@article{12832,
abstract = {The development of cost-effective, high-activity and stable bifunctional catalysts for the oxygen reduction and evolution reactions (ORR/OER) is essential for zinc–air batteries (ZABs) to reach the market. Such catalysts must contain multiple adsorption/reaction sites to cope with the high demands of reversible oxygen electrodes. Herein, we propose a high entropy alloy (HEA) based on relatively abundant elements as a bifunctional ORR/OER catalyst. More specifically, we detail the synthesis of a CrMnFeCoNi HEA through a low-temperature solution-based approach. Such HEA displays superior OER performance with an overpotential of 265 mV at a current density of 10 mA/cm2, and a 37.9 mV/dec Tafel slope, well above the properties of a standard commercial catalyst based on RuO2. This high performance is partially explained by the presence of twinned defects, the incidence of large lattice distortions, and the electronic synergy between the different components, being Cr key to decreasing the energy barrier of the OER rate-determining step. CrMnFeCoNi also displays superior ORR performance with a half-potential of 0.78 V and an onset potential of 0.88 V, comparable with commercial Pt/C. The potential gap (Egap) between the OER overpotential and the ORR half-potential of CrMnFeCoNi is just 0.734 V. Taking advantage of these outstanding properties, ZABs are assembled using the CrMnFeCoNi HEA as air cathode and a zinc foil as the anode. The assembled cells provide an open-circuit voltage of 1.489 V, i.e. 90% of its theoretical limit (1.66 V), a peak power density of 116.5 mW/cm2, and a specific capacity of 836 mAh/g that stays stable for more than 10 days of continuous cycling, i.e. 720 cycles @ 8 mA/cm2 and 16.6 days of continuous cycling, i.e. 1200 cycles @ 5 mA/cm2.},
author = {He, Ren and Yang, Linlin and Zhang, Yu and Wang, Xiang and Lee, Seungho and Zhang, Ting and Li, Lingxiao and Liang, Zhifu and Chen, Jingwei and Li, Junshan and Ostovari Moghaddam, Ahmad and Llorca, Jordi and Ibáñez, Maria and Arbiol, Jordi and Xu, Ying and Cabot, Andreu},
issn = {2405-8297},
journal = {Energy Storage Materials},
number = {4},
pages = {287--298},
publisher = {Elsevier},
title = {{A CrMnFeCoNi high entropy alloy boosting oxygen evolution/reduction reactions and zinc-air battery performance}},
doi = {10.1016/j.ensm.2023.03.022},
volume = {58},
year = {2023},
}
@phdthesis{12885,
abstract = {High-performance semiconductors rely upon precise control of heat and charge transport. This can be achieved by precisely engineering defects in polycrystalline solids. There are multiple approaches to preparing such polycrystalline semiconductors, and the transformation of solution-processed colloidal nanoparticles is appealing because colloidal nanoparticles combine low cost with structural and compositional tunability along with rich surface chemistry. However, the multiple processes from nanoparticle synthesis to the final bulk nanocomposites are very complex. They involve nanoparticle purification, post-synthetic modifications, and finally consolidation (thermal treatments and densification). All these properties dictate the final material’s composition and microstructure, ultimately affecting its functional properties. This thesis explores the synthesis, surface chemistry and consolidation of colloidal semiconductor nanoparticles into dense solids. In particular, the transformations that take place during these processes, and their effect on the material’s transport properties are evaluated. },
author = {Calcabrini, Mariano},
isbn = {978-3-99078-028-2},
issn = {2663-337X},
pages = {82},
publisher = {Institute of Science and Technology Austria},
title = {{Nanoparticle-based semiconductor solids: From synthesis to consolidation}},
doi = {10.15479/at:ista:12885},
year = {2023},
}
@phdthesis{13107,
abstract = {Within the human body, the brain exhibits the highest rate of energy consumption amongst all organs, with the majority of generated ATP being utilized to sustain neuronal activity. Therefore, the metabolism of the mature cerebral cortex is geared towards preserving metabolic homeostasis whilst generating significant amounts of energy. This requires a precise interplay between diverse metabolic pathways, spanning from a tissue-wide scale to the level of individual neurons. Disturbances to this delicate metabolic equilibrium, such as those resulting from maternal malnutrition
