Optimizing metastatic-cascade-dependent Rac1 targeting in breast cancer: guidance using optical window intravital FRET imaging

Assessing drug response within live native tissue provides increased fidelity with regards to optimizing efficacy while minimizing off-target effects. Here, using longitudinal intravital imaging of a Rac1-Förster resonance energy transfer (FRET) biosensor mouse coupled with in vivo photoswitching to track intratumoral movement, we help guide treatment scheduling in a live breast cancer setting to impair metastatic progression. We uncover altered Rac1 activity at the center versus invasive border of tumors and demonstrate enhanced Rac1 activity of cells in close proximity to live tumor vasculature using optical window imaging. We further reveal that Rac1 inhibition can enhance tumor cell vulnerability to fluid-flow-induced shear stress and therefore improves overall anti-metastatic response to therapy during transit to secondary sites such as the lung. Collectively, this study demonstrates the utility of single-cell intravital imaging in vivo to demonstrate that Rac1 inhibition can reduce tumor progression and metastases in an autochthonous setting to improve overall survival.Alessia Floerchinger … Michael S. Sasmuel … et al

Monitoring AKT activity and targeting in live tissue and disease contexts using a real-time Akt-FRET biosensor mouse

Aberrant AKT activation occurs in a number of cancers, metabolic syndrome, and immune disorders, making it an important target for the treatment of many diseases. To monitor spatial and temporal AKT activity in a live setting, we generated an Akt-FRET biosensor mouse that allows longitudinal assessment of AKT activity using intravital imaging in conjunction with image stabilization and optical window technology. We demonstrate the sensitivity of the Akt-FRET biosensor mouse using various cancer models and verify its suitability to monitor response to drug targeting in spheroid and organotypic models. We also show that the dynamics of AKT activation can be monitored in real time in diverse tissues, including in individual islets of the pancreas, in the brown and white adipose tissue, and in the skeletal muscle. Thus, the Akt-FRET biosensor mouse provides an important tool to study AKT dynamics in live tissue contexts and has broad preclinical applications

Using the present to interpret the past: the role of ethnographic studies in Andean archaeology

Within Andean research it is common to use ethnographic analogies to aid the interpretation of archaeological remains, and ethnographers and archaeologists have developed shared research in technology, material culture and material practice. Although most of this research does not follow the detailed recording methods of spatial patterning envisioned in earlier formulations of ethnoarchaeology, it has had a profound effect on how archaeology in the region has been interpreted. This paper uses examples from the study of pottery production to address earlier debates about the use of ethnographic analogy, discusses the dangers of imposing an idealised or uniform vision of traditional Andean societies onto earlier periods (‘Lo Andino’) but stresses the benefits of combining ethnographic and archaeological research to explore continuities and changes in cultural practice and regional variations

Tracking SARS-CoV-2: Novel Trends and Diagnostic Strategies

The COVID-19 pandemic has had an enormous impact on economies and health systems globally, therefore a top priority is the development of increasingly better diagnostic and surveillance alternatives to slow down the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In order to establish massive testing and contact tracing policies, it is crucial to have a clear view of the diagnostic options available and their principal advantages and drawbacks. Although classical molecular methods such as RT-qPCR are broadly used, diagnostic alternatives based on technologies such as LAMP, antigen, serological testing, or the application of novel technologies such as CRISPR-Cas for diagnostics, are also discussed. The present review also discusses the most important automation strategies employed to increase testing capability. Several serological-based diagnostic kits are presented, as well as novel nanotechnology-based diagnostic methods. In summary, this review provides a clear diagnostic landscape of the most relevant tools to track COVID-19

Auditoría financiera del rubro cuentas por cobrar ingresos de una empresa que se dedica a la comercialización y distribución de derivados de petróleo durante el período terminado al 31 de diciembre del 2007 en la ciudad de guayaquil

