155 research outputs found

    Ehe- und familienbezogene Leistungen in der Alterssicherung: Wichtig für die wirtschaftliche Stabilität von Familien

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    Familienbedingte Erwerbsunterbrechungen führen in Zusammenhang mit der Alterssicherung insbesondere für Mütter oft zu niedrigeren gesetzlichen Rentenansprüchen. Vor diesem Hintergrund hat der Gesetzgeber ehe- und familienbezogene Leistungen konzipiert, die solche Defizite in der Altersversorgung ausgleichen sollen. Diese Leistungen mit unmittelbarem Bezug zur Alterssicherung haben eine wesentliche Bedeutung für die wirtschaftliche Stabilität von Familien im Alter. Das trifft insbesondere auf die Kindererziehungszeiten zu und in begrenztem Maß auch auf den Kinderzuschlag bei der Witwenrente, die Kinderberücksichtigungszeiten im Zusammenhang mit der Höherbewertung unterdurchschnittlicher Erwerbseinkommen sowie den Nachteilsausgleich bei Mehrfacherziehung und die Kinderzulage bei der Riester-Rente. Deutlich geringere Bedeutung haben hingegen die Kinderberücksichtigungszeiten für die Berechtigung zu einem Renteneintritt vor Erreichen des Regelrenteneintrittsalters.Family-related breaks in employment often lead to lower statutory pension entitlements, especially for retired mothers. Against this background, the legislation for marriage- and family-related payments has been designed to compensate for such deficits in old-age provision. These payments are directly related to old-age pensions and can be of relevant importance for the economic stability of families in retirement. This applies in particular to child-rearing periods and, to a limited degree, also to supplementary child allowance for widow's pensions and credited child-raising periods in relation to revaluation and bringing up several children. In contrast, credited child-raising periods have less relevance for the entitlements of those retiring before the default retirement age

    The Ca2+ sensor protein Swiprosin-1/EFhd2 is present in neurites and involved in kinesin-mediated transport in neurons

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    This work was supported by grants from the German Science Foundation (Deutsche Forschungsgemeinschaft, DFG; FOR832, to DM), the German Federal Ministry of Education and Research (01GQ113; to BW), the Bavarian Ministry of Sciences, Research and the Arts in the framework of the Bavarian Molecular Biosystems Reseach Network, the Interdisciplinary Center for Clinical Research (IZKF, Universitatsklinikum Erlangen; E8, to DM; NIII, to BW; Lab rotation to MR), the ELAN Fonds (Universitatsklinikum Erlangen; 11.08.19.1, to IP), and the Alzheimer’s Research UK (EB, FGM).Swiprosin-1/EFhd2 (EFhd2) is a cytoskeletal Ca2+ sensor protein strongly expressed in the brain. It has been shown to interact with mutant tau, which can promote neurodegeneration, but nothing is known about the physiological function of EFhd2 in the nervous system. To elucidate this question, we analyzed EFhd2-/-/lacZ reporter mice and showed that lacZ was strongly expressed in the cortex, the dentate gyrus, the CA1 and CA2 regions of the hippocampus, the thalamus, and the olfactory bulb. Immunohistochemistry and western blotting confirmed this pattern and revealed expression of EFhd2 during neuronal maturation. In cortical neurons, EFhd2 was detected in neurites marked by MAP2 and co-localized with preand post-synaptic markers. Approximately one third of EFhd2 associated with a biochemically isolated synaptosome preparation. There, EFhd2 was mostly confined to the cytosolic and plasma membrane fractions. Both synaptic endocytosis and exocytosis in primary hippocampal EFhd2-/- neurons were unaltered but transport of synaptophysin-GFP containing vesicles was enhanced in EFhd2-/- primary hippocampal neurons, and notably, EFhd2 inhibited kinesin mediated microtubule gliding. Therefore, we found that EFhd2 is a neuronal protein that interferes with kinesin-mediated transport.Peer reviewe

    Preclinical transgenic and patient-derived xenograft models recapitulate the radiological features of human adamantinomatous craniopharyngioma

