Publications by authors named "JM Richardson"

Artificial metalloenzymes (ArMs) have emerged as a promising avenue in the field of biocatalysis, offering new reactivity. However, their design remains challenging due to the limited understanding of their protein dynamics and how the introduced cofactors alter the protein scaffold structure. Here we present the structures and catalytic activity of novel copper ArMs capable of ()- or ()-stereoselective control, utilizing a steroid carrier protein (SCP) scaffold.

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Extensive theory exists regarding population sex ratio evolution that predicts equal sex ratio (when parental investment is equal). In most animals, sex chromosomes determine the sex of offspring, and this fixed genotype for sex has made theory difficult to test since genotypic variance for the trait (sex) is lacking. It has long been argued that the genotype has become fixed in most animals due to the strong selection for equal sex ratios.

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Tyrosyl DNA phosphodiesterase (TDP1) is a DNA repair enzyme that hydrolyzes the phosphotyrosyl linkage between 3'-DNA-protein crosslinks such as stalled topoisomerase 1 cleavage complexes (Top1cc). Here, we present a fluorescence-resonance-energy-transfer-(FRET) based assay to estimate modulation of TDP1 activity through arginine methylation. We describe steps for TDP1 expression and purification and estimating TDP1 activity using fluorescence-quenched probes mimicking Top1cc.

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Tyrosyl-DNA phosphodiesterase (TDP1) hydrolyzes the phosphodiester bond between a DNA 3' end and a tyrosyl moiety and is implicated in the repair of trapped topoisomerase I (Top1)-DNA covalent complexes (Top1cc). Protein arginine methyltransferase 5 (PRMT5) catalyzes arginine methylation of TDP1 at the residues R361 and R586. Here, we establish mechanistic crosstalk between TDP1 arginine methylation and ubiquitylation, which is critical for TDP1 homeostasis and cellular responses to Top1 poisons.

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Science, Technology, Engineering and Mathematics (STEM) disciplines recognize the need for leadership development, but the lack of a professionally endorsed model has led to a patchwork of programmes across the nation, each with its unique brand of skills development. Leadership programmes in six diverse STEM fields are included.

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Objective: Diffuse correlation spectroscopy (DCS) is an optical technique that allows for the non-invasive measurement of blood flow. Recent work has shown that utilizing longer wavelengths beyond the traditional NIR range provides a significant improvement to signal-to-noise ratio (SNR). However, current detectors both sensitive to longer wavelengths and suitable for clinical applications (InGaAs/InP SPADs) suffer from suboptimal afterpulsing and dark noise characteristics.

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Introduction: Self-monitoring of blood glucose (BG) is important in diabetes management, allowing people with diabetes (PWD) to assess responses to diabetes therapy and to inform if they are attaining their glycemic targets. This study assessed the accuracy and user performance (UP) of a new blood glucose monitoring system (BGMS), CONTOUR®PLUS ELITE, according to International Organization for Standardization (ISO) 15197:2013 criteria and also more stringent criteria.

Methods: In laboratory Study 1, capillary fingertip blood samples from 100 PWD were evaluated using the new BGMS.

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The self-renewal efficiency of mouse embryonic stem cells (ESCs) is determined by the concentration of the transcription factor NANOG. While NANOG binds thousands of sites in chromatin, the regulatory systems that control DNA binding are poorly characterised. Here, we show that NANOG is phosphorylated by casein kinase I, and identify target residues.

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Animal studies are essential to biomedical research and the cornerstone is a reproducible animal model. While there are many reports on rodent peripheral nerve injury models, a large animal model is essential to confirm the effects of nerve regeneration over the longer distances of regeneration required in humans. Swine have long been used as a large animal model for other surgical and biomedical studies.

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Objective: To compare time efficiency and nociceptive input between digital strumming (DS) and sharp transection (ST) of the suspensory ligament during ovariohysterectomy (OVH).

Study Design: Randomized controlled trial.

Animals: 30 adult female dogs.

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The high rate of new HIV infections, particularly in Sub-Saharan Africa, emphasizes the need for a safe and effective vaccine to prevent acquired immunodeficiency syndrome (AIDS). To date, the only HIV vaccine trial that has exhibited protective efficacy in humans was the RV144 study completed in Thailand. The finding that protection correlated with antibodies to gp120 suggested that increasing the quality or magnitude of the antibody response that recognize gp120 might improve the modest yet significant protection (31.

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Objective: To examine psychosocial mediators of the effect of a culturally tailored dietary intervention on dietary change among Hispanic/Latina breast cancer survivors.

Methods: Hispanic/Latina breast cancer survivors (n = 70) were randomized to receive either a 12-week theory-based and culturally tailored dietary change program (intervention group, n = 34), or standard-of-care printed recommendations (control group, n = 36) (ClinicalTrials.gov NCT01414062).

