GFZ Underground Laboratory in the Research and Education Mine “Reiche Zeche” Freiberg

The GFZ Underground Laboratory is operated by the Helmholtz Centre Potsdam GFZ German Research Centre for Geosciences. It is located in the research and education mine “Reiche Zeche” in Freiberg, Germany allows testing of geophysical and geotechnical tools and methods in boreholes and galleries. The lab is ideally suited for seismic system components such as receivers and sources for three-dimensional high resolution seismic imaging and tomography surveying. The lab layout of a basement rock block surrounded by galleries around a vertical as well as two horizontal boreholes enables the realization of various underground survey geometries e.g. well-to-well and well-to-gallery. The galleries are equipped with thirty 3-component geophone anchors installed in 1 m and 2 m depths for tomographic measurements or the recording of radiation pattern of seismic borehole sources

Erythropoetin und die Rolle von Sauerstoff bei der Proliferation und Differenzierung der humanen mesenzephalen Progenitorzellen ReNcell VM

Im Rahmen der Dissertation wurde die Interaktion von Hypoxie und EPO und deren Effekte auf die Proliferation und Differenzierung von human neuronalen Progenitorzellen untersucht. Weiterhin wurden die Effekte des als neuroprotektiv beschriebenen CEPO analysiert. Insbesondere die Proliferationsrate, der Zellzyklus, die neuronale Differenzierung sowie die metabolische Aktivität unter verschiedenen Kulturbedingungen wurden untersucht. Hypoxie führte in vitro zu einer verstärkten neuronalen Differenzierung, zum Teil wurde dies durch die Applikation von EPO unter normoxischen Bedingungen imitiert

Die chinesische Führung bekräftigt ihren Kurs

"Vom 5. bis 16. März 2007 tagte in Beijing der 10. Nationale Volkskongress (NVK). Internationale Aufmerksamkeit erregte vor allem die Verabschiedung eines Gesetzes zum Schutz privaten Eigentums. Die NVK-Tagung machte als letzte große Tagung vor dem voraussichtlich Ende September stattfindenden 17. Parteitag der KP Chinas die Prioritäten der gegenwärtigen Partei- und Staatsführung deutlich und kann damit auch als Indikator für den Stand intraelitärer Debatten um politische Schwerpunktsetzungen und Richtungsentscheidungen gelten. Die Agenda und die Beschlüsse der diesjährigen NVK-Tagung entsprechen der seit 2002 erarbeiteten Entwicklungskonzeption der 'harmonischen sozialistischen Gesellschaft'. Im ideologischen Richtungsstreit um die Fortführung des Reformkurses mit liberalen und konservativen Kritikern gelang der Führungsspitze ein Durchbruch. Mit einer Bestätigung ihrer Reformpolitik ist somit auch auf dem Parteitag zu rechnen. Mit der Ratifizierung des Gesetzes zum Schutz privater Eigentumsrechte setzte sich die Führung um Partei- und Staatschef Hu Jintao und Ministerpräsident Wen Jiabao gegen Kritiker durch und bekräftigte, dass sie ihren marktorientierten Reformkurs fortführen werde. Von der neuen Gesetzgebung werden insbesondere Unternehmer und die entstehende Mittelklasse profitieren. Die Partei- und Staatsführung ist sich deutlich bewusst, dass sie zur eigenen Absicherung die Vergrößerung der Kluft zwischen Stadt und Land und das Anwachsen sozialer Widersprüche stoppen muss. Ob ihr dies allerdings gelingen wird, ist zweifelhaft. Andererseits hat sie nach der Öffnung der KP-Mitgliedschaft für Privatunternehmer ihre Mittelstandsorientierung eindringlich unterstrichen." (Autorenreferat

Erythropoietin and the effect of oxygen during proliferation and differentiation of human neural progenitor cells

