The knockout mouse project

Mouse knockout technology provides a powerful means of elucidating gene function in vivo, and a publicly available genome-wide collection of mouse knockouts would be significantly enabling for biomedical discovery. To date, published knockouts exist for only about 10% of mouse genes. Furthermore, many of these are limited in utility because they have not been made or phenotyped in standardized ways, and many are not freely available to researchers. It is time to harness new technologies and efficiencies of production to mount a high-throughput international effort to produce and phenotype knockouts for all mouse genes, and place these resources into the public domain.     

BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-beta-catenin signaling

In humans, mutations in BMPR1A, SMAD4 and PTEN are responsible for juvenile polyposis syndrome, juvenile intestinal polyposis and Cowden disease, respectively. The development of polyposis is a common feature of these diseases, suggesting that there is an association between BMP and PTEN pathways. The mechanistic link between BMP and PTEN pathways and the related etiology of juvenile polyposis is unresolved. Here we show that conditional inactivation of Bmpr1a in mice disturbs homeostasis of intestinal epithelial regeneration with an expansion of the stem and progenitor cell populations, eventually leading to intestinal polyposis resembling human juvenile polyposis syndrome. We show that BMP signaling suppresses Wnt signaling to ensure a balanced control of stem cell self-renewal. Mechanistically, PTEN, through phosphatidylinosital-3 kinase-Akt, mediates the convergence of the BMP and Wnt pathways on control of beta-catenin. Thus, BMP signaling may control the duplication of intestinal stem cells, thereby preventing crypt fission and the subsequent increase in crypt number.     

Meteoric smoke fallout over the Holocene epoch revealed by iridium and platinum in Greenland ice

An iridium anomaly at the Cretaceous/Tertiary boundary layer has been attributed to an extraterrestrial body that struck the Earth some 65 million years ago. It has been suggested that, during this event, the carrier of iridium was probably a micrometre-sized silicate-enclosed aggregate or the nanophase material of the vaporized impactor. But the fate of platinum-group elements (such as iridium) that regularly enter the atmosphere via ablating meteoroids remains largely unknown. Here we report a record of iridium and platinum fluxes on a climatic-cycle timescale, back to 128,000 years ago, from a Greenland ice core. We find that unexpectedly constant fallout of extraterrestrial matter to Greenland occurred during the Holocene, whereas a greatly enhanced input of terrestrial iridium and platinum masked the cosmic flux in the dust-laden atmosphere of the last glacial age. We suggest that nanometre-sized meteoric smoke particles, formed from the recondensation of ablated meteoroids in the atmosphere at altitudes >70 kilometres, are transported into the winter polar vortices by the mesospheric meridional circulation and are preferentially deposited in the polar ice caps. This implies an average global fallout of 14 +/- 5 kilotons per year of meteoric smoke during the Holocene.     

Mercury's capture into the 3/2 spin-orbit resonance as a result of its chaotic dynamics

Mercury is locked into a 3/2 spin-orbit resonance where it rotates three times on its axis for every two orbits around the sun. The stability of this equilibrium state is well established, but our understanding of how this state initially arose remains unsatisfactory. Unless one uses an unrealistic tidal model with constant torques (which cannot account for the observed damping of the libration of the planet) the computed probability of capture into 3/2 resonance is very low (about 7 per cent). This led to the proposal that core-mantle friction may have increased the capture probability, but such a process requires very specific values of the core viscosity. Here we show that the chaotic evolution of Mercury's orbit can drive its eccentricity beyond 0.325 during the planet's history, which very efficiently leads to its capture into the 3/2 resonance. In our numerical integrations of 1,000 orbits of Mercury over 4 Gyr, capture into the 3/2 spin-orbit resonant state was the most probable final outcome of the planet's evolution, occurring 55.4 per cent of the time.     

