bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypoxic postconditioning promotes mitophagy against transient global cerebral ischemia via PINK1/Parkin-induced mitochondrial ubiquitination in adult rats
Authors: Wen Haixia , Li Luxi , Zhan Lixuan , Zuo Yunyan , Li Kongping , Qiu Meiqian , Li Heying , Sun Weiwen , Xu En
Published: June 2021

Mitophagy alleviates neuronal damage after cerebral ischemia by selectively removing dysfunctional mitochondria. Phosphatase and tensin homolog (PTEN) induced putative kinase 1 (PINK1)/Parkin-mediated mitophagy is the most well-known type of mitophagy. However, little is known about the role of PINK1/Parkin-mediated mitophagy in ischemic tolerance induced by hypoxic postconditioning (HPC) with 8% O2 against transient global cerebral ischemia (tGCI). Hence, we aimed to test the hypothesis that HPC-mediated PINK1/Parkin-induced mitochondrial ubiquitination and promotes mitophagy, thus exerting neuroprotection in the hippocampal CA1 subregion against tGCI. We found that mitochondrial clearance was disturbed at the late phase of reperfusion after tGCI, which was reversed by HPC, as evidenced by the reduction of the translocase of outer mitochondrial membrane 20 homologs (TOMM20), translocase of inner mitochondrial membrane 23 (TIMM23) and heat shock protein 60 (HSP60) in CA1 after HPC. In addition, HPC further increased the ratio of LC3II/I in mitochondrial fraction and promoted the formation of mitophagosomes in CA1 neurons after tGCI. The administration of lysosome inhibitor chloroquine (CQ) intraperitoneally or mitophagy inhibitor (Mdivi-1) intracerebroventricularly abrogated HPC-induced mitochondrial turnover and neuroprotection in CA1 after tGCI. We also found that HPC activated PINK1/Parkin pathway after tGCI, as shown by the augment of mitochondrial PINK1 and Parkin and the promotion of mitochondrial ubiquitination in CA1. In addition, PINK1 or Parkin knockdown with small-interfering RNA (siRNA) suppressed the activation of PINK1/Parkin pathway and hampered mitochondrial clearance and attenuated neuroprotection induced by HPC, whereas PINK1 overexpression promoted PINK1/Parkin-mediated mitophagy and ameliorated neuronal damage in CA1 after tGCI. Taken together, the new finding in this study is that HPC-induced neuroprotection against tGCI through promoting mitophagy mediated by PINK1/Parkin-dependent pathway.
Circ_0008542 in osteoblast exosomes promotes osteoclast-induced bone resorption through m6A methylation
Authors: Wang Wei , Qiao Shi-Chong , Wu Xiang-Bing , Sun Bao , Yang Jin-Gang , Li Xing , Zhang Xiao , Qian Shu-Jiao , Gu Ying-Xin , Lai Hong-Chang
Published: June 2021

With an increasing aging society, China is the world’s fastest growing markets for oral implants. Compared with traditional oral implants, immediate implants cause marginal bone resorption and increase the failure rate of osseointegration, but the mechanism is still unknown. Therefore, it is important to further study mechanisms of tension stimulus on osteoblasts and osteoclasts at the early stage of osseointegration to promote rapid osseointegration around oral implants. The results showed that exosomes containing circ_0008542 from MC3T3-E1 cells with prolonged tensile stimulation promoted osteoclast differentiation and bone resorption. Circ_0008542 upregulated Tnfrsf11a (RANK) gene expression by acting as a miR-185-5p sponge. Meanwhile, the circ_0008542 1916-1992 bp segment exhibited increased m6A methylation levels. Inhibiting the RNA methyltransferase METTL3 or overexpressing the RNA demethylase ALKBH5 reversed osteoclast differentiation and bone resorption induced by circ_0008542. Injection of circ_0008542 + ALKBH5 into the tail vein of mice reversed the same effects in vivo. Site-directed mutagenesis study demonstrated that 1956 bp on circ_0008542 is the m6A functional site with the abovementioned biological functions. In conclusion, the RNA methylase METTL3 acts on the m6A functional site of 1956 bp in circ_0008542, promoting competitive binding of miRNA-185-5p by circ_0008542, and leading to an increase in the target gene RANK and the initiation of osteoclast bone absorption. In contrast, the RNA demethylase ALKBH5 inhibits the binding of circ_0008542 with miRNA-185-5p to correct the bone resorption process. The potential value of this study provides methods to enhance the resistance of immediate implants through use of exosomes releasing ALKBH5.
A chromosome-level genome assembly of rugged rose (Rosa rugosa) provides insights into its evolution, ecology, and floral characteristics
Authors: Chen Fei , Su Liyao , Hu Shuaiya , Xue Jia-Yu , Liu Hui , Liu Guanhua , Jiang Yifan , Du Jianke , Qiao Yushan , Fan Yannan , Liu Huan , Yang Qi , Lu Wenjie , Shao Zhu-Qing , Zhang Jian , Zhang Liangsheng , Chen Feng , Cheng Zong-Ming
Published: June 2021

