Fivebranes and 4-manifolds

We describe rules for building 2d theories labeled by 4-manifolds. Using the proposed dictionary between building blocks of 4-manifolds and 2d N=(0,2) theories, we obtain a number of results, which include new 3d N=2 theories T[M_3] associated with rational homology spheres and new results for Vafa-Witten partition functions on 4-manifolds. In particular, we point out that the gluing measure for the latter is precisely the superconformal index of 2d (0,2) vector multiplet and relate the basic building blocks with coset branching functions. We also offer a new look at the fusion of defect lines / walls, and a physical interpretation of the 4d and 3d Kirby calculus as dualities of 2d N=(0,2) theories and 3d N=2 theories, respectivelyComment: 81 pages, 18 figures. v2: misprints corrected, clarifications and references added. v3: additions and corrections about lens space theory, 4-manifold gluing, smooth structure

Global Transcription Analysis of Krebs Tricarboxylic Acid Cycle Mutants Reveals an Alternating Pattern of Gene Expression and Effects on Hypoxic and Oxidative Genes

To understand the many roles of the Krebs tricarboxylic acid (TCA) cycle in cell function, we used DNA microarrays to examine gene expression in response to TCA cycle dysfunction. mRNA was analyzed from yeast strains harboring defects in each of 15 genes that encode subunits of the eight TCA cycle enzymes. The expression of >400 genes changed at least threefold in response to TCA cycle dysfunction. Many genes displayed a common response to TCA cycle dysfunction indicative of a shift away from oxidative metabolism. Another set of genes displayed a pairwise, alternating pattern of expression in response to contiguous TCA cycle enzyme defects: expression was elevated in aconitase and isocitrate dehydrogenase mutants, diminished in α-ketoglutarate dehydrogenase and succinyl-CoA ligase mutants, elevated again in succinate dehydrogenase and fumarase mutants, and diminished again in malate dehydrogenase and citrate synthase mutants. This pattern correlated with previously defined TCA cycle growth–enhancing mutations and suggested a novel metabolic signaling pathway monitoring TCA cycle function. Expression of hypoxic/anaerobic genes was elevated in α-ketoglutarate dehydrogenase mutants, whereas expression of oxidative genes was diminished, consistent with a heme signaling defect caused by inadequate levels of the heme precursor, succinyl-CoA. These studies have revealed extensive responses to changes in TCA cycle function and have uncovered new and unexpected metabolic networks that are wired into the TCA cycle