Probability of mast cells to mediate anaphylaxis in skeletal muscle

Are there enough mast cells in denervated skeletal muscle to account for autopharmacological mediation of the antigen potentials (APs) elicited by microtaps? Through rough qualitative estimations, some authors have suggested a positive answer to this question. However, in view of measurements performed in this investigation of both the density of mast cells and the diffusion coefficient of antigens, the probability of such mediated effects was found to be relatively low:P=0.016 for egg albumin andP=0.004 for ferritin. Therefore, most APs induced by microtaps should be attributed to the direct effect of antigen over the sensitized muscle fibers. Yet, both the density of mast cells found in this work and the known amount of histamine they are capable of releasing when challenged with antigen, support the hypothesis regarding the involvement of these cells when antigen is massively superfused so as to induce Schultz-Dale reactions in muscle strips. Under this circumstance, the direct and mediated mechanisms may coexist.     

Clonal analysis in hybrids between Drosophila melanogaster and Drosophila simulans

We have analysed the viability of cellular clones induced by mitotic recombination in Drosophila melanogaster/D. simulans hybrid females during larval growth. These clones contain a portion of either melanogaster or simulans genomes in homozygosity. Analysis has been carried out for the X and the second chromosomes, as well as for the 3L chromosome arm. Clones were not found in certain structures, and in others they appeared in a very low frequency. Only in abdominal tergites was a significant number of clones observed, although their frequency was lower than in melanogaster abdomens. The bigger the portion of the genome that is homozygous, the less viable is the recombinant melano-gaster/simulans hybrid clone. The few clones that appeared may represent cases in which mitotic recombination took place in distal chromosome intervals, so that the clones contained a small portion of either melanogaster or simulans chromosomes in homozygosity. Moreover, Lhr, a gene of D. simulans that suppresses the lethality of male and female melanogaster/simulans hybrids, does not suppress the lethality of the recombinant melanogaster/simulans clones. Thus, it appears that there is not just a single gene, but at least one per tested chromosome arm (and maybe more) that cause hybrid lethality. Therefore, the two species, D. melanogaster and D. simulans, have diverged to such a degree that the absence of part of the genome of one species cannot be substituted by the corresponding part of the genome of the other, probably due to the formation of co-adapted gene complexes in both species following their divergent evolution after speciation. The disruption of those coadapted gene complexes would cause the lethality of the recombinant hybrid clones.     

Volume changes correlate with entropies and enthalpies in the formation of nucleic acid homoduplexes: Differential hydration of A and B conformations

We have used a combination of densimetric, calorimetric, and uv absorption techniques to obtain a complete thermodynamic characterization for the formation of nucleic acid homoduplexes of known sequence and conformation. The volume change ΔV accompanying the formation of four duplexes was interpreted to reflect changes in hydration based on the electrostriction phenomenon. In 10 mM sodium phosphate buffer at pH 7, the magnitude of the measured ΔV's ranged from ?2.0 to +7.2 ml/mol base pair and followed the order of poly(rA) · poly(dT) ～ poly(dA) · poly(dT) < poly(rA) · poly(dU) ～ poly(rA) · poly(rU). Inclusion of 100 mM NaCl in the same buffer gave the range of ?17.4 to ?2.3 mL/mol base pair and the following order: poly(dA) · poly(dT) < poly(rA) · poly(dT) < poly(rA) · poly(rU) ～ poly(rA) ～ polyr(dU). Standard thermodynamic profiles of forming these duplexes from their corresponding complementary single strands indicated similar free energies that resulted from the compensation of favorable enthalpies with unfavorable entropies along with a similar counterion uptake at both ionic strengths. The differences in these compensating effects of entropy and enthalpy correlated very well with the volume change measurements in a manner suggesting that the homoduplexes in the B conformation are more hydrated than are those in the A conformation. Moreover, the increased thermal stability of these homoduplexes resulted from an increase in the salt concentration corresponding to larger hydration levels as reflected by the ΔV results. © 1993 John Wiley & Sons, Inc.     

Erk1/2 signaling mediates the HGF-induced protection against ethanol and acetaldehyde-induced toxicity in the pancreatic RINm5F cell line

Alcohol-induced pancreas damage remains as one of the main risk factors for pancreatitis development. This disorder is poorly understood, particularly the effect of acetaldehyde, the primary alcohol metabolite, in the endocrine pancreas. Hepatocyte growth factor (HGF) is a protective protein in many tissues, displaying antioxidant, antiapoptotic, and proliferative responses. In the present work, we were focused on characterizing the response induced by HGF and its protective mechanism in the RINm5F pancreatic cell line treated with ethanol and acetaldehyde. RINm5F cells were treated with ethanol or acetaldehyde for 12 h in the presence or not of HGF (50 ng/ml). Cells under HGF treatment decreased the content of reactive oxygen species and lipid peroxidation induced by both toxics, improving cell viability. This effect was correlated to an improvement in insulin expression impaired by ethanol and acetaldehyde. Using a specific inhibitor of Erk1/2 abrogated the effects elicited by the growth factor. In conclusion, the work provides mechanistic evidence of the HGF-induced-protective response to the alcohol-induced damage in the main cellular component of the endocrine pancreas.     

The mouse Dlx-2 (Tes-1) gene is expressed in spatially restricted domains of the forebrain, face and limbs in midgestation mouse embryos

The pattern of RNA expression of the murine Dlx-2 (Tes-1) homeobox gene is described in embryos ranging in age from E8.5 through E11.5. Dlx-2 is a vertebrate homologue of the Drosophila Distal-less (Dll) gene. Dll expression in the Drosophila embryo is principally limited to the primordia of the brain, head and limbs. Dlx-2 is also expressed principally in the primordia of the forebrain, head and limbs. Within these regions it is expressed in spatially restricted domains. These include two discontinuous regions of the forebrain (basal telencephalon and ventral diencephalon), the branchial arches, facial ectoderm, cranial ganglia and limb ectoderm. Several mouse and human disorders have phenotypes which potentially are the result of mutations in the Dlx genes.     

The gene coding for the α1 subunit of the skeletal dihydropyridine receptor (Cchl1a3=mdg) maps to mouse Chromosome 1 and human 1q32

Using both chromosomal in situ hybridization and molecular techniques, we report the genetic localization of the gene coding for the alpha 1 subunit of the skeletal slow Ca²⁺ current channel/DHP receptor gene (Cchl1a3) on human Chromosome (Chr) 1 (1q31–1q32 region) and on mouse Chr 1 region (F-G). On the basis of single-strand conformation polymorphism (SSCP-PCR) analysis in an interspecific backcross, we have determined that the Cchl1a3=mdg (muscular dysgenesis) locus is very closely linked to the myogenin (Myog) locus.