Challenging Varieties of Capitalism's Account of Business Interests: The New Social Market Initiative and German Employers' Quest for Liberalization, 2000-2014

Do employers in coordinated market economies (CME's) actively defend the non-liberal, market- constraining institutions upon which their strategic coordination and competitive success depends? This paper revisits the debate over firms' employer preferences with an in-depth examination of employers in Germany - a paradigmatic CME and crucial "test case" for Varieties of Capitalism. It is based on interviews with key officials and an in-depth examination of a large-scale campaign - the New Social Market Initiative or INMS - founded and funded by German metalworking employers to shape public opinion. The paper argues that German employers have a strong preference for liberalization: they have pushed hard for the liberalization of labor markets, the reduction of government expenditures, the expansion of market-oriented freedoms, and cuts to social protection, employment protection and benefit entitlements. I find no empirical support for the claim that the INSM is an attempt to appease discontented firms within employers' associations. On the contrary: for many employers, the Agenda 2010 reforms did not go far enough. Following the discrediting of the Anglo-American model in the financial crisis, far-reaching concessions by employees, and the unexpected revitalization of the German economy, employers have moderated their demands - but liberalization remains their default preference. This paper also addresses the role of ideas and the conditions under which employer campaigns can influence policy.Verteidigen Arbeitgeber in koordinierten Marktwirtschaften aktiv die nichtliberalen, marktbeschränkenden Institutionen, von denen ihre Möglichkeiten zur strategischen Koordination und ihr Erfolg im Wettbewerb abhängen? Mit einer umfassenden Untersuchung der Präferenzen von Arbeitgebern in Deutschland, das als typisches Beispiel einer koordinierten Marktwirtschaft und wegweisender "Testfall" für die Theorie über Spielarten des Kapitalismus gilt, greift dieses Discussion Paper die Debatte über die Präferenzen von Unternehmen in ihrer Eigenschaft als Arbeitgeber auf. Es basiert auf Interviews mit führenden Arbeitgeberfunktionären sowie einer detaillierten Untersuchung der Initiative Neue Soziale Marktwirtschaft (INSM): einer groß angelegten, von deutschen Metallarbeitgebern initiierten und finanzierten Kampagne zur öffentlichen Meinungsbildung. Der Beitrag belegt eine deutliche Präferenz deutscher Arbeitgeber für die Liberalisierung. Mit Nachdruck haben sie sich für eine Liberalisierung der Arbeitsmärkte, eine Senkung der Staatsausgaben und eine Ausweitung marktorientierter Gestaltungsfreiheiten ebenso eingesetzt wie für Einschnitte bei der sozialen Sicherung, dem Kündigungsschutz und den Versorgungsansprüchen. Die Behauptung, die INSM sei ein Versuch, unzufriedene Unternehmen innerhalb der Arbeitgeberverbände zu beschwichtigen, lässt sich durch die empirischen Befunde nicht stützen. Im Gegenteil: Vielen Arbeitgebern gingen die Reformen im Zuge der Agenda 2010 nicht weit genug. Zwar haben die deutschen Arbeitgeber nach der Diskreditierung des angloamerikanischen Modells während der Finanzkrise, weitreichenden Zugeständnissen seitens der Arbeitnehmer sowie der unerwarteten Wiederbelebung der deutschen Wirtschaft ihre Forderungen gemäßigt - doch bleibt ihre grundlegende Präferenz für die Liberalisierung bestehen. Dieser Beitrag befasst sich außerdem mit der Rolle von Ideen sowie den Bedingungen, unter denen Arbeitgeberkampagnen politische Maßnahmen beeinflussen können

Muscle regulates mTOR dependent axonal local translation in motor neurons via CTRP3 secretion: implications for a neuromuscular disorder, spinal muscular atrophy

Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder, which causes dysfunction/loss of lower motor neurons and muscle weakness as well as atrophy. While SMA is primarily considered as a motor neuron disease, recent data suggests that survival motor neuron (SMN) deficiency in muscle causes intrinsic defects. We systematically profiled secreted proteins from control and SMN deficient muscle cells with two combined metabolic labeling methods and mass spectrometry. From the screening, we found lower levels of C1q/TNF-related protein 3 (CTRP3) in the SMA muscle secretome and confirmed that CTRP3 levels are indeed reduced in muscle tissues and serum of an SMA mouse model. We identified that CTRP3 regulates neuronal protein synthesis including SMN via mTOR pathway. Furthermore, CTRP3 enhances axonal outgrowth and protein synthesis rate, which are well-known impaired processes in SMA motor neurons. Our data revealed a new molecular mechanism by which muscles regulate the physiology of motor neurons via secreted molecules. Dysregulation of this mechanism contributes to the pathophysiology of SMA

Neuronal activity regulates DROSHA via autophagy in spinal muscular atrophy

Dysregulated miRNA expression and mutation of genes involved in miRNA biogenesis have been reported in motor neuron diseases including spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). Therefore, identifying molecular mechanisms governing miRNA expression is important to understand these diseases. Here, we report that expression of DROSHA, which is a critical enzyme in the microprocessor complex and essential for miRNA biogenesis, is reduced in motor neurons from an SMA mouse model. We show that DROSHA is degraded by neuronal activity induced autophagy machinery, which is also dysregulated in SMA. Blocking neuronal activity or the autophagy-lysosome pathway restores DROSHA levels in SMA motor neurons. Moreover, reducing DROSHA levels enhances axonal growth. As impaired axonal growth is a well described phenotype of SMA motor neurons, these data suggest that DROSHA reduction by autophagy may mitigate the phenotype of SMA. In summary, these findings suggest that autophagy regulates RNA metabolism and neuronal growth via the DROSHA/miRNA pathway and this pathway is dysregulated in SMA

