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At least 379 records · Page 21

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Glyphosate is widely used as a herbicide, but recent studies begin to reveal its detrimental side effects on animals by targeting the shikimate pathway of associated gut microorganisms. However, its impact on nutritional endosymbionts in insects remains poorly understood. Here, we sequenced the tiny, shikimate pathway encoding symbiont genome of the sawtoothed grain beetle Oryzaephilus surinamensis. Decreased titers of the aromatic amino acid tyrosine in symbiont-depleted beetles underscore the symbionts’ ability to synthesize prephenate as the precursor for host tyrosine synthesis and its importance for cuticle sclerotization and melanization. Glyphosate exposure inhibited symbiont establishment during host development and abolished the mutualistic benefit on cuticle synthesis in adults, which could be partially rescued by dietary tyrosine supplementation. Furthermore, phylogenetic analyses indicate that the shikimate pathways of many nutritional endosymbionts likewise contain a glyphosate sensitive 5-enolpyruvylshikimate-3-phosphate synthase. These findings highlight the importance of symbiont-mediated tyrosine supplementation for cuticle biosynthesis in insects, but also paint an alarming scenario regarding the use of glyphosate in light of recent declines in insect populations.

59 BASIC BIOLOGICAL SCIENCES↗

Global trends in Akkermansia muciniphila research: A bibliometric visualization

Background Akkermansia muciniphila is a member of the gut microbiome, using mucin as sources of carbon, nitrogen, and energy. Since the first discovery of this unique bacterium in 2004, A. muciniphila has been extensively studied. It is considered a promising “next-generation beneficial microbe.” The purpose of this paper is to sort out the research status and summarize the hotspots through bibliometric analysis of the publications of A. muciniphila. Methods The publications about A. muciniphila from January 2004 to February 2022 were obtained from the Web of Science Core Collection. Visualization analyses were performed using three bibliometric tools and GraphPad Prism. Results A total of 1,478 published documents were analyzed. Annual publication number grew from 1 in 2004 to 336 in 2021, with China being the leading producer (33.36%). De Vos, Willem M was the most productive author with the highest H-index (documents = 56, H-index = 37), followed by Cani, Patrice D (documents = 35, H-index = 25). And Scientific Reports published the most papers. PNAS was the keystone taxa in this field, with high betweenness centrality (0.11) and high frequency. The keywords with high frequency in recent years include: oxidative stress, diet, metformin, fecal microbiota transplantation, short-chain fatty acids, polyphenols, microbiota metabolites and so on. The keyword “oxidative stress” was observed to be increasing in frequency recently. Conclusion Over time, the scope of the research on the clinical uses of A. muciniphila has gradually increased, and was gradually deepened and developed toward a more precise level. A. muciniphila is likely to remain a research hotspot in the foreseeable future and may contribute to human health.

Li, Zitong↗

Extracellular electron uptake from a cathode by the lactic acid bacterium Lactiplantibacillus plantarum

A subset of microorganisms that perform respiration can endogenously utilize insoluble electron donors, such as Fe(II) or a cathode, in a process called extracellular electron transfer (EET). However, it is unknown whether similar endogenous EET can be performed by primarily fermentative species like lactic acid bacteria. We report for the first time electron uptake from a cathode by Lactiplantibacillus plantarum, a primarily fermentative bacteria found in the gut of mammals and in fermented foods. L. plantarum consumed electrons from a cathode and coupled this oxidation to the reduction of both an endogenous organic (pyruvate) and an exogenous inorganic electron acceptor (nitrate). This electron uptake from a cathode reroutes glucose fermentation toward lactate degradation and provides cells with a higher viability upon sugar exhaustion. Moreover, the associated genes and cofactors indicate that this activity is mechanistically different from that one employed by lactic acid bacteria to reduce an anode and to perform respiration. Our results expand our knowledge of the diversity of electroactive species and of the metabolic and bioenergetic strategies used by lactic acid bacteria.

