A5069241881- Enzyme Structure and Function
- Protein Structure and Dynamics
- RNA and protein synthesis mechanisms
- Genomics and Phylogenetic Studies
- Metabolomics and Mass Spectrometry Studies
- DNA and Nucleic Acid Chemistry
- Advanced NMR Techniques and Applications
- Photosynthetic Processes and Mechanisms
- Bacterial Genetics and Biotechnology
- DNA Repair Mechanisms
- Viral Infections and Vectors
- Microbial Community Ecology and Physiology
- RNA modifications and cancer
- Machine Learning in Bioinformatics
- NMR spectroscopy and applications
- Advanced MRI Techniques and Applications
- Microbial Natural Products and Biosynthesis
- Virus-based gene therapy research
- Cancer Research and Treatments
- Viral gastroenteritis research and epidemiology
- CAR-T cell therapy research
- Bacteriophages and microbial interactions
- Cancer, Hypoxia, and Metabolism
- RNA Research and Splicing
- Clostridium difficile and Clostridium perfringens research
Miami University
2016-2025
Anthony Nolan
2024
South Dakota State University
2024
University College London
2024
Ottawa Hospital
2009-2023
Ottawa Hospital Research Institute
2009-2023
University of Ottawa
2009-2018
University of Cincinnati
2017
University of California, Davis
2005-2016
Pfizer (United Kingdom)
2014
The measurement of dipolar contributions to the splitting 15N resonances 1H-15N amide pairs in multidimensional high-field NMR spectra field-oriented cyanometmyoglobin is reported. splittings appear as small field-dependent perturbations normal scalar couplings. Assignment more than 90 specific sequential sites protein allows correlation with predictions based on known susceptibility and structure protein. Implications an additional source information for determination solution are discussed.
Clostridium difficile is a major cause of health care-associated infection, but disagreement between diagnostic tests an ongoing barrier to clinical decision making and public reporting. Molecular are increasingly used diagnose C infection (CDI), many molecular test-positive patients lack toxins that historically defined disease, it unclear if they need treatment.To determine the natural history for treatment who toxin immunoassay negative polymerase chain reaction (PCR) positive (Tox-/PCR+)...
Necrotizing enterocolitis (NEC) is a devastating intestinal disease that afflicts 10% of extremely preterm infants. The contribution early colonization to NEC onset not understood, and predictive biomarkers guide prevention are lacking. We analyzed banked stool urine samples collected prior from infants <29 weeks gestational age, including 11 who developed 21 matched controls survived free NEC. Stool bacterial communities were profiled by 16S rRNA gene sequencing. Urinary metabolomic...
Conventional protein structure determination from nuclear magnetic resonance data relies heavily on side-chain proton-to-proton distances. The necessary assignment, however, is labor intensive and prone to error. Here we show that structures can be accurately determined without (NMR) information the side chains for proteins up 25 kilodaltons by incorporating backbone chemical shifts, residual dipolar couplings, amide proton distances into Rosetta modeling methodology. These data, which are...
The influx of genomic sequence information has led to the concept structural proteomics, determination protein structures on a genome-wide scale. Here we describe an approach proteomics small proteins using NMR spectroscopy. Over 500 from several organisms were cloned, expressed, purified, and evaluated by NMR. Although there was variability among proteomes, overall 20% these found be readily amenable structure determination. sample preparation centralized in one facility, distributive used...
Recent advances in molecular modeling of protein structures are changing the field structural biology. AlphaFold-2 (AF2), an AI system developed by DeepMind, Inc., utilizes attention-based deep learning to predict models with high accuracy relative determined X-ray crystallography and cryo-electron microscopy (cryoEM). Comparing AF2 using solution NMR data, both similarities distinct differences have been observed. Since was trained on crystal cryoEM structures, we assessed how accurately...
The human gastrointestinal tract is home to hundreds of species bacteria and the balance between beneficial pathogenic plays a critical role in health disease. infant, however, born with sterile gut complex host/bacterial ecosystem only established after birth by rapid bacterial colonization. Composition newborn flora depends on several factors including type (Ceasarian or natural), manner early feeding (breast milk formula), exposure local, physical environment. Imbalance normal, healthy...
Surgical stress results in a significant reduction natural killer (NK) cell cytotoxicity (NKC), which has been linked to postoperative cancer metastases. However, few studies have measured the impact of surgical upon NK IFNγ secretion (NKA), cytokine with essential roles controlling infection and The objective this study was investigate on NKA colorectal (CRC) surgery patients.Peripheral blood collected from CRC patients (n = 42) preoperatively day (POD) 1, 3, 5, 28, 56. Healthy donor 27)...
Hsp90 is a homodimeric ATP-dependent molecular chaperone that remodels its substrate ‘client’ proteins, facilitating their folding and activating them for biological function. Despite decades of research, the mechanism connecting ATP hydrolysis function remains elusive. Particularly puzzling has been apparent lack cooperativity in each protomer. A crystal structure mitochondrial Hsp90, TRAP1, revealed catalytically active state closed highly strained asymmetric conformation. This asymmetry,...
Despite improvements in chemotherapy and radical surgical debulking, peritoneal carcinomatosis (PC) remains among the most common causes of death from abdominal cancers. Immunotherapies have been effective for selected solid malignancies, but their potential PC has little explored. Here, we report that intraperitoneal injection an infected cell vaccine (ICV), consisting autologous tumor cells ex vivo with oncolytic Maraba MG1 virus expressing IL12, promotes migration activated natural killer...
A combination of structural, biochemical, and genetic studies in model organisms was used to infer a cellular role for the human protein (SBDS) responsible Shwachman-Bodian-Diamond syndrome. The crystal structure SBDS homologue Archaeoglobus fulgidus, AF0491, revealed three domain protein. N-terminal domain, which harbors majority disease-linked mutations, has novel three-dimensional fold. central common winged helix-turn-helix motif, C-terminal shares structural homology with known...
The P[19] genotype belongs to the P[II] genogroup of group A rotaviruses (RVs). However, unlike other RVs, which mainly infect humans, RVs commonly animals (pigs), making unique for study RV diversity and host ranges. Through in vitro binding assays saturation transfer difference (STD) nuclear magnetic resonance (NMR), we found that could bind mucin cores 2, 4, 6, as well type 1 histo-blood antigens (HBGAs). common sequences these glycans serve minimal units, while additional residues, such...
K-Ras, a molecular switch that regulates cell growth, apoptosis and metabolism, is activated when it undergoes conformation change upon binding GTP deactivated following the hydrolysis of to GDP. Hydrolysis in water accelerated by coordination where adopts high-energy approaching transition state. The G12A mutation reduces intrinsic K-Ras an unexplained mechanism. Here, crystal structures complex with GDP, GTP, GTPγS GppNHp, Q61A are reported. In K-Ras-GTP complex, I region significant...
Despite curative intent resection in patients with non-small cell lung cancer (NSCLC), recurrence leading to mortality remains too common. Melatonin has shown promise for the treatment of cancer; however, its effect following not been studied. We evaluated if melatonin taken after complete reduces and mortality, or impacts quality life (QOL), symptomatology immune function. Participants received (20 mg) placebo nightly one year surgical primary NSCLC. The outcome was two-year disease-free...
Background: Pancreatic cancer is the most lethal of all human cancers. The disease has no obvious symptoms in its early stages and majority cases, goes undetected until it advanced to point that surgery longer a viable option or metastasized other organs. absence reliable sensitive biomarkers for detection pancreatic contributes poor ability detect before progresses an untreatable stage. Objectives: Here, orthotopic xenograft mouse model was investigated determine if urinary metabolic could...