RESUMO
Leaves play a central role in plant fitness, allowing efficient light capture, gas exchange and thermoregulation, ensuring optimal growing conditions for the plant. Phenotypic variability in leaf shape and size has been linked to environmental heterogeneity and habitat characteristics. Therefore, the study of foliar morphology in plant populations can help us to identify the environmental factors that may have influenced the process of species diversification. In this study, we used European wild pear (Pyrus pyraster (L.) Burgsd., Rosaceae) as a model species to investigate the phenotypic variability of leaves under different environmental conditions. Using leaf morphometric data from 19 natural populations from the north-western part of the Balkan Peninsula, a high level of variability among and within populations were found. Leaf traits related to leaf size were more variable compared to leaf shape traits, with both influenced by geographic and environmental factors. Consequently, patterns of isolation by environment (IBE) and distance (IBD) were identified, with IBE showing a stronger influence on leaf variability. Multivariate statistical analysis revealed that European wild pear populations from the north-western part of the Balkan Peninsula can be divided into two morphological clusters, consistent with their geographical distance and environmental conditions. Our results confirm a high level of phenotypic variability in European wild pear populations, providing additional data on this poorly studied species, emphasizing phenotypic plasticity as a major driver in the adaptation of this noble hardwood species to rapid climate change.
RESUMO
Ertugliflozin, a sodium glucose cotransporter-2 inhibitor, is approved in the United States for treatment of type 2 diabetes mellitus. A novel two-period study design with 14 C microtracer dosing in each period was used to determine absolute oral bioavailability (F) and fraction absorbed (Fa ) of ertugliflozin. Eight healthy adult men received 100-µg i.v. 14 C-ertugliflozin (400 nCi) dose 1 h after a 15-mg oral unlabeled ertugliflozin dose (period 1), followed by 100 µg 14 C-ertugliflozin orally along with 15 mg oral unlabeled ertugliflozin (period 2). Unlabeled ertugliflozin plasma concentrations were determined using high-performance liquid-chromatography tandem mass spectrometry (HPLC-MS/MS). 14 C-ertugliflozin plasma concentrations were determined using HPLC-accelerator mass spectrometry (AMS) and 14 C urine concentrations were determined using AMS. F ((area under the curve (AUC)p.o. /14 C-AUCi.v. )*(14 C-Dosei.v. /Dosep.o. )) and Fa ((14 C_Total_Urinep.o. /14 C_Total_Urinei.v. )* (14 C-Dosei.v. /14 C-Dosep.o. )) were estimated. Estimates of F and Fa were 105% and 111%, respectively. Oral absorption of ertugliflozin was complete under fasted conditions and F was â¼100%. Ertugliflozin was well tolerated.
