Tracing lineages to uncover neuronal identity

Many previous studies have focused on understanding how midbrain dopamine neurons, which are implicated in many neurological conditions, are generated during embryogenesis. One of the remaining questions concerns how different dopamine neuron subtypes are specified. A recent paper in Neural Development has revealed features of a spatial and temporal lineage map that, together with other studies, begins to elucidate the developmental origin of distinct neuronal subtypes within the developing midbrain

Zertifikat B1 Deutschprüfung für Jugendliche und Erwachsene: Standard Setting. Ein Arbeitsbericht

Neue Sprachprüfungen haben in der Regel den Anspruch, sich auf ein externes Referenzsystem zu beziehen. In Europa ist dieses Referenzsystem seit mehr als einer Dekade der Gemeinsame europäische Referenzrahmen für Sprachen (GER). Um diesem Anspruch gerecht zu werden, sind Testanbieter bemüht, ihre Bezüge auf den GER mithilfe von Standards zum Sprachentesten generell und Standards der Association of Language Testers in Europe (ALTE) im Besonderen nachzuweisen. Der Europarat empfiehlt Sprachtestanbietern einen methodologischen Leitfaden, das sogenannte Manual for Relating Language Examinations to the Common Framework of Reference for Languages (CEFR), der sie bei der „Eichung“ ihrer Sprachprüfung unterstützt. Kapitel 5 und 6 des Leitfadens beschreiben Methoden zum Benchmarking und Standard Setting. Das Ziel dieses Berichts ist es zu zeigen, mit welchen Methoden die neu entwickelte Prüfung für Deutsch als Fremdsprache Zertifikat B1 auf die Stufe B1 des Referenzrahmens bezogen wurde und welche Ergebnisse dabei erreicht wurden

Assessing Immigrant Assimilation: New Empirical and Theoretical Challenges

This review examines research on the assimilation of immigrant groups. We review research on four primary benchmarks of assimilation: socioeconomic status, spatial concentration, language assimilation, and intermarriage. The existing literature shows that today's immigrants are largely assimilating into American society along each of these dimensions. This review also considers directions for future research on the assimilation of immigrant groups in new southern and midwestern gateways and how sociologists measure immigrant assimilation. We document the changing geography of immigrant settlement and review the emerging body of research in this area. We argue that examining immigrant assimilation in these new immigrant gateways is crucial for the development of theories about immigrant assimilation. We also argue that we are likely to see a protracted period of immigrant replenishment that may change the nature of assimilation. Studying this change requires sociologists to use both birth cohort and generation as temporal markers of assimilation.Sociolog

The Local Geographic Origins of Russian-Jewish Immigrants, Circa 1900

This working paper concerns the local origins of Russian-Jewish immigrants to the United States, circa 1900. New evidence is drawn from a large random sample of Russian-Jewish immigrant arrivals in the United States. It provides information on origins not merely by large regions, or even by the provinces of the Pale of Settlement (where nearly all Russian Jews lived), some 25 in number; rather, most analysis is conducted in terms of some 230 districts that made up the administrative subdivisions of provinces. The sample evidence is coordinated with district-level data from the detailed publications of the 1897 Census of the Russian Empire. Finally, all of this evidence has been entered into digitized maps

Lmx1a-Dependent Activation of miR-204/211 Controls the Timing of Nurr1-Mediated Dopaminergic Differentiation

The development of midbrain dopaminergic (DA) neurons requires a fine temporal and spatial regulation of a very specific gene expression program. Here, we report that during mouse brain development, the microRNA (miR-) 204/211 is present at a high level in a subset of DA precursors expressing the transcription factor Lmx1a, an early determinant for DA-commitment, but not in more mature neurons expressing Th or Pitx3. By combining different in vitro model systems of DA differentiation, we show that the levels of Lmx1a influence the expression of miR-204/211. Using published transcriptomic data, we found a significant enrichment of miR-204/211 target genes in midbrain dopaminergic neurons where Lmx1a was selectively deleted at embryonic stages. We further demonstrated that miR-204/211 controls the timing of the DA differentiation by directly downregulating the expression of Nurr1, a late DA differentiation master gene. Thus, our data indicate the Lmx1a-miR-204/211-Nurr1 axis as a key component in the cascade of events that ultimately lead to mature midbrain dopaminergic neurons differentiation and point to miR-204/211 as the molecular switch regulating the timing of Nurr1 expression

