Determination of Fatty Acid Oxidation and Lipogenesis in Mouse Primary Hepatocytes

Lipid metabolism in liver is complex. In addition to importing and exporting lipid via lipoproteins, hepatocytes can oxidize lipid via fatty acid oxidation, or alternatively, synthesize new lipid via de novo lipogenesis. The net sum of these pathways is dictated by a number of factors, which in certain disease states leads to fatty liver disease. Excess hepatic lipid accumulation is associated with whole body insulin resistance and coronary heart disease. Tools to study lipid metabolism in hepatocytes are useful to understand the role of hepatic lipid metabolism in certain metabolic disorders. In the liver, hepatocytes regulate the breakdown and synthesis of fatty acids via beta-fatty oxidation and de novo lipogenesis, respectively. Quantifying metabolism in these pathways provides insight into hepatic lipid handling. Unlike in vitro quantification, using primary hepatocytes, making measurements in vivo is technically challenging and resource intensive. Hence, quantifying beta-fatty acid oxidation and de novo lipogenesis in cultured mouse hepatocytes provides a straight forward method to assess hepatocyte lipid handling. Here we describe a method for the isolation of primary mouse hepatocytes, and we demonstrate quantification of beta-fatty acid oxidation and de novo lipogenesis, using radiolabeled substrates

Semiquantum Chaos in the Double-Well

The new phenomenon of semiquantum chaos is analyzed in a classically regular double-well oscillator model. Here it arises from a doubling of the number of effectively classical degrees of freedom, which are nonlinearly coupled in a Gaussian variational approximation (TDHF) to full quantum mechanics. The resulting first-order nondissipative autonomous flow system shows energy dependent transitions between regular behavior and semiquantum chaos, which we monitor by Poincar\'e sections and a suitable frequency correlation function related to the density matrix. We discuss the general importance of this new form of deterministic chaos and point out the necessity to study open (dissipative) quantum systems, in order to observe it experimentally.Comment: LaTeX, 25 pages plus 7 postscript figures. Replaced figure 3 with a non-bitmapped versio

A map of the day-night contrast of the extrasolar planet HD 189733b

"Hot Jupiter" extrasolar planets are expected to be tidally locked because they are close (<0.05 astronomical units, where 1 AU is the average Sun-Earth distance) to their parent stars, resulting in permanent daysides and nightsides. By observing systems where the planet and star periodically eclipse each other, several groups have been able to estimate the temperatures of the daysides of these planets. A key question is whether the atmosphere is able to transport the energy incident upon the dayside to the nightside, which will determine the temperature at different points on the planet's surface. Here we report observations of HD 189733, the closest of these eclipsing planetary systems, over half an orbital period, from which we can construct a 'map' of the distribution of temperatures. We detected the increase in brightness as the dayside of the planet rotated into view. We estimate a minimum brightness temperature of 973 +/- 33 K and a maximum brightness temperature of 1212 +/- 11 K at a wavelength of 8 microns, indicating that energy from the irradiated dayside is efficiently redistributed throughout the atmosphere, in contrast to a recent claim for another hot Jupiter. Our data indicate that the peak hemisphere-integrated brightness occurs 16$\pm$6 degrees before opposition, corresponding to a hot spot shifted east of the substellar point. The secondary eclipse (when the planet moves behind the star) occurs 120 +/- 24 s later than predicted, which may indicate a slightly eccentric orbit.Comment: To appear in the May 10 2007 issue of Nature, 10 pages, 2 black and white figures, 1 colo

Automation and robotics considerations for a lunar base

An envisioned lunar outpost shares with other NASA missions many of the same criteria that have prompted the development of intelligent automation techniques with NASA. Because of increased radiation hazards, crew surface activities will probably be even more restricted than current extravehicular activity in low Earth orbit. Crew availability for routine and repetitive tasks will be at least as limited as that envisioned for the space station, particularly in the early phases of lunar development. Certain tasks are better suited to the untiring watchfulness of computers, such as the monitoring and diagnosis of multiple complex systems, and the perception and analysis of slowly developing faults in such systems. In addition, mounting costs and constrained budgets require that human resource requirements for ground control be minimized. This paper provides a glimpse of certain lunar base tasks as seen through the lens of automation and robotic (A&R) considerations. This can allow a more efficient focusing of research and development not only in A&R, but also in those technologies that will depend on A&R in the lunar environment

OXPHOS-Mediated Induction of NAD+ Promotes Complete Oxidation of Fatty Acids and Interdicts Non-Alcoholic Fatty Liver Disease

