bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cryo-EM structures of intermediates suggest an alternative catalytic reaction cycle for cytochrome c oxidase
Authors: Kolbe F. , Safarian S. , Piórek Ż. , Welsch S. , Müller H. , Michel H. 
Published: November 2021

AbstractCytochrome c oxidases are among the most important and fundamental enzymes of life. Integrated into membranes they use four electrons from cytochrome c molecules to reduce molecular oxygen (dioxygen) to water. Their catalytic cycle has been considered to start with the oxidized form. Subsequent electron transfers lead to the E-state, the R-state (which binds oxygen), the P-state (with an already split dioxygen bond), the F-state and the O-state again. Here, we determined structures of up to 1.9 Å resolution of these intermediates by single particle cryo-EM. Our results suggest that in the O-state the active site contains a peroxide dianion and in the P-state possibly an intact dioxygen molecule, the F-state may contain a superoxide anion. Thus, the enzyme’s catalytic cycle may have to be turned by 180 degrees.
A structured RNA motif locks Argonaute2:miR-122 onto the 5’ end of the HCV genome
Authors: Gebert Luca F. R. , Law Mansun , MacRae Ian J. 
Published: November 2021

AbstractmicroRNAs (miRNAs) form regulatory networks in metazoans. Viruses engage miRNA networks in numerous ways, with Flaviviridae members exploiting direct interactions of their RNA genomes with host miRNAs. For hepatitis C virus (HCV), binding of liver-abundant miR-122 stabilizes the viral RNA and regulates viral translation. Here, we investigate the structural basis for these activities, taking into consideration that miRNAs function in complex with Argonaute (Ago) proteins. The crystal structure of the Ago2:miR-122:HCV complex reveals a structured RNA motif that traps Ago2 on the viral RNA, masking its 5’ end from enzymatic attack. The trapped Ago2 can recruit host factor PCBP2, implicated in viral translation, while binding of a second Ago2:miR-122 competes with PCBP2, creating a potential molecular switch for translational control. Combined results reveal a viral RNA structure that modulates Ago2:miR-122 dynamics and repurposes host proteins to generate a functional analog of the mRNA cap-binding complex.
Spike residue 403 affects binding of coronavirus spikes to human ACE2
Authors: Zech Fabian , Schniertshauer Daniel , Jung Christoph , Herrmann Alexandra , Cordsmeier Arne , Xie Qinya , Nchioua Rayhane , Prelli Bozzo Caterina , Volcic Meta , Koepke Lennart , Müller Janis A. , Krüger Jana , Heller Sandra , Stenger Steffen , Hoffmann Markus , Pöhlmann Stefan , Kleger Alexander , Jacob Timo , Conzelmann Karl-Klaus , Ensser Armin , Sparrer Konstantin M. J. , Kirchhoff Frank 
Published: November 2021

AbstractThe bat sarbecovirus RaTG13 is a close relative of SARS-CoV-2, the cause of the COVID-19 pandemic. However, this bat virus was most likely unable to directly infect humans since its Spike (S) protein does not interact efficiently with the human ACE2 receptor. Here, we show that a single T403R mutation increases binding of RaTG13 S to human ACE2 and allows VSV pseudoparticle infection of human lung cells and intestinal organoids. Conversely, mutation of R403T in the SARS-CoV-2 S reduces pseudoparticle infection and viral replication. The T403R RaTG13 S is neutralized by sera from individuals vaccinated against COVID-19 indicating that vaccination might protect against future zoonoses. Our data suggest that a positively charged amino acid at position 403 in the S protein is critical for efficient utilization of human ACE2 by S proteins of bat coronaviruses. This finding could help to better predict the zoonotic potential of animal coronaviruses.
Cross-feeding between intestinal pathobionts promotes their overgrowth during undernutrition
Authors: Huus K. E. , Hoang T. T. , Creus-Cuadros A. , Cirstea M. , Vogt S. L. , Knuff-Janzen K. , Sansonetti P. J. , Vonaesch P. , Finlay B. B. 
Published: November 2021

