Effects of catecholaminergic drugs on systems of reward and punishment in experiments on cats

A common assumption in special education is that temporal limits for a task should be expanded so that ample time is provided for completing the work. This study describes the opposite strategy of restricting temporal limits to augment academic performance. Three educable retarded children received token reinforcement contingent on the number of correct math problems answered during daily sessions. A reversal design was used to assess the effects of an abrupt reduction in time limits (20-5-20 min) and a graduated sequence of reductions (20-15-10-5-20 min). The graduated sequence resulted in rate increases of correct responding ranging from 125% to 266% and these gains endured when temporal limits were again expanded. In contrast, the abrupt shift produced interfering emotional behaviors and rate decreases in academic performance of 25% to 80%. The findings indicate that systematically restricting temporal limits for an academic task can further enhance the performance of slow learners already maintained by a token system.     

Studies in Germanium Oxide Systems: IV, Phase Equilibria in the System K,O-GeO,

Phase relations in the binary system K₂O-GeO₂ were determined by conventional quenching techniques. Three compounds, K₂O.2GeO₂, 3K₂O.11GeO₂, and K₂O.7GeO₂, exist in the composition range 65 to 100% GeOn. The compound 3K₂O.1lGeO₂ melts congruently at 1055°C, whereas K₂O.2GeO₂ and K₂O.7GeO₂ melt incongruently at 761° and 950°C, respectively. Thermal expansion data for the crystalline compounds are presented. The structure of potassium germanate glasses is discussed.     

Hormonal regulation of sex differentiated parameters in liver nodules from rats treated in the resistant hepatocyte model

Sex differentiation of liver functions has been shown to be attenuated in preneoplastic rat liver nodules. The present study was performed to investigate whether nodules from male rats are to some extent withdrawn from the normal growth hormone (GH) regulation of these functions. Male and female Wistar rats were treated according to a modified resistant hepatocyte model (RH-model), with diethylnitrosamine initiation and promotion with intragastric administration of 2-acetylaminofluorene (2-AAF) combined with partial hepatectomy (PH). Eleven months post-initiation male rats were treated with either human (hGH) or bovine growth hormone (bGH) or ovine prolactin (oPRL) by continuous infusion for 1 week. The mRNA expression of a number of genes known to be sex differentiated in liver from adult control rats was compared in nodular and surrounding tissue from nodule-bearing male, female and hormone-treated male rats. The basal mRNA expression of the female-predominant cytochrome P4502C12 (CYP2C12) was increased and the male-predominant CYP2C11 was decreased in liver nodules from male rats compared with the surrounding liver. Expression of the prolactin receptor (PRL-r; female > male) and the steroid 5 alpha-reductase (female > male) genes was decreased in male nodules, whereas no difference was observed with respect to GH-receptor (GH-r; female > male) expression in nodules versus surrounding tissue. Early nodules obtained from males treated according to the original RH-model (dietary 2-AAF, 0.02%) and isolated 2 weeks after completion of the 2-AAF/PH treatment showed significantly lower GH-r mRNA levels than the total liver tissue. In hepatocellular carcinomas from hormonally unmanipulated males 11 months post-initiation the decrease in PRL-r expression was even more pronounced than in the nodules and a significant decrease in GH-r expression was seen. In female nodules the only significant difference with respect to the sex differentiated parameters was a lower 5 alpha-reductase expression than in the surrounding tissue. Continuous infusion of both hGH and bGH feminized the expression of all the sex differentiated genes in male tissues and eliminated the previously detected differences between nodules and surrounding tissue. oPRL also eliminated the differences between nodules and surrounding tissue in males and partly feminized the expression of both the 5 alpha-reductase and the PRL-r genes.(ABSTRACT TRUNCATED AT 400 WORDS)     

An evaluation of clinical laboratory services in sub-Saharan Africa. Ex africa semper aliquid novi?

Pathology services represent the rational, scientific basis of the practice of clinical care. It does not represent deus ex machina, an implausible solution to a complex plot, but rather the way in which clinical care can be audited, controlled, guided and kept appropriate to the funds and the skills available. Arguments are presented to support this statement as well as to analyse what is wrong with health care, from the point of view of laboratory medicine, in sub-Saharan Africa. In most African countries 'first world' technology has to be imported by economies barely able to sustain the basic requirements of human life. Badly needed foreign exchange is obtained by growing export crops at the cost of traditional lifestyle, disenfranchising communities, urbanisation, and even at the cost not being able to grow food. War, corruption, lack of accountability even in the Western sense of being able to go to the polls every so often, lack of empowerment, low literacy rate etc all debase the communities, with minimal exceptions, of Africa. Health care is under the same capricious rule as all other public services: investment in laboratories is poor and most have no access to a professional laboratory at all. More investment, not less; expansion of pathology services not restricting them, is needed throughout the continent.     

