Impact of Plant-Based Dietary Fibers on Metabolic Homeostasis in High-Fat Diet Mice via Alterations in the Gut Microbiota and Metabolites.

BACKGROUND: The gut microbiota contributes to metabolic disease, and diet shapes the gut microbiota, emphasizing the need to better understand how diet impacts metabolic disease via gut microbiota alterations. Fiber intake is linked with improvements in metabolic homeostasis in rodents and humans, which is associated with changes in the gut microbiota. However, dietary fiber is extremely heterogeneous, and it is imperative to comprehensively analyze the impact of various plant-based fibers on metabolic homeostasis in an identical setting and compare the impact of alterations in the gut microbiota and bacterially derived metabolites from different fiber sources. OBJECTIVES: The objective of this study was to analyze the impact of different plant-based fibers (pectin, ß-glucan, wheat dextrin, resistant starch, and cellulose as a control) on metabolic homeostasis through alterations in the gut microbiota and its metabolites in high-fat diet (HFD)-fed mice. METHODS: HFD-fed mice were supplemented with 5 different fiber types (pectin, ß-glucan, wheat dextrin, resistant starch, or cellulose as a control) at 10% (wt/wt) for 18 wk (n = 12/group), measuring body weight, adiposity, indirect calorimetry, glucose tolerance, and the gut microbiota and metabolites. RESULTS: Only ß-glucan supplementation during HFD-feeding decreased adiposity and body weight gain and improved glucose tolerance compared with HFD-cellulose, whereas all other fibers had no effect. This was associated with increased energy expenditure and locomotor activity in mice compared with HFD-cellulose. All fibers supplemented into an HFD uniquely shifted the intestinal microbiota and cecal short-chain fatty acids; however, only ß-glucan supplementation increased cecal butyrate concentrations. Lastly, all fibers altered the small-intestinal microbiota and portal bile acid composition. CONCLUSIONS: These findings demonstrate that ß-glucan consumption is a promising dietary strategy for metabolic disease, possibly via increased energy expenditure through alterations in the gut microbiota and bacterial metabolites in mice.

Environmental DNA as an emerging tool in botanical research.

Over the past quarter century, environmental DNA (eDNA) has been ascendant as a tool to detect, measure, and monitor biodiversity (species and communities), as a means of elucidating biological interaction networks, and as a window into understanding past patterns of biodiversity. However, only recently has the potential of eDNA been realized in the botanical world. Here we synthesize the state of eDNA applications in botanical systems with emphases on aquatic, ancient, contemporary sediment, and airborne systems, and focusing on both single-species approaches and multispecies community metabarcoding. Further, we describe how abiotic and biotic factors, taxonomic resolution, primer choice, spatiotemporal scales, and relative abundance influence the utilization and interpretation of airborne eDNA results. Lastly, we explore several areas and opportunities for further development of eDNA tools for plants, advancing our knowledge and understanding of the efficacy, utility, and cost-effectiveness, and ultimately facilitating increased adoption of eDNA analyses in botanical systems.

Chromosome-level reference genome of stinkwort, Dittrichia graveolens (L.) Greuter: A resource for studies on invasion, range expansion, and evolutionary adaptation under global change.

Dittrichia graveolens (L.) Greuter, or stinkwort, is a weedy annual plant within the family Asteraceae. The species is recognized for the rapid expansion of both its native and introduced ranges: in Europe, it has expanded its native distribution northward from the Mediterranean basin by nearly 7 °C latitude since the mid-20th century, while in California and Australia the plant is an invasive weed of concern. Here, we present the first de novo D. graveolens genome assembly (1N = 9 chromosomes), including complete chloroplast (151,013 bp) and partial mitochondrial genomes (22,084 bp), created using Pacific Biosciences HiFi reads and Dovetail Omni-C data. The final primary assembly is 835 Mbp in length, of which 98.1% are represented by 9 scaffolds ranging from 66 to 119 Mbp. The contig N50 is 74.9 Mbp and the scaffold N50 is 96.9 Mbp, which, together with a 98.8% completeness based on the BUSCO embryophyta10 database containing 1,614 orthologs, underscores the high quality of this assembly. This pseudo-molecule-scale genome assembly is a valuable resource for our fundamental understanding of the genomic consequences of range expansion under global change, as well as comparative genomic studies in the Asteraceae.

