Lung dendritic cells induce migration of protective T cells to the gastrointestinal tract

Developing efficacious vaccines against enteric diseases is a global challenge that requires a better understanding of cellular recruitment dynamics at the mucosal surfaces. The current paradigm of T cell homing to the gastrointestinal (GI) tract involves the induction of α4β7 and CCR9 by Peyer\u27s patch and mesenteric lymph node (MLN) dendritic cells (DCs) in a retinoic acid-dependent manner. This paradigm, however, cannot be reconciled with reports of GI T cell responses after intranasal (i.n.) delivery of antigens that do not directly target the GI lymphoid tissue. To explore alternative pathways of cellular migration, we have investigated the ability of DCs from mucosal and nonmucosal tissues to recruit lymphocytes to the GI tract. Unexpectedly, we found that lung DCs, like CD103+ MLN DCs, up-regulate the gut-homing integrin α4β7 in vitro and in vivo, and induce T cell migration to the GI tract in vivo. Consistent with a role for this pathway in generating mucosal immune responses, lung DC targeting by i.n. immunization induced protective immunity against enteric challenge with a highly pathogenic strain of Salmonella. The present report demonstrates novel functional evidence of mucosal cross talk mediated by DCs, which has the potential to inform the design of novel vaccines against mucosal pathogens

Interacção entre duas espécies exóticas de lagostins (pacifastacus leniusculus e procambarus clarkii): estudo experimental com recurso à PIT-telemetria

No rio Maçãs (bacia do Rio Douro), no Nordeste de Portugal, coexistem duas espécies de lagostins exóticos, o lagostim vermelho da Louisiana (Procambarus clarkii) e o lagostim sinal (Pacifastacus leniusculus). Para estudar o movimento e padrão de actividade de ambas as espécies foi desenvolvida uma experiência num espaço confinado (300 x 100 cm) e aplicada a técnica da PIT-telemetria (Passive Integrated Technology, UKID Systems, U.K.), com recurso a um MPD (Data-logger) e oito antenas circulares de detecção de transmissores (PIT-tags). Seleccionou-se um local de alimentação e alguns refúgios capazes de fornecer isolamento visual entre lagostins. Foram implantados PIT-tags, com identificação individual, em 5 machos e 5 fêmeas de cada espécie e monitorizado o seu comportamento de forma contínua (dia e noite) ao longo de 15 dias, durante o período estival de dois anos consecutivos. Obtiveram-se cerca de 30 000 dados, diferenciados em termos de frequência de dados repetidos (registos contínuos na mesma antena) e não repetidos por cada animal. A análise dos dados sugere um comportamento diferenciado entre espécies e sexos com dominância do lagostim vermelho relativamente ao lagostim sinal e dos machos sobre as fêmeas. As interacções entre espécies podem estar na origem do afastamento e menor actividade de P. leniusculus dos locais mais próximos da área de alimentação. Por outro lado, as fêmeas de ambas as espécies demonstraram ser menos activas do que os machos

Transcription Factor T-bet Regulates Intraepithelial Lymphocyte Functional Maturation

SummaryThe intestinal epithelium harbors large populations of activated and memory lymphocytes, yet these cells do not cause tissue damage in the steady state. We investigated how intestinal T cell effector differentiation is regulated upon migration to the intestinal epithelium. Using gene loss- and gain-of-function strategies, as well as reporter approaches, we showed that cooperation between the transcription factors T-bet and Runx3 resulted in suppression of conventional CD4+ T helper functions and induction of an intraepithelial lymphocyte (IEL) program that included expression of IEL markers such as CD8αα homodimers. Interferon-γ sensing and T-bet expression by CD4+ T cells were both required for this program, which was distinct from conventional T helper differentiation but shared by other IEL populations, including TCRαβ+CD8αα+ IELs. We conclude that the gut environment provides cues for IEL maturation through the interplay between T-bet and Runx3, allowing tissue-specific adaptation of mature T lymphocytes

Application of one and two-dimensional hydrodynamic models to rio Grande-MG river basin

