Evidence for recombinant GRP78, CALR, PDIA3 and GPI as mediators of genetic instability in human CD34+ cells

Soluble factors released from irradiated human mesenchymal stromal cells (MSC) may induce genetic instability in human CD34+ cells, potentially mediating hematologic disorders. Recently, we identified four key proteins in the secretome of X-ray-irradiated MSC, among them three endoplasmic reticulum proteins, the 78 kDa glucose-related protein (GRP78), calreticulin (CALR), and protein disulfide-isomerase A3 (PDIA3), as well as the glycolytic enzyme glucose-6-phosphate isomerase (GPI). Here, we demonstrate that exposition of CD34+ cells to recombinant GRP78, CALR, PDIA3 and GPI induces substantial genetic instability. Increased numbers of γH2AX foci (p < 0.0001), centrosome anomalies (p = 0.1000) and aberrant metaphases (p = 0.0022) were detected in CD34+ cells upon incubation with these factors. Specifically, γH2AX foci were found to be induced 4–5-fold in response to any individual of the four factors, and centrosome anomalies by 3–4 fold compared to control medium, which contained none of the recombinant proteins. Aberrant metaphases, not seen in the context of control medium, were detected to a similar extent than centrosome anomalies across the four factors. Notably, the strongest effects were observed when all four factors were collectively provided. In summary, our data suggest that specific components of the secretome from irradiated MSC act as mediators of genetic instability in CD34+ cells, thereby possibly contributing to the pathogenesis of radiation-induced hematologic disorders beyond direct radiation-evoked DNA strand breaks

Pacific offshore record of plinian arc volcanism in Central America: 1. Along-arc correlations

We collected 56 marine gravity cores from the Pacific seafloor offshore Central America which contain a total of 213 volcanic ash beds. Ash-layer correlations between cores and with their parental tephras on land use stratigraphic, lithologic, and compositional criteria. In particular, we make use of our newly built database of bulk-rock, mineral, and glass major and trace element compositions of plinian and similarly widespread tephras erupted since the Pleistocene along the Central American Volcanic Arc. We thus identify the distal ashes of 11 Nicaraguan, 8 El Salvadorian, 6 Guatemalan, and 1 Costa Rican eruptions. Relatively uniform pelagic sedimentation rates allow us to determine ages of 10 previously undated tephras by their relative position between ash layers of known age. Linking the marine and terrestrial records yields a tephrostratigraphic framework for the Central American volcanic arc from Costa Rica to Guatemala. This is a useful tool and prerequisite to understand the evolution of volcanism at a whole-arc scale

Detection of Aspergillus DNA in Cerebrospinal Fluid from Patients with Cerebral Aspergillosis by a Nested PCR Assay

Invasive aspergillosis (IA), a complication with high mortality rates, especially in disseminated IA with cerebral involvement, is difficult to diagnose. Biopsy of cerebral lesions is often not feasible, and culture of Aspergillus spp. from cerebrospinal fluid (CSF) is frequently negative. New molecular methods have emerged for diagnosing IA. So far, there are only few reports of Aspergillus DNA detection in CSF. After modifying the DNA extraction protocol, we detected Aspergillus DNA in CSF samples by a previously described nested PCR assay. In six patients with hematologic malignancy and cerebral aspergillosis, CSF samples were investigated for Aspergillus DNA. IA was classified according to the EORTC/MSG 2002 criteria. Two patients each had proven, probable, and possible IA. Thirty-five CSF samples were investigated for Aspergillus DNA by nested PCR. Samples with positive results in the nested PCR assay were quantified by LightCycler PCR assay. Fourteen CSF samples showed positive results in the nested PCR assay. Of these, six samples gave positive results in real-time PCR. The range of CFU per ml was 2,154 to 63,100,000. The highest number of CFU per ml was found in a CSF sample of a patient with acute lymphocytic leukemia and probable cerebral aspergillosis. Detection of Aspergillus DNA in CSF samples is thus possible and has the potential to improve diagnosis of cerebral aspergillosis. Further prospective studies with larger numbers of patients must be performed to evaluate the clinical significance of Aspergillus PCR with CSF samples

