Synthesis and biological studies of new quinazolines with ether functions in position 2

International audienc

Last Men Standing: Chlamydatus Portraits and Public Life in Late Antique Corinth

Notable among the marble sculptures excavated at Corinth are seven portraits of men wearing the long chlamys of Late Antique imperial office. This unusual costume, contemporary portrait heads, and inscribed statue bases all help confirm that new public statuary was created and erected at Corinth during the 4th and 5th centuries. These chlamydatus portraits, published together here for the first time, are likely to represent the Governor of Achaia in his capital city, in the company of local benefactors. Among the last works of the ancient sculptural tradition, they form a valuable source of information on public life in Late Antique Corinth

30-day morbidity and mortality of sleeve gastrectomy, Roux-en-Y gastric bypass and one anastomosis gastric bypass: a propensity score-matched analysis of the GENEVA data

Background: There is a paucity of data comparing 30-day morbidity and mortality of sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and one anastomosis gastric bypass (OAGB). This study aimed to compare the 30-day safety of SG, RYGB, and OAGB in propensity score-matched cohorts. Materials and methods: This analysis utilised data collected from the GENEVA study which was a multicentre observational cohort study of bariatric and metabolic surgery (BMS) in 185 centres across 42 countries between 01/05/2022 and 31/10/2020 during the Coronavirus Disease-2019 (COVID-19) pandemic. 30-day complications were categorised according to the Clavien–Dindo classification. Patients receiving SG, RYGB, or OAGB were propensity-matched according to baseline characteristics and 30-day complications were compared between groups. Results: In total, 6770 patients (SG 3983; OAGB 702; RYGB 2085) were included in this analysis. Prior to matching, RYGB was associated with highest 30-day complication rate (SG 5.8%; OAGB 7.5%; RYGB 8.0% (p = 0.006)). On multivariate regression modelling, Insulin-dependent type 2 diabetes mellitus and hypercholesterolaemia were associated with increased 30-day complications. Being a non-smoker was associated with reduced complication rates. When compared to SG as a reference category, RYGB, but not OAGB, was associated with an increased rate of 30-day complications. A total of 702 pairs of SG and OAGB were propensity score-matched. The complication rate in the SG group was 7.3% (n = 51) as compared to 7.5% (n = 53) in the OAGB group (p = 0.68). Similarly, 2085 pairs of SG and RYGB were propensity score-matched. The complication rate in the SG group was 6.1% (n = 127) as compared to 7.9% (n = 166) in the RYGB group (p = 0.09). And, 702 pairs of OAGB and RYGB were matched. The complication rate in both groups was the same at 7.5 % (n = 53; p = 0.07). Conclusions: This global study found no significant difference in the 30-day morbidity and mortality of SG, RYGB, and OAGB in propensity score-matched cohorts

30-Day morbidity and mortality of bariatric metabolic surgery in adolescence during the COVID-19 pandemic – The GENEVA study

Background: Metabolic and bariatric surgery (MBS) is an effective treatment for adolescents with severe obesity. Objectives: This study examined the safety of MBS in adolescents during the coronavirus disease 2019 (COVID-19) pandemic. Methods: This was a global, multicentre and observational cohort study of MBS performed between May 01, 2020, and October 10,2020, in 68 centres from 24 countries. Data collection included in-hospital and 30-day COVID-19 and surgery-specific morbidity/mortality. Results: One hundred and seventy adolescent patients (mean age: 17.75 ± 1.30 years), mostly females (n = 122, 71.8%), underwent MBS during the study period. The mean pre-operative weight and body mass index were 122.16 ± 15.92 kg and 43.7 ± 7.11 kg/m2, respectively. Although majority of patients had pre-operative testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n = 146; 85.9%), only 42.4% (n = 72) of the patients were asked to self-isolate pre-operatively. Two patients developed symptomatic SARS-CoV-2 infection post-operatively (1.2%). The overall complication rate was 5.3% (n = 9). There was no mortality in this cohort. Conclusions: MBS in adolescents with obesity is safe during the COVID-19 pandemic when performed within the context of local precautionary procedures (such as pre-operative testing). The 30-day morbidity rates were similar to those reported pre-pandemic. These data will help facilitate the safe re-introduction of MBS services for this group of patients

Screening for antimitotic compounds using the cdc25 tyrosine phosphatase, an activator of the mitosis-inducing p34cdc2/cyclin Bcdc13 protein kinase

