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Jan 2021 • International Journal of Molecular Sciences 22 (4), 2050, 2021

Advances in Understanding of the Copper Homeostasis in Pseudomonas aeruginosa

Lukas Hofmann, Melanie Hirsch, Sharon Ruthstein

Thirty-five thousand people die as a result of more than 2.8 million antibiotic-resistant infections in the United States of America per year. Pseudomonas aeruginosa (P. aeruginosa) is classified a serious threat, the second-highest threat category of the US Department of Health and Human Services. Among others, the World Health Organization (WHO) encourages the discovery and development of novel antibiotic classes with new targets and mechanisms of action without cross-resistance to existing classes. To find potential new target sites in pathogenic bacteria, such as P. aeruginosa, it is inevitable to fully understand the molecular mechanism of homeostasis, metabolism, regulation, growth, and resistances thereof. P. aeruginosa maintains a sophisticated copper defense cascade comprising three stages, resembling those of public safety organizations. These stages include copper scavenging, first responder, and second responder. Similar mechanisms are found in numerous pathogens. Here we compare the copper-dependent transcription regulators cueR and copRS of Escherichia coli (E. coli) and P. aeruginosa. Further, phylogenetic analysis and structural modelling of mexPQ-opmE reveal that this efflux pump is unlikely to be involved in the copper export of P. aeruginosa. Altogether, we present current understandings of the copper homeostasis in P. aeruginosa and potential new target sites for antimicrobial agents or a combinatorial drug regimen in the fight against multidrug resistant pathogens. View Full-Text

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Jan 2021 • bioRxiv

immuneML: an ecosystem for machine learning analysis of adaptive immune receptor repertoires

Milena Pavlovic, Lonneke Scheffer, Keshav Motwani, Chakravarthi Kanduri, Radmila Kompova, Nikolay Vazov, Knut Waagan, Fabian LM Bernal, Alexandre Almeida Costa, Brian Corrie, Rahmad Akbar, Ghadi S Al Hajj, Gabriel Balaban, Todd M Brusko, Maria Chernigovskaya, Scott Christley, Lindsay G Cowell, Robert Frank, Ivar Grytten, Sveinung Gundersen, Ingrid Hobæk Haff, Sepp Hochreiter, Eivind Hovig, Ping-Han Hsieh, Gunter Klambauer, Marieke L Kuijjer, Christin Lund-Andersen, Antonio Martini, Thomas Minotto, Johan Pensar, Knut Rand, Enrico Riccardi, Philippe A Robert, Artur Rocha, Andrei Slabodkin, Igor Snapkov, Ludvig M Sollid, Dmytro Titov, Cédric R Weber, Michael Widrich, Gur Yaari, Victor Greiff, Geir Kjetil Sandve

Adaptive immune receptor repertoires (AIRR) are key targets for biomedical research as they record past and ongoing adaptive immune responses. The capacity of machine learning (ML) to identify complex discriminative sequence patterns renders it an ideal approach for AIRR-based diagnostic and therapeutic discovery. To date, widespread adoption of AIRR ML has been inhibited by a lack of reproducibility, transparency, and interoperability. immuneML ( addresses these concerns by implementing each step of the AIRR ML process in an extensible, open-source software ecosystem that is based on fully specified and shareable workflows. To facilitate widespread user adoption, immuneML is available as a command-line tool and through an intuitive Galaxy web interface, and extensive documentation of workflows is provided. We demonstrate the broad applicability of immuneML by (i) reproducing a large-scale study on immune state prediction, (ii) developing, integrating, and applying a novel method for antigen specificity prediction, and (iii) showcasing streamlined interpretability-focused benchmarking of AIRR ML.

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Jan 2021 • Advanced Materials

Mutually Reinforced Polymer–Graphene Bilayer Membranes for Energy‐Efficient Acoustic Transduction

Assad U Khan, Gabriel Zeltzer, Gavriel Speyer, Zacary L Croft, Yichen Guo, Yehiel Nagar, Vlada Artel, Adi Levi, Chen Stern, Doron Naveh, Guoliang Liu

Graphene holds promise for thin, ultralightweight, and high‐performance nanoelectromechanical transducers. However, graphene‐only devices are limited in size due to fatigue and fracture of suspended graphene membranes. Here, a lightweight, flexible, transparent, and conductive bilayer composite of polyetherimide and single‐layer graphene is prepared and suspended on the centimeter scale with an unprecedentedly high aspect ratio of 105. The coupling of the two components leads to mutual reinforcement and creates an ultrastrong membrane that supports 30 000 times its own weight. Upon electromechanical actuation, the membrane pushes a massive amount of air and generates high‐quality acoustic sound. The energy efficiency is ≈10–100 times better than state‐of‐the‐art electrodynamic speakers. The bilayer membrane's combined properties of electrical conductivity, mechanical strength, optical …

