Utility of serum biomarker indices for staging of hepatic fibrosis before and after venesection in patients with hemochromatosis caused by variants in HFE

Background & Aims Hemochromatosis that is associated with variants in the homeostatic iron regulator gene (HFE) is characterized by intestinal absorption of iron and excessive body and hepatic iron stores; it can lead to hepatic fibrosis and cirrhosis. Fibrosis has been staged by analysis of liver biopsies, but non-invasive staging methods are available. We evaluated the ability of aspartate aminotransferase:platelet ratio index (APRI), the fibrosis-4 (FIB-4) index, and gamma-glutamyl transferase:platelet ratio (GPR) to assess hepatic fibrosis staging in subjects with HFE-associated hemochromatosis, using liver biopsy-staged fibrosis as the reference standard. Methods We performed a retrospective, cross-sectional analysis of 181 subjects with HFE-associated hemochromatosis and hepatic fibrosis staged by biopsy analysis and available serum samples. We calculated APRI, FIB-4, and GPR at diagnosis for all 181 subjects and following venesection therapy in 64 of these subjects (7 subjects had follow-up biopsy analysis). We used area under the receiver operating characteristic curve (AUROC) analysis to assess the relationships between APRI score, FIB-4 score, and GPR and advanced (F3–F4) fibrosis and to select cut-off values. Results Hepatic fibrosis stage correlated with APRI score (r = 0.54; P \u3c .0001), FIB-4 score (r = 0.35; P \u3c .0001), and GPR (r = 0.36, P \u3c .0001). An APRI score above 0.44 identified patients with advanced fibrosis with an AUROC of 0.88, 79.4% sensitivity, 79.4% specificity, and 81% accuracy. A FIB-4 score above 1.1 identified patients with advanced fibrosis with an AUROC of 0.86, 80% sensitivity, 80.3% specificity, and 81% accuracy. A GPR above 0.27 identified patients with advanced fibrosis with an AUROC of 0.76, 67.7% sensitivity, 70.3% specificity, and 69% accuracy. APRI score was significantly more accurate than GPR (P = .05) in detecting advanced fibrosis; there was no difference between APRI and FIB-4. Venesection treatment was associated with significant reductions in APRI (P \u3c .0001) and GPR (P\u3c .001), paralleling fibrosis regression observed in available liver biopsies. Post-venesection APRI identified 87% of subjects with advanced fibrosis that decreased to levels that indicate stage F1–F2 fibrosis. Conclusions In a retrospective study of 181 subjects with HFE-associated hemochromatosis, we found that APRI and FIB-4 scores identified patients with advanced hepatic fibrosis with 81% accuracy. APRI scores might also be used to monitor fibrosis regression following venesection

Mass-sensitive particle tracking to elucidate the membrane-associated MinDE reaction cycle

An iSCAT image processing and analysis strategy enables mass-sensitive particle tracking (MSPT) of single unlabeled biomolecules on a supported lipid bilayer. MSPT was used to observe the (dis-)assembly of membrane complexes in real-time. In spite of their great importance in biology, methods providing access to spontaneous molecular interactions with and on biological membranes have been sparse. The recent advent of mass photometry to quantify mass distributions of unlabeled biomolecules landing on surfaces raised hopes that this approach could be transferred to membranes. Here, by introducing a new interferometric scattering (iSCAT) image processing and analysis strategy adapted to diffusing particles, we enable mass-sensitive particle tracking (MSPT) of single unlabeled biomolecules on a supported lipid bilayer. We applied this approach to the highly nonlinear reaction cycles underlying MinDE protein self-organization. MSPT allowed us to determine the stoichiometry and turnover of individual membrane-bound MinD/MinDE protein complexes and to quantify their size-dependent diffusion. This study demonstrates the potential of MSPT to enhance our quantitative understanding of membrane-associated biological systems.We thank D. Bollschweiler (Cryo-EM MPIB Core Facility) for the initial introduction to the commercial Refeyn OneMP mass photometer, the MPIB Biochemistry Core Facility (Recombinant Protein Production)

The Mt John University Observatory Search For Earth-mass Planets In The Habitable Zone Of Alpha Centauri

The "holy grail" in planet hunting is the detection of an Earth-analog: a planet with similar mass as the Earth and an orbit inside the habitable zone. If we can find such an Earth-analog around one of the stars in the immediate solar neighborhood, we could potentially even study it in such great detail to address the question of its potential habitability. Several groups have focused their planet detection efforts on the nearest stars. Our team is currently performing an intensive observing campaign on the alpha Centauri system using the Hercules spectrograph at the 1-m McLellan telescope at Mt John University Observatory (MJUO) in New Zealand. The goal of our project is to obtain such a large number of radial velocity measurements with sufficiently high temporal sampling to become sensitive to signals of Earth-mass planets in the habitable zones of the two stars in this binary system. Over the past years, we have collected more than 45,000 spectra for both stars combined. These data are currently processed by an advanced version of our radial velocity reduction pipeline, which eliminates the effect of spectral cross-contamination. Here we present simulations of the expected detection sensitivity to low-mass planets in the habitable zone by the Hercules program for various noise levels. We also discuss our expected sensitivity to the purported Earth-mass planet in an 3.24-d orbit announced by Dumusque et al.~(2012).Comment: 16 pages, 7 figures, accepted for publication in the International Journal of Astrobiolog

Trapped ions in optical lattices for probing oscillator chain models

We show that a chain of trapped ions embedded in microtraps generated by an optical lattice can be used to study oscillator models related to dry friction and energy transport. Numerical calculations with realistic experimental parameters demonstrate that both static and dynamic properties of the ion chain change significantly as the optical lattice power is varied. Finally, we lay out an experimental scheme to use the spin degree of freedom to probe the phase space structure and quantum critical behavior of the ion chain