Genome assembly and characterization of a complex zfBED-NLR gene-containing disease resistance locus in Carolina Gold Select rice with Nanopore sequencing.

Long-read sequencing facilitates assembly of complex genomic regions. In plants, loci containing nucleotide-binding, leucine-rich repeat (NLR) disease resistance genes are an important example of such regions. NLR genes constitute one of the largest gene families in plants and are often clustered, evolving via duplication, contraction, and transposition. We recently mapped the Xo1 locus for resistance to bacterial blight and bacterial leaf streak, found in the American heirloom rice variety Carolina Gold Select, to a region that in the Nipponbare reference genome is NLR gene-rich. Here, toward identification of the Xo1 gene, we combined Nanopore and Illumina reads and generated a high-quality Carolina Gold Select genome assembly. We identified 529 complete or partial NLR genes and discovered, relative to Nipponbare, an expansion of NLR genes at the Xo1 locus. One of these has high sequence similarity to the cloned, functionally similar Xa1 gene. Both harbor an integrated zfBED domain, and the repeats within each protein are nearly perfect. Across diverse Oryzeae, we identified two sub-clades of NLR genes with these features, varying in the presence of the zfBED domain and the number of repeats. The Carolina Gold Select genome assembly also uncovered at the Xo1 locus a rice blast resistance gene and a gene encoding a polyphenol oxidase (PPO). PPO activity has been used as a marker for blast resistance at the locus in some varieties; however, the Carolina Gold Select sequence revealed a loss-of-function mutation in the PPO gene that breaks this association. Our results demonstrate that whole genome sequencing combining Nanopore and Illumina reads effectively resolves NLR gene loci. Our identification of an Xo1 candidate is an important step toward mechanistic characterization, including the role(s) of the zfBED domain. Finally, the Carolina Gold Select genome assembly will facilitate identification of other useful traits in this historically important variety.

Small intestinal metabolomics analysis reveals differentially regulated metabolite profiles in obese rats and with prebiotic supplementation.

INTRODUCTION: Obesity occurs partly due to consumption of a high-fat, high-sugar and low fiber diet and is associated with an altered gut microbiome. Prebiotic supplementation can reverse obesity and beneficially alter the gut microbiome, evidenced by previous studies in rodents. However, the role of the small intestinal metabolome in obese and prebiotic supplemented rodents has never been investigated. OBJECTIVES: To investigate and compare the small intestinal metabolome of healthy and obese rats, as well as obese rats supplemented with the prebiotic oligofructose (OFS). METHODS: Untargeted metabolomics was performed on small intestinal contents of healthy chow-fed, high fat diet-induced obese, and obese rats supplemented with oligofructose using UPLC-MS/MS. Quantification of enterohepatic bile acids was performed with UPLC-MS to determine specific effects of obesity and fiber supplementation on the bile acid pool composition. RESULTS: The small intestinal metabolome of obese rats was distinct from healthy rats. OFS supplementation did not significantly alter the small intestinal metabolome but did alter levels of several metabolites compared to obese rats, including bile acid metabolites, amino acid metabolites, and metabolites related to the gut microbiota. Further, obese rats had lower total bile acids and increased taurine-conjugated bile acid species in enterohepatic circulation; this effect was reversed with OFS supplementation in high fat-feeding. CONCLUSION: Obesity is associated with a distinct small intestinal metabolome, and OFS supplementation reverses some metabolite levels that were altered in obese rats. Future research into the effects of specific metabolites identified in this study will provide deeper insight into the mechanism of fiber supplementation on improved body weight.

Large-scale genomic analysis reveals the genetic cost of chicken domestication.

