The behaviour of political parties and MPs in the parliaments of the Weimar Republic

Copyright @ 2012 The Authors. This is the author's accepted manuscript. The final published article is available from the link below.Analysing the roll-call votes of the MPs of the Weimar Republic we find: (1) that party competition in the Weimar parliaments can be structured along two dimensions: an economic left–right and a pro-/anti-democratic. Remarkably, this is stable throughout the entire lifespan of the Republic and not just in the later years and despite the varying content of votes across the lifespan of the Republic, and (2) that nearly all parties were troubled by intra-party divisions, though, in particular, the national socialists and communists became homogeneous in the final years of the Republic.Zukunftskolleg, University of Konstan

FREE ORAL COMMUNICATIONS 2: ALCOHOL AND LIVER—CLINICAL RESEARCHO2.1RAPID DECLINE OF LIVER STIFFNESS WITH ALCOHOL WITHDRAWAL IN HEAVY DRINKERS

Background and aims. Measurement of liver stiffness using real-time elastography appears as a promising tool to evaluate the severity of chronic liver diseases. Previous studies in patients with alcoholic liver disease have suggested that fibrosis was the only histological parameter to influence liver stiffness. To challenge this hypothesis, we have prospectively tested the short-term impact of alcohol withdrawal on liver stiffness value. Methods. All patients hospitalized for alcohol withdrawal in our Liver Unit between September 2008 and December 2010 had a liver stiffness determination (using a FibroScan® device) at entry (D0) and 7 days after alcohol withdrawal (D7). Stiffness values were compared using non-parametric test for paired-values. We compared (i) the 10 measures performed at D0 and at D7 for each patient; (ii) the variation of the median result of all patients (using Wilcoxon test in both cases). Results. A total of 138 patients were included in the study [median alcohol consumption: 150g/day (range: 40-400); hepatitis C: n=22 (15.9%); cirrhosis: n=29 (21.0%)]. From D0 to D7, the liver stiffness decreased significantly in 61 patients (44.2%) and increased significantly in 18 (13.0%). Considering all patients, median liver stiffness value decreased from 7.25 to kPa (P<0.001). The stage of fibrosis indicated by liver stiffness changed in 47 patients between D0 and D7 (decrease in 33 and increase in 14). Conclusion. Liver stiffness decreases significantly in nearly half of alcoholic patients after only 7 days of abstinence. This result strongly suggests that non-fibrotic lesions (such as inflammatory ones) may influence liver stiffness. From a practical point of view, it also shows that variation in alcohol consumption must be taken into account for the interpretation of liver stiffness valu

Classical Mus musculus Igκ Enhancers Support Transcription but not High Level Somatic Hypermutation from a V-Lambda Promoter in Chicken DT40 Cells

Somatic hypermutation (SHM) of immunoglobulin genes is initiated by activation-induced cytidine deaminase (AID) in activated B cells. This process is strictly dependent on transcription. Hence, cis-acting transcriptional control elements have been proposed to target SHM to immunoglobulin loci. The Mus musculus Igκ locus is regulated by the intronic enhancer (iE/MAR) and the 3′ enhancer (3′E), and multiple studies using transgenic and knock-out approaches in mice and cell lines have reported somewhat contradictory results about the function of these enhancers in AID-mediated sequence diversification. Here we show that the M. musculus iE/MAR and 3′E elements are active solely as transcriptional enhancer when placed in the context of the IGL locus in Gallus gallus DT40 cells, but they are very inefficient in targeting AID-mediated mutation events to this locus. This suggests that either key components of the cis-regulatory targeting elements reside outside the murine Igκ transcriptional enhancer sequences, or that the targeting of AID activity to Ig loci occurs by largely species-specific mechanisms

Nuclear pore component Nup98 is a potential tumor suppressor and regulates posttranscriptional expression of select p53 target genes

