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Article ; Online: Giants in Chest Medicine: Peter J. Barnes, MA, DM, DSc, Master FCCP.

Irwin, Richard S

2014 Volume 145, Issue 1, Page(s) 24–26

MeSH term(s)	History, 20th Century ; History, 21st Century ; Pulmonary Medicine/history
Language	English
Publishing date	2014-01
Publishing country	United States
Document type	Biography ; Historical Article ; Journal Article ; Portraits ; Video-Audio Media
ZDB-ID	1032552-9
ISSN	1931-3543 ; 0012-3692
ISSN (online)	1931-3543
ISSN	0012-3692
DOI	10.1378/chest.13-2215
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Book ; Online: On Liberal Education and the Autopoiesis of Universities

Jirsa, Jakub / Balazs, Peter / Carvalho, Cláudio Alexandre S / Görlach, Alexander / Irwin, Jones / Lewis-Martin, Jimmy / Lomová, Olga / McKinnon-Crowley, Saralyn / Noble, Ivana / Polišenská, Milada / Přibáň, Jiří / Riemen, Rob / Šubrt, Jiří

2023

Keywords	Humanities ; higher education ; universities ; quantification of education ; education ; autopoiesis ; university system ; capitalism ; neoliberalism
Language	English
Size	1 electronic resource (208 pages)
Publisher	Karolinum Press
Publishing place	Prague
Document type	Book ; Online
Note	English
HBZ-ID	HT030377267
ISBN	9788024654867 ; 8024654865
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: An invasive human commensal and a native marsupial maintain tick populations at the urban fringe.

Taylor, Casey L / Egan, Siobhon L / Gofton, Alexander W / Irwin, Peter J / Oskam, Charlotte L / Hochuli, Dieter F / Banks, Peter B

Medical and veterinary entomology

2023 Volume 37, Issue 3, Page(s) 460–471

Abstract: Ticks (Acari: Ixodidae) are major disease vectors globally making it increasingly important to understand how altered vertebrate communities in urban areas shape tick population dynamics. In urban landscapes of Australia, little is known about which ... ...

Abstract	Ticks (Acari: Ixodidae) are major disease vectors globally making it increasingly important to understand how altered vertebrate communities in urban areas shape tick population dynamics. In urban landscapes of Australia, little is known about which native and introduced small mammals maintain tick populations preventing host-targeted tick management and leading to human-wildlife conflict. Here, we determined (1) larval, nymphal, and adult tick burdens on host species and potential drivers, (2) the number of ticks supported by the different host populations, and (3) the proportion of medically significant tick species feeding on the different host species in Northern Sydney. We counted 3551 ticks on 241 mammals at 15 sites and found that long-nosed bandicoots (Perameles nasuta) hosted more ticks of all life stages than other small mammals but introduced black rats (Rattus rattus) were more abundant at most sites (33%-100%) and therefore important in supporting larval and nymphal ticks in our study areas. Black rats and bandicoots hosted a greater proportion of medically significant tick species including Ixodes holocyclus than other hosts. Our results show that an introduced human commensal contributes to maintaining urban tick populations and suggests ticks could be managed by controlling rat populations on urban fringes.
MeSH term(s)	Humans ; Animals ; Rats ; Marsupialia ; Ixodes ; Ixodidae ; Larva ; Disease Vectors ; Nymph ; Tick Infestations/veterinary ; Tick Infestations/epidemiology
Language	English
Publishing date	2023-01-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	286021-1
ISSN	1365-2915 ; 0269-283X
ISSN (online)	1365-2915
ISSN	0269-283X
DOI	10.1111/mve.12643
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Article ; Online: It shouldn't happen to a dog … or a veterinarian: clinical paradigms for canine vector-borne diseases.

Irwin, Peter J

Trends in parasitology

2014 Volume 30, Issue 2, Page(s) 104–112

Abstract: Canine vector-borne diseases (CVBDs) comprise a diverse group of viral, bacterial, protozoal, and helminth pathogens, transmitted predominantly by ticks and fleas, and cause significant health problems for dogs worldwide. Growing numbers of reports ... ...