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    To assess the clinical relevance of transgenic and patient-derived xenograft models of adamantinomatous craniopharyngioma (ACP) using serial magnetic resonance imaging (MRI) and high resolution post-mortem microcomputed tomography (μ-CT), with correlation with histology and human ACP imaging. The growth patterns and radiological features of tumors arising in Hesx1(Cre/+) ;Ctnnb1(lox(ex3)/+) transgenic mice, and of patient-derived ACP xenografts implanted in the cerebral cortex, were monitored longitudinally in vivo with anatomical and functional MRI, and by ex vivo μ-CT at study end. Pathological correlates with hematoxylin and eosin stained sections were investigated. Early enlargement and heterogeneity of Hesx1(Cre/+) ;Ctnnb1(lox(ex3)/+) mouse pituitaries was evident at initial imaging at 8 weeks, which was followed by enlargement of a solid tumor, and development of cysts and hemorrhage. Tumors demonstrated MRI features that recapitulated those of human ACP, specifically, T1 -weighted signal enhancement in the solid tumor component following Gd-DTPA administration, and in some animals, hyperintense cysts on FLAIR and T1 -weighted images. Ex vivo μ-CT correlated with MRI findings and identified smaller cysts, which were confirmed by histology. Characteristic histological features, including wet keratin and calcification, were visible on μ-CT and verified by histological sections of patient-derived ACP xenografts. The Hesx1(Cre/+) ;Ctnnb1(lox(ex3)/+) transgenic mouse model and cerebral patient-derived ACP xenografts recapitulate a number of the key radiological features of the human disease and provide promising foundations for in vivo trials of novel therapeutics for the treatment of these tumors

    Genetic and epigenetic characterization of posterior pituitary tumors

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    Pituicytoma (PITUI), granular cell tumor (GCT), and spindle cell oncocytoma (SCO) are rare tumors of the posterior pituitary. Histologically, they may be challenging to distinguish and have been proposed to represent a histological spectrum of a single entity. We performed targeted next-generation sequencing, DNA methylation profiling, and copy number analysis on 47 tumors (14 PITUI; 12 GCT; 21 SCO) to investigate molecular features and explore possibilities of clinically meaningful tumor subclassification. We detected two main epigenomic subgroups by unsupervised clustering of DNA methylation data, though the overall methylation differences were subtle. The largest group (n = 23) contained most PITUIs and a subset of SCOs and was enriched for pathogenic mutations within genes in the MAPK/PI3K pathways (12/17 [71%] of sequenced tumors: FGFR1 (3), HRAS (3), BRAF (2), NF1 (2), CBL (1), MAP2K2 (1), PTEN (1)) and two with accompanying TERT promoter mutation. The second group (n = 16) contained most GCTs and a subset of SCOs, all of which mostly lacked identifiable genetic drivers. Outcome analysis demonstrated that the presence of chromosomal imbalances was significantly associated with reduced progression-free survival especially within the combined PITUI and SCO group (p = 0.031). In summary, we observed only subtle DNA methylation differences between posterior pituitary tumors, indicating that these tumors may be best classified as subtypes of a single entity. Nevertheless, our data indicate differences in mutation patterns and clinical outcome. For a clinically meaningful subclassification, we propose a combined histo-molecular approach into three subtypes: one subtype is defined by granular cell histology, scarcity of identifiable oncogenic mutations, and favorable outcome. The other two subtypes have either SCO or PITUI histology but are segregated by chromosomal copy number profile into a favorable group (no copy number changes) and a less favorable group (copy number imbalances present). Both of the latter groups have recurrent MAPK/PI3K genetic alterations that represent potential therapeutic targets

    Differential Income Taxation and Household Asset Allocation

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    This paper empirically investigates the effects of differential income taxation on households' portfolio choice and asset allocation applying a two-stage budgeting model of asset demand to German survey data. The model is structured into the discrete asset choice and the continuous asset choice, and the marginal income tax rate is simulated in a module of income taxation. Households that face relatively higher tax rates are found to have relatively greater demand for tax-privileged assets than households in the lower tax brackets. The higher the marginal tax rate the greater demand is for non-owner-occupied housing, for mortgage repayments, for building society deposits, for stocks, for insurances, and for consumer credits, whereas demand is lower for owner-occupied housing, bank deposits, and bonds

