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  Subjects -> SCIENCES: COMPREHENSIVE WORKS (Total: 426 journals)
Showing 1 - 200 of 265 Journals sorted alphabetically
AAS Open Research     Open Access   (Followers: 2)
ABC Journal of Advanced Research     Open Access  
Academic Voices : A Multidisciplinary Journal     Open Access   (Followers: 2)
Accountability in Research: Policies and Quality Assurance     Hybrid Journal   (Followers: 20)
Acta Materialia Transilvanica     Open Access  
Acta Nova     Open Access   (Followers: 1)
Acta Scientifica Malaysia     Open Access   (Followers: 1)
Acta Scientifica Naturalis     Open Access   (Followers: 3)
Adıyaman University Journal of Science     Open Access  
Advanced Science     Open Access   (Followers: 13)
Advanced Science, Engineering and Medicine     Partially Free   (Followers: 10)
Advanced Theory and Simulations     Hybrid Journal   (Followers: 5)
Advances in Research     Open Access  
Advances in Science and Technology     Full-text available via subscription   (Followers: 17)
African Journal of Science, Technology, Innovation and Development     Hybrid Journal   (Followers: 8)
Afrique Science : Revue Internationale des Sciences et Technologie     Open Access   (Followers: 2)
AFRREV STECH : An International Journal of Science and Technology     Open Access   (Followers: 4)
American Academic & Scholarly Research Journal     Open Access   (Followers: 6)
American Journal of Applied Sciences     Open Access   (Followers: 27)
American Journal of Humanities and Social Sciences     Open Access   (Followers: 14)
ANALES de la Universidad Central del Ecuador     Open Access   (Followers: 3)
Anales del Instituto de la Patagonia     Open Access  
Applied Mathematics and Nonlinear Sciences     Open Access   (Followers: 1)
Apuntes de Ciencia & Sociedad     Open Access  
Arab Journal of Basic and Applied Sciences     Open Access  
Arabian Journal for Science and Engineering     Hybrid Journal   (Followers: 5)
Archives Internationales d'Histoire des Sciences     Partially Free   (Followers: 6)
Archives of Current Research International     Open Access  
ARO. The Scientific Journal of Koya University     Open Access  
ARPHA Conference Abstracts     Open Access   (Followers: 6)
ARPHA Proceedings     Open Access   (Followers: 4)
ArtefaCToS : Revista de estudios sobre la ciencia y la tecnología     Open Access   (Followers: 1)
Asia-Pacific Journal of Science and Technology     Open Access  
Asian Journal of Advanced Research and Reports     Open Access   (Followers: 2)
Asian Journal of Applied Science and Engineering     Open Access   (Followers: 2)
Asian Journal of Scientific Research     Open Access   (Followers: 3)
Asian Journal of Technology Innovation     Hybrid Journal   (Followers: 7)
Australian Field Ornithology     Full-text available via subscription   (Followers: 4)
Australian Journal of Social Issues     Hybrid Journal   (Followers: 7)
Avances en Ciencias e Ingeniería     Open Access  
AZimuth     Full-text available via subscription   (Followers: 2)
Bangladesh Journal of Scientific Research     Open Access   (Followers: 1)
Beni-Suef University Journal of Basic and Applied Sciences     Open Access   (Followers: 3)
Berichte Zur Wissenschaftsgeschichte     Hybrid Journal   (Followers: 10)
Berkeley Scientific Journal     Full-text available via subscription  
BIBECHANA     Open Access   (Followers: 2)
BibNum     Open Access  
Bilge International Journal of Science and Technology Research     Open Access   (Followers: 1)
Bioethics Research Notes     Full-text available via subscription   (Followers: 16)
Bistua : Revista de la Facultad de Ciencias Básicas     Open Access  
BJHS Themes     Open Access  
Black Sea Journal of Engineering and Science     Open Access  
Borneo Journal of Resource Science and Technology     Open Access  
Brazilian Journal of Science and Technology     Open Access   (Followers: 2)
Bulletin de la Société Royale des Sciences de Liège     Open Access  
Bulletin of the National Research Centre     Open Access  
Butlletí de la Institució Catalana d'Història Natural     Open Access  
Central European Journal of Clinical Research     Open Access  
Chain Reaction     Full-text available via subscription  
Ciencia & Natura     Open Access   (Followers: 1)
Ciencia Amazónica (Iquitos)     Open Access   (Followers: 1)
Ciencia en Desarrollo     Open Access   (Followers: 2)
Ciencia en su PC     Open Access   (Followers: 1)
Ciencia Ergo Sum     Open Access  
Ciência ET Praxis     Open Access  
Ciencia y Tecnología     Open Access  
Ciencia, Docencia y Tecnología     Open Access  
Ciencias Holguin     Open Access   (Followers: 2)
CienciaUAT     Open Access   (Followers: 1)
Citizen Science : Theory and Practice     Open Access   (Followers: 2)
Communications Faculty of Sciences University of Ankara Series A2-A3 Physical Sciences and Engineering     Open Access  
Communications in Applied Sciences     Open Access  
Comprehensive Therapy     Hybrid Journal   (Followers: 3)
Comunicata Scientiae     Open Access   (Followers: 1)
ConCiencia     Open Access  
Conference Papers in Science     Open Access   (Followers: 2)
Configurations     Full-text available via subscription   (Followers: 10)
COSMOS     Hybrid Journal  
Crea Ciencia Revista Científica     Open Access   (Followers: 2)
Cuadernos de Investigación UNED     Open Access  
Current Issues in Criminal Justice     Hybrid Journal   (Followers: 15)
Current Research in Geoscience     Open Access   (Followers: 8)
Dalat University Journal of Science     Open Access  
Data     Open Access   (Followers: 3)
Data Curation Profiles Directory     Open Access   (Followers: 4)
Dhaka University Journal of Science     Open Access  
Dharmakarya     Open Access  
Diálogos Interdisciplinares     Open Access  
Digithum     Open Access   (Followers: 2)
Discover Sustainability     Open Access   (Followers: 3)
Einstein (São Paulo)     Open Access  
Ekaia : EHUko Zientzia eta Teknologia aldizkaria     Open Access  
Elkawnie : Journal of Islamic Science and Technology     Open Access  
Emergent Scientist     Open Access  
Enhancing Learning in the Social Sciences     Open Access   (Followers: 9)
Enseñanza de las Ciencias : Revista de Investigación y Experiencias Didácticas     Open Access  
Entramado     Open Access  
Entre Ciencia e Ingeniería     Open Access   (Followers: 1)
Epiphany     Open Access   (Followers: 4)
Episteme Transversalis     Open Access  
Ergo     Open Access  
Estação Científica (UNIFAP)     Open Access   (Followers: 1)
Ethiopian Journal of Education and Sciences     Open Access   (Followers: 6)
Ethiopian Journal of Science and Technology     Open Access  
Ethiopian Journal of Sciences and Sustainable Development     Open Access   (Followers: 6)
European Online Journal of Natural and Social Sciences     Open Access   (Followers: 12)
European Scientific Journal     Open Access   (Followers: 10)
Evidência - Ciência e Biotecnologia - Interdisciplinar     Open Access  
Exchanges : the Warwick Research Journal     Open Access   (Followers: 2)
Experimental Results     Open Access  
Extensionismo, Innovación y Transferencia Tecnológica     Open Access   (Followers: 3)
Facets     Open Access  
Fides et Ratio : Revista de Difusión Cultural y Científica     Open Access   (Followers: 1)
Fırat University Turkish Journal of Science & Technology     Open Access  
Fontanus     Open Access  
Forensic Science Policy & Management: An International Journal     Hybrid Journal   (Followers: 372)
Frontiers for Young Minds     Open Access  
Frontiers in Climate     Open Access   (Followers: 3)
Frontiers in Science     Open Access   (Followers: 1)
Futures & Foresight Science     Hybrid Journal   (Followers: 4)
Gaudium Sciendi     Open Access   (Followers: 1)
Gazi University Journal of Science     Open Access  
Ghana Studies     Full-text available via subscription   (Followers: 15)
Global Journal of Pure and Applied Sciences     Full-text available via subscription  
Global Journal of Science Frontier Research     Open Access   (Followers: 2)
Globe, The     Full-text available via subscription   (Followers: 4)
HardwareX     Open Access  
Heidelberger Jahrbücher Online     Open Access  
Heliyon     Open Access  
Himalayan Journal of Science and Technology     Open Access   (Followers: 1)
History of Science and Technology     Open Access  
Hoosier Science Teacher     Open Access  
Iberoamerican Journal of Science Measurement and Communication     Open Access  
Impact     Open Access   (Followers: 2)
Indian Journal of History of Science     Hybrid Journal  
Indonesian Journal of Fundamental Sciences     Open Access  
Indonesian Journal of Science and Mathematics Education     Open Access   (Followers: 4)
Indonesian Journal of Science and Technology     Open Access  
Ingenieria y Ciencia     Open Access   (Followers: 1)
Innovare : Revista de ciencia y tecnología     Open Access  
Instruments     Open Access  
Integrated Research Advances     Open Access  
Interciencia     Open Access   (Followers: 1)
Interface Focus     Full-text available via subscription  
International Annals of Science     Open Access  
International Archives of Science and Technology     Open Access  
International Journal of Academic Research in Business, Arts & Science     Open Access   (Followers: 2)
International Journal of Advanced Multidisciplinary Research and Review     Open Access  
International Journal of Advancement in Education and Social Sciences     Open Access   (Followers: 1)
International Journal of Advances in Engineering, Science and Technology     Open Access   (Followers: 3)
International Journal of Applied Science     Open Access  
International Journal of Basic and Applied Sciences     Open Access   (Followers: 4)
International Journal of Computational and Experimental Science and Engineering (IJCESEN)     Open Access  
International Journal of Culture and Modernity     Open Access  
International Journal of Engineering, Science and Technology     Open Access  
International Journal of Innovation and Applied Studies     Open Access   (Followers: 12)
International Journal of Innovative Research and Scientific Studies     Open Access   (Followers: 6)
International Journal of Innovative Research in Social and Natural Sciences     Open Access   (Followers: 2)
International Journal of Network Science     Hybrid Journal   (Followers: 3)
International Journal of Recent Contributions from Engineering, Science & IT     Open Access   (Followers: 1)
International Journal of Research in Science     Open Access   (Followers: 2)
International Journal of Science & Emerging Technologies     Open Access   (Followers: 1)
International Journal of Sciences : Basic and Applied Research     Open Access  
International Journal of Social Sciences and Management     Open Access   (Followers: 3)
International Journal of Technology Policy and Law     Hybrid Journal   (Followers: 7)
International Letters of Social and Humanistic Sciences     Open Access   (Followers: 1)
International Review of Applied Sciences     Open Access  
InterSciencePlace     Open Access   (Followers: 1)
Investiga : TEC     Open Access  
Investigación Joven     Open Access  
Investigación Valdizana     Open Access  
Investigacion y Ciencia     Open Access   (Followers: 1)
Iranian Journal of Science and Technology, Transactions A : Science     Hybrid Journal  
iScience     Open Access   (Followers: 1)
Issues in Science & Technology     Free   (Followers: 7)
Istituto Lombardo - Accademia di Scienze e Lettere - Rendiconti di Scienze     Open Access  
Ithaca : Viaggio nella Scienza     Open Access  
J : Multidisciplinary Scientific Journal     Open Access  
Jaunujų mokslininkų darbai     Open Access  
Journal de la Recherche Scientifique de l'Universite de Lome     Full-text available via subscription   (Followers: 2)
Journal for New Generation Sciences     Open Access   (Followers: 3)
Journal of Chromatography & Separation Techniques     Open Access   (Followers: 12)
Journal of Advanced Research     Open Access   (Followers: 3)
Journal of Al-Qadisiyah for Pure Science     Open Access   (Followers: 1)
Journal of Alasmarya University     Open Access  
Journal of Analytical Science & Technology     Open Access   (Followers: 6)
Journal of Applied Science and Technology     Full-text available via subscription   (Followers: 1)
Journal of Applied Sciences and Environmental Management     Open Access   (Followers: 3)
Journal of Big History     Open Access   (Followers: 3)
Journal of Composites Science     Open Access   (Followers: 3)
Journal of Critical Thought and Praxis     Open Access   (Followers: 2)
Journal of Deliberative Mechanisms in Science     Open Access  
Journal of Diversity Management     Open Access   (Followers: 6)
Journal of Indian Council of Philosophical Research     Hybrid Journal  
Journal of Institute of Science and Technology     Open Access  
Journal of Integrated Science and Technology     Open Access  
Journal of Interaction Science     Open Access   (Followers: 1)
Journal of Kerbala University     Open Access   (Followers: 1)
Journal of King Saud University - Science     Open Access   (Followers: 1)
Journal of Law, Information and Science     Full-text available via subscription   (Followers: 20)