The p53 tumor suppressor utilizes multiple mechanisms to selectively regulate its myriad target genes, which in turn mediate diverse cellular processes. Here, using conventional and single-molecule mRNA analyses, we demonstrate that the nucleoporin Nup98 is required for full expression of p21, a key effector of the p53 pathway, but not several other p53 target genes. Nup98 regulates p21 mRNA levels by a posttranscriptional mechanism in which a complex containing Nup98 and the p21 mRNA 3\u27UTR protects p21 mRNA from degradation by the exosome. An in silico approach revealed another p53 target (14-3-3sigma) to be similarly regulated by Nup98. The expression of Nup98 is reduced in murine and human hepatocellular carcinomas (HCCs) and correlates with p21 expression in HCC patients. Our study elucidates a previously unrecognized function of wild-type Nup98 in regulating select p53 target genes that is distinct from the well-characterized oncogenic properties of Nup98 fusion proteins

The DNA Glycosylases Ogg1 and Nth1 Do Not Contribute to Ig Class Switching in Activated Mouse Splenic B Cells

During activation of B cells to undergo class switching, B cell metabolism is increased, and levels of reactive oxygen species (ROS) are increased. ROS can oxidize DNA bases resulting in substrates for the DNA glycosylases Ogg1 and Nth1. Ogg1 and Nth1 excise oxidized bases, and nick the resulting abasic sites, forming single-strand DNA breaks (SSBs) as intermediates during the repair process. In this study, we asked whether splenic B cells from mice deficient in these two enzymes would show altered class switching and decreased DNA breaks in comparison with wild-type mice. As the c-myc gene frequently recombines with the IgH S region in B cells induced to undergo class switching, we also analyzed the effect of deletion of these two glycosylases on DSBs in the c-myc gene. We did not detect a reduction in S region or c-myc DSBs or in class switching in splenic B cells from Ogg1- or Nth1-deficient mice or from mice deficient in both enzymes

Assessing the Impact of Holocaust Education on Adolescents’ Civic Values: Experimental Evidence from Arkansas

American adults overwhelmingly agree that the Holocaust should be taught in schools, yet few studies investigate the potential benefits of Holocaust education. We evaluate the impact of Holocaust education on several civic outcomes, including “upstander” efficacy (willingness to intervene on behalf of others), likelihood of exercising civil disobedience, empathy for the suffering of others, and tolerance of others with different values and lifestyles. We recruit students from two local high schools and randomize access to the Arkansas Holocaust Education Conference, where students have the chance to hear from a Holocaust survivor and to participate in breakout sessions with leading Holocaust experts. We find that students randomly assigned to attend the conference become more knowledgeable about the Holocaust and are more willing to act as an upstander on behalf of others. In our subgroup analysis, we find that minority students are significantly more willing to act as an upstander relative to their white peers

Genetic Evidence for Single-Strand Lesions Initiating Nbs1-Dependent Homologous Recombination in Diversification of Ig V in Chicken B Lymphocytes

Homologous recombination (HR) is initiated by DNA double-strand breaks (DSB). However, it remains unclear whether single-strand lesions also initiate HR in genomic DNA. Chicken B lymphocytes diversify their Immunoglobulin (Ig) V genes through HR (Ig gene conversion) and non-templated hypermutation. Both types of Ig V diversification are initiated by AID-dependent abasic-site formation. Abasic sites stall replication, resulting in the formation of single-stranded gaps. These gaps can be filled by error-prone DNA polymerases, resulting in hypermutation. However, it is unclear whether these single-strand gaps can also initiate Ig gene conversion without being first converted to DSBs. The Mre11-Rad50-Nbs1 (MRN) complex, which produces 3′ single-strand overhangs, promotes the initiation of DSB-induced HR in yeast. We show that a DT40 line expressing only a truncated form of Nbs1 (Nbs1p70) exhibits defective HR-dependent DSB repair, and a significant reduction in the rate—though not the fidelity—of Ig gene conversion. Interestingly, this defective gene conversion was restored to wild type levels by overproduction of Escherichia coli SbcB, a 3′ to 5′ single-strand–specific exonuclease, without affecting DSB repair. Conversely, overexpression of chicken Exo1 increased the efficiency of DSB-induced gene-targeting more than 10-fold, with no effect on Ig gene conversion. These results suggest that Ig gene conversion may be initiated by single-strand gaps rather than by DSBs, and, like SbcB, the MRN complex in DT40 may convert AID-induced lesions into single-strand gaps suitable for triggering HR. In summary, Ig gene conversion and hypermutation may share a common substrate—single-stranded gaps. Genetic analysis of the two types of Ig V diversification in DT40 provides a unique opportunity to gain insight into the molecular mechanisms underlying the filling of gaps that arise as a consequence of replication blocks at abasic sites, by HR and error-prone polymerases

