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

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

Environmental Enrichment Preceding Early Adulthood Methylphenidate Treatment Leads to Long Term Increase of Corticosterone and Testosterone in the Rat

Attention-deficit/hyperactivity disorder (ADD/ADHD) has been emerging as a world-wide psychiatric disorder. There appears to be an increasing rate of stimulant drug abuse, specifically methylphenidate (MPH) which is the most common treatment for ADHD, among individuals who do not meet the criteria for ADHD and particularly for cognitive enhancement among university students. However, the long term effects of exposure to MPH are unknown. Thus, in light of a developmental approach in humans, we aimed to test the effects of adolescence exposure to enriched environment (EE) followed by MPH administration during early adulthood, on reactions to stress in adulthood. Specifically, at approximate adolescence [post natal days (PND) 30–60] rats were reared in EE and were treated with MPH during early adulthood (PND 60–90). Adult (PND 90–92) rats were exposed to mild stress and starting at PND 110, the behavioral and endocrine effects of the combined drug and environmental conditions were assessed. Following adolescence EE, long term exposure to MPH led to decreased locomotor activity and increased sucrose preference. EE had a beneficial effect on PPI (attentive abilities), which was impaired by long term exposure to MPH. Finally, the interaction between EE and, exposure to MPH led to long-term elevated corticosterone and testosterone levels. In view of the marked increase in MPH consumption over the past decade, vigilance is crucial in order to prevent potential drug abuse and its long term detrimental consequences

Could chiropractors screen for adverse drug events in the community? Survey of US chiropractors

Abstract Background The "Put Prevention into Practice" campaign of the US Public Health Service (USPHS) was launched with the dissemination of the Clinician's Handbook of Preventive Services that recommended standards of clinical care for various prevention activities, including preventive clinical strategies to reduce the risk of adverse drug events. We explored whether nonprescribing clinicians such as chiropractors may contribute to advancing drug safety initiatives by identifying potential adverse drug events in their chiropractic patients, and by bringing suspected adverse drug events to the attention of the prescribing clinicians. Methods Mail survey of US chiropractors about their detection of potential adverse drug events in their chiropractic patients. Results Over half of responding chiropractors (62%) reported having identified a suspected adverse drug event occurring in one of their chiropractic patients. The severity of suspected drug-related events detected ranged from mild to severe. Conclusions Chiropractors or other nonprescribing clinicians may be in a position to detect potential adverse drug events in the community. These detection and reporting mechanisms should be standardized and policies related to clinical case management of suspected adverse drug events occurring in their patients should be developed