Novel signaling pathways mediating reciprocal control of keratinocyte migration and wound epithelialization through M3 and M4 muscarinic receptors

To test the hypothesis that keratinocyte (KC) migration is modulated by distinct muscarinic acetylcholine (ACh) receptor subtypes, we inactivated signaling through specific receptors in in vitro and in vivo models of reepithelialization by subtype-selective antagonists, small interfering RNA, and gene knockout in mice. KC migration and wound reepithelialization were facilitated by M4 and inhibited by M3. Additional studies showed that M4 increases expression of “migratory” integrins α5β1, αVβ5, and αVβ6, whereas M3 up-regulates “sedentary” integrins α2β1 and α3β1. Inhibition of migration by M3 was mediated through Ca2+-dependent guanylyl cyclase–cyclic GMP–protein kinase G signaling pathway. The M4 effects resulted from inhibition of the inhibitory pathway involving the adenylyl cyclase–cyclic AMP–protein kinase A pathway. Both signaling pathways intersected at Rho, indicating that Rho kinase provides a common effector for M3 and M4 regulation of cell migration. These findings offer novel insights into the mechanisms of ACh-mediated modulation of KC migration and wound reepithelialization, and may aid the development of novel methods to promote wound healing

Special features of the 9^9Be→\to2He fragmentation in emulsion at an energy of 1.2~A~GeV

The results of investigations of the relativistic $^9$Be nucleus fragmentation in emulsion which entails the production of two He fragments of an energy of 1.2~A~GeV are presented. The results of the angular measurements of the $^9$Be$\to$2He events are analyzed. The $^9$Be$\to^8$Be+n fragmentation channel involving the $^8$Be decay from the ground (0$^+$) and the first excited (2$^+$) states to two $\alpha$ particles is observed to be predominant.Comment: 10 pages, 6 figures, conference: Conference on Physics of Fundamental Interactions, Moscow, Russia, 5-9 Dec 2005 (Author's translation

Anti-Inflammatory Effects of the Nicotinergic Peptides SLURP-1 and SLURP-2 on Human Intestinal Epithelial Cells and Immunocytes

A search for novel and more efficient therapeutic modalities of inflammatory bowel disease (IBD) is one of the most important tasks of contemporary medicine. The anti-inflammatory action of nicotine in IBD might be therapeutic, but its toxicity due to off-target and nonreceptor effects limited its use and prompted a search for nontoxic nicotinergic drugs. We tested the hypothesis that SLURP-1 and -2—the physiological nicotinergic substances produced by the human intestinal epithelial cells (IEC) and immunocytes—can mimic the anti-inflammatory effects of nicotine. We used human CCL-241 enterocytes, CCL-248 colonocytes, CCRF-CEM T-cells, and U937 macrophages. SLURP-1 diminished the TLR9-dependent secretion of IL-8 by CCL-241, and IFNγ-induced upregulation of ICAM-1 in both IEC types. rSLURP-2 inhibited IL-1β-induced secretion of IL-6 and TLR4- and TLR9-dependent induction of CXCL10 and IL-8, respectively, in CCL-241. rSLURP-1 decreased production of TNFα by T-cells, downregulated IL-1β and IL-6 secretion by macrophages, and moderately upregulated IL-10 production by both types of immunocytes. SLURP-2 downregulated TNFα and IFNγR in T-cells and reduced IL-6 production by macrophages. Combining both SLURPs amplified their anti-inflammatory effects. Learning the pharmacology of SLURP-1 and -2 actions on enterocytes, colonocytes, T cells, and macrophages may help develop novel effective treatments of IBD

Electromagnetic dissociation of relativistic 8^8B nuclei in nuclear track emulsion

Experimental data on fragmentation channels in peripheral interactions of $^8$B nuclei in nuclear track emulsions are presented. A detailed analysis made it possible to justify selections of events of the electromagnetic-dissociation process $^8$B $\to^7$Be + \emph{p} and to estimate its cross section. Events of $^{10}$C peripheral dissociation that were observed in the same exposure are described.Comment: 12 pages, 10 figures, 4 tables, Published in Phys.Atom.Nucl.72:690-701,200

Clustering in light nuclei in fragmentation above 1 A GeV

The relativistic invariant approach is applied to analyzing the 3.3 A GeV $^{22}$Ne fragmentation in a nuclear track emulsion. New results on few-body dissociations have been obtained from the emulsion exposures to 2.1 A GeV $^{14}$N and 1.2 A GeV $^{9}$Be nuclei. It can be asserted that the use of the invariant approach is an effective means of obtaining conclusions about the behavior of systems involving a few He nuclei at a relative energy close to 1 MeV per nucleon. The first observations of fragmentation of 1.2 A GeV $^{8}$B and $^{9}$C nuclei in emulsion are described. The presented results allow one to justify the development of few-body aspects of nuclear astrophysics.Comment: 7 pages, 8 figures, 3 tables, Nuclear Physics in Astrophysics-2, 16-20 May, 2005 (ATOMKI), Debrecen, Hungar