β‐Ionone: Its Occurrence and Biological Function and Metabolic Engineering

β‐Ionone is a natural plant volatile compound, and it is the 9,10 and 9’,10’ cleavage prod-uct of β‐carotene by the carotenoid cleavage dioxygenase. β‐Ionone is widely distributed in flowers, fruits, and vegetables. β‐Ionone and other apocarotenoids comprise flavors, aromas, pigments, growth regulators, and defense compounds; serve as ecological cues; have roles as insect attractants or repellants, and have antibacterial and fungicidal properties. In recent years, β‐ionone has also received increased attention from the biomedical community for its potential as an anticancer treatment and for other human health benefits. However, β‐ionone is typically produced at relatively low levels in plants. Thus, expressing plant biosynthetic pathway genes in microbial hosts and engineering the metabolic pathway/host to increase metabolite production is an appealing alternative. In the present review, we discuss β‐ionone occurrence, the biological activities of β‐ionone, empha-sizing insect attractant/repellant activities, and the current strategies and achievements used to re-construct enzyme pathways in microorganisms in an effort to to attain higher amounts of the de-sired β‐ionone

Translational medicine: from discovery to health

System requirements: Windows Media Player version 9 or above.Jamal Ibdah spoke on the topic "National Movement of Clinical and Translational Science and Drug Discovery.

On preservation of moduli of continuity by parabolic evolution

In this work, we study how Lipschitz continuity propagates by a certain class of nonlinear, nonlocal parabolic equations. This work draws inspiration from ideas developed in recent years by Kiselev, Nazarov, Volberg and Shterenberg to address issues relating to the regularity of solutions of critical active scalar equations such as the the surface quasi-geostrophic equation and Burgers model. Namely, we will extend and improve on such techniques in order for them to be applicable to combustion models as well as other fluid equations such as the incompressible Navier-Stokes system and Burgers-Hilbert flow. The main problem we address here is proving a global regularity result relating to a slight modification of the so called Michelson-Sivashinsky equation. We also give outlines of how can one use similar ideas to obtain various new regularity and partial regularity criteria for the incompressible Navier-Stokes system, as well as provide a different proof to a known criterion in terms of critical H\"older-type norms. We also outline how to extend the technique to a viscous, multi-dimensional Burgers-Hilbert problem in order to prove global regularity for this model

Uniform in time error estimates for fully discrete numerical schemes of a data assimilation algorithm

We consider fully discrete numerical schemes for a downscaling data assimilation algorithm aimed at approximating the velocity field of the 2D Navier-Stokes equations corresponding to given coarse mesh observational measurements. The time discretization is done by considering semi- and fully-implicit Euler schemes, and the spatial discretization is based on a spectral Galerkin method. The two fully discrete algorithms are shown to be unconditionally stable, with respect to the size of the time step, number of time steps and the number of Galerkin modes. Moreover, explicit, uniform in time error estimates between the fully discrete solution and the reference solution corresponding to the observational coarse mesh measurements are obtained, in both the $L^2$ and $H^1$ norms. Notably, the two-dimensional Navier-Stokes equations, subject to the no-slip Dirichlet or periodic boundary conditions, are used in this work as a paradigm. The complete analysis that is presented here can be extended to other two- and three-dimensional dissipative systems under the assumption of global existence and uniqueness

Intrinsic high aerobic capacity protects against lipid induced hepatic insulin resistance [abstract]

Hepatic steatosis is commonly linked to hepatic insulin resistance. However, recent studies have found that increased hepatic triacylglycerol (TAG) accumulation is not always associated with impaired hepatic insulin signaling, leading to a hypothesis that partitioning of lipids into TAG in the liver matched with high rates of fatty acid oxidation (FAO) under high lipid exposure conditions may protect against hepatic insulin resistance. We examined this hypothesis in the livers of high and low capacity running (HCR/LCR) rats which were created by artificial selection based on differences in intrinsic aerobic capacity

Exercise and Omega-3 Polyunsaturated Fatty Acid Supplementation for the Treatment of Hepatic Steatosis in Hyperphagic OLETF Rats

Background and Aims. This study examined if exercise and omega-3 fatty acid (n3PUFA) supplementation is an effective treatment for hepatic steatosis in obese, hyperphagic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Methods. Male OLETF rats were divided into 4 groups (n=8/group): (1) remained sedentary (SED), (2) access to running wheels; (EX) (3) a diet supplemented with 3% of energy from fish oil (n3PUFA-SED); and (4) n3PUFA supplementation plus EX (n3PUFA+EX). The 8 week treatments began at 13 weeks, when hepatic steatosis is present in OLETF-SED rats. Results. EX alone lowered hepatic triglyceride (TAG) while, in contrast, n3PUFAs failed to lower hepatic TAG and blunted the ability of EX to decrease hepatic TAG levels in n3PUFAs+EX. Insulin sensitivity was improved in EX animals, to a lesser extent in n3PUFA+EX rats, and did not differ between n3PUFA-SED and SED rats. Only the EX group displayed higher complete hepatic fatty acid oxidation (FAO) to CO2 and carnitine palmitoyl transferase-1 activity. EX also lowered hepatic fatty acid synthase protein while both EX and n3PUFA+EX decreased stearoyl CoA desaturase-1 protein. Conclusions. Exercise lowers hepatic steatosis through increased complete hepatic FAO, insulin sensitivity, and reduced expression of de novo fatty acid synthesis proteins while n3PUFAs had no effect

