Zeta functions and Bernstein-Sato polynomials for ideals in dimension two

For a nonzero ideal I of C[x_1,...,x_n], with 0 in supp I, a generalization of a conjecture of Igusa - Denef - Loeser predicts that every pole of its topological zeta function is a root of its Bernstein-Sato polynomial. However, typically only a few roots are obtained this way. Following ideas of Veys, we study the following question. Is it possible to find a collection G of polynomials g in C[x_1,...,x_n], such that, for all g in G, every pole of the topological zeta function associated to I and the volume form gdx on the affine n-space, is a root of the Bernstein-Sato polynomial of I, and such that all roots are realized in this way. We obtain a negative answer to this question, providing counterexamples for monomial and principal ideals in dimension two, and give a partial positive result as well.Comment: 19 pages, 8 figure

Igusa's p-adic local zeta function associated to a polynomial mapping and a polynomial integration measure

For p prime, we give an explicit formula for Igusa's local zeta function associated to a polynomial mapping f=(f_1,...,f_t): Q_p^n -> Q_p^t, with f_1,...,f_t in Z_p[x_1,...,x_n], and an integration measure on Z_p^n of the form |g(x)||dx|, with g another polynomial in Z_p[x_1,...,x_n]. We treat the special cases of a single polynomial and a monomial ideal separately. The formula is in terms of Newton polyhedra and will be valid for f and g sufficiently non-degenerated over F_p with respect to their Newton polyhedra. The formula is based on, and is a generalization of results of Denef - Hoornaert, Howald et al., and Veys - Zuniga-Galindo.Comment: 20 pages, 5 figures, 2 table

Clonal Groupings in Serogroup X Neisseria meningitidis

The genetic diversity of 134 serogroup X Neisseria meningitis isolates from Africa, Europe, and North America was analyzed by multilocus sequence typing and pulsed-field gel electrophoresis. Although most European and American isolates were highly diverse, one clonal grouping was identified in sporadic disease and carrier strains isolated over the last 2 decades in the United Kingdom, the Netherlands, Germany, and the United States. In contrast to the diversity in the European and American isolates, most carrier and disease isolates recovered during the last 30 years in countries in the African meningitis belt belonged to a second clonal grouping. During the last decade, these bacteria have caused meningitis outbreaks in Niger and Ghana. These results support the development of a comprehensive conjugate vaccine that would include serogroup X polysaccharide

Transanal endoscopic microsurgery versus endoscopic mucosal resection for large rectal adenomas (TREND-study)

Background: Recent non-randomized studies suggest that extended endoscopic mucosal resection (EMR) is equally effective in removing large rectal adenomas as transanal endoscopic microsurgery (TEM). If equally effective, EMR might be a more cost-effective approach as this strategy does not require expensive equipment, general anesthesia and hospital admission. Furthermore, EMR appears to be associated with fewer complications. The aim of this study is to compare the cost-effectiveness and cost-utility of TEM and EMR for the resection of large rectal adenomas. Methods/design. Multicenter randomized trial among 15 hospitals in the Netherlands. Patients with a rectal adenoma 3 cm, located between 115 cm ab ano, will be randomized to a TEM- or EMR-treatment strategy. For TEM, patients will be treated under general anesthesia, adenomas will be dissected en-bloc by a full-thickness excision, and patients will be admitted to the hospital. For EMR, no or conscious sedation is used, lesions will be resected through the submucosal plane i

Igusa's p-adic local zeta function and the Monodromy Conjecture for non-degenerate surface singularities

In 2011 Lemahieu and Van Proeyen proved the Monodromy Conjecture for the local topological zeta function of a non-degenerate surface singularity. We start from their work and obtain the same result for Igusa's p-adic and the motivic zeta function. In the p-adic case, this is, for a polynomial f in Z[x,y,z] satisfying f(0,0,0)=0 and non-degenerate with respect to its Newton polyhedron, we show that every pole of the local p-adic zeta function of f induces an eigenvalue of the local monodromy of f at some point of the complex zero locus of f close to the origin. Essentially the entire paper is dedicated to proving that, for f as above, certain candidate poles of Igusa's p-adic zeta function of f, arising from so-called B_1-facets of the Newton polyhedron of f, are actually not poles. This turns out to be much harder than in the topological setting. The combinatorial proof is preceded by a study of the integral points in three-dimensional fundamental parallelepipeds. Together with the work of Lemahieu and Van Proeyen, this main result leads to the Monodromy Conjecture for the p-adic and motivic zeta function of a non-degenerate surface singularity.119 pages, 11 figures, 2 tablesstatus: publishe

Impaired alternative macrophage differentiation of peripheral blood mononuclear cells from obese subjects.: Macrophage alternative differentiation and obesity

