Binding of high-risk human papillomavirus E6 oncoproteins to the human homologue of the Drosophila discs large tumor suppressor protein

In the majority of cervical cancers, DNAs of high-risk mucosotpropic human papillomaviruses (HPVs), such as type 16, are maintained so as to express two viral proteins, E6 and E7, suggesting an essential importance to carcinogenesis. The high-risk HPV E6 proteins are known to inactivate p53 tumor suppressor protein but appear to have an additional, molecularly unknown function(s). In this study, we demonstrate that these E6 proteins can bind to the second PDZ domain of the human homologue of the Drosophila discs large tumor suppressor protein (hDLG) through their C-terminal XS/TXV/L (where X represents any amino acid, S/T serine or threonine, and V/L valine or leucine) motif. This finding is similar to the interaction between the adenomatous polyposis coli gene product and hDLG. E6 mutants losing the ability to bind to hDLG are no longer able to induce E6-dependent transformation of rodent cells. These results suggest an intriguing possibility that interaction between the E6 protein and hDLG or other PDZ domain-containing proteins could be an underlying mechanism in the development of HPV-associated cancers.

A recombinant bcl-x s adenovirus selectively induces apoptosis in cancer cells but not in normal bone marrow cells.

Many cancers overexpress a member of the bcl-2 family of inhibitors of apoptosis. To determine the role of these proteins in maintaining cancer cell viability, an adenovirus vector that expresses bcl-xs, a functional inhibitor of these proteins, was constructed. Even in the absence of an exogenous apoptotic signal such as x-irradiation, this virus specifically and efficiently kills carcinoma cells arising from multiple organs including breast, colon, stomach, and neuroblasts. In contrast, normal hematopoietic progenitor cells and primitive cells capable of repopulating severe combined immunodeficient mice were refractory to killing by the bcl-xs adenovirus. These results suggest that Bcl-2 family members are required for survival of cancer cells derived from solid tissues. The bcl-xs adenovirus vector may prove useful in killing cancer cells contaminating the bone marrow of patients undergoing autologous bone marrow transplantation.

10Be records of sediment cores from high northern latitudes

The 10Be records of four sediment cores forming a transect from the Norwegian Sea at 70°N (core 23059) via the Fram Strait (core 23235) to the Arctic Ocean at 86°N (cores 1533 and 1524) were measured at a high depth resolution. Although the material in all the cores was controlled by different sedimentological regimes, the 10Be records of these cores were superimposed by glacial/interglacial changes in the sedimentary environment. Core sections with high 10Be concentrations ( >1 * 10**9 at/g) are related to interglacial stages and core sections with low10Be concentrations ( <0.5 * 10**9 at/g) are related to glacial stages. Climatic transitions (e.g., Termination II, 5/6) are marked by drastic changes in the 10Be concentrations of up to one order of magnitude. The average 10Be concentrations for each climatic stage show an inverse relationship to their corresponding sedimentation rates, indicating that the 10Be records are the result of dilution with more or less terrigenous ice-rafted material. However, there are strong changes in the 10Be fluxes (e.g., Termination II) into the sediments which may also account for the observed oscillations. Most likely, both processes affected the 10Be records equally, amplifying the contrast between lower (glacials) and higher (interglacials) 10Be concentrations. The sharp contrast of high and low 10Be concentrations at climatic stage boundaries are an independent proxy for climatic and sedimentary change in the Nordic Seas and can be applied for stratigraphic dating (10Be stratigraphy) of sediment cores from the northern North Atlantic and the Arctic Ocean.

Geochemistry of Baltic Sea sediments and porewaters

Patterns of regeneration and burial of phosphorus (P) in the Baltic Sea are strongly dependent on redox conditions. Redox varies spatially along water depth gradients and temporally in response to the seasonal cycle and multidecadal hydrographic variability. Alongside the well-documented link between iron oxyhydroxide dissolution and release of P from Baltic Sea sediments, we show that preferential remineralization of P with respect to carbon (C) and nitrogen (N) during degradation of organic matter plays a key role in determining the surplus of bioavailable P in the water column. Preferential remineralization of P takes place both in the water column and upper sediments and its rate is shown to be redox-dependent, increasing as reducing conditions become more severe at greater water-depth in the deep basins. Existing Redfield-based biogeochemical models of the Baltic may therefore underestimate the imbalance between N and P availability for primary production, and hence the vulnerability of the Baltic to sustained eutrophication via the fixation of atmospheric N. However, burial of organic P is also shown to increase during multidecadal intervals of expanded hypoxia, due to higher net burial rates of organic matter around the margins of the deep basins. Such intervals may be characterized by basin-scale acceleration of all fluxes within the P cycle, including productivity, regeneration and burial, sustained by the relative accessibility of the water column P pool beneath a shallow halocline.

