Proposal for a definitive search for GUT-scale QCD axions
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72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
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Fermion mass, axion dark matter, and leptogenesis in SO(10) GUT
SO(10) grand unified theory with minimum parameters in the Yukawa sector employs the Peccei-Quinn symmetry that solves the strong C P problem. Such an economical Yukawa sector is highly appealing and has been extensively studied in the literature. However, when the running of the renormalization group equations of the Yukawa couplings are considered, this scenario shows some tension with the observed fermion masses and mixing. In this work, we propose an extension of the minimal framework that utilizes lower dimensional representations and alleviates this tension by introducing only a few new parameters. The proposed model consists of a fermion in the fundamental and a scalar in the spinorial representations. While the latter is needed to implement the Peccei-Quinn symmetry successfully, the presence of both is essential in obtaining an excellent fit to the fermion mass spectrum. In our model, axions serve the role of dark matter, and the out-of-equilibrium decays of the right-handed neutrinos successfully generate the matter-antimatter symmetry of the Universe. Published by the American Physical Society 2024
Astronomy & Astrophysics↗
Molecular insights into the evolution of woody plant decay in the gut of termites
Plant cell walls represent the most abundant pool of organic carbon in terrestrial ecosystems but are highly recalcitrant to utilization by microbes and herbivores owing to the physical and chemical barrier provided by lignin biopolymers. Termites are a paradigmatic example of an organism’s having evolved the ability to substantially degrade lignified woody plants, yet atomic-scale characterization of lignin depolymerization by termites remains elusive. We report that the phylogenetically derived termite Nasutitermes sp. efficiently degrades lignin via substantial depletion of major interunit linkages and methoxyls by combining isotope-labeled feeding experiments and solution-state and solid-state nuclear magnetic resonance spectroscopy. Exploring the evolutionary origin of lignin depolymerization in termites, we reveal that the early-diverging woodroach Cryptocercus darwini has limited capability in degrading lignocellulose, leaving most polysaccharides intact. Conversely, the phylogenetically basal lineages of “lower” termites are able to disrupt the lignin-polysaccharide inter- and intramolecular bonding while leaving lignin largely intact. These findings advance knowledge on the elusive but efficient delignification in natural systems with implications for next-generation ligninolytic agents.
59 BASIC BIOLOGICAL SCIENCES↗
Cell Surface Xyloglucan Recognition and Hydrolysis by the Human Gut Commensal Bacteroides uniformis
Explore the source record for details and available documents.
Grondin, Julie M.↗
Trust your gut: Establishing confidence in gastrointestinal models - An overview of the state of the science and contexts of use
Not provided.
Research & Experimental Medicine↗
Towards engineering phages for modulation of Bacteroides thetaiotaomicron and the human gut.
Draft version of conference poster
Steczynska, Joanna Patrycja [Sandia National Labor↗
Interaction of Wheat Bran Particle Size and Stimbiotic Supplementation on Growth Performance and Gut Health Parameters in Broilers
A 42-day study was conducted with 720-day-old Cobb male broiler chicks allocated to treatments in a 3 × 2 factorial, with the factors as wheat bran (WB) inclusion (no WB, 50 g/kg coarse WB, or 50 g/kg fine WB) and stimbiotic (STB) supplementation in corn-based diets. The inclusion of WB (p < 0.05) or STB supplementation (p < 0.05) increased the FCR and feed intake in the day 0–10 phase. During the day 0–28 phase, coarse-WB inclusion increased (p < 0.05) the FCR, compared to fine WB or diets without WB. In the day 0–42 phase, WB marginally decreased weight gain in diets without STB supplementation, but the STB-supplemented diet, weight gain was greater (p < 0.05) the diet with fine WB compared with diets with coarse WB. Fine-WB inclusion increased the ileal nitrogen and energy digestibility determined at day 18 compared to coarse WB or diets without WB. Supplementation with STB (p < 0.05) or fine WB (p < 0.05) inclusion increased the villi height compared to diets without STB supplementation or coarse WB, or the diet without WB. Coarse or fine WB decreased (p < 0.05) cecal branched-chain fatty acids compared to diets without WB. In conclusion, stimbiotic supplementation to fine WB improved the performance and nutrient digestibility of broilers compared to coarse WB with no effects on the caeca total SCFA concentration.
