Congenic rats reveal three independent Copenhagen alleles within the Mcs1 quantitative trait locus that confer resistance to mammary cancer

It has previously been shown that the Copenhagen (COP) rat contains several genetic loci that contribute to its mammary tumor-resistant phenotype after 7,12-dimethylbenz(a)anthracene (DMBA) administration. One of these loci, mammary carcinoma susceptibility 1 (Mcs1), is located on the centromeric end of chromosome 2 and appears to act in a semidominant fashion. To confirm the existence and independent action of this locus and also aid in the identification of the physical location of the Mcs1 gene, congenic lines were generated by transferring the Mcs1 COP allele onto a Wistar Furth (WF) genetic background. Male carriers were genotyped using microsatellite markers spanning 20-30 cM of the Mcs1 locus. One of the congenic lines minimally retained the COP allele at D2Mit29 on the centromeric end of chromosome 2 and extended distally to D2Rat201. Heterozygous Mcs1 carrier rats were interbred, and the female offspring were treated with DMBA. The female rats from the Mcs1 congenic line that carried one or two COP alleles of the Mcs1 region had a significantly reduced (65 and 85%, respectively) tumor development (P < 0.001) compared with rats carrying zero COP alleles at this locus. A WF.COP-D2Mit29/D2Rat201 homozygous congenic strain derived at the N10 generation was treated with DMBA, and the COP homozygous rats developed 1.5 +/- 0.3 carcinomas/rat versus 6.3 +/- 0.5 in WF control rats (P < 0.0001). Fine mapping of this congenic interval using several recombinant lines identified three genetic loci within the Mcs1 congenic region that independently supported a tumor resistance phenotype. These genetic loci have been termed Mcs1a, Mcs1b, and Mcs1c. In rats for which each locus was homozygous for the COP allele, tumor development was reduced by approximately 60% compared with littermate controls. The identification of these independent loci within the Mcs1 COP allele provide a model of the genetic complexity of cancer.     

Posttraumatic stress disorders in Vietnam veterans: Selected bibliographical addendum to Fairbank et al., Silver, and Arnold.

J. A. Fairbank et al (see record 1982-12226-001), presented a selected bibliography on contributions relevant to posttraumatic stress disorder (PTSD) in Vietnam veterans. Their selection included research and clinical reports found in psychological and medical journals, books and government publications, which were pertinent to epidemiology, etiology, symptomatology, and treatment of PTSD in Vietnam veterans, plus narratives by Vietnam veterans and research germane to PTSD from other conflicts. S. M. Silver (see record 1983-03626-001) updated Fairbank et al., with 171 since-published articles, reports, and other references. A. Arnold's (1987) bibliograpy contains over 1,000 clinical references, as well as accounts of the Vietnam War. This addendum is an attempt to update the enormous body of PTSD literature. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Analysis of the induction period of oxidation of edible oils by differential scanning calorimetry

Oxidation of rapeseed and sunflower oils has been studied by differential scanning calorimetry under non-isothermal conditions and by Oxidograph under isothermal conditions for various temperatures. The parameters of an Arrhenius-like equation describing the temperature dependence of induction period have been obtained. A new method for evaluation of the parameters from nonisothermal diffential scanning calorimetry measurements, based on the dependence of onset temperature of the oxidation peak on heating rate, is presented. It has been shown that the method gives parameters not affected by systematic errors. These can be used in modeling the oxidation process where the effects of oxygen diffusion, heat transfer, and evolution of reaction heat are explicity involved. The results obtained by differential scanning calorimetry are compared with the Oxidograph measurements. The discrepancies between the results obtained by the two methods are accounted for by oxygen diffusion within the samples.     

Decreased survivability and a DNA repair defect in the cells of patients with xeroderma pigmentosum and Cockayne syndrome under the action of radiation and chemical mutagens

The action of ionizing radiation and chemical mutagens--epoxides (ethylene oxide, propylene oxide, epichlorohydrin)--upon survival and repair processes in xeroderma pigmentosum (XP2SP) and Cockayne syndrome (CS1SP) patients' cells was studied, compared to healthy donor's cells VH-10 and C5RO. Ionizing radiation was demonstrated to enhance significantly higher survival decrease of XP2SP and CS1SP fibroblasts, compared to healthy donor's cells, according to the cloning efficiency criterion. In contrast to this, no significant difference between XP2SP and healthy donor's cells was found, according to cells' ability to replicative DNA synthesis after gamma irradiation. Differences in survival of mutant cells and healthy donor's cells after treatment by epoxides were found significant only following XP2SP being treated by ethylene oxide. DNA single-string breaks in XP2SP and in CS1SP cells treated by mutagens studied were proved to occur with the same frequency as in the DNA of the control cells; however the DNA repair according to this criterion was significantly suppressed in mutant cells.     

