bluuebunny/crossref_metadata_2025 huggingface dataset:
Pumping up the charge density of a triboelectric nanogenerator by charge-shuttling
Authors: Wang Huamei , Xu Liang , Bai Yu , Wang Zhong Lin
Published: August 2020

As an emerging technology for harvesting mechanical energy, low surface charge density greatly hinders the practical applications of triboelectric nanogenerators (TENGs). Here, a high-performance TENG based on charge shuttling is demonstrated. Unlike conventional TENGs with static charges fully constrained on the dielectric surface, the device works based on the shuttling of charges corralled in conduction domains. Driven by the interaction of two quasi-symmetrical domains, shuttling of two mirror charge carriers can be achieved to double the charge output. Based on the mechanism, an ultrahigh projected charge density of 1.85 mC m−2 is obtained in ambient conditions. An integrated device for water wave energy harvesting is also presented, confirming its feasibility for practical applications. The device provides insights into new modes of TENGs using unfixed charges in domains, shedding a new light on high-performance mechanical energy harvesting technology.
OTUD5 cooperates with TRIM25 in transcriptional regulation and tumor progression via deubiquitination activity
Authors: Li Fangzhou , Sun Qianqian , Liu Kun , Zhang Ling , Lin Ning , You Kaiqiang , Liu Mingwei , Kon Ning , Tian Feng , Mao Zebin , Li Tingting , Tong Tanjun , Qin Jun , Gu Wei , Li Dawei , Zhao Wenhui
Published: August 2020

Oncogenic processes exert their greatest effect by targeting regulators of cell proliferation. Studying the mechanism underlying growth augmentation is expected to improve clinical therapies. The ovarian tumor (OTU) subfamily deubiquitinases have been implicated in the regulation of critical cell-signaling cascades, but most OTUs functions remain to be investigated. Through an unbiased RNAi screen, knockdown of OTUD5 is shown to significantly accelerate cell growth. Further investigation reveals that OTUD5 depletion leads to the enhanced transcriptional activity of TRIM25 and the inhibited expression of PML by altering the ubiquitination level of TRIM25. Importantly, OTUD5 knockdown accelerates tumor growth in a nude mouse model. OTUD5 expression is markedly downregulated in tumor tissues. The reduced OTUD5 level is associated with an aggressive phenotype and a poor clinical outcome for cancers patients. Our findings reveal a mechanism whereby OTUD5 regulates gene transcription and suppresses tumorigenesis by deubiquitinating TRIM25, providing a potential target for oncotherapy.
Frataxin gene editing rescues Friedreich’s ataxia pathology in dorsal root ganglia organoid-derived sensory neurons
Authors: Mazzara Pietro Giuseppe , Muggeo Sharon , Luoni Mirko , Massimino Luca , Zaghi Mattia , Valverde Parisa Tajalli-Tehrani , Brusco Simone , Marzi Matteo Jacopo , Palma Cecilia , Colasante Gaia , Iannielli Angelo , Paulis Marianna , Cordiglieri Chiara , Giannelli Serena Gea , Podini Paola , Gellera Cinzia , Taroni Franco , Nicassio Francesco , Rasponi Marco , Broccoli Vania
Published: August 2020

Friedreich’s ataxia (FRDA) is an autosomal-recessive neurodegenerative and cardiac disorder which occurs when transcription of the FXN gene is silenced due to an excessive expansion of GAA repeats into its first intron. Herein, we generate dorsal root ganglia organoids (DRG organoids) by in vitro differentiation of human iPSCs. Bulk and single-cell RNA sequencing show that DRG organoids present a transcriptional signature similar to native DRGs and display the main peripheral sensory neuronal and glial cell subtypes. Furthermore, when co-cultured with human intrafusal muscle fibers, DRG organoid sensory neurons contact their peripheral targets and reconstitute the muscle spindle proprioceptive receptors. FRDA DRG organoids model some molecular and cellular deficits of the disease that are rescued when the entire FXN intron 1 is removed, and not with the excision of the expanded GAA tract. These results strongly suggest that removal of the repressed chromatin flanking the GAA tract might contribute to rescue FXN total expression and fully revert the pathological hallmarks of FRDA DRG neurons.
An excess of niche differences maximizes ecosystem functioning
Authors: Godoy Oscar , Gómez-Aparicio Lorena , Matías Luis , Pérez-Ramos Ignacio M. , Allan Eric
Published: August 2020

Ecologists have long argued that higher functioning in diverse communities arises from the niche differences stabilizing species coexistence and from the fitness differences driving competitive dominance. However, rigorous tests are lacking. We couple field-parameterized models of competition between 10 annual plant species with a biodiversity-functioning experiment under two contrasting environmental conditions, to study how coexistence determinants link to biodiversity effects (selection and complementarity). We find that complementarity effects positively correlate with niche differences and selection effects differences correlate with fitness differences. However, niche differences also contribute to selection effects and fitness differences to complementarity effects. Despite this complexity, communities with an excess of niche differences (where niche differences exceeded those needed for coexistence) produce more biomass and have faster decomposition rates under drought, but do not take up nutrients more rapidly. We provide empirical evidence that the mechanisms determining coexistence correlate with those maximizing ecosystem functioning.
Interface chemistry of an amide electrolyte for highly reversible lithium metal batteries
Authors: Wang Qidi , Yao Zhenpeng , Zhao Chenglong , Verhallen Tomas , Tabor Daniel P. , Liu Ming , Ooms Frans , Kang Feiyu , Aspuru-Guzik Alán , Hu Yong-Sheng , Wagemaker Marnix , Li Baohua
Published: August 2020