60 APPLIED LIFE SCIENCES↗
Catecholamine exposure and the gut microbiota in obstructive sleep apnea
Patients with obstructive sleep apnea (OSA) have increased mortality from chronic inflammatory and cardiovascular diseases. Excess catecholamine exposure contributes to the disease associations of OSA, but the underlying mechanism is unknown. This study tested the hypothesis that increased catecholamine exposure is associated with Enterobacteriaceae abundance in OSA. We compared urinary norepinephrine and the fecal microbiota in 24 patients with OSA and 23 controls. Urinary norepinephrine was elevated in OSA patients, consistent with increased sympathetic activation in those patients. OSA patients did not show changes in the community structure of the microbiome or in Enterobacteriaceae abundance compared to controls. Longitudinal changes in Enterobacteriaceae abundance in OSA patients were significantly associated with within-subject changes in norepinephrine, but this association was absent in controls. These results provide a preliminary association between norepinephrine exposure and Enterobacteriaceae in patients with disordered sleep.
Science & Technology - Other Topics↗
Fine scale transitions of the microbiota and metabolome along the gastrointestinal tract of herbivorous fishes
Abstract Background Gut microorganisms aid in the digestion of food by providing exogenous metabolic pathways to break down organic compounds. An integration of longitudinal microbial and chemical data is necessary to illuminate how gut microorganisms supplement the energetic and nutritional requirements of animals. Although mammalian gut systems are well-studied in this capacity, the role of microbes in the breakdown and utilization of recalcitrant marine macroalgae in herbivorous fish is relatively understudied and an emerging priority for bioproduct extraction. Here we use a comprehensive survey of the marine herbivorous fish gut microbial ecosystem via parallel 16S rRNA gene amplicon profiling (microbiota) and untargeted tandem mass spectrometry (metabolomes) to demonstrate consistent transitions among 8 gut subsections across five fish of the genus of Kyphosus . Results Integration of microbial phylogenetic and chemical diversity data reveals that microbial communities and metabolomes covaried and differentiated continuously from stomach to hindgut, with the midgut containing multiple distinct and previously uncharacterized microenvironments and a distinct hindgut community dominated by obligate anaerobes. This differentiation was driven primarily by anaerobic gut endosymbionts of the classes Bacteroidia and Clostridia changing in concert with bile acids, small peptides, and phospholipids: bile acid deconjugation associated with early midgut microbiota, small peptide production associated with midgut microbiota, and phospholipid production associated with hindgut microbiota. Conclusions The combination of microbial and untargeted metabolomic data at high spatial resolution provides a new view of the diverse fish gut microenvironment and serves as a foundation to understand functional partitioning of microbial activities that contribute to the digestion of complex macroalgae in herbivorous marine fish.
Sparagon, Wesley J. (ORCID:0000000296274174)↗
Glucuronidase Function in Clinical Samples
The purpose of this CRADA is to expand upon the work previously performed through CRADA No. PNNL/381. As explained in the previous CRADA, Glucuronidase enzymes are important for contributing to enterohepatic recycling of numerous therapeutic drug compounds, resulting in impaired or prolonged drug activity. Further, other pathways within the gut, such as bile acid metabolism through the action of bile salt hydrolase enzymes (BSH), have shown to impact both the development of colon cancers and impact recovery. Adapting the activity-based protein profiling (ABPP) technologies developed at PNNL to a microtiter plate-based chemical probe assay was the first step in demonstrating the clinical usability of the technology. With assay proof-of-concept complete through CRADA No. PNNL/381, clinical cohort testing using the developed assay is the next step towards commercialization of this technology. Some chemotherapeutic agents are mediated by gut-produced microbiota through enterohepatic circulation. For example, irinotecan, the first line treatment for many colon and other cancers, can be recycled into a patient’s system through gut microbiota produced glucuronidase enzymes. A significant percentage of patients subjected to irinotecan treatment experience dose-limiting diarrhea and gastric distress that limits treatment options and delays effective intervention. Relatedly, bile salt hydrolases modify ratios of bile acids in the gut, which alter nutrient and pharmaceutical uptake by the intestines and impact patient response to treatment. Coupled together these gut-mediated disorders can significantly decrease patient outcomes. In this project, we propose to investigate a clinical cohort of samples from colon cancer patients to better understand gut microbiome activities surrounding microbiota produced glucuronidases to aid clinician decisions and enhance therapeutic intervention. Our project will measure glucuronidase activity of individual patients and compare this activity to a variety of factors, including patient medical history, treatment response, and overall outcomes. Data will be compared with metagenomic, metabolomic, and proteomic analyses to fully defined the entire gut microbiome space and correlate results with the glucuronidase activity. Resultant analysis is expected to provide actionable information to direct decision making towards therapeutic intervention.
