bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liquid crystal-templated chiral nanomaterials: from chiral plasmonics to circularly polarized luminescence
Authors: Zhang Xuan , Xu Yiyi , Valenzuela Cristian , Zhang Xinfang , Wang Ling , Feng Wei , Li Quan 
Published: July 2022

AbstractChiral nanomaterials with intrinsic chirality or spatial asymmetry at the nanoscale are currently in the limelight of both fundamental research and diverse important technological applications due to their unprecedented physicochemical characteristics such as intense light-matter interactions, enhanced circular dichroism, and strong circularly polarized luminescence. Herein, we provide a comprehensive overview of the state-of-the-art advances in liquid crystal-templated chiral nanomaterials. The chiroptical properties of chiral nanomaterials are touched, and their fundamental design principles and bottom-up synthesis strategies are discussed. Different chiral functional nanomaterials based on liquid-crystalline soft templates, including chiral plasmonic nanomaterials and chiral luminescent nanomaterials, are systematically introduced, and their underlying mechanisms, properties, and potential applications are emphasized. This review concludes with a perspective on the emerging applications, challenges, and future opportunities of such fascinating chiral nanomaterials. This review can not only deepen our understanding of the fundamentals of soft-matter chirality, but also shine light on the development of advanced chiral functional nanomaterials toward their versatile applications in optics, biology, catalysis, electronics, and beyond.
2.7 Å cryo-EM structure of ex vivo RML prion fibrils
Authors: Manka Szymon W. , Zhang Wenjuan , Wenborn Adam , Betts Jemma , Joiner Susan , Saibil Helen R. , Collinge John , Wadsworth Jonathan D. F. 
Published: July 2022

AbstractMammalian prions propagate as distinct strains and are composed of multichain assemblies of misfolded host-encoded prion protein (PrP). Here, we present a near-atomic resolution cryo-EM structure of PrP fibrils present in highly infectious prion rod preparations isolated from the brains of RML prion-infected mice. We found that prion rods comprise single-protofilament helical amyloid fibrils that coexist with twisted pairs of the same protofilaments. Each rung of the protofilament is formed by a single PrP monomer with the ordered core comprising PrP residues 94–225, which folds to create two asymmetric lobes with the N-linked glycans and the glycosylphosphatidylinositol anchor projecting from the C-terminal lobe. The overall architecture is comparable to that of recently reported PrP fibrils isolated from the brain of hamsters infected with the 263K prion strain. However, there are marked conformational variations that could result from differences in PrP sequence and/or represent distinguishing features of the distinct prion strains.
Instant diagnosis of gastroscopic biopsy via deep-learned single-shot femtosecond stimulated Raman histology
Authors: Liu Zhijie , Su Wei , Ao Jianpeng , Wang Min , Jiang Qiuli , He Jie , Gao Hua , Lei Shu , Nie Jinshan , Yan Xuefeng , Guo Xiaojing , Zhou Pinghong , Hu Hao , Ji Minbiao 
Published: July 2022

AbstractGastroscopic biopsy provides the only effective method for gastric cancer diagnosis, but the gold standard histopathology is time-consuming and incompatible with gastroscopy. Conventional stimulated Raman scattering (SRS) microscopy has shown promise in label-free diagnosis on human tissues, yet it requires the tuning of picosecond lasers to achieve chemical specificity at the cost of time and complexity. Here, we demonstrate that single-shot femtosecond SRS (femto-SRS) reaches the maximum speed and sensitivity with preserved chemical resolution by integrating with U-Net. Fresh gastroscopic biopsy is imaged in <60 s, revealing essential histoarchitectural hallmarks perfectly agreed with standard histopathology. Moreover, a diagnostic neural network (CNN) is constructed based on images from 279 patients that predicts gastric cancer with accuracy >96%. We further demonstrate semantic segmentation of intratumor heterogeneity and evaluation of resection margins of endoscopic submucosal dissection (ESD) tissues to simulate rapid and automated intraoperative diagnosis. Our method holds potential for synchronizing gastroscopy and histopathological diagnosis.
A visible-light activated secondary phosphine oxide ligand enabling Pd-catalyzed radical cross-couplings
Authors: Kuribara Takahito , Nakajima Masaya , Nemoto Tetsuhiro 
Published: July 2022

