bluuebunny/crossref_metadata_2025 huggingface dataset:
Rethinking the Rethinking of Legal Pluralism: Toward a Manifesto for a Pluri-Legal Perspective
Authors: Shahar Ido , Yefet Karin Carmit
Published: June 2023

The paper addresses the perpetual discontent evoked by the concept of legal pluralism, one which, in turn, brings about incessant efforts to “rethink” it. We suggest that one of the sources of this discontent is the erroneous view that legal pluralism is a theory, and the consequent misguided expectations that it should provide scholars of law and society with causal hypotheses and explanations. We argue that legal pluralism is not a theory but a research perspective, and, as such, is not meant to provide us with explanatory propositions, but rather to increase our awareness of the plurality and inter-relationality of socio-legal spheres and of the implications thereof. We further identify—and briefly discuss—the four core principles of a pluri-legal perspective: plurality, relationality, power, and agency. Taken together, these four premises constitute a manifesto of sorts for a pluri-legal perspective.
Molecular Clouds with CO-dark Envelopes in the Extended Ultraviolet (XUV) Disk of M83
Authors: Koda Jin
Published: June 2023

We report a CO(3-2) detection of 23 molecular clouds in the extended ultraviolet (XUV) disk of the spiral galaxy M83 with ALMA. The observed 1 kpc2 region is at about 1.24R25 from the disk center, where CO(2-1) was previously not detected. The detection and non-detection, as well as the level of star formation (SF) activity in the region, can be explained consistently if the clouds have the mass distribution common among Galactic clouds, such as Orion A – with star-forming dense clumps embedded in thick layers of bulk molecular gas, but in a low-metallicity regime where their outer layers are CO-deficient and CO-dark. The cloud masses, estimated from CO(3-2), range from 8.2×102 to 2.3×104M⊙. The most massive clouds appear similar to Orion A in SF activity as well as in gas mass. The common cloud mass structure also justifies the use of high-J CO transitions to trace the total gas mass of clouds, or galaxies, even in the high-z universe. This study is the first demonstration that CO(3-2) is an efficient tracer of molecular clouds even in low-metallicity environments. This study is published in the Astronomical Journal, entitled “First Detection of the Molecular Cloud Population in the Extended Ultraviolet (XUV) Disk of M83" by J. Koda, L. Watson, F. Combes, M. Rubio, S. Boissier, M. Yagi, D. Thilker, A. M Lee, Y. Komiyama, K. Morokuma-Matsui, and C. Verdugo.
Gas-Star Formation Cycle in Nearby Galaxies
Authors: Pan Hsi-An , Schinnerer Eva , Hughes Annie , Leroy Adam , Groves Brent ,   The PHANGS Team
Published: June 2023

Star formation, from cold giant molecular clouds to diverse population of stars, is a complex process involving a wide variety of physical processes. In this work, we constrain the link between the gas-star formation cycle and several secular and environmental probe of galaxies. Specifically, we quantify the spatial correlation between molecular gas and star-forming regions for 49 nearby galaxies using the ALMA and narrowband-Hα imaging from the PHANGS survey. At the resolution (150 pc) at which the individual molecular clouds and star-forming regions can be identified, we find that molecular clouds and star-forming regions do not necessarily coexist. The decoupled molecular clouds and star-forming regions are a signature of evolutionary cycling and feedback of the star formation process. Therefore, the impact of galactic-scale conditions and environments must be considered for a complete understanding of how stars form in galaxies and how this process influences the evolution of the host galaxies.
Formation of the Stellar System and the Central Gravitation-Potential Vessel of Galaxies
Authors: Kodaira Keiichi , Kalinova Veselina
Published: June 2023

The formation of the global stellar system of galaxies are studied through the circular velocity curves of CALIFA nearby galaxies by sequencing the depth and size of the central gravitation-potential vessel and its dynamical mass, relative to the masses of the stellar system and of the parent halo, with the population or age parameters, to explore the dynamical characteristics of the dissipative contracting baryonic matter.
The local and global relations between Σ*, ΣSFR and Σmol that regulate star-formation
Authors: Sánchez Sebastián F. , Gómez Medina Daysi C. , Barrera-Ballesteros J.K. , Galbany L. , Bolatto A. , Wong T.
Published: June 2023

