Tiina O'Neill - Academia.edu (original) (raw)

Papers by Tiina O'Neill

Research paper thumbnail of An Investigation into the Acidity-Induced Insulin Agglomeration: Implications for Drug Delivery and Translation

Research paper thumbnail of A novel antiviral formulation containing caprylic acid inhibits SARS-CoV-2 infection of a human bronchial epithelial cell model

Journal of General Virology

A novel proprietary formulation, ViruSAL, has previously been demonstrated to inhibit diverse env... more A novel proprietary formulation, ViruSAL, has previously been demonstrated to inhibit diverse enveloped viral infections in vitro and in vivo. We evaluated the ability of ViruSAL to inhibit SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) infectivity, using physiologically relevant models of the human bronchial epithelium, to model early infection of the upper respiratory tract. ViruSAL potently inhibited SARS-CoV-2 infection of human bronchial epithelial cells cultured as an air–liquid interface (ALI) model, in a concentration- and time-dependent manner. Viral infection was completely inhibited when ViruSAL was added to bronchial airway models prior to infection. Importantly, ViruSAL also inhibited viral infection when added to ALI models post-infection. No evidence of cellular toxicity was detected in ViruSAL-treated cells at concentrations that completely abrogated viral infectivity. Moreover, intranasal instillation of ViruSAL to a rat model did not result in any tox...

Research paper thumbnail of Crystallisation pathways of a mixed La Nd carbonate – Ambient temperature synthesis of the mineral lanthanite

Research paper thumbnail of A novel antiviral formulation inhibits SARS-CoV-2 infection of human bronchial epithelium

A novel proprietary formulation, ViruSAL, has previously been demonstrated to inhibit diverse env... more A novel proprietary formulation, ViruSAL, has previously been demonstrated to inhibit diverse enveloped viral infections in vitro and in vivo. We evaluated the ability of ViruSAL to inhibit SARS-CoV-2 infectivity, using physiologically relevant models of the human bronchial epithelium, to model early infection of the upper respiratory tract. ViruSAL potently inhibited SARS-CoV-2 infection of human bronchial epithelial cells cultured as an air-liquid interface (ALI) model, in a concentration- and time-dependent manner. Viral infection was completely inhibited when ViruSAL was added to bronchial airway models prior to infection. Importantly, ViruSAL also inhibited viral infection when added to ALI models post-infection. No evidence of in vitro cellular toxicity was detected in ViruSAL treated cells at concentrations that completely abrogated viral infectivity. Moreover, intranasal instillation of ViruSAL to a rat model did not result in any toxicity or pathological changes. Together t...

Research paper thumbnail of Case Report: Hypergranular Platelets in Vaccine-Induced Thrombotic Thrombocytopenia After ChAdOx1 nCov-19 Vaccination

Frontiers in Cardiovascular Medicine, 2022

BackgroundVaccine-induced thrombotic thrombocytopenia (VITT) post SARS-CoV-2 vaccination is chara... more BackgroundVaccine-induced thrombotic thrombocytopenia (VITT) post SARS-CoV-2 vaccination is characterized by thrombocytopenia and severe thrombosis. Platelet function during patient recovery in the medium-/long-term has not been investigated fully. Here, we undertook a 3-month study, assessing the recovery of a VITT patient and assessing platelet morphology, granule content and dense-granule release at two distinct time points during recovery.Case PresentationA 61 year-old female was admitted to hospital 15 days post ChAdOx1 nCov-19 vaccination. Hematological parameters and peripheral blood smears were monitored over 3 months. Platelet morphology and granule populations were assessed using transmission electron microscopy (TEM) at two distinct time points during recovery, as was agonist-induced platelet dense-granule release. Upon admission, the patient had reduced platelet counts, increased D-dimer and high anti-PF4 antibodies with multiple sites of cerebral venous sinus thrombosis...

Research paper thumbnail of One particle, two targets: A combined action of functionalised gold nanoparticles, against Pseudomonas fluorescens biofilms

Journal of colloid and interface science, Jan 8, 2018

Attempts to deal with the problem of detrimental biofilms using nanoparticle technologies have ge... more Attempts to deal with the problem of detrimental biofilms using nanoparticle technologies have generally focussed on exploiting biocidal approaches. However, it is now recognised that biofilm matrix-components may be targets for the disruption or dispersion of biofilms. Here, we show that the functionalization of gold nanoparticles with the enzyme, proteinase-K (PK) led to both biocidal and matrix disruption effects within Pseudomonas fluorescens biofilms and released cells. This study highlights the potential mechanisms underpinning the properties of Proteinase-K functionalized gold nanoparticles. With the emergence of biocide-resistant biofilm-forming organisms, novel nanoparticle strategies may provide the ideal solution for disrupting and inactivating biofilm cells, thereby minimising the use of biocides or antibiotics.

