Muscle thixotropy: more than just cross-bridges?

AbstractAlthough Campbell and Lakie in a Comment to the Editor in this issue of Biophysical Journal suggested that exclusive cross-bridge action is behind muscle thixotropy, recent findings and our preliminary observations suggest that additional mechanisms could also be involved

The effect of lysergic acid diethylamide (LSD) on whole-brain functional and effective connectivity

Psychedelics have emerged as promising candidate treatments for various psychiatric conditions, and given their clinical potential, there is a need to identify biomarkers that underlie their effects. Here, we investigate the neural mechanisms of lysergic acid diethylamide (LSD) using regression dynamic causal modelling (rDCM), a novel technique that assesses whole-brain effective connectivity (EC) during resting-state functional magnetic resonance imaging (fMRI). We modelled data from two randomised, placebo-controlled, double-blind, cross-over trials, in which 45 participants were administered 100 μg LSD and placebo in two resting-state fMRI sessions. We compared EC against whole-brain functional connectivity (FC) using classical statistics and machine learning methods. Multivariate analyses of EC parameters revealed predominantly stronger interregional connectivity and reduced self-inhibition under LSD compared to placebo, with the notable exception of weakened interregional connectivity and increased self-inhibition in occipital brain regions as well as subcortical regions. Together, these findings suggests that LSD perturbs the Excitation/Inhibition balance of the brain. Notably, whole-brain EC did not only provide additional mechanistic insight into the effects of LSD on the Excitation/Inhibition balance of the brain, but EC also correlated with global subjective effects of LSD and discriminated experimental conditions in a machine learning-based analysis with high accuracy (91.11%), highlighting the potential of using whole-brain EC to decode or predict subjective effects of LSD in the future

Photon Radiation with MadDipole

We present the automation of a subtraction method for photon radiation using the dipole formalism within the MadGraph framework. The subtraction terms are implemented both in dimensional regularization and mass regularization for massless and massive cases and non-collinear-safe observables are accounted for.Comment: 23 pages, 2 figures, minor additions, references added, version published in JHE

Antenna subtraction with massive fermions at NNLO: Double real initial-final configurations

We derive the integrated forms of specific initial-final tree-level four-parton antenna functions involving a massless initial-state parton and a massive final-state fermion as hard radiators. These antennae are needed in the subtraction terms required to evaluate the double real corrections to $t\bar{t}$ hadronic production at the NNLO level stemming from the partonic processes $q\bar{q}\to t\bar{t}q'\bar{q}'$ and $gg\to t\bar{t}q\bar{q}$.Comment: 24 pages, 1 figure, 1 Mathematica file attache

TRIGA-SPEC: A setup for mass spectrometry and laser spectroscopy at the research reactor TRIGA Mainz

The research reactor TRIGA Mainz is an ideal facility to provide neutron-rich nuclides with production rates sufficiently large for mass spectrometric and laser spectroscopic studies. Within the TRIGA-SPEC project, a Penning trap as well as a beam line for collinear laser spectroscopy are being installed. Several new developments will ensure high sensitivity of the trap setup enabling mass measurements even on a single ion. Besides neutron-rich fission products produced in the reactor, also heavy nuclides such as 235-U or 252-Cf can be investigated for the first time with an off-line ion source. The data provided by the mass measurements will be of interest for astrophysical calculations on the rapid neutron-capture process as well as for tests of mass models in the heavy-mass region. The laser spectroscopic measurements will yield model-independent information on nuclear ground-state properties such as nuclear moments and charge radii of neutron-rich nuclei of refractory elements far from stability. This publication describes the experimental setup as well as its present status.Comment: 20 pages, 17 figure

Crystal structure, biochemical and cellular activities demonstrate separate functions of MTH1 and MTH2

Deregulated redox metabolism in cancer leads to oxidative damage to cellular components including deoxyribonucleoside triphosphates (dNTPs). Targeting dNTP pool sanitizing enzymes, such as MTH1, is a highly promising anticancer strategy. The MTH2 protein, known as NUDT15, is described as the second human homologue of bacterial MutT with 8-oxo-dGTPase activity. We present the first NUDT15 crystal structure and demonstrate that NUDT15 prefers other nucleotide substrates over 8-oxo-dGTP. Key structural features are identified that explain different substrate preferences for NUDT15 and MTH1. We find that depletion of NUDT15 has no effect on incorporation of 8-oxo-dGTP into DNA and does not impact cancer cell survival in cell lines tested. NUDT17 and NUDT18 were also profiled and found to have far less activity than MTH1 against oxidized nucleotides. We show that NUDT15 is not a biologically relevant 8-oxo-dGTPase, and that MTH1 is the most prominent sanitizer of the cellular dNTP pool known to date

Bead arrays for antibody and complement profiling reveal joint contribution of antibody isotypes to C3 deposition