biocathode↗

Limited effects of tannin supplementation on the dairy cattle fecal microbiome with modulation of metabolites

Tannins are plant secondary metabolites that bind organic carbon (C) and nitrogen (N), potentially altering substrate bioavailability for enteric fermentation in ruminants. This interaction may reduce greenhouse gas (GHG) emissions and influence nitrogen partitioning. Given tannins' resistance to ruminal degradation and persistence through the gastrointestinal tract, this study investigated the effects of a tannin-based feed additive on fecal microbial diversity, fecal chemical composition, and GHG emissions. Twenty-four early- to mid-lactation dairy cows were randomized to receive either a tannin-based feed additive (TRT; containing condensed and hydrolyzable tannins from Schinopsis quebracho-colorado [Schltdl.]) or a control diet (CON) for 64 days. Cows were blocked by parity, dry matter intake, milk yield, body weight, and days in milk. Fecal samples were collected on days 0, 16, 32, and 64 and analyzed using 16S rRNA gene amplicon sequencing. Fecal C, N, and indole-3-lactate were measured, and GHG emissions (N2O, CH4, CO2) were assessed via 14-day laboratory incubation. A total of 1,538 amplicon sequence variants were identified, with Firmicutes as the dominant phylum. Fecal phylogenetic diversity showed a significant treatment × day interaction (p < 0.01), with TRT cows exhibiting reduced microbial diversity from day 16 to 64. Fecal C and N concentrations were significantly lower (p < 0.01) in TRT cows on day 16, while indole-3-lactate levels were higher on day 64 (p = 0.02). GHG emissions did not differ significantly between treatments. The tannin-based feed additive influenced fecal microbial community structure and select chemical parameters but did not significantly affect GHG emissions from feces. These findings suggest that dietary tannins may modulate gut microbial ecology with minimal impact on downstream manure-related emissions.

Klein, Matthew L↗

Beyond microbial abundance: metadata integration enhances disease prediction in human microbiome studies

Multiple studies have highlighted the interaction of the human microbiome with physiological systems such as the gut, immune, liver, and skin, via key axes. Advances in sequencing technologies and high-performance computing have enabled the analysis of large-scale metagenomic data, facilitating the use of machine learning to predict disease likelihood from microbiome profiles. However, challenges such as compositionality, high dimensionality, sparsity, and limited sample sizes have hindered the development of actionable models. One strategy to improve these models is by incorporating key metadata from both the human host and sample collection/processing protocols. This remains challenging due to sparsity and inconsistency in metadata annotation and availability. In this paper, we introduce a machine learning-based pipeline for predicting human disease states by integrating host and protocol metadata with microbiome abundance profiles from 68 different studies, processed through a consistent pipeline. Our findings indicate that metadata can enhance machine learning predictions, particularly at higher taxonomic ranks like Kingdom and Phylum, though this effect diminishes at lower ranks. Our study leverages a large collection of microbiome datasets comprising 11,208 samples, therefore enhancing the robustness and statistical confidence of our findings. This work is a critical step toward utilizing microbiome and metadata for predicting diseases such as gastrointestinal infections, diabetes, cancer, and neurological disorders.

Mathematics and Computing↗

Using X-ray Micro-Computed Tomography to Three-Dimensionally Visualize the Foregut of the Glassy-Winged Sharpshooter ( Homalodisca vitripennis )

Dissecting the heads of small insects belonging to the order Hemiptera for detailed anatomical investigation with light or scanning electron microscopy is difficult, time-consuming, and destructive, often resulting in sample preparation artifacts. Nevertheless, the structural details of these insects often hold critical information regarding their interactions with bacterial pathogens. For example, the glassy-winged sharpshooter (GWSS) is an efficient vector of the bacterium Xylella fastidiosa, the causal agent of Pierce’s disease in grape vines, but the foregut of this species is exceptionally difficult to dissect. Here, we describe a simple, non-destructive method to investigate the structure of the anterior gut of GWSS using high-resolution micro-computed X-ray tomography (microCT). The use of microCT eliminates the need for destructive dissection and reveals the morphology of small insects in three dimensions, allowing the user to virtually dissect the sample. The use of microCT imaging is a promising and powerful tool in the entomological sciences for studying the structures of vector insects, especially for difficult-to-dissect regions such as the foregut.

