Anti-ROR1 CAR-T cells: Architecture and performance.

The receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a membrane receptor that plays a key role in development. It is highly expressed during the embryonic stage and relatively low in some normal adult tissues. Malignancies such as leukemia, lymphoma, and some solid tumors overexpress ROR1, making it a promising target for cancer treatment. Moreover, immunotherapy with autologous T-cells engineered to express a ROR1-specific chimeric antigen receptor (ROR1 CAR-T cells) has emerged as a personalized therapeutic option for patients with tumor recurrence after conventional treatments. However, tumor cell heterogeneity and tumor microenvironment (TME) hinder successful clinical outcomes. This review briefly describes the biological functions of ROR1 and its relevance as a tumor therapeutic target, as well as the architecture, activity, evaluation, and safety of some ROR1 CAR-T cells used in basic research and clinical trials. Finally, the feasibility of applying the ROR1 CAR-T cell strategy in combination with therapies targeting other tumor antigens or with inhibitors that prevent tumor antigenic escape is also discussed. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT02706392.

Urban expansion and its impact on water security: The case of the Paraíba do Sul River Basin, São Paulo, Brazil.

Increasing demand for water is one of the most challenging problems that human societies face today and has encouraged new studies to examine water security and water management. Seeking to discuss this important issue in the Brazilian context, we analyzed the impacts of urban expansion on water security in a basin located in the most populated region of Brazil. To quantify increased water demand, we combined urban sprawl and regional population increase projections. In this context, our study contributes to discussions on water security by addressing the importance of integration between water and urban planning. Simulations indicate good performance in reproducing actual water system conditions. The finding demonstrates that urban expansion in the region is mainly driven by road proximity. Urban occupation is projected to increase in 170% by 2050, increasing water demands for domestic use in 38%. Results indicate the feasibility of including landscape and socioeconomic constrains in order to obtain potential domestic water demand scenarios by using land use and land cover change modelling to assess urban expansion and population growth. For the study region, our findings suggest that although urban sprawl increases water demand, urban supply will not be compromised given the large volume of available water in the basin. However, the indirect consequences of urban sprawl, such as industrialization and agricultural intensification, may compromise the quality of this resource and require better water use management in the region.

Bisphenol-A promotes antiproliferative effects during neonatal prostate development in male and female gerbils.

The aim of this study was to evaluate the development of male and female neonatal gerbil prostate under normal conditions and exposed to bisphenol-A (BPA). Normal postnatal development of the female gerbil prostate occurs earlier than and is morphologically distinct from that occurring in males. In BPA-exposed PND8 gerbils, we have not observed evidence of alterations in the ductal branching in either gender. However, the exposure to BPA alters the immunolabeling pattern of AR, ERα, and PCNA. In males, the exposure to high dosages of BPA resulted in a decrease in the proliferative status of the developing ventral prostate. In females, both high and low dosages were sufficient to decrease the proliferation of paraurethral buds in the branching process by more than 50%. Therefore, the obtained data indicate that BPA promotes antiproliferative effects during the neonatal development of the gerbil prostate, with more sensitivity to this endocrine disruptor in females.

Assessment of climate change impacts on water resources of the Purus Basin in the southwestern Amazon / Avaliação de impactos de mudanças climáticas nos recursos hídricos da Bacia do Purus no sudoeste da Amazônia

ABSTRACT Knowledge about water resources is critical for climate adaptation in face of long-term changes and more frequent extreme events occurrence. During the major droughts of 2005 and 2010, a large epicenter was located in the southwestern Amazon over the Purus River Basin. In this sense, we conducted a hydrological simulation in this basin to assess the climate change impacts on its water resources throughout the 21st century. The water balance was simulated using the Distributed Hydrological Model (MHD-INPE). The future climate projections were simulated by the regional ETA-INPE model driven by a 4-member HadCM3 global model regarding the A1B-AR4/IPCC scenario of greenhouse gases emissions. As simulated by the ETA-INPE/HadCM3, the 4-members mean response for the A1B scenario represents a rainfall reduction of up to 11.1%, a temperature increase of up to 4.4 °C, and a wind speed increase of up to 8.4% in the Purus Basin by the end of 21st century. Under these conditions, the discharge projections represent an overall 27% decrease in the Purus Basin with different patterns between dry and wet season, as well as changes in seasonality trends. The consequences of projected climate change are severe and will probably have a great impact upon natural ecosystem maintenance and human subsistence. In a climate change adaptation process, the preservation of the natural forest cover of the Purus Basin may have great importance in water retention.

RESUMO O conhecimento sobre os recursos hídricos é crítico para a adaptação diante das mudanças de longo prazo e ocorrência mais frequente de eventos extremos. Nas grandes secas de 2005 e 2010, um grande epicentro foi localizado no sudoeste da Amazônia sobre a Bacia do Rio Purus. Nesse sentido, foi realizada uma simulação hidrológica nessa bacia, para avaliar os impactos das mudanças climáticas sobre seus recursos hídricos ao longo do século 21. O balanço hídrico foi simulado utilizando o modelo hidrológico distribuído (MHD-INPE). As projeções climáticas futuras foram simuladas pelo modelo regional ETA-INPE forçado por 4 membros do modelo global HadCM3 sobre o cenário de emissões de gases de efeito estufa A1B-AR4/IPCC. Como simulado pelo ETA-INPE/HadCM3, a resposta média dos 4 membros para o cenário A1B representa uma redução de chuvas em até 11,1%, aumento de temperatura em até 4,4 °C, e aumento da velocidade do vento em até 8,4% para a Bacia do Purus até o fim do século 21. Sob essas condições, as projeções de descarga representam uma diminuição global de 27% na Bacia do Purus, com diferentes padrões entre as estações seca e úmida, bem como mudanças nas tendências sazonais. As consequências das mudanças climáticas projetadas são severas e provavelmente terão um grande impacto sobre a manutenção dos ecossistemas naturais e subsistência humana. Em um processo de adaptação a mudanças climáticas, a preservação da cobertura florestal natural da Bacia do Purus pode ter grande importância na retenção de água.