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Label-free Brillouin endo-microscopy for the quantitative 3D imaging of sub-micrometre biology (2024)
Journal Article
La Cavera III, S., Chauhan, V. M., Hardiman, W., Yao, M., Fuentes-Domínguez, R., Setchfield, K., …Clark, M. (2024). Label-free Brillouin endo-microscopy for the quantitative 3D imaging of sub-micrometre biology. Communications Biology, 7, Article 451. https://doi.org/10.1038/s42003-024-06126-4

This report presents an optical fibre-based endo-microscopic imaging tool that simultaneously measures the topographic profile and 3D viscoelastic properties of biological specimens through the phenomenon of time-resolved Brillouin scattering. This u... Read More about Label-free Brillouin endo-microscopy for the quantitative 3D imaging of sub-micrometre biology.

Mechano-sensitivity of β2-adrenoceptors enhances constitutive activation of cAMP generation that is inhibited by inverse agonists (2024)
Journal Article
Cullum, S. A., Platt, S., Dale, N., Isaac, O. C., Wragg, E. S., Soave, M., …Hill, S. J. (2024). Mechano-sensitivity of β2-adrenoceptors enhances constitutive activation of cAMP generation that is inhibited by inverse agonists. Communications Biology, 7(1), Article 417. https://doi.org/10.1038/s42003-024-06128-2

The concept of agonist-independent signalling that can be attenuated by inverse agonists is a fundamental element of the cubic ternary complex model of G protein-coupled receptor (GPCR) activation. This model shows how a GPCR can exist in two conform... Read More about Mechano-sensitivity of β2-adrenoceptors enhances constitutive activation of cAMP generation that is inhibited by inverse agonists.

Salt-Dependent Self-Association of Trinucleotide Repeat RNA Sequences (2024)
Journal Article
Maity, H., Nguyen, H. T., Hori, N., & Thirumalai, D. (in press). Salt-Dependent Self-Association of Trinucleotide Repeat RNA Sequences. Journal of Physical Chemistry Letters, 15(14), 3820–3827. https://doi.org/10.1021/acs.jpclett.3c03553

Repeat RNA sequences self-associate to form condensates. Simulations of a coarse-grained single-interaction site model for (CAG)n (n = 30 and 31) show that the salt-dependent free energy gap, ΔGS, between the ground (perfect hairpin) and the excited... Read More about Salt-Dependent Self-Association of Trinucleotide Repeat RNA Sequences.

Discovery of α-Amidobenzylboronates as Highly Potent Covalent Inhibitors of Plasma Kallikrein (2024)
Journal Article
Allison, M., Davie, R. L., Mogg, A. J., Hampton, S. L., Emsley, J., & Stocks, M. J. (2024). Discovery of α-Amidobenzylboronates as Highly Potent Covalent Inhibitors of Plasma Kallikrein. ACS Medicinal Chemistry Letters, 15(4), 501–509. https://doi.org/10.1021/acsmedchemlett.3c00572

Hereditary angioedema (HAE), a rare genetic disorder, is associated with uncontrolled plasma kallikrein (PKa) enzyme activity leading to the generation of bradykinin swelling in subcutaneous and submucosal membranes in various locations of the body.... Read More about Discovery of α-Amidobenzylboronates as Highly Potent Covalent Inhibitors of Plasma Kallikrein.

CXCL17 is an allosteric inhibitor of CXCR4 through a mechanism of action involving glycosaminoglycans (2024)
Journal Article
White, C. W., Platt, S., Kilpatrick, L. E., Dale, N., Abhayawardana, R. S., Dekkers, S., …Hill, S. J. (2024). CXCL17 is an allosteric inhibitor of CXCR4 through a mechanism of action involving glycosaminoglycans. Science Signaling, 17(828), Article abl3758. https://doi.org/10.1126/scisignal.abl3758

CXCL17 is a chemokine principally expressed by mucosal tissues, where it facilitates chemotaxis of monocytes, dendritic cells, and macrophages and has antimicrobial properties. CXCL17 is also implicated in the pathology of inflammatory disorders and... Read More about CXCL17 is an allosteric inhibitor of CXCR4 through a mechanism of action involving glycosaminoglycans.