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iScience
Number of Followers: 1  

  This is an Open Access Journal Open Access journal
ISSN (Online) 2589-0042
Published by Elsevier Homepage  [3304 journals]
  • COMMD10-Guided Phagolysosomal Maturation Promotes Clearance of
           Staphylococcus aureus in Macrophages

    • Abstract: Publication date: 26 April 2019Source: iScience, Volume 14Author(s): Shani Ben Shlomo, Odelia Mouhadeb, Keren Cohen, Chen Varol, Nathan GluckSummaryStaphylococcus aureus is a major cause of infectious disease. Liver Kupffer cells (KCs) are responsible for sequestering and destroying S. aureus through the phagolysosomal pathway. Proteins belonging to the COMMD family emerge as key intracellular regulators of protein trafficking, but the role of COMMD10 in macrophage-mediated S. aureus eradication is unknown. Here we report that COMMD10 in macrophages was necessary for its timely elimination, as demonstrated with two different S. aureus subspecies. In vivo, COMMD10-deficient liver KCs exhibited impaired clearance of systemic S. aureus infection. S. aureus-infected COMMD10-deficient macrophages exhibited impaired activation of the transcription factor EB, resulting in reduced lysosomal biogenesis. Moreover, S. aureus-initiated phagolysosomal maturation and function were significantly attenuated in COMMD10-deficient macrophages. Finally, expression of COMMD/CCDC22/CCDC93 complex, linked to phagolysosomal maturation, was reduced by COMMD10 deficiency. Collectively, these results support an important role for COMMD10 in instructing macrophage phagolysosomal biogenesis and maturation during S. aureus infection.Graphical Graphical abstract for this article
       
  • Sodium Dodecyl Sulfate Preferentially Promotes Enclathration of Methane in
           Mixed Methane-Tetrahydrofuran Hydrates

    • Abstract: Publication date: 26 April 2019Source: iScience, Volume 14Author(s): Asheesh Kumar, Rajnish Kumar, Praveen LingaSummaryMethane storage in mixed hydrates is advantageous due to faster kinetics and added stability. However, capacity needs to be improved. Here we study mixed hydrates of methane (CH4) and tetrahydrofuran (THF), in the presence of sodium dodecyl sulfate (SDS) as a kinetic promoter for hydrate formation. We report the co-existence of pure methane (sI) and mixed CH4-THF hydrates (sII) in the presence of SDS; however, in the absence of SDS, co-existence of pure THF (sII) and mixed CH4-THF hydrates (sII) was observed. Thus the presence of SDS preferentially promotes the enclathration of methane over that of THF. Furthermore, through in situ Raman spectrometry, complemented by high-pressure differential scanning calorimeter, we present temperature-dependent methane occupancy in small and large cages of sI and sII hydrates. Our findings offer new insights for enhancing the methane storage capacity in more stable sII hydrate configuration for large-scale methane storage via solidified natural gas technology.Graphical Graphical abstract for this article
       
  • Decoding the Inversion Symmetry Underlying Transcription Factor
           DNA-Binding Specificity and Functionality in the Genome

    • Abstract: Publication date: Available online 6 April 2019Source: iScienceAuthor(s): Laurel A. Coons, Adam B. Burkholder, Sylvia C. Hewitt, Donald P. McDonnell, Kenneth S. KorachSummaryUnderstanding why a transcription factor (TF) binds to a specific DNA element in the genome and whether that binding event affects transcriptional output remains a great challenge. In this study, we demonstrate that TF binding in the genome follows inversion symmetry (IS). In addition, the specific DNA elements where TFs bind in the genome is determined by internal IS within the DNA element. These DNA-binding rules quantitatively define how TFs select the appropriate regulatory targets from a large number of similar DNA elements in the genome to elicit specific transcriptional and cellular responses. Importantly, we also demonstrate that these DNA-binding rules extend to DNA elements which do not support transcriptional activity. That is, the DNA-binding rules are obeyed, but the retention time of the TF at these nonfunctional DNA elements is not long enough to initiate/maintain transcription. We further demonstrate that IS is universal within the genome. Thus, IS is the DNA code that TFs use to interact with the genome, and dictates (in conjunction with known DNA sequence constraints) which of those interactions are functionally active.Graphical Graphical abstract for this article
       
  • Ants use multiple spatial memories and chemical pointers to navigate their
           nest

    • Abstract: Publication date: Available online 5 April 2019Source: iScienceAuthor(s): Yael Heyman, Yael Vilk, Ofer FeinermanSummaryAnimal navigation relies on the available environmental cues and, where present, visual cues typically dominate. While much is known about vision-assisted navigation, knowledge of navigation in the dark is scarce. Here, we combine individual tracking, dynamic modular nest structures, and spatially resolved chemical profiling to study how Camponotus fellah ants navigate within the dark labyrinth of their nest. We find that, contrary to ant navigation above ground, underground navigation cannot rely on long-range information. This limitation emphasizes the ants’ capabilities associated with other navigational strategies. Indeed, apart from gravity, underground navigation relies on self-referenced memories of multiple locations and on socially generated chemical cues placed at decision points away from the target. Moreover, the ants quickly readjust the weights attributed to these information sources in response to environmental changes. Generally, studying well-known behaviors in a variety of environmental contexts holds the potential of revealing new insights into animal cognition.Graphical Graphical abstract for this article
       
  • Enhanced fermion pairing and superfluidity by an imaginary magnetic field

    • Abstract: Publication date: Available online 3 April 2019Source: iScienceAuthor(s): Lihong Zhou, Xiaoling CuiWe show that an imaginary magnetic field(IMF), which can be generated in non-Hermitian systems with spin-dependent dissipations, can greatly enhance the s-wave pairing and superfluidity of spin-1/2 fermions, in distinct contrast to the effect of a real magnetic field. The enhancement can be attributed to the increased coupling constant in low-energy space and the reduced spin gap in forming singlet pairs. We have demonstrated this effect in a number of different fermion systems with and without spin-orbit coupling, using both the two-body exact solution and many-body mean-field theory. Our results suggest an alternative route towards strong fermion superfluid with high superfluid transition temperature.Graphical Graphical abstract for this article
       
  • Liquid Crystals Comprising π-Electronic Ions from
           Porphyrin–AuIII Complexes

    • Abstract: Publication date: Available online 1 April 2019Source: iScienceAuthor(s): Yohei Haketa, Yuya Bando, Yoshifumi Sasano, Hiroki Tanaka, Nobuhiro Yasuda, Ichiro Hisaki, Hiromitsu MaedaSummaryPorphyrin–AuIII complexes were found to act as π-electronic cations which can combine with various counteranions, including π-electronic anions. Single-crystal X-ray analyses revealed the formation of assemblies with contributions of charge-by-charge and charge-segregated assemblies, depending on the geometry and electronic state of the counteranions. Porphyrin–AuIII complexes possessing aliphatic alkyl chains formed dimension-controlled ion-pairing assemblies as thermotropic liquid crystals, whose ionic components were highly organized by π–π stacking and electrostatic interactions.Graphical Graphical abstract for this article
       
  • Vitamin K2-dependent GGCX and MGP are required for homeostatic calcium
           regulation of sperm maturation

    • Abstract: Publication date: Available online 29 March 2019Source: iScienceAuthor(s): He Ma, Bao Li Zhang, Bao Ying Liu, Shuo Shi, Da Yuan Gao, Tian Cheng Zhang, Hui Juan Shi, Zhen Li, Winnie Waichi ShumSummaryLow calcium microenvironment is essential for spermatozoa to mature in the epididymis, however, it remains unclear how dysregulation of epididymal luminal calcium is associated with male infertility. Using a warfarin-induced vitamin K2 deficiency rat model, we found that vitamin K dependent γ-glutamyl carboxylase (GGCX) and matrix Gla protein (MGP) were essential in extracellular calcium signalling of the intercellular communication required for epididymal sperm maturation. We found that GGCX and MGP co-localized in the vesicular structures of epididymal cells and spermatozoa. Calcium-regulated MGP binds to proteins in a biphasic-manner; sub-millimolar calcium enhances whereas excessive calcium inhibits the binding. Bioinformatic analysis of the calcium-dependent MGP-bound proteome revealed that vesicle-mediated transport and membrane trafficking underlie the intercellular communication networks. We also identified an SNP mutation, rs699664, in the GGCX gene of infertile men with asthenozoospermia. Overall, we revealed that the GGCX-MGP system is integrated with the intercellular calcium signalling to promote sperm maturation.Graphical Graphical abstract for this article
       
  • Anomalous Dome-like Superconductivity in RE2(Cu1-x Ni x )5As3O2 (RE=La,
           Pr, Nd)

    • Abstract: Publication date: Available online 29 March 2019Source: iScienceAuthor(s): Xu Chen, Jiangang Guo, Chunsheng Gong, Erjian Cheng, Congcong Le, Ning Liu, Tianping Ying, Qinghua Zhang, Jiangping Hu, Shiyan Li, Xiaolong ChenSummarySignificant manifestation of interplay of superconductivity and charge density wave, spin density wave or magnetism is dome-like superconducting critical temperature (Tc) in cuprate, iron-based and heavy Fermion superconductors. Pesudogap, quantum critical point and strange metal emerge in different doping ranges. Exploring dome-like Tc in new superconductors is of interest to detect emergent effects. Here, we report that the observation of superconductivity in new layered Cu-based compound RE2Cu5As3O2 (RE=La, Pr, Nd), in which the Tc exhibits dome-like variation with maximum Tc of 2.5 K, 1.2 K and 1.0 K as substituting Cu by large amount of Ni ions. Simultaneously, the structural parameters like As-As bond length and c/a ratio exhibit unusual variations as Ni-doping level goes through the optimal value. The robustness of superconductivity, up to 60% of Ni doping, reveals the unexpected impurity effect on inducing and enhancing superconductivity in this novel layered materials.Graphical Graphical abstract for this article
       
  • BODIPY-Decorated Nanoscale Covalent Organic Frameworks for Photodynamic
           Therapy

