Previously, experimental DNA-DNA hybridization (DDH) between Shewanellahaliotis JCM 14758 and Shewanellaalgae JCM 21037 had suggested that the two strains could be considered different species, despite minimal phenotypic differences. The recent isolation of Shewanella sp. MN-01, with 99 % 16S rRNA gene identity to S. algae and S. haliotis, revealed a potential taxonomic problem between these two species. In this study, we reassessed the nomenclature of S. haliotis and S. algae using available whole-genome sequences. The whole-genome sequence of S. haliotis JCM 14758 and ten S. algae strains showed ≥97.7 % average nucleotide identity and >78.9 % digital DDH, clearly above the recommended species thresholds. According to the rules of priority and in view of the results obtained, S. haliotis is to be considered a later heterotypic synonym of S. algae. Because the whole-genome sequence of Shewanella sp. strain MN-01 shares >99 % ANI with S. algae JCM 14758, it can be confidently identified as S. algae.

Early life stress (ELS) is associated with cardiovascular disease (CVD) risk in adulthood, but the underlying vascular mechanisms are poorly understood. Increased hemoglobin and heme have recently been implicated to mediate endothelial dysfunction in several vascular diseases. Chronic physiological stress is associated with alterations in the heme pathway that have been well-described in the literature. However, very little is known about the heme pathway with exposure to ELS or chronic psychosocial stress. Utilizing a mouse model of ELS, maternal separation with early weaning (MSEW), we previously reported that MSEW induces endothelial dysfunction via increased superoxide production. We reasoned that heme dysregulation may be one of the culprits induced by MSEW and sustained throughout adulthood; thus, we hypothesized that MSEW induces heme dysfunction. We investigated whether circulating levels of heme, a circulating pro-oxidant mediator, are increased by MSEW and examined the role of the heme metabolic pathway and heme homeostasis in this process.We found that circulating levels of heme are increased in mice exposed to MSEW and that plasma from MSEW mice stimulated higher superoxide production in cultured mouse aortic endothelial cells (MAECs) compared to plasma from normally reared mice. The heme scavenger hemopexin blunted this enhanced superoxide production. Splenic haptoglobin abundance was significantly lower and hemoglobin levels per red blood cell were significantly higher in MSEW versus control mice. These findings lead us to propose that ELS induces increased circulating heme through dysregulation of the haptoglobin-hemoglobin system representing a mechanistic link between ELS

Background Early life stress (ELS) is an environmental trigger believed to promote increased risk of IBD. Our goal was to identify mechanisms whereby ELS in mice affects susceptibility to and/or severity of gut inflammation. Methods We utilized 2 published animal models of ELS. In the first model, newborn mice were separated from the dam daily for 4 to 8 hours starting on postnatal day 2 and then weaned early on postnatal day 17. Control mice were left undisturbed with the dams until weaning on postnatal day 21. In the second model, dams were fed dexamethasone or vehicle ad libitum in drinking water on postpartum days 1 to 14. Plasma and colonic corticosterone were measured in juvenile and adult mice. Colitis was induced in 4-week-old mice via intraperitoneal injection of interleukin (IL)-10 receptor blocking antibody every 5 days for 15 days. Five or 15 days later, colitis scores and transcripts for Tnf, glucocorticoid receptors, and steroidogenic enzymes were measured. Results Mice exposed to ELS displayed reduced plasma and colonic corticosterone. Control animals showed improvements in indices of inflammation following cessation of interleukin-10 receptor blockade, whereas ELS-exposed animals maintained high levels of Tnf and histological signs of colitis. In colitic animals, prior exposure to ELS was associated with significantly lower expression of genes associated with corticosterone synthesis and responsiveness. Finally, TNF stimulation of colonic crypt cells from ELS mice led to increased inhibition of corticosterone synthesis. Conclusions Our study identifies impaired local glucocorticoid production and responsiveness as a potential mechanism whereby ELS predisposes to chronic colitis in susceptible hosts.