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Jan 2021 • PLoS computational biology

Breast cancer is marked by specific, Public T-cell receptor CDR3 regions shared by mice and humans

Miri Gordin, Hagit Philip, Alona Zilberberg, Moriah Gidoni, Raanan Margalit, Christopher Clouser, Kristofor Adams, Francois Vigneault, Irun R Cohen, Gur Yaari, Sol Efroni

The partial success of tumor immunotherapy induced by checkpoint blockade, which is not antigen-specific, suggests that the immune system of some patients contain antigen receptors able to specifically identify tumor cells. Here we focused on T-cell receptor (TCR) repertoires associated with spontaneous breast cancer. We studied the alpha and beta chain CDR3 domains of TCR repertoires of CD4 T cells using deep sequencing of cell populations in mice and applied the results to published TCR sequence data obtained from human patients. We screened peripheral blood T cells obtained monthly from individual mice spontaneously developing breast tumors by 5 months. We then looked at identical TCR sequences in published human studies; we used TCGA data from tumors and healthy tissues of 1,256 breast cancer resections and from 4 focused studies including sequences from tumors, lymph nodes, blood and healthy tissues, and from single cell dataset of 3 breast cancer subjects. We now report that mice spontaneously developing breast cancer manifest shared, Public CDR3 regions in both their alpha and beta and that a significant number of women with early breast cancer manifest identical CDR3 sequences. These findings suggest that the development of breast cancer is associated, across species, with biomarker, exclusive TCR repertoires.

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Jan 2021 • Materials

Wear behavior characterization of hydrogels constructs for cartilage tissue replacement

Saverio Affatato, Diego Trucco, Paola Taddei, Lorenzo Vannozzi, Leonardo Ricotti, Gilbert Daniel Nessim, Gina Lisignoli

This paper aims to characterize the wear behavior of hydrogel constructs designed for human articular cartilage replacement. To this purpose, poly (ethylene glycol) diacrylate (PEGDA) 10% w/v and gellan gum (GG) 1.5% w/v were used to reproduce the superior (SUP) cartilage layer and PEGDA 15% w/v and GG 1.5% w/v were used to reproduce the deep (DEEP) cartilage layer, with or without graphene oxide (GO). These materials (SUP and DEEP) were analyzed alone and in combination to mimic the zonal architecture of human articular cartilage. The developed constructs were tested using a four-station displacement control knee joint simulator under bovine calf serum. Roughness and micro-computer tomography (µ-CT) measurements evidenced that the hydrogels with 10% w/v of PEGDA showed a worse behavior both in terms of roughness increase and loss of uniformly distributed density than 15% w/v of PEGDA. The simultaneous presence of GO and 15% w/v PEGDA contributed to keeping the hydrogel construct’s characteristics. The Raman spectra of the control samples showed the presence of unreacted C= C bonds in all the hydrogels. The degree of crosslinking increased along the series SUP< DEEP+ SUP< DEEP without GO. The Raman spectra of the tested hydrogels showed the loss of diacrylate groups in all the samples, due to the washout of unreacted PEGDA in bovine calf serum aqueous environment. The loss decreased along the series SUP> DEEP+ SUP> DEEP, further confirming that the degree of photo-crosslinking of the starting materials plays a key role in determining their wear behavior. μ-CT and Raman …

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Jan 2021 • bioRxiv

Sexual deprivation modulates social interaction and reproductive physiology

Liora Omesi, Mali Levi, Assa Bentzur, Yong-Kyu Kim, Shir Ben-Shaanan, Reza Azanchi, Ulrike Heberlein, Galit Shohat-Ophir

Jan 2021 • Nature communications

Alternating quarantine for sustainable epidemic mitigation

Dror Meidan, Nava Schulmann, Reuven Cohen, Simcha Haber, Eyal Yaniv, Ronit Sarid, Baruch Barzel

Absent pharmaceutical interventions, social distancing, lock-downs and mobility restrictions remain our prime response in the face of epidemic outbreaks. To ease their potentially devastating socioeconomic consequences, we propose here an alternating quarantine strategy: at every instance, half of the population remains under lockdown while the other half continues to be active-maintaining a routine of weekly succession between activity and quarantine. This regime minimizes infectious interactions, as it allows only half of the population to interact for just half of the time. As a result it provides a dramatic reduction in transmission, comparable to that achieved by a population-wide lockdown, despite sustaining socioeconomic continuity at~ 50% capacity. The weekly alternations also help address the specific challenge of COVID-19, as their periodicity synchronizes with the natural SARS-CoV-2 disease time-scales …

