A5082802243- Liver Disease Diagnosis and Treatment
- Liver Disease and Transplantation
- Hepatitis C virus research
- Monoclonal and Polyclonal Antibodies Research
- Amino Acid Enzymes and Metabolism
- Advanced biosensing and bioanalysis techniques
- Biochemical and Molecular Research
- Hepatitis B Virus Studies
- Glycosylation and Glycoproteins Research
- Carbohydrate Chemistry and Synthesis
- Metalloenzymes and iron-sulfur proteins
- Parasitic Infections and Diagnostics
- Pneumocystis jirovecii pneumonia detection and treatment
- HIV Research and Treatment
- Wastewater Treatment and Nitrogen Removal
- HIV/AIDS drug development and treatment
- Enzyme Catalysis and Immobilization
- Hemoglobinopathies and Related Disorders
- Chemical Reactions and Isotopes
- Drug-Induced Hepatotoxicity and Protection
- RNA Interference and Gene Delivery
- Healthcare Policy and Management
- HIV, Drug Use, Sexual Risk
- Microbial metabolism and enzyme function
- Foreign Body Medical Cases
University of Dundee
2020-2025
University of Hawaii System
2023-2025
Ninewells Hospital
2020-2024
Edinburgh Royal Infirmary
2022
University of Hawaiʻi at Mānoa
2017-2020
Andrews University
2020
NHS Forth Valley
2019
Brandeis University
2008-2017
Honolulu University
2017
Ludwig-Maximilians-Universität München
2014
Abstract Cirrhosis is a major cause of morbidity and mortality; however, there are no approved therapies except orthotopic liver transplantation. Preclinical studies showed that bone-marrow-derived macrophage injections reduce inflammation, resolve fibrosis stimulate regeneration. In multicenter, open-label, parallel-group, phase 2 randomized controlled trial ( ISRCTN10368050 ) in n = 51 adult patients with compensated cirrhosis Model for End-Stage Liver Disease (MELD) score ≥10 ≤17, we...
Background & AimsIn community pathways for detection of liver disease the most common reason referral is fibrosis assessment. We investigated impact adding Enhanced Liver Fibrosis (ELF) score as a second-line test (after indeterminate or high fibrosis-4 index (FIB-4) and/or non-alcoholic fatty score) to guide and prognostication in our multi-aetiology pathway.MethodsPatients with ELF results from intelligent Function Testing (iLFT) pathway were recruited. Case note review was undertaken...
A vast number of biological processes are mediated by multivalent ligand-receptor interactions, including cell adhesion, host invasion pathogens, pathogen neutralization and numerous regulatory signaling pathways. [1]Multivalency is especially important for carbohydrate-receptor interactions: whereas individual glycans [2] may bind with low affinity to a single binding site, the clustering creates high-avidity interaction clustered sites.This "carbohydrate cluster effect" [1b] has been...
DNA-based nanostructures have received great attention as molecular vehicles for cellular delivery of biomolecules and cancer drugs. Here, we report on the uptake tubule-like DNA tile-assembled 27 nm in length 8 diameter that carry siRNA molecules, folic acid fluorescent dyes. In our observations, structures are delivered to endosome do not reach cytosol GFP-expressing HeLa cells were used experiments. Consistent with this observation, no elevated silencing GFP gene could be detected....
Cryptosporidium parvum is a potential biowarfare agent, an important AIDS pathogen, and major cause of diarrhea malnutrition. No vaccines or effective drug treatment exist to combat infection. This parasite relies on inosine 5′-monophosphate dehydrogenase (IMPDH) obtain guanine nucleotides, inhibition this enzyme blocks proliferation. Here, we report the first crystal structures CpIMPDH. These reveal structural basis inhibitor selectivity suggest strategy for further optimization. Using...
SELMA (SELection with Modified Aptamers) is a directed evolution method which can be used to develop DNA-supported clusters of carbohydrates in the geometry clustering optimized for strong recognition by lectin interest. Herein, we report modification results glycoclusters achieve dramatically stronger target (100-fold) fewer glycans (2–3-fold). Our first applications yielded 5–10 oligomannose were recognized broadly neutralizing HIV antibody 2G12 moderate affinities (150–500 nM Kd's). In...
