The magic of naming

Peer reviewe

Competition: a test of freedom

Peer reviewe

The significance of regionality : Challenges and strenghts of development

Peer reviewe

Roma people

Peer reviewe

HRES-1/Rab4-mediated depletion of Drp1 impairs mitochondrial homeostasis and represents a target for treatment in SLE.

OBJECTIVE: Accumulation of mitochondria underlies T-cell dysfunction in systemic lupus erythematosus (SLE). Mitochondrial turnover involves endosomal traffic regulated by HRES-1/Rab4, a small GTPase that is overexpressed in lupus T cells. Therefore, we investigated whether (1) HRES-1/Rab4 impacts mitochondrial homeostasis and (2) Rab geranylgeranyl transferase inhibitor 3-PEHPC blocks mitochondrial accumulation in T cells, autoimmunity and disease development in lupus-prone mice. METHODS: Mitochondria were evaluated in peripheral blood lymphocytes (PBL) of 38 SLE patients and 21 healthy controls and mouse models by flow cytometry, microscopy and western blot. MRL/lpr mice were treated with 125 μg/kg 3-PEHPC or 1 mg/kg rapamycin for 10 weeks, from 4 weeks of age. Disease was monitored by antinuclear antibody (ANA) production, proteinuria, and renal histology. RESULTS: Overexpression of HRES-1/Rab4 increased the mitochondrial mass of PBL (1.4-fold; p=0.019) and Jurkat cells (2-fold; p=0.000016) and depleted the mitophagy initiator protein Drp1 both in human (-49%; p=0.01) and mouse lymphocytes (-41%; p=0.03). Drp1 protein levels were profoundly diminished in PBL of SLE patients (-86±3%; p=0.012). T cells of 4-week-old MRL/lpr mice exhibited 4.7-fold over-expression of Rab4A (p=0.0002), the murine homologue of HRES-1/Rab4, and depletion of Drp1 that preceded the accumulation of mitochondria, ANA production and nephritis. 3-PEHPC increased Drp1 (p=0.03) and reduced mitochondrial mass in T cells (p=0.02) and diminished ANA production (p=0.021), proteinuria (p=0.00004), and nephritis scores of lupus-prone mice (p<0.001). CONCLUSIONS: These data reveal a pathogenic role for HRES-1/Rab4-mediated Drp1 depletion and identify endocytic control of mitophagy as a treatment target in SLE

Lacking rule of law in the lawyers’ regime : Hungary

The article argues that the current problems regarding the rule of law under the Fidesz-regime (2010–2018) are due to continuities of legal thought of the 19th century. The Western liberal conception of the rule of law has little ground to become rooted in Hungary because of the country’s incompatible legal and political traditions, lack of intellectual receptiveness to host the idea and weak institutions to anchor it. The analysis focuses on five angles that affect the Hungarian perception of the rule of law: (1) the traditional conceptual understanding of the rule of law and statecraft; (2) the special trust in lawyers and the legal profession; (3) the relevance of the way the system changed in 1989–1990 in terms of democratisation and legislative culture; (4) the constitutional change carried out by the Fidesz administration in 2010–2014 and (5) a new era of nationalism, as the second phase of the Fidesz-revolution, which can be regarded as a declaration of paradigm-change in the conception of democracy. The overproduction of laws was the means of authoritarian development, thus, technically the core problem of democracy is the ‘rule of law’.Peer reviewe

Defining the new polity : constitutional memory in Hungary and beyond

This article examines constitutions as a special effort of constructing long-lasting national memories. These images of the past become, with the assistance of the constitutions, canonised in the heart of the entire legal system that should be obeyed by each and every citizen. The conceptions of history represented by the Constitution are effectively spread by the government machinery and maintained unchanged for a relatively long time due to the solid character of constitutions. This study focuses on the characteristics of Eastern European constitutions and more specifically on the Hungarian Constitution’s history-images and their relation to identity. The Hungarian Constitution is the most recent European case that has been brought into the limelight of the international media because of its questionable jurisdiction process that ran against the contemporary democratic values of legal thinking in the Western hemisphere. The present study draws on legal sources and debates of legal experts in the making and assessment of this legal document. In addition, the analysis also relies on public discourse related to the reception of the troubled legislation and its modification process.Peer reviewe

Cleavage of transaldolase by granzyme B causes the loss of enzymatic activity with retention of antigenicity for multiple sclerosis patients

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the CNS resulting from a progressive loss of oligodendrocytes. Transaldolase (TAL) is expressed at selectively high levels in oligodendrocytes of the brain, and postmortem sections show concurrent loss of myelin basic protein and TAL from sites of demyelination. Infiltrating CD8(+) CTLs are thought to play a key role in oligodendrocyte cell death. Cleavage by granzyme B (GrB) is predictive for autoantigenicity of self-proteins, thereby further implicating CTL-induced death in the initiation and propagation of autoimmunity. The precursor frequency and CTL activity of HLA-A2–restricted TAL 168–176–specific CD8(+) T cells is increased in MS patients. In this paper, we show that TAL, but not myelin basic protein, is specifically cleaved by human GrB. The recognition site of GrB that resulted in the cleavage of a dominant TAL fragment was mapped to a VVAD motif at aa residue 27 by N-terminal sequencing and confirmed by site-directed mutagenesis. The major C-terminal GrB cleavage product, residues 28–337, had no enzymatic activity but retained the antigenicity of full-length TAL, effectively stimulating the proliferation and CTL activity of PBMCs and of CD8(+) T cell lines from patients with MS. Sera of MS patients exhibited similar binding affinity to wild-type and GrB-cleaved TAL. Because GrB mediates the killing of target cells and cleavage by GrB is predictive of autoantigen status of self proteins, GrB-cleaved TAL-specific T cell-mediated cytotoxicity may contribute to the progressive destruction of oligodendrocytes in patients with MS