Rosa rugosa, commonly known as rugged rose, is a perennial ornamental shrub. It produces beautiful flowers with a mild fragrance and colorful seed pods. Unlike many other cultivated roses, R. rugosa adapts to a wide range of habitat types and harsh environmental conditions such as salinity, alkaline, shade, drought, high humidity, and frigid temperatures. Here, we produced and analyzed a high-quality genome sequence for R. rugosa to understand its ecology, floral characteristics and evolution. PacBio HiFi reads were initially used to construct the draft genome of R. rugosa, and then Hi-C sequencing was applied to assemble the contigs into 7 chromosomes. We obtained a 382.6 Mb genome encoding 39,704 protein-coding genes. The genome of R. rugosa appears to be conserved with no additional whole-genome duplication after the gamma whole-genome triplication (WGT), which occurred ~100 million years ago in the ancestor of core eudicots. Based on a comparative analysis of the high-quality genome assembly of R. rugosa and other high-quality Rosaceae genomes, we found a unique large inverted segment in the Chinese rose R. chinensis and a retroposition in strawberry caused by post-WGT events. We also found that floral development- and stress response signaling-related gene modules were retained after the WGT. Two MADS-box genes involved in floral development and the stress-related transcription factors DREB2A-INTERACTING PROTEIN 2 (DRIP2) and PEPTIDE TRANSPORTER 3 (PTR3) were found to be positively selected in evolution, which may have contributed to the unique ability of this plant to adapt to harsh environments. In summary, the high-quality genome sequence of R. rugosa provides a map for genetic studies and molecular breeding of this plant and enables comparative genomic studies of Rosa in the near future.
A Japanese adult and two girls with NEDMIAL caused by de novo missense variants in DHX30
Authors: Ueda Kimiko , Araki Atsushi , Fujita Atsushi , Matsumoto Naomichi , Uehara Tomoko , Suzuki Hisato , Takenouchi Toshiki , Kosaki Kenjiro , Okamoto Nobuhiko
Published: June 2021

Lessel et al. reported a novel neurodevelopmental disorder with severe motor impairment and absent language (NEDMIAL) in 12 individuals and identified six different de novo heterozygous missense variants in DHX30. The other clinical features included muscular hypotonia, feeding difficulties, brain anomalies, autistic features, sleep disturbances, and joint hypermobility. We report a Japanese adult with a novel missense variant and two girls with de novo missense variants in DHX30.
High-responsivity graphene photodetectors integrated on silicon microring resonators
Authors: Schuler S. , Muench J. E. , Ruocco A. , Balci O. , Thourhout D. van , Sorianello V. , Romagnoli M. , Watanabe K. , Taniguchi T. , Goykhman I. , Ferrari A. C. , Mueller T.
Published: June 2021

Graphene integrated photonics provides several advantages over conventional Si photonics. Single layer graphene (SLG) enables fast, broadband, and energy-efficient electro-optic modulators, optical switches and photodetectors (GPDs), and is compatible with any optical waveguide. The last major barrier to SLG-based optical receivers lies in the current GPDs’ low responsivity when compared to conventional PDs. Here we overcome this by integrating a photo-thermoelectric GPD with a Si microring resonator. Under critical coupling, we achieve >90% light absorption in a ~6 μm SLG channel along a Si waveguide. Cavity-enhanced light-matter interactions cause carriers in SLG to reach ~400 K for an input power ~0.6 mW, resulting in a voltage responsivity ~90 V/W, with a receiver sensitivity enabling our GPDs to operate at a 10−9 bit-error rate, on par with mature semiconductor technology, but with a natural generation of a voltage, rather than a current, thus removing the need for transimpedance amplification, with a reduction of energy-per-bit, cost, and foot-print.
Vimentin intermediate filaments stabilize dynamic microtubules by direct interactions
Authors: Schaedel Laura , Lorenz Charlotta , Schepers Anna V. , Klumpp Stefan , Köster Sarah
Published: June 2021

The cytoskeleton determines cell mechanics and lies at the heart of important cellular functions. Growing evidence suggests that the manifold tasks of the cytoskeleton rely on the interactions between its filamentous components—actin filaments, intermediate filaments, and microtubules. However, the nature of these interactions and their impact on cytoskeletal dynamics are largely unknown. Here, we show in a reconstituted in vitro system that vimentin intermediate filaments stabilize microtubules against depolymerization and support microtubule rescue. To understand these stabilizing effects, we directly measure the interaction forces between individual microtubules and vimentin filaments. Combined with numerical simulations, our observations provide detailed insight into the physical nature of the interactions and how they affect microtubule dynamics. Thus, we describe an additional, direct mechanism by which cells establish the fundamental cross talk of cytoskeletal components alongside linker proteins. Moreover, we suggest a strategy to estimate the binding energy of tubulin dimers within the microtubule lattice.
Impact of carbon dioxide removal technologies on deep decarbonization of the electric power sector
Authors: Bistline John E. T. , Blanford Geoffrey J.
Published: June 2021

Carbon dioxide removal technologies, such as bioenergy with carbon capture and direct air capture, are valuable for stringent climate targets. Previous work has examined implications of carbon removal, primarily bioenergy-based technologies using integrated assessment models, but not investigated the effects of a portfolio of removal options on power systems in detail. Here, we explore impacts of carbon removal technologies on electric sector investments, costs, and emissions using a detailed capacity planning and dispatch model with hourly resolution. We show that adding carbon removal to a mix of low-carbon generation technologies lowers the costs of deep decarbonization. Changes to system costs and investments from including carbon removal are larger as policy ambition increases, reducing the dependence on technologies like advanced nuclear and long-duration storage. Bioenergy with carbon capture is selected for net-zero electric sector emissions targets, but direct air capture deployment increases as biomass supply costs rise.
Memory effect assisted imaging through multimode optical fibres
Authors: Li Shuhui , Horsley Simon A. R. , Tyc Tomáš , Čižmár Tomáš , Phillips David B.
Published: June 2021

