bluuebunny/crossref_metadata_2025 huggingface dataset:
Radio Galaxy Zoo: Tagging radio subjects using text
Authors: Chen Dawei , Kerai Vinay , Alger Matthew J. , Wong O. Ivy , Ong Cheng Soon
Published: October 2023

RadioTalk is a communication platform that enabled members of the Radio Galaxy Zoo (RGZ) citizen science project to engage in discussion threads and provide further descriptions of the radio subjects they were observing in the form of tags and comments. It contains a wealth of auxiliary information which is useful for the morphology identification of complex and extended radio sources. In this paper, we present this new dataset, and for the first time in radio astronomy, we combine text and images to automatically classify radio galaxies using a multi-modal learning approach. We found incorporating text features improved classification performance which demonstrates that text annotations are rare but valuable sources of information for classifying astronomical sources, and suggests the importance of exploiting multi-modal information in future citizen science projects. We also discovered over 10000 new radio sources beyond the RGZ-DR1 catalogue in this dataset.
ABSOLUTE CHRONOLOGY OF THE RAMPART OF THE EARLY IRON AGE HILLFORT IN CHOTYNIEC NEAR RADYMNO (SOUTHEASTERN POLAND) IN THE CONTEXT OF RADIOCARBON DATING
Authors: Czopek Sylwester , Krąpiec Marek , Pawlyta Jacek , Tokarczyk Tomasz
Published: October 2023

The Early Iron Age hillfort in Chotyniec (SE Poland) is the westernmost permanent settlement of the Scythian cultural circle. Recognizing the construction of the fortified settlement’s ramparts and their chronology was considered one of the priorities of the systematic research conducted since 2016. Based on 18 radiocarbon dated samples from different parts of the rampart, a chronological model of its functioning was made. It indicates that the construction of this monumental fortifications protecting the settlement in Chotyniec should be dated to between 651–595 or 531–409 BC. This dating synchronizes well with the chronology of the most important ritual and ceremonial object within the Chotyniec settlement—the so-called zolnik and other Scythian settlements from the East European forest-steppe zone.
A Group-Based Approach to Measuring Polarization
Authors: MEHLHAFF ISAAC D.
Published: October 2023

Despite polarization’s growing importance in social science, its quantitative measurement has lagged behind its conceptual development. Political and social polarization are group-based phenomena characterized by intergroup heterogeneity and intragroup homogeneity, but existing measures capture only one of these features or make it difficult to compare across cases or over time. To bring the concept and measurement of polarization into closer alignment, I introduce the cluster-polarization coefficient (CPC), a measure of multimodality that allows scholars to incorporate multiple variables and compare across contexts with varying numbers of parties or social groups. Three applications to elite and mass polarization demonstrate that the CPC returns substantively sensible results, and an open-source software package implements the measure.
Decolonising the History of Internationalism: Transnational Activism across the South
Authors: Lewis Su Lin
Published: October 2023

The history of internationalism has tended to focus on power centres in the Global North – London, Geneva, New York, Paris – and institutions like the League of Nations, United Nations and UNESCO. What happens when we flip our perspective, and view internationalism from the point of view of the decolonising South? What do we get when we shift our focus from world leaders to the internationalism of activists, intellectuals, feminists, poets, artists, rebels and insurgents operating in Asia and Africa? Moreover, how are our methods of researching and debating international history – in universities, archives and conferences in the Global North – structured by economic inequalities, colonial legacies and visa regimes that limit participation by scholars from the South? This paper considers how we might decolonise both the content and the methods of international history, focusing especially on leftist internationalism and South–South connections in Southeast Asia and the wider Global South.
Teaching Modern British Political History in a Politically Polarised and ‘Post-Truth’ Environment
Authors: Jobson Richard
Published: October 2023

This article assesses the challenges that university-level teachers of modern British political history currently face in what is often described as a ‘post-truth’ and polarised political environment. It argues that, whilst these challenges do not always present entirely new pedagogical considerations, the sociocultural and political terrain in Britain today requires careful navigation, particularly in an academic field which addresses recent historical topics that are routinely politicised and contested in contemporary discourse. Although there is a lack of scholarly literature on the topic of teaching modern British political history in a higher education setting, this article draws upon a wide array of educational studies to map out the contours of a successful pedagogical strategy that could facilitate ‘deep’ learning in the current contextual environment. To this end, it suggests that by utilising modern British political history's interdisciplinary foundations, applying teaching techniques that help students to explore topics from multiple viewpoints, devising new and stimulating interactive tasks, and capitalising on the opportunities afforded by the Internet age, learning can be enhanced and many of the more academically problematic features and characteristics of the current political climate can be counteracted.
States as bystanders of legal change: Alternative paths for the human rights to water and sanitation in international law
Authors: Reiners Nina
Published: October 2023

