A5033339412- Hypothalamic control of reproductive hormones
- stochastic dynamics and bifurcation
- Nonlinear Dynamics and Pattern Formation
- Neural dynamics and brain function
- Neuroscience and Neuropharmacology Research
- Neuroendocrine regulation and behavior
- Gene Regulatory Network Analysis
- Gut microbiota and health
- Ion channel regulation and function
- Ovarian function and disorders
- Plant Reproductive Biology
- Motor Control and Adaptation
- Action Observation and Synchronization
- Neurobiology and Insect Physiology Research
- Estrogen and related hormone effects
- Photoreceptor and optogenetics research
- Antibiotic Resistance in Bacteria
- Stress Responses and Cortisol
- Cystic Fibrosis Research Advances
- Circadian rhythm and melatonin
- Receptor Mechanisms and Signaling
- Evolution and Genetic Dynamics
- Bacterial Genetics and Biotechnology
- Molecular Biology Techniques and Applications
- Memory and Neural Mechanisms
Engineering and Physical Sciences Research Council
2016-2025
University of Exeter
2016-2025
Brigham and Women's Hospital
2024
Harvard University
2024
Living Systems (United States)
2019-2024
Phillips Exeter Academy
2020-2024
Bulgarian Academy of Sciences
2018-2023
Institute of Biophysics and Biomedical Engineering
2018-2023
British Library
2020-2023
The Alan Turing Institute
2020-2023
To establish whether there is any change in mortality from infection with a new variant of SARS-CoV-2, designated concern (VOC-202012/1) December 2020, compared circulating SARS-CoV-2 variants.
In medicine, artificial intelligence (AI) research is becoming increasingly focused on applying machine learning (ML) techniques to complex problems, and so allowing computers make predictions from large amounts of patient data, by their own associations.1 Estimates the impact AI wider economy globally vary wildly, with a recent report suggesting 14% effect global gross domestic product 2030, half which coming productivity improvements.2 These create political appetite for rapid development...
Phenotypic variations between individual microbial cells play a key role in the resistance of pathogens to pharmacotherapies. Nevertheless, little is known about cell individuality antibiotic accumulation. Here, we hypothesise that phenotypic diversification can be driven by fundamental cell-to-cell differences drug transport rates. To test this hypothesis, employed microfluidics-based single-cell microscopy, libraries fluorescent probes and mathematical modelling. This approach allowed us...
Abstract Infertility affects 1-in-6 couples, with repeated intensive cycles of assisted reproductive technology (ART) required by many to achieve a desired live birth. In ART, typically, clinicians and laboratory staff consider patient characteristics, previous treatment responses, ongoing monitoring determine decisions. However, the reproducibility, weighting, interpretation these characteristics are contentious, highly operator-dependent, resulting in considerable reliance on clinical...
Large-scale collective behaviors such as synchronization and coordination spontaneously arise in many bacterial populations. With systems biology attempting to understand these phenomena, synthetic opening up the possibility of engineering them for our own benefit, there is growing interest how populations are best modeled. Here we introduce BSim, a highly flexible agent-based computational tool analyzing relationships between single-cell dynamics population level features. BSim includes...
The formation and deposition of tau protein aggregates is proposed to contribute cognitive impairments in dementia by disrupting neuronal function brain regions, including the hippocampus. We used a battery vivo vitro electrophysiological recordings rTg4510 transgenic mouse model, which overexpresses mutant form human protein, investigate effects pathology on hippocampal area CA1 7- 8-month-old mice, an age point at animals exhibit advanced progressive neurodegeneration. In revealed shifted...
Human movement has been studied for decades, and dynamic laws of motion that are common to all humans have derived. Yet, every individual moves differently from everyone else (faster/slower, harder/smoother, etc.). We propose here an index such variability, namely motor signature (IMS) able capture the subtle differences in way each us moves. show IMS a person is time-invariant it significantly differs those other individuals. This allows quantify similarity, measure rapport between dynamics...
Rationale: Long-term antibiotic use for managing chronic respiratory disease is increasing; however, the role of airway resistome and its relationship to host microbiomes remains unknown.Objectives: To evaluate resistomes relate them environmental using ultradeep metagenomic shotgun sequencing.Methods: Airway specimens from 85 individuals with without (severe asthma, obstructive pulmonary disease, bronchiectasis) were subjected sequencing an average depth exceeding 20 million reads....
