Refine
Language
- English (6)
Has Fulltext
- yes (6)
Is part of the Bibliography
- no (6)
Keywords
- gallbladder cancer (2)
- gallbladder cancer xenografts (2)
- 17-AAG (1)
- Agathotanaidae (1)
- European black slug (1)
- Gastropoda (1)
- HSP90 inhibitors (1)
- Pacific banana slug (1)
- Paranarthrura (1)
- Paranarthrurellidae (1)
- Tanaidomorpha (1)
- Tirana (1)
- WYE-354 (1)
- biogeographic legaciese (1)
- forest classification (1)
- forest functional similarity (1)
- geldanamycin (1)
- generalist herbivores (1)
- invasive species (1)
- mTOR inhibitors (1)
- metabolic rate (1)
- phylogenetic community distance (1)
- rapamycin (1)
- tropical forests (1)
Knowledge about the biogeographic affinities of the world’s tropical forests helps to better understand regional differences in forest structure, diversity, composition, and dynamics. Such understanding will enable anticipation of region-specific responses to global environmental change. Modern phylogenies, in combination with broad coverage of species inventory data, now allow for global biogeographic analyses that take species evolutionary distance into account. Here we present a classification of the world’s tropical forests based on their phylogenetic similarity. We identify five principal floristic regions and their floristic relationships: (i) Indo-Pacific, (ii) Subtropical, (iii) African, (iv) American, and (v) Dry forests. Our results do not support the traditional neo- versus paleotropical forest division but instead separate the combined American and African forests from their Indo-Pacific counterparts. We also find indications for the existence of a global dry forest region, with representatives in America, Africa, Madagascar, and India. Additionally, a northern-hemisphere Subtropical forest region was identified with representatives in Asia and America, providing support for a link between Asian and American northern-hemisphere forests.
The impacts of invasive alien species are greatest when they become dominant members of a community, introduce novel traits, and displace native species. Invasions by alien mollusks represent a novel context by which to compare trait differences between generalist native and introduced herbivores in terrestrial ecosystems. Here, we determined the abundance, habitat, feeding preferences, as well as the metabolic rate of the native Pacific banana slug (Ariolimax columbianus) and the alien black slug (Arion rufus) in the coastal forests of British Columbia, Canada. Through a series of observational and experimental studies, we found that alien slugs are more abundant, differ in their habitat preferences, and consumed more fungi (mushrooms) than native banana slugs. Conversely, in an enclosures experiment we found that herbivory damage by native slugs was higher compared to enclosures with alien only and control enclosures. Finally, metabolic rates were similar for both slug species. These results suggest that alien black slugs possess a suite of traits that make them functionally different from native banana slugs.
The Tanaidacea are ubiquitous and amongst the most abundant taxa in the deep sea. However, their diversity in submarine canyons remains largely unknown. Here, two new species and a new genus of Paratanaoidea are described. Paranarthrura cousteaui sp. nov. is distinguished by the combination of the following characters: post-cheliped sclerites not fused, presence of one seta in the maxilliped endite, one long midventral seta in cheliped, one penicillate seta in the basis of pereopods 4–6, uropod endopod bi-articulated and uropod exopod shorter than endopod article 1. This species was found at the upper reaches of three Portuguese canyons, Cascais, Setúbal and Nazaré Canyons, and the adjacent open slope, between 897 and 1001 m water depths. Tirana vallis gen. et sp. nov. presents a combination of the characters that define the other two genera of Paranarthrurellidae, Paranarthrurella and Armatognathia, but also unique characters within the family: the antenna, cheliped and uropod are more elongate than the rest of the species; the pereopods 4–6 carpus spines reach at least half of the length of the propodus and the propodus of pereopods 4–6 have ramified subdistal spines. This species was found at the middle reaches of Setúbal Canyon (3214–3219 m water depth).
