Determination of fetal chromosome aberrations from fetal DNA in maternal blood: has the challenge finally been met?

The analysis of cell-free fetal nucleic acids in maternal blood for prenatal diagnosis has been transformed by several recent profound technology developments. The most noteworthy of these are ‘digital PCR' and ‘next-generation sequencing' (NGS), which might finally deliver the long-sought goal of noninvasive detection of fetal aneuploidy. Recent data, however, indicate that NGS might even be able to offer a much more detailed appraisal of the fetal genome, including paternal and maternal inheritance of point mutations for mendelian disorders such as β-thalassaemia. Although these developments are very exciting, in their current form they are still too complex and costly, and will need to be simplified considerably for their optimal translation to the clinic. In this regard, targeted NGS does appear to be a step in the right direction, although this should be seen in the context of ongoing progress with the isolation of fetal cells and with proteomic screening marker

Enthusiasmus, der Berge versetzt? Die polnische EU-Ratspräsidentschaft 2011

Der Krisengipfel der EU-Staats- und Regierungschefs am 21. Juli war auch eine erste Bewährungsprobe für die polnische Ratspräsidentschaft. Polen will die finanzpolitischen Probleme durch eine Stärkung der Union lösen, mit seiner proeuropäischen Haltung die EU-Kollegen mitreißen und zudem eigene Akzente setzen. Irene Hahn und Anna Quirin werfen einen Blick auf die ambitionierte Agenda Warschaus und weisen auf die Herausforderungen hin, die sich bei der Umsetzung ergeben

Zivilgesellschaftliches Forum der Östlichen Partnerschaft: Wichtiges Instrument mit ambivalenter Zwischenbilanz

300 Vertreter der Zivilgesellschaft kamen Ende November 2012 zum vierten Zivilgesellschaftlichen Forum zusammen. Von autoritären Regierungen für überflüssig erklärt, und mit strukturellen Defiziten, kann das Forum nicht als etabliert gelten. Ihm den Stempel "gescheitert" aufzudrücken wäre allerdings fahrlässig. Das Forum leistet einen entscheidenden Beitrag zur politischen Willensbildung in den östlichen EU-Nachbarländern. Für die EU lohnt es sich, dies als langfristigen Prozess zu unterstützen

Reale Gefahr oder Scheindebatte? Zum Wirklichkeitsgehalt eines drohenden Polexit

Seit der Auseinandersetzung um die Entscheidung des polnischen Verfassungstribunals zum Vorrang polnischen Rechts über EU-Recht im Oktober 2021 wird sowohl innerhalb als auch außerhalb Polens verstärkt über die mögliche Gefahr eines Austritts unseres Nachbarlands aus der EU spekuliert. Nach Jahren der Auseinandersetzung mit EU-Kommission, EU-Parlament und Europäischem Gerichtshof stellt das kompromisslose Auftreten der polnischen Regierung die Institutionen und Partnerstaaten vor die Herausforderung, wie in den Fragen um Gewaltenteilung und unabhängige Justiz mit ihrem östlichen Mitgliedsstaat weiter umgegangen werden sollte. Auch die Bundesregierung ist konkret gefordert, die in der Ära Merkel verfolgte Politik der vorsichtigen Beschwichtigung grundlegend zu überdenken. Dafür ist aber zunächst einmal zu klären, welche Interessen hinter den unterschiedlichen Argumentationslinien im Diskurs der verschiedenen polnischen Parteien und Akteure liegen, wenn sie mit dem politischen Kampfbegriff »Polexit« hantieren

Quantitative Proteomic (iTRAQ) Analysis of 1st Trimester Maternal Plasma Samples in Pregnancies at Risk for Preeclampsia

A current major obstacle is that no reliable screening markers exist to detect pregnancies at risk for preeclampsia. Quantitative proteomic analysis employing isobaric labelling (iTRAQ) has been suggested to be suitable for the detection of potential plasma biomarkers, a feature we recently verified in analysis of pregnancies with Down syndrome foetuses. We have now examined whether this approach could yield biomarkers to screen pregnancies at risk for preeclampsia. In our study, we used maternal plasma samples obtained at 12 weeks of gestation, six from women who subsequently developed preeclampsia and six with uncomplicated deliveries. In our analysis, we observed elevations in 10 proteins out of 64 proteins in the preeclampsia study group when compared to the healthy control group. These proteins included clusterin, fibrinogen, fibronectin, and angiotensinogen, increased levels of which are known to be associated with preeclampsia. An elevation in the immune-modulatory molecule, galectin 3 binding protein, was also noted. Our pilot study, therefore, indicates that quantitative proteomic iTRAQ analysis could be a useful tool for the detection of new preeclampsia screening markers

Recording visual evoked potentials and auditory evoked P300 at 9.4T static magnetic field.

peer reviewedSimultaneous recording of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) has shown a number of advantages that make this multimodal technique superior to fMRI alone. The feasibility of recording EEG at ultra-high static magnetic field up to 9.4 T was recently demonstrated and promises to be implemented soon in fMRI studies at ultra high magnetic fields. Recording visual evoked potentials are expected to be amongst the most simple for simultaneous EEG/fMRI at ultra-high magnetic field due to the easy assessment of the visual cortex. Auditory evoked P300 measurements are of interest since it is believed that they represent the earliest stage of cognitive processing. In this study, we investigate the feasibility of recording visual evoked potentials and auditory evoked P300 in a 9.4 T static magnetic field. For this purpose, EEG data were recorded from 26 healthy volunteers inside a 9.4 T MR scanner using a 32-channel MR compatible EEG system. Visual stimulation and auditory oddball paradigm were presented in order to elicit evoked related potentials (ERP). Recordings made outside the scanner were performed using the same stimuli and EEG system for comparison purposes. We were able to retrieve visual P100 and auditory P300 evoked potentials at 9.4 T static magnetic field after correction of the ballistocardiogram artefact using independent component analysis. The latencies of the ERPs recorded at 9.4 T were not different from those recorded at 0 T. The amplitudes of ERPs were higher at 9.4 T when compared to recordings at 0 T. Nevertheless, it seems that the increased amplitudes of the ERPs are due to the effect of the ultra-high field on the EEG recording system rather than alteration in the intrinsic processes that generate the electrophysiological responses