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Jan 2021 • Israel Journal of Chemistry 61 (1-2), 11-25, 2021

Horizons for Modern Electrochemistry Related to Energy Storage and Conversion, a Review

David Malka, Ran Attias, Netanel Shpigel, Fyodor Malchick, Mikhael D Levi, Doron Aurbach

The purpose of this paper is to suggest frontier inter‐disciplinary research directions that can be considered as important horizons of modern electrochemistry in the field of energy storage and conversion. We selected several topics that call for advancements in solid‐state, interfacial, analytical and energy‐related electrochemical science. A dramatic improvement in the performance of energy storage and conversion devices is needed to meet the urgent demands of our society. Significantly more efficient devices are needed to meet two major challenges: electro‐mobility, namely electrochemical propulsion of electric vehicles, and the ability to store and convert large quantities of energy generated from sustainable sources such as sun and wind. We suggest promotion of breakthroughs in several important directions. The examples chosen include: Development of novel in‐situ methodologies for design and testing …

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Jan 2021 • Nontraditional Activation Methods in Green and Sustainable Applications, 171-239, 2021

The catalytic production of biofuels (biodiesel and bioethanol) using sonochemical, microwave, and mechanical methods

Indra Neel Pulidindi, Aharon Gedanken

The advent of microwave technology and its application to transesterification reaction has revolutionized the biodiesel production process. Unambiguously the microwave-activated solid base catalyzed process is recommended for industrial adaptation. Several solid base catalysts were developed among which SrO-based catalyst supported on millimetric silica beads and SrO supported on porous titanium matrix stand out. Sonochemical methods of activation have the potential for acceleration of biodiesel production. However, the use of homogenization reactor outperformed sonication technology for large-scale utility of biodiesel production. Use of activation methods like microfluidic reactor and solar energy for biodiesel production should not be neglected and should be developed on a par with microwave technology. State-of-the-art methods developed for the production of biodiesel using nontraditional methods …

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Jan 2021 • Applied Sciences

Protective Measurement—A New Quantum Measurement Paradigm: Detailed Description of the First Realization

Enrico Rebufello, Fabrizio Piacentini, Alessio Avella, Rudi Lussana, Federica Villa, Alberto Tosi, Marco Gramegna, Giorgio Brida, Eliahu Cohen, Lev Vaidman, Ivo Pietro Degiovanni, Marco Genovese

We present a detailed description of the experiment realizing for the first time a protective measurement, a novel measurement protocol which combines weak interactions with a “protection mechanism” preserving the measured state coherence during the whole measurement process. Furthermore, protective measurement allows finding the expectation value of an observable, ie, an inherently statistical quantity, by measuring a single particle, without the need for any statistics. This peculiar property, in sharp contrast to the framework of traditional (projective) quantum measurement, might constitute a groundbreaking advance for several quantum technology related fields. View Full-Text

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Jan 2021 • Nature Communications

Observation of anti-parity-time-symmetry, phase transitions and exceptional points in an optical fibre

Arik Bergman, Robert Duggan, Kavita Sharma, Moshe Tur, Avi Zadok, Andrea Alù

The exotic physics emerging in non-Hermitian systems with balanced distributions of gain and loss has recently drawn a great deal of attention. These systems exhibit phase transitions and exceptional point singularities in their spectra, at which eigen-values and eigen-modes coalesce and the overall dimensionality is reduced. So far, these principles have been implemented at the expense of precise fabrication and tuning requirements, involving tailored nano-structured devices with controlled optical gain and loss. In this work, anti-parity-time symmetric phase transitions and exceptional point singularities are demonstrated in a single strand of single-mode telecommunication fibre, using a setup consisting of off-the-shelf components. Two propagating signals are amplified and coupled through stimulated Brillouin scattering, enabling exquisite control over the interaction-governing non-Hermitian parameters …

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2021 • Chemical Communications

Correction: Thiadiazole containing N-and S-rich highly ordered periodic mesoporous organosilica for efficient removal of Hg (II) from polluted water

Surajit Das, Sauvik Chatterjee, Saptarsi Mondal, Arindam Modak, Bijan Krishna Chandra, Suparna Das, Gilbert Daniel Nessim, Adinath Majee, Asim Bhaumik

Correction for ‘Thiadiazole containing N- and S-rich highly ordered periodic mesoporous organosilica for efficient removal of Hg(II) from polluted water’ by Asim Baumik et al., Chem. Commun., 2020, 56, 3963–3966, DOI 10.1039/D0CC00407C.