or mutations affecting metabolic enzymes, often result in neuropathological variants of neurodevelopment. For instance, mutations in SLC7A5, a transporter of metabolically essential large neutral amino acids (LNAAs), have been associated with autism and microcephaly. However, despite recent progress in the field, the extent of metabolic restructuring that occurs within the developing brain and the corresponding alterations in nutrient demands during various critical periods remain largely unknown. To investigate this, we performed metabolomic profiling of the murine cerebral cortex to characterize the metabolic state of the forebrain at different developmental stages. We found that the developing cortex undergoes substantial metabolic reprogramming, with specific sets of metabolites displaying stage-specific changes. According to our observations, we determined a distinct temporal period in postnatal development during which the cortex displays heightened reliance on LNAAs. Hence, using a conditional knock-out mouse model, we deleted Slc7a5 in neural cells, allowing us to monitor the impact of a perturbed neuronal metabolic state across multiple developmental stages of corticogenesis. We found that manipulating the levels of essential LNAAs in cortical neurons in vivo affects one particular perinatal developmental period critical for cortical network refinement. Abnormally low intracellular LNAA levels result in cell-autonomous alterations in neuronal lipid metabolism, excitability, and survival during this particular time window. Although most of the effects of Slc7a5 deletion on neuronal physiology are transient, derailment of these processes during this brief but crucial window leads to long-term circuit dysfunction in mice. In conclusion, out data indicate that the cerebral cortex undergoes significant metabolic reorganization during development. This process involves the intricate integration of multiple metabolic pathways to ensure optimal neuronal function throughout different developmental stages. Our findings offer a paradigm for understanding how neurons synchronize the expression of nutrient-related genes with their activity to allow proper brain maturation. Further, our results demonstrate that disruptions in these precisely calibrated metabolic processes during critical periods of brain development may result in neuropathological outcomes in mice and in humans.},
author = {Knaus, Lisa},
issn = {2663-337X},
pages = {147},
publisher = {Institute of Science and Technology Austria},
title = {{The metabolism of the developing brain : How large neutral amino acids modulate perinatal neuronal excitability and survival}},
doi = {10.15479/at:ista:13107},
year = {2023},
}
@article{13202,
abstract = {Phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) plays an essential role in neuronal activities through interaction with various proteins involved in signaling at membranes. However, the distribution pattern of PI(4,5)P2 and the association with these proteins on the neuronal cell membranes remain elusive. In this study, we established a method for visualizing PI(4,5)P2 by SDS-digested freeze-fracture replica labeling (SDS-FRL) to investigate the quantitative nanoscale distribution of PI(4,5)P2 in cryo-fixed brain. We demonstrate that PI(4,5)P2 forms tiny clusters with a mean size of ∼1000 nm2 rather than randomly distributed in cerebellar neuronal membranes in male C57BL/6J mice. These clusters show preferential accumulation in specific membrane compartments of different cell types, in particular, in Purkinje cell (PC) spines and granule cell (GC) presynaptic active zones. Furthermore, we revealed extensive association of PI(4,5)P2 with CaV2.1 and GIRK3 across different membrane compartments, whereas its association with mGluR1α was compartment specific. These results suggest that our SDS-FRL method provides valuable insights into the physiological functions of PI(4,5)P2 in neurons.},
author = {Eguchi, Kohgaku and Le Monnier, Elodie and Shigemoto, Ryuichi},
issn = {1529-2401},
journal = {The Journal of Neuroscience},
number = {23},
pages = {4197--4216},
publisher = {Society for Neuroscience},
title = {{Nanoscale phosphoinositide distribution on cell membranes of mouse cerebellar neurons}},
doi = {10.1523/JNEUROSCI.1514-22.2023},
volume = {43},
year = {2023},
}
@article{13968,
abstract = {The use of multimodal readout mechanisms next to label-free real-time monitoring of biomolecular interactions can provide valuable insight into surface-based reaction mechanisms. To this end, the combination of an electrolyte-gated field-effect transistor (EG-FET) with a fiber optic-coupled surface plasmon resonance (FO-SPR) probe serving as gate electrode has been investigated to deconvolute surface mass and charge density variations associated to surface reactions. However, applying an electrochemical potential on such gold-coated FO-SPR gate electrodes can induce gradual morphological changes of the thin gold film, leading to an irreversible blue-shift of the SPR wavelength and a substantial signal drift. We show that mild annealing leads to optical and electronic signal stabilization (20-fold lower signal drift than as-sputtered fiber optic gates) and improved overall analytical performance characteristics. The thermal treatment prevents morphological changes of the thin gold-film occurring during operation, hence providing reliable and stable data immediately upon gate voltage application. Thus, the readout output of both transducing principles, the optical FO-SPR and electronic EG-FET, stays constant throughout the whole sensing time-window and the long-term effect of thermal treatment is also improved, providing stable signals even after 1 year of storage. Annealing should therefore be considered a necessary modification for applying fiber optic gate electrodes in real-time multimodal investigations of surface reactions at the solid-liquid interface.},