A universal intracellular factor, the > (MPF), triggers the G2/M transition of the cell cycle in all organisms. In late G2, it is present as an inactive complex of tyrosine-phosphorylated p34cdc2 and unphosphorylated cyclin B(cdc13). In M phase, its activation as an active MPF displaying histone H1 kinase activity originates from the specific tyrosine dephosphorylation of the p34cdc2 subunit by the tyrosine phosphatase p80cdc25. We describe here a colorimetric assay of recombinant human cdc25A tyrosine phosphatase used as a cell cycle-specific target to screen for antimitotic compounds. The glutathione-S-transferase/cdc25A tyrosine phosphatase fusion protein is produced in large amounts in Escherichia coli and easily purified by affinity chromatography on glutathione-agarose. Optimal purification, storage and assay conditions (concentrations of enzyme, p-nitrophenylphosphate and dithiothreitol; duration of assay) have been determined. Using this system we tested 15 compounds currently used in cancer treatment; none of them displayed any inhibitory activity. However, the assay detected the inhibitory activity of vanadate, a reported tyrosine phosphatase inhibitor. The simplicity, speed and possible extensive automation of this assay using an essential cell cycle-regulating component provide a highly specific mechanism-based screen for antimitotic drugs discovery

Structure and expression of an Otx5-related gene in the dogfish Scyliorhinus canicula: evidence for a conserved role of Otx5 and Crxgenes in the specification of photoreceptors.

We report the full-length coding sequence and the expression pattern during neurulation and early organogenesis of ScOtx5, a novel member of the Otx gene family in the dogfish Scyliorhinus canicula. Phylogenetic analyses confirm that ScOtx5 is closely related to the Xenopus XlOtx5/ 5bgenes, and also to the Crx genes characterized in mammals and zebrafish. This supports the hypothesis that these genes define a third gnathostome Otx orthology class. During neurulation, ScOtx5 transcripts are detected in the foregut diverticulum and the anterior neuroectoderm. At the onset of organogenesis, ScOtx5 is transcribed over a broad domain spanning the whole prosencephalon and mesencephalon, albeit with a much lower signal intensity than its paralogues Otx1 and Otx2. At later stages, four major expression sites are observed: the developing eye and epiphysis, the olfactory placodes and a broad epidermal domain in the dorsal part of the head. In the embryonic eye, the signal is first detected in the presumptive pigmented retina and slightly later in the adjacent outer layer of the neural retina, fated to photoreceptors. The comparison of this expression pattern with those of osteichthyan Otx genes suggests that a role in the specification of photoreceptors may correspond to a functional specialization of Otx5and Crx genes, fixed early in the gnathostome lineage, prior to the splitting of chondrichthyans and osteichthyans. In contrast, the roles played by ScOtx5 in the retinal pigmented epithelium or in the olfactory placodes may be fulfilled by different combinations of paralogous genes in other gnathostome taxa

Characterization of Brachyury genes in the dogfish S. canicula and the lamprey L. fluviatilis. Insights into gastrulation in a chondrichthyan.

In order to gain insights into the evolution of gastrulation mechanisms among vertebrates, we have characterized a Brachyury-related gene in a lamprey, Lampetra fluviatilis, and in a chondrichthyan, Scyliorhinus canicula. These two genes, respectively termed LfT and ScT, share with their osteichthyan counterparts prominent expression sites in the developing notochord, the tailbud, but also a transient expression in the prechordal plate, which is likely to be ancestral among vertebrates. In addition, the lamprey LfT gene is transcribed in the endoderm of the pharyngeal arches and the epiphysis, two expression sites that have not been reported thus far in gnathostomes, and, as in the chick, in the differentiating nephrotomes. Since Brachyury expression in nascent mesoderm and endoderm is highly conserved among vertebrates as well as cephalochordates, we have used this marker to identify these cell populations during gastrulation in the dogfish. The results suggest that these cells are initially present over the whole margin of the blastoderm and are displaced during gastrulation to its posterior part, which may correspond to the site of mesoderm and endoderm internalization. These data provide the first molecular characterization of gastrulation in a chondrichthyan. They indicate that gastrulation in the dogfish and in some amniotes shares striking similarities despite the phylogenetic distance between these species. This supports the hypothesis that the extensively divergent morphologies of gastrulae among vertebrates largely result from adaptations to the presence of yolk