SPARC Controls Melanoma Cell Plasticity through Rac1.

Cell transition to a more aggressive mesenchymal-like phenotype is a hallmark of cancer progression that involves different steps and requires tightly regulated cell plasticity. SPARC (Secreted Protein Acidic and Rich in Cysteine) is a matricellular protein that promotes this transition in various malignant cell types, including melanoma cells. We found that suppression of SPARC expression in human melanoma cells compromised cell migration, adhesion, cytoskeleton structure, and cell size. These changes involved the Akt/mTOR pathway. Re-expression of SPARC or protein addition restored all the cell features. Suppression of SPARC expression was associated with increased Rac1-GTP levels and its membrane localization. Expression of the dominant negative mutant of Rac1 counteracted almost all the changes observed in SPARC-deficient cells. Overall, these data suggest that most of the SPARC-mediated effects occurred mainly through the blockade of Rac1 activity.Fil: Salvatierra Colussi, Edgardo Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Alvarez, Mariano J.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Leishman, Claudia C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Rivas Baquero, Elvia Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Lutzky, Viviana P.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina. The Royal Brisbane Hospital; AustraliaFil: Chuluyan, Hector Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentin

Isotopic fractionation of carbonyl sulfide in the atmosphere: Implications for the source of background stratospheric sulfate aerosol

In order to assess the contribution of carbonyl sulfide to stratospheric sulfate aerosol (SSA), we examined the stratospheric OC^(34)S and OC^(32)S concentration profiles in the infrared limb-transmittance spectra acquired by the JPL MkIV instrument. We found that OC^(34)S is preferentially depleted by solar photolysis. The derived ^(34)S enrichment factor: ε = +73.8 ± 8.6‰, in conjunction with literature values of δ^(34)S ∼ +11‰ for tropospheric OCS, and a ∼ 10% net processing of the OCS transported upwardly into the stratosphere, suggests that aerosol sulfate proceeding from OCS should be highly enriched in δ^(34)S ∼ 80‰, comparing our prediction with previous reports of δ^(34)S ∼ +2.6‰ for background SSA, we infer either that OCS is a minor contributor to SSA or that current views about its ^(34)S-abundance and atmospheric circulation are seriously flawed

Electrospray Mass Spectrometric Detection of Products and Short-Lived Intermediates in Aqueous Aerosol Microdroplets Exposed to a Reactive Gas

The intermediates ISO_3^- (m/z = 207) and IS2O3- (m/z = 239) generated in aqueous (NaI/Na_2S2O_3) microdroplets traversing dilute O_3 gas plumes are detected via online electrospray mass spectrometry within ∼1 ms, and their stabilities gauged by collisionally induced dissociation. The simultaneous detection of anionic reactants and the S_2O_6^(2-), HSO_4^-, IO_3^-, and I_3^- products as a function of experimental conditions provides evidence of genuinely interfacial reaction kinetics. Although O_3(aq) reacts about 3 times faster with I- than with S_2O_3^(2-) in bulk solution, only S_2O_3^(2-) is significantly depleted in the interfacial layers of [I^-]/[S_2O_3^(2-)] = 10 microdroplets below [O_3(g)] ∼ 50 ppm

COVID-19 Accelerated Cognitive Decline in Elderly Patients with Pre-Existing Dementia Followed up in an Outpatient Memory Care Facility

Introduction: Coronavirus disease 2019 (COVID-19) may affect the cognitive function and activities of daily living (ADL) of elderly patients. This study aimed to establish the COVID-19 effect on cognitive decline and the velocity of cognitive function and ADL changes in elderly patients with dementia followed up in an outpatient memory care facility. Methods: In total, 111 consecutive patients (age 82 ± 5 years, 32% males) with a baseline visit before infection were divided into those who had or did not have COVID-19. Cognitive decline was defined as a five-point loss of Mini-Mental State Examination (MMSE) score and ADL comprising basic and instrumental ADL indexes (BADL and IADL, respectively). COVID-19 effect on cognitive decline was weighted for confounding variables by the propensity score, whereas the effect on change in the MMSE score and ADL indexes was analyzed using multivariate mixed-effect linear regression. Results: COVID-19 occurred in 31 patients and a cognitive decline in 44. Cognitive decline was about three and a half times more frequent in patients who had COVID-19 (weighted hazard ratio 3.56, 95% confidence interval 1.50–8.59, p = 0.004). The MMSE score lowered on average by 1.7 points/year, independently of COVID-19, but it lowered twice faster in those who had COVID-19 (3.3 vs. 1.7 points/year, respectively, p < 0.050). BADL and IADL indexes lowered on average less than 1 point/year, independently of COVID-19 occurrence. Patients who had COVID-19 had a higher incidence of new institutionalization than those who did not have the disease (45% versus 20%, p = 0.016, respectively). Conclusions: COVID-19 had a significant impact on cognitive decline and accelerated MMSE reduction in elderly patients with dementia