54 ENVIRONMENTAL SCIENCES↗

Structural Basis of Clostridium perfringens Enterotoxin Activation and Oligomerization by Trypsin

Clostridium perfringens enterotoxin (CpE) is a β-pore forming toxin that disrupts gastrointestinal homeostasis in mammals by binding membrane protein receptors called claudins. Although structures of CpE fragments bound to claudins have been determined, the mechanisms that trigger CpE activation and oligomerization that lead to the formation of cytotoxic β-pores remain undetermined. Proteolysis of CpE in the gut by trypsin has been shown to play a role in this and subsequent cytotoxicity processes. Here, we report solution structures of full-length and trypsinized CpE using small-angle X-ray scattering (SAXS) and crystal structures of trypsinized CpE and its C-terminal claudin-binding domain (cCpE) using X-ray crystallography. Mass spectrometry and SAXS uncover that removal of the CpE N-terminus by trypsin alters the CpE structure to expose areas that are normally unexposed. Crystal structures of trypsinized CpE and cCpE reveal unique dimer interfaces that could serve as oligomerization sites. Moreover, comparisons of these structures to existing ones predict the functional implications of oligomerization in the contexts of cell receptor binding and β-pore formation. This study sheds light on trypsin’s role in altering CpE structure to activate its function via inducing oligomerization on its path toward cytotoxic β-pore formation. Its findings can incite new approaches to inhibit CpE-based cytotoxicity with oligomer-disrupting therapeutics.

59 BASIC BIOLOGICAL SCIENCES↗

Neutrino Flavor Model Building and the Origins of Flavor and CP Violation

The neutrino sector offers one of the most sensitive probes of new physics beyond the Standard Model of Particle Physics (SM). The mechanism of neutrino mass generation is still unknown. The observed suppression of neutrino masses hints at a large scale, conceivably of the order of the scale of a rand unified theory (GUT), which is a unique feature of neutrinos that is not shared by the charged fermions. The origin of neutrino masses and mixing is part of the outstanding puzzle of fermion masses and mixings, which is not explained ab initio in the SM. Flavor model building for both quark and lepton sectors is important in order to gain a better understanding of the origin of the structure of mass hierarchy and flavor mixing, which constitute the dominant fraction of the SM parameters. Recent activities in neutrino flavor model building based on non-Abelian discrete flavor symmetries and modular flavor symmetries have been shown to be a promising direction to explore. The emerging models provide a framework that has a significantly reduced number of undetermined parameters in the flavor sector. In addition, such a framework affords a novel origin of CP violation from group theory due to the intimate connection between physical CP transformation and group theoretical properties of non-Abelian discrete groups. Model building based on non-Abelian discrete flavor symmetries and their modular variants enables the particle physics community to interpret the current and anticipated upcoming data from neutrino experiments. Non-Abelian discrete flavor symmetries and their modular variants can result from compactification of a higher-dimensional theory. Pursuit of flavor model building based on such frameworks thus also provides the connection to possible UV completions: in particular, to string theory. We emphasize the importance of constructing models in which the uncertainties of theoretical predictions are smaller than, or at most compatible with, the error bars of measurements in neutrino experiments. While there exist proof-of-principle versions of bottom-up models in which the theoretical uncertainties are under control, it is remarkable that the key ingredients of such constructions were discovered first in top-down model building. We outline how a successful unification of bottom-up and top-down ideas and techniques may guide us towards a new era of precision flavor model building in which future experimental results can give us crucial insights into the UV completion of the SM.

