Susceptibility to testicular germ-cell tumours in a 129.MOLF-Chr 19 chromosome substitution strain.

The identification of genes that control susceptibility to testicular germ-cell tumours (TGCTs), the most common cancer affecting young men, has been difficult. In laboratory mice, TGCTs arise from primordial germ cells in only the 129 inbred strains, and susceptibility is under multigenic control. The spontaneously arising mutation Ter (ref. 5) on mouse chromosome 18 (Refs 6,7) increases TGCT frequency on a 129/Sv background. We originally used Ter in genetic crosses to identify loci that control tumorigenesis. A genome scan of tumour-bearing progeny from backcrosses between the 129/Sv-Ter/+ and MOLF/Ei strains provided modest evidence that MOLF-derived alleles on chromosome 19 enhance development of bilateral TGCTs (ref. 9). To obtain independent evidence for linkage to the MOLF chromosome, we made an autosomal chromosome substitution strain (CSS; or 'consomic strain') in which chromosome 19 of 129/Sv+/+ was replaced by its MOLF-derived homologue. The unusually high frequency of TGCTs in this CSS (even in the absence of the Ter mutation) provides evidence confirming the genome survey results, identifies linkage for a naturally occurring strain variant allele that confers susceptibility to TGCTs and illustrates the power of CSSs in complex trait analysis.     

Meiotic instability of human minisatellite CEB1 in yeast requires DNA double-strand breaks.

Minisatellites are tandemly repeated DNA sequences of 10-100-bp units. Some minisatellite loci are highly unstable in the human germ line, and structural analysis of mutant alleles has suggested that repeat instability results from a recombination-based process. To provide insights into the molecular mechanism of human minisatellite instability, we developed Saccharomyces cerevisiae strains carrying alleles of the most unstable human minisatellite locus, CEB1 (ref. 2). We observed that CEB1 is destabilized in meiosis, resulting in a variety of intra- and inter-allelic gains or losses of repeat units, similar to rearrangements described in humans. Using mutations affecting the initiation of recombination (spo11) or mismatch repair (msh2 pms1 ), we demonstrate that meiotic destabilization depends on the initiation of homologous recombination at nearby DNA double-strand break (DSBs) sites and involves a 'rearranged heteroduplex' intermediate. Most of the human and yeast data can be explained and unified in the context of DSB repair models.     

改良型9Cr-1Mo钢的形变热处理强化机制

采用形变热处理技术有效地提高改良型T91 耐热钢的高温回火抗力和室温综合力学性能。该钢经形变热处理后性能提高的主要机制是细晶强化和伴随晶粒细化而产生的马氏体组织的细化以及析出物的弥散分布。     

Direct multicriteria clustering algorithms

In a multicriteria clustering problem, optimization over more than one criterion is required. The problem can be treated in different ways: by reduction to a clustering problem with the single criterion obtained as a combination of the given criteria; by constrained clustering algorithms where a selected critetion is considered as the clustering criterion and all others determine the constraints; or by direct algorithms. In this paper two types of direct algorithms for solving multicriteria clustering problem are proposed: the modified relocation algorithm, and the modified agglomerative algorithm. Different elaborations of these two types of algorithms are discussed and compared. Finally, two applications of the proposed algorithms are presented. Elaborated version of the talks presented at the First Conference of the International Federation of Classification Societies, Aachen, 1987, at the International Conference on Social Science Methodology, Dubrovnik, 1988, and at the Second Conference of the International Federation of Classification Societies, Charlottesville, 1989. This work was supported in part by the Research Council of Slovenia.     

The runt test for multimodality

Single linkage clusters on a set of points are the maximal connected sets in a graph constructed by connecting all points closer than a given threshold distance. The complete set of single linkage clusters is obtained from all the graphs constructed using different threshold distances. The set of clusters forms a hierarchical tree, in which each non-singleton cluster divides into two or more subclusters; the runt size for each single linkage cluster is the number of points in its smallest subcluster. The maximum runt size over all single linkage clusters is our proposed test statistic for assessing multimodality. We give significance levels of the test for two null hypotheses, and consider its power against some bimodal alternatives. Research partially supported by NSF Grant No. DMS-8617919.     

