Recuperação de campos nativos suprimidos por agricultura no bioma Pampa: manejo versus regeneração natural.

Os valores médios de riqueza nas áreas de regeneração natural foram inferiores aos das áreas manejadas, e em termos de composição, áreas manejadas tiveram maior similaridade às áreas de referência, indicando que o manejo propiciou aumento na riqueza e composição de espécies em relação às áreas de exclusão, e melhor trajetória dere cuperação

Recuperação de campos nativos suprimidos no Bioma Pampa: um estudo de caso em escala de paisagem em Rosário do Sul (RS).

Uma parceria entre Exército Brasileiro, Ibama, Embrapa Pecuária Sul, Unipampa e UFRGS conduziu um Projeto de Recuperação de Área Degradada (Prad) no Campo de Instrução Barão de São Borja, em Rosário do Sul/RS, visando recuperar campos nativos com histórico de uso com lavouras de arroz e soja. A hipótese central trabalhada no Prad é de que o pastejo pode ser um instrumento para restaurar as formações campestres, impedindo que a vegetação evolua para uma fisionomia arbustiva e acelerando a regeneração natural. O gado bovino foi usado como ?roçadeira biológica? e dispersor de sementes, prática complementada por roçadas mecânicas, nivelamento do solo e isolamento temporário da área em recuperação. O monitoramento da estrutura e da riqueza da vegetação norteou o ajuste de carga animal e os períodos de diferimento. Passados cinco anos, a área apresenta fisionomia campestre desejada, tendo sido observado aumento na riqueza de espécies nativas, e composição botânica com maior similaridade à da área de referência, com aumento na cobertura de espécies das famílias Poaceae e Fabaceae. Houve diminuição do solo exposto, com o aumento da cobertura vegetal, e registrado o aumento da cobertura de Eragrostis plana (capim-annoni), gramínea exótica invasora

A single nucleotide polymorphism genotyping platform for the authentication of patient derived xenografts

Patient derived xenografts (PDXs) have become a vital, frequently used, component of anti-cancer drug development. PDXs can be serially passaged in vivo for years, and shared across laboratories. As a consequence, the potential for mis-identification and cross-contamination is possible, yet authentication of PDXs appears limited. We present a PDX Authentication System (PAS), by combining a commercially available OpenArray assay of single nucleotide polymorphisms (SNPs) with in-house R studio programs, to validate PDXs established in individual mice from acute lymphoblastic leukemia biopsies. The PAS is sufficiently robust to identify contamination at levels as low as 3%, similar to the gold standard of short tandem repeat (STR) profiling. We have surveyed a panel of PDXs established from 73 individual leukemia patients, and found that the PAS provided sufficient discriminatory power to identify each xenograft. The identified SNP-discrepant PDXs demonstrated distinct gene expression profiles, indicating a risk of contamination for PDXs at high passage number. The PAS also allows for the authentication of tumor cells with complex karyotypes from solid tumors including prostate cancer and Ewing's sarcoma. This study highlights the demands of authenticating PDXs for cancer research, and evaluates a reliable authentication platform that utilizes a commercially available and cost-effective system

A single nucleotide polymorphism genotyping platform for the authentication of patient derived xenografts.

Patient derived xenografts (PDXs) have become a vital, frequently used, component of anti-cancer drug development. PDXs can be serially passaged in vivo for years, and shared across laboratories. As a consequence, the potential for mis-identification and cross-contamination is possible, yet authentication of PDXs appears limited. We present a PDX Authentication System (PAS), by combining a commercially available OpenArray assay of single nucleotide polymorphisms (SNPs) with in-house R studio programs, to validate PDXs established in individual mice from acute lymphoblastic leukemia biopsies. The PAS is sufficiently robust to identify contamination at levels as low as 3%, similar to the gold standard of short tandem repeat (STR) profiling. We have surveyed a panel of PDXs established from 73 individual leukemia patients, and found that the PAS provided sufficient discriminatory power to identify each xenograft. The identified SNP-discrepant PDXs demonstrated distinct gene expression profiles, indicating a risk of contamination for PDXs at high passage number. The PAS also allows for the authentication of tumor cells with complex karyotypes from solid tumors including prostate cancer and Ewing's sarcoma. This study highlights the demands of authenticating PDXs for cancer research, and evaluates a reliable authentication platform that utilizes a commercially available and cost-effective system

AKR1C3 is a biomarker of sensitivity to PR-104 in preclinical models of T-cell acute lymphoblastic leukemia

PR-104, a phosphate ester of the nitrogen mustard prodrug PR-104A, has shown evidence of efficacy in adult leukemia clinical trials. Originally designed to target hypoxic cells, PR-104A is independently activated by aldo-keto-reductase 1C3 (AKR1C3). The aim of this study was to test whether AKR1C3 is a predictive biomarker of in vivo PR-104 sensitivity. In a panel of 7 patient-derived pediatric acute lymphoblastic leukemia (ALL) xenografts, PR-104 showed significantly greater efficacy against T-lineage ALL (T-ALL) than B-cell-precursor ALL (BCP-ALL) xenografts. Single-agent PR-104 was more efficacious against T-ALL xenografts compared with a combination regimen of vincristine, dexamethasone, and L-asparaginase. Expression of AKR1C3 was significantly higher in T-ALL xenografts compared with BCP-ALL, and correlated with PR-104/PR-104A sensitivity in vivo and in vitro. Overexpression of AKR1C3 in a resistant BCP-ALL xenograft resulted in dramatic sensitization to PR-104 in vivo. Testing leukemic blasts from 11 patients confirmed that T-ALL cells were more sensitive than BCP-ALL to PR-104A in vitro, and that sensitivity correlated with AKR1C3 expression. Collectively, these results indicate that PR-104 shows promise as a novel therapy for relapsed/refractory T-ALL, and that AKR1C3 expression could be used as a biomarker to select patients most likely to benefit from such treatment in prospective clinical trials

Lymphocyte-Specific Chromatin Accessibility Pre-determines Glucocorticoid Resistance in Acute Lymphoblastic Leukemia

© 2018 Elsevier Inc. Glucocorticoids play a critical role in the treatment of lymphoid malignancies. While glucocorticoid efficacy can be largely attributed to lymphocyte-specific apoptosis, its molecular basis remains elusive. Here, we studied genome-wide lymphocyte-specific open chromatin domains (LSOs), and integrated LSOs with glucocorticoid-induced RNA transcription and chromatin modulation using an in vivo patient-derived xenograft model of acute lymphoblastic leukemia (ALL). This led to the identification of LSOs critical for glucocorticoid-induced apoptosis. Glucocorticoid receptor cooperated with CTCF at these LSOs to mediate DNA looping, which was inhibited by increased DNA methylation in glucocorticoid-resistant ALL and non-lymphoid cell types. Our study demonstrates that lymphocyte-specific epigenetic modifications pre-determine glucocorticoid resistance in ALL and may account for the lack of glucocorticoid sensitivity in other cell types. Jing et al. identified lymphocyte-specific open chromatin domains (LSOs) critical for glucocorticoid (GC)-induced acute lymphoblastic leukemia (ALL) apoptosis. GC receptor cooperated with CTCF at these LSOs to mediate DNA looping, which was inhibited by DNA methylation in GC-resistant ALL and non-lymphoid cell types