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Screening of small molecules using the inhibition of oligomer formation in α-synuclein aggregation as a selection parameter
Roxine Staats, Thomas C. T. Michaels, Patrick Flagmeier, Sean Chia, Robert I. Horne, Johnny Habchi, Sara Linse, Tuomas P. J. Knowles, Christopher M. Dobson, Michele Vendruscolo
Dec 22, 2020
Abstract: The aggregation of α-synuclein is a central event in Parkinsons’s disease and related synucleinopathies. Since pharmacologically targeting this process, however, has not yet resulted in approved disease-modifying...
Asgard archaea shed light on the evolutionary origins of the eukaryotic ubiquitin-ESCRT machinery.
Tomoyuki Hatano, Saravanan Palani, Dimitra Papatziamou, Ralf Salzer, Diorge P Souza, Daniel Tamarit, Mehul Makwana, Antonia Potter, Alexandra Haig, Wenjue Xu, David Townsend, David Rochester, Dom Bellini, Hamdi MA Hussain, Thijs JG Ettema, Jan Löwe, Buzz Baum, Nicholas P Robinson, Mohan Balasubramanian
Jun 14, 2022
Structure and efflux mechanism of the yeast pleiotropic drug resistance transporter Pdr5
Andrzej Harris, Manuel Wagner, Dijun Du, Stefanie Raschka, Lea-Marie Nentwig, Holger Gohlke, Sander H. J. Smits, Ben F. Luisi, Lutz Schmitt
Sep 08, 2021
Abstract: Pdr5, a member of the extensive ABC transporter superfamily, is representative of a clinically relevant subgroup involved in pleiotropic drug resistance. Pdr5 and its homologues drive drug efflux through uncoupled...
A therapeutic antibody targeting osteoprotegerin attenuates severe experimental pulmonary arterial hypertension
Nadine D. Arnold, Josephine A. Pickworth, Laura E. West, Sarah Dawson, Joana A. Carvalho, Helen Casbolt, Adam T. Braithwaite, James Iremonger, Lewis Renshall, Volker Germaschewski, Matthew McCourt, Philip Bland-Ward, Hager Kowash, Abdul G. Hameed, Alexander M. K. Rothman, Maria G. Frid, A. A. Roger Thompson, Holly R. Evans, Mark Southwood, Nicholas W. Morrell, David C. Crossman, Moira K. B. Whyte, Kurt R. Stenmark, Christopher M. Newman, David G. Kiely, Sheila E. Francis, Allan Lawrie
Nov 14, 2020
Abstract: Pulmonary arterial hypertension (PAH) is a rare but fatal disease. Current treatments increase life expectancy but have limited impact on the progressive pulmonary vascular remodelling that drives PAH. Osteoprotegerin...
Infrared nanospectroscopy reveals the molecular interaction fingerprint of an aggregation inhibitor with single Aβ42 oligomers
Francesco Simone Ruggeri, Johnny Habchi, Sean Chia, Robert I. Horne, Michele Vendruscolo, Tuomas P. J. Knowles
Jan 29, 2021
Abstract: Significant efforts have been devoted in the last twenty years to developing compounds that can interfere with the aggregation pathways of proteins related to misfolding disorders, including Alzheimer’s and Parkinson’s...
Red reflex examination in reproductive and child health clinics for early detection of paediatric cataract and ocular media disorders
Extent of myosin penetration within the actin cortex regulates cell surface mechanics
Binh An Truong Quang, Ruby Peters, Davide A. D. Cassani, Priyamvada Chugh, Andrew G. Clark, Meghan Agnew, Guillaume Charras, Ewa K. Paluch
Nov 12, 2021
Abstract: In animal cells, shape is mostly determined by the actomyosin cortex, a thin cytoskeletal network underlying the plasma membrane. Myosin motors generate tension in the cortex, and tension gradients result in cellular...
Reentrant liquid condensate phase of proteins is stabilized by hydrophobic and non-ionic interactions
Georg Krainer, Timothy J. Welsh, Jerelle A. Joseph, Jorge R. Espinosa, Sina Wittmann, Ella de Csilléry, Akshay Sridhar, Zenon Toprakcioglu, Giedre Gudiškytė, Magdalena A. Czekalska, William E. Arter, Jordina Guillén-Boixet, Titus M. Franzmann, Seema Qamar, Peter St George-Hyslop, Anthony A. Hyman, Rosana Collepardo-Guevara, Simon Alberti, Tuomas P. J. Knowles
Feb 17, 2021
Engineering the protein dynamics of an ancestral luciferase
Andrea Schenkmayerova, Gaspar P. Pinto, Martin Toul, Martin Marek, Lenka Hernychova, Joan Planas-Iglesias, Veronika Daniel Liskova, Daniel Pluskal, Michal Vasina, Stephane Emond, Mark Dörr, Radka Chaloupkova, David Bednar, Zbynek Prokop, Florian Hollfelder, Uwe T. Bornscheuer, Jiri Damborsky
Jun 14, 2021
Abstract: Protein dynamics are often invoked in explanations of enzyme catalysis, but their design has proven elusive. Here we track the role of dynamics in evolution, starting from the evolvable and thermostable ancestral...
