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Now showing 1 - 8 of 8
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    Affinity for the Interface Underpins Potency of Antibodies Operating In Membrane Environments
    (Maryland Heights, MO : Cell Press, 2020) Rujas, Edurne; Insausti, Sara; Leaman, Daniel P.; Carravilla, Pablo; González-Resines, Saul; Monceaux, Valérie; Sánchez-Eugenia, Rubén; Garcıá-Porras, Miguel; Iloro, Ibon; Zhang, Lei; Elortza, Félix; Julien, Jean-Philippe; Saéz-Cirión, Asier; Zwick, Michael B.; Eggeling, Christian; Ojida, Akio; Domene, Carmen; Caaveiro, Jose M.M.; Nieva, José L.
    The contribution of membrane interfacial interactions to recognition of membrane-embedded antigens by antibodies is currently unclear. This report demonstrates the optimization of this type of antibodies via chemical modification of regions near the membrane but not directly involved in the recognition of the epitope. Using the HIV-1 antibody 10E8 as a model, linear and polycyclic synthetic aromatic compounds are introduced at selected sites. Molecular dynamics simulations predict the favorable interactions of these synthetic compounds with the viral lipid membrane, where the epitope of the HIV-1 glycoprotein Env is located. Chemical modification of 10E8 with aromatic acetamides facilitates the productive and specific recognition of the native antigen, partially buried in the crowded environment of the viral membrane, resulting in a dramatic increase of its capacity to block viral infection. These observations support the harnessing of interfacial affinity through site-selective chemical modification to optimize the function of antibodies that target membrane-proximal epitopes. © 2020 The Author(s)Rujas et al. describe the site-selective chemical modification of antibodies to improve the molecular recognition of epitopes at membrane surfaces. The modification using aromatic compounds dramatically enhanced the virus neutralization potency and native antigen binding efficiency of HIV-1 antibodies directed against the membrane-embedded MPER epitope. © 2020 The Author(s)
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    Electrocatalytic fuel cell desalination for continuous energy and freshwater generation
    (Maryland Heights, MO : Cell Press, 2021) Zhang, Yuan; Wang, Lei; Presser, Volker
    Advanced hydrogen technologies contribute essentially to the decarbonization of our industrialized world. Large-scale hydrogen production would benefit from using the abundantly available water reservoir of our planet’s oceans. Current seawater-desalination technologies suffer from high energy consumption, high cost, or low performance. Here, we report technology for water desalination at seawater molarity, based on a polymer ion-exchange membrane fuel cell. By continuously supplying hydrogen and oxygen to the cell, a 160-mM concentration decrease from an initial value of 600 mM is accomplished within 40 h for a 55-mL reservoir. This device’s desalination rate in 600 mM NaCl and substitute ocean water are 18 g/m2/h and 16 g/m2/h, respectively. In addition, by removing 1 g of NaCl, 67 mWh of electric energy is generated. This proof-of-concept work shows the high application potential for sustainable fuel-cell desalination (FCD) using hydrogen as an energy carrier.
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    Flotillin-Dependent Membrane Microdomains Are Required for Functional Phagolysosomes against Fungal Infections
    (Maryland Heights, MO : Cell Press, 2020) Schmidt, Franziska; Thywißen, Andreas; Goldmann, Marie; Cunha, Cristina; Cseresnyés, Zoltán; Schmidt, Hella; Rafiq, Muhammad; Galiani, Silvia; Gräler, Markus H.; Chamilos, Georgios; Lacerda, João; Campos, António, Jr.; Eggeling, Christian; Figge, Marc Thilo; Heinekamp, Thorsten; Filler, Scott G.; Carvalho, Agostinho; Brakhage, Axel A.
