A New Velocity Map for Byrd Glacier, East Antarctica, from Sequential Aster Satellite Imagery

New ice-velocity measurements are obtained for the main trunk of Byrd Glacier, East Antarctica, using recently acquired Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) imagery. The velocities are derived from the application of a cross-correlation technique to sequential images acquired in 2000 and 2001. Images were co-registered and ortho-rectified with the aid of a digital elevation model (DEM) generated from ASTER stereo imagery. This paper outlines the process of DEM generation, image co-registration and correction, and the application of the cross-correlation technique to obtain ice velocities. Comparison of the new velocity map with earlier measurements of velocity from 1978 indicates that the glacier has undergone a substantial deceleration between observations. Portions of the glacier flowing at speeds of similar to 850 m a(-1) in 1978/79 were flowing at similar to 650 m a(-1) in 2000/01. The cause of this change in ice dynamics is not known, but the observation shows that East Antarctic outlet glaciers can undergo substantial changes on relatively short timescales.

The secretome of endothelial progenitor cells promotes brain endothelial cell activity through PI3-kinase and MAP-kinase

BACKGROUND Angiogenesis and vascular remodelling are crucial events in tissue repair mechanisms promoted by cell transplantation. Current evidence underscores the importance of the soluble factors secreted by stem cells in tissue regeneration. In the present study we investigated the effects of paracrine factors derived from cultured endothelial progenitor cells (EPC) on rat brain endothelial cell properties and addressed the signaling pathways involved. METHODS Endothelial cells derived from rat brain (rBCEC4) were incubated with EPC-derived conditioned medium (EPC-CM). The angiogenic response of rBCEC4 to EPC-CM was assessed as effect on cell number, migration and tubular network formation. In addition, we have compared the outcome of the in vitro experiments with the effects on capillary sprouting from rat aortic rings. The specific PI3K/AKT inhibitor LY294002 and the MEK/ERK inhibitor PD98059 were used to study the involvement of these two signaling pathways in the transduction of the angiogenic effects of EPC-CM. RESULTS Viable cell number, migration and tubule network formation were significantly augmented upon incubation with EPC-CM. Similar findings were observed for aortic ring outgrowth with significantly longer sprouts. The EPC-CM-induced activities were significantly reduced by the blockage of the PI3K/AKT and MEK/ERK signaling pathways. Similarly to the outcome of the rBCEC4 experiments, inhibition of the PI3K/AKT and MEK/ERK pathways significantly interfered with capillary sprouting induced by EPC-CM. CONCLUSION The present study demonstrates that EPC-derived paracrine factors substantially promote the angiogenic response of brain microvascular endothelial cells. In addition, our findings identified the PI3K/AKT and MEK/ERK pathways to play a central role in mediating these effects.

Detergent-induced stabilization and improved 3D map of the human heteromeric amino acid transporter 4F2hc-LAT2.

Human heteromeric amino acid transporters (HATs) are membrane protein complexes that facilitate the transport of specific amino acids across cell membranes. Loss of function or overexpression of these transporters is implicated in several human diseases such as renal aminoacidurias and cancer. HATs are composed of two subunits, a heavy and a light subunit, that are covalently connected by a disulphide bridge. Light subunits catalyse amino acid transport and consist of twelve transmembrane α-helix domains. Heavy subunits are type II membrane N-glycoproteins with a large extracellular domain and are involved in the trafficking of the complex to the plasma membrane. Structural information on HATs is scarce because of the difficulty in heterologous overexpression. Recently, we had a major breakthrough with the overexpression of a recombinant HAT, 4F2hc-LAT2, in the methylotrophic yeast Pichia pastoris. Microgram amounts of purified protein made possible the reconstruction of the first 3D map of a human HAT by negative-stain transmission electron microscopy. Here we report the important stabilization of purified human 4F2hc-LAT2 using a combination of two detergents, i.e., n-dodecyl-β-D-maltopyranoside and lauryl maltose neopentyl glycol, and cholesteryl hemisuccinate. The superior quality and stability of purified 4F2hc-LAT2 allowed the measurement of substrate binding by scintillation proximity assay. In addition, an improved 3D map of this HAT could be obtained. The detergent-induced stabilization of the purified human 4F2hc-LAT2 complex presented here paves the way towards its crystallization and structure determination at high-resolution, and thus the elucidation of the working mechanism of this important protein complex at the molecular level.

