A5047635072- Mosquito-borne diseases and control
- Viral Infections and Vectors
- Bacterial Genetics and Biotechnology
- Bacteriophages and microbial interactions
- Biochemical and Molecular Research
- Cancer therapeutics and mechanisms
- Receptor Mechanisms and Signaling
- Legume Nitrogen Fixing Symbiosis
- Insect symbiosis and bacterial influences
- Tuberculosis Research and Epidemiology
- Mass Spectrometry Techniques and Applications
- RNA and protein synthesis mechanisms
- Malaria Research and Control
- Antimicrobial Resistance in Staphylococcus
- Pancreatic function and diabetes
- Monoclonal and Polyclonal Antibodies Research
- Musculoskeletal synovial abnormalities and treatments
- Sarcoma Diagnosis and Treatment
- Diabetes and associated disorders
- Antibiotic Resistance in Bacteria
- Neuropeptides and Animal Physiology
- Diabetes Management and Research
- Macrophage Migration Inhibitory Factor
- Chronic Disease Management Strategies
- Hematopoietic Stem Cell Transplantation
University of Northampton
2025
O.N. Diagnostics (United States)
2023
Stanford University
1997-2019
The Christie Hospital
2017
Children's Mercy Hospital
2010
University of Alberta
1994-2002
Icahn School of Medicine at Mount Sinai
2002
Blank Children's Hospital
1965
Taylor Wimpey (United Kingdom)
1965
Bentley (Germany)
1965
Significance G protein-coupled receptors (GPCRs) represent both the largest class of drug targets and family human membrane proteins. Recent three-dimensional structures have revealed presence many water molecules buried inside GPCRs, but functional role these has been unclear. Using extensive atomic-level computer simulations, we find that, although most waters are highly mobile, a few stable. These stable mediate state-dependent state-independent polar networks that conserved across...
West Nile virus, a member of the Flavivirus genus, causes fever that can progress to life-threatening encephalitis. The major envelope glycoprotein, E, these viruses mediates viral attachment and entry by membrane fusion. We have determined crystal structure soluble fragment virus E. adopts same overall fold as E proteins from dengue tick-borne encephalitis viruses. conformation domain II is different in other prefusion structures, however, resembles postfusion structures. epitopes...
ABSTRACT Dengue virus relies on a conformational change in its envelope protein, E, to fuse the viral lipid membrane with endosomal and thereby deliver genome into cytosol. We have determined crystal structure of soluble fragment E (sE) dengue type 1 (DEN-1). The protein is postfusion conformation even though it was not exposed or detergent. At domain I-domain III interface, 4 polar residues form tight cluster that absent other flaviviral structures. Two these residues, His-282 His-317, are...
Abstract The number of structures and molecular dynamics simulations proteins is exploding owing to dramatic advances in cryo-electron microscopy, crystallography, computing. One the most powerful ways analyze structural information involves comparisons interatomic interactions across different or same protein related from family ( e.g. GPCRs). Such comparative analyses are interest a wide range researchers but currently prove challenging for all few. To facilitate analyses, we have...
Summary The effects of defined mutations In the lipopolysaccharide (LPS) and outer membrane protein OmpA recipient cell on mating‐pair formation in liquid media by transfer systems F‐Iike plasmids pOX38 (F), ColB2 R100‐1 were investigated. Transfer all three was affected differently rfa locus cell, F plasmid being most sensitive to that rfaP gene expression which is responslbie for addition pyrophosphorylethanolamine (PPEA) heptose I inner core LPS. CoIB2 more strongly II‐heptose III region...
ABSTRACT F and R100-1 are closely related, derepressed, conjugative plasmids from the IncFI IncFII incompatibility groups, respectively. Heteroduplex mapping genetic analyses have revealed that transfer regions extremely similar between two plasmids. Plasmid specificity can occur at level of relaxosome formation, regulation, surface exclusion systems. There also differences in pilus serology, pilus-specific phage sensitivity, requirements for OmpA lipopolysaccharide components recipient...
Abstract The immune response against viral infection relies on the early production of cytokines that induce an antiviral state and trigger activation cells. This is initiated by recognition virus-associated molecular patterns such as dsRNA, a replication intermediate recognized TLR3 certain RNA helicases. Infection with West Nile virus (WNV) can lead to lethal encephalitis in susceptible individuals constitutes emerging health threat. In this study, we report WNV envelope protein (WNV-E)...