Neuronal activity regulates DROSHA via autophagy in spinal muscular atrophy

Dysregulated miRNA expression and mutation of genes involved in miRNA biogenesis have been reported in motor neuron diseases including spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). Therefore, identifying molecular mechanisms governing miRNA expression is important to understand these diseases. Here, we report that expression of DROSHA, which is a critical enzyme in the microprocessor complex and essential for miRNA biogenesis, is reduced in motor neurons from an SMA mouse model. We show that DROSHA is degraded by neuronal activity induced autophagy machinery, which is also dysregulated in SMA. Blocking neuronal activity or the autophagy-lysosome pathway restores DROSHA levels in SMA motor neurons. Moreover, reducing DROSHA levels enhances axonal growth. As impaired axonal growth is a well described phenotype of SMA motor neurons, these data suggest that DROSHA reduction by autophagy may mitigate the phenotype of SMA. In summary, these findings suggest that autophagy regulates RNA metabolism and neuronal growth via the DROSHA/miRNA pathway and this pathway is dysregulated in SMA

De Novo and Inherited Variants in GBF1 are Associated with Axonal Neuropathy Caused by Golgi Fragmentation

Distal hereditary motor neuropathies (HMNs) and axonal Charcot-Marie-Tooth neuropathy (CMT2) are clinically and genetically heterogeneous diseases characterized primarily by motor neuron degeneration and distal weakness. The genetic cause for about half of the individuals affected by HMN/CMT2 remains unknown. Here, we report the identification of pathogenic variants in GBF1 (Golgi brefeldin A-resistant guanine nucleotide exchange factor 1) in four unrelated families with individuals affected by sporadic or dominant HMN/CMT2. Genomic sequencing analyses in seven affected individuals uncovered four distinct heterozygous GBF1 variants, two of which occurred de novo. Other known HMN/CMT2-implicated genes were excluded. Affected individuals show HMN/CMT2 with slowly progressive distal muscle weakness and musculoskeletal deformities. Electrophysiological studies confirmed axonal damage with chronic neurogenic changes. Three individuals had additional distal sensory loss. GBF1 encodes a guanine-nucleotide exchange factor that facilitates the activation of members of the ARF (ADP-ribosylation factor) family of small GTPases. GBF1 is mainly involved in the formation of coatomer protein complex (COPI) vesicles, maintenance and function of the Golgi apparatus, and mitochondria migration and positioning. We demonstrate that GBF1 is present in mouse spinal cord and muscle tissues and is particularly abundant in neuropathologically relevant sites, such as the motor neuron and the growth cone. Consistent with the described role of GBF1 in Golgi function and maintenance, we observed marked increase in Golgi fragmentation in primary fibroblasts derived from all affected individuals in this study. Our results not only reinforce the existing link between Golgi fragmentation and neurodegeneration but also demonstrate that pathogenic variants in GBF1 are associated with HMN/CMT2

Effects of Specific Multi-Nutrient Enriched Diets on Cerebral Metabolism, Cognition and Neuropathology in AbetaPPswe-PS1dE9 Mice

Contains fulltext : 119269.pdf (publisher's version ) (Open Access)Recent studies have focused on the use of multi-nutrient dietary interventions in search of alternatives for the treatment and prevention of Alzheimer's disease (AD). In this study we investigated to which extent long-term consumption of two specific multi-nutrient diets can modulate AD-related etiopathogenic mechanisms and behavior in 11-12-month-old AbetaPPswe-PS1dE9 mice. Starting from 2 months of age, male AbetaPP-PS1 mice and wild-type littermates were fed either a control diet, the DHA+EPA+UMP (DEU) diet enriched with uridine monophosphate (UMP) and the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), or the Fortasyn(R) Connect (FC) diet enriched with the DEU diet plus phospholipids, choline, folic acid, vitamins and antioxidants. We performed behavioral testing, proton magnetic resonance spectroscopy, immunohistochemistry, biochemical analyses and quantitative real-time PCR to gain a better understanding of the potential mechanisms by which these multi-nutrient diets exert protective properties against AD. Our results show that both diets were equally effective in changing brain fatty acid and cholesterol profiles. However, the diets differentially affected AD-related pathologies and behavioral measures, suggesting that the effectiveness of specific nutrients may depend on the dietary context in which they are provided. The FC diet was more effective than the DEU diet in counteracting neurodegenerative aspects of AD and enhancing processes involved in neuronal maintenance and repair. Both diets elevated interleukin-1beta mRNA levels in AbetaPP-PS1 and wild-type mice. The FC diet additionally restored neurogenesis in AbetaPP-PS1 mice, decreased hippocampal levels of unbound choline-containing compounds in wild-type and AbetaPP-PS1 animals, suggesting diminished membrane turnover, and decreased anxiety-related behavior in the open field behavior. In conclusion, the current data indicate that specific multi-nutrient diets can influence AD-related etiopathogenic processes. Intervention with the FC diet might be of interest for several other neurodegenerative and neurological disorders