The bi-directional relationship between gut microbiota and autoimmunity

Humans serve as a major reservoir for a vast number of microbiota. These microbes have evolved symbiotic relationships with humans due to their close proximity with their host. As a result, the immune system adapts to the microbiota thus modulating immunological function. Autoimmunity is a state in which there are aberrant immune responses produced against host tissue. Intestinal bacteria are directly impacted by instances of inflammation brought on by autoimmunity. The complicated nature between autoimmunity and bacterial modulation demonstrates a bi-directional relationship. Here, we utilize experimental autoimmune encephalomyelitis, a model for multiple sclerosis, to explore the bi-directional relationship that disease and microbiota share. We demonstrate that disease severity, as well as time point post disease induction, shapes the structure and function of the gut microbiome. Additionally, antibiotic intervention modulates the symptoms of disease by upregulating the expression of T regulatory cells. Further, we show that a genetically engineered Lactococcus lactis expressing the colonization factor antigen I from Escherichia coli acting as an immunomodulatory probiotic reduced the severity of disease

Nutrient synergy: definition, evidence, and future directions

Nutrient synergy refers to the concept that the combined effects of two or more nutrients working together have a greater physiological impact on the body than when each nutrient is consumed individually. While nutrition science traditionally focuses on isolating single nutrients to study their effects, it is recognized that nutrients interact in complex ways, and their combined consumption can lead to additive effects. Additionally, the Dietary Reference Intakes (DRIs) provide guidelines to prevent nutrient deficiencies and excessive intake but are not designed to assess the potential synergistic effects of consuming nutrients together. Even the term synergy is often applied in different manners depending on the scientific discipline. Considering these issues, the aim of this narrative review is to investigate the potential health benefits of consuming different nutrients and nutrient supplements in combination, a concept we define as nutrient synergy, which has gained considerable attention for its impact on overall well-being. We will examine how nutrient synergy affects major bodily systems, influencing systemic health. Additionally, we will address the challenges associated with promoting and conducting research on this topic, while proposing potential solutions to enhance the quality and quantity of scientific literature on nutrient synergy

Low exposure long-baseline neutrino oscillation sensitivity of the DUNE experiment

The Deep Underground Neutrino Experiment (DUNE) will produce world-leading neutrino oscillation measurements over the lifetime of the experiment. In this work, we explore DUNE's sensitivity to observe charge-parity violation (CPV) in the neutrino sector, and to resolve the mass ordering, for exposures of up to 100 kiloton-megawatt-years (kt-MW-yr). The analysis includes detailed uncertainties on the flux prediction, the neutrino interaction model, and detector effects. We demonstrate that DUNE will be able to unambiguously resolve the neutrino mass ordering at a 3$\sigma$ (5$\sigma$) level, with a 66 (100) kt-MW-yr far detector exposure, and has the ability to make strong statements at significantly shorter exposures depending on the true value of other oscillation parameters. We also show that DUNE has the potential to make a robust measurement of CPV at a 3$\sigma$ level with a 100 kt-MW-yr exposure for the maximally CP-violating values \delta_{\rm CP}} = \pm\pi/2. Additionally, the dependence of DUNE's sensitivity on the exposure taken in neutrino-enhanced and antineutrino-enhanced running is discussed. An equal fraction of exposure taken in each beam mode is found to be close to optimal when considered over the entire space of interest

Identification and reconstruction of low-energy electrons in the ProtoDUNE-SP detector

Measurements of electrons from $\nu_e$ interactions are crucial for the Deep Underground Neutrino Experiment (DUNE) neutrino oscillation program, as well as searches for physics beyond the standard model, supernova neutrino detection, and solar neutrino measurements. This article describes the selection and reconstruction of low-energy (Michel) electrons in the ProtoDUNE-SP detector. ProtoDUNE-SP is one of the prototypes for the DUNE far detector, built and operated at CERN as a charged particle test beam experiment. A sample of low-energy electrons produced by the decay of cosmic muons is selected with a purity of 95%. This sample is used to calibrate the low-energy electron energy scale with two techniques. An electron energy calibration based on a cosmic ray muon sample uses calibration constants derived from measured and simulated cosmic ray muon events. Another calibration technique makes use of the theoretically well-understood Michel electron energy spectrum to convert reconstructed charge to electron energy. In addition, the effects of detector response to low-energy electron energy scale and its resolution including readout electronics threshold effects are quantified. Finally, the relation between the theoretical and reconstructed low-energy electron energy spectrum is derived and the energy resolution is characterized. The low-energy electron selection presented here accounts for about 75% of the total electron deposited energy. After the addition of lost energy using a Monte Carlo simulation, the energy resolution improves from about 40% to 25% at 50~MeV. These results are used to validate the expected capabilities of the DUNE far detector to reconstruct low-energy electrons.Comment: 19 pages, 10 figure

