A5022666420- Prion Diseases and Protein Misfolding
- Herpesvirus Infections and Treatments
- Neurological diseases and metabolism
- Trace Elements in Health
- Cytomegalovirus and herpesvirus research
- Toxin Mechanisms and Immunotoxins
- RNA regulation and disease
- Animal Genetics and Reproduction
- Dermatology and Skin Diseases
- Bacteriophages and microbial interactions
- Viral Infections and Immunology Research
- Alzheimer's disease research and treatments
- Polyomavirus and related diseases
- Food Allergy and Anaphylaxis Research
- Electrostatics and Colloid Interactions
- Acne and Rosacea Treatments and Effects
- Vector-Borne Animal Diseases
- RNA Research and Splicing
- T-cell and Retrovirus Studies
- HIV Research and Treatment
- Signaling Pathways in Disease
- Immune Cell Function and Interaction
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Animal Virus Infections Studies
- Neuroinflammation and Neurodegeneration Mechanisms
University of Cambridge
2014-2024
Cambridge Science Centre
1996-2000
Nanopores can be used to detect and analyze single molecules in solution. We have glass nanopores made by laser-assisted capillary-pulling, as a high-throughput low cost method, range of label-free proteins: lysozyme, avidin, IgG, β-lactoglobulin, ovalbumin, bovine serum albumin (BSA), β-galactosidase Furthermore, we show for the first time solid state nanopore measurements mammalian prion protein, which its abnormal form is associated with transmissible spongiform encephalopathies. Our...
Four specific pathogen-free ponies were infected intranasally with equine herpesvirus 1 (EHV-1) and two similarly an EHV-1 thymidine kinase deletion mutant. The primary infections characterized by a transient fever accompanied virus shedding into nasal mucus viraemia. No was detected in clinical specimens after 15 days post-infection. Two months later reactivation stimulus administered to all six only the four that had been previously inoculated wild-type shed (for 10 days), proving presence...
The prion protein (PrP) has been shown to bind copper. In the present study we have investigated whether disease in a mouse scrapie model resulted modification of metal concentrations. We found changes levels copper and manganese brains scrapie-infected mice prior onset clinical symptoms. Interestingly, noted major increase blood early stages disease. Analysis purified PrP from also showed reduction binding proportional decrease antioxidant activity between 30 60 days post-inoculation....
Atypical/Nor98 scrapie (AS) is a prion disease of small ruminants. Currently there are no efficient measures to control this form disease, and, importantly, the zoonotic potential and risk that AS might represent for other farmed animal species remains largely unknown. In study, we investigated capacity propagate in bovine PrP transgenic mice. Unexpectedly, transmission isolates originating from 5 different European countries mice resulted propagation classical BSE (c-BSE) agent. Detection...
The prion protein (PrP) has been shown to bind copper. In the present study we have investigated whether disease in a mouse scrapie model resulted modification of metal concentrations. We found changes levels copper and manganese brains scrapie-infected mice prior onset clinical symptoms. Interestingly, noted major increase blood early stages disease. Analysis purified PrP from also showed reduction binding proportional decrease antioxidant activity between 30 60 days post-inoculation....
The infectious agent associated with prion diseases such as ovine scrapie shows strain diversity. Ovine strains have typically been identified by their transmission properties in wild-type mice. However, typing of isolates mice may not reveal the they exist original host. This could be circumvented if are passaged protein (PrP)-transgenic study used incubation time, lesion profile, immunohistochemistry disease-associated PrP (PrP(Sc)) and molecular profile to compare range that emerged from...
We have compared the transmission characteristics of two mouse-adapted scrapie isolates, ME7 and Rocky Mountain Laboratory (RML), in tga20 mice. These mice express elevated levels PrP protein to wild-type display a relatively short disease incubation period following intracerebral prion inoculation. Terminal induced by or RML was characterized distinct pattern clinical signs different times. High-dose inoculated intracerebrally into most rapid onset signs, with succumbing terminal after only...
PrPSc [abnormal disease-specific conformation of PrP (prion-related protein)] accumulates in prion-affected individuals the form amorphous aggregates. Limited proteolysis results a protease-resistant core molecular mass 27–30 kDa (PrP27–30). Aggregated forms co-purify with prion infectivity, although infectivity does not always correlate presence PrP27–30. This suggests that discrimination between PrPC (normal cellular PrP) and by may underestimate repertoire quantity subtypes. We have...
The identity of pro- and anti-inflammatory cytokines in the neuropathogenesis prion diseases remains undefined. Here we have investigated role on progression disease through use mice that lack interleukin-4 (IL-4), IL-10, IL-13, or both IL-4 IL-13. Collectively our data show among these cytokines, IL-10 plays a prominent regulation disease. Mice deficient are highly susceptible to development markedly shortened incubation time. In addition, correlated cytokine gene expression...