Menu labelling and healthy food choices: a randomised controlled trial

The purpose of this study was to examine the effect of different menu labelling formats on healthy food choices in a real restaurant setting. This cross-sectional, randomised and controlled parallel-group trial was conducted in Brazil in 2013. 313 university students were randomly assigned to one of three parallel groups with different menu labelling formats. Of these, data from 233 students were analysed. The others did not attend and were excluded. Intervention group 1 (n=88) received information in the form of a traffic light system plus guideline daily amounts, while intervention group 2 (n=74) was presented with an ingredients list plus highlighted symbols. The control group (n=71) received a menu with no menu labelling. Data were collected on one weekday in a restaurant setting. Trial outcomes were assessed by healthy food choices. Healthy food choices were significantly higher among students who received the menu showing an ingredients list plus highlighted symbols. The same menu labelling format positively affected healthy food choices in women, not overweight participants and who often ate out more than twice a week. A menu labelling format that presented an ingredients list and highlighted symbols was positively associated with healthy food choices among university students in Brazil. This type of labelling could be adopted in future legislation on menu labelling in Brazil and around the world

Polyphenols rich diets and risk of type 2 diabetes

Type 2 diabetes is an increasing health concern worldwide. Both genetic and environmental risk factors as improper dietary habits or physical inactivity are known to be crucial in the pathogen-esis of type 2 diabetes. Polyphenols are a group of plant-derived compounds with anti-inflammatory and antioxidant properties that are associated with a low prevalence of metabolic conditions charac-terized by insulin resistance, including obesity, diabetes, and hypertension. Moreover, there is now full awareness that foods that are rich in phytochemicals and polyphenols could play an important role in preserving human cardiovascular health and substantial clinical evidence indicates that regu-lar dietary consumption of such foods affects favorably carbohydrate metabolism. This review briefly summarizes the evidence relating dietary patterns rich in polyphenols with glucose metabolism and highlights the potential benefits of these compounds in the prevention of type 2 diabetes

GATA3 protein as a MUC1 transcriptional regulator in breast cancer cells

INTRODUCTION: Recent studies have demonstrated that members of the GATA-binding protein (GATA) family (GATA4 and GATA5) might have pivotal roles in the transcriptional upregulation of mucin genes (MUC2, MUC3 and MUC4) in gastrointestinal epithelium. The zinc-finger GATA3 transcription factor has been reported to be involved in the growth control and differentiation of breast epithelial cells. In SAGE (serial analysis of gene expression) studies we observed an intriguing significant correlation between GATA3 and MUC1 mRNA expression in breast carcinomas. We therefore designed the present study to elucidate whether MUC1 expression is regulated by GATA3 in breast cancer cells. METHODS: Promoter sequence analysis of the MUC1 gene identified six GATA cis consensus elements in the 5' flanking region (GATA1, GATA3 and four GATA-like sequences). Chromatin immunoprecipitation and electrophoretic mobility-shift assays were employed to study the presence of a functional GATA3-binding site. GATA3 and MUC1 expression was analyzed in vitro with a GATA3 knockdown assay. Furthermore, expression of GATA3 and MUC1 genes was analyzed by real-time RT-PCR and immunohistochemistry on breast cancer-specific tissue microarrays. RESULTS: We confirmed the presence of a functional GATA3-binding site on the MUC1 promoter region in the MCF7 cell line. We determined that GATA3 knockdown assays led to a decrease in MUC1 protein expression in MCF7 and T47D cells. In addition, we detected a statistically significant correlation in expression between GATA3 and MUC1 genes at the mRNA and protein levels both in normal breast epithelium and in breast carcinomas (p = 0.01). GATA3 expression was also highly associated with estrogen receptor and progesterone receptor status (p = 0.0001) and tumor grade (p = 0.004) in breast carcinomas. CONCLUSION: Our study provides evidence indicating that GATA3 is probably a mediator for the transcriptional upregulation of MUC1 expression in some breast cancers

Short-term cardiac outcome in survivors of COVID-19: a systematic study after hospital discharge