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

The DUNE Far Detector Interim Design Report, Volume 3: Dual-Phase Module

The DUNE IDR describes the proposed physics program and technical designs of the DUNE far detector modules in preparation for the full TDR to be published in 2019. It is intended as an intermediate milestone on the path to a full TDR, justifying the technical choices that flow down from the high-level physics goals through requirements at all levels of the Project. These design choices will enable the DUNE experiment to make the ground-breaking discoveries that will help to answer fundamental physics questions. Volume 3 describes the dual-phase module's subsystems, the technical coordination required for its design, construction, installation, and integration, and its organizational structure

Long-baseline neutrino oscillation physics potential of the DUNE experiment

The sensitivity of the Deep Underground Neutrino Experiment (DUNE) to neutrino oscillation is determined, based on a full simulation, reconstruction, and event selection of the far detector and a full simulation and parameterized analysis of the near detector. Detailed uncertainties due to the flux prediction, neutrino interaction model, and detector effects are included. DUNE will resolve the neutrino mass ordering to a precision of 5σ, for all ΑCP values, after 2 years of running with the nominal detector design and beam configuration. It has the potential to observe charge-parity violation in the neutrino sector to a precision of 3σ (5σ) after an exposure of 5 (10) years, for 50% of all ΑCP values. It will also make precise measurements of other parameters governing long-baseline neutrino oscillation, and after an exposure of 15 years will achieve a similar sensitivity to sin22θ13 to current reactor experiments

A Gaseous Argon-Based Near Detector to Enhance the Physics Capabilities of DUNE

This document presents the concept and physics case for a magnetized gaseous argon-based detector system (ND-GAr) for the Deep Underground Neutrino Experiment (DUNE) Near Detector. This detector system is required in order for DUNE to reach its full physics potential in the measurement of CP violation and in delivering precision measurements of oscillation parameters. In addition to its critical role in the long-baseline oscillation program, ND-GAr will extend the overall physics program of DUNE. The LBNF high-intensity proton beam will provide a large flux of neutrinos that is sampled by ND-GAr, enabling DUNE to discover new particles and search for new interactions and symmetries beyond those predicted in the Standard Model

First results on ProtoDUNE-SP liquid argon time projection chamber performance from a beam test at the CERN Neutrino Platform

The ProtoDUNE-SP detector is a single-phase liquid argon time projection chamber with an active volume of 7.2× 6.1× 7.0 m3. It is installed at the CERN Neutrino Platform in a specially-constructed beam that delivers charged pions, kaons, protons, muons and electrons with momenta in the range 0.3 GeV/c to 7 GeV/c. Beam line instrumentation provides accurate momentum measurements and particle identification. The ProtoDUNE-SP detector is a prototype for the first far detector module of the Deep Underground Neutrino Experiment, and it incorporates full-size components as designed for that module. This paper describes the beam line, the time projection chamber, the photon detectors, the cosmic-ray tagger, the signal processing and particle reconstruction. It presents the first results on ProtoDUNE-SP\u27s performance, including noise and gain measurements, dE/dx calibration for muons, protons, pions and electrons, drift electron lifetime measurements, and photon detector noise, signal sensitivity and time resolution measurements. The measured values meet or exceed the specifications for the DUNE far detector, in several cases by large margins. ProtoDUNE-SP\u27s successful operation starting in 2018 and its production of large samples of high-quality data demonstrate the effectiveness of the single-phase far detector design

Long-baseline neutrino oscillation physics potential of the DUNE experiment

The sensitivity of the Deep Underground Neutrino Experiment (DUNE) to neutrino oscillation is determined, based on a full simulation, reconstruction, and event selection of the far detector and a full simulation and parameterized analysis of the near detector. Detailed uncertainties due to the flux prediction, neutrino interaction model, and detector effects are included. DUNE will resolve the neutrino mass ordering to a precision of 5σ, for all δ_(CP) values, after 2 years of running with the nominal detector design and beam configuration. It has the potential to observe charge-parity violation in the neutrino sector to a precision of 3σ (5σ) after an exposure of 5 (10) years, for 50% of all δ_(CP) values. It will also make precise measurements of other parameters governing long-baseline neutrino oscillation, and after an exposure of 15 years will achieve a similar sensitivity to sin²θ₁₃ to current reactor experiments