Permutative categories, multicategories, and algebraic K-theory

We show that the $K$-theory construction of arXiv:math/0403403, which preserves multiplicative structure, extends to a symmetric monoidal closed bicomplete source category, with the multiplicative structure still preserved. The source category of arXiv:math/0403403, whose objects are permutative categories, maps fully and faithfully to the new source category, whose objects are (based) multicategories

Diagram spaces, diagram spectra, and spectra of units

This article compares the infinite loop spaces associated to symmetric spectra, orthogonal spectra, and EKMM S-modules. Each of these categories of structured spectra has a corresponding category of structured spaces that receives the infinite loop space functor \Omega^\infty. We prove that these models for spaces are Quillen equivalent and that the infinite loop space functors \Omega^\infty agree. This comparison is then used to show that two different constructions of the spectrum of units gl_1 R of a commutative ring spectrum R agree.Comment: 62 pages. The definition of the functor \mathbb{Q} is changed. Sections 8, 9, 17 and 18 contain revisions and/or new materia

Homology of E_n Ring Spectra and Iterated THH

We describe an iterable construction of THH for an E_n ring spectrum. The reduced version is an iterable bar construction and its n-th iterate gives a model for the shifted cotangent complex at the augmentation, representing reduced topological Quillen homology of an augmented E_n algebra.Comment: Some additional exposition added. Minor correction

Hexosamines Provoke Membrane Cholesterol Accrual, Filamentous Actin Loss, and GLUT4 Dysregulation in Adipocytes through Transcriptional Activation of Specificity Protein 1

poster abstractThe hexosamine biosynthesis pathway (HBP) serves as a sensor of excess nutrient bioavailability and has been implicated in the pathogenesis of type 2 diabetes. Previous study observed that hyperinsulinemic culturing conditions akin to those seen clinically activate the HBP provoking gains in plasma membrane (PM) cholesterol content in L6 myotubes and 3T3-L1 adipocytes. This, in turn, compromised the cortical filamentous actin (F-actin) structure necessary for the proper incorporation of the insulin sensitive glucose transporter GLUT4 into the membrane. The mechanism(s), however, by which HBP activation provokes PM cholesterol accrual, remains unclear. Here, the hypothesis that HBP engages a cholesterolgenic transcriptional response resulting in PM cholesterol accrual/toxicity was tested. In 3T3-L1 adipocytes, pathophysiologically relevant doses of hyperinsulinemia (0.25, 0.5, and 5 nM) resulted in a dose-dependent gain in PM cholesterol as well as mRNA and protein levels of HMG-CoA reductase (HMGR), the rate limiting enzyme in cholesterol synthesis. Immunoprecipitation experiments demonstrated that hyperinsulinemia induced elevations in O-linked N-acetylglucosamine post-translational modification of the cholesterolgenic transcription factor specificity protein 1 (Sp1). This modification was prevented in cells in which the HBP was inhibited. Chromatin immunoprecipitation demonstrated that hyperinsulinemia induced a ~4 fold increase in the affinity of Sp1 to the promoter region of HMGR, which was lost with HBP inhibition. Luciferase assays confirmed that this altered binding resulted in a ~50% increase in promoter activity of this cholesterolgenic gene. Hyperinsulinemia also augmented Sp1 binding to the promoter of the sterol response element binding protein gene, resulting in increased total and nuclear content of this factor. To further delineate the role of Sp1 in this process, a specific inhibitor, mithramycin (MTR), of Sp1 binding to DNA was employed. This inhibitor prevented against hyperinsulinemia-induced gains in HMGR and PM cholesterol as well as F-actin loss. Importantly, this treatment corrected the impaired insulin-stimulated GLUT4 translocation and glucose transport induced by hyperinsulinemia. These data suggest hyperinsulinemia-induced HBP activity provokes cholesterol synthesis and PM cholesterol accrual/F-actin loss that compromises GLUT4/glucose transport regulation by insulin

New aspects of cellular cholesterol regulation on blood glucose control- review and perspective on the impact of statin medications on metabolic health