Erratum to: Modulation of neutrophil NETosis: interplay between infectious agents and underlying host physiology

The ability of neutrophils and other leucocyte members of the innate immune system to expel their DNA into the extracellular environment in a controlled manner in order to trap and kill pathogenic microorganisms lead to a paradigm shift in our understanding of host microbe interactions. Surprisingly, the neutrophil extracellular trap (NET) cast by neutrophils is very wide and extends to the entrapment of viruses as well as multicellular eukaryotic parasites. Not unexpectedly, it has emerged that pathogenic microorganisms can employ a wide array of strategies to avoid ensnarement, including expression of DNAse enzymes that destroy the lattice backbone of NETs. Alternatively, they may use molecular mimicry to avoid detection or trigger events leading to the expression of immune modulatory cytokines such as IL-10, which dampen the NETotic response of neutrophils. In addition, the host microenvironment may contribute to the innate immune response by the production of lectin-like molecules that bind to bacteria and promote their entrapment on NETs. An example of this is the production of surfactant protein D by the lung epithelium. In addition, pregnancy provides a different challenge, as the mother needs to mount an effective response against pathogens, without harming her unborn child. An examination of these decoy and host response mechanisms may open the path for new therapies to treat pathologies mediated by overt NETosi

Effects of orally administered fumonisin B1 (FB1), partially hydrolysed FB1, hydrolysed FB1 and N-(1-deoxy-D-fructos-1-yl) FB1 on the sphingolipid metabolism in rats

Fumonisin B1 (FB1) is a Fusarium mycotoxin frequently occurring in maize-based food and feed. Alkaline processing like nixtamalisation of maize generates partially and fully hydrolysed FB1 (pHFB1 and HFB1) and thermal treatment in the presence of reducing sugars leads to formation of N-(1-deoxy-D-fructos- 1-yl) fumonisin B1 (NDF). The toxicity of these metabolites, in particular their effect on the sphingolipid metabolism, is either unknown or discussed controversially.We produced high purity FB1, pHFB1a+b, HFB1 and NDF and fed them to male Sprague Dawley rats for three weeks. Once a week, urine and faeces samples were collected over 24 h and analysed for fumonisin metabolites as well as for the sphinganine (Sa) to sphingosine (So) ratio by validated LC–MS/MS based methods. While the latter was significantly increased in the FB1 positive control group, the Sa/So ratios of the partially and fully hydrolysed fumonisins were indifferent from the negative control group. Although NDF was partly cleaved during digestion, the liberated amounts of FB1 did not raise the Sa/So ratio. These results show that the investigated alkaline and thermal processing products of FB1 were, at the tested concentrations, non-toxic for rats, and suggest that according food processing can reduce fumonisin toxicity for humans

The miR-17-92 cluster counteracts quiescence and chemoresistance in a distinct subpopulation of pancreatic cancer stem cells

Objective Cancer stem cells (CSCs) represent the root of many solid cancers including pancreatic ductal adenocarcinoma, are highly chemoresistant and represent the cellular source for disease relapse. However the mechanisms involved in these processes still need to be fully elucidated. Understanding the mechanisms implicated in chemoresistance and metastasis of pancreatic cancer is critical to improving patient outcomes. Design Micro-RNA (miRNA) expression analyses were performed to identify functionally defining epigenetic signatures in pancreatic CSC-enriched sphere-derived cells and gemcitabine-resistant pancreatic CSCs. Results We found the miR-17-92 cluster to be downregulated in chemoresistant CSCs versus non-CSCs and demonstrate its crucial relevance for CSC biology. In particular, overexpression of miR-17-92 reduced CSC self-renewal capacity, in vivo tumourigenicity and chemoresistance by targeting multiple NODAL/ACTIVIN/TGF-beta 1 signalling cascade members as well as directly inhibiting the downstream targets p21, p57 and TBX3. Overexpression of miR-17-92 translated into increased CSC proliferation and their eventual exhaustion via downregulation of p21 and p57. Finally, the translational impact of our findings could be confirmed in preclinical models for pancreatic cancer. Conclusions Our findings therefore identify the miR-17-92 cluster as a functionally determining family of miRNAs in CSCs, and highlight the putative potential of developing modulators of this cluster to overcome drug resistance in pancreatic CSCs.CH: ERC Advanced Investigator Grant (Pa-CSC 233460), European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement No 256974 (EPC-TM-NET) and No 602783 (CAM-PaC), the Subdireccion General de Evaluacion y Fomento de la Investigacion, Fondo de Investigacion Sanitaria (PS09/02129 \& PI12/02643), and the Programa Nacional de Internacionalizacion de la I+D, Subprogramma: FCCI 2009 (PLE2009-0105; Ministerio de Economia y Competitividad, Spain). MC: La Caixa Predoctoral Fellowship.S