Developmental Patterns of Catechol-O-Methyltransferase in Genetically Different Rat Strains: Enzymatic and Immunochemical Studies

Abstract: Catechol- O -methyltransferase (COMT) activity in the liver and kidneys of adult Fischer-344 (F-344) rats is only half of that in the same organs of Wistar-Furth (W-F) rats. The trait of low COMT activity in these animals is inherited in an autosomal recessive fashion. A comprehensive study of patterns of change in COMT activity during growth and development was performed to determine whether "temporal gene" effects might play a role in the inherited differences in enzyme activity present in adult animals. The COMT activity expressed per mg protein in liver and kidneys of newborn F-344 rats is only 50–60% of that in the same organs of W-F animals. The liver and the kidneys of newborn rats of both strains have COMT activity an order of magnitude higher than those in brain, heart, or blood. In addition, in both strains there are much larger increases in liver and kidney COMT activities during growth and development (5–10 fold) than in blood, brain, or heart (one- to twofold). Immunotitration with antibodies against rat COMT demonstrates that differences in immunoreactive COMT parallel differences in COMT activity, both between strains and within strains during growth and development. However, when the temporal patterns of change in enzyme activities in the liver and the kidneys of the two strains of rat are compared at multiple times during growth and development, no differences in the patterns are present. These results make it unlikely that temporal gene effects can explain the inherited differences in COMT activity in liver and kidneys of F-344 and W-F rats.     

Multiomic Metabolic Enrichment Network Analysis Reveals Metabolite–Protein Physical Interaction Subnetworks Altered in Cancer

Metabolism is recognized as an important driver of cancer progression and other complex diseases, but global metabolite profiling remains a challenge. Protein expression profiling is often a poor proxy since existing pathway enrichment models provide an incomplete mapping between the proteome and metabolism. To overcome these gaps, we introduce multiomic metabolic enrichment network analysis (MOMENTA), an integrative multiomic data analysis framework for more accurately deducing metabolic pathway changes from proteomics data alone in a gene set analysis context by leveraging protein interaction networks to extend annotated metabolic models. We apply MOMENTA to proteomic data from diverse cancer cell lines and human tumors to demonstrate its utility at revealing variation in metabolic pathway activity across cancer types, which we verify using independent metabolomics measurements. The novel metabolic networks we uncover in breast cancer and other tumors are linked to clinical outcomes, underscoring the pathophysiological relevance of the findings.     

Muscle damage and repair in voluntarily running mice: strain and muscle differences

Summary Soleus, extensor digitorum longus and tibialis anterior muscles of mice voluntarily running in wheels for periods of 5 to 120 days were studied in spaced serial and serial cross-sections. Shortly after the onset of running and during the next 2 weeks, degeneration, necrosis, phagocytosis and regeneration of muscle fibers, satellite cell proliferation and cellular infiltration were found in soleus muscles of mice from all strains investigated (CBA/J, NMRI, C57b, NIH, SWS and Balb/c). Tibialis anterior but not extensor digitorum longus muscles were also damaged. Predominantly high-oxidative fibers were affected (both slow-oxidative and fast oxidative glycolytic in soleus, fast-oxidative glycolytic in tibialis anterior). Denervated soleus muscles that had been passively stretched during running were not damaged. Evidence was found that, during the early period of running, split fibers form by myogenesis within (regeneration) or outside (satellite cell proliferation) necrotic muscle fiber segments. Split fibers persisted in solei of long-term (2 to 3 months) exercised CBA/J but not NMRI mice. In 6 out of 20 solei of CBA/J runners exercised for 2 months or longer, fiber-type grouping was observed in the areas where extensive damage usually occurred in the early periods. The results show that different muscles are damaged and repaired to varying degrees and that marked interstrain and inter-individual differences are present. It appears that acute muscle injury occurring upon onset of voluntary running is a usual event in the adaptation of muscles to altered use.     

Performance of recombinant inbred lines in Brussels sprouts (Brassica oleracea var. gemmifera)

Summary Performance of a random array of recombinant inbred lines derived by single seed descent from five different source populations of Brussels sprouts (Brassica oleracea var. gemmifera) is presented. A total of 2,356 lines were tested in trials during 1985 and 1986. Three of the source populations were derived from double crosses between F₁ hybrids. These hybrids show a considerable heterotic advantage over their inbred parents for the most important agronomic traits. The recombinant inbred lines performed, on average, less well than the parental inbred material, indicating that additive x additive genie interactions may make a significant contribution to the performance of current inbred material. Nevertheless, the very large variation among the recombinant inbred lines permitted many lines to be identified which outperformed the best parental inbred for all traits. Two lines outperformed the reference F₁ hybrid, Gower, for an index that included marketable yield and quality. Consideration was also given to the dangers of misinterpreting phenotypically based proportions. Accordingly, response equations were used to ascertain the real genetic progress that was made. Advance seemed small when compared with the large heterotic effect, which is consistent with the segregation of a large number of loci. The distribution of the recombinant inbred lines was compared to predictions made from early generation trials. There was broad agreement but significant discrepancies existed which, it is suggested, may arise from the effects of genotype-environment interactions.     