When light propagates through opaque material, the spatial information it holds becomes scrambled, but not necessarily lost. Two classes of techniques have emerged to recover this information: methods relying on optical memory effects, and transmission matrix (TM) approaches. Here we develop a general framework describing the nature of memory effects in structures of arbitrary geometry. We show how this framework, when combined with wavefront shaping driven by feedback from a guide-star, enables estimation of the TM of any such system. This highlights that guide-star assisted imaging is possible regardless of the type of memory effect a scatterer exhibits. We apply this concept to multimode fibres (MMFs) and identify a ‘quasi-radial’ memory effect. This allows the TM of an MMF to be approximated from only one end - an important step for micro-endoscopy. Our work broadens the applications of memory effects to a range of novel imaging and optical communication scenarios.
Principled approach to the selection of the embedding dimension of networks
Authors: Gu Weiwei , Tandon Aditya , Ahn Yong-Yeol , Radicchi Filippo
Published: June 2021

Network embedding is a general-purpose machine learning technique that encodes network structure in vector spaces with tunable dimension. Choosing an appropriate embedding dimension – small enough to be efficient and large enough to be effective – is challenging but necessary to generate embeddings applicable to a multitude of tasks. Existing strategies for the selection of the embedding dimension rely on performance maximization in downstream tasks. Here, we propose a principled method such that all structural information of a network is parsimoniously encoded. The method is validated on various embedding algorithms and a large corpus of real-world networks. The embedding dimension selected by our method in real-world networks suggest that efficient encoding in low-dimensional spaces is usually possible.
Coordination of two enhancers drives expression of olfactory trace amine-associated receptors
Authors: Fei Aimei , Wu Wanqing , Tan Longzhi , Tang Cheng , Xu Zhengrong , Huo Xiaona , Bao Hongqiang , Kong Yalei , Johnson Mark , Hartmann Griffin , Talay Mustafa , Yang Cheng , Riegler Clemens , Herrera Kristian J. , Engert Florian , Xie X. Sunney , Barnea Gilad , Liberles Stephen D. , Yang Hui , Li Qian
Published: June 2021

Olfactory sensory neurons (OSNs) are functionally defined by their expression of a unique odorant receptor (OR). Mechanisms underlying singular OR expression are well studied, and involve a massive cross-chromosomal enhancer interaction network. Trace amine-associated receptors (TAARs) form a distinct family of olfactory receptors, and here we find that mechanisms regulating Taar gene choice display many unique features. The epigenetic signature of Taar genes in TAAR OSNs is different from that in OR OSNs. We further identify that two TAAR enhancers conserved across placental mammals are absolutely required for expression of the entire Taar gene repertoire. Deletion of either enhancer dramatically decreases the expression probabilities of different Taar genes, while deletion of both enhancers completely eliminates the TAAR OSN populations. In addition, both of the enhancers are sufficient to drive transgene expression in the partially overlapped TAAR OSNs. We also show that the TAAR enhancers operate in cis to regulate Taar gene expression. Our findings reveal a coordinated control of Taar gene choice in OSNs by two remote enhancers, and provide an excellent model to study molecular mechanisms underlying formation of an olfactory subsystem.
Tick extracellular vesicles enable arthropod feeding and promote distinct outcomes of bacterial infection
Authors: Oliva Chávez Adela S. , Wang Xiaowei , Marnin Liron , Archer Nathan K. , Hammond Holly L. , Carroll Erin E. McClure , Shaw Dana K. , Tully Brenden G. , Buskirk Amanda D. , Ford Shelby L. , Butler L. Rainer , Shahi Preeti , Morozova Kateryna , Clement Cristina C. , Lawres Lauren , Neal Anya J. O’ , Mamoun Choukri Ben , Mason Kathleen L. , Hobbs Brandi E. , Scoles Glen A. , Barry Eileen M. , Sonenshine Daniel E. , Pal Utpal , Valenzuela Jesus G. , Sztein Marcelo B. , Pasetti Marcela F. , Levin Michael L. , Kotsyfakis Michail , Jay Steven M. , Huntley Jason F. , Miller Lloyd S. , Santambrogio Laura , Pedra Joao H. F.
Published: June 2021

Extracellular vesicles are thought to facilitate pathogen transmission from arthropods to humans and other animals. Here, we reveal that pathogen spreading from arthropods to the mammalian host is multifaceted. Extracellular vesicles fromIxodes scapularisenable tick feeding and promote infection of the mildly virulent rickettsial agentAnaplasma phagocytophilumthrough the SNARE proteins Vamp33 and Synaptobrevin 2 and dendritic epidermal T cells. However, extracellular vesicles from the tickDermacentor andersonimitigate microbial spreading caused by the lethal pathogenFrancisella tularensis. Collectively, we establish that tick extracellular vesicles foster distinct outcomes of bacterial infection and assist in vector feeding by acting on skin immunity. Thus, the biology of arthropods should be taken into consideration when developing strategies to control vector-borne diseases.
Cell-specific and divergent roles of the CD40L-CD40 axis in atherosclerotic vascular disease
Authors: Lacy Michael , Bürger Christina , Shami Annelie , Ahmadsei Maiwand , Winkels Holger , Nitz Katrin , van Tiel Claudia M. , Seijkens Tom T. P. , Kusters Pascal J. H. , Karshovka Ela , Prange Koen H. M. , Wu Yuting , Brouns Sanne L. N. , Unterlugauer Sigrid , Kuijpers Marijke J. E. , Reiche Myrthe E. , Steffens Sabine , Edsfeldt Andreas , Megens Remco T. A. , Heemskerk Johan W. M. , Goncalves Isabel , Weber Christian , Gerdes Norbert , Atzler Dorothee , Lutgens Esther
Published: June 2021