author = {Hasler, Roger and Steger-Polt, Marie Helene and Reiner-Rozman, Ciril and Fossati, Stefan and Lee, Seungho and Aspermair, Patrik and Kleber, Christoph and Ibáñez, Maria and Dostalek, Jakub and Knoll, Wolfgang},
issn = {2296-424X},
journal = {Frontiers in Physics},
publisher = {Frontiers},
title = {{Optical and electronic signal stabilization of plasmonic fiber optic gate electrodes: Towards improved real-time dual-mode biosensing}},
doi = {10.3389/fphy.2023.1202132},
volume = {11},
year = {2023},
}
@article{14040,
abstract = {Robust oxygenic photosynthesis requires a suite of accessory factors to ensure efficient assembly and repair of the oxygen-evolving photosystem two (PSII) complex. The highly conserved Ycf48 assembly factor binds to the newly synthesized D1 reaction center polypeptide and promotes the initial steps of PSII assembly, but its binding site is unclear. Here we use cryo-electron microscopy to determine the structure of a cyanobacterial PSII D1/D2 reaction center assembly complex with Ycf48 attached. Ycf48, a 7-bladed beta propeller, binds to the amino-acid residues of D1 that ultimately ligate the water-oxidising Mn4CaO5 cluster, thereby preventing the premature binding of Mn2+ and Ca2+ ions and protecting the site from damage. Interactions with D2 help explain how Ycf48 promotes assembly of the D1/D2 complex. Overall, our work provides valuable insights into the early stages of PSII assembly and the structural changes that create the binding site for the Mn4CaO5 cluster.},
author = {Zhao, Ziyu and Vercellino, Irene and Knoppová, Jana and Sobotka, Roman and Murray, James W. and Nixon, Peter J. and Sazanov, Leonid A and Komenda, Josef},
issn = {2041-1723},
journal = {Nature Communications},
publisher = {Springer Nature},
title = {{The Ycf48 accessory factor occupies the site of the oxygen-evolving manganese cluster during photosystem II biogenesis}},
doi = {10.1038/s41467-023-40388-6},
volume = {14},
year = {2023},
}
@article{14255,
abstract = {Toscana virus is a major cause of arboviral disease in humans in the Mediterranean basin during summer. However, early virus-host cell interactions and entry mechanisms remain poorly characterized. Investigating iPSC-derived human neurons and cell lines, we found that virus binding to the cell surface was specific, and 50% of bound virions were endocytosed within 10 min. Virions entered Rab5a+ early endosomes and, subsequently, Rab7a+ and LAMP-1+ late endosomal compartments. Penetration required intact late endosomes and occurred within 30 min following internalization. Virus entry relied on vacuolar acidification, with an optimal pH for viral membrane fusion at pH 5.5. The pH threshold increased to 5.8 with longer pre-exposure of virions to the slightly acidic pH in early endosomes. Strikingly, the particles remained infectious after entering late endosomes with a pH below the fusion threshold. Overall, our study establishes Toscana virus as a late-penetrating virus and reveals an atypical use of vacuolar acidity by this virus to enter host cells.},
author = {Koch, Jana and Xin, Qilin and Obr, Martin and Schäfer, Alicia and Rolfs, Nina and Anagho, Holda A. and Kudulyte, Aiste and Woltereck, Lea and Kummer, Susann and Campos, Joaquin and Uckeley, Zina M. and Bell-Sakyi, Lesley and Kräusslich, Hans Georg and Schur, Florian Km and Acuna, Claudio and Lozach, Pierre Yves},
issn = {1553-7374},
journal = {PLoS Pathogens},
number = {8},
publisher = {Public Library of Science},
title = {{The phenuivirus Toscana virus makes an atypical use of vacuolar acidity to enter host cells}},
doi = {10.1371/journal.ppat.1011562},
volume = {19},
year = {2023},
}
@article{14434,
abstract = {High entropy alloys (HEAs) are highly suitable candidate catalysts for oxygen evolution and reduction reactions (OER/ORR) as they offer numerous parameters for optimizing the electronic structure and catalytic sites. Herein, FeCoNiMoW HEA nanoparticles are synthesized using a solution‐based low‐temperature approach. Such FeCoNiMoW nanoparticles show high entropy properties, subtle lattice distortions, and modulated electronic structure, leading to superior OER performance with an overpotential of 233 mV at 10 mA cm−2 and 276 mV at 100 mA cm−2. Density functional theory calculations reveal the electronic structures of the FeCoNiMoW active sites with an optimized d‐band center position that enables suitable adsorption of OOH* intermediates and reduces the Gibbs free energy barrier in the OER process. Aqueous zinc–air batteries (ZABs) based on this HEA demonstrate a high open circuit potential of 1.59 V, a peak power density of 116.9 mW cm−2, a specific capacity of 857 mAh gZn−1, and excellent stability for over 660 h of continuous charge–discharge cycles. Flexible and solid ZABs are also assembled and tested, displaying excellent charge–discharge performance at different bending angles. This work shows the significance of 4d/5d metal‐modulated electronic structure and optimized adsorption ability to improve the performance of OER/ORR, ZABs, and beyond.},
