Aims/hypothesis The role of IL-6 in the development of obesity and hepatic insulin resistance is unclear and still the subject of controversy. We aimed to determine whether global deletion of Il6 in ...mice (Il6 ⁻/⁻) results in standard chow-induced and high-fat diet (HFD)-induced obesity, hepatosteatosis, inflammation and insulin resistance. Methods Male, 8-week-old Il6 ⁻/⁻ and littermate control mice were fed a standard chow or HFD for 12 weeks and phenotyped accordingly. Results Il6 ⁻/⁻ mice displayed obesity, hepatosteatosis, liver inflammation and insulin resistance when compared with control mice on a standard chow diet. When fed a HFD, the Il6 ⁻/⁻ and control mice had marked, equivalent gains in body weight, fat mass and ectopic lipid deposition in the liver relative to chow-fed animals. Despite this normalisation, the greater liver inflammation, damage and insulin resistance observed in chow-fed Il6 ⁻/⁻ mice relative to control persisted when both were fed the HFD. Microarray analysis from livers of mice fed a HFD revealed that genes associated with oxidative phosphorylation, the electron transport chain and tricarboxylic acid cycle were uniformly decreased in Il6 ⁻/⁻ relative to control mice. This coincided with reduced maximal activity of the mitochondrial enzyme β-hydroxyacyl-CoA-dehydrogenase and decreased levels of mitochondrial respiratory chain proteins. Conclusions/interpretation Our data suggest that IL-6 deficiency exacerbates HFD-induced hepatic insulin resistance and inflammation, a process that appears to be related to defects in mitochondrial metabolism.
Circulating microRNAs (miRNAs) have attracted major interest as biomarkers for cardiovascular diseases. Since RNases are abundant in circulating blood, there needs to be a mechanism protecting miRNAs ...from degradation. We hypothesized that microparticles (MP) represent protective transport vehicles for miRNAs and that these are specifically packaged by their maternal cells.
Conventional plasma preparations, such as the ones used for biomarker detection, are shown to contain substantial numbers of platelet-, leucocyte-, and endothelial cell-derived MP. To analyse the widest spectrum of miRNAs, Next Generation Sequencing was used to assess miRNA profiles of MP and their corresponding stimulated and non-stimulated cells of origin. THP-1 (monocytic origin) and human umbilical vein endothelial cell (HUVEC) MP were used for representing circulating MP at a high purity. miRNA profiles of MP differed significantly from those of stimulated and non-stimulated maternal THP-1 cells and HUVECs, respectively. Quantitative reverse transcription-polymerase chain reaction of miRNAs which have been associated with cardiovascular diseases also demonstrated significant differences in miRNA profiles between platelets and their MP. Notably, the main fraction of miRNA in plasma was localized in MP. Furthermore, miRNA profiles of MP differed significantly between patients with stable and unstable coronary artery disease.
Circulating MP represent transport vehicles for large numbers of specific miRNAs, which have been associated with cardiovascular diseases. miRNA profiles of MP are significantly different from their maternal cells, indicating an active mechanism of selective 'packaging' from cells into MP. These findings describe an interesting mechanism for transferring gene-regulatory function from MP-releasing cells to target cells via MP circulating in blood.
A good understanding of the luminosity performance in a collider, as well as reliable tools to analyse, predict, and optimise the performance, is of great importance for the successful planning and ...execution of future runs. In this article, we present two different models for the evolution of the beam parameters and the luminosity in heavy-ion colliders. The first, Collider Time Evolution is a particle tracking code, while the second, the Multi-Bunch Simulation is based on the numerical solution of ordinary differential equations for beam parameters. As a benchmark, we compare simulations and data for a large number of physics fills in the 2018 Pb–Pb run at the CERN Large Hadron Collider (LHC), finding excellent agreement for most parameters, both between the simulations and with the measured data. Both codes are then used independently to predict the performance in future heavy-ion operation, with both Pb–Pb and p–Pb collisions, at the LHC and its upgrade, the high-luminosity LHC. The use of two independent codes based on different principles gives increased confidence in the results.
During its Run 2 (2015–2018), the Large Hadron Collider (LHC) operated at almost twice higher energy, and provided Pb-Pb collisions with an order of magnitude higher luminosity, than in the previous ...Run 1. In consequence, the power of the secondary beams emitted from the interaction points by the bound-free pair production (BFPP) process increased by a factor∼20, while the propensity of the bending magnets to quench increased with the higher magnetic field. This beam power is about 35 times greater than that contained in the luminosity debris from hadronic interactions and is focused on specific locations that fall naturally inside superconducting magnets. The risk of quenching these magnets has long been recognized as severe and there are operational limitations due to the dynamic heat load that must be evacuated by the cryogenic system. High-luminosity operation was nevertheless possible thanks to orbit bumps that were introduced in the dispersion suppressors around the ATLAS and CMS experiments to prevent quenches by displacing and spreading out these beam losses. Further, in 2015, the BFPP beams were manipulated to induce a controlled quench, thus providing the first direct measurement of the steady-state quench level of an LHC dipole magnet. The same experiment demonstrated the need for new collimators that are being installed around the ALICE experiment to intercept the secondary beams in the future. This paper discusses the experience with BFPP at luminosities very close to the future High Luminosity LHC (HL-LHC) target, gives results on the risk reduction by orbit bumps and presents a detailed analysis of the controlled quench experiment.