EEG functional connectivity metrics wPLI and wSMI account for distinct types of brain functional interactions
Laura Sophie Imperatori, Monica Betta, Luca Cecchetti, Andrés Canales-Johnson, Emiliano Ricciardi, Francesca Siclari, Pietro Pietrini, Srivas Chennu, Giulio Bernardi
Jun 19, 2020
Abstract: The weighted Phase Lag Index (wPLI) and the weighted Symbolic Mutual Information (wSMI) represent two robust and widely used methods for MEG/EEG functional connectivity estimation. Interestingly, both methods have been...
Autocatalytic amplification of Alzheimer-associated Aβ42 peptide aggregation in human cerebrospinal fluid
A single-progenitor model as the unifying paradigm of epidermal and esophageal epithelial maintenance in mice
Gabriel Piedrafita, Vasiliki Kostiou, Agnieszka Wabik, Bartomeu Colom, David Fernandez-Antoran, Albert Herms, Kasumi Murai, Benjamin A. Hall, Philip H. Jones
Mar 18, 2021
Abstract: In adult skin epidermis and the epithelium lining the esophagus cells are constantly shed from the tissue surface and replaced by cell division. Tracking genetically labelled cells in transgenic mice has given insight...
A dopamine metabolite stabilizes neurotoxic amyloid-β oligomers
Rodrigo Cataldi, Sean Chia, Katarina Pisani, Francesco S. Ruggeri, Catherine K. Xu, Tomas Šneideris, Michele Perni, Sunehera Sarwat, Priyanka Joshi, Janet R. Kumita, Sara Linse, Johnny Habchi, Tuomas P. J. Knowles, Benedetta Mannini, Christopher M. Dobson, Michele Vendruscolo
Mar 18, 2021
Abstract: Aberrant soluble oligomers formed by the amyloid-β peptide (Aβ) are major pathogenic agents in the onset and progression of Alzheimer’s disease. A variety of biomolecules can influence the formation of these oligomers...
Mechanism and evolution of the Zn-fingernail required for interaction of VARP with VPS29
Mechanism and evolution of the Zn-fingernail required for interaction of VARP with VPS29
RORγt + Treg to Th17 ratios correlate with susceptibility to Giardia infection
Ivet A. Yordanova, Alba Cortés, Christian Klotz, Anja A. Kühl, Markus M. Heimesaat, Cinzia Cantacessi, Susanne Hartmann, Sebastian Rausch
Dec 29, 2020
Substrate binding in the mitochondrial ADP/ATP carrier is a step-wise process guiding the structural changes in the transport cycle.
Vasiliki Mavridou, Martin King, Sotiria Tavoulari, Jonathan Ruprecht, Shane M Palmer, Edmund Kunji
Jun 29, 2022
Mitochondrial ADP/ATP carriers import ADP into the mitochondrial matrix and export ATP to the cytosol to fuel cellular processes. Structures of the inhibited cytoplasmic- and matrix-open states have confirmed an alternating...
Perceptual and conceptual processing of visual objects across the adult lifespan
Rose Bruffaerts, Lorraine K. Tyler, Meredith Shafto, Kamen A. Tsvetanov, Alex Clarke, Carol Brayne, Edward T. Bullmore, Andrew C. Calder, Rhodri Cusack, Tim Dalgleish, John Duncan, Richard N. Henson, Fiona E. Matthews, William D. Marslen-Wilson, James B. Rowe, Karen Campbell, Teresa Cheung, Simon Davis, Linda Geerligs, Rogier Kievit, Anna McCarrey, Abdur Mustafa, Darren Price, David Samu, Jason R. Taylor, Matthias Treder, Janna Van Belle, Nitin Williams, Lauren Bates, Tina Emery, Sharon Erzinçlioglu, Andrew Gadie, Sofia Gerbase, Stanimira Georgieva, Claire Hanley, Beth Parkin, David Troy, Tibor Auer, Marta Correia, Lu Gao, Emma Green, Rafael Henriques, Jodie Allen, Gillian Amery, Liana Amunts, Anne Barcroft, Amanda Castle, Cheryl Dias, Jonathan Dowrick, Melissa Fair, Hayley Fisher, Anna Goulding, Adarsh Grewal, Geoff Hale, Andrew Hilton, Frances Johnson, Patricia Johnston, Thea Kavanagh-Williamson, Magdalena Kwasniewska, Alison McMinn, Kim Norman, Jessica Penrose, Fiona Roby, Diane Rowland, John Sargeant, Maggie Squire, Beth Stevens, Aldabra Stoddart, Cheryl Stone, Tracy Thompson, Ozlem Yazlik, Dan Barnes, Marie Dixon, Jaya Hillman, Joanne Mitchell, Laura Villis
Sep 23, 2020
Abstract: Making sense of the external world is vital for multiple domains of cognition, and so it is crucial that object recognition is maintained across the lifespan. We investigated age differences in perceptual and...
AMPA receptor anchoring at CA1 synapses is determined by N-terminal domain and TARP γ8 interactions
Abstract: AMPA receptor (AMPAR) abundance and positioning at excitatory synapses regulates the strength of transmission. Changes in AMPAR localisation can enact synaptic plasticity, allowing long-term information storage, and is...
Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor.
Beatriz Herguedas, Bianka K Kohegyi, Jan-Niklas Dohrke, Jake F Watson, Danyang Zhang, Hinze Ho, Saher A Shaikh, Remigijus Lape, James M Krieger, Ingo H Greger
Feb 09, 2022
AMPA-type glutamate receptors (AMPARs) mediate rapid signal transmission at excitatory synapses in the brain. Glutamate binding to the receptor's ligand-binding domains (LBDs) leads to ion channel activation and desensitization....
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