author = {He, Ren and Yang, Linlin and Zhang, Yu and Jiang, Daochuan and Lee, Seungho and Horta, Sharona and Liang, Zhifu and Lu, Xuan and Ostovari Moghaddam, Ahmad and Li, Junshan and Ibáñez, Maria and Xu, Ying and Zhou, Yingtang and Cabot, Andreu},
issn = {1521-4095},
journal = {Advanced Materials},
keywords = {Mechanical Engineering, Mechanics of Materials, General Materials Science},
number = {46},
publisher = {Wiley},
title = {{A 3d‐4d‐5d high entropy alloy as a bifunctional oxygen catalyst for robust aqueous zinc–air batteries}},
doi = {10.1002/adma.202303719},
volume = {35},
year = {2023},
}
@article{10639,
abstract = {With more than 80 members worldwide, the Orthobunyavirus genus in the Peribunyaviridae family is a large genus of enveloped RNA viruses, many of which are emerging pathogens in humans and livestock. How orthobunyaviruses (OBVs) penetrate and infect mammalian host cells remains poorly characterized. Here, we investigated the entry mechanisms of the OBV Germiston (GERV). Viral particles were visualized by cryo-electron microscopy and appeared roughly spherical with an average diameter of 98 nm. Labeling of the virus with fluorescent dyes did not adversely affect its infectivity and allowed the monitoring of single particles in fixed and live cells. Using this approach, we found that endocytic internalization of bound viruses was asynchronous and occurred within 30-40 min. The virus entered Rab5a+ early endosomes and, subsequently, late endosomal vacuoles containing Rab7a but not LAMP-1. Infectious entry did not require proteolytic cleavage, and endosomal acidification was sufficient and necessary for viral fusion. Acid-activated penetration began 15-25 min after initiation of virus internalization and relied on maturation of early endosomes to late endosomes. The optimal pH for viral membrane fusion was slightly below 6.0, and penetration was hampered when the potassium influx was abolished. Overall, our study provides real-time visualization of GERV entry into host cells and demonstrates the importance of late endosomal maturation in facilitating OBV penetration.},
author = {Windhaber, Stefan and Xin, Qilin and Uckeley, Zina M. and Koch, Jana and Obr, Martin and Garnier, Céline and Luengo-Guyonnot, Catherine and Duboeuf, Maëva and Schur, Florian KM and Lozach, Pierre-Yves},
issn = {1098-5514},
journal = {Journal of Virology},
keywords = {virology, insect science, immunology, microbiology},
number = {5},
publisher = {American Society for Microbiology},
title = {{The Orthobunyavirus Germiston enters host cells from late endosomes}},
doi = {10.1128/jvi.02146-21},
volume = {96},
year = {2022},
}
@article{10703,
abstract = {When crawling through the body, leukocytes often traverse tissues that are densely packed with extracellular matrix and other cells, and this raises the question: How do leukocytes overcome compressive mechanical loads? Here, we show that the actin cortex of leukocytes is mechanoresponsive and that this responsiveness requires neither force sensing via the nucleus nor adhesive interactions with a substrate. Upon global compression of the cell body as well as local indentation of the plasma membrane, Wiskott-Aldrich syndrome protein (WASp) assembles into dot-like structures, providing activation platforms for Arp2/3 nucleated actin patches. These patches locally push against the external load, which can be obstructing collagen fibers or other cells, and thereby create space to facilitate forward locomotion. We show in vitro and in vivo that this WASp function is rate limiting for ameboid leukocyte migration in dense but not in loose environments and is required for trafficking through diverse tissues such as skin and lymph nodes.},
author = {Gaertner, Florian and Dos Reis Rodrigues, Patricia and De Vries, Ingrid and Hons, Miroslav and Aguilera, Juan and Riedl, Michael and Leithner, Alexander F and Tasciyan, Saren and Kopf, Aglaja and Merrin, Jack and Zheden, Vanessa and Kaufmann, Walter and Hauschild, Robert and Sixt, Michael K},
issn = {1878-1551},
journal = {Developmental Cell},
number = {1},
pages = {47--62.e9},
publisher = {Cell Press},
title = {{WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues}},
doi = {10.1016/j.devcel.2021.11.024},
volume = {57},
year = {2022},
}
@article{10766,
abstract = {Tension of the actomyosin cell cortex plays a key role in determining cell–cell contact growth and size. The level of cortical tension outside of the cell–cell contact, when pulling at the contact edge, scales with the total size to which a cell–cell contact can grow [J.-L. Maître et al., Science 338, 253–256 (2012)]. Here, we show in zebrafish primary germ-layer progenitor cells that this monotonic relationship only applies to a narrow range of cortical tension increase and that above a critical threshold, contact size inversely scales with cortical tension. This switch from cortical tension increasing to decreasing progenitor cell–cell contact size is caused by cortical tension promoting E-cadherin anchoring to the actomyosin cytoskeleton, thereby increasing clustering and stability of E-cadherin at the contact. After tension-mediated E-cadherin stabilization at the contact exceeds a critical threshold level, the rate by which the contact expands in response to pulling forces from the cortex sharply drops, leading to smaller contacts at physiologically relevant timescales of contact formation. Thus, the activity of cortical tension in expanding cell–cell contact size is limited by tension-stabilizing E-cadherin–actin complexes at the contact.},