Star-formation is one of the main processes that shape galaxies, defining its stellar population and metallicity production and enrichment. It is nowadays known that this process is ruled by a set of relations that connect three parameters: the molecular gas mass, the stellar mass and the star-formation rate itself. These relations are fulfilled at a wide range of scales in galaxies, from galaxy wide to kpc-scales. At which scales they are broken, and how universal they are (i.e., if they change at different scales or for different galaxy types) it is still an open question. We explore here how those relations compare at different scales using as proxy the new analysis done using Integral Field Spectroscopy data and CO observations data from the EDGE-CALIFA survey and the AMUSSING++ compilation.
The cold gas supply through cosmic time: insights on the galaxy assembly at early epochs
Authors: Aravena Manuel
Published: June 2023

Remarkable progress has been made in the last few years in understanding the global properties of galaxies and how they evolve through cosmic time. Major focus has been given to studies of how the availability of molecular gas regulates star-forming activity and galaxy growth, the eventual quenching of star formation, and how these mechanisms evolve through cosmic time. Most of these advances have been made thanks to ALMA and the upgraded capabilities of NOEMA. In this contribution, I briey review the latest constraints on the molecular gas content based on dierent tracers of the interstellar medium (ISM; dust continuum and CO, [CI] and [CII] line emission), including recent determinations of the molecular gas fraction, gas depletion timescales, and molecular gas cosmic density provided by the recent ALMA programs out to z ∼ 7. Finally, I concentrate on recent and ongoing studies aiming to spatially and kinematically resolve the cold ISM and star formation activity down to kpc scales in galaxies out to z ∼ 6 – 7, which represent an unprecedented view of the galaxy assembly and feedback processes in the early universe.
The dust properties of star-forming galaxies in the first billion years
Authors: da Cunha Elisabete
Published: June 2023

The Atacama Large Millimetre/Sub-millimetre Array (ALMA) is obtaining the deepest observations of early galaxies ever achieved at (sub-)millimetre wavelengths, and detecting the dust emission of young galaxies in the first billion years of cosmic history, well in the epoch of reionization. Here I review some of the latest results from these observations, with special focus on the REBELS large programme, which targets a sample of 40 star-forming galaxies at z ⋍ 7. ALMA detects significant amounts of dust in very young galaxies, and this dust might have different properties to dust in lower-redshift galaxies. I describe the evidence for this, and discuss theoretical/modelling efforts to explain the dust properties of these young galaxies. Finally, I describe two additional surprising results to come out of the REBELS survey: (i) a new population of completely dust-obscured galaxies at z ⋍ 7, and (ii) the prevalence of spatial offsets between the ultraviolet and infrared emission of UV-bright, high-redshift star-forming galaxies.
The Extragalactic Database for Galaxy Evolution (EDGE)
Authors: Wong Tony , Cao Yixian , Luo Yufeng , Bolatto Alberto D. , Sánchez Sebastián F. ,   the EDGE-CALIFA Collaboration
Published: June 2023

The EDGE-CALIFA collaboration has obtained resolved IFU and CO spectroscopy for 126 nearby galaxies, selected from the CALIFA main sample. We have assembled the spatially resolved products of the survey into Astropy-compatible pixel tables that reduce the oversampling in the original FITS images and facilitate comparison of pixels across different images. By joining these pixel tables to lower dimensional tables that provide profiles, integrated spectra, or global properties, it is possible to investigate the dependence of star formation rate on both local and global conditions. In this short video talk I provide an overview of EDGE, with examples of the use of the database to conduct analysis and generate plots.
Extended neutral hydrogen filamentary network in NGC 2403
Authors: Veronese Simone , de Blok W. J. G.
Published: June 2023

We present new neutral hydrogen (Hi) observations of the nearby galaxy NGC 2403 to determine the nature of a low-column density cloud that was detected earlier by the Green Bank Telescope.

We find that this cloud is the tip of a complex of filaments of extraplanar gas that is coincident with the main disk. The total Hi mass of the complex is 2 × 107 M⊙ or 0.6% of the total Hi mass of the galaxy. The main structure, previously referred to as the 8-kpc filament, is now seen to be even more extended, along a 20 kpc stream.
On the H i Content of MaNGA Major Merger Pairs
Authors: Yu Qingzheng , Fang Taotao , Feng Shuai , Zhang Bo , Kevin Xu C. , Wang Yunting , Hao Lei
Published: June 2023

