TAC102 is a novel component of the mitochondrial genome segregation machinery in trypanosomes

Trypanosomes show an intriguing organization of their mitochondrial DNA into a catenated network, the kinetoplast DNA (kDNA). While more than 30 proteins involved in kDNA replication have been described, only few components of kDNA segregation machinery are currently known. Electron microscopy studies identified a high-order structure, the tripartite attachment complex (TAC), linking the basal body of the flagellum via the mitochondrial membranes to the kDNA. Here we describe TAC102, a novel core component of the TAC, which is essential for proper kDNA segregation during cell division. Loss of TAC102 leads to mitochondrial genome missegregation but has no impact on proper organelle biogenesis and segregation. The protein is present throughout the cell cycle and is assembled into the newly developing TAC only after the pro-basal body has matured indicating a hierarchy in the assembly process. Furthermore, we provide evidence that the TAC is replicated de novo rather than using a semi-conservative mechanism. Lastly, we demonstrate that TAC102 lacks an N-terminal mitochondrial targeting sequence and requires sequences in the C-terminal part of the protein for its proper localization

Conflict perceptions across 27 OECD countries: the roles of socioeconomic inequality and collective stratification beliefs

Socioeconomic inequality and conflicts regarding distributional issues have resurfaced in many OECD countries over the past three decades. Whereas most research has focused on the objective determinants of perceived social conflicts, we contribute a new facet to this discussion by assessing the relevance of collective stratification beliefs as an independent driver of vertical conflict perceptions. After formulating theoretical positions that give precedence to two factors in explaining the perceptions of social conflicts - objective inequality and the collective stratification belief - we use individual-level data from the 2009 International Social Survey Programme, along with suitable country-level indicators to evaluate both hypotheses. Amid the diverse collective stratification beliefs, we focus on the role of an egalitarian (middle-) class imagery. We are particularly interested in the extent to which such a class imagery can mediate the relationship between socioeconomic inequality and individual conflict perceptions. The results of our multilevel analyses of 27 OECD countries indicate that an egalitarian (middle-) class imagery held by a certain share of a country’s population constitutes a distinct dimension of reality and clearly dominates country-level objective inequality in the explanation of individually perceived social conflicts

Does selective inhibition training reduce relapse rates when added to standard treatment of alcohol use disorder? A randomized controlled trial

Background: Alcohol-dependent individuals tend to selectively approach alcohol cues in the environment, demonstrating an alcohol approach bias. Approach Bias Modification (ApBM) training can reduce the approach bias and decrease relapse rates in alcohol-dependent patients when added to abstinence-focused treatment. It has therefore become part of regular treatment. Moreover, in Selective Inhibition (SI-) Training, responses to one category of stimuli (i.e., alcohol stimuli) are selectively inhibited in an adapted Go/No-Go-Task. SI-Training has been found to effectively devalue the inhibited category, and to reduce consumption of alcohol in social drinkers. This study investigated whether SI-Training can further improve treatment effects of treatment-as-usual that includes ApBM, and if so, whether the effect is mediated by a devaluation of the inhibited alcohol stimuli. Methods: For 6 sessions, 434 abstinent alcohol-dependent inpatients were randomly assigned to receive either active (n = 214, 32% female) or sham (n= 220, 38% female) SI-Training, in addition to standard treatment including active ApBM. Ratings were used to assess changes in the evaluation of alcohol stimuli after the training. Relapse rates were assessed three months and twelve months after treatment discharge. Results: Alcohol stimuli were rated negatively before and after the training, and the training did not influence these ratings. Evaluation of nonalcoholic drinks became more positive after active SI-Training. Both ApBM and SI-Training showed the expected training effects on reaction times. Contrary to expectations, SI-Training conditions did not yield different abstinence rates three or twelve months after treatment. Conclusions: No evidence was found for the hypothesis that SI-Training would amplify the relapse-preventing effect of ApBM. Moreover, alcohol stimuli were rated negatively before and after treatment and were not influenced by SI-Training

Purification and characterization of a trypanothione-glutathione thioltransferase from Trypanosoma cruzi.

Although trypanothione [T(S)2] is the major thiol component in trypanosomatidae, significant amounts of glutathione are present in Trypanosoma cruzi. This could be explained by the existence of enzymes using glutathione or both glutathione and T(S)2 as cofactors. To assess these hypotheses, a cytosolic fraction of T. cruzi epimastigotes was subjected to affinity chromatography columns using as ligands either S-hexylglutathione or a non-reducible analogue of trypanothione disulphide. A similar protein of 52 kDa was eluted in both cases. Its partial amino acid sequence indicated that it was identical with the protein encoded by the TcAc2 cDNA previously described [Schoneck, Plumas-Marty, Taibi et al. (1994) Biol. Cell 80, 1-10]. This protein showed no significant glutathione transferase activity but surprisingly catalysed the thiol-disulphide exchange between dihydrotrypanothione and glutathione disulphide. The kinetic parameters were in the same range as those determined for trypanothione reductase toward its natural substrate. This trypanothione-glutathione thioltransferase provides a new target for a specific chemotherapy against Chagas' disease and may constitute a link between the glutathione-based metabolism of the host and the trypanothione-based metabolism of the parasite