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Resumo Este artigo trata do lago de óleo, um desastre decorrente das atividades de uma empresa de refino de óleo que, há mais de três décadas, vulnerabiliza a Comunidade Quilombola Ilhotinha, localizada no município de Capivari de Baixo, Santa Catarina. Desenvolvido por meio do método etnográfico, objetivou analisar se o lago de óleo revela mecanismos de poder e controle operacionalizados pela colonialidade. O estudo aponta aspectos que sustentam essa faceta específica da colonialidade, dentre os quais, a produção de vulnerabilidades e a instrumentalização dos racismos. Argumenta que o ideário do desenvolvimento tem produzido, ao longo de sua regência, desastres que revelam mecanismos de ação e manutenção da colonialidade. Por fim, evidencia a emergência de movimentos articulados pela própria comunidade que transcendem o sentido mais elementar de restauração dos danos causados pelo desastre, vislumbrando a construção de uma nova realidade, na qual seus direitos sejam contemplados e a produção da vida, garantida.

PRECONNECT is a multicenter study demonstrating the efficacy and tolerability of trifluridine/tipiracil in adult patients with histologically confirmed adenocarcinoma of the colon or rectum and pretreated metastatic lesions. The current article describes the characteristics and outcomes of the Brazilian cohort of patients who underwent trifluridine/tipiracil therapy within PRECONNECT. Brazilian patients (n=55) received oral trifluridine/tipiracil 35mg/m2 twice daily on days 1-5 and 8-12 of each 28-day cycle. The primary endpoint was safety including time to ECOG (Eastern Cooperative Oncology Group) PS (performance status) deterioration, and the secondary endpoints included progression-free survival (PFS) and quality of life (QoL). Baseline characteristics showed only 34.5% of patients underwent ≥3 lines of treatment, 29.1% presented ≥3 metastatic sites and 52.7% showed an ECOG PS of 0. The disease control rate (DCR) was 32.0% and 28.6% in patients with one and two metastatic sites, respectively, the median PFS was 3.0 months (95%CI: 2.5-3.4), and the time to ECOG PS deterioration (≥2) was 5.4 months. Drug-related treatment-emergent adverse events (TEAE) were observed at least once in 87.3% of patients, and the most common (≥40% of patients) hematological TEAEs were neutropenia and anemia; there was no febrile neutropenia case. The shorter time to ECOG PS deterioration showed in the Brazilian subset of patients is likely due to late diagnosis setting compared to the global population, despite that trifluridine/tipiracil showed good DCR results, including patients with two metastatic sites. In conclusion, safety and efficacy results provide confidence in routine practice use and are in line with the PRECONNECT study

Abstract This study analyzed the relations between social representations of the body and the body care practices of older adults. Forty older adults, with ages varying from 60 to 84 years (M = 69; SD = 7), matched by sex, took part in the study. The data were collected by means of in-depth thematic interviews, with the corpus analyzed using the IRaMuTeQ software. Differences between men and women were verified in representational contents and body practices. The male participants’ social representations of the body were associated with biological functionality and health concerns, while the women emphasized the importance of physical appearance in their social relationships. Regarding body care practices, there was a higher incidence of food concerns in the men and the performance of physical activities in the women. Therefore, the results indicated that the body care practices vary according to the socials representations of the body and the sex of the participant.

Resenha da obra Pluriverse: a post-development dictionary, de Ashish Khotari, Ariel Salleh, Arturo Escobar; Federico Demaria e Alberto Acosta. A coletânea reúne mais de 100 verbetes de autores, escolhidos e convidados por serem pesquisadores e/ou ativistas engajados com lutas e movimentos sociais do Sul global, e comprometidos com uma perspectiva decolonial e crítica das estruturas do sistema capitalista, da modernidade ocidental e do patriarcado. A partir dessa linha, o livro propõe uma compilação de conceitos, visões de mundo e práticas que se opõem à ontologia eurocêntrica universalista, apresentando alternativas transformadoras para os processos atualmente dominantes de desenvolvimento globalizado.

Summary: Sickle cell anemia affects millions of people worldwide and is an emerging global health burden. As part of a large NIH-funded NextGen Consortium, we generated a diverse, comprehensive, and fully characterized library of sickle-cell-disease-specific induced pluripotent stem cells (iPSCs) from patients of different ethnicities, β-globin gene (HBB) haplotypes, and fetal hemoglobin (HbF) levels. iPSCs stand to revolutionize the way we study human development, model disease, and perhaps eventually, treat patients. Here, we describe this unique resource for the study of sickle cell disease, including novel haplotype-specific polymorphisms that affect disease severity, as well as for the development of patient-specific therapeutics for this phenotypically diverse disorder. As a complement to this library, and as proof of principle for future cell- and gene-based therapies, we also designed and employed CRISPR/Cas gene editing tools to correct the sickle hemoglobin (HbS) mutation. : In this resource article, Mostoslavsky, Murphy, and colleagues of the NextGen consortium describe a diverse, comprehensive, and characterized library of sickle cell disease-specific induced pluripotent stem cells (iPSCs) from patients of different ethnicities, β-globin gene (HBB) haplotypes and fetal hemoglobin (HbF) levels. This bank is readily available and accessible to all investigators. Keywords: induced pluripotent stem cells, iPSCs, sickle cell disease, disease modeling, directed differentiation, gene correction