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2021 • Catalysis Science & Technology

Operando X-ray absorption spectroscopy of a Pd/γ-NiOOH 2 nm cubes hydrogen oxidation catalyst in an alkaline membrane fuel cell

Maria Alesker, Istvan Bakos, Veronica Davies, Qingying Jia, Luba Burlaka, Valeria Yarmiayev, Anya Muzikansky, Anna Kitayev, Miles Page, Sanjeev Mukerjee, David Zitoun

A fundamental understanding of the hydrogen oxidation reaction (HOR) mechanism requires the synthesis of model catalysts with designed surfaces, and advanced characterization techniques of the active sites. Although HOR are fast under acidic conditions, HOR kinetics are sluggish under alkaline conditions, even on platinum group metals (PGMs). Herein, we propose the use of an effective high-surface-area carbon supported Pd/γ-NiOOH HOR electrocatalyst, made from organometallic precursors. The enhanced activity, provided by nickel oxy-hydroxide (γ-NiOOH) 2 nm nanocubes, was confirmed experimentally in an alkaline exchange membrane fuel cell. Contrary to previous reports, the phase and crystallographic orientation of the γ-NiOOH nanocubes (<2 nm in size) were fully ascribed through high-resolution transmission electron microscopy. Operando X-ray absorption spectroscopy revealed a redox …

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2021 • RNA Editing: Methods and Protocols, 213-227, 2021

Detection of A-to-I Hyper-edited RNA Sequences

Roni Cohen-Fultheim, Erez Y Levanon

Following A-to-I editing of double-stranded RNA (dsRNA) molecules, sequencing reactions interpret the edited inosine (I) as guanosine (G). For this reason, current methods to detect A-to-I editing sites work to align RNA sequences to their reference DNA sequence in order to reveal A-to-G mismatches. However, areas with heavily edited reads produce dense clusters of A-to-G mismatches that hinder alignment, and complicate correct identification of the sites. The presented approach employs prudent alignment and examination of excessive mismatch events, enabling high-accuracy detection of hyper-edited reads and sites.

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2021 • Frontiers in cellular and infection microbiology

Extracellular Vesicles in Infectious Diseases

Neta Regev-Rudzki, Shulamit Michaeli, Ana Claudia Torrecilhas

Extracellular vesicles (EVs) isolated from pathogens mediate communication between parasites and their hosts under a variety of physiological and pathological conditions. EVs deliver cell-free messages via a transfer of RNA, proteins, and even DNA to modulate and induce inflammation and to control the host infection process. EVs can provide valuable information on how a pathogen sends messages to other pathogens and hosts (Torrecilhas et al., 2012; Campos et al., 2015; Ofir-Birin and Regev-Rudzki, 2019; Torrecilhas et al. 2020). This Research Topic provides an overview of the mechanism of EV-mediated communication between hosts and viruses, parasites, and fungi. This Research Topic consists of 17 papers, including 8 reviews and 9 original papers. Several studies on this topic assessed the effects of EVs on the interactions between pathogens and hosts, and the mechanisms of EV-mediated communication between hosts and pathogens were also addressed. The first original article published in this Frontiers in Cellular and Infection Microbiology Parasite and Host issue is from Duguet’s group (Duguet et al.). They showed that EVs isolated from Caenorhabditis elegans contain microRNAs and small regulators that affect biological processes and comment on their role in host-nematode communication. Parasite-derived miRNAs regulate host immune system mRNAs.The paper by Zhang et al. discusses how Echinococcus granulosus protoscoleces (PSCs) and hydatid cysts release EVs that are exosome-like based on size and morphology. The authors analyzed the miRNA, circRNA, and lncRNA profiles of the 20 most abundant …

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2021 • Frontiers in Energy Research

Na0.44MnO2/Polyimide Aqueous Na-ion Batteries for Large Energy Storage Applications

Satyanarayana Maddukuri, Amey Nimkar, Munseok S Chae, Tirupathi Rao Penki, Shalom Luski, Doron Aurbach

Aqueous salt batteries with high concentration of salt or water in salt aqueous systems have received considerable attention with focus on improving working voltage range and energy density. Here, the effect of concentration on electrochemical performance and stability of tunnel-type Na0.44MnO2 (NMO) cathode and organic polyimide (PI) derivative as an anode was studied. High capacity retention and 100% coulombic efficiency are shown for NMO/PI full cell in saturated NaClO4 electrolyte. A high stable capacity of 115 mAh/g was achieved for the PI anode material, and the full cell showed stable capacity of 41 mAh/g at 2C rate for 430 cycles (calculated for the weight of NMO cathode). Even at fast 5C rate, a discharge capacity of 33 mAh/g was maintained for 2,400 prolonged cycles with nearly 100% efficiency. The full cell device can achieve an average voltage of 1 V with energy density of 24 Wh/kg. This study highlights concentrated sodium perchlorate as a promising electrolyte solution for stabilization of electrodes and enhancement of electrochemical performance in aqueous media.

