Resistance to oxidative stress shows low heritability and high common environmental variance in a wild bird

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.Oxidative stress was recently demonstrated to affect several fitness-related traits and is now well recognized to shape animal life-history evolution. However, very little is known about how much resistance to oxidative stress is determined by genetic and environmental effects and hence about its potential for evolution, especially in wild populations. In addition, our knowledge of phenotypic sexual dimorphism and cross-sex genetic correlations in resistance to oxidative stress remains extremely limited despite important evolutionary implications. In free-living great tits (Parus major), we quantified heritability, common environmental effect, sexual dimorphism and cross-sex genetic correlation in offspring resistance to oxidative stress by performing a split-nest cross-fostering experiment where 155 broods were split, and all siblings (n = 791) translocated and raised in two other nests. Resistance to oxidative stress was measured as both oxidative damage to lipids and erythrocyte resistance to a controlled free-radical attack. Both measurements of oxidative stress showed low additive genetic variances, high common environmental effects and phenotypic sexual dimorphism with males showing a higher resistance to oxidative stress. Cross-sex genetic correlations were not different from unity, and we found no substantial heritability in resistance to oxidative stress at adult age measured on 39 individuals that recruited the subsequent year. Our study shows that individual ability to resist to oxidative stress is primarily influenced by the common environment and has a low heritability with a consequent low potential for evolution, at least at an early stage of life.This work was conducted under licence of the Ethical Committee of the Agricultural Office of the Canton Bern. Ringing permits were provided by the Swiss Federal Agency for Environment, Forests and Landscapes. The authors thank Julien Martin and Matthew Wolak for helpful advice and David Costantini and two anonymous reviewers for constructive comments on previous versions of the manuscript. The study was financially supported by the Swiss National Science Foundation. SL was supported by a Swiss NSF and a Marie Curie IEF Post-Doctoral Fellowships. JDB was supported by a Royal Society Research Fellowship. The authors have declared no conflict of interest

Quantitative Flow Ratio to Predict Nontarget Vessel-Related Events at 5 Years in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Angiography-Guided Revascularization.

Background In ST-segment-elevation myocardial infarction, angiography-based complete revascularization is superior to culprit-lesion-only percutaneous coronary intervention. Quantitative flow ratio (QFR) is a novel, noninvasive, vasodilator-free method used to assess the hemodynamic significance of coronary stenoses. We aimed to investigate the incremental value of QFR over angiography in nonculprit lesions in patients with ST-segment-elevation myocardial infarction undergoing angiography-guided complete revascularization. Methods and Results This was a retrospective post hoc QFR analysis of untreated nontarget vessels (any degree of diameter stenosis [DS]) from the randomized multicenter COMFORTABLE AMI (Comparison of Biolimus Eluted From an Erodible Stent Coating With Bare Metal Stents in Acute ST-Elevation Myocardial Infarction) trial by assessors blinded for clinical outcomes. The primary end point was cardiac death, spontaneous nontarget vessel myocardial infarction, and clinically indicated nontarget vessel revascularization (ie, ≥70% DS by 2-dimensional quantitative coronary angiography or ≥50% DS and ischemia) at 5 years. Of 1161 patients with ST-segment-elevation myocardial infarction, 946 vessels in 617 patients were analyzable by QFR. At 5 years, the rate of the primary end point was significantly higher in patients with QFR ≤0.80 (n=35 patients, n=36 vessels) versus QFR >0.80 (n=582 patients, n=910 vessels) (62.9% versus 12.5%, respectively; hazard ratio [HR], 7.33 [95% CI, 4.54-11.83], P30% DS by 3-dimensional quantitative coronary angiography. Conclusions Our study suggests incremental value of QFR over angiography-guided percutaneous coronary intervention for nonculprit lesions among patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention

Impact of alirocumab on neoatherosclerosis formation and vessel healing after drug-eluting stent implantation in patients with acute myocardial infarction:a substudy of the PACMAN-AMI trial

Higher on-treatment levels of low-density lipoprotein cholesterol in statin-treated patients were reportedly associated with the occurrence of neoatherosclerosis after drug-eluting stent (DES) implantation. We aimed to investigate the impact of alirocumab added to high-intensity statin therapy on neoatherosclerosis formation among patients with acute myocardial infarction (AMI) treated with DES. This was a pre-specified substudy of the PACMAN-AMI trial, a randomized, double-blind trial comparing alirocumab versus placebo added to high-intensity statin therapy in AMI patients. The present study included patients undergoing optical coherence tomography assessment of DES in the culprit lesion at one year. The frequency of neoatherosclerosis, neointimal thickness, and strut malapposition were compared between treatment groups. Among 191 patients (95 with alirocumab and 96 with placebo), neoatherosclerosis was observed in 13 patients (6.8%) at one year. There was no significant difference in the frequency of neoatherosclerosis between treatment groups (alirocumab 4.2% vs. placebo 9.4%, P = 0.25). Among 11 patients with lipid-laden neointima, minimal fibrous cap thickness was greater in the alirocumab group than in the placebo group (217.5 ± 122.5 vs. 87.8 ± 49.1 μm, P = 0.02). Neointimal thickness (136.2 ± 71.1 vs. 151.4 ± 101.4 μm, P = 0.45) and the frequency of malapposed struts (0.94 vs. 0.53%, P = 0.27) were comparable between treatment groups. Among AMI patients treated with DES, there was no significant impact of alirocumab on the frequency of neoatherosclerosis and vessel healing at one year. The observed numerical difference and the finding of more stable neoatheroma in the alirocumab group need further investigation in larger studies with extended follow-up.</p