Metallic lithium is a promising anode to increase the energy density of rechargeable lithium batteries. Despite extensive efforts, detrimental reactivity of lithium metal with electrolytes and uncontrolled dendrite growth remain challenging interconnected issues hindering highly reversible Li-metal batteries. Herein, we report a rationally designed amide-based electrolyte based on the desired interface products. This amide electrolyte achieves a high average Coulombic efficiency during cycling, resulting in an outstanding capacity retention with a 3.5 mAh cm−2 high-mass-loaded LiNi0.8Co0.1Mn0.1O2 cathode. The interface reactions with the amide electrolyte lead to the predicted solid electrolyte interface species, having favorable properties such as high ionic conductivity and high stability. Operando monitoring the lithium spatial distribution reveals that the highly reversible behavior is related to denser deposition as well as top-down stripping, which decreases the formation of porous deposits and inactive lithium, providing new insights for the development of interface chemistries for metal batteries.
Associations between aversive learning processes and transdiagnostic psychiatric symptoms in a general population sample
Authors: Wise Toby , Dolan Raymond J.
Published: August 2020

Symptom expression in psychiatric conditions is often linked to altered threat perception, however how computational mechanisms that support aversive learning relate to specific psychiatric symptoms remains undetermined. We answer this question using an online game-based aversive learning task together with measures of common psychiatric symptoms in 400 subjects. We show that physiological symptoms of anxiety and a transdiagnostic compulsivity-related factor are associated with enhanced safety learning, as measured using a probabilistic computational model, while trait cognitive anxiety symptoms are associated with enhanced learning from danger. We use data-driven partial least squares regression to identify two separable components across behavioural and questionnaire data: one linking enhanced safety learning and lower estimated uncertainty to physiological anxiety, compulsivity, and impulsivity; the other linking enhanced threat learning and heightened uncertainty estimation to symptoms of depression and social anxiety. Our findings implicate aversive learning processes in the expression of psychiatric symptoms that transcend diagnostic boundaries.
Room-temperature formation of CdS magic-size clusters in aqueous solutions assisted by primary amines
Authors: Wan Wushuang , Zhang Meng , Zhao Min , Rowell Nelson , Zhang Chunchun , Wang Shanling , Kreouzis Theo , Fan Hongsong , Huang Wen , Yu Kui
Published: August 2020

Aqueous-phase approaches to semiconductor CdS magic-size clusters (MSCs) and the formation pathway have remained relatively unexplored. Here, we report the demonstration of an aqueous-phase, room-temperature approach to CdS MSCs, together with an exploration of their evolution pathway. The resulting CdS MSCs display a sharp optical absorption peak at about 360 nm and are labeled MSC-360. With CdCl2 and thiourea as the respective Cd and S sources, and 3-mercarpotopropionic acid as the ligand, CdS MSC-360 develops in a mixture of a primary amine and water. We argue that the primary amine facilitates room-temperature decomposition of thiourea when CdCl2 is present, and the formation pathway of MSCs is similar to that in organic-phase approaches. Our findings show there is a viable avenue to room-temperature aqueous-phase formation of CdS MSCs. Providing explanations of the procedure developed including the formation of large aggregates, the present study represents an important advance towards a mechanistic understanding of nanocrystal synthesis.
Continuous bioactivity-dependent evolution of an antibiotic biosynthetic pathway
Authors: Johnston Chad W. , Badran Ahmed H. , Collins James J.
Published: August 2020

Antibiotic biosynthetic gene clusters (BGCs) produce bioactive metabolites that impart a fitness advantage to their producer, providing a mechanism for natural selection. This selection drives antibiotic evolution and adapts BGCs for expression in different organisms, potentially providing clues to improve heterologous expression of antibiotics. Here, we use phage-assisted continuous evolution (PACE) to achieve bioactivity-dependent adaptation of the BGC for the antibiotic bicyclomycin (BCM), facilitating improved production in a heterologous host. This proof-of-principle study demonstrates that features of natural bioactivity-dependent evolution can be engineered to access unforeseen routes of improving metabolic pathways and product yields.
Taf14 recognizes a common motif in transcriptional machineries and facilitates their clustering by phase separation
Authors: Chen Guochao , Wang Duo , Wu Bin , Yan Fuxiang , Xue Hongjuan , Wang Quanmeng , Quan Shu , Chen Yong
Published: August 2020

Saccharomyces cerevisiae TBP associated factor 14 (Taf14) is a well-studied transcriptional regulator that controls diverse physiological processes and that physically interacts with at least seven nuclear complexes in yeast. Despite multiple previous Taf14 structural studies, the nature of its disparate transcriptional regulatory functions remains opaque. Here, we demonstrate that the extra-terminal (ET) domain of Taf14 (Taf14ET) recognizes a common motif in multiple transcriptional coactivator proteins from several nuclear complexes, including RSC, SWI/SNF, INO80, NuA3, TFIID, and TFIIF. Moreover, we show that such partner binding promotes liquid-liquid phase separation (LLPS) of Taf14ET, in a mechanism common to YEATS-associated ET domains (e.g., AF9ET) but not Bromo-associated ET domains from BET-family proteins. Thus, beyond identifying the molecular mechanism by which Taf14ET associates with many transcriptional regulators, our study suggests that Taf14 may function as a versatile nuclear hub that orchestrates transcriptional machineries to spatiotemporally regulate diverse cellular pathways.
Adaptive self-healing electronic epineurium for chronic bidirectional neural interfaces
Authors: Song Kang-Il , Seo Hyunseon , Seong Duhwan , Kim Seunghoe , Yu Ki Jun , Kim Yu-Chan , Kim Jinseok , Kwon Seok Joon , Han Hyung-Seop , Youn Inchan , Lee Hyojin , Son Donghee
Published: August 2020

