Villadsenliu2024

Exclusion diets are becoming increasingly popular in the management of irritable bowel syndrome (IBS). Several mechanisms exist by which food items might cause gastrointestinal symptoms, such as direct osmotic effects of food in the gut lumen, changes to the gut microbiota and immune activation. These effects have been demonstrated in animal models and in human studies, particularly in the case of gluten-free diets and diets low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs). Indeed, randomized controlled trials (RCTs) suggest that gluten-free diets and low-FODMAP diets improve IBS symptoms, and guidelines recommend the latter approach for treating symptoms in some patients with IBS. Designing such RCTs is challenging as participants need to eat so an 'inert' placebo is not an option. Blinding is also an issue with these studies; in the future, new exclusion diets should not advertise what the diet consists of until it is proved to reduce symptoms. In this Review, we outline the advantages and disadvantages of each choice of control group and emphasize the importance of collecting mechanistic data (regarding direct effects of food on the gut lumen, changes in gut microbiota and intestinal inflammation) as well as symptom data in RCTs of exclusion diets in IBS.An amendment to this paper has been published and can be accessed via a link at the top of the paper.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Mucosal-associated invariant T (MAIT) cells are activated by microbial riboflavin-based metabolite antigens when presented by MR1. How modifications to the potent antigen 5-OP-RU affect presentation by MR1 and MAIT cell activation remains unclear. Here we design 20 derivatives, termed altered metabolite ligands (AMLs), to dissect the impact of different antigen components on the human MAIT-MR1 axis. Analysis of 11 crystal structures of MAIT T cell antigen receptor (TCR)-MR1-AML ternary complexes, along with biochemical and functional assays, shows that MR1 cell-surface upregulation is influenced by ribityl and non-ribityl components of the ligand and the hydrophobicity of the MR1-AML interface. The polar ribityl chain of the AML strongly influences MAIT cell activation potency through dynamic compensatory interactions within a MAIT TCR-MR1-AML interaction triad. We define the basis by which the MAIT TCR can differentially recognize AMLs, thereby providing insight into MAIT cell antigen specificity and potency.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Large-scale energy storage is becoming increasingly critical to balancing renewable energy production and consumption1. Organic redox flow batteries, made from inexpensive and sustainable redox-active materials, are promising storage technologies that are cheaper and less environmentally hazardous than vanadium-based batteries, but they have shorter lifetimes and lower energy density2,3. Thus, fundamental insight at the molecular level is required to improve performance4,5. Here we report two in situ nuclear magnetic resonance (NMR) methods of studying redox flow batteries, which are applied to two redox-active electrolytes 2,6-dihydroxyanthraquinone (DHAQ) and 4,4'-((9,10-anthraquinone-2,6-diyl)dioxy) dibutyrate (DBEAQ). In the first method, we monitor the changes in the 1H NMR shift of the liquid electrolyte as it flows out of the electrochemical cell. In the second method, we observe the changes that occur simultaneously in the positive and negative electrodes in the full electrochemical cell. Using the bulk magnetization changes (observed via the 1H NMR shift of the water resonance) and the line broadening of the 1H shifts of the quinone resonances as a function of the state of charge, we measure the potential differences of the two single-electron couples, identify and quantify the rate of electron transfer between the reduced and oxidized species, and determine the extent of electron delocalization of the unpaired spins over the radical anions. These NMR techniques enable electrolyte decomposition and battery self-discharge to be explored in real time, and show that DHAQ is decomposed electrochemically via a reaction that can be minimized by limiting the voltage used on charging. We foresee applications of these NMR methods in understanding a wide range of redox processes in flow and other electrochemical systems.Engineered, highly controllable quantum systems are promising simulators of emergent physics beyond the simulation capabilities of classical computers1. An important problem in many-body physics is itinerant magnetism, which originates purely from long-range interactions of free electrons and whose existence in real systems has been debated for decades2,3. Here we use a quantum simulator consisting of a four-electron-site square plaquette of quantum dots4 to demonstrate Nagaoka ferromagnetism5. This form of itinerant magnetism has been rigorously studied theoretically6-9 but has remained unattainable in experiments. We load the plaquette with three electrons and demonstrate the predicted emergence of spontaneous ferromagnetic correlations through pairwise measurements of spin. We find that the ferromagnetic ground state is remarkably robust to engineered disorder in the on-site potentials and we can induce a transition to the low-spin state by changing the plaquette topology to an open chain. This demonstration of Nagaoka ferromagnetism highlights that quantum simulators can be used to study physical phenomena that have not yet been observed in any experimental system. The work also constitutes an important step towards large-scale quantum dot simulators of correlated electron systems.Solar energy harnessed by oxygenic photosynthesis supports most of the life forms on Earth. In eukaryotes, photosynthesis occurs in chloroplasts and is achieved by membrane-embedded macromolecular complexes that contain core and peripheral antennae with multiple pigments. The structure of photosystem