2025

1. Behavioural separation of face memory and face perception

   Kadlec J., Walsh C., Wilf M., Rissman J., Ramot R.

   (2025) bioRxiv, 2025.02.17.638018. DOI: 10.1101/2025.02.17.638018

   Abstract (Click to open)

   A long-standing debate in neuropsychology concerns whether perception and memory function as independent systems or interact to support cognition. To investigate this, we developed the Face Memory and Perception (FMP) task, a novel paradigm designed to systematically disentangle whether and how these processes interact under different conditions. Across four independent datasets with over 800 participants in total, we observed consistent evidence that face perception and working memory operate independently when task demands are low, but in more complex conditions, these processes appear to interact. Notably, this interaction emerged only when the interference directly involved face-processing mechanisms, and did not arise from a general increase in cognitive load. Rather than the use of shared resources by overlapping cognitive processes, this interaction was driven by a shift in behavioural strategy from holistic to feature-based face processing as a result of maintenance-disrupting interference. These results underscore the fundamental independence of perception and working memory while also explaining some of the conditions under which interactions might be observed.

2024

2. A measure of reliability convergence to select and optimize cognitive tasks for individual differences research

   Kadlec J., Walsh C., Sadé U., Amir A., Rissman J., Ramot R.

   (2024) Commun Psychol, 2, 64 . DOI: https://doi.org/10.1038/s44271-024-00114-4

   Abstract (Click to open)

   Surging interest in individual differences has faced setbacks in light of recent replication crises in psychology, for example in brain-wide association studies exploring brain-behavior correlations. A crucial component of replicability for individual differences studies, which is often assumed but not directly tested, is the reliability of the measures we use. Here, we evaluate the reliability of different cognitive tasks on a dataset with over 250 participants, who each completed a multi-day task battery. We show how reliability improves as a function of number of trials, and describe the convergence of the reliability curves for the different tasks, allowing us to score tasks according to their suitability for studies of individual differences. We further show the effect on reliability of measuring over multiple time points, with tasks assessing different cognitive domains being differentially affected. Data collected over more than one session may be required to achieve trait-like stability.

2022

3. Pharmacokinetics of Intramuscularly Administered Thermoresponsive Polymers

   Groborz O., Kolouchová K., Pankrác J., Keša P., Kadlec J., Krunclová T., Pierzynová A., Šrámek J., Hovořáková M., Dalecká L., Pavlíková Z., Matouš P., Páral P., Loukotová L., Švec P., Beneš H., Štěpánek L., Dunlop D., Melo C. V., Šefc L., Slanina T., Beneš J., Van Vlierberghe S., Hoogenboom R., Hrubý M.

   (2022) Advanced Healthcare Materials, 2201344. DOI: 10.1002/adhm.202201344

   Abstract

   Aqueous solutions of some polymers exhibit a lower critical solution temperature (LCST); that is, they form phase separated aggregates when heated above a threshold temperature. Such polymers have many promising (bio)medical applications, including in situ thermogelling with controlled drug-release, cell/ tissue cultures, polymer-supported radiotherapy (brachytherapy), immunotherapy, wound dressing and healing, and cell tracking, among others. Yet, despite extensive research of medicinal applications of thermoresponsive polymers, their biodistribution and fate after administration remain largely unknown. Thus, we studied the pharmacokinetics of four different thermoresponsive polyacrylamides after intramuscular administration in mice. In vivo, these thermoresponsive polymers formed depots of various densities, which subsequently dissolved with two-phase kinetics (depot maturation, slow redissolution). Their half-lives ranged from 2 weeks to 5 months, depending on their structure and thermal properties as vitrified depots led to longer half-lives. Additionally, the density of intramuscular depots increased with the decrease in the TCP of the polymer solution. Moreover, we detected secondary polymer depots in the kidneys and liver. The evolution of these secondary depots also followed a two-phase kinetics (depot maturation and slow dissolution), with half-lives ranging from 8 to 38 days (kidneys) and from 15 to 22 days (liver). Overall, our findings may be used to tailor the properties of thermoresponsive polymers to meet the demands of their medicinal applications, and our method may become a benchmark for future studies of polymer biodistribution.

2021

4. The glycine arginine-rich domain of the RNA-binding protein nucleolin regulates its subcellular localization

   Doron-Mandel E., Koppel I., Abraham O., Rishal I., Smith T.P., Buchanan C.N., Sahoo P.K., Kadlec J., Oses-Prieto J.A., Kawaguchi R., Alber S., Zahavi E.E., DiMatteo P., DiPizio A., Song D.-A., Okladnikov N., Gordon D., Ben-Dor S., Haffner-Krausz R., Coppola G., Burlingame A. L., Jungwirth P., Twiss J. L., Fainzilber M.

   (2021) The EMBO Journal, 00: e107158. DOI: 10.15252/embj.2020107158

   Abstract

   Nucleolin is a multifunctional RNA Binding Protein (RBP) with diverse subcellular localizations, including the nucleolus in all eukaryotic cells, the plasma membrane in tumor cells, and the axon in neurons. Here we show that the glycine arginine rich (GAR) domain of nucleolin drives subcellular localization via protein-protein interactions with a kinesin light chain. In addition, GAR sequences mediate plasma membrane interactions of nucleolin. Both these modalities are in addition to the already reported involvement of the GAR domain in liquid-liquid phase separation in the nucleolus. Nucleolin transport to axons requires the GAR domain, and heterozygous GAR deletion mice reveal reduced axonal localization of nucleolin cargo mRNAs and enhanced sensory neuron growth. Thus, the GAR domain governs axonal transport of a growth controlling RNA-RBP complex in neurons, and is a versatile localization determinant for different subcellular compartments. Localization determination by GAR domains may explain why GAR mutants in diverse RBPs are associated with neurodegenerative disease.

