How to Meet the City – Urban Spaces for Friendly Encounters

As urbanists, we observe public spaces every day with an eye toward their purpose; we critically gauge their facilities, features and sociocultural connotations. Are they used on a frequent basis? Do people rest, do they gather, do they linger, do they mingle? Is there any social interaction? Do these places contribute to an objective sense of well-being, welcoming those who temporarily reside there? Do they replace a piece of nature? In comparison to closed architectural structures which are reserved for private or semi private use, public spaces have the important role of hosting a wide range of people from different social and cultural backgrounds. While architecture usually predicts its type of use, open space has the potential of being unpredictable and can trigger dynamics within its urban framework that greatly influence the way a city is perceived. In order to obtain a positive result when transforming an open space, we have to focus on those who use the space on a daily basis, the people who give it its character. The users must be the focus of our investigations, their various needs must be the vision to begin with. In the end, it is the people who constitute the identity and authenticity of a place. Whether or not there are smart city solutions for the inhabitants of an urban space, it only serves the users if it is made for their specific needs. We want to optimize sustainability, respond to climate change facts and enhance urban well being while allowing people to notice the individual features of a space. This reaction is very individual to each city and has its own energy which makes a place special and unique. The ambience of a city is hence the reflection of the behavior of its city dweller

Relações Água-Rocha e a Hidrogeoquímica do Cromo na Água Subterrânea de Poços de Monitoramento Multiníveis de Urânia, SP, Brasil

Teores anômalos e naturais de cromo ocorrem nas águas subterrâneas do Aquífero Adamantina no município de Urânia (SP) e em uma ampla região do oeste do Estado de São Paulo, algumas vezes ultrapassando o limite de potabilidade (0,05 mg.L-1). Visando identificar as possíveis reações geoquímicas que justificam a ocorrência do cromo na água subterrânea em Urânia, foram realizadas perfurações com coleta de amostras contínuas de rocha para a condução de análises mineralógicas e químicas, construídos poços de monitoramento multiníveis e realizadas coletas e análises de amostras estratificadas de água subterrânea. Análises das amostras de testemunhos de sondagem indicaram a ocorrência de uma anomalia geoquímica de cromo (concentrações médias de 221 ppm), sendo o diopsídio cromífero provavelmente o mineral geoquimicamente mais reativo que contribui para esta anomalia, apresentando concentrações de cromo de 1.000 a 6.000 ppm. As análises químicas de amostras de água coletadas dos poços de monitoramento indicaram uma estratificação hidroquímica do aquífero: águas na base do aquífero apresentam pH anomalamente alcalino (superior a 10), enquanto águas mais rasas possuem pH neutro a ligeiramente ácido. O cromo ocorre predominantemente na forma hexavalente e alcança concentrações máximas de 0,13 mg.L-1. As reações geoquímicas que explicam a passagem do cromo da fase sólida para a água provavelmente envolvem a dissolução de minerais contendo Cr3+ (diopsídios), seguida de uma reação redox que oxida o Cr3+ para o Cr6+, provavelmente relacionada com a redução de óxidos de manganês presentes no aquífero. Adicionalmente, devem também ocorrer reações de adsorção, sendo que os ambientes de pH elevados favorecem a dessorção e mobilização do Cr6+ para a águaAnomalous natural concentrations of chromium, sometimes exceeding the potability limit (0.05 mg.L-1), have been detected in the groundwater of Adamantina Aquifer in the municipality of Urânia, and in a wide region of the western part of the State of São Paulo. In order to identify the possible geochemical reactions that may explain the occurrence of chromium in groundwater, chemical and mineralogical analyses were conducted in rock samples collected from deep boreholes drilled in the city of Urânia. Multilevel monitoring wells were installed in the boreholes, and stratified groundwater samples were collected for chemical analyses. The analyses of the borehole samples indicated the occurrence of a geochemical anomaly of chromium (average concentrations of 221 ppm) and pointed to chrome-diopside containing from 1,000 to 6,000 ppm Cr as the main reactive mineral that contributes to this anomaly. Groundwater chemical analyses indicated the occurrence of a hydrochemical stratification of the aquifer: waters from the base of the aquifer are alkaline (pH higher than 10) whereas in the shallow zone of the aquifer, pH is neutral to mildly acid. Chromium has been identified in its hexavalent form, and prevails in the aquifer, reaching the maximum concentration of 0.13 mg.L-1. The geochemical reactions that explain the release of chromium from the solid phase to the water probably involve the dissolution of Cr3+ minerals such as diopside, followed by a redox reaction that oxidizes Cr3+ to Cr6+ and reduces manganese oxide minerals. Additionally, adsorption reactions may take place, and desorption and mobilization of Cr6+ may be favored in some portions of the deep aquifer where pH is anomalously alkalin