BACKGROUND: Species domestication is generally characterized by the exploitation of high-impact mutations through processes that involve complex shifting demographics of domesticated species. These include not only inbreeding and artificial selection that may lead to the emergence of evolutionary bottlenecks, but also post-divergence gene flow and introgression. Although domestication potentially affects the occurrence of both desired and undesired mutations, the way wild relatives of domesticated species evolve and how expensive the genetic cost underlying domestication is remain poorly understood. Here, we investigated the demographic history and genetic load of chicken domestication. RESULTS: We analyzed a dataset comprising over 800 whole genomes from both indigenous chickens and wild jungle fowls. We show that despite having a higher genetic diversity than their wild counterparts (average π, 0.00326 vs. 0.00316), the red jungle fowls, the present-day domestic chickens experienced a dramatic population size decline during their early domestication. Our analyses suggest that the concomitant bottleneck induced 2.95% more deleterious mutations across chicken genomes compared with red jungle fowls, supporting the "cost of domestication" hypothesis. Particularly, we find that 62.4% of deleterious SNPs in domestic chickens are maintained in heterozygous states and masked as recessive alleles, challenging the power of modern breeding programs to effectively eliminate these genetic loads. Finally, we suggest that positive selection decreases the incidence but increases the frequency of deleterious SNPs in domestic chicken genomes. CONCLUSION: This study reveals a new landscape of demographic history and genomic changes associated with chicken domestication and provides insight into the evolutionary genomic profiles of domesticated animals managed under modern human selection.

Characterizing Polyoxovanadate-Alkoxide Clusters Using Vanadium K-Edge X-Ray Absorption Spectroscopy.

A number of technologies would benefit from developing inorganic compounds and materials with specific electronic and magnetic exchange properties. Unfortunately, designing compounds with these properties is difficult because metal⋅⋅⋅metal coupling schemes are hard to predict and control. Fully characterizing communication between metals in existing compounds that exhibit interesting properties could provide valuable insight and advance those predictive capabilities. One such class of molecules are the series of Lindqvist iron-functionalized and hexavanadium polyoxovanadate-alkoxide clusters, which we characterized here using V K-edge X-ray absorption spectroscopy. Substantial changes in the pre-edge peak intensities were observed that tracked with the V 3d-electron count. The data also suggested substantial delocalization between the vanadium cations. Meanwhile, the FeIII cations were electronically isolated from the polyoxovanadate core.

Landscape analyses using eDNA metabarcoding and Earth observation predict community biodiversity in California.

Ecosystems globally are under threat from ongoing anthropogenic environmental change. Effective conservation management requires more thorough biodiversity surveys that can reveal system-level patterns and that can be applied rapidly across space and time. Using modern ecological models and community science, we integrate environmental DNA and Earth observations to produce a time snapshot of regional biodiversity patterns and provide multi-scalar community-level characterization. We collected 278 samples in spring 2017 from coastal, shrub, and lowland forest sites in California, a complex ecosystem and biodiversity hotspot. We recovered 16,118 taxonomic entries from eDNA analyses and compiled associated traditional observations and environmental data to assess how well they predicted alpha, beta, and zeta diversity. We found that local habitat classification was diagnostic of community composition and distinct communities and organisms in different kingdoms are predicted by different environmental variables. Nonetheless, gradient forest models of 915 families recovered by eDNA analysis and using BIOCLIM variables, Sentinel-2 satellite data, human impact, and topographical features as predictors, explained 35% of the variance in community turnover. Elevation, sand percentage, and photosynthetic activities (NDVI32) were the top predictors. In addition to this signal of environmental filtering, we found a positive relationship between environmentally predicted families and their numbers of biotic interactions, suggesting environmental change could have a disproportionate effect on community networks. Together, these analyses show that coupling eDNA with environmental predictors including remote sensing data has capacity to test proposed Essential Biodiversity Variables and create new landscape biodiversity baselines that span the tree of life.

O2 Activation with a Sterically Encumbered, Oxygen-Deficient Polyoxovanadate-Alkoxide Cluster.

