Coevolution between native and invasive plant competitors: implications for invasive species management

Invasive species may establish in communities because they are better competitors than natives, but in order to remain community dominants, the competitive advantage of invasive species must be persistent. Native species that are not extirpated when highly invasive species are introduced are likely to compete with invaders. When population sizes and genetic diversity of native species are large enough, natives may be able to evolve traits that allow them to co-occur with invasive species. Native species may also evolve to become significant competitors with invasive species, and thus affect the fitness of invaders. Invasive species may respond in turn, creating either transient or continuing coevolution between competing species. In addition to demographic factors such as population size and growth rates, a number of factors including gene flow, genetic drift, the number of selection agents, encounter rates, and genetic diversity may affect the ability of native and invasive species to evolve competitive ability against one another. We discuss how these factors may differ between populations of native and invasive plants, and how this might affect their ability to respond to selection. Management actions that maintain genetic diversity in native species while reducing population sizes and genetic diversity in invasive species could promote the ability of natives to evolve improved competitive ability

Functional interdependence of BRD4 and DOT1L in MLL leukemia.

Targeted therapies against disruptor of telomeric silencing 1-like (DOT1L) and bromodomain-containing protein 4 (BRD4) are currently being evaluated in clinical trials. However, the mechanisms by which BRD4 and DOT1L regulate leukemogenic transcription programs remain unclear. Using quantitative proteomics, chemoproteomics and biochemical fractionation, we found that native BRD4 and DOT1L exist in separate protein complexes. Genetic disruption or small-molecule inhibition of BRD4 and DOT1L showed marked synergistic activity against MLL leukemia cell lines, primary human leukemia cells and mouse leukemia models. Mechanistically, we found a previously unrecognized functional collaboration between DOT1L and BRD4 that is especially important at highly transcribed genes in proximity to superenhancers. DOT1L, via dimethylated histone H3 K79, facilitates histone H4 acetylation, which in turn regulates the binding of BRD4 to chromatin. These data provide new insights into the regulation of transcription and specify a molecular framework for therapeutic intervention in this disease with poor prognosis

Cancer Stem Cell–Directed Therapies: Recent Data From the Laboratory and Clinic

Cancer stem cells (CSCs) are defined by their ability to (i) fully recapitulate the tumor of origin when transplanted into immunodeficient mouse hosts, and (ii) self-renew, demonstrated by their ability to be serially transplanted. These properties suggest that CSCs are required for tumor maintenance and metastasis; thus, it has been predicted that CSC elimination is required for cure. This prediction has profoundly altered paradigms for cancer research, compelling investigators to prospectively isolate CSCs to characterize the molecular pathways regulating their behavior. Many potential strategies for CSC-directed therapy have been proposed, but few studies have rigorously demonstrated their efficacy using in vivo models. Herein, we highlight recent studies that demonstrate the utility of CSC-directed therapies and discuss the implications of the CSC hypothesis to experimental design and therapeutic strategies