2020

5. Scaling exchange and correlation in the on-top density functional of multiconfiguration pair-density functional theory: effect on electronic excitation energies and bond energies

   Presti D., Kadlec J., Truhlar D., Gagliardi L.

   (2020) Theoretical Chemistry Accounts, 139 (2). DOI: 10.1007/s00214-019-2539-6

   Abstract

   Multiconfiguration pair-density functional (MC-PDFT) theory provides an economical way to calculate the ground-state and excited-state energetics of strongly correlated systems. The energy is calculated from the kinetic energy, density, and on-top pair-density of a multiconfiguration wave function as the sum of kinetic energy, classical Coulomb energy, and on-top density functional energy. We have usually found good results with the translated Perdew–Burke–Ernzerhof (tPBE) on-top density functional, and in this article, we examine whether the results can be systematically improved by introducing scaling constants into the exchange and correlation terms. We find that only a small improvement is possible for electronic excitation energies and that no improvement is possible for bond energies.

2018

6. Calcium Sensing by Recoverin: Effect of Protein Conformation on Ion Affinity

   Timr Š., Kadlec J., Srb P., Ollila O. H. S., Jungwirth P.

   (2018) J. Phys. Chem. Lett., 9 (7), p. 1613–1619, DOI: 10.1021/acs.jpclett.8b00495

   Abstract

   The detailed functional mechanism of recoverin, which acts as a myristoyl switch at the rod outer-segment disk membrane, is elucidated by direct and replica-exchange molecular dynamics. In accord with NMR structural evidence and calcium binding assays, simulations point to the key role of enhanced calcium binding to the EF3 loop of the semiopen state of recoverin as compared to the closed state. This 2–4-order decrease in calcium dissociation constant stabilizes the semiopen state in response to the increase of cytosolic calcium concentration in the vicinity of recoverin. A second calcium ion then binds to the EF2 loop and, consequently, the structure of the protein changes from the semiopen to the open state. The latter has the myristoyl chain extruded to the cytosol, ready to act as a membrane anchor of recoverin.

2017

7. Membrane Binding of Recoverin: From Mechanistic Understanding to Biological Functionality

   Timr Š., Pleskot R., Kadlec J., Kohagen M., Magarkar A., Jungwirth P.

   (2017) ACS Central Science, 3 (8), p. 868-874, DOI: 10.1021/acscentsci.7b00210

   Abstract

   Recoverin is a neuronal calcium sensor involved in vision adaptation that reversibly associates with cellular membranes via its calcium-activated myristoyl switch. While experimental evidence shows that the myristoyl group significantly enhances membrane affinity of this protein, molecular details of the binding process are still under debate. Here, we present results of extensive molecular dynamics simulations of recoverin in the proximity of a phospholipid bilayer. We capture multiple events of spontaneous membrane insertion of the myristoyl moiety and confirm its critical role in the membrane binding. Moreover, we observe that the binding strongly depends on the conformation of the N-terminal domain. We propose that a suitable conformation of the N-terminal domain can be stabilized by the disordered C-terminal segment or by binding of the target enzyme, i.e., rhodopsin kinase. Finally, we find that the presence of negatively charged lipids in the bilayer stabilizes a physiologically functional orientation of the membrane-bound recoverin.

2016

8. Molecular aspects of the interaction between Mason-Pfizer monkey virus matrix protein and artificial phospholipid membrane

   Junková, P., Prchal, J., Spiwok, V., Pleskot, R., Kadlec, J., Krásný, L., Hynek, R., Hrabal, R., Ruml, T.

   (2016) Proteins, 84: p. 1717-1727, DOI: doi:10.1002/prot.25156

   Abstract

   The Mason–Pfizer monkey virus is a type D retrovirus, which assembles its immature particles in the cytoplasm prior to their transport to the host cell membrane. The association with the membrane is mediated by the N-terminally myristoylated matrix protein. To reveal the role of particular residues which are involved in the capsid-membrane interaction, covalent labelling of arginine, lysine and tyrosine residues of the Mason–Pfizer monkey virus matrix protein bound to artificial liposomes containing 95% of phosphatidylcholine and 5% phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P2) was performed. The experimental results were interpreted by multiscale molecular dynamics simulations. The application of these two complementary approaches helped us to reveal that matrix protein specifically recognizes the PI(4,5)P2 molecule by the residues K20, K25, K27, K74, and Y28, while the residues K92 and K93 stabilizes the matrix protein orientation on the membrane by the interaction with another PI(4,5)P2 molecule. Residues K33, K39, K54, Y66, Y67, and K87 appear to be involved in the matrix protein oligomerization. All arginine residues remained accessible during the interaction with liposomes which indicates that they neither contribute to the interaction with membrane nor are involved in protein oligomerization. Proteins 2016; 84:1717–1727. © 2016 Wiley Periodicals, Inc.

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