| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Licciardello, Marco P., et al.
(författare)
-
A combinatorial screen of the CLOUD uncovers a synergy targeting the androgen receptor
- 2017
-
Ingår i: Nature Chemical Biology. - : Nature Publishing Group. - 1552-4450 .- 1552-4469. ; 13:7, s. 771-778
-
Tidskriftsartikel (refereegranskat)abstract
- Approved drugs are invaluable tools to study biochemical pathways, and further characterization of these compounds may lead to repurposing of single drugs or combinations. Here we describe a collection of 308 small molecules representing the diversity of structures and molecular targets of all FDA-approved chemical entities. The CeMM Library of Unique Drugs (CLOUD) covers prodrugs and active forms at pharmacologically relevant concentrations and is ideally suited for combinatorial studies. We screened pairwise combinations of CLOUD drugs for impairment of cancer cell viability and discovered a synergistic interaction between flutamide and phenprocoumon (PPC). The combination of these drugs modulates the stability of the androgen receptor (AR) and resensitizes AR-mutant prostate cancer cells to flutamide. Mechanistically, we show that the AR is a substrate for gamma-carboxylation, a post-translational modification inhibited by PPC. Collectively, our data suggest that PPC could be repurposed to tackle resistance to antiandrogens in prostate cancer patients.
|
|
| 8. |
- Matos-Maraví, Pável, et al.
(författare)
-
Mesoamerica is a cradle and the Atlantic Forest is a museum of Neotropical butterfly diversity: insights from the evolution and biogeography of Brassolini (Lepidoptera: Nymphalidae)
- 2021
-
Ingår i: Biological Journal of the Linnean Society. - : Oxford University Press (OUP). - 0024-4066 .- 1095-8312. ; 133:3, s. 704-724
-
Tidskriftsartikel (refereegranskat)abstract
- Regional species diversity is explained ultimately by speciation, extinction and dispersal. Here, we estimate dispersal and speciation rates of Neotropical butterflies to propose an explanation for the distribution and diversity of extant species. We focused on the tribe Brassolini (owl butterflies and allies), a Neotropical group that comprises 17 genera and 108 species, most of them endemic to rainforest biomes. We inferred a robust species tree using the multispecies coalescent framework and a dataset including molecular and morphological characters. This formed the basis for three changes in Brassolini classification: (1) Naropina syn. nov. is subsumed within Brassolina; (2) Aponarope syn. nov. is subsumed within Narope; and (3) Selenophanes orgetorix comb. nov. is reassigned from Catoblepia to Selenophanes. By applying biogeographical stochastic mapping, we found contrasting species diversification and dispersal dynamics across rainforest biomes, which might be explained, in part, by the geological and environmental history of each bioregion. Our results revealed a mosaic of biome-specific evolutionary histories within the Neotropics, where butterfly species have diversified rapidly (cradles: Mesoamerica), have accumulated gradually (museums: Atlantic Forest) or have diversified and accumulated alternately (Amazonia). Our study contributes evidence from a major butterfly lineage that the Neotropics are a museum and a cradle of species diversity.
|
|
| 9. |
- Matos-Maraví, Pável, et al.
(författare)
-
Species limits in butterflies (Lepidoptera: Nymphalidae): reconciling classical taxonomy with the multispecies coalescent
- 2019
-
Ingår i: Systematic Entomology. - : Wiley. - 0307-6970 .- 1365-3113. ; 44:4, s. 745-756
-
Tidskriftsartikel (refereegranskat)abstract
- Species delimitation is at the core of biological sciences. During the last decade, molecular-based approaches have advanced the field by providing additional sources of evidence to classical, morphology-based taxonomy. However, taxonomy has not yet fully embraced molecular species delimitation beyond threshold-based, single-gene approaches, and taxonomic knowledge is not commonly integrated into multilocus species delimitation models. Here we aim to bridge empirical data (taxonomic and genetic) with recently developed coalescent-based species delimitation approaches. We use the multispecies coalescent model as implemented in two Bayesian methods (dissect/stacey and bp&p) to infer species hypotheses. In both cases, we account for phylogenetic uncertainty (by not using any guide tree) and taxonomic uncertainty (by measuring the impact of using a priori taxonomic assignments to specimens). We focus on an entire Neotropical tribe of butterflies, the Haeterini (Nymphalidae: Satyrinae). We contrast divergent taxonomic opinion - splitting, lumping and misclassifying species - in the light of different phenotypic classifications proposed to date. Our results provide a solid background for the recognition of 22 species. The synergistic approach presented here overcomes limitations in both traditional taxonomy (e.g. by recognizing cryptic species) and molecular-based methods (e.g. by recognizing structured populations, and not raising them to species). Our framework provides a step forward towards standardization and increasing reproducibility of species delimitations.
|
|
| 10. |
|
|