The development of antigen arrays has provided researchers with great tools to identify reactivities against self or foreign antigens from body fluids. Yet, these approaches mostly do not address antibody isotypes and their effector functions even though these are key points for a more detailed understanding of disease processes. Here, we present a bead array-based assay for a multiplexed determination of antigen-specific antibody levels in parallel with their properties for complement activation. We measured the deposition of C3 fragments from serum samples to reflect the degree of complement activation via all three complement activation pathways. We utilized the assay on a bead array containing native and citrullinated peptide antigens to investigate the levels of IgG, IgM and IgA autoantibodies along with their complement activating properties in serum samples of 41 rheumatoid arthritis patients and 40 controls. Our analysis revealed significantly higher IgG reactivity against the citrullinated fibrinogen β and filaggrin peptides as well as an IgA reactivity that was exclusive for citrullinated fibrinogen β peptide and C3 deposition in rheumatoid arthritis patients. In addition, we characterized the humoral immune response against the viral EBNA-1 antigen to demonstrate the applicability of this assay beyond autoimmune conditions. We observed that particular buffer compositions were demanded for separate measurement of antibody reactivity and complement activation, as detection of antigen-antibody complexes appeared to be masked due to C3 deposition. We also found that rheumatoid factors of IgM isotype altered C3 deposition and introduced false-positive reactivities against EBNA-1 antigen. In conclusion, the presented bead-based assay setup can be utilized to profile antibody reactivities and immune-complex induced complement activation in a high-throughput manner and could facilitate the understanding and diagnosis of several diseases where complement activation plays role in the pathomechanism

Conceptual Design of the Modular Detector and Readout System for the CMB-S4 survey experiment

We present the conceptual design of the modular detector and readout system for the Cosmic Microwave Background Stage 4 (CMB-S4) ground-based survey experiment. CMB-S4 will map the cosmic microwave background (CMB) and the millimeter-wave sky to unprecedented sensitivity, using 500,000 superconducting detectors observing from Chile and Antarctica to map over 60 percent of the sky. The fundamental building block of the detector and readout system is a detector module package operated at 100 mK, which is connected to a readout and amplification chain that carries signals out to room temperature. It uses arrays of feedhorn-coupled orthomode transducers (OMT) that collect optical power from the sky onto dc-voltage-biased transition-edge sensor (TES) bolometers. The resulting current signal in the TESs is then amplified by a two-stage cryogenic Superconducting Quantum Interference Device (SQUID) system with a time-division multiplexer to reduce wire count, and matching room-temperature electronics to condition and transmit signals to the data acquisition system. Sensitivity and systematics requirements are being developed for the detector and readout system over a wide range of observing bands (20 to 300 GHz) and optical powers to accomplish CMB-S4's science goals. While the design incorporates the successes of previous generations of CMB instruments, CMB-S4 requires an order of magnitude more detectors than any prior experiment. This requires fabrication of complex superconducting circuits on over 10 square meters of silicon, as well as significant amounts of precision wiring, assembly and cryogenic testing.Comment: 25 pages, 15 figures, presented at and published in the proceedings of SPIE Astronomical Telescopes and Instrumentation 202

Induction of isoprenyl diphosphate synthases, plant hormones and defense signalling genes correlates with traumatic resin duct formation in Norway spruce (Picea abies)

Norway spruce (Picea abies) defends itself against herbivores and pathogens by formation of traumatic resin ducts filled with terpenoid-based oleoresin. An important group of enzymes in terpenoid biosynthesis are the short-chain isoprenyl diphosphate synthases which produce geranyl diphosphate (C10), farnesyl diphosphate (C15), and geranylgeranyl diphosphate (C20) as precursors of monoterpenes, sesquiterpenes, and diterpene resin acids, respectively. After treatment with methyl jasmonate (MJ) we investigated the expression of all isoprenyl diphosphate synthase genes characterized to date from Norway spruce and correlated this with formation of traumatic resin ducts and terpene accumulation. Formation of traumatic resin ducts correlated with higher amounts of monoterpenes, sesquiterpenes and diterpene resin acids and an upregulation of isoprenyl diphosphate synthase genes producing geranyl diphosphate or geranylgeranyl diphosphate. Among defense hormones, jasmonate and jasmonate-isoleucine conjugate accumulated to higher levels in trees with extensive traumatic resin duct formation, whereas salicylate did not. Jasmonate and ethylene are likely to both be involved in formation of traumatic resin ducts based on elevated transcripts of genes encoding lipoxygenase and 1-aminocyclopropane-1-carboxylic acid oxidase associated with resin duct formation. Other genes involved in defense signalling in other systems, mitogen-activated protein kinase3 and nonexpressor of pathogenesis-related gene1, were also associated with traumatic resin duct formation. These responses were detected not only at the site of MJ treatment, but also systemically up to 60 cm above the site of treatment on the trunk