Realizing a clinical-grade electronic medicine for peripheral nerve disorders is challenging owing to the lack of rational material design that mimics the dynamic mechanical nature of peripheral nerves. Electronic medicine should be soft and stretchable, to feasibly allow autonomous mechanical nerve adaptation. Herein, we report a new type of neural interface platform, an adaptive self-healing electronic epineurium (A-SEE), which can form compressive stress-free and strain-insensitive electronics-nerve interfaces and enable facile biofluid-resistant self-locking owing to dynamic stress relaxation and water-proof self-bonding properties of intrinsically stretchable and self-healable insulating/conducting materials, respectively. Specifically, the A-SEE does not need to be sutured or glued when implanted, thereby significantly reducing complexity and the operation time of microneurosurgery. In addition, the autonomous mechanical adaptability of the A-SEE to peripheral nerves can significantly reduce the mechanical mismatch at electronics-nerve interfaces, which minimizes nerve compression-induced immune responses and device failure. Though a small amount of Ag leaked from the A-SEE is observed in vivo (17.03 ppm after 32 weeks of implantation), we successfully achieved a bidirectional neural signal recording and stimulation in a rat sciatic nerve model for 14 weeks. In view of our materials strategy and in vivo feasibility, the mechanically adaptive self-healing neural interface would be considered a new implantable platform for a wide range application of electronic medicine for neurological disorders in the human nervous system.
Probing consequences of anion-dictated electrochemistry on the electrode/monolayer/electrolyte interfacial properties
Authors: Wong Raymond A. , Yokota Yasuyuki , Wakisaka Mitsuru , Inukai Junji , Kim Yousoo
Published: August 2020

Altering electrochemical interfaces by using electrolyte effects or so-called “electrolyte engineering” provides a versatile means to modulate the electrochemical response. However, the long-standing challenge is going “beyond cyclic voltammetry” where electrolyte effects are interrogated from the standpoint of the interfacial properties of the electrode/electrolyte interface. Here, we employ ferrocene-terminated self-assembled monolayers as a molecular probe and investigate how the anion-dictated electrochemical responses are translated in terms of the electronic and structural properties of the electrode/monolayer/electrolyte interface. We utilise a photoelectron-based spectroelectrochemical approach that is capable of capturing “snapshots” into (1) anion dependencies of the ferrocene/ferrocenium (Fc/Fc+) redox process including ion-pairing with counter anions (Fc+–anion) caused by differences in Fc+–anion interactions and steric constraints, and (2) interfacial energetics concerning the electrostatic potential across the electrode/monolayer/electrolyte interface. Our work can be extended to provide electrolyte-related structure-property relationships in redox-active polymers and functionalised electrodes for pseudocapacitive energy storage.
Printable microscale interfaces for long-term peripheral nerve mapping and precision control
Authors: Otchy Timothy M. , Michas Christos , Lee Blaire , Gopalan Krithi , Nerurkar Vidisha , Gleick Jeremy , Semu Dawit , Darkwa Louis , Holinski Bradley J. , Chew Daniel J. , White Alice E. , Gardner Timothy J.
Published: August 2020

The nascent field of bioelectronic medicine seeks to decode and modulate peripheral nervous system signals to obtain therapeutic control of targeted end organs and effectors. Current approaches rely heavily on electrode-based devices, but size scalability, material and microfabrication challenges, limited surgical accessibility, and the biomechanically dynamic implantation environment are significant impediments to developing and deploying peripheral interfacing technologies. Here, we present a microscale implantable device – the nanoclip – for chronic interfacing with fine peripheral nerves in small animal models that begins to meet these constraints. We demonstrate the capability to make stable, high signal-to-noise ratio recordings of behaviorally-linked nerve activity over multi-week timescales. In addition, we show that multi-channel, current-steering-based stimulation within the confines of the small device can achieve multi-dimensional control of a small nerve. These results highlight the potential of new microscale design and fabrication techniques for realizing viable devices for long-term peripheral interfacing.
Understanding colossal barocaloric effects in plastic crystals
Authors: Li F. B. , Li M. , Xu X. , Yang Z. C. , Xu H. , Jia C. K. , Li K. , He J. , Li B. , Wang Hui
Published: August 2020

Plastic crystal neopentylglycol (NPG) exhibits colossal barocaloric effects (BCEs) with record-high entropy changes, offering exciting prospects for the field of solid-state cooling through the application of moderate pressures. Here, we show that the intermolecular hydrogen bond plays a key role in the orientational order of NPG molecules, while its broken due to thermal perturbation prominently weakens the activation barrier of orientational disorder. The analysis of hydrogen bond strength, rotational entropy free energy and entropy changes provides insightful understanding of BCEs in order-disorder transition. External pressure reduce the hydsrogen bond length and enhance the activation barrier of orientational disorder, which serves as a route of varying intermolecular interaction to tune the order-disorder transition. Our work provides atomic-scale insights on the orientational order-disorder transition of NPG as the prototypical plastic crystal with BCEs, which is helpful to achieve superior caloric materials by molecular designing in the near future.
NIR-II bioluminescence for in vivo high contrast imaging and in situ ATP-mediated metastases tracing
Authors: Lu Lingfei , Li Benhao , Ding Suwan , Fan Yong , Wang Shangfeng , Sun Caixia , Zhao Mengyao , Zhao Chun-Xia , Zhang Fan
Published: August 2020

