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Mar 2021 • Nature communications 12 (1), 1-9, 2021

Aging power spectrum of membrane protein transport and other subordinated random walks

Zachary Fox, Eli Barkai, Diego Krapf

Single-particle tracking offers detailed information about the motion of molecules in complex environments such as those encountered in live cells, but the interpretation of experimental data is challenging. One of the most powerful tools in the characterization of random processes is the power spectral density. However, because anomalous diffusion processes in complex systems are usually not stationary, the traditional Wiener-Khinchin theorem for the analysis of power spectral densities is invalid. Here, we employ a recently developed tool named aging Wiener-Khinchin theorem to derive the power spectral density of fractional Brownian motion coexisting with a scalefree continuous time random walk, the two most typical anomalous diffusion processes. Using this analysis, we characterize the motion of voltage-gated sodium channels on the surface of hippocampal neurons. Our results show aging where the power spectral density can either increase or decrease with observation time depending on the specific parameters of both underlying processes.

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Mar 2021 • Physical Review Research

Experimental tests of multiplicative Bell inequalities and the fundamental role of local correlations

Dilip Paneru, Amit Te'eni, Bar Y Peled, James Hubble, Yingwen Zhang, Avishy Carmi, Eliahu Cohen, Ebrahim Karimi

Bell inequalities are mathematical constructs that demarcate the boundary between quantum and classical physics. A new class of multiplicative Bell inequalities originating from a volume maximization game (based on products of correlators within bipartite systems) has been recently proposed. For these new Bell parameters, it is relatively easy to find the classical and quantum, ie, Tsirelson, limits. Here, we experimentally test the Tsirelson bounds of these inequalities using polarization-entangled photons for a different number of measurements (n), each party can perform. For n= 2, 3, 4, we report the experimental violation of local hidden variable theories. In addition, we experimentally compare the results with the parameters obtained from a fully deterministic strategy, and observe the conjectured nature of the ratio. Finally, utilizing the principle of “relativistic independence” encapsulating the locality of uncertainty …

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Mar 2021 • Journal of Experimental Medicine

Inherited SLP76 deficiency in humans causes severe combined immunodeficiency, neutrophil and platelet defects

Atar Lev, Yu Nee Lee, Guangping Sun, Enas Hallumi, Amos J Simon, Keren S Zrihen, Shiran Levy, Tal Beit Halevi, Maria Papazian, Neta Shwartz, Ido Somekh, Sarina Levy-Mendelovich, Baruch Wolach, Ronit Gavrieli, Helly Vernitsky, Ortal Barel, Elisheva Javasky, Tali Stauber, Chi A Ma, Yuan Zhang, Ninette Amariglio, Gideon Rechavi, Ayal Hendel, Deborah Yablonski, Joshua D Milner, Raz Somech

The T cell receptor (TCR) signaling pathway is an ensemble of numerous proteins that are crucial for an adequate immune response. Disruption of any protein involved in this pathway leads to severe immunodeficiency and unfavorable clinical outcomes. Here, we describe an infant with severe immunodeficiency who was found to have novel biallelic mutations in SLP76. SLP76 is a key protein involved in TCR signaling and in other hematopoietic pathways. Previous studies of this protein were performed using Jurkat-derived human leukemic T cell lines and SLP76-deficient mice. Our current study links this gene, for the first time, to a human immunodeficiency characterized by early-onset life-threatening infections, combined T and B cell immunodeficiency, severe neutrophil defects, and impaired platelet aggregation. Hereby, we characterized aspects of the patient's immune phenotype, modeled them with an …

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Mar 2021 • Neuromolecular medicine

Specific susceptibility to COVID-19 in adults with down syndrome

Tomer Illouz, Arya Biragyn, Milana Frenkel-Morgenstern, Orly Weissberg, Alessandro Gorohovski, Eugene Merzon, Ilan Green, Florencia Iulita, Lisi Flores-Aguilar, Mara Dierssen, Ilario De Toma, Hefziba Lifshitz, Stylianos E Antonarakis, Eugene Yu, Yann Herault, Marie-Claude Potier, Alexandra Botté, Randall Roper, Benjamin Sredni, Ronit Sarid, Jacqueline London, William Mobley, Andre Strydom, Eitan Okun