El presente trabajo corresponde a nuestra tesis de grado, que consiste en realizar una auditoría financiera al rubro de cuentas por cobrar/ingresos en una compañía del sector petrolero. nuestra tesis proporciona una breve descripción de la empresa en la cual se mencionarán su modelo de negocio, participación en el mercado, sus objetivos, los factores externos y los riesgos a la que está expuesta; se verificarán y validarán los controles que posee la compañía para mitigar los riesgos que se presentan en las cuentas más significativas de los estados financieros. por medio de un análisis comparativo entre estados financieros del periodo pasado y el periodo actual, se va a determinar cuales fueron las cuentas que variaron de forma significativa y el motivo por el cual han cambiado de un periodo a otro. se evaluará el control interno de la empresa a través del coso, específicamente los controles implantados para el proceso de cuentas por cobrar/ventas.GuayaquilAUDITOR - CONTADOR PÚBLICO AUTORIZAD

Auditoria financiera del rubro cuentas por cobrar ingresos de uan empresa que se dedica a la coemrcializacion y distribucion de derivados de petroleo durante el periodo terminado al 31 de diciembre del 2007 en la ciudad de Guayaquil

El presente trabajo corresponde a una Auditoría Financiera al rubro de cuentas por cobrar/ingresos en una compañía del sector petrolero, proporciona una breve descripción de la empresa en la cual se mencionarán los factores externos y los riesgos a la que está expuesta; otro objetivo es hacer un análisis comparativo entre estados financieros del periodo pasado y el periodo actual, el análisis a realizar se denomina análisis de tendencia, que nos va a ayudar a determinar cuales fueron las cuentas que variaron de forma significativa y el motivo por el cual han cambiado de un periodo a otro; otro objetivo va a ser verificar y validar los controles que posee la compañía para mitigar los riesgos que se presentan en torno a las cuentas más significativas de los estados financieros.GuayaquilAuditor Contador Público Autorizad

Atrial septal defect closure is associated with improved clinical status in patients ≤ 10 kg with bronchopulmonary dysplasia

Abstract Patients with bronchopulmonary dysplasia (BPD) have shown clinical improvement after secundum atrial septal defect (ASD) closure. We sought to determine if this post‐ASD closure improvement is secondary to the expected course in BPD patients or related to the closure itself. A novel BPD‐ASD score was created to assess patients' clinical status (higher score = worse disease) and applied to 10 BPD‐ASD inpatients weighing ≤ 10 kg who underwent ASD closure. The score and its subcomponents were retrospectively calculated serially ranging from 8 weeks pre‐ to 8 weeks post‐intervention, and pre‐ and post‐intervention score slopes were created. These slopes were compared using mixed regression modeling with an interaction term. There was a significant difference in pre‐ versus post‐intervention slope with the most score drop the first week post‐intervention (−2.1 + /− 0.8, p = 0.014). The mean score also dropped through weeks 2 (slope −0.8 + /− 0.8, p = 0.013) and 4 (slope −1.0 + /− 0.5, p = 0.001) post‐intervention. There was a significant difference in pre‐ and post‐intervention slopes for diuretics (p = 0.018) and the combined score of respiratory support, FiO2 need, and respiratory symptoms (p = 0.018). This study demonstrated significant improvement in BPD‐ASD score, diuretic need, and respiratory status after ASD closure in BPD‐ASD patients ≤ 10 kg that was outside of the natural course of BPD. Our study was limited by its small, single‐center, retrospective nature. Future studies should be performed in a larger multicenter population to both validate the scoring system and compare to non‐intervention infants

Current landscape and future directions of synthetic biology in South America

Synthetic biology (SynBio) is a rapidly advancing multidisciplinary field in which South American countries such as Chile, Argentina, and Brazil have made notable contributions and have established leadership positions in the region. In recent years, efforts have strengthened SynBio in the rest of the countries, and although progress is significant, growth has not matched that of the aforementioned countries. Initiatives such as iGEM and TECNOx have introduced students and researchers from various countries to the foundations of SynBio. Several factors have hindered progress in the field, including scarce funding from both public and private sources for synthetic biology projects, an underdeveloped biotech industry, and a lack of policies to promote bio-innovation. However, open science initiatives such as the DIY movement and OSHW have helped to alleviate some of these challenges. Similarly, the abundance of natural resources and biodiversity make South America an attractive location to invest in and develop SynBio projects.</p