Atherosclerosis is a major underlying cause of cardiovascular disease. Previous studies showed that inhibition of the co-stimulatory CD40 ligand (CD40L)-CD40 signaling axis profoundly attenuates atherosclerosis. As CD40L exerts multiple functions depending on the cell-cell interactions involved, we sought to investigate the function of the most relevant CD40L-expressing cell types in atherosclerosis: T cells and platelets. Atherosclerosis-prone mice with a CD40L-deficiency in CD4+ T cells display impaired Th1 polarization, as reflected by reduced interferon-γ production, and smaller atherosclerotic plaques containing fewer T-cells, smaller necrotic cores, an increased number of smooth muscle cells and thicker fibrous caps. Mice with a corresponding CD40-deficiency in CD11c+ dendritic cells phenocopy these findings, suggesting that the T cell-dendritic cell CD40L-CD40 axis is crucial in atherogenesis. Accordingly, sCD40L/sCD40 and interferon-γ concentrations in carotid plaques and plasma are positively correlated in patients with cerebrovascular disease. Platelet-specific deficiency of CD40L does not affect atherogenesis but ameliorates atherothrombosis. Our results establish divergent and cell-specific roles of CD40L-CD40 in atherosclerosis, which has implications for therapeutic strategies targeting this pathway.
Designed and biologically active protein lattices
Authors: Wang Shih-Ting , Minevich Brian , Liu Jianfang , Zhang Honghu , Nykypanchuk Dmytro , Byrnes James , Liu Wu , Bershadsky Lev , Liu Qun , Wang Tong , Ren Gang , Gang Oleg
Published: June 2021

Versatile methods to organize proteins in space are required to enable complex biomaterials, engineered biomolecular scaffolds, cell-free biology, and hybrid nanoscale systems. Here, we demonstrate how the tailored encapsulation of proteins in DNA-based voxels can be combined with programmable assembly that directs these voxels into biologically functional protein arrays with prescribed and ordered two-dimensional (2D) and three-dimensional (3D) organizations. We apply the presented concept to ferritin, an iron storage protein, and its iron-free analog, apoferritin, in order to form single-layers, double-layers, as well as several types of 3D protein lattices. Our study demonstrates that internal voxel design and inter-voxel encoding can be effectively employed to create protein lattices with designed organization, as confirmed by in situ X-ray scattering and cryo-electron microscopy 3D imaging. The assembled protein arrays maintain structural stability and biological activity in environments relevant for protein functionality. The framework design of the arrays then allows small molecules to access the ferritins and their iron cores and convert them into apoferritin arrays through the release of iron ions. The presented study introduces a platform approach for creating bio-active protein-containing ordered nanomaterials with desired 2D and 3D organizations.
Photon upconversion through triplet exciton-mediated energy relay
Authors: Han Sanyang , Yi Zhigao , Zhang Jiangbin , Gu Qifei , Liang Liangliang , Qin Xian , Xu Jiahui , Wu Yiming , Xu Hui , Rao Akshay , Liu Xiaogang
Published: June 2021

Exploration of upconversion luminescence from lanthanide emitters through energy migration has profound implications for fundamental research and technology development. However, energy migration-mediated upconversion requires stringent experimental conditions, such as high power excitation and special migratory ions in the host lattice, imposing selection constraints on lanthanide emitters. Here we demonstrate photon upconversion of diverse lanthanide emitters by harnessing triplet exciton-mediated energy relay. Compared with gadolinium-based systems, this energy relay is less dependent on excitation power and enhances the emission intensity of Tb3+ by 158-fold. Mechanistic investigations reveal that emission enhancement is attributable to strong coupling between lanthanides and surface molecules, which enables fast triplet generation (<100 ps) and subsequent near-unity triplet transfer efficiency from surface ligands to lanthanides. Moreover, the energy relay approach supports long-distance energy transfer and allows upconversion modulation in microstructures. These findings enhance fundamental understanding of energy transfer at molecule-nanoparticle interfaces and open exciting avenues for developing hybrid, high-performance optical materials.
City footprints and SDGs provide untapped potential for assessing city sustainability
Authors: Wiedmann Thomas , Allen Cameron
Published: June 2021

Cities are recognised as central to determining the sustainability of human development. However, assessment concepts that are able to ascertain whether or not a city is sustainable are only just emerging. Here we review literature since the Sustainable Development Goals (SDGs) were agreed in 2015 and identify three strands of scientific inquiry and practice in assessing city sustainability. We find that further integration is needed. SDG monitoring and assessment of cities should take advantage of both consumption-based (footprint) accounting and benchmarking against planetary boundaries and social thresholds in order to achieve greater relevance for designing sustainable cities and urban lifestyles.
A platform for on-the-complex annulation reactions with transient aryne intermediates
Authors: Chari Jason V. , Spence Katie A. , Susick Robert B. , Garg Neil K.
Published: June 2021

Organometallic complexes are ubiquitous in chemistry and biology. Whereas their preparation has historically relied on ligand synthesis followed by coordination to metal centers, the ability to efficiently diversify their structures remains a synthetic challenge. A promising yet underdeveloped strategy involves the direct manipulation of ligands that are already bound to a metal center, also known as chemistry-on-the-complex. Herein, we introduce a versatile platform for on-the-complex annulation reactions using transient aryne intermediates. In one variant, organometallic complexes undergo transition metal-catalyzed annulations with in situ generated arynes to form up to six new carbon–carbon bonds. In the other variant, an organometallic complex bearing a free aryne is generated and intercepted in cycloaddition reactions to access unique scaffolds. Our studies, centered around privileged polypyridyl metal complexes, provide an effective strategy to annulate organometallic complexes and access complex metal–ligand scaffolds, while furthering the synthetic utility of strained intermediates in chemical synthesis.
Access to enantioenriched compounds bearing challenging tetrasubstituted stereocenters via kinetic resolution of auxiliary adjacent alcohols
Authors: Niu Shengtong , Zhang Hao , Xu Weici , Bagdi Prasanta Ray , Zhang Guoxiang , Liu Jinggong , Yang Shuang , Fang Xinqiang
Published: June 2021