Research paper thumbnail of FPR2/ALX receptor expression and internalization are critical for lipoxin A4and annexin‐derived peptide‐stimulated phagocytosis

Research paper thumbnail of A safe-by-design approach to the development of gold nanoboxes as carriers for internalization into cancer cells

Biomaterials, 2014

Gold nanomaterials are currently raising a significant interest for human welfare in the field of... more Gold nanomaterials are currently raising a significant interest for human welfare in the field of clinical diagnosis, therapeutics for chronic pathologies, as well as of many other biomedical applications. In particular, gold nanomaterials are becoming a promising technology for developing novel approaches and treatments against widespread societal diseases such as cancer. In this study, we investigated the potential of proprietary gold nanoboxes (AuNBs) as carriers for their perspective translation into multifunctional, pre-clinical nano-enabled systems for personalized medicine approaches against lung cancer. A safe-by-design, tiered approach, with systematic tests conducted in the early phases on uncoated AuNBs and more focused testing on the coated, drug-loaded nanomaterial toward the end, was adopted. Our results showed that uncoated AuNBs could effectively penetrate into human lung adenocarcinoma (A549) cells when in simple (mono-cultures) or complex (co-and three-dimensionalcultures) in vitro microenvironments mimicking the alveolar region of human lungs. Uncoated AuNBs were biologically inert in A549 cells and demonstrated signs of biodegradability. Concurrently, preliminary data revealed that coated, drug-loaded AuNBs could efficiently deliver a chemotherapeutic agent to A549 cells, corroborating the hypothesis that AuNBs could be used in the future for the development of personalized nano-enabled systems for lung cancer treatment.

Research paper thumbnail of Immunogold labeling reveals subcellular localisation of silica nanoparticles in a human blood–brain barrier model

Nanoscale, 2015

The pre-embedding immunogold labeling electron microscopy was employed to investigate subcellular... more The pre-embedding immunogold labeling electron microscopy was employed to investigate subcellular transport pathways of nanoparticles in a blood–brain barrier model.

Research paper thumbnail of Joubert syndrome Arl13b functions at ciliary membranes and stabilizes protein transport in Caenorhabditis elegans

The Journal of Cell Biology, 2010

subtypes is restricted to the proximal ciliary region. Furthermore, we find that C. elegans ARL-1... more subtypes is restricted to the proximal ciliary region. Furthermore, we find that C. elegans ARL-13 maintains cilium structure/ morphology and provide evidence that ARL-13 is required for ciliary transmembrane protein localizations/abundance and the stabilization of anterograde IFT assemblies. From these data, we propose that ARL-13/Arl13b functions at ciliary membranes to stabilize ciliary protein transport processes. Results ARL-13 is homologous to JS-associated Arl13b BLAST analyses identified ARL-13 (Y37E3.5) sequence homologues in mice (Arl13b), zebrafish (Scorpion), Xenopus laevis, and Chlamydomonas reinhardtii, each possessing an extended tail (100-300 residues) C-terminal to the GTPase domain (Fig. S1 A). In contrast, the top hits in Drosophila melanogaster and Tetrahymena thermophila returned lower BLAST scores and lacked extended tails, indicating that ARL-13 homologues are not present in all ciliates (Fig. S1 A). Sequence alignment showed that all ARL-13 homologues contain an N-terminal palmitoylation (Pal) modification motif (not found in most G proteins), possess the three residues (R79, W82, and R200) mutated in patients with Arl13b-associated JS (Cantagrel et al., 2008), and lack the switch two Gln residue critical for GTPase activity in most Arl/Arfs (Fig. S1 B). Together with previous findings that nematode ARL-13 and vertebrate Arl13b localize exclusively to cilia (

Research paper thumbnail of Reactive oxygen species induce signals that lead to apoptotic DNA degradation in primary CD4+ T cells

