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Studies of the role of actin in tumour progression have highlighted its key contribution in cell softening associated with cell invasion. Here, using a human breast cell line with conditional Src induction, we demonstrate that cells undergo a stiffening state prior to acquiring malignant features. This state is characterized by the transient accumulation of stress fibres and upregulation of Ena/VASP-like (EVL). EVL, in turn, organizes stress fibres leading to transient cell stiffening, ERK-dependent cell proliferation, as well as enhancement of Src activation and progression towards a fully transformed state. Accordingly, EVL accumulates predominantly in premalignant breast lesions and is required for Src-induced epithelial overgrowth in Drosophila . While cell softening allows for cancer cell invasion, our work reveals that stress fibre-mediated cell stiffening could drive tumour growth during premalignant stages. A careful consideration of the mechanical properties of tumour cells could therefore offer new avenues of exploration when designing cancer-targeting therapies. When cells acquire a malignant phenotype they become less stiff and this helps migration and invasion favouring metastasis. Here the authors show that Src-driven cell transformation and transition to a less stiff state follows an event of membrane stiffening due to stress fibres accumulation.

Dense and aligned Collagen I fibers are associated with collective cancer invasion led by protrusive tumor cells, leader cells. In some breast tumors, a population of cancer cells (basal-like cells) maintain several epithelial characteristics and express the myoepithelial/basal cell marker Keratin 14 (K14). Emergence of leader cells and K14 expression are regarded as interconnected events triggered by Collagen I, however the underlying mechanisms remain unknown. Using breast carcinoma organoids, we show that Collagen I drives a force-dependent loop, specifically in basal-like cancer cells. The feed-forward loop is centered around the mechanotransducer Yap and independent of K14 expression. Yap promotes a transcriptional program that enhances Collagen I alignment and tension, which further activates Yap. Active Yap is detected in invading breast cancer cells in patients and required for collective invasion in 3D Collagen I and in the mammary fat pad of mice. Our work uncovers an essential function for Yap in leader cell selection during collective cancer invasion. Aligned collagen I is associated with the emergence of leader cells that are responsible for collective invasion. Here, the authors show that Collagen I and Yap signalling are in a feed-forward loop to drive the collective invasion of basal-like tumour cells.

The shell surrounding fruits of the jatobá-do-cerrado tree, in its natural state, was modified by the addition of HNO 3 and NaOH and used as an adsorbent in the removal of Cu(II) and Ni(II) from aqueous solutions. The untreated (JIN) and chemically modified (JCT) fruit shell samples were characterized by Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and X-ray diffraction. Their efficiency as adsorbents in the removal of Cu(II) and Ni(II) ions from aqueous solutions was studied under different conditions of pH (2-9) and it was observed that the optimal pH for Cu (II) adsorption was 5.5 and for Ni (II) it was 6.0. The adsorption isotherms were obtained at different temperatures (298, 308, 318 K) and the q max values ranged from 33.96 to 41.00 mg g -1 . The adsorbents presented higher selectivity toward Cu ions (II). The thermodynamic analysis results suggest that the adsorption process studied is of a physical nature. Supported by quantum mechanical calculations, the interaction sites of the ion-cellulose and ion-lignin complexes were identified, evidencing the central role of water molecules in stabilization of the complexes. The experimental and theorical results indicate that JIN and JCT have good potential for the adsorption of Cu(II) and Ni(II) ions and are thus promising materials for the removal of other metal ions in aqueous systems.

Ehlers-Danlos Syndrome (EDS) are a heterogeneous group of genetic connective tissue disorders, and typically manifests as weak joints that subluxate/dislocate, stretchy and/or fragile skin, organ/systems dysfunction, and significant widespread pain. Historically, this syndrome has been poorly understood and often overlooked. As a result, people living with EDS had difficulty obtaining an accurate diagnosis and appropriate treatment, leading to untold personal suffering as well as ineffective health care utilization. The GoodHope EDS clinic addresses systemic gaps in the diagnosis and treatment of EDS. This paper describes a leap forward—from lack of awareness, diagnosis, and treatment—to expert care that is tailored to meet the specific needs of patients with EDS. The GoodHope EDS clinic consists of experts from various medical specialties who work together to provide comprehensive care that addresses the multi-systemic nature of the syndrome. In addition, EDS-specific self-management programs have been developed that draw on exercise science, rehabilitation, and health psychology to improve physical and psychosocial wellbeing and overall quality of life. Embedded into the program are research initiatives to shed light on the clinical presentation, underlying mechanisms of pathophysiology, and syndrome management. We also lead regular educational activities for community health care providers to increase awareness and competence in the interprofessional management of EDS beyond our doors and throughout the province and country.