Competition between stacking and divalent cation mediated electrostatic interactions determines the conformations of short DNA sequences (2024)
Journal Article
Mondal, B., Chakraborty, D., Hori, N., Nguyen, H. T., & Thirumalai, D. (2024). Competition between stacking and divalent cation mediated electrostatic interactions determines the conformations of short DNA sequences. Journal of Chemical Theory and Computation, https://doi.org/10.1021/acs.jctc.3c01193

Interplay between divalent cations (Mg2+ and Ca2+) and single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA), as well as stacking interactions, is important in nucleosome stability and phase separation in nucleic acids. Quantitative techniques... Read More about Competition between stacking and divalent cation mediated electrostatic interactions determines the conformations of short DNA sequences.

Deep Learning‐Driven Exploration of Pyrroloquinoline Quinone Neuroprotective Activity in Alzheimer's Disease (2024)
Journal Article
Li, X., Sun, Y., Zhou, Z., Li, J., Liu, S., Chen, L., …Lu, Q. (2024). Deep Learning‐Driven Exploration of Pyrroloquinoline Quinone Neuroprotective Activity in Alzheimer's Disease. Advanced Science, https://doi.org/10.1002/advs.202308970

Alzheimer's disease (AD) is a pressing concern in neurodegenerative research. To address the challenges in AD drug development, especially those targeting Aβ, this study uses deep learning and a pharmacological approach to elucidate the potential of... Read More about Deep Learning‐Driven Exploration of Pyrroloquinoline Quinone Neuroprotective Activity in Alzheimer's Disease.

Use of Magnetic Resonance Imaging for Visualization of Oral Dosage Forms in the Human Stomach: A Scoping Review (2024)
Journal Article
Akbar, T., Gershkovich, P., Stamatopoulos, K., Gowland, P. A., Stolnik, S., Butler, J., & Marciani, L. (2024). Use of Magnetic Resonance Imaging for Visualization of Oral Dosage Forms in the Human Stomach: A Scoping Review. Molecular Pharmaceutics, https://doi.org/10.1021/acs.molpharmaceut.3c01123

Oral dosage forms are the most widely and frequently used formulations to deliver active pharmaceutical ingredients (APIs), due to their ease of administration and noninvasiveness. Knowledge of intragastric release rates and gastric mixing is crucial... Read More about Use of Magnetic Resonance Imaging for Visualization of Oral Dosage Forms in the Human Stomach: A Scoping Review.

Glycerol- and diglycerol-based polyesters: Evaluation of backbone alterations upon nano-formulation performance (2024)
Journal Article
Axioti, E., Dixon, E. G., Reynolds-Green, M., Alexander, E. C., Brugnoli, B., Keddie, D. J., …Taresco, V. (2024). Glycerol- and diglycerol-based polyesters: Evaluation of backbone alterations upon nano-formulation performance. Colloids and Surfaces B: Biointerfaces, 236, Article 113828. https://doi.org/10.1016/j.colsurfb.2024.113828

Despite the success of polyethylene glycol-based (PEGylated) polyesters in the drug delivery and biomedical fields, concerns have arisen regarding PEG's immunogenicity and limited biodegradability. In addition, inherent limitations, including limited... Read More about Glycerol- and diglycerol-based polyesters: Evaluation of backbone alterations upon nano-formulation performance.

Triblock copolymer micelles enhance solubility, permeability and activity of a quorum sensing inhibitor against Pseudomonas aeruginosa biofilms (2024)
Journal Article
Kasza, K., Soukarieh, F., Romero, M., Hardie, K. R., Gurnani, P., Cámara, M., & Alexander, C. (2024). Triblock copolymer micelles enhance solubility, permeability and activity of a quorum sensing inhibitor against Pseudomonas aeruginosa biofilms. RSC Applied Polymers, https://doi.org/10.1039/D3LP00208J

Antimicrobial resistance is a threat to public health for which new treatments are urgently required. The capability of bacteria to form biofilms is of particular concern as it enables high bacterial tolerance to conventional therapies by reducing dr... Read More about Triblock copolymer micelles enhance solubility, permeability and activity of a quorum sensing inhibitor against Pseudomonas aeruginosa biofilms.