O presente artigo faz uma análise da calibração do modelo hidrodinâmico uni e bidimensional aplicado à bacia do Rio Grande , na localidade da cidade de Ribeirão Vermelho em Minas Gerais . O software SOBE K foi utilizado para a implementação dos modelos que foram devidamente calibrados. Apresenta-se a discretização utilizada para Representar adequadamente uma ponte rodoferroviária inundável, uma vez que a utilização de uma única estrutura não se revelou suficiente para simular as características de escoamento da forma desejada. Além disso, foram analisados em detalhe os métodos que o software SOBEK possui para transmitir as informações entre os modelos uni e bidimensional. Com o objetivo de aprimorar a modelagem foram utilizados artifícios do software para determinar a partir de qual elevação os modelos 1D e 2D seriam utilizados. Os resultados indicam que a consideração do escoamento bidimensional favorece o desempenho do modelo, visto que proporciona um maior detalhamento na representação da regiãoThis paper analyzes the calibration of a one and two - dimensional hydrodynamic model of Rio Grande - MG river basin, near the city of Ribeirão Vermelho in Minas Gerais. The SOBEK software was used for the implemen tation of the models that was properly calibrated. The discretization to adequately represent flooding over a road - railway bridge is characterized, since the use of a unique structure it was not sufficient to simulate the flow characteristics as desired near the bridge. In addition available software options for sharing of data between one and two - dimensional models are analyzed. In order t o improve the modeling results proper software options were used to determine the water surface elevation to activate the 1D and 2D modules. Results indicate that considerat ion of two - dimensional flow improve the model performance, since it provides a more detailed representation of the flooded are

Do borrão às aguadas: os engenheiros militares e a representação da Capitania de São Paulo

A análise do papel dos engenheiros militares perpassa as discussões sobre regiões específicas, mesmo quando eles, aparentemente, estão ausentes delas. Sua presença ou ausência sempre foi sinônimo de interesse e de projeto colonizador mais ou menos dirigido. Este ensaio tem como objeto de estudo a cartografia dos engenheiros militares atuantes na Capitania de São Paulo, território comumente visto como economicamente periférico e mais autônomo face aos desígnios da Coroa portuguesa. Com foco no corpus cartográfico de alguns profissionais que aqui atuaram, trata indiretamente da multifacetada atuação desses engenheiros, bem como do processo de feitura das cartas geográficas, corográficas e topográficas, do borrão às aguadas. Investigar a cartografia de alguns desses profissionais permite não apenas explorar a riqueza de suas biografias, como, também, acompanhar o processo de produção técnica dos mapas e os desígnios políticos envolvidos no devassamento e representação das terras descobertas no Novo Mundo.Analyzing the role of military engineers means venturing into discussions about specific regions, even those from which they are apparently absent. Their presence or absence has always been synonymous with interest and a more or less directed colonization project. This essay examines the maps produced by the military engineers working in the Captaincy of São Paulo, a territory often looked upon as one of little economic import and a rather autonomous area in light of the plans of the Portuguese Crown. By focusing on the cartographic corpus bequeathed by certain professionals serving in this region, we deal indirectly with the multifaceted role of these engineers as well as with the process of making geographic, chorographic and topographic charts - all the way from the sketch to watercolored maps. Perusing the charts constructed by some of these professionals enabled us not only to delve into the rich details of their biographies but also to observe the technical mapmaking process and to unravel the political designs behind the exploration and representation of the lands discovered in the New World

Acoustic Telemetry Unravels Movements and Habitat Use Patterns of Juvenile Meagre (A. regius) in the Tagus Estuary

The meagre is among the largest Sciaenidae in the world (max: 230 cm, 103 kg), with a wide distribution range encompassing the NE and CE Atlantic Ocean and the Mediterranean Sea. The life cycle in Atlantic waters includes migratory movements from feeding and overwintering areas at sea to spawning and nursery areas in estuaries and coastal waters. However, significant spawning aggregations are only observed in five locations, among which is the Tagus estuary (Portugal). The meagre fishery that takes place within the Tagus estuary is significant, accounting for approximately two-thirds of Portuguese meagre catches. Despite its economic relevance, the meagre movements in that region remain largely unknown. The existence of a target fishery inside the estuary alongside a lack of routine biological data collection targeting the species and incipient fisheries control in the area, highlight an urgency to adopt innovative methodologies to unravel meagre migrations and its use of critical areas. We present the first insights of movement patterns and habitat use in the Tagus estuary using acoustic biotelemetry data collected between 2019 and 2021. The acoustic receiver array obtained a total of 142.183 registers from a total of 34 individuals tagged. From the tagged specimens, 33% revisited the Tagus estuary in subsequent years at least once, during the spring and summer, and 49% remained in the Tagus at least until autumn. Further analysis was conducted with juveniles tracked over 3 years to identify critical nursery areas using dynamic Brownian bridge movement models (utilization distribution estimations). The effects of abiotic conditions on the meagre behaviour were assessed using in situ sensor data (e.g., temperature and salinity) and other environmental predictors (e.g., photoperiod and tide cycle) and an explanatory model was developed that helps to understand the use of the Tagus estuary by juveniles. The information collected will be discussed in light of possible applications to promote sustainable management of meagre fisheries in the Tagus estuary and adjacent coastal areas