Background: COVID-19 has caused considerable morbidity and mortality worldwide and cardiac involvement has been reported during infection. The short-term cardiac outcome in survivors of COVID-19 is not known. Objective: To examine the heart of patients who survived COVID-19 and to compare the cardiac outcome between patients who recovered from mild-to-moderate or severe illness. Methods: With use of ECG and echocardiography, we examined the heart of 105 patients who had been hospitalized with COVID-19 and were consecutively recruited after hospital discharge while attending follow-up visits. Survivors of COVID-19 were compared with 105 matched controls. We also compared the cardiac outcome and lung ultrasound scan between COVID-19 patients who had mild-to-moderate or severe illness. Results: Cardiac data were collected a median of 41\ua0days from the first detection of COVID-19. Symptoms were present in a low percentage of patients. In comparison with matched controls, no considerable structural or functional differences were observed in the heart of survivors of COVID-19. Lung ultrasound scan detected significantly greater residual pulmonary involvement in COVID-19 patients who had recovered from severe than mild-to-moderate illness. No significant differences were detected in ECG tracings nor were found in the left and right ventricular function of patients who had recovered from mild-to-moderate or severe illness. Conclusions: In a short-term follow-up, no abnormalities were identified in the heart of survivors of COVID-19, nor cardiac differences were detected between patients who had different severity of illness. With the limitations of a cross-sectional study, these findings suggest that patients who recover from COVID-19 do not have considerable cardiac sequelae. Graphic abstract: [Figure not available: see fulltext.

EUS-guided drainage using lumen apposing metal stent and percutaneous endoscopic necrosectomy as dual approach for the management of complex walled-off necrosis: a case report and a review of the literature

Background: Endoscopic ultrasound-guided drainage is suggested as the first approach in the management of symptomatic and complex walled-off pancreatic necrosis. Dual approach with percutaneous drainage could be the best choice when the necrosis is deep extended till the pelvic paracolic gutter; however, the available catheter could not be large enough to drain solid necrosis neither to perform necrosectomy, entailing a higher need for surgery. Therefore, percutaneous endoscopic necrosectomy through a large bore percutaneous self-expandable metal stent has been proposed. Case presentation: In this study, we present the case of a 61-year-old man admitted to our hospital with a history of sepsis and persistent multiorgan failure secondary to walled-off pancreatic necrosis due to acute necrotizing pancreatitis. Firstly, the patient underwent transgastric endoscopic ultrasound-guided drainage using a lumen-apposing metal stent and three sessions of direct endoscopic necrosectomy. Because of recurrence of multiorgan failure and the presence of the necrosis deeper to the pelvic paracolic gutter at computed tomography scan, we decided to perform percutaneous endoscopic necrosectomy using an esophageal self-expandable metal stent. After four sessions of necrosectomy, the collection was resolved without complications. Therefore, we perform a revision of the literature, in order to provide the state-of-art on this technique. The available data are, to date, derived by case reports and case series, which showed high rates both of technical and clinical success. However, a not negligible rate of adverse events has been reported, mainly represented by fistulas and abdominal pain. Conclusion: Dual approach, using lumen apposing metal stent and percutaneous self-expandable metal stent, is a compelling option of treatment for patients affected by symptomatic, complex walled-off pancreatic necrosis, allowing to directly remove large amounts of necrosis avoiding surgery. Percutaneous endoscopic necrosectomy seems a promising technique that could be part of the step-up-approach, before emergency surgery. However, to date, it should be reserved in referral centers, where a multidisciplinary team is disposable

GATA3 protein as a MUC1 transcriptional regulator in breast cancer cells

Introduction Recent studies have demonstrated that members of the GATA-binding protein (GATA) family (GATA4 and GATA5) might have pivotal roles in the transcriptional upregulation of mucin genes (MUC2, MUC3 and MUC4) in gastrointestinal epithelium. The zinc-finger GATA3 transcription factor has been reported to be involved in the growth control and differentiation of breast epithelial cells. In SAGE (serial analysis of gene expression) studies we observed an intriguing significant correlation between GATA3 and MUC1 mRNA expression in breast carcinomas. We therefore designed the present study to elucidate whether MUC1 expression is regulated by GATA3 in breast cancer cells. Methods: Promoter sequence analysis of the MUC1 gene identified six GATA cis consensus elements in the 5′ flanking region (GATA1, GATA3 and four GATA-like sequences). Chromatin immunoprecipitation and electrophoretic mobility-shift assays were employed to study the presence of a functional GATA3-binding site. GATA3 and MUC1 expression was analyzed in vitro with a GATA3 knockdown assay. Furthermore, expression of GATA3 and MUC1 genes was analyzed by realtime RT-PCR and immunohistochemistry on breast cancer-specific tissue microarrays. Results: We confirmed the presence of a functional GATA3-binding site on the MUC1 promoter region in the MCF7 cell line. We determined that GATA3 knockdown assays led to a decrease in MUC1 protein expression in MCF7 and T47D cells. In addition, we detected a statistically significant correlation in expression between GATA3 and MUC1 genes at the mRNA and protein levels both in normal breast epithelium and in breast carcinomas (p = 0.01). GATA3 expression was also highly associated with estrogen receptor and progesterone receptor status (p = 0.0001) and tumor grade (p = 0.004) in breast carcinomas. Conclusion: Our study provides evidence indicating that GATA3 is probably a mediator for the transcriptional upregulation of MUC1 expression in some breast cancers.Facultad de Ciencias Médica