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2021 • Materials Horizons

Ultra-small natural product based coordination polymer nanodots for acute kidney injury relief

Rui Zhang, Liang Cheng, Ziliang Dong, Linqian Hou, Shaohua Zhang, Zhouqi Meng, Oshra Betzer, Yihua Wang, Rachela Popovtzer, Zhuang Liu

Acute kidney injury (AKI) is frequently associated with reactive oxygen species (ROS) and causes high mortality in clinics annually, and nanotechnology-mediated antioxidative therapy is emerging as a novel strategy for AKI treatment. Herein, four kinds of natural antioxidants are able to coordinate with iron (Fe) ions to form ultra-small coordination polymer nanodots (CPNs) with good water dispersibility and strong ROS scavenging ability. In particular, Fe–curcumin CPNs (Fe–Cur CPNs) are applied for cellular ROS scavenging and rhabdomyolysis-induced AKI relief.

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2021 • Chemical Communications

Combining polarized low-frequency Raman with XRD to identify directional structural motifs in a pyrolysis precursor

Tal Ben Uliel, Eliyahu M Farber, Hagit Aviv, Wowa Stroek, Marilena Farbinteanu, Yaakov R Tischler, David Eisenberg

Long–range structures and dynamics are central to coordination chemistry, yet are hard to identify experimentally. By combining polarized low-frequency Raman spectroscopy with single crystal XRD to study barium nitrilotriacetate, a metal–organic coordination polymer and a useful pyrolysis precursor, we could assign Raman peaks experimentally to layer shear motions and perpendicular hydrogen bond vibrations. These directional long–range interactions further determined the preferred fracture directions during crystallization, establishing an important link between structural motifs in the precursor, and the porosity of the carbon it yields upon pyrolysis.

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2021 • Deep Sequencing Data Analysis, 59-80, 2021

Applications of community detection algorithms to large biological datasets

Itamar Kanter, Gur Yaari, Tomer Kalisky

2021 • International Journal of Nanomedicine

Diffusion reflection method for early detection of oral squamous cell carcinoma specifically targeted by circulating gold-nanorods bio-conjugated to anti-epidermal growth …

Shiran Sudri, Hamootal Duadi, Florin Altman, Irit Allon, Ariel Ashkenazy, Ruchira Chakraborty, Ilya Novikov, Dror Fixler, Abraham Hirshberg

BackgroundTranslation of nanomedical developments into clinical application is receiving an increasing interest. However, its use for oral squamous cell carcinoma (OSCC) diagnosis remains limited. We present an advanced nanophotonic method for oral cancer detection, based on diffusion reflection (DR) measurements of gold-nanorods bio-conjugated to anti-epidermal growth factor receptor (C-GNRs) specifically attached to OSCC cells.ObjectiveTo investigate in a rat model of oral carcinogenesis the targeting potential of C-GNRs to OSCC by using the DR optical method.Materials and MethodsOSCC was induced by the carcinogen 4-nitroquinoline-N-oxide (4NQO). C-GNRs were introduced locally and systemically and DR measurements were recorded from the surface of the rat tongue following illumination with red laser beam. Rats were divided into experimental and control groups. The results were …

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2021 • Quantum Electronics

Interaction of laser radiation and complexes of gold nanoparticles linked with proteins

Sergei Vladimirovich Zar'kov, Yu A Avetisyan, Aleksandr Nikolaevich Yakunin, Irina Gennad'evna Meerovich, D Fixler, Aleksandr Pavlovich Savitsky, Valerii Viktorovich Tuchin

The results of numerical simulation of the near-field distribution inside and in the vicinity of two types of gold nanoparticles (nanospheres and nanorods) intended for producing complexes of gold nanoparticles linked with proteins and exciting photosensitizers in the wavelength range of 532–770 nm are presented. Quantitative estimates of the field localisation (enhancement) are obtained depending on the type of gold nanoparticles and dimensional factors. The tendency of the red shift of the wavelength at which the maximum local field enhancement is achieved relative to the positions of the maxima of the absorption and scattering cross sections of nanoparticles and complexes is described.

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