Phosphorus components, trace metals and Ba excess of ODP Site 202-1237 sediments

We determined the sedimentary concentrations of phosphorus (P), barium (Ba), manganese (Mn), titanium (Ti), aluminum (Al), and uranium (U) for sediment samples from the southeast Pacific Nazca Ridge, Ocean Drilling Program Site 1237. This unique record extends to 31 Ma over 360 meters composite depth (mcd), recording depositional history as the site progressed eastward over its paleohistory. We sampled with a temporal resolution of ~0.2 m.y. throughout the sequence, equivalent to an average spacing of 1.63 m/sample. Concentrations of sequentially extracted components of P (oxide-associated, authigenic, organic, and detrital) increase toward the modern. Al/Ti ratios indicate that the background detrital source material is consistent with upper continental crust. U enrichment factors (U EFs) generally exceed crustal values and indicate slightly reducing environments. However, authigenic U precipitation can also be influenced by the organic carbon rain rate and may not be solely an indicator of redox conditions. Dramatic changes in Mn EFs at ~162 mcd, from values between 12 and 93 to values <12 after this depth, and a sharp color contact boundary lead us to believe that a paleoredox boundary from an oxygenated to a more reducing depositional environment occurred near this depth. Estimates of biogenic barite concentrations from a total sediment digestion technique (Ba excess) are greater than those from a barite extraction (Ba barite) for selected samples across the entire depth range. Applying a range of Ba/Ti ratios from different source materials to correct for detrital inputs does not change the lack of agreement with Ba barite concentrations. Reactive P (P reactive) concentrations (the sum of oxide-associated, authigenic, and organic P concentrations) increase toward the modern with values typically <12 µmol P/g from the base of our record through ~100 mcd, with a gradual increase to concentrations >15 µmol P/g. Ba excess follows the same general trends as Preactive, with concentrations <14 µmol Ba/g in the lower portion of the record to values >15 µmol Ba/g. Accumulation rate records of these proxies will be needed to infer paleoproductivity. P reactive/Ba excess ratios, an indicator of the relative burial of the nutrient P to organic carbon export, exhibit higher values, similar to modern, from the base of our record through ~180 mcd. The remainder of the record exhibits values lower than modern, indicating that organic carbon export to the sediments was higher relative to nutrient burial.

Age determination and paleotemperatures of sediment cores TTR17-1_384B and TTR17-1_436B in the Alboran Sea

Climate conditions in the westernmost Mediterranean (Alboran Sea basin) over the last two millennia have been reconstructed through integration of molecular proxies applied for the first time in this region at such high resolution. Two temperature proxies, one based on isoprenoid membrane lipids of marine Thaumarchaeota (TEXH86-tetraether index of compounds consisting of 86 carbons) and the other on alkenones produced by haptophytes (UK'37 ratio) were applied to reconstruct sea surface temperature (SST). Both records reveal a progressive long term decline in SST over the last two millennia and an increased rate of warming during the second half of the twentieth century. This is in accord with previous temperature reconstructions for the Northern Hemisphere. TEXH86 temperature values are higher than those inferred from UK'37, probably due to differences in the bloom season of haptophytes and Thaumarchaeota, and reflect summer SST. The branched vs. isoprenoid tetraether index (BIT index) suggests a low contribution of soil organic matter (OM) to the sedimentary OM. The stable carbon isotopic composition of long chain n-alkanes indicates a predominant C3 plant contribution, with no major change in vegetation over the last 2000 yr. The distribution of long chain 1,14-diols (most likely sourced by Proboscia species in this setting) provided insight into variation in upwelling conditions during the last 2000 yr and depicts a correlation with the North Atlantic Oscillation (NAO) index, providing evidence of enhanced wind induced upwelling during periods of a persistent positive mode of the NAO.

Uranium, Thorium and Protactinium isotopes of ODP Site 172-1063

Ocean circulation may have undergone reductions and reinvigorations in the past closely tied to regional climate changes. Measurements of 231Pa/230Th ratios in a sediment core from the Bermuda Rise have been interpreted as evidence that the Atlantic Meridional Overturning Circulation (AMOC) was weakened or completely eliminated during a period of catastrophic iceberg discharges (Heinrich-Event 1, H1). Here we present new data from the Bermuda Rise that show further 231Pa/230Th peaks during Heinrich-2 (H2) and Heinrich-3 (H3). Additionally, a tight correlation between diatom abundances (biogenic silica) and 231Pa/230Th is discovered in this core. Our results redirect the interpretation of 231Pa/230Th from the Bermuda Rise as a proxy for ocean circulation towards a proxy that reacts highly sensitive to changes of particle composition and water mass properties.

