Michael Hutton
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View article: Discovery and clinical translation of ceperognastat, an O‐GlcNAcase (OGA) inhibitor, for the treatment of Alzheimer's disease
Discovery and clinical translation of ceperognastat, an O‐GlcNAcase (OGA) inhibitor, for the treatment of Alzheimer's disease Open
INTRODUCTION The aggregation and spread of hyperphosphorylated, pathological tau in the human brain is hypothesized to play a key role in Alzheimer's disease (AD) as well as other neurogenerative tauopathies. O‐GlcNAcylation, an important …
View article: Using video analytics to standardise complexity of Gallbladder surgery
Using video analytics to standardise complexity of Gallbladder surgery Open
Background: Cholecystitis is a widespread disease with an associated spectrum of complications; hence, laparoscopic cholecystectomies are commonly performed. Current grading scales are quantitative and objective. There is a need for a dyna…
View article: BS P01 Case Report: Emergency Laparotomy for Retrograde Intussusception after Roux-en-Y Gastric Bypass
BS P01 Case Report: Emergency Laparotomy for Retrograde Intussusception after Roux-en-Y Gastric Bypass Open
Background Roux-en-Y gastric bypass (RYGB) is a common operation performed to treat obesity and associated co-morbidities. When done with weight management programs, it is associated with 60% excess weight loss. A rare complication is retr…
View article: FTP1.4 Computer Blast wave and Shrapnel Simulation in Unity
FTP1.4 Computer Blast wave and Shrapnel Simulation in Unity Open
Aims A computer simulation to show the effects of an explosive device's blast wave and shrapnel injuries to humans. Methods Unity 3D project written in C# with real time physics showing the effects on people and listing probable injuries s…
View article: Identification of Intervention Opportunities through Assessment of the Appropriateness of Antibiotic Prescribing in Surgical Patients in a UK Hospital Using a National Audit Tool: A Single Centre Retrospective Audit
Identification of Intervention Opportunities through Assessment of the Appropriateness of Antibiotic Prescribing in Surgical Patients in a UK Hospital Using a National Audit Tool: A Single Centre Retrospective Audit Open
Identifying opportunities to safely reduce antibiotic prescribing is necessary for prescribers and antibiotic stewardship teams to minimise unwarranted antibiotic use. We aimed to quantify excess antibiotic use in General Surgery. We retro…
View article: Metabotropic Glutamate Receptors Modulate Exocytotic Tau Release and Propagation
Metabotropic Glutamate Receptors Modulate Exocytotic Tau Release and Propagation Open
View article: Deletion of the Ubiquitin Ligase CHIP Leads to the Accumulation, But Not the Aggregation, of Both Endogenous Phospho- and Caspase-3-Cleaved Tau Species
Deletion of the Ubiquitin Ligase CHIP Leads to the Accumulation, But Not the Aggregation, of Both Endogenous Phospho- and Caspase-3-Cleaved Tau Species Open
Accumulation of the microtubule-associated protein tau into neurofibrillary lesions is a pathological consequence of several neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. Hereditary mutations in the
View article: A clinical, molecular genetics and pathological study of a FTDP-17 family with a heterozygous splicing variant c.823-10G>T at the intron 9/exon 10 of the MAPT gene
A clinical, molecular genetics and pathological study of a FTDP-17 family with a heterozygous splicing variant c.823-10G>T at the intron 9/exon 10 of the MAPT gene Open
We report the first clinical-radiological-genetic-molecular-pathological study of a kindred with c.823-10G>T MAPT intronic variant (rs63749974) associated with frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). We …
View article: The high-affinity HSP90-CHIP complex recognizes and selectively degrades phosphorylated tau client proteins
The high-affinity HSP90-CHIP complex recognizes and selectively degrades phosphorylated tau client proteins Open
A primary pathologic component of Alzheimer’s disease (AD) is the formation of neurofibrillary tangles composed of hyperphosphorylated tau (p-tau). Expediting the removal of these p-tau species may be a relevant therapeutic strategy. Here …
View article: Lab-in-a-Box: Techniques and Technologies to Manage Large and Not So Large Laboratory Courses
Lab-in-a-Box: Techniques and Technologies to Manage Large and Not So Large Laboratory Courses Open