Lack of effects of typical and atypical antipsychotics in DARPP-32 and NCS-1 levels in PC12 cells overexpressing NCS-1

<p>Abstract</p> <p>Background</p> <p>Schizophrenia is the major psychiatry disorder, which the exact cause remains unknown. However, it is well known that dopamine-mediated neurotransmission imbalance is associated with this pathology and the main target of antipsychotics is the dopamine receptor D₂. Recently, it was described alteration in levels of two dopamine signaling related proteins in schizophrenic prefrontal cortex (PFC): Neuronal Calcium Sensor-1 (NCS-1) and DARPP-32. NCS-1, which is upregulated in PFC of schizophrenics, inhibits D₂internalization. DARPP-32, which is decreased in PFC of schizophrenics, is a key downstream effector in transducing dopamine signaling. We previously demonstrated that antipsychotics do not change levels of both proteins in rat's brain. However, since NCS-1 and DARPP-32 levels are not altered in wild type rats, we treated wild type PC12 cells (PC12 WT) and PC12 cells stably overexpressing NCS-1 (PC12 Clone) with antipsychotics to investigate if NCS-1 upregulation modulates DARPP-32 expression in response to antipsychotics treatment.</p> <p>Results</p> <p>We chronically treated both PC12 WT and PC12 Clone cells with typical (Haloperidol) or atypical (Clozapine and Risperidone) antipsychotics for 14 days. Using western blot technique we observed that there is no change in NCS-1 and DARPP-32 protein levels in both PC12 WT and PC12 Clone cells after typical and atypical antipsychotic treatments.</p> <p>Conclusions</p> <p>Because we observed no alteration in NCS-1 and DARPP-32 levels in both PC12 WT and Clone cells treated with typical or atypical antipsychotics, we suggest that the alteration in levels of both proteins in schizophrenic's PFC is related to psychopathology but not with antipsychotic treatment.</p

The germline mutational landscape of BRCA1 and BRCA2 in Brazil

The detection of germline mutations in BRCA1 and BRCA2 is essential to the formulation of clinical management strategies, and in Brazil, there is limited access to these services, mainly due to the costs/availability of genetic testing. Aiming at the identification of recurrent mutations that could be included in a low-cost mutation panel, used as a first screening approach, we compiled the testing reports of 649 probands with pathogenic/likely pathogenic variants referred to 28 public and private health care centers distributed across 11 Brazilian States. Overall, 126 and 103 distinct mutations were identified in BRCA1 and BRCA2, respectively. Twenty-six novel variants were reported from both genes, and BRCA2 showed higher mutational heterogeneity. Some recurrent mutations were reported exclusively in certain geographic regions, suggesting a founder effect. Our findings confirm that there is significant molecular heterogeneity in these genes among Brazilian carriers, while also suggesting that this heterogeneity precludes the use of screening protocols that include recurrent mutation testing only. This is the first study to show that profiles of recurrent mutations may be unique to different Brazilian regions. These data should be explored in larger regional cohorts to determine if screening with a panel of recurrent mutations would be effective.This work was supported in part by grants from Barretos Cancer Hospital (FINEP - CT-INFRA, 02/2010), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, 2013/24633-2 and 2103/23277-8), Fundação de Apoio à Pesquisa do Rio Grande do Norte (FAPERN), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), Ministério da Saúde, the Breast Cancer Research Foundation (Avon grant #02-2013-044) and National Institute of Health/National Cancer Institute (grant #RC4 CA153828-01) for the Clinical Cancer Genomics Community Research Network. Support in part was provided by grants from Fundo de Incentivo a Pesquisa e Eventos (FIPE) from Hospital de Clínicas de Porto Alegre, by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, BioComputacional 3381/2013, Rede de Pesquisa em Genômica Populacional Humana), Secretaria da Saúde do Estado da Bahia (SESAB), Laboratório de Imunologia e Biologia Molecular (UFBA), INCT pra Controle do Câncer and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). RMR and PAP are recipients of CNPq Productivity Grants, and Bárbara Alemar received a grant from the same agencyinfo:eu-repo/semantics/publishedVersio