Association of Lipoprotein(a) With Changes in Coronary Atherosclerosis in Patients Treated With Alirocumab

BACKGROUND: Elevated Lp(a) (lipoprotein[a]) is a risk marker for atherosclerotic disease, but the underlying mechanisms remain elusive. We examined the association of Lp(a) with changes in coronary atherosclerosis following intensive lipid-lowering therapy. METHODS: In the PACMAN-AMI trial (Effects of the PCSK9 Antibody Alirocumab on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction), 300 patients with acute myocardial infarction were randomized to receive biweekly alirocumab 150 mg or placebo in addition to high-intensity statins. Patients underwent serial 2-vessel intravascular ultrasound, optical coherence tomography, and near-infrared spectroscopy in the non-infarct-related arteries at baseline and after 52 weeks. The main end points were percent atheroma volume by intravascular ultrasound, minimum fibrous cap thickness by optical coherence tomography, and maximum lipid core burden index within 4 mm (maxLCBI4mm) by near-infrared spectroscopy. RESULTS: A total of 265 patients had serial intravascular ultrasound data (mean age, 58±9 years; 16% women). Alirocumab resulted in greater reductions in percent atheroma volume and maxLCBI4mm, as well as a greater increase in minimum fibrous cap thickness, compared with placebo. In the alirocumab group, the reduction in maxLCBI4mm was smaller in patients with higher baseline Lp(a), defined by the highest quartile (Q4, ≥98 nmol/L; n=30), than in those with lower baseline Lp(a) (Q1-Q3, &lt;98 nmol/L; n=99; -40.2 [-91.1 to 10.7] versus -91.4 [-113.9 to -68.9], respectively; P=0.01 after adjustment for clinically relevant baseline variables), and was comparable to the maxLBI4mm reduction in the placebo group (-37.60 [-57.40 to -17.80]; n=134). These findings were consistent when higher baseline Lp(a) was defined by cut-off values of ≥75 versus &lt;75 nmol/L (n=35 versus 94, respectively, in the alirocumab group) and ≥125 versus &lt;125 nmol/L (n=23 versus 106, respectively). Changes in percent atheroma volume and minimum fibrous cap thickness did not differ in relation to baseline Lp(a). CONCLUSIONS: In patients with acute myocardial infarction, elevated Lp(a) at baseline is associated with attenuation of plaque lipid regression despite intensive treatment with alirocumab plus high-intensity statin. This finding may explain the residual cardiovascular risk associated with high Lp(a) despite optimal control of lipid levels.REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03067844.</p

Ejaculate Economics: Testing the Effects of Male Sexual History on the Trade-Off between Sperm and Immune Function in Australian Crickets

Trade-offs between investment into male sexual traits and immune function provide the foundation for some of the most prominent models of sexual selection. Post-copulatory sexual selection on the male ejaculate is intense, and therefore trade-offs should occur between investment into the ejaculate and the immune system. Examples of such trade-offs exist, including that between sperm quality and immunity in the Australian cricket, Teleogryllus oceanicus. Here, we explore the dynamics of this trade-off, examining the effects that increased levels of sexual interaction have on the viability of a male's sperm across time, and the concomitant effects on immune function. Males were assigned to a treatment, whereby they cohabited with females that were sexually immature, sexually mature but incapable of copulation, or sexually mature and capable of copulation. Sperm viability of each male was then assessed at two time points: six and 13 days into the treatment, and immune function at day 13. Sperm viability decreased across the time points, but only for males exposed to treatment classes involving sexually mature females. This decrease was similar in magnitude across both sexually mature classes, indicating that costs to the expression of high sperm viability are incurred largely through levels of pre-copulatory investment. Males exposed to immature females produced sperm of low viability at both time points. Although we confirmed a weak negative association between sperm viability and lytic activity (a measure of immune response to bacterial infection) at day 13, this relationship was not altered across the mating treatment. Our results highlight that sperm viability is a labile trait, costly to produce, and subject to strategic allocation in these crickets

