A Note on Mirror Symmetry for Manifolds with Spin(7) Holonomy

Starting from the superconformal algebras associated with $G_2$ manifolds, I extend the algebra to the manifolds with spin(7) holonomy. I show how the mirror symmetry in manifolds with spin(7) holonomy arises as the automorphism in the extended sperconformal algebra. The automorphism is realized as 14 kinds of T-dualities on the supersymmetric $T^4$ toroidal fibrations. One class of Joyce's orbifolds are pairwise identified under the symmetry.Comment: 12 pages, harvmac bi

G2 Hitchin functionals at one loop

We consider the quantization of the effective target space description of topological M-theory in terms of the Hitchin functional whose critical points describe seven-manifolds with G2 structure. The one-loop partition function for this theory is calculated and an extended version of it, that is related to generalized G2 geometry, is compared with the topological G2 string. We relate the reduction of the effective action for the extended G2 theory to the Hitchin functional description of the topological string in six dimensions. The dependence of the partition functions on the choice of background G2 metric is also determined.Comment: 58 pages, LaTeX; v2: Acknowledgments adde

Colitis and Colon Cancer in WASP-Deficient Mice Require Helicobacter Species

Background: Wiskott–Aldrich syndrome protein–deficient patients and mice are immunodeficient and can develop inflammatory bowel disease. The intestinal microbiome is critical to the development of colitis in most animal models, in which Helicobacter spp. have been implicated in disease pathogenesis. We sought to determine the role of Helicobacter spp. in colitis development in Wiskott–Aldrich syndrome protein–deficient (WKO) mice. Methods: Feces from WKO mice raised under specific pathogen-free conditions were evaluated for the presence of Helicobacter spp., after which a subset of mice were rederived in Helicobacter spp.–free conditions. Helicobacter spp.–free WKO animals were subsequently infected with Helicobacter bilis. Results: Helicobacter spp. were detected in feces from WKO mice. After rederivation in Helicobacter spp.–free conditions, WKO mice did not develop spontaneous colitis but were susceptible to radiation-induced colitis. Moreover, a T-cell transfer model of colitis dependent on Wiskott–Aldrich syndrome protein–deficient innate immune cells also required Helicobacter spp. colonization. Helicobacter bilis infection of rederived WKO mice led to typhlitis and colitis. Most notably, several H. bilis–infected animals developed dysplasia with 10% demonstrating colon carcinoma, which was not observed in uninfected controls. Conclusions: Spontaneous and T-cell transfer, but not radiation-induced, colitis in WKO mice is dependent on the presence of Helicobacter spp. Furthermore, H. bilis infection is sufficient to induce typhlocolitis and colon cancer in Helicobacter spp.–free WKO mice. This animal model of a human immunodeficiency with chronic colitis and increased risk of colon cancer parallels what is seen in human colitis and implicates specific microbial constituents in promoting immune dysregulation in the intestinal mucosa.National Institutes of Health (U.S.) (R01OD011141)National Institutes of Health (U.S.) (R01CA067529)National Institutes of Health (U.S.) (P01CA026731)National Institutes of Health (U.S.) (P30ES02109

Experimental Helicobacter marmotae infection in A/J mice causes enterohepatic disease

Helicobacter marmotae has been identified in the inflamed livers of Eastern woodchucks (Marmota monax) infected with woodchuck hepatitis virus (WHV), as well as from the livers of WHV-negative woodchucks. Because the majority of WHV-positive woodchucks with hepatic tumours were culture or PCR positive for this helicobacter, and WHV-negative woodchucks with H. marmotae had hepatitis, the bacterium may have a role in tumour promotion related to chronic inflammation. In this study, the type strain of H. marmotae was inoculated intraperitoneally into 48 male and female A/J mice, a strain noted to be susceptible to Helicobacter hepaticus-induced liver tumours. Sixteen mice served as mock-dosed controls. At 6, 12 and 18 months post-inoculation (p.i.), there were statistically significant (P<0.05) differences in mean inflammation scores for the caecum and proximal colon between experimentally infected and control mice. Differences in hepatic inflammation were significant (P<0.05) at 6 and 12 months p.i. between the two groups but not at the 18 month time point. Two infected male mice had livers with severe hepatitis, and the liver samples were culture positive for H. marmotae. Serum IgG levels in the mice dosed with H. marmotae were elevated for the duration of the study. These results demonstrate that the woodchuck helicobacter can successfully colonize mice and cause enterohepatic disease. In the future, a mouse-adapted strain of H. marmotae could be selected to maximize colonization and lesion development. Such a woodchuck helicobacter-infected mouse model could be used to dissect potential mechanisms of microbial co-carcinogenesis involved in tumour development in woodchucks with WHV and in humans with hepatitis B virus

