RESUMO
Identifying sources is crucial for proposing effective actions to combat marine litter pollution. Here, we used an innovative approach to identify hotspots of mismanaged plastic waste (MPW) within Brazil and subsequent leakage to the ocean, based on population density, socio-economic conditions, municipal solid waste management and environmental parameters. We estimated plastic waste generation and MPW for each of the 5570 Brazilian municipalities, which totaled 3.44 million metric tons per year. Then, we estimated the probability of litter mobilization and transport (P) and the relative risk of leakage to the ocean (MPW × P). The Guanabara Bay and La Plata River comprised the main oceanic entry hotspots of litter produced in Brazil. The use of national databases allowed us to increase spatial and temporal granularity, offering a detailed baseline for the application of prevention and mitigation actions. However, overcoming data limitations is still a challenge in Brazil as in other Global South countries.
Assuntos
Plásticos , Gerenciamento de Resíduos , Brasil , Poluição Ambiental , Resíduos Sólidos , Resíduos , Monitoramento AmbientalRESUMO
p16 is a tumor suppressor encoded by the CDKN2A gene whose expression is lost in ~50% of all human cancers. In its canonical role, p16 inhibits the G1-S phase cell cycle progression through suppression of cyclin dependent kinases. Interestingly, p16 also has roles in metabolic reprogramming, and we previously published that loss of p16 promotes nucleotide synthesis via the pentose phosphate pathway. Whether other nucleotide metabolic genes and pathways are affected by p16/CDKN2A loss and if these can be specifically targeted in p16/CDKN2A-low tumors has not been previously explored. Using CRISPR KO libraries in multiple isogenic human and mouse melanoma cell lines, we determined that many nucleotide metabolism genes are negatively enriched in p16/CDKN2A knockdown cells compared to controls. Indeed, many of the genes that are required for survival in the context of low p16/CDKN2A expression based on our CRISPR screens are upregulated in p16 knockdown melanoma cells and those with endogenously low CDKN2A expression. We determined that cells with low p16/Cdkn2a expression are sensitive to multiple inhibitors of de novo purine synthesis, including anti-folates. Tumors with p16 knockdown were more sensitive to the anti-folate methotrexate in vivo than control tumors. Together, our data provide evidence to reevaluate the utility of these drugs in patients with p16/CDKN2A-low tumors as loss of p16/CDKN2A may provide a therapeutic window for these agents.
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Otaria flavescens (SASL) and Arctocephalus australis (SAFS) are endemic of South America. The aims were to assess Cd concentrations in red blood cells (RBC) and plasma from free living females of both species; and to establish metallothioneins (MT) levels in blood fractions and the possible relationship between MTs and Cd. Blood of fifteen SASL and eight SAFS females from Isla de Lobos were analyzed (years 2010-2011). All animals showed Cd levels above the detection limit. Cd concentrations on SAFS were higher than those of SASL, however, no significant differences were observed on metal concentrations between cell fractions by species. Metal levels were associated with a natural presence and ecological-trophic habits of the prey items. On SASL the MT concentrations between fractions were similar; whereas, SAFS plasma concentrations were higher than RBC. The results reported constitute the first information on Cd and MT blood levels in these species.
Assuntos
Cádmio/sangue , Caniformia/fisiologia , Metalotioneína/sangue , Poluentes Químicos da Água/sangue , Animais , Feminino , Metais , América do Sul , ZincoRESUMO
During the first 7 years of the Diabetes Prevention Program Outcomes Study (DPPOS), diabetes incidence rates, when compared with the Diabetes Prevention Program (DPP), decreased in the placebo (-42%) and metformin (-25%), groups compared with the rates in the intensive lifestyle intervention (+31%) group. Participants in the placebo and metformin groups were offered group intensive lifestyle intervention prior to entering the DPPOS. The following two hypotheses were explored to explain the rate differences: "effective intervention" (changes in weight and other factors due to intensive lifestyle intervention) and "exhaustion of susceptible" (changes in mean genetic and diabetes risk scores). No combination of behavioral risk factors (weight, physical activity, diet, smoking, and antidepressant or statin use) explained the lower DPPOS rates of diabetes progression in the placebo and metformin groups, whereas weight gain was the factor associated with higher rates of progression in the intensive lifestyle intervention group. Different patterns in the average genetic risk score over time were consistent with exhaustion of susceptibles. Results were consistent with exhaustion of susceptibles for the change in incidence rates, but not the availability of intensive lifestyle intervention to all persons before the beginning of the DPPOS. Thus, effective intervention did not explain the lower diabetes rates in the DPPOS among subjects in the placebo and metformin groups compared with those in the DPP.