Eradicating tumor drug resistance at its YAP-biomechanical roots

Treatment with BRAF kinase inhibitors leads to rapid resistance and tumor regression in BRAF V600E mutant melanoma patients. However, the underlying mechanism of the developed tumor resistance is not fully clear. In this issue of The EMBO Journal, Kim and colleagues show that melanoma cells acquire resistance to BRAF inhibitors by changing cell shape, modifying their cytoskeleton and, in turn, activating the YAP/TAZ mechanotransduction pathway (Kim et al, 2016)

YAP/TAZ at the Roots of Cancer

YAP and TAZ are highly related transcriptional regulators pervasively activated in human malignancies. Recent work indicates that, remarkably, YAP/TAZ are essential for cancer initiation or growth of most solid tumors. Their activation induces cancer stem cell attributes, proliferation, chemoresistance, and metastasis. YAP/TAZ are sensors of the structural and mechanical features of the cell microenvironment. A number of cancer-associated extrinsic and intrinsic cues conspire to overrule the YAP-inhibiting microenvironment of normal tissues, including changes in mechanotransduction, inflammation, oncogenic signaling, and regulation of the Hippo pathway. Addiction to YAP/TAZ thus potentially represents a central cancer vulnerability that may be exploited therapeutically

Smart Cities and M³: Rapid Research, Meaningful Metrics and Co-Design

The research described in this paper is undertaken under the banner of the smart city, a concept that captures the way urban spaces are re-made by the incursion of new technology. Much of smart is centred on converting everyday activities into data, and using this data to generate knowledge mediated by technology. Ordinary citizens, those that may have their lives impacted by the technology, usually are not properly involved in the ‘smartification’ process. Their perceptions, concerns and expectations should inform the conception and development of smart technologies at the same extent. How to engage general public with smart cities research is the central challenge for the Making Metrics Meaningful (MMM) project. Applying a rapid participatory method, ‘Imagine’ over a five-month period (March – July) the research sought to gain insights from the general public into novel forms of information system innovation. This brief paper describes the nature of the accelerated research undertaken and explores some of the themes which emerged in the analysis. Generic themes, beyond the remit of an explicit transport focus, are developed and pointers towards further research directions are discussed. Participatory methods, including engaging with self- selected transport users actively through both picture creation and programmatically specific musical ‘signatures’ as well as group discussion, were found to be effective in eliciting users’ own concerns, needs and ideas for novel information systems

YAP/TAZ as therapeutic targets in cancer

The biology and regulation of YAP and TAZ, two closely related transcriptional regulators, are receiving increasing attention owing to their fundamental roles in organ growth, tissue repair and cancer. In particular, the widespread activation of YAP/TAZ in carcinomas, and the crucial role of YAP/TAZ activation for many 'hallmarks' of cancer are indicating YAP/TAZ as prime targets for designing anti-cancer drugs. Here, we start from the known modalities to regulate YAP/TAZ to highlight possible routes of therapeutic intervention

A Comprehensive and Systematic Diagnostic Campaign for a New Acquisition of Contemporary Art—The Case of Natura Morta by Andreina Rosa (1924–2019) at the International Gallery of Modern Art Ca’ Pesaro, Venice

A multi-analytical approach has been employed to investigate the painting Natura Morta (1954–1955) by Andreina Rosa (1924–2019) to assess the state of conservation and to understand more about the painting materials and techniques of this artwork, which was recently donated by the painter’s heirs to the International Gallery of Modern Art Ca’ Pesaro (Venice-Italy). A comprehensive and systematic diagnostic campaign was carried out, mainly adopting non-invasive imaging and spectroscopic methods, such as technical photography, optical microscopy, Hyperspectral Imaging Spectroscopy (HIS), fiber optics reflectance spectroscopy (FORS), External Reflectance Fourier Transform Infrared (ER-FTIR), and Raman spectroscopies. Microsamples, collected from the edges of the canvas in areas partially detached, were studied by Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR) spectroscopy and Gas Chromatography-Mass Spectrometry (GC-MS). By crossing the information gained, it was possible to make inferences about the composition of the groundings and the painted layers, the state of conservation of the artwork, and the presence of degradation phenomena. Hence, the present study may be of interest for conservation purposes as well as for enhancing the artistic activity of Andreina Rosa. The final aim was to provide useful information for the Gallery which recently included this painting in its permanent collection

Somatic indexes, chemical-nutritive characteristics and metal content in caught and reared sharpsnout seabream (Diplodus puntazzo)

