Glycoprotein IIb-IIIa Is Expressed on Avian Multilineage Hematopoietic Progenitor Cells

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A unified classification approach rating clinical utility of protein biomarkers across neurologic diseases

A major evolution from purely clinical diagnoses to biomarker supported clinical diagnosing has been occurring over the past years in neurology. High-throughput methods, such as next-generation sequencing and mass spectrometry-based proteomics along with improved neuroimaging methods, are accelerating this development. This calls for a consensus framework that is broadly applicable and provides a spot-on overview of the clinical validity of novel biomarkers. We propose a harmonized terminology and a uniform concept that stratifies biomarkers according to clinical context of use and evidence levels, adapted from existing frameworks in oncology with a strong focus on (epi)genetic markers and treatment context. We demonstrate that this framework allows for a consistent assessment of clinical validity across disease entities and that sufficient evidence for many clinical applications of protein biomarkers is lacking. Our framework may help to identify promising biomarker candidates and classify their applications by clinical context, aiming for routine clinical use of (protein) biomarkers in neurology

Leukotriene B-4-Neutrophil Elastase Axis Drives Neutrophil Reverse Transendothelial Cell Migration In Vivo

This work was supported by generous funds from the Wellcome Trust (098291/Z/12/Z to S.N.). T.C. was supported by the ERC (ENDHORET). The work was also supported in part by funds from the William Harvey Research Foundation

L-Ilf3 and L-NF90 Traffic to the Nucleolus Granular Component: Alternatively-Spliced Exon 3 Encodes a Nucleolar Localization Motif

Ilf3 and NF90, two proteins containing double-stranded RNA-binding domains, are generated by alternative splicing and involved in several functions. Their heterogeneity results from posttranscriptional and posttranslational modifications. Alternative splicing of exon 3, coding for a 13 aa N-terminal motif, generates for each protein a long and short isoforms. Subcellular fractionation and localization of recombinant proteins showed that this motif acts as a nucleolar localization signal. Deletion and substitution mutants identified four arginines, essential for nucleolar targeting, and three histidines to stabilize the proteins within the nucleolus. The short isoforms are never found in the nucleoli, whereas the long isoforms are present in the nucleoplasm and the nucleoli. For Ilf3, only the posttranslationally-unmodified long isoform is nucleolar, suggesting that this nucleolar targeting is abrogated by posttranslational modifications. Confocal microscopy and FRAP experiments have shown that the long Ilf3 isoform localizes to the granular component of the nucleolus, and that L-Ilf3 and L-NF90 exchange rapidly between nucleoli. The presence of this 13 aminoacid motif, combined with posttranslational modifications, is responsible for the differences in Ilf3 and NF90 isoforms subcellular localizations. The protein polymorphism of Ilf3/NF90 and the various subcellular localizations of their isoforms may partially explain the various functions previously reported for these proteins

Antibiotika-Therapie in der Schwangerschaft: teratogene Risiken von Makroliden, Doxycyclin und Cotrimoxazol

Drug exposure during first trimester of pregnancy ranges from 10 % in Germany to 50 % in the USA. Antibiotics are among the most commonly used substances. Objective was to investigate possible teratogenic risks of some currently used antibiotics. Data were collected prospectively by following up pregnant women, who had been counselled on the use of erythromycin, rorithromycin, clarithromycin, azithromycin, doxycycline or co-trimoxazole in first trimester of pregnancy by the Teratology Information Service of the University of Ulm, now located at the Krankenhaus St. Elisabeth Ravensburg. Women who were not exposed or were exposed to evidentially non-teratogenic agents served as controls. They were matched for maternal age and gestational age at call and compared by using Fisher´s exact test. No significant differences were found concerning exposure to erythromycin (n = 41), roxithromycin (n = 163), clarithromycin (n = 131), azithromycin (n = 105), doxycycline (n = 435) and co-trimoxazole (n = 356) in the rates of spontaneous abortions, congenital anomalies and birth weights relating to gestational age at birth. However, the rates of congenital anomalies after exposure to erythromycin and roxithromycin tended to be significantly higher: 8.3 vs. 0 % (p = 0.11) and 8.2 vs. 3.5 % (p = 0,08). Induced abortion rates were higher in nearly all study groups; they were significantly higher after exposure to clarithromycin, doxycycline and co-trimoxazole. These results suggest that the use of these antibiotics during first trimester of pregnancy causes no significant fetal risks. However, attention should be focussed on exposure to erythromycin and roxithromycin, and further investigation is needed to detect possible small risks. Based on these data there is no indication for induced abortion after exposure to any of these substances. Higher rates of induced abortions possibly indicate that exposed women are scared by warnings on package inserts