59 BASIC BIOLOGICAL SCIENCES↗
The global anaerobic metabolism regulator fnr is necessary for the degradation of food dyes and drugs by Escherichia coli
ABSTRACT The microbiome is an underappreciated contributor to intestinal drug metabolism with broad implications for drug efficacy and toxicity. While considerable progress has been made toward identifying the gut bacterial genes and enzymes involved, the role of environmental factors in shaping their activity remains poorly understood. Here, we focus on the gut bacterial reduction of azo bonds (R-N = N-R’), found in diverse chemicals in both food and drugs. Surprisingly, the canonical azoR gene in Escherichia coli was dispensable for azo bond reduction. Instead, azoreductase activity was controlled by the fumarate and nitrate reduction ( fnr ) regulator, consistent with a requirement for the anoxic conditions found within the gastrointestinal tract. Paired transcriptomic and proteomic analysis of the fnr regulon revealed that in addition to altering the expression of multiple reductases, FNR is necessary for the metabolism of L-Cysteine to hydrogen sulfide, enabling the degradation of azo bonds. Furthermore, we found that FNR indirectly regulates this process through the small noncoding regulatory RNA fnrS . Taken together, these results show how gut bacteria sense and respond to their intestinal environment to enable the metabolism of chemical groups found in both dietary and pharmaceutical compounds. IMPORTANCE This work has broad relevance due to the ubiquity of dyes containing azo bonds in food and drugs. We report that azo dyes can be degraded by human gut bacteria through both enzymatic and nonenzymatic mechanisms, even from a single gut bacterial species. Furthermore, we revealed that environmental factors, oxygen, and L-Cysteine control the ability of E. coli to degrade azo dyes due to their impacts on bacterial transcription and metabolism. These results open up new opportunities to manipulate the azoreductase activity of the gut microbiome through the manipulation of host diet, suggest that azoreductase potential may be altered in patients suffering from gastrointestinal disease, and highlight the importance of studying bacterial enzymes for drug metabolism in their natural cellular and ecological context.
59 BASIC BIOLOGICAL SCIENCES↗
Gravitational Waves and Proton Decay: Complementary Windows into Grand Unified Theories
Proton decay is a smoking gun signature of grand unified theories (GUTs). Searches by Super-Kamiokande have resulted in stringent limits on the GUT symmetry-breaking scale. The large-scale multipurpose neutrino experiments DUNE, Hyper-Kamiokande, and JUNO will either discover proton decay or further push the symmetry-breaking scale above 10 16 GeV. Another possible observational consequence of GUTs is the formation of a cosmic string network produced during the breaking of the GUT to the standard model gauge group. The evolution of such a string network in the expanding Universe produces a stochastic background of gravitational waves which will be tested by a number of gravitational wave detectors over a wide frequency range. We demonstrate the nontrivial complementarity between the observation of proton decay and gravitational waves produced from cosmic strings in determining SO(10) GUT-breaking chains. We show that such observations could exclude SO(10) breaking via flipped SU(5) × U(1) or standard SU(5), while breaking via a Pati-Salam intermediate symmetry, or standard SU(5) × U(1), may be favored if a large separation of energy scales associated with proton decay and cosmic strings is indicated. We note that recent results by the NANOGrav experiment have been interpreted as evidence for cosmic strings at a scale of ~10 14 GeV. This would strongly point toward the existence of GUTs, with SO(10) being the prime candidate. We show that the combination with already available constraints from proton decay allows us to identify preferred symmetry-breaking routes to the standard model.