The aim of this study was to compare some somatic indexes, chemical-nutritive characteristics and the contents of some metals (Pb, Cu, Cr and Zn) in the whole body and fillet from caught and reared sharpsnout seabream (Diplodus puntazzo). The fish came from three different conditions: reared in marine cages (R), captured in a natural lagoon (L) and in the Mediterranean sea (S). Thirty fish per group, divided into three weight categories (100±15.3, 200±18.7 and 300±20.4g), were used for the trial. Reared sharpsnout seabream showed higher amounts of celomatic fat (3.41%, 2.43%, 0.21%, respectively for R, L and S) and total lipid (13.86%, 11.23% and 5.06% respectively for R, L and S), and lower moisture (64.14%, 65.54%, 71.53%) and protein (17.73, 19.03 and 19.17%) than those caught in the lagoon and sea. The whole body of reared fish contained lower amounts of lead (0.70, 0.75 and 0.97mg/kg, respectively for R, L and S), copper (0.15, 0.38, 0.25mg/kg) chrome (2.19, 3.52, 3.77mg/kg) and higher zinc contents (63.47, 53.42, 47.31mg/kg) than caught fish. Fatty acids from sharpsnout seabream fillets showed a high lipid quality as confirmed also by low values of Thrombogenic index (0.36, 0.30 and 0.22, respectively for L, S, R) and Atherogenic index (0.47, 0.42 and 0.33, respectively for L, S, R). Reared sharpsnout seabream showed lower saturated fatty acid values (26.44%, 32.21%, 34.85%, respectively for R, S, L) and higher oleic acid amount (21.61%, 19.15%, 11.99%, respectively for R, L and S). The subjects captured in the sea had a higher arachidonic acid content (5.44%, 1.76%, 0.59%, respectively for S, L, R). In the weight categories, the 100g subjects, showed higher incidence of viscera (VSI: 4.32%, 3.12% and 2.92%, respectively for 100, 200 and 300g) and liver (HIS: 2.20%, 1.97%, and 1.77%, respectively for 100, 200 and 300g), higher moisture (69.49%, 67.03%, 64.69%) and lower lipid rate (7.64%, 10.18%, 12.32%)

Experiences, Emotions, and Health Consequences among COVID-19 Survivors after Intensive Care Unit Hospitalization

Literature suggested that COVID-19 patients experienced hospitalization as a physically and psychologically stressful event, with the risk to develop post-traumatic stress symptoms. The study aimed to understand psychological experiences of COVID-19 survivors with severe complications during and after ICU hospitalization, and any relevant health consequences. From October 2020 to January 2021, a qualitative study was conducted in Italy via semi-structured interviews by phone or video call addressed to COVID-19 survivors, randomly enrolled among people who released their stories publicly on newspapers, television, or social media. Fifteen individuals (three women and twelve men with average age of 56.4 years) were interviewed. Four main themes emerged: (i) emotion of fear; (ii) isolation and loneliness; (iii) unawareness about the gravity of the situation as a protective factor; (iv) "Long COVID" as consequences of the disease on physical and psychological health. During hospitalization, 66.7% of participants had mild or moderate values of anxiety and depression. After discharge, 86.7% moved to normal values. The results suggest that long-COVID is an important problem to manage to improve patients' quality of life. It is essential to guarantee a holistic take in charge starting before the discharge and continuing care after discharge in the community where they live

YAP/TAZ link cell mechanics to Notch signalling to control epidermal stem cell fate

AbstractHow the behaviour of somatic stem cells (SCs) is influenced by mechanical signals remains a black-box in cell biology. Here we show that YAP/TAZ regulation by cell shape and rigidity of the extracellular matrix (ECM) dictates a pivotal SC decision: to remain undifferentiated and grow, or to activate a terminal differentiation programme. Notably, mechano-activation of YAP/TAZ promotes epidermal stemness by inhibition of Notch signalling, a key factor for epidermal differentiation. Conversely, YAP/TAZ inhibition by low mechanical forces induces Notch signalling and loss of SC traits. As such, mechano-dependent regulation of YAP/TAZ reflects into mechano-dependent regulation of Notch signalling. Mechanistically, at least in part, this is mediated by YAP/TAZ binding to distant enhancers activating the expression of Delta-like ligands, serving as ‘in cis’ inhibitors of Notch. Thus YAP/TAZ mechanotransduction integrates with cell–cell communication pathways for fine-grained orchestration of SC decisions.</jats:p