Free drug and ROS-responsive nanoparticle delivery of synergistic doxorubicin and olaparib combinations to triple negative breast cancer models (2024)
Journal Article
Cavanagh, R. J., Monteiro, P. F., Moloney, C., Travanut, A., Mehradnia, F., Taresco, V., …Alexander, C. (2024). Free drug and ROS-responsive nanoparticle delivery of synergistic doxorubicin and olaparib combinations to triple negative breast cancer models. Biomaterials Science, 12(7), 1822-1840. https://doi.org/10.1039/d3bm01931d

Combinations of the topoisomerase II inhibitor doxorubicin and the poly (ADP-ribose) polymerase inhibitor olaparib offer potential drug-drug synergy for the treatment of triple negative breast cancers (TNBC). In this study we performed in vitro scree... Read More about Free drug and ROS-responsive nanoparticle delivery of synergistic doxorubicin and olaparib combinations to triple negative breast cancer models.

Probing the Mechanism of Action of Bis(phenolato) Amine (ONO Donor Set) Titanium(IV) Anticancer Agents (2024)
Journal Article
Musa, M., Abid, M., Bradshaw, T. D., Boocock, D. J., Coveney, C., Argent, S. P., & Woodward, S. (2024). Probing the Mechanism of Action of Bis(phenolato) Amine (ONO Donor Set) Titanium(IV) Anticancer Agents. Journal of Medicinal Chemistry, 67(4), 2732-2744. https://doi.org/10.1021/acs.jmedchem.3c01874

The need for anticancer therapies that overcome metallodrug resistance while minimizing adverse toxicities is targeted, herein, using titanium coordination complexes. Octahedral titanium­(IV) trans, mer-[Ti­{R1N­(CH2–2-MeO-4-R1-C6H2)2}2] [R1 = Et, al... Read More about Probing the Mechanism of Action of Bis(phenolato) Amine (ONO Donor Set) Titanium(IV) Anticancer Agents.

Evaluating the role of primary care pharmacy technicians in antimicrobial stewardship (AMS) and acne management using TARGET resources (2024)
Journal Article
Lakha, A., Fleming, N., Sonnex, K., Thornley, T., Anderson, C., Hand, . K., & Ashiru-Oredope, D. (2024). Evaluating the role of primary care pharmacy technicians in antimicrobial stewardship (AMS) and acne management using TARGET resources. JAC-Antimicrobial Resistance, 6(1), Article dlae011. https://doi.org/10.1093/jacamr/dlae011

Background: Inappropriate antibiotic prescribing is accelerating antimicrobial resistance (AMR) (Antibiotic resistant infections and associated deaths increase https://www.gov.uk/government/news/antibiotic-resistant-infections-And-Associated-deaths-i... Read More about Evaluating the role of primary care pharmacy technicians in antimicrobial stewardship (AMS) and acne management using TARGET resources.

Audio-based AI classifiers show no evidence of improved COVID-19 screening over simple symptoms checkers (2024)
Journal Article
Coppock, H., Nicholson, G., Kiskin, I., Koutra, V., Baker, K., Budd, J., …Holmes, C. (2024). Audio-based AI classifiers show no evidence of improved COVID-19 screening over simple symptoms checkers. Nature Machine Intelligence, 6, 229-242. https://doi.org/10.1038/s42256-023-00773-8

Recent work has reported that respiratory audio-trained AI classifiers can accurately predict SARS-CoV-2 infection status. However, it has not yet been determined whether such model performance is driven by latent audio biomarkers with true causal li... Read More about Audio-based AI classifiers show no evidence of improved COVID-19 screening over simple symptoms checkers.

Top ten research priorities for alcohol use disorder and alcohol-related liver disease: results of a multistakeholder research priority setting partnership (2024)
Journal Article
Subhani, M., Dhanda, A., Olaru, A., Dunford, L., Ahmad, N., Wragg, A., …Ryder, S. D. (2024). Top ten research priorities for alcohol use disorder and alcohol-related liver disease: results of a multistakeholder research priority setting partnership. The Lancet Gastroenterology & Hepatology, https://doi.org/10.1016/S2468-1253%2824%2900009-8

Alcohol is a preventable leading cause of liver disease and over 200 other acute or chronic medical conditions. 1 In the UK, 25% of the population drinks at an increasing risk level (ie, 15–34 units per week for women and 15–49 units per week for men... Read More about Top ten research priorities for alcohol use disorder and alcohol-related liver disease: results of a multistakeholder research priority setting partnership.

