bluuebunny/crossref_metadata_2025_split huggingface dataset:
Practical Implications of CLIMCAPS Cloud Clearing and Derived Quality Metrics
Authors: Smith N. , Barnet C. D. 
Published: June 2023

AbstractClouds present one of the largest sources of uncertainty in infrared (IR) measurements of the vertical atmospheric state. Hyperspectral instruments onboard Earth orbiting satellites, such as the Atmospheric Infrared Sounder (AIRS) on Aqua (2002–present), measure the top of atmosphere (TOA) radiances emitted by Earth surface and atmosphere. IR measurements are limited in their ability to distinguish different cloud structures. Lack of prior knowledge about clouds at the time of measurement can therefore significantly reduce the quality of retrieved soundings. The Community Long‐term Infrared Microwave Atmospheric Product System (CLIMCAPS) uses the AIRS Science Team (AST) cloud clearing methodology to remove the radiative effect of clouds from TOA IR measurements to improve the quality of its sounding retrievals and enable vertical observations in clear and partly cloudy conditions. In this paper we discuss how AST cloud clearing affects CLIMCAPS soundings and enable a global product for long‐term analysis of the atmospheric state.
Metal Preservation and Mobilization in Sediments at the TAG Hydrothermal Field, Mid‐Atlantic Ridge
Authors: Dutrieux Adeline Marie , Lichtschlag Anna , Barriga Fernando J. A. S. , Martins Sofia , Milinovic Jelena , Murton Bramley J. 
Published: June 2023

AbstractAt the Trans‐Atlantic Geotraverse hydrothermal field, metalliferous sediments cover extinct hydrothermal mounds and the surrounding seafloor. Here, we report the morphological, mineralogical and geochemical processes that deposit these sediments, remobilize their metals, and affect their preservation. We found that the initial sediment metal tenor is controlled by physical transport of hydrothermal material from its source, followed by diagenetic redistribution and potentially diffuse fluid flow after high‐temperature hydrothermal activity has ceased. We distinguished three different environments: (a) proximal metalliferous sediments on top of extinct mounds are mainly derived from oxidative weathering of primary sulfide structures and are predominantly composed of Fe oxyhydroxides with low contents of Cu, Co, and Zn; metal enrichments in specific layers are likely related to upward flow of low‐temperature hydrothermal fluids; (b) medial distant metalliferous sediments found at the base of the mounds, deposited by mass transport, contain cm‐thick layers of unsorted sulfide sands with high base metal contents (e.g., up to 28% Cu); these buried sulfides continue to undergo dissolution, resulting in metal release into porewaters; (c) distal metalliferous sediments, found in depositional basins a few hundreds of meters from the extinct mounds, include fining‐upwards sequences of thin sulfide sand layers with Fe oxyhydroxides and were deposited by recurrent turbiditic flows. Dissolved metals (e.g., Cu2+ and Mn2+) diffuse upwards under reducing conditions and precipitate within the sediment. Hence, when using hydrothermal sediments to construct reliable geochronological records of hydrothermal activity, distance from source, local seafloor morphology, mass‐transport and depositional, and diagenetic modification should all be considered.
SIRPα blockade improves the antitumor immunity of radiotherapy in colorectal cancer
Authors: Ji Kai , Zhang Yuhan , Jiang Shengpeng , Sun Lin , Zhang Baozhong , Hu Dongzhi , Wang Jun , Zhao Lujun , Wang Ping , Tao Zhen 
Published: June 2023

AbstractHigh-dose hypofractionated radiotherapy (HRT) is an important anticancer treatment modality that activates antitumor host immune responses. However, HRT for oligometastases of colorectal cancer (CRC) has shown frustrating results in the clinic. As part of immune evasion, myeloid cells express signal regulatory protein α (SIRPα) to inhibit phagocytosis by phagocytes in the tumor microenvironment (TME). We postulated that SIRPα blockade enhances HRT by alleviating the inhibitory action of SIRPα on phagocytes. We demonstrated that SIRPα on myeloid cells was upregulated in the TME after HRT. When SIRPα blockade was administered with HRT, we observed superior antitumor responses compared with anti-SIRPα or HRT alone. When anti-SIRPα was administered to local HRT, the TME could become a tumoricidal niche that was heavily infiltrated by activated CD8+ T cells, but with limited myeloid-derived suppressor cells and tumor-associated macrophages. While CD8+ T cells were required for the effectiveness of the anti-SIRPα + HRT combination. The triple therapy with anti-SIRPα + HRT + anti-PD-1 had superior antitumor responses compared with the combination of any two therapies and established a strong and long-lasting adaptive immunological memory. Collectively, SIRPα blockade provides a novel way to overcome HRT resistance in oligometastatic CRC patients. Our results herein provide a valuable cancer treatment strategy that has the potential to be translated into clinical practice.
Molecular dynamics simulation of complexation between plasmid DNA and cationic peptides
Authors: Tsuchiya Kousuke , Gimenez-Dejoz Joan , Numata Keiji 
Published: June 2023

