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Crista junctions (CJs) are important for mitochondrial organization and function, but the molecular basis of their formation and architecture is obscure. We have identified and characterized a mitochondrial membrane protein in yeast, Fcj1 (formation of CJ protein 1), which is specifically enriched in CJs. Cells lacking Fcj1 lack CJs, exhibit concentric stacks of inner membrane in the mitochondrial matrix, and show increased levels of F1FO–ATP synthase (F1FO) supercomplexes. Overexpression of Fcj1 leads to increased CJ formation, branching of cristae, enlargement of CJ diameter, and reduced levels of F1FO supercomplexes. Impairment of F1FO oligomer formation by deletion of its subunits e/g (Su e/g) causes CJ diameter enlargement and reduction of cristae tip numbers and promotes cristae branching. Fcj1 and Su e/g genetically interact. We propose a model in which the antagonism between Fcj1 and Su e/g locally modulates the F1FO oligomeric state, thereby controlling membrane curvature of cristae to generate CJs and cristae tips.
This paper reports on Monte Carlo simulation results for future measurements of the moduli of time-like proton electromagnetic form factors, |GE | and |GM|, using the ¯pp → μ+μ− reaction at PANDA (FAIR). The electromagnetic form factors are fundamental quantities parameterizing the electric and magnetic structure of hadrons. This work estimates the statistical and total accuracy with which the form factors can be measured at PANDA, using an analysis of simulated data within the PandaRoot software framework. The most crucial background channel is ¯pp → π+π−,due to the very similar behavior of muons and pions in the detector. The suppression factors are evaluated for this and all other relevant background channels at different values of antiproton beam momentum. The signal/background separation is based on a multivariate analysis, using the Boosted Decision Trees method. An expected background subtraction is included in this study, based on realistic angular distribuations of the background contribution. Systematic uncertainties are considered and the relative total uncertainties of the form factor measurements are presented.
Challenges of FAIR phase 0
(2018)
After two-year's shutdown, the GSI accelerators plus the latest addition of storage ring CRYRING, will be back into operation in 2018 as the FAIR phase 0 with the goal to fulfill the needs of scientific community and the FAIR accelerators and detector development. Even though GSI has been well known for its operation of a variety of ion beams ranging from proton up to uranium for multi research areas such as nuclear physics, astrophysics, biophysics, material science, the upcoming beam time faces a number of challenges in re-commissioning its existing circular accelerators with brand new control system and upgrade of beam instrumentations, as well as in rising failures of dated components and systems. The cycling synchrotron SIS18 has been undergoing a set of upgrade measures for fulfilling future FAIR operation, among which many measures will also be commissioned during the upcoming beam time. This paper presents the highlights of the challenges such as re-establishing the high intensity heavy ion operation as well as parallel operation mode for serving multi users. The status of preparation including commissioning results will also be reported.
Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls.
Principal findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10−6) and 14 (IGHV1-67 p = 7.9×10−8) which indexed novel susceptibility loci.
Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
Mapping cortical brain asymmetry in 17,141 healthy individuals worldwide via the ENIGMA Consortium
(2017)
Background: Although being considered as a rarely observed HIV-1 protease mutation in clinical isolates, the L76V-prevalence increased 1998-2008 in some European countries most likely due to the approval of Lopinavir, Amprenavir and Darunavir which can select L76V. Beside an enhancement of resistance, L76V is also discussed to confer hypersusceptibility to the drugs Atazanavir and Saquinavir which might enable new treatment strategies by trying to take advantage of particular mutations. Results: Based on a cohort of 47 L76V-positive patients, we examined if there might exist a clinical advantage for L76V-positive patients concerning long-term success of PI-containing regimens in patients with limited therapy options. Genotypic- and phenotypic HIV-resistance tests from 47 mostly multi-resistant, L76V-positive patients throughout Germany were accomplished retrospectively 1999-2009. Five genotype-based drug-susceptibility predictions received from online interpretation-tools for Atazanavir, Saquinavir, Amprenavir and Lopinavir, were compared to phenotype-based predictions that were determined by using a recombinant virus assay along with a Virtual Phenotype™(Virco). The clinical outcome of the L76V-adapted follow-up therapy was determined by monitoring viral load for 96 weeks. Conclusions: In this analysis, the mostly used interpretation systems overestimated the L76V-mutation concerning Atazanavir- and SQV resistance. In fact, a clear benefit in drug susceptibility for these drugs was observed in phenotype analysis after establishment of L76V. More importantly, long-term therapy success was significantly higher in patients receiving Atazanavir and/or Saquinavir plus one L76V-selecting drug compared to patients without L76V-selecting agents (p = 0.002). In case of L76V-occurrence ATV and/or SQV may represent encouraging options for patients in deep salvage situations.
Background and objectives: Our study aimed at examining the long-time inflammatory effects of rheumatoid arthritis (RA) as chronic immune-mediated disease on pain sensation and neuropathy development compared to healthy subjects (HS).
Methods: We used the quantitative sensory testing (QST) protocol of the German Research Network on Neuropathic Pain and Electroencephalography (EEG)–based contact heat evoked potentials (CHEPs) before and after topical capsaicin application. We recruited 16 RA patients in remission or low disease activity state (mean age: 59.38 years [± 10.18]) and 16 healthy subjects (mean age: 56.69 years [± 8.92]).
Results: The application of capsaicin cream on the thigh provoked a stronger effect in HS for both mechanical and heat pain thresholds (MPT and HPT, resp.), according to the area under the receiver operation characteristic (AUROC) (HS: HPT: 0.8965, MPT: 0.7402; RA: HPT: 0.7012, MPT: 0.6113). We observed contrary effects regarding changes in CHEPs (HS: g*max = − 0.65; RA patients: g*max = 0.72).
Conclusion: As the overall effect of topical capsaicin application was higher in HS for QST, we suggest the existence of a sensitization of TRPV1 channels in RA patients caused by long-time chronical inflammation, despite a lack of clinical signs of inflammation due to adequate treatment. The effect in CHEPs probably uncovers neuropathic symptoms. The effect of topical capsaicin on HPTs and CHEPs can act as a marker for the extent of sensitization and the development of neuropathic symptoms. Further studies are needed to prove if our proposed method can act as a marker for the success of anti-inflammatory treatment.