A resonant-term-based model including a nascent disk, precession, and oblateness: application to GJ 876

Investigations of two resonant planets orbiting a star or two resonant satellites orbiting a planet often rely on a few resonant and secular terms in order to obtain a representative quantitative description of the system's dynamical evolution. We present a semianalytic model which traces the orbital evolution of any two resonant bodies in a first- through fourth-order eccentricity or inclination-based resonance dominated by the resonant and secular arguments of the user's choosing. By considering the variation of libration width with different orbital parameters, we identify regions of phase space which give rise to different resonant ''depths,'' and propose methods to model libration profiles. We apply the model to the GJ 876 extrasolar planetary system, quantify the relative importance of the relevant resonant and secular contributions, and thereby assess the goodness of the common approximation of representing the system by just the presumably dominant terms. We highlight the danger in using ''order'' as the metric for accuracy in the orbital solution by revealing the unnatural libration centers produced by the second-order, but not first-order, solution, and by demonstrating that the true orbital solution lies somewhere ''in-between'' the third- and fourth-order solutions. We also present formulas used to incorporate perturbations from central-body oblateness and precession, and a protoplanetary or protosatellite thin disk with gaps, into a resonant system. We quantify these contributions to the GJ 876 system, and thereby highlight the conditions which must exist for multi-planet exosystems to be significantly influenced by such factors. We find that massive enough disks may convert resonant libration into circulation; such disk-induced signatures may provide constraints for future studies of exoplanet systems.Comment: 39 pages of body text, 21 figures, 5 tables, 1 appendix, accepted for publication in Celestial Mechanics and Dynamical Astronom

Baroreflex buffering is reduced with age in healthy men

Background— Baroreflex buffering is an important mechanism in arterial blood pressure control. The effect of healthy (physiological) aging on tonic baroreflex buffering in humans is unknown. Methods and Results— Baroreflex buffering was determined in 27 young (aged 25±1 years) and 16 older (aged 65±1 years) healthy normotensive men by measuring the potentiation of the systolic blood pressure (SBP) responses to a phenylephrine bolus (BRBbolus) and incremental infusion (BRBslope) during compared with before ganglionic blockade with trimethaphan. The SBP responses to phenylephrine either were not different or greater in the older men before ganglionic blockade, but smaller during ganglionic blockade. BRBbolus (2.1±0.4 versus 5.1±0.7, P<0.001) and BRBslope (1.6±0.2 versus 3.5±0.4, P<0.0001) were ≈115% smaller in the older men. Baroreflex buffering was not consistently related to mean levels or variability of blood pressure or heart rate, or to cardiovagal baroreflex sensitivity, but correlated with muscle sympathetic nerve activity (BRBbolus: r=−0.55, BRBslope: r=−0.69, P<0.005) and the SBP responses to phenylephrine during ganglionic blockade (BRBbolus: r=0.53; BRBslope: r=0.98, P<0.0001). BRBbolus was also inversely related to the SBP response to phenylephrine before ganglionic blockade (r=−0.78, P<0.0001). Conclusions— Physiological aging in men is associated with a marked reduction in baroreflex buffering. The decrease in baroreflex buffering with aging is related to increases in basal sympathetic nerve activity and reductions in systemic α1–adrenergic vascular responsiveness. These findings are helpful for interpreting changes in baroreflex buffering in older patients with cardiovascular disease, as well as changes in responsiveness to vasoactive drugs with aging

Women have lower tonic autonomic support of arterial blood pressure and less effective baroreflex buffering than men

BACKGROUND: Short-term and tonic regulation of arterial blood pressure (BP) differ in premenopausal women and men of similar age. The autonomic nervous system (ANS) plays a critical role in BP regulation. METHODS AND RESULTS: To test the hypothesis that women have lower tonic ANS support of BP (reduction in intra-arterial BP during acute ganglionic blockade [GB] with intravenous trimethaphan) and less effective baroreflex buffering (BRB) of BP (potentiation of the systolic BP [SBP] response to bolus phenylephrine during versus before GB) than men, 51 healthy adults, 22 premenopausal women (aged 28+/-1 years, mean+/-SE) and 29 men (aged 27+/-1 years), were studied. Women had lower baseline SBP and plasma catecholamine concentrations than men (P<0.05). Tonic ANS support of BP was approximately 50% to 65% lower in the women (P<0.001). The reductions in BP during GB were related to baseline plasma catecholamine concentrations (r=-0.31 to -0.41, P<0.05). Acute BRB of BP was 47% smaller in the women (3.3+/-0.5 versus 6.3+/-0.9, P=0.006) and was related to the SBP responses to phenylephrine before GB (R2=0.71, P<0.0001). Systemic alpha1-adrenergic vascular responsiveness (SBP response to bolus phenylephrine during GB) was not different (women 21.5+/-2 mm Hg versus men 18.6+/-2 mm Hg, P=0.3). CONCLUSIONS: Premenopausal women have lower tonic sympathoadrenal activity-related ANS support of BP and less effective BRB of BP than men of similar age. The lower tonic ANS support of BP could contribute to the lower chronic BP levels of premenopausal women, whereas attenuated BRB of BP may help explain less effective BP regulation in women in response to vasoactive drugs and acute stress

