Fire in the Quill

How has our understanding of the brain evolved? And what can its progress tell us about the way science works? Armin Schneider explores these questions in his review of Charles Gross' new collection of essays on the history of neuroscience in Fire in the Quill

A screen for peptide agonists of the G-CSF receptor

<p>Abstract</p> <p>Background</p> <p>Granulocyte-colony stimulating factor (G-CSF) is one of the most important pharmacologically used proteins. Potential uses beyond the stimulation of neutrophilic granulocytes are the treatment of CNS disorders. Disadvantages of the G-CSF protein as a drug are its moderate plasma half-life time and considerable production costs. We therefore conducted a screen for peptide agonists derived from the sequence of human G-CSF.</p> <p>Findings</p> <p>Despite of the high sensitivity of our screening system we could not detect any positive hits in a single peptide approach. In a multiplex approach using a permutation of any combination of 10 different peptides we could also not detect a positive block.</p> <p>Conclusions</p> <p>We conclude that larger coherent parts of the protein or dimerising peptides may be needed to achieve activation of the receptor.</p

Reanalysis of the association of high-redshift 1-Jansky quasars with IRAS galaxies

We develop a new statistical method to reanalyse angular correlations between background QSOs and foreground galaxies that are supposed to be a consequence of dark matter inhomogeneities acting as weak gravitational lenses. The method is based on a weighted average over the galaxy positions and is optimized to distinguish between a random distribution of galaxies around QSOs and a distribution which follows an assumed QSO-galaxy two-point correlation function, by choosing an appropriate weight function. With simulations we demonstrate that this weighted average is slightly more significant than Spearman's rank-order test which was used in previous investigations. In particular, the advantages of the weighted average show up if the two-point correlation function is weak. We then reanalyze the correlation between high-redshift 1-Jansky QSOs and IRAS galaxies, taken from the IRAS Faint Source Catalog; these samples were analyzed previously using Spearman's rank-order test. In agreement with the previous work, we find moderate to strong correlations between these two samples; considering the angular two-point correlation function of these samples, we find a typical scale of order $5'$ from which most of the correlation signal derives. However, the statistical significance of the correlation changes with the redshift slices of the QSO sample one considers. Comparing with simple theoretical estimates of the expected correlation, we find that the signal we derive is considerably stronger than expected. On the other hand, recent direct verifications of the overdensity of matter in the line-of-sight to high-redshift radio QSOs obtained from the shear field around these sources, indicates that the observed association can be attributed to a gravitational lens effect.Comment: 29 pages, LaTex, including 9 figures, submitted to Astronomy and Astrophysic

The receptor for Granulocyte-colony stimulating factor (G-CSF) is expressed in radial glia during development of the nervous system

<p>Abstract</p> <p>Background</p> <p>Granulocyte colony-stimulating (G-CSF) factor is a well-known hematopoietic growth factor stimulating the proliferation and differentiation of myeloid progenitors. Recently, we uncovered that G-CSF acts also as a neuronal growth factor in the brain, which promotes adult neural precursor differentiation and enhances regeneration of the brain after insults. In adults, the receptor for G-CSF is predominantly expressed in neurons in many brain areas. We also described expression in neurogenic regions of the adult brain, such as the subventricular zone and the subgranular layer of the dentate gyrus. In addition, we found close co-localization of the G-CSF receptor and its ligand G-CSF. Here we have conducted a systematic expression analysis of G-CSF receptor and its ligand in the developing embryo.</p> <p>Results</p> <p>Outside the central nervous system (CNS) we found G-CSF receptor expression in blood vessels, muscles and their respective precursors and neurons. The expression of the G-CSF receptor in the developing CNS was most prominent in radial glia cells.</p> <p>Conclusion</p> <p>Our data imply that in addition to the function of G-CSF and its receptor in adult neurogenesis, this system also has a role in embryonic neurogenesis and nervous system development.</p

Workfare – praktikabel und gerecht

Dieses Modell stellt das Niveau des Arbeitslosengeldes II nicht in Frage, macht aber seine Gewährung von einer Gegenleistung in Form von Workfare (d.h. öffentlich organisierter Vollzeitbeschäftigung) abhängig. Wer das Workfare-Angebot nicht annimmt, muss aber auf sein Arbeitslosengeld II verzichten.Workfare, Arbeitslosigkeit, Ungelernte Arbeitskräfte, Niedriglohn, Deutschland, Kombilohn

G-CSF protects motoneurons against axotomy-induced apoptotic death in neonatal mice