Lab-in-a-Box: Techniques and Technologies to Manage Large and Not soLarge Laboratory CoursesA project known as Lab-in-a-Box (LiaB) was developed in 2004 by faculty members in the XElectrical and Computer Engineering (ECE) Department to imp…
View article: Quantitative propagation of assembled human Tau from Alzheimer's disease brain in microfluidic neuronal cultures
Quantitative propagation of assembled human Tau from Alzheimer's disease brain in microfluidic neuronal cultures Open
Tau aggregation and hyperphosphorylation is a key neuropathological hallmark of Alzheimer's disease (AD), and the temporospatial spread of Tau observed during clinical manifestation suggests that Tau pathology may spread along the axonal n…
View article: Differential aberrant structural synaptic plasticity in axons and dendrites ahead of their degeneration in tauopathy
Differential aberrant structural synaptic plasticity in axons and dendrites ahead of their degeneration in tauopathy Open
Neurodegeneration driven by aberrant tau is a key feature of many dementias. Pathological stages of tauopathy are characterised by reduced synapse density and altered synapse function. Furthermore, changes in synaptic plasticity have been …
View article: Imbalance in the response of pre- and post-synaptic components to amyloidopathy
Imbalance in the response of pre- and post-synaptic components to amyloidopathy Open
Alzheimer’s disease (AD)-associated synaptic dysfunction drives the progression of pathology from its earliest stages. Amyloid β (Aβ) species, both soluble and in plaque deposits, have been causally related to the progressive, structural a…
View article: Imbalance in the response of pre- and post-synaptic components to amyloidopathy
Imbalance in the response of pre- and post-synaptic components to amyloidopathy Open
Alzheimer’s disease (AD)-associated synaptic dysfunction drives the progression of pathology from its earliest stages. Aβ species, both soluble and in plaque deposits, have been causally related to the progressive, structural and functiona…
View article: Alzheimer's Disease–Related Dementias Summit 2016: National research priorities
Alzheimer's Disease–Related Dementias Summit 2016: National research priorities Open
Goal 1 of the National Plan to Address Alzheimer's Disease is to prevent and effectively treat Alzheimer disease and Alzheimer disease-related dementias by 2025. To help inform the research agenda toward achieving this goal, the NIH hosts …
View article: [P4–102]: CHARACTERISATION OF MOLECULAR MECHANISMS THAT ARE TRIGGERED AND CONTRIBUTE TO TAU PATHOLOGY IN A CELL MODEL OF TAU AGGREGATION
[P4–102]: CHARACTERISATION OF MOLECULAR MECHANISMS THAT ARE TRIGGERED AND CONTRIBUTE TO TAU PATHOLOGY IN A CELL MODEL OF TAU AGGREGATION Open
Aggregation of tau is the characteristic feature of all human tauopathies. It is known that in Alzheimer's disease (AD) several cellular mechanisms can be triggered and drive tau conformational alterations, aggregation and propagation. Her…
View article: [P3–081]: ESTABLISHING MICROFLUIDIC DEVICES AS AN <i>IN VITRO</i> NEURONAL MODEL FOR STUDYING MOLECULAR AND FUNCTIONAL ASPECTS OF TRANSNEURONAL TAU PROPAGATION
[P3–081]: ESTABLISHING MICROFLUIDIC DEVICES AS AN <i>IN VITRO</i> NEURONAL MODEL FOR STUDYING MOLECULAR AND FUNCTIONAL ASPECTS OF TRANSNEURONAL TAU PROPAGATION Open
A hallmark of neurodegenerative diseases, such as Alzheimer's disease and frontotemporal dementia, is aggregation and accumulation of tau protein as intracellular neurofibrillary tangles. Recent scientific evidence suggests the propagation…
View article: [P3–178]: <i>IN VIVO</i> TWO‐PHOTON IMAGING OF THE EFFECTS OF TAUOPATHY AND AMYLOIDOPATHY ON SYNAPSES
[P3–178]: <i>IN VIVO</i> TWO‐PHOTON IMAGING OF THE EFFECTS OF TAUOPATHY AND AMYLOIDOPATHY ON SYNAPSES Open
A progressive loss of synapses occurs at the early clinical stages of Alzheimer's Disease and has been correlated with cognitive deficits in patients. However, it is relatively unknown how synapse dynamics are affected by the two main path…
View article: Altered Synapse Stability in the Early Stages of Tauopathy
Altered Synapse Stability in the Early Stages of Tauopathy Open
View article: Influence of Chronic Heat Acclimatization on Occupational Thermal Strain in Tropical Field Conditions
Influence of Chronic Heat Acclimatization on Occupational Thermal Strain in Tropical Field Conditions Open
The apparent tolerance of greater physiological strain by HA responders occurred in the absence of perceptual differences.