author = {Slovakova, Jana and Sikora, Mateusz K and Arslan, Feyza N and Caballero Mancebo, Silvia and Krens, Gabriel and Kaufmann, Walter and Merrin, Jack and Heisenberg, Carl-Philipp J},
issn = {1091-6490},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = {8},
publisher = {National Academy of Sciences},
title = {{Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor cells}},
doi = {10.1073/pnas.2122030119},
volume = {119},
year = {2022},
}
@article{9794,
abstract = {Lymph nodes (LNs) comprise two main structural elements: fibroblastic reticular cells that form dedicated niches for immune cell interaction and capsular fibroblasts that build a shell around the organ. Immunological challenge causes LNs to increase more than tenfold in size within a few days. Here, we characterized the biomechanics of LN swelling on the cellular and organ scale. We identified lymphocyte trapping by influx and proliferation as drivers of an outward pressure force, causing fibroblastic reticular cells of the T-zone (TRCs) and their associated conduits to stretch. After an initial phase of relaxation, TRCs sensed the resulting strain through cell matrix adhesions, which coordinated local growth and remodeling of the stromal network. While the expanded TRC network readopted its typical configuration, a massive fibrotic reaction of the organ capsule set in and countered further organ expansion. Thus, different fibroblast populations mechanically control LN swelling in a multitier fashion.},
author = {Assen, Frank P and Abe, Jun and Hons, Miroslav and Hauschild, Robert and Shamipour, Shayan and Kaufmann, Walter and Costanzo, Tommaso and Krens, Gabriel and Brown, Markus and Ludewig, Burkhard and Hippenmeyer, Simon and Heisenberg, Carl-Philipp J and Weninger, Wolfgang and Hannezo, Edouard B and Luther, Sanjiv A. and Stein, Jens V. and Sixt, Michael K},
issn = {1529-2916},
journal = {Nature Immunology},
pages = {1246--1255},
publisher = {Springer Nature},
title = {{Multitier mechanics control stromal adaptations in swelling lymph nodes}},
doi = {10.1038/s41590-022-01257-4},
volume = {23},
year = {2022},
}
@article{10841,
abstract = {In eukaryotes, clathrin-coated vesicles (CCVs) facilitate the internalization of material from the cell surface as well as the movement of cargo in post-Golgi trafficking pathways. This diversity of functions is partially provided by multiple monomeric and multimeric clathrin adaptor complexes that provide compartment and cargo selectivity. The adaptor-protein assembly polypeptide-1 (AP-1) complex operates as part of the secretory pathway at the trans-Golgi network (TGN), while the AP-2 complex and the TPLATE complex jointly operate at the plasma membrane to execute clathrin-mediated endocytosis. Key to our further understanding of clathrin-mediated trafficking in plants will be the comprehensive identification and characterization of the network of evolutionarily conserved and plant-specific core and accessory machinery involved in the formation and targeting of CCVs. To facilitate these studies, we have analyzed the proteome of enriched TGN/early endosome-derived and endocytic CCVs isolated from dividing and expanding suspension-cultured Arabidopsis (Arabidopsis thaliana) cells. Tandem mass spectrometry analysis results were validated by differential chemical labeling experiments to identify proteins co-enriching with CCVs. Proteins enriched in CCVs included previously characterized CCV components and cargos such as the vacuolar sorting receptors in addition to conserved and plant-specific components whose function in clathrin-mediated trafficking has not been previously defined. Notably, in addition to AP-1 and AP-2, all subunits of the AP-4 complex, but not AP-3 or AP-5, were found to be in high abundance in the CCV proteome. The association of AP-4 with suspension-cultured Arabidopsis CCVs is further supported via additional biochemical data.},
author = {Dahhan, DA and Reynolds, GD and Cárdenas, JJ and Eeckhout, D and Johnson, Alexander J and Yperman, K and Kaufmann, Walter and Vang, N and Yan, X and Hwang, I and Heese, A and De Jaeger, G and Friml, Jiří and Van Damme, D and Pan, J and Bednarek, SY},
issn = {1532-298x},
journal = {Plant Cell},
number = {6},
pages = {2150--2173},
publisher = {Oxford University Press},
title = {{Proteomic characterization of isolated Arabidopsis clathrin-coated vesicles reveals evolutionarily conserved and plant-specific components}},
doi = {10.1093/plcell/koac071},
volume = {34},
year = {2022},
}
@article{11155,