Apoptosis, 2005

Reactive oxygen species are toxic to cells but they may also have active roles in transducing apo... more Reactive oxygen species are toxic to cells but they may also have active roles in transducing apoptotic events. To study the role of reactive oxygen species in growth factor depletion induced apoptosis of human primary CD4+ T cells, we used a synthetic manganese porphyrin superoxide dismutase mimetic to detoxify superoxide anions formed during apoptosis. Apoptosis of primary CD4+ T cells was characterized by generation of superoxide anions, plasma membrane phosphatidyl-serine translocation, loss of mitochondrial membrane potential, activation of caspase 3, condensation of chromatin, as well as DNA degradation. The detoxification of superoxide anions did not influence plasma membrane phosphatidyl-serine translocation, or chromatin condensation, and only marginally inhibited the loss of mitochondrial membrane potential and the formation of DNA strand breaks. In contrast, the detoxification of superoxide anions significantly reduced caspase 3 activity and almost completely inhibited the apoptotic decrease in total cellular DNA content as measured by propidium iodide staining. Our results indicate that reactive oxygen anions induce signals leading to efficient DNA degradation after the initial formation of DNA strand breaks. Thus, reactive oxygen anions have active roles in signaling that lead to the apoptotic events.

Research paper thumbnail of One particle, two targets: a combined action of functionalised gold nanoparticles, against Pseudomonas fluorescens biofilms

Journal of Colloid and Interface Science, 2018

Attempts to deal with the problem of detrimental biofilms using nanoparticle technologies have ge... more Attempts to deal with the problem of detrimental biofilms using nanoparticle technologies have generally focussed on exploiting biocidal approaches. However, it is now recognised that biofilm matrix-components may be targets for the disruption or dispersion of biofilms. Here, we show that the functionalization of gold nanoparticles with the enzyme, proteinase-K (PK) led to both biocidal and matrix disruption effects within Pseudomonas fluorescens biofilms and released cells. This study highlights the potential mechanisms underpinning the properties of Proteinase-K functionalized gold nanoparticles. With the emergence of biocide-resistant biofilm-forming organisms, novel nanoparticle strategies may provide the ideal solution for disrupting and inactivating biofilm cells, thereby minimising the use of biocides or antibiotics.

Research paper thumbnail of An Investigation into the Acidity-Induced Insulin Agglomeration: Implications for Drug Delivery and Translation

Research paper thumbnail of A novel antiviral formulation containing caprylic acid inhibits SARS-CoV-2 infection of a human bronchial epithelial cell model

Journal of General Virology

A novel proprietary formulation, ViruSAL, has previously been demonstrated to inhibit diverse env... more A novel proprietary formulation, ViruSAL, has previously been demonstrated to inhibit diverse enveloped viral infections in vitro and in vivo. We evaluated the ability of ViruSAL to inhibit SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) infectivity, using physiologically relevant models of the human bronchial epithelium, to model early infection of the upper respiratory tract. ViruSAL potently inhibited SARS-CoV-2 infection of human bronchial epithelial cells cultured as an air–liquid interface (ALI) model, in a concentration- and time-dependent manner. Viral infection was completely inhibited when ViruSAL was added to bronchial airway models prior to infection. Importantly, ViruSAL also inhibited viral infection when added to ALI models post-infection. No evidence of cellular toxicity was detected in ViruSAL-treated cells at concentrations that completely abrogated viral infectivity. Moreover, intranasal instillation of ViruSAL to a rat model did not result in any tox...

Research paper thumbnail of Crystallisation pathways of a mixed La Nd carbonate – Ambient temperature synthesis of the mineral lanthanite

Research paper thumbnail of A novel antiviral formulation inhibits SARS-CoV-2 infection of human bronchial epithelium

A novel proprietary formulation, ViruSAL, has previously been demonstrated to inhibit diverse env... more A novel proprietary formulation, ViruSAL, has previously been demonstrated to inhibit diverse enveloped viral infections in vitro and in vivo. We evaluated the ability of ViruSAL to inhibit SARS-CoV-2 infectivity, using physiologically relevant models of the human bronchial epithelium, to model early infection of the upper respiratory tract. ViruSAL potently inhibited SARS-CoV-2 infection of human bronchial epithelial cells cultured as an air-liquid interface (ALI) model, in a concentration- and time-dependent manner. Viral infection was completely inhibited when ViruSAL was added to bronchial airway models prior to infection. Importantly, ViruSAL also inhibited viral infection when added to ALI models post-infection. No evidence of in vitro cellular toxicity was detected in ViruSAL treated cells at concentrations that completely abrogated viral infectivity. Moreover, intranasal instillation of ViruSAL to a rat model did not result in any toxicity or pathological changes. Together t...