The current SARS-CoV-2 outbreak, which causes COVID-19, is particularly devastating for individuals with chronic medical conditions, in particular those with Down Syndrome (DS) who often exhibit a higher prevalence of respiratory tract infections, immune dysregulation and potential complications. The incidence of Alzheimer’s disease (AD) is much higher in DS than in the general population, possibly increasing further the risk of COVID-19 infection and its complications. Here we provide a biological overview with regard to specific susceptibility of individuals with DS to SARS-CoV-2 infection as well as data from a recent survey on the prevalence of COVID-19 among them. We see an urgent need to protect people with DS, especially those with AD, from COVID-19 and future pandemics and focus on developing protective measures, which also include interventions by health systems worldwide for reducing …

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Feb 2021 • Current Opinion in Electrochemistry 25, 100620, 2021

Methods for assessment and measurement of the active site density in platinum group metal–free oxygen reduction reaction catalysts

Alisa Kozhushner, Noam Zion, Lior Elbaz

The recent rise in the activity of platinum group metal–free oxygen reduction reaction catalysts for polymer electrolyte fuel cells, made them very interesting alternative for Pt-based catalysts. Currently, the application of this family of catalysts in fuel cells is impeded by their relatively low durability and stability. The lack of simple methods to follow the specific degradation of these catalysts in situ and in operando fuel cells inhibits durability and stability studies, where the key catalyst performance descriptor is the turnover frequency, for which the electrochemical site density needs to be accurately measured. Herein, the most commonly available techniques for measuring the active site density were surveyed, along with their advantages and disadvantages, leading to the conclusion that only electrochemical techniques such as square wave voltammetry and Fourier transform alternating current voltammetry can be used …

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Feb 2021 • Optics Express

Remote photonic sensing of blood oxygen saturation via tracking of anomalies in micro-saccades patterns

Zeev Kalyuzhner, Sergey Agdarov, Aviya Bennett, Yafim Beiderman, Zeev Zalevsky

Speckle pattern analysis has been found by many researchers to be applicable to remote sensing of various biomedical parameters. This paper shows how analysis of dynamic differential speckle patterns scattered from subjects’ sclera illuminated by a laser beam allows extraction of micro-saccades movement in the human eye. Analysis of micro-saccades movement using advanced machine learning techniques based on convolutional neural networks offers a novel approach for non-contact assessment of human blood oxygen saturation level (SpO2). Early stages of hypoxia can rapidly progress into pneumonia and death, and lives can be saved by advance remote detection of reduced blood oxygen saturation.

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Feb 2021 • Current Opinion in Electrochemistry 25, 100620, 2021

Methods for assessment and measurement of the active site density in platinum group metal–free oxygen reduction reaction catalysts

Alisa Kozhushner, Noam Zion, Lior Elbaz

The recent rise in the activity of platinum group metal–free oxygen reduction reaction catalysts for polymer electrolyte fuel cells, made them very interesting alternative for Pt-based catalysts. Currently, the application of this family of catalysts in fuel cells is impeded by their relatively low durability and stability. The lack of simple methods to follow the specific degradation of these catalysts in situ and in operando fuel cells inhibits durability and stability studies, where the key catalyst performance descriptor is the turnover frequency, for which the electrochemical site density needs to be accurately measured. Herein, the most commonly available techniques for measuring the active site density were surveyed, along with their advantages and disadvantages, leading to the conclusion that only electrochemical techniques such as square wave voltammetry and Fourier transform alternating current voltammetry can be used …

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Feb 2021 • The Journal of Physical Chemistry B

Temperature-Dependent Kinetic Isotope Effects in R67 Dihydrofolate Reductase from Path-Integral Simulations