<p>Abstract</p> <p>Background</p> <p>Granulocyte colony stimulating factor (G-CSF) is a growth factor essential for generation of neutrophilic granulocytes. Apart from this hematopoietic function, we have recently uncovered potent neuroprotective and regenerative properties of G-CSF in the central nervous system (CNS). The G-CSF receptor and G-CSF itself are expressed in α motoneurons, G-CSF protects motoneurons, and improves outcome in the SOD1(G93A) transgenic mouse model for amyotrophic lateral sclerosis (ALS). In vitro, G-CSF acts anti-apoptotically on motoneuronal cells. Due to the pleiotrophic effects of G-CSF and the complexity of the SOD1 transgenic ALS models it was however not possible to clearly distinguish between directly mediated anti-apoptotic and indirectly protective effects on motoneurons. Here we studied whether G-CSF is able to protect motoneurons from purely apoptotic cell death induced by a monocausal paradigm, neonatal sciatic nerve axotomy.</p> <p>Results</p> <p>We performed sciatic nerve axotomy in neonatal mice overexpressing G-CSF in the CNS and found that G-CSF transgenic mice displayed significantly higher numbers of surviving lumbar motoneurons 4 days following axotomy than their littermate controls. Also, surviving motoneurons in G-CSF overexpressing animals were larger, suggesting additional trophic effects of this growth factor.</p> <p>Conclusions</p> <p>In this model of pure apoptotic cell death the protective effects of G-CSF indicate direct actions of G-CSF on motoneurons in vivo. This shows that G-CSF exerts potent anti-apoptotic activities towards motoneurons in vivo and suggests that the protection offered by G-CSF in ALS mouse models is due to its direct neuroprotective activity.</p

Über den Einfluss der Ungewissheit möglichen Scheiterns und Irrens auf die aktive Gestaltung eines guten Lebens

Schneider AHR. Über den Einfluss der Ungewissheit möglichen Scheiterns und Irrens auf die aktive Gestaltung eines guten Lebens. Bielefeld: Universität Bielefeld; 2017

Neurotrophic Growth Factors for the Treatment of Amyotrophic Lateral Sclerosis: Where Do We Stand?

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that results in progressive loss of motoneurons, motor weakness and death within 3–5 years after disease onset. Therapeutic options remain limited despite substantial number of approaches that have been tested clinically. Many neurotrophic growth factors are known to promote the survival of neurons and foster regeneration in the central nervous system. Various neurotrophic factors have been investigated pre-clinically and clinically for the treatment of ALS. Although pre-clinical data appeared promising, no neurotrophic factors succeeded yet in a clinical phase III trial. In this review we discuss the rationale behind those factors, possible reasons for clinical failures, and argue for a renewal of hope in this powerful class of drugs for the treatment of ALS

The IZA Evaluation Dataset: Towards Evidence-Based Labor Policy-Making

The evaluation of labor market policies has become an important issue in many European countries. In recent years, a number of them have opened their administrative databases for evaluation studies. The advantages of administrative data are straightforward: they are accurate, contain a large number of observations (in some cases the whole population) and usually cover a long period of time. However, the information contained in administrative data is normally limited to administrative purposes. Therefore, information that might be relevant for economic modeling is often absent. The IZA Evaluation Dataset aims to overcome such limitations for Germany by complementing administrative data from the Federal Employment Agency with innovative survey data. The administrative part of the dataset consists of a large random sample of inflows into unemployment in Germany from 2001 to 2008 and contains around 920,000 individuals. The complementary survey covers a panel of more than 17,000 individuals who entered unemployment between June 2007 and May 2008. They were initially interviewed shortly after becoming unemployed and then again one year later. In addition, a quarter of individuals were interviewed already after six months. The survey data also contain information on search behavior, ethnic and social networks, psychological factors, (non-)cognitive abilities, and attitudes. This paper describes the sampling and contents of the IZA Evaluation Dataset and outlines the future development.survey and administrative data, labor market policies, evaluation, attitudes, behavior, skills

The hematopoietic factor GM-CSF (Granulocyte-macrophage colony-stimulating factor) promotes neuronal differentiation of adult neural stem cells in vitro

BACKGROUND: Granulocyte-macrophage colony stimulating factor (GM-CSF) is a hematopoietic growth factor involved in the generation of granulocytes, macrophages, and dendritic cells from hematopoietic progenitor cells. We have recently demonstrated that GM-CSF has anti-apoptotic functions on neurons, and is neuroprotective in animal stroke models. RESULTS: The GM-CSF receptor α is expressed on adult neural stem cells in the rodent brain, and in culture. Addition of GM-CSF to NSCs in vitro increased neuronal differentiation in a dose-dependent manner as determined by quantitative PCR, reporter gene assays, and FACS analysis. CONCLUSION: Similar to the hematopoietic factor Granulocyte-colony stimulating factor (G-CSF), GM-CSF stimulates neuronal differentiation of adult NSCs. These data highlight the astonishingly similar functions of major hematopoietic factors in the brain, and raise the clinical attractiveness of GM-CSF as a novel drug for neurological disorders