Inhibitors of osteoblastogenesis in early human milk and maternal serum: evidence for protective properties of mother’s milk on bone

Objective: Lactation is associated with a dramatic increase of maternal bone turnover, leading to a reversible bone loss. Early life nutrition may influence later osteoporosis risk. Proteins synthesized by the group of wingless (Wnt) genes are key mediators of osteoblastogenesis and bone formation. We aimed to investigate maternal milk and serum concentrations of the inhibitors of the Wnt signaling pathway, Dickkopf-1 (DKK-1) and sclerostin. Material and methods: In 80 women, maternal milk and serum concentrations of DKK-1 and sclerostin were determined by ELISA on the 3rd–4th day postpartum. Concentrations were associated with various maternal, gestational and neonatal characteristics. Results: DKK-1 and sclerostin were detectable in early milk [mean ± SD: 817.17 ± 259.61 pg/mL, median (range) 258.04 (2452.40–53.17) pg/mL, respectively] at significantly lower concentrations than in maternal serum [mean ± SD: 3375.36 ± 416.75 pg/mL, median (range) 16 200.54 (58 832.00–3012.60) pg/mL, respectively], (p &lt;.000). Maternal milk sclerostin concentrations positively correlated with respective serum ones (r = 0.599, p =.000). Maternal serum and milk sclerostin concentrations positively correlated with maternal body mass index (r = 0.37, p =.001 and r =0.38, p =.000, respectively), while maternal serum sclerostin concentrations were higher in primiparas (p =.002). Conclusion: DKK-1 and sclerostin are present in early human milk at significantly lower concentrations, compared with maternal serum, probably contributing to the short- and long-term benefits of mother’s milk for bone health. Moreover, the large amounts of both substances in maternal serum may represent disruption of the Wnt cascade, contributing to the well-known lactation-associated bone loss, which seems to be greater in primiparas and obese mothers. © 2018, © 2018 Informa UK Limited, trading as Taylor &amp; Francis Group

Adipokines and metabolic regulators in human and experimental pulmonary arterial hypertension

Pulmonary hypertension (PH) is associated with meta-inflammation related to obesity but the role of adipose tissue in PH pathogenesis is unknown. We hypothesized that adipose tissue-derived metabolic regulators are altered in human and experimental PH. We measured circulating levels of fatty acid binding protein 4 (FABP-4), fibroblast growth factor-21 (FGF-21), adiponectin, and the mRNA levels of FABP-4, FGF-21, and peroxisome proliferator-activated receptor γ (PPARγ) in lung tissue of patients with idiopathic PH and healthy controls. We also evaluated lung and adipose tissue expression of these mediators in the three most commonly used experimental rodent models of pulmonary hypertension. Circulating levels of FABP-4, FGF-21, and adiponectin were significantly elevated in PH patients compared to controls and the mRNA levels of these regulators and PPARγ were also significantly increased in human PH lungs and in the lungs of rats with experimental PH compared to controls. These findings were coupled with increased levels of adipose tissue mRNA of genes related to glucose uptake, glycolysis, tricarboxylic acid cycle, and fatty acid oxidation in experimental PH. Our results support that metabolic alterations in human PH are recapitulated in rodent models of the disease and suggest that adipose tissue may contribute to PH pathogenesis. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Preadipocyte factor-1 in maternal, umbilical cord serum and breast milk: The impact of fetal growth

