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Book: Rhinoviruses

Jans, David A.

methods and protocols

(Methods in molecular biology ; 1221 ; Springer protocols)

2015

Author's details	ed. by David A. Jans
Series title	Methods in molecular biology ; 1221 Springer protocols
Collection
Language	English
Size	XII, 190 S. : Ill., graph. Darst.
Publisher	Humana Press
Publishing place	New York u.a.
Publishing country	United States
Document type	Book
HBZ-ID	HT018450205
ISBN	978-1-4939-1570-5 ; 9781493915712 ; 1-4939-1570-3 ; 1493915711
Database	Catalogue ZB MED Medicine, Health

In stock of ZB MED Cologne/Königswinter

Shelf mark	Loan status	Location
Zs A 7042 -1221-	verfügbar in Königswinter	Königswinter

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Article ; Online: The Nuclear Transporter Importin 13 Can Regulate Stress-Induced Cell Death through the Clusterin/KU70 Axis.

Gajewska, Katarzyna A / Jans, David A / Wagstaff, Kylie M

Cells

2023 Volume 12, Issue 2

Abstract: The cellular response to environmental stresses, such as heat and oxidative stress, is dependent on extensive trafficking of stress-signalling molecules between the cytoplasm and nucleus, which potentiates stress-activated signalling pathways, eventually ...

Abstract	The cellular response to environmental stresses, such as heat and oxidative stress, is dependent on extensive trafficking of stress-signalling molecules between the cytoplasm and nucleus, which potentiates stress-activated signalling pathways, eventually resulting in cell repair or death. Although Ran-dependent nucleocytoplasmic transport mediated by members of the importin (IPO) super family of nuclear transporters is believed to be responsible for nearly all macromolecular transit between nucleus and cytoplasm, it is paradoxically known to be significantly impaired under conditions of stress. Importin 13 (IPO13) is a unique bidirectional transporter that binds to and releases cargo in a Ran-dependent manner, but in some cases, cargo release from IPO13 is affected by loading of another cargo. To investigate IPO13's role in stress-activated pathways, we performed cell-based screens to identify a multitude of binding partners of IPO13 from human brain, lung, and testes. Analysis of the IPO13 interactome intriguingly indicated more than half of the candidate binding partners to be annotated for roles in stress responses; these included the pro-apoptotic protein nuclear clusterin (nCLU), as well as the nCLU-interacting DNA repair protein KU70. Here, we show, for the first time, that unlike other IPOs which are mislocalised and non-functional, IPO13 continues to translocate between the nucleus and cytoplasm under stress, retaining the capacity to import certain cargoes, such as nCLU, but not export others, such as KU70, as shown by analysis using fluorescence recovery after photobleaching. Importantly, depletion of IPO13 reduces stress-induced import of nCLU and protects against stress-induced cell death, with concomitant protection from DNA damage during stress. Overexpression/FACS experiments demonstrate that nCLU is dependent on IPO13 to trigger stress-induced cell death via apoptosis. Taken together, these results implicate IPO13 as a novel functional nuclear transporter in cellular stress, with a key role thereby in cell fate decision.
MeSH term(s)	Humans ; Clusterin/metabolism ; Cell Nucleus/metabolism ; Cell Death ; Karyopherins/metabolism ; Active Transport, Cell Nucleus
Chemical Substances	Clusterin ; Karyopherins
Language	English
Publishing date	2023-01-11
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12020279
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Respiratory Syncytial Virus Matrix Protein Is Sufficient and Necessary to Remodel Host Mitochondria in Infection.

Hu, MengJie / Bogoyevitch, Marie A / Jans, David A

Cells

2023 Volume 12, Issue 9

Abstract: Although respiratory syncytial virus (RSV) is the most common cause of respiratory infection in infants, immunosuppressed adults and the elderly worldwide, there is no licensed RSV vaccine or widely applicable antiviral therapeutics We previously ... ...

