Unlabelled: Populations are capable of responding to environmental change over ecological timescales via adaptive tracking. However, the translation from patterns of allele frequency change to rapid adaptation of complex traits remains unresolved. We used abdominal pigmentation in as a model phenotype to address the nature, genetic architecture, and repeatability of rapid adaptation in the field.
View Article and Find Full Text PDFNontyphoidal salmonellosis is one of the most significant foodborne diseases in the United States and globally. There are no vaccines available for human use to prevent this disease, and only broad-spectrum antibiotics are available to treat complicated cases of the disease. However, antibiotic resistance is on the rise and new therapeutics are needed.
View Article and Find Full Text PDFAlthough salmonellosis, an infectious disease, is a significant global healthcare burden, there are no -specific vaccines or therapeutics for humans. Motivated by our finding that FraB, a deglycase responsible for fructose-asparagine catabolism, is a viable drug target, we initiated experimental and computational efforts to identify inhibitors of FraB. To this end, our recent high-throughput screening initiative yielded almost exclusively uncompetitive inhibitors of FraB.
View Article and Find Full Text PDFDrosophila melanogaster is a leading model in population genetics and genomics, and a growing number of whole-genome data sets from natural populations of this species have been published over the last years. A major challenge is the integration of disparate data sets, often generated using different sequencing technologies and bioinformatic pipelines, which hampers our ability to address questions about the evolution of this species. Here we address these issues by developing a bioinformatics pipeline that maps pooled sequencing (Pool-Seq) reads from D.
View Article and Find Full Text PDFA simplified two-step synthesis of 3,6-di-hydroxy-picolinic acid (3-hy-droxy-6-oxo-1,6-di-hydro-pyridine-2-carb-oxy-lic acid), CHNO (), an inter-mediate in the metabolism of picolinic acid, is described. The crystal structure of , along with that of a labile inter-mediate, dipotassium 3-hy-droxy-6-(sulfonato-oxy)pyridine-2-carboxyl-ate monohydrate, 2K·CHNOS·HO (), is also described. Compound comprises a pyridine ring with carboxyl-ate, hydroxyl (connected by an intra-molecular O-H⋯O hydrogen bond), and sulfate groups at the 2-, 3-, and 6-positions, respectively, along with two potassium cations for charge balance and one water mol-ecule of crystallization.
View Article and Find Full Text PDFTo advance our understanding of adaptation to temporally varying selection pressures, we identified signatures of seasonal adaptation occurring in parallel among populations. Specifically, we estimated allele frequencies genome-wide from flies sampled early and late in the growing season from 20 widely dispersed populations. We identified parallel seasonal allele frequency shifts across North America and Europe, demonstrating that seasonal adaptation is a general phenomenon of temperate fly populations.
View Article and Find Full Text PDFIEEE Trans Neural Netw Learn Syst
November 2022
Acta Crystallogr E Crystallogr Commun
September 2020
The title compound, CHN ·2Br·HO () is a member of the class of compounds called viologens. Viologens are quaternary salts of di-pyridyls and are especially useful as redox indicators as a result of their large negative one-electron reduction potentials. Compound consists of a dication composed of a pair of 4-methyl-pyridine rings mutually joined at the 2-position, with a dihedral angle between the pyridine rings of 62.
View Article and Find Full Text PDFThe trimethylamine methyltransferase MttB is the first described member of a superfamily comprising thousands of microbial proteins. Most members of the MttB superfamily are encoded by genes that lack the codon for pyrrolysine characteristic of trimethylamine methyltransferases, raising questions about the activities of these proteins. The superfamily member MtcB is found in the human intestinal isolate ATCC 8486, an acetogen that can grow by demethylation of l-carnitine.
View Article and Find Full Text PDFThe power of quantum computers is still somewhat speculative. Although they are certainly faster than classical ones at some tasks, the class of problems they can efficiently solve has not been mapped definitively onto known classical complexity theory. This means that we do not know for which calculations there will be a "quantum advantage," once an algorithm is found.
View Article and Find Full Text PDFThe trimethylamine methyltransferase MttB is the founding member of a widely distributed superfamily of microbial proteins. Genes encoding most members of the MttB superfamily lack the codon for pyrrolysine that distinguishes previously characterized trimethylamine methyltransferases, leaving the function(s) of most of the enzymes in this superfamily unknown. Here, investigating the MttB family member MtpB from the human intestinal isolate ATCC 8486, an acetogen that excretes methyl proline during growth on proline betaine, we demonstrate that MtpB catalyzes anoxic demethylation of proline betaine.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
April 2019
To fulfill their biological functions, proteins must interact with their specific binding partners and often function as large assemblies composed of multiple proteins or proteins plus other biomolecules. Structural characterization of these complexes, including identification of all binding partners, their relative binding affinities, and complex topology, is integral for understanding function. Understanding how proteins assemble and how subunits in a complex interact is a cornerstone of structural biology.
View Article and Find Full Text PDFUnderstanding the rate of evolutionary change and the genetic architecture that facilitates rapid adaptation is a current challenge in evolutionary biology. Comparative studies show that genes with immune function are among the most rapidly evolving genes across a range of taxa. Here, we use immune defence in natural populations of to understand the rate of evolution in natural populations and the genetics underlying rapid change.
View Article and Find Full Text PDFThe food-borne bacterial pathogen, Salmonella enterica, can utilize fructose-asparagine (F-Asn) as its sole carbon and nitrogen source. F-Asn is the product of an Amadori rearrangement following the nonenzymatic condensation of glucose and asparagine. Heating converts F-Asn via complex Maillard reactions to a variety of molecules that contribute to the color, taste, and aroma of heated foods.
View Article and Find Full Text PDFcan utilize fructose-asparagine (F-Asn) as a source of carbon and nitrogen. This capability has been attributed to five genes in the locus. Previously, we determined that mutations in (deglycase), (kinase), or (transporter) eliminated the ability of to grow on F-Asn, while a mutation in allowed partial growth.
View Article and Find Full Text PDFVery little information exists for long-term changes in genetic variation in natural populations. Here we take the unique opportunity to compare a set of data for SNPs in 15 metabolic genes from eastern US collections of Drosophila melanogaster that span a large latitudinal range and represent two collections separated by 12 to 13 years. We also expand this to a 22-year interval for the Adh gene and approximately 30 years for the G6pd and Pgd genes.
View Article and Find Full Text PDFSalmonella can utilize fructose-asparagine (F-Asn), a naturally occurring Amadori product, as its sole carbon and nitrogen source. Conversion of F-Asn to the common intermediates glucose-6-phosphate, aspartate, and ammonia was predicted to involve the sequential action of an asparaginase, a kinase, and a deglycase. Mutants lacking the deglycase are highly attenuated in mouse models of intestinal inflammation owing to the toxic build-up of the deglycase substrate.
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