Partial leptin deficiency and human adiposity.

The adipocyte-derived hormone leptin is crucial for energy homeostasis in mammals; mice and humans without it suffer from a voracious appetite and extreme obesity. The effect on energy balance of variations in plasma leptin above a minimal threshold is uncertain, however, particularly in humans. Here we examine a group of individuals who are genetically partially deficient in leptin, and show that differences in circulating leptin levels within the range found in normal human populations can directly influence the laying down of fat tissue (adiposity).     

DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage

Chromosome 17 is unusual among the human chromosomes in many respects. It is the largest human autosome with orthology to only a single mouse chromosome, mapping entirely to the distal half of mouse chromosome 11. Chromosome 17 is rich in protein-coding genes, having the second highest gene density in the genome. It is also enriched in segmental duplications, ranking third in density among the autosomes. Here we report a finished sequence for human chromosome 17, as well as a structural comparison with the finished sequence for mouse chromosome 11, the first finished mouse chromosome. Comparison of the orthologous regions reveals striking differences. In contrast to the typical pattern seen in mammalian evolution, the human sequence has undergone extensive intrachromosomal rearrangement, whereas the mouse sequence has been remarkably stable. Moreover, although the human sequence has a high density of segmental duplication, the mouse sequence has a very low density. Notably, these segmental duplications correspond closely to the sites of structural rearrangement, demonstrating a link between duplication and rearrangement. Examination of the main classes of duplicated segments provides insight into the dynamics underlying expansion of chromosome-specific, low-copy repeats in the human genome.     

A screen of the complete protein kinase gene family identifies diverse patterns of somatic mutations in human breast cancer

We examined the coding sequence of 518 protein kinases, approximately 1.3 Mb of DNA per sample, in 25 breast cancers. In many tumors, we detected no somatic mutations. But a few had numerous somatic mutations with distinctive patterns indicative of either a mutator phenotype or a past exposure.     

Real-time forecasts of tomorrow's earthquakes in California

Despite a lack of reliable deterministic earthquake precursors, seismologists have significant predictive information about earthquake activity from an increasingly accurate understanding of the clustering properties of earthquakes. In the past 15 years, time-dependent earthquake probabilities based on a generic short-term clustering model have been made publicly available in near-real time during major earthquake sequences. These forecasts describe the probability and number of events that are, on average, likely to occur following a mainshock of a given magnitude, but are not tailored to the particular sequence at hand and contain no information about the likely locations of the aftershocks. Our model builds upon the basic principles of this generic forecast model in two ways: it recasts the forecast in terms of the probability of strong ground shaking, and it combines an existing time-independent earthquake occurrence model based on fault data and historical earthquakes with increasingly complex models describing the local time-dependent earthquake clustering. The result is a time-dependent map showing the probability of strong shaking anywhere in California within the next 24 hours. The seismic hazard modelling approach we describe provides a better understanding of time-dependent earthquake hazard, and increases its usefulness for the public, emergency planners and the media.     

The genome sequence of Schizosaccharomyces pombe

We have sequenced and annotated the genome of fission yeast (Schizosaccharomyces pombe), which contains the smallest number of protein-coding genes yet recorded for a eukaryote: 4,824. The centromeres are between 35 and 110 kilobases (kb) and contain related repeats including a highly conserved 1.8-kb element. Regions upstream of genes are longer than in budding yeast (Saccharomyces cerevisiae), possibly reflecting more-extended control regions. Some 43% of the genes contain introns, of which there are 4,730. Fifty genes have significant similarity with human disease genes; half of these are cancer related. We identify highly conserved genes important for eukaryotic cell organization including those required for the cytoskeleton, compartmentation, cell-cycle control, proteolysis, protein phosphorylation and RNA splicing. These genes may have originated with the appearance of eukaryotic life. Few similarly conserved genes that are important for multicellular organization were identified, suggesting that the transition from prokaryotes to eukaryotes required more new genes than did the transition from unicellular to multicellular organization.     

Australian goats detoxify the goitrogen 3-hydroxy-4(1H) pyridone (DHP) after rumen infusion from an Indonesian goat

The failure of Australian goats fed Leucaena leucocephala (leucaena) to degrade 3-hydroxy-4(1H) pyridone (DHP), the goitrogenic metabolite of mimosine, was overcome when they were infused with rumen fluid from an Indonesian goat. The leucaena toxicity problem in Australia may well be solved by transfer of specific bacteria capable of degrading DHP anaerobically.     

On the nature of biological clocks?

Zusammenfassung Feststellung, dass schlafende Goldhamster einen höheren ATP-Gehalt in Gehirn und Leber besitzen als wache Tiere und dass Zeitgeber, wie Licht und Temperatur, sowohl Zellviskosität als auch ATP-Niveau verändern.