72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
Randomized control trial of moderate dose vitamin D alters microbiota stability and metabolite networks in healthy adults
ABSTRACT Evidence indicates that both vitamin D and the gut microbiome are involved in the process of colon carcinogenesis. However, it is unclear what effects supplemental vitamin D 3 has on the gut microbiome and its metabolites in healthy adults. We conducted a double-blind, randomized, placebo-controlled trial to identify the acute and long-term microbiota structural and metabolite changes that occur in response to a moderate dose (4,000 IU) of vitamin D 3 for 12 weeks in healthy adults. Our results demonstrated a significant increase in serum 25-hydroxy-vitamin D (25(OH)D) in the treatment group compared to placebo ( P < 0.0001). Vitamin D 3 significantly increased compositional similarity ( P < 0.0001) in the treatment group, and enriched members of the Bifidobacteriaceae family. We also identified a significant inverse relationship between the percent change in serum 25(OH)D and microbial stability in the treatment group ( R = −0.52, P < 0.019). Furthermore, vitamin D 3 supplementation resulted in notable metabolic shifts, in addition to resulting in a drastic rewiring of key gut microbial-metabolic associations. In conclusion, we show that a moderate dose of vitamin D 3 among healthy adults has unique acute and persistent effects on the fecal microbiota, and suggest novel mechanisms by which vitamin D may affect the host-microbiota relationship. IMPORTANCE Preventative measures to reduce the rise in early-onset colorectal cancer are of critical need. Both vitamin D, dietary and serum levels, and the gut microbiome are implicated in the etiology of colorectal cancer. By understanding the intimate relationship between vitamin D, the gut microbiome, and its metabolites, we may be able to identify key mechanisms that can be targeted for intervention, including inflammation and metabolic dysfunction. Furthermore, the similarity of vitamin D to cholesterol, which is metabolized by the gut microbiome, gives precedence to its ability to produce metabolites that can be further studied and leveraged for controlling colorectal cancer incidence and mortality.
Wyatt, Madhur↗
Growth phase estimation for abundant bacterial populations sampled longitudinally from human stool metagenomes
Longitudinal sampling of the stool has yielded important insights into the ecological dynamics of the human gut microbiome. However, human stool samples are available approximately once per day, while commensal population doubling times are likely on the order of minutes-to-hours. Despite this mismatch in timescales, much of the prior work on human gut microbiome time series modeling has assumed that day-to-day fluctuations in taxon abundances are related to population growth or death rates, which is likely not the case. Here, we propose an alternative model of the human gut as a stationary system, where population dynamics occur internally and the bacterial population sizes measured in a bolus of stool represent a steady-state endpoint of these dynamics. We formalize this idea as stochastic logistic growth. We show how this model provides a path toward estimating the growth phases of gut bacterial populations in situ. We validate our model predictions using an in vitro Escherichia coli growth experiment. Finally, we show how this method can be applied to densely-sampled human stool metagenomic time series data. We discuss how these growth phase estimates may be used to better inform metabolic modeling in flow-through ecosystems, like animal guts or industrial bioreactors.
59 BASIC BIOLOGICAL SCIENCES↗
Neotropical termite microbiomes as sources of novel plant cell wall degrading enzymes
In this study, we used shotgun metagenomic sequencing to characterise the microbial metabolic potential for lignocellulose transformation in the gut of two colonies of Argentine higher termite species with different feeding habits, Cortaritermes fulviceps and Nasutitermes aquilinus. Our goal was to assess the microbial community compositions and metabolic capacity, and to identify genes involved in lignocellulose degradation. Individuals from both termite species contained the same five dominant bacterial phyla (Spirochaetes, Firmicutes, Proteobacteria, Fibrobacteres and Bacteroidetes) although with different relative abundances. However, detected functional capacity varied, with C. fulviceps (a grass-wood-feeder) gut microbiome samples containing more genes related to amino acid metabolism, whereas N. aquilinus (a wood-feeder) gut microbiome samples were enriched in genes involved in carbohydrate metabolism and cellulose degradation. The C. fulviceps gut microbiome was enriched specifically in genes coding for debranching- and oligosaccharide-degrading enzymes. These findings suggest an association between the primary food source and the predicted categories of the enzymes present in the gut microbiomes of each species. To further investigate the termite microbiomes as sources of biotechnologically relevant glycosyl hydrolases, a putative GH10 endo-β-1,4-xylanase, Xyl10E, was cloned and expressed in Escherichia coli. Functional analysis of the recombinant metagenome-derived enzyme showed high specificity towards beechwood xylan (288.1 IU/mg), with the optimum activity at 50 °C and a pH-activity range from 5 to 10. These characteristics suggest that Xy110E may be a promising candidate for further development in lignocellulose deconstruction applications.