Abstract	Canine vector-borne diseases (CVBDs) comprise a diverse group of viral, bacterial, protozoal, and helminth pathogens, transmitted predominantly by ticks and fleas, and cause significant health problems for dogs worldwide. Growing numbers of reports indicate that CVBDs are emerging in regions where they previously did not exist and this, combined with pathogens that are inherently difficult to detect, is providing companion animal veterinarians with some significant diagnostic challenges. This review discusses six paradigms concerning the diagnosis, treatment, prevention, and zoonotic implications of CVBDs from a veterinary clinical perspective.
MeSH term(s)	Animals ; Communicable Diseases, Emerging/diagnosis ; Communicable Diseases, Emerging/prevention & control ; Communicable Diseases, Emerging/veterinary ; Dog Diseases/diagnosis ; Dog Diseases/microbiology ; Dog Diseases/parasitology ; Dog Diseases/prevention & control ; Dog Diseases/virology ; Dogs ; Ectoparasitic Infestations/microbiology ; Ectoparasitic Infestations/parasitology ; Ectoparasitic Infestations/veterinary ; Ectoparasitic Infestations/virology ; Siphonaptera/microbiology ; Siphonaptera/parasitology ; Siphonaptera/virology ; Ticks/microbiology ; Ticks/parasitology ; Ticks/virology ; Zoonoses/prevention & control
Language	English
Publishing date	2014-02
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2036227-4
ISSN	1471-5007 ; 1471-4922
ISSN (online)	1471-5007
ISSN	1471-4922
DOI	10.1016/j.pt.2013.12.001
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Article: Structure-based discovery of CFTR potentiators and inhibitors.

Liu, Fangyu / Kaplan, Anat Levit / Levring, Jesper / Einsiedel, Jürgen / Tiedt, Stephanie / Distler, Katharina / Omattage, Natalie S / Kondratov, Ivan S / Moroz, Yurii S / Pietz, Harlan L / Irwin, John J / Gmeiner, Peter / Shoichet, Brian K / Chen, Jue

bioRxiv : the preprint server for biology

2024

Abstract: The cystic fibrosis transmembrane conductance regulator (CFTR) is a crucial ion channel whose loss of function leads to cystic fibrosis, while its hyperactivation leads to secretory diarrhea. Small molecules that improve CFTR folding (correctors) or ... ...

Abstract	The cystic fibrosis transmembrane conductance regulator (CFTR) is a crucial ion channel whose loss of function leads to cystic fibrosis, while its hyperactivation leads to secretory diarrhea. Small molecules that improve CFTR folding (correctors) or function (potentiators) are clinically available. However, the only potentiator, ivacaftor, has suboptimal pharmacokinetics and inhibitors have yet to be clinically developed. Here we combine molecular docking, electrophysiology, cryo-EM, and medicinal chemistry to identify novel CFTR modulators. We docked ~155 million molecules into the potentiator site on CFTR, synthesized 53 test ligands, and used structure-based optimization to identify candidate modulators. This approach uncovered novel mid-nanomolar potentiators as well as inhibitors that bind to the same allosteric site. These molecules represent potential leads for the development of more effective drugs for cystic fibrosis and secretory diarrhea, demonstrating the feasibility of large-scale docking for ion channel drug discovery.
Language	English
Publishing date	2024-03-11
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.09.09.557002
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Article ; Online: Electrical Impedance Tomography as a monitoring tool during weaning from mechanical ventilation: an observational study during the spontaneous breathing trial.

Wisse, Jantine J / Goos, Tom G / Jonkman, Annemijn H / Somhorst, Peter / Reiss, Irwin K M / Endeman, Henrik / Gommers, Diederik

Respiratory research

2024 Volume 25, Issue 1, Page(s) 179

Abstract: Background: Prolonged weaning from mechanical ventilation is associated with poor clinical outcome. Therefore, choosing the right moment for weaning and extubation is essential. Electrical Impedance Tomography (EIT) is a promising innovative lung ... ...

Abstract	Background: Prolonged weaning from mechanical ventilation is associated with poor clinical outcome. Therefore, choosing the right moment for weaning and extubation is essential. Electrical Impedance Tomography (EIT) is a promising innovative lung monitoring technique, but its role in supporting weaning decisions is yet uncertain. We aimed to evaluate physiological trends during a T-piece spontaneous breathing trail (SBT) as measured with EIT and the relation between EIT parameters and SBT success or failure. Methods: This is an observational study in which twenty-four adult patients receiving mechanical ventilation performed an SBT. EIT monitoring was performed around the SBT. Multiple EIT parameters including the end-expiratory lung impedance (EELI), delta Tidal Impedance (ΔZ), Global Inhomogeneity index (GI), Rapid Shallow Breathing Index (RSBI Results: EELI values dropped after the start of the SBT (p < 0.001) and did not recover to baseline after restarting mechanical ventilation. The ΔZ dropped (p < 0.001) but restored to baseline within seconds after restarting mechanical ventilation. Five patients failed the SBT, the GI (p = 0.01) and transcutaneous CO Conclusion: EIT has the potential to assess changes in ventilation distribution and quantify the inhomogeneity of the lungs during the SBT. High lung inhomogeneity was found during SBT failure. Insight into physiological trends for the individual patient can be obtained with EIT during weaning from mechanical ventilation, but its role in predicting weaning failure requires further study.
MeSH term(s)	Humans ; Ventilator Weaning/methods ; Electric Impedance ; Male ; Female ; Middle Aged ; Aged ; Tomography/methods ; Monitoring, Physiologic/methods ; Adult ; Respiration, Artificial/methods ; Respiration ; Aged, 80 and over ; Lung/physiopathology ; Lung/diagnostic imaging ; Lung/physiology
Language	English
Publishing date	2024-04-25
Publishing country	England
Document type	Observational Study ; Journal Article
ZDB-ID	2041675-1
ISSN	1465-993X ; 1465-993X
ISSN (online)	1465-993X
ISSN	1465-993X
DOI	10.1186/s12931-024-02801-6
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Article ; Online: Docking for Molecules That Bind in a Symmetric Stack with SymDOCK.