Regulation of sodium and body fluid homeostasis during development: Implications for the pathogenesis of hypertension

The spontaneously hypertensive rat (SHR) is an important animal model of human essential hypertension. During the first month of life, increased retention of sodium is present in the SHR which appears to be mediated by the renin-angiotensin system. The present review will discuss the role that increased activity of the renin-angiotensin system plays in sodium/body fluid regulation during early development. It is hypothesized that disordered regulation of sodium/body fluid homeostasis during this stage leads to pathological cardiovascular regulation in adulthood. Through an understanding of the relationship between sodium/body fluid balance in the young and cardiovascular function in the adult insights may be gained into both the pathological state of hypertension and the critical role played by early development in shaping homeostatic mechanisms in adulthood.     

Trail-following responses ofLeptogenys diminuta to stereoisomers of 4-methyl-3-heptanol

Behavioral tests carried out with the four stereoisomers of 4-methyl-3-heptanol revealed thatLeptogenys diminuta ants respond specifically only to the (3R, 4S)-isomer.     

Timed bromocriptine administration reduces body fat stores in obese subjects and hyperglycemia in type II diabetics

Obese postmenopausal female volunteers were given timed daily oral dosages of bromocriptine, and tested for reduction of body fat stores. This dopamine agonist has been shown to reset circadian rhythms that are altered in obese animals and to reduce body fat levels in several animal models. The participants were instructed not to alter their existing exercise and eating behavior during treatment. Skinfold measurements were taken on 33 subjects as indices of body fat. The measurements (e.g., suprailiac) were reduced after six weeks by about 25%, which represents a reduction of 11.7% of the total body fat. These dramatic decreases in body fat, which are equivalent to that produced by severe caloric restriction, were accompanied by more modest reductions of body weight (2.5%), indicating a possible conservation of protein that is usually lost as a consequence of such caloric restriction. The effects of bromocriptine treatment on body fat and hyperglycemia were also examined in non-insulin dependent diabetics being treated with oral hypoglycemics (7 subjects) or insulin (7 subjects). Total body fat was reduced by 10.7% and 5.1% in diabetics on oral hypoglycemics and insulin, respectively, without any significant reductions in body weight.Hyperglycemia was reduced in most of the 15 diabetic subjects treated leading to euglycemia and even cessation of hypoglycemic drugs in 3 of the 7 subjects during 4–8 weeks of bromocriptine treatment. These findings support the hypothesis that obesity and type II diabetes may be treated effectively with bromocriptine when administered at the proper times and dosages.This is a process patented by Louisiana State University and licensed to Ergo, Inc., Newport, Rhode island. A. H. Meier and A. H. Cincotta have financial interest in the process.     

Intercellular communication in smooth muscle.

The functioning of a group of cells as a tissue depends on intercellular communication; an example is the spread of action potentials through intestinal tissue resulting in synchronized contraction. Recent evidence for cell heterogeneity within smooth muscle tissues has renewed research into cell coupling. Electrical coupling is essential for propagation of action potentials in gastrointestinal smooth muscle. Metabolic coupling may be involved in generation of pacemaker activity. This review deals with the role of cell coupling in tissue function and some of the issues discussed are the relationship between electrical synchronization and gap junctions, metabolic coupling, and the role of interstitial cells of Cajal in coupling.     

Regulation of sodium and body fluid homeostasis during development: implications for the pathogenesis of hypertension.

The spontaneously hypertensive rat (SHR) is an important animal model of human essential hypertension. During the first month of life, increased retention of sodium is present in the SHR which appears to be mediated by the renin-angiotensin system. The present review will discuss the role that increased activity of the renin-angiotensin system plays in sodium/body fluid regulation during early development. It is hypothesized that disordered regulation of sodium/body fluid homeostasis during this stage leads to pathological cardiovascular regulation in adulthood. Through an understanding of the relationship between sodium/body fluid balance in the young and cardiovascular function in the adult insights may be gained into both the pathological state of hypertension and the critical role played by early development in shaping homeostatic mechanisms in adulthood.