Long-term man–environment interactions in the Bolivian Amazon: 8000 years of vegetation dynamics

Only few studies documenting the vegetation history of the Llanos de Moxos, one of the largest seasonally flooded wetland areas in South America, are available and little is known about the environmental impact of pre-Columbian settlements. We use radiocarbon-dated terrestrial plant macrofossils to establish a sound chronology and palynological analyses to reconstruct the vegetation and fire history of the Lago Rogaguado area. The sedimentary pollen and spore record suggests that wetland and wooded savannah (Cerrado) environments occurred around the lake between 8100 and 5800 cal BP. Fire activity was high during this period and was probably connected to the dry Cerrado environments. The pollen evidence suggests early plant cultivation (Zea mays, Annonaceae and Cucurbitaceae) from 6500 cal BP onwards, which is significantly earlier than hitherto assumed for Amazonia. Gallery forests expanded after 5800 cal BP, when fire activity strongly declined. Forest expansion intensified around 2800 cal BP and continued until 2000 cal BP, when forest cover reached its maximum and fire activity its minimum. The late-Holocene forest expansion to the south and the decrease of fire activity may have resulted from a climatic shift to moister conditions (possibly a shorter dry season). New crops (e.g. Avena-type) or adventive plants (e.g. Rumex acetosella-type) document the impact of European economies after ca. 500 cal BP. Land use intensity remained rather stable over the most recent centuries, arguing against a collapse of settlements in response to the arrival of Europeans, as reconstructed from other Amazonian pollen records.

Disease evolution and outcomes in familial AML with germline CEBPA mutations

In-depth molecular investigation of familial leukemia has been limited by the rarity of recognized cases. This study examines the genetic events initiating leukemia and details the clinical progression of disease across multiple families harboring germ-line CEBPA mutations. Clinical data were collected from 10 CEBPA-mutated families, representing 24 members with acute myeloid leukemia (AML). Whole-exome (WES) and deep sequencing were performed to genetically profile tumors and define patterns of clonal evolution. Germline CEBPA mutations clustered within the N-terminal and were highly penetrant, with AML presenting at a median age of 24.5 years (range, 1.75-46 years). In all diagnostic tumors tested (n = 18), double CEBPA mutations (CEBPAdm) were detected, with acquired (somatic) mutations preferentially targeting the C-terminal. Somatic CEBPA mutations were unstable throughout the disease course, with different mutations identified at recurrence. Deep sequencing of diagnostic and relapse paired samples confirmed that relapse-associated CEBPA mutations were absent at diagnosis, suggesting recurrence was triggered by novel, independent clones. Integrated WES and deep sequencing subsequently revealed an entirely new complement of mutations at relapse, verifying the presentation of a de novo leukemic episode. The cumulative incidence of relapse in familial AML was 56% at 10 years (n = 11), and 3 patients experienced ≥3 disease episodes over a period of 17 to 20 years. Durable responses to secondary therapies were observed, with prolonged median survival after relapse (8 years) and long-term overall survival (10-year overall survival, 67%). Our data reveal that familial CEBPA-mutated AML exhibits a unique model of disease progression, associated with favorable long-term outcomes.