AbstractAlthough transition metal-catalyzed reactions have evolved with ligand development, ligand design for palladium-catalyzed photoreactions remains less explored. Here, we report a secondary phosphine oxide ligand bearing a visible-light sensitization moiety and apply it to Pd-catalyzed radical cross-coupling reactions. The tautomeric phosphinous acid coordinates to palladium in situ, allowing for pseudo-intramolecular single-electron transfer between the ligand and palladium. Molecular design of the metal complexes aided by time-dependent density functional theory calculations enables the involvement of allyl radicals from π-allyl palladium(II) complexes, and alkyl and aryl radicals from the corresponding halides and palladium(0) complex. This complex enables radical cross-couplings by ligand-to-Pd(II) and Pd(0)-to-ligand single-electron transfer under visible-light irradiation.
Prolonging valley polarization lifetime through gate-controlled exciton-to-trion conversion in monolayer molybdenum ditelluride
Authors: Zhang Qiyao , Sun Hao , Tang Jiacheng , Dai Xingcan , Wang Zhen , Ning Cun-Zheng 
Published: July 2022

AbstractMonolayer 2D semiconductors provide an attractive option for valleytronics due to valley-addressability. But the short valley-polarization lifetimes for excitons have hindered potential valleytronic applications. In this paper, we demonstrate a strategy for prolonging the valley-polarization lifetime by converting excitons to trions through efficient gate control and exploiting the much longer valley-polarization lifetimes for trions than for excitons. At charge neutrality, the valley lifetime of monolayer MoTe2 increases by a factor of 1000 to the order of nanoseconds from excitons to trions. The exciton-to-trion conversion changes the dominant depolarization mechanism from the fast electron-hole exchange for excitons to the slow spin-flip process for trions. Moreover, the degree of valley polarization increases to 38% for excitons and 33% for trions through electrical manipulation. Our results reveal the depolarization dynamics and the interplay of various depolarization channels for excitons and trions, providing an effective strategy for prolonging the valley polarization.
Cell-autonomous Hedgehog signaling controls Th17 polarization and pathogenicity
Authors: Hanna Joachim , Beke Flavio , O’Brien Louise M. , Kapeni Chrysa , Chen Hung-Chang , Carbonaro Valentina , Kim Alexander B. , Kishore Kamal , Adolph Timon E. , Skjoedt Mikkel-Ole , Skjoedt Karsten , de la Roche Marc , de la Roche Maike 
Published: July 2022

AbstractTh17 cells are key drivers of autoimmune disease. However, the signaling pathways regulating Th17 polarization are poorly understood. Hedgehog signaling regulates cell fate decisions during embryogenesis and adult tissue patterning. Here we find that cell-autonomous Hedgehog signaling, independent of exogenous ligands, selectively drives the polarization of Th17 cells but not other T helper cell subsets. We show that endogenous Hedgehog ligand, Ihh, signals to activate both canonical and non-canonical Hedgehog pathways through Gli3 and AMPK. We demonstrate that Hedgehog pathway inhibition with either the clinically-approved small molecule inhibitor vismodegib or genetic ablation of Ihh in CD4+ T cells greatly diminishes disease severity in two mouse models of intestinal inflammation. We confirm that Hedgehog pathway expression is upregulated in tissue from human ulcerative colitis patients and correlates with Th17 marker expression. This work implicates Hedgehog signaling in Th17 polarization and intestinal immunopathology and indicates the potential therapeutic use of Hedgehog inhibitors in the treatment of inflammatory bowel disease.
Identifying multicellular spatiotemporal organization of cells with SpaceFlow
Authors: Ren Honglei , Walker Benjamin L. , Cang Zixuan , Nie Qing 
Published: July 2022

AbstractOne major challenge in analyzing spatial transcriptomic datasets is to simultaneously incorporate the cell transcriptome similarity and their spatial locations. Here, we introduce SpaceFlow, which generates spatially-consistent low-dimensional embeddings by incorporating both expression similarity and spatial information using spatially regularized deep graph networks. Based on the embedding, we introduce a pseudo-Spatiotemporal Map that integrates the pseudotime concept with spatial locations of the cells to unravel spatiotemporal patterns of cells. By comparing with multiple existing methods on several spatial transcriptomic datasets at both spot and single-cell resolutions, SpaceFlow is shown to produce a robust domain segmentation and identify biologically meaningful spatiotemporal patterns. Applications of SpaceFlow reveal evolving lineage in heart developmental data and tumor-immune interactions in human breast cancer data. Our study provides a flexible deep learning framework to incorporate spatiotemporal information in analyzing spatial transcriptomic data.
Bromodomain factor 5 is an essential regulator of transcription in Leishmania
Authors: Jones Nathaniel G. , Geoghegan Vincent , Moore Gareth , Carnielli Juliana B. T. , Newling Katherine , Calderón Félix , Gabarró Raquel , Martín Julio , Prinjha Rab K. , Rioja Inmaculada , Wilkinson Anthony J. , Mottram Jeremy C. 
Published: July 2022