    • Abstract: Publication date: Available online 29 March 2019Source: iScienceAuthor(s): Qun Guan, Dan-Dan Fu, Yan-An Li, Xiang-Mei Kong, Zhi-Yuan Wei, Wen-Yan Li, Shao-Jun Zhang, Yu-Bin DongSummaryCovalent organic frameworks (COFs), an emerging class of organic porous materials, have attracted intense attention due to their versatile applications. However, the deliberate fabrication of COF-based nanomaterials for nanomedical application remains challenging due to difficulty in their size- and structure-controlled synthesis, and poor aqueous dispersibility. Herein, we report two BODIPY-decorated nanoscale COFs (NCOFs) which were prepared by the Schiff-base condensation of the free end –CHO (bonding defects in COFs) on the established imine-based NCOFs with the amino-substituted organic photosensitizer BODIPY via “bonding defects functionalization” approach. Thus, BODIPY has been successfully nanocrystallized via NCOF platform, and can be used for photodynamic therapy (PDT) to treat tumors. These NCOF-based PDT agents featured nanometer size (∼110 nm), low dark toxicity and high phototoxicity as evidenced by in vitro and in vivo experiments. Moreover, the “bonding defects functionalization” approach might open up new avenues for the fabrication of additional COF-based platforms for biomedical treatment.Graphical Graphical abstract for this article
       
  • Imaging through the whole brain of Drosophila at λ/20
           super-resolution

    • Abstract: Publication date: Available online 28 March 2019Source: iScienceAuthor(s): Han-Yuan Lin, Li-An Chu, Hsuan Yang, Kuo-Jen Hsu, Yen-Yin Lin, Keng-Hui Lin, Shi-Wei Chu, Ann-Shyn Chiang Recently, many super-resolution technologies were demonstrated, significantly impacting biological studies by observation of cellular structures down to nanometer precision. However, current super-resolution techniques mostly rely on wavefront engineering or wide-field imaging of signal blinking/fluctuation, and thus imaging depths are limited due to tissue scattering/aberration. Here we present a technique that is capable of imaging through an intact Drosophila brain with 20 nm lateral resolution at ∼200 μm depth. The spatial resolution is provided by molecular localization of a photoconvertible fluorescent protein Kaede, whose red-form is found to exhibit blinking state. The deep-tissue observation is enabled by optical sectioning of spinning disk microscopy, as well as reduced scattering from optical clearing. Together these techniques are readily available for many biologists, providing three-dimensional resolution of densely entangled dendritic fibers in a complete Drosophila brain. The method paves the way toward whole-brain neural network studies, and is applicable to other high-resolution bio-imaging.Graphical Graphical abstract for this article
       
  • Estimating sample-specific regulatory networks

    • Abstract: Publication date: Available online 28 March 2019Source: iScienceAuthor(s): Marieke Lydia Kuijjer, Matthew George Tung, GuoCheng Yuan, John Quackenbush, Kimberly GlassSummaryBiological systems are driven by intricate interactions among molecules. Many methods have been developed that draw on large numbers of expression samples to infer connections between genes (or their products). The result is an aggregate network representing a single estimate for the likelihood of each interaction, or “edge,” in the network. While informative, aggregate models fail to capture population heterogeneity. Here we propose a method to reverse engineer sample-specific networks from aggregate networks. We demonstrate our approach in several contexts, including simulated, yeast microarray, and human lymphoblastoid cell line RNA-seq data. We use these sample-specific networks to study changes in network topology across time and to characterize shifts in gene regulation that were not apparent in the expression data. We believe generating sample-specific networks will greatly facilitate the application of network methods to large, complex, and heterogeneous multi-omic data sets, supporting the emerging field of precision network medicine.Graphical Graphical abstract for this article
       
  • Tumor-derived extracellular vesicles require β1 integrins to promote
           anchorage-independent growth

    • Abstract: Publication date: Available online 27 March 2019Source: iScienceAuthor(s): Rachel M. DeRita, Aejaz Sayeed, Vaughn Garcia, Shiv Ram Krishn, Christopher D. Shields, Srawasti Sarker, Andrea Friedman, Peter McCue, Sudheer Kumar Molugu, Ulrich Rodeck, Adam P. Dicker, Lucia R. LanguinoSummaryThe β1 integrins, known to promote cancer progression, are abundant in extracellular vesicles (EVs). We investigated whether prostate cancer (PrCa) EVs affect anchorage-independent growth and whether β1 integrins are required for this effect. Specifically using a cell line-based genetic rescue and an in vivo PrCa model, we show that gradient purified small EVs (sEVs) from either cancer cells or blood from tumor-bearing TRAMP mice promote anchorage-independent growth of PrCa cells. In contrast, sEVs from cultured PrCa cells harboring a shRNA to β1, from wild-type mice or from TRAMP mice carrying a β1 conditional ablation in the prostatic epithelium (β1pc-/-), do not. We find that sEVs, from cancer cells or TRAMP blood, are functional and co-express β1 and sEV markers; in contrast, sEVs from β1pc-/- /TRAMP or wild-type mice lack β1 and sEV markers. Our results demonstrate that β1 integrins in tumor cell-derived sEVs are required for stimulation of anchorage-independent growth.Graphical Graphical abstract for this article
       
  • The Transcription Factor ATF7 Controls Adipocyte Differentiation and
           Thermogenic Gene Programming

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Yang Liu, Toshio Maekawa, Keisuke Yoshida, Masafumi Muratani, Bruno Chatton, Shunsuke IshiiSummaryAdipocytes function as major players in the regulation of metabolic homeostasis, and factors contributing to adipocyte differentiation and function are promising targets for combatting obesity and associated metabolic disorders. Activating transcription factor 7 (ATF7), a stress-responsive chromatin regulator, is involved in energy metabolism, but the underlying mechanisms remain unknown. Herein, we showed that ATF7 is required for adipocyte differentiation and interacts with histone dimethyltransferase G9a in adipocytes to repress the expression of interferon-stimulated genes, which in turn suppress adipogenesis. Ablation of ATF7 promotes beige fat biogenesis in inguinal white adipose tissue. ATF7 binds to transcriptional regulatory regions of the gene encoding uncoupling protein 1, silencing it by controlling histone H3K9 dimethylation. Our findings demonstrate that ATF7 is a multifunctional adipocyte protein involved in the epigenetic control of development and function in adipose tissues.Graphical Graphical abstract for this article
       
  • Advanced Membranes and Learning Scale Required for Cost-Effective
           Post-combustion Carbon Capture

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Haibo ZhaiSummaryThis study offers an integrated vision for advanced membrane technology for post-combustion carbon capture. To inform development of new-generation materials, a plant-level techno-economic analysis is performed to explore major membrane property targets required for cost-effective CO2 capture. To be competitive with amine-based nth-of-a-kind (NOAK) technology or meet a more ambitious cost target for 90% CO2 capture, advanced membranes should have a higher CO2 permeance than 2,250 GPU and a higher CO2/N2 selectivity than 30 if their installed prices are higher than $50/m2. To assess learning experience required for advanced technology using such high-performance membranes toward commercialization, a hybrid approach that combines learning curves with the techno-economic analysis is applied to project the cumulative installed capacity necessary for the evolution from first-of-a-kind to NOAK systems. The estimated learning scale for advanced membrane technology is more than 10 GW, depending on multiple factors. Implications for research, development, and policy are discussed.Graphical Graphical abstract for this article
       
  • The RNA Processing Factor Y14 Participates in DNA Damage Response and
           Repair

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Tzu-Wei Chuang, Chia-Chen Lu, Chun-Hao Su, Pei-Yu Wu, Sarasvathi Easwvaran, Chi-Chieh Lee, Hung-Che Kuo, Kuan-Yang Hung, Kuo-Ming Lee, Ching-Yen Tsai, Woan-Yuh TarnSummaryDNA repair deficiency leads to genome instability and hence human disease. Depletion of the RNA processing factor Y14/RBM8A in cultured cells or Rbm8a haplodeficiency in the developing mouse cortex results in the accumulation of DNA damage. Y14 depletion differentially affected the expression of DNA damage response (DDR) factors and induced R-loops, both of which threaten genomic stability. Immunoprecipitation coupled with mass spectrometry revealed DDR factors as potential Y14-interacting partners. Further results confirmed that Y14 interacts with Ku and several DDR factors in an ATM-dependent manner. Y14 co-fractionated with Ku in chromatin-enriched fractions and further accumulated on chromatin upon DNA damage. Y14 knockdown delayed recruitment of DDR factors to DNA damage sites and formation of γH2AX foci and also led to Ku retention on chromatin. Accordingly, Y14 depletion compromised the efficiency of DNA end joining. Therefore Y14 likely plays a direct role in DNA damage repair via its interaction with DDR factors.Graphical Graphical abstract for this article
       
  • Dysregulation of Microglial Function Contributes to Neuronal Impairment in
           Mcoln1a-Deficient Zebrafish

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Wan Jin, Yimei Dai, Funing Li, Lu Zhu, Zhibin Huang, Wei Liu, Jianchao Li, Mingjie Zhang, Jiulin Du, Wenqing Zhang, Zilong WenSummaryType IV mucolipidosis (ML-IV) is a neurodegenerative lysosome storage disorder caused by mutations in the MCOLN1 gene. However, the cellular and molecular bases underlying the neuronal phenotypes of ML-IV disease remain elusive. Using a forward genetic screening, we identified a zebrafish mutant, biluo, that harbors a hypomorphic mutation in mcoln1a, one of the two zebrafish homologs of mammalian MCOLN1. The mcoln1a-deficient mutants display phenotypes partially recapitulating the key features of ML-IV disorder, including the accumulation of enlarged late endosomes in microglia and aberrant neuronal activities in both spontaneous and visual-evoking conditions in optic tectal neurons. We further show that the accumulation of enlarged late endosomes in microglia is caused by the impairment of late endosome and lysosome fusion and the aberrant neuronal activities can be partially rescued by the reconstitution of Mcoln1a function in microglia. Our findings suggest that dysregulation of microglial function may contribute to the development and progression of ML-IV disease.Graphical Graphical abstract for this article
       
  • Extracytoplasmic Function σ Factors Can Be Implemented as Robust
           Heterologous Genetic Switches in Bacillus subtilis

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Daniela Pinto, Franziska Dürr, Friederike Froriep, Dayane Araújo, Qiang Liu, Thorsten MascherSummaryIn bacteria, the promoter specificity of RNA polymerase is determined by interchangeable σ subunits. Extracytoplasmic function σ factors (ECFs) form the largest and most diverse family of alternative σ factors, and their suitability for constructing genetic switches and circuits was already demonstrated. However, a systematic study on how genetically determined perturbations affect the behavior of these switches is still lacking, which impairs our ability to predict their behavior in complex circuitry. Here, we implemented four ECF switches in Bacillus subtilis and comprehensively characterized their robustness toward genetic perturbations, including changes in copy number, protein stability, or antisense transcription. All switches show characteristic dose-response behavior that varies depending on the individual ECF-promoter pair. Most perturbations had performance costs. Although some general design rules could be derived, a detailed characterization of each ECF switch before implementation is recommended to understand and thereby accommodate its individual behavior.Graphical Graphical abstract for this article
       
  • Matching Mitochondrial DNA Haplotypes for Circumventing Tissue-Specific
           Segregation Bias

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Jianxin Pan, Li Wang, Charles Lu, Yanming Zhu, Zhunyuan Min, Xi Dong, Hongying ShaSummaryMitochondrial DNA (mtDNA) segregation associated with donor-recipient mtDNA mismatch in mitochondria replacement therapy leads to unknown risks. Here, to explore whether matching mtDNA haplotypes contributes to ameliorating segregation, we reproduced various degrees of heteroplasmic mice with three single nucleotide polymorphisms to monitor segregation severity. “Segregation” presented in tissues of heteroplasmic mice containing low-level donor mtDNA heteroplasmy, and disappeared as donor mtDNA heteroplasmy levels ascended. Meanwhile, we found that distribution of donor mtDNA among the blastomeres of preimplantation embryos from the heteroplasmic mice shared the same tendency as that in adult tissues. Statistical analysis showed that no selective replication of donor mtDNA occurred during lifespan. Tracking donor mtDNA distribution showed that uneven distribution of donor mtDNA among embryonic blastomeres gradually became even as donor mtDNA heteroplasmy increased, indicating that the “segregation” in tissues was inherited from the uneven distribution. Our finding suggested that donor-recipient mtDNA matching could circumvent segregation in mitochondria replacement therapy.Graphical Graphical abstract for this article
       
