cytokines in reproductive tissues, including the epididymus (IL-6, IL-1β and IL-1α), testicles (INF-γ and IL-12), bulbourethral glands (IL-6 and TNF-α) and ampolae (INF-γ, IL-10, IL-1β and IL-1α). During the development of infection, cytokine gene expression levels decreased, providing evidence of immunosuppression and evidence of immune evasion that favoured persistence of chronic R- B. ovis infection. During the chronic phase of R- B. ovis infection (120 and 240. dpi), cytokine production was down-regulated in the epididymus (IL-1β and IL-1α), testicles (INF-γ and IL-12), and ampolae (INF-γ, IL-10, IL-1β and IL-1α), with the exception of the bulbourethral glands (IL-6 and TNF-α) and epididymus (IL-6); in these tissues, R- B. ovis infection resulted in up-regulation of the pro-inflammatory cytokine IL-6. Herein, we report cytokine expression profiles in tissues of rams experimentally infected with the rough strain of B. ovis, which are associated with bacterial persistence and macrophage activation. © 2012 Elsevier B.V.

Infliximab prevents increased systolic blood pressure and upregulates the AKT/eNOS pathway in the aorta of spontaneously hypertensive rats

High systolic blood pressure caused by endothelial dysfunction is a comorbidity of metabolic syndrome that is mediated by local inflammatory signals. Insulin-induced vasorelaxation due to endothelial nitric oxide synthase (eNOS) activation is highly dependent on the activation of the upstream insulin-stimulated serine/threonine kinase (AKT) and is severely impaired in obese, hypertensive rodents and humans. Neutralisation of circulating tumor necrosis factor-α (TNFα) with infliximab improves glucose homeostasis, but the consequences of this pharmacological strategy on systolic blood pressure and eNOS activation are unknown. To address this issue, we assessed the temporal changes in the systolic pressure of spontaneously hypertensive rats (SHR) treated with infliximab. We also assessed the activation of critical proteins that mediate insulin activity and TNFα-mediated insulin resistance in the aorta and cardiac left ventricle. Our data demonstrate that infliximab prevents the upregulation of both systolic pressure and left ventricle hypertrophy in SHR. These effects paralleled an increase in AKT/eNOS phosphorylation and a reduction in the phosphorylation of inhibitor of nuclear factor-κB (Iκβ) and c-Jun N-terminal kinase (JNK) in the aorta. Overall, our study revealed the cardiovascular benefits of infliximab in SHR. In addition, the present findings further suggested that the reduction of systolic pressure and left ventricle hypertrophy by infliximab are secondary effects to the reduction of endothelial inflammation and the recovery of AKT/eNOS pathway activation. © 2012 Elsevier B.V.

An Integrative Genomic and Transcriptomic Analysis Reveals Potential Targets Associated with Cell Proliferation in Uterine Leiomyomas

Background: Uterine Leiomyomas (ULs) are the most common benign tumours affecting women of reproductive age. ULs represent a major problem in public health, as they are the main indication for hysterectomy. Approximately 40-50% of ULs have non-random cytogenetic abnormalities, and half of ULs may have copy number alterations (CNAs). Gene expression microarrays studies have demonstrated that cell proliferation genes act in response to growth factors and steroids. However, only a few genes mapping to CNAs regions were found to be associated with ULs. Methodology: We applied an integrative analysis using genomic and transcriptomic data to identify the pathways and molecular markers associated with ULs. Fifty-one fresh frozen specimens were evaluated by array CGH (JISTIC) and gene expression microarrays (SAM). The CONEXIC algorithm was applied to integrate the data. Principal Findings: The integrated analysis identified the top 30 significant genes (P<0.01), which comprised genes associated with cancer, whereas the protein-protein interaction analysis indicated a strong association between FANCA and BRCA1. Functional in silico analysis revealed target molecules for drugs involved in cell proliferation, including FGFR1 and IGFBP5. Transcriptional and protein analyses showed that FGFR1 (P = 0.006 and P<0.01, respectively) and IGFBP5 (P = 0.0002 and P = 0.006, respectively) were up-regulated in the tumours when compared with the adjacent normal myometrium. Conclusions: The integrative genomic and transcriptomic approach indicated that FGFR1 and IGFBP5 amplification, as well as the consequent up-regulation of the protein products, plays an important role in the aetiology of ULs and thus provides data for potential drug therapies development to target genes associated with cellular proliferation in ULs. © 2013 Cirilo et al.