abstract = {The potential of energy filtering and direct electron detection for cryo-electron microscopy (cryo-EM) has been well documented. Here, we assess the performance of recently introduced hardware for cryo-electron tomography (cryo-ET) and subtomogram averaging (STA), an increasingly popular structural determination method for complex 3D specimens. We acquired cryo-ET datasets of EIAV virus-like particles (VLPs) on two contemporary cryo-EM systems equipped with different energy filters and direct electron detectors (DED), specifically a Krios G4, equipped with a cold field emission gun (CFEG), Thermo Fisher Scientific Selectris X energy filter, and a Falcon 4 DED; and a Krios G3i, with a Schottky field emission gun (XFEG), a Gatan Bioquantum energy filter, and a K3 DED. We performed constrained cross-correlation-based STA on equally sized datasets acquired on the respective systems. The resulting EIAV CA hexamer reconstructions show that both systems perform comparably in the 4–6 Å resolution range based on Fourier-Shell correlation (FSC). In addition, by employing a recently introduced multiparticle refinement approach, we obtained a reconstruction of the EIAV CA hexamer at 2.9 Å. Our results demonstrate the potential of the new generation of energy filters and DEDs for STA, and the effects of using different processing pipelines on their STA outcomes.},
author = {Obr, Martin and Hagen, Wim J.H. and Dick, Robert A. and Yu, Lingbo and Kotecha, Abhay and Schur, Florian KM},
issn = {1047-8477},
journal = {Journal of Structural Biology},
keywords = {Structural Biology},
number = {2},
publisher = {Elsevier},
title = {{Exploring high-resolution cryo-ET and subtomogram averaging capabilities of contemporary DEDs}},
doi = {10.1016/j.jsb.2022.107852},
volume = {214},
year = {2022},
}
@phdthesis{11196,
abstract = {One of the fundamental questions in Neuroscience is how the structure of synapses and their physiological properties are related. While synaptic transmission remains a dynamic process, electron microscopy provides images with comparably low temporal resolution (Studer et al., 2014). The current work overcomes this challenge and describes an improved “Flash and Freeze” technique (Watanabe et al., 2013a; Watanabe et al., 2013b) to study synaptic transmission at the hippocampal mossy fiber-CA3 pyramidal neuron synapses, using mouse acute brain slices and organotypic slices culture. The improved method allowed for selective stimulation of presynaptic mossy fiber boutons and the observation of synaptic vesicle pool dynamics at the active zones. Our results uncovered several intriguing morphological features of mossy fiber boutons. First, the docked vesicle pool was largely depleted (more than 70%) after stimulation, implying that the docked synaptic vesicles pool and readily releasable pool are vastly overlapping in mossy fiber boutons. Second, the synaptic vesicles are skewed towards larger diameters, displaying a wide range of sizes. An increase in the mean diameter of synaptic vesicles, after single and repetitive stimulation, suggests that smaller vesicles have a higher release probability. Third, we observed putative endocytotic structures after moderate light stimulation, matching the timing of previously described ultrafast endocytosis (Watanabe et al., 2013a; Delvendahl et al., 2016).
In addition, synaptic transmission depends on a sophisticated system of protein machinery and calcium channels (Südhof, 2013b), which amplifies the challenge in studying synaptic communication as these interactions can be potentially modified during synaptic plasticity. And although recent study elucidated the potential correlation between physiological and morphological properties of synapses during synaptic plasticity (Vandael et al., 2020), the molecular underpinning of it remains unknown. Thus, the presented work tries to overcome this challenge and aims to pinpoint changes in the molecular architecture at hippocampal mossy fiber bouton synapses during short- and long-term potentiation (STP and LTP), we combined chemical potentiation, with the application of a cyclic adenosine monophosphate agonist (i.e. forskolin) and freeze-fracture replica immunolabelling. This method allowed the localization of membrane-bound proteins with nanometer precision within the active zone, in particular, P/Q-type calcium channels and synaptic vesicle priming proteins Munc13-1/2. First, we found that the number of clusters of Munc13-1 in the mossy fiber bouton active zone increased significantly during STP, but decreased to lower than the control value during LTP. Secondly, although the distance between the calcium channels and Munc13-1s did not change after induction of STP, it shortened during the LTP phase. Additionally, forskolin did not affect Munc13-2 distribution during STP and LTP. These results indicate the existence of two distinct mechanisms that govern STP and LTP at mossy fiber bouton synapses: an increase in the readily realizable pool in the case of STP and a potential increase in release probability during LTP. “Flash and freeze” and functional electron microscopy, are versatile methods that can be successfully applied to intact brain circuits to study synaptic transmission even at the molecular level.