To study the role of H i content in galaxy interactions, we select galaxy pairs and control galaxies from the SDSS-IV MaNGA IFU survey, adopting kinematic asymmetry as a new effective indicator to describe the merger stage. With archival data from the HI-MaNGA survey and new observations from the Five-hundred-meter Aperture Spherical radio Telescope (FAST), we investigate the differences in H i gas fraction (fH i), star formation rate (SFR), and H i star formation efficiency (SFEH i) between pairs and controls. Our results suggest that on average the H i gas fraction of major-merger pairs is marginally decreased by ∼ 15% relative to isolated galaxies, and paired galaxies during pericentric passage show weakly decreased fH i (−0.10 ± 0.05 dex), significantly enhanced SFR (0.42 ± 0.11 dex), and SFEH i (0.48 ± 0.12 dex). We propose the marginally detected H i depletion may originate from the gas consumption in fueling the enhanced H2 reservoir of galaxy pairs.
Exploring the evolution of giant molecular clouds in one of the nearest spiral galaxies M33
Authors: Konishi Ayu , Muraoka Kazuyuki , Tokuda Kazuki , Fujita Shinji , Yamada Rin I. , Demachi Fumika , Tachihara Kengo , Fukui Yasuo , Kobayashi Masato I. N. , Kisetsu Tsuge , Kawamura Akiko , Onishi Toshikazu
Published: June 2023

The evolution of giant molecular clouds (GMCs), which are the main sites of star formation, is essential for unraveling how stars form and how galaxies evolve. We analyzed the M33 CO(J = 2–1) data with spatial resolution of 39 pc obtained by ALMA-ACA 7 m array combined with IRAM 30 m. We identified 736 GMCs and classified them into three types; Type I: associated with no Hii regions, Type II: associated with Hii regions with the Hα luminosity L(Hα) < 1037.5 erg s-1, Type III: associated with Hii regions with L(Hα) > 1037.5erg s-1. We found that mass, size, and velocity dispersion of GMCs slightly increase in the order of Type I, II, and III GMCs. Type III GMCs mainly exist in the spiral arm, while many of Type I and Type II GMCs are distributed in the inter-arm. Assuming that the star formation proceeds steadily, we roughly estimated the total GMC lifetime of 30 Myr.
New era of LSST data: Estimating the physical properties of main-sequence galaxies
Authors: Riccio G.
Published: June 2023

The main goal of the Vera C. Rubin observatory is to perform the 10 year Legacy Survey of Space and Time (LSST). This future state-of-art observatory will open the new window to study billions of galaxies from Local Universe as well as the high redshift objects. In this work we employ simulated LSST observations and uncertainties, based on the 50 385 real galaxies within the redshift range 0 < z < 2.5 from the ELAIS-N1 and COSMOS fields of the Herschel Extragalactic Legacy Project (HELP) survey, to constrain the physical properties of normal star-forming galaxies, such as their star formation rate (SFR), stellar mass (Mstar), and dust luminosity (Ldust). We fit their spectral energy distributions (SEDs) using the Code Investigating GALaxy Emission (CIGALE). The stellar masses estimated based on the LSST measurements agree with the full UV to far-IR SED, while we obtain a clear overestimate of the dust-related properties (SFR, Ldust) estimated with LSST. We investigate the cause of this result and find that it is necessary to employ auxiliary rest-frame mid-IR observations, simulated UV observations, or the far-UV attenuation (AFUV)-Mstar relation to correct for the overestimate.
Diverse Star Formation History in Presence of Cold-Mode Gas Accretion: From Solar Neighborhood to Distant Galaxies
Authors: Noguchi Masafumi
Published: June 2023

Existence of cold-mode gas accretion along with the hot-mode accretion of the shock-heated gas can explain the bimodality in the elemental abundance of the Milky Way disk stars as well as the mass-dependence of galaxy morphology represented by mass ratios of thin disks, thick disks, and bulges.
Star Formation History in the Illustris TNG Simulation
Authors: Joó András Péter , Koncz Bendegúz , Pinter Sandor , Tóth L. Viktor
Published: June 2023

We processed the catalogue data for all snapshots of the Illustris TNG100 cosmological simulation and collected every calculated property of the galaxies formed at different redshifts. With this dataset we can statistically analyze parameters for galaxy samples at given redshifts, as well as trace sample parameters over the entire time range of the simulation. Focusing first on star formation rate (SFR) and metallicity, we see the cosmic star formation history with the mean maximum at around z ≈ 1.6 and the reionization bump at around z ≈ 5, while metallicity increases. For a sample of strongly star-forming galaxies with SFR > 10 M⊙ yr−1 we found different characteristics compared to the whole sample. The mean metallicity of highly star-forming galaxies is higher and changes less, and the mean SFR has its maximum at around the reionization bump.
Detectable Anthropogenic Intensification of the Summer Compound Hot and Dry Events Over Global Land Areas
Authors: Pan Rongyun , Li Wei , Wang Qirong , Ailiyaer Aihaiti
Published: June 2023