Contemporary asymmetric catalysis faces huge challenges when prochiral substrates bear electronically and sterically unbiased substituents and when substrates show low reactivities. One of the inherent limitations of chiral catalysts and ligands is their incapability in recognizing prochiral substrates bearing similar groups. This has rendered many enantiopure substances bearing several similar substituents inaccessible. Here we report the rationale, scope, and applications of the strategy of kinetic resolution of auxiliary adjacent alcohols (KRA*) that can be used to solve the above troubles. Using this method, a large variety of optically enriched tertiary alcohols, epoxides, esters, ketones, hydroxy ketones, epoxy ketones, β-ketoesters, and tetrasubstituted methane analogs with two, three, and four spatially and electronically similar groups can be readily obtained (totally 96 examples). At the current stage, the strategy serves as the optimal solution that can complement the inability caused by direct asymmetric catalysis in getting chiral molecules with challenging fully substituted stereocenters.
Magnetic field reveals vanishing Hall response in the normal state of stripe-ordered cuprates
Authors: Shi Zhenzhong , Baity P. G. , Terzic J. , Pokharel Bal K. , Sasagawa T. , Popović Dragana
Published: June 2021

The origin of the weak insulating behavior of the resistivity, i.e. $${\rho }_{xx}\propto {\mathrm{ln}}\,(1/T)$$

ρ

x
x

∝
ln

(

1
/
T

)

, revealed when magnetic fields (H) suppress superconductivity in underdoped cuprates has been a longtime mystery. Surprisingly, the high-field behavior of the resistivity observed recently in charge- and spin-stripe-ordered La-214 cuprates suggests a metallic, as opposed to insulating, high-field normal state. Here we report the vanishing of the Hall coefficient in this field-revealed normal state for all $$T\ <\ (2-6){T}_{{\rm{c}}}^{0}$$
T

<

(

2
−
6

)

T

c

0

, where $${T}_{{\rm{c}}}^{0}$$

T

c

0

is the zero-field superconducting transition temperature. Our measurements demonstrate that this is a robust fundamental property of the normal state of cuprates with intertwined orders, exhibited in the previously unexplored regime of T and H. The behavior of the high-field Hall coefficient is fundamentally different from that in other cuprates such as YBa2Cu3O6+x and YBa2Cu4O8, and may imply an approximate particle-hole symmetry that is unique to stripe-ordered cuprates. Our results highlight the important role of the competing orders in determining the normal state of cuprates.
Combining machine learning and nanopore construction creates an artificial intelligence nanopore for coronavirus detection
Authors: Taniguchi Masateru , Minami Shohei , Ono Chikako , Hamajima Rina , Morimura Ayumi , Hamaguchi Shigeto , Akeda Yukihiro , Kanai Yuta , Kobayashi Takeshi , Kamitani Wataru , Terada Yutaka , Suzuki Koichiro , Hatori Nobuaki , Yamagishi Yoshiaki , Washizu Nobuei , Takei Hiroyasu , Sakamoto Osamu , Naono Norihiko , Tatematsu Kenji , Washio Takashi , Matsuura Yoshiharu , Tomono Kazunori
Published: June 2021

High-throughput, high-accuracy detection of emerging viruses allows for the control of disease outbreaks. Currently, reverse transcription-polymerase chain reaction (RT-PCR) is currently the most-widely used technology to diagnose the presence of SARS-CoV-2. However, RT-PCR requires the extraction of viral RNA from clinical specimens to obtain high sensitivity. Here, we report a method for detecting novel coronaviruses with high sensitivity by using nanopores together with artificial intelligence, a relatively simple procedure that does not require RNA extraction. Our final platform, which we call the artificially intelligent nanopore, consists of machine learning software on a server, a portable high-speed and high-precision current measuring instrument, and scalable, cost-effective semiconducting nanopore modules. We show that artificially intelligent nanopores are successful in accurately identifying four types of coronaviruses similar in size, HCoV-229E, SARS-CoV, MERS-CoV, and SARS-CoV-2. Detection of SARS-CoV-2 in saliva specimen is achieved with a sensitivity of 90% and specificity of 96% with a 5-minute measurement.
Collisionless relaxation of a disequilibrated current sheet and implications for bifurcated structures
Authors: Yoon Young Dae , Yun Gunsu S. , Wendel Deirdre E. , Burch James L.
Published: June 2021

Current sheets are ubiquitous plasma structures that play the crucial role of being energy sources for various magnetic phenomena. Although a plethora of current sheet equilibrium solutions have been found, the collisionless process through which a disequilibrated current sheet relaxes or equilibrates remains largely unknown. Here we show, through analyses of phase-space distributions of single-particle orbit classes and particle-in-cell simulations, that collisionless transitions among the orbit classes are responsible for this process. Bifurcated current sheets, which are readily observed in geospace but whose origins remain controversial, are shown to naturally arise from the equilibration process and thus are likely to be the underlying structures in various phenomena; comparisons of spacecraft observations to particle-in-cell simulations support this fact. The bearing of this result on previous explanations of bifurcated structures is also discussed.
Observed increasing water constraint on vegetation growth over the last three decades
Authors: Jiao Wenzhe , Wang Lixin , Smith William K. , Chang Qing , Wang Honglang , D’Odorico Paolo
Published: June 2021