Comparative study of embryonic thermoresistance of two inbred strains of the medaka (Oryzias latipes)

Summary By using inbred strains (HO4C and HB32C) of the medaka,Oryzias latipes, the involvement of genetic factor(s) in the determination of thermoresistance of fish was investigated. The thermoresistance of embryos of the medaka was quantitated by the fraction of the embryos surviving 1 day after heat treatment. At early stages of development (st. 13 and st. 20–21), the HO4C strain was more resistant than the HB32C strain. At st. 20–21, the HO4C strain was more resistant than the HB32C strain at all temperatures used (42, 43, and 44°C). At later stages of development (st. 27 and st. 32), however, the HB32C strain was more resistant than the HO4C strain.The results of genetic cross experiments raised the following possibilities; the thermoresistance of embryos at early developmental stages can be lowered by some factor(s) inherited in the HO4C strain and/or increased by those in the HB32C strain. By contrast, the sensitivity of embryos at later stages of development was not affected by factor(s) of their parents, but by their own genetic constitution.     

Line and crossing effects in a diallel mating system with highly inbred lines of White Leghorn chickens

Summary Seven highly inbred lines of White Leghorn chickens were used in a near complete diallel mating plan during eight years. The lines originated from three different base populations selected for egg weight. Average inbreeding coefficients of parents of chicks hatching in successive years were 0.75, 0.80, 0.84, 0.86, 0.89, 0.91, 0.93 and 0.94. The composition of line, specific combining ability and reciprocal effects and their estimated values are given. These effects were estimated for age at first egg (AFE), average weight of all eggs laid to 40 weeks (EW40), body weight at 40 weeks (BW40), number of eggs to 40 weeks (EP40) and number of eggs between 41 and 60 weeks (EP60). Records of 3247 hens surviving to 40 weeks and of 3133 birds to 60 weeks could be used. Large differences between line effects could be found in all traits. They were only partly due to the preceding selection in the base populations. All specific combining effects were in the expected direction, negative for AFE and positive for EW40, BW40, EP40 and EP60. Recovery of inbreeding depression inflated these effects rather substancially. Average heterosis, defined as the relative superiority of a line combination over the mid parent value, was –11.3%, 5.8%, 7.8%, 45.1% and 35.8% for AFE, EW40, BW40, EP40 and EP60 respectively. One line showed a relative superiority in AFE of -19.3% compared to about –7.9% for all other combinations. Reciprocal or sex-linked effects were generally smaller in all traits than specific combining effects, they were considerably smaller in AFE, EP40 and EP60. General reciprocal effects could be found for several lines in one or more traits. Offspring of two lines, when used as sire lines, showed a negative correlation between reciprocal effects of egg weight and body weight.     

Predicting mean and variance of all possible lines and hybrids from designs with partially inbred progenies

Two-factor mating designs at consecutive S_n and S_(n+1) levels (S₀ and S₁ S₁ and S₂, or F₂ and F₃) allow estimation of all components of the variation among homozygous lines and F₁ hybrids that can be derived from a given population. They also allow for the prediction of the mean of these lines and single-cross hybrids. Some tests for the presence of epistasis are possible at the levels of means and of variances. Such mating designs can be very useful for predicting the value of the best possible lines or the best possible F₁ hybrids when it is difficult to produce, at an experimental level for exploratory purposes, either lines or hybrids.     

杨树苗期合理密度与合理密度线研究

 本文以加杨(Populus Canadensis),I—214(Populus euramericana(Dode)Guinier CV—214),中保14等杨树密度试验(1988—1991)为依据,分析了初植密度、竞争对生长的抑制作用,阐述了合理密度、合理密度范围、缓冲作用、上限合理密度线的形成过程。指出在双对数图上,上限合理密度线遵从Logistic分布(1nw=K/1+e(0.732·lnN-2.429),呈左侧伸展的S型曲线。该曲线可划分为近似于lnw一lnN直线的上中下三部分,其中间部分直线式的斜率为-1.5左右,称作合理密度直线式。对密度与生长的动态作了分析、概述与讨论。     

23个实验小鼠和大鼠近交系的保种研究

从1985年开始,陆续从国外实验动物著名机构引进常用近交系小鼠共23个品系(亚系和亚群)。在多年来保种繁殖过程中,根据修饰平行线系统选择留种动物,同时对动物进行全兄妹近亲交配繁殖,保持完整的谱系记录,控制饲养环境条件,成功地保持了绝大多数品系。同时对多数品系的繁殖性能和体重增长进行了观察,为这些品系的实验应用提供基本参数。