Compound hot and dry events (CHDEs) pose an increasing threat to global warming and have received growing attention in recent decades. We conducted a detection and attribution analysis (D&A) using the optimal fingerprint technique to analyze the changes in observed CHDEs at continental and sub‐continental scales from 1961 to 2014. The responses of CHDEs changes to anthropogenic (ANT), greenhouse gases (GHG), aerosols (AER), and natural (NAT) forcings were obtained from the Coupled Model Intercomparison Project phase 6 forcing experiment. In a two‐signal D&A analysis that considered ANT and NAT simultaneously, ANT signals were robustly detected and separated from NAT in all continental domains and more than 65% of subcontinental domains (29 out of 44 domains). The trend attributed to the ANT forcing is comparable to the observed trend over domains where the ANT signal is detectable. We also conducted a three‐signal D&A analysis that regressed observation onto GHG, AER, and NAT simultaneously. The GHG signals were detectable in all continents except Oceania, and it contributed dominantly to the observed trend over 22 out of 29 regions where ANT signals had emerged. Multivariate biases correction can largely reduce the models' biases in simulating the marginal distribution and the dependence structure, which can provide a more accurate future risk of CDHEs. We found that limiting global warming to 1.5℃ rather than 2.0℃ can significantly mitigate the impact of compound events in most areas of global land, particularly in South America, Africa, and Oceania.
Important Contribution of Bacterial Carbon and Nitrogen to Sinking Particle Export
Authors: Shen Yuan , Guilderson Thomas P. , Chavez Francisco P. , McCarthy Matthew D.
Published: June 2023

Photosynthesis in the surface ocean converts atmospheric CO2 into organic particles, with the fraction sinking to depth representing a major part of the ocean's biological pump. Although sinking particles are known to be altered by attached‐bacteria during transit, most prior organic geochemical data indicated only minor replacement of plankton‐derived particles by bacterial material. We exploit bacteria‐specific biomarkers (d‐amino acids) in a multi‐year sediment trap in the Pacific Ocean (1,200 m) and suggest a different view. Major d‐amino acids were consistently measured at abundance demonstrating widespread accumulation of bacterial material in sinking particles. Bacterial detritus was estimated to account for up to 19% of particulate organic carbon and up to 36% of particulate nitrogen, much higher than cell count‐based values. The bacterial relative contribution increased with decreasing export production. Our results indicate that bacterial material constitutes an underappreciated component of the biological pump, a role expected to rise as the ocean warms.
A Mixed‐Flux‐Based Nodal Discontinuous Galerkin Method for 3D Dynamic Rupture Modeling
Authors: Zhang Wenqiang , Liu Yajing , Chen Xiaofei
Published: June 2023

Numerical simulation of rupture dynamics provides critical insights for understanding earthquake physics, while the complex geometry and heterogeneous material properties of natural faults make numerical method development challenging. The discontinuous Galerkin (DG) method is suitable for handling these complexities. In the DG method, the fault boundary conditions can be conveniently imposed through the upwind flux by solving a Riemann problem based on a velocity‐strain elastodynamic equation. However, the universal adoption of upwind flux can cause spatial oscillations in cases where elements on adjacent sides of the fault surface are not nearly symmetric. Here we propose a nodal DG method with an upwind/central mixed‐flux scheme to solve the spatial oscillation problem and thus reduce the dependence on mesh quality. Our method can achieve high scalability in parallel computing under different orders of accuracy. We verify the new method by comparing simulation results with those from other methods on a series of published benchmark problems with complex fault geometries, heterogeneous materials, off‐fault plasticity, roughness, thermal pressurization, and various versions of fault friction laws. Finally, we demonstrate that our method can be applied to simulate the dynamic rupture process of the 2008 Mw 7.9 Wenchuan earthquake along realistic fault geometry, including branches, step‐overs and a previously neglected sub‐parallel fault segment, offering a high potential to systematically explore the influences of fault zone properties on earthquake rupture dynamics.
Practical Implications of CLIMCAPS Cloud Clearing and Derived Quality Metrics
Authors: Smith N. , Barnet C. D.
Published: June 2023

Clouds 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

At 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

High-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

The 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

Numerous 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

Compact 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

Chimeric 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

Banking 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

Elucidating 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

Magnons, 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

Squamous 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

In 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

Filter-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

Inhibitory 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

Recent 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

Optical 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.
A Cas3-base editing tool for targetable in vivo mutagenesis
Authors: Zimmermann Anna , Prieto-Vivas Julian E. , Cautereels Charlotte , Gorkovskiy Anton , Steensels Jan , Van de Peer Yves , Verstrepen Kevin J.
Published: June 2023

