Regulation of neuronal ion channels via P2Y receptors

Within the last 15 years, at least 8 different G protein-coupled P2Y receptors have been characterized. These mediate slow metabotropic effects of nucleotides in neurons as well as non-neural cells, as opposed to the fast ionotropic effects which are mediated by P2X receptors. One class of effector systems regulated by various G protein-coupled receptors are voltage-gated and ligand-gated ion channels. This review summarizes the current knowledge about the modulation of such neuronal ion channels via P2Y receptors. The regulated proteins include voltage-gated Ca2+ and K+ channels, as well as N-methyl-d-aspartate, vanilloid, and P2X receptors, and the regulating entities include most of the known P2Y receptor subtypes. The functional consequences of the modulation of ion channels by nucleotides acting at pre- or postsynaptic P2Y receptors are changes in the strength of synaptic transmission. Accordingly, ATP and related nucleotides may act not only as fast transmitters (via P2X receptors) in the nervous system, but also as neuromodulators (via P2Y receptors). Hence, nucleotides are as universal transmitters as, for instance, acetylcholine, glutamate, or γ-aminobutyric acid

Parallel algorithms for normalization

Given a reduced affine algebra A over a perfect field K, we present parallel algorithms to compute the normalization \bar{A} of A. Our starting point is the algorithm of Greuel, Laplagne, and Seelisch, which is an improvement of de Jong's algorithm. First, we propose to stratify the singular locus Sing(A) in a way which is compatible with normalization, apply a local version of the normalization algorithm at each stratum, and find \bar{A} by putting the local results together. Second, in the case where K = Q is the field of rationals, we propose modular versions of the global and local-to-global algorithms. We have implemented our algorithms in the computer algebra system SINGULAR and compare their performance with that of the algorithm of Greuel, Laplagne, and Seelisch. In the case where K = Q, we also discuss the use of modular computations of Groebner bases, radicals, and primary decompositions. We point out that in most examples, the new algorithms outperform the algorithm of Greuel, Laplagne, and Seelisch by far, even if we do not run them in parallel.Comment: 19 page

Cushing's Disease Management: Glimpse Into 2051

Major advancements are expected in medicine and healthcare in the 21st century- "Digital Age", mainly due to the application of data technologies and artificial intelligence into healthcare. In this perspective article we share a short story depicting the future Cushings' Disease patient and the postulated diagnostic and management approaches. In the discussion, we explain the advances in recent times which makes this future state plausible. We postulate that endocrinology care will be completely reinvented in the Digital Age

Immunopathological properties of the Campylobacter jejuni flagellins and the adhesin CadF as assessed in a clinical murine infection model

Background: Campylobacter jejuni infections constitute serious threats to human health with increasing prevalences worldwide. Our knowledge regarding the molecular mechanisms underlying host-pathogen interactions is still limited. Our group has established a clinical C. jejuni infection model based on abiotic IL-10-/- mice mimicking key features of human campylobacteriosis. In order to further validate this model for unraveling pathogen-host interactions mounting in acute disease, we here surveyed the immunopathological features of the important C. jejuni virulence factors FlaA and FlaB and the major adhesin CadF (Campylobacter adhesin to fibronectin), which play a role in bacterial motility, protein secretion and adhesion, respectively. Methods and results: Therefore, abiotic IL-10-/- mice were perorally infected with C. jejuni strain 81-176 (WT) or with its isogenic flaA/B (ΔflaA/B) or cadF (ΔcadF) deletion mutants. Cultural analyses revealed that WT and ΔcadF but not ΔflaA/B bacteria stably colonized the stomach, duodenum and ileum, whereas all three strains were present in the colon at comparably high loads on day 6 post-infection. Remarkably, despite high colonic colonization densities, murine infection with the ΔflaA/B strain did not result in overt campylobacteriosis, whereas mice infected with ΔcadF or WT were suffering from acute enterocolitis at day 6 post-infection. These symptoms coincided with pronounced pro-inflammatory immune responses, not only in the intestinal tract, but also in other organs such as the liver and kidneys and were accompanied with systemic inflammatory responses as indicated by increased serum MCP-1 concentrations following C. jejuni ΔcadF or WT, but not ΔflaA/B strain infection. Conclusion: For the first time, our observations revealed that the C. jejuni flagellins A/B, but not adhesion mediated by CadF, are essential for inducing murine campylobacteriosis. Furthermore, the secondary abiotic IL-10-/- infection model has been proven suitable not only for detailed investigations of immunological aspects of campylobacteriosis, but also for differential analyses of the roles of distinct C. jejuni virulence factors in induction and progression of disease