The isolation of the oxygen-deficient, polyoxovanadate-alkoxide (POV-alkoxide) cluster, [nBu4N][V6O6(OMe)12(MeCN)], and its subsequent reactivity with oxygen (O2), has demonstrated the utility of these assemblies as molecular models for heterogeneous metal oxide catalysts. However, the mechanism through which this cluster activates and reduces O2 to generate the oxygenated species is poorly understood. Currently it is speculated that this POV-alkoxide mediates the four-electron O-O bond cleavage through an O2 bridged dimeric intermediate, a mechanism which is not viable for O2 reduction at solid-state metal oxide surfaces. Here, we report the successful activation and reduction of O2 by the calix-functionalized POV-alkoxide cluster, [nBu4N][(calix)V6O6(OMe)8](MeCN)] (calix = 4-tert-butylcalix[4]arene). The steric hindrance imparted to the open vanadium site by the calix motif eliminates the possibility of cooperative, bimolecular O2 activation, allowing for a comparison of the reactivity of this system with that of the nonfunctionalized POV-alkoxide described previously. Rigorous characterization of the calix-substituted assembly, enabled by its newfound solubility in organic solvent, reveals that the incorporation of the tetradentate aryloxide ligand into the POV-alkoxide scaffold perturbs the electronic communication between the site-differentiated vanadium(III) ion and the cluster core. Collectively, our results provide insight into the physiochemical factors that are important during the O2 reduction reaction at oxygen-deficient sites in reduced POV-alkoxide clusters.

Measuring Quality in Kidney Care: An Evaluation of Existing Quality Metrics and Approach to Facilitating Improvements in Care Delivery.

BACKGROUND: Leveraging quality metrics can be a powerful approach to identify substantial performance gaps in kidney disease care that affect patient outcomes. However, metrics must be meaningful, evidence-based, attributable, and feasible to improve care delivery. As members of the American Society of Nephrology Quality Committee, we evaluated existing kidney quality metrics and provide a framework for quality measurement to guide clinicians and policy makers. METHODS: We compiled a comprehensive list of national kidney quality metrics from multiple established kidney and quality organizations. To assess the measures' validity, we conducted two rounds of structured metric evaluation, on the basis of the American College of Physicians criteria: importance, appropriate care, clinical evidence base, clarity of measure specifications, and feasibility and applicability. RESULTS: We included 60 quality metrics, including seven for CKD prevention, two for slowing CKD progression, two for CKD management, one for advanced CKD and kidney replacement planning, 28 for dialysis management, 18 for broad measures, and two patient-reported outcome measures. We determined that on the basis of defined criteria, 29 (49%) of the metrics have high validity, 23 (38%) have medium validity, and eight (13%) have low validity. CONCLUSIONS: We rated less than half of kidney disease quality metrics as highly valid; the others fell short because of unclear attribution, inadequate definitions and risk adjustment, or discordance with recent evidence. Nearly half of the metrics were related to dialysis management, compared with only one metric related to kidney replacement planning and two related to patient-reported outcomes. We advocate refining existing measures and developing new metrics that better reflect the spectrum of kidney care delivery.

Site-Selective Halogenation of Polyoxovanadate Clusters: Atomically Precise Models for Electronic Effects of Anion Doping in VO2.

We report the synthesis and characterization of a monochloride-functionalized polyoxovanadate-alkoxide (POV-alkoxide) cluster, which can serve as a molecular model for halogen-doped vanadium oxide (VO2) materials that have recently attracted great interest as advanced materials for energy-saving smart window applications. Chloride-substituted variants of the Lindqvist vanadium-oxide cluster were obtained via two distinct chemical pathways: (1) direct halogenation of the isovalent parent POV-alkoxide architecture, [V6O7(OC2H5)12]-2 with AlCl3 and (2) coordination of a chloride ion to a coordinatively unsaturated vanadium center within a cluster that bears a single oxygen-atom vacancy, [V6O6(OC2H5)12]0. Notably, our direct halogenation constitutes the first example of selective, single-site halide doping of homometallic metal oxide clusters. The chloride-containing compound, [V6O6Cl(OC2H5)12]-1, was characterized by 1H NMR spectroscopy and X-ray crystallography. The electronic structure of the chloride-functionalized POV-alkoxide cluster was established by infrared, electronic absorption, and X-ray photoelectron spectroscopy and revealed formation of a site-differentiated VIII ion upon halogenation. Cyclic voltammetry was employed to assess the electrochemical response of halide doping. A comparison of the Cl-VO2 model to the fully oxygenated cluster, [V6O7(OC2H5)12]-2, provides molecular-level insights into a new proposed mechanism by which halogenation increases the carrier density in solid VO2, namely, through prompting charge separation within the material.

