mTORC1-independent Raptor prevents hepatic steatosis by stabilizing PHLPP2

Mechanistic target of rapamycin complex 1 (mTORC1), defined by the presence of Raptor, is an evolutionarily conserved and nutrient-sensitive regulator of cellular growth and other metabolic processes. To date, all known functions of Raptor involve its scaffolding mTOR kinase with substrate. Here we report that mTORC1-independent (‘free’) Raptor negatively regulates hepatic Akt activity and lipogenesis. Free Raptor levels in liver decline with age and in obesity; restoration of free Raptor levels reduces liver triglyceride content, through reduced β-TrCP-mediated degradation of the Akt phosphatase, PHLPP2. Commensurately, forced PHLPP2 expression ameliorates hepatic steatosis in diet-induced obese mice. These data suggest that the balance of free and mTORC1-associated Raptor governs hepatic lipid accumulation, and uncover the potentially therapeutic role of PHLPP2 activators in non-alcoholic fatty liver disease

Very Extended E8E_8 and A8A_8 at low levels, Gravity and Supergravity

We define a level for a large class of Lorentzian Kac-Moody algebras. Using this we find the representation content of very extended $A_{D-3}$ and $E_8$ (i.e. $E_{11}$) at low levels in terms of $A_{D-1}$ and $A_{10}$ representations respectively. The results are consistent with the conjectured very extended $A_8$ and $E_{11}$ symmetries of gravity and maximal supergravity theories given respectively in hep-th/0104081 and hep-th/0107209. We explain how these results provided further evidence for these conjectures.Comment: 16 pages, plain tex (equation 3.3 modified and one reference expanded

Anti-self-dual conformal structures with null Killing vectors from projective structures

Using twistor methods, we explicitly construct all local forms of four--dimensional real analytic neutral signature anti--self--dual conformal structures $(M,[g])$ with a null conformal Killing vector. We show that $M$ is foliated by anti-self-dual null surfaces, and the two-dimensional leaf space inherits a natural projective structure. The twistor space of this projective structure is the quotient of the twistor space of $(M,[g])$ by the group action induced by the conformal Killing vector. We obtain a local classification which branches according to whether or not the conformal Killing vector is hyper-surface orthogonal in $(M, [g])$. We give examples of conformal classes which contain Ricci--flat metrics on compact complex surfaces and discuss other conformal classes with no Ricci--flat metrics.Comment: 43 pages, 4 figures. Theorem 2 has been improved: ASD metrics are given in terms of general projective structures without needing to choose special representatives of the projective connection. More examples (primary Kodaira surface, neutral Fefferman structure) have been included. Algebraic type of the Weyl tensor has been clarified. Final version, to appear in Commun Math Phy

3-dimensional Cauchy-Riemann structures and 2nd order ordinary differential equations

The equivalence problem for second order ODEs given modulo point transformations is solved in full analogy with the equivalence problem of nondegenerate 3-dimensional CR structures. This approach enables an analog of the Feffereman metrics to be defined. The conformal class of these (split signature) metrics is well defined by each point equivalence class of second order ODEs. Its conformal curvature is interpreted in terms of the basic point invariants of the corresponding class of ODEs

Currents and Superpotentials in classical gauge invariant theories I. Local results with applications to Perfect Fluids and General Relativity

E. Noether's general analysis of conservation laws has to be completed in a Lagrangian theory with local gauge invariance. Bulk charges are replaced by fluxes of superpotentials. Gauge invariant bulk charges may subsist when distinguished one-dimensional subgroups are present. As a first illustration we propose a new {\it Affine action} that reduces to General Relativity upon gauge fixing the dilatation (Weyl 1918 like) part of the connection and elimination of auxiliary fields. It allows a comparison of most gravity superpotentials and we discuss their selection by the choice of boundary conditions. A second and independent application is a geometrical reinterpretation of the convection of vorticity in barotropic nonviscous fluids. We identify the one-dimensional subgroups responsible for the bulk charges and thus propose an impulsive forcing for creating or destroying selectively helicity. This is an example of a new and general Forcing Rule.Comment: 64 pages, LaTeX. Version 2 has two more references and one misprint corrected. Accepted in Classical and Quantum Gravit

Physical activity and long-term survival in older men and women: A 21 year longitudinal study

The NLSAA survey was conducted in 1985 with 1,042 participants. As of 31st May 2006 (21 years from baseline), there were 919 recorded deaths (368 men and 551 women). Mortality analyses were from baseline interview to death or censorship (May 2006). Men and women were analysed separately in unadjusted models and adjusting for demographic and health-related variables. In separate unadjusted models, participation in outdoor activities, indoor productive activities, leisure activities, walking, undertaking activities requiring flexibility, and physical effort each were associated with reduced long-term mortality among both men and women. In adjusted models, participation in physical activities had no significant association with mortality risk for men. Among women, participation in outdoor activities and leisure activities remained significantly associated with long-term survival in adjusted models. Among men, the benefits of physical activities for mortality risk were explained through demographic, health, and psychosocial variables. However, participation in outdoor and leisure physical activities was beneficial for women and had a significant association with survival, even when controlling for demographic, health and psychosocial variables. Therefore, encouraging participation in specific physical activities, such as gardening, swimming, and dancing among older women may improve long-term survival