Almumin, Yahya (ORCID:0000000196396772)↗

Presence and Persistence of Putative Lytic and Temperate Bacteriophages in Vaginal Metagenomes from South African Adolescents

The interaction between gut bacterial and viral microbiota is thought to be important in human health. While fluctuations in female genital tract (FGT) bacterial microbiota similarly determine sexual health, little is known about the presence, persistence, and function of vaginal bacteriophages. We conducted shotgun metagenome sequencing of cervicovaginal samples from South African adolescents collected longitudinally, who received no antibiotics. We annotated viral reads and circular bacteriophages, identified CRISPR loci and putative prophages, and assessed their diversity, persistence, and associations with bacterial microbiota composition. Siphoviridae was the most prevalent bacteriophage family, followed by Myoviridae, Podoviridae, Herelleviridae, and Inoviridae. Full-length siphoviruses targeting bacterial vaginosis (BV)-associated bacteria were identified, suggesting their presence in vivo. CRISPR loci and prophage-like elements were common, and genomic analysis suggested higher diversity among Gardnerella than Lactobacillus prophages. We found that some prophages were highly persistent within participants, and identical prophages were present in cervicovaginal secretions of multiple participants, suggesting that prophages, and thus bacterial strains, are shared between adolescents. The number of CRISPR loci and prophages were associated with vaginal microbiota stability and absence of BV. Our analysis suggests that (pro)phages are common in the FGT and vaginal bacteria and (pro)phages may interact.

59 BASIC BIOLOGICAL SCIENCES↗

Bayesian chain graph models to characterize microbe-environment dynamics

Microbiome data require statistical models that can simultaneously decode microbes' reaction to the environment and interactions among microbes. While a multiresponse linear regression model seems like a straight-forward solution, we argue that treating it as a graphical model is problematic given that the regression coefficient matrix does not encode the conditional dependence structure between response and predictor nodes. This observation is especially important in biological settings when we have prior knowledge on the edges from specific experimental interventions that can only be properly encoded under a conditional dependence model. Here, we propose a chain graph model with two sets of nodes (predictors and responses) whose solution yields a graph with edges that indeed represent conditional dependence, thus agreeing with the experimenter's intuition on the average behavior of nodes under treatment. The solution to our model is sparse via the Bayesian linear regression (LASSO). In addition, we propose an adaptive extension so that different shrinkages can be applied to different edges to incorporate edge-specific prior knowledge. Our model is computationally inexpensive through an efficient Gibbs sampling algorithm and can account for binary, counting, and compositional responses via an appropriate hierarchical structure. We test the performance of our model in a variety of simulated datasets, thereby showing superior performance to state-of-the-art approaches. We further apply our model to human gut and soil microbial compositional datasets, and we highlight that CG-LASSO can estimate biologically meaningful network structures in the data.

compositional data↗

A new aerial approach for quantifying and attributing methane emissions: implementation and validation

Methane (CH 4 ) is a powerful greenhouse gas that is produced by a diverse set of natural and anthropogenic emission sources. Biogenic methane sources generally involve anaerobic decay processes such as those occurring in wetlands, melting permafrost, or the digestion of organic matter in the guts of ruminant animals. Thermogenic CH 4 sources originate from the breakdown of organic material at high temperatures and pressure within the Earth's crust, a process which also produces more complex trace hydrocarbons such as ethane (C 2 H 6 ). Here, we present the development and deployment of an uncrewed aerial system (UAS) that employs a fast (1 Hz) and sensitive (1–0.5 ppb s -1 ) CH 4 and C 2 H 6 sensor and ultrasonic anemometer. The UAS platform is a vertical-takeoff, hexarotor drone (DJI Matrice 600 Pro, M600P) capable of vertical profiling to 120 m altitude and plume sampling across scales up to 1 km. Simultaneous measurements of CH 4 and C 2 H 6 concentrations, vector winds, and positional data allow for source classification (biogenic versus thermogenic), differentiation, and emission rates without the need for modeling or a priori assumptions about winds, vertical mixing, or other environmental conditions. The system has been used for direct quantification of methane point sources, such as orphan wells, and distributed emitters, such as landfills and wastewater treatment facilities. With detectable source rates as low as 0.04 and up to ~1500 kg h -1 , this UAS offers a direct and repeatable method of horizontal and vertical profiling of emission plumes at scales that are complementary to regional aerial surveys and localized ground-based monitoring.

