1,606 research outputs found
On positivity of Ehrhart polynomials
Ehrhart discovered that the function that counts the number of lattice points
in dilations of an integral polytope is a polynomial. We call the coefficients
of this polynomial Ehrhart coefficients, and say a polytope is Ehrhart positive
if all Ehrhart coefficients are positive (which is not true for all integral
polytopes). The main purpose of this article is to survey interesting families
of polytopes that are known to be Ehrhart positive and discuss the reasons from
which their Ehrhart positivity follows. We also include examples of polytopes
that have negative Ehrhart coefficients and polytopes that are conjectured to
be Ehrhart positive, as well as pose a few relevant questions.Comment: 40 pages, 7 figures. To appear in in Recent Trends in Algebraic
Combinatorics, a volume of the Association for Women in Mathematics Series,
Springer International Publishin
Mechanism-Based Treatment Strategies for IBD: Cytokines, Cell Adhesion Molecules, JAK Inhibitors, Gut Flora, and More
Background
Although TNF inhibitors revolutionized the therapy of inflammatory bowel disease (IBD), we have been reaching a point where other therapies with different mechanisms of action are necessary. A rising number of elderly IBD patients with contraindications to established therapies and a growing group of patients losing response to anti-TNF therapy compel us to find safer, better-tolerated, and, ideally, personalized treatment options. However, in order to choose the right drug to fit a patient, it is indispensable to understand the pathomechanism involved in IBD.
Summary
The aim of this review is to explain the inflammatory signaling pathways in IBD and how to inhibit them with current and future therapeutic approaches. Next to biologic agents targeting inflammatory cytokines (anti-TNF agents, anti-IL-12/-23 agents, and specific inhibitors of IL-23), biologics blocking leukocyte trafficking to the gut (anti-integrin antibodies) are available nowadays. More recently, small molecules inhibiting the JAK-STAT pathway (JAK inhibitors) or preventing lymphocyte trafficking (sphingosine-1-phosphate modulators) have been approved or are under investigation. Furthermore, modifying the microbiota has potential therapeutic effects on IBD, and autologous hematopoietic or mesenchymal stem cell transplantation may be considered for a highly selected group of IBD patients.
Key Message
Physicians should understand the different mechanisms of action of the potential therapies for IBD to select the right drug for the right patient
On Witten multiple zeta-functions associated with semisimple Lie algebras IV
In our previous work, we established the theory of multi-variable Witten
zeta-functions, which are called the zeta-functions of root systems. We have
already considered the cases of types , , , and . In
this paper, we consider the case of -type. We define certain analogues of
Bernoulli polynomials of -type and study the generating functions of them
to determine the coefficients of Witten's volume formulas of -type. Next
we consider the meromorphic continuation of the zeta-function of -type and
determine its possible singularities. Finally, by using our previous method, we
give explicit functional relations for them which include Witten's volume
formulas.Comment: 22 pag
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Inducible colitis-associated glycome capable of stimulating the proliferation of memory CD4+ T cells
Immune responses are modified by a diverse and abundant repertoire of carbohydrate structures on the cell surface, which is known as the glycome. In this study, we propose that a unique glycome that can be identified through the binding of galectin-4 is created on local, but not systemic, memory CD4+ T cells under diverse intestinal inflammatory conditions, but not in the healthy state. The colitis-associated glycome (CAG) represents an immature core 1–expressing O-glycan. Development of CAG may be mediated by down-regulation of the expression of core-2 β1,6-N-acetylglucosaminyltransferase (C2GnT) 1, a key enzyme responsible for the production of core-2 O-glycan branch through addition of N-acetylglucosamine (GlcNAc) to a core-1 O-glycan structure. Mechanistically, the CAG seems to contribute to super raft formation associated with the immunological synapse on colonic memory CD4+ T cells and to the consequent stabilization of protein kinase C θ activation, resulting in the stimulation of memory CD4+ T cell expansion in the inflamed intestine. Functionally, CAG-mediated CD4+ T cell expansion contributes to the exacerbation of T cell–mediated experimental intestinal inflammations. Therefore, the CAG may be an attractive therapeutic target to specifically suppress the expansion of effector memory CD4+ T cells in intestinal inflammation such as that seen in inflammatory bowel disease
Few smooth d-polytopes with n lattice points
We prove that, for fixed n there exist only finitely many embeddings of
Q-factorial toric varieties X into P^n that are induced by a complete linear
system. The proof is based on a combinatorial result that for fixed nonnegative
integers d and n, there are only finitely many smooth d-polytopes with n
lattice points. We also enumerate all smooth 3-polytopes with at most 12
lattice points. In fact, it is sufficient to bound the singularities and the
number of lattice points on edges to prove finiteness.Comment: 20+2 pages; major revision: new author, new structure, new result
Decomposition of semigroup algebras
Let A \subseteq B be cancellative abelian semigroups, and let R be an
integral domain. We show that the semigroup ring R[B] can be decomposed, as an
R[A]-module, into a direct sum of R[A]-submodules of the quotient ring of R[A].