I (PSI) comprises the core and light-harvesting (LHCI) complexes, which together form PSI-LHCI. Here we determined the structure of PSI-LHCI from the salt-tolerant green alga Dunaliella salina using X-ray crystallography and electron cryo-microscopy. Our results reveal a previously undescribed configuration of the PSI core. It is composed of only 7 subunits, compared with 14-16 subunits in plants and the alga Chlamydomonas reinhardtii, and forms the smallest known PSI. The LHCI is poorly conserved at the sequence level and binds to pigments that form new energy pathways, and the interactions between the individual Lhca1-4 proteins are weakened. Overall, the data indicate the PSI of D. salina represents a different type of the molecular organization that provides important information for reconstructing the plasticity and evolution of PSI.Plants are the foundation of terrestrial ecosystems, and their colonization of land was probably facilitated by mutualistic associations with arbuscular mycorrhizal fungi. Following this founding event, plant diversification has led to the emergence of a tremendous diversity of mutualistic symbioses with microorganisms, ranging from extracellular associations to the most intimate intracellular associations, where fungal or bacterial symbionts are hosted inside plant cells. Here, through analysis of 271 transcriptomes and 116 plant genomes spanning the entire land-plant diversity, we demonstrate that a common symbiosis signalling pathway co-evolved with intracellular endosymbioses, from the ancestral arbuscular mycorrhiza to the more recent ericoid and orchid mycorrhizae in angiosperms and ericoid-like associations of bryophytes. By contrast, species forming exclusively extracellular symbioses, such as ectomycorrhizae, and those forming associations with cyanobacteria, have lost this signalling pathway. This work unifies intracellular symbioses, revealing conservation in their evolution across 450 million yr of plant diversification.Plant laccases catalyse the oxidation of monolignols in lignification, a process reinforcing the cell wall of many different cell types that provide mechanical support, nutrient transportation and defence against pathogens in plants1. The isozymes display a broad range of substrate preferences. Here, the substrate preference of a laccase (ZmLac3) from Zea mays (maize) was characterized. The crystal structure of ZmLac3 revealed a compact and deep substrate-binding pocket, and the binding modes of sinapyl alcohol (SinA) and coniferyl alcohol (ConA) were solved. On the basis of structural data and kinetics analysis, we propose that the regionalization of polar and hydrophobic surfaces in the binding pocket of ZmLac3 is vital for defining the orientation of SinA/ConA binding. The extra methoxyl group in SinA makes substantial contributions to interactions between SinA and ZmLac3, which are absent in the ZmLac3-ConA complex. In summary, the polar and hydrophobic interactions between SinA/ConA and ZmLac3 determine the binding positions of the monolignols in ZmLac3. These results provide valuable insight about ZmLac3 catalysis and should aid industrial processes that use plant laccases.In this issue we would like to thank all those listed below for taking the time to review for IJIR Your Sexual Medicine Journal in 2019 - your generosity is much appreciated and we hope your association with the journal continues in the future.The innate immune system fights infection with inflammasomes and interferons. Facultative bacterial pathogens that inhabit the host cytosol avoid inflammasomes1-6 and are often insensitive to type I interferons (IFN-I), but are restricted by IFN-γ7-11. However, it remains unclear how obligate cytosolic bacterial pathogens, including Rickettsia species, interact with innate immunity. Here, we report that the human pathogen Rickettsia parkeri is sensitive to IFN-I and benefits from inflammasome-mediated host cell death that antagonizes IFN-I. R. parkeri-induced cell death requires the cytosolic lipopolysaccharide (LPS) receptor caspase-11 and antagonizes IFN-I production mediated by the DNA sensor cGAS. The restrictive effects of IFN-I require the interferon regulatory factor IRF5, which upregulates genes encoding guanylate-binding proteins (GBPs) and inducible nitric oxide synthase (iNOS), which we found to inhibit R. parkeri. Mice lacking both IFN-I and IFN-γ receptors succumb to R. parkeri, revealing critical and overlapping roles for these cytokines in vivo. The interactions of R. parkeri with inflammasomes and interferons are similar to those of viruses, which can exploit the inflammasome to avoid IFN-I12, are restricted by IFN-I via IRF513,14, and are controlled by IFN-I and IFN-γ in vivo15-17. Our results suggest that the innate immune response to an obligate cytosolic bacterial pathogen lies at the intersection of antibacterial and antiviral responses.BACKGROUND Increasing attention has been drawn on the assessment of body composition phenotypes, since the distribution of soft tissue influences cardio-metabolic risk. Dual-energy X-ray absorptiometry (DXA) is a validated technique to assess body composition. European reference values from population-based cohorts are rare. Selleck CC-90001 AIMS To provide age- and sex-related reference values of body composition parameters and visceral adipose tissue (VAT) mass, and for lean mass index (LMI) with regard to fat mass index (FMI) quantities and BMI categories. METHODS GE-Lunar Prodigy DXA scans of 10.894 participants, aged 18-81 years, recruited from 2011 to 2019 by the Austrian LEAD study, a population-based cohort study, have been used to construct reference curves using the LMS method. Parameters assessed are FMI, LMI, appendicular LMI, fat mass ratios android/gynoid and trunk/limbs, and VAT. RESULTS All lean mass and fat mass parameters indicating central fat accumulation were higher in men, whereas other fat mass indices were higher in women.