Bioluminescence imaging has been widely used in life sciences and biomedical applications. However, conventional bioluminescence imaging usually operates in the visible region, which hampers the high-performance in vivo optical imaging due to the strong tissue absorption and scattering. To address this challenge, here we present bioluminescence probes (BPs) with emission in the second near infrared (NIR-II) region at 1029 nm by employing bioluminescence resonance energy transfer (BRET) and two-step fluorescence resonance energy transfer (FRET) with a specially designed cyanine dye FD-1029. The biocompatible NIR-II-BPs are successfully applied to vessels and lymphatics imaging in mice, which gives ~5 times higher signal-to-noise ratios and ~1.5 times higher spatial resolution than those obtained by NIR-II fluorescence imaging and conventional bioluminescence imaging. Their capability of multiplexed imaging is also well displayed. Taking advantage of the ATP-responding character, the NIR-II-BPs are able to recognize tumor metastasis with a high tumor-to-normal tissue ratio at 83.4.
A cross-reactive human IgA monoclonal antibody blocks SARS-CoV-2 spike-ACE2 interaction
Authors: Ejemel Monir , Li Qi , Hou Shurong , Schiller Zachary A. , Tree Julia A. , Wallace Aaron , Amcheslavsky Alla , Kurt Yilmaz Nese , Buttigieg Karen R. , Elmore Michael J. , Godwin Kerry , Coombes Naomi , Toomey Jacqueline R. , Schneider Ryan , Ramchetty Anudeep S. , Close Brianna J. , Chen Da-Yuan , Conway Hasahn L. , Saeed Mohsan , Ganesa Chandrashekar , Carroll Miles W. , Cavacini Lisa A. , Klempner Mark S. , Schiffer Celia A. , Wang Yang
Published: August 2020

COVID-19 caused by SARS-CoV-2 has become a global pandemic requiring the development of interventions for the prevention or treatment to curtail mortality and morbidity. No vaccine to boost mucosal immunity, or as a therapeutic, has yet been developed to SARS-CoV-2. In this study, we discover and characterize a cross-reactive human IgA monoclonal antibody, MAb362. MAb362 binds to both SARS-CoV and SARS-CoV-2 spike proteins and competitively blocks ACE2 receptor binding, by overlapping the ACE2 structural binding epitope. Furthermore, MAb362 IgA neutralizes both pseudotyped SARS-CoV and SARS-CoV-2 in 293 cells expressing ACE2. When converted to secretory IgA, MAb326 also neutralizes authentic SARS-CoV-2 virus while the IgG isotype shows no neutralization. Our results suggest that SARS-CoV-2 specific IgA antibodies, such as MAb362, may provide effective immunity against SARS-CoV-2 by inducing mucosal immunity within the respiratory system, a potentially critical feature of an effective vaccine.
A machine learning-based chemoproteomic approach to identify drug targets and binding sites in complex proteomes
Authors: Piazza Ilaria , Beaton Nigel , Bruderer Roland , Knobloch Thomas , Barbisan Crystel , Chandat Lucie , Sudau Alexander , Siepe Isabella , Rinner Oliver , de Souza Natalie , Picotti Paola , Reiter Lukas
Published: August 2020

Chemoproteomics is a key technology to characterize the mode of action of drugs, as it directly identifies the protein targets of bioactive compounds and aids in the development of optimized small-molecule compounds. Current approaches cannot identify the protein targets of a compound and also detect the interaction surfaces between ligands and protein targets without prior labeling or modification. To address this limitation, we here develop LiP-Quant, a drug target deconvolution pipeline based on limited proteolysis coupled with mass spectrometry that works across species, including in human cells. We use machine learning to discern features indicative of drug binding and integrate them into a single score to identify protein targets of small molecules and approximate their binding sites. We demonstrate drug target identification across compound classes, including drugs targeting kinases, phosphatases and membrane proteins. LiP-Quant estimates the half maximal effective concentration of compound binding sites in whole cell lysates, correctly discriminating drug binding to homologous proteins and identifying the so far unknown targets of a fungicide research compound.
An adenovirus-vectored COVID-19 vaccine confers protection from SARS-COV-2 challenge in rhesus macaques
Authors: Feng Liqiang , Wang Qian , Shan Chao , Yang Chenchen , Feng Ying , Wu Jia , Liu Xiaolin , Zhou Yiwu , Jiang Rendi , Hu Peiyu , Liu Xinglong , Zhang Fan , Li Pingchao , Niu Xuefeng , Liu Yichu , Zheng Xuehua , Luo Jia , Sun Jing , Gu Yingying , Liu Bo , Xu Yongcun , Li Chufang , Pan Weiqi , Zhao Jincun , Ke Changwen , Chen Xinwen , Xu Tao , Zhong Nanshan , Guan Suhua , Yuan Zhiming , Chen Ling
Published: August 2020

