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  1. Article ; Online: A (cross)link in the chains.

    Watkins, Christopher P / Flynn, Ryan A

    Nature chemistry

    2023  Volume 15, Issue 1, Page(s) 5–6

    MeSH term(s) Proteins/chemistry
    Chemical Substances Proteins
    Language English
    Publishing date 2023-01-06
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 2464596-5
    ISSN 1755-4349 ; 1755-4330
    ISSN (online) 1755-4349
    ISSN 1755-4330
    DOI 10.1038/s41557-022-01116-7
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  2. Article ; Online: Imaging glycosylated RNAs at the subcellular scale.

    Hristov, Petar / Flynn, Ryan A

    Nature biotechnology

    2023  Volume 42, Issue 4, Page(s) 574–575

    MeSH term(s) RNA/genetics ; RNA, Messenger ; Subcellular Fractions
    Chemical Substances RNA (63231-63-0) ; RNA, Messenger
    Language English
    Publishing date 2023-10-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1311932-1
    ISSN 1546-1696 ; 1087-0156
    ISSN (online) 1546-1696
    ISSN 1087-0156
    DOI 10.1038/s41587-023-02021-1
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  3. Article ; Online: RNA Crossing Membranes: Systems and Mechanisms Contextualizing Extracellular RNA and Cell Surface GlycoRNAs.

    Chai, Peiyuan / Lebedenko, Charlotta G / Flynn, Ryan A

    Annual review of genomics and human genetics

    2023  Volume 24, Page(s) 85–107

    Abstract: The subcellular localization of a biopolymer often informs its function. RNA is traditionally confined to the cytosolic and nuclear spaces, where it plays critical and conserved roles across nearly all biochemical processes. Our recent observation of ... ...

    Abstract The subcellular localization of a biopolymer often informs its function. RNA is traditionally confined to the cytosolic and nuclear spaces, where it plays critical and conserved roles across nearly all biochemical processes. Our recent observation of cell surface glycoRNAs may further explain the extracellular role of RNA. While cellular membranes are efficient gatekeepers of charged polymers such as RNAs, a large body of research has demonstrated the accumulation of specific RNA species outside of the cell, termed extracellular RNAs (exRNAs). Across various species and forms of life, protein pores have evolved to transport RNA across membranes, thus providing a mechanistic path for exRNAs to achieve their extracellular topology. Here, we review types of exRNAs and the pores capable of RNA transport to provide a logical and testable path toward understanding the biogenesis and regulation of cell surface glycoRNAs.
    MeSH term(s) Humans ; RNA/genetics ; Cell Membrane ; Membranes ; Cytosol ; Polymers
    Chemical Substances RNA (63231-63-0) ; Polymers
    Language English
    Publishing date 2023-04-17
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2037670-4
    ISSN 1545-293X ; 1527-8204
    ISSN (online) 1545-293X
    ISSN 1527-8204
    DOI 10.1146/annurev-genom-101722-101224
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  4. Article ; Online: Surgical Approach for Partial Nephrectomy in the Management of Small Renal Masses: A Systematic Review and Network Meta-Analysis.

    Naughton, Ailish / Ryan, Éanna J / Keenan, Robert / Thomas, Arun Z / Smyth, Lisa G / Manecksha, Rustom P / Flynn, Robert J / Casey, Rowan G

    Journal of endourology

    2024  Volume 38, Issue 4, Page(s) 358–370

    Abstract: Background: ...

    Abstract Background:
    MeSH term(s) Humans ; Kidney Neoplasms/surgery ; Kidney Neoplasms/pathology ; Treatment Outcome ; Network Meta-Analysis ; Neoplasm Recurrence, Local/surgery ; Laparoscopy/methods ; Nephrectomy/methods
    Language English
    Publishing date 2024-03-18
    Publishing country United States
    Document type Meta-Analysis ; Systematic Review ; Journal Article
    ZDB-ID 356931-7
    ISSN 1557-900X ; 0892-7790
    ISSN (online) 1557-900X
    ISSN 0892-7790
    DOI 10.1089/end.2023.0107
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  5. Article ; Online: Synergistic antimicrobial interactions of nisin A with biopolymers and solubilising agents for oral drug delivery.