Eggplant Domestication: Pervasive Gene Flow, Feralization, and Transcriptomic Divergence.

In the context of food security, examining the genomics of domestication will help identify genes underlying adaptive and economically important phenotypes, for example, larger fruit, improved taste, and loss of agronomically inferior phenotypes. Examination of genome-scale single nucleotide polymorphisms demonstrates the relationships between wild ancestors of eggplant (Solanum melongena L.), confirming that Solanum insanum L. is the wild progenitor. This species is split roughly into an Eastern (Malaysian, Thai, and Vietnamese) and Western (Indian, Madagascan, and Sri Lankan) group, with domesticates derived from the former. Additional "wild" accessions from India appear to be feral escapes, derived multiple times from domesticated varieties through admixture. Accessions with small egg-shaped fruit are generally found intermixed with East Asian Solanum insanum confirming they are primitive relative to the large-fruited domesticates. Comparative transcriptomics was used to track the loci under selection. Sequence analysis revealed a genetic bottleneck reducing variation by almost 50% in the primitive accessions relative to the wild species and a further 10% in the landraces. We also show evidence for selection on genes with a role in response to wounding and apoptosis. Genes showing a significant difference in expression between wild and primitive or between primitive and landrace genepools were mostly (>75%) downregulated in the derived populations and enriched for gene ontologies related to defense, flowering, signaling, and response to biotic and abiotic stimuli. This work reveals genomic changes involved in crop domestication and improvement, and the population genetics work explains why defining the eggplant domestication trajectory has been so challenging.

Electronic Consequences of Ligand Substitution at Heterometal Centers in Polyoxovanadium Clusters: Controlling the Redox Properties through Heterometal Coordination Number.

The rational control of the electrochemical properties of polyoxovanadate-alkoxide clusters is dependent on understanding the influence of various synthetic modifications on the overall redox processes of these systems. In this work, the electronic consequences of ligand substitution at the heteroion in a heterometal-functionalized cluster was examined. The redox properties of [V5 O6 (OCH3 )12 FeCl] (1-[V5 FeCl]) and [V5 O6 (OCH3 )12 Fe]X (2-[V5 Fe]X; X=ClO4 , OTf) were compared in order to assess the effects of changing the coordination environment around the iron center on the electrochemical properties of the cluster. Coordination of a chloride anion to iron leads to an anodic shift in redox events. Theoretical modelling of the electronic structure of these heterometal-functionalized clusters reveals that differences in the redox profiles of 1-[V5 FeCl] and 2-[V5 Fe]X arise from changes in the number of ligands surrounding the iron center (e.g., 6-coordinate vs. 5-coordinate). Specifically, binding of the chloride to the sixth coordination site appears to change the orbital interaction between the iron and the delocalized electronic structure of the mixed-valent polyoxovanadate core. Tuning the heterometal coordination environment can therefore be used to modulate the redox properties of the whole cluster.

A novel hydroxycinnamoyl transferase for synthesis of hydroxycinnamoyl spermine conjugates in plants.

BACKGROUND: Hydroxycinnamoyl-spermine conjugates (HCSpm) are a class of hydroxycinnamic acid amides (HCAAs), which not only are instrumental in plant development and stress response, but also benefit human health. However, HCSpm are not commonly produced in plants, and the mechanism of their biosynthesis remains unclear. In previous investigations of phenolics in Solanum fruits related to eggplant (Solanum melongena L.), we discovered that Solanum richardii, an African wild relative of eggplant, was rich in HCSpms in fruits. RESULTS: The putative spermine hydroxycinnamoyl transferase (HT) SpmHT was isolated from S. richardii and eggplant. SrSpmHT expression was high in flowers and fruit, and was associated with HCSpm accumulation in S. richardii; however, SpmHT was hardly detected in eggplant cultivars and other wild relatives. Recombinant SpmHT exclusively selected spermine as the acyl acceptor substrate, while showing donor substrate preference in the following order: caffeoyl-CoA, feruloyl-CoA, and p-coumaroyl-CoA. Molecular docking revealed that substrate binding pockets of SpmHT could properly accommodate spermine but not the shorter, more common spermidine. CONCLUSION: SrSpmHT is a novel spermine hydroxycinnamoyl transferase that uses Spm exclusively as the acyl acceptor substrate to produce HCSpms. Our findings shed light on the HCSpm biosynthetic pathway that may allow an increase of health beneficial metabolites in Solanum crops via methods such as introgression or engineering HCAA metabolism.