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Tyrosyl-DNA phosphodiesterase (Tdp1) is a DNA 3'-end processing enzyme that repairs topoisomerase 1B-induced DNA damage. We use a new tool combining site-specific DNA-protein cross-linking with mass spectrometry to identify Tdp1 interactions with DNA. A conserved phenylalanine (F259) of Tdp1, required for efficient DNA processing in biochemical assays, cross-links to defined positions in DNA substrates.

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Case Summary: An approximately 3-year-old, male domestic longhair cat was presented to a mobile veterinary unit for routine neuter. Preoperative physical examination revealed an approximately 5 cm × 2 cm scab on the craniolateral portion of the left antebrachium. The cat was anesthetized for the neuter using an injectable anesthesia protocol.

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While next-generation sequencing has accelerated the discovery of human disease genes, progress has been largely limited to the "low hanging fruit" of mutations with obvious exonic coding or canonical splice site impact. In contrast, the lack of high-throughput, unbiased approaches for functional assessment of most noncoding variants has bottlenecked gene discovery. We report the integration of transcriptome sequencing (RNA-seq), which surveys all mRNAs to reveal functional impacts of variants at the transcription level, into the gene discovery framework for a unique human disease, microcephaly-micromelia syndrome (MMS).

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The periwinkle, , is found throughout the intertidal zone, often in isolated subpopulations. The majority of trematode parasites use snails as intermediate hosts, and decreased survivorship is often observed in snails infected with trematodes. Sampling from four sites in Barkley Sound, British Columbia, Canada, we test the effects of parasitic infection on snail survival using maximum likelihood and Bayesian approaches using the software MARK and WinBUGS.

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Delivery of DNA to cells and its subsequent integration into the host genome is a fundamental task in molecular biology, biotechnology and gene therapy. Here we describe an IP-free one-step method that enables stable genome integration into either prokaryotic or eukaryotic cells. A synthetic mariner transposon is generated by flanking a DNA sequence with short inverted repeats.

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Background: Among Hispanic breast cancer survivors, we examined the long-term effects of a short-term culturally based dietary intervention on increasing fruits/vegetables (F/V), decreasing fat, and changing biomarkers associated with breast cancer recurrence risk.

Methods: Spanish-speaking women (n = 70) with a history of stage 0-III breast cancer who completed treatment were randomized to ¡Cocinar Para Su Salud! (n = 34), a culturally based 9-session program (24 hours over 12 weeks, including nutrition education, cooking classes, and food-shopping field trips), or a control group (n = 36, written dietary recommendations for breast cancer survivors). Diet recalls, fasting blood, and anthropometric measures were collected at baseline, 6, and 12 months.

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Cut-and-paste DNA transposons of the mariner/Tc1 family are useful tools for genome engineering and are inserted specifically at TA target sites. A crystal structure of the mariner transposase Mos1 (derived from Drosophila mauritiana), in complex with transposon ends covalently joined to target DNA, portrays the transposition machinery after DNA integration. It reveals severe distortion of target DNA and flipping of the target adenines into extra-helical positions.

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Sex-determining systems are remarkably diverse and may evolve rapidly. Polygenic sex-determination systems are predicted to be transient and evolutionarily unstable, yet examples have been reported across a range of taxa. Here, we provide the first direct evidence of polygenic sex determination in Tigriopus californicus, a harpacticoid copepod with no heteromorphic sex chromosomes.

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We have investigated the various morphological changes of helical nanofilament (HNF; B4) phases in multiscale nanochannels made of porous anodic aluminum oxide (AAO) film. Single or multihelical structures could be manipulated depending on the AAO pore size and the higher-temperature phase of each molecule. Furthermore, the nanostructures of HNFs affected by the chemical affinity between the molecule and surface were drastically controlled in surface-modified nanochannels.

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Background: There is a need for culturally relevant nutrition programs targeted to underserved cancer survivors.

Objective: Our aim was to examine the effect of a culturally based approach to dietary change on increasing fruit/vegetable (F/V) intake and decreasing fat intake among Hispanic breast cancer survivors.

Design: Participants were randomized to Intervention and Control groups.

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Article Synopsis
  • The study focuses on how different inverted repeat (IR) sequences impact the activity of mariner DNA transposons and their associated enzymes, specifically Mos1 and Mboumar-9.
  • Researchers utilized a 3.1 Å resolution crystal structure to analyze why Mos1 shows a reduced affinity for its left IR compared to its right IR during transposition.
  • The findings indicate that both transposases work more efficiently when preferred IR sequences are present at both ends and that changing a specific nucleotide can significantly enhance transposition efficiency for Mboumar-9.
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Helical nanofilaments (HNFs) have attracted much interest because of their unique optical properties, but there have been many hurdles to overcome in using them for the practical applications due to their structural complexity. Here we demonstrate that the molecular configuration and layer conformation of a modulated HNF (HNFs(mod)) can be studied using a physicochemical confinement system. The layer directions affected by the chemical affinity between the mesogen and surface were drastically controlled in surface-modified nanochannels.

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