Smith, Matthew S / Knight, Ian S / Kormos, Rian C / Pepe, Joseph G / Kunach, Peter / Diamond, Marc I / Shahmoradian, Sarah H / Irwin, John J / DeGrado, William F / Shoichet, Brian K

Journal of chemical information and modeling

2024 Volume 64, Issue 2, Page(s) 425–434

Abstract: ... In retrospective calculations, symmetry docking can reproduce the poses of three tau PET tracers whose structures ...

Abstract	Discovering ligands for amyloid fibrils, such as those formed by the tau protein, is an area of great current interest. In recent structures, ligands bind in stacks in the tau fibrils to reflect the rotational and translational symmetry of the fibril itself; in these structures, the ligands make few interactions with the protein but interact extensively with each other. To exploit this symmetry and stacking, we developed SymDOCK, a method to dock molecules that follow the protein's symmetry. For each prospective ligand pose, we apply the symmetry operation of the fibril to generate a self-interacting and fibril-interacting stack, checking that doing so will not cause a clash between the original molecule and its image. Absent a clash, we retain that pose and add the ligand-ligand van der Waals energy to the ligand's docking score (here using DOCK3.8). We can check these geometries and energies using an implementation of ANI, a neural-network-based quantum-mechanical evaluation of the ligand stacking energies. In retrospective calculations, symmetry docking can reproduce the poses of three tau PET tracers whose structures have been determined. More convincingly, in a
MeSH term(s)	Prospective Studies ; Ligands ; Retrospective Studies ; Proteins/chemistry ; Molecular Docking Simulation ; Protein Binding ; Binding Sites
Chemical Substances	Ligands ; Proteins
Language	English
Publishing date	2024-01-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	190019-5
ISSN	1549-960X ; 0095-2338
ISSN (online)	1549-960X
ISSN	0095-2338
DOI	10.1021/acs.jcim.3c01749
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Article ; Online: Alpha-cells and therapy of diabetes: Inhibition, antagonism or death?

Klempel, Natalie / Thomas, Keith / Conlon, J Michael / Flatt, Peter R / Irwin, Nigel

Peptides

2022 Volume 157, Page(s) 170877

Abstract: Absolute or relative hyperglucagonaemia is a characteristic of both Type 1 and Type 2 diabetes, resulting in fasting hyperglycaemia due in part to increased hepatic glucose production and lack of postprandial suppression of circulating glucagon ... ...