Anil R Mhashal, Dan Thomas Major

Calculation of temperature-dependent kinetic isotope effects (KIE) in enzymes presents a significant theoretical challenge. Additionally, it is not trivial to identify enzymes with available experimental accurate intrinsic KIEs in a range of temperatures. In the current work, we present a theoretical study of KIEs in the primitive R67 dihydrofolate reductase (DHFR) enzyme and compare with experimental work. The advantage of R67 DHFR is its significantly lower kinetic complexity compared to more evolved DHFR isoforms. We employ mass-perturbation-based path-integral simulations in conjunction with umbrella sampling and a hybrid quantum mechanics–molecular mechanics Hamiltonian. We obtain temperature-dependent KIEs in good agreement with experiments and ascribe the temperature-dependent KIEs primarily to zero-point energy effects. The active site in the primitive enzyme is found to be poorly …

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Feb 2021 • Energy Technology

Hydrogen‐Bromine Redox‐Flow Battery Cycling with Bromine Complexing Agent: on the Benefits of Nanoporous Separator Versus Proton Exchange Membrane

Kobby Saadi, Michael Kuettinger, Peter Fischer, David Zitoun

The reversible and fast redox kinetics of bromine/bromide makes it a desirable couple as a catholyte in redox‐flow batteries (RFBs). In principle, the highest possible energy density is obtained with hydrogen‐bromine RFBs. Bromine sequestration agents, also called bromine complexing agents (BCAs), bind bromine in a non‐miscible phase and can, therefore, reduce the vapor pressure of bromine, mitigate its crossover, and result in higher practical range of electrolyte concentration. Therefore, BCAs can enhance the battery's safety and competitivity by significantly decreasing the cost of components. To date, BCAs are commonly used in membrane‐free bromine systems, which cannot provide the high current density demonstrated in hydrogen‐bromine RFBs. Herein, the drastic limitations encountered are shown while operating a hydrogen‐bromine RFB with a standard perfluorinated sulfonic acid membrane due …

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Feb 2021 • Nanomaterials

Green synthesis of multifunctional carbon dots with antibacterial activities

Arumugam Saravanan, Moorthy Maruthapandi, Poushali Das, John HT Luong, Aharon Gedanken

Carbon dots (CDs) were obtained from medicinal turmeric leaves (Curcuma longa) by a facile one-step hydrothermal method and evaluated for their bactericidal activities against two gram-negative; Escherichia coli, Klebsiella pneumoniae, and two gram-positive counterparts; Staphylococcus aureus, S. epidermidis. The CDs exhibited spherical shapes with a mean size of 2.6 nm. The fluorescence spectra of CDs revealed intense fluorescence at λ ex/em= 362/429 nm with a bright blue color in an aqueous solution. The CDs showed strong photostability under various environmental conditions (pH, salt, and UV-radiation). The complete bactericidal potency of CDs was 0.25 mg/mL for E. coli and S. aureus after 8 h of exposure, while for K. pneumoniae, and S. epidermidis, the CDs at 0.5 mg/mL good antibacterial effect within 8 h and complete eradication after 24 h of exposure is observed. The release of reactive oxygen species played a crucial role in the death of the bacterial cell. The present study provides a strategy for the preparation of CDs from a medicinal plant and their potential antibacterial activities against four common contagious pathogens. View Full-Text

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Feb 2021 • Entropy

Cusp of non-Gaussian density of particles for a diffusing diffusivity model

M Hidalgo-Soria, Eli Barkai, Stanislav Burov

We study a two state “jumping diffusivity” model for a Brownian process alternating between two different diffusion constants, D+> D−, with random waiting times in both states whose distribution is rather general. In the limit of long measurement times, Gaussian behavior with an effective diffusion coefficient is recovered. We show that, for equilibrium initial conditions and when the limit of the diffusion coefficient D−⟶ 0 is taken, the short time behavior leads to a cusp, namely a non-analytical behavior, in the distribution of the displacements P (x, t) for x⟶ 0. Visually this cusp, or tent-like shape, resembles similar behavior found in many experiments of diffusing particles in disordered environments, such as glassy systems and intracellular media. This general result depends only on the existence of finite mean values of the waiting times at the different states of the model. Gaussian statistics in the long time limit is achieved due to ergodicity and convergence of the distribution of the temporal occupation fraction in state D+ to a δ-function. The short time behavior of the same quantity converges to a uniform distribution, which leads to the non-analyticity in P (x, t). We demonstrate how super-statistical framework is a zeroth order short time expansion of P (x, t), in the number of transitions, that does not yield the cusp like shape. The latter, considered as the key feature of experiments in the field, is found with the first correction in perturbation theory.