54 ENVIRONMENTAL SCIENCES↗

Bioengineered algal lipids enriched in structured medium- and long-chain triacylglycerols, linoleate, and sn -2 palmitate for human milk fat substitutes

Human milk fat (HMF) contains triacylglycerol (TAG) as its primary component, providing over 50% of the calories for infant nutrition, along with structural and bioactive lipids that are important for immune and nervous system development. Palmitic acid, comprising 20-25% of the fatty acid complement of HMF, is predominantly esterified to the sn -2 position on the glycerol backbone. This regiospecific positioning facilitates absorption as 2-palmitoyl-monoacylglycerol after hydrolysis of the fatty acids at sn -1 and sn -2 by gut lipases. Other features of HMF include enrichment in structured medium- and long-chain triglycerides (MLCTs), and variation in the ratio of oleic acid to linoleic acid with maternal diet and geography. We have engineered Auxenochlorella, an oleaginous green alga, for biosynthesis of an MLCT- and sn -2 palmitate-enriched HMF substitute for infant formula, matching the regioisomeric composition and proportions of the most abundant fatty acids in HMF.

Lin, Jon Y-T [University of California, Berkeley;]↗

Molecular basis for catabolism of the abundant metabolite trans-4-hydroxy-L-proline by a microbial glycyl radical enzyme

The glycyl radical enzyme (GRE) superfamily utilizes a glycyl radical cofactor to catalyze difficult chemical reactions in a variety of anaerobic microbial metabolic pathways. Recently, a GRE, trans-4-hydroxy-L-proline (Hyp) dehydratase (HypD), was discovered that catalyzes the dehydration of Hyp to (S)-Δ 1 -pyrroline-5-carboxylic acid (P5C). This enzyme is abundant in the human gut microbiome and also present in prominent bacterial pathogens. However, we lack an understanding of how HypD performs its unusual chemistry. Here, we have solved the crystal structure of HypD from the pathogen Clostridioides difficile with Hyp bound in the active site. Biochemical studies have led to the identification of key catalytic residues and have provided insight into the radical mechanism of Hyp dehydration.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Metabolic model-based ecological modeling for probiotic design

The microbial community composition in the human gut has a profound effect on human health. This observation has lead to extensive use of microbiome therapies, including over-the-counter ‘probiotic’ treatments intended to alter the composition of the microbiome. Despite so much promise and commercial interest, the factors that contribute to the success or failure of microbiome-targeted treatments remain unclear. We investigate the biotic interactions that lead to successful engraftment of a novel bacterial strain introduced to the microbiome as in probiotic treatments. We use pairwise genome-scale metabolic modeling with a generalized resource allocation constraint to build a network of interactions between taxa that appear in an experimental engraftment study. We create induced sub-graphs using the taxa present in individual samples and assess the likelihood of invader engraftment based on network structure. To do so, we use a generalized Lotka-Volterra model, which we show has strong ability to predict if a particular invader or probiotic will successfully engraft into an individual’s microbiome. Furthermore, we show that the mechanistic nature of the model is useful for revealing which microbe-microbe interactions potentially drive engraftment.