  • PRISMA: Protein Interaction Screen on Peptide Matrix Reveals Interaction
           Footprints and Modifications- Dependent Interactome of Intrinsically
           Disordered C/EBPb

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Gunnar Dittmar, Daniel Perez Hernandez, Elisabeth Kowenz-Leutz, Marieluise Kirchner, Günther Kahlert, Radoslaw Wesolowski, Katharina Baum, Maria Knoblich, Maria Hofstätter, Arnaud Muller, Jana Wolf, Ulf Reimer, Achim LeutzSummaryCCAAT enhancer-binding protein beta (C/EBPβ) is a pioneer transcription factor that specifies cell differentiation. C/EBPβ is intrinsically unstructured, a molecular feature common to many proteins involved in signal processing and epigenetics. The structure of C/EBPβ differs depending on alternative translation initiation and multiple post-translational modifications (PTM). Mutation of distinct PTM sites in C/EBPβ alters protein interactions and cell differentiation, suggesting that a C/EBPβ PTM indexing code determines epigenetic outcomes. Herein, we systematically explored the interactome of C/EBPβ using an array technique based on spot-synthesized C/EBPβ-derived linear tiling peptides with and without PTM, combined with mass spectrometric proteomic analysis of protein interactions. We identified interaction footprints of ∼1,300 proteins in nuclear extracts, many with chromatin modifying, chromatin remodeling, and RNA processing functions. The results suggest that C/EBPβ acts as a multi-tasking molecular switchboard, integrating signal-dependent modifications and structural plasticity to orchestrate interactions with numerous protein complexes directing cell fate and function.Graphical Graphical abstract for this article
       
  • Loss of the TAM Receptor Axl Ameliorates Severe Zika Virus Pathogenesis
           and Reduces Apoptosis in Microglia

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Andrew K. Hastings, Katherine Hastings, Ryuta Uraki, Jesse Hwang, Hallie Gaitsch, Khushwant Dhaliwal, Eric Williamson, Erol FikrigSummaryThe TAM receptor, Axl, has been implicated as a candidate entry receptor for Zika virus (ZIKV) infection but has been shown as inessential for virus infection in mice. To probe the role of Axl in murine ZIKV infection, we developed a mouse model lacking the Axl receptor and the interferon alpha/beta receptor (Ifnar−/−Axl−/−), conferring susceptibility to ZIKV. This model validated that Axl is not required for murine ZIKV infection and that mice lacking Axl are resistant to ZIKV pathogenesis. This resistance correlates to lower pro-interleukin-1β production and less apoptosis in microglia of ZIKV-infected mice. This apoptosis occurs through both intrinsic (caspase 9) and extrinsic (caspase 8) manners, and is age dependent, as younger Axl-deficient mice are susceptible to ZIKV pathogenesis. These findings suggest that Axl plays an important role in pathogenesis in the brain during ZIKV infection and indicates a potential role for Axl inhibitors as therapeutics during viral infection.Graphical Graphical abstract for this article
       
  • Functional Heterogeneity of Mouse Prostate Stromal Cells Revealed by
           Single-Cell RNA-Seq

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Oh-Joon Kwon, Yiqun Zhang, Yumei Li, Xing Wei, Li Zhang, Rui Chen, Chad J. Creighton, Li XinSummaryWe perform a single-cell RNA sequencing analysis to investigate the phenotypic and functional heterogeneity of the adult mouse prostate stromal cells. Our analysis identifies three major cell populations representing the smooth muscle cells and two types of fibroblast cells enriched by Sca-1 and CD90. The Sca-1+CD90+ fibroblast cells are in direct contact with the epithelial cells and express growth factors and genes associated with cell motility, developmental process, and androgen biosynthesis. This suggests that they may regulate epithelial cell survival and growth. The Sca-1+CD90-/low myofibroblast-like cells highly express genes associated with the extracellular matrix and cytokine-mediated signaling pathways, indicating a role in tissue repair and immune responses. The Sca-1+CD90-/low cells significantly suppress the capacity of the basal cells for bipotent differentiation in the prostate organoid assay. Collectively, we identify the surface markers enabling physical separation of stromal subpopulations and generate the gene expression profiles implying their cellular functions.Graphical Graphical abstract for this article
       
  • Wnt Signaling Directs Neuronal Polarity and Axonal Growth

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Eliana Stanganello, Eitan Erez Zahavi, Mithila Burute, Jasper Smits, Ingrid Jordens, Madelon M. Maurice, Lukas C. Kapitein, Casper C. HoogenraadSummaryThe establishment of neuronal polarity is driven by cytoskeletal remodeling that stabilizes and promotes the growth of a single axon from one of the multiple neurites. The importance of the local microtubule stabilization in this process has been revealed however, the external signals initiating the cytoskeletal rearrangements are not completely understood. In this study, we show that local activation of the canonical Wnt pathway regulates neuronal polarity and axonal outgrowth. We found that in the early stages of neuronal polarization, Wnt3a accumulates in one of the neurites of unpolarized cells and thereby could determine axon positioning. Subsequently, Wnt3a localizes to the growing axon, where it activates the canonical Wnt pathway and controls axon positioning and axonal length. We propose a model in which Wnt3a regulates the formation and growth of the axon by activating local intracellular signaling events leading to microtubule remodeling.Graphical Graphical abstract for this article
       
  • Context-Specific Requirement of Forty-Four Two-Component Loci in
           Pseudomonas aeruginosa Swarming

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Ameen M. Kollaran, Shubham Joge, Harshitha S. Kotian, Divakar Badal, Deep Prakash, Ayushi Mishra, Manoj Varma, Varsha SinghSummarySwarming in Pseudomonas aeruginosa is a coordinated movement of bacteria over semisolid surfaces (0.5%–0.7% agar). On soft agar, P. aeruginosa exhibits a dendritic swarm pattern, with multiple levels of branching. However, the swarm patterns typically vary depending upon the experimental design. In the present study, we show that the pattern characteristics of P. aeruginosa swarm are highly environment dependent. We define several quantifiable, macroscale features of the swarm to study the plasticity of the swarm, observed across different nutrient formulations. Furthermore, through a targeted screen of 113 two-component system (TCS) loci of the P. aeruginosa strain PA14, we show that forty-four TCS genes regulate swarming in PA14 in a contextual fashion. However, only four TCS genes—fleR, fleS, gacS, and PA14_59770—were found essential for swarming. Notably, many swarming-defective TCS mutants were found highly efficient in biofilm formation, indicating opposing roles for many TCS loci.Graphical Graphical abstract for this article
       
  • The Circadian Clock Protein CRY1 Is a Negative Regulator of HIF-1α

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Elitsa Y. Dimova, Mirza Jakupovic, Kateryna Kubaichuk, Daniela Mennerich, Tabughang Franklin Chi, Filippo Tamanini, Małgorzata Oklejewicz, Jens Hänig, Nadiya Byts, Kari A. Mäkelä, Karl-Heinz Herzig, Peppi Koivunen, Ines Chaves, Gijsbertus van der Horst, Thomas KietzmannSummaryThe circadian clock and the hypoxia-signaling pathway are regulated by an integrated interplay of positive and negative feedback limbs that incorporate energy homeostasis and carcinogenesis. We show that the negative circadian regulator CRY1 is also a negative regulator of hypoxia-inducible factor (HIF). Mechanistically, CRY1 interacts with the basic-helix-loop-helix domain of HIF-1α via its tail region. Subsequently, CRY1 reduces HIF-1α half-life and binding of HIFs to target gene promoters. This appeared to be CRY1 specific because genetic disruption of CRY1, but not CRY2, affected the hypoxia response. Furthermore, CRY1 deficiency could induce cellular HIF levels, proliferation, and migration, which could be reversed by CRISPR/Cas9- or short hairpin RNA-mediated HIF knockout. Altogether, our study provides a mechanistic explanation for genetic association studies linking a disruption of the circadian clock with hypoxia-associated processes such as carcinogenesis.Graphical Graphical abstract for this article
       
  • Regulation of Two-Dimensional Lattice Deformation Recovery

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Jinxin Liu, Lu Zhou, Ke Huang, Xianyin Song, Yunxu Chen, Xiaoyang Liang, Jin Gao, Xiangheng Xiao, Mark H. Rümmeli, Lei FuSummaryThe lattice directly determines the electronic structure, and it enables controllably tailoring the properties by deforming the lattices of two-dimensional (2D) materials. Owing to the unbalanced electrostatic equilibrium among the dislocated atoms, the deformed lattice is thermodynamically unstable and would recover to the initial state. Here, we demonstrate that the recovery of deformed 2D lattices could be directly regulated via doping metal donors to reconstruct electrostatic equilibrium. Compared with the methods that employed external force fields with intrinsic instability and nonuniformity, the stretched 2D molybdenum diselenide (MoSe2) could be uniformly retained and permanently preserved via doping metal atoms with more outermost electrons and smaller electronegativity than Mo. We believe that the proposed strategy could open up a new avenue in directly regulating the atomic-thickness lattice and promote its practical applications based on 2D crystals.Graphical Graphical abstract for this article
       
  • ZnO Nanoparticles Encapsulated in Nitrogen-Doped Carbon Material and
           Silicalite-1 Composites for Efficient Propane Dehydrogenation

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Dan Zhao, Yuming Li, Shanlei Han, Yaoyuan Zhang, Guiyuan Jiang, Yajun Wang, Ke Guo, Zhen Zhao, Chunming Xu, Ranjia Li, Changchun Yu, Jian Zhang, Binghui Ge, Evgenii V. KondratenkoSummaryNon-oxidative propane dehydrogenation (PDH) is an attractive reaction from both an industrial and a scientific viewpoint because it allows direct large-scale production of propene and fundamental analysis of C-H activation respectively. The main challenges are related to achieving high activity, selectivity, and on-stream stability of environment-friendly and cost-efficient catalysts without non-noble metals. Here, we describe an approach for the preparation of supported ultrasmall ZnO nanoparticles (2–4 nm, ZnO NPs) for high-temperature applications. The approach consists of encapsulation of NPs into a nitrogen-doped carbon (NC) layer in situ grown from zeolitic imidazolate framework-8 on a Silicalite-1 support. The NC layer was established to control the size of ZnO NPs and to hinder their loss to a large extent at high temperatures. The designed catalysts exhibited high activity, selectivity, and on-stream stability in PDH. Propene selectivity of about 90% at 44.4% propane conversion was achieved at 600°C after nearly 6 h on stream.
       