Mitochondrial dysfunction in adult midbrain dopamine neurons triggers an early immune response

Dopamine (DA) neurons of the midbrain are at risk to become affected by mitochondrial damage over time and mitochondrial defects have been frequently reported in Parkinson\u27s disease (PD) patients. However, the causal contribution of adult-onset mitochondrial dysfunction to PD remains uncertain. Here, we developed a mouse model lacking Mitofusin 2 (MFN2), a key regulator of mitochondrial network homeostasis, in adult midbrain DA neurons. The knockout mice develop severe and progressive DA neuron-specific mitochondrial dysfunction resulting in neurodegeneration and parkinsonism. To gain further insights into pathophysiological events, we performed transcriptomic analyses of isolated DA neurons and found that mitochondrial dysfunction triggers an early onset immune response, which precedes mitochondrial swelling, mtDNA depletion, respiratory chain deficiency and cell death. Our experiments show that the immune response is an early pathological event when mitochondrial dysfunction is induced in adult midbrain DA neurons and that neuronal death may be promoted non-cell autonomously by the cross-talk and activation of surrounding glial cells

Immunological assays for chemokine detection in in-vitro culture of CNS cells

Herein we review the various methods currently in use for determining the expression of chemokines by CNS cells in vitro. Chemokine detection assays are used in conjuction with one another to provide a comprehensive, biologically relevant assessment of the chemokines which is necessary for correct data interpretation of a specific observed biological effect. The methods described include bioassays for soluble chemokine receptors, RNA extraction, RT-PCR, Real - time quantitative PCR, gene array analysis, northern blot analysis, Ribonuclease Protection assay, Flow cytometry, ELISPOT, western blot analysis, and ELISA. No single method of analysis meets the criteria for a comprehensive, biologically relevant assessment of the chemokines, therefore more than one assay might be necessary for correct data interpretation, a choice that is based on development of a scientific rationale for the method with emphasis on the reliability and relevance of the method

Lmx1a-Dependent Activation of miR-204/211 Controls the Timing of Nurr1-Mediated Dopaminergic Differentiation

The development of midbrain dopaminergic (DA) neurons requires a fine temporal and spatial regulation of a very specific gene expression program. Here, we report that during mouse brain development, the microRNA (miR-) 204/211 is present at a high level in a subset of DA precursors expressing the transcription factor Lmx1a, an early determinant for DA-commitment, but not in more mature neurons expressing Th or Pitx3. By combining different in vitro model systems of DA differentiation, we show that the levels of Lmx1a influence the expression of miR-204/211. Using published transcriptomic data, we found a significant enrichment of miR-204/211 target genes in midbrain dopaminergic neurons where Lmx1a was selectively deleted at embryonic stages. We further demonstrated that miR-204/211 controls the timing of the DA differentiation by directly downregulating the expression of Nurr1, a late DA differentiation master gene. Thus, our data indicate the Lmx1a-miR-204/211-Nurr1 axis as a key component in the cascade of events that ultimately lead to mature midbrain dopaminergic neurons differentiation and point to miR-204/211 as the molecular switch regulating the timing of Nurr1 expression

ICM Web: the interactive chromatin modeling web server

The interactive chromatin modeling web server (ICM Web) is an interactive tool that allows users to rapidly assess nucleosome stability and fold sequences of DNA into putative chromatin templates. ICM Web takes a sequence composed of As, Cs, Gs, and Ts as input and generates (i) a nucleosome energy level diagram, (ii) coarse-grained representations of free DNA and chromatin and (iii) plots of the helical parameters (Tilt, Roll, Twist, Shift, Slide and Rise) as a function of position. The user can select from several different energy models, nucleosome structures and methods for placing nucleosomes in the energy landscape. Alternatively, if nucleosome footprints are known from experiment, ICM Web can use these positions to create a nucleosome array. The default energy model achieves a correlation coefficient of 0.7 with 100 experimentally determined values of stability and properly predicts the location of six positioned nucleosomes in the mouse mammary tumor virus (MMTV) promoter. ICM Web is suitable for interactively investigating nucleosome stability and chromatin folding for sequences up to tens of kilobases in length. No login is required to use ICM Web