59 BASIC BIOLOGICAL SCIENCES↗

Probe-Enabled Approaches for Function-Dependent Cell Sorting and Characterization of Microbiome Subpopulations

Understanding the roles that individual species or communities play within a microbiome is a significant challenge. The complexity and heterogeneity of microbiomes presents a challenge to researchers looking to unravel the function that microbiomes serve within larger environments. While identification of the species and proteins present in a microbiome can be accomplished through genomics approaches, strategies that report on enzyme activity are limited. In this chapter, we describe the application of small molecule chemical probes in the isolation and subsequent characterization of microbiome subpopulations based on enzymatic function. We will cover protocols for labeling microbes with appropriate probes, microbiome sample preparation, and using fluorescence-activated cell sorting to isolate subpopulations based on function. We hope that the strategies outlined here will serve as a resource for researchers studying the functional role that microbiomes play in the gut and soil.

Steiger, Andrea K.↗

Leveraging Environmental Monitoring Results from Department of Energy Sites for Research on the Food-Energy-Water Nexus

The Annual Site Environmental Report (ASER) from a U.S. Department of Energy (DOE) Site summarizes environmental data; environmental management performance; compliance with applicable DOE, federal, state, and local regulations; and restoration and surveillance monitoring programs. The Savannah River Site (SRS) produces ASERs that include results of monitoring mercury levels in fish samples obtained in the vicinity of SRS. Mercury is a toxic trace metal and the methylated organic form is a neurotoxin that bioaccumulates in the food web, endangering humans and other organisms. In United States, power plants are the largest source of mercury emissions. Research Objective: To determine the patterns of mercury levels in fish samples reported in the SRS environmental monitoring reports. We developed box plot visualizations to make sense of the data as well as identify fish species, dates and location with outlier mercury content. The integration and visual representation of multi-year datasets can support decision making processes on environmental compliance and environmental sustainability conducted at U.S. DOE Sites. We are constructing datasets from textual, image and multivariable data sources in the multi-year ASERs of the U.S. DOE Savannah River Site (SRS https://www.srs.gov/general/pubs/ERsum/index.html). The Fish Surveillance for mercury presents a case study for the intersection of food, energy and water systems. The dataset of 864 records (2008 and 2009) of mercury levels includes water location of fish, fish species, collection date and mercury content of fish sample. The patterns of mercury levels in the fish species as well as locations provide knowledge for further investigations. A research area for future studies is the composition of microbial communities in fish guts of varying levels of mercury.

54 ENVIRONMENTAL SCIENCES↗

Responding to the US national pollinator plan: a case study in Michigan

The long‐term health of pollinators is a critical issue for the functioning of natural habitats and for agricultural production. In response to widespread public concern about the future of these ecologically and economically important animals, in 2015 the US Government released a national strategy to support pollinators, including research priorities, directives for funding, and timelines for achieving three overarching goals. Five years after this strategic plan was released, we evaluate progress toward the national targets for improved honey bee ( Apis mellifera ) overwintering survival, expanded pollinator habitat, and larger monarch butterfly ( Danaus plexippus ) populations, and find that the three goals of the plan have not yet been reached. Our research and extension programs to improve the health of honey bees, wild bees, and monarch butterflies in the US state of Michigan are described, providing opportunities to contribute to the national pollinator goals.

Bloom, Elias H.↗

Primordial monopoles and strings, inflation, and gravity waves

We consider magnetic monopoles and strings that appear in non-supersymmetric SO(10) and E 6 grand unified models paying attention to gauge coupling unification and proton decay in a variety of symmetry breaking schemes. The dimensionless string tension parameter Gμ spans the range 10 –6 – 10 –30 , where G is Newton’s constant and μ is the string tension. We show how intermediate scale monopoles with mass ~ 10 13 – 10 14 GeV and flux ≲ 2.8 × 10 –16 cm –2 s –1 sr –1 , and cosmic strings with Gμ ~ 10 –11 – 10 –10 survive inflation and are present in the universe at an observable level. We estimate the gravity wave spectrum emitted from cosmic strings taking into account inflation driven by a Coleman-Weinberg potential. The tensor-to-scalar ratio r lies between 0.06 and 0.003 depending on the details of the inflationary scenario.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