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Feb 2021 • ChemElectroChem

Determining the Electrochemical Oxygen Evolution Reaction Kinetics of Fe3S4@Ni3S2 Using Distribution Function of Relaxation Times

Bibhudatta Malik, Kalimuthu Vijaya Sankar, Rajashree Konar, Yoed Tsur, Gilbert Daniel Nessim

We designed a heterostructure of Fe3S4@ Ni3S2, as a potent oxygen evolution reaction (OER) electrocatalyst in an alkaline medium. Intriguingly, Fe3S4@ Ni3S2 exhibits low onset potential of290 mV and overpotential of 360 mV at a current density of 10 mA cm-2. We examined the OER kinetics of Fe3S4@ Ni3S2 using distribution function of relaxation times (DFRT), which are attained with the help of impedance spectroscopy genetic programming (ISGP). ISGP reveals the occurrences of three events of OER, manifested as peaks in the DFRT, such as active material or pores (P2), charge transfer (P1’), and production rate of intermediates (P1) in case of Fe3S4@ Ni3S2 at different faradic overpotentials. The effective resistance of each phenomenon can be easily calculated. It decreases with an increase in conductivity at high overpotentials for all the three, which suggests the high performance of the as-synthesized composite due to faster kinetics.

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Feb 2021 • Advanced Functional Materials

Understanding the Role of Alumina (Al2O3), Pentalithium Aluminate (Li5AlO4), and Pentasodium Aluminate (Na5AlO4) Coatings on the Li and Mn‐Rich NCM Cathode Material 0.33 …

Sandipan Maiti, Hadar Sclar, Rosy Sharma, Noam Vishkin, Miryam Fayena‐Greenstein, Judith Grinblat, Michael Talianker, Larisa Burstein, Nickolay Solomatin, Ortal Tiurin, Yair Ein‐Eli, Malachi Noked, Boris Markovsky, Doron Aurbach

The active role of alumina, pentalithium aluminate (Li5AlO4, Li‐aluminate), and pentasodium aluminate (Na5AlO4, Na‐aluminate) as the surface protection coatings produced via atomic layer deposition on Li and Mn‐rich NCM cathode materials 0.33Li2MnO3·0.67LiNi0.4Co0.2Mn0.4O2 is discussed. A notable improvement in the electrochemical behavior of the coated cathodes has been found while tested in Li‐coin cells at 30 °C. Though all the coated cathodes demonstrate enhanced electrochemical cycling and rate performances, Na‐aluminate coated cathodes exhibit exemplary behavior. Prolonged cycling and rate capability testing demonstrate that after more than 400 cycles at 1 C rate, the uncoated cathode delivers only 63 mAh g−1, while those with alumina, Li‐aluminate, and Na‐aluminate coatings exhibit approximately two times higher specific capacities. The coated cathodes display steady average …

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Feb 2021 • The FASEB Journal

TMF1 is upregulated by insulin and is required for a sustained glucose homeostasis

Roni Rahimi, Israel Malek, Tali Lerrer‐Goldshtein, Yoav Elkis, Irit Shoval, Avi Jacob, Sally Shpungin, Uri Nir

Insulin‐regulated glucose homeostasis is a critical and intricate physiological process, of which not all regulatory components have been deciphered. One of the key players in modulating glucose uptake by cells is the glucose transporter‐GLUT4. In this study, we aimed to explore the regulatory role of the trans‐Golgi‐associated protein‐TATA Element Modulatory Factor (TMF1) in the GLUT4 mediated, insulin‐directed glucose uptake. By establishing and using TMF1−/− myoblasts and mice, we examined the effect of TMF1 absence on the insulin driven functioning of GLUT4. We show that TMF1 is upregulated by insulin in myoblasts, and is essential for the formation of insulin responsive, glucose transporter GLUT4‐containing vesicles. Absence of TMF1 leads to the retention of GLUT4 in perinuclear compartments, and to severe impairment of insulin‐stimulated GLUT4 trafficking throughout the cytoplasm and to the …