Despite the growing interest in predicting global and regional trends in vegetation productivity in response to a changing climate, changes in water constraint on vegetation productivity (i.e., water limitations on vegetation growth) remain poorly understood. Here we conduct a comprehensive evaluation of changes in water constraint on vegetation growth in the extratropical Northern Hemisphere between 1982 and 2015. We document a significant increase in vegetation water constraint over this period. Remarkably divergent trends were found with vegetation water deficit areas significantly expanding, and water surplus areas significantly shrinking. The increase in water constraints associated with water deficit was also consistent with a decreasing response time to water scarcity, suggesting a stronger susceptibility of vegetation to drought. We also observed shortened water surplus period for water surplus areas, suggesting a shortened exposure to water surplus associated with humid conditions. These observed changes were found to be attributable to trends in temperature, solar radiation, precipitation, and atmospheric CO2. Our findings highlight the need for a more explicit consideration of the influence of water constraints on regional and global vegetation under a warming climate.
Charge order textures induced by non-linear couplings in a half-doped manganite
Authors: El Baggari Ismail , Baek David J. , Zachman Michael J. , Lu Di , Hikita Yasuyuki , Hwang Harold Y. , Nowadnick Elizabeth A. , Kourkoutis Lena F.
Published: June 2021

The self-organization of strongly interacting electrons into superlattice structures underlies the properties of many quantum materials. How these electrons arrange within the superlattice dictates what symmetries are broken and what ground states are stabilized. Here we show that cryogenic scanning transmission electron microscopy (cryo-STEM) enables direct mapping of local symmetries and order at the intra-unit-cell level in the model charge-ordered system Nd1/2Sr1/2MnO3. In addition to imaging the prototypical site-centered charge order, we discover the nanoscale coexistence of an exotic intermediate state which mixes site and bond order and breaks inversion symmetry. We further show that nonlinear coupling of distinct lattice modes controls the selection between competing ground states. The results demonstrate the importance of lattice coupling for understanding and manipulating the character of electronic self-organization and that cryo-STEM can reveal local order in strongly correlated systems at the atomic scale.
Room-temperature single-photon source with near-millisecond built-in memory
Authors: Dideriksen Karsten B. , Schmieg Rebecca , Zugenmaier Michael , Polzik Eugene S.
Published: June 2021

Non-classical photon sources are a crucial resource for distributed quantum networks. Photons generated from matter systems with memory capability are particularly promising, as they can be integrated into a network where each source is used on-demand. Among all kinds of solid state and atomic quantum memories, room-temperature atomic vapours are especially attractive due to their robustness and potential scalability. To-date room-temperature photon sources have been limited either in their memory time or the purity of the photonic state. Here we demonstrate a single-photon source based on room-temperature memory. Following heralded loading of the memory, a single photon is retrieved from it after a variable storage time. The single-photon character of the retrieved field is validated by the strong suppression of the two-photon component with antibunching as low as $${g}_{{\rm{RR| W = 1}}}^{(2)}=0.20\pm 0.07$$

g

RR∣W=1

(

2

)

=
0.20
±
0.07
. Non-classical correlations between the heralding and the retrieved photons are maintained for up to $${\tau }_{{\rm{NC}}}^{{\mathcal{R}}}=(0.68\pm 0.08)\ {\rm{ms}}$$

τ

NC

R

=

(

0.68
±
0.08

)

ms
, more than two orders of magnitude longer than previously demonstrated with other room-temperature systems. Correlations sufficient for violating Bell inequalities exist for up to τBI = (0.15 ± 0.03) ms.
Fusion transcripts FYN-TRAF3IP2 and KHDRBS1-LCK hijack T cell receptor signaling in peripheral T-cell lymphoma, not otherwise specified
Authors: Debackere Koen , Marcelis Lukas , Demeyer Sofie , Vanden Bempt Marlies , Mentens Nicole , Gielen Olga , Jacobs Kris , Broux Michael , Verhoef Gregor , Michaux Lucienne , Graux Carlos , Wlodarska Iwona , Gaulard Philippe , de Leval Laurence , Tousseyn Thomas , Cools Jan , Dierickx Daan
Published: June 2021

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of non-Hodgkin lymphomas with poor prognosis. Up to 30% of PTCL lack distinctive features and are classified as PTCL, not otherwise specified (PTCL-NOS). To further improve our understanding of the genetic landscape and biology of PTCL-NOS, we perform RNA-sequencing of 18 cases and validate results in an independent cohort of 37 PTCL cases. We identifyFYN-TRAF3IP2,KHDRBS1-LCKandSIN3A-FOXO1as new in-frame fusion transcripts, withFYN-TRAF3IP2as a recurrent fusion detected in 8 of 55 cases. Using ex vivo and in vivo experiments, we demonstrate thatFYN-TRAF3IP2andKHDRBS1-LCKactivate signaling pathways downstream of the T cell receptor (TCR) complex and confer therapeutic vulnerability to clinically available drugs.
α-Helical peptidic scaffolds to target α-synuclein toxic species with nanomolar affinity
Authors: Santos Jaime , Gracia Pablo , Navarro Susanna , Peña-Díaz Samuel , Pujols Jordi , Cremades Nunilo , Pallarès Irantzu , Ventura Salvador
Published: June 2021

α-Synuclein aggregation is a key driver of neurodegeneration in Parkinson’s disease and related syndromes. Accordingly, obtaining a molecule that targets α-synuclein toxic assemblies with high affinity is a long-pursued objective. Here, we exploit the biophysical properties of toxic oligomers and amyloid fibrils to identify a family of α-helical peptides that bind to these α-synuclein species with low nanomolar affinity, without interfering with the monomeric functional protein. This activity is translated into a high anti-aggregation potency and the ability to abrogate oligomer-induced cell damage. Using a structure-guided search we identify a human peptide expressed in the brain and the gastrointestinal tract with analogous binding, anti-aggregation, and detoxifying properties. The chemical entities we describe here may represent a therapeutic avenue for the synucleinopathies and are promising tools to assist diagnosis by discriminating between native and toxic α-synuclein species.
Multi-omics profiling of primary small cell carcinoma of the esophagus reveals RB1 disruption and additional molecular subtypes
Authors: Li Renda , Yang Zhenlin , Shao Fei , Cheng Hong , Wen Yaru , Sun Sijin , Guo Wei , Li Zitong , Zhang Fan , Xue Liyan , Bi Nan , Wang Jie , Sun Yingli , Li Yin , Tan Fengwei , Xue Qi , Gao Shugeng , Shi Susheng , Gao Yibo , He Jie
Published: June 2021

