Physical and functional mapping of a novel tumor suppressor locus for prostate cancer within chromosome 10p12.31-q11

Prostate cancer remains the second leading cause of male cancer deaths in the United States, yet the molecular mechanisms underlying this disease remain largely unknown. Cytogenetic and molecular analyses of prostate tumors suggest a consistent association with the loss of chromosome 10. Previously, we have defined a novel tumor suppressor locus PAC-1 within chromosome 10pter-q11. Introduction of the short arm of chromosome 10 into a prostatic adenocarcinoma cell line PC-3H resulted in dramatic tumor suppression and restoration of a programmed cell death pathway. Using a combined approach of comparative genomic hybridization and microsatellite analysis of PC-3H, I have identified a region of hemizygosity within 10p12-p15. This region has been shown to be involved in frequent loss of heterozygosity in gliomas and melanoma. To functionally dissect the region within chromosome 10p containing PAC-1, we developed a strategy of serial microcell fusion, a technique that allows the transfer of defined fragments of chromosome 10p into PC-3H. Serial microcell fusion was used to transfer defined 10p fragments into a mouse A9 fibrosarcoma cell line. Once characterized by FISH and microsatellite analyses, the 10p fragments were subsequently transferred into PC-3H to generate a panel of microcell hybrid clones containing overlapping deletions of chromosome 10p. In vivo and microsatellite analyses of these PC hybrids identified a small chromosome 10p fragment (an estimated 31 Mb in size inclusive of the centromere) that when transferred into the PC-3H background, resulted in significant tumor suppression and limited a region of functional tumor suppressor activity to chromosome 10p12.31-q11. This region coincides with a region of LOH demonstrated in prostate cancer. These studies demonstrate the utility of this approach as a powerful tool to limit regions of functional tumor suppressor activity. Furthermore, these data used in conjunction with data generated by the Human Genome Project lent a focused approach to identify candidate tumor suppressor genes involved in prostate cancer. ^

Rubidium and Strontium chemistry of oceanic crust

Times of vein mineral deposition in the ocean crust have been determined both by Rb-Sr isochron ages of vein smectites and by comparison of 87Sr/86Sr ratios of vein calcites with the known variations of seawater 87Sr/86Sr ratio with time. Results from drilling sites 105, 332B and 418A, Atlantic Ocean, which have basement formation ages of 155 m.y., 3.5 m.y., and 110 m.y., respectively, show that vein deposition is essenrially complete within 5-10 m.y. after formation of the basaltic crust. This provids direct evidence that hydrothermal circulation of sea-water through the oceanic crust is an important process for only 5-10 m.y. after crust formation.

Physical and geotechnical properties of Norwegian Sea sediments

Sediment composition and rate of deposition are the primary factors responsible for determining the spatial distribution of geotechnical properties on the Wring Plateau. Grain size and depth of burial have no significant influence. Vertical and lateral changes in geotechnical properties are associated with vertical and lateral composition changes in which biogenic silica is the most important variable. Anomalous trends of decreasing density and increasing porosity and water content with depth are associated with increasing silica content downsection. Void ratios, inferred in-situ permeability, and change in void ratio during consolidation testing are relatively high in siliceous sediments and tend to increase as the biogenic silica content increases. Portions of the section are overconsolidated, probably as a result of changes in sediment accumulation rates. However, the higher permeabilities of siliceous sediments may also be a factor influencing consolidation state.

Carbon and Lead chemistry of sediments from the Middle Atlantic Bight

A mass budget was constructed for organic carbon on the upper slope of the Middle Atlantic Bight, a region thought to serve as a depocenter for fine-grained material exported from the adjacent shelf. Various components of the budget are internally consistent, and observed differences can be attributed to natural spatial variability or to the different time scales over which measurements were made. The flux of organic carbon to the sediments in the core of the depocenter zone, at a water depth of 1000 m, was measured with sediment traps to be 65 mg C m**-2 day**-1, of which 6-24 mg C m**-2 day**-1 is buried. Oxygen fluxes into the sediments, measured with incubation chambers attached to a free vehicle lander, correspond to total carbon remineralization rates of 49-70 mg C m**-2 day**-1. Carbon remineralization rates estimated from gradients of Corg within the mixed layer, and from gradients of dissolved ammonia and phosphate in pore waters, sum to only 4-6 mg C m**-2 day**-1. Most of the Corg remineralization in slope sediments is mediated by bacteria and takes place within a few mm of the sediment-water interface. Most of the Corg deposited on the upper slope sediments is supplied by lateral transport from other regions, but even if all of this material were derived from the adjacent shelf, it represents <2% of the mean annual shelf productivity. This value is further lowered by recognizing that as much as half of the Corg deposited on the slope is refractory, having originated by reworking from older deposits. Refractory Corg arrives at the sea bed with an average 14C age 600-900 years older than the pre-bomb 14C age of DIC in seawater, and has a mean life in the sediments with respect to biological remineralization of at least 1000 years. Labile carbon supplied to the slope, on the other hand, is rapidly and (virtually) completely remineralized, with a mean life of < 1 year. Carbon-14 ages of fine-grained carbonate and organic carbon present within the interstices of shelf sands are consistent with this material acting as a source for the old carbon supplied to the slope. Winnowing and export of reworked carbon may contribute to the often-described relationship between organic carbon preservation and accumulation rate of marine sediments.