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Feb 2021 • arXiv preprint arXiv:2102.01370

Efficient Interaction of Heralded X-ray Photons with a Beam Splitter

E Strizhevsky, D Borodin, A Schori, S Francoual, R Röhlsberger, S Shwartz

We report the experimental demonstration of efficient interaction of multi kilo electron Volt heralded x-ray photons with a beam splitter. The measured heralded photon rate at the outputs of the beam splitter is about 0.01 counts/s which is comparable to the rate in the absence of the beam splitter. We use this beam splitter together with photon number and photon energy resolving detectors to show directly that single x ray photons cannot split. Our experiment demonstrates the major advantage of x rays for quantum optics: the possibility to observe experimental results with high fidelity and with negligible background.

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Feb 2021 • PLoS pathogens

Multi-clonal SARS-CoV-2 neutralization by antibodies isolated from severe COVID-19 convalescent donors

Michael Mor, Michal Werbner, Joel Alter, Modi Safra, Elad Chomsky, Jamie C Lee, Smadar Hada-Neeman, Ksenia Polonsky, Cameron J Nowell, Alex E Clark, Anna Roitburd-Berman, Noam Ben-Shalom, Michal Navon, Dor Rafael, Hila Sharim, Evgeny Kiner, Eric R Griffis, Jonathan M Gershoni, Oren Kobiler, Sandra Lawrynowicz Leibel, Oren Zimhony, Aaron F Carlin, Gur Yaari, Moshe Dessau, Meital Gal-Tanamy, David Hagin, Ben A Croker, Natalia T Freund

The interactions between antibodies, SARS-CoV-2 and immune cells contribute to the pathogenesis of COVID-19 and protective immunity. To understand the differences between antibody responses in mild versus severe cases of COVID-19, we analyzed the B cell responses in patients 1.5 months post SARS-CoV-2 infection. Severe, and not mild, infection correlated with high titers of IgG against Spike receptor binding domain (RBD) that were capable of ACE2:RBD inhibition. B cell receptor (BCR) sequencing revealed that VH3-53 was enriched during severe infection. Of the 22 antibodies cloned from two severe donors, six exhibited potent neutralization against authentic SARS-CoV-2, and inhibited syncytia formation. Using peptide libraries, competition ELISA and mutagenesis of RBD, we mapped the epitopes of the neutralizing antibodies (nAbs) to three different sites on the Spike. Finally, we used combinations of nAbs targeting different immune-sites to efficiently block SARS-CoV-2 infection. Analysis of 49 healthy BCR repertoires revealed that the nAbs germline VHJH precursors comprise up to 2.7% of all VHJHs. We demonstrate that severe COVID-19 is associated with unique BCR signatures and multi-clonal neutralizing responses that are relatively frequent in the population. Moreover, our data support the use of combination antibody therapy to prevent and treat COVID-19.

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Feb 2021 • arXiv preprint arXiv:2102.07755

Chemical element mapping by x-ray ghost fluorescence

Y Klein, O Sefi, H Schwartz, S Shwartz

Chemical element mapping is an imaging tool that provides essential information on composite materials and it is crucial for a broad range of fields ranging from fundamental science to numerous applications. Methods that exploit x-ray fluorescence are very advantageous and are widely used, but require focusing of the input beam and raster scanning of the sample. Thus the methods are slow and exhibit limited resolution due to focusing challenges. We demonstrate a new focusing free x-ray fluorescence method based ghost imaging that overcomes those limitations. We combine our procedure with compressed sensing to reduce the measurement time and the exposure to radiation by more than 80%. Since our method does not require focusing, it opens the possibility for improving the resolution and image quality of chemical element maps with tabletop x-ray sources and for extending the applicability of x-ray fluorescence detection to new fields such as medical imaging and homeland security applications

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Feb 2021 • Biosensors and Bioelectronics

