Characterizaton of the vessel geometry, flow mechanics and wall shear stress in the great arteries of wildtype prenatal mouse

Introduction: Abnormal fluid mechanical environment in the pre-natal cardiovascular system is hypothesized to play a significant role in causing structural heart malformations. It is thus important to improve our understanding of the prenatal cardiovascular fluid mechanical environment at multiple developmental time-points and vascular morphologies. We present such a study on fetal great arteries on the wildtype mouse from embryonic day 14.5 (E14.5) to near-term (E18.5). Methods: Ultrasound bio-microscopy (UBM) was used to measure blood velocity of the great arteries. Subsequently, specimens were cryo-embedded and sectioned using episcopic fluorescent image capture (EFIC) to obtain high-resolution 2D serial image stacks, which were used for 3D reconstructions and quantitative measurement of great artery and aortic arch dimensions. EFIC and UBM data were input into subject-specific computational fluid dynamics (CFD) for modeling hemodynamics. Results: In normal mouse fetuses between E14.5-18.5, ultrasound imaging showed gradual but statistically significant increase in blood velocity in the aorta, pulmonary trunk (with the ductus arteriosus ), and descending aorta. Measurement by EFIC imaging displayed a similar increase in cross sectional area of these vessels. However, CFD modeling showed great artery average wall shear stress and wall shear rate remain relatively constant with age and with vessel size, indicating that hemodynamic shear had a relative constancy over gestational period considered here. Conclusion: Our EFIC-UBM-CFD method allowed reasonably detailed characterization of fetal mouse vascular geometry and fluid mechanics. Our results suggest that a homeostatic mechanism for restoring vascular wall shear magnitudes may exist during normal embryonic development. We speculate that this mechanism regulates the growth of the great vessels. © 2014 Yap et al

Total coloring of 1-toroidal graphs of maximum degree at least 11 and no adjacent triangles

A {\em total coloring} of a graph $G$ is an assignment of colors to the vertices and the edges of $G$ such that every pair of adjacent/incident elements receive distinct colors. The {\em total chromatic number} of a graph $G$, denoted by \chiup''(G), is the minimum number of colors in a total coloring of $G$. The well-known Total Coloring Conjecture (TCC) says that every graph with maximum degree $\Delta$ admits a total coloring with at most $\Delta + 2$ colors. A graph is {\em $1$-toroidal} if it can be drawn in torus such that every edge crosses at most one other edge. In this paper, we investigate the total coloring of $1$-toroidal graphs, and prove that the TCC holds for the $1$-toroidal graphs with maximum degree at least~$11$ and some restrictions on the triangles. Consequently, if $G$ is a $1$-toroidal graph with maximum degree $\Delta$ at least~$11$ and without adjacent triangles, then $G$ admits a total coloring with at most $\Delta + 2$ colors.Comment: 10 page

Oxidative stress in cardiac hypertrophy: From molecular mechanisms to novel therapeutic targets.

When faced with increased workload the heart undergoes remodelling, where it increases its muscle mass in an attempt to preserve normal function. This is referred to as cardiac hypertrophy and if sustained, can lead to impaired contractile function. Experimental evidence supports oxidative stress as a critical inducer of both genetic and acquired forms of cardiac hypertrophy, a finding which is reinforced by elevated levels of circulating oxidative stress markers in patients with cardiac hypertrophy. These observations formed the basis for using antioxidants as a therapeutic means to attenuate cardiac hypertrophy and improve clinical outcomes. However, the use of antioxidant therapies in the clinical setting has been associated with inconsistent results, despite antioxidants having been shown to exert protection in several animal models of cardiac hypertrophy. This has forced us to revaluate the mechanisms, both upstream and downstream of oxidative stress, where recent studies demonstrate that apart from conventional mediators of oxidative stress, metabolic disturbances, mitochondrial dysfunction and inflammation as well as dysregulated autophagy and protein homeostasis contribute to disease pathophysiology through mechanisms involving oxidative stress. Importantly, novel therapeutic targets have been identified to counteract oxidative stress and attenuate cardiac hypertrophy but more interestingly, the repurposing of drugs commonly used to treat metabolic disorders, hypertension, peripheral vascular disease, sleep disorders and arthritis have also been shown to improve cardiac function through suppression of oxidative stress. Here, we review the latest literature on these novel mechanisms and intervention strategies with the aim of better understanding the complexities of oxidative stress for more precise targeted therapeutic approaches to prevent cardiac hypertrophy

