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  1. Article ; Online: Cyclic di-AMP traps proton-coupled K

    Fuss, Michael F / Wieferig, Jan-Philip / Corey, Robin A / Hellmich, Yvonne / Tascón, Igor / Sousa, Joana S / Stansfeld, Phillip J / Vonck, Janet / Hänelt, Inga

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 3683

    Abstract: ... potassium and osmolyte transporters involved in osmoregulation. In Bacillus subtilis, the K ...

    Abstract Cyclic di-AMP is the only known essential second messenger in bacteria and archaea, regulating different proteins indispensable for numerous physiological processes. In particular, it controls various potassium and osmolyte transporters involved in osmoregulation. In Bacillus subtilis, the K
    MeSH term(s) Cyclic AMP ; Protons ; Bacterial Proteins/metabolism ; Second Messenger Systems/physiology ; Membrane Transport Proteins/metabolism ; Potassium/metabolism ; Dinucleoside Phosphates/metabolism
    Chemical Substances Cyclic AMP (E0399OZS9N) ; Protons ; Bacterial Proteins ; Membrane Transport Proteins ; Potassium (RWP5GA015D) ; Dinucleoside Phosphates
    Language English
    Publishing date 2023-06-21
    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/s41467-023-38944-1
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  2. Article ; Online: Cyclic di-AMP traps proton-coupled K+ transporters of the KUP family in an inward-occluded conformation

    Michael F. Fuss / Jan-Philip Wieferig / Robin A. Corey / Yvonne Hellmich / Igor Tascón / Joana S. Sousa / Phillip J. Stansfeld / Janet Vonck / Inga Hänelt

    Nature Communications, Vol 14, Iss 1, Pp 1-

    2023  Volume 12

    Abstract: ... various potassium and osmolyte transporters involved in osmoregulation. In Bacillus subtilis, the K+/H+ ... at low external pH by mediating potassium ion uptake. However, at elevated intracellular K+ ... concentrations, further K+ accumulation would be toxic. In this study, we reveal the molecular basis of how c-di ...

    Abstract Abstract Cyclic di-AMP is the only known essential second messenger in bacteria and archaea, regulating different proteins indispensable for numerous physiological processes. In particular, it controls various potassium and osmolyte transporters involved in osmoregulation. In Bacillus subtilis, the K+/H+ symporter KimA of the KUP family is inactivated by c-di-AMP. KimA sustains survival at potassium limitation at low external pH by mediating potassium ion uptake. However, at elevated intracellular K+ concentrations, further K+ accumulation would be toxic. In this study, we reveal the molecular basis of how c-di-AMP binding inhibits KimA. We report cryo-EM structures of KimA with bound c-di-AMP in detergent solution and reconstituted in amphipols. By combining structural data with functional assays and molecular dynamics simulations we reveal how c-di-AMP modulates transport. We show that an intracellular loop in the transmembrane domain interacts with c-di-AMP bound to the adjacent cytosolic domain. This reduces the mobility of transmembrane helices at the cytosolic side of the K+ binding site and therefore traps KimA in an inward-occluded conformation.
    Keywords Science ; Q
    Subject code 500
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Helical jackknives control the gates of the double-pore K

    Diskowski, Marina / Mehdipour, Ahmad Reza / Wunnicke, Dorith / Mills, Deryck J / Mikusevic, Vedrana / Bärland, Natalie / Hoffmann, Jan / Morgner, Nina / Steinhoff, Heinz-Jürgen / Hummer, Gerhard / Vonck, Janet / Hänelt, Inga

    eLife

    2017  Volume 6

    Abstract: ... In some eukaryotic and most bacterial ligand-gated K ...

    Abstract Ion channel gating is essential for cellular homeostasis and is tightly controlled. In some eukaryotic and most bacterial ligand-gated K
    Language English
    Publishing date 2017-05-16
    Publishing country England
    Document type Journal Article
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.24303
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  4. Article ; Online: Helical jackknives control the gates of the double-pore K+ uptake system KtrAB

    Marina Diskowski / Ahmad Reza Mehdipour / Dorith Wunnicke / Deryck J Mills / Vedrana Mikusevic / Natalie Bärland / Jan Hoffmann / Nina Morgner / Heinz-Jürgen Steinhoff / Gerhard Hummer / Janet Vonck / Inga Hänelt

    eLife, Vol

    2017  Volume 6

    Abstract: ... In some eukaryotic and most bacterial ligand-gated K+ channels, RCK domains regulate ion fluxes. Until now, a single ... Exchange of activating ATP to inactivating ADP triggers short helical segments in the K+-translocating KtrB ...