View article: Structure guided design of a series of selective pyrrolopyrimidinone MARK inhibitors
Structure guided design of a series of selective pyrrolopyrimidinone MARK inhibitors Open
View article: Halting of Caspase Activity Protects Tau from MC1-Conformational Change and Aggregation
Halting of Caspase Activity Protects Tau from MC1-Conformational Change and Aggregation Open
Intracellular neurofibrillary tangles (NFTs) are the hallmark of Alzheimer’s disease and other tauopathies in which tau, a microtubule-associated protein, loses its ability to stabilize microtubules. Several post-translational modification…
View article: MARK inhibitors: Declaring a No-Go decision on a chemical series based on extensive DMPK experimentation
MARK inhibitors: Declaring a No-Go decision on a chemical series based on extensive DMPK experimentation Open
View article: P4‐079: <i>In Vivo</i> Two‐Photon Imaging of the Effects of Tauopathy and Amyloidopathy on Synapse Dynamics in the RTG4510 and J20 Transgenic Models, Respectively
P4‐079: <i>In Vivo</i> Two‐Photon Imaging of the Effects of Tauopathy and Amyloidopathy on Synapse Dynamics in the RTG4510 and J20 Transgenic Models, Respectively Open
A progressive loss of synapses occurs at the early clinical stages of Alzheimer's Disease (AD) and has been correlated with cognitive deficits in AD patients. However, it is relatively unknown how synapse dynamics are affected by the two m…
View article: Optimization of microtubule affinity regulating kinase (MARK) inhibitors with improved physical properties
Optimization of microtubule affinity regulating kinase (MARK) inhibitors with improved physical properties Open
View article: Short Fibrils Constitute the Major Species of Seed-Competent Tau in the Brains of Mice Transgenic for Human P301S Tau
Short Fibrils Constitute the Major Species of Seed-Competent Tau in the Brains of Mice Transgenic for Human P301S Tau Open
The interneuronal propagation of aggregated tau is believed to play an important role in the pathogenesis of human tauopathies. It requires the uptake of seed-competent tau into cells, seeding of soluble tau in recipient neurons and releas…
View article: Closing the tau loop: the missing tau mutation
Closing the tau loop: the missing tau mutation Open
Frontotemporal lobar degeneration comprises a group of disorders characterized by behavioural, executive, language impairment and sometimes features of parkinsonism and motor neuron disease. In 1994 we described an Irish-American family wi…
View article: O4‐04‐02: Investigation of dose‐responses and longitudinal effects of combination therapy with a plaque‐specific amyloid beta antibody and bace inhibitor in aged transgenic mice
O4‐04‐02: Investigation of dose‐responses and longitudinal effects of combination therapy with a plaque‐specific amyloid beta antibody and bace inhibitor in aged transgenic mice Open
The utilization of combination therapies in the clinic is an exciting new avenue for the Alzheimer's disease field. Although there are non-clinical data in transgenic mice that support the rationale for combination therapy, the design of t…