A5053822769- Genetic and phenotypic traits in livestock
- Monoclonal and Polyclonal Antibodies Research
- Genetic Mapping and Diversity in Plants and Animals
- Toxin Mechanisms and Immunotoxins
- Click Chemistry and Applications
- Chemical Synthesis and Analysis
- Peptidase Inhibition and Analysis
- Immunotherapy and Immune Responses
- Cancer-related molecular mechanisms research
- Polyamine Metabolism and Applications
- Glycosylation and Glycoproteins Research
- Genetics and Plant Breeding
- RNA and protein synthesis mechanisms
- CAR-T cell therapy research
- RNA modifications and cancer
- Axon Guidance and Neuronal Signaling
- Advanced biosensing and bioanalysis techniques
- Cancer Immunotherapy and Biomarkers
- Computational Drug Discovery Methods
- Advanced Image and Video Retrieval Techniques
- Probabilistic and Robust Engineering Design
- Meat and Animal Product Quality
- Model Reduction and Neural Networks
- Cancer Cells and Metastasis
- Biochemical and Molecular Research
Bicycle Therapeutics (United Kingdom)
2017-2024
Huazhong University of Science and Technology
2021-2024
Prairie View A&M University
2024
Shanghai Normal University
2022-2024
Cedars-Sinai Medical Center
2023
Australian National University
2023
Fudan University
2021-2022
Agriculture and Agri-Food Canada
2015-2020
Photochemistry Center
2020
Weatherford College
2020
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDirect identification of the active-site nucleophile in a DNA (cytosine-5)-methyltransferaseLin Chen, Andrew M. MacMillan, Wilbur Chang, K. Ezaz-Nikpay, William S. Lane, and Gregory L. VerdineCite this: Biochemistry 1991, 30, 46, 11018–11025Publication Date (Print):November 19, 1991Publication History Published online1 May 2002Published inissue 19 November...
Abstract The EphA2 receptor is found at high levels in tumors and low normal tissue expression biopsies a predictor of poor outcome patients. Drug discovery groups have therefore sought to develop EphA2-based therapies using small molecule, peptide, nanoparticle-based approaches (1–3). However, until now only EphA2-targeting antibody–drug conjugates (ADC) entered clinical development. For example, MEDI-547 an ADC that displayed encouraging antitumor activity preclinical models progressed...
Abstract Background Genome wide association studies (GWAS) on residual feed intake (RFI) and its component traits including daily dry matter (DMI), average gain (ADG), metabolic body weight (MWT) were conducted in a population of 7573 animals from multiple beef cattle breeds based 7,853,211 imputed whole genome sequence variants. The GWAS results used to elucidate genetic architectures the efficiency related cattle. Results DNA variant allele substitution effects approximated bell-shaped...
Bicycle toxin conjugates (BTCs) are a promising new class of molecules for targeted delivery payloads into tumors. Herein we describe the discovery BT8009, Nectin-4 targeting BTC currently under clinical evaluation. is overexpressed in multiple tumor types and clinically validated target selective cytotoxic payloads. A bicyclic peptide was identified by phage display, which showed highly binding but suffered from low plasma stability poor physicochemical properties. Multiparameter chemical...
Bicycles are constrained bicyclic peptides that represent a promising binding modality for use in targeted drug conjugates. A phage display screen against EphA2, receptor tyrosine kinase highly expressed number of solid tumors, identified Bicycle families with low nanomolar affinity. toxin conjugate (BTC) was generated by derivatization one these the potent cytotoxin DM1 via cleavable linker. This BTC demonstrated antitumor activity vivo but poorly tolerated, which hypothesized to be result...
Abstract Multiple tumor types overexpress Nectin-4 and the antibody–drug conjugate (ADC), enfortumab vedotin (EV) shows striking efficacy in clinical trials for metastatic urothelial cancer, which expresses high levels of Nectin-4, validating as a target toxin delivery this indication. Despite excellent data little are reported EV other expressing tumors therapy can produce significant toxicities many patients, frequently leading to discontinuation treatment. Thus, additional approaches with...
The aim of this study was to evaluate the impact genotype imputation on performance GBLUP and Bayesian methods for genomic prediction. A total 10,309 Holstein bulls were genotyped BovineSNP50 BeadChip (50 k). Five low density single nucleotide polymorphism (SNP) panels, containing 6,177, 2,480, 1,536, 768 384 SNPs, simulated from 50 k panel. fraction 0%, 33% 66% animals randomly selected training sets have genotypes which then imputed into genotypes. a method used predict direct values (DGV)...
Heterosis has been suggested to be caused by dominance effects. We performed a joint genome-wide association analysis (GWAS) using data from multi-breed and crossbred beef cattle identify single nucleotide polymorphisms (SNPs) with significant effects associated variation in growth carcass traits understand the mode of action these associations.Illumina BovineSNP50 genotypes phenotypes for 11 were available 6796 cattle. After performing quality control, 42,610 SNPs 6794 animals used further...
Abstract Molecular imaging of cancers using probes specific for tumor-associated target proteins offers a powerful solution providing information regarding selection targeted therapy, patient stratification, and response to therapy. Here we demonstrate the power bicyclic peptides as targeting probes, exemplified with tumor-overexpressed matrix metalloproteinase MT1-MMP target. A peptide subnanomolar affinity towards was identified, its radioconjugate showed selective tumor uptake in an...