The influence of ridge migration on the magmatic segmentation of mid-ocean ridges

The Earth's mid-ocean ridges display systematic changes in depth and shape, which subdivide the ridges into discrete spreading segments bounded by transform faults and smaller non-transform offsets of the axis. These morphological changes have been attributed to spatial variations in the supply of magma from the mantle, although the origin of the variations is poorly understood. Here we show that magmatic segmentation of ridges with fast and intermediate spreading rates is directly related to the migration velocity of the spreading axis over the mantle. For over 9,500 km of mid-ocean ridge examined, leading ridge segments in the 'hotspot' reference frame coincide with the shallow magmatically robust segments across 86 per cent of all transform faults and 73 per cent of all second-order discontinuities. We attribute this relationship to asymmetric mantle upwelling and melt production due to ridge migration, with focusing of melt towards ridge segments across discontinuities. The model is consistent with variations in crustal structure across discontinuities of the East Pacific Rise, and may explain variations in depth of melting and the distribution of enriched lavas.     

Early association of electrocardiogram alteration with infarct size and cardiac function after myocardial infarction

OBJECTIVE: Myocardial infarction (MI) is the main cause of heart failure, but the relationship between the extent of MI and cardiac function has not been clearly determined. The present study was undertaken to investigate early changes in the electrocardiogram associated with infarct size and cardiac function after MI. METHODS: MI was induced by ligating the left anterior descending coronary artery in rats. Electrocardiograms, echocardiographs and hemodynamic parameters were assessed and myocardial infarct size was measured from mid-transverse sections stained with Masson's trichrome. RESULTS: The sum of pathological Q wave amplitudes was strongly correlated with myocardial infarct size (r = 0.920, P < 0.0001), left ventricular ejection fraction (r = -0.868, P < 0.0001) and left ventricular end diastolic pressure (r = 0.835, P < 0.0004). Furthermore, there was close relationship between MI size and cardiac function as assessed by left ventricular ejection fraction (r = -0.913, P < 0.0001) and left ventricular end diastolic pressure (r = 0.893, P < 0.0001). CONCLUSION: The sum of pathological Q wave amplitudes after MI can be used to estimate the extent of MI as well as cardiac function.     

Lower Paleozoic oil relationships within Williston Basin, Canada

The Williston Basin is a significant petroleum province, containing oil production zones that include the Middle Cambrian to Lower ()rdovician, Upper Ordovician, Middle Devonian, Upper Devonian and Mississippian and within the Jurassic and Cretaceous. The oils of the Williston Basin exhibit a wide range of geochemical characteristics defined as “oil families“, although the geochemical signature of the Cambrian Deadwood Formation and Lower Ordovician Winnipeg reservoired oils does not match any “oil family“. Despite their close stratigraphic proximity, it is evident that the oils of the/rower Palaeozoic within the Williston Basin are distinct. This suggests the presence of a new “oil family“ within the Williston Basin. Diagnostic geochemical signatures occur in the gasoline range chromatograms, within saturate fraction gas chromatograms and biomarker fingerprints. However, some of the established criteria and cross-plots that are currently used to segregate oils into distinct genetic families within the basin do not always meet with success, particularly when applied to the Lower Palaeozoic oils of the Deadwood and Winnipeg Formation.     

Variation of the fine structure in granulocytes of great apes

Zusammenfassung Elektronenmikroskopische Untersuchungen der Granulocyten anthropoider Affen ergaben Unterschiede in der Struktur der eosinophilen Granula und eine bisher unbekannte fibrilläre Granulationsform in Orangutan Neutrophilen.

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These studies were supported by U.S. Public Health Service Grant No. FR 00165 from the National Institutes of Health and Atomic Energy Commission grant No. AT (30-1) 3808.     

Étude biochimique des poissons: 1. Variations semestrielles de la teneur en eau et en protéines du tissu musculaire de la truite Arc-en-ciel (Salmo gairdnerii Rich)

Summary The authors have noted, during the reproductive cycle of the Rainbow trout (Salmo gairdnerii Rich), important variations concerning water and total proteins content. This study shows a great correlation between the biological process and biochemical variations.