IFN-α induces a preferential long-lasting expression of MHC class I in human pancreatic beta cells

Aims/hypothesis IFN-α, a cytokine expressed in human islets from individuals affected by type 1 diabetes, plays a key role in the pathogenesis of diabetes by upregulating inflammation, endoplasmic reticulum (ER) stress and MHC class I overexpression, three hallmarks of islet histology in early type 1 diabetes. We tested whether expression of these mediators of beta cell loss is reversible upon IFN-α withdrawal or IFN-α pathway inhibition. Methods IFN-α-induced MHC class I overexpression, ER stress and inflammation were evaluated by flow cytometry, immunofluorescence and real-time PCR in human EndoC-βH1 cells or human islets exposed to IFN-α with or without the presence of Janus kinase (JAK) inhibitors. Protein expression was evaluated by western blot. Results IFN-α-induced expression of inflammatory and ER stress markers returned to baseline after 24–48 h following cytokine removal. In contrast, MHC class I overexpression at the cell surface persisted for at least 7 days. Treatment with JAK inhibitors, when added with IFN-α, prevented MHC class I overexpression, but when added 24 h after IFN-α exposure these inhibitors failed to accelerate MHC class I return to baseline. Conclusions/interpretation IFN-α mediates a long-lasting and preferential MHC class I overexpression in human beta cells, which is not affected by the subsequent addition of JAK inhibitors. These observations suggest that IFN-α-stimulated long-lasting MHC class I expression may amplify beta cell antigen presentation during the early phase of type 1 diabetes and that IFN-α inhibitors might need to be used at very early stages of the disease to be effective

Imbalance of naive and memory T lymphocytes with sustained high cellular activation during the first year of life from uninfected children born to HIV-1-infected mothers on HAART

The immune consequences of in utero HIV exposure to uninfected children whose mothers were submitted to highly active antiretroviral therapy (HAART) during gestation are not well defined. We evaluated 45 HIV-exposed uninfected (ENI) neonates and 45 healthy unexposed control (CT) neonates. All HIV-infected mothers received HAART during pregnancy, and the viral load at delivery was <50 copies/mL for 56.8%. Twenty-three ENI neonates were further evaluated after 12 months and compared to 23 unexposed healthy age-matched infants. Immunophenotyping was performed by flow cytometry in cord and peripheral blood. Cord blood lymphocyte numbers did not differ between groups. However, ENI neonates had a lower percentage of naive T cells than CT neonates (CD4+, 76.6 vs 83.1%, P < 0.001; CD8+, 70.9 vs 79.6%, P = 0.003) and higher percentages of central memory T cells than CT neonates (CD4+, 13.9 vs 8.7%, P < 0.001; CD8+, 8.6 vs 4.8%, P = 0.001). CD38 mean fluorescence intensity of T cells was higher in ENI neonates (CD4+, 62.2 vs 52.1, P = 0.007; CD8+, 47.7 vs 35.3, P < 0.001). At 12 months, ENI infants still had higher mean fluorescence intensity of CD38 on T cells (CD4+, 34.2 vs 23.3, P < 0.001; CD8+, 26.8 vs 19.4, P = 0.035). Despite effective maternal virologic control at delivery, HIV-exposed uninfected children were born with lower levels of naive T cells. Immune activation was present at birth and remained until at least 12 months of age, suggesting that in utero exposure to HIV causes subtle immune abnormalities.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo (UNIFESP) Disciplina de Infectologia PediátricaUniversidade Federal de São Paulo (UNIFESP) Departamento de Pediatria Disciplina de Pediatria NeonatalUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de MedicinaUniversidade de São Paulo Instituto de Medicina Tropical de São Paulo Laboratório de VirologiaUNIFESP, Disciplina de Infectologia PediátricaUNIFESP, Depto. de Pediatria Disciplina de Pediatria NeonatalUNIFESP, EPM, Depto. de MedicinaFAPESP: 01/11011-6SciEL

Análise de neossolo para fins de fertilidade em função de critérios de amostragem e do instrumento de coleta das amostras no município de Guarabira - PB.

A prática de amostragem de solo para fins agrícolas deve representar com exatidão a fertilidade. Nesse contexto foram determinados diferentes critérios de amostragem de solo com objetivo de estabelecer dentre eles o mais preciso, sendo esses constituídos por: a) três amostras simples; b) duas amostras compostas provenientes de cinco simples; c) duas amostras compostas proveniente de dez simples e d) duas amostras compostas proveniente de vinte simples em uma área homogênea de 250m2. Utilizou-se para a coleta das amostras um trado de caneca e uma pá de corte com profundidade de 20 cm, em um Neossolo Flúvico Ta Eutrófico, situado no município de Guarabira - PB

Warifteine therapeutic treatment reduced leukocyte recruitment and anxiety-like response in ovalbumin-induced allergic pulmonary inflammation / Tratamento terapêutico com warifteína reduz recrutamento de leucócitos e resposta semelhante á ansiedade na inflamação pulmonar alérgica induzida por ovalbumina