BACKGROUNDKisspeptin is a key regulator of hypothalamic gonadotropin-releasing hormone (GnRH) neurons and essential for reproductive health. A specific kisspeptin receptor (KISS1R) agonist could significantly expand the potential clinical utility therapeutics targeting pathway. Herein, we investigate effects KISS1R agonist, MVT-602, in healthy women with disorders.METHODSWe conducted vivo vitro studies to characterize action MVT-602 comparison native kisspeptin-54 (KP54). We determined...
Rationale: Emerging data support the existence of a microbial "gut-lung" axis that remains unexplored in bronchiectasis. Methods: Prospective and concurrent sampling gut (stool) lung (sputum) was performed cohort n = 57 individuals with bronchiectasis subjected to bacteriome (16S rRNA) mycobiome (18S Internal Transcribed Spacer) sequencing (total, 228 microbiomes). Shotgun metagenomics subset (n 15; 30 Data from compartments were integrated by weighted similarity network fusion, clustered,...
In this opinion piece, we examine the pivotal role that uncertainty quantification (UQ) plays in informing clinical decision-making processes. We explore challenges associated with healthcare data and potential barriers to widespread adoption of UQ methodologies. doing so, highlight how these techniques can improve precision reliability medical evaluations. delve into crucial understanding managing uncertainties present (such as measurement error), diagnostic tools treatment outcomes....
It is known that Ca 2+ influx plays an important role in the modulation of inositol trisphosphate-generated oscillations, but controversy over mechanisms underlying these effects exists. In addition, blocking membrane transport or reducing entry vary from one cell type to another; some types oscillations persist absence (although their frequency affected), whereas other depend on entry. We present theoretical and experimental evidence can control by controlling total amount (the load). Our...
We describe a phenomenological model of seizure initiation, consisting bistable switch between stable fixed point and limit-cycle attractors. determine quasi-analytic formula for the exit time problem our in presence noise. This formula--which we equate to frequency--is then validated numerically, before extend study explore combined effects noise network structure on escape times. Here, observe that weakly connected networks 2, 3 4 nodes with equivalent first transitive components all have...
Understanding the influence of stress on human performance is theoretical and practical importance. An individual's reaction to predicts their subsequent performance; with a "challenge" response leading better than "threat" response. However, this contention has not been tested in truly stressful environments highly skilled individuals. Furthermore, effect challenge threat responses attentional control during visuomotor tasks poorly understood.Thus, study aimed examine individual reactions...
Abstract Normal reproductive functioning is critically dependent on pulsatile secretion of luteinising hormone (LH). Assessment LH pulsatility important for the clinical diagnosis disorders, but current methods are hampered by frequent blood sampling coupled to expensive serial immunochemical analysis. Here, we report development and application a Robotic APTamer-enabled Electrochemical Reader (RAPTER) electrochemical analysis system determine pulsatility. Through selective evolution ligands...
A novel, rapid single-cell assay for quantifying antibiotic accumulation in Gram-negative bacteria reveals important insights about bacterial drug accumulation.
Fertility critically depends on the gonadotropin-releasing hormone (GnRH) pulse generator, a neural construct comprised of hypothalamic neurons coexpressing kisspeptin, neurokoinin-B and dynorphin. Here, using mathematical modeling in vivo optogenetics we reveal for first time how this initiates sustains appropriate ultradian frequency essential reproduction. Prompted by modeling, show experimentally female estrous mice that robust pulsatile release luteinizing hormone, proxy GnRH, emerges...
Background Nintedanib slows progression of lung function decline in patients with progressive fibrosing (PF) interstitial disease (ILD) and was recommended for this indication within the United Kingdom (UK) National Health Service Scotland June 2021 England, Wales Northern Ireland November 2021. To date, there has been no national evaluation use nintedanib PF-ILD a real-world setting. Methods 26 UK centres were invited to take part service between 17 30 September 2022. Summary data regarding...
In some cell types, oscillations in the concentration of free intracellular calcium ([Ca 2+ ]) are accompanied by inositol 1,4,5-trisphosphate ([IP 3 ]). However, most types it is still an open question as to whether [IP ] necessary for Ca vivo , or they merely follow passively. Using a wide range models, we show that response artificially applied pulse IP can be used distinguish between these two cases. Hence, muscarinic receptor-mediated, long-period pancreatic acinar cells depend on...
Cultured pituitary somatotrophs release growth hormone in response to spontaneous Ca(2+) entry through voltage-gated calcium channels (VGCCs) that is governed by plateau-bursting electrical activity and regulated several neurohormones, including GH-releasing (GHRH) somatostatin. Here we combine experiments theory clarify the mechanisms underlying receptor-controlled activity. Experiments support a role of Na(+)-conducting tetrodotoxin-insensitive channel controlling GHRH-stimulated...