A captured room temperature stable Wheland intermediate as a key structure for the orthogonal decoration of 4-amino-pyrido[2,3-d]pyrimidin-7 (8H)-ones

Wheland intermediates are usually unstable compounds and only a few have been isolated at very low temperatures. During our work on tyrosine kinase inhibitors, we studied the bromination of 7 in order to obtain a dibromo substituted pyrido[2,3-d]pyrimidin-7(8H)-one which could be orthogonally decorated. Surprisingly, treatment of 7 with 3 equiv. of Br2 in acetic acid (AcOH) afforded 12, a captured room temperature stable Wheland bromination intermediate stabilized by the bromination of the imino tautomer of the amino group at C4 of the pyridopyrimidine skeleton. The structure was confirmed by crystal structure determination from powder X-ray diffraction data. Treatment of 12 with DMSO afforded the dibromo substituted compound 13 presenting a bromine atom at C6 and C5-C6 unsaturation. 13 was directly accessed by treating 7 with N-bromosuccinimide (NBS), a protocol extended to other compounds using NBS or N-iodosuccinimide (NIS) to afford 6-halo substituted systems. 26, bearing an iodine at C6 and a p-bromophenylamino at C2, allows the orthogonal decoration of pyridopyrimidines

Rewinding the invasion history of monk parakeets in Barcelona city: 1976-2022

Predicting the future abundance and distribution of introduced alien species is crucial to mitigate their impact on ecosystems, but this has been shown to be highly challenging. A good approach to obtain crucial clues to the root causes behind dynamic changes over time and space of invasive species is historical resurveys. Barcelona holds one of the largest densities in Europe of monk parakeets Myiopsitta monachus, a highly successful invasive avian alien species. In this study, we evaluate population size, population growth rates and range expansion across the city, performing periodic nest and chamber counts from detection of the first nest in 1976 to 2022. Population estimates of monk parakeets during the study period showed a steady increase, reaching 6,444 ± 449 individuals in 2022. The population exhibited exponential growth with a mean population growth rate of r = 0.19 per year, which means a population doubling time of 3.7 years. Furthermore, two phases were evident: the first from 1976 to 1994 with a growth rate of 0.37 and a population doubling time of 1.9 years; and the second from 1999 to 2022 with a growth rate of 0.08 and a time to double the population of nine years. Moreover, we document the expansion of the range during our study through the colonisation of new areas, which fitted to a diffusion model for the whole period. Currently, the growth rate of the invasive monk parakeet population does not appear to be limited by resources, nest availability, disease, or predators and we expect them to continue increasing and expanding their range if no control measures are take

The reproductive capacity of Monk Parakeets Myiopsitta monachus is higher in their invasive range

Breeding parameters for Monk Parakeets Myiopsitta monachus nesting in Barcelona, Spain, were collected for 651 nests over five breeding seasons. This invasive population has a high reproductive capacity compared with the species in the native range: fledging success was double, the percentage of pairs attempting second broods three times higher and 55% of first-year birds bred compared with almost zero in South America

Integrative analysis reveals novel pathways mediating the interaction between adipose tissue and pancreatic islets in obesity in rats

10.1007/s00125-014-3205-0Aims/hypothesis: Comprehensive characterisation of the interrelation between the peripancreatic adipose tissue and the pancreatic islets promises novel insights into the mechanisms that regulate beta cell adaptation to obesity. Here, we sought to determine the main pathways and key molecules mediating the crosstalk between these two tissues during adaptation to obesity by the way of an integrated inter-tissue, multi-platform analysis. Methods: Wistar rats were fed a standard or cafeteria diet for 30 days. Transcriptomic variations by diet in islets and peripancreatic adipose tissue were examined through microarray analysis. The secretome from peripancreatic adipose tissue was subjected to a non-targeted metabolomic and proteomic analysis. Gene expression variations in islets were integrated with changes in peripancreatic adipose tissue gene expression and protein and metabolite secretion using an integrated inter-tissue pathway and network analysis. Results: The highest level of data integration, linking genes differentially expressed in both tissues with secretome variations, allowed the identification of significantly enriched canonical pathways, such as the activation of liver/retinoid X receptors, triacylglycerol degradation, and regulation of inflammatory and immune responses, and underscored interaction network hubs, such as cholesterol and the fatty acid binding protein 4, which were unpredicted through single-tissue analysis and have not been previously implicated in the peripancreatic adipose tissue crosstalk with beta cells. Conclusions/interpretation: The integrated analysis reported here allowed the identification of novel mechanisms and key molecules involved in peripancreatic adipose tissue interrelation with beta cells during the development of obesity;