Rivers have been suggested to have played an important role in shaping present-day patterns of ecological and genetic variation among Amazonian species and communities. Recent molecular studies have provided mixed support for the hypothesis that large lowland Amazonian rivers have functioned as significant impediments to gene flow among populations of neotropical species. To date, no study has systematically evaluated the impact that riverine barriers might have on structuring whole Amazonian communities. Our analyses of the phylogeography of frogs and small mammals indicate that a putative riverine barrier (the Juruá River) does not relate to present-day patterns of community similarity and species richness. Rather, our results imply a significant impact of the Andean orogenic axis and associated thrust-and-fold lowland dynamics in shaping patterns of biotic diversity along the Juruá . Combined results of this and other studies significantly weaken the postulated role of rivers as major drivers of Amazonian diversification.
Purpose: The Vd1 þ subset of gd T lymphocytes is a promising candidate for cancer immunotherapy, but the lack of suitable expansion/differentiation methods has precluded therapeutic application. We set out to develop and test (preclinically) a Vd1 þ T-cell-based protocol that is good manufacturing practice compatible and devoid of feeder cells for prompt clinical translation. Experimental design: We tested multiple combinations of clinical-grade agonist antibodies and cytokines for their capacity to expand and differentiate (more than 2-3 weeks) Vd1 þ T cells from the peripheral blood of healthy donors and patients with chronic lymphocytic leukemia (CLL). We characterized the phenotype and functional potential of the final cellular product, termed Delta One T (DOT) cells, in vitro and in vivo (xenograft models of CLL).Results: We describe a very robust two-step protocol for the selective expansion (up to 2,000-fold in large clinicalgrade cell culture bags) and differentiation of cytotoxic Vd1
Among patients with previously untreated follicular lymphoma, efficacy results were similar with rituximab plus lenalidomide and rituximab plus chemotherapy (with both regimens followed by rituximab maintenance therapy). The safety profile differed in the two groups. (Funded by Celgene; RELEVANCE ClinicalTrials.gov numbers, NCT01476787 and NCT01650701 , and EudraCT number, 2011-002792-42 .).
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