  • Hollow N-doped Carbon Polyhedrons with Hierarchically Porous Shell for
           Confinement of Polysulfides in Lithium–Sulfur Batteries

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Dong-Hui Yang, Hang-Yu Zhou, Hu Liu, Bao-Hang HanSummaryHerein, hollow N-doped carbon polyhedrons with hierarchical pores were fabricated by etching ZIF-8 crystals and were first used as the host of sulfur for lithium-sulfur batteries. This host possesses both micropores and mesopores, and inner wide cavities, which enable the sulfur to effectively immerse into the polyhedrons without obstacles and simultaneously restrict the escaping of polysulfides by outer carbon shell and abundant N sites. Hence, the polyhedron host combines the physical confinement and chemical interaction for polysulfides by virtue of the unique architecture. As a result, the hierarchically porous polyhedron enables a sulfur content of 72 wt% and achieves a faster polysulfide trapping and better electrochemical performance than the ZIF-8-derived microporous host at the sulfur loading of 1 and 5 mg cm−2.Graphical Graphical abstract for this article
       
  • Loss of RNA-Binding Protein Sfpq Causes Long-Gene Transcriptopathy in
           Skeletal Muscle and Severe Muscle Mass Reduction with Metabolic Myopathy

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Motoyasu Hosokawa, Akihide Takeuchi, Jun Tanihata, Kei Iida, Shin'ichi Takeda, Masatoshi HagiwaraSummaryGrowing evidences are suggesting that extra-long genes in mammals are vulnerable for full-gene length transcription and dysregulation of long genes is a mechanism underlying human genetic disorders. How long-distance transcription is achieved is a fundamental question to be elucidated. In previous study, we had discovered that RNA-binding protein SFPQ preferentially binds to long pre-mRNAs and specifically regulates the cluster of neuronal genes>100 kbp. Here we investigated the roles of SFPQ for long gene expression, target specificities, and also physiological functions in skeletal muscle. Loss of Sfpq selectively downregulated genes>100 kbp including Dystrophin, which is 2.26 Mbp in length. Sfpq knockout (KO) mice showed progressive muscle mass reduction and metabolic myopathy characterized by glycogen accumulation and decreased abundance of mitochondrial oxidative phosphorylation complexes. Functional clustering analysis identified energy metabolism pathway genes as SFPQ's targets. These findings indicate target gene specificities and tissue-specific physiological functions of SFPQ in skeletal muscle.Graphical Graphical abstract for this article
       
  • Visco-Node-Pore Sensing: A Microfluidic Rheology Platform to Characterize
           Viscoelastic Properties of Epithelial Cells

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Junghyun Kim, Brian Li, Olivia J. Scheideler, Youngbin Kim, Lydia L. SohnSummaryViscoelastic properties of cells provide valuable information regarding biological or clinically relevant cellular characteristics. Here, we introduce a new, electronic-based, microfluidic platform—visco-node-pore sensing (visco-NPS)—which quantifies cellular viscoelastic properties under periodic deformation. We measure the storage (G′) and loss (G″) moduli (i.e., elasticity and viscosity, respectively) of cells. By applying a wide range of deformation frequencies, our platform quantifies the frequency dependence of viscoelastic properties. G′ and G″ measurements show that the viscoelastic properties of malignant breast epithelial cells (MCF-7) are distinctly different from those of non-malignant breast epithelial cells (MCF-10A). With its sensitivity, visco-NPS can dissect the individual contributions of different cytoskeletal components to whole-cell mechanical properties. Moreover, visco-NPS can quantify the mechanical transitions of cells as they traverse the cell cycle or are initiated into an epithelial-mesenchymal transition. Visco-NPS identifies viscoelastic characteristics of cell populations, providing a biophysical understanding of cellular behavior and a potential for clinical applications.Graphical Graphical abstract for this article
       
  • Tonotopic Differentiation of Coupling between Ca2+ and Kv1.1 Expression in
           Brainstem Auditory Circuit

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Ryota Adachi, Rei Yamada, Hiroshi KubaSummaryTonotopic differentiations of ion channels ensure sound processing across frequencies. Afferent input plays a critical role in differentiations. We demonstrate here in organotypic culture of chicken cochlear nucleus that expression of Kv1.1 was coupled with Ca2+ to a different degree depending on tonotopic regions, thereby differentiating the level of expression within the nucleus. In the culture, Kv1.1 was down-regulated and not differentiated tonotopically. Chronic depolarization increased Kv1.1 expression in a level-dependent manner. Moreover, the dependence was steeper at higher-frequency regions, which restored the differentiation. The depolarization increased Kv1.1 via activation of Cav1 channels, whereas basal Ca2+ level elevated similarly irrespective of tonotopic regions. Thus, the efficiency of Ca2+-dependent Kv1.1 expression would be fine-tuned in a tonotopic-region-specific manner, emphasizing the importance of neuronal tonotopic identity as well as pattern of afferent input in the tonotopic differentiation of the channel in the auditory circuit.Graphical Graphical abstract for this article
       
  • Nanocarbon-Edge-Anchored High-Density Pt Atoms for 3-nitrostyrene
           Hydrogenation: Strong Metal-Carbon Interaction

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Yang Lou, Honglu Wu, Jingyue LiuSummaryStrong metal-support interaction (SMSI) has been widely used to improve catalytic performance and to identify reaction mechanisms. We report that single Pt atoms anchored onto hollow nanocarbon (h-NC) edges possess strong metal-carbon interaction, which significantly modifies the catalytic behavior of the anchored Pt atoms for selective hydrogenation reactions. The strong Pt-C bonding not only stabilizes single Pt atoms but also modifies their electronic structure, tunes their adsorption properties, and enhances activation of reactants. The fabricated Pt1/h-NC single-atom catalysts (SACs) demonstrated excellent activity for hydrogenation of 3-nitrostyrene to 3-vinylaniline with a turnover number>31,000/h, 20 times higher than that of the best catalyst for such selective hydrogenation reactions reported in the literature. The strategy to strongly anchor Pt atoms by edge carbon atoms of h-NCs is general and can be extended to construct strongly anchored metal atoms, via SMSI, onto surfaces of various types of support materials to develop robust SACs.Graphical Graphical abstract for this article
       
  • Cysteine Dioxygenase Regulates the Epithelial Morphogenesis of Mammary
           Gland via Cysteine Sulfinic Acid

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Jianjun Zhao, Yuzhu Han, Xingyu Ma, Yang Zhou, Shukai Yuan, Qian Shen, Guogen Ye, Hongrun Liu, Penghui Fu, Gongwei Zhang, Bingke Qiao, Anfang LiuSummaryEpithelial morphogenesis is a common feature in various organs and contributes to functional formation. However, the molecular mechanisms behind epithelial morphogenesis remain largely unknown. Mammary gland is an excellent model system to investigate the molecular mechanisms of epithelial morphogenesis. In this study, we found that cysteine dioxygenase (CDO), a key enzyme in cysteine oxidative metabolism, was involved in mammary epithelial morphogenesis. CDO knockout (KO) females exhibited severe defects in mammary branching morphogenesis and ductal elongation, resulting in poor lactation. CDO contributes to the luminal epithelial cell differentiation, proliferation, and apoptosis mainly through its downstream product cysteine sulfinic acid (CSA). Exogenous supplementation of CSA not only rescued the defects in CDO KO mouse but also enhanced ductal growth in wild-type mouse. It suggests that CDO regulates luminal epithelial differentiation and regeneration via CSA and consequently contributes to mammary development, which raises important implications for epithelial morphogenesis and pathogenesis of breast cancer.Graphical Graphical abstract for this article
       
  • Sensitivity to Oxygen in Microbial Electrochemical Systems Biofilms

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Jiawei Yang, Shaoan Cheng, Peng Li, Haobin Huang, Kefa CenSummaryThe formation and bioelectric performance of anode biofilms in microbial electrochemical systems (MESs) are sensitive to oxygen. Investigating the temporal-spatial structure of anode biofilms will help elucidate the interfaces between oxygen and bacteria, thereby facilitating the applications of MESs in wastewater treatment and energy recovery. Here, use of optical coherence tomography, frozen sections, and a microsensor revealed that the aerobic biofilms exhibited a multilayered sandwich structure with a sparse gap between the aerobe- and amphimicrobe-enriched outer layer and the dense exoelectrogen-enriched inner layer, whereas the anaerobic biofilm consisted of only a single dense layer. Our results showed that the inner layer of aerobic anode biofilms performed electricity generation, whereas the outer layer only consumed oxygen. In this case, electron donor diffusion through the outer layer became the limiting factor in electricity generation by the bioanode. Consequently, as the anode biofilms matured, current generation decreased.Graphical Graphical abstract for this article
       
  • The Hidden Control Architecture of Complex Brain Networks

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Byeongwook Lee, Uiryong Kang, Hongjun Chang, Kwang-Hyun ChoSummaryThe brain controls various cognitive functions in a robust and efficient way. What is the control architecture of brain networks that enables such robust and optimal control? Is this brain control architecture distinct from that of other complex networks? Here, we developed a framework to delineate a control architecture of a complex network that is compatible with the behavior of the network and applied the framework to structural brain networks and other complex networks. As a result, we revealed that the brain networks have a distributed and overlapping control architecture governed by a small number of control nodes, which may be responsible for the robust and efficient brain functions. Moreover, our artificial network evolution analysis showed that the distributed and overlapping control architecture of the brain network emerges when it evolves toward increasing both robustness and efficiency.Graphical Graphical abstract for this article
       
  • Septin 9 has Two Polybasic Domains Critical to Septin Filament Assembly
           and Golgi Integrity

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Mohyeddine Omrane, Amanda Souza Camara, Cyntia Taveneau, Nassima Benzoubir, Thibault Tubiana, Jinchao Yu, Raphaël Guérois, Didier Samuel, Bruno Goud, Christian Poüs, Stéphane Bressanelli, Richard Charles Garratt, Abdou Rachid Thiam, Ama Gassama-DiagneSummarySeptins are GTP-binding proteins involved in several membrane remodeling mechanisms. They associate with membranes, presumably using a polybasic domain (PB1) that interacts with phosphoinositides (PIs). Membrane-bound septins assemble into microscopic structures that regulate membrane shape. How septins interact with PIs and then assemble and shape membranes is poorly understood. Here, we found that septin 9 has a second polybasic domain (PB2) conserved in the human septin family. Similar to PB1, PB2 binds specifically to PIs, and both domains are critical for septin filament formation. However, septin 9 membrane association is not dependent on these PB domains, but on putative PB-adjacent amphipathic helices. The presence of PB domains guarantees protein enrichment in PI-contained membranes, which is critical for PI-enriched organelles. In particular, we found that septin 9 PB domains control the assembly and functionality of the Golgi apparatus. Our findings offer further insight into the role of septins in organelle morphology.Graphical Graphical abstract for this article
       
  • Key Amino Acid Substitution for Infection-Enhancing Activity-Free Designer
           Dengue Vaccines

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Atsushi Yamanaka, Eiji KonishiSummaryDengue is a globally important disease caused by four serotypes of dengue virus. Dengue vaccine development has been hampered by antigenic cross-reactivity among serotypes, which potentially causes antibody-dependent enhancement of infection and disease severity. Here we found that a single amino acid substitution in the envelope protein at position 87 from aspartic acid to asparagine or at position 107 from leucine to phenylalanine is critical for suppressing the induction of infection-enhancing antibody in a mouse model. The site and type of amino acid substitution were determined via neutralization escape using an enhancing-activity-only monoclonal antibody that was engineered to reveal neutralizing activity. Mutated dengue type 1 DNA vaccines containing either or both amino acid substitutions induced neutralizing antibodies devoid of enhancing activity against all serotypes. The effect of substitution was further demonstrated using other serotypes and a tetravalent formulation. This finding may contribute to the development of infection-enhancing-activity-free dengue vaccines.Graphical Graphical abstract for this article
       
  • Olfactory Object Recognition Based on Fine-Scale Stimulus Timing in
           Drosophila

