WP 87 - Emigration and labour shortages. An opportunity for trade unions in new member states?

The paper explores whether and how unions in the post-socialist EU member states have responded to the opportunity of improving their situation, offered by the increased emigration after the recent EU enlargements. Migration influences the labour force composition and unemployment rates, which could facilitate union organizing and bargaining position, and in consequence enhance union legitimacy and bargaining institutions. We adopt an actor-oriented framework to examine union strategies and actions, and we test the above hypotheses in the public healthcare sector largely affected by migration in Slovakia, Poland and Hungary. We argue that variation in union strategies depends mainly on the interplay of union capacities and state strategies. Slovak unions used migration-triggered labour shortages to obtain wage increases and to consolidate existing bargaining channels. In contrast, Polish unions responded to migration-induced labour shortages through industrial action, while Hungarian healthcare unions remained the least active in seizing migration-related opportunities to enhance legitimacy or bargaining institutions.

Post-translational modifications of RINT1 (RAD50-interacting protein 1)

Initially found to regulate G2/M cell cycle checkpoint upon irradiation-induced DNA damage, RINT1 (RAD50-interacting protein 1) was later shown to be a multifunctional protein. RINT1 participates in telomerase-independent telomere length maintenance, membrane trafficking between Golgi apparatus and endoplasmic reticulum and ER-Golgi homeostasis. Inactivation of Rint1 leads to an early embryonic lethality. RINT1 can act as tumor suppressor, since heterozygous inactivation results in tumor formation in mice, while in humans mutant RINT1 variants predispose to development of breast- and Lynch syndrome-related cancers. RINT1 was also proposed to be an oncogene for glioblastoma development. Nevertheless, despite its involvement in a variety of biological pathways, no data regarding post-translational modifications (PTM) of RINT1 or their impact on the protein’s function was reported. The present study shows that RINT1 is subjected to two kinds of post-translational modifications: ubiquitination and, putatively, SUMOylation. It was found that RINT1 is a short-lived protein with a half-life (approx. 40 min) regulated by a proteasomal degradation pathway. RINT1 is ubiquitinated by several ubiquitin linkage types. Since K48-mediated polyubiquitin (polyUb) chains as well as K63- and K29-mediated polyUb chains were detected, functional significance of RINT1 ubiquitination is not limited to proteasomal degradation (K48-mediated polyUb chains) but could also serve to regulate multiple cellular functions of RINT1 (K63- and K29-mediated polyUb chains). Interestingly, RINT1 was also found to interact with lysineless ubiquitin mutant. Thus, monoubiquitination or linear ubiquitination (a less characterized and newly discovered PTM) of RINT1 could also be postulated. Furthermore, analysis of in silico predicted ubiquitination sites of RINT1 by co-immunoprecipitation of mutant versions (truncated mutants and site-directed mutagenesis) revealed that RINT1 is ubiquitinated at different sites within the protein. Two E3 ubiquitin ligases, HUWE1 and RNF20/RNF40E3 complex, were identified by mass spectrometry assay as binding partners mediating ubiquitination of RINT1. The specificity of these interactions was subsequently confirmed by co-immunoprecipitation experiments. Importantly, shRNA-induced down-regulation of HUWE1 and RNF20 or RNF40 protein levels resulted in enhanced RINT1 stability, thus indicated their novel role as regulators of proteasomal degradation of RINT1. Moreover, mass spectrometry analysis and yeast two-hybrid assay identified SUMOylation as another covalent modification of RINT1. First experiments suggested covalent modification of RINT1 by SUMO proteins. In conclusion, the present study demonstrated that human RINT1 is a protein of a short-half life, heavily ubiquitinated at different sites within the protein and via different ubiquitin chain linkage types (K29, K48, K63). It is also modified by a lysineless ubiquitin mutant and potentially SUMOylation. Importantly, RINT1 interacts with HUWE1 and RNF20/40 E3 ubiquitin ligases, which tightly control its cellular levels. This study reveals crucial mechanisms governing homeostatic RINT1 turnover and, in this respect, is the first to address the presence and functionality of RINT1 polyubiquitination

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Identification of the first in Poland CACNA1A gene mutation in familial hemiplegic migraine. Case report

Introduction Migraine is a common neurological disorder characterized by a particular phenotype, complex pathophysiology and a heterogeneous genetic background. Among several heritable forms, familial hemiplegic migraine is the best described one. In the majority of cases it is caused by mutations in one of three different genes. Case report Clinical symptoms of a 47 year old proband (and independently described in his 20 year old son) as well as differential diagnosis are discussed in the presented report. The most characteristic were recurrent attacks of blurred vision, paresthesias and hemiparesis often accompanied by speech disturbances and followed by severe headache with vomiting. Advanced morphological and genetic procedures were required to exclude MELAS, CADASIL and Call-Fleming syndrome. Finally, the definite diagnosis was possible after the application of the whole exome sequencing technique. It confirmed, for the first time in the Polish population, a heterozygous T666M mutation (c.1997C>T; p.Thr666Met) in the CACNA1A gene in the proband, the proband's son and in several other family members. Conclusion The presented report provides clinical and genetic insight into familial hemiplegic migraine 1 resulting from a mutation in the CACNA1A gene

CAV3 mutation in a patient with transient hyperCKemia and myalgia

Mutations in caveolin-3 (CAV3) can lead to different clinical phenotypes affecting skeletal or cardiac muscles. Here, we describe a patient with Klinefelter syndrome, ulcerative colitis and Sjögren syndrome, who developed transient hyperCKemia, myalgia and mild muscular weakness. Using whole exome sequencing (WES), a missense mutation G169A was found in the CAV3 gene. In addition, we identified a homozygous frameshift deletion in MS4A12 that may contribute to inflammatory bowel disease, further demonstrating usefulness of WES in dual molecular diagnoses