Primary small cell carcinoma of the esophagus (PSCCE) is a lethal neuroendocrine carcinoma. Previous studies proposed a genetic similarity between PSCCE and esophageal squamous cell carcinoma (ESCC) but provided little evidence for differences in clinical course and neuroendocrine differentiation. We perform whole-exome sequencing, RNA sequencing and immunohistochemistry profiling on 46 PSCCE cases. Integrated analyses enable the discovery of multiple mechanisms ofRB1disruption in 98% (45/46) of cases. The transcriptomic landscape of PSCCE closely resembles small cell lung cancer (SCLC) but differs from ESCC or esophageal adenocarcinoma (EAC). Distinct gene expression patterns regulated byASCL1andNEUROD1define two molecular subtypes, PSCCE-A and PSCCE-N, which are highly similar to SCLC subtypes. A T cell excluded phenotype is widely observed in PSCCE. In conclusion, PSCCE has genomic alterations, transcriptome features and molecular subtyping highly similar to SCLC but distinct from ESCC or EAC. These observations are relevant to oncogenesis mechanisms and therapeutic vulnerability.
Wittichenite semiconductor of Cu3BiS3 films for efficient hydrogen evolution from solar driven photoelectrochemical water splitting
Authors: Huang Dingwang , Li Lintao , Wang Kang , Li Yan , Feng Kuang , Jiang Feng
Published: June 2021

A highly efficient, low-cost and environmentally friendly photocathode with long-term stability is the goal of practical solar hydrogen evolution applications. Here, we found that the Cu3BiS3 film-based photocathode meets the abovementioned requirements. The Cu3BiS3-based photocathode presents a remarkable onset potential over 0.9 VRHE with excellent photoelectrochemical current densities (~7 mA/cm2 under 0 VRHE) and appreciable 10-hour long-term stability in neutral water solutions. This high onset potential of the Cu3BiS3-based photocathode directly results in a good unbiased operating photocurrent of ~1.6 mA/cm2 assisted by the BiVO4 photoanode. A tandem device of Cu3BiS3-BiVO4 with an unbiased solar-to-hydrogen conversion efficiency of 2.04% is presented. This tandem device also presents high stability over 20 hours. Ultimately, a 5 × 5 cm2 large Cu3BiS3-BiVO4 tandem device module is fabricated for standalone overall solar water splitting with a long-term stability of 60 hours.
Importance of the renal ion channel TRPM6 in the circadian secretion of renin to raise blood pressure
Authors: Funato Yosuke , Yamazaki Daisuke , Okuzaki Daisuke , Yamamoto Nobuhiko , Miki Hiroaki
Published: June 2021

Blood pressure has a daily pattern, with higher values in the active period. Its elevation at the onset of the active period substantially increases the risk of fatal cardiovascular events. Renin secretion stimulated by renal sympathetic neurons is considered essential to this process; however, its regulatory mechanism remains largely unknown. Here, we show the importance of transient receptor potential melastatin-related 6 (TRPM6), a Mg2+-permeable cation channel, in augmenting renin secretion in the active period. TRPM6 expression is significantly reduced in the distal convoluted tubule of hypotensiveCnnm2-deficient mice. We generate kidney-specificTrpm6-deficient mice and observe a decrease in blood pressure and a disappearance of its circadian variation. Consistently, renin secretion is not augmented in the active period. Furthermore, renin secretion after pharmacological activation of β-adrenoreceptor, the target of neuronal stimulation, is abrogated, and the receptor expression is decreased in renin-secreting cells. These results indicate crucial roles of TRPM6 in the circadian regulation of blood pressure.
Influenza virus infection expands the breadth of antibody responses through IL-4 signalling in B cells
Authors: Miyauchi Kosuke , Adachi Yu , Tonouchi Keisuke , Yajima Taiki , Harada Yasuyo , Fukuyama Hidehiro , Deno Senka , Iwakura Yoichiro , Yoshimura Akihiko , Hasegawa Hideki , Yugi Katsuyuki , Fujii Shin-ichiro , Ohara Osamu , Takahashi Yoshimasa , Kubo Masato
Published: June 2021

Influenza viruses are a major public health problem. Vaccines are the best available countermeasure to induce effective immunity against infection with seasonal influenza viruses; however, the breadth of antibody responses in infection versus vaccination is quite different. Here, we show that nasal infection controls two sequential processes to induce neutralizing IgG antibodies recognizing the hemagglutinin (HA) of heterotypic strains. The first is viral replication in the lung, which facilitates exposure of shared epitopes that are otherwise hidden from the immune system. The second process is the germinal center (GC) response, in particular, IL-4 derived from follicular helper T cells has an essential role in the expansion of rare GC-B cells recognizing the shared epitopes. Therefore, the combination of exposure of the shared epitopes and efficient proliferation of GC-B cells is critical for generating broadly-protective antibodies. These observations provide insight into mechanisms promoting broad protection from virus infection.
Detecting structural heterogeneity in single-molecule localization microscopy data
Authors: Huijben Teun A.P.M. , Heydarian Hamidreza , Auer Alexander , Schueder Florian , Jungmann Ralf , Stallinga Sjoerd , Rieger Bernd
Published: June 2021