Genetic dissection of a mammalian replicator in the human beta-globin locus

The timing and localization of DNA replication initiation in mammalian cells are heritable traits, but it is not known whether initiation requires specific DNA sequences. A site-specific recombination strategy was used to show that DNA sequences previously identified as replication initiation sites could initiate replication when transferred to new chromosomal locations. An 8-kilobase DNA sequence encompassing the origin of DNA replication in the human beta-globin locus initiated replication in the simian genome. Specific deletions within the globin origin did not initiate replication in these chromosomal sites. These data suggest that initiation of DNA replication in mammalian cells requires specific sequence information and extend the replicon hypothesis to higher eukaryotes.     

The Escherichia coli RecA protein complements recombination defective phenotype of the Saccharomyces cerevisiae rad52 mutant cells

The Saccharomyces cerevisiae rad52 mutants are sensitive to many DNA damaging agents, mainly to those that induce DNA double-strand breaks (DSBs). In the yeast, DSBs are repaired primarily by homologous recombination (HR). Since almost all HR events are significantly reduced in the rad52 mutant cells, the Rad52 protein is believed to be a key component of HR in S. cerevisiae. Similarly to the S. cerevisiae Rad52 protein, RecA is the main HR protein in Escherichia coli. To address the question of whether the E. coli RecA protein can rescue HR defective phenotype of the rad52 mutants of S. cerevisiae, the recA gene was introduced into the wild-type and rad52 mutant cells. Cell survival and DSBs induction and repair were studied in the RecA-expressing wild-type and rad52 mutant cells after exposure to ionizing radiation (IR) and methyl methanesulphonate (MMS). Here, we show that expression of the E. coli RecA protein partially complemented sensitivity and fully complemented DSB repair defect of the rad52 mutant cells after exposure to IR and MMS. We suggest that in the absence of Rad52, when all endogenous HR mechanisms are knocked out in S. cerevisiae, the heterologous E. coli RecA protein itself presumably takes over the broken DNA.     

Gallium-Suboxide Attack of Stainless Steel and Nickel Alloys at 800–1200°C

Failure of furnace parts composed of stainless steel or nickel-base alloys has been observed following treatment of gallium-containing compounds at 800 to 1200°C. This work examines the effect of gallium suboxide (Ga₂O) and gallium oxide (Ga₂O₃) on the chemical and mechanical properties of 304 SS, 316 SS, and Hastelloy C-276 in an effort to elucidate a failure mechanism. Results indicate that all three materials are subject to attack by gallium compounds. Elemental segregation, oxidation, and Ga uptake all occur following exposure. Ga₂O gas appears to play the dominant role in alloy attack under reducing conditions. Increasing temperature is shown to increase the magnitude of attack, as measured by oxide thickness and gallium-metal uptake. Calculations of the system thermodynamics suggest that Cr, Mn, Si, and V alloying components are responsible for metal oxidation and concurrent gallium absorption. A homogeneous, large (>30 wt.%) gallium uptake resulted in brittle failure of 304 SS. Therefore, exposure to gallium compounds can result in premature failure of iron- and nickel-base structural alloys.     

Polysubstituted Pyrimidines as Potent Inhibitors of Prostaglandin E2 Production: Increasing Aqueous Solubility

Water solubility is one of the key features of potential therapeutic agents. In order to enhance the low water solubility of the parent 5-butyl-4-(4-methoxyphenyl)-6-phenylpyrimidin-2-amine, a potent inhibitor of prostaglandin E₂ (PGE₂) production, we synthesized and evaluated a new series of derivatives in which the butyl group at the C5 position of the pyrimidine ring was replaced with a less lipophilic substituent, preferably with a hydrophilic aliphatic moiety. Except for the 5-cyanopyrimidine derivative, all target compounds exhibited increased (2.7–87-fold) water solubility relative to the parent compound. Although nontoxic in mouse peritoneal cells, the prepared compounds were either equipotent or weaker inhibitors of PGE₂ production than the parent compound. The most promising compound from the series was found to be the 5-(2,5,8,11-tetraoxadodecyl)pyrimidine derivative (with three polyethylene glycol units at the C5 position), which exhibited 32-fold higher water solubility and only slightly weaker inhibitory activity (22 % of remaining PGE₂ production) compared with the parent compound (15 % of remaining PGE₂ production).     

Study of phase changes in plasma sprayed deposits

The formation of a plasma-sprayed coating that exhibits predictable properties requires the control of many process variables. The phase changes that take place during plasma spraying are significant material variables that should be controlled. Several different materials were deposited in air with a water-stabilized plasma torch (model PAL 160). Usually, air was used as a carrier gas for the powder; however, argon was also used for some coatings. The injected powders (NiAl, Ni, ZrSiO₄-based, Al₂O₃-based, etc.) as well as the coatings were studied for, among other properties, their structure, particle size, microhardness, and chemical and phase composition. Phase changes induced by the different cooling rates of molten particles after their impact on a substrate are illustrated for ZrSiO₄. It has also been found that the oxidizing power of the water-stabilized torch is less than previously believed. For example, coatings produced with nickel powder injected with argon as the carrier gas exhibited almost no oxides. Significant element redistribution during plasma spraying was demonstrated with a two-phase NiAl feedstock powder. The coating exhibited almost all the phases that are present in the binary NiAl alloy as well as envelopes of oxides and traces of amorphous phase.