From video recordings to whisker stable isotopes: a critical evaluation of timescale in assessing individual foraging specialisation in Australian fur seals

International audienceEstimating the degree of individual specialisationis likely to be sensitive to the methods used, as theyrecord individuals’ resource use over different time-periods.We combined animal-borne video cameras, GPS/TDRloggers and stable isotope values of plasma, red cells andsub-sampled whiskers to investigate individual foragingspecialisation in female Australian fur seals (Arctocephaluspusillus doriferus) over various timescales. Combiningthese methods enabled us to (1) provide quantitative informationon individuals’ diet, allowing the identification ofprey, (2) infer the temporal consistency of individual specialisation,and (3) assess how different methods and timescalesaffect our estimation of the degree of specialisation.Short-term inter-individual variation in diet was observedin the video data (mean pairwise overlap = 0.60), with thesampled population being composed of both generalist andspecialist individuals (nested network). However, the brevityof the temporal window is likely to artificially increase the level of specialisation by not recording the entire dietof seals. Indeed, the correlation in isotopic values wastighter between the red cells and whiskers (mid- to longtermforaging ecology) than between plasma and red cells(short- to mid-term) (R2 = 0.93–0.73 vs. 0.55–0.41). δ13Cand δ15N values of whiskers confirmed the temporal consistencyof individual specialisation. Variation in isotopicniche was consistent across seasons and years, indicatinglong-term habitat (WIC/TNW = 0.28) and dietary (WIC/TNW = 0.39) specialisation. The results also highlighttime-averaging issues (under-estimation of the degree ofspecialisation) when calculating individual specialisationindices over long time-periods, so that no single timescalemay provide a complete and accurate picture, emphasisingthe benefits of using complementary methods

Apolipoprotein A-I proteolysis in aortic valve stenosis: role of cathepsin S

Aortic valve stenosis (AVS) is the most common valvular heart disease in the Western world. Therapy based on apolipoprotein A-I (apoA-I), the major protein component of high-density lipoproteins, results in AVS regression in experimental models. Nevertheless, apoA-I degradation by proteases might lead to suboptimal efficacy of such therapy. An activatable probe using a quenched fluorescently labeled full-length apoA-I protein was generated to assess apoA-I-degrading protease activity in plasma derived from 44 men and 20 women with severe AVS (age 65.0 ± 10.4 years) as well as from a rabbit model of AVS. In human and rabbit AVS plasma, apoA-I-degrading protease activity was significantly higher than in controls (humans: 0.038 ± 0.009 vs 0.022 ± 0.005 RFU/s, p < 0.0001; rabbits: 0.033 ± 0.016 vs 0.017 ± 0.005 RFU/s, p = 0.041). Through the use of protease inhibitors, we identified metalloproteinases (MMP) as exerting the most potent proteolytic effect on apoA-I in AVS rabbits (67%, p < 0.05 vs control), while the cysteine protease cathepsin S accounted for 54.2% of apoA-I degradation in human plasma (p < 0.05 vs control) with the maximum effect seen in women (68.8%, p < 0.05 vs men). Accordingly, cathepsin S activity correlated significantly with mean transaortic pressure gradient in women (r = 0.5, p = 0.04) but not in men (r = - 0.09, p = 0.60), and was a significant independent predictor of disease severity in women (standardized beta coefficient 0.832, p < 0.001) when tested in a linear regression analysis. ApoA-I proteolysis is increased in AVS. Targeting circulating cathepsin S may lead to new therapies for human aortic valve disease

Beneficial Effects of High-Density Lipoproteins on Acquired von Willebrand Syndrome in Aortic Valve Stenosis

BACKGROUND Infusions of apolipoprotein A-I (apoA-I), the major protein component of high-density lipoproteins (HDL), result in aortic valve stenosis (AVS) regression in experimental models. Severe AVS can be complicated by acquired von Willebrand syndrome, a haemorrhagic disorder associated with loss of high-molecular-weight von Willebrand factor (vWF) multimers (HMWM), the latter being a consequence of increased shear stress and enhanced vWF-cleaving protease (ADAMTS-13) activity. Although antithrombotic actions of HDL have been described, its effects on ADAMTS-13 and vWF in AVS are unknown. METHODS AND RESULTS We assessed ADAMTS-13 activity in plasma derived from a rabbit model of AVS ( = 29) as well as in plasma collected from 64 patients with severe AVS (age 65.0 ± 10.4 years, 44 males) undergoing aortic valve replacement (AVR). In both human and rabbit AVS plasma, ADAMTS-13 activity was higher than that in controls ( < 0.05). Accordingly, AVS patients had less HMWM than controls (66.3 ± 27.2% vs. 97.2 ± 24.1%,  < 0.0001). Both ADAMTS-13 activity and HMWM correlated significantly with aortic transvalvular gradients, thereby showing opposing correlations ( = 0.3,  = 0.018 and  = -0.4,  = 0.003, respectively). Administration of an apoA-I mimetic peptide reduced ADAMTS-13 activity in AVS rabbits as compared with the placebo group (2.0 ± 0.5 RFU/sec vs. 3.8 ± 0.4 RFU/sec,  < 0.05). Similarly, a negative correlation was found between ADAMTS-13 activity and HDL cholesterol levels in patients with AVS ( = -0.3,  = 0.045). CONCLUSION Our data indicate that HDL levels are associated with reduced ADAMTS-13 activity and increased HMWM. HDL-based therapies may reduce the haematologic abnormalities of the acquired von Willebrand syndrome in AVS