Complex pelvic traumas: Data linkage of the German Pelvic Injury Register and the TraumaRegister DGU®

BACKGROUND Complex pelvic traumas, i.e., pelvic fractures accompanied by pelvic soft tissue injuries, still have an unacceptably high mortality rate of about 18 %. PATIENTS AND METHODS We retrospectively evaluated an intersection set of data from the TraumaRegister DGU® and the German Pelvic Injury Register from 2004-2009. Patients with complex and noncomplex pelvic traumas were compared regarding their vital parameters, emergency management, stay in the ICU, and outcome. RESULTS From a total of 344 patients with pelvic injuries, 21 % of patients had a complex and 79 % a noncomplex trauma. Complex traumas were significantly less likely to survive (16.7 % vs. 5.9 %). Whereas vital parameters and emergency treatment in the preclinical setting did not differ substantially, patients with complex traumas were more often in shock and showed acute traumatic coagulopathy on hospital arrival, which resulted in more fluid volumes and transfusions when compared to patients with noncomplex traumas. Furthermore, patients with complex traumas had more complications and longer ICU stays. CONCLUSION Prevention of exsanguination and complications like multiple organ dysfunction syndrome still pose a major challenge in the management of complex pelvic traumas.

Map positions of third chromosomal female sterile and lethal mutations of Drosophila melanogaster

Chromosomal mutations induced by ethyl methanesulfonate (EMS) treatment can cause female sterility or maternal-effect lethality in Drosophila. EMS is particularly useful to researchers because it creates mutations independent of position effects. However, because researchers have little control over the chromosomal site of mutation, post-mutagenic genetic mapping is required to determine the cytological location of the mutation. To make a valuable set of mutants more useful to the research community, we have mapped the uncharacterized part of the female-sterile – maternal-effect lethal Tübingen collection. We mapped 49 female-sterile – maternal-effect lethal alleles and 72 lethal alleles to individual deficiency intervals on the third chromosome. In addition, we analyzed the phenotype of ovaries resulting from female sterile mutations. The observed phenotypes range from tumorous ovaries and early blocks in oogenesis, to later blocks, slow growth, blocks in stage 10, to apparently full development of the ovary. The mapping and phenotypic characterization of these 121 mutations provide the necessary information for the researcher to consider a specific mutant as a candidate for their gene of interest.Key words: Drosophila melanogaster, oogenesis, female sterile, maternal-effect lethal, EMS-induced mutations.

Privacy Preserving Probabilistic Record Linkage (P3RL): a novel method for linking existing health-related data and maintaining participant confidentiality.

BACKGROUND Record linkage of existing individual health care data is an efficient way to answer important epidemiological research questions. Reuse of individual health-related data faces several problems: Either a unique personal identifier, like social security number, is not available or non-unique person identifiable information, like names, are privacy protected and cannot be accessed. A solution to protect privacy in probabilistic record linkages is to encrypt these sensitive information. Unfortunately, encrypted hash codes of two names differ completely if the plain names differ only by a single character. Therefore, standard encryption methods cannot be applied. To overcome these challenges, we developed the Privacy Preserving Probabilistic Record Linkage (P3RL) method. METHODS In this Privacy Preserving Probabilistic Record Linkage method we apply a three-party protocol, with two sites collecting individual data and an independent trusted linkage center as the third partner. Our method consists of three main steps: pre-processing, encryption and probabilistic record linkage. Data pre-processing and encryption are done at the sites by local personnel. To guarantee similar quality and format of variables and identical encryption procedure at each site, the linkage center generates semi-automated pre-processing and encryption templates. To retrieve information (i.e. data structure) for the creation of templates without ever accessing plain person identifiable information, we introduced a novel method of data masking. Sensitive string variables are encrypted using Bloom filters, which enables calculation of similarity coefficients. For date variables, we developed special encryption procedures to handle the most common date errors. The linkage center performs probabilistic record linkage with encrypted person identifiable information and plain non-sensitive variables. RESULTS In this paper we describe step by step how to link existing health-related data using encryption methods to preserve privacy of persons in the study. CONCLUSION Privacy Preserving Probabilistic Record linkage expands record linkage facilities in settings where a unique identifier is unavailable and/or regulations restrict access to the non-unique person identifiable information needed to link existing health-related data sets. Automated pre-processing and encryption fully protect sensitive information ensuring participant confidentiality. This method is suitable not just for epidemiological research but also for any setting with similar challenges.

A high-resolution map of direct and indirect connectivity of erosion risk areas to surface waters in Switzerland: A risk assessment tool for planning and policy-making