The rapid spread of coronavirus SARS-CoV-2 greatly threatens global public health but no prophylactic vaccine is available. Here, we report the generation of a replication-incompetent recombinant serotype 5 adenovirus, Ad5-S-nb2, carrying a codon-optimized gene encoding Spike protein (S). In mice and rhesus macaques, intramuscular injection with Ad5-S-nb2 elicits systemic S-specific antibody and cell-mediated immune (CMI) responses. Intranasal inoculation elicits both systemic and pulmonary antibody responses but weaker CMI response. At 30 days after a single vaccination with Ad5-S-nb2 either intramuscularly or intranasally, macaques are protected against SARS-CoV-2 challenge. A subsequent challenge reveals that macaques vaccinated with a 10-fold lower vaccine dosage (1 × 1010 viral particles) are also protected, demonstrating the effectiveness of Ad5-S-nb2 and the possibility of offering more vaccine dosages within a shorter timeframe. Thus, Ad5-S-nb2 is a promising candidate vaccine and warrants further clinical evaluation.
CORE GREML for estimating covariance between random effects in linear mixed models for complex trait analyses
Authors: Zhou Xuan , Im Hae Kyung , Lee S. Hong
Published: August 2020

As a key variance partitioning tool, linear mixed models (LMMs) using genome-based restricted maximum likelihood (GREML) allow both fixed and random effects. Classic LMMs assume independence between random effects, which can be violated, causing bias. Here we introduce a generalized GREML, named CORE GREML, that explicitly estimates the covariance between random effects. Using extensive simulations, we show that CORE GREML outperforms the conventional GREML, providing variance and covariance estimates free from bias due to correlated random effects. Applying CORE GREML to UK Biobank data, we find, for example, that the transcriptome, imputed using genotype data, explains a significant proportion of phenotypic variance for height (0.15, p-value = 1.5e-283), and that these transcriptomic effects correlate with the genomic effects (genome-transcriptome correlation = 0.35, p-value = 1.2e-14). We conclude that the covariance between random effects is a key parameter for estimation, especially when partitioning phenotypic variance by multi-omics layers.
In situ nanoscale imaging of moiré superlattices in twisted van der Waals heterostructures
Authors: Luo Yue , Engelke Rebecca , Mattheakis Marios , Tamagnone Michele , Carr Stephen , Watanabe Kenji , Taniguchi Takashi , Kaxiras Efthimios , Kim Philip , Wilson William L.
Published: August 2020

Direct visualization of nanometer-scale properties of moiré superlattices in van der Waals heterostructure devices is a critically needed diagnostic tool for study of the electronic and optical phenomena induced by the periodic variation of atomic structure in these complex systems. Conventional imaging methods are destructive and insensitive to the buried device geometries, preventing practical inspection. Here we report a versatile scanning probe microscopy employing infrared light for imaging moiré superlattices of twisted bilayers graphene encapsulated by hexagonal boron nitride. We map the pattern using the scattering dynamics of phonon polaritons launched in hexagonal boron nitride capping layers via its interaction with the buried moiré superlattices. We explore the origin of the double-line features imaged and show the mechanism of the underlying effective phase change of the phonon polariton reflectance at domain walls. The nano-imaging tool developed provides a non-destructive analytical approach to elucidate the complex physics of moiré engineered heterostructures.
A neural network oracle for quantum nonlocality problems in networks
Authors: Kriváchy Tamás , Cai Yu , Cavalcanti Daniel , Tavakoli Arash , Gisin Nicolas , Brunner Nicolas
Published: August 2020

Characterizing quantum nonlocality in networks is a challenging, but important problem. Using quantum sources one can achieve distributions which are unattainable classically. A key point in investigations is to decide whether an observed probability distribution can be reproduced using only classical resources. This causal inference task is challenging even for simple networks, both analytically and using standard numerical techniques. We propose to use neural networks as numerical tools to overcome these challenges, by learning the classical strategies required to reproduce a distribution. As such, a neural network acts as an oracle for an observed behavior, demonstrating that it is classical if it can be learned. We apply our method to several examples in the triangle configuration. After demonstrating that the method is consistent with previously known results, we give solid evidence that a quantum distribution recently proposed by Gisin is indeed nonlocal as conjectured. Finally we examine the genuinely nonlocal distribution recently presented by Renou et al., and, guided by the findings of the neural network, conjecture nonlocality in a new range of parameters in these distributions. The method allows us to get an estimate on the noise robustness of all examined distributions.
Nickelate superconductors—a renaissance of the one-band Hubbard model
Authors: Kitatani Motoharu , Si Liang , Janson Oleg , Arita Ryotaro , Zhong Zhicheng , Held Karsten
Published: August 2020

The recently discovered nickelate superconductors appear, at first glance, to be even more complicated multi-orbital systems than cuprates. To identify the simplest model describing the nickelates, we analyse the multi-orbital system and find that it is instead the nickelates which can be described by a one-band Hubbard model, albeit with an additional electron reservoir and only around the superconducting regime. Our calculations of the critical temperature TC are in good agreement with experiment, and show that optimal doping is slightly below 20% Sr-doping. Even more promising than 3d nickelates are 4d palladates.
The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics
Authors: Swanson Kelly S. , Gibson Glenn R. , Hutkins Robert , Reimer Raylene A. , Reid Gregor , Verbeke Kristin , Scott Karen P. , Holscher Hannah D. , Azad Meghan B. , Delzenne Nathalie M. , Sanders Mary Ellen
Published: August 2020