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Aarti Sehdev, Yunusa G. Mohammed, Tilman Triphan, Paul SzyszkaSummaryOdorants of behaviorally relevant objects (e.g., food sources) intermingle with those from other sources. Therefore to determine whether an odor source is good or bad—without actually visiting it—animals first need to segregate the odorants from different sources. To do so, animals could use temporal stimulus cues, because odorants from one source exhibit correlated fluctuations, whereas odorants from different sources are less correlated. However, the behaviorally relevant timescales of temporal stimulus cues for odor source segregation remain unclear. Using behavioral experiments with free-flying flies, we show that (1) odorant onset asynchrony increases flies' attraction to a mixture of two odorants with opposing innate or learned valence and (2) attraction does not increase when the attractive odorant arrives first. These data suggest that flies can use stimulus onset asynchrony for odor source segregation and imply temporally precise neural mechanisms for encoding odors and for segregating them into distinct objects.Graphical Graphical abstract for this article
       
  • Simultaneous Photoradiochemical Labeling of Antibodies for Immuno-Positron
           Emission Tomography

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Malay Patra, Simon Klingler, Larissa S. Eichenberger, Jason P. HollandSummaryA method for the simultaneous (one-step) photochemical conjugation and 89Zr-radiolabeling of antibodies is introduced. A photoactivatable chelate based on the functionalization of desferrioxamine B with an arylazide moiety (DFO-ArN3, [1]) was synthesized. The radiolabeled complex, 89Zr-1+, was produced and characterized. Density functional theory calculations were used to investigate the mechanism of arylazide photoactivation. 89Zr-radiolabeling experiments were also used to determine the efficiency of photochemical conjugation. A standard two-step approach gave a measured conjugation efficiency of 3.5% ± 0.4%. In contrast, the one-step process gave a higher photoradiolabeling efficiency of ∼76%. Stability measurements, cellular saturation binding assays, positron emission tomographic imaging, and biodistribution studies in mice bearing SK-OV-3 tumors confirmed the biochemical viability and tumor specificity of photoradiolabeled [89Zr]ZrDFO-azepin-trastuzumab. Experimental data support the conclusion that the combination of photochemistry and radiochemistry is a viable strategy for producing radiolabeled proteins for imaging and therapy.Graphical Graphical abstract for this article
       
  • Kinesin-1 Regulates Extrasynaptic Targeting of NMDARs and Neuronal
           Vulnerability Toward Excitotoxicity

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Raozhou Lin, Zhigang Duan, Haitao Sun, Man-Lung Fung, Hansen Chen, Jing Wang, Chi-Fai Lau, Di Yang, Yu Liu, Yanxiang Ni, Zai Wang, Ju Cui, Wutian Wu, Wing-Ho Yung, Ying-Shing Chan, Amy C.Y. Lo, Jun Xia, Jiangang Shen, Jian-Dong HuangSummaryN-methyl-D-aspartate (NMDA) receptor (NMDAR) is highly compartmentalized in neurons, and its dysfunction has been implicated in various neuropsychiatric and neurodegenerative disorders. Recent failure to exploit NMDAR antagonization as a potential therapeutic target has driven the need to identify molecular mechanisms that regulate NMDAR compartmentalization. Here, we report that the reduction of Kif5b, the heavy chain of kinesin-1, protected neurons against NMDA-induced excitotoxicity and ischemia-provoked neurodegeneration. Direct binding of kinesin-1 to the GluN2B cytoplasmic tails regulated the levels of NMDAR at extrasynaptic sites and the subsequent influx of calcium mediated by extrasynaptic NMDAR by regulating the insertion of NMDARs into neuronal surface. Transient increase of Kif5b restored the surface levels of NMDAR and the decreased neuronal susceptibility to NMDA-induced excitotoxicity. The expression of Kif5b was repressed in cerebral ischemia preconditioning. Our findings reveal that kinesin-1 regulates extrasynaptic NMDAR targeting and signaling, and the reduction of kinesin-1 could be exploited to defer neurodegeneration.Graphical Graphical abstract for this article
       
  • Non-muscle Myosin-II Is Required for the Generation of a Constriction Site
           for Subsequent Abscission

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Kangji Wang, Carsten Wloka, Erfei BiSummaryIt remains unknown when, where, and how the site of abscission is generated during cytokinesis. Here, we show that the sites of constriction, i.e., the sites of future abscission, are initially formed at the ends of the intercellular bridge during early midbody stage, and that these sites are associated with the non-muscle myosin-IIB (not myosin-IIA), actin filaments, and septin 9 until abscission. The ESCRT-III component CHMP4B localizes to the midbody and “spreads” to the site of abscission only during late midbody stage. Strikingly, inhibition of myosin-II motor activity by a low dose of Blebbistatin completely abolishes the formation of the constriction sites, resulting in the localization of all the above-mentioned components to the midbody region. These data strongly suggest that a secondary actomyosin ring provides the primary driving force for the thinning of the intercellular bridge to allow ESCRT-mediated membrane fission.Graphical Graphical abstract for this article
       
  • CdpR Inhibits CRISPR-Cas Adaptive Immunity to Lower Anti-viral Defense
           while Avoiding Self-Reactivity

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Ping Lin, Qinqin Pu, Guanwang Shen, Rongpeng Li, Kai Guo, Chuanmin Zhou, Haihua Liang, Jianxin Jiang, Min WuSummaryCRISPR-Cas systems as adaptive immunity in bacteria and archaea battle against bacteriophages. However, little is known how CRISPR-Cas systems are precisely regulated to effectively eliminate intruders while not inducing self-reactivity. Here, we identify intrinsic negative modulator of CRISPR-Cas that influences interference and adaptation functions. LasI/RhlI-derived autoinducers activate cas operon by enhancing the binding of virulence factor regulator (Vfr) cis-response elements to cas1 promoter, whereas CdpR represses this intracellular signaling and blocks transcription of cas operon. Importantly, inhibition of Vfr reduces cas1 expression and impairs immunization and immune memory mediated by CRISPR-Cas, leading to more severe phage infection but lower self-targeting activities. In addition, CdpR-mediated LasI/RhlI/Vfr intracellular signaling represses cleavage of bacterial endogenous sequences by impeding Cas3 RNA cleavage activity. Thus, CdpR renders important inhibitory effects on CRISPR-Cas systems to avoid possible self-reactivity but potentially heightening infection risk. Our study provides insight into fine regulation of CRISPR-Cas systems for maintaining homeostasis.Graphical Graphical abstract for this article
       
  • HDAC2 Regulates Site-Specific Acetylation of MDM2 and Its Ubiquitination
           Signaling in Tumor Suppression

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Nikita Patel, Juehong Wang, Kumiko Shiozawa, Kevin B. Jones, Yanfeng Zhang, Jeremy W. Prokop, George G. Davenport, Naoe T. Nihira, Zhenyue Hao, Derek Wong, Laurel Brandsmeier, Sarah K. Meadows, Arthur V. Sampaio, Ryan Vander Werff, Makoto Endo, Mario R. Capecchi, Kelly M. McNagny, Tak W. Mak, Torsten O. Nielsen, T. Michael UnderhillSummaryHistone deacetylases (HDACs) are promising targets for cancer therapy, although their individual actions remain incompletely understood. Here, we identify a role for HDAC2 in the regulation of MDM2 acetylation at previously uncharacterized lysines. Upon inactivation of HDAC2, this acetylation creates a structural signal in the lysine-rich domain of MDM2 to prevent the recognition and degradation of its downstream substrate, MCL-1 ubiquitin ligase E3 (MULE). This mechanism further reveals a therapeutic connection between the MULE ubiquitin ligase function and tumor suppression. Specifically, we show that HDAC inhibitor treatment promotes the accumulation of MULE, which diminishes the t(X; 18) translocation-associated synovial sarcomagenesis by directly targeting the fusion product SS18-SSX for degradation. These results uncover a new HDAC2-dependent pathway that integrates reversible acetylation signaling to the anticancer ubiquitin response.Graphical Graphical abstract for this article
       
  • Conjugated Polymers with Oligoethylene Glycol Side Chains for Improved
           Photocatalytic Hydrogen Evolution

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Zhicheng Hu, Zhenfeng Wang, Xi Zhang, Haoran Tang, Xiaocheng Liu, Fei Huang, Yong CaoSummaryConjugated polymers are emerging as promising organic photocatalysts for hydrogen evolution from water. However, it is still very challenging for conjugated polymers to realize highly efficient photocatalytic hydrogen evolution. Herein, we demonstrate an efficient strategy of hydrophilic side chain functionalization to boost the hydrogen evolution rates of conjugated polymers. By functionalizing conjugated polymers with hydrophilic oligo (ethylene glycol) monomethyl ether (OEG) side chains, a 90-fold improvement in hydrogen evolution rate has been achieved than that of alkyl-functionalized conjugated polymer. It is found that the OEG side chains interact robustly with Pt co-catalysts, resulting in more efficient charge transfer. Moreover, OEG side chains in conjugated polymers can adsorb H+ from water, resulting in significantly lowered energy levels on the surfaces of conjugated polymers, which enables cascade energy levels and enhances charge separation and photocatalytic performance. Our results indicate that rational side-chain engineering could facilitate the design of improved organic photocatalysts for hydrogen evolution.Graphical Graphical abstract for this article
       
  • A Likely Ancient Genome Duplication in the Speciose Reef-Building Coral
           Genus, Acropora

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Yafei Mao, Noriyuki SatohSummaryWhole-genome duplication (WGD) has been recognized as a significant evolutionary force in the origin and diversification of multiple organisms. Acropora, a speciose reef-building coral genus, is suspected to have originated by polyploidy. Yet, there is no genetic evidence to support this hypothesis. Using comprehensive phylogenomic and comparative genomic approaches, we analyzed six Acroporid genomes and found that a WGD event likely occurred ∼31 million years ago in the most recent common ancestor of Acropora, concurrent with a worldwide coral extinction. We found that duplicated genes were highly enriched in gene regulation functions, including those of stress responses. The functional clusters of duplicated genes are related to the divergence of gene expression patterns during development. Some proteinaceous toxins were generated by WGD in Acropora compared with other cnidarian species. Collectively, this study provides evidence for an ancient WGD event in corals, which helps explain the origin and diversification of Acropora.Graphical Graphical abstract for this article
       
  • Spatiotemporally Controlled Myosin Relocalization and Internal Pressure
           Generate Sibling Cell Size Asymmetry

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Tri Thanh Pham, Arnaud Monnard, Jonne Helenius, Erik Lund, Nicole Lee, Daniel J. Müller, Clemens CabernardSummaryMetazoan cells can generate unequal-sized sibling cells during cell division. This form of asymmetric cell division depends on spindle geometry and Myosin distribution, but the underlying mechanics are unclear. Here, we use atomic force microscopy and live cell imaging to elucidate the biophysical forces involved in the establishment of physical asymmetry in Drosophila neural stem cells. We show that initial apical cortical expansion is driven by hydrostatic pressure, peaking shortly after anaphase onset, and enabled by a relief of actomyosin contractile tension on the apical cell cortex. An increase in contractile tension at the cleavage furrow combined with the relocalization of basally located Myosin initiates basal and sustains apical extension. We propose that spatiotemporally controlled actomyosin contractile tension and hydrostatic pressure enable biased cortical expansion to generate sibling cell size asymmetry. However, dynamic cleavage furrow repositioning can compensate for the lack of biased expansion to establish physical asymmetry.Graphical Graphical abstract for this article
       
  • eDetect: A Fast Error Detection and Correction Tool for Live Cell Imaging
           Data Analysis

