Expedient synthesis of an atypical oxazolidinone compound library

In order to address the current downturn in the drug discovery pipeline, initiatives are being undertaken to synthesise screening libraries of sp3-rich, low molecular weight compounds. As part of the European Lead Factory initiative, the synthesis and derivatisation of a simple hexahydrooxazolo[5,4-c]pyridin-2(1H)-one bicyclic carbamate has been achieved. The synthetic route employed involved a telescoped hetero-Diels-Alder/[2,3]-sigmatropic rearrangement/cyclisation sequence to deliver the desired core scaffold containing two points for further diversification. When applied, this synthesis was found to be robust and scalable which allowed the production of a 155 compound library

The Atlantic salmon genome provides insights into rediploidization

The whole-genome duplication 80 million years ago of the common ancestor of salmonids (salmonid-specific fourth vertebrate whole-genome duplication, Ss4R) provides unique opportunities to learn about the evolutionary fate of a duplicated vertebrate genome in 70 extant lineages. Here we present a high-quality genome assembly for Atlantic salmon (Salmo salar), and show that large genomic reorganizations, coinciding with bursts of transposon-mediated repeat expansions, were crucial for the post-Ss4R rediploidization process. Comparisons of duplicate gene expression patterns across a wide range of tissues with orthologous genes from a pre-Ss4R outgroup unexpectedly demonstrate far more instances of neofunctionalization than subfunctionalization. Surprisingly, we find that genes that were retained as duplicates after the teleost-specific whole-genome duplication 320 million years ago were not more likely to be retained after the Ss4R, and that the duplicate retention was not influenced to a great extent by the nature of the predicted protein interactions of the gene products. Finally, we demonstrate that the Atlantic salmon assembly can serve as a reference sequence for the study of other salmonids for a range of purposes.publishedVersio

Splenic artery embolization: technically feasible but not necessarily advantageous.

The spleen is the second most commonly injured organ in cases of abdominal trauma. Management of splenic injury depends on the clinical status of the patient and can include nonoperative management (NOM), splenic artery embolization (SAE), surgery (operative splenic salvage or splenectomy), or a combination of these treatments. In nonoperatively managed cases, SAE is sometimes used to control haemorrhage. However, the indications for SAE have not been clearly defined and, in some cases, the potential complications of the procedure may outweigh its benefits.This article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site

Exposure to metal mixture and growth indicators at 4-5 years. A study in the INMA-Asturias cohort

Exposure to toxic and non-toxic metals impacts childhood growth and development, but limited data exists on exposure to metal mixtures. Here, we investigated the effects of exposure to individual metals and a mixture of barium, cadmium, cobalt, lead, molybdenum, zinc, and arsenic on growth indicators in children 4-5 years of age.The authors would particularly like to thank the staff from Hospital San Agustin in Aviles for their valuable support and all the participants enrolled in the INMA-Asturias cohort for their generous collaboration. This research was funded by grants from, CIBERESP (PhD-employment-contract and fellowship for short stays abroad-2019), ISCIII: PI04/2018, PI09/02311, PI13/02429, PI18/00909 co-funded by the European Regional Development Fund (FEDER), “A way to make Europe"/"Investing in your future”; Obra Social Cajastur/Fundación Liberbank, and Universidad de Oviedo. A.J.S.P. and M.R.K. are funded by the following projects P01ES022832, RD83544201, R25CA134286, and P42ES007373. A.J.S.P. is also funded by CIDEGENT /2020/050. We thank Katherine Thieltges from Edanz (https://www.edanz.com/ac) for editing a draft of this manuscript.Peer reviewe