In May 2019, the International Scientific Association for Probiotics and Prebiotics (ISAPP) convened a panel of nutritionists, physiologists and microbiologists to review the definition and scope of synbiotics. The panel updated the definition of a synbiotic to “a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host”. The panel concluded that defining synbiotics as simply a mixture of probiotics and prebiotics could suppress the innovation of synbiotics that are designed to function cooperatively. Requiring that each component must meet the evidence and dose requirements for probiotics and prebiotics individually could also present an obstacle. Rather, the panel clarified that a complementary synbiotic, which has not been designed so that its component parts function cooperatively, must be composed of a probiotic plus a prebiotic, whereas a synergistic synbiotic does not need to be so. A synergistic synbiotic is a synbiotic for which the substrate is designed to be selectively utilized by the co-administered microorganisms. This Consensus Statement further explores the levels of evidence (existing and required), safety, effects upon targets and implications for stakeholders of the synbiotic concept.
Arctic tidal current atlas
Authors: Baumann Till M. , Polyakov Igor V. , Padman Laurie , Danielson Seth , Fer Ilker , Janout Markus , Williams William , Pnyushkov Andrey V.
Published: August 2020

Tidal and wind-driven near-inertial currents play a vital role in the changing Arctic climate and the marine ecosystems. We compiled 429 available moored current observations taken over the last two decades throughout the Arctic to assemble a pan-Arctic atlas of tidal band currents. The atlas contains different tidal current products designed for the analysis of tidal parameters from monthly to inter-annual time scales. On shorter time scales, wind-driven inertial currents cannot be analytically separated from semidiurnal tidal constituents. Thus, we include 10–30 h band-pass filtered currents, which include all semidiurnal and diurnal tidal constituents as well as wind-driven inertial currents for the analysis of high-frequency variability of ocean dynamics. This allows for a wide range of possible uses, including local case studies of baroclinic tidal currents, assessment of long-term trends in tidal band kinetic energy and Arctic-wide validation of ocean circulation models. This atlas may also be a valuable tool for resource management and industrial applications such as fisheries, navigation and offshore construction.
Silicon tackles butachlor toxicity in rice seedlings by regulating anatomical characteristics, ascorbate-glutathione cycle, proline metabolism and levels of nutrients
Authors: Tripthi Durgesh Kumar , Varma Rishi Kumar , Singh Swati , Sachan Manisha , Guerriero Gea , Kushwaha Bishwajit Kumar , Bhardwaj Shruti , Ramawat Naleeni , Sharma Shivesh , Singh Vijay Pratap , Prasad Sheo Mohan , Chauhan Devendra Kumar , Dubey Nawal Kishore , Sahi Shivendra
Published: August 2020

Reckless use of herbicides like butachlor (Buta) in the fields represents a serious threat to crop plants, and hence to their productivity. Silicon (Si) is well known for its implication in the alleviation of the effects of abiotic stresses; however, its role in mitigating Buta toxicity is not yet known. Therefore, this study was carried out to explore the role of Si (10 µM) in regulating Buta (4 µM) toxicity in rice seedlings. Buta reduced growth and photosynthesis, altered nitric oxide (NO) level and leaf and root anatomy, inhibited enzyme activities of the ascorbate-glutathione cycle (while transcripts of associated enzymes, increased except OsMDHAR), as well as its metabolites (ascorbate and glutathione) and uptake of nutrients (Mg, P, K, S, Ca, Fe, etc. except Na), while addition of Si reversed Buta-induced alterations. Buta stimulated the expression of Si channel and efflux transporter genes- Lsi1 and Lsi2 while the addition of Si further greatly induced their expression under Buta toxicity. Buta increased free proline accumulation by inducing the activity of Δ1-pyrroline-5-carboxylate synthetase (P5CS) and decreasing proline dehydrogenase (PDH) activity, while Si reversed these effects caused by Buta. Our results suggest that Si-governed mitigation of Buta toxicity is linked with favorable modifications in energy flux parameters of photosynthesis and leaf and root anatomy, up-regulation of Si channel and transporter genes, ascorbate-glutathione cycle and nutrient uptake, and lowering in oxidative stress. We additionally demonstrate that NO might have a crucial role in these responses.
Obesity and ethnicity alter gene expression in skin
Authors: Walker Jeanne M. , Garcet Sandra , Aleman Jose O. , Mason Christopher E. , Danko David , Butler Daniel , Zuffa Simone , Swann Jonathan R. , Krueger James , Breslow Jan L. , Holt Peter R.
Published: August 2020

Obesity is accompanied by dysfunction of many organs, but effects on the skin have received little attention. We studied differences in epithelial thickness by histology and gene expression by Affymetrix gene arrays and PCR in the skin of 10 obese (BMI 35–50) and 10 normal weight (BMI 18.5–26.9) postmenopausal women paired by age and ethnicity. Epidermal thickness did not differ with obesity but the expression of genes encoding proteins associated with skin blood supply and wound healing were altered. In the obese, many gene expression pathways were broadly downregulated and subdermal fat showed pronounced inflammation. There were no changes in skin microbiota or metabolites. African American subjects differed from European Americans with a trend to increased epidermal thickening. In obese African Americans, compared to obese European Americans, we observed altered gene expression that may explain known differences in water content and stress response. African Americans showed markedly lower expression of the gene encoding the cystic fibrosis transmembrane regulator characteristic of the disease cystic fibrosis. The results from this preliminary study may explain the functional changes found in the skin of obese subjects and African Americans.
Dose reconstruction supports the interpretation of decreased abundance of mammals in the Chernobyl Exclusion Zone
Authors: Beaugelin-Seiller Karine , Garnier-Laplace Jacqueline , Della-Vedova Claire , Métivier Jean-Michel , Lepage Hugo , Mousseau Timothy A. , Møller Anders Pape
Published: August 2020