International audienceVisceral obesity is a chronic, low-grade inflammatory disease that predisposes people to the metabolic syndrome, type 2 diabetes and its cardiovascular complications. Adipose tissue is not a passive storehouse for fat, but an endocrine organ synthesizing and releasing a variety of bioactive molecules, some of which are produced by infiltrated immune-inflammatory cells including macrophages. Two different subpopulations of macrophages have been identified in adipose tissue: pro-inflammatory 'classical' M1 and anti-inflammatory 'alternative' M2 macrophages, and their ratio is suggested to influence the metabolic complications of obesity. These macrophages derive primarily from peripheral blood mononuclear cells (PBMCs). We hypothesised that obesity and the metabolic syndrome modulate PBMC functions. Therefore, alteration of the monocyte response, and more specifically their ability to differentiate toward alternative anti-inflammatory macrophages, was assessed in PBMCs isolated from lean and obese subjects with or without alterations in glucose homeostasis. Our results indicate that PBMCs from obese subjects have an altered expression of M2 markers and that their monocytes are less susceptible to differentiate toward an alternative phenotype. Thus PBMCs in obesity are programmed, which may contribute to the inflammatory dysregulation and increased susceptibility to inflammatory diseases in these patients

: LXR controls macrophage iron metabolism

International audienceRATIONALE: In atherosclerotic plaques, iron preferentially accumulates in macrophages where it can exert pro-oxidant activities. OBJECTIVE: The objective of this study was, first, to better characterize the iron distribution and metabolism in macrophage subpopulations in human atherosclerotic plaques and, second, to determine whether iron homeostasis is under the control of nuclear receptors, such as the liver X receptors (LXRs). METHODS AND RESULTS: Here we report that iron depots accumulate in human atherosclerotic plaque areas enriched in CD68 and mannose receptor (MR)-positive (CD68(+)MR(+)) alternative M2 macrophages. In vitro IL-4 polarization of human monocytes into M2 macrophages also resulted in a gene expression profile and phenotype favoring iron accumulation. However, M2 macrophages on iron exposure acquire a phenotype favoring iron release, through a strong increase in ferroportin expression, illustrated by a more avid oxidation of extracellular low-density lipoprotein by iron-loaded M2 macrophages. In line, in human atherosclerotic plaques, CD68(+)MR(+) macrophages accumulate oxidized lipids, which activate LXRα and LXRβ, resulting in the induction of ABCA1, ABCG1, and apolipoprotein E expression. Moreover, in iron-loaded M2 macrophages, LXR activation induces nuclear factor erythroid 2-like 2 expression, thereby increasing ferroportin expression, which, together with a decrease of hepcidin mRNA levels, promotes iron export. CONCLUSIONS: These data identify a role for M2 macrophages in iron handling, a process regulated by LXR activation

Human atherosclerotic plaque alternative macrophages display low cholesterol handling but high phagocytosis because of distinct activities of the PPARγ and LXRα pathways.: Atherosclerotic plaque alternative macrophages

International audienceRATIONALE: A crucial step in atherogenesis is the infiltration of the subendothelial space of large arteries by monocytes where they differentiate into macrophages and transform into lipid-loaded foam cells. Macrophages are heterogeneous cells that adapt their response to environmental cytokines. Th1 cytokines promote monocyte differentiation into M1 macrophages, whereas Th2 cytokines trigger an "alternative" M2 phenotype. OBJECTIVE: We previously reported the presence of CD68(+) mannose receptor (MR)(+) M2 macrophages in human atherosclerotic plaques. However, the function of these plaque CD68(+)MR(+) macrophages is still unknown. METHODS AND RESULTS: Histological analysis revealed that CD68(+)MR(+) macrophages locate far from the lipid core of the plaque and contain smaller lipid droplets compared to CD68(+)MR(-) macrophages. Interleukin (IL)-4-polarized CD68(+)MR(+) macrophages display a reduced capacity to handle and efflux cellular cholesterol because of low expression levels of the nuclear receptor liver x receptor (LXR)α and its target genes, ABCA1 and apolipoprotein E, attributable to the high 15-lipoxygenase activity in CD68(+)MR(+) macrophages. By contrast, CD68(+)MR(+) macrophages highly express opsonins and receptors involved in phagocytosis, resulting in high phagocytic activity. In M2 macrophages, peroxisome proliferator-activated receptor (PPAR)γ activation enhances the phagocytic but not the cholesterol trafficking pathways. CONCLUSIONS: These data identify a distinct macrophage subpopulation with a low susceptibility to become foam cells but high phagocytic activity resulting from different regulatory activities of the PPARγ-LXRα pathways

Human adipose tissue macrophages display activation of cancer-related pathways.: ATM link obesity and cancer?

International audienceObesity is associated with a significantly increased risk for cancer suggesting that adipose tissue dysfunctions might play a crucial role therein. Macrophages play important roles in adipose tissue as well as in cancers. Here, we studied whether human adipose tissue macrophages (ATM) modulate cancer cell function. Therefore, ATM were isolated and compared with monocyte-derived macrophages (MDM) from the same obese patients. ATM, but not MDM, were found to secrete factors inducing inflammation and lipid accumulation in human T47D and HT-29 cancer cells. Gene expression profile comparison of ATM and MDM revealed overexpression of functional clusters, such as cytokine-cytokine receptor interaction (especially CXC-chemokine) signaling as well as cancer-related pathways, in ATM. Comparison with gene expression profiles of human tumor-associated macrophages showed that ATM, but not MDM resemble tumor-associated macrophages. Indirect co-culture experiments demonstrated that factors secreted by preadipocytes, but not mature adipocytes, confer an ATM-like phenotype to MDM. Finally, the concentrations of ATM-secreted factors related to cancer are elevated in serum of obese subjects. In conclusion, ATM may thus modulate the cancer cell phenotype