    Schmidt el al. show that lipid rafts in phagolysosomal membranes of macrophages depend on flotillins. Lipid rafts are required for assembly of vATPase and NADPH oxidase. Conidia of the human-pathogenic fungus Aspergillus fumigatus dysregulate assembly of flotillin-dependent lipid rafts in the phagolysosomal membrane and can thereby escape phagolysosomal digestion. © 2020 The Author(s)Lipid rafts form signaling platforms on biological membranes with incompletely characterized role in immune response to infection. Here we report that lipid-raft microdomains are essential components of phagolysosomal membranes of macrophages and depend on flotillins. Genetic deletion of flotillins demonstrates that the assembly of both major defense complexes vATPase and NADPH oxidase requires membrane microdomains. Furthermore, we describe a virulence mechanism leading to dysregulation of membrane microdomains by melanized wild-type conidia of the important human-pathogenic fungus Aspergillus fumigatus resulting in reduced phagolysosomal acidification. We show that phagolysosomes with ingested melanized conidia contain a reduced amount of free Ca2+ ions and that inhibition of Ca2+-dependent calmodulin activity led to reduced lipid-raft formation. We identify a single-nucleotide polymorphism in the human FLOT1 gene resulting in heightened susceptibility for invasive aspergillosis in hematopoietic stem cell transplant recipients. Collectively, flotillin-dependent microdomains on the phagolysosomal membrane play an essential role in protective antifungal immunity. © 2020 The Author(s)
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    During early stages of cancer, neutrophils initiate anti-tumor immune responses in tumor-draining lymph nodes
    (Maryland Heights, MO : Cell Press, 2022) Pylaeva, Ekaterina; Korschunow, Georg; Spyra, Ilona; Bordbari, Sharareh; Siakaeva, Elena; Ozel, Irem; Domnich, Maksim; Squire, Anthony; Hasenberg, Anja; Thangavelu, Kruthika; Hussain, Timon; Goetz, Moritz; Lang, Karl S; Gunzer, Matthias; Hansen, Wiebke; Buer, Jan; Bankfalvi, Agnes; Lang, Stephan; Jablonska, Jadwiga
    Tumor-draining lymph nodes (LNs) play a crucial role during cancer spread and in initiation of anti-cancer adaptive immunity. Neutrophils form a substantial population of cells in LNs with poorly understood functions. Here, we demonstrate that, during head and neck cancer (HNC) progression, tumor-associated neutrophils transmigrate to LNs and shape anti-tumor responses in a stage-dependent manner. In metastasis-free stages (N0), neutrophils develop an antigen-presenting phenotype (HLA-DR+CD80+CD86+ICAM1+PD-L1-) and stimulate T cells (CD27+Ki67highPD-1-). LN metastases release GM-CSF and via STAT3 trigger development of PD-L1+ immunosuppressive neutrophils, which repress T cell responses. The accumulation of neutrophils in T cell-rich zones of LNs in N0 constitutes a positive predictor for 5-year survival, while increased numbers of neutrophils in LNs of N1-3 stages predict poor prognosis in HNC. These results suggest a dual role of neutrophils as essential regulators of anti-cancer immunity in LNs and argue for approaches fostering immunostimulatory activity of these cells during cancer therapy.
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    Ionophobicity of carbon sub-nanometer pores enables efficient desalination at high salinity
    (Maryland Heights, MO : Cell Press, 2022) Zhang, Yuan; Prehal, Christian; Jiang, Huili; Liu, Yang; Feng, Guang; Presser, Volker
    Electrochemical seawater desalination has drawn significant attention as an energy-efficient technique to address the global issue of water remediation. Microporous carbons, that is, carbons with pore sizes smaller than 2 nm, are commonly used for capacitive deionization. However, micropores are ineffective for capacitive deionization at high molar strength because of their inability to permselectively uptake ions. In our work, we combine experimental work with molecular dynamics simulation and reveal the ability of sub-nanometer pores (ultramicropores) to effectively desalinate aqueous media at seawater-like molar strength. This is done without any ion-exchange membrane. The desalination capacity in 600 mM reaches 12 mg/g, with a charge efficiency of 94% and high cycling stability over 200 cycles (97% of charge efficiency retention). Using molecular dynamic simulations and providing experimental data, our work makes it possible both to understand and to calculate desalination capacity and charge efficiency at high molar strength as a function of pore size.
