Milieu-adopted in vitro and in vivo differentiation of mesenchymal tissues derived from different adult human CD34-negative progenitor cell clones

Adult mesenchymal stem cells with multilineage differentiation potentially exist in the bone marrow, but have also been isolated from the peripheral blood. The differentiation of stem cells after leaving their niches depends predominately on the local milieu and its new microenvironment, and is facilitated by soluble factors but also by the close cell-cell interaction in a three-dimensional tissue or organ system. We have isolated CD34-negative, mesenchymal stem cell lines from human bone marrow and peripheral blood and generated monoclonal cell populations after immortalization with the SV40 large T-antigen. The cultivation of those adult stem cell clones in an especially designed in vitro environment, including self-constructed glass capillaries with defined growth conditions, leads to the spontaneous establishment of pleomorphic three-dimensional cell aggregates ( spheroids) from the monoclonal cell population, which consist of cells with an osteoblast phenotype and areas of mineralization along with well-vascularized tissue areas. Modifications of the culture conditions favored areas of bone-like calcifications. After the transplantation of the at least partly mineralized human spheroids into different murine soft tissue sites but also a dorsal skinfold chamber, no further bone formation could be observed, but angiogenesis and neovessel formation prevailed instead, enabling the transplanted cells and cell aggregates to survive. This study provides evidence that even monoclonal adult human CD34-negative stem cells from the bone marrow as well as peripheral blood can potentially differentiate into different mesenchymal tissues depending on the local milieu and responding to the needs within the microenvironment. Copyright (C) 2005 S. Karger AG, Basel

The solar oxygen-isotopic composition: Predictions and implications for solar nebula processes

The outer layers of the Sun are thought to preserve the average isotopic and chemical composition of the solar system. The solar O-isotopic composition is essentially unmeasured, though models based on variations in meteoritic materials yield several predictions. These predictions are reviewed and possible variations on these predictions are explored. In particular, the two-component mixing model of Clayton and Mayeda (1984) (slightly revised here) predicts solar compositions to lie along an extension of the calcium-aluminum-rich inclusion (CAI) ^(16)O line between (δ^(18)O, δ^(17)O) = (16.4, 11.4)%0 and (12.3, 7.5)%0. Consideration of data from ordinary chondrites suggests that the range of predicted solar composition should extend to slightly lower δ^(18)O values. The predicted solar composition is critically sensitive to the solid/gas ratio in the meteorite-forming region, which is often considered to be significantly enriched over solar composition. A factor of two solid/gas enrichment raises the predicted solar (δ^(18)O, δ^(17)O) values along an extension of the CAI ^(16)O line to (33, 28)%0. The model is also sensitive to the nebular O gas phase. If conversion of most of the gaseous O from CO to H_2O occurred at relatively low temperatures and was incomplete at the time of CM aqueous alteration, the predicted nebular gas composition (and hence the solar composition) would be isotopically heavier along a slope 1/2 line. The likelihood of having a single solid nebular O component is discussed. A distribution of initial solid compositions along the CAI ^(16)O line (rather than simply as an end-member) would not significantly change the predictions above in at least one scenario. Even considering these variations within the mixing model, the predicted range of solar compositions is distinct from that expected if the meteoritic variations are due to non-mass-dependent fractionation. Thus, a measurement of the solar O composition to a precision of several permil would clearly distinguish between these theories and should clarify a number of other important issues regarding solar system formation

Global glacier volume projections under high-end climate change scenarios

The Paris agreement aims to hold global warming to well below 2°C and to pursue efforts to limit it to 1.5°C relative to the pre-industrial period. Recent estimates based on population growth and intended carbon emissions from participant countries, suggest global warming may exceed this ambitious target. Here we present glacier volume projections for the end of this century, under a range of high-end climate change scenarios, defined as exceeding +2°C global average warming relative to the preindustrial period. Glacier volume is modelled by developing an elevation-dependent mass balance model for the Joint UK Land Environmental Simulator (JULES). To do this, we modify JULES to include glaciated and un-glaciated surfaces that can exist at multiple heights within a single grid-box. Present day mass balance is calibrated by tuning albedo, wind speed, precipitation and temperature lapse rates to obtain the best agreement with observed mass balance profiles. JULES is forced with an ensemble of six Coupled Model Intercomparison Project Phase 5 (CMIP5) models which were downscaled using the high resolution HadGEM3-A atmosphere only global climate model. The ensemble mean volume loss at the end of the century plus/minus one standard deviation is, minus;64±5% for all glaciers excluding those on the peripheral of the Antarctic ice sheet. The uncertainty in the multi-model mean is rather small and caused by the sensitivity of HadGEM3-A to the boundary conditions supplied by the CMIP5 models. The regions which lose more than 75% of their initial volume by the end of the century are; Alaska, Western Canada and US, Iceland, Scandinavia, Russian Arctic, Central Europe, Caucasus, High Mountain Asia, Low Latitudes, Southern Andes and New Zealand. The ensemble mean ice loss expressed in sea-level equivalent contribution is 215.2±21.3mm. The largest contributors to sea level rise are Alaska (44.6±1.1mm), Arctic Canada North and South (34.9±3.0mm), Russian Arctic (33.3±4.8mm), Greenland (20.1±4.4), High Mountain Asia (combined Central Asia, South Asia East and West), (18.0±0.8mm), Southern Andes (14.4±0.1mm) and Svalbard (17.0±4.6mm). Including parametric uncertainty in the calibrated mass balance parameters, gives an upper bound global volume loss of 247.3mm, sea-level equivalent by the end of the century. Such large ice losses will have inevitable consequences for sea-level rise and for water supply in glacier-fed river systems

