DNA sequence and analysis of human chromosome 18

Chromosome 18 appears to have the lowest gene density of any human chromosome and is one of only three chromosomes for which trisomic individuals survive to term. There are also a number of genetic disorders stemming from chromosome 18 trisomy and aneuploidy. Here we report the finished sequence and gene annotation of human chromosome 18, which will allow a better understanding of the normal and disease biology of this chromosome. Despite the low density of protein-coding genes on chromosome 18, we find that the proportion of non-protein-coding sequences evolutionarily conserved among mammals is close to the genome-wide average. Extending this analysis to the entire human genome, we find that the density of conserved non-protein-coding sequences is largely uncorrelated with gene density. This has important implications for the nature and roles of non-protein-coding sequence elements.     

Absence of perilipin results in leanness and reverses obesity in Lepr(db/db) mice

Obesity is a disorder of energy balance. Hormone-sensitive lipase (HSL) mediates the hydrolysis of triacylglycerol, the major form of stored energy in the body. Perilipin (encoded by the gene Plin), an adipocyte protein, has been postulated to modulate HSL activity. We show here that targeted disruption of Plin results in healthy mice that have constitutively activated fat-cell HSL. Plin -/- mice consume more food than control mice, but have normal body weight. They are much leaner and more muscular than controls, have 62% smaller white adipocytes, show elevated basal lipolysis that is resistant to beta-adrenergic agonist stimulation, and are cold-sensitive except when fed. They are also resistant to diet-induced obesity. Breeding the Plin -/- alleles into Leprdb/db mice reverses the obesity by ncreasing the metabolic rate of the mice. Our results demonstrate a role for perilipin in reining in basal HSL activity and regulating lipolysis and energy balance; thus, agents that inactivate perilipin may prove useful as anti-obesity medications.     

Fluorescing valvular nerves in the guinea-pig heart

Résumé Des plexus fluorescents de nerfs dans les valvules du cur du Cobaye sont décrits. Bien que du tissu musculaire et des nerfs cholinergiques fussent présents dans les valvules atrioventriculaires, les nerfs adrénergiques de la valvule pulmonaire ne se rapportaient qu'au tissu connectif fibreux. Puisque dans cette situation il n'y a pas d'emplacement effecteur évident ou que ces nerfs influencement des nerfs dont la présence n'est pas révélée par des techniques de cholinesterase ou qu'ils sont de caractère afférent.

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Acknowledgment. The author thanks Prof.G. A. G. Mitchell for his continued interest.