Cholesterol is an essential component of cell membranes, and during the past several years, diabetes researchers have found that membrane cholesterol levels in adipocytes, skeletal muscle fibers and pancreatic beta cells influence insulin action and insulin secretion. Consequently, it is thought that dysregulated cell cholesterol homeostasis could represent a determinant of type 2 diabetes (T2D). Recent clinical findings compellingly add to this notion by finding increased T2D susceptibility in individuals with alterations in a variety of cholesterol metabolism genes. While it remains imperfectly understood how statins influence glucose metabolism, the fact that they display an influence on blood glucose levels and diabetes susceptibility seems to intensify the emerging importance of understanding cellular cholesterol in glucose metabolism. Taking this into account, this review first presents cell system and animal model findings that demonstrate the negative impact of cellular cholesterol accumulation or diminution on insulin action and insulin secretion. With this framework, a description of how changes in cholesterol metabolism genes are associated with T2D susceptibility will be presented. In addition, the connection between statins and T2D risk will be reviewed with expanded information on pitavastatin, a newer statin medication that displays actions favoring metabolic healt

The smash product for derived categories in stable homotopy theory

An E_1 (or A-infinity) ring spectrum R has a derived category of modules D_R. An E_2 structure on R endows D_R with a monoidal product. An E_3 structure on R endows the monoidal product with a braiding. If the E_3 structure extends to an E_4 structure then the braided monoidal product is symmetric monoidal.Comment: Minor correction

Modules in Monoidal Model Categories

This paper studies the existence of and compatibility between derived change of ring, balanced product, and function module derived functors on module categories in monoidal model categories

Yang-Mills theory over surfaces and the Atiyah-Segal theorem

In this paper we explain how Morse theory for the Yang-Mills functional can be used to prove an analogue, for surface groups, of the Atiyah-Segal theorem. Classically, the Atiyah-Segal theorem relates the representation ring R(\Gamma) of a compact Lie group $\Gamma$ to the complex K-theory of the classifying space $B\Gamma$. For infinite discrete groups, it is necessary to take into account deformations of representations, and with this in mind we replace the representation ring by Carlsson's deformation $K$--theory spectrum \K (\Gamma) (the homotopy-theoretical analogue of $R(\Gamma)$). Our main theorem provides an isomorphism in homotopy \K_*(\pi_1 \Sigma)\isom K^{-*}(\Sigma) for all compact, aspherical surfaces $\Sigma$ and all $*>0$. Combining this result with work of Tyler Lawson, we obtain homotopy theoretical information about the stable moduli space of flat unitary connections over surfaces.Comment: 43 pages. Changes in v4: improved results in Section 7, simplified arguments in the Appendix, various minor revision

Effect of Corncob bedding on feed conversion efficiency in a high-fat diet-induced prediabetic model in C57Bl/6J mice

Laboratory facilities use many varieties of contact bedding, including wood chips, paper products, and corncob, each with its own advantages and disadvantages. Corncob bedding, for example, is often used because of its high absorbency, ability to minimize detectable ammonia, and low cost. However, observations that mice eat the corncob lead to concerns that its use can interfere with dietary studies. We evaluated the effect of corncob bedding on feed conversion (change in body weight relative to the apparent number of kcal consumed over 7 d) in mice. Four groups of mice (6 to 12 per group) were housed in an individually ventilated caging system: (1) low-fat diet housed on recycled paper bedding, (2) low-fat diet housed on corncob bedding, (3) high-fat diet housed on recycled paper bedding, and (4) high-fat diet housed on corncob bedding. After 4 wk of the high-fat diet, feed conversion and percentage body weight change both were lower in corncob-bedded mice compared with paper-bedded mice. Low-fat-fed mice on corncob bedding versus paper bedding did not show statistically significant differences in feed conversion or change in percentage body weight. Average apparent daily feed consumption did not differ among the 4 groups. In conclusion, these data suggest that corncob bedding reduces the efficiency of feed conversion in mice fed a high-fat diet and that other bedding choices should be favored in these models