Embryonic stem cells (ESCs) possess a distinct chromatin conformation maintained by specialized chromatin proteins. To identify chromatin regulators in ESCs, we developed a simple biochemical assay named D-CAP (differential chromatin-associated proteins), using brief micrococcal nuclease digestion of chromatin, followed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Using D-CAP, we identified several differentially chromatin-associated proteins between undifferentiated and differentiated ESCs, including the chromatin remodeling protein SMARCD1. SMARCD1 depletion in ESCs led to altered chromatin and enhanced endodermal differentiation. Gene expression and chromatin immunoprecipitation sequencing (ChIP-seq) analyses suggested that SMARCD1 is both an activator and a repressor and is enriched at developmental regulators and that its chromatin binding coincides with H3K27me3. SMARCD1 knockdown caused H3K27me3 redistribution and increased H3K4me3 around the transcription start site (TSS). One of the identified SMARCD1 targets was Klf4. In SMARCD1-knockdown clones, KLF4, as well as H3K4me3 at the Klf4 locus, remained high and H3K27me3 was abolished. These results propose a role for SMARCD1 in restricting pluripotency and activating lineage pathways by regulating H3K27 methylation.

Mutations in the gene Adenomatous Polyposis Coli or APC appear in most sporadic cases of colorectal cancer and it is the most frequent mutation causing hereditary Familial Adenomatous Polyposis. The detailed molecular mechanism by which APC mutations predispose to the development of colorectal cancer is not completely understood. This is in part due to the lack of accessibility to appropriate models that recapitulate the early events associated with APC mediated intestinal transformation. We have established a novel platform utilizing human induced Pluripotent Stem cells or iPSC from normal or FAP-specific APC mutant individuals and evaluated the effect of the mutation in the cells before and after differentiation into intestinal organoids. In order to minimize genetic background effects, we also established an isogenic platform using TALEN-mediated gene editing. Comparison of normal and APC mutant iPSC revealed a significant defect in cell identity and polarity due to the presence of APC in heterozygosity as well as chromosomal aberrations including abnormal anaphases and centrosome numbers. Importantly, upon specification into intestinal progeny, APC heterozygosity was responsible for a major change in the transcriptional identity of the cells with dysregulation of key signaling pathways, including metabolic reprogramming, abnormal lipid metabolism and intestinal-specific cadherin expression. In conclusion, we have developed a novel iPSC/intestinal model of APC mutagenesis and provide strong evidence that APC in heterozygosity imparts a clear phenotypic and molecular defect, affecting basic cellular functions and integrity, providing novel insights in the earlier events of APC-mediated tumorigenesis.

Este trabalho analisa detalhadamente o problema de balanceamento / rebalanceamento das linhas de montagem operadas por grupos de trabalho autogerenciados propondo um modelo otimizante de programação inteira que é tratado computacionalmente com êxito por meio da linguagem de modelagem GAMS ("General Algebraic Modeling System") e solver Zoom. Não encontramos na literatura trabalhos que tenham modelado matematicamente, de forma exata ou heurística, tal problema. Para se estimar a eficiência futura da linha, um dos dados que o modelo necessita, propomos o uso de dois métodos utilizados em outras áreas (curva de aprendizagem e previsão de demanda). Mostra-se a diferença entre problema de balanceamento e de rebalanceamento bem como é feita uma revisão bibliográfica complementar a respeito do problema de balanceamento de linhas. Ela complementa a última revisão dos métodos exatos que é de 1986 e a última dos métodos heurísticos que é de 1998.This paper analyses in details the balancing and rebalancing problem of assembly lines operated by self-managed work groups. It proposes an optimizing integer programming model that is treated computationally with success by means of the modeling language GAMS (General Algebraic Modeling System) and solver ZOOM. We have not found other works that have presented a heuristic or exact mathematical model for such a problem. For estimating the future line efficiency, one of the parameters that the model requires, we propose the use of two methods used in other areas (learning curve and demand forecasting). Differences between balancing and rebalancing problems are shown and also a complementary bibliographical review about line balancing is accomplished. It complements the last review of exact methods dated on 1986 and the last review of heuristic methods dated on 1998.

Delivery of the transcription factors Oct4, Klf4, Sox2 and c-Myc via integrating viral vectors has been widely employed to generate induced pluripotent stem cell (iPSC) lines from both normal and disease-specific somatic tissues, providing an invaluable resource for medical research and drug development. Residual reprogramming transgene expression from integrated viruses nevertheless alters the biological properties of iPSCs and has been associated with a reduced developmental competence both in vivo and in vitro. We performed transcriptional profiling of mouse iPSC lines before and after excision of a polycistronic lentiviral reprogramming vector to systematically define the overall impact of persistent transgene expression on the molecular features of iPSCs. We demonstrate that residual expression of the Yamanaka factors prevents iPSCs from acquiring the transcriptional program exhibited by embryonic stem cells (ESCs) and that the expression profiles of iPSCs generated with and without c-Myc are indistinguishable. After vector excision, we find 36% of iPSC clones show normal methylation of the Gtl2 region, an imprinted locus that marks ESC-equivalent iPSC lines. Furthermore, we show that the reprogramming factor Klf4 binds to the promoter region of Gtl2. Regardless of Gtl2 methylation status, we find similar endodermal and hepatocyte differentiation potential comparing syngeneic Gtl2(ON) vs Gtl2(OFF) iPSC clones. Our findings provide new insights into the reprogramming process and emphasize the importance of generating iPSCs free of any residual transgene expression.