Mineralocorticoid receptor antagonism attenuates vascular apoptosis and injury via rescuing protein kinase B activation

This article may also be found at the publisher's website at http://hyper.ahajournals.org/cgi/content/abstract/53/2/158?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=habibi&searchid=1&FIRSTINDEX=0&resourcetype=HWCITEmerging evidence indicates that mineralocorticoid receptor (MR) blockade reduces the risk of cardiovascular events beyond those predicted by its blood pressure-lowering actions; however, the underlying mechanisms remain unclear. To investigate whether protection elicited by MR blockade is through attenuation of vascular apoptosis and injury, independently of blood pressure lowering, we administered a low dose of the MR antagonist spironolactone or vehicle for 21 days to hypertensive transgenic Ren2 rats with elevated plasma aldosterone levels. Although Ren2 rats developed higher systolic blood pressures compared with Sprague-Dawley littermates, low-dose spironolactone treatment did not reduce systolic blood pressure compared with untreated Ren2 rats. Ren2 rats exhibited vascular injury as evidenced by increased apoptosis, hemidesmosome-like structure loss, mitochondrial abnormalities, and lipid accumulation compared with Sprague-Dawley rats, and these abnormalities were attenuated by MR antagonism. Protein kinase B activation is critical to vascular homeostasis via regulation of cell survival and expression of apoptotic genes. Protein kinase B serine473 phosphorylation was impaired in Ren2 aortas and restored with MR antagonism. In vivo MR antagonist treatment promoted antiapoptotic effects by increasing phosphorylation of BAD serine136 and expression of Bcl-2 and Bcl-xL, decreasing cytochrome c release and BAD expression, and suppressing caspase-3 activation. Furthermore, MR antagonism substantially reduced the elevated NADPH oxidase activity and lipid peroxidation, expression of angiotensin II, angiotensin type 1 receptor, and MR in Ren2 vasculature. These results demonstrate that MR antagonism protects the vasculature from aldosterone-induced vascular apoptosis and structural injury via rescuing protein kinase B activation, independent of blood pressure effects

Translational Approach to Examine the Importance of Aerobic Fitness on Nonalcoholic Fatty Liver Disease [abstract]

Comparative Medicine - OneHealth and Comparative Medicine Poster Session.Low cardiorespiratory fitness, independent of physical activity levels, is the best predictor of early mortality and is linked to type 2 diabetes and CVD. In the absence of exercise training, it is believed that genetic inheritance accounts for up to 70% of the variation in intrinsic aerobic fitness. Recent cross-sectional reports in humans also have linked low aerobic fitness with nonalcoholic fatty liver disease (NAFLD). NAFLD, fatty liver not due to alcohol consumption, encompasses a gamut of liver maladaptations and is a primary cause of chronic liver disease and liver-related morbidity and mortality. NAFLD occurs in ~30% of US adults, 75-100% of obese and extremely obese individuals, and is considered the hepatic component of the metabolic syndrome. Despite the recent observations in humans between low fitness and NAFLD, there is a paucity of mechanistic information detailing this link. In order to address this important clinical problem, we have developed an interdisciplinary team across multiple institutions and fields of study and have taken a translational approach, employing both novel whole animal model studies and isolated primary hepatocyte cell culture experiments, to gain mechanistic insight into the human observational studies. We have utilized a novel rat model in which rats are artificially selected over several generations for high and low intrinsic endurance capacity, resulting in high capacity runners (HCR) with high aerobic fitness and low capacity runners (LCR) with significantly lower aerobic fitness (Science, 307:418-20, 2005). These rats display contrasting phenotypes without the influence of exercise training, making them an excellent model to mechanistically assess the role of aerobic fitness on NAFLD. Utilizing this model, we have provided the first mechanistic evidence that the LCR rats have reduced hepatic mitochondrial content and oxidative capacity, increased hepatic de novo lipogenic profiles, and develop hepatic steatosis with progression to greater fibrosis and apoptosis compared to the HCR rats. The LCR rats also are unable to maintain systemic insulin sensitivity following exposure to high-fat feeding. However, since it is impossible to completely eliminate the influence of peripheral factors on liver metabolism, we have subsequently isolated primary hepatocytes from HCR and LCR rats. We have observed a similar phenotype in the primary hepatocytes from LCR animals, with significant reductions in fatty acid oxidation and the inability to maintain insulin signaling in response to lipid exposure compared with HCR hepatocytes. These findings have important clinical implications, as low aerobic fitness due to physical inactivity and/or genetic inheritability may lead to increased susceptibility to NAFLD, and suggest that the clinical measurement of aerobic fitness may serve as a valuable prognostic tool. We are currently conducting a human clinical trial to assess the efficacy of exercise in improving aerobic fitness and reducing NAFLD, and because exercise is the proven method to increase aerobic fitness, it should remain the cornerstone therapy for fatty liver disease