AbstractThe elucidation of the process by which cationic peptides condense plasmid DNA (pDNA) is important for unraveling the mechanism of peptide/pDNA complex formation, which plays a vital role in gene delivery for the genetic transformation of living cells. We performed atomic MD simulations of the complexation of pDNA in the presence of two cationic peptides, KH9 (with an alternating sequence of lysine and histidine) and Cytcox (functioning as a mitochondria-targeting signal), to investigate the mechanism of pDNA condensation. The simulations revealed that the cationic peptides bound to the pDNA and that defects in pDNA formed in response to the densely packed cationic peptides, presumably initiating the folding of the double-stranded pDNA into a globule morphology. The decrease in the radius of gyration and the number of hydrogen bonds and the increase in the writhe structure, with a slightly higher tendency for the Cytcox/pDNA system, strongly support the formation of pDNA defects leading to the bending of the double helix. The results provided insight into the mechanism of pDNA complexation with cationic peptides, which should contribute to the future design of highly efficient gene delivery systems using peptide-mediated nanocarriers.
Genomics of cold adaptations in the Antarctic notothenioid fish radiation
Authors: Bista Iliana , Wood Jonathan M. D. , Desvignes Thomas , McCarthy Shane A. , Matschiner Michael , Ning Zemin , Tracey Alan , Torrance James , Sims Ying , Chow William , Smith Michelle , Oliver Karen , Haggerty Leanne , Salzburger Walter , Postlethwait John H. , Howe Kerstin , Clark Melody S. , William Detrich H. , Christina Cheng C.-H. , Miska Eric A. , Durbin Richard 
Published: June 2023

AbstractNumerous novel adaptations characterise the radiation of notothenioids, the dominant fish group in the freezing seas of the Southern Ocean. To improve understanding of the evolution of this iconic fish group, here we generate and analyse new genome assemblies for 24 species covering all major subgroups of the radiation, including five long-read assemblies. We present a new estimate for the onset of the radiation at 10.7 million years ago, based on a time-calibrated phylogeny derived from genome-wide sequence data. We identify a two-fold variation in genome size, driven by expansion of multiple transposable element families, and use the long-read data to reconstruct two evolutionarily important, highly repetitive gene family loci. First, we present the most complete reconstruction to date of the antifreeze glycoprotein gene family, whose emergence enabled survival in sub-zero temperatures, showing the expansion of the antifreeze gene locus from the ancestral to the derived state. Second, we trace the loss of haemoglobin genes in icefishes, the only vertebrates lacking functional haemoglobins, through complete reconstruction of the two haemoglobin gene clusters across notothenioid families. Both the haemoglobin and antifreeze genomic loci are characterised by multiple transposon expansions that may have driven the evolutionary history of these genes.
Systematic detection of tertiary structural modules in large RNAs and RNP interfaces by Tb-seq
Authors: Patel Shivali , Sexton Alec N. , Strine Madison S. , Wilen Craig B. , Simon Matthew D. , Pyle Anna Marie 
Published: June 2023

AbstractCompact RNA structural motifs control many aspects of gene expression, but we lack methods for finding these structures in the vast expanse of multi-kilobase RNAs. To adopt specific 3-D shapes, many RNA modules must compress their RNA backbones together, bringing negatively charged phosphates into close proximity. This is often accomplished by recruiting multivalent cations (usually Mg2+), which stabilize these sites and neutralize regions of local negative charge. Coordinated lanthanide ions, such as terbium (III) (Tb3+), can also be recruited to these sites, where they induce efficient RNA cleavage, thereby revealing compact RNA 3-D modules. Until now, Tb3+cleavage sites were monitored via low-throughput biochemical methods only applicable to small RNAs. Here we present Tb-seq, a high-throughput sequencing method for detecting compact tertiary structures in large RNAs. Tb-seq detects sharp backbone turns found in RNA tertiary structures and RNP interfaces, providing a way to scan transcriptomes for stable structural modules and potential riboregulatory motifs.
Neutralizing IFNγ improves safety without compromising efficacy of CAR-T cell therapy in B-cell malignancies
Authors: Manni Simona , Del Bufalo Francesca , Merli Pietro , Silvestris Domenico Alessandro , Guercio Marika , Caruso Simona , Reddel Sofia , Iaffaldano Laura , Pezzella Michele , Di Cecca Stefano , Sinibaldi Matilde , Ottaviani Alessio , Quadraccia Maria Cecilia , Aurigemma Mariasole , Sarcinelli Andrea , Ciccone Roselia , Abbaszadeh Zeinab , Ceccarelli Manuela , De Vito Rita , Lodi Maria Chiara , Cefalo Maria Giuseppina , Mastronuzzi Angela , De Angelis Biagio , Locatelli Franco , Quintarelli Concetta 
Published: June 2023