AbstractChild undernutrition is a global health issue associated with a high burden of infectious disease. Undernourished children display an overabundance of intestinal pathogens and pathobionts, and these bacteria induce enteric dysfunction in undernourished mice; however, the cause of their overgrowth remains poorly defined. Here, we show that disease-inducing human isolates of Enterobacteriaceae and Bacteroidales spp. are capable of multi-species symbiotic cross-feeding, resulting in synergistic growth of a mixed community in vitro. Growth synergy occurs uniquely under malnourished conditions limited in protein and iron: in this context, Bacteroidales spp. liberate diet- and mucin-derived sugars and Enterobacteriaceae spp. enhance the bioavailability of iron. Analysis of human microbiota datasets reveals that Bacteroidaceae and Enterobacteriaceae are strongly correlated in undernourished children, but not in adequately nourished children, consistent with a diet-dependent growth synergy in the human gut. Together these data suggest that dietary cross-feeding fuels the overgrowth of pathobionts in undernutrition.
Accelerated discovery of superoxide-dismutase nanozymes via high-throughput computational screening
Authors: Wang Zhenzhen , Wu Jiangjiexing , Zheng Jia-Jia , Shen Xiaomei , Yan Liang , Wei Hui , Gao Xingfa , Zhao Yuliang 
Published: November 2021

AbstractThe activity of nanomaterials (NMs) in catalytically scavenging superoxide anions mimics that of superoxide dismutase (SOD). Although dozens of NMs have been demonstrated to possess such activity, the underlying principles are unclear, hindering the discovery of NMs as the novel SOD mimics. In this work, we use density functional theory calculations to study the thermodynamics and kinetics of the catalytic processes, and we develop two principles, namely, an energy level principle and an adsorption energy principle, for the activity. The first principle quantitatively describes the role of the intermediate frontier molecular orbital in transferring electrons for catalysis. The second one quantitatively describes the competition between the desired catalytic reaction and undesired side reactions. The ability of the principles to predict the SOD-like activities of metal-organic frameworks were verified by experiments. Both principles can be easily implemented in computer programs to computationally screen NMs with the intrinsic SOD-like activity.
Functional convalescent plasma antibodies and pre-infusion titers shape the early severe COVID-19 immune response
Authors: Herman Jonathan D. , Wang Chuangqi , Loos Carolin , Yoon Hyunah , Rivera Johanna , Eugenia Dieterle M. , Haslwanter Denise , Jangra Rohit K. , Bortz Robert H. , Bar Katharine J. , Julg Boris , Chandran Kartik , Lauffenburger Douglas , Pirofski Liise-anne , Alter Galit 
Published: November 2021

AbstractTransfer of convalescent plasma (CP) had been proposed early during the SARS-CoV-2 pandemic as an accessible therapy, yet trial results worldwide have been mixed, potentially due to the heterogeneous nature of CP. Here we perform deep profiling of SARS-CoV-2-specific antibody titer, Fc-receptor binding, and Fc-mediated functional assays in CP units, as well as in plasma from hospitalized COVID-19 patients before and after CP administration. The profiling results show that, although all recipients exhibit expanded SARS-CoV-2-specific humoral immune responses, CP units contain more functional antibodies than recipient plasma. Meanwhile, CP functional profiles influence the evolution of recipient humoral immunity in conjuncture with the recipient’s pre-existing SARS-CoV2-specific antibody titers: CP-derived SARS-CoV-2 nucleocapsid-specific antibody functions are associated with muted humoral immune evolution in patients with high titer anti-spike IgG. Our data thus provide insights into the unexpected impact of CP-derived functional anti-spike and anti-nucleocapsid antibodies on the evolution of SARS-CoV-2-specific response following severe infection.
Single-photon detection and cryogenic reconfigurability in lithium niobate nanophotonic circuits
Authors: Lomonte Emma , Wolff Martin A. , Beutel Fabian , Ferrari Simone , Schuck Carsten , Pernice Wolfram H. P. , Lenzini Francesco 
Published: November 2021

AbstractLithium-Niobate-On-Insulator (LNOI) is emerging as a promising platform for integrated quantum photonic technologies because of its high second-order nonlinearity and compact waveguide footprint. Importantly, LNOI allows for creating electro-optically reconfigurable circuits, which can be efficiently operated at cryogenic temperature. Their integration with superconducting nanowire single-photon detectors (SNSPDs) paves the way for realizing scalable photonic devices for active manipulation and detection of quantum states of light. Here we demonstrate integration of these two key components in a low loss (0.2 dB/cm) LNOI waveguide network. As an experimental showcase of our technology, we demonstrate the combined operation of an electrically tunable Mach-Zehnder interferometer and two waveguide-integrated SNSPDs at its outputs. We show static reconfigurability of our system with a bias-drift-free operation over a time of 12 hours, as well as high-speed modulation at a frequency up to 1 GHz. Our results provide blueprints for implementing complex quantum photonic devices on the LNOI platform.
Interlayer exciton mediated second harmonic generation in bilayer MoS2
Authors: Shree Shivangi , Lagarde Delphine , Lombez Laurent , Robert Cedric , Balocchi Andrea , Watanabe Kenji , Taniguchi Takashi , Marie Xavier , Gerber Iann C. , Glazov Mikhail M. , Golub Leonid E. , Urbaszek Bernhard , Paradisanos Ioannis 
Published: November 2021