Gallbladder cancer (GBC) is a lethal cancer with poor prognosis associated with high invasiveness and poor response to chemotherapy and radiotherapy. New therapeutic approaches are urgently needed in order to improve survival and response rates of GBC patients. We screened 130 small molecule inhibitors on a panel of seven GBC cell lines and identified the HSP90 inhibitor 17-AAG as one of the most potent inhibitory drugs across the different lines. We tested the antitumor efficacy of 17-AAG and geldanamycin (GA) in vitro and in a subcutaneous preclinical tumor model NOD-SCID mice. We also evaluated the expression of HSP90 by immunohistochemistry in human GBC tumors.
In vitro assays showed that 17-AAG and GA significantly reduced the expression of HSP90 target proteins, including EGFR, AKT, phospho-AKT, Cyclin B1, phospho-ERK and Cyclin D1. These molecular changes were consistent with reduced cell viability and cell migration and promotion of G2/M cell cycle arrest and apoptosis observed in our in vitro studies.
In vivo, 17-AAG showed efficacy in reducing subcutaneous tumors size, exhibiting a 69.6% reduction in tumor size in the treatment group compared to control mice (p < 0.05).
The HSP90 immunohistochemical staining was seen in 182/209 cases of GBC (87%) and it was strongly expressed in 70 cases (33%), moderately in 58 cases (28%), and weakly in 54 cases (26%).
Our pre-clinical observations strongly suggest that the inhibition of HSP90 function by HSP90 inhibitors is a promising therapeutic strategy for gallbladder cancer that may benefit from new HSP90 inhibitors currently in development.
Gallbladder cancer (GBC) is a highly malignant tumor characterized by a poor response to chemotherapy and radiotherapy. We evaluated the in vitro and in vivo antitumor efficacy of mTOR inhibitors, rapamycin and WYE-354. In vitro assays showed WYE-354 significantly reduced cell viability, migration and invasion and phospho-P70S6K expression in GBC cells. Mice harboring subcutaneous gallbladder tumors, treated with WYE-354 or rapamycin, exhibited a significant reduction in tumor mass. A short-term treatment with a higher dose of WYE-354 decreased the tumor size by 68.6% and 52.4%, in mice harboring G-415 or TGBC-2TKB tumors, respectively, compared to the control group. By contrast, treatment with a prolonged-low-dose regime of rapamycin almost abrogated tumor growth, exhibiting 92.7% and 97.1% reduction in tumor size, respectively, compared to control mice. These results were accompanied by a greater decrease in the phosphorylation status of P70S6K and a lower cell proliferation Ki67 index, compared to WYE-354 treated mice, suggesting a more effective mTOR pathway inhibition. These findings provide a proof of concept for the use of rapamycin or WYE-354 as potentially good candidates to be studied in clinical trials in GBC patients.
The change in allele frequencies within a population over time represents a fundamental process of evolution. By monitoring allele frequencies, we can analyze the effects of natural selection and genetic drift on populations. To efficiently track time-resolved genetic change, large experimental or wild populations can be sequenced as pools of individuals sampled over time using high-throughput genome sequencing (called the Evolve & Resequence approach, E&R). Here, we present a set of experiments using hundreds of natural genotypes of the model plant Arabidopsis thaliana to showcase the power of this approach to study rapid evolution at large scale. First, we validate that sequencing DNA directly extracted from pools of flowers from multiple plants -- organs that are relatively consistent in size and easy to sample -- produces comparable results to other, more expensive state-of-the-art approaches such as sampling and sequencing of individual leaves. Sequencing pools of flowers from 25-50 individuals at ∼40X coverage recovers genome-wide frequencies in diverse populations with accuracy r > 0.95. Secondly, to enable analyses of evolutionary adaptation using E&R approaches of plants in highly replicated environments, we provide open source tools that streamline sequencing data curation and calculate various population genetic statistics two orders of magnitude faster than current software. To directly demonstrate the usefulness of our method, we conducted a two-year outdoor evolution experiment with A. thaliana to show signals of rapid evolution in multiple genomic regions. We demonstrate how these laboratory and computational Pool-seq-based methods can be scaled to study hundreds of populations across many climates.