    Flynn, James / Ryan, Aoibhín / Hudson, Sarah P

    European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V

    2022  Volume 171, Page(s) 29–38

    Abstract: In order to develop bacteriocins, like the lantibiotic nisin A, into effective alternatives to existing antibiotics, their biophysical and physicochemical properties must first be assessed, from solubility, to susceptibility and absorption. It has been ... ...

    Abstract In order to develop bacteriocins, like the lantibiotic nisin A, into effective alternatives to existing antibiotics, their biophysical and physicochemical properties must first be assessed, from solubility, to susceptibility and absorption. It has been well established that formulation strategies at early drug development stages can be crucial for successful outcomes during preclinical and clinical phases of development, particularly for molecules with challenging physicochemical properties. This work elucidates the physicochemical challenges of nisin A in terms of its susceptibility to digestive enzymes like pepsin, pancreatin and proteinase K and its poor solubility at physiological pHs. Low solution concentrations, below the minimum inhibitory concentration against Staphylococcus aureus, were obtained in phosphate buffered saline (PBS, pH 7.4) and in fasted state simulated intestinal fluid (FaSSIF, pH 6.5), while higher solubilities at more acidic pH's such as in a KCl/HCl buffer (pH 2) and in fasted state simulated gastric fluid (FaSSGF, pH 1.6) are observed. Tween® 80 (0.01% v/v) significantly increased the solution concentration of nisin A in PBS (pH 7.4, 24 hr). Pancreatin doubled nisin A's solution concentration at pH 7.4 (PBS) but reduced its' inhibitory activity to ∼ 20%, and pepsin almost completely degraded nisin (after 24 hr), but retained activity at biologically relevant exposure times (∼15 min). Harnessing synergism between nisin A and either glycol chitosan or ε-poly lysine, combined with the solubilizing effect of Tween®, increased the antimicrobial activity of nisin A six fold in an in vitro oral administration model.
    MeSH term(s) Administration, Oral ; Anti-Bacterial Agents/administration & dosage ; Anti-Bacterial Agents/chemistry ; Anti-Bacterial Agents/pharmacology ; Biopolymers ; Drug Delivery Systems ; Drug Synergism ; Humans ; Microbial Sensitivity Tests ; Nisin/administration & dosage ; Nisin/chemistry ; Nisin/pharmacology ; Staphylococcus aureus/drug effects
    Chemical Substances Anti-Bacterial Agents ; Biopolymers ; Nisin (1414-45-5)
    Language English
    Publishing date 2022-01-02
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1065368-5
    ISSN 1873-3441 ; 0939-6411
    ISSN (online) 1873-3441
    ISSN 0939-6411
    DOI 10.1016/j.ejpb.2021.12.010
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    Zs.B 1651: Show issues Location:
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  6. Article ; Online: Examining Factors Associated with Cannabis Use Among Sexual and Gender Minority and Cisgender Heterosexual Emerging Adults in California.

    Jauregui, Juan C / Hong, Chenglin / Assaf, Ryan D / Cunningham, Nicole J / Krueger, Evan A / Flynn, Risa / Holloway, Ian W

    LGBT health

    2024  

    Abstract: Purpose: ...

    Abstract Purpose:
    Language English
    Publishing date 2024-02-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2727303-9
    ISSN 2325-8306 ; 2325-8292
    ISSN (online) 2325-8306
    ISSN 2325-8292
    DOI 10.1089/lgbt.2023.0050
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  7. Article ; Online: Pre-formulation and delivery strategies for the development of bacteriocins as next generation antibiotics.

