Charles University in Prague

About: Charles University in Prague is a education organization based out in Prague, Czechia. It is known for research contribution in the topics: Population & Large Hadron Collider. The organization has 32392 authors who have published 74435 publications receiving 1804208 citations.

Global hotspots and correlates of alien species richness across taxonomic groups

Abstract: Human-mediated transport beyond biogeographic barriers has led to the introduction and establishment of alien species in new regions worldwide. However, we lack a global picture of established alien species richness for multiple taxonomic groups. Here, we assess global patterns and potential drivers of established alien species richness across eight taxonomic groups (amphibians, ants, birds, freshwater fishes, mammals, vascular plants, reptiles and spiders) for 186 islands and 423 mainland regions. Hotspots of established alien species richness are predominantly island and coastal mainland regions. Regions with greater gross domestic product per capita, human population density, and area have higher established alien richness, with strongest effects emerging for islands. Ants and reptiles, birds and mammals, and vascular plants and spiders form pairs of taxonomic groups with the highest spatial congruence in established alien richness, but drivers explaining richness differ between the taxa in each pair. Across all taxonomic groups, our results highlight the need to prioritize prevention of further alien species introductions to island and coastal mainland regions globally. Analysis of eight taxonomic groups across 186 islands and 423 mainland regions reveals that those with the greatest gross domestic product per capita, human population density and area have the highest established alien species richness, with the strongest effects on islands.

Induction of cancer cell apoptosis by α-tocopheryl succinate: molecular pathways and structural requirements

Abstract: The vitamin E analog a-tocopheryl succinate (a-TOS) can induce apoptosis. We show that the proapoptotic activity of a-TOS in hematopoietic and cancer cell lines involves inhibition of protein kinase C (PKC), since phorbol myristyl acetate prevented a-TOS-triggered apoptosis. More selective effectors indicated that a-TOS reduced PKCa isotype activity by increasing protein phosphatase 2A (PP2A) activity. The role of PKCa inhibition in a-TOS-induced apoptosis was confirmed using antisense oligonucleotides or PKCa overexpression. Gain- or loss-of-function bcl-2 mutants implied modulation of bcl-2 activity by PKC/PP2A as a mitochondrial target of a-TOS-induced proapoptotic signals. Structural analogs revealed that a-tocopheryl and succinyl moieties are both required for maximizing these effects. In mice with colon cancer xenografts, a-TOS suppressed tumor growth by 80%. This epitomizes cancer cell killing by a pharmacologically relevant compound without known side effects.

Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma.

Abstract: Background The role of adjuvant treatment in high-risk muscle-invasive urothelial carcinoma after radical surgery is not clear. Methods In a phase 3, multicenter, double-blind, randomized, controlled trial, we assigned patients with muscle-invasive urothelial carcinoma who had undergone radical surgery to receive, in a 1:1 ratio, either nivolumab (240 mg intravenously) or placebo every 2 weeks for up to 1 year. Neoadjuvant cisplatin-based chemotherapy before trial entry was allowed. The primary end points were disease-free survival among all the patients (intention-to-treat population) and among patients with a tumor programmed death ligand 1 (PD-L1) expression level of 1% or more. Survival free from recurrence outside the urothelial tract was a secondary end point. Results A total of 353 patients were assigned to receive nivolumab and 356 to receive placebo. The median disease-free survival in the intention-to-treat population was 20.8 months (95% confidence interval [CI], 16.5 to 27.6) with nivolumab and 10.8 months (95% CI, 8.3 to 13.9) with placebo. The percentage of patients who were alive and disease-free at 6 months was 74.9% with nivolumab and 60.3% with placebo (hazard ratio for disease recurrence or death, 0.70; 98.22% CI, 0.55 to 0.90; P Conclusions In this trial involving patients with high-risk muscle-invasive urothelial carcinoma who had undergone radical surgery, disease-free survival was longer with adjuvant nivolumab than with placebo in the intention-to-treat population and among patients with a PD-L1 expression level of 1% or more. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 274 ClinicalTrials.gov number, NCT02632409.).