Sialidase activity in aerobic vaginitis is equal to levels during bacterial vaginosis

Objective: To evaluate levels of proinflammatory cytokines and sialidase activity in aerobic vaginitis (AV) in relation to normal vaginal flora and bacterial vaginosis (BV). Study design: In this cross-sectional study, a total of 682 consecutive non-pregnant women attending the gynecology service were assessed and 408 women were included. Vaginal rinsing samples were collected from 223 women with microscopic finding of BV (n = 98), aerobic vaginitis (n = 25) and normal flora (n = 100). Samples were tested for interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, and sialidase activity. Results: Compared to women with normal flora, vaginal levels of IL-1β were highly increased in both BV and AV (p < 0.0001). Significantly higher vaginal IL-6 was detected in AV (p < 0.0001) but not in BV, in relation to normal flora. Women with AV also presented increased IL-8 levels (p < 0.001), while those with BV presented levels similar to normal flora. Sialidase was increased in BV and AV compared with the normal group (p < 0.0001) but no difference in sialidase activity was observed between BV and AV. Conclusion: A more intense inflammatory host response occurs for AV than for BV when compared with normal flora. Furthermore, the increased sialidase activity in AV and BV indicates that both abnormal vaginal flora types can be harmful to the maintenance of a healthy vaginal environment. © 2012 Elsevier B.V.

Osteogenesis-inducing calcium phosphate nanoparticle precursors applied to titanium surfaces

This study investigated the effects of the morphology and physicochemical properties of calcium phosphate (CaP) nanoparticles on osteogenesis. Two types of CaP nanoparticles were compared, namely amorphous calcium phosphate (ACP) nano-spheres (diameter: 9-13 nm) and poorly crystalline apatite (PCA) nano-needles (30-50 nm x 2-4 nm) that closely resemble bone apatite. CaP particles were spin-coated onto titanium discs and implants; they were evaluated in cultured mouse calvarial osteoblasts, as well as after implantation in rabbit femurs. A significant dependence of CaP coatings was observed in osteoblast-related gene expression (Runx2, Col1a1 and Spp1). Specifically, the PCA group presented an up-regulation of the osteospecific genes, while the ACP group suppressed the Runx2 and Col1a1 expression when compared to blank titanium substrates. Both the ACP and PCA groups presented a more than three-fold increase of calcium deposition, as suggested by Alizarin red staining. The removal torque results implied a slight tendency in favour of the PCA group. Different forms of CaP nanostructures presented different biologic differences; the obtained information can be used to optimize surface coatings on biomaterials. © 2013 IOP Publishing Ltd.

Maternal protein restriction during pregnancy affects gene expression and immunolocalization of intestinal nutrient transporters in rats

Intrauterine dietary restriction may cause changes in the functioning of offspring organs and systems later in life, an effect known as fetal programming. The present study evaluated mRNA abundance and immunolocalization of nutrient transporters as well as enterocytes proliferation in the proximal, median and distal segments of small intestine of rats born to protein-restricted dams. Pregnant rats were fed hypoproteic (6% protein) or control (17% protein) diets, and offspring rats were evaluated at 3 and 16 weeks of age. The presence of SGLT1 (sodium-glucose co-transporter 1), GLUT2 (glucose transporter 2), PEPT1 (peptide transporter 1) and the intestinal proliferation were evaluated by immunohistochemical techniques and the abundance of specific mRNA for SGLT1, GLUT2 and PEPT1 was assessed by the real-time PCR technique. Rats born to protein-restricted dams showed higher cell proliferation in all intestinal segments and higher gene expression of SGLT1 and PEPT1 in the duodenum. Moreover, in adult animals born to protein-restricted dams the immunoreactivity of SGLT1, GLUT2 and PEPT1in the duodenum was more intense than in control rats. Taken together, the results indicate that changes in the small intestine observed in adulthood can be programmed during the gestation. In addition, they show that this response is caused by both up-regulation in transporter gene expression, a specific adaptation mechanism, and intestinal proliferation, an unspecific adaptation mechanism.