    Flynn, James / Ryan, Aoibhín / Hudson, Sarah P

    European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V

    2021  Volume 165, Page(s) 149–163

    Abstract: Bacteriocins, a class of antimicrobial peptide produced by bacteria, may offer a potential alternative to traditional antibiotics, an important step towards mitigating the ever-increasing antimicrobial resistance crisis. They are active against a range ... ...

    Abstract Bacteriocins, a class of antimicrobial peptide produced by bacteria, may offer a potential alternative to traditional antibiotics, an important step towards mitigating the ever-increasing antimicrobial resistance crisis. They are active against a range of clinically relevant Gram-positive and Gram-negative bacteria. Bacteriocins have been discussed in the literature for over a century. Although they are used as preservatives in food, no medicine based on their antimicrobial activity exists on the market today. In order to formulate them into clinical antibiotics, pre-formulation studies on their biophysical and physicochemical properties that will influence their activity in vivo and their stability during manufacture must be elucidated. Thermal, pH and enzymatic stability of bacteriocins are commonly studied and regularly reported in the literature. Solubility, permeability and aggregation properties on the other hand are less frequently reported for many bacteriocins, which may contribute to their poor clinical progression. Promising cytotoxicity studies report that bacteriocins exhibit few cytotoxic effects on a variety of mammalian cell lines, at active concentrations. This review highlights the lack of quantitative data and in many cases even qualitative data, on bacteriocins' solubility, stability, aggregation, permeability and cytotoxicity. The formulation strategies that have been explored to date, proposed routes of administration, trends in in vitro/in vivo behaviour and efforts in clinical development are discussed. The future promise of bacteriocins as a new generation of antibiotics may require tailored local delivery strategies to fulfil their potential as a force to combat antimicrobial-resistant bacterial infections.
    MeSH term(s) Animals ; Anti-Bacterial Agents/administration & dosage ; Anti-Bacterial Agents/chemistry ; Anti-Bacterial Agents/pharmacokinetics ; Bacterial Infections/drug therapy ; Bacteriocins/administration & dosage ; Bacteriocins/chemistry ; Bacteriocins/pharmacokinetics ; Biological Availability ; Disease Models, Animal ; Drug Carriers/chemistry ; Drug Compounding/methods ; Drug Development/trends ; Drug Evaluation, Preclinical ; Drug Resistance, Bacterial ; Drug Stability ; Humans
    Chemical Substances Anti-Bacterial Agents ; Bacteriocins ; Drug Carriers
    Language English
    Publishing date 2021-05-18
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 1065368-5
    ISSN 1873-3441 ; 0939-6411
    ISSN (online) 1873-3441
    ISSN 0939-6411
    DOI 10.1016/j.ejpb.2021.05.015
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  8. Article ; Online: Rural health and rural industries: Opportunities for partnership and action.

    Scott, Kenneth A / Elliott, K C / Lincoln, Jennifer / Flynn, Michael A / Hill, Ryan / Hall, Diane M

    The Journal of rural health : official journal of the American Rural Health Association and the National Rural Health Care Association

    2023  Volume 40, Issue 2, Page(s) 401–405

    MeSH term(s) Humans ; Rural Health ; Rural Health Services ; Community-Based Participatory Research ; Rural Population
    Language English
    Publishing date 2023-09-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 639160-6
    ISSN 1748-0361 ; 0890-765X
    ISSN (online) 1748-0361
    ISSN 0890-765X
    DOI 10.1111/jrh.12791
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    Zs.B 3102: Show issues Location:
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  9. Article ; Online: A re-activation model for

    Flynn, Ryan T / Smith, Blake R / Adams, Quentin E / Patwardhan, Kaustubh / Graves, Stephen A / Hopfensperger, Karolyn M

    Medical physics

    2024  

    Abstract: Background: Intensity modulated brachytherapy based on partially shielded intracavitary and interstitial applicators is possible with a cost-effective : Purpose: To introduce a generalized model of radioactive source production that accounts for ... ...