Killing-Yano equations and G-structures

We solve the Killing-Yano equation on manifolds with a $G$-structure for $G=SO(n), U(n), SU(n), Sp(n)\cdot Sp(1), Sp(n), G_2$ and $Spin(7)$. Solutions include nearly-K\"ahler, weak holonomy $G_2$, balanced SU(n) and holonomy $G$ manifolds. As an application, we find that particle probes on $AdS_4\times X$ compactifications of type IIA and 11-dimensional supergravity admit a ${\cal W}$-type of symmetry generated by the fundamental forms. We also explore the ${\cal W}$-symmetries of string and particle actions in heterotic and common sector supersymmetric backgrounds. In the heterotic case, the generators of the ${\cal W}$-symmetries completely characterize the solutions of the gravitino Killing spinor equation, and the structure constants of the ${\cal W}$-symmetry algebra depend on the solution of the dilatino Killing spinor equation.Comment: 10 pages, minor change

A web-accessible computer program for calculating electrical potentials and ion activities at cell-membrane surfaces

Increasing evidence indicates that plant responses to ions (uptake/transport, inhibition, and alleviation of inhibition) are dependent upon ion activities at the outer surface of root-cell plasma membranes (PMs) rather than activities in the bulk-phase rooting medium

Negotiating Value: Comparing Human and Animal Fracture Care in Industrial Societies

At the beginning of the twentieth-century, human and veterinary surgeons faced the challenge of a medical marketplace transformed by technology. The socio-economic value ascribed to their patients – people and domestic animals – was changing, reflecting the increasing mechanisation of industry and the decreasing dependence of society upon non-human animals for labour. In human medicine, concern for the economic consequences of fractures “pathologised” any significant level of post-therapeutic disability, a productivist perspective contrary to the traditional corpus of medical values. In contrast, veterinarians adapted to the mechanisation of horse-power by shifting their primary professional interest to companion animals; a type of veterinary patient generally valued for the unique emotional attachment of the owner, and not the productive capacity of the animal. The economic rationalisation of human fracture care and the “sentimental” transformation of veterinary orthopaedic expertise indicates how these specialists utilised increasingly convergent rhetorical arguments to justify the application of innovative fracture care technologies to their humans and animal patients. Keywords: Fracture care, Industrialisation, Veterinary History, Human/animal relation

The over-representation of binary DNA tracts in seven sequenced chromosomes

BACKGROUND: DNA tracts composed of only two bases are possible in six combinations: A+G (purines, R), C+T (pyrimidines, Y), G+T (Keto, K), A+C (Imino, M), A+T (Weak, W) and G+C (Strong, S). It is long known that all-pyrimidine tracts, complemented by all-purines tracts ("R.Y tracts"), are excessively present in analyzed DNA. We have previously shown that R.Y tracts are in vast excess in yeast promoters, and brought evidence for their role in gene regulation. Here we report the systematic mapping of all six binary combinations on the level of complete sequenced chromosomes, as well as in their different subregions. RESULTS: DNA tracts composed of the above binary base combinations have been mapped in seven sequenced chromosomes: Human chromosomes 21 and 22 (the major contigs); Drosophila melanogaster chr. 2R; Caenorhabditis elegans chr. I; Arabidopsis thaliana chr. II; Saccharomyces cerevisiae chr. IV and M. jannaschii. A huge over-representation, reaching million-folds, has been found for very long tracts of all binary motifs except S, in each of the seven organisms. Long R.Y tracts are the most excessive, except in D. melanogaster, where the K.M motif predominates. S (G, C rich) tracts are in excess mainly in CpG islands; the W motif predominates in bacteria. Many excessively long W tracts are nevertheless found also in the archeon and in the eukaryotes. The survey of complete chromosomes enables us, for the first time, to map systematically the intergenic regions. In human and other chromosomes we find the highest over-representation of the binary DNA tracts in the intergenic regions. These over-representations are only partly explainable by the presence of interspersed elements. CONCLUSIONS: The over-representation of long DNA tracts composed of five of the above motifs is the largest deviation from randomness so far established for DNA, and this in a wide range of eukaryotic and archeal chromosomes. A propensity for ready DNA unwinding is proposed as the functional role, explaining the evolutionary conservation of the huge excesses observed