CDK-inhibitor independent cell cycle progression in an experimental haematopoietic stem cell leukaemia despite unaltered Rb-phosphorylation

A CD34-negative haematopoietic progenitor cell line, D064, derived from canine bone marrow stromal cells is able to differentiate into haematopoietic progenitors under the influence of growth factor-mediated signalling. While differentiating, these cells eventually start to express MHC class II molecules (DR homologues) on their surface. The stable transfection of the fibroblast-like wild-type cells with retroviral constructs containing the cDNA for the canine MHC class II DR-genes (DRA and DRB) induces a change in morphology, accelerates cell cycle progression and leads to a loss of anchorage-dependent growth. Transfected cells show features of an immature stem cell leukaemia, such as giant cell formation. In wild-type D064 cells the accumulation of the cyclin-dependent kinase inhibitor (cdki) p27kip-1 induces differentiation, which is dependent upon signalling via the ligand for the tyrosine kinase receptor c-kit (stem cell factor). DR-transfected cells instead apparently grow independently of any growth factor-mediated signals and express high levels of the cdkis p27kip-1 and especially p21waf-1/cip-1, concurrently with accelated cell cycle progression. In contrast to the overexpression of cdkis and despite accelerated cell cycle progression, the expression of the G2/M phase transition kinase p34cdc2 is significantly reduced in DR-transfected and transformed cells as compared to the haematopoietic wild-type cell line D064. This might suggest a possible alternative cell cycle progression pathway in this experimental stem cell leukaemia by by-passing the G0/G1 phase arrest, although retinoblastoma (Rb)-phosphorylation remains unaltered. These results provide evidence that mechanisms normally controlling the cell cycle and early haematopoietic differentiation are disrupted by the constitutive transcription and expression of MHC class II genes (DR) leading to a progression and growth of this experimental stem cell leukaemia independent from cell cycle controlling regulators such as p27 and p21. © 1999 Cancer Research Campaig

An Ion Microprobe Study of CAIs from CO3 Meteorites

When attempting to interpret the history of Ca, Al-rich inclusions (CAIs) it is often difficult to distinguish between primary features inherited from the nebula and those produced during secondary processing on the parent body. We have undertaken a systematic study of CAIs from 10 CO chondrites, believed to represent a metamorphic sequence [e.g., 1], with the goal of distinguishing primary and secondary features. ALHA 77307 (3.0), Colony (3.0), Kainsaz (3.1), Felix (3.2), ALH 82101 (3.3), Omans (3.3), Lancé (3.4), ALHA 77003 (3.5), Warrenton (3.6), and Isna (3. 7) were examined by SEM and optical microscopy. We have identified 141 CAIs within these samples, and studied in detail the petrology of 34 inclusions

128Xe and 130Xe: Testing He-shell burning in AGB stars

The s-process branching at 128I has been investigated on the basis of new, precise experimental (n,g) cross sections for the s-only isotopes 128Xe and 130Xe. This branching is unique, since it is essentially determined by the temperature- and density-sensitive stellar decay rates of 128I and only marginally affected by the specific stellar neutron flux. For this reason it represents an important test for He-shell burning in AGB stars. The description of the branching by means of the complex stellar scenario reveals a significant sensitivity to the time scales for convection during He shell flashes, thus providing constraints for this phenomenon. The s-process ratio 128Xe/130Xe deduced from stellar models allows for a (9+-3)% p-process contribution to solar 128Xe, in agreement with the Xe-S component found in meteoritic presolar SiC grains.Comment: 24 pages, 9 figures, accepted for publication in Astophysical Journa

Determining the Elemental and Isotopic Composition of the preSolar Nebula from Genesis Data Analysis: The Case of Oxygen

We compare element and isotopic fractionations measured in solar wind samples collected by NASA's Genesis mission with those predicted from models incorporating both the ponderomotive force in the chromosphere and conservation of the first adiabatic invariant in the low corona. Generally good agreement is found, suggesting that these factors are consistent with the process of solar wind fractionation. Based on bulk wind measurements, we also consider in more detail the isotopic and elemental abundances of O. We find mild support for an O abundance in the range 8.75 - 8.83, with a value as low as 8.69 disfavored. A stronger conclusion must await solar wind regime specific measurements from the Genesis samples.Comment: 6 pages, accepted by Astrophysical Journal Letter

Phase correlation of laser waves with arbitrary frequency spacing

The theoretically predicted correlation of laser phase fluctuations in Lambda-type interaction schemes is experimentally demonstrated. We show, that the mechanism of correlation in a Lambda scheme is restricted to high frequency noise components, whereas in a double-$\Lambda$ scheme, due to the laser phase locking in closed-loop interaction, it extends to all noise frequencies. In this case the correlation is weakly sensitive to coherence losses. Thus the double-Lambda scheme can be used to correlate e.m. fields with carrier frequency differences beyond the GHz regime.Comment: 4 pages, 4 figure