Placental transfer of parathyroid hormone

Peer Reviewe

Non-Invasive In Vivo Imaging of Tumor-Associated CD133/Prominin

detection of cancer stem cells is of great importance. detection of CD133/prominin, a cancer stem cell surface marker for a variety of tumor entities. The CD133-specific monoclonal antibody AC133.1 was used for quantitative fluorescence-based optical imaging of mouse xenograft models based on isogenic pairs of CD133 positive and negative cell lines. A first set consisted of wild-type U251 glioblastoma cells, which do not express CD133, and lentivirally transduced CD133-overexpressing U251 cells. A second set made use of HCT116 colon carcinoma cells, which uniformly express CD133 at levels comparable to primary glioblastoma stem cells, and a CD133-negative HCT116 derivative. Not surprisingly, visualization and quantification of CD133 in overexpressing U251 xenografts was successful; more importantly, however, significant differences were also found in matched HCT116 xenograft pairs, despite the lower CD133 expression levels. The binding of i.v.-injected AC133.1 antibodies to CD133 positive, but not negative, tumor cells isolated from xenografts was confirmed by flow cytometry. imaging of tumor-associated CD133 is feasible and that CD133 antibody-based tumor targeting is efficient. This should facilitate developing clinically applicable cancer stem cell imaging methods and CD133 antibody-based therapeutics

Neotectonics of the Owen Fracture Zone (NW Indian Ocean): structural evolution of an oceanic strike-slip plate boundary

International audienceThe Owen Fracture Zone is a 800 km-long fault system that accommodates the dextral strike-slip motion between India and Arabia plates. Because of slow pelagic sedimentation rates that preserve the seafloor expression of the fault since the Early Pliocene, the fault is clearly observed on bathymetric data. It is made up of a series of fault segments separated by releasing and restraining bends, including a major pull-apart basin at latitude 20°N. Some distal turbiditic channels from the Indus deep-sea fan overlap the fault system and are disturbed by its activity, thus providing landmarks to date successive stages of fault activity and structural evolution of the Owen Fracture Zone from Pliocene to Present. We determine the durability of relay structures and the timing of their evolution along the principal displacement zone, from their inception to their extinction. We observe subsidence migration in the 20°N basin, and alternate activation of fault splays in the vicinity of the Qalhat seamount. The present-day Owen Fracture Zone is the latest stage of structural evolution of the 20-Myr-old strike-slip fault system buried under Indus turbiditic deposits whose activity started at the eastern foot of the Owen Ridge when the Gulf of Aden opened. The evolution of the Owen Fracture Zone since 3-6 Myr reflects a steady state plate motion between Arabia and India, such as inferred by kinematics for the last 20 Myr period. The structural evolution of the Owen Fracture Zone since 20 Myr- including fault segments propagation and migration, pull-apart basin opening and extinction - seems to be characterized by a progressive reorganisation of the fault system, and does not require any major kinematics change

Gene Expression Profiling in Cells with Enhanced γ-Secretase Activity

BACKGROUND: Processing by gamma-secretase of many type-I membrane protein substrates triggers signaling cascades by releasing intracellular domains (ICDs) that, following nuclear translocation, modulate the transcription of different genes regulating a diverse array of cellular and biological processes. Because the list of gamma-secretase substrates is growing quickly and this enzyme is a cancer and Alzheimer's disease therapeutic target, the mapping of gamma-secretase activity susceptible gene transcription is important for sharpening our view of specific affected genes, molecular functions and biological pathways. METHODOLOGY/PRINCIPAL FINDINGS: To identify genes and molecular functions transcriptionally affected by gamma-secretase activity, the cellular transcriptomes of Chinese hamster ovary (CHO) cells with enhanced and inhibited gamma-secretase activity were analyzed and compared by cDNA microarray. The functional clustering by FatiGO of the 1,981 identified genes revealed over- and under-represented groups with multiple activities and functions. Single genes with the most pronounced transcriptional susceptibility to gamma-secretase activity were evaluated by real-time PCR. Among the 21 validated genes, the strikingly decreased transcription of PTPRG and AMN1 and increased transcription of UPP1 potentially support data on cell cycle disturbances relevant to cancer, stem cell and neurodegenerative diseases' research. The mapping of interactions of proteins encoded by the validated genes exclusively relied on evidence-based data and revealed broad effects on Wnt pathway members, including WNT3A and DVL3. Intriguingly, the transcription of TERA, a gene of unknown function, is affected by gamma-secretase activity and was significantly altered in the analyzed human Alzheimer's disease brain cortices. CONCLUSIONS/SIGNIFICANCE: Investigating the effects of gamma-secretase activity on gene transcription has revealed several affected clusters of molecular functions and, more specifically, 21 genes that hold significant potential for a better understanding of the biology of gamma-secretase and its roles in cancer and Alzheimer's disease pathology

Problem-based collaborative learning with virtual patients in pediatrics: a practical example

The peadiatric curricula at the Charité have developed a number of changes in the recent years due to the introduction of the new licensing rules in 2004 and the development of two new curricula - the traditional curriculum and the reformed medical track. The teaching was focused on bedside teaching in the traditional curriculum, therefore different didac-tic, pedagogic and infrastructural needs were identified. The federally funded project ELWIS-MED developed e-Learning at the Charité technically and infrastructurally that a curricular implementation into regular teaching units could be evaluated. Bedside teaching was supplemented online by virtual teaching cases (patients). Students had to discuss clinical problems online with their pediatric tutors. First experiences with the new concept show that best practices were applied to online discussion by teachers and students. Further studies should evaluate the effect on knowledge acquisition by students using this learning method. Opportunities to foster participation in online discussion should be developed.Der studentische Unterricht in der Kinderheilkunde an der Charité hat seit 1999 mehrere Umstrukturierungen durchlaufen. Mit der Einführung der neuen ärztlichen Approbationsordnung 2004 im Regelstudiengang (RSG) und dem Modellcurriculum Reformstudiengang Medizin (RSM) 1999 müssen zwei Curricula parallel neu konzipiert und gepflegt werden. Durch den Schwerpunkt Unterricht am Krankenbett (UaK) im RSG ergaben sich neue didaktische, pädagogische und infrastrukturelle Anforderungen. Die technische und inhaltliche Weiterentwicklung der Einsatzmöglichkeiten elektronischer Lernszenarien durch e-Learning im Rahmen des BMBF-geförderten Projektes ELWIS-MED, ermöglichte die Erprobung der curricularen Implementierung von e-Learning-Modulen im Pflichtunterricht. Der UaK wurde durch die Bearbeitung kinderheilkundlicher elektronischer Lernfälle online ergänzt. Die Studierenden sollten tutoriell betreute Diskussionen zu fachlichen Aufgabenstellungen online führen. In der ersten Erprobungsstufe wurde der Einsatz der Diskussionsforen in Verbindung mit den Lernfällen von den Studierenden und Lehrenden als sinnvolle Ergänzung betrachtet. In zukünftigen Einsatzszenarien sollte eine Messung des studentischen Lernerfolgs mit dieser Methode erfolgen