AbstractLeishmania are unicellular parasites that cause human and animal diseases. Like other kinetoplastids, they possess large transcriptional start regions (TSRs) which are defined by histone variants and histone lysine acetylation. Cellular interpretation of these chromatin marks is not well understood. Eight bromodomain factors, the reader modules for acetyl-lysine, are found across Leishmania genomes. Using L. mexicana, Cas9-driven gene deletions indicate that BDF1–5 are essential for promastigotes. Dimerisable, split Cre recombinase (DiCre)-inducible gene deletion of BDF5 show it is essential for both promastigotes and murine infection. ChIP-seq identifies BDF5 as enriched at TSRs. XL-BioID proximity proteomics shows the BDF5 landscape is enriched for BDFs, HAT2, proteins involved in transcriptional activity, and RNA processing; revealing a Conserved Regulators of Kinetoplastid Transcription (CRKT) Complex. Inducible deletion of BDF5 causes global reduction in RNA polymerase II transcription. Our results indicate the requirement of Leishmania to interpret histone acetylation marks through the bromodomain-enriched CRKT complex for normal gene expression and cellular viability.
Integration of tumor extrinsic and intrinsic features associates with immunotherapy response in non-small cell lung cancer
Authors: Lau Denise , Khare Sonal , Stein Michelle M. , Jain Prerna , Gao Yinjie , BenTaieb Aicha , Rand Tim A. , Salahudeen Ameen A. , Khan Aly A. 
Published: July 2022

AbstractThe efficacy of immune checkpoint blockade (ICB) varies greatly among metastatic non-small cell lung cancer (NSCLC) patients. Loss of heterozygosity at the HLA-I locus (HLA-LOH) has been identified as an important immune escape mechanism. However, despite HLA-I disruptions in their tumor, many patients have durable ICB responses. Here we seek to identify HLA-I-independent features associated with ICB response in NSCLC. We use single-cell profiling to identify tumor-infiltrating, clonally expanded CD4+T cells that express a canonical cytotoxic gene program and NSCLC cells with elevated HLA-II expression. We postulate cytotoxic CD4+T cells mediate anti-tumor activity via HLA-II on tumor cells and augment HLA-I-dependent cytotoxic CD8+T cell interactions to drive ICB response in NSCLC. We show that integrating tumor extrinsic cytotoxic gene expression with tumor mutational burden is associated with longer time to progression in a real-world cohort of 123 NSCLC patients treated with ICB regimens, including those with HLA-LOH.
Microglia coordinate cellular interactions during spinal cord repair in mice
Authors: Brennan Faith H. , Li Yang , Wang Cankun , Ma Anjun , Guo Qi , Li Yi , Pukos Nicole , Campbell Warren A. , Witcher Kristina G. , Guan Zhen , Kigerl Kristina A. , Hall Jodie C. E. , Godbout Jonathan P. , Fischer Andy J. , McTigue Dana M. , He Zhigang , Ma Qin , Popovich Phillip G. 
Published: July 2022

AbstractTraumatic spinal cord injury (SCI) triggers a neuro-inflammatory response dominated by tissue-resident microglia and monocyte derived macrophages (MDMs). Since activated microglia and MDMs are morphologically identical and express similar phenotypic markers in vivo, identifying injury responses specifically coordinated by microglia has historically been challenging. Here, we pharmacologically depleted microglia and use anatomical, histopathological, tract tracing, bulk and single cell RNA sequencing to reveal the cellular and molecular responses to SCI controlled by microglia. We show that microglia are vital for SCI recovery and coordinate injury responses in CNS-resident glia and infiltrating leukocytes. Depleting microglia exacerbates tissue damage and worsens functional recovery. Conversely, restoring select microglia-dependent signaling axes, identified through sequencing data, in microglia depleted mice prevents secondary damage and promotes recovery. Additional bioinformatics analyses reveal that optimal repair after SCI might be achieved by co-opting key ligand-receptor interactions between microglia, astrocytes and MDMs.
Cluster-type analogue memristor by engineering redox dynamics for high-performance neuromorphic computing
Authors: Kang Jaehyun , Kim Taeyoon , Hu Suman , Kim Jaewook , Kwak Joon Young , Park Jongkil , Park Jong Keuk , Kim Inho , Lee Suyoun , Kim Sangbum , Jeong YeonJoo 
Published: July 2022