AbstractSecond-harmonic generation (SHG) is a non-linear optical process, where two photons coherently combine into one photon of twice their energy. Efficient SHG occurs for crystals with broken inversion symmetry, such as transition metal dichalcogenide monolayers. Here we show tuning of non-linear optical processes in an inversion symmetric crystal. This tunability is based on the unique properties of bilayer MoS2, that shows strong optical oscillator strength for the intra- but also interlayer exciton resonances. As we tune the SHG signal onto these resonances by varying the laser energy, the SHG amplitude is enhanced by several orders of magnitude. In the resonant case the bilayer SHG signal reaches amplitudes comparable to the off-resonant signal from a monolayer. In applied electric fields the interlayer exciton energies can be tuned due to their in-built electric dipole via the Stark effect. As a result the interlayer exciton degeneracy is lifted and the bilayer SHG response is further enhanced by an additional two orders of magnitude, well reproduced by our model calculations. Since interlayer exciton transitions are highly tunable also by choosing twist angle and material combination our results open up new approaches for designing the SHG response of layered materials.
Risk-stratification of febrile African children at risk of sepsis using sTREM-1 as basis for a rapid triage test
Authors: Leligdowicz Aleksandra , Conroy Andrea L. , Hawkes Michael , Richard-Greenblatt Melissa , Zhong Kathleen , Opoka Robert O. , Namasopo Sophie , Bell David , Liles W. Conrad , da Costa Bruno R. , Jüni Peter , Kain Kevin C. 
Published: November 2021

AbstractIdentifying febrile children at risk of sepsis in low-resource settings can improve survival, but recognition triage tools are lacking. Here we test the hypothesis that measuring circulating markers of immune and endothelial activation may identify children with sepsis at risk of all-cause mortality. In a prospective cohort study of 2,502 children in Uganda, we show that Soluble Triggering Receptor Expressed on Myeloid cells-1 (sTREM-1) measured at first clinical presentation, had high predictive accuracy for subsequent in-hospital mortality. sTREM-1 had the best performance, versus 10 other markers, with an AUROC for discriminating children at risk of death of 0.893 in derivation (95% CI 0.843–0.944) and 0.901 in validation (95% CI 0.856–0.947) cohort. sTREM-1 cutoffs corresponding to a negative likelihood ratio (LR) of 0.10 and a positive LR of 10 classified children into low (1,306 children, 53.1%), intermediate (942, 38.3%) and high (212, 8.6%) risk zones. The estimated incidence of death was 0.5%, 3.9%, and 31.8%, respectively, suggesting sTREM-1 could be used to risk-stratify febrile children. These findings do not attempt to derive a risk prediction model, but rather define sTREM-1 cutoffs as the basis for rapid triage test for all cause fever syndromes in children in low-resource settings.
Axonal TDP-43 condensates drive neuromuscular junction disruption through inhibition of local synthesis of nuclear encoded mitochondrial proteins
Authors: Altman Topaz , Ionescu Ariel , Ibraheem Amjad , Priesmann Dominik , Gradus-Pery Tal , Farberov Luba , Alexandra Gayster , Shelestovich Natalia , Dafinca Ruxandra , Shomron Noam , Rage Florence , Talbot Kevin , Ward Michael E. , Dori Amir , Krüger Marcus , Perlson Eran 
Published: November 2021

AbstractMislocalization of the predominantly nuclear RNA/DNA binding protein, TDP-43, occurs in motor neurons of ~95% of amyotrophic lateral sclerosis (ALS) patients, but the contribution of axonal TDP-43 to this neurodegenerative disease is unclear. Here, we show TDP-43 accumulation in intra-muscular nerves from ALS patients and in axons of human iPSC-derived motor neurons of ALS patient, as well as in motor neurons and neuromuscular junctions (NMJs) of a TDP-43 mislocalization mouse model. In axons, TDP-43 is hyper-phosphorylated and promotes G3BP1-positive ribonucleoprotein (RNP) condensate assembly, consequently inhibiting local protein synthesis in distal axons and NMJs. Specifically, the axonal and synaptic levels of nuclear-encoded mitochondrial proteins are reduced. Clearance of axonal TDP-43 or dissociation of G3BP1 condensates restored local translation and resolved TDP-43-derived toxicity in both axons and NMJs. These findings support an axonal gain of function of TDP-43 in ALS, which can be targeted for therapeutic development.
The telomere length landscape of prostate cancer
Authors: Livingstone Julie , Shiah Yu-Jia , Yamaguchi Takafumi N. , Heisler Lawrence E. , Huang Vincent , Lesurf Robert , Gebo Tsumugi , Carlin Benjamin , Eng Stefan , Drysdale Erik , Green Jeffrey , van der Kwast Theodorus , Bristow Robert G. , Fraser Michael , Boutros Paul C. 
Published: November 2021

