Nuclear WRAP53 promotes neuronal survival and functional recovery after stroke

Failure of neurons to efficiently repair DNA double-strand breaks (DSBs) contributes to cerebral damage after stroke. However, the molecular machinery that regulates DNA repair in this neurological disorder is unknown. Here, we found that DSBs in oxygen/glucose-deprived (OGD) neurons spatiotemporally correlated with the up-regulation of WRAP53 (WD40-encoding p53-antisense RNA), which translocated to the nucleus to activate the DSB repair response. Mechanistically, OGD triggered a burst in reactive oxygen species that induced both DSBs and translocation of WRAP53 to the nucleus to promote DNA repair, a pathway that was confirmed in an in vivo mouse model of stroke. Noticeably, nuclear translocation of WRAP53 occurred faster in OGD neurons expressing the Wrap53 human nonsynonymous single-nucleotide polymorphism (SNP) rs2287499 (c.202C>G). Patients carrying this SNP showed less infarct volume and better functional outcome after stroke. These results indicate that WRAP53 fosters DNA repair and neuronal survival to promote functional recovery after stroke

Synthesis and biological evaluation of oligosaccharides related to the molecule signals in plant defence and the Rhizobium-legume symbiosis

Microbial Biotechnolog

The Right to Code and Share Arms

Glycerol is, to date, the most widely used cryoprotectant to freeze stallion spermatozoa at concentrations between 2% and 5%. Cryoprotectant toxicity has been claimed to be the single most limiting factor for the success of cryopreservation. In order to evaluate the toxic effects of the concentrations of glycerol used in practice, stallion spermatozoa were incubated in Biggers Whitten and Whittingham (BWW) media supplemented with 0%, 0.5%, 1.5%, 2.5%, 3.5%, and 5% glycerol. In two additional experiments, a hyposmotic (75 mOsm/kg) and a hyperosmotic (900 mOsm/kg) control media were included. Sperm parameters evaluated included cell volume, membrane integrity, lipid peroxidation, caspase 3, 7, and 8 activation, mitochondrial membrane potential, and integrity of the cytoskeleton. Glycerol exerted toxicity at concentrations 3.5% and the maximal toxicity was observed at 5%. The actin cytoskeleton was especially sensitive to glycerol presence, inducing rapid F actin depolymerization at concentrations over 1.5%. The sperm membrane and the mitochondria were other structures affected. The toxicity of glycerol is apparently related to osmotic and nonosmotic effects. In view of our results the concentration of glycerol in the freezing media for stallion spermatozoa should not surpass 2.5%.Funding Agencies|Ministerio de Ciencia e Innovacion-FEDER Madrid, Spain|AGL 2010 20758 (GAN)|Inia|RZ2008-00018-00-00|Junta de Extremadura FEDER GR|10010

Impact of cooking method on phenolic composition and antioxidant potential of four varieties of Phaseolus vulgaris L. and Glycine max L.

The present study aimed to investigate the effects of different cooking conditions - atmospheric (100°C) and pressure cooking (115°C) - on the phenolic composition and antioxidant activity of methanolic extracts of four Phaseolus vulgaris varieties and soy (Glycine max). Contrary to soy, in P. vulgaris varieties both cooking methods increased drastically the total phenolic, flavonoid, and ortho-diphenol content, as well as antioxidant capacity. These results were corroborated by HPLC analysis, where an overall increase of phenolic acids and flavonoids was detected in processed samples. However, draining the cooking water significantly decreased phenolic acids, flavonoids and antioxidant activity in all P. vulgaris varieties and as well as soy. The hypothesis that cooking increases the compound accessibility and nutritional value through increased release of phytochemicals was verified in the present study for P. vulgaris varieties. Keeping the cooking water is crucial to the increased nutritional value of all Phaseolus varieties. Overall, compared with the tested varieties of Phaseolus, soy, to which many health benefits are attributed, is not the best legume source of antioxidants.The author Catarina I. Teixeira-Guedes acknowledges the financial support provided FCT-Portuguese Foundation for Science and Technology (SFRH/BD/52544/2014), under the Doctoral Program “Agricultural Production Chains – from fork to farm” (PD/00122/ 2012). This work was supported by the European Investment Funds FEDER/COMPETE/POCI– Operational Competitiveness and Internationalization Programme [POCI-01-0145-FEDER-006958] and Portuguese Foundation for Science and Technology (FCT) [UID/AGR/ 04033/2019]; Project I&D Interact - Integrative Research in Environment, Agro-Chain and Technology [NORTE-01-0145-FEDER000017], co-financed by European Regional Development Fund (FEDER) through NORTE 2020 (Programa Operacional Regional do Norte 2014/2020).info:eu-repo/semantics/publishedVersio

An Atlas of Epithelial Cell States and Plasticity in Lung Adenocarcinoma

Understanding the cellular processes that underlie early lung adenocarcinoma (LUAD) development is needed to devise intervention strategies1. Here we studied 246,102 single epithelial cells from 16 early-stage LUADs and 47 matched normal lung samples. Epithelial cells comprised diverse normal and cancer cell states, and diversity among cancer cells was strongly linked to LUAD-specific oncogenic drivers. KRAS mutant cancer cells showed distinct transcriptional features, reduced differentiation and low levels of aneuploidy. Non-malignant areas surrounding human LUAD samples were enriched with alveolar intermediate cells that displayed elevated KRT8 expression (termed KRT8+ alveolar intermediate cells (KACs) here), reduced differentiation, increased plasticity and driver KRAS mutations. Expression profiles of KACs were enriched in lung precancer cells and in LUAD cells and signified poor survival. In mice exposed to tobacco carcinogen, KACs emerged before lung tumours and persisted for months after cessation of carcinogen exposure. Moreover, they acquired Kras mutations and conveyed sensitivity to targeted KRAS inhibition in KAC-enriched organoids derived from alveolar type 2 (AT2) cells. Last, lineage-labelling of AT2 cells or KRT8+ cells following carcinogen exposure showed that KACs are possible intermediates in AT2-to-tumour cell transformation. This study provides new insights into epithelial cell states at the root of LUAD development, and such states could harbour potential targets for prevention or intervention