A major goal for the vaccine field is elicitation of broadly neutralizing antibodies (bnAbs) against pathogens that exhibit extensive antigenic diversity. In this study, we designed a rigid divalent immunogen high avidity binding to bnAb, VRC01, which targets CD4 site (CD4bs) HIV spike protein. This was accomplished by covalently linking two HIV-1 gp120 antigens complementary antibody and crosslinking light chains. The exhibits higher affinity VRC01-class compared non-Fab-Fab-crosslinked...
Early diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD), especially with advanced fibrosis, is crucial due to increased risk complications and mortality. Serum alanine aminotransferase (ALT) commonly used; however, many patients have normal ranges (<55 U/L) who may remain undetected. We investigated the clinical implications a lower ALT cut-off (>30 using intelligent function testing (iLFT) identify MASLD without fibrosis in primary care. All entering iLFT...
Optimizing multivalency: Clusters of Man9 glycans, which are recognized by broadly neutralizing anti-HIV antibody 2G12, have potential as HIV vaccines. However, optimal recognition 2G12 requires optimum clustering glycans. Using the recently described SELMA technique (SELection with Modified Aptamers), clusters been developed, in glycans supported DNA sequences selected from among 2×1013 variants (see scheme).
Abstract Chronic liver disease (CLD) is a significant health problem affecting millions of people worldwide. In Scotland, CLD major cause premature mortality. Liver function tests (LFTs) are panel frequently requested blood which may indicate disease. However, LFTs commonly contain at least one abnormal result, and abnormalities rarely investigated to the extent recommended by national guidelines. The intelligent Function Testing (iLFT) pathway novel, automated system designed improve early...
Directed evolution methods were developed for Cu-containing nitrite reductase (NiR) from Alcaligenes faecalis S-6. The PCR cloning strategy allows the efficient production of libraries 100 000 clones by a modification megaprimer-based whole-plasmid synthesis reaction. high-throughput screen includes colony lift onto nylon membrane and subsequent lysis NiR-expressing colonies in presence Cu2+ ions copper incorporation into intracellularly expressed NiR. Addition chromogenic substrate, 3,...
Copper-containing nitrite reductase harbors a type-1 and type-2 Cu site. The former acts as the electron acceptor site of enzyme, latter is catalytic action. effect methionine ligand on reorganization energy was explored by studying electron-transfer kinetics between NiR (wild type (wt) variants Met150Gly Met150Thr) with Fe(II)EDTA Fe(II)HEDTA. mutations increased 0.3 eV (30 kJ mol-1). A similar increase found from pulse radiolysis experiments wt NIR three (Met150Gly, Met150His, Met150Thr)....
Inosine monophosphate dehydrogenase (IMPDH) catalyzes an essential step in the biosynthesis of guanine nucleotides. This reaction involves two different chemical transformations, NAD-linked redox and a hydrolase reaction, that utilize mutually exclusive protein conformations with distinct catalytic residues. How did Nature construct such complicated catalyst? Here we employ "Wang-Landau" metadynamics algorithm hybrid quantum mechanical/molecular mechanical (QM/MM) simulations to investigate...
DoxG, an extradiol dioxygenase involved in the aerobic catabolism of naphthalene, possesses a weak ability to cleave 3,4-dihydroxybiphenyls (3,4-DHB), critical polychlorinated biphenyl metabolites. A directed evolution strategy combining error-prone PCR, saturation mutagenesis, and DNA shuffling was used improve biphenyl-degrading potential DoxG. Screening facilitated through analysis filtered, digital imaging plated colonies. simple scheme, which is readily adaptable other activities,...
Selektion mit modifizierten Aptameren: Eine Methode für die Entwicklung von Glycoclusterliganden durch gerichtete Evolution wird beschrieben. Glycanazide werden einer Bibliothek alkinylierter DNA-Sequenzen kombiniert und nach der Bindungsstärke DNA-Glycocluster selektiert amplifiziert. Die wurde zur mannosereicher Cluster genutzt, den HIV-neutralisierenden Antikörper 2G12 binden. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents...
The efficacy of direct-acting antivirals (DAA) provides an excellent opportunity to scale up HCV diagnosis and treatment, achieving the WHO target elimination by 2030. However, reinfection among people who inject drugs (PWID) remains a concern may impede efforts. We assessed rates PWID across six specialized treatment pathways, following DAA-based interferon-based therapies in Tayside, Scotland. Data were collected retrospectively for every episode that resulted sustained viral response...