Record of anthropogenic impact on the Western Irish Sea mud belt

Six cores, geophysical data (multibeam bathymetry), surface grab samples and video photography were collected from the area of the Western Irish Sea Mud Belt (WISMB). These data were analysed to determine the radionuclide input from the Sellafield nuclear facility on the eastern (UK) seaboard of the Irish Sea, and subsequently to assess the influence of bottom trawling and bioturbation on the surface and near-surface sediments. Results show significant changes in the sedimentation and geochemical regime in the WISMB due to anthropogenic causes (bottom trawling and radionuclides derived from the power plant). These changes are consistent with the concept of the Anthropocene time period. Levels of anthropogenic radionuclides measured in two of the cores enabled construction of a chronology correlated with recorded values of discharge from the Sellafield facility. Excess 210Pb and the anthropogenic radionuclide 137Cs proved useful as stratigraphic marker tools. These radionuclide data also enabled quantification of the effects of trawling, which was visible on acoustic seabed maps. Bottom trawling has removed an estimated 20–50 cm of the upper seabed

Solitonic supercontinuum of femtosecond mid-IR pulses in W-type index tellurite fibers with two zero dispersion wavelengths

We present a detailed experimental parameter study on mid-IR supercontinuum generation in W-type index tellurite fibers, which reveals how the core diameter, pump wavelength, fiber length, and pump power dramatically influence the spectral broadening. As pump source, we use femtosecond mid-IR pulses from a post-amplified optical parametric oscillator tunable between 1.7 μm and 4.1 μm at 43 MHz repetition rate. We are able to generate red-shifted dispersive waves up to a wavelength of 5.1 μm by pumping a tellurite fiber in the anomalous dispersion regime between its two zero dispersion wavelengths. Distinctive soliton dynamics can be identified as the main broadening mechanism resulting in a maximum spectral width of over 2000 nm with output powers of up to 160 mW. We experimentally demonstrated that efficient spectral broadening with considerably improved power proportion in the important first atmospheric transmission window between 3 and 5 μm can be achieved in robust W-type tellurite fibers pumped at long wavelengths by ultra-fast lasers

First Results of the Geotechnical In Situ Investigation for Soil Characterisation Along the Upper Slope Off Vesterålen: Northern Norway

High-resolution geophysical data reveal the presence of several spatially-isolated, small-scale landslides along the gently dipping (~3–4°) upper slope off Vesterålen, Northern Norway. Dynamic slope stability analysis suggests that seismicity may be largely responsible for the occurrence of these slope failures. The landslides are clustered in two groups, with one group of parallel features with their headwalls in ~500 m water depths. The second group is found in ~800 m water depths. We present first results of geotechnical in situ Cone Penetration Test (CPTU) data and TOPAS sub-bottom profiles collected during two cruises in summer 2013/2014. We obtained a total of six static CPTU profiles penetrating the top 20 m of soil. Three of these were taken across one of the landslide complexes (SL3) from the slide scar down to the depositional area. The other three are reference sites in the adjacent undisturbed areas. The combination of geophysical and geotechnical data allows us to divide the well-stratified glacio-marine slope deposits into three different sediment-mechanical units, and reveals the occurrence of mechanically weaker zones (MWZ). These zones are interbedded by coarser layers with high values of cone tip resistance. The occurrence of sensitive fine-grained material may be responsible for the loss of strength in the deeper portion. One-dimensional pseudo-static stability analysis attests that the Vesterålen slope is stable except for exceptionally large earthquakes, that induce a peak-ground acceleration (PGA) of 0.224 g or larger to the MWZ. The depth levels of the MWZ correspond well with the slide planes of the landslides

Integration of very-high-resolution seismic and CPTU data from a coastal area affected by shallow landsliding: The finneidfjord natural laboratory

In 1996, a retrogressive landslide claimed four lives near the village of Finneidfjord, northern Norway. Since then, the area has been developed into a prime natural field laboratory for investigating submarine slope instabilities. Research activities adopt an integrated approach inwhichwe aim to characterize the slip planes involved in the landsliding and understanding the sedimentary processes contributing to failure, including human activity (e.g., road works), the presence of quick clay deposits in the near-shore area as well as shallow gas accumulations in the fjord. In this paper, we focus on the spatial variability of soil conditions in general and the slip plane in particular as evidenced from different vintages of seismic data (very-high-resolution 3D chirp data and multi-channel sparker and boomer data) tied with soil samples and 1D in situ geotechnical logs (CPTU) across the landslide complex and shallow gas accumulation zone. The slip planes correspond to composite, thin event beds characterized by subtle variations in lithology. These event beds demonstrate a laterally variable character across the landslide complex, both in the seismic data and particularly in the CPTU response. Through impedance inversion and modelling and using the geological and geotechnical data as calibration, we have developed methods to derive geotechnical properties (e.g., partial gas saturation, lithology, density) from the seismic data. The integrated approach can be used to investigate similar landslides in coastal areas