Off-site effects of soil erosion are becoming increasingly important, particularly the pollution of surface waters. In order to develop environmentally efficient and cost effective mitigation options it is essential to identify areas that bear both a high erosion risk and high connectivity to surface waters. This paper introduces a simple risk assessment tool that allows the delineation of potential critical source areas (CSA) of sediment input into surface waters concerning the agricultural areas of Switzerland. The basis are the erosion risk map with a 2 m resolution (ERM2) and the drainage network, which is extended by drained roads, farm tracks, and slope depressions. The probability of hydrological and sedimentological connectivity is assessed by combining soil erosion risk and extended drainage network with flow distance calculation. A GIS-environment with multiple-flow accumulation algorithms is used for routing runoff generation and flow pathways. The result is a high resolution connectivity map of the agricultural area of Switzerland (888,050 ha). Fifty-five percent of the computed agricultural area is potentially connected with surface waters, 45% is not connected. Surprisingly, the larger part of 34% (62% of the connected area) is indirectly connected with surface waters through drained roads, and only 21% are directly connected. The reason is the topographic complexity and patchiness of the landscape due to a dense road and drainage network. A total of 24% of the connected area and 13% of the computed agricultural area, respectively, are rated with a high connectivity probability. On these CSA an adapted land use is recommended, supported by vegetated buffer strips preventing sediment load. Even areas that are far away from open water bodies can be indirectly connected and need to be included in planning of mitigation measures. Thus, the connectivity map presented is an important decision-making tool for policy-makers and extension services. The map is published on the web and thus available for application.

Thiazolides promote apoptosis in colorectal tumor cells via MAP kinase-induced Bim and Puma activation

While many anticancer therapies aim to target the death of tumor cells, sophisticated resistance mechanisms in the tumor cells prevent cell death induction. In particular enzymes of the glutathion-S-transferase (GST) family represent a well-known detoxification mechanism, which limit the effect of chemotherapeutic drugs in tumor cells. Specifically, GST of the class P1 (GSTP1-1) is overexpressed in colorectal tumor cells and renders them resistant to various drugs. Thus, GSTP1-1 has become an important therapeutic target. We have recently shown that thiazolides, a novel class of anti-infectious drugs, induce apoptosis in colorectal tumor cells in a GSTP1-1-dependent manner, thereby bypassing this GSTP1-1-mediated drug resistance. In this study we investigated in detail the underlying mechanism of thiazolide-induced apoptosis induction in colorectal tumor cells. Thiazolides induce the activation of p38 and Jun kinase, which is required for thiazolide-induced cell death. Activation of these MAP kinases results in increased expression of the pro-apoptotic Bcl-2 homologs Bim and Puma, which inducibly bind and sequester Mcl-1 and Bcl-xL leading to the induction of the mitochondrial apoptosis pathway. Of interest, while an increase in intracellular glutathione levels resulted in increased resistance to cisplatin, it sensitized colorectal tumor cells to thiazolide-induced apoptosis by promoting increased Jun kinase activation and Bim induction. Thus, thiazolides may represent an interesting novel class of anti-tumor agents by specifically targeting tumor resistance mechanisms, such as GSTP1-1.

A 4,103 marker integrated physical and comparative map of the horse genome

A comprehensive second-generation whole genome radiation hybrid (RH II), cytogenetic and comparative map of the horse genome (2n = 64) has been developed using the 5000rad horse x hamster radiation hybrid panel and fluorescence in situ hybridization (FISH). The map contains 4,103 markers (3,816 RH; 1,144 FISH) assigned to all 31 pairs of autosomes and the X chromosome. The RH maps of individual chromosomes are anchored and oriented using 857 cytogenetic markers. The overall resolution of the map is one marker per 775 kilobase pairs (kb), which represents a more than five-fold improvement over the first-generation map. The RH II incorporates 920 markers shared jointly with the two recently reported meiotic maps. Consequently the two maps were aligned with the RH II maps of individual autosomes and the X chromosome. Additionally, a comparative map of the horse genome was generated by connecting 1,904 loci on the horse map with genome sequences available for eight diverse vertebrates to highlight regions of evolutionarily conserved syntenies, linkages, and chromosomal breakpoints. The integrated map thus obtained presents the most comprehensive information on the physical and comparative organization of the equine genome and will assist future assemblies of whole genome BAC fingerprint maps and the genome sequence. It will also serve as a tool to identify genes governing health, disease and performance traits in horses and assist us in understanding the evolution of the equine genome in relation to other species.

A comparative radiation hybrid map of sheep chromosome 10

Comparative radiation hybrid (RH) maps of individual ovine chromosomes are essential to identify genes governing traits of economic importance in sheep, a livestock species for which whole genome sequence data are not yet available. The USUoRH5000 radiation hybrid panel was used to generate a RH map of sheep chromosome 10 (OAR10) with 59 markers that span 1,422 cR over an estimated 92 Mb of the chromosome, thus providing markers every 2 Mb (equivalent to every 24 cR). The markers were derived from 46 BAC end sequences (BESs), a single EST, and 12 microsatellites. Comparative analysis showed that OAR10 shares remarkable conservation of gene order along the entire length of cattle chromosome 12 and that OAR10 contains four major homologous synteny blocks, each related to segments of the homologous human chromosome 13. Extending the comparison to the horse, dog, mouse, and chicken genome showed that these blocks share conserved synteny across species.