    Abstract Background: Intensity modulated brachytherapy based on partially shielded intracavitary and interstitial applicators is possible with a cost-effective
    Purpose: To introduce a generalized model of radioactive source production that accounts for spatiotemporal variation in isotopic source composition to improve the efficiency estimate of the
    Methods and materials: A time-dependent thermal neutron transport, isotope transmutation, and decay model was developed. Thermal neutron flux within partitioned sub-volumes of a cylindrical active source was calculated by raytracing through the spatiotemporal dependent isotopic composition throughout the source, accounting for thermal neutron attenuation along each ray. The model was benchmarked, generalized, and applied to a variety of active source dimensions with radii ranging from 0.4 to 1.0 mm, lengths from 2.5 to 10.5 mm, and volumes from 0.31 to 7.85 mm
    Results: The average clinical
    Conclusions: Accounting for spatiotemporal isotopic composition effects within the RRS results in a 28% reduction in the reactor time per clinic-year relative to the case in which such changes are not accounted for. Smaller volume sources had a disadvantage in that average clinical
    Language English
    Publishing date 2024-04-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 188780-4
    ISSN 2473-4209 ; 0094-2405
    ISSN (online) 2473-4209
    ISSN 0094-2405
    DOI 10.1002/mp.17048
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  10. Article ; Online: Galectin-3 does not interact with RNA directly.

    Peltan, Egan L / Riley, Nicholas M / Flynn, Ryan A / Roberts, David S / Bertozzi, Carolyn R

    Glycobiology

    2023  Volume 34, Issue 1

    Abstract: Galectin-3, well characterized as a glycan binding protein, has been identified as a putative RNA binding protein, possibly through participation in pre-mRNA maturation through interactions with splicosomes. Given recent developments with cell surface ... ...

    Abstract Galectin-3, well characterized as a glycan binding protein, has been identified as a putative RNA binding protein, possibly through participation in pre-mRNA maturation through interactions with splicosomes. Given recent developments with cell surface RNA biology, the putative dual-function nature of galectin-3 evokes a possible non-classical connection between glycobiology and RNA biology. However, with limited functional evidence of a direct RNA interaction, many molecular-level observations rely on affinity reagents and lack appropriate genetic controls. Thus, evidence of a direct interaction remains elusive. We demonstrate that antibodies raised to endogenous human galectin-3 can isolate RNA-protein crosslinks, but this activity remains insensitive to LGALS3 knock-out. Proteomic characterization of anti-galectin-3 IPs revealed enrichment of galectin-3, but high abundance of hnRNPA2B1, an abundant, well-characterized RNA-binding protein with weak homology to the N-terminal domain of galectin-3, in the isolate. Genetic ablation of HNRNPA2B1, but not LGALS3, eliminates the ability of the anti-galectin-3 antibodies to isolate RNA-protein crosslinks, implying either an indirect interaction or cross-reactivity. To address this, we introduced an epitope tag to the endogenous C-terminal locus of LGALS3. Isolation of the tagged galectin-3 failed to reveal any RNA-protein crosslinks. This result suggests that the galectin-3 does not directly interact with RNA and may be misidentified as an RNA-binding protein, at least in HeLa where the putative RNA associations were first identified. We encourage further investigation of this phenomenon employ gene deletions and, when possible, endogenous epitope tags to achieve the specificity required to evaluate potential interactions.
    MeSH term(s) Humans ; Epitopes ; Galectin 3/genetics ; Galectin 3/metabolism ; Galectins/metabolism ; Proteomics ; RNA ; RNA-Binding Proteins
    Chemical Substances Epitopes ; Galectin 3 ; Galectins ; RNA (63231-63-0) ; RNA-Binding Proteins ; LGALS3 protein, human
    Language English
    Publishing date 2023-10-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 1067689-2
    ISSN 1460-2423 ; 0959-6658
    ISSN (online) 1460-2423
    ISSN 0959-6658
    DOI 10.1093/glycob/cwad076
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