Physical and chemical oceanography in the Arctic Ocean

Data from sections across the Eurasian Basin of the Arctic Ocean occupied by the German Research Vessel Polarstern in 1987 and by the Swedish icebreaker Oden in 1991 are used to derive information on the freshwater balance of the Arctic Ocean halocline and on the sources of the deep waters of the Nansen, Amundsen and Makarov basins. Salinity, d18O and mass balances allow separation of the river-runoff and the sea-ice meltwater fractions contained in the Arctic halocline. This provides the basis for tracking the river-runoff signal from the shelf seas across the central Arctic Ocean to Fram Strait. The halocline has to be divided into at least three lateral regimes: the southern Nansen Basin with net sea-ice melting, the northern Nansen Basin and Amundsen Basin with net sea-ice formation and increasing river-runoff fractions, and the Canadian Basin with minimum sea-ice meltwater and maximum river-runoff fractions and water of Pacific origin. In the Canadian Basin, silicate is used as a tracer to identify Pacific water entering through Bering Strait and an attempt is made to quantify its influence on the halocline waters of the Canadian Basin. For this purpose literature data from the CESAR and LOREX ice camps are used. Based on mass balances and depending on the value of precipitation over the area of the Arctic Ocean the average mean residence time of the river-runoff fraction contained in the Arctic Ocean halocline is determined to be about 14 or 11 years. Water column inventories of river-runoff and sea-ice meltwater are calculated for a section just north of Fram Strait and implications for the ice export rate through Fram Strait are discussed. Salinity, tritium, 3He and the d18O ratio of halocline waters sampled during the 1987 Polarstern cruise to the Nansen Basin are used to estimate the mean residence time of the river-runoff component in the halocline and on the shelves of the Arctic Ocean. These estimates are done by comparing ages of the halocline waters based on a combination of tracers yielding different time information: the tritium 'vintage' age which records the time that has passed since the river-runoff entered the shelf and the tritium/3He age which reflects the time since the shelf waters left the shelf. The difference between the ages determined by these two methods is about 3 to 6 years. Correction for the initial tritium/3He age of the shelf waters (about 0.5 to 1.5 years) yields a mean residence time of the river-runoff on the shelves of about 3.5 ± 2 years. Comparison of the 18O/16O ratios of shelf water, Atlantic water and the deep waters of the Arctic Ocean indicate that the sources of the deep and bottom waters of the Eurasian Basin are located in the Barents and Kara seas.

Interstitial water and sediment chemistry at DSDP Sites 87-582 and 87-584

Two trenches off Japan were explored during DSDP Leg 87. One is the Nankai Trough and the other is the Japan Trench; Site 582 is located on the floor of the former and Site 584 is situated on the deep-sea terrace of the latter. Cores from Site 582 and 584 consist mainly of hemipelagic sediments and diatomaceous silts and mudstone, respectively. In this report we analyze the chemistry of the interstitial water and sediments, as well as the sediment mineralogy. Sulfate reduction is accompanied by the production of secondary pyrite, which is rich in the sediment at both sites. Dissolved Ca concentration is relatively low and changes only slightly at both sites, probably because of the formation of carbonate with high alkalinity. Concentrations of dissolved Mg decrease with depth at Site 584. The dissolved Mg depletion probably results from the formation of Mg-rich carbonate and/or ion exchange and reaction between interstitial water and clay minerals. Higher Si/Al values are due to biogenic opal in the sediments and roughly correlate with higher values of interstitial water SiO2. Increases in dissolved Li concentrations may be related to its release from clay minerals, to advection that results from dewatering, and/or to fluid transport.