Covariance properties and regularization of conserved currents in tetrad gravity

We discuss the properties of the gravitational energy-momentum 3-form within the tetrad formulation of general relativity theory. We derive the covariance properties of the quantities describing the energy-momentum content under Lorentz transformations of the tetrad. As an application, we consider the computation of the total energy (mass) of some exact solutions of Einstein's general relativity theory which describe compact sources with asymptotically flat spacetime geometry. As it is known, depending on the choice of tetrad frame, the formal total integral for such configurations may diverge. We propose a natural regularization method which yields finite values for the total energy-momentum of the system and demonstrate how it works on a number of explicit examples.Comment: 36 pages, Revtex, no figures; small changes, published versio

Role of extracellular iron in the action of the quinone antibiotic streptonigrin: mechanisms of killing and resistance of Neisseria gonorrhoeae.

The quinone antibiotic streptonigrin is believed to kill bacteria by promoting formation of oxygen radicals. This antibiotic has also been used to select resistant bacterial mutants, some of which vary in iron utilization. We examined the effects of streptonigrin on Neisseria gonorrhoeae and several types of gonococcal mutants. Streptonigrin (0.025 microgram/ml) efficiently killed gonococcal strain FA1090, and this effect depended on iron. Streptonigrin-resistant mutant FA6271 had normal iron uptake but was moderately deficient in total iron. Resistance most likely resulted from failure of FA6271 to divert electrons to streptonigrin, as demonstrated by a reduction in KCN-insensitive respiration (a hallmark of the action of quinones) and superoxide formation. Other mutants selected for inability to use human iron-binding proteins (strains FA6273 and FA6275) had no increase in streptonigrin MIC and no decrease in KCN-insensitive respiration. Mutants did not demonstrate an increase in superoxide dismutase or catalase. Streptonigrin killing of gonococci depended on a reaction(s) in which extracellular iron was important, presumably because iron was required for catalysis of hydroxyl radical. The results suggest that a membrane component may be a target for the actions of streptonigrin

Tropospheric Carbon Monoxide Measurements from the Scanning High-Resolution Interferometer Sounder on 7 September 2000 in Southern Africa During SAFARI 2000

[1] Retrieved tropospheric carbon monoxide (CO) column densities are presented for more than 9000 spectra obtained by the University of Wisconsin-Madison (UWis) Scanning High-Resolution Interferometer Sounder (SHIS) during a flight on the NASA ER-2 on 7 September 2000 as part of the Southern African Regional Science Initiative (SAFARI 2000) dry season field campaign. Enhancements in tropospheric column CO were detected in the vicinity of a controlled biomass burn in the Timbavati Game Reserve in northeastern South Africa and over the edge of the river of smoke in south central Mozambique. Relatively clean air was observed over the far southern coast of Mozambique. Quantitative comparisons are presented with in situ measurements from five different instruments flying on two other aircraft: the University of Washington Convair-580 (CV) and the South African Aerocommander JRB in the vicinity of the Timbavati fire. Measured tropospheric CO columns (extrapolated from 337 to 100 mb) of 2.1 × 1018 cm−2 in background air and up to 1.5 × 1019 cm−2 in the smoke plume agree well with SHIS retrieved tropospheric CO columns of (2.3 ± 0.25) × 1018 cm−2 over background air near the fire and (1.5 ± 0.35) × 1019 cm−2 over the smoke plume. Qualitative comparisons are presented with three other in situ CO profiles obtained by the South African JRA aircraft over Mozambique and northern South Africa showing the influence of the river of smoke

Sedentary time in older men and women: an international consensus statement and research priorities

Sedentary time is a modifiable determinant of poor health, and in older adults, reducing sedentary time may be an important first step in adopting and maintaining a more active lifestyle. The primary purpose of this consensus statement is to provide an integrated perspective on current knowledge and expert opinion pertaining to sedentary behaviour in older adults on the topics of measurement, associations with health outcomes, and interventions. A secondary yet equally important purpose is to suggest priorities for future research and knowledge translation based on gaps identified. A five-step Delphi consensus process was used. Experts in the area of sedentary behaviour and older adults (n=15) participated in three surveys, an in-person consensus meeting, and a validation process. The surveys specifically probed measurement, health outcomes, interventions, and research priorities. The meeting was informed by a literature review and conference symposium, and it was used to create statements on each of the areas addressed in this document. Knowledge users (n=3) also participated in the consensus meeting. Statements were then sent to the experts for validation. It was agreed that self-report tools need to be developed for understanding the context in which sedentary time is accumulated. For health outcomes, it was agreed that the focus of sedentary time research in older adults needs to include geriatric-relevant health outcomes, that there is insufficient evidence to quantify the dose-response relationship, that there is a lack of evidence on sedentary time from older adults in assisted facilities, and that evidence on the association between sedentary time and sleep is lacking. For interventions, research is needed to assess the impact that reducing sedentary time, or breaking up prolonged bouts of sedentary time has on geriatric-relevant health outcomes. Research priorities listed for each of these areas should be considered by researchers and funding agencies