    Abstract Ion channel gating is essential for cellular homeostasis and is tightly controlled. In some eukaryotic and most bacterial ligand-gated K+ channels, RCK domains regulate ion fluxes. Until now, a single regulatory mechanism has been proposed for all RCK-regulated channels, involving signal transduction from the RCK domain to the gating area. Here, we present an inactive ADP-bound structure of KtrAB from Vibrio alginolyticus, determined by cryo-electron microscopy, which, combined with EPR spectroscopy and molecular dynamics simulations, uncovers a novel regulatory mechanism for ligand-induced action at a distance. Exchange of activating ATP to inactivating ADP triggers short helical segments in the K+-translocating KtrB dimer to organize into two long helices that penetrate deeply into the regulatory RCK domains, thus connecting nucleotide-binding sites and ion gates. As KtrAB and its homolog TrkAH have been implicated as bacterial pathogenicity factors, the discovery of this functionally relevant inactive conformation may advance structure-guided drug development.
    Keywords ligand-gated ion channel ; potassium transport ; cryo-electron microscopy ; pulsed EPR ; MD simulations ; membrane transport ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Subject code 500
    Language English
    Publishing date 2017-05-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
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  5. Article ; Online: The gut-microbiota-brain axis: An introduction to a special issue on its role in neurological disorders.

    De Looze, Katrien / Tanasescu, Radu / Vonck, Kristl

    European journal of neurology

    2023  Volume 30, Issue 11, Page(s) 3411–3416

    MeSH term(s) Humans ; Nervous System Diseases ; Microbiota ; Brain
    Language English
    Publishing date 2023-10-10
    Publishing country England
    Document type Editorial
    ZDB-ID 1280785-0
    ISSN 1468-1331 ; 1351-5101 ; 1471-0552
    ISSN (online) 1468-1331
    ISSN 1351-5101 ; 1471-0552
    DOI 10.1111/ene.16080
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  6. Article ; Online: Neurostimulation for childhood epilepsy.

    Mertens, Ann / Boon, Paul / Vonck, Kristl

    Developmental medicine and child neurology

    2023  Volume 66, Issue 4, Page(s) 440–444

    Abstract: The experience with neurostimulation for childhood epilepsy is far less extensive than for adults. Nevertheless, the implementation of these techniques could be of great value, especially considering the detrimental effects of ongoing seizures on the ... ...

    Abstract The experience with neurostimulation for childhood epilepsy is far less extensive than for adults. Nevertheless, the implementation of these techniques could be of great value, especially considering the detrimental effects of ongoing seizures on the developing brain. In this review, we discuss the available evidence for neurostimulation for childhood epilepsy. Vagus nerve stimulation (VNS) is the most studied neurostimulation modality in children. Based on mostly retrospective, open-label studies, we can conclude that VNS has a similar safety and efficacy profile in children compared to adults. Although there is little available evidence for deep brain stimulation (DBS) and responsive neurostimulation (RNS) in children, both DBS and RNS show promise in reducing seizure frequency with few complications. The implementation of non-invasive techniques with a more appealing safety profile has gained interest. Small randomized control trials and open-label studies have investigated transcranial direct current simulation for childhood epilepsy, demonstrating promising but inconsistent findings.
    MeSH term(s) Child ; Humans ; Deep Brain Stimulation/adverse effects ; Epilepsy/therapy ; Retrospective Studies ; Seizures ; Vagus Nerve Stimulation/adverse effects ; Vagus Nerve Stimulation/methods ; Randomized Controlled Trials as Topic
    Language English
    Publishing date 2023-07-14
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 80369-8
    ISSN 1469-8749 ; 0012-1622
    ISSN (online) 1469-8749
    ISSN 0012-1622
    DOI 10.1111/dmcn.15692
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  7. Article ; Online: Response to "Negative Results Call for More Delicate Experimental Design in Cortical Excitability Change of taVNS Intervention".