We re-analyzed field data concerning potential effects of ionizing radiation on the abundance of mammals collected in the Chernobyl Exclusion Zone (CEZ) to interpret these findings from current knowledge of radiological dose–response relationships, here mammal response in terms of abundance. In line with recent work at Fukushima, and exploiting a census conducted in February 2009 in the CEZ, we reconstructed the radiological dose for 12 species of mammals observed at 161 sites. We used this new information rather than the measured ambient dose rate (from 0.0146 to 225 µGy h−1) to statistically analyze the variation in abundance for all observed species as established from tracks in the snow in previous field studies. All available knowledge related to relevant confounding factors was considered in this re-analysis. This more realistic approach led us to establish a correlation between changes in mammal abundance with both the time elapsed since the last snowfall and the dose rate to which they were exposed. This relationship was also observed when distinguishing prey from predators. The dose rates resulting from our re-analysis are in agreement with exposure levels reported in the literature as likely to induce physiological disorders in mammals that could explain the decrease in their abundance in the CEZ. Our results contribute to informing the Weight of Evidence approach to demonstrate effects on wildlife resulting from its field exposure to ionizing radiation.
Biological responses to extreme weather events are detectable but difficult to formally attribute to anthropogenic climate change
Authors: Harris R. M. B. , Loeffler F. , Rumm A. , Fischer C. , Horchler P. , Scholz M. , Foeckler F. , Henle K.
Published: August 2020

As the frequency and intensity of extreme events such as droughts, heatwaves and floods have increased over recent decades, more extreme biological responses are being reported, and there is widespread interest in attributing such responses to anthropogenic climate change. However, the formal detection and attribution of biological responses to climate change is associated with many challenges. We illustrate these challenges with data from the Elbe River floodplain, Germany. Using community turnover and stability indices, we show that responses in plant, carabid and mollusc communities are detectable following extreme events. Community composition and species dominance changed following the extreme flood and summer heatwave of 2002/2003 (all taxa); the 2006 flood and heatwave (molluscs); and after the recurring floods and heatwave of 2010 and the 2013 flood (plants). Nevertheless, our ability to attribute these responses to anthropogenic climate change is limited by high natural variability in climate and biological data; lack of long-term data and replication, and the effects of multiple events. Without better understanding of the mechanisms behind change and the interactions, feedbacks and potentially lagged responses, multiple-driver attribution is unlikely. We discuss whether formal detection and/or attribution is necessary and suggest ways in which understanding of biological responses to extreme events could progress.
RETRACTED ARTICLE: A newly isolated strain of Halomonas sp. (HA1) exerts anticancer potential via induction of apoptosis and G2/M arrest in hepatocellular carcinoma (HepG2) cell line
Authors: El-Garawani Islam M. , El-Sabbagh Sabha M. , Abbas Nasser H. , Ahmed Hany S. , Eissa Omaima A. , Abo-Atya Doaa M. , Khalifa Shaden A. M. , El-Seedi Hesham R.
Published: August 2020

Marine bacterial strains are of great interest for their ability to produce secondary metabolites with anticancer potentials. Isolation, identification, characterization and anticancer activities of isolated bacteria from El-Hamra Lake, Wadi El-Natrun (Egypt) were the objectives of this study. The isolated bacteria were identified as a moderately halophilic alkaliphilic strain. Ethyl acetate extraction was performed and identified by liquid chromatography-mass spectrophotometry (LC–MS–MS) and nuclear magnetic resonance analysis (NMR). Cytotoxicity of the extract was assessed on the HepG2 cell line and normal human peripheral lymphocytes (HPBL) in vitro. Halomonas sp. HA1 extract analyses revealed anticancer potential. Many compounds have been identified including cyclo-(Leu-Leu), cyclo-(Pro-Phe), C17-sphinganine, hexanedioic acid, bis (2-ethylhexyl) ester, surfactin C14 and C15. The extract exhibited an IC50 of 68 ± 1.8 μg/mL and caused marked morphological changes in treated HepG2 cells. For mechanistic anticancer evaluation, 20 and 40 µg/mL of bacterial extract were examined. The up-regulation of apoptosis-related genes' expression, P53, CASP-3, and BAX/BCL-2 at mRNA and protein levels proved the involvement of P53-dependant mitochondrial apoptotic pathway. The anti-proliferative properties were confirmed by significant G2/M cell cycle arrest and PCNA down-regulation in the treated cells. Low cytotoxicity was observed in HPBL compared to HepG2 cells. In conclusion, results suggest that the apoptotic and anti-proliferative effects of Halomonas sp. HA1 extract on HepG2 cells can provide it as a candidate for future pharmaceutical industries.
The D2.mdx mouse as a preclinical model of the skeletal muscle pathology associated with Duchenne muscular dystrophy
Authors: Hammers David W. , Hart Cora C. , Matheny Michael K. , Wright Lillian A. , Armellini Megan , Barton Elisabeth R. , Sweeney H. Lee
Published: August 2020