<p>Abstract</p> <p>Background</p> <p>Hypoxia plays a critical role in various cellular mechanisms, including proliferation and differentiation of neural stem and progenitor cells. In the present study, we explored the impact of lowered oxygen on the differentiation potential of human neural progenitor cells, and the role of erythropoietin in the differentiation process.</p> <p>Results</p> <p>In this study we demonstrate that differentiation of human fetal neural progenitor cells under hypoxic conditions results in an increased neurogenesis. In addition, expansion and proliferation under lowered oxygen conditions also increased neuronal differentiation, although proliferation rates were not altered compared to normoxic conditions. Erythropoietin partially mimicked these hypoxic effects, as shown by an increase of the metabolic activity during differentiation and protection of differentiated cells from apoptosis.</p> <p>Conclusion</p> <p>These results provide evidence that hypoxia promotes the differentiation of human fetal neural progenitor cells, and identifies the involvement of erythropoietin during differentiation as well as different cellular mechanisms underlying the induction of differentiation mediated by lowered oxygen levels.</p

Spatial Signature of White Matter Hyperintensities in Stroke Patients

Purpose: White matter hyperintensity (WMH) is a common phenotype across a variety of neurological diseases, particularly prevalent in stroke patients; however, vascular territory dependent variation in WMH burden has not yet been identified. Here, we sought to investigate the spatial specificity of WMH burden in patients with acute ischemic stroke (AIS).Materials and Methods: We created a novel age-appropriate high-resolution brain template and anatomically delineated the cerebral vascular territories. We used WMH masks derived from the clinical T2 Fluid Attenuated Inverse Recovery (FLAIR) MRI scans and spatial normalization of the template to discriminate between WMH volume within each subject's anterior cerebral artery (ACA), middle cerebral artery (MCA), and posterior cerebral artery (PCA) territories. Linear regression modeling including age, sex, common vascular risk factors, and TOAST stroke subtypes was used to assess for spatial specificity of WMH volume (WMHv) in a cohort of 882 AIS patients.Results: Mean age of this cohort was 65.23 ± 14.79 years, 61.7% were male, 63.6% were hypertensive, 35.8% never smoked. Mean WMHv was 11.58c ± 13.49 cc. There were significant differences in territory-specific, relative to global, WMH burden. In contrast to PCA territory, age (0.018 ± 0.002, p &lt; 0.001) and small-vessel stroke subtype (0.212 ± 0.098, p &lt; 0.001) were associated with relative increase of WMH burden within the anterior (ACA and MCA) territories, whereas male sex (−0.275 ± 0.067, p &lt; 0.001) was associated with a relative decrease in WMHv.Conclusions: Our data establish the spatial specificity of WMH distribution in relation to vascular territory and risk factor exposure in AIS patients and offer new insights into the underlying pathology

A novel, highly sensitive and specific biomarker for Niemann-Pick type C1 disease

Background Lysosomal storage disorders (LSDs), are a heterogeneous group of rare disorders caused by defects in genes encoding for proteins involved in the lysosomal degradation of macromolecules. They occur at a frequency of about 1 in 5,000 live births, though recent neonatal screening suggests a higher incidence. New treatment options for LSDs demand a rapid, early diagnosis of LSDs if maximal clinical benefit is to be achieved. Methods Here, we describe a novel, highly specific and sensitive biomarker for Niemann-Pick Type C disease type 1 (NPC1), lyso-sphingomyelin-509. We cross-validate this biomarker with cholestane-3β,5α,6β-triol and relative lysosomal volume. The primary cohort for establishment of the biomarker contained 135 NPC1 patients, 66 NPC1 carriers, 241 patients with other LSDs and 46 healthy controls. Results With a sensitivity of 100.0% and specificity of 91.0% a cut-off of 1.4 ng/ml was established. Comparison with cholestane-3β,5α,6β-triol and relative acidic compartment volume measurements were carried out with a subset of 125 subjects. Both cholestane-3β,5α,6β-triol and lyso-Sphingomyelin-509 were sufficient in establishing the diagnosis of NPC1 and correlated with disease severity. Conclusion In summary, we have established a new biomarker for the diagnosis of NPC1, and further studies will be conducted to assess correlation to disease progress and monitoring treatment

Glucosylsphingosine Is a Highly Sensitive and Specific Biomarker for Primary Diagnostic and Follow-Up Monitoring in Gaucher Disease in a Non-Jewish, Caucasian Cohort of Gaucher Disease Patients