59 BASIC BIOLOGICAL SCIENCES↗
Generating Ectropis obliqua axenic larvae in support of functional microbiome studies
Abstract Ectropis obliqua Prout (Lepidoptera: Geometridae) is a serious leaf‐eating pest in tea gardens throughout China, with rich bacterial communities in the larval gut. Few studies have investigated whether these bacteria play an important role in growth, development, and adaptability of E. obliqua . Axenic larval models are a useful tool for the study of interactions between gut bacteria and host insects. At present, artificial diet and antibiotics are typically used to remove larval gut bacteria for study; however, this method may change the natural food of insects and the habitat provided by their host plants, and cannot completely eliminate insect gut bacteria. Therefore, in order to establish an axenic insect feeding model, we first investigated the effects of egg age, different disinfectant concentration, and treatment time on the eggs of E. obliqua through orthogonal experiments. Next, we fed E. obliqua larvae tissue‐cultured tea seedlings under aseptic conditions. Thus, we successfully generated a feeding model of gut axenic larvae in the laboratory. Based on it, we then compared the mortality of axenic and non‐axenic E. obliqua larvae infected with the entomopathogenic fungus Beauveria bassiana (Balsamo) Vuill. These results demonstrated the feasibility of this axenic larval model and that B. bassiana is a broad‐spectrum entomogenous fungus with a toxic effect on E. obliqua .
Su, Qingqing↗
A minimal supersymmetric SU(5) missing-partner model
We explore a missing-partner model based on the minimal SU(5) gauge group with 75, 50 and 50¯ Higgs representations, assuming a super-GUT CMSSM scenario in which soft supersymmetry-breaking parameters are universal at some high scale Min above the GUT scale MGUT. We identify regions of parameter space that are consistent with the cosmological dark matter density, the measured Higgs mass and the experimental lower limit on τ(p → K + ν). These constraints can be satisfied simultaneously along stop coannihilation strips in the super-GUT CMSSM with tanβ ~ 3.5–5 where the input gaugino mass m 1/2 ~15–25 TeV, corresponding after strong renormalization by the large GUT Higgs representations between M in and M GUT to m LSP ,m t ~ 1 ~ 2.5–5 TeV and m g ~ ~ 13–20 TeV, with the light-flavor squarks significantly heavier. We find that τ(p → K + ν) ≲ 3 × 10 34 years throughout the allowed range of parameter space, within the range of the next generation of searches with the JUNO, DUNE and Hyper-Kamiokande experiments.
72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
Proton decay: flipped vs. unflipped SU(5)
We analyze nucleon decay modes in a no-scale supersymmetric flipped SU(5) GUT model, and contrast them with the predictions for proton decays via dimension-6 operators in a standard unflipped supersymmetric SU(5) GUT model. We find that these GUT models make very different predictions for the ratios Γ(p → π 0 µ + )/Γ(p → π 0 e + ), Γ(p → π + ν - )/Γ(p → π 0 e + ), Γ(p → K 0 e + )/Γ(p → π 0 e + ) and Γ(p → K 0 µ + )/Γ(p → π 0 µ + ), and that predictions for the ratios Γ(p → π 0 µ + )/Γ(p → π 0 e + ) and Γ(p → π + ν - )/Γ(p → π 0 e + ) also differ in variants of the flipped SU(5) model with normal- or inverse-ordered light neutrino masses. Upcoming large neutrino experiments may have interesting opportunities to explore both GUT and flavour physics in proton and neutron decays.
71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