In the case of a finite extension of positive affine semigroup rings we obtain
an algorithm computing the decomposition. When R[A] is a polynomial ring over a
field we explain how to compute many ring-theoretic properties of R[B] in terms
of this decomposition. In particular we obtain a fast algorithm to compute the
Castelnuovo-Mumford regularity of homogeneous semigroup rings. As an
application we confirm the Eisenbud-Goto conjecture in a range of new cases.
Our algorithms are implemented in the Macaulay2 package MonomialAlgebras.Comment: 12 pages, 2 figures, minor revisions. Package may be downloaded at
http://www.math.uni-sb.de/ag/schreyer/jb/Macaulay2/MonomialAlgebras/html
Blockade of T-cell activation by dithiocarbamates involves novel mechanisms of inhibition of nuclear factor of activated T cells.
Dithiocarbamates (DTCs) have recently been reported as powerful inhibitors of NF-kappaB activation in a number of cell types. Given the role of this transcription factor in the regulation of gene expression in the inflammatory response, NF-kappaB inhibitors have been suggested as potential therapeutic drugs for inflammatory diseases. We show here that DTCs inhibited both interleukin 2 (IL-2) synthesis and membrane expression of antigens which are induced during T-cell activation. This inhibition, which occurred with a parallel activation of c-Jun transactivating functions and expression, was reflected by transfection experiments at the IL-2 promoter level, and involved not only the inhibition of NF-kappaB-driven reporter activation but also that of nuclear factor of activated T cells (NFAT). Accordingly, electrophoretic mobility shift assays (EMSAs) indicated that pyrrolidine DTC (PDTC) prevented NF-kappaB, and NFAT DNA-binding activity in T cells stimulated with either phorbol myristate acetate plus ionophore or antibodies against the CD3-T-cell receptor complex and simultaneously activated the binding of AP-1. Furthermore, PDTC differentially targeted both NFATp and NFATc family members, inhibiting the transactivation functions of NFATp and mRNA induction of NFATc. Strikingly, Western blotting and immunocytochemical experiments indicated that PDTC promoted a transient and rapid shuttling of NFATp and NFATc, leading to their accelerated export from the nucleus of activated T cells. We propose that the activation of an NFAT kinase by PDTC could be responsible for the rapid shuttling of the NFAT, therefore transiently converting the sustained transactivation of this transcription factor that occurs during lymphocyte activation, and show that c-Jun NH2-terminal kinase (JNK) can act by directly phosphorylating NFATp. In addition, the combined inhibitory effects on NFAT and NF-KB support a potential use of DTCs as immunosuppressants
Monoubiquitination of syntaxin 3 leads to retrieval from the basolateral plasma membrane and facilitates cargo recruitment to exosomes
Syntaxin 3 (Stx3), a SNARE protein located and functioning at the apical plasma membrane of epithelial cells, is required for epithelial polarity. A fraction of Stx3 is localized to late endosomes/lysosomes, although how it traffics there and its function in these organelles is unknown. Here we report that Stx3 undergoes monoubiquitination in a conserved polybasic domain. Stx3 present at the basolateral—but not the apical—plasma membrane is rapidly endocytosed, targeted to endosomes, internalized into intraluminal vesicles (ILVs), and excreted in exosomes. A nonubiquitinatable mutant of Stx3 (Stx3-5R) fails to enter this pathway and leads to the inability of the apical exosomal cargo protein GPRC5B to enter the ILV/exosomal pathway. This suggests that ubiquitination of Stx3 leads to removal from the basolateral membrane to achieve apical polarity, that Stx3 plays a role in the recruitment of cargo to exosomes, and that the Stx3-5R mutant acts as a dominant-negative inhibitor. Human cytomegalovirus (HCMV) acquires its membrane in an intracellular compartment and we show that Stx3-5R strongly reduces the number of excreted infectious viral particles. Altogether these results suggest that Stx3 functions in the transport of specific proteins to apical exosomes and that HCMV exploits this pathway for virion excretion
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