Duchenne muscular dystrophy (DMD) is an X-linked, lethal muscle degenerative disease caused by loss of dystrophin protein. DMD has no cure and few treatment options. Preclinical efforts to identify potential DMD therapeutics have been hampered by lack of a small animal model that recapitulates key features of the human disease. While the dystrophin-deficient mdx mouse on the C57BL/10 genetic background (B10.mdx) is mildly affected, a more severe muscle disease is observed when the mdx mutation is crossed onto the DBA/2J genetic background (D2.mdx). In this study, the functional and histological progression of the D2.mdx skeletal muscle pathology was evaluated to determine the distinguishing features of disease. Data herein details the muscular weakness and wasting exhibited by D2.mdx skeletal muscle, as well as severe histopathological features, which include the rapid progression of fibrosis and calcifications in the diaphragm and progressive fibrosis accumulation in limb muscles. Furthermore, a timeline of D2.mdx progression is provided that details distinct stages of disease progression. These data support the D2.mdx as a superior small animal model for DMD, as compared to the B10.mdx model. The insights provided in this report should facilitate the design of preclinical evaluations for potential DMD therapeutics.
TGF-β is insufficient to induce adipocyte state loss without concurrent PPARγ downregulation
Authors: Taylor Brooks , Shah Arnav , Bielczyk-Maczyńska Ewa
Published: August 2020

Cell plasticity, the ability of differentiated cells to convert into other cell types, underlies the pathogenesis of many diseases including the transdifferentiation of adipocytes (fat cells) into myofibroblasts in the pathogenesis of dermal fibrosis. Loss of adipocyte identity is an early step in different types of adipocyte plasticity. In this study, we determine the dynamics of adipocyte state loss in response to the profibrotic cytokine TGF-β. We use two complementary approaches, lineage tracing and live fluorescent microscopy, which both allow for robust quantitative tracking of adipocyte identity loss at the single-cell level. We find that the intracellular TGF-β signaling in adipocytes is inhibited by the transcriptional factor PPARγ, specifically by its ubiquitously expressed isoform PPARγ1. However, TGF-β can lead to adipocyte state loss when it is present simultaneously with another stimulus. Our findings establish that an integration of stimuli occurring in a specific order is pivotal for adipocyte state loss which underlies adipocyte plasticity. Our results also suggest the possibility of a more general switch-like mechanism between adipogenic and profibrotic molecular states.
The oligomeric assembly of galectin-11 is critical for anti-parasitic activity in sheep (Ovis aries)
Authors: Sakthivel Dhanasekaran , Preston Sarah , Gasser Robin B. , Costa Tatiana P. Soares da , Hernandez Julia N. , Shahine Adam , Shakif-Azam M. D. , Lock Peter , Rossjohn Jamie , Perugini Matthew A. , González Jorge Francisco , Meeusen Els , Piedrafita David , Beddoe Travis
Published: August 2020

Galectins are a family of glycan-binding molecules with a characteristic affinity for ß-D-glycosides that mediate a variety of important cellular functions, including immune and inflammatory responses. Galectin-11 (LGALS-11) has been recently identified as a mediator induced specifically in animals against gastrointestinal nematodes and can interfere with parasite growth and development. Here, we report that at least two natural genetic variants of LGALS-11 exist in sheep, and demonstrate fundamental differences in anti-parasitic activity, correlated with their ability to dimerise. This study improves our understanding of the role of galectins in the host immune and inflammatory responses against parasitic nematodes and provides a basis for genetic studies toward selective breeding of animals for resistance to parasites.
Proteosomal degradation of NSD2 by BRCA1 promotes leukemia cell differentiation
Authors: Park Jin Woo , Kang Joo-Young , Hahm Ja Young , Kim Hyun Jeong , Seo Sang-Beom
Published: August 2020

The human myelogenous leukemic cell line, K562 undergoes erythroid differentiation by exposure to hemin. Here, we uncovered NSD2 as an innate erythroid differentiation-related factor through a genome-wide CRISPR library screen and explored the regulatory role of NSD2 during myeloid leukemia cell differentiation. We found that NSD2 stability was disrupted by poly-ubiquitination in differentiated K562 cells. Proteomic analysis revealed an interaction between NSD2 and an E3 ubiquitin ligase, BRCA1, which ubiquitylates NSD on K292. Depletion of BRCA1 stabilized NSD2 protein and suppressed K562 cell differentiation. Furthermore, BRCA1 protein level was decreased in bone marrow tumor, while NSD2 level was elevated. Surprisingly, among BRCA1 mutation(s) discovered in lymphoma patients, BRCA1 K1183R prevented its translocation into the nucleus, failed to reduce NSD2 protein levels in hemin-treated K562 cells and eventually disrupted cell differentiation. Our results indicate the regulation of NSD2 stability by BRCA1-mediated ubiquitination as a potential therapeutic target process in multiple myeloma.
Glycovariant-based lateral flow immunoassay to detect ovarian cancer–associated serum CA125
Authors: Bayoumy Sherif , Hyytiä Heidi , Leivo Janne , Talha Sheikh M. , Huhtinen Kaisa , Poutanen Matti , Hynninen Johanna , Perheentupa Antti , Lamminmäki Urpo , Gidwani Kamlesh , Pettersson Kim
Published: August 2020

Cancer antigen 125 (CA125) is a widely used biomarker in monitoring of epithelial ovarian cancer (EOC). Due to insufficient cancer specificity of CA125, its diagnostic use is severely compromised. Abnormal glycosylation of CA125 is a unique feature of ovarian cancer cells and could improve differential diagnosis of the disease. Here we describe the development of a quantitative lateral flow immunoassay (LFIA) of aberrantly glycosylated CA125 which is widely superior to the conventional CA125 immunoassay (CA125IA). With a 30 min read-out time, the LFIA showed 72% sensitivity, at 98% specificity using diagnostically challenging samples with marginally elevated CA125 (35–200 U/mL), in comparison to 16% sensitivity with the CA125IA. We envision the clinical use of the developed LFIA to be based on the substantially enhanced disease specificity against the many benign conditions confounding the diagnostic evaluation and against other cancers.