},
author = {Kim, Olena},
issn = {2663-337X},
pages = {132},
publisher = {Institute of Science and Technology Austria},
title = {{Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses}},
doi = {10.15479/at:ista:11196},
year = {2022},
}
@phdthesis{11393,
abstract = {AMPA receptors (AMPARs) mediate fast excitatory neurotransmission and their role is
implicated in complex processes such as learning and memory and various neurological
diseases. These receptors are composed of different subunits and the subunit composition can
affect channel properties, receptor trafficking and interaction with other associated proteins.
Using the high sensitivity SDS-digested freeze-fracture replica labeling (SDS-FRL) for
electron microscopy I investigated the number, density, and localization of AMPAR subunits,
GluA1, GluA2, GluA3, and GluA1-3 (panAMPA) in pyramidal cells in the CA1 area of mouse
hippocampus. I have found that the immunogold labeling for all of these subunits in the
postsynaptic sites was highest in stratum radiatum and lowest in stratum lacunosummoleculare. The labeling density for the all subunits in the extrasynaptic sites showed a gradual
increase from the pyramidal cell soma towards the distal part of stratum radiatum. The densities
of extrasynaptic GluA1, GluA2 and panAMPA labeling reached 10-15% of synaptic densities,
while the ratio of extrasynaptic labeling for GluA3 was significantly lower compared than those
for other subunits. The labeling patterns for GluA1, GluA2 and GluA1-3 are similar and their
densities were higher in the periphery than center of synapses. In contrast, the GluA3-
containing receptors were more centrally localized compared to the GluA1- and GluA2-
containing receptors.
The hippocampus plays a central role in learning and memory. Contextual learning has been
shown to require the delivery of AMPA receptors to CA1 synapses in the dorsal hippocampus.
However, proximodistal heterogeneity of this plasticity and particular contribution of different
AMPA receptor subunits are not fully understood. By combining inhibitory avoidance task, a
hippocampus-dependent contextual fear-learning paradigm, with SDS-FRL, I have revealed an
increase in synaptic density specific to GluA1-containing AMPA receptors in the CA1 area.
The intrasynaptic distribution of GluA1 also changed from the periphery to center-preferred
pattern. Furthermore, this synaptic plasticity was evident selectively in stratum radiatum but
not stratum oriens, and in the CA1 subregion proximal but not distal to CA2. These findings
further contribute to our understanding of how specific hippocampal subregions and AMPA
receptor subunits are involved in physiological learning.
Although the immunolabeling results above shed light on subunit-specific plasticity in
AMPAR distribution, no tools to visualize and study the subunit composition at the single
channel level in situ have been available. Electron microscopy with conventional immunogold
labeling approaches has limitations in the single channel analysis because of the large size of
antibodies and steric hindrance hampering multiple subunit labeling of single channels. I
managed to develop a new chemical labeling system using a short peptide tag and small
synthetic probes, which form specific covalent bond with a cysteine residue in the tag fused to
proteins of interest (reactive tag system). I additionally made substantial progress into adapting
this system for AMPA receptor subunits.},
author = {Jevtic, Marijo},
issn = {2663-337X},
pages = {108},
publisher = {Institute of Science and Technology Austria},
title = {{Contextual fear learning induced changes in AMPA receptor subtypes along the proximodistal axis in dorsal hippocampus}},
doi = {10.15479/at:ista:11393},
year = {2022},
}
@article{11705,
abstract = {The broad implementation of thermoelectricity requires high-performance and low-cost materials. One possibility is employing surfactant-free solution synthesis to produce nanopowders. We propose the strategy of functionalizing “naked” particles’ surface by inorganic molecules to control the nanostructure and, consequently, thermoelectric performance. In particular, we use bismuth thiolates to functionalize surfactant-free SnTe particles’ surfaces. Upon thermal processing, bismuth thiolates decomposition renders SnTe-Bi2S3 nanocomposites with synergistic functions: 1) carrier concentration optimization by Bi doping; 2) Seebeck coefficient enhancement and bipolar effect suppression by energy filtering; and 3) lattice thermal conductivity reduction by small grain domains, grain boundaries and nanostructuration. Overall, the SnTe-Bi2S3 nanocomposites exhibit peak z T up to 1.3 at 873 K and an average z T of ≈0.6 at 300–873 K, which is among the highest reported for solution-processed SnTe.},
author = {Chang, Cheng and Liu, Yu and Lee, Seungho and Spadaro, Maria and Koskela, Kristopher M. and Kleinhanns, Tobias and Costanzo, Tommaso and Arbiol, Jordi and Brutchey, Richard L. and Ibáñez, Maria},
issn = {1521-3773},
journal = {Angewandte Chemie - International Edition},
number = {35},
publisher = {Wiley},
title = {{Surface functionalization of surfactant-free particles: A strategy to tailor the properties of nanocomposites for enhanced thermoelectric performance}},