OXPHOS is believed to play an important role in non-alcoholic fatty liver disease (NAFLD), however, precise mechanisms whereby OXPHOS influences lipid homeostasis are incompletely understood. We previously reported that ectopic expression of LRPPRC, a protein that increases cristae density and OXPHOS, promoted fatty acid oxidation in cultured primary hepatocytes. To determine the biological significance of that observation and define underlying mechanisms, we have ectopically expressed LRPPRC in mouse liver in the setting of NAFLD. Interestingly, ectopic expression of LRPPRC in mouse liver completely interdicted NAFLD, including inflammation. Consistent with mitigation of NAFLD, two markers of hepatic insulin resistance-ROS and PKCepsilon activity-were both modestly reduced. As reported by others, improvement of NAFLD was associated with improved whole-body insulin sensitivity. Regarding hepatic lipid homeostasis, the ratio of NAD+ to NADH was dramatically increased in mouse liver replete with LRPPRC. Pharmacological activators and inhibitors of the cellular respiration respectively increased and decreased the [NAD+]/[NADH] ratio, indicating respiration-mediated control of the [NAD+]/[NADH] ratio. Supporting a prominent role for NAD+, increasing the concentration of NAD+ stimulated complete oxidation of fatty acids. Importantly, NAD+ rescued impaired fatty acid oxidation in hepatocytes deficient for either OXPHOS or SIRT3. These data are consistent with a model whereby augmented hepatic OXPHOS increases NAD+, which in turn promotes complete oxidation of fatty acids and protects against NAFLD

Age, Period, and Cohort Trends in Mood Disorder and Suicide-Related Outcomes in a Nationally Representative Dataset, 2005-2017

Drawing from the National Survey on Drug Use and Health (NSDUH; N = 611,880), a nationally representative survey of U.S. adolescents and adults, we assess age, period, and cohort trends in mood disorder and suicide-related outcomes since the mid-2000s. Rates of major depressive episode in the last year among adolescents aged 12 to 17 increased by 52% 2005-2017; major depressive episode in the last year increased 63% between 2009 and 2017 among young adults 18-25. Serious psychological distress in the last month and suicide-related outcomes (suicidal ideation, plans, attempts, and deaths by suicide) in the last year also increased among young adults 18-25 between 2008 and 2017, with less consistent and weaker increases among adults ages 26 and over. Hierarchical linear modeling analyses separating the effects of age, period, and birth cohort suggest the trends among adults are primarily due to cohort, with a steady rise in mood disorder and suicide-related outcomes over birth cohorts from the early 1980s to the late 1990s. Cultural trends contributing to an increase in mood disorders and suicidal thoughts and behaviors since the mid-2000s, including the rise of electronic communication and digital media and declines in sleep duration, may have had a larger impact on younger people, creating a cohort effect

The process of establishing implementing and maintaining a social support infant feeding programme

Objective To describe the process of establishing and implementing a social support infant feeding intervention. Design This paper outlines the initial stages of a randomised controlled trial which assessed the effectiveness of a social support intervention on a range of infant feeding outcomes. Details are presented of the processes involved in recruiting, training and supporting a group of volunteers who provided support to the study sample. Setting Camden and Islington, London, UK. Results Initial networking with local agencies and organisations provided invaluable information and contacts. Employing a dedicated volunteer co-ordinator is vitally important in the recruitment, training and support of volunteers. Providing child care and travel expenses is an essential incentive for volunteers with young children. Advertisements placed in local newspapers were the most successful means of recruiting volunteers. Appropriate training is needed to equip volunteers with the necessary knowledge and skills to provide effective support. Particular emphasis in the training focused upon developing the necessary interpersonal skills and self-confidence. The evaluation of the training programme demonstrated that it improved volunteers’ knowledge and reported confidence. The provision of ongoing support is also essential to maintain volunteers’ interest and enthusiasm. The retention of volunteers is, however, a key challenge. Conclusions The processes outlined in this paper have demonstrated the feasibility of successfully establishing, implementing and maintaining a community-based social support infant feeding programme. The experiences described provide useful insights into the practical issues that need to be addressed in setting up a social support intervention

Technical Challenges Associated with In-Air Wingtip Docking of Aircraft in Forward Flight

Autonomous in-air wingtip docking of aircraft offers significant opportunity for system level performance gains for numerous aircraft applications. Several of the technical challenges facing wingtip docking of fixed-wing aircraft are addressed in this paper, including: close proximity aerodynamic coupling; mechanisms and operations for robust docking; and relative state estimation methods. A simulation framework considering the aerodynamics, rigid-body dynamics, and vehicle controls is developed and used to perform docking sensitivity studies for a system of two 5.5% scale NASA Generic Transport Model aircraft. Additionally, proof of- concept testing of a candidate docking mechanism designed to move the primary wingtip vortex inboard suggests the viability of such an approach for achieving robust docking