A vida social do espaço público: desenho urbano e space syntax

A redescoberta dos centros urbanos, enquanto espaços pedonais e de sociabilização, é um fenómeno mais ou menos universal desde os anos 60. Copenhaga é um exemplo surpreendente que deve o seu sucesso a um desenho urbano com características bottom-up liderado por Jan Gehl e que se baseia essencialmente na observação de comportamentos das pessoas face ao ambiente exterior. Projectistas (arquitectos e urbanistas) e observadores (cientistas sociais) executam tarefas mais ou menos separadas e/ou complementares com consequentes efeitos ao nível da vida das cidades. Acreditando que a cidade não é um problema mas sim uma solução para promover a sociabilização, e que o desenho urbano é uma ferramenta capaz de promover a cooperação entre diversas disciplinas, o objectivo deste estudo consiste na análise de padrões emergentes que resultam das relações entre as pessoas e o espaço. Procura-se compreender quais as características físicas do espaço público urbano que actuam como estímulos da sociabilização partindo do pressuposto que a cidade resulta do somatório de acções individuais e colectivas, planeadas e/ou emergentes e que os lugares são tanto melhor sucedidos quanto mais e melhor forem ocupados e vividos pelas pessoas. Pretende-se ainda mostrar como as teorias Space Syntax (Hillier and Hanson, 1984) permitem compreender as leis espaciais presentes no sistema do espaço urbano, nomeadamente os movimentos pedonais, a localização de actividades, etc. O modelo espacial Space Syntax, permite-nos perceber padrões e testar estratégias de desenho que melhorem a interacção e sociabilização entre as pessoas. Através do Space Syntax é possível analisar espaços individuais mas de um modo integrado na rede global da cidade compreendendo de que modo uma acção local pode influenciar toda a rede. Esta análise, que recorre a dados mensuráveis como a integração, a acessibilidade e a visibilidade, permite-nos identificar as razões do sucesso da promoção de sociabilização de determinadas áreas em detrimento de outras. Com este conhecimento é possível basear decisões futuras ao nível da regeneração do desenho do espaço urbano de modo a criar espaços mais atractivos e dinâmicos que promovam a sociabilização da população e onde se aprecie andar a pé e passar o tempo livre. Pretende-se apresentar a análise de um espaço público da cidade de Lisboa cujo desenho urbano contribui visivelmente para o seu sucesso enquanto espaço promotor da sociabilização. Este estudo procura identificar os factores físicos que promovem a ida das pessoas a estes espaços e que fomentam a sua permanência. Apresentar-se-ão também outros exemplos apoiados na análise Space Syntax que conduziram a espaços públicos mais agregadores e complementares à dinâmica urbana

T Cell Priming by Activated Nlrc5-Deficient Dendritic Cells Is Unaffected despite Partially Reduced MHC Class I Levels.

NLRC5, a member of the NOD-like receptor (NLR) protein family, has recently been characterized as the master transcriptional regulator of MHCI molecules in lymphocytes, in which it is highly expressed. However, its role in activated dendritic cells (DCs), which are instrumental to initiate T cell responses, remained elusive. We show in this study that, following stimulation of DCs with inflammatory stimuli, not only did NLRC5 level increase, but also its importance in directing MHCI transcription. Despite markedly reduced mRNA and intracellular H2-K levels, we unexpectedly observed nearly normal H2-K surface display in Nlrc5(-/-) DCs. Importantly, this discrepancy between a strong intracellular and a mild surface defect in H2-K levels was observed also in DCs with H2-K transcription defects independent of Nlrc5. Hence, alongside with demonstrating the importance of NLRC5 in MHCI transcription in activated DCs, we uncover a general mechanism counteracting low MHCI surface expression. In agreement with the decreased amount of neosynthesized MHCI, Nlrc5(-/-) DCs exhibited a defective capacity to display endogenous Ags. However, neither T cell priming by endogenous Ags nor cross-priming ability was substantially affected in activated Nlrc5(-/-) DCs. Altogether, these data show that Nlrc5 deficiency, despite significantly affecting MHCI transcription and Ag display, is not sufficient to hinder T cell activation, underlining the robustness of the T cell priming process by activated DCs

Associazione adenocarcinoma polmonare ovino-maedi in polmoni ovini naturalmente infetti: topologia di Jaagsiekte sheep retrovirus