Unidirectional electron injection and accelerated proton transport in bacteriorhodopsin based Bio-pn junctions

Yujia Lv, Dawei Liang, Shanfu Lu, Doron Aurbach, Yan Xiang

Hampered by the absence of evidence and theoretical model of biological semiconductors, the unidirectional electron transport via the p-n junction between functional proteins and abiotic materials remains a challenge for bioelectronics. Bacteriorhodopsin (bR), a representative transmembrane protein, has demonstrated exceptional optoelectronic effects in bR/semiconductor hybrid materials and offers a possible pathway for addressing this challenge. In the present work, for the first time, bR is proved to be an n-type semiconductor with an indirect electron transition. Through the photo-electrochemical method used for studying the p-n junction effect in the bR and p-type semiconductor combined electrodes, we reached several important conclusions: The self-corrosion of bR integrated Cu2O electrodes is delayed for about 36 times; The photocurrent of bR integrated CuSCN electrodes is enhanced by about 400 …

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Feb 2021 • Viruses

An Efficient, Counter-Selection-Based Method for Prophage Curing in Pseudomonas aeruginosa Strains

Esther Shmidov, Itzhak Zander, Ilana Lebenthal-Loinger, Sarit Karako-Lampert, Sivan Shoshani, Ehud Banin

Prophages are bacteriophages in the lysogenic state, where the viral genome is inserted within the bacterial chromosome. They contribute to strain genetic variability and can influence bacterial phenotypes. Prophages are highly abundant among the strains of the opportunistic pathogen Pseudomonas aeruginosa and were shown to confer specific traits that can promote strain pathogenicity. The main difficulty of studying those regions is the lack of a simple prophage-curing method for P. aeruginosa strains. In this study, we developed a novel, targeted-curing approach for prophages in P. aeruginosa. In the first step, we tagged the prophage for curing with an ampicillin resistance cassette (ampR) and further used this strain for the sacB counter-selection marker's temporal insertion into the prophage region. The sucrose counter-selection resulted in different variants when the prophage-cured mutant is the sole variant that lost the ampR cassette. Next, we validated the targeted-curing with local PCR amplification and Whole Genome Sequencing. The application of the strategy resulted in high efficiency both for curing the Pf4 prophage of the laboratory wild-type (WT) strain PAO1 and for PR2 prophage from the clinical, hard to genetically manipulate, 39016 strain. We believe this method can support the research and growing interest in prophage biology in P. aeruginosa as well as additional Gram-negative bacteria.

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Feb 2021 • arXiv preprint arXiv:2102.12856

Supercontinuum Generation by Saturated χ (2) Interactions

Marc Jankowski, Carsten Langrock, Boris Desiatov, Marko Loncar, MM Fejer

We demonstrate a new approach to supercontinuum generation and carrier-envelope-offset detection in dispersion-engineered nanophotonic waveguides based on saturated second-harmonic generation of femtosecond pulses. In contrast with traditional approaches based on self-phase modulation, this technique simultaneously broadens both harmonics by generating rapid amplitude modulations of the field envelopes. The generated supercontinuum produces coherent carrier-envelope-offset beatnotes in the overlap region that remain in phase across 100's of nanometers of bandwidth while requiring 10 picojoules of pulse energy.

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Feb 2021 • Current Biology

Early life experience shapes male behavior and social networks in Drosophila

Assa Bentzur, Shir Ben-Shaanan, Jennifer IC Benichou, Eliezer Costi, Mali Levi, Amiyaal Ilany, Galit Shohat-Ophir

Living in a group creates a complex and dynamic environment in which behavior of individuals is influenced by and affects the behavior of others. Although social interaction and group living are fundamental adaptations exhibited by many organisms, little is known about how prior social experience, internal states, and group composition shape behavior in groups. Here, we present an analytical framework for studying the interplay between social experience and group interaction in Drosophila melanogaster. We simplified the complexity of interactions in a group using a series of experiments in which we controlled the social experience and motivational states of individuals to compare behavioral patterns and social networks of groups under different conditions. We show that social enrichment promotes the formation of distinct group structure that is characterized by high network modularity, high inter-individual and …

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