The renin-angiotensin system plays a major role in voiding dysfunction of ovariectomized rats

Aims: The renin-angiotensin system (RAS) plays a major role in cardiovascular diseases in postmenopausal women, but little is known about its importance to lower urinary tract symptoms. In this study we have used the model of ovariectomized (OVX) estrogen-deficient rats to investigate the role of RAS in functional and molecular alterations in the urethra and bladder. Main methods: Responses to contractile and relaxant agents in isolated urethra and bladder, as well as cystometry were evaluated in 4-month OVX Sprague-Dawley rats. Angiotensin-converting enzyme activity and Western blotting for AT1/AT2 receptors were examined. Key findings: Cystometric evaluations in OVX rats showed increases in basal pressure, capacity and micturition frequency, as well as decreased voiding pressure. Angiotensin II and phenylephrine produced greater urethral contractions in OVX compared with Sham group. Carbachol-induced bladder contractions were significantly reduced in OVX group. Relaxations of urethra and bladder to sodium nitroprusside and BAY 41-2272 were unaffected by OVX. Angiotensin-converting enzyme activity was 2.6-fold greater (p < 0.05) in urethral tissue of OVX group, whereas enzyme activity in plasma and bladder remained unchanged. Expressions of AT1 and AT2 receptors in the urethra were markedly higher in OVX group. In bladder, AT1 receptors were not detected, whereas AT2 receptor expression was unchanged between groups. 17β-Estradiol replacement (0.1 mg/kg, weekly) or losartan (30 mg/kg/day) largely attenuated most of the alterations seen in OVX group. Significance: Prolonged estrogen deprivation leads to voiding dysfunction and urethral hypercontractility that are associated with increased ACE activity and up-regulation of angiotensin AT1/AT2 receptor in the urethral tissue. © 2013 Elsevier Inc. All rights reserved.

Relação de custo/benefício na interação entre a aranha Peucetia flava (Oxyopidae) e a planta Rhynchanthera dichotoma (Melastomataceae)

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

Avaliação da expressão gênica em leucócitos de eqüinos: análise pela técnica do microarray em modelo ex vivo de endotoxemia

Pós-graduação em Ciência Animal - FMVA

Estratégias didáticas de leitura utilizadas pelos professores e a competência leitora de alunos na 4. série do ensino fundamental

Pós-graduação em Educação - IBRC

Expressão gênica de citocinas no encéfalo de cães com leishmaniose visceral

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

An assessment of the economic impact of climate change on the tourism sector in the Bahamas

The Bahamas is at great risk and vulnerability given its geographical features as a low-lying, sea encircled country. If projected sea level rise is reached by 2050, between 10-12% of territory will be lost, especially in coastal zones where the main tourism assets are located. Vulnerability could also be manifested if flight carbon emission taxes are established in the main source markets, representing an economic threat to the tourism sector for the islands. The impact of climate change on main tourism demand variables will cause some losses to the country‟s income and government revenues. This would be acting conjointly with some local threats to tourism assets and trends in future global tourism demand. The second and no less important threat is tropical cyclones, which may be associated with raising sea level. Estimations posited the amount of losses in excess of 2400 million US$ for the four decades under examination. It is to be pointed out that there is still a lack of comparatively accurate data collection and analysis on this subject, a point deserving more attention in order to deepen the understanding of, and to extract better lessons from these extreme events. In the same period, total estimated impacts of progressive climate change are between 17 and 19 billions of B$ with estimated discount rates applied. The Bahamas is a Small Island Developing State with low growth on GHG emissions (second in Latin America), as well as a relative short capacity to lower emissions in the future. The country has a relative delay in the application of renewable energy systems, a solution that, provided documented studies on-site, might turn out to be fundamental in the country‟s efforts to establish mitigation related policies. The Bahamas currently has institutions and organizations that deal with climate change-related issues and an important number of measures and courses of action have been set up by the government. Nevertheless, more coordination among them is needed and should include international institutions. This coordination is essential even for the first steps, i.e. to conduct studies with a bottom-up approach in order to draw more accurate programs on adaptation and mitigation. It is fundamental for tourism to keep track of potential losses in tourist attractions (and to act accordingly), related to correspondent losses in biodiversity, water resources and coastal erosion. Also, actions to fight climate change impacts might improve the islands security standards, quality of living and protect cultural and heritage assets. These elements may definitely shape the future of the country‟s competitiveness as a tourism destination. It is possible and necessary to decide about the options with good cost-benefit ratio and reasonable payback periods, notwithstanding that cost-benefit analysis requires more refined and accurate data to provide precise and locally adapted options.