L'Adenocarcinoma Polmonare Ovino (OPAC) o Adenomatosi Polmonare, è un tumore contagioso dei piccoli ruminanti a lento sviluppo e basso indice di metastatizzazione, il cui agente eziologico è un retrovirus tipo-D denominato Jaagsiekte Sheep Retrovirus (JSRV). Nel il 10% circa dei casi, la patologia risulta associata a pneumopatie interstiziali croniche causate da Maedi Visna Virus (MVV), lentivirus tipo-B responsabile anche di lesioni encefaliche, mammarie e articolari (1). L'esistenza e la qualità di eventuali sinergie fra i due virus è stata più volte sospettata ma non ha ancora trovato convincenti conferme sperimentali. Con l'obiettivo di verificare la distribuzione cellulare di JSRV in corso di OPAC associato a Maedi, abbiamo condotto prove ibridocitochimiche ed immunoistochimiche su polmoni ovini naturalmente infetti dai due virus e su controlli negativi e di reagente. Sono stati utilizzati a tal scopo: i) un protocollo di PCR-in situ specifico per DNA provirale di JSRV esogeno (Sanna et al, 2001); ii) un anticorpo policlonale sviluppato contro il major capsid antigen (MCA) di JSRV e gentilmente messo a disposizione dal Dr. Chris Cousens del Moredun Research Institute, Edinburgh (UK)

NLRC5 promotes transcription of BTN3A1-3 genes and Vγ9Vδ2 T cell-mediated killing

BTN3A molecules-BTN3A1 in particular-emerged as important mediators of Vγ9Vδ2 T cell activation by phosphoantigens. These metabolites can originate from infections, e.g. with Mycobacterium tuberculosis, or by alterations in cellular metabolism. Despite the growing interest in the BTN3A genes and their high expression in immune cells and various cancers, little is known about their transcriptional regulation. Here we show that these genes are induced by NLRC5, a regulator of MHC class I gene transcription, through an atypical regulatory motif found in their promoters. Accordingly, a robust correlation between NLRC5 and BTN3A gene expression was found in healthy, in M. tuberculosis-infected donors' blood cells, and in primary tumors. Moreover, forcing NLRC5 expression promoted Vγ9Vδ2 T-cell-mediated killing of tumor cells in a BTN3A-dependent manner. Altogether, these findings indicate that NLRC5 regulates the expression of BTN3A genes and hence open opportunities to modulate antimicrobial and anticancer immunity

Total temporomandibular joint prosthesis as a surgical option for severe mouth opening restriction. A case report of a bilateral intervention

Temporomandibular disorders (TMD) are a heterogeneous group of pathologies affecting the temporomandibular joint (TMJ) and/or the masticator muscles, characterized by a molteplicity of signs and symptoms, the most common of which are pain localized in the preauricular area and/or in the masticatory muscles; jaw motion abnormalities; articular sounds, such as click and/or crepitus, during mandibular movements (1). A specific etiolpathogenesis is detectable in a minority of cases, since the occurrence of TMD symptoms is often..

Spatial variability of nitrogen dioxide and formaldehydeand residential exposure of children in the industrial area of Viadana, Northern Italy

Chipboard production is a source of ambient air pollution. We assessed the spatial variability of outdoor pollutants and residentialexposure of children living in proximity to the largest chipboard industry in Italy and evaluated the reliability of exposureestimates obtained from a number of available models. We obtained passive sampling data on NO2and formaldehyde collectedby the Environmental Protection Agency of Lombardy region at 25 sites in the municipality of Viadana during 10 weeks (2017-2018) and compared NO2measurements with average weekly concentrations from continuous monitors. We compared interpo-lated NO2and formaldehyde surfaces with previous maps for 2010. We assessed the relationship between residential proximity tothe industry and pollutant exposures assigned using these maps, as well as other available countrywide/continental models basedon routine data on NO2, PM10, andPM2.5. The correlation between NO2concentrations from continuous and passive samplingwas high (Pearson'sr= 0.89), although passive sampling underestimated NO2especially during winter. For both 2010 and 2017-2018, we observed higher NO2and formaldehyde concentrations in the south of Viadana, with hot-spots in proximity to theindustry. PM10and PM2.5exposures were higher for children at 3.5 km to theindustry, whereas NO2exposure was higher at 1-1.7 km to the industry. Road and population densities were also higher close tothe industry. Findings from a variety of exposure models suggest that children living in proximity to the chipboard industry inViadana are more exposed to air pollution and that exposure gradients are relatively stable over time

NLRC5 shields T lymphocytes from NK-cell-mediated elimination under inflammatory conditions.

NLRC5 is a transcriptional regulator of MHC class I (MHCI), which maintains high MHCI expression particularly in T cells. Recent evidence highlights an important NK-T-cell crosstalk, raising the question on whether NLRC5 specifically modulates this interaction. Here we show that NK cells from Nlrc5-deficient mice exhibit moderate alterations in inhibitory receptor expression and responsiveness. Interestingly, NLRC5 expression in T cells is required to protect them from NK-cell-mediated elimination upon inflammation. Using T-cell-specific Nlrc5-deficient mice, we show that NK cells surprisingly break tolerance even towards 'self' Nlrc5-deficient T cells under inflammatory conditions. Furthermore, during chronic LCMV infection, the total CD8(+) T-cell population is severely decreased in these mice, a phenotype reverted by NK-cell depletion. These findings strongly suggest that endogenous T cells with low MHCI expression become NK-cell targets, having thus important implications for T-cell responses in naturally or therapeutically induced inflammatory conditions