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    Best practice for electrochemical water desalination data generation and analysis
    (Maryland Heights, MO : Cell Press, 2023) Torkamanzadeh, Mohammad; Kök, Cansu; Burger, Peter Rolf; Ren, Panyu; Zhang, Yuan; Lee, Juhan; Kim, Choonsoo; Presser, Volker
    Electrochemical desalination shows promise for ion-selective, energy-efficient water desalination. This work reviews performance metrics commonly used for electrochemical desalination. We provide a step-by-step guide on acquiring, processing, and calculating raw desalination data, emphasizing informative and reliable figures of merit. A typical experiment uses calibrated conductivity probes to relate measured conductivity to concentration. Using a standard electrochemical desalination cell with activated carbon electrodes, we demonstrate the calculation of desalination capacity, charge efficiency, energy consumption, and ion selectivity metrics. We address potential pitfalls in performance metric calculations, including leakage current (charge) considerations and aging of conductivity probes, which can lead to inaccurate results. The relationships between pH, temperature, and conductivity are explored, highlighting their influence on final concentrations. Finally, we provide a checklist for calculating performance metrics and planning electrochemical desalination tests to ensure accuracy and reliability. Additionally, we offer simplified spreadsheet tools to aid data processing, system design, estimations, and upscaling.
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    An engineered coccolith-based hybrid that transforms light into swarming motion
    (Maryland Heights, MO : Cell Press, 2021) Lomora, Mihai; Larrañaga, Aitor; Rodriguez-Emmenegger, Cesar; Rodriguez, Brian; Dinu, Ionel Adrian; Sarasua, Jose-Ramon; Pandit, Abhay
    Translating energy into swarming motion for miniature entities remains a challenge. This translation requires simultaneously breaking the symmetry of the system to enable locomotion and a coupling effect between the objects that are part of the population to induce the collective motion. Here, we report on Robocoliths, engineered Emiliania huxleyi (EHUX) coccolith-based miniature hybrid entities capable of swarming behavior. EHUX coccoliths are characterized by an asymmetric morphology that allows breaking symmetry, playing a central role in generating a net force and directed motion. Their activation with the bioinspired material polydopamine not only endows the asymmetric coccoliths with advanced functionalities, such as thermal- and energy-harvesting responsiveness under visible light exposure to display a collective behavior (i.e., swarming), but it also provides a functional surface from which antifouling polymer brushes are grown. In this context, Robocoliths pave the way for the next generation of multifunctional swarming bio-micromachines. © 2021 The Author(s)Establishment of controlled nano- and mesoscopic energized entities that gather, in a concerted effort, into motile aggregated patterns is at the forefront of scientific discovery. Lomora et al. report on coccolith-polydopamine hybrids (Robocoliths) that heat and move collectively upon light excitation and accommodate antifouling brushes on their surface. © 2021 The Author(s)
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    Engineered living hydrogels for robust biocatalysis in pure organic solvents
    (Maryland Heights, MO : Cell Press, 2022) Gao, Liang; Feng, Lilin; Sauer, Daniel F.; Wittwer, Malte; Hu, Yong; Schiffels, Johannes; Li, Xin
    Engineered living hydrogels that can protect cells from harsh environments have achieved preliminary successes in biomedicine and environmental remediation. However, their biocatalytic applications in pure organic solvents have not been explored. Here, living hydrogels were engineered by integrating genetically modified Escherichia coli cells into alginate hydrogels for robust biocatalysis in pure organic solvents. The biocompatible hydrogels could not only support cell growth and diminish cell escape but could also act as protective matrices to improve organic solvent tolerance, thereby prolonging catalytic activity of whole-cell biocatalysts. Moreover, the influence of hydrogel microenvironments on biocatalytic efficiency was thoroughly investigated. Importantly, the versatility of engineered living hydrogels paves the way to achieve robust biocatalytic efficiency in a variety of pure organic co-solvents. Overall, we are able to engineer living hydrogels for regio-selective synthesis in pure organic solvents, which may be particularly useful for the innovation of living hydrogels in biocatalysis.