Background In an effort to discover new drugs treat tuberculosis (TB) we chose alanine racemase as the target of our drug discovery efforts. Mycobacterium tuberculosis, causative agent TB, plays essential role in cell wall synthesis it racemizes L-alanine into D-alanine, a key building block biosynthesis peptidoglycan. Good antimicrobial effects have been achieved by inhibition this enzyme with suicide substrates, but clinical utility class inhibitors is limited due their lack specificity...
West Nile virus is an emerging pathogen that can cause fatal neurological disease. A recombinant human mAb, mAb11, has been described as a candidate for the prevention and treatment of Using yeast surface display epitope mapping assay neutralization escape mutant, we show mAb11 recognizes fusion loop, at distal end domain II envelope protein. Ab cross-reacts with all four dengue viruses provides protection against (serotypes 2 4) viruses. In contrast to parental virus, variant failed lethal...
Summary The F‐pilus has been implicated in recipient cell recognition during the establishment of a stable mating pair before conjugation as well forming part conjugative pore for DNA transfer. is site attachment filamentous phages (M13, f1 and fd), which attach to tip, RNA phages, R17 Q β , different sites exposed on sides pilus. shown undergo eclipse, or capsid release, outside pili attached cells. New existing mutants traA combined with natural variants F‐pilin were assayed pilin...
Synovial sarcoma accounts for 5%-10 % of malignant soft-tissue tumours. Curative treatment includes surgery, with radiotherapy and/or chemotherapy. With no specific regimen synovial sarcoma, the primary aim this research was to describe characteristics a regional population in UK, and investigate clinicopathological variables associated overall survival. Ninety-four patients from East Midlands Sarcoma Service database were pseudo anonymised extracted. Kaplan-Meier Cox regression statistical...
Clostridium difficile , a Gram-positive, spore-forming anaerobic bacterium, is the leading cause of infectious diarrhea among hospitalized patients. C. frequently associated with antibiotic treatment, and causes diseases ranging from antibiotic-associated to life-threatening pseudomembranous colitis. The severity infections exacerbated by emergence hypervirulent multidrug-resistant strains, which are difficult treat often increased mortality rates. Alanine racemase (Alr)...
The flavivirus envelope (E) protein mediates cellular attachment and fusion with host cell membranes is recognized by virus-neutralizing antibodies. We raised antibodies against a broad range of epitopes immunizing horse recombinant West Nile virus (WNV) E protein. To define protective antibodies, we selected, affinity chromatography, immunoglobulins immobilized linear peptides derived from parts the Immunoglobulins binding 9 different domains I, II, III neutralized WNV in vitro. This...
Human Macrophage Migration Inhibitory Factor (MIF) is a trimeric cytokine implicated in number of inflammatory and autoimmune diseases cancer. We previously reported that the dye p425 (Chicago Sky Blue), which bound MIF at interface two trimers covering tautomerase allosteric pockets, revealed unique strategy to block MIF's pro-inflammatory activities. Structural liabilities, including large size, precluded as medicinal chemistry lead for drug development. report here rational design linking...
The sequence of a region the F plasmid containing traLEKBP genes involved in transfer was compared to equivalent regions two IncFII plasmids, R100-1 and ColB2. traLEK gene products all three plasmids were virtually identical, with most changes occurring TraE. TraB also nearly identical except for an 11-codon extension at 3' end traB gene. TraP protein R100-l differed from those ColB2 its N terminus, while contained change predicted loop which shown be exposed periplasmic space by TnphoA...
The authors report a case of 13-year-old female with recurrent Burkitt lymphoma who was heavily pretreated chemotherapy. During chemotherapy for relapse, she developed serious aspergillus infection the palate and sinuses. Despite 10 μg/kg filgrastim 5 days, peripheral blood CD34+ cells remained ≤1/μL. Hematopoietic progenitor were subsequently successfully mobilized combination AMD3100 without tumor or fungus contamination. After transplantation, patient achieved complete engraftment...
Pseudomonas aeruginosa is intrinsically resistant to many classes of antibiotics, reflecting the restrictive nature its outer membrane and action numerous efflux systems. However, dynamics compound uptake, retention, in this bacterium remain incompletely understood. Here, we exploited sensor capabilities a Z-nucleotide-sensing riboswitch create an experimental system able identify physicochemical structural properties compounds that permeate bacterial cell, avoid efflux, perturb folate cycle...