Abstract Background Genome wide association studies (GWAS) were conducted on 7,853,211 imputed whole genome sequence variants in a population of 3354 to 3984 animals from multiple beef cattle breeds for five carcass merit traits including hot weight (HCW), average backfat thickness (AFAT), rib eye area (REA), lean meat yield (LMY) and marbling score (CMAR). Based the GWAS results, genetic architectures elucidated. Results The distributions DNA variant allele substitution effects approximated...
COVID-19 has stimulated the rapid development of new antibody and small molecule therapeutics to inhibit SARS-CoV-2 infection. Here we describe a third antiviral modality that combines drug-like advantages both. Bicycles are entropically constrained peptides stabilized by central chemical scaffold into bi-cyclic structure. Rapid screening diverse bacteriophage libraries against Spike yielded unique Bicycle binders across entire protein. Exploiting Bicycles' inherent combinability, converted...
The ATLAS detector has been designed for operation at CERN's Large Hadron Collider. includes a complex system of liquid argon calorimeters. This paper describes the architecture and implementation custom front end electronics developed readout
Riboswitches are regions of mRNA that directly bind metabolites, leading to alteration gene expression. We have developed fragment-based methods screen for compounds the Escherichia coli thiM riboswitch. Using complementary biophysical techniques we identified several ligands with K(D) <100 microM. From these there is potential develop potent and selective modulators riboswitch function.
Background In contrast to immune checkpoint inhibitors, the use of antibodies as agonists costimulatory receptors cancer therapeutics has largely failed. We sought address this problem using a new class modular synthetic drugs, termed tumor-targeted cell (TICAs), based on constrained bicyclic peptides ( Bicycles ). Methods Phage libraries displaying were panned for binders against tumor necrosis factor (TNF) superfamily CD137 and OX40, antigens EphA2, Nectin-4 programmed death ligand 1. The...
Riboswitches are regions of mRNA that bind selectively certain metabolites, thereby regulating gene expression. We have developed a method, which uses combination biophysical techniques (equilibrium dialysis, waterLOGSY and T2 relaxation-edited NMR spectroscopy isothermal titration calorimetry) allows screening identification novel ligands for riboswitches. By this method library 1300 fragments was screened on the E. colithiamine pyrophosphate (TPP) riboswitchthiM, resulting in 17 hits. The...
The Escherichia coli thiM riboswitch forms specific contacts with its natural ligand, thiamine pyrophosphate (TPP or diphosphate), allowing it to generate not only nanomolar binding affinity, but also a high degree of discrimination against similar small molecules. A range synthetic TPP analogues have been used probe each the riboswitch-ligand interactions. results show that pyrimidine-sensing helix is exquisitely tuned select for by recognising H-bonding donor and acceptors around...
Background: Identification of genetic variants that are associated with fatty acid composition in beef will enhance our understanding host influence on the trait and also allow for more effective improvement profiles through genomic selection marker-assisted diet management.In this study, 81 83 traits were measured subcutaneous adipose (SQ) longissimus lumborum muscle (LL), respectively, from 1366 purebred crossbred steers heifers genotyped Illumina BovineSNP50 Beadchip.The objective was to...
An objective of commercial beef cattle crossbreeding programs is to simultaneously optimize use additive (breed differences) and non-additive (heterosis) effects. A total 6,794 multibreed crossbred with phenotype Illumina BovineSNP50 genotype data were used predict genomic heterosis for growth carcass traits by applying two methods assumed be linearly proportional heterosis. The as follows: 1) retained heterozygosity predicted from breed fractions (HET1) 2) deviation adjusted midparent value...
Thymic stromal lymphopoietin (TSLP) is an epithelial-derived pro-inflammatory cytokine involved in the development of asthma and other atopic diseases. We used Bicycle Therapeutics' proprietary phage display platform to identify bicyclic peptides (Bicycles) with high affinity for TSLP, a target that difficult drug conventional small molecules due extended protein–protein interactions it forms both receptors. The hit series was shown bind TSLP hotspot, also by IL-7Rα. Guided first X-ray...
The objectives of this study were to evaluate fixed risk factors associated with PWM and estimate genetic parameters for PWM. A total 927 birth records from a mixed population purebred crossbred Boer Spanish goats born between 2016 2023 at the International Goat Research Center (IGRC) used study. Four binary traits studied: D0–3 (death within 3 days after birth), D4–60 4 60 days), D61–90 61 90 D0–90 days). Logistic regression models traits. Bayesian threshold Gibbs sampling parameters. Birth...
In this study, a Cu2O/TiO2 (CuTi) visible-light photocatalytic composite was employed for the treatment of Xanthomonas campestris and X. campestris-infected Brassica napus seedlings. The minimum inhibitory concentration (MIC) bactericidal (MBC) values against were determined to be 8 32 μg ml-1, respectively. Transmission electron microscopy analysis demonstrated direct correlation between extent bacterial cell damage CuTi. Noteworthily, rate 100% achieved at 150 ml-1 over duration 120 min....
This study examined the feasibility and accuracy of using Illumina BovineSNP50 genotypes to estimate individual cattle breed composition heterosis relative from pedigree. First, pedigree was used compute fractions for 1124 crossbred cattle. Given sires dams, retained heterozygosity were computed all individuals. Second, animals' individual's genomic by applying a cross-validation method. Average genome-wide based on fraction computed. Lastly, accuracies composition, assessed as Pearson's...
Genomic prediction in multiple populations can be viewed as a multi-task learning problem where tasks are to derive equations for each population and property improved by sharing information across populations. The goal of this study was develop Bayesian model multi-population genomic with strategy effectively share Simulation studies real data from Holstein Ayrshire dairy breeds phenotypes on five milk production traits were used evaluate the proposed compare single-task simple pooling...