Abstract	Although respiratory syncytial virus (RSV) is the most common cause of respiratory infection in infants, immunosuppressed adults and the elderly worldwide, there is no licensed RSV vaccine or widely applicable antiviral therapeutics We previously reported a staged redistribution of mitochondria with compromised respiratory activities and increased reactive oxygen species (ROS) generation during RSV infection. Here, we show for the first time that the RSV matrix protein (M) is sufficient and necessary to induce these effects. Ectopically expressed M, but not other RSV proteins, was able to induce mitochondrial perinuclear clustering, inhibition of mitochondrial respiration, loss of mitochondrial membrane potential (Δψ
MeSH term(s)	Humans ; Aged ; Reactive Oxygen Species/metabolism ; Lysine ; Respiratory Syncytial Virus, Human ; Respiratory Syncytial Virus Infections ; Mitochondria/metabolism ; Arginine
Chemical Substances	Reactive Oxygen Species ; Lysine (K3Z4F929H6) ; Arginine (94ZLA3W45F)
Language	English
Publishing date	2023-05-04
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12091311
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Nuclear Transporter

Gajewska, Katarzyna A / Haynes, John M / Jans, David A

Cells

2022 Volume 11, Issue 12

Abstract: Molecular transport between the nucleus and cytoplasm of the cell is mediated by the importin superfamily of transport receptors, of which the bidirectional transporter Importin 13 (IPO13) is a unique member, with a critical role in early embryonic ... ...

Abstract	Molecular transport between the nucleus and cytoplasm of the cell is mediated by the importin superfamily of transport receptors, of which the bidirectional transporter Importin 13 (IPO13) is a unique member, with a critical role in early embryonic development through nuclear transport of key regulators, such as transcription factors Pax6, Pax3, and ARX. Here, we examined the role of IPO13 in neuronal differentiation for the first time, using a mouse embryonic stem cell (ESC) model and a monolayer-based differentiation protocol to compare IPO13
MeSH term(s)	Active Transport, Cell Nucleus ; Animals ; Cell Differentiation ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; Karyopherins/metabolism ; Mice ; Neural Stem Cells/metabolism
Chemical Substances	Karyopherins ; importin 13 protein, mouse
Language	English
Publishing date	2022-06-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11121904
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Bimolecular Fluorescence Complementation: Quantitative Analysis of In Cell Interaction of Nuclear Transporter Importin α with Cargo Proteins.

Lee, Alexander / Bogoyevitch, Marie A / Jans, David A

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

2022 Volume 2502, Page(s) 215–233

Abstract: Bimolecular fluorescence complementation utilizes the ability of two complementary nonfluorescent fragments to reconstitute and emit fluorescence when brought together through specific interaction of attached protein fragments of interest. It has been ... ...

Abstract	Bimolecular fluorescence complementation utilizes the ability of two complementary nonfluorescent fragments to reconstitute and emit fluorescence when brought together through specific interaction of attached protein fragments of interest. It has been used in several different contexts to study protein-protein interaction. Here we apply the method for the first time to study interaction of the nuclear transporter importin α and its cargoes in a cellular context. By using image analysis to quantify the extent of nuclear complexation, it is possible to gain insight into the strength of interaction in cells.
MeSH term(s)	Cell Communication/physiology ; Cell Nucleus/metabolism ; Protein Binding ; Proteins/metabolism ; Spectrometry, Fluorescence/methods ; alpha Karyopherins/metabolism
Chemical Substances	Proteins ; alpha Karyopherins
Language	English
Publishing date	2022-04-12
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-2337-4_14
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Ivermectin as a Broad-Spectrum Host-Directed Antiviral: The Real Deal?

Jans, David A / Wagstaff, Kylie M

Cells

2020 Volume 9, Issue 9

Abstract: The small molecule macrocyclic lactone ivermectin, approved by the US Food and Drug Administration for parasitic infections, has received renewed attention in the last eight years due to its apparent exciting potential as an antiviral. It was identified ... ...