    Mertens, Ann / Vonck, Kristl

    Neuromodulation : journal of the International Neuromodulation Society

    2021  Volume 24, Issue 8, Page(s) 1499–1500

    MeSH term(s) Cortical Excitability ; Humans ; Male ; Negative Results ; Research Design ; Transcutaneous Electric Nerve Stimulation/methods ; Vagus Nerve/physiology ; Vagus Nerve Stimulation/methods
    Language English
    Publishing date 2021-12-13
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 1500372-3
    ISSN 1525-1403 ; 1094-7159
    ISSN (online) 1525-1403
    ISSN 1094-7159
    DOI 10.1111/ner.13545
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  8. Article ; Online: Lessons from the past to understand the future.

    Leys, Didier / Sommer, Claudia / Borroni, Barbara / Chan, Andrew / Edwards, Mark / Tessitore, Alessandro / Vonck, Kristl

    European journal of neurology

    2024  , Page(s) e16270

    Language English
    Publishing date 2024-03-05
    Publishing country England
    Document type Editorial
    ZDB-ID 1280785-0
    ISSN 1468-1331 ; 1351-5101 ; 1471-0552
    ISSN (online) 1468-1331
    ISSN 1351-5101 ; 1471-0552
    DOI 10.1111/ene.16270
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    Zs.A 4738: Show issues Location:
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  9. Article ; Online: MS@Work in Flanders: The Development of a MS Toolkit for a Stable Employment.

    Vonck, Sharona / Theuwissen, Goele / Bosmans, Roel / Daniels, Kim / Spooren, Annemie

    Studies in health technology and informatics

    2023  Volume 306, Page(s) 160–167

    Abstract: Persons with MS have the highest unemployment rates compared to other chronic diseases. We want to develop a MS Toolkit with several aids for persons with MS to help them gain a sustainable employment with sufficient and permanent attention and guidance ... ...

    Abstract Persons with MS have the highest unemployment rates compared to other chronic diseases. We want to develop a MS Toolkit with several aids for persons with MS to help them gain a sustainable employment with sufficient and permanent attention and guidance for the daily obstacles in the workplace. Therefore, the opportunities and bottlenecks were mapped through a survey with persons with MS and employers, a diary and expert interviews. There were 3 major problems identified: Persons with MS find it difficult to ask for help in time; they have little or no concrete knowledge about who they can turn to for support and healthcare professionals do not always possess the expertise to guide their patients through problems experienced on the work floor. These problems were used as fundaments in a cocreation session to create the content of the MS Toolkit: a screening tool and dashboard. The screening tool ensures an annual reflection of the work situation. The dashboard links each problem to the most appropriate service.
    MeSH term(s) Humans ; Employment ; Workplace ; Health Personnel ; Knowledge
    Language English
    Publishing date 2023-08-28
    Publishing country Netherlands
    Document type Journal Article
    ISSN 1879-8365
    ISSN (online) 1879-8365
    DOI 10.3233/SHTI230612
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  10. Article ; Online: Cenobamate in refractory epilepsy: Overview of treatment options and practical considerations.

    Schmitz, Bettina / Lattanzi, Simona / Vonck, Kristl / Kälviäinen, Reetta / Nashef, Lina / Ben-Menachem, Elinor

    Epilepsia open

    2023  Volume 8, Issue 4, Page(s) 1241–1255

    Abstract: Management of drug resistant epilepsy (DRE) represents a challenge to the treating clinician. This manuscript addresses DRE and provides an overview of treatment options, medical, surgical, and dietary. It addresses treatment strategies in polytherapy, ... ...

    Abstract Management of drug resistant epilepsy (DRE) represents a challenge to the treating clinician. This manuscript addresses DRE and provides an overview of treatment options, medical, surgical, and dietary. It addresses treatment strategies in polytherapy, then focuses on the role cenobamate (CNB) may play in reducing the burden of DRE while providing practical advice for its introduction. CNB is a recently approved, third generation, anti-seizure medication (ASM), a tetrazole-derived carbamate, thought to have a dual mechanism of action, through its effect on sodium channels as well as on GABA
    MeSH term(s) Humans ; Anticonvulsants ; Drug Resistant Epilepsy/drug therapy ; Epilepsies, Partial/drug therapy ; Epilepsies, Partial/chemically induced ; Carbamates/pharmacology ; Carbamates/therapeutic use ; Tetrazoles/adverse effects
    Chemical Substances Anticonvulsants ; Cenobamate (P85X70RZWS) ; Carbamates ; Tetrazoles
    Language English
    Publishing date 2023-10-03
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2470-9239
    ISSN (online) 2470-9239
    DOI 10.1002/epi4.12830
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