This article argues for international legal change in human rights as a consequence of a states-as-bystander effect: When states do neither actively drive nor block change processes, and alternative state-empowered authorities exist in a legal field, states’ position at the sidelines opens a path for non-state actors to enact substantive change. In human rights law, this is a process they route through General Comments, a powerful instrument of the human rights treaty bodies to set, expand, and redefine standards for global human rights. This article bears its core argument of a states-as-bystander effect by taking a single norm, the necessity of water for human life, and tracing its change process from non-existent in human rights law, to a non-right, to a condition for other rights, and, finally, to the recognition of water and sanitation as independent rights at the international level. Ultimately, the analysis shows that non-actors can enact change to law, and do so, on the heels of states’ relegation to the periphery of the human rights system. This opened the door for certain actors – transnational coalitions of expert body members, human rights advocates and issue professionals – to use General Comments in a way that not only impacts international legal change but can also withstand state opposition.
Between ‘Indubitably Certain’ and ‘Quite Detrimental’ to Philosophy: Kant on the Guise of the Good Thesis
Authors: Carvalho Vinicius
Published: October 2023

Kant clearly endorses some version of the ‘old formula of the schools’, according to which all volition is sub ratione boni. There has been a debate whether he holds this only for morally good actions. I argue that a closer look at the distinction between the good and the agreeable does not support this conclusion. Considering Kant’s account of the detrimental and the correct use of this thesis, I argue that rational beings always will sub ratione boni, even when they act immorally, because they act on principles. I argue that Kant’s accounts of self-love and self-conceit support this view.
Estimating the Genetic Contribution to Astigmatism and Myopia in the Mexican Population
Authors: Román-López Talía V. , García-Vilchis Brisa , Murillo-Lechuga Vanessa , Chiu-Han Enrique , López-Camaño Xanat , Aldana-Assad Oscar , Diaz-Torres Santiago , Caballero-Sánchez Ulises , Ortega-Mora Ivett , Ramírez-González Diego , Zenteno Diego , Espinosa-Valdés Zaida , Tapia-Atilano Andrea , Pradel-Jiménez Sofía , Rentería Miguel E. , Medina-Rivera Alejandra , Ruiz-Contreras Alejandra E. , Alcauter Sarael
Published: October 2023

Astigmatism and myopia are two common ocular refractive errors that can impact daily life, including learning and productivity. Current knowledge suggests that the etiology of these conditions is the result of a complex interplay between genetic and environmental factors. Studies in populations of European ancestry have demonstrated a higher concordance of refractive errors in monozygotic (MZ) twins compared to dizygotic (DZ) twins. However, there is a lack of studies on genetically informative samples of multi-ethnic ancestry. This study aimed to estimate the genetic contribution to astigmatism and myopia in the Mexican population. A sample of 1399 families, including 243 twin pairs and 1156 single twins, completed a medical questionnaire about their own and their co-twin’s diagnosis of astigmatism and myopia. Concordance rates for astigmatism and myopia were estimated, and heritability and genetic correlations were determined using a bivariate ACE Cholesky decomposition method, decomposed into A (additive genetic), C (shared environmental) and E (unique environmental) components. The results showed a higher concordance rate for astigmatism and myopia for MZ twins (.74 and .74, respectively) than for DZ twins (.50 and .55). The AE model, instead of the ACE model, best fitted the data. Based on this, heritability estimates were .81 for astigmatism and .81 for myopia, with a cross-trait genetic correlation of rA = .80, nonshared environmental correlation rE = .89, and a phenotypic correlation of rP = .80. These results are consistent with previous findings in other populations, providing evidence for a similar genetic architecture of these conditions in the multi-ethnic Mexican population.
Series-elastic actuator with two degree-of-freedom PID control improves torque control in a powered knee exoskeleton
Authors: Sarkisian Sergei V. , Gabert Lukas , Lenzi Tommaso
Published: October 2023

Powered exoskeletons need actuators that are lightweight, compact, and efficient while allowing for accurate torque control. To satisfy these requirements, researchers have proposed using series elastic actuators (SEAs). SEAs use a spring in series with rotary or linear actuators. The spