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Article ; Online: Injectable MSC Spheroid and Microgel Granular Composites for Engineering Tissue.

Caprio, Nikolas Di / Davidson, Matthew D / Daly, Andrew C / Burdick, Jason A

Advanced materials (Deerfield Beach, Fla.)

2024 Volume 36, Issue 14, Page(s) e2312226

Abstract: Many cell types require direct cell-cell interactions for differentiation and function; yet, this can be challenging to incorporate into 3-dimensional (3D) structures for the engineering of tissues. Here, a new approach is introduced that combines ... ...

Abstract	Many cell types require direct cell-cell interactions for differentiation and function; yet, this can be challenging to incorporate into 3-dimensional (3D) structures for the engineering of tissues. Here, a new approach is introduced that combines aggregates of cells (spheroids) with similarly-sized hydrogel particles (microgels) to form granular composites that are injectable, undergo interparticle crosslinking via light for initial stabilization, permit cell-cell contacts for cell signaling, and allow spheroid fusion and growth. One area where this is important is in cartilage tissue engineering, as cell-cell contacts are crucial to chondrogenesis and are missing in many tissue engineering approaches. To address this, granular composites are developed from adult porcine mesenchymal stromal cell (MSC) spheroids and hyaluronic acid microgels and simulations and experimental analyses are used to establish the importance of initial MSC spheroid to microgel volume ratios to balance mechanical support with tissue growth. Long-term chondrogenic cultures of granular composites produce engineered cartilage tissue with extensive matrix deposition and mechanical properties within the range of cartilage, as well as integration with native tissue. Altogether, a new strategy of injectable granular composites is developed that leverages the benefits of cell-cell interactions through spheroids with the mechanical stabilization afforded with engineered hydrogels.
MeSH term(s)	Animals ; Swine ; Tissue Engineering/methods ; Microgels ; Spheroids, Cellular ; Cartilage ; Hydrogels/chemistry ; Chondrogenesis
Chemical Substances	Microgels ; Hydrogels
Language	English
Publishing date	2024-01-04
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1474949-X
ISSN	1521-4095 ; 0935-9648
ISSN (online)	1521-4095
ISSN	0935-9648
DOI	10.1002/adma.202312226
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Article ; Online: Broad-spectrum antiviral activity of two structurally analogous CYP3A inhibitors against pathogenic human coronaviruses in vitro.

Gallucci, Lara / Bazire, James / Davidson, Andrew D / Shytaj, Iart Luca

Antiviral research

2023 Volume 221, Page(s) 105766

Abstract: Coronaviruses pose a permanent risk of outbreaks, with three highly pathogenic species and strains (SARS-CoV, MERS-CoV, SARS-CoV-2) having emerged in the last twenty years. Limited antiviral therapies are currently available and their efficacy in ... ...

Abstract	Coronaviruses pose a permanent risk of outbreaks, with three highly pathogenic species and strains (SARS-CoV, MERS-CoV, SARS-CoV-2) having emerged in the last twenty years. Limited antiviral therapies are currently available and their efficacy in randomized clinical trials enrolling SARS-CoV-2 patients has not been consistent, highlighting the need for more potent treatments. We previously showed that cobicistat, a clinically approved inhibitor of Cytochrome P450-3A (CYP3A), has direct antiviral activity against early circulating SARS-CoV-2 strains in vitro and in Syrian hamsters. Cobicistat is a derivative of ritonavir, which is co-administered as pharmacoenhancer with the SARS-CoV-2 protease inhibitor nirmatrelvir, to inhibit its metabolization by CPY3A and preserve its antiviral efficacy. Here, we used automated image analysis for a screening and parallel comparison of the anti-coronavirus effects of cobicistat and ritonavir. Our data show that both drugs display antiviral activity at low micromolar concentrations against multiple SARS-CoV-2 variants in vitro, including epidemiologically relevant Omicron subvariants. Despite their close structural similarity, we found that cobicistat is more potent than ritonavir, as shown by significantly lower EC50 values in monotherapy and higher levels of viral suppression when used in combination with nirmatrelvir. Finally, we show that the antiviral activity of both cobicistat and ritonavir is maintained against other human coronaviruses, including HCoV-229E and the highly pathogenic MERS-CoV. Overall, our results demonstrate that cobicistat has more potent anti-coronavirus activity than ritonavir and suggest that dose adjustments could pave the way to the use of both drugs as broad-spectrum antivirals against highly pathogenic human coronaviruses.
MeSH term(s)	Humans ; Antiviral Agents/therapeutic use ; Ritonavir/pharmacology ; Cytochrome P-450 CYP3A Inhibitors/pharmacology ; Cytochrome P-450 CYP3A Inhibitors/therapeutic use ; Coronavirus Infections/drug therapy ; Middle East Respiratory Syndrome Coronavirus ; Cobicistat/therapeutic use
Chemical Substances	Antiviral Agents ; Ritonavir (O3J8G9O825) ; Cytochrome P-450 CYP3A Inhibitors ; Cobicistat (LW2E03M5PG)
Language	English
Publishing date	2023-11-30
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	306628-9
ISSN	1872-9096 ; 0166-3542
ISSN (online)	1872-9096
ISSN	0166-3542
DOI	10.1016/j.antiviral.2023.105766
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Article ; Online: Cyclic nucleotide-induced bidirectional long-term synaptic plasticity in Drosophila mushroom body.

Yamada, Daichi / Davidson, Andrew M / Hige, Toshihide

The Journal of physiology

2024

Abstract: Activation of the cAMP pathway is one of the common mechanisms underlying long-term potentiation (LTP). In the Drosophila mushroom body, simultaneous activation of odour-coding Kenyon cells (KCs) and reinforcement-coding dopaminergic neurons activates ... ...

Abstract	Activation of the cAMP pathway is one of the common mechanisms underlying long-term potentiation (LTP). In the Drosophila mushroom body, simultaneous activation of odour-coding Kenyon cells (KCs) and reinforcement-coding dopaminergic neurons activates adenylyl cyclase in KC presynaptic terminals, which is believed to trigger synaptic plasticity underlying olfactory associative learning. However, learning induces long-term depression (LTD) at these synapses, contradicting the universal role of cAMP as a facilitator of transmission. Here, we developed a system to electrophysiologically monitor both short-term and long-term synaptic plasticity at KC output synapses and demonstrated that they are indeed an exception in which activation of the cAMP-protein kinase A pathway induces LTD. Contrary to the prevailing model, our cAMP imaging found no evidence for synergistic action of dopamine and KC activity on cAMP synthesis. Furthermore, we found that forskolin-induced cAMP increase alone was insufficient for plasticity induction; it additionally required simultaneous KC activation to replicate the presynaptic LTD induced by pairing with dopamine. On the other hand, activation of the cGMP pathway paired with KC activation induced slowly developing LTP, proving antagonistic actions of the two second-messenger pathways predicted by behavioural study. Finally, KC subtype-specific interrogation of synapses revealed that different KC subtypes exhibit distinct plasticity duration even among synapses on the same postsynaptic neuron. Thus, our work not only revises the role of cAMP in synaptic plasticity by uncovering the unexpected convergence point of the cAMP pathway and neuronal activity, but also establishes the methods to address physiological mechanisms of synaptic plasticity in this important model. KEY POINTS: Although presynaptic cAMP increase generally facilitates synapses, olfactory associative learning in Drosophila, which depends on dopamine and cAMP signalling genes, induces long-term depression (LTD) at the mushroom body output synapses. By combining electrophysiology, pharmacology and optogenetics, we directly demonstrate that these synapses are an exception where activation of the cAMP-protein kinase A pathway leads to presynaptic LTD. Dopamine- or forskolin-induced cAMP increase alone is not sufficient for LTD induction; neuronal activity, which has been believed to trigger cAMP synthesis in synergy with dopamine input, is required in the downstream pathway of cAMP. In contrast to cAMP, activation of the cGMP pathway paired with neuronal activity induces presynaptic long-term potentiation, which explains behaviourally observed opposing actions of transmitters co-released by dopaminergic neurons. Our work not only revises the role of cAMP in synaptic plasticity, but also provides essential methods to address physiological mechanisms of synaptic plasticity in this important model system.
Language	English
Publishing date	2024-03-15
Publishing country	England
Document type	Journal Article
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/JP285745
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Article: Cyclic nucleotide-induced bidirectional long-term synaptic plasticity in

Yamada, Daichi / Davidson, Andrew M / Hige, Toshihide

bioRxiv : the preprint server for biology

2024

Abstract: Activation of the cAMP pathway is one of the common mechanisms underlying long-term potentiation (LTP). In ... ...

Abstract	Activation of the cAMP pathway is one of the common mechanisms underlying long-term potentiation (LTP). In the
Language	English
Publishing date	2024-01-03
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.09.28.560058
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Article: A Highly Active and Selective Zirconium-Based Catalyst System for the Industrial Production of Poly(lactic acid).

Buchard, Antoine / Chuck, Christopher J / Davidson, Matthew G / Gobius du Sart, Gerrit / Jones, Matthew D / McCormick, Strachan N / Russell, Andrew D

ACS catalysis

2023 Volume 13, Issue 4, Page(s) 2681–2695

Abstract: The biodegradable, aliphatic polyester poly(lactic acid), PLA, is a leading bio-based alternative to petrochemical-derived plastic materials across a range of applications. Widely reported in the available literature as a benchmark for PLA ... ...

Abstract	The biodegradable, aliphatic polyester poly(lactic acid), PLA, is a leading bio-based alternative to petrochemical-derived plastic materials across a range of applications. Widely reported in the available literature as a benchmark for PLA production
Language	English
Publishing date	2023-02-07
Publishing country	United States
Document type	Journal Article
ISSN	2155-5435
ISSN	2155-5435
DOI	10.1021/acscatal.2c05690
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Article ; Online: 3D bioprinting of high cell-density heterogeneous tissue models through spheroid fusion within self-healing hydrogels.

Daly, Andrew C / Davidson, Matthew D / Burdick, Jason A

Nature communications

2021 Volume 12, Issue 1, Page(s) 753

Abstract: Cellular models are needed to study human development and disease in vitro, and to screen drugs for toxicity and efficacy. Current approaches are limited in the engineering of functional tissue models with requisite cell densities and heterogeneity to ... ...

Abstract	Cellular models are needed to study human development and disease in vitro, and to screen drugs for toxicity and efficacy. Current approaches are limited in the engineering of functional tissue models with requisite cell densities and heterogeneity to appropriately model cell and tissue behaviors. Here, we develop a bioprinting approach to transfer spheroids into self-healing support hydrogels at high resolution, which enables their patterning and fusion into high-cell density microtissues of prescribed spatial organization. As an example application, we bioprint induced pluripotent stem cell-derived cardiac microtissue models with spatially controlled cardiomyocyte and fibroblast cell ratios to replicate the structural and functional features of scarred cardiac tissue that arise following myocardial infarction, including reduced contractility and irregular electrical activity. The bioprinted in vitro model is combined with functional readouts to probe how various pro-regenerative microRNA treatment regimes influence tissue regeneration and recovery of function as a result of cardiomyocyte proliferation. This method is useful for a range of biomedical applications, including the development of precision models to mimic diseases and the screening of drugs, particularly where high cell densities and heterogeneity are important.
MeSH term(s)	Biomedical Engineering/methods ; Bioprinting/methods ; Cardiovascular Diseases ; Drug Delivery Systems/methods ; Drug Evaluation, Preclinical/methods ; Hydrogels/chemistry ; Pluripotent Stem Cells/cytology ; Pluripotent Stem Cells/metabolism ; Spheroids, Cellular/cytology ; Tissue Engineering/methods
Chemical Substances	Hydrogels
Language	English
Publishing date	2021-02-02
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-21029-2
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Article ; Online: De novo assembly and annotation of the Patagonian toothfish (Dissostichus eleginoides) genome.

Ryder, David / Stone, David / Minardi, Diana / Riley, Ainsley / Avant, Justin / Cross, Lisa / Soeffker, Marta / Davidson, Deborah / Newman, Andrew / Thomson, Peter / Darby, Chris / van Aerle, Ronny

BMC genomics

2024 Volume 25, Issue 1, Page(s) 233

Abstract: ... quality D. eleginoides genome was generated using a combination of Illumina, PacBio and Omni-C sequencing ... that the anti-freeze glycoprotein (AFGP) locus of D. eleginoides does not contain any AFGP proteins compared ...

Abstract	Background: Patagonian toothfish (Dissostichus eleginoides) is an economically and ecologically important fish species in the family Nototheniidae. Juveniles occupy progressively deeper waters as they mature and grow, and adults have been caught as deep as 2500 m, living on or in just above the southern shelves and slopes around the sub-Antarctic islands of the Southern Ocean. As apex predators, they are a key part of the food web, feeding on a variety of prey, including krill, squid, and other fish. Despite its importance, genomic sequence data, which could be used for more accurate dating of the divergence between Patagonian and Antarctic toothfish, or establish whether it shares adaptations to temperature with fish living in more polar or equatorial climes, has so far been limited. Results: A high-quality D. eleginoides genome was generated using a combination of Illumina, PacBio and Omni-C sequencing technologies. To aid the genome annotation, the transcriptome derived from a variety of toothfish tissues was also generated using both short and long read sequencing methods. The final genome assembly was 797.8 Mb with a N50 scaffold length of 3.5 Mb. Approximately 31.7% of the genome consisted of repetitive elements. A total of 35,543 putative protein-coding regions were identified, of which 50% have been functionally annotated. Transcriptomics analysis showed that approximately 64% of the predicted genes (22,617 genes) were found to be expressed in the tissues sampled. Comparative genomics analysis revealed that the anti-freeze glycoprotein (AFGP) locus of D. eleginoides does not contain any AFGP proteins compared to the same locus in the Antarctic toothfish (Dissostichus mawsoni). This is in agreement with previously published results looking at hybridization signals and confirms that Patagonian toothfish do not possess AFGP coding sequences in their genome. Conclusions: We have assembled and annotated the Patagonian toothfish genome, which will provide a valuable genetic resource for ecological and evolutionary studies on this and other closely related species.
MeSH term(s)	Animals ; Perciformes/genetics ; Genomics ; Antarctic Regions ; Biological Evolution ; Antifreeze Proteins
Chemical Substances	Antifreeze Proteins
Language	English
Publishing date	2024-03-04
Publishing country	England
Document type	Journal Article
ZDB-ID	2041499-7
ISSN	1471-2164 ; 1471-2164
ISSN (online)	1471-2164
ISSN	1471-2164
DOI	10.1186/s12864-024-10141-4
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Article ; Online: Development and application of dengue virus reverse genetic systems.

Davidson, Andrew D

Methods in molecular biology (Clifton, N.J.)

2014 Volume 1138, Page(s) 113–130

Abstract: The development of dengue virus "reverse genetic" systems based on full-length cDNA clones corresponding to the viral RNA genome has been an important technological platform for advancing dengue virus research. Mutations can be introduced into the genome ...

Abstract	The development of dengue virus "reverse genetic" systems based on full-length cDNA clones corresponding to the viral RNA genome has been an important technological platform for advancing dengue virus research. Mutations can be introduced into the genome to study their effect on virus replication and pathogenesis while attenuated or chimeric viruses can be constructed that are potential vaccine candidates. The deletion of the virus structural genes has led to the production of noninfectious, but replication competent viral subgenomes (termed replicons) that have been used to study viral replication and are useful for the screening of antiviral compounds. This article describes the development of dengue virus reverse genetic systems and protocols to manipulate the viral genome, recover infectious virus, and produce replicon-containing cell lines.
MeSH term(s)	Animals ; Base Sequence ; Cell Line ; DNA, Complementary/genetics ; Dengue Virus/genetics ; Genome, Viral/genetics ; Molecular Sequence Data ; Plasmids/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Replicon/genetics ; Reverse Genetics/methods
Chemical Substances	DNA, Complementary ; RNA, Messenger
Language	English
Publishing date	2014
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-0348-1_8
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Article ; Online: Muscimol inactivation of dorsal striatum in young and aged male rats does not affect paired associates learning performance.