Pulmonary inflammation plays a fundamental role in the pathophysiology of allergic asthma, which is characterized by lower airway obstruction, bronchial hyperresponsiveness, tissue remodeling, recruitment of inflammatory cells, with a predominance of eosinophils, in addition to behavioral disorders such as anxiety. The aim of this study was to evaluate the therapeutic effect of the alkaloid warifteine, from the medicinal plant Cissampelos sympodialis, on anxiety-like behavior, respiratory frequency and leukocyte recruitment in an experimental model of allergic pulmonary inflammation. Swiss female mice were sensitized and challenged with ovalbumin (OVA) throughout the experimental protocol. The animals were treated orally with warifteine (2 mg / kg), subcutaneously with dexamethasone (2 mg / kg) or intraperitoneally with diazepam (1 mg / kg), 1 h after the OVA-challenges. On the last day of the antigenic challenge, the mice were tested for behavior using the Elevated Plus Maze (EPM) and for respiratory rate using full body plethysmography. The following day, the mice were euthanized to collect the bronchoalveolar lavage fluid (BALF) and leukocyte count. The data obtained showed that OVA-sensitization induced a behavior similar to anxiety in mice since the EPM test showed that the OVA group increased the number of entries and the time spent in the closed arms (CA) of the apparatus and reduced these parameters in the open arms (OA) compared to the Salina group. Warifteine treatment reversed both parameters analyzed, increasing the time spent (p &lt;0.0001) and number of entries (p &lt;0.01) in OA, decreasing the time spent (p &lt;0.01) and number of entries (p &lt;0.0001) in the CA, similarly to dexamethasone and diazepam standard drugs. Warifteine also reduced the respiratory rate (p &lt;0.01) compared to the OVA group. The behavioral and breathing changes of the tested animals showed a relationship with the increase in the total and differential inflammatory leukocyte number in the OVA group compared to the Saline group. Therapeutic treatment with warifteine decreased the inflammatory process, reducing the number of total cells (p &lt;0.0001) dependent of eosinophils and neutrophils numbers (p &lt;0.001), as well as the percentage of eosinophils (p &lt;0.0001). These data show that therapeutic treatment with warifteine is able to inhibit anxiety-like behavior and respiratory rate, due to a mechanism related to the inhibition of eosinophilic migration in an experimental model of allergic pulmonary inflammation.Pulmonary inflammation plays a fundamental role in the pathophysiology of allergic asthma, which is characterized by lower airway obstruction, bronchial hyperresponsiveness, tissue remodeling, recruitment of inflammatory cells, with a predominance of eosinophils, in addition to behavioral disorders such as anxiety. The aim of this study was to evaluate the therapeutic effect of the alkaloid warifteine, from the medicinal plant Cissampelos sympodialis, on anxiety-like behavior, respiratory frequency and leukocyte recruitment in an experimental model of allergic pulmonary inflammation. Swiss female mice were sensitized and challenged with ovalbumin (OVA) throughout the experimental protocol. The animals were treated orally with warifteine (2 mg / kg), subcutaneously with dexamethasone (2 mg / kg) or intraperitoneally with diazepam (1 mg / kg), 1 h after the OVA-challenges. On the last day of the antigenic challenge, the mice were tested for behavior using the Elevated Plus Maze (EPM) and for respiratory rate using full body plethysmography. The following day, the mice were euthanized to collect the bronchoalveolar lavage fluid (BALF) and leukocyte count. The data obtained showed that OVA-sensitization induced a behavior similar to anxiety in mice since the EPM test showed that the OVA group increased the number of entries and the time spent in the closed arms (CA) of the apparatus and reduced these parameters in the open arms (OA) compared to the Salina group. Warifteine treatment reversed both parameters analyzed, increasing the time spent (p &lt;0.0001) and number of entries (p &lt;0.01) in OA, decreasing the time spent (p &lt;0.01) and number of entries (p &lt;0.0001) in the CA, similarly to dexamethasone and diazepam standard drugs. Warifteine also reduced the respiratory rate (p &lt;0.01) compared to the OVA group. The behavioral and breathing changes of the tested animals showed a relationship with the increase in the total and differential inflammatory leukocyte number in the OVA group compared to the Saline group. Therapeutic treatment with warifteine decreased the inflammatory process, reducing the number of total cells (p &lt;0.0001) dependent of eosinophils and neutrophils numbers (p &lt;0.001), as well as the percentage of eosinophils (p &lt;0.0001). These data show that therapeutic treatment with warifteine is able to inhibit anxiety-like behavior and respiratory rate, due to a mechanism related to the inhibition of eosinophilic migration in an experimental model of allergic pulmonary inflammation

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

A ética do silêncio racial no contexto urbano: políticas públicas e desigualdade social no Recife, 1900-1940

Mais de meio século após o preconceito racial ter se tornado o principal alvo dos movimentos urbanos pelos direitos civis nos Estados Unidos e na África do Sul, e décadas depois do surgimento dos movimentos negros contemporâneos no Brasil, o conjunto de ferramentas legislativas criado no Brasil para promover o direito à cidade ainda adere à longa tradição brasileira de silêncio acerca da questão racial. Este artigo propõe iniciar uma exploração das raízes históricas desse fenômeno, remontando ao surgimento do silêncio sobre a questão racial na política urbana do Recife, Brasil, durante a primeira metade do século XX. O Recife foi eé um exemplo paradigmático do processo pelo qual uma cidade amplamente marcada por traços negros e africanos chegou a ser definida política e legalmente como um espaço pobre, subdesenvolvido e racialmente neutro, onde as desigualdades sociais originaram na exclusão capitalista, e não na escravidão e nas ideologias do racismo científico. Neste sentido, Recife lança luzes sobre a política urbana que se gerou sob a sombra do silêncio racial.More than half a century after racial prejudice became central to urban civil rights movements in the United States and South Africa, and decades after the emergence of Brazil’s contemporary Black movements, Brazil's internationally recognized body of rights-to-the-city legislation still adheres to the country's long historical tradition of racial silence. This article explores the historical roots of this phenomenon by focusing on the emergence of racial silence in Recife, Brazil during the first half of the 20th Century. Recife was and remains a paradigmatic example of the process through which a city marked by its Black and African roots came to be legally and politically defined as a poor, underdeveloped and racially neutral space, where social inequalities derived from capitalist exclusion rather than from slavery and scientific racism. As such, Recife'sexperience sheds light on the urban policies that were generated in the shadow of racial silence