Endo-epsilon-(gamma-Glu)Lys-isopeptidolysis as a sign of highly-specific proteolysis

Catalytic activity of destabilase has been studied in hydrolyses of synthetic and natural substrates. High specificity of the enzyme is shown in hydrolysis of endo-epsilon-(gamma-Glu)Lys isopeptide bonds.     

交通网络弹复度与易碎度的测算与分析

弹复性是系统在失效或被破坏之后能够恢复正常工作的能力.弹复性工程是当今国际上研究的热点.本文提出了基于节点对间的独立路径可靠度和交通网络的弹复度的定量测算方法,提出了反映节点和路段对交通网络影响大小的易碎性的概念和测算方法.论文还就弹复度和易碎度的几个相关性质提出了几个重要定理.针对我国的铁路网络,计算了所有节点城市和路段的弹复度和易碎度,并对弹复度和易碎度高的节点的分布规律进行了探讨,得出了一些有益的结论.     

Presence and consequence of uracil in preneoplastic DNA from folate/methyl-deficient rats

Uracil can arise in DNA by misincorporation of dUTP into nascent DNA and/or by cytosine deamination in established DNA. Based on recent findings, both pathways appear to be promoted in the methyl-deficient model of hepatocarcinogenesis. A chronic increase in the ratio dUTP:dTTP with folate/methyl deficiency can result in a futile cycle of excision and reiterative uracil misincorporation leading to premutagenic apyrimidinic (AP) sites, DNA strand breaks, DNA fragmentation and apoptotic cell death. The progressive accumulation of unmethylated cytosines with chronic methyl deficiency will increase the potential for cytosine deamination to uracil and further stress uracil mismatch repair mechanisms. Uracil is removed by a highly specific uracil-DNA glycosylase (UDG) leaving an AP site that is subsequently repaired by sequential action of AP endonuclease, 5'-phosphodiesterase, a DNA polymerase and DNA ligase. Since the DNA polymerases cannot distinguish between dUTP and dTTP, an increase in dUTP:dTTP ratio will promote uracil misincorporation during both DNA replication and repair synthesis. The misincorporation of uracil for thymine (5-methyluracil) may constitute a genetically significant form of DNA hypomethylation distinct from cytosine hypomethylation. In the present study a significant increase in the level of uracil in liver DNA as early as 3 weeks after initiation of folate/methyl deficiency was accompanied by parallel increases in DNA strand breaks, AP sites and increased levels of AP endonuclease mRNA. In addition, uracil was also detected within the p53 gene sequence using UDG PCR techniques. Increased levels of uracil in DNA implies that the capacity for uracil base excision repair is exceeded with chronic folate/methyl deficiency. It is possible that enzyme-induced extrahelical bases, AP sites and DNA strand breaks interact to negatively affect the stability of the DNA helix and stress the structural limits of permissible uracil base excision repair activity. Thus substitution of uracil for thymine induces repair-related premutagenic lesions and a novel form of DNA hypomethylation that may relate to tumor promotion in the methyl-deficient model of hepatocarcinogenesis.     

Detection of the local H+ gradients on the internal mitochondrial membrane

Respiration-dependent responses of a pH probe (fluorescein isothiocyanate, FITC), covalently bound to the membrane proteins of mitochondria and submitochondrial particles (SMP) have been studied. A spectral shift indicating FITC deprotonation was observed when respiration was activated in coupled mitochondria. Such a response was increased by valinomycin and reduced by uncoupler. Some FITC deprotonation was detected in the presence of excess of an uncoupler, but the response was smaller and insensitive to valinomycin. FITC deprotonation was also observed in submitochondrial particles after succinate addition. In this case it was not affected by uncoupler. Increase in the buffer concentration was found to (i) decrease the FITC response and (ii) increase the rate of uncoupled respiration in both mitochondria and submitochondrial particles. The results are consistent with the assumption that respiration initiates appearance of local H+ activity gradients on the inner side of the internal mitochondrial membrane during the steady-state H+ pumping. We suggest that the formation of this gradient is due to kinetic barrier to proton transfer from the bulk phase to the respiratory proton pump vicinity.