AbstractChimeric antigen receptor T (CAR-T) cell therapy may achieve long-lasting remission in patients with B-cell malignancies not responding to conventional therapies. However, potentially severe and hard-to-manage side effects, including cytokine release syndrome (CRS), neurotoxicity and macrophage activation syndrome, and the lack of pathophysiological experimental models limit the applicability and development of this form of therapy. Here we present a comprehensive humanized mouse model, by which we show that IFNγ neutralization by the clinically approved monoclonal antibody, emapalumab, mitigates severe toxicity related to CAR-T cell therapy. We demonstrate that emapalumab reduces the pro-inflammatory environment in the model, thus allowing control of severe CRS and preventing brain damage, characterized by multifocal hemorrhages. Importantly, our in vitro and in vivo experiments show that IFNγ inhibition does not affect the ability of CD19-targeting CAR-T (CAR.CD19-T) cells to eradicate CD19+ lymphoma cells. Thus, our study provides evidence that anti-IFNγ treatment might reduce immune related adverse effect without compromising therapeutic success and provides rationale for an emapalumab-CAR.CD19-T cell combination therapy in humans.
Vitrification and nanowarming enable long-term organ cryopreservation and life-sustaining kidney transplantation in a rat model
Authors: Han Zonghu , Rao Joseph Sushil , Gangwar Lakshya , Namsrai Bat-Erdene , Pasek-Allen Jacqueline L. , Etheridge Michael L. , Wolf Susan M. , Pruett Timothy L. , Bischof John C. , Finger Erik B. 
Published: June 2023

AbstractBanking cryopreserved organs could transform transplantation into a planned procedure that more equitably reaches patients regardless of geographical and time constraints. Previous organ cryopreservation attempts have failed primarily due to ice formation, but a promising alternative is vitrification, or the rapid cooling of organs to a stable, ice-free, glass-like state. However, rewarming of vitrified organs can similarly fail due to ice crystallization if rewarming is too slow or cracking from thermal stress if rewarming is not uniform. Here we use “nanowarming,” which employs alternating magnetic fields to heat nanoparticles within the organ vasculature, to achieve both rapid and uniform warming, after which the nanoparticles are removed by perfusion. We show that vitrified kidneys can be cryogenically stored (up to 100 days) and successfully recovered by nanowarming to allow transplantation and restore life-sustaining full renal function in nephrectomized recipients in a male rat model. Scaling this technology may one day enable organ banking for improved transplantation.
Empowering drug off-target discovery with metabolic and structural analysis
Authors: Chowdhury Sourav , Zielinski Daniel C. , Dalldorf Christopher , Rodrigues Joao V. , Palsson Bernhard O. , Shakhnovich Eugene I. 
Published: June 2023

AbstractElucidating intracellular drug targets is a difficult problem. While machine learning analysis of omics data has been a promising approach, going from large-scale trends to specific targets remains a challenge. Here, we develop a hierarchic workflow to focus on specific targets based on analysis of metabolomics data and growth rescue experiments. We deploy this framework to understand the intracellular molecular interactions of the multi-valent dihydrofolate reductase-targeting antibiotic compound CD15-3. We analyse global metabolomics data utilizing machine learning, metabolic modelling, and protein structural similarity to prioritize candidate drug targets. Overexpression and in vitro activity assays confirm one of the predicted candidates, HPPK (folK), as a CD15-3 off-target. This study demonstrates how established machine learning methods can be combined with mechanistic analyses to improve the resolution of drug target finding workflows for discovering off-targets of a metabolic inhibitor.
Nonlinear multi-magnon scattering in artificial spin ice
Authors: Lendinez Sergi , Kaffash Mojtaba T. , Heinonen Olle G. , Gliga Sebastian , Iacocca Ezio , Jungfleisch M. Benjamin 
Published: June 2023