AbstractReplicative immortality is a hallmark of cancer, and can be achieved through telomere lengthening and maintenance. Although the role of telomere length in cancer has been well studied, its association to genomic features is less well known. Here, we report the telomere lengths of 392 localized prostate cancer tumours and characterize their relationship to genomic, transcriptomic and proteomic features. Shorter tumour telomere lengths are associated with elevated genomic instability, including single-nucleotide variants, indels and structural variants. Genes involved in cell proliferation and signaling are correlated with tumour telomere length at all levels of the central dogma. Telomere length is also associated with multiple clinical features of a tumour. Longer telomere lengths in non-tumour samples are associated with a lower rate of biochemical relapse. In summary, we describe the multi-level integration of telomere length, genomics, transcriptomics and proteomics in localized prostate cancer.
Planar photonic chips with tailored angular transmission for high-contrast-imaging devices
Authors: Kuai Yan , Chen Junxue , Fan Zetao , Zou Gang , Lakowicz Joseph. R. , Zhang Douguo 
Published: November 2021

AbstractA limitation of standard brightfield microscopy is its low contrast images, especially for thin specimens of weak absorption, and biological species with refractive indices very close in value to that of their surroundings. We demonstrate, using a planar photonic chip with tailored angular transmission as the sample substrate, a standard brightfield microscopy can provide both darkfield and total internal reflection (TIR) microscopy images with one experimental configuration. The image contrast is enhanced without altering the specimens and the microscope configurations. This planar chip consists of several multilayer sections with designed photonic band gaps and a central region with dielectric nanoparticles, which does not require top-down nanofabrication and can be fabricated in a larger scale. The photonic chip eliminates the need for a bulky condenser or special objective to realize darkfield or TIR illumination. Thus, it can work as a miniaturized high-contrast-imaging device for the developments of versatile and compact microscopes.
Single-cell analysis identifies dynamic gene expression networks that govern B cell development and transformation
Authors: Lee Robin D. , Munro Sarah A. , Knutson Todd P. , LaRue Rebecca S. , Heltemes-Harris Lynn M. , Farrar Michael A. 
Published: November 2021

AbstractIntegration of external signals and B-lymphoid transcription factor activities organise B cell lineage commitment through alternating cycles of proliferation and differentiation, producing a diverse repertoire of mature B cells. We use single-cell transcriptomics/proteomics to identify differentially expressed gene networks across B cell development and correlate these networks with subtypes of B cell leukemia. Here we show unique transcriptional signatures that refine the pre-B cell expansion stages into pre-BCR-dependent and pre-BCR-independent proliferative phases. These changes correlate with reciprocal changes in expression of the transcription factor EBF1 and the RNA binding protein YBX3, that are defining features of the pre-BCR-dependent stage. Using pseudotime analysis, we further characterize the expression kinetics of different biological modalities across B cell development, including transcription factors, cytokines, chemokines, and their associated receptors. Our findings demonstrate the underlying heterogeneity of developing B cells and characterise developmental nodes linked to B cell transformation.
A H2O2-activatable nanoprobe for diagnosing interstitial cystitis and liver ischemia-reperfusion injury via multispectral optoacoustic tomography and NIR-II fluorescent imaging
Authors: Chen Junjie , Chen Longqi , Wu Yinglong , Fang Yichang , Zeng Fang , Wu Shuizhu , Zhao Yanli 
Published: November 2021