Research paper thumbnail of Case Report: Hypergranular Platelets in Vaccine-Induced Thrombotic Thrombocytopenia After ChAdOx1 nCov-19 Vaccination

Frontiers in Cardiovascular Medicine, 2022

BackgroundVaccine-induced thrombotic thrombocytopenia (VITT) post SARS-CoV-2 vaccination is chara... more BackgroundVaccine-induced thrombotic thrombocytopenia (VITT) post SARS-CoV-2 vaccination is characterized by thrombocytopenia and severe thrombosis. Platelet function during patient recovery in the medium-/long-term has not been investigated fully. Here, we undertook a 3-month study, assessing the recovery of a VITT patient and assessing platelet morphology, granule content and dense-granule release at two distinct time points during recovery.Case PresentationA 61 year-old female was admitted to hospital 15 days post ChAdOx1 nCov-19 vaccination. Hematological parameters and peripheral blood smears were monitored over 3 months. Platelet morphology and granule populations were assessed using transmission electron microscopy (TEM) at two distinct time points during recovery, as was agonist-induced platelet dense-granule release. Upon admission, the patient had reduced platelet counts, increased D-dimer and high anti-PF4 antibodies with multiple sites of cerebral venous sinus thrombosis...

Research paper thumbnail of One particle, two targets: A combined action of functionalised gold nanoparticles, against Pseudomonas fluorescens biofilms

Journal of colloid and interface science, Jan 8, 2018

Attempts to deal with the problem of detrimental biofilms using nanoparticle technologies have ge... more Attempts to deal with the problem of detrimental biofilms using nanoparticle technologies have generally focussed on exploiting biocidal approaches. However, it is now recognised that biofilm matrix-components may be targets for the disruption or dispersion of biofilms. Here, we show that the functionalization of gold nanoparticles with the enzyme, proteinase-K (PK) led to both biocidal and matrix disruption effects within Pseudomonas fluorescens biofilms and released cells. This study highlights the potential mechanisms underpinning the properties of Proteinase-K functionalized gold nanoparticles. With the emergence of biocide-resistant biofilm-forming organisms, novel nanoparticle strategies may provide the ideal solution for disrupting and inactivating biofilm cells, thereby minimising the use of biocides or antibiotics.

Research paper thumbnail of FPR2/ALX receptor expression and internalization are critical for lipoxin A4and annexin‐derived peptide‐stimulated phagocytosis

Research paper thumbnail of A safe-by-design approach to the development of gold nanoboxes as carriers for internalization into cancer cells

Biomaterials, 2014

Gold nanomaterials are currently raising a significant interest for human welfare in the field of... more Gold nanomaterials are currently raising a significant interest for human welfare in the field of clinical diagnosis, therapeutics for chronic pathologies, as well as of many other biomedical applications. In particular, gold nanomaterials are becoming a promising technology for developing novel approaches and treatments against widespread societal diseases such as cancer. In this study, we investigated the potential of proprietary gold nanoboxes (AuNBs) as carriers for their perspective translation into multifunctional, pre-clinical nano-enabled systems for personalized medicine approaches against lung cancer. A safe-by-design, tiered approach, with systematic tests conducted in the early phases on uncoated AuNBs and more focused testing on the coated, drug-loaded nanomaterial toward the end, was adopted. Our results showed that uncoated AuNBs could effectively penetrate into human lung adenocarcinoma (A549) cells when in simple (mono-cultures) or complex (co-and three-dimensionalcultures) in vitro microenvironments mimicking the alveolar region of human lungs. Uncoated AuNBs were biologically inert in A549 cells and demonstrated signs of biodegradability. Concurrently, preliminary data revealed that coated, drug-loaded AuNBs could efficiently deliver a chemotherapeutic agent to A549 cells, corroborating the hypothesis that AuNBs could be used in the future for the development of personalized nano-enabled systems for lung cancer treatment.