Utilização de técnicas de análise de agrupamento do risco de geada no Estado do Paraná para a cultura do milho safrinha

Pós-graduação em Agronomia (Energia na Agricultura) - FCA

A avaliação da compreensão leitora em espanhol língua estrangeira: análise de provas de vestibular

Analisa quantitativa e qualitativamente a avaliação da compreensão leitora do Espanhol Língua Estrangeira em provas de vestibular da região norte do Brasil, para assim evidenciar os tipos de operações e, dessa maneira, os tipos de modelos de leitura privilegiados nos testes analisados; estabelecer uma relação entre as provas coletadas e as concepções didáticas subjacentes; identificar problemas nos itens das provas com base em uma série de parâmetros de qualidade; analisar a validade dos testes selecionados; e detectar possíveis diferenças entre as provas elaboradas por Instituições de Ensino Superior públicas e privadas. Essa análise evidencia, por um lado, a tendência a se priorizarem, nessas provas, modelos ascendentes de leitura, com valorização das operações cognitivas de baixo nível e de aspectos léxico-gramaticais da língua, como conseqüência de uma concepção didática de leitura baseada em um enfoque estruturalista. Por outro lado, o estudo empreendido mostra a existência de sérias deficiências nos itens das provas de vestibular, afetando assim sua validade.

A modalização em e-mails pruduzidos em ambiente organizacional: uma abordagem na perspectiva do interacionismo sociodiscursivo

Este trabalho se inscreve no campo das investigações acerca do papel da linguagem em atividades de trabalho e fundamenta-se nos pressupostos teórico-metodológicos do interacionismosociodiscursivo (BRONCKART, 2009), cujos estudos se voltam, de forma especial, para a análise da materialidade do texto e, consequentemente, para a atividade de textualização. Com base no pressuposto de que todo texto empírico traz marcas das representações dos agentes verbais acerca da situação de ação particular em que se encontram inseridos (BRONCKART, 2009), estabeleceu-se, como objetivo geral deste trabalho, investigar, na materialidade do texto escrito, as unidades linguísticas modalizadoras como um indício das representações do enunciador frente aos parâmetros de sua situação de interlocução. De forma particular, o objetivo estabelecido foi o de, por meio de uma metodologia descendente de análise, investigar, no gênero de texto e-mail produzido em situação de trabalho, se ocorre ou não a modalização e que tipos são mais utilizados pelo enunciador (se lógicas, deônticas, apreciativas ou pragmáticas), tentando-se inferir o porquê de sua ocorrência, ou não ocorrência, assim como de seu tipo, com base nas possíveis representações do agente-produtor acerca dos parâmetros de interlocução relativos: ao papel social que ele mesmo desempenha no ato interlocutivo; ao papel social do seu destinatário; ao lugar social que ambos ocupam no ambiente de trabalho e ao conteúdo temático veiculado no texto. A hipótese aqui levantada é a de que a modalização, estando relacionada a essas representações do enunciador, esteja mais presente nas produções textuais que percorrem, no fluxo hierárquico da empresa, o caminho vertical ascendente (de subordinado para a chefia), e menos presente, ou, até mesmo, ausente, nas produções textuais que percorrem o caminho vertical descendente (de chefia para subordinado).