Background/Objective: To study the concentrations of preadipocyte factor-1 (Pref-1) -an inhibitor of adipocyte differentiation, implicated in adipose tissue metabolism, late metabolic disorders and fetal growth- in maternal and umbilical cord serum, as well as maternal milk and correlate above concentrations with intrauterine growth and other perinatal parameters. Material and methods: Pref-1 concentrations were determined by ELISA in antepartum maternal and umbilical cord serum, as well as day 3 to 4 postpartum breast milk, deriving from 80 women, who delivered 40 appropriate (AGA), 20 large for gestational age (LGA) and 20 intrauterine growth restricted (IUGR) neonates, classified by the use of customized birth-weight standards adjusted for significant determinants of fetal growth. Results: Umbilical cord serum Pref-1 concentrations were significantly higher than antepartum maternal ones (p &lt; 0.001), while breast milk concentrations were the lowest (p &lt; 0.001 concerning umbilical serum, p &lt; 0.001 concerning maternal serum). Umbilical cord serum Pref-1 concentrations were significantly lower in the LGA group than in the AGA one (p = 0.044). Breast milk and maternal serum Pref-1 concentrations did not differ between the three intrauterine growth groups. Maternal serum and breast milk Pref-1 concentrations did not correlate with maternal age, body mass index before and after gestation, birth weight, body length, and customized centile. A positive weak correlation was recorded between maternal serum and milk Pref-1 concentrations (r = 0.238, p = 0.034). Conclusions: Pref-1 concentrations in umbilical cord serum are higher than in antepartum maternal serum, probably pointing to its fetal origin and role in intrauterine growth. Breast milk concentrations, being extremely low, and possibly implying infant protection from metabolic disorders, positively correlate with maternal serum ones, conceivably suggesting a transfer of the substance from the circulation to the breast. Umbilical cord serum Pref-1 concentrations were lower in LGA fetuses/neonates, as compared to respective AGA ones. © 2018 Elsevier Lt

Cord blood fatty acid-binding protein-4 levels are upregulated at both ends of the birthweight spectrum

Aim: Fatty acid-binding protein-4 (FABP4) is an adipokine associated with obesity and signs of the metabolic syndrome. We aimed to investigate at birth in term neonates with normal and abnormal intrauterine growth concentrations of FABP4 and associate them with various perinatal parameters. Methods: Serum cord blood FABP4 levels were prospectively determined by ELISA in 80 singleton term appropriate-for-gestational-age (AGA), intrauterine growth-restricted (IUGR) and large-for-gestational-age (LGA) neonates. Results: Compared to the AGA group, cord blood FABP4 levels were increased in the IUGR and LGA groups. Additionally, they were higher in early-term than full-term neonates. A significant U-shaped correlation was recorded between serum FABP4 levels and birthweight. A significant negative correlation between cord blood FABP4 and gestational age in the whole study population was noted. Conclusion: Cord blood FABP4 levels were significantly higher at the extremes of foetal growth at term and negatively correlated with gestational age, being increased in early-term versus full-term neonates. Further longitudinal studies with larger sample sizes are required to elucidate FABP4 implication in foetal growth and its association with future adverse cardiometabolic outcomes in the offspring. ©2019 Foundation Acta Pædiatrica. Published by John Wiley &amp; Sons Lt

Perinatal lipocalin-2 profile at the extremes of fetal growth

Background: Lipocalin-2 (LCN-2) has been identified as an osteoblast-secreted hormone regulating immunity, inflammation and metabolic homeostasis and has emerged as a diagnostic and prognostic biomarker for acute kidney injury in neonates. We investigated the impact of fetal growth on antepartum maternal serum, cord serum and breast milk LCN-2 concentrations and the associations of the latter with perinatal parameters. Methods: Maternal serum, cord serum and breast milk LCN-2 concentrations were measured by ELISA in samples from 80 mothers who delivered 40 appropriate (AGA), 20 large for gestational age (LGA) and 20 intrauterine growth restricted (IUGR) neonates, classified by customized weight centiles. LCN-2 concentrations were associated with birth weight, customized centile, gender, maternal age and delivery mode. Results: Antepartum maternal serum LCN-2 concentrations were significantly higher in women delivering AGA infants compared to the other two groups. Cord blood LCN-2 concentrations were significantly higher compared to maternal ones; furthermore, they were significantly elevated in the IUGR group compared to the LGA one (p =.019). Lowest concentrations were detected in breast milk, which did not differ between the three growth groups. A negative correlation was documented between cord blood LCN-2 concentrations and customized centiles (r: −0.304, p =.007). Conclusions: The higher cord serum LCN-2 concentrations, compared to maternal ones, may point to its fetal origin and potential role in intrauterine growth. The negative correlation of cord LCN-2 concentrations with customized centiles, possibly implies reduced nephron endowment/subclinical kidney damage in IUGR neonates. The extremely low LCN-2 breast milk concentrations could imply that the secretion of LCN-2 from maternal circulation to breast milk is not influenced by factors leading to intrauterine growth pathology. © 2019 Informa UK Limited, trading as Taylor &amp; Francis Group

The orbit of asteroid (317) Roxane’s satellite Olympias from Gemini, Keck, VLT and the SOR, and (22) Kalliope’s Linus from the SOR

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