AbstractDeveloping high-quality NIR-II fluorophores (emission in 1000–1700 nm) for in vivo imaging is of great significance. Benzothiadiazole-core fluorophores are an important class of NIR-II dyes, yet ongoing limitations such as aggregation-caused quenching in aqueous milieu and non-activatable response are still major obstacles for their biological applications. Here, we devise an activatable nanoprobe to address these limitations. A molecular probe named BTPE-NO2 is synthesized by linking a benzothiadiazole core with two tetraphenylene groups serving as hydrophobic molecular rotors, followed by incorporating two nitrophenyloxoacetamide units at both ends of the core as recognition moieties and fluorescence quenchers. An FDA-approved amphiphilic polymer Pluronic F127 is then employed to encapsulate the molecular BTPE-NO2 to render the nanoprobe BTPE-NO2@F127. The pathological levels of H2O2 in the disease sites cleave the nitrophenyloxoacetamide groups and activate the probe, thereby generating strong fluorescent emission (950~1200 nm) and ultrasound signal for multi-mode imaging of inflammatory diseases. The nanoprobe can therefore function as a robust tool for detecting and imaging the disease sites with NIR-II fluorescent and multispectral optoacoustic tomography (MSOT) imaging. Moreover, the three-dimensional MSOT images can be obtained for visualizing and locating the disease foci.
Dormant spores sense amino acids through the B subunits of their germination receptors
Authors: Artzi Lior , Alon Assaf , Brock Kelly P. , Green Anna G. , Tam Amy , Ramírez-Guadiana Fernando H. , Marks Debora , Kruse Andrew , Rudner David Z. 
Published: November 2021

AbstractBacteria from the orders Bacillales and Clostridiales differentiate into stress-resistant spores that can remain dormant for years, yet rapidly germinate upon nutrient sensing. How spores monitor nutrients is poorly understood but in most cases requires putative membrane receptors. The prototypical receptor from Bacillus subtilis consists of three proteins (GerAA, GerAB, GerAC) required for germination in response to L-alanine. GerAB belongs to the Amino Acid-Polyamine-Organocation superfamily of transporters. Using evolutionary co-variation analysis, we provide evidence that GerAB adopts a structure similar to an L-alanine transporter from this superfamily. We show that mutations in gerAB predicted to disrupt the ligand-binding pocket impair germination, while mutations predicted to function in L-alanine recognition enable spores to respond to L-leucine or L-serine. Finally, substitutions of bulkier residues at these positions cause constitutive germination. These data suggest that GerAB is the L-alanine sensor and that B subunits in this broadly conserved family function in nutrient detection.
Tuning organic crystal chirality by the molar masses of tailored polymeric additives
Authors: Ye Xichong , Li Bowen , Wang Zhaoxu , Li Jing , Zhang Jie , Wan Xinhua 
Published: November 2021

AbstractHierarchically ordered chiral crystals have attracted intense research efforts for their huge potential in optical devices, asymmetric catalysis and pharmaceutical crystal engineering. Major barriers to the application have been the use of costly enantiomerically pure building blocks and the difficulty in precise control of chirality transfer from molecular to macroscopic level. Herein, we describe a strategy that offers not only the preferred formation of one enantiomorph from racemic solution but also the subsequent enantiomer-specific oriented attachment of this enantiomorph by balancing stereoselective and non-stereoselective interactions. It is demonstrated by on-demand switching the sign of fan-shaped crystal aggregates and the configuration of their components only by changing the molar mass of tailored polymeric additives. Owing to the simplicity and wide scope of application, this methodology opens an immediate opportunity for facile and efficient fabrication of one-handed macroscopic aggregates of homochiral organic crystals from racemic starting materials.
Breaking the symmetry to suppress the Plateau–Rayleigh instability and optimize hydropower utilization
Authors: Zhao Zhipeng , Li Huizeng , Li An , Fang Wei , Cai Zheren , Li Mingzhu , Feng Xiqiao , Song Yanlin 
Published: November 2021

AbstractDroplet impact on solid surfaces is essential for natural and industrial processes. Particularly, controlling the instability after droplet impact, and avoiding the satellite drops generation, have aroused great interest for its significance in inkjet printing, pesticide spraying, and hydroelectric power collection. Herein, we found that breaking the symmetry of the droplet impact dynamics using patterned-wettability surfaces can suppress the Plateau–Rayleigh instability during the droplet rebounding and improve the energy collection efficiency. Systematic experimental investigation, together with mechanical modeling and numerical simulation, revealed that the asymmetric wettability patterns can regulate the internal liquid flow and reduce the vertical velocity gradient inside the droplet, thus suppressing the instability during droplet rebounding and eliminating the satellite drops. Accordingly, the droplet energy utilization was promoted, as demonstrated by the improved hydroelectric power generation efficiency by 36.5%. These findings deepen the understanding of the wettability-induced asymmetrical droplet dynamics during the liquid–solid interactions, and facilitate related applications such as hydroelectric power generation and materials transportation.