Quantification of the influence of drugs on zebrafish larvae swimming kinematics and energetics

The use of zebrafish larvae has aroused wide interest in the medical field for its potential role in the development of new therapies. The larvae grow extremely quickly and the embryos are nearly transparent which allows easy examination of its internal structures using fluorescent imaging techniques. Medical treatment of zebrafish larvae can directly influence its swimming behaviours. These behaviour changes are related to functional changes of central nervous system and transformations of the zebrafish body such as muscle mechanical power and force variation, which cannot be measured directly by pure experiment observation. To quantify the influence of drugs on zebrafish larvae swimming behaviours and energetics, we have developed a novel methodology to exploit intravital changes based on observed zebrafish locomotion. Specifically, by using an in-house MATLAB code to process the recorded live zebrafish swimming video, the kinematic locomotion equation of a 3D zebrafish larvae was obtained, and a customised Computational Fluid Dynamics tool was used to solve the fluid flow around the fish model which was geometrically the same as experimentally tested zebrafish. The developed methodology was firstly verified against experiment, and further applied to quantify the fish internal body force, torque and power consumption associated with a group of normal zebrafish larvae vs. those immersed in acetic acid and two neuroactive drugs. As indicated by our results, zebrafish larvae immersed in 0.01% acetic acid display approximately 30% higher hydrodynamic power and 10% higher cost of transport than control group. In addition, 500 μM diphenylhydantoin significantly decreases the locomotion activity for approximately 50% lower hydrodynamic power, whereas 100 mg/L yohimbine has not caused any significant influences on 5 dpf zebrafish larvae locomotion. The approach has potential to evaluate the influence of drugs on the aquatic animal’s behaviour changes and thus support the development of new analgesic and neuroactive drugs

Primordial black holes and scalar-induced gravitational waves from the perturbations on the inflaton potential in peak theory

A perturbation on the background inflaton potential can lead inflation into the ultraslow-roll stage and can thus remarkably enhance the power spectrum ${\cal P}_{\cal R}(k)$ of the primordial curvature perturbation on small scales. Such an enhanced ${\cal P}_{\cal R}(k)$ will result in primordial black holes (PBHs), contributing a significant fraction of dark matter, and will simultaneously generate sizable scalar-induced gravitational waves (SIGWs) as a secondorder effect. In this work, we calculate the PBH abundances $f_{\rm PBH}(M)$ and SIGW spectra $\Omega_{\rm GW}(f)$ in peak theory. We obtain the PBHs with desirable abundances in one or two typical mass windows at $10^{-17}\, M_\odot$, $10^{-13}\, M_\odot$, and $30\, M_\odot$, respectively. At the same time, the relevant SIGWs are expected to be observed by the next-generation gravitational wave detectors, without spoiling the current constraint. Especially, the SIGW associated with the PBH of $30\, M_\odot$ can also interpret the potential isotropic stochastic gravitational wave background from the NANOGrav 12.5-year dataset.Comment: 22 pages, 6 figure

Glomerular C1q deposition and serum anti-C1q antibodies in anti-glomerular basement membrane disease

BACKGROUND: Anti-glomerular basement membrane (GBM) disease is a well-known antibody-induced autoimmune disease. A few patients have glomerular C1q deposition, but it is usually absent on renal histopathology. The role of C1q deposition in kidney injury is unclear. Recently, anti-C1q antibodies are demonstrated to be pathogenic in the target organ damage of many autoimmune diseases, by facilitating C1q deposition and enhancing complement activation via classical pathway. In the current study, we investigated the associations between anti-C1q antibodies in sera and C1q deposition in kidney of patients with anti-GBM disease. RESULTS: It was shown that the severity of kidney injury was comparable between patients with and without C1q deposition, including the prevalence of oliguria/auria, the median percentage of crescents in glomeruli and the mean concentration of serum creatinine. Serum anti-C1q antibodies were detected in 15/25 (60%) patients with a low titer. The prevalence of C1q deposition in kidney was comparable between patients with and without serum anti-C1q antibodies (26.7% vs. 30.0%, p > 0.05). No association was found between anti-C1q antibodies and the severity of kidney injury. CONCLUSIONS: The classical pathway of complement may not play a pathogenic role in the kidney injury of human anti-GBM disease. Anti-C1q antibodies could be detected in more than half of patients, which need further investigations