AbstractMagnons, the quantum-mechanical fundamental excitations of magnetic solids, are bosons whose number does not need to be conserved in scattering processes. Microwave-induced parametric magnon processes, often called Suhl instabilities, have been believed to occur in magnetic thin films only, where quasi-continuous magnon bands exist. Here, we reveal the existence of such nonlinear magnon-magnon scattering processes and their coherence in ensembles of magnetic nanostructures known as artificial spin ice. We find that these systems exhibit effective scattering processes akin to those observed in continuous magnetic thin films. We utilize a combined microwave and microfocused Brillouin light scattering measurement approach to investigate the evolution of their modes. Scattering events occur between resonance frequencies that are determined by each nanomagnet’s mode volume and profile. Comparison with numerical simulations reveals that frequency doubling is enabled by exciting a subset of nanomagnets that, in turn, act as nanosized antennas, an effect that is akin to scattering in continuous films. Moreover, our results suggest that tunable directional scattering is possible in these structures.
Variants in SART3 cause a spliceosomopathy characterised by failure of testis development and neuronal defects
Authors: Ayers Katie L. , Eggers Stefanie , Rollo Ben N. , Smith Katherine R. , Davidson Nadia M. , Siddall Nicole A. , Zhao Liang , Bowles Josephine , Weiss Karin , Zanni Ginevra , Burglen Lydie , Ben-Shachar Shay , Rosensaft Jenny , Raas-Rothschild Annick , Jørgensen Anne , Schittenhelm Ralf B. , Huang Cheng , Robevska Gorjana , van den Bergen Jocelyn , Casagranda Franca , Cyza Justyna , Pachernegg Svenja , Wright David K. , Bahlo Melanie , Oshlack Alicia , O’Brien Terrence J. , Kwan Patrick , Koopman Peter , Hime Gary R. , Girard Nadine , Hoffmann Chen , Shilon Yuval , Zung Amnon , Bertini Enrico , Milh Mathieu , Ben Rhouma Bochra , Belguith Neila , Bashamboo Anu , McElreavey Kenneth , Banne Ehud , Weintrob Naomi , BenZeev Bruria , Sinclair Andrew H. 
Published: June 2023

AbstractSquamous cell carcinoma antigen recognized by T cells 3 (SART3) is an RNA-binding protein with numerous biological functions including recycling small nuclear RNAs to the spliceosome. Here, we identify recessive variants in SART3 in nine individuals presenting with intellectual disability, global developmental delay and a subset of brain anomalies, together with gonadal dysgenesis in 46,XY individuals. Knockdown of the Drosophila orthologue of SART3 reveals a conserved role in testicular and neuronal development. Human induced pluripotent stem cells carrying patient variants in SART3 show disruption to multiple signalling pathways, upregulation of spliceosome components and demonstrate aberrant gonadal and neuronal differentiation in vitro. Collectively, these findings suggest that bi-allelic SART3 variants underlie a spliceosomopathy which we tentatively propose be termed INDYGON syndrome (Intellectual disability, Neurodevelopmental defects and Developmental delay with 46,XYGONadal dysgenesis). Our findings will enable additional diagnoses and improved outcomes for individuals born with this condition.
Operator growth from global out-of-time-order correlators
Authors: Zhou Tianci , Swingle Brian 
Published: June 2023

AbstractIn chaotic many-body systems, scrambling or the operator growth can be diagnosed by out-of-time-order correlators of local operators. We show that operator growth also has a sharp imprint in out-of-time-order correlators of global operators. In particular, the characteristic spacetime shape of growing local operators can be accessed using global measurements without any local control or readout. Building on an earlier conjectured phase diagram for operator growth in chaotic systems with power-law interactions, we show that existing nuclear spin data for out-of-time-order correlators of global operators are well fit by our theory. We also predict super-polynomial operator growth in dipolar systems in 3d and discuss the potential observation of this physics in future experiments with nuclear spins and ultra-cold polar molecules.
Long-wave infrared photothermoelectric detectors with ultrahigh polarization sensitivity
Authors: Dai Mingjin , Wang Chongwu , Qiang Bo , Jin Yuhao , Ye Ming , Wang Fakun , Sun Fangyuan , Zhang Xuran , Luo Yu , Wang Qi Jie 
Published: June 2023