The generation of genetic diversity via mutagenesis is routinely used for protein engineering and pathway optimization. Current technologies for random mutagenesis often target either the whole genome or relatively narrow windows. To bridge this gap, we developed CoMuTER (Confined Mutagenesis using a Type I-E CRISPR-Cas system), a tool that allows inducible and targetable, in vivo mutagenesis of genomic loci of up to 55 kilobases. CoMuTER employs the targetable helicase Cas3, signature enzyme of the class 1 type I-E CRISPR-Cas system, fused to a cytidine deaminase to unwind and mutate large stretches of DNA at once, including complete metabolic pathways. The tool increases the number of mutations in the target region 350-fold compared to the rest of the genome, with an average of 0.3 mutations per kilobase. We demonstrate the suitability of CoMuTER for pathway optimization by doubling the production of lycopene in Saccharomyces cerevisiae after a single round of mutagenesis.
Intranasal or airborne transmission-mediated delivery of an attenuated SARS-CoV-2 protects Syrian hamsters against new variants
Authors: Stauft Charles B. , Selvaraj Prabhuanand , D’Agnillo Felice , Meseda Clement A. , Liu Shufeng , Pedro Cyntia L. , Sangare Kotou , Lien Christopher Z. , Weir Jerry P. , Starost Matthew F. , Wang Tony T.
Published: June 2023

Detection of secretory antibodies in the airway is highly desirable when evaluating mucosal protection by vaccines against a respiratory virus, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We show that intranasal delivery of an attenuated SARS-CoV-2 (Nsp1-K164A/H165A) induces both mucosal and systemic IgA and IgG in male Syrian hamsters. Interestingly, either direct intranasal immunization or airborne transmission-mediated delivery of Nsp1-K164A/H165A in Syrian hamsters offers protection against heterologous challenge with variants of concern (VOCs) including Delta, Omicron BA.1, BA.2.12.1 and BA.5. Vaccinated animals show significant reduction in both tissue viral loads and lung inflammation. Similarly attenuated viruses bearing BA.1 and BA.5 spike boost variant-specific neutralizing antibodies in male mice that were first vaccinated with modified vaccinia virus Ankara vectors (MVA) expressing full-length WA1/2020 Spike protein. Together, these results demonstrate that our attenuated virus may be a promising nasal vaccine candidate for boosting mucosal immunity against future SARS-CoV-2 VOCs.
Asymptomatic immunodeficiency-associated vaccine-derived poliovirus infections in two UK children
Authors: Singanayagam Anika , Klapsa Dimitra , Burton-Fanning Shirelle , Hand Julian , Wilton Thomas , Stephens Laura , Mate Ryan , Shillitoe Benjamin , Celma Cristina , Slatter Mary , Flood Terry , Gopal Robin , Martin Javier , Zambon Maria
Published: June 2023

Increasing detections of vaccine-derived poliovirus (VDPV) globally, including in countries previously declared polio free, is a public health emergency of international concern. Individuals with primary immunodeficiency (PID) can excrete polioviruses for prolonged periods, which could act as a source of cryptic transmission of viruses with potential to cause neurological disease. Here, we report on the detection of immunodeficiency-associated VDPVs (iVDPV) from two asymptomatic male PID children in the UK in 2019. The first child cleared poliovirus with increased doses of intravenous immunoglobulin, the second child following haematopoetic stem cell transplantation. We perform genetic and phenotypic characterisation of the infecting strains, demonstrating intra-host evolution and a neurovirulent phenotype in transgenic mice. Our findings highlight a pressing need to strengthen polio surveillance. Systematic collection of stool from asymptomatic PID patients who are at high risk for poliovirus excretion could improve the ability to detect and contain iVDPVs.
Spectral signatures of a unique charge density wave in Ta2NiSe7
Authors: Watson Matthew D. , Louat Alex , Cacho Cephise , Choi Sungkyun , Lee Young Hee , Neumann Michael , Kim Gideok
Published: June 2023

Charge Density Waves (CDW) are commonly associated with the presence of near-Fermi level states which are separated from others, or “nested", by a wavector of q. Here we use Angle-Resolved Photo Emission Spectroscopy (ARPES) on the CDW material Ta2NiSe7 and identify a total absence of any plausible nesting of states at the primary CDW wavevector q. Nevertheless we observe spectral intensity on replicas of the hole-like valence bands, shifted by a wavevector of q, which appears with the CDW transition. In contrast, we find that there is a possible nesting at 2q, and associate the characters of these bands with the reported atomic modulations at 2q. Our comprehensive electronic structure perspective shows that the CDW-like transition of Ta2NiSe7 is unique, with the primary wavevector q being unrelated to any low-energy states, but suggests that the reported modulation at 2q, which would plausibly connect low-energy states, might be more important for the overall energetics of the problem.