Abstract	Absolute or relative hyperglucagonaemia is a characteristic of both Type 1 and Type 2 diabetes, resulting in fasting hyperglycaemia due in part to increased hepatic glucose production and lack of postprandial suppression of circulating glucagon concentrations. Consequently, therapeutics that target glucagon secretion or biological action may be effective antidiabetic agents. In this regard, specific glucagon receptor (GCGR) antagonists have been developed that exhibit impressive glucose-lowering actions, but unfortunately may cause off-target adverse effects in humans. Further to this, several currently approved antidiabetic agents, including GLP-1 mimetics, DPP-4 inhibitors, metformin, sulphonylureas and pramlintide likely exert part of their glucose homeostatic actions through direct or indirect inhibition of GCGR signalling. In addition to agents that inhibit the release of glucagon, compounds that enhance the transdifferentiation of glucagon secreting alpha-cells towards an insulin positive beta-cell phenotype could also help curb excess glucagon secretion in diabetes. Use of alpha-cell toxins represents another possible strategy to address hyperglucagonaemia in diabetes. In that respect, research from the 1920 s with diguanides such as synthalin A demonstrated effective glucose-lowering with alpha-cell ablation in both animal models and humans with diabetes. However, further clinical use of synthalin A was curtailed due its adverse effects and the increased availability of insulin. Overall, these observations with therapeutics that directly target alpha-cells, or GCGR signaling, highlight a largely untapped potential for diabetes therapy that merits further detailed consideration.
MeSH term(s)	Animals ; Diabetes Mellitus, Type 2/drug therapy ; Dipeptidyl-Peptidase IV Inhibitors/therapeutic use ; Glucagon/therapeutic use ; Glucagon-Like Peptide 1/therapeutic use ; Glucose ; Guanidines ; Humans ; Hypoglycemic Agents/therapeutic use ; Insulin/therapeutic use ; Metformin/therapeutic use ; Receptors, Glucagon/genetics
Chemical Substances	Dipeptidyl-Peptidase IV Inhibitors ; Guanidines ; Hypoglycemic Agents ; Insulin ; Receptors, Glucagon ; synthalin A (111-23-9) ; Glucagon-Like Peptide 1 (89750-14-1) ; Glucagon (9007-92-5) ; Metformin (9100L32L2N) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2022-09-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	769028-9
ISSN	1873-5169 ; 0196-9781
ISSN (online)	1873-5169
ISSN	0196-9781
DOI	10.1016/j.peptides.2022.170877
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Article ; Online: Rapid nanopore sequencing and predictive susceptibility testing of positive blood cultures from intensive care patients with sepsis.

Harris, Patrick N A / Bauer, Michelle J / Lüftinger, Lukas / Beisken, Stephan / Forde, Brian M / Balch, Ross / Cotta, Menino / Schlapbach, Luregn / Raman, Sainath / Shekar, Kiran / Kruger, Peter / Lipman, Jeff / Bialasiewicz, Seweryn / Coin, Lachlan / Roberts, Jason A / Paterson, David L / Irwin, Adam D

Microbiology spectrum

2024 Volume 12, Issue 2, Page(s) e0306523

Abstract: We aimed to evaluate the performance of Oxford Nanopore Technologies (ONT) sequencing from positive blood culture (BC) broths for bacterial identification and antimicrobial susceptibility prediction. Patients with suspected sepsis in four intensive care ... ...

Abstract	We aimed to evaluate the performance of Oxford Nanopore Technologies (ONT) sequencing from positive blood culture (BC) broths for bacterial identification and antimicrobial susceptibility prediction. Patients with suspected sepsis in four intensive care units were prospectively enrolled. Human-depleted DNA was extracted from positive BC broths and sequenced using ONT (MinION). Species abundance was estimated using Kraken2, and a cloud-based system (AREScloud) provided
MeSH term(s)	Humans ; Blood Culture/methods ; Nanopore Sequencing ; Microbial Sensitivity Tests ; Sepsis/microbiology ; Anti-Bacterial Agents ; Critical Care
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2024-01-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.03065-23
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Article ; Online: Evolutionary dynamics and adaptive benefits of deleterious mutations in crop gene pools

Dwivedi, Sangam L. / Heslop-Harrison, J. / Spillane, Charlie / McKeown, Peter C. / Edwards, David / Goldman, Irwin / Ortiz, Rodomiro

Trends in Plant Science. 2023 Feb. 08,

2023

Abstract: Mutations with deleterious consequences in nature may be conditionally deleterious in crop plants. That is, while some genetic variants may reduce fitness under wild conditions and be subject to purifying selection, they can be under positive selection ... ...

Abstract	Mutations with deleterious consequences in nature may be conditionally deleterious in crop plants. That is, while some genetic variants may reduce fitness under wild conditions and be subject to purifying selection, they can be under positive selection in domesticates. Such deleterious alleles can be plant breeding targets, particularly for complex traits. The difficulty of distinguishing favorable from unfavorable variants reduces the power of selection, while favorable trait variation and heterosis may be attributable to deleterious alleles. Here, we review the roles of deleterious mutations in crop breeding and discuss how they can be used as a new avenue for crop improvement with emerging genomic tools, including HapMaps and pangenome analysis, aiding the identification, removal, or exploitation of deleterious mutations.
Keywords	genes ; genomics ; heterosis ; crop improvement ; deleterious variants ; genome editing ; genomic prediction ; HapMaps ; mating system ; propagation ; selective sweeps ; wild relatives
Language	English
Dates of publication	2023-0208
Publishing place	Elsevier Ltd
Document type	Article ; Online
Note	Pre-press version ; Use and reproduction
ZDB-ID	1305448-x
ISSN	1878-4372 ; 1360-1385
ISSN (online)	1878-4372
ISSN	1360-1385
DOI	10.1016/j.tplants.2023.01.006
Database	NAL-Catalogue (AGRICOLA)

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