Biology subjects

McGregor, H.

Publications and source records attributed to McGregor, H..

6 recordsLinked to original sources

bioRxiv2026

A panel of genotypically and phenotypically characterised WHO priority Gram-negative bacteria to facilitate antimicrobial and diagnostic development

Background Antimicrobial-resistant Gram-negative bacteria pose a major threat to global health. In the WHO Bacterial Priority Pathogen List (BPPL) 2024, several species were classified as critical or high priority for research and development of new antimicrobial therapeutics and diagnostics. However, access to well-characterised and clinically relevant bacterial isolate panels remains an unmet need for development and validation. Methods We constructed five panels of Gram-negative bacterial isolates, cultured from samples originally referred to the UK Health Security Agency Antimicrobial Resistance and Healthcare-Associated Infections Reference Unit for analysis between 2014 and 2025. For each isolate, antimicrobial susceptibilities were determined against a range of clinically relevant antibiotics, including third-generation cephalosporins, carbapenems, colistin and other last-line antibiotics. WGS was performed on all isolates, and previously described resistance determinants were characterised. Results The five panels consist of 145 isolates and represent 81 sequence types across Escherichia coli (30 isolates), Klebsiella pneumoniae (30 isolates), carbapenem-resistant Acinetobacter baumannii (30 isolates), carbapenem-resistant Pseudomonas aeruginosa (30 isolates), and a mixed panel of other healthcare-associated Enterobacterales species (25 isolates). Panels are highly representative of globally relevant strains, including those currently in circulation and on the WHO BPPL 2024, and of resistance mechanisms of public health importance. Conclusion The panels provide a diverse, comprehensive set of multidrug-resistant Gram-negative bacterial isolates, representative of strains currently in circulation globally. Selected isolates carry a breadth of important resistance mechanisms and are highly relevant to the current epidemiological landscape. The isolates and associated metadata are available to industry, academia, and other laboratories for use in developing novel antimicrobial compounds and diagnostic assays.

microbiology↗

bioRxiv2024

Pre and Post antibiotic epoch: insights into the historical spread of antimicrobial resistance

Plasmids are now the primary vectors of antimicrobial resistance, but our understanding of how human industrialisation of antibiotics influenced this is limited by a paucity of data predating the antibiotic era (PAE). By investigating plasmids from clinically relevant bacteria isolated between 1917 and 1954 and comparing them to modern plasmids, we captured over 100 years of evolution. We show that while all PAE plasmids were devoid of resistance genes and most never acquired them, a small minority evolved to drive the global spread of resistance to first-line and last-resort antibiotics in Gram-negative bacteria. They have evolved through complex microevolution and fusion events into a distinct group of highly recombinogenic, multi-replicon, self-transmissible plasmids that now pose the highest risk to resistance dissemination, and therefore human health. One Sentence SummaryPre-antibiotic era bacteria reveal the origin and evolution of drug-resistance vectors.

genomics↗

bioRxiv2022

Daily Artificial Gravity is Associated with Greater Neural Efficiency during Sensorimotor Adaptation

Altered vestibular signaling and body unloading in microgravity results in sensory reweighting and adaptation. Microgravity effects are well-replicated in head-down tilt bed rest (HDBR). Artificial gravity (AG) is a potential countermeasure to mitigate effects of microgravity. We examined the effectiveness of daily AG for mitigating brain and/or behavioral changes in 60 days of HDBR. One group received AG for 30 minutes daily (AG; n=16) and a control group spent the same time in HDBR but received no AG (CTRL; n=8). All participants performed a sensorimotor adaptation task 5 times during fMRI scanning: twice prior to HDBR twice during HDBR, and once following HDBR. The AG group showed similar behavioral adaptation effects compared with the CTRLs. We identified decreased brain activation in the AG group from pre to late HDBR in the cerebellum for the task baseline portion and in the thalamus, calcarine, cuneus, premotor cortices, and superior frontal gyrus in the AG group during the early adaptation phase. The two groups also exhibited differential brain-behavior correlations. Together, these results suggest that AG may result in a reduced recruitment of brain activity for basic motor processes and sensorimotor adaptation. These effects may stem from somatosensory and vestibular stimulation from AG.