AbstractFilter-free miniaturized polarization-sensitive photodetectors have important applications in the next-generation on-chip polarimeters. However, their polarization sensitivity is thus far limited by the intrinsic low diattenuation and inefficient photon-to-electron conversion. Here, we implement experimentally a miniaturized detector based on one-dimensional tellurium nanoribbon, which can significantly improve the photothermoelectric responses by translating the polarization-sensitive absorption into a large temperature gradient together with the finite-size effect of a perfect plasmonic absorber. Our devices exhibit a zero-bias responsivity of 410 V/W and an ultrahigh polarization ratio (2.5 × 104), as well as a peak polarization angle sensitivity of 7.10 V/W•degree, which is one order of magnitude higher than those reported in the literature. Full linear polarimetry detection is also achieved with the proposed device in a simple geometrical configuration. Polarization-coded communication and optical strain measurement are demonstrated showing the great potential of the proposed devices. Our work presents a feasible solution for miniaturized room-temperature infrared photodetectors with ultrahigh polarization sensitivity.
Distinct neural mechanisms construct classical versus extraclassical inhibitory surrounds in an inhibitory nucleus in the midbrain attention network
Authors: Schryver Hannah M. , Mysore Shreesh P. 
Published: June 2023

AbstractInhibitory neurons in the midbrain spatial attention network, called isthmi pars magnocellularis (Imc), control stimulus selection by the sensorimotor and attentional hub, the optic tectum (OT). Here, we investigate in the barn owl how classical as well as extraclassical (global) inhibitory surrounds of Imc receptive fields (RFs), fundamental units of Imc computational function, are constructed. We find that focal, reversible blockade of GABAergic input onto Imc neurons disconnects their extraclassical inhibitory surrounds, but leaves intact their classical inhibitory surrounds. Subsequently, with paired recordings and iontophoresis, first at spatially aligned site-pairs in Imc and OT, and then, at mutually distant site-pairs within Imc, we demonstrate that classical inhibitory surrounds of Imc RFs are inherited from OT, but their extraclassical inhibitory surrounds are constructed within Imc. These results reveal key design principles of the midbrain spatial attention circuit and highlight the critical importance of competitive interactions within Imc for its operation.
Waves traveling over a map of visual space can ignite short-term predictions of sensory input
Authors: Benigno Gabriel B. , Budzinski Roberto C. , Davis Zachary W. , Reynolds John H. , Muller Lyle 
Published: June 2023

AbstractRecent analyses have found waves of neural activity traveling across entire visual cortical areas in awake animals. These traveling waves modulate the excitability of local networks and perceptual sensitivity. The general computational role of these spatiotemporal patterns in the visual system, however, remains unclear. Here, we hypothesize that traveling waves endow the visual system with the capacity to predict complex and naturalistic inputs. We present a network model whose connections can be rapidly and efficiently trained to predict individual natural movies. After training, a few input frames from a movie trigger complex wave patterns that drive accurate predictions many frames into the future solely from the network’s connections. When the recurrent connections that drive waves are randomly shuffled, both traveling waves and the ability to predict are eliminated. These results suggest traveling waves may play an essential computational role in the visual system by embedding continuous spatiotemporal structures over spatial maps.
Transparent tissue in solid state for solvent-free and antifade 3D imaging
Authors: Hsiao Fu-Ting , Chien Hung-Jen , Chou Ya-Hsien , Peng Shih-Jung , Chung Mei-Hsin , Huang Tzu-Hui , Lo Li-Wen , Shen Chia-Ning , Chang Hsiu-Pi , Lee Chih-Yuan , Chen Chien-Chia , Jeng Yung-Ming , Tien Yu-Wen , Tang Shiue-Cheng 
Published: June 2023

AbstractOptical clearing with high-refractive-index (high-n) reagents is essential for 3D tissue imaging. However, the current liquid-based clearing condition and dye environment suffer from solvent evaporation and photobleaching, causing difficulties in maintaining the tissue optical and fluorescent features. Here, using the Gladstone-Dale equation [(n−1)/density=constant] as a design concept, we develop a solid (solvent-free) high-n acrylamide-based copolymer to embed mouse and human tissues for clearing and imaging. In the solid state, the fluorescent dye-labeled tissue matrices are filled and packed with the high-n copolymer, minimizing scattering in in-depth imaging and dye fading. This transparent, liquid-free condition provides a friendly tissue and cellular environment to facilitate high/super-resolution 3D imaging, preservation, transfer, and sharing among laboratories to investigate the morphologies of interest in experimental and clinical conditions.