Bulk sediment element analysis of sediment cores GeoB10065-9 and GeoB10065-7, offshore northwest Sumba Island, Indonesia

The Australian-Indonesian monsoon has a governing influence on the agricultural practices and livelihood in the highly populated islands of Indonesia. However, little is known about the factors that have influenced past monsoon activity in southern Indonesia. Here, we present a ~6000 years high-resolution record of Australian-Indonesian summer monsoon (AISM) rainfall variations based on bulk sediment element analysis in a sediment archive retrieved offshore northwest Sumba Island (Indonesia). The record suggests lower riverine detrital supply and hence weaker AISM rainfall between 6000 yr BP and ~3000 yr BP compared to the Late Holocene. We find a distinct shift in terrigenous sediment supply at around 2800 yr BP indicating a reorganization of the AISM from a drier Mid Holocene to a wetter Late Holocene in southern Indonesia. The abrupt increase in rainfall at around 2800 yr BP coincides with a grand solar minimum. An increase in southern Indonesian rainfall in response to a solar minimum is consistent with climate model simulations that provide a possible explanation of the underlying mechanism responsible for the monsoonal shift. We conclude that variations in solar activity play a significant role in monsoonal rainfall variability at multi-decadal and longer timescales. The combined effect of orbital and solar forcing explains important details in the temporal evolution of AISM rainfall during the last 6000 years. By contrast, we find neither evidence for volcanic forcing of AISM variability nor for a control by long-term variations in the El Niño-Southern Oscillation (ENSO).

Radiocarbon ages, dose rates, water isotopic composition and hydrochemistry of samples from Komakuk Beach and Herschel Island

Terrestrial permafrost archives along the Yukon Coastal Plain (northwest Canada) have recorded landscape development and environmental change since the Late Wisconsinan at the interface of unglaciated Beringia (i.e. Komakuk Beach) and the northwestern limit of the Laurentide Ice Sheet (i.e. Herschel Island). The objective of this paper is to compare the late glacial and Holocene landscape development on both sides of the former ice margin based on permafrost sequences and ground ice. Analyses at these sites involved a multi-proxy approach including: sedimentology, cryostratigraphy, palaeoecology of ostracods, stable water isotopes in ground ice, hydrochemistry, and AMS radiocarbon and infrared stimulated luminescence (IRSL) dating. AMS and IRSL age determinations yielded full glacial ages at Komakuk Beach that is the northeastern limit of ice-free Beringia. Herschel Island to the east marks the Late Wisconsinan limit of the northwest Laurentide Ice Sheet and is composed of ice-thrust sediments containing plant detritus as young as 16.2 cal ka BP that might provide a maximum age on ice arrival. Late Wisconsinan ice wedges with sediment-rich fillings on Herschel Island are depleted in heavy oxygen isotopes (mean d18O of -29.1 per mil); this, together with low d-excess values, indicates colder-than-modern winter temperatures and probably reduced snow depths. Grain-size distribution and fossil ostracod assemblages indicate that deglaciation of the Herschel Island ice-thrust moraine was accompanied by alluvial, proluvial, and eolian sedimentation on the adjacent unglaciated Yukon Coastal Plain until ~11 cal ka BP during a period of low glacio-eustatic sea level. The late glacial-Holocene transition was marked by higher-than-modern summer temperatures leading to permafrost degradation that began no later than 11.2 cal ka BP and caused a regional thaw unconformity. Cryostructures and ice wedges were truncated while organic matter was incorporated and soluble ions were leached in the thaw zone. Thermokarst activity led to the formation of ice-wedge casts and deposition of thermokarst lake sediments. These were subsequently covered by rapidly accumulating peat during the early Holocene Thermal Maximum. A rising permafrost table, reduced peat accumulation, and extensive ice-wedge growth resulted from climate cooling starting in the middle Holocene until the late 20th century. The reconstruction of palaeolandscape dynamics on the Yukon Coastal Plain and the eastern Beringian edge contributes to unraveling the linkages between ice sheet, ocean, and permafrost that have existed since the Late Wisconsinan.

Radionuclides in the water column at stations near the Antarctic Polar Front in the South Atlantic

Vertical profiles of dissolved and particulate 230Th and 231Pa were obtained across the Antarctic Circumpolar Current (ACC) in the southern Atlantic. North of the Polar Front, dissolved and total 230Th increase with depth in conformity with published scavenging models. There is no depletion of 230Th or 231Pa in the water column south of the Polar Front, thought to be an area of enhanced biological productivity. 230Th concentrations increase three-fold to the Weddell Sea across the ACC. Dissolved and total 231Pa concentrations are relatively constant below 500 m depth at about 0.3 dpm m**-3, and change little with depth or latitude. The results from the Weddell Gyre are explained by a mixing-scavenging model that takes into account the input of lower Circumpolar Deep Water through upwelling, which is the main source of water in the Weddell Gyre and is enriched in 230Th but not in 231Pa. 230Th accumulates in the Weddell Gyre as a result of a reduction in the scavenging rate and by ingrowth from 234U. Ingrowth is more significant for 230Th than for 231Pa because the residence time of water in the gyre (about 35 years) is similar to the scavenging residence time of Th in the south Atlantic (29 years) but shorter than that of Pa (120 years). It is argued that changes in 230Th accumulation in the past may reflect changes in water residence time and in the formation rate of Weddell Sea Deep Water.