Abstract	The small molecule macrocyclic lactone ivermectin, approved by the US Food and Drug Administration for parasitic infections, has received renewed attention in the last eight years due to its apparent exciting potential as an antiviral. It was identified in a high-throughput chemical screen as inhibiting recognition of the nuclear localizing Human Immunodeficiency Virus-1 (HIV-1) integrase protein by the host heterodimeric importin (IMP) α/β1 complex, and has since been shown to bind directly to IMPα to induce conformational changes that prevent its normal function in mediating nuclear import of key viral and host proteins. Excitingly, cell culture experiments show robust antiviral action towards HIV-1, dengue virus (DENV), Zika virus, West Nile virus, Venezuelan equine encephalitis virus, Chikungunya virus, Pseudorabies virus, adenovirus, and SARS-CoV-2 (COVID-19). Phase III human clinical trials have been completed for DENV, with >50 trials currently in progress worldwide for SARS-CoV-2. This mini-review discusses the case for ivermectin as a host-directed broad-spectrum antiviral agent for a range of viruses, including SARS-CoV-2.
MeSH term(s)	Animals ; Antiviral Agents/pharmacology ; Betacoronavirus/drug effects ; COVID-19 ; Cell Line ; Chlorocebus aethiops ; Coronavirus Infections/drug therapy ; Dengue/drug therapy ; Dengue Virus/drug effects ; HIV Infections/drug therapy ; HIV Integrase/drug effects ; HIV Integrase Inhibitors/pharmacology ; HIV-1/drug effects ; Humans ; Ivermectin/pharmacology ; Pandemics ; Pneumonia, Viral/drug therapy ; SARS-CoV-2 ; Vero Cells ; Zika Virus/drug effects ; Zika Virus Infection/drug therapy
Chemical Substances	Antiviral Agents ; HIV Integrase Inhibitors ; Ivermectin (70288-86-7) ; HIV Integrase (EC 2.7.7.-)
Keywords	covid19
Language	English
Publishing date	2020-09-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells9092100
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Antivirals that target the host IMPα/β1-virus interface.

Martin, Alexander J / Jans, David A

Biochemical Society transactions

2020 Volume 49, Issue 1, Page(s) 281–295

Abstract: Although transport into the nucleus mediated by the importin (IMP) α/β1-heterodimer is central to viral infection, small molecule inhibitors of IMPα/β1-dependent nuclear import have only been described and shown to have antiviral activity in the last ... ...

Abstract	Although transport into the nucleus mediated by the importin (IMP) α/β1-heterodimer is central to viral infection, small molecule inhibitors of IMPα/β1-dependent nuclear import have only been described and shown to have antiviral activity in the last decade. Their robust antiviral activity is due to the strong reliance of many different viruses, including RNA viruses such as human immunodeficiency virus-1 (HIV-1), dengue (DENV), and Zika (ZIKV), on the IMPα/β1-virus interface. High-throughput compound screens have identified many agents that specifically target this interface. Of these, agents targeting IMPα/β1 directly include the FDA-approved macrocyclic lactone ivermectin, which has documented broad-spectrum activity against a whole range of viruses, including HIV-1, DENV1-4, ZIKV, West Nile virus (WNV), Venezuelan equine encephalitis virus, chikungunya, and most recently, SARS-CoV-2 (COVID-19). Ivermectin has thus far been tested in Phase III human clinical trials for DENV, while there are currently close to 80 trials in progress worldwide for SARS-CoV-2; preliminary results for randomised clinical trials (RCTs) as well as observational/retrospective studies are consistent with ivermectin affording clinical benefit. Agents that target the viral component of the IMPα/β1-virus interface include N-(4-hydroxyphenyl) retinamide (4-HPR), which specifically targets DENV/ZIKV/WNV non-structural protein 5 (NS5). 4-HPR has been shown to be a potent inhibitor of infection by DENV1-4, including in an antibody-dependent enhanced animal challenge model, as well as ZIKV, with Phase II clinical challenge trials planned. The results from rigorous RCTs will help determine the therapeutic potential of the IMPα/β1-virus interface as a target for antiviral development.
MeSH term(s)	Animals ; Antiviral Agents/pharmacology ; Humans ; Ivermectin/pharmacology ; Protein Binding/drug effects ; Viral Nonstructural Proteins/metabolism ; Virus Diseases/metabolism ; Virus Diseases/prevention & control ; Virus Diseases/virology ; Viruses/metabolism ; Viruses/pathogenicity ; alpha Karyopherins/metabolism ; beta Karyopherins/metabolism
Chemical Substances	Antiviral Agents ; TNPO1 protein, human ; Viral Nonstructural Proteins ; alpha Karyopherins ; beta Karyopherins ; karyopherin alpha 2 ; Ivermectin (70288-86-7)
Language	English
Publishing date	2020-12-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	184237-7
ISSN	1470-8752 ; 0300-5127
ISSN (online)	1470-8752
ISSN	0300-5127
DOI	10.1042/BST20200568
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 944: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: The broad spectrum host-directed agent ivermectin as an antiviral for SARS-CoV-2 ?

Jans, David A / Wagstaff, Kylie M

Biochemical and biophysical research communications

2020 Volume 538, Page(s) 163–172

Abstract: FDA approved for parasitic indications, the small molecule ivermectin has been the focus of growing attention in the last 8 years due to its potential as an antiviral. We first identified ivermectin in a high throughput compound library screen as an ... ...