Early life stress (ELS) is an under‐appreciated risk factor for cardiovascular disease (CVD). In humans, adverse childhood experiences (ACEs) or ELS is recognized as inducing behavioral or emotional stress. We reported that young adults exposed to ACEs display enhanced vascular stiffness, increased peripheral resistance, and elevated plasma ET‐1. We hypothesized that vascular endothelial‐derived ET‐1 is associated with vascular dysfunction after exposure to ELS. We hypothesized that endothelial‐derived ET‐1 is linked to vascular dysfunction in ELS. To test this hypothesis, we utilized vascular endothelial‐specific ET‐1 knockout (VEETKO) and flox control mice exposed to normal rearing (NR) or maternal separation with early weaning (MSEW). Briefly, MSEW involves maternal separation for 4h/day (postnatal (PD) 2 to 5), 8h/day (PD6 to 16), and weaned at PD17. NR litters were weaned at PD21. Male and female adult NR and MSEW, flox control (n=3–5) and VEETKO (n=5) mice were used to study acetylcholine (Ach)‐ and sodium nitroprusside (SNP)‐mediated aortic vasorelaxation. Interestingly, aorta from MSEW flox mice showed significantly greater maximal Ach‐mediated vasorelaxation compared to NR flox mice (Flox‐control 74.7% SEM 4.15, Flox‐MSEW 93.7% SEM 1.63, VEETKO‐control 78.0% SEM 6.81, VEETKO‐MSEW 86.9% SEM 2.05; p=0.0023). EC50 responses to Ach were not significantly different (Flox‐NR −6.22 SEM 0.330, Flox‐MSEW −6.88 SEM 0.124, VEETKO‐NR −6.70 SEM 0.144, VEETKO‐MSEW −6.88 SEM 0.268; p=0.066). All responses to SNP were similar. The VEETKO and flox control mice are on a Sv129 background. We previously reported that C57Bl/6J mice exposed to MSEW displayed endothelial dysfunction when compared to NR. Thus, these data suggest that exposure to MSEW has a different mechanistic response to the MSEW protocol with different strains of mice. Future studies will include behavioral studies to determine whether the MSEW protocol in Sv129 mice is distinct from the pro‐anxiety response reported in C57Bl/6J mice. Support or Funding Information Funding K01‐DK‐105038 KAH, RO1 HL136936 JSP and DMPPROmoTE R25 DK 112731

Adverse childhood experiences (ACEs) include exposure to abuse (verbal and physical), neglect, and household dysfunction during childhood. ACEs have long-lasting health impacts including increased risk for cardiovascular disease (CVD) and hypertension in adulthood. However, it is not clear how ACE exposure impacts CVD risk earlier in the life course, particularly in adolescence. To address this gap in knowledge, in this study we hypothesized that ACE exposure is associated with abnormal ambulatory blood pressure (ABP) profiles in adolescents, with an increased incidence of ambulatory hypertension phenotypes that have normal casual clinic BP [e.g., masked hypertension (MH) or blunted nocturnal dipping (BND)]. We utilized 24-h ambulatory BP monitoring (ABPM; Spacelabs) and casual clinic BP to construct a profile of adolescents with and without ACEs. Abnormal ABP profiles included the following categories: ambulatory hypertension (AH, elevated ABP and casual clinic BP ≥95 th percentile for age, sex, and height), white-coat hypertension (WCH, elevated casual clinic BP with normal ABP), MH (normal casual clinic BP with elevated ABP), or BND (drop in ABP < 10% during sleep). This study included 78 male and female adolescents (median age=16) recruited from Children’s of Alabama Pediatric Clinics. Exclusion criteria included known CVD and antihypertensive medication. Participants recorded wake and sleep times in a diary. Based on the ACE questionnaire, 51 (65%) of adolescents experienced at least 1 ACE. The prevalence of abnormal ABP profiles was similar between the group with ACE exposures vs. the group without ACE exposures (34% vs. 36%; P =0.87). In participants with ACE exposure (n=51), 9% had AH, 6% had MH, 19% had WCH, 43.1% had systolic BND and 22% had diastolic BND. In participants without ACEs (n=27), 4% had AH, 4% had MH, 29% had WCH, 37% had systolic BND and 15% had diastolic BND. Further analysis with covariates are necessary. These results suggest that adolescents with ACEs have similar prevalence of abnormal ABP overall, but higher prevalence of individual ABP phenotypes such as AH, MH, and BND compared to adolescents without ACEs.