AbstractMemristors, or memristive devices, have attracted tremendous interest in neuromorphic hardware implementation. However, the high electric-field dependence in conventional filamentary memristors results in either digital-like conductance updates or gradual switching only in a limited dynamic range. Here, we address the switching parameter, the reduction probability of Ag cations in the switching medium, and ultimately demonstrate a cluster-type analogue memristor. Ti nanoclusters are embedded into densified amorphous Si for the following reasons: low standard reduction potential, thermodynamic miscibility with Si, and alloy formation with Ag. These Ti clusters effectively induce the electrochemical reduction activity of Ag cations and allow linear potentiation/depression in tandem with a large conductance range (~244) and long data retention (~99% at 1 hour). Moreover, according to the reduction potentials of incorporated metals (Pt, Ta, W, and Ti), the extent of linearity improvement is selectively tuneable. Image processing simulation proves that the Ti4.8%:a-Si device can fully function with high accuracy as an ideal synaptic model.
A time-resolved multi-omics atlas of Acanthamoeba castellanii encystment
Authors: Bernard Clément , Locard-Paulet Marie , Noël Cyril , Duchateau Magalie , Giai Gianetto Quentin , Moumen Bouziane , Rattei Thomas , Hechard Yann , Jensen Lars Juhl , Matondo Mariette , Samba-Louaka Ascel 
Published: July 2022

AbstractEncystment is a common stress response of most protists, including free-living amoebae. Cyst formation protects the amoebae from eradication and can increase virulence of the bacteria they harbor. Here, we mapped the global molecular changes that occur in the facultatively pathogenic amoeba Acanthamoeba castellanii during the early steps of the poorly understood process of encystment. By performing transcriptomic, proteomic, and phosphoproteomic experiments during encystment, we identified more than 150,000 previously undescribed transcripts and thousands of protein sequences absent from the reference genome. These results provide molecular details to the regulation of expected biological processes, such as cell proliferation shutdown, and reveal new insights such as a rapid phospho-regulation of sites involved in cytoskeleton remodeling and translation regulation. This work constitutes the first time-resolved molecular atlas of an encysting organism and a useful resource for further investigation of amoebae encystment to allow for a better control of pathogenic amoebae.
Human-type sialic acid receptors contribute to avian influenza A virus binding and entry by hetero-multivalent interactions
Authors: Liu Mengying , Huang Liane Z. X. , Smits Anthony A. , Büll Christian , Narimatsu Yoshiki , van Kuppeveld Frank J. M. , Clausen Henrik , de Haan Cornelis A. M. , de Vries Erik 
Published: July 2022

AbstractEstablishment of zoonotic viruses, causing pandemics like the Spanish flu and Covid-19, requires adaptation to human receptors. Pandemic influenza A viruses (IAV) that crossed the avian-human species barrier switched from binding avian-type α2-3-linked sialic acid (2-3Sia) to human-type 2-6Sia receptors. Here, we show that this specificity switch is however less dichotomous as generally assumed. Binding and entry specificity were compared using mixed synthetic glycan gradients of 2-3Sia and 2-6Sia and by employing a genetically remodeled Sia repertoire on the surface of a Sia-free cell line and on a sialoglycoprotein secreted from these cells. Expression of a range of (mixed) 2-3Sia and 2-6Sia densities shows that non-binding human-type receptors efficiently enhanced avian IAV binding and entry provided the presence of a low density of high affinity avian-type receptors, and vice versa. Considering the heterogeneity of sialoglycan receptors encountered in vivo, hetero-multivalent binding is physiologically relevant and will impact evolutionary pathways leading to host adaptation.
Personality profile and its association with conversion to neurodegenerative disorders in idiopathic REM sleep behavior disorder
Authors: Zhou Li , Chau Steven W. H. , Liu Yaping , Wang Jing , Zhang Jihui , Chan Ngan Yin , Chan Joey W. Y. , Huang Bei , Chen Sijing , Li Shirley Xin , Mok Vincent Chung Tong , Wing Yun Kwok 
Published: July 2022