Abstract
A two-day test of operation with Pb ion beams was carried out in the CERN Large Hadron Collider (LHC) in 2022, with the aim of gaining experience in view of the future high luminosity ...heavy-ion physics runs from 2023 onwards. The LHC experiments received the first Pb-Pb collisions at a record energy of 5.36 TeV centre-of-mass energy per colliding nucleon pair (beam energy 6.8
Z
TeV). Bunch trains created with a new production scheme in the injectors, including slip-stacking, were injected into the LHC, with the collimation of nuclear beams with bent crystals tested along with a new collimation scheme for collision products. This paper describes the conditions and outcomes of these tests, which are critical steps in the upgrade to higher luminosity.
The Large Hadron Collider (LHC) at CERN pushes forward to new regimes in terms of beam energy and intensity. In view of the combination of very energetic and intense beams together with sensitive ...machine components, in particular the superconducting magnets, the LHC is equipped with a collimation system to provide protection and intercept uncontrolled beam losses. Beam losses could cause a superconducting magnet to quench, or in the worst case, damage the hardware. The collimation system, which is optimized to provide a good protection with proton beams, has shown a cleaning efficiency with heavy-ion beams which is worse by up to two orders of magnitude. The reason for this reduced cleaning efficiency is the fragmentation of heavy-ion beams into isotopes with a different mass to charge ratios because of the interaction with the collimator material. In order to ensure sufficient collimation performance in future ion runs, a detailed theoretical understanding of ion collimation is needed. The simulation of heavy-ion collimation must include processes in which Pb82+208 ions fragment into dozens of new isotopes. The ions and their fragments must be tracked inside the magnetic lattice of the LHC to determine their loss positions. This paper gives an overview of physical processes important for the description of heavy-ion loss patterns. Loss maps simulated by means of the two tools ICOSIM 1,2 and the newly developed STIER (SixTrack with Ion-Equivalent Rigidities) are compared with experimental data measured during LHC operation. The comparison shows that the tool STIER is in better agreement.
When ecosystems are under severe pressure or environments change, trophic position and intraspecific niche width may decrease or narrow, signalling that conservation action is required. In New ...Zealand, alpine and subalpine ecosystems have been extensively modified through farming since 19th‐century European settlement, with consequences for indigenous species such as the kea Nestor notabilis.
We investigated feather stable isotope values in the kea and predicted a lower trophic position in modern kea populations, to reflect reduced lowland habitat and a mixed diet with more plant material. We predicted that size and sex would influence trophic values in this sexually dimorphic species, with larger birds more likely to have a high protein diet.
We examined potential dietary changes in 68 museum collected kea from 1880s to 2000s, first recording accession details including provenance and sex and measuring culmen length. We used bulk carbon and nitrogen stable isotope analyses (BSIAs) of feathers and a further feather subset using compound‐specific stable isotope analyses of amino acids (CSIA‐AA) to obtain isotopic values and estimate trophic position.
BSIA showed δ15N values in kea feathers declined through time and could indicate that early century kea were highly omnivorous, with δ15N values on average higher than in modern kea. Variance in δ15N values was greater after 1950, driven by a few individuals. Few differences between males and females were evident, although females in the south region had lower δ15N values. There was a tendency for large male birds to have higher trophic values, perhaps reflecting dominant male bird behaviour noted in historical records. Nonetheless, CSIA‐AA performed on a subset of the data suggested that variation in BSIA is likely due to baseline changes rather than relative trophic position which may be more homogenous than these data indicate. Although there was more variability in modern kea, we suggest caution in interpretation.
Stable isotope data, particularly CSIA‐AA, from museum specimens can reveal potential change in ecological networks as well as sexually dimorphic feeding patterns within species. The data can reveal temporal and regional variation in species trophic position and changes in ecosystem integrity to inform conservation decision‐making.
Kea parrots in New Zealand were hunted as sheep killers for more than 100 years, while forest and high country habitat were destroyed for farming. We analysed carbon and nitrogen isotope ‘fingerprints’ in feathers from museum collections to recreate past kea diets, and found that kea are generally omnivorous.
Monte Carlo shower simulations are essential for understanding and predicting the consequences of beam losses in high-energy proton and ion colliders. Shower simulations are routinely used at CERN ...for estimating the beam-induced energy deposition, radiation damage, and radioactivity in the Large Hadron Collider (LHC). Comparing these shower simulations against beam loss measurements is an important prerequisite for assessing the predictive ability of model calculations. This paper validates fluka simulation predictions of beam loss monitor (BLM) signals against BLM measurements from proton fills at 3.5 and 4 TeV andPb20882+ion fills at1.38ATeV. The paper addresses typical loss scenarios and loss mechanisms encountered in LHC operation, including proton collisions with dust particles liberated into the beams, halo impact on collimators in the betatron cleaning insertion, proton-proton collisions in the interaction points, and dispersive losses due to bound-free pair production in heavy ion collisions. Model predictions and measured signals generally match within a few tens of percent, although systematic differences were found to be as high as a factor of 3 for some regions and source terms.
In an enclosed glasshouse with sucrose provisioned artificial flowers, we observed nectar-foraging bumble bees and honey bees under several resource conditions to determine potential for ...displacement. Different responses were displayed for varying resource treatments. Overall, bumble bees did not show reduced foraging in the presence of honey bees. When resources were reduced, bumble bees did not change their foraging behavior, whereas honey bees responded by decreasing their visitation rate. When a food resource of higher quality was introduced, bumble bee foragers shifted their foraging effort to the high-quality resources, whereas honey bees continued to forage on the lower quality resources they had been foraging on. We discuss these results by considering how the individual strategy of bumble bees compared with the colony-based strategy of honey bees may explain observed differences and highlight the potential advantages of each strategy in the natural environment.
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