Particle fusion for single molecule localization microscopy improves signal-to-noise ratio and overcomes underlabeling, but ignores structural heterogeneity or conformational variability. We present a-priori knowledge-free unsupervised classification of structurally different particles employing the Bhattacharya cost function as dissimilarity metric. We achieve 96% classification accuracy on mixtures of up to four different DNA-origami structures, detect rare classes of origami occuring at 2% rate, and capture variation in ellipticity of nuclear pore complexes.
Enhanced specificity of clinical high-sensitivity tumor mutation profiling in cell-free DNA via paired normal sequencing using MSK-ACCESS
Authors: Rose Brannon A. , Jayakumaran Gowtham , Diosdado Monica , Patel Juber , Razumova Anna , Hu Yu , Meng Fanli , Haque Mohammad , Sadowska Justyna , Murphy Brian J. , Baldi Tessara , Johnson Ian , Ptashkin Ryan , Hasan Maysun , Srinivasan Preethi , Rema Anoop Balakrishnan , Rijo Ivelise , Agarunov Aaron , Won Helen , Perera Dilmi , Brown David N. , Samoila Aliaksandra , Jing Xiaohong , Gedvilaite Erika , Yang Julie L. , Stephens Dennis P. , Dix Jenna-Marie , DeGroat Nicole , Nafa Khedoudja , Syed Aijazuddin , Li Alan , Lebow Emily S. , Bowman Anita S. , Ferguson Donna C. , Liu Ying , Mata Douglas A. , Sharma Rohit , Yang Soo-Ryum , Bale Tejus , Benhamida Jamal K. , Chang Jason C. , Dogan Snjezana , Hameed Meera R. , Hechtman Jaclyn F. , Moung Christine , Ross Dara S. , Vakiani Efsevia , Vanderbilt Chad M. , Yao JinJuan , Razavi Pedram , Smyth Lillian M. , Chandarlapaty Sarat , Iyer Gopa , Abida Wassim , Harding James J. , Krantz Benjamin , O’Reilly Eileen , Yu Helena A. , Li Bob T. , Rudin Charles M. , Diaz Luis , Solit David B. , Arcila Maria E. , Ladanyi Marc , Loomis Brian , Tsui Dana , Berger Michael F. , Zehir Ahmet , Benayed Ryma
Published: June 2021

Circulating cell-free DNA from blood plasma of cancer patients can be used to non-invasively interrogate somatic tumor alterations. Here we develop MSK-ACCESS (Memorial Sloan Kettering - Analysis of Circulating cfDNA to Examine Somatic Status), an NGS assay for detection of very low frequency somatic alterations in 129 genes. Analytical validation demonstrated 92% sensitivity in de-novo mutation calling down to 0.5% allele frequency and 99% for a priori mutation profiling. To evaluate the performance of MSK-ACCESS, we report results from 681 prospective blood samples that underwent clinical analysis to guide patient management. Somatic alterations are detected in 73% of the samples, 56% of which have clinically actionable alterations. The utilization of matched normal sequencing allows retention of somatic alterations while removing over 10,000 germline and clonal hematopoiesis variants. Our experience illustrates the importance of analyzing matched normal samples when interpreting cfDNA results and highlights the importance of cfDNA as a genomic profiling source for cancer patients.
Preventing corneal blindness caused by keratitis using artificial intelligence
Authors: Li Zhongwen , Jiang Jiewei , Chen Kuan , Chen Qianqian , Zheng Qinxiang , Liu Xiaotian , Weng Hongfei , Wu Shanjun , Chen Wei
Published: June 2021

Keratitis is the main cause of corneal blindness worldwide. Most vision loss caused by keratitis can be avoidable via early detection and treatment. The diagnosis of keratitis often requires skilled ophthalmologists. However, the world is short of ophthalmologists, especially in resource-limited settings, making the early diagnosis of keratitis challenging. Here, we develop a deep learning system for the automated classification of keratitis, other cornea abnormalities, and normal cornea based on 6,567 slit-lamp images. Our system exhibits remarkable performance in cornea images captured by the different types of digital slit lamp cameras and a smartphone with the super macro mode (all AUCs>0.96). The comparable sensitivity and specificity in keratitis detection are observed between the system and experienced cornea specialists. Our system has the potential to be applied to both digital slit lamp cameras and smartphones to promote the early diagnosis and treatment of keratitis, preventing the corneal blindness caused by keratitis.
Ionic contrast across a lipid membrane for Debye length extension: towards an ultimate bioelectronic transducer
Authors: Lee Donggeun , Jung Woo Hyuk , Lee Suho , Yu Eui-Sang , Lee Taikjin , Kim Jae Hun , Song Hyun Seok , Lee Kwan Hyi , Lee Seok , Han Sang-Kook , Choi Myung Chul , Ahn Dong June , Ryu Yong-Sang , Kim Chulki
Published: June 2021

Despite technological advances in biomolecule detections, evaluation of molecular interactions via potentiometric devices under ion-enriched solutions has remained a long-standing problem. To avoid severe performance degradation of bioelectronics by ionic screening effects, we cover probe surfaces of field effect transistors with a single film of the supported lipid bilayer, and realize respectable potentiometric signals from receptor–ligand bindings irrespective of ionic strength of bulky solutions by placing an ion-free water layer underneath the supported lipid bilayer. High-energy X-ray reflectometry together with the circuit analysis and molecular dynamics simulation discovered biochemical findings that effective electrical signals dominantly originated from the sub-nanoscale conformational change of lipids in the course of receptor–ligand bindings. Beyond thorough analysis on the underlying mechanism at the molecular level, the proposed supported lipid bilayer-field effect transistor platform ensures the world-record level of sensitivity in molecular detection with excellent reproducibility regardless of molecular charges and environmental ionic conditions.