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.     

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.     

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.     

A potent attractant of zoospores ofAphanomyces cochlioides isolated from its host,Spinacia oleracea

A highly potent attractant of zoospores ofAphanomyces cochlioides, a causal fungus of the root rot disease of spinach (Spinacia oleracea), was isolated from spinach roots, and its structure was determined by spectroscopic evidence and chemical synthesis as cochliophilin A (5-hydroxy-6,7-methylenedioxyflavone,1). A chromosorb particle prepared by soaking in solution of1 showed a potent attracting activity toward the zoospores using concentrations of1 above 10^–9 or 10^–10 M.     

Effect of monensin and diabetes on asialoglycoprotein degradation in rat hepatocytes

We have studied the effects of two modulations — streptozotocin-induced diabetes in vivo, and the presence of the carboxylic proton ionophore monensin in vitro — on the degradation of³H-asialoorosomucoid ligand in isolated rat hepatocytes.The ligand was internalized by means of a synchronous wave procedure. Diabetes was associated with a marked decrease in the amount of total degraded radioactive ligand compared to that in normal cells (3.6% and 37.3% of internalized ligand respectively, at 60 min), together with increased secretion of degradation products into the incubation medium (87% and 46.3% of the total degraded ligand was secreted by diabetic and normal cells, respectively). Monensin induced similar effects in normal cells, but had no apparent effect in diabetic cells.     

Human slow wave sleep: A review and appraisal of recent findings,with implications for sleep functions,and psychiatric illness

Recent findings concerning human slow wave sleep (hSWS-stages 3+4; delta EEG activity) are critically reviewed. Areas covered include the significance of the first hSWS cycle; hSWS in extended sleep; relationship between hSWS, prior wakefulness and sleep loss; hSWS influence on sleep length; problems with hSWS deprivation; influence of the circadian rhythm; individual differences in hSWS, especially, age, gender and constitutional variables such as physical fitness and body composition. Transient increases in hSWS can be produced by increasing both the quality and quantity of prior wakefulness, with an underlying mechanism perhaps relating to the waking level of brain metabolism. Whilst there may also be thermoregulatory influences on hSWS, hypotheses that energy conservation and brain cooling are major roles for hSWS are debatable. hSWS seems to offer some form of cerebral recovery, with the prefrontal cortex being particularly implicated. The hSWS characteristics of certain forms of major psychiatric disorders may well endorse this prefrontal link.     

Effects of the adenylate cyclase activator forskolin and its inactive derivative 1,9-dideoxyforskolin on insect cytochrome P-450 dependent steroid hydroxylase activity

The adenylate cyclase activator forskolin and its pharmacologically inactive derivative 1,9-dideoxyforskolin were found to inhibit in a dose-dependent fashion the ecdysone 20-monooxygenase activity associated with wandering stage larvae ofDrosophila melanogaster and fat body and midgut from last instar larvae of the tobacco hornworm,Manduca sexta. The concentrations of these labdane diterpenes required to elicit a 50% inhibition of the cytochrome P-450 dependent steroid hydroxylase activity in the insect tissues ranged from approximately 5×10^–6 to 5×10^–4 M.     

Evidence for the induction and release of pancreatic folylpolyglutamate hydrolase by the ingestion of folyl polyglutamates in the rat

Pteroyl polyglutamate hydrolase (folyl conjugase), which hydrolyses the dietary polyglutamyl folates into simple forms prior to absorption, has been shown to be induced in rat pancreas in response to dietary polyglutamyl folates but not by ingestion of synthetic unconjugated folates. Folate absorption, as measured by the rise in serum folate levels after ingestion, of dietary conjugated folates is impaired in pancreatectomised animals whereas absorption of synthetic simple folate is not. A severe build-up of folyl conjugase is observed in the lumen of control but not in pancreatectomised animals after dietary folate ingestion. These results taken together would suggest that dietary folates are hydrolysed to monoglutamyl forms suitable for absorption in the lumen; the hydrolysis is catalysed by a luminal folyl conjugase of pancreatic origin induced by dietary conjugated folates.     

Evaluation of the hepatotoxicological effects of a drug in an in vivo/in vitro model.

Both in vivo and in vitro models have certain disadvantages for the study of the chronic hepatotoxicity of drugs. The aim of this work was to evaluate a new approach based on an in vivo/in vitro model. After chronic in vivo treatment of rats with Vincamine and Vindeburnol (an eburnamenine derivative which exhibits hepatotoxic properties in man) liver cells were isolated, and functional and metabolic disorders (metabolic utilization of fructose and protein biosynthesis) were studied to determine injury. The results showed no modification of blood parameters, but a direct relationship between the dose of Vindeburnol administered in vivo and the metabolic disorders observed in vitro, evidencing the high sensitivity and reliability of this model.     

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.