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Hongqing Han, Guoyu Wu, Yuchao Li, Zhike ZiSummaryLive cell imaging has been widely used to generate data for quantitative understanding of cellular dynamics. Various applications have been developed to perform automated imaging data analysis, which often requires tedious manual correction. It remains a challenge to develop an efficient curation method that can analyze massive imaging datasets with high accuracy. Here, we present eDetect, a fast error detection and correction tool that provides a powerful and convenient solution for the curation of live cell imaging analysis results. In eDetect, we propose a gating strategy to distinguish correct and incorrect image analysis results by visualizing image features based on principal component analysis. We demonstrate that this approach can substantially accelerate the data correction process and improve the accuracy of imaging data analysis. eDetect is well documented and designed to be user friendly for non-expert users. It is freely available at https://sites.google.com/view/edetect/ and https://github.com/Zi-Lab/eDetect.Graphical Graphical abstract for this article
       
  • Foundation Species, Non-trophic Interactions, and the Value of Being
           Common

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Aaron M. EllisonFoundation species define ecosystems, control the biological diversity of associated species, modulate critical ecosystem processes, and often have important cultural values and resonance. This review summarizes current understanding of the characteristics and traits of foundation species and how to distinguish them from other “important” species in ecological systems (e.g., keystone, dominant, and core species); illustrates how analysis of the structure and function of ecological networks can be improved and enriched by explicit incorporation of foundation species and their non-trophic interactions; discusses the importance of pro-active identification and management of foundation species as a cost-effective and efficient method of sustaining valuable ecosystem processes and services and securing populations of associated rare, threatened, or endangered species; and suggests broader engagement of citizen-scientists and non-specialists in the identification and study of foundation species and their biological and cultural values.Graphical Graphical abstract for this article
       
  • Interfacial Effects on the Band Edges of Ta3N5 Photoanodes in an Aqueous
           Environment: A Theoretical View

    • Abstract: Publication date: 29 March 2019Source: iScience, Volume 13Author(s): Guozheng Fan, Tao Fang, Xin Wang, Yaodong Zhu, Hongwei Fu, Jianyong Feng, Zhaosheng Li, Zhigang ZouSummaryTa3N5, as a fascinating photoanode for solar hydrogen production, is expected to split water without any bias, because its band edge potentials straddle H2O redox potentials. Unfortunately, Ta3N5 photoanodes can split water only when a bias of at least 0.6–0.9 V is applied. It means that they exhibit an onset potential as high as 0.6–0.9 VRHE (reversible hydrogen electrode). In this study, density functional theory calculations show that the band edge potentials of Ta3N5 have a shift of approximately −0.42 eV relative to vacuum level when exposed to water. The increased ratio of dissociated water at Ta3N5-water interface will further make the band edge potentials shift −0.85 eV relative to vacuum level, implying the anodic shifts of the onset potential for water oxidation. The findings may reveal the mystery of the unexpectedly high onset potential of Ta3N5, as high as 0.6–0.9 VRHE.Graphical Graphical abstract for this article
       
  • Two new plasmid post-segregational killing mechanisms for the
           implementation of synthetic gene networks in Escherichia coli

    • Abstract: Publication date: Available online 22 March 2019Source: iScienceAuthor(s): Alex J.H. Fedorec, Tanel Ozdemir, Anjali Doshi, Yan-Kay Ho, Luca Rosa, Jack Rutter, Oscar Velazquez, Vitor B. Pinheiro, Tal Danino, Chris P. BarnesSummaryPlasmids are the workhorse of both industrial biotechnology and synthetic biology, but ensuring they remain in bacterial cells is a challenge. Antibiotic selection cannot be used to stabilise plasmids in most real-world applications and inserting dynamical gene networks into the genome remains challenging. Plasmids have evolved several mechanisms for stability, one of which, post-segregational killing (PSK), ensures that plasmid-free cells do not survive. Here we demonstrate the plasmid-stabilising capabilities of the axe/txe toxin-antitoxin system and the microcin-V bacteriocin system in the probiotic bacteria Escherichia coli Nissle 1917 and show they can outperform the commonly used hok/sok. Using plasmid-stability assays, automated flow cytometry analysis, mathematical models and Bayesian statistics we quantified plasmid stability in vitro. Furthermore, we used an in vivo mouse cancer model to demonstrate plasmid stability in a real-world therapeutic setting. These new PSK systems, plus the developed Bayesian methodology, will have wide applicability in clinical and industrial biotechnology.Graphical Graphical abstract for this article
       
  • Latent model-based clustering for biological discovery

    • Abstract: Publication date: Available online 21 March 2019Source: iScienceAuthor(s): Xin Bing, Florentina Bunea, Martin Royer, Jishnu Das LOVE, a robust, scalable latent model-based clustering method for biological discovery, can be used across a range of datasets to generate both overlapping and non-overlapping clusters. In our formulation, a cluster comprises variables associated with the same latent factor and is determined from an allocation matrix that indexes our latent model. We prove that the allocation matrix and corresponding clusters are uniquely defined. We apply LOVE to biological datasets (gene expression, serological responses measured from HIV controllers and chronic progressors, vaccine-induced humoral immune responses) resulting in meaningful biological output. For all three datasets, the clusters generated by LOVE remain stable across tuning parameters. Finally, we compared LOVE’s performance to that of 13 state-of-the-art methods using previously established benchmarks and found that LOVE outperformed these methods across datasets. Our results demonstrate that LOVE can be broadly used across large-scale biological datasets to generate accurate and meaningful overlapping and non-overlapping clusters.Graphical Graphical abstract for this article
       
  • The FG Loop of PD-1 Serves as a ‘Hot-Spot’ for Therapeutic Monoclonal
           Antibodies in Tumor Immune Checkpoint Therapy

    • Abstract: Publication date: Available online 21 March 2019Source: iScienceAuthor(s): Danqing Chen, Shuguang Tan, Hao Zhang, Haiyuan Wang, Weiwu He, Rui Shi, Zhou Tong, Jianhua Zhu, Hao Cheng, Shan Gao, Yan Chai, Jianxun Qi, Minghui Xiao, Jinghua Yan, George F. GaoSummaryPD-1/PD-L1 blocking monoclonal antibodies (MAbs) have taken center stage for tumor immune checkpoint therapy. Identification of the ‘hot-spots’ on PD-1 for MAbs will help to develop next-generation oral deliverable agents with long-lasting efficacy. Here, we identified two PD-1-targeting MAbs, GY-5 and GY-14, with PD-1/PD-L1 blocking efficacy. Complex structural information revealed that both MAbs mainly bind to the FG loop of PD-1, which also contributes multiple interactions with PD-L1. The FG loop adopts substantially varied conformations upon binding to different MAbs, providing a novel targetable region for the development of PD-1-specific biologics and small chemical molecules. Glycosylation modifications of PD-1 could be observed in three out of the four potential N-linked glycosylation sites. However, the binding of GY-5 and GY-14 to PD-1 was not affected by glycosylation. These findings broaden our understanding of the mechanism of anti-PD-1 MAbs and provide insight into the development of agents targeting PD-1.Graphical Graphical abstract for this article
       
  • A Heavily Surface-Doped Polymer with The Bifunctional Catalytic Mechanism
           in Li-O2 Batteries

    • Abstract: Publication date: Available online 20 March 2019Source: iScienceAuthor(s): Chengyang Xu, Langyuan Wu, Shifan Hu, Huamei Xie, Xiaogang ZhangSummaryThe application of conducting polymers (CPs) in energy storage systems is greatly limited by insufficient reversibility and stability. Here, we successfully incorporated functionalized dopants (Fe(CN)63- (FCN) and PO43- ions) in CPs matrixes to achieve a preferable electrochemical performance. A stable cation inserting/expulsing behavior of surface-doped polycarbazole (PCz) is demonstrated in our work, where doping levels and semiconductor properties of PCz are effectively controlled to adjust their redox properties and stability. With carbon nanotube (CNT) films as the substrate, the CNT/PCz:FCN composite is initially adopted as a free-standing catalytic electrode in Li-O2 cells. The molecule-level dispersed FCN dopants on the surface can work as bifunctional redox mediators on the charge-discharge process. Thus, this composite can not only achieve a low charge plateau of 3.62 V and a regular growth of capacities from 1800 to 4800 mAh/gCNT, but also maintain the most of charge voltages under 4.0 V for 150 cycles.Graphical Graphical abstract for this article
       
  • Electrically Sorted Single-walled Carbon Nanotubes Based Electron
           Transporting Layers for Perovskite Solar Cells

    • Abstract: Publication date: Available online 20 March 2019Source: iScienceAuthor(s): Abdulaziz S.R. Bati, LePing Yu, Sherif Abdulkader Tawfik, Michelle J.S. Spencer, Paul E. Shaw, Munkhbayar Batmunkh, Joseph G. ShapterSummaryIncorporation of as prepared single walled carbon nanotubes (SWCNTs) into the electron transporting layer (ETL) is an effective strategy to enhance the photovoltaic performance of perovskite solar cells (PSCs). However, the fundamental role of the SWCNT electrical types in the PSCs is not well understood. Herein, we prepared semiconducting (s-) and metallic (m-) SWCNT families and integrated them into TiO2 photoelectrodes of the PSCs. Based on experimental and theoretical studies, we found that the electrical type of the nanotubes plays an important role in the devices. In particular, the mixture of s-SWCNTs and m-SWCNTs (2:1 w/w) based PSCs exhibited a remarkable efficiency of up to 19.35%, which was significantly higher than that of the best control cell (17.04%). In this class of PSCs, semiconducting properties of s-SWCNTs play a critical role in extracting and transporting electrons, while m-SWCNTs provide high conductance throughout the electrode.Graphical Graphical abstract for this article
       
  • Werner Syndrome Helicase Is Required for the Survival of Cancer Cells with
           Microsatellite Instability

    • Abstract: Publication date: Available online 18 March 2019Source: iScienceAuthor(s): Lorn Kategaya, Senthil K. Perumal, Jeffrey H. Hager, Lisa D. BelmontSummaryWerner syndrome protein (WRN) is a RecQ enzyme involved in the maintenance of genome integrity. Germline loss-of-function mutations in WRN led to premature aging and predisposition to cancer. We evaluated synthetic lethal (SL) interactions between WRN and another human RecQ helicase, BLM, with DNA damage response genes in cancer cell lines. We found that WRN was SL with a DNA mismatch repair protein MutL homolog 1, loss of which is associated with high microsatellite instability (MSI-H). MSI-H cells exhibited increased double-stranded DNA breaks, altered cell cycles, and decreased viability in response to WRN knockdown, in contrast to microsatellite stable (MSS) lines, which tolerated depletion of WRN. Although WRN is the only human RecQ enzyme with a distinct exonuclease domain, only loss of helicase activity drives the MSI SL interaction. This SL interaction in MSI cancer cells positions WRN as a relevant therapeutic target in patients with MSI-H tumors.Graphical Graphical abstract for this article
       
  • Asymmetric Vinylogous Aldol-Type Reactions of Aldehydes with Allyl
           Phosphonate and Sulfone

    • Abstract: Publication date: Available online 16 March 2019Source: iScienceAuthor(s): Wen-Jun Yue, Cheng-Yuan Zhang, Liang YinSummaryTwo catalytic asymmetric vinylogous aldol-type reactions of aldehydes with allyl phosphonate and allyl sulfone have been uncovered in good to high yields for the first time. The bulky ligand—(R)-DTBM-SEGPHOS was found to be the key to perfectly control both regio- and enantioselectivities. Transformations of the vinylogous products (including Horner-Wadsworth-Emmons olefination and Julia olefination) were successfully realized by virtue of the phosphonate and the sulfone moieties. Moreover, the present methodology was successful applied in the asymmetric synthesis of natural products.Graphical Graphical abstract for this article
       
  • Distinct roles of myosin-II isoforms in cytokinesis under normal and
           stressed conditions