A mouse model of herpes simplex virus type 1 infection in an immunocompromised host was established by using cyclosporin-A to impair T-cell function. Following inoculation into the skin ear pinna, prolonged replication and neural tissues compared with that immunocompetent mice. This used investigate activity famciclovir (FCV) valaciclovir (VACV), which are oral products antiherpesvirus agents penciclovir acyclovir, respectively. Both prodrugs gave similar blood profiles normal...
ABSTRACT A more complete assessment of ovine prion strain diversity will be achieved by complementing biological typing in conventional and PrP transgenic mice with a biochemical analysis the resultant PrPSc. This provide correlation between phenotype molecular nature different conformers associated particular strains. Here, we have compared transmission characteristics ARQ/ARQ VRQ/VRQ scrapie isolates following primary passage tg338 (VRQ) tg59 (ARQ) mouse lines C57BL/6 ( Prnp ), RIII VM b...
The ability of famciclovir and valaciclovir to affect the establishment maintenance latency in mice with a cutaneous herpes simplex type 1 (HSV-1) infection was examined. Mice were treated via drinking water starting at various times between days 5 terminating on day 10 after inoculation. Clinical signs viral replication target tissues monitored. Three four months later, trigeminal dorsal root ganglia explanted from groups 16 examined for latent virus by cocultivation. two compounds differed...
ABSTRACT The agent responsible for prion disease may exist in different forms, commonly referred to as strains, with each carrying the specific information that determines its own distinct biological properties, such incubation period and lesion profile. Biological strain typing of ovine scrapie isolates by serial passage conventional mice has shown some diversity strains. However, this remains poorly supported biochemical typing. protein-only hypothesis predicts variation between strains...
Prions are believed to propagate when an assembly of prion protein (PrP) enters a cell and replicates produce two or more fibrils, leading exponential increase in PrP aggregate number with time. However, the molecular basis this process has not yet been established detail. Here, we use single-aggregate imaging study fibril fragmentation elongation individual murine aggregates from seeded aggregation vitro. We found that occurs via structural conversion PK-sensitive PK-resistant conformer....
The aggregation of the prion protein (PrP) plays a key role in development diseases.
Abstract The metazoan Hsp70 disaggregase protects neurons from proteotoxicity that arises the accumulation of misfolded protein aggregates. and its co-chaperones disassemble extract polypeptides aggregates for refolding or degradation. effectiveness chaperone system decreases with age leads to rather than removal neurotoxic Therapeutic enhancement disassembly machinery is proposed counter late-onset misfolding neurodegenerative disease may arise. In context prion disease, it not known...
ABSTRACT Famciclovir (FCV) and valaciclovir (VACV) have previously been shown to be potent inhibitors of herpes simplex virus type 1 (HSV-1) in a murine cutaneous model. In the present study, mice were inoculated skin left ear pinna with (HSV) 1. Antiviral therapy was started on different days postinoculation (p.i.), terminating at end day 10 p.i. The compounds administered twice daily by oral gavage 50 mg/kg body weight/dose. Mice sampled 5 p.i., during acute phase infection, titers...
Prion diseases are characterized by conformational change in the copper-binding protein PrP (prion protein). Polymorphisms ovine at amino acid residues 136, 154 and 171 associated with variation susceptibility to scrapie. PrPVRQ [PrP(Val136/Arg154/Gln171)] or PrPARQ [PrP(Ala136/Arg154/Gln171)] animals show scrapie, whereas those that express Ala136/Arg154/Arg171 (PrPARR) resistance. Results presented here PrPARR display different responses metal-ion interaction. At 37 °C copper induced...
Drosophila have emerged as a model system to study mammalian neurodegenerative diseases. In the present we generated transgenic for ovine PrP (prion protein) begin establish an invertebrate of prion disease. We polymorphic variants by PhiC31 site-specific germ-line transformation under expression control bi-partite GAL4/UAS (upstream activating sequence) system. Site-specific transgene insertion in fly genome allowed us test hypothesis that single amino acid codon changes modulate protein...
ABSTRACT Natural transmission of prion disease is believed to occur by peripheral infection such as oral inoculation. Following this route inoculation, both the nervous system and lymphoreticular may be involved in subsequent neuroinvasion central prions, which not necessarily result clinical signs terminal disease. Subclinical disease, characterized presence infectivity PrP Sc absence overt signs, occur. It known host factors contribute whether with prions culminates a or subclinical state....
The effects of famciclovir (FCV) and valaciclovir (VACV) were compared in a cutaneous infection model for herpes simplex virus type 2 (HSV-2). compounds administered orally from day 1 to 5 postinfection. Both reduced local inflammation replication the skin. FCV markedly mortality nervous system. On cessation therapy after days, when levels infectious tissues below level detection, there followed rebound ganglia brain stems mice that had been treated with VACV. recurrence stem occurred on...