neuroscience↗

bioRxiv2021

MRI-Visible Perivascular Space (PVS) Changes with Long-Duration Spaceflight

Humans are exposed to extreme environmental stressors during spaceflight and return with alterations in brain structure and shifts in intracranial fluids. To date, no studies have evaluated the effects of spaceflight on perivascular spaces (PVSs) within the brain, which are believed to facilitate fluid drainage and brain homeostasis. Here, we examined how the number and morphology of magnetic resonance imaging (MRI)-visible PVSs are affected by spaceflight, including prior spaceflight experience. Fifteen astronauts underwent six T1-weighted 3T MRI scans, twice prior to launch and four times following their return to Earth after [~]6-month missions to the International Space Station. White matter MRI-visible PVS number and morphology were calculated using an established automated segmentation algorithm. We found that novice astronauts showed an increase in total PVS volume from pre- to post-flight, whereas experienced crewmembers did not (adjusted for age, sex, and time between landing and first MRI scan). Moreover, experienced astronauts exhibited a significant correlation between more previous flight days and greater PVS median length at baseline, suggesting that experienced astronauts exhibit holdover effects from prior spaceflight(s). There was also a significant positive correlation between pre- to post-flight increases in PVS median length and increases in right lateral ventricular volume. The presence of spaceflight associated neuro-ocular syndrome (SANS) was not associated with PVS number or morphology. Together, these findings demonstrate that spaceflight is associated with PVS morphological changes, and specifically that spaceflight experience is an important factor in determining PVS characteristics.

neuroscience↗

bioRxiv2021

The effects of long duration spaceflight on sensorimotor control and cognition

Astronauts returning from spaceflight typically show transient declines in mobility and balance. These whole-body postural control behaviors have been investigated thoroughly, while study of the effects of spaceflight on other sensorimotor behaviors is prevalent. Here, we tested the effects of the spaceflight environment of microgravity on various sensorimotor and cognitive tasks during and after missions to the International Space Station (ISS). We obtained mobility (Functional Mobility Test), balance (Sensory Organization Test-5), bimanual coordination (bimanual Purdue Pegboard), cognitive-motor dual-tasking and various cognitive measures (Digit Symbol Substitution Test, Cube Rotation, Card Rotation, Rod and Frame Test) before, during and after 15 astronauts completed 6+ month missions aboard the ISS. We used linear mixed effect models to analyze performance changes due to entering the microgravity environment, behavioral adaptations aboard the ISS and subsequent recovery from microgravity. We identified declines in mobility and balance from pre- to post-flight, suggesting possible disruption and/or downweighting of vestibular inputs; these behaviors recovered to baseline levels within 30 days post-flight. We also identified bimanual coordination declines from pre- to post-flight and recovery to baseline levels within 30 days post-flight. There were no changes in dual-task performance during or following spaceflight. Cube rotation response time significantly improved from pre- to post-flight, suggestive of practice effects. There was a trend for better in-flight cube rotation performance on the ISS when crewmembers had their feet in foot loops on the "floor" throughout the task. This suggests that tactile inputs to the foot sole aided orientation. Overall, these results suggest that sensory reweighting due to the microgravity environment of spaceflight affected sensorimotor performance, while cognitive performance was maintained. A shift from exocentric (gravity) spatial references on Earth towards an egocentric spatial reference may also occur aboard the ISS. Upon return to Earth, microgravity adaptions become maladaptive for certain postural tasks, resulting in transient sensorimotor performance declines that recover within 30 days.

neuroscience↗

bioRxiv2018

Somatosensory Perceptual Training Enhances Motor Learning by Observing

Neuroimaging and neurophysiological studies in humans have demonstrated that action observation activates brain regions involved in sensory-motor control. A growing body of work has shown that action observation can also facilitate motor learning; observing a tutor undergoing motor learning results in functional plasticity within the motor system and gains in subsequent motor performance. However, the effects of observing motor learning extend beyond the motor domain. Converging evidence suggests that learning also results in somatosensory functional plasticity and somatosensory perceptual changes. This work has raised the possibility that the somatosensory system is also involved in motor learning that results from observation. Here we tested this hypothesis using a somatosensory perceptual training paradigm. If the somatosensory system is indeed involved in motor learning by observing, then improving subjects' somatosensory function before observation should enhance subsequent observation-related gains in motor performance. Subjects performed a proprioceptive discrimination task in which a robotic manipulandum moved the subjects passive upper limb and he or she made judgments about the position of the hand. Subjects in a Trained Learning group received trial-by-trial feedback to improve their proprioceptive acuity. Subjects in an Untrained Learning group performed the same task without feedback. All subjects then observed a learning video showing a tutor adapting her reaches to a left force field (FF). We found that subjects in the Trained Learning group, who had superior proprioceptive acuity prior to observation, benefited more from observing learning compared to subjects in the Untrained Learning group. Improving somatosensory function can therefore enhance subsequent observation-related gains in motor learning. This study provides further evidence in favor of the involvement of the somatosensory system in motor learning by observing.\n\nAbbreviationsThe authors report no financial interests or conflicts of interests.

neuroscience↗