    • Abstract: Publication date: Available online 16 March 2019Source: iScienceAuthor(s): Hiroki Okada, Carsten Wloka, Jian-Qiu Wu, Erfei BiSummaryTo address the question of why more than one myosin-II isoform is expressed in a single cell to drive cytokinesis, we analyzed the roles of the myosin-II isoforms, Myo2 and Myp2, of the fission yeast Schizosaccharomyces pombe, in cytokinesis under normal and stressed conditions. We found that Myp2 controls the disassembly, stability, and constriction initiation of the Myo2 ring in response to high-salt stress. A C-terminal coiled-coil domain of Myp2 is required for its immobility and contractility during cytokinesis, and when fused to the tail of the dynamic Myo2, renders the chimera the low-turnover property. We also found, by following distinct processes in real time at the single-cell level, that Myo2 and Myp2 are differentially required but collectively essential for guiding extracellular matrix remodeling during cytokinesis. These results suggest that the dynamic and immobile myosin-II isoforms are evolved to carry out cytokinesis with robustness under different growth conditions.Graphical Graphical abstract for this article
       
  • Realizing formation and decomposition of Li2O2 on its own surface with a
           highly dispersed catalyst for high round-trip efficiency Li-O2 batteries

    • Abstract: Publication date: Available online 15 March 2019Source: iScienceAuthor(s): Li-Na Song, Lian-Chun Zou, Xiao-Xue Wang, Nan Luo, Ji-Jing Xu, Ji-Hong YuSummaryThe rapid and effective formation/decomposition of Li2O2 during cycling is crucial to solve the problems associated with the practical limitation of lithium-oxygen (Li-O2) batteries. In this work, a highly dispersed electrocatalyst with the Ru nanoclusters inside the special organic molecular cage (RuNCs@RCC3) through a reverse double solvent method for Li-O2 batteries has been proposed for the first time. This RuNCs@RCC3 shows an effective catalyst enabling reversible formation/decomposition of the Li2O2 at the interface between the Li2O2 and the liquid electrolyte, rather than the sluggish solid-solid interface reactions on commonly used solid catalysts. As a result, the Li-O2 cells with RuNCs@RCC3 show enhanced electrochemical performance, including low overpotential (310 mV at a current density of 100 mA g-1), high specific capacity (15068 mAh g-1), good rate capability (1800 mAh g-1 at a current density of 2.8 A g-1) and especially superior cycle stability up to 470 cycles.Graphical Graphical abstract for this article
       
  • Biased signaling of the mu opioid receptor revealed in native neurons

    • Abstract: Publication date: Available online 15 March 2019Source: iScienceAuthor(s): Aliza T. Ehrlich, Meriem Semache, Florence Gross, Dillon F. Da Fonte, Leonie Runtz, Christine Colley, Amina Mezni, Christian LeGouill, Viktoriya Lukashova, Mireille Hogue, Emmanuel Darcq, Michel Bouvier, Brigitte L. KiefferSummaryG protein-coupled receptors are key signaling molecules and major targets for pharmaceuticals. The concept of ligand-dependant biased signaling raises the possibility of developing drugs with improved efficacy and safety profiles, yet translating this concept to native tissues remains a major challenge. Whether drug activity profiling in recombinant cell-based assays, traditionally used for drug discovery, has any relevance to physiology is unknown. Here we focused on the mu opioid receptor, the unrivalled target for pain treatment but also the key driver for the current opioid crisis. We selected a set of clinical and novel mu agonists, and profiled their activities in transfected cell assays using advanced biosensors, and in native neurons from knock-in mice expressing traceable receptors endogenously. Our data identify Gi-biased agonists, including buprenorphine, and further show highly correlated drug activities in the two otherwise very distinct experimental systems, supporting in vivo translatability of biased signaling for mu opioid drugs.Graphical Graphical abstract for this article
       
  • Injectable Peptide Hydrogel Enables Integrated Tandem Enzymes
           Superactivity for Cancer Therapy

    • Abstract: Publication date: Available online 15 March 2019Source: iScienceAuthor(s): Qingcong Wei, Shan Jiang, Rongrong Zhu, Xia Wang, Shilong Wang, Qigang WangSummaryElevation of ROS level and other toxic radicals is an emerging strategy to treat certain cancers by modulating the redox status of cancer cells. The biocatalytic upregulation of singlet oxygen by neutrophilic leukocytes should utilize robust enzymes and design carriers with protective microenvironment. Here, we utilize GOx-CPO as integrated tandem enzymes to in situ generate singlet oxygen, which could be not only for oxidative cross-linking of injectable hydrogel carriers, but also for continuous tumor treatment by adjustable bioconversion of blood oxygen, glucose and chloride ion. The tandem enzymes self-restrained within peptide hydrogel exhibited superactivity for upregulating singlet oxygen relative to free enzymes, which also avoid the diffusion of enzymes from tumor. This work will not only deepen the study of enzymes in biocatalysis but also offer an enzyme therapeutic modality for treating cancers.Graphical Graphical abstract for this article
       
  • Solid-state, Low-cost and Green Synthesis and Robust Photochemical
           Hydrogen Evolution Performance of Ternary TiO2/MgTiO3/C Photocatalysts

    • Abstract: Publication date: Available online 14 March 2019Source: iScienceAuthor(s): Zhongmei Yang, Yunhong Jiang, Wei Zhang, Yanhuai Ding, Yong Jiang, Jiuren Yin, Ping Zhang, Hean Luo Solar-driven photochemical hydrogen evolution is a promising route to sustainable hydrogen fuel production. Large-scale preparation of highly active photocatalysts using elementally abundant and less expensive materials is urgently required for widespread practical application. Here, we report a highly efficient and low-cost TiO2/MgTiO3/C heterostructure photocatalyst for photochemical water splitting, which was synthesized on a gram scale via a facile mechanochemical method. The heterostructure and carbon sensitization offer excellent photoconversion efficiency as well as good photostability. Under irradiation of one AM 1.5G sunlight, the optimal TiO2/MgTiO3/C photocatalyst can show a great solar-driven hydrogen evolution rate (33.3 mmol∙h-1∙g-1), which is much higher than the best yields ever reported for MgTiO3-related photocatalysts or pure TiO2 (P-25). We hope this work will attract more attention to inspire further work by others for the development of low-cost, efficient and robust photocatalysts for producing hydrogen in artificial photosynthetic systems.Graphical Graphical abstract for this article
       
  • Single-strand DNA-binding protein and exogenous RecBCD inhibitors enhance
           phage-derived homologous recombination in Pseudomonas

    • Abstract: Publication date: Available online 12 March 2019Source: iScienceAuthor(s): Jia Yin, Wentao Zheng, Yunsheng Gao, Chanjuan Jiang, Hongbo Shi, Xiaotong Diao, Shanshan Li, Hanna Chen, Hailong Wang, Ruijuan Li, Aiying Li, Liqiu Xia, Yulong Yin, A.Francis Stewart, Youming Zhang, Jun FuSummaryThe limited efficiency of the available tools for genetic manipulation of Pseudomonas, limits fundamental research and utilization of this genus. We explored the properties of a lambda Red-like operon (BAS) from Pseudomonas aeruginosa phage Ab31 and a Rac bacteriophage RecET-like operon (RecTEPsy) from Pseudomonas syringae pv. syringae B728a. Compared to RecTEPsy, the BAS operon was functional at a higher temperature indicating potential to be a generic system for Pseudomonas. Due to the lack of RecBCD inhibitor in the BAS operon, we added Redγ or Pluγ and found increased recombineering efficiencies in P. aeruginosa and P. fluorescens but not in P. putida and P. syringae. Overexpression of single-strand DNA-binding protein enhanced recombineering in several contexts including RecET recombination in E. coli. The utility of these systems was demonstrated by engineering Pseudomonas aeruginosa genomes to create an attenuated rhamnolipid producer. Our work enhances the potential for functional genomics in Pseudomonas.Graphical Graphical abstract for this article
       
  • Mechanical communication acts as a noise filter

    • Abstract: Publication date: Available online 2 March 2019Source: iScienceAuthor(s): Hen Viner, Ido Nitsan, Liel Sapir, Stavit Drori, Shelly TzlilSummaryCells can communicate mechanically by responding to mechanical deformations generated by their neighbors. Here, we describe a new role for mechanical communication by demonstrating that mechanical coupling between cells acts as a signaling cue that reduces intrinsic noise in the interacting cells. We measure mechanical interaction between beating cardiac cells cultured on a patterned flexible substrate and find that beat-to-beat variability decays exponentially with coupling strength. To demonstrate that such noise reduction is indeed a direct consequence of mechanical coupling, we reproduce the exponential decay in an assay where a beating cell interacts mechanically with an artificial stochastic ‘mechanical cell’. The ‘mechanical cell’ consists of a probe that mimics the deformations generated by a stochastically beating neighboring cardiac cell. We show that noise reduction through mechanical coupling persists long after stimulation stops and identify microtubule integrity, NOX2 and CaMKII as mediators of noise reduction.Graphical Graphical abstract for this article
       
  • Alzheimer Aβ Assemblies Accumulate in Excitatory Neurons upon Proteasome
           Inhibition and Kill Nearby NAKα3 Neurons by Secretion

    • Abstract: Publication date: Available online 28 February 2019Source: iScienceAuthor(s): Hitomi Komura, Shota Kakio, Tomoya Sasahara, Yoshie Arai, Naomi Takino, Michio Sato, Kaori Satomura, Takayuki Ohnishi, Yo-ichi Nabeshima, Shin-ichi Muramatsu, Isao Kii, Minako HoshiSummaryWe identified ∼30-mer amyloid-β protein (Aβ) assemblies, termed amylospheroids, from brains of patients with Alzheimer disease (AD) as toxic entities responsible for neurodegeneration and showed that Na+,K+-ATPase α3 (NAKα3) is the sole target of amylospheroid-mediated neurodegeneration. However, it remains unclear where in neurons amylospheroids form and how they reach their targets to induce neurodegeneration. Here, we present an in vitro culture system designed to chronologically follow amylospheroid formation in mature neurons expressing amyloid precursor protein bearing early-onset AD mutations. Amylospheroids were found to accumulate mainly in the trans-Golgi network of excitatory neurons and were initially transported in axons. Proteasome inhibition dramatically increased amylospheroid amounts in trans-Golgi by increasing Aβ levels and induced dendritic transport. Amylospheroids were secreted and caused the degeneration of adjacent NAKα3-expressing neurons. Interestingly, the ASPD-producing neurons later died non-apoptotically. Our findings demonstrate a link between ASPD levels and proteasome function, which may have important implications for AD pathophysiology.Graphical Graphical abstract for this article
       
  • Firefly-Inspired Approach to Develop New Chemiluminescence Materials

    • Abstract: Publication date: Available online 7 February 2019Source: iScienceAuthor(s): Yuxing Yan, Shuo Wang, Fuli Xie, Xiaofeng Fang, Yu-Mo Zhang, Sean Xiao-An ZhangSummaryBioluminescence, wherein marine and terrestrial organisms chemically produce light for communication, is a burgeoning area of research. Herein, we demonstrate a new series of artificial chemiluminescent compounds inspired by the enol-degradation reaction of natural bioluminescent molecules, luciferins. Based on systematic optical experiments, isotope labeling, and theoretical calculations, the chemiluminescent mechanism of these new materials and the relationship of enol-degradation reaction and chemiluminescence are fully discussed. The color and efficiency of the artificial chemiluminescent materials can be easily adjusted, and blue (486 nm), yellow (565 nm), and near-infrared (756 nm) luminescence can thus be obtained. The findings and in-depth understanding herein may accelerate the development of bio/chemiluminescent materials for analytical applications and non-invasive bioluminescence imaging.Graphical Graphical abstract for this article
       
 
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