    Would a Flat Tax Stimulate Entrepreneurship in Germany?: A Behavioural Microsimulation Analysis Allowing for Risk

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    In debates about possible tax reforms, the impact on entrepreneurship is a primary concern. This paper estimates the ex-ante effects of the German tax reform 2000 and of two hypothetical flat tax scenarios on entries into and exits out of self-employment in Germany. For the estimation I apply a microsimulation model based on the tax-benefit model STSM and on structural microeconometric transition models. These structural models include an estimated parameter of risk aversion. The simulation results indicate that flatter tax systems discourage people from choosing self-employment, which is explained by the reduction of entrepreneurs ’ income risk through progressive taxation

    The ubiquitin proteasome system in neuropathology

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    The ubiquitin proteasome system (UPS) orchestrates the turnover of innumerable cellular proteins. In the process of ubiquitination the small protein ubiquitin is attached to a target protein by a peptide bond. The ubiquitinated target protein is subsequently shuttled to a protease complex known as the 26S proteasome and subjected to degradative proteolysis. The UPS facilitates the turnover of proteins in several settings. It targets oxidized, mutant or misfolded proteins for general proteolytic destruction, and allows for the tightly controlled and specific destruction of proteins involved in development and differentiation, cell cycle progression, circadian rhythms, apoptosis, and other biological processes. In neuropathology, alteration of the UPS, or mutations in UPS target proteins may result in signaling abnormalities leading to the initiation or progression of tumors such as astrocytomas, hemangioblastomas, craniopharyngiomas, pituitary adenomas, and medulloblastomas. Dysregulation of the UPS may also contribute to tumor progression by perturbation of DNA replication and mitotic control mechanisms, leading to genomic instability. In neurodegenerative diseases caused by the expression of mutant proteins, the cellular accumulation of these proteins may overload the UPS, indirectly contributing to the disease process, e.g., sporadic Parkinsonism and prion diseases. In other cases, mutation of UPS components may directly cause pathological accumulation of proteins, e.g., autosomal recessive Parkinsonism and spinocerebellar ataxias. Defects or dysfunction of the UPS may also underlie cognitive disorders such as Angelman syndrome, Rett syndrome and autism, and muscle and nerve diseases, e.g., inclusion body myopathy and giant axon neuropathy. This paper describes the basic biochemical mechanisms comprising the UPS and reviews both its theoretical and proven involvement in neuropathological diseases. The potential for the UPS as a target of pharmacological therapy is also discussed

    Potential Effects of a Statutory Minimum Wage on the Gender Pay Gap A Simulation-Based Study for Germany

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    In a simulation-based study with data from the German Socio-Economic Panel Study (SOEP), we analyze the effects of the newly introduced statutory minimum wage of 8.50 Euro per working hour in Germany on the gender wage gap. In our first scenario where we abstain from employment effects, the pay differential is reduced by 2.5 percentage points from 19.6 % to 17.1 %, due to a reduction of the sticky-floor effect at the bottom of the wage distribution. In more realistic scenarios where we incorporate minimum wage effects on labor demand, a further reduction of the pay gap by 0.2 pp (1.2 pp) in case of a monopsonistic (neoclassical) labor market is achieved. However, this comes at the cost of job losses by which women are more strongly affected than men. The magnitude of job losses ranges between 0.2 % and 3.0 % of all employees. It is higher in a neoclassical market setting and positively related to the assumed wage elasticity

    Household Savings Decision and Income Uncertainty

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    This paper empirically investigates the effects of changes in the interest rate as well as transitory income uncertainty on households' consumption-savings decision. Applying a structural demand model to German survey data, we estimate the uncompensated interest rate elasticity for savings, in line with the literature, to around zero. Accordingly, any policy-induced variation of net returns to savings is expected to have no significant effects on the level of savings. Moreover, we find significant effects of precautionary savings on the consumption-savings decision. As a result of a doubling of transitory income uncertainty, an average household increases savings by 4:4%. These effects vary by household composition and social status
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