Research paper thumbnail of Immunogold labeling reveals subcellular localisation of silica nanoparticles in a human blood–brain barrier model

Nanoscale, 2015

The pre-embedding immunogold labeling electron microscopy was employed to investigate subcellular... more The pre-embedding immunogold labeling electron microscopy was employed to investigate subcellular transport pathways of nanoparticles in a blood–brain barrier model.

Research paper thumbnail of Joubert syndrome Arl13b functions at ciliary membranes and stabilizes protein transport in Caenorhabditis elegans

The Journal of Cell Biology, 2010

subtypes is restricted to the proximal ciliary region. Furthermore, we find that C. elegans ARL-1... more subtypes is restricted to the proximal ciliary region. Furthermore, we find that C. elegans ARL-13 maintains cilium structure/ morphology and provide evidence that ARL-13 is required for ciliary transmembrane protein localizations/abundance and the stabilization of anterograde IFT assemblies. From these data, we propose that ARL-13/Arl13b functions at ciliary membranes to stabilize ciliary protein transport processes. Results ARL-13 is homologous to JS-associated Arl13b BLAST analyses identified ARL-13 (Y37E3.5) sequence homologues in mice (Arl13b), zebrafish (Scorpion), Xenopus laevis, and Chlamydomonas reinhardtii, each possessing an extended tail (100-300 residues) C-terminal to the GTPase domain (Fig. S1 A). In contrast, the top hits in Drosophila melanogaster and Tetrahymena thermophila returned lower BLAST scores and lacked extended tails, indicating that ARL-13 homologues are not present in all ciliates (Fig. S1 A). Sequence alignment showed that all ARL-13 homologues contain an N-terminal palmitoylation (Pal) modification motif (not found in most G proteins), possess the three residues (R79, W82, and R200) mutated in patients with Arl13b-associated JS (Cantagrel et al., 2008), and lack the switch two Gln residue critical for GTPase activity in most Arl/Arfs (Fig. S1 B). Together with previous findings that nematode ARL-13 and vertebrate Arl13b localize exclusively to cilia (

Research paper thumbnail of Reactive oxygen species induce signals that lead to apoptotic DNA degradation in primary CD4+ T cells

Apoptosis, 2005

Reactive oxygen species are toxic to cells but they may also have active roles in transducing apo... more Reactive oxygen species are toxic to cells but they may also have active roles in transducing apoptotic events. To study the role of reactive oxygen species in growth factor depletion induced apoptosis of human primary CD4+ T cells, we used a synthetic manganese porphyrin superoxide dismutase mimetic to detoxify superoxide anions formed during apoptosis. Apoptosis of primary CD4+ T cells was characterized by generation of superoxide anions, plasma membrane phosphatidyl-serine translocation, loss of mitochondrial membrane potential, activation of caspase 3, condensation of chromatin, as well as DNA degradation. The detoxification of superoxide anions did not influence plasma membrane phosphatidyl-serine translocation, or chromatin condensation, and only marginally inhibited the loss of mitochondrial membrane potential and the formation of DNA strand breaks. In contrast, the detoxification of superoxide anions significantly reduced caspase 3 activity and almost completely inhibited the apoptotic decrease in total cellular DNA content as measured by propidium iodide staining. Our results indicate that reactive oxygen anions induce signals leading to efficient DNA degradation after the initial formation of DNA strand breaks. Thus, reactive oxygen anions have active roles in signaling that lead to the apoptotic events.

Research paper thumbnail of One particle, two targets: a combined action of functionalised gold nanoparticles, against Pseudomonas fluorescens biofilms

Journal of Colloid and Interface Science, 2018

Attempts to deal with the problem of detrimental biofilms using nanoparticle technologies have ge... more Attempts to deal with the problem of detrimental biofilms using nanoparticle technologies have generally focussed on exploiting biocidal approaches. However, it is now recognised that biofilm matrix-components may be targets for the disruption or dispersion of biofilms. Here, we show that the functionalization of gold nanoparticles with the enzyme, proteinase-K (PK) led to both biocidal and matrix disruption effects within Pseudomonas fluorescens biofilms and released cells. This study highlights the potential mechanisms underpinning the properties of Proteinase-K functionalized gold nanoparticles. With the emergence of biocide-resistant biofilm-forming organisms, novel nanoparticle strategies may provide the ideal solution for disrupting and inactivating biofilm cells, thereby minimising the use of biocides or antibiotics.