AbstractPatients with Parkinson’s disease (PD) were described less extraverted and more neurotic. It remained unclear whether similar personality traits could be found in idiopathic rapid eye movement sleep behavior disorder (iRBD), a prodromal stage of PD, and could predict phenoconversion to neurodegenerative disorders. We aimed to investigate the personality profile and its association with future neurodegenerative phenoconversion in iRBD patients. One hundred and eighty-five video-polysomnography confirmed iRBD patients and 91 age- and sex-matched controls underwent personality assessment using the NEO five-factor inventory, and 171 iRBD patients were followed up. Our results showed that iRBD was marginally negatively associated with extraverted personality trait (B = −0.28, 95% confidence interval (CI) = −0.55, −0.001). During a median follow-up of 5.9 years, 47 iRBD patients (27.5%) had phenoconversion. More neurotic (adjusted hazard ratio (HR) = 2.0, 95% CI = 1.3, 3.1) and less extraverted personality traits (adjusted HR = 0.53, 95% CI = 0.36, 0.77) were associated with an increased risk of phenoconversion in iRBD patients. Our findings suggest that personality profile may be a potential prodromal marker of iRBD.
Prediction of degradation pathways of phenolic compounds in the human gut microbiota through enzyme promiscuity methods
Authors: Balzerani Francesco , Hinojosa-Nogueira Daniel , Cendoya Xabier , Blasco Telmo , Pérez-Burillo Sergio , Apaolaza Iñigo , Francino M. Pilar , Rufián-Henares José Ángel , Planes Francisco J. 
Published: July 2022

AbstractThe relevance of phenolic compounds in the human diet has increased in recent years, particularly due to their role as natural antioxidants and chemopreventive agents in different diseases. In the human body, phenolic compounds are mainly metabolized by the gut microbiota; however, their metabolism is not well represented in public databases and existing reconstructions. In a previous work, using different sources of knowledge, bioinformatic and modelling tools, we developed AGREDA, an extended metabolic network more amenable to analyze the interaction of the human gut microbiota with diet. Despite the substantial improvement achieved by AGREDA, it was not sufficient to represent the diverse metabolic space of phenolic compounds. In this article, we make use of an enzyme promiscuity approach to complete further the metabolism of phenolic compounds in the human gut microbiota. In particular, we apply RetroPath RL, a previously developed approach based on Monte Carlo Tree Search strategy reinforcement learning, in order to predict the degradation pathways of compounds present in Phenol-Explorer, the largest database of phenolic compounds in the literature. Reactions predicted by RetroPath RL were integrated with AGREDA, leading to a more complete version of the human gut microbiota metabolic network. We assess the impact of our improvements in the metabolic processing of various foods, finding previously undetected connections with output microbial metabolites. By means of untargeted metabolomics data, we present in vitro experimental validation for output microbial metabolites released in the fermentation of lentils with feces of children representing different clinical conditions.
Using PVA and captive breeding to balance trade-offs in the rescue of the island dibbler onto a new island ark
Authors: Aisya Zahra , White Daniel J. , Thavornkanlapachai Rujiporn , Friend J. Anthony , Rick Kate , Mitchell Nicola J. 
Published: July 2022

AbstractIn the face of the current global extinction crisis, it is critical we give conservation management strategies the best chance of success. Australia is not exempt from global trends with currently the world’s greatest mammal extinction rate (~ 1 per 8 years). Many more are threatened including the dibbler (Parantechinus apicalis) whose remnant range has been restricted to Western Australia at just one mainland site and two small offshore islands—Whitlock Island (5 ha) and Boullanger Island (35 ha). Here, we used 14 microsatellite markers to quantify genetic variation in the remaining island populations from 2013 to 2018 and incorporated these data into population viability analysis (PVA) models, used to assess factors important to dibbler survival and to provide guidance for translocations. Remnant population genetic diversity was low (< 0.3), and populations were highly divergent from each other (pairwise FSTs 0.29–0.52). Comparison of empirical data to an earlier study is consistent with recent declines in genetic diversity and models projected increasing extinction risk and declining genetic variation in the next century. Optimal translocation scenarios recommend 80 founders for new dibbler populations—provided by captive breeding—and determined the proportion of founders from parental populations to maximise genetic diversity and minimise harvesting impact. The goal of our approach is long-term survival of genetically diverse, self-sustaining populations and our methods are transferable. We consider mixing island with mainland dibblers to reinforce genetic variation.