The Non-Perturbative N=2{\cal N} = 2 SUSY Yang-Mills Theory from Semiclassical Absorption of Supergravity by Wrapped D Branes

The imaginary part of the two point functions of the superconformal anomalous currents are extracted from the cross-sections of semiclassical absorption of dilaton, RR-2 form and gravitino by the wrapped D5 branes. From the central terms of the two point functions anomalous Ward identity is established which relates the exact pre-potential of the ${\cal N}=2$ SUSY Yang-Mills theory with the vacuum expectation value of the anomaly multiplet. From the Ward identity, WDVV (Witten-Dijkgraaf-Verlinde-Verlinde) equation can be derived which is solved for the exact pre-potential.Comment: 11 pages, late

The Gravity dual of the Non-Perturbative N=2 N = 2 SUSY Yang-Mills Theory

The anomalous Ward identity is derived for $N = 2$ SUSY Yang-Mills theories, which is resulted out of Wrapping of $D_5$ branes on Supersymmetric two cycles. From the Ward identity One obtains the Witten-Dijkgraaf-Verlinde-Verlinde equation and hence can solve for the pre-potential. This way one avoids the problem of enhancon which maligns the non-perturbative behaviour of the Yang-Mills theory resulted out of Wrapped branes.Comment: 4 pages, LaTeX. Talk given at the IXth International Symposium on Particles, Strings and Cosmology PASCOS '03, Mumbai-India, January 3-8 2003. v2:some reference adde

Temporal orchestration of circadian autophagy rhythm by C/EBPβ

Temporal organization of tissue metabolism is important for maintaining nutrient and energy homeostasis in mammals. Autophagy is a conserved cellular pathway that is activated in response to nutrient limitation, resulting in the degradation of cytoplasmic components and the release of amino acids and other nutrients. Here, we show that autophagy exhibits robust circadian rhythm in mouse liver, which is accompanied by cyclic induction of genes involved in various steps of autophagy. Functional analyses of transcription factors and cofactors identified C/EBPβ as a potent activator of autophagy. C/EBPβ is rhythmically expressed in the liver and is regulated by both circadian and nutritional signals. In cultured primary hepatocytes, C/EBPβ stimulates the program of autophagy gene expression and is sufficient to activate autophagic protein degradation. Adenoviral-mediated RNAi knockdown of C/EBPβ in vivo abolishes diurnal autophagy rhythm in the liver. Further, circadian regulation of C/EBPβ and autophagy is disrupted in mice lacking a functional liver clock. We have thus identified C/EBPβ as a key factor that links autophagy to biological clock and maintains nutrient homeostasis throughout light/dark cycles

Temporal orchestration of circadian autophagy rhythm by C/EBPβ

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102116/1/embj2011322.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102116/2/embj2011322-sup-0001.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102116/3/embj2011322-reviewer_comments.pd

Neuronal reprogramming of mouse and human fibroblasts using transcription factors involved in suprachiasmatic nucleus development

Summary: The hypothalamic suprachiasmatic nucleus (SCN) is composed of heterogenous populations of neurons that express signaling peptides such as vasoactive intestinal polypeptide (VIP) and arginine vasopressin (AVP) and regulate circadian rhythms in behavior and physiology. SCN neurons acquire functional and morphological specializations from waves of transcription factors (TFs) that are expressed during neurogenesis. However, the in vitro generation of SCN neurons has never been achieved. Here we supplemented a highly efficient neuronal conversion protocol with TFs that are expressed during SCN neurogenesis, namely Six3, Six6, Dlx2, and Lhx1. Neurons induced from mouse and human fibroblasts predominantly exhibited neuronal properties such as bipolar or multipolar morphologies, GABAergic neurons with expression of VIP. Our study reveals a critical contribution of these TFs to the development of vasoactive intestinal peptide (Vip) expressing neurons in the SCN, suggesting the regenerative potential of neuronal subtypes contained in the SCN for future SCN regeneration and in vitro disease remodeling

The RNA-Binding Protein NONO Coordinates Hepatic Adaptation to Feeding

The mechanisms by which feeding and fasting drive rhythmic gene expression for physiological adaptation to daily rhythm in nutrient availability are not well understood. Here we show that, upon feeding, the RNA-binding protein NONO accumulates within speckle-like structures in liver cell nuclei. Combining RNA-immunoprecipitation and sequencing (RIP-seq), we find that an increased number of RNAs are bound by NONO after feeding. We further show that NONO binds and regulates the rhythmicity of genes involved in nutrient metabolism post-transcriptionally. Finally, we show that disrupted rhythmicity of NONO target genes has profound metabolic impact. Indeed, NONO-deficient mice exhibit impaired glucose tolerance and lower hepatic glycogen and lipids. Accordingly, these mice shift from glucose storage to fat oxidation, and therefore remain lean throughout adulthood. In conclusion, our study demonstrates that NONO post-transcriptionally coordinates circadian mRNA expression of metabolic genes with the feeding/fasting cycle, thereby playing a critical role in energy homeostasis