Greater engagement with health information is associated with adoption and maintenance of healthy lifestyle behaviours in people with MS

Health communication offers an important means for patients to make informed decisions for illness self-management. We assessed how the level of engagement with selected health information at baseline is associated with the adoption and maintenance of lifestyle behaviours at a 5-year follow-up in people with multiple sclerosis (MS). Non-engagers were compared to engagers of information delivered online and print (medium), and with engagers who additionally attended a live-in workshop (high). Engagement was assessed against lifestyle behaviours by log-binomial regression. Information engagers had higher education, and were less likely to have severe disability, clinically significant fatigue, or obesity. Medium and high baseline engagement was associated with adopting healthy behaviours for omega 3 supplementation (RR = 1.70; 95%CI: 1.02-2.84), physical activity (RR = 2.16; 95%CI: 1.03-4.55), and dairy non-consumption (RR = 3.98; 95%CI: 1.85-8.56) at 5 years; associations were stronger among high engagers. Only high baseline engagement was associated with maintaining behaviours from baseline to 5 years, specifically for omega-3 (RR = 1.26; 95%CI: 1.06-1.49) and vitamin D supplementation (RR = 1.26; 95%CI: 1.04-1.54) and dairy non-consumption (RR = 1.47; 95%CI: 1.03-2.10). Health communication that includes face-to-face information delivery and practical tools for implementation in daily living may be optimal for adopting and maintaining lifestyle behaviours in people with MS

Investigation of Fiber Reinforced Composite Using Multi-Material 3D Printing

Fiber reinforced composite materials have been commonly fabricated by laying and curing the stiff and high strength fibers within tough matrix to enhance the elastic modulus. The strength and elasticity of the fiber reinforced polymers are dependent on the intrinsic mechanical properties of matrix and fiber, the fiber layup pattern as well as the volume percentage of the matrix and fiber. In this paper, the effects of these factors on the 3D printed fiber reinforced composite materials were investigated. The fiber reinforced polymers were fabricated using multi-material inkjet printer with rubbery material as matrix and rigid strong polymer as the fiber reinforcement. Two types of fiber layup configurations and fiber/matrix volume ratios were designed for this study. The experimental result shows that both tensile strength and elastic modulus of the fiber reinforced polymers could be largely enhanced by varying the fiber/matrix ratio and layup pattern.Mechanical Engineerin

Rhesus TRIM5α disrupts the HIV-1 capsid at the inter-hexamer interfaces

TRIM proteins play important roles in the innate immune defense against retroviral infection, including human immunodeficiency virus type-1 (HIV-1). Rhesus macaque TRIM5α (TRIM5αrh) targets the HIV-1 capsid and blocks infection at an early post-entry stage, prior to reverse transcription. Studies have shown that binding of TRIM5α to the assembled capsid is essential for restriction and requires the coiled-coil and B30.2/SPRY domains, but the molecular mechanism of restriction is not fully understood. In this study, we investigated, by cryoEM combined with mutagenesis and chemical cross-linking, the direct interactions between HIV-1 capsid protein (CA) assemblies and purified TRIM5αrh containing coiled-coil and SPRY domains (CC-SPRYrh). Concentration-dependent binding of CC-SPRYrh to CA assemblies was observed, while under equivalent conditions the human protein did not bind. Importantly, CC-SPRYrh, but not its human counterpart, disrupted CA tubes in a non-random fashion, releasing fragments of protofilaments consisting of CA hexamers without dissociation into monomers. Furthermore, such structural destruction was prevented by inter-hexamer crosslinking using P207C/T216C mutant CA with disulfide bonds at the CTD-CTD trimer interface of capsid assemblies, but not by intra-hexamer crosslinking via A14C/E45C at the NTD-NTD interface. The same disruption effect by TRIM5αrh on the inter-hexamer interfaces also occurred with purified intact HIV-1 cores. These results provide insights concerning how TRIM5α disrupts the virion core and demonstrate that structural damage of the viral capsid by TRIM5α is likely one of the important components of the mechanism of TRIM5α-mediated HIV-1 restriction. © 2011 Zhao et al