Rupture of cerebral aneurysms (CAs) is a major cause of life-threatening subarachnoid hemorrhage. It is still difficult to predict CA rupture since little is known about the risk factors. Although the mechanism of development, enlargement and rupture of CAs remains unclear, a series of pioneering investigations using animal models of experimentally induced CAs have revealed that hemodynamics are significant in the development of CAs. There have been a number of investigations into the hemodynamics of CAs, which have provided insight into the mechanisms of CA formation. Here, we review experimental and computational work in this field. We first introduce animal models of experimentally induced CAs and studies into the role of hemodynamic stress in the formation of CAs. We also discuss the animal model-based studies on biochemical contributors to CA induction at the cellular and molecular level. We go on to describe hemodynamic studies of CAs using computational fluid dynamics (CFD), including patient-specific CFD models of blood flow, the non-Newtonian viscous nature of blood, and the elastic properties of vessel walls, as well as boundary conditions for CFD simulations. Finally, we review computational studies into risk factors for the development, enlargement and rupture of CAs, and discuss endovascular treatments.
The line tension of the pore in a phospholipid bilayer is important for pore-mediated molecular transport techniques. To understand the cholesterol effects on the line tension of the pore edge at the molecular level, we perform molecular dynamics simulations of phospholipid bilayers with a pore containing cholesterol in different concentrations (0, 20, and 40 mol%). The bilayer with a pore is prepared by using an equibiaxial stretching simulation. The stretched bilayer with a pore is subsequently compressed and the pore spontaneously closes when the applied areal strain of the bilayer is below a certain value. Using the pore closure areal strain and a free energy model of a stretched bilayer with a pore, the upper and lower limits of the line tensions for the bilayers containing cholesterol at 0, 20, and 40 mol% are estimated to be 17.0-48.2, 54.5-100, and 170-261 pN, respectively. The increasing tendency of the line tension qualitatively agrees with that observed experimentally. The pores in the cholesterol-containing bilayers are lined with several cholesterol molecules, which might increase the bending rigidity of the pore edge, and result in the higher line tension of the cholesterol-containing bilayer. The considerable dependency of the line tension on the bilayer compositions might be useful to explain the large variations of the transduction efficiency observed with sonoporation treatment.
The action of the forearm is to transfer force and torque across the elbow and wrist, resulting in axial rotation at the distal and proximal radioulnar joints, called pronation and supination. Pronation and supination are important functions as they allow many kinds of activities of daily living. Three-dimensional (3D) motion analysis of pronation and supination is essential for a better understating of the biomechanics of the forearm to describe the physiological range of motion and optimize clinical options for disorders of the forearm. Although numerous in vitro studies have contributed to gain insights into the forearm pronation and supination, in vivo investigations are still limited. In this study, three-dimensional (3D) motion of the distal radioulnar joint (DRUJ) during forearm pronation and supination was analyzed in vivo using biplanar radiography and 3D models of the ulna and radius. Twelve healthy subjects (6 men and 6 women) were recruited for the study. Each subject's right forearm (dominant hand) underwent a computed tomography (CT) scan to create 3D surface models of the ulna and radius. Each subject was imaged using a calibrated biplanar radiographic system at 90° pronation, 45° pronation, neutral, 45° supination, and 90° supination while the elbow was in extension or flexion. The 3D positions of the radius and ulna were obtained using a 2D-to-3D image registration method. The relative translations of the radius in the radioulnar, dorsopalmar, and proximodistal directions and the relative rotations of the radius about the radioulnar, dorsopalmar, and proximodistal axes were evaluated with respect to the ulna during pronation and supination. In general, the radius translated towards the ulnar side throughout forearm rotation, and moved towards the palmar side as pronation increased and moved dorsally as supination increased, and was positioned proximally during pronation and distally during supination. The rotation of the radius was dominant about the proximodistal axis. These kinematic variables were affected by elbow position and sex of the subject. The current findings regarding the 3D kinematics of the DRUJ during forearm pronation and supination may contribute to further understanding of the physiological biomechanics of the upper limb.
The interaction for protein glycosylphosphatidylinositol (GPI) modification between the premature GPI-anchored proteins and the active sites in PIG-K, one of the GPI transamidase proteins, is discussed in this study by the homology modeling method and amino acid propensity analysis in the space around the ω-sites in premature GPI-anchored proteins. In particular, the direct interaction between ω-sites of GPI-anchored proteins and PIG-K was focused on, the root-mean-square deviation (RMSD) and three-dimensional amino acid propensity around the ω-sites were analyzed in the present study. As the results, PIG-K was considered to recognize the specific structure around the ω-sites of the GPI-anchored proteins, the positively-charged Lys (K) and Arg (R) residues around the ω-sites have the possibility to interact with the negatively-charged Asp (D) and Glu (E) residues around an active site of PIG-K, and Tyr (Y) and Ala (A) residues around the ω-sites are thought to be essential for molecular recognition by PIG-K. The findings in this study that structural recognition around the ω-site in the mature GPI-anchored proteins by PIG-K are useful for understanding the local mechanism of the GPI modification enzyme and can be applied for the development of cell-surface-engineering.
Dynamic exercise influences the cardiovascular system in various ways, and the attitude of our body also affect the hemodynamics. In this study, we adopted and integrated a double-closed-loop model consisting of the cardiovascular system (CVS), and the autonomic nervous system (ANS), along with the mathematical models of exercise and body attitude for hemodynamic prediction and cardiovascular regulation. The CVS-ANS-exercise coupling model is validated with two cases of the hemodynamic response to exercises: two different kinds of exercises (one-leg extension and one-leg cycling), and the recovery from one-leg cycling under two different attitudes (supine and standing). The results show that the transition of blood pressure varies during different exercises; the recovery from exercise is more rapid in the supine attitude. We confirmed by comparing simulation results to experimental data, that the simulation model in this study is effective. Furthermore, a simulation-based exercise model can potentially reduce the risk of performing an exercise test in clinical practice.