Gaucher disease (GD) is the most common lysosomal storage disorder (LSD). Based on a deficient β-glucocerebrosidase it leads to an accumulation of glucosylceramide. Standard diagnostic procedures include measurement of enzyme activity, genetic testing as well as analysis of chitotriosidase and CCL18/PARC as biomarkers. Even though chitotriosidase is the most well-established biomarker in GD, it is not specific for GD. Furthermore, it may be false negative in a significant percentage of GD patients due to mutation. Additionally, chitotriosidase reflects the changes in the course of the disease belatedly. This further enhances the need for a reliable biomarker, especially for the monitoring of the disease and the impact of potential treatments.Here, we evaluated the sensitivity and specificity of the previously reported biomarker Glucosylsphingosine with regard to different control groups (healthy control vs. GD carriers vs. other LSDs).Only GD patients displayed elevated levels of Glucosylsphingosine higher than 12 ng/ml whereas the comparison controls groups revealed concentrations below the pathological cut-off, verifying the specificity of Glucosylsphingosine as a biomarker for GD. In addition, we evaluated the biomarker before and during enzyme replacement therapy (ERT) in 19 patients, demonstrating a decrease in Glucosylsphingosine over time with the most pronounced reduction within the first 6 months of ERT. Furthermore, our data reveals a correlation between the medical consequence of specific mutations and Glucosylsphingosine.In summary, Glucosylsphingosine is a very promising, reliable and specific biomarker for GD

Towards a 21st-century roadmap for biomedical research and drug discovery:consensus report and recommendations

Decades of costly failures in translating drug candidates from preclinical disease models to human therapeutic use warrant reconsideration of the priority placed on animal models in biomedical research. Following an international workshop attended by experts from academia, government institutions, research funding bodies, and the corporate and nongovernmental organisation (NGO) sectors, in this consensus report, we analyse, as case studies, five disease areas with major unmet needs for new treatments. In view of the scientifically driven transition towards a human pathway-based paradigm in toxicology, a similar paradigm shift appears to be justified in biomedical research. There is a pressing need for an approach that strategically implements advanced, human biology-based models and tools to understand disease pathways at multiple biological scales. We present recommendations to help achieve this

Environmental considerations and current status of grouping and regulation of engineered nanomaterials

This article reviews the current status of nanotechnology with emphasis on application and related environmental considerations as well as legislation. Application and analysis of nanomaterials in infrastructure (construction, building coatings, and water treatment) is discussed, and in particular nanomaterial release during the lifecycle of these applications. Moreover, possible grouping approaches with regard to ecotoxicological and toxicological properties, and the fate of nanomaterials in the environment are evaluated. In terms of potential exposure, the opportunities that arise from leveraging advances in several key areas, such as water treatment and construction are addressed. Additionally, this review describes challenges with regard to the European Commission’s definition of ‘nanomaterial’. The revised REACH information requirements, intended to enable a comprehensive risk assessment of nanomaterials, are outlined

Acute Cerebrovascular Disease in the Young The Stroke in Young Fabry Patients Study

Background and Purpose-Strokes have especially devastating implications if they occur early in life; however, only limited information exists on the characteristics of acute cerebrovascular disease in young adults. Although risk factors and manifestation of atherosclerosis are commonly associated with stroke in the elderly, recent data suggests different causes for stroke in the young. We initiated the prospective, multinational European study Stroke in Young Fabry Patients (sifap) to characterize a cohort of young stroke patients. Methods-Overall, 5023 patients aged 18 to 55 years with the diagnosis of ischemic stroke (3396), hemorrhagic stroke (271), transient ischemic attack (1071) were enrolled in 15 European countries and 47 centers between April 2007 and January 2010 undergoing a detailed, standardized, clinical, laboratory, and radiological protocol. Results-Median age in the overall cohort was 46 years. Definite Fabry disease was diagnosed in 0.5% (95% confidence interval, 0.4%-0.8%; n=27) of all patients; and probable Fabry disease in additional 18 patients. Males dominated the study population (2962/59%) whereas females outnumbered men (65.3%) among the youngest patients (18-24 years). About 80.5% of the patients had a first stroke. Silent infarcts on magnetic resonance imaging were seen in 20% of patients with a first-ever stroke, and in 11.4% of patients with transient ischemic attack and no history of a previous cerebrovascular event. The most common causes of ischemic stroke were large artery atherosclerosis (18.6%) and dissection (9.9%). Conclusions-Definite Fabry disease occurs in 0.5% and probable Fabry disease in further 0.4% of young stroke patients. Silent infarcts, white matter intensities, and classical risk factors were highly prevalent, emphasizing the need for new early preventive strategies