Immune Activation Reduces Sperm Quality in the Great Tit

Mounting an immune response against pathogens incurs costs to organisms by its effects on important life-history traits, such as reproductive investment and survival. As shown recently, immune activation produces large amounts of reactive species and is suggested to induce oxidative stress. Sperm are highly susceptible to oxidative stress, which can negatively impact sperm function and ultimately male fertilizing efficiency. Here we address the question as to whether mounting an immune response affects sperm quality through the damaging effects of oxidative stress. It has been demonstrated recently in birds that carotenoid-based ornaments can be reliable signals of a male's ability to protect sperm from oxidative damage. In a full-factorial design, we immune-challenged great tit males while simultaneously increasing their vitamin E availability, and assessed the effect on sperm quality and oxidative damage. We conducted this experiment in a natural population and tested the males' response to the experimental treatment in relation to their carotenoid-based breast coloration, a condition-dependent trait. Immune activation induced a steeper decline in sperm swimming velocity, thus highlighting the potential costs of an induced immune response on sperm competitive ability and fertilizing efficiency. We found sperm oxidative damage to be negatively correlated with sperm swimming velocity. However, blood resistance to a free-radical attack (a measure of somatic antioxidant capacity) as well as plasma and sperm levels of oxidative damage (lipid peroxidation) remained unaffected, thus suggesting that the observed effect did not arise through oxidative stress. Towards the end of their breeding cycle, swimming velocity of sperm of more intensely colored males was higher, which has important implications for the evolution of mate choice and multiple mating in females because females may accrue both direct and indirect benefits by mating with males having better quality sperm

Senescence in cell oxidative status in two bird species with contrasting life expectancy.

Oxidative stress occurs when the production of reactive oxygen species (ROS) by an organism exceeds its capacity to mitigate the damaging effects of the ROS. Consequently, oxidative stress hypotheses of ageing argue that a decline in fecundity and an increase in the likelihood of death with advancing age reported at the organism level are driven by gradual disruption of the oxidative balance at the cellular level. Here, we measured erythrocyte resistance to oxidative stress in the same individuals over several years in two free-living bird species with contrasting life expectancy, the great tit (known maximum life expectancy is 15.4 years) and the Alpine swift (26 years). In both species, we found evidence for senescence in cell resistance to oxidative stress, with patterns of senescence becoming apparent as subjects get older. In the Alpine swift, there was also evidence for positive selection on cell resistance to oxidative stress, the more resistant subjects being longer lived. The present findings of inter-individual selection and intra-individual deterioration in cell oxidative status at old age in free-living animals support a role for oxidative stress in the ageing of wild animals

Derivation and validation of myocardial bridge characteristics by optical coherence tomography: a prospective multimodality imaging study

Abstract Background Optical coherence tomography (OCT) findings of myocardial bridge (MB) have not been established. Purpose We aimed to establish the OCT appearance of MB compared with the half-moon sign derived by intravascular ultrasound (IVUS) and to assess the prevalence among patients undergoing coronary angiography and OCT in clinical practice. Methods For derivation of the OCT appearance of MB, imaging data obtained from 122 patients undergoing OCT and IVUS for the left anterior descending artery (LAD) enrolled in two prospective imaging studies were analyzed. To assess the prevalence of OCT-derived MB, 470 patients undergoing OCT for LAD in clinical routine were analyzed. Results We found a homogeneous band with intermediate light intensity surrounding the vessel wall as assessed by OCT corresponding to half-moon sign derived by IVUS. Mean length, angle, and thickness of OCT-MB were 21.2±10.8mm, 205.7±56.5°, and 0.39±0.06mm, respectively. Mean length of IVUS-MB was significantly longer as compared with OCT-MB (23.7±11.9, P=0.010), while there were no significant differences in angle and thickness. MB angle was &amp;gt;180° in approximately 50% of frames with MB. There was a strong/moderate correlation between OCT-MB and half-moon sign (MB length: r=0.81, P=0.001, MB angle: r=0.58, P=0.001). In the derivation cohort, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of OCT-MB for the milking effect by angiography were 96.3%, 62.1%, 41.9%, 98.3%, and 69.7%, respectively, and much comparable with the IVUS half-moon sign. In the validation cohort, OCT-detected MB was observed in 139 (29.6%) patients, of whom 57.6% (n=80) did not have angiographic evidence of milking effect. Conclusion OCT is able to identify IVUS-defined MB as homogenous band with intermediate light intensity surrounding the vessel wall. There was a high concordance in terms of MB angle and thickness between OCT and IVUS. In clinically-indicated OCT cases of the LAD, more than half of OCT-MBs were angiographically silent. OCT assessment of MB may facilitate the accurate diagnosis of MB and thus provide useful information in determining the subsequent treatment strategy for the patients with MB. Funding Acknowledgement Type of funding sources: None. Representative imaging of MBCase of OCT-MB without milking effect </jats:sec

Evaluation of woodlice diversity and abundance in natural and managed Atlantic grasslands

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