Biogenesis of Pro-senescent Microparticles by Endothelial Colony Forming Cells from Premature Neonates is driven by SIRT1-Dependent Epigenetic Regulation of MKK6.

Senescent cells may exert detrimental effect on microenvironment through the secretion of soluble factors and the release of extracellular vesicles, such as microparticles, key actors in ageing and cardiovascular diseases. We previously reported that sirtuin-1 (SIRT1) deficiency drives accelerated senescence and dysfunction of endothelial colony-forming cells (ECFC) in PT neonates. Because preterm birth (PT) increases the risk for cardiovascular diseases during neonatal period as well as at adulthood, we hypothesized that SIRT1 deficiency could control the biogenesis of microparticles as part of a senescence-associated secretory phenotype (SASP) of PT-ECFC and investigated the related molecular mechanisms. Compared to control ECFC, PT-ECFC displayed a SASP associated with increased release of endothelial microparticles (EMP), mediating a paracrine induction of senescence in naïve endothelial cells. SIRT1 level inversely correlated with EMP release and drives PT-ECFC vesiculation. Global transcriptomic analysis revealed changes in stress response pathways, specifically the MAPK pathway. We delineate a new epigenetic mechanism by which SIRT1 deficiency regulates MKK6/p38 <sup>MAPK</sup> /Hsp27 pathway to promote EMP biogenesis in senescent ECFC. These findings deepen our understanding of the role of ECFC senescence in the disruption of endothelial homeostasis and provide potential new targets towards the control of cardiovascular risk in individuals born preterm

Corrective shoeing in horses: analysis of the adaptation period to the new condition imposed

Corrective shoeing is a method commonly used to alter the locomotion pattern in animals or as therapy for various disorders of the locomotive system of horses. However, to date, there have been no scientific studies discussing the period during which animals adapt to this type of intervention. The goal of this study was to evaluate the horseshoe adaptation period with the toe or heel elevated by six degrees at 0, 48, and 96 hours after each type of shoeing. For this analysis, the horses were recorded while walking on a treadmill. Stride length and gait qualitative analyzes were performed using Dvideow software. The level of significance adopted was 5%. In the present study, there was no significant difference between the evaluation times; elevating the toe or heel by six degrees do not generates discomfort during locomotion, therefore, horses are able to return to a regular exercise or training routine immediately after shoeing

Aging and individual differences in binding during sentence understanding: Evidence from temporary and global syntactic attachment ambiguities

We report an investigation of aging and individual differences in binding information during sentence understanding. An age-continuous sample of adults (N=91), ranging from 18 to 81 years of age, read sentences in which a relative clause could be attached high to a head noun NP1, attached low to its modifying prepositional phrase NP2 (e.g., The son of the princess who scratched himself/herself in public was humiliated), or in which the attachment site of the relative clause was ultimately indeterminate (e.g., The maid of the princess who scratched herself in public was humiliated). Word-by-word reading times and comprehension (e.g., who scratched?) were measured. A series of mixed-effects models were fit to the data, revealing: (1) that, on average, NP1-attached sentences were harder to process and comprehend than NP2-attached sentences; (2) that these average effects were independently moderated by verbal working memory capacity and reading experience, with effects that were most pronounced in the oldest participants and; (3) that readers on average did not allocate extra time to resolve global ambiguities, though older adults with higher working memory span did. Findings are discussed in relation to current models of lifespan cognitive development, working memory, language experience, and the role of prosodic segmentation strategies in reading. Collectively, these data suggest that aging brings differences in sentence understanding, and these differences may depend on independent influences of verbal working memory capacity and reading experience