Abstract	FDA approved for parasitic indications, the small molecule ivermectin has been the focus of growing attention in the last 8 years due to its potential as an antiviral. We first identified ivermectin in a high throughput compound library screen as an agent potently able to inhibit recognition of the nuclear localizing Human Immunodeficiency Virus-1 (HIV-1) integrase protein by the host importin (IMP) α/β1 heterodimer, and recently demonstrated its ability to bind directly to IMPα to cause conformational changes that prevent its function in nuclear import of key viral as well as host proteins. Cell culture experiments have shown robust antiviral action towards a whole range of viruses, including HIV-1, dengue, Zika and West Nile Virus, Venezuelan equine encephalitis virus, Chikungunya, pseudorabies virus, adenovirus, and SARS-CoV-2 (COVID-19). Close to 70 clinical trials are currently in progress worldwide for SARS-CoV-2. Although few of these studies have been completed, the results that are available, as well as those from observational/retrospective studies, indicate clinical benefit. Here we discuss the case for ivermectin as a host-directed broad-spectrum antiviral agent, including for SARS-CoV-2.
MeSH term(s)	Antiparasitic Agents/pharmacology ; Antiparasitic Agents/therapeutic use ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; COVID-19/drug therapy ; Humans ; Ivermectin/pharmacology ; Ivermectin/therapeutic use ; SARS-CoV-2/drug effects ; alpha Karyopherins/antagonists & inhibitors
Chemical Substances	Antiparasitic Agents ; Antiviral Agents ; alpha Karyopherins ; Ivermectin (70288-86-7)
Language	English
Publishing date	2020-10-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2020.10.042
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 116: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Book: The mobile receptor hypothesis

Jans, David A.

the role of membrane receptor lateral movement in signal transduction

(Molecular biology intelligence unit)

1997

Author's details	David A. Jans
Series title	Molecular biology intelligence unit
Keywords	Cell Membrane / metabolism ; Membrane Proteins / metabolism ; Signal Transduction / physiology ; Signaltransduktion ; Membranrezeptor ; Motilität
Subject	Bewegungsfähigkeit ; Beweglichkeit ; Motility ; Signalübertragung ; Signalvermittlung
Language	English
Size	224 S. : Ill., graph. Darst.
Publisher	Springer u.a.
Publishing place	New York u.a.
Publishing country	United States
Document type	Book
Note	Literaturangaben
HBZ-ID	HT008081834
ISBN	3-540-62732-4 ; 978-3-540-62732-6
Database	Catalogue ZB MED Medicine, Health

In stock of ZB MED Cologne/Königswinter

Shelf mark	Loan status	Location
1998 A 896	order for loan	Magazin

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Article ; Online: Transcriptomic profile dataset of embryonic stem cells (Wild-type and IPO13-Knock Out) with and without oxidative stress.

Gajewska, Katarzyna A / Ramialison, Mirana / Wagstaff, Kylie M / Jans, David A

Data in brief

2022 Volume 42, Page(s) 108099

Abstract: The transcriptional response to cellular stress relies upon trafficking of regulators of transcription between the nuclear and cytoplasmic compartments, which occurs through action of members of the importin (IPO) superfamily. As a result of stresses ... ...

Abstract	The transcriptional response to cellular stress relies upon trafficking of regulators of transcription between the nuclear and cytoplasmic compartments, which occurs through action of members of the importin (IPO) superfamily. As a result of stresses such as oxidative or osmotic stress, one consequence is that importins become mislocalised, leading to inhibition of conventional nuclear transport. Here, we examine IPO13, which has a number of nonconventional characteristics, in the context of cell stress. We used Next Generation RNA Sequencing using the Illumina platform to compare the transcriptomes of Wild-type (WT) and IPO13-Knockout (KO) mouse embryonic stem cells in the absence and presence of oxidative stress. Differences in the mRNA expression profiles were observed between the cell lines in the absence and in the presence of stress. This data will be a key resource to enable characterization of the contribution of nuclear transporter IPO13 to cellular transcription in the absence and presence of oxidative stress, as well as more broadly, in the study of stem cell biology and effect of stress on embryonic stem cell transcription.
Language	English
Publishing date	2022-03-28
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2786545-9
ISSN	2352-3409 ; 2352-3409
ISSN (online)	2352-3409
ISSN	2352-3409
DOI	10.1016/j.dib.2022.108099
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