Ciprofloxacin poly(β-amino ester) conjugates enhance antibiofilm activity and slow the development of resistance (2024)
Journal Article
Kasza, K., Richards, B., Jones, S., Romero, M., Robertson, S. N., Hardie, K. R., …Alexander, C. (2024). Ciprofloxacin poly(β-amino ester) conjugates enhance antibiofilm activity and slow the development of resistance. ACS Applied Materials and Interfaces, 16(5), 5412-5425. https://doi.org/10.1021/acsami.3c14357

To tackle the emerging antibiotic resistance crisis, novel antimicrobial approaches are urgently needed. Bacterial biofilms are a particular concern in this context as they are responsible for over 80% of bacterial infections and are inherently more... Read More about Ciprofloxacin poly(β-amino ester) conjugates enhance antibiofilm activity and slow the development of resistance.

Conformational activation and inhibition of von Willebrand factor by targeting its autoinhibitory module (2024)
Journal Article
Arce, N. A., Markham-Lee, Z., Liang, Q., Najmudin, S., Legan, E. R., Dean, G., …Li, R. (2024). Conformational activation and inhibition of von Willebrand factor by targeting its autoinhibitory module. Blood, https://doi.org/10.1182/blood.2023022038

Activation of von Willebrand factor (VWF) is a tightly controlled process governed primarily by local elements around its A1 domain. Recent studies suggest that the O-glycosylated sequences flanking the A1 domain constitute a discontinuous and force-... Read More about Conformational activation and inhibition of von Willebrand factor by targeting its autoinhibitory module.

Student Co-creation of Digital Learning Resources: An evaluation and reflection of veterinary pharmacy and care home pharmacy interprofessional education packages (2024)
Journal Article
Chandarana, P., Rickaby, R., Sonnex, K., Allegrucci, C., & Garcia-Ara, A. (2024). Student Co-creation of Digital Learning Resources: An evaluation and reflection of veterinary pharmacy and care home pharmacy interprofessional education packages. Student Engagement in Higher Education Journal, 5(2), 203-227

Funding secured from the University of Nottingham was used to enable students to work together with academics to develop two interprofessional education (IPE) e-learning resources using XerteTM. One project focussed on veterinary pharmacy and involve... Read More about Student Co-creation of Digital Learning Resources: An evaluation and reflection of veterinary pharmacy and care home pharmacy interprofessional education packages.

Combined biolistic and cell penetrating peptide delivery for the development of scalable intradermal DNA vaccines (2024)
Journal Article
So, R. B., Li, G., Brentville, V., Daly, J. M., & Dixon, J. E. (2024). Combined biolistic and cell penetrating peptide delivery for the development of scalable intradermal DNA vaccines. Journal of Controlled Release, 367, 209-222. https://doi.org/10.1016/j.jconrel.2024.01.031

Physical-based gene delivery via biolistic methods (such as the Helios gene gun) involve precipitation of nucleic acids onto microparticles and direct transfection through cell membranes of exposed tissue (e.g. skin) by high velocity acceleration. Th... Read More about Combined biolistic and cell penetrating peptide delivery for the development of scalable intradermal DNA vaccines.

Spatially resolved molecular analysis of host response to medical device implantation using the 3D OrbiSIMS highlights a critical role for lipids (2024)
Journal Article
Suvannapruk, W., Fisher, L. E., Luckett, J. C., Edney, M. K., Kotowska, A. M., Kim, D., …Alexander, M. R. (in press). Spatially resolved molecular analysis of host response to medical device implantation using the 3D OrbiSIMS highlights a critical role for lipids. Advanced Science, https://doi.org/10.1101/2023.08.18.553860

A key goal for implanted medical devices is that they do not elicit a detrimental immune response. Macrophages play critical roles in modulation of the host immune response and are the major cells responsible for persistent inflammatory reactions to... Read More about Spatially resolved molecular analysis of host response to medical device implantation using the 3D OrbiSIMS highlights a critical role for lipids.