A5010638836- Neuroscience and Neuropharmacology Research
- Drug Solubulity and Delivery Systems
- Receptor Mechanisms and Signaling
- Functional Brain Connectivity Studies
- Neurotransmitter Receptor Influence on Behavior
- Tryptophan and brain disorders
- Granular flow and fluidized beds
- Genetics and Neurodevelopmental Disorders
- Crystallization and Solubility Studies
- Powder Metallurgy Techniques and Materials
- Protein purification and stability
- Alzheimer's disease research and treatments
- Autism Spectrum Disorder Research
- Neural dynamics and brain function
- Tracheal and airway disorders
- Nerve injury and regeneration
- Phosphodiesterase function and regulation
- Treatment of Major Depression
- Injection Molding Process and Properties
- Mineral Processing and Grinding
- Computational Drug Discovery Methods
- Bioinformatics and Genomic Networks
- RNA Interference and Gene Delivery
- Medical Imaging Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
Pfizer (United Kingdom)
2004-2024
Lancaster University
2015-2024
University of Strathclyde
2010-2020
University of Glasgow
2010-2020
University of Edinburgh
2008-2010
Medway School of Pharmacy
2004
University of Greenwich
2004
Pfizer (United States)
2002
University of California, San Diego
1994
Abstract Meta-analysis of genome-wide association study data has implicated PDE4B in the pathogenesis Alzheimer’s disease (AD), leading cause senile dementia. encodes one four subtypes cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase-4 (PDE4A–D). To interrogate involvement manifestation AD-related phenotypes, effects a hypomorphic mutation ( Pde4b Y358C ) that decreases PDE4B’s cAMP hydrolytic activity were evaluated App NL-G-F knock-in mouse model AD using Barnes maze test...
Background: Acute treatment with subanaesthetic doses of NMDA receptor antagonists, such as ketamine, provides a translational model relevance to many the symptoms schizophrenia. Previous studies have focused specifically on prefrontal cortex (PFC) because this region is implicated in functional deficits associated disorder and shows reduced activity (hypofrontality) schizophrenia patients. Chronic antagonist rodents can also induce hypofrontality, although paradoxically acute administration...
Five pharmaceutical materials, including two salts and three neutral compounds, have been subjected to nanoindentation analysis on a single-crystal scale. The experiments were used calculate brittleness index for each of the five materials. These results compared size reductions that obtained pilot-plant scale mill. A good correlation between single crystal large was range materials studied.
Compromised functional integration between cerebral subsystems and dysfunctional brain network organization may underlie the neurocognitive deficits seen in psychiatric disorders. Applying topological measures from science to imaging data allows quantification of complex connectivity. While this approach has recently been used further elucidate nature dysfunction schizophrenia, value applying preclinical models disease not recognized. For first time, we apply both established derived...
In the present study, we employ mathematical modeling (partial least squares regression, PLSR) to elucidate functional connectivity signatures of discrete brain regions in order identify networks subserving PCP-induced disruption distinct cognitive functions and their restoration by procognitive drug modafinil.We examine that show overt alterations metabolism, as measured semiquantitative 2-deoxyglucose autoradiography, an animal model (subchronic phencyclidine [PCP] treatment), which shows...
Missense mutations in ATP1A3 encoding Na+,K+-ATPase α3 have been identified as the primary cause of alternating hemiplegia childhood (AHC), a motor disorder with onset typically before age 6 months. Affected children tend to be short stature and can also epilepsy, ataxia learning disability. The has well-known role maintaining electrochemical gradients across cell membranes, but our understanding how AHC is limited. Myshkin mutant mice carry an amino acid change (I810N) that affects same...
Abstract Considerable evidence implicates DISC1 as a susceptibility gene for multiple psychiatric diseases. has been intensively studied at the molecular, cellular and behavioral level, but its role in regulating brain connectivity network function remains unknown. Here, we utilize set of complementary approaches to assess functional abnormalities present mice expressing truncated Disc1 ( Disc1tr Hemi mice). exhibited hypometabolism prefrontal cortex (PFC) reticular thalamus along with...
Elucidating how cannabinoids affect brain function is instrumental for the development of therapeutic tools aiming to mitigate 'on target' side effects cannabinoid-based therapies. A single treatment with cannabinoid receptor agonist, WIN 55,212-2, disrupts recognition memory in mice. Here, we evaluate prolonged, intermittent (30 days) exposure 55,212-2 (1 mg/kg) alters and impacts on metabolism functional connectivity. We show that chronic, (Novel Object Recognition Test) without affecting...
Abstract 2p16.3 deletion, involving NEUREXIN1 ( NRXN1 ) heterozygous substantially increases the risk of developing autism and other neurodevelopmental disorders. We have a poor understanding how heterozygosity impacts on brain function cognition to increase disorder. Here we characterize impact Nrxn1α cerebral metabolism, in mice, using 14 C‐2‐deoxyglucose imaging. also assess performance an olfactory‐based discrimination reversal learning (OB‐DaRL) task locomotor activity. use decision...
Chromosome 16p11.2 duplications dramatically increase risk for schizophrenia, but the mechanisms remain largely unknown. Here, we show that mice with an equivalent genetic mutation (16p11.2 duplication mice) exhibit impaired hippocampal-orbitofrontal and hippocampal-amygdala functional connectivity. Expression of schizophrenia-relevant GABAergic cell markers (parvalbumin calbindin) is selectively decreased in orbitofrontal cortex, while somatostatin expression lateral amygdala. When are...
Punch sticking during tablet manufacturing is a common problem facing the pharmaceutical industry. Using several model compounds, effects of crystal size and shape active ingredients (API) on punch propensity were systematically investigated in this work to provide molecular insights into punch-sticking phenomenon. In contrast belief that smaller API particles aggravate sticking, results show particle reduction can either reduce or enhance depending complex interplay among surface area,...
The solvent-mediated crystal morphologies of the α and β polymorphic forms l-glutamic acid are presented. This work applies a digital mechanistically based workflow that encompasses calculation lattice energy its constituent intermolecular synthons, their interaction energies, key role in understanding predicting morphology as well assessing surface chemistry, topology, solvent binding on habit growth surfaces. Through comparison between contrasting conformational polymorphs acid, this...
The morphology of free-flowed and gravity consolidated crystal powder beds the alpha beta polymorphic forms l-glutamic acid, together with a detailed analysis particle density microstructure within form tablets using state -of-the-art X-ray computed tomography (XCT), is presented. Carr's index measured to be 19.7 35.2 for bulk powders prismatic needle-like form, respectively, revealing increased flowability versus form. XCT reveals consolidates under more efficiently than beta, where final...