Developing cardiac and skeletal muscle share fast-skeletal myosin heavy chain and cardiac troponin-I expression

Skeletal muscle derived stem cells (MDSCs) transplanted into injured myocardium can differentiate into fast skeletal muscle specific myosin heavy chain (sk-fMHC) and cardiac specific troponin-I (cTn-I) positive cells sustaining recipient myocardial function. We have recently found that MDSCs differentiate into a cardiomyocyte phenotype within a three-dimensional gel bioreactor. It is generally accepted that terminally differentiated myocardium or skeletal muscle only express cTn-I or sk-fMHC, respectively. Studies have shown the presence of non-cardiac muscle proteins in the developing myocardium or cardiac proteins in pathological skeletal muscle. In the current study, we tested the hypothesis that normal developing myocardium and skeletal muscle transiently share both sk-fMHC and cTn-I proteins. Immunohistochemistry, western blot, and RT-PCR analyses were carried out in embryonic day 13 (ED13) and 20 (ED20), neonatal day 0 (ND0) and 4 (ND4), postnatal day 10 (PND10), and 8 week-old adult female Lewis rat ventricular myocardium and gastrocnemius muscle. Confocal laser microscopy revealed that sk-fMHC was expressed as a typical striated muscle pattern within ED13 ventricular myocardium, and the striated sk-fMHC expression was lost by ND4 and became negative in adult myocardium. cTn-I was not expressed as a typical striated muscle pattern throughout the myocardium until PND10. Western blot and RT-PCR analyses revealed that gene and protein expression patterns of cardiac and skeletal muscle transcription factors and sk-fMHC within ventricular myocardium and skeletal muscle were similar at ED20, and the expression patterns became cardiac or skeletal muscle specific during postnatal development. These findings provide new insight into cardiac muscle development and highlight previously unknown common developmental features of cardiac and skeletal muscle. © 2012 Clause et al

Keratin 8/18 Regulation of Cell Stiffness-Extracellular Matrix Interplay through Modulation of Rho-Mediated Actin Cytoskeleton Dynamics

Cell mechanical activity generated from the interplay between the extracellular matrix (ECM) and the actin cytoskeleton is essential for the regulation of cell adhesion, spreading and migration during normal and cancer development. Keratins are the intermediate filament (IF) proteins of epithelial cells, expressed as pairs in a lineage/differentiation manner. Hepatic epithelial cell IFs are made solely of keratins 8/18 (K8/K18), hallmarks of all simple epithelia. Notably, our recent work on these epithelial cells has revealed a key regulatory function for K8/K18 IFs in adhesion/migration, through modulation of integrin interactions with ECM, actin adaptors and signaling molecules at focal adhesions. Here, using K8-knockdown rat H4 hepatoma cells and their K8/K18-containing counterparts seeded on fibronectin-coated substrata of different rigidities, we show that the K8/K18 IF-lacking cells lose their ability to spread and exhibit an altered actin fiber organization, upon seeding on a low-rigidity substratum. We also demonstrate a concomitant reduction in local cell stiffness at focal adhesions generated by fibronectin-coated microbeads attached to the dorsal cell surface. In addition, we find that this K8/K18 IF modulation of cell stiffness and actin fiber organization occurs through RhoA-ROCK signaling. Together, the results uncover a K8/K18 IF contribution to the cell stiffness-ECM rigidity interplay through a modulation of Rho-dependent actin organization and dynamics in simple epithelial cells

Increased intestinal permeability and tight junction disruption by altered expression and localization of occludin in a murine graft versus host disease model

<p>Abstract</p> <p>Background</p> <p>Hematopoietic stem cell transplantation is increasingly performed for hematologic diseases. As a major side effect, acute graft versus host disease (GvHD) with serious gastrointestinal symptoms including diarrhea, gastrointestinal bleeding and high mortality can be observed. Because surveillance and biopsies of human gastrointestinal GvHD are difficult to perform, rare information of the alterations of the gastrointestinal barrier exists resulting in a need for systematic animal models.</p> <p>Methods</p> <p>To investigate the effects of GvHD on the intestinal barrier of the small intestine we utilized an established acute semi allogenic GvHD in C57BL/6 and B6D2F1 mice.</p> <p>Results</p> <p>By assessing the differential uptake of lactulose and mannitol in the jejunum, we observed an increased paracellular permeability as a likely mechanism for disturbed intestinal barrier function. Electron microscopy, immunohistochemistry and PCR analysis indicated profound changes of the tight-junction complex, characterized by downregulation of the tight junction protein occludin without any changes in ZO-1. Furthermore TNF-α expression was significantly upregulated.</p> <p>Conclusions</p> <p>This analysis in a murine model of GvHD of the small intestine demonstrates serious impairment of intestinal barrier function in the jejunum, with an increased permeability and morphological changes through downregulation and localization shift of the tight junction protein occludin.</p