doi = {10.1002/anie.202207002},
volume = {61},
year = {2022},
}
@article{11843,
abstract = {A key attribute of persistent or recurring bacterial infections is the ability of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and establish persistent infections. However, the molecular mechanisms and strategies by which bacteria actively circumvent the immune response of the host remain poorly understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide detection, on mouse dendritic cells (DCs) as a binding partner of FimH, the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids involved in CD14 binding are highly conserved across pathogenic and non-pathogenic strains. Binding of the pathogenic strain CFT073 to CD14 reduced DC migration by overactivation of integrins and blunted expression of co-stimulatory molecules by overactivating the NFAT (nuclear factor of activated T-cells) pathway, both rate-limiting factors of T cell activation. This response was binary at the single-cell level, but averaged in larger populations exposed to both piliated and non-piliated pathogens, presumably via the exchange of immunomodulatory cytokines. While defining an active molecular mechanism of immune evasion by pathogens, the interaction between FimH and CD14 represents a potential target to interfere with persistent and recurrent infections, such as urinary tract infections or Crohn’s disease.},
author = {Tomasek, Kathrin and Leithner, Alexander F and Glatzová, Ivana and Lukesch, Michael S. and Guet, Calin C and Sixt, Michael K},
issn = {2050-084X},
journal = {eLife},
publisher = {eLife Sciences Publications},
title = {{Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14}},
doi = {10.7554/eLife.78995},
volume = {11},
year = {2022},
}
@article{12065,
abstract = {Capacity, rate performance, and cycle life of aprotic Li–O2 batteries critically depend on reversible electrodeposition of Li2O2. Current understanding states surface-adsorbed versus solvated LiO2 controls Li2O2 growth as surface film or as large particles. Herein, we show that Li2O2 forms across a wide range of electrolytes, carbons, and current densities as particles via solution-mediated LiO2 disproportionation, bringing into question the prevalence of any surface growth under practical conditions. We describe a unified O2 reduction mechanism, which can explain all found capacity relations and Li2O2 morphologies with exclusive solution discharge. Determining particle morphology and achievable capacities are species mobilities, true areal rate, and the degree of LiO2 association in solution. Capacity is conclusively limited by mass transport through the tortuous Li2O2 rather than electron transport through a passivating Li2O2 film. Provided that species mobilities and surface growth are high, high capacities are also achieved with weakly solvating electrolytes, which were previously considered prototypical for low capacity via surface growth.},
author = {Prehal, Christian and Mondal, Soumyadip and Lovicar, Ludek and Freunberger, Stefan Alexander},
issn = {2380-8195},
journal = {ACS Energy Letters},
number = {9},
pages = {3112--3119},
publisher = {American Chemical Society},
title = {{Exclusive solution discharge in Li-O₂ batteries?}},
doi = {10.1021/acsenergylett.2c01711},
volume = {7},
year = {2022},
}
@article{12138,
abstract = {Complex I is the first enzyme in the respiratory chain, which is responsible for energy production in mitochondria and bacteria1. Complex I couples the transfer of two electrons from NADH to quinone and the translocation of four protons across the membrane2, but the coupling mechanism remains contentious. Here we present cryo-electron microscopy structures of Escherichia coli complex I (EcCI) in different redox states, including catalytic turnover. EcCI exists mostly in the open state, in which the quinone cavity is exposed to the cytosol, allowing access for water molecules, which enable quinone movements. Unlike the mammalian paralogues3, EcCI can convert to the closed state only during turnover, showing that closed and open states are genuine turnover intermediates. The open-to-closed transition results in the tightly engulfed quinone cavity being connected to the central axis of the membrane arm, a source of substrate protons. Consistently, the proportion of the closed state increases with increasing pH. We propose a detailed but straightforward and robust mechanism comprising a ‘domino effect’ series of proton transfers and electrostatic interactions: the forward wave (‘dominoes stacking’) primes the pump, and the reverse wave (‘dominoes falling’) results in the ejection of all pumped protons from the distal subunit NuoL. This mechanism explains why protons exit exclusively from the NuoL subunit and is supported by our mutagenesis data. We contend that this is a universal coupling mechanism of complex I and related enzymes.},
author = {Kravchuk, Vladyslav and Petrova, Olga and Kampjut, Domen and Wojciechowska-Bason, Anna and Breese, Zara and Sazanov, Leonid A},
issn = {1476-4687},
journal = {Nature},
keywords = {Multidisciplinary},
number = {7928},
pages = {808--814},
publisher = {Springer Nature},
title = {{A universal coupling mechanism of respiratory complex I}},
doi = {10.1038/s41586-022-05199-7},
volume = {609},
year = {2022},
}