Critical assessment of the elemental composition of Corning archeological reference glasses by LA-ICP-MS

Corning archeological reference glasses A, B, C, and D have been made to simulate different historic technologies of glass production and are used as standards in historic glass investigations. In this work, nanoseconds (193, 266 nm) and femtosecond (800 nm) laser ablation were used to study the elemental composition of Corning glasses using laser ablation inductively coupled plasma mass spectrometry. The determined concentrations of 26 oxides (Li2O, B2O3, Na2O, MgO, Al2O3, SiO2, P2O5, K2O, CaO, TiO2, V2O5, Cr2O3, MnO, Fe2O3, CoO, NiO, CuO, ZnO, Rb2O, SrO, ZrO2, SnO2, Sb2O5, BaO, PbO, Bi2O3) are compared with values reported in the literature. Results show variable discrepancies between the data, with the largest differences found for Cr2O3 in Corning A; Li2O, B2O3, and Cr2O3 in Corning B; and MnO, Sb2O5, Cr2O3, and Bi2O3 in Corning C. The best agreement between the measured and literature values was found for Corning D. However, even for this reference, glass re-evaluation of the data was necessary and new values for PbO, BaO, and Bi2O3 are proposed

Unique DNA Repair Gene Variations and Potential Associations with the Primary Antibody Deficiency Syndromes IgAD and CVID

BACKGROUND: Despite considerable effort, the genetic factors responsible for >90% of the antibody deficiency syndromes IgAD and CVID remain elusive. To produce a functionally diverse antibody repertoire B lymphocytes undergo class switch recombination. This process is initiated by AID-catalyzed deamination of cytidine to uridine in switch region DNA. Subsequently, these residues are recognized by the uracil excision enzyme UNG2 or the mismatch repair proteins MutSalpha (MSH2/MSH6) and MutLalpha (PMS2/MLH1). Further processing by ubiquitous DNA repair factors is thought to introduce DNA breaks, ultimately leading to class switch recombination and expression of a different antibody isotype. METHODOLOGY/PRINCIPAL FINDINGS: Defects in AID and UNG2 have been shown to result in the primary immunodeficiency hyper-IgM syndrome, leading us to hypothesize that additional, potentially more subtle, DNA repair gene variations may underlie the clinically related antibody deficiencies syndromes IgAD and CVID. In a survey of twenty-seven candidate DNA metabolism genes, markers in MSH2, RAD50, and RAD52 were associated with IgAD/CVID, prompting further investigation into these pathways. Resequencing identified four rare, non-synonymous alleles associated with IgAD/CVID, two in MLH1, one in RAD50, and one in NBS1. One IgAD patient carried heterozygous non-synonymous mutations in MLH1, MSH2, and NBS1. Functional studies revealed that one of the identified mutations, a premature RAD50 stop codon (Q372X), confers increased sensitivity to ionizing radiation. CONCLUSIONS: Our results are consistent with a class switch recombination model in which AID-catalyzed uridines are processed by multiple DNA repair pathways. Genetic defects in these DNA repair pathways may contribute to IgAD and CVID