Evolution of crop species: genetics of domestication and diversification.

Domestication is a good model for the study of evolutionary processes because of the recent evolution of crop species (<12,000 years ago), the key role of selection in their origins, and good archaeological and historical data on their spread and diversification. Recent studies, such as quantitative trait locus mapping, genome-wide association studies and whole-genome resequencing studies, have identified genes that are associated with the initial domestication and subsequent diversification of crops. Together, these studies reveal the functions of genes that are involved in the evolution of crops that are under domestication, the types of mutations that occur during this process and the parallelism of mutations that occur in the same pathways and proteins, as well as the selective forces that are acting on these mutations and that are associated with geographical adaptation of crop species.

Photochemical Dynamics of a Trimethyl-Phosphine Derivatized [FeFe]-Hydrogenase Model Compound.

Though there have been many studies on photosensitizers coupled to model complexes of the [FeFe]-hydrogenases, few have looked at how the models react upon exposure to light. To extract photoreaction information, ultrafast time-resolved UV/visible pump, IR probe spectroscopy was performed on Fe2(µ-S2C2H4)(CO)4(PMe3)2 (2b) dissolved in heptane and acetonitrile and the photochemical dynamics were determined. Excitation with 532 and 355 nm light produces bleaches and new absorptions that decay to half their original intensity with time constants of 300 ± 120 ps and 380 ± 210 ps in heptane and acetonitrile, respectively. These features persist to the microsecond timescale. The dynamics of 2b are assigned to formation of an initial set of photoproducts, which were a mixture of excited-state tricarbonyl isomers. These isomers decay into another set of long-lived photoproducts in which approximately half the excited-state tricarbonyl isomers recombine with CO to form another complex mixture of tricarbonyl and tetracarbonyl isomers.

Neurocognitive functioning among HIV-positive adults in southern India.

The validity of a comprehensive international neuropsychological (NP) test battery for detection of HIV-associated neurocognitive disorders (HAND) in a Tamil speaking southern Indian cohort (69 HIV+ and 67 HIV-) was explored. The prevalence of HAND was significantly higher in the HIV+ vs. HIV- group (33 vs.13%; p < 0.01). Impairment rates were highest in the motor and speed of information processing domains. An NP battery translated into Tamil appears to be a valid tool for assessing HAND because the prevalence it found of HAND in southern India is similar to that found elsewhere.

Overcoming Barriers in Kidney Health-Forging a Platform for Innovation.

Innovation in kidney diseases is not commensurate with the effect of these diseases on human health and mortality or innovation in other key therapeutic areas. A primary cause of the dearth in innovation is that kidney diseases disproportionately affect a demographic that is largely disenfranchised, lacking sufficient advocacy, public attention, and funding. A secondary and likely consequent cause is that the existing infrastructure supporting nephrology research pales in comparison with those for other internal medicine specialties, especially cardiology and oncology. Citing such inequities, however, is not enough. Changing the status quo will require a coordinated effort to identify and redress the existing deficits. Specifically, these deficits relate to the need to further develop and improve the following: understanding of the disease mechanisms and pathophysiology, patient engagement and activism, clinical trial infrastructure, and investigational clinical trial designs as well as coordinated efforts among critical stakeholders. This paper identifies potential solutions to these barriers, some of which are already underway through the Kidney Health Initiative. The Kidney Health Initiative is unique and will serve as a current and future platform from which to overcome these barriers to innovation in nephrology.