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

An empirical model for rainfall maximums conditioned to tropospheric water vapor over the Eastern Pacific Ocean

One of the most difficult weather variables to predict is rain, particularly intense rain. The main limitation is the complexity of the fluid dynamic equations used by predictive models with increasing uncertainties over time, especially in the description of brief, local, and high intensity precipitation events. Although computational, instrumental and theoretical improvements have been developed for models, it is still a challenge to estimate high intensity rainfall events, especially in terms of determining the maximum rainfall rates and the location of the event. Within this context, this research presents a statistical and relationship analysis of rainfall intensity rates, total precipitable water (TPW), and sea surface temperature (SST) over the ocean. An empirical model to estimate the maximum rainfall rates conditioned to TPW values is developed. The performance of the maximum rainfall rate model is spatially evaluated for a case study. High-resolution TRMM 2A12 satellite data with a resolution of 5.1 x 5.1 km and 1.67 s was used from January 2009 to December 2012, over the Eastern Pacific Nino area in the tropical Pacific Ocean (0-5 degrees S; 90-81 degrees W), comprising 326,092 rain pixels. After applying the model selection methodology, i.e., the Akaike Information Criterion (AIC) and the Bayesian Information Criterion (BIC), an empirical exponential model between the maximum possible rain rates conditioned to TPW was found with R-2 = 0.96, indicating that the amount of TPW determines the maximum amount of rain that the atmosphere can precipitate exponentially. Spatially, this model unequivocally locates the rain event; however, the rainfall intensity is underestimated in the convective nucleus of the cloud. Thus, these results provide an additional constraint for maximum rain intensity values that should be adopted in dynamic models, improving the quantification of heavy rainfall event intensities and the correct location of these events

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