Transcriptional Silencing of the Wnt-Antagonist DKK1 by Promoter Methylation Is Associated with Enhanced Wnt Signaling in Advanced Multiple Myeloma

The Wnt/β-catenin pathway plays a crucial role in the pathogenesis of various human cancers. In multiple myeloma (MM), aberrant auto-and/or paracrine activation of canonical Wnt signaling promotes proliferation and dissemination, while overexpression of the Wnt inhibitor Dickkopf1 (DKK1) by MM cells contributes to osteolytic bone disease by inhibiting osteoblast differentiation. Since DKK1 itself is a target of TCF/β-catenin mediated transcription, these findings suggest that DKK1 is part of a negative feedback loop in MM and may act as a tumor suppressor. In line with this hypothesis, we show here that DKK1 expression is low or undetectable in a subset of patients with advanced MM as well as in MM cell lines. This absence of DKK1 is correlated with enhanced Wnt pathway activation, evidenced by nuclear accumulation of β-catenin, which in turn can be antagonized by restoring DKK1 expression. Analysis of the DKK1 promoter revealed CpG island methylation in several MM cell lines as well as in MM cells from patients with advanced MM. Moreover, demethylation of the DKK1 promoter restores DKK1 expression, which results in inhibition of β-catenin/TCF-mediated gene transcription in MM lines. Taken together, our data identify aberrant methylation of the DKK1 promoter as a cause of DKK1 silencing in advanced stage MM, which may play an important role in the progression of MM by unleashing Wnt signaling

LIF-Dependent Signaling: New Pieces in the Lego

LIF, a member of the IL6 family of cytokine, displays pleiotropic effects on various cell types and organs. Its critical role in stem cell models (e.g.: murine ES, human mesenchymal cells) and its essential non redundant function during the implantation process of embryos, in eutherian mammals, put this cytokine at the core of many studies aiming to understand its mechanisms of action, which could benefit to medical applications. In addition, its conservation upon evolution raised the challenging question concerning the function of LIF in species in which there is no implantation. We present the recent knowledge about the established and potential functions of LIF in different stem cell models, (embryonic, hematopoietic, mesenchymal, muscle, neural stem cells and iPSC). We will also discuss EVO-DEVO aspects of this multifaceted cytokine

Anterolateral Ligament Expert Group consensus paper on the management of internal rotation and instability of the anterior cruciate ligament - deficient knee

Purpose of this paper is to provide an overview of the latest research on the anterolateral ligament (ALL) and present the consensus of the ALL Expert Group on the anatomy, radiographic landmarks, biomechanics, clinical and radiographic diagnosis, lesion classification, surgical technique and clinical outcomes. A consensus on controversial subjects surrounding the ALL and anterolateral knee instability has been established based on the opinion of experts, the latest publications on the subject and an exchange of experiences during the ALL Experts Meeting (November 2015, Lyon, France). The ALL is found deep to the iliotibial band. The femoral origin is just posterior and proximal to the lateral epicondyle; the tibial attachment is 21.6 mm posterior to Gerdy's tubercle and 4-10 mm below the tibial joint line. On a lateral radiographic view the femoral origin is located in the postero-inferior quadrant and the tibial attachment is close to the centre of the proximal tibial plateau. Favourable isometry of an ALL reconstruction is seen when the femoral position is proximal and posterior to the lateral epicondyle, with the ALL being tight upon extension and lax upon flexion. The ALL can be visualised on ultrasound, or on T2-weighted coronal MRI scans with proton density fat-suppressed evaluation. The ALL injury is associated with a Segond fracture, and often occurs in conjunction with acute anterior cruciate ligament (ACL) injury. Recognition and repair of the ALL lesions should be considered to improve the control of rotational stability provided by ACL reconstruction. For high-risk patients, a combined ACL and ALL reconstruction improves rotational control and reduces the rate of re-rupture, without increased postoperative complication rates compared to ACL-only reconstruction. In conclusion this paper provides a contemporary consensus on all studied features of the ALL. The findings warrant future research in order to further test these early observations, with the ultimate goal of improving the long-term outcomes of ACL-injured patients. Level of evidence Level V-Expert opinion