Smith, Samantha M / Garcia, Elena L / Montelongo, Anna / Davidson, Caroline G / Bakhtiar, Denna / Lovett, Sarah D / Maurer, Andrew P / Burke, Sara N

Behavioral neuroscience

2023 Volume 137, Issue 6, Page(s) 356–363

Abstract: Improving cognitive health for older adults requires understanding the neurobiology of age-related cognitive decline and the mechanisms underlying preserved cognition in old age. During spatial learning tasks, aged humans and rodents shift navigation ... ...

Abstract	Improving cognitive health for older adults requires understanding the neurobiology of age-related cognitive decline and the mechanisms underlying preserved cognition in old age. During spatial learning tasks, aged humans and rodents shift navigation preferences in favor of a stimulus-response learning strategy. This has been hypothesized to result from competitive interactions of the caudate nucleus/dorsal striatum (DS) memory system with the hippocampus (HPC)-dependent spatial/allocentric memory system. In support of this hypothesis, a recent study reported that inactivation of the DS in aged rodents rescued HPC-dependent spatial learning on a T-maze (Gardner, Gold, & Korol, 2020). Currently, it is unclear whether a shift from HPC-dependent to DS-dependent behavior also contributes to age-related cognitive decline outside of spatial learning and memory. To test the hypothesis that inactivation of the DS can restore age-related cognitive function outside of spatial behavior, the present study bilaterally inactivated the DS of young (
MeSH term(s)	Humans ; Rats ; Male ; Animals ; Aged ; Muscimol/pharmacology ; Spatial Learning/physiology ; Spatial Memory/physiology ; Cognition ; Spatial Navigation ; Hippocampus/physiology ; Maze Learning/physiology
Chemical Substances	Muscimol (2763-96-4)
Language	English
Publishing date	2023-06-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	230159-3
ISSN	1939-0084 ; 0735-7044
ISSN (online)	1939-0084
ISSN	0735-7044
DOI	10.1037/bne0000561
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Zs.A 1837: Show issues

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Article ; Online: Ambient carbon dioxide concentration correlates with SARS-CoV-2 aerostability and infection risk.

Haddrell, Allen / Oswin, Henry / Otero-Fernandez, Mara / Robinson, Joshua F / Cogan, Tristan / Alexander, Robert / Mann, Jamie F S / Hill, Darryl / Finn, Adam / Davidson, Andrew D / Reid, Jonathan P

Nature communications

2024 Volume 15, Issue 1, Page(s) 3487

Abstract: An improved understanding of the underlying physicochemical properties of respiratory aerosol that influence viral infectivity may open new avenues to mitigate the transmission of respiratory diseases such as COVID-19. Previous studies have shown that an ...

Abstract	An improved understanding of the underlying physicochemical properties of respiratory aerosol that influence viral infectivity may open new avenues to mitigate the transmission of respiratory diseases such as COVID-19. Previous studies have shown that an increase in the pH of respiratory aerosols following generation due to changes in the gas-particle partitioning of pH buffering bicarbonate ions and carbon dioxide is a significant factor in reducing SARS-CoV-2 infectivity. We show here that a significant increase in SARS-CoV-2 aerostability results from a moderate increase in the atmospheric carbon dioxide concentration (e.g. 800 ppm), an effect that is more marked than that observed for changes in relative humidity. We model the likelihood of COVID-19 transmission on the ambient concentration of CO
MeSH term(s)	Carbon Dioxide/metabolism ; Carbon Dioxide/analysis ; COVID-19/transmission ; COVID-19/virology ; Humans ; SARS-CoV-2 ; Hydrogen-Ion Concentration ; Aerosols ; Humidity ; Ventilation ; Respiratory Aerosols and Droplets/metabolism ; Respiratory Aerosols and Droplets/virology ; Atmosphere/chemistry
Chemical Substances	Carbon Dioxide (142M471B3J) ; Aerosols
Language	English
Publishing date	2024-04-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-47777-5
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