Systemic Macrophage Depletion Inhibits Helicobacter bilis-Induced Proinflammatory Cytokine-Mediated Typhlocolitis and Impairs Bacterial Colonization Dynamics in a BALB/c Rag2(-/-) Mouse Model of Inflammatory Bowel Disease

Helicobacter bilis, an enterohepatic helicobacter, is associated with chronic hepatitis in aged immunocompetent inbred mice and inflammatory bowel disease (IBD) in immunodeficient mice. To evaluate the role of macrophages in H. bilis-induced IBD, Rag2(−/−) BALB/c or wild-type (WT) BALB/c mice were either sham dosed or infected with H. bilis Missouri strain under specific-pathogen-free conditions, followed by an intravenous injection of a 0.2-ml suspension of liposomes coated with either phosphate-buffered saline (control) or clodronate (a macrophage depleting drug) at 15 weeks postinfection (wpi). At 16 wpi, the ceca of H. bilis-infected Rag2(−/−) mice treated with control liposomes had significantly higher histopathological lesional scores (for cumulative typhlitis index, inflammation, edema, epithelial defects, and hyperplasia) and higher counts of F4/80(+) macrophages and MPO(+) neutrophils compared to H. bilis-infected Rag2(−/−) mice treated with clodronate liposomes. In addition, cecal quantitative PCR analyses revealed a significant suppression in the expression of macrophage-related cytokine genes, namely, Tnfa, Il-1β, Il-10, Cxcl1, and iNos, in the clodronate-treated H. bilis-infected Rag2(−/−) mice compared to the H. bilis-infected Rag2(−/−) control mice. Finally, cecal quantitative PCR analyses also revealed a significant reduction in bacterial colonization in the clodronate-treated Rag2(−/−) mice. Taken together, our results suggest that macrophages are critical inflammatory cellular mediators for promoting H. bilis-induced typhlocolitis in mice

The chemokine receptor CXCR5 is pivotal for ectopic mucosa-associated lymphoid tissue neogenesis in chronic Helicobacter pylori-induced inflammation

Ectopic lymphoid follicles are a key feature of chronic inflammatory autoimmune and infectious diseases, such as rheumatoid arthritis, Sjögren's syndrome, and Helicobacter pylori-induced gastritis. Homeostatic chemokines are considered to be involved in the formation of such tertiary lymphoid tissue. High expression of CXCL13 and its receptor, CXCR5, has been associated with the formation of ectopic lymphoid follicles in chronic infectious diseases. Here, we defined the role of CXCR5 in the development of mucosal tertiary lymphoid tissue and gastric inflammation in a mouse model of chronic H. pylori infection. CXCR5-deficient mice failed to develop organized gastric lymphoid follicles despite similar bacterial colonization density as infected wild-type mice. CXCR5 deficiency altered Th17 responses but not Th1-type cellular immune responses to H. pylori infection. Furthermore, CXCR5-deficient mice exhibited lower H. pylori-specific serum IgG and IgA levels and an overall decrease in chronic gastric immune responses. In conclusion, the development of mucosal tertiary ectopic follicles during chronic H. pylori infection is strongly dependent on the CXCL13/CXCR5 signaling axis, and lack of de novo lymphoid tissue formation attenuates chronic immune responses