Castleman disease is a rare lymphoproliferative disorder presenting with localized or disseminated lymphadenopathy and systemic symptoms. It can be categorized clinically as unicentric or multicentric, histopathologically as hyaline vascular, plasma cell, or mixed variant, and etiologically, considering the subtypes based on causative viral agents and associated syndromes. The multicentric type can mimic other haematological malignancies, ranging from asymptomatic to multiple organ involvement. Although its pathophysiology is not well known, the current approved treatments are directed towards interleukin-6, CD-20, and viral agents. The authors present an 82-year-old leucodermic man presented with a 2-week history of constitutional symptoms. Examination revealed pallor, hepatosplenomegaly, and palpable left axillary lymphadenopathy. Investigation showed anaemia, thrombocytopenia, polyclonal hypergammaglobulinemia, hypoalbuminemia, and high acute phase reactants, with image study revealing multiple axillary, mediastinal, inguinal, and pelvic lymphadenopathies. The lymph node biopsy was consistent with hyaline vascular-type Castleman disease without human herpersvirus-8 markers. He started prednisolone with initial improvement evolved poorly on a short term. Castleman disease has a broad spectrum of clinical manifestations, associations, and complications that bring a diagnostic challenge, requiring a multidisciplinary approach. Clinicians should be familiar with its features because proper diagnosis and aggressive targeted treatment are the pillars of proper management of these patients.

Low-order streams located near urban areas usually receive domestic, industrial, and agricultural wastewaters that negatively affect river water quality. Additionally, water pollution is associated with land-use variations around the river, which is characterized by unplanned urbanization, intense agricultural activities, and deforestation. This work correlated land-use patterns with physicochemical quality and genotoxic potential of water at four points (P1 to P4) along the Extrema River, located in an industrial and agricultural area of Central Brazil. Physicochemical analyses indicated that the water collected from the Extrema River is inappropriate for human consumption. Using the Allium cepa model, no evidence of cytotoxicity was observed at any point; in contrast, the genotoxic potential of these water samples was observed. The correlation of these results with land use showed that the water collected at P3 was the most contaminated; this is probably due to the inflow of wastewater from municipal, industrial, and agriculture activities. Different results were observed for P2 and P4, where land-use analysis attributed the water quality to forest burns. We concluded that differential use of the land changed the characteristics of the associated river water, and A. cepa parameters were more related to land-use characteristics than to physicochemical parameters. This study highlighted the importance of associating land use with the cyto genotoxic potential of water.

Brazil is a world benchmark in combating smoking and promoting actions through the National Program for Tobacco Control and other Risk Factors for Cancer (PNCTOFR). This literature review was conducted in order to outline the actions of PNCTOFR and identify evidence of their effectiveness in reducing the prevalence of smoking in Brazil. The documents available in the electronic portals of INCA, the National Policy on Health Promotion, the National Tobacco Control Observatory, the World Health Organization and the Pan American Health Organization were used, in addition to the Lilacs, PubMed Central, SciELO and ScienceDirect databases. The reference bases for analysis of the actions were the areas/dimensions proposed by the International Union for Health Promotion and Education. The restriction of the availability, control of marketing and commercialization, educational activities in schools, assistance in primary care for health professionals and the general population, control of consumption in public places and work are some of the actions that contributed to reduction in the prevalence of smoking in Brazil from 32.7% in 1997 to 14.8% in 2011. The results indicate the effectiveness of the actions of PNCTOFR, albeit smoking is still a public health problem and needs to be curbed.

Introduction. Pseudohypoparathyroidism type 1a is caused by GNAS mutations leading to target organ resistance to multiple hormones rather than parathyroid hormone, resulting not only in hypocalcemia, but also in Albright’s hereditary osteodystrophy phenotype. Materials and Methods. DNA sequencing of the GNAS gene identified a novel heterozygous mutation in peripheral blood leukocytes in the family presented in this case report. Results. We present a case of a 25-year-old woman with pseudohypoparathyroidism type 1a admitted with seizures, whose family presents an autosomal dominant transmission of a novel heterozygous GNAS mutation (c.524_530+3del). Conclusion. Pseudohypoparathyroidism type 1a is mostly caused by inactivating GNAS mutations that have been gradually reported in the literature that lead to a typical and complex clinical phenotype and resistance to multiple hormones. The deletion caused by the mutation identified in the presented case has not been reported previously.

This study provides a relevant contribution to literature on the macroeconomic determinants of multidimensional deprivation in developed countries; this type of analysis is not as frequent in the literature as that explaining poverty stricto sensu . After a review of the macroeconomic mechanisms of poverty, we propose a composite index to capture multidimensional poverty as to allow a comparative assessment of deprivation across European Union countries. Relying on the macroeconomic transmission mechanisms that influence poverty, a panel data econometric approach is implemented to study the relation between the proposed composite index and macroeconomic variables. Results show that a multidimensional poverty concept is relevant for assessing deprivation in Europe and that the dynamics of main macroeconomic variables crucially affect deprivation performances. The latter result is robust, holding for different poverty measures.

In the last two decades, there has been a noticeable increase in published research on evolutionary economics. The general perception is that formalization lags behind appreciative work. Notwithstanding, this general reading has yet to be supported by real data analysis. This work presents a survey on evolutionary economics, aimed at exploring the main research paths and contributions using bibliometric methods. The documentation is based on an extensive review of the abstracts from articles published in all economic journals over the past 50 years gathered from the Econlit database. Evolutionary contributions have apparently not converged to an integrated approach. Two rather extreme main research strands emerged: ‘History of Economic Thought and Methodology’ and ‘Games’. Whereas formal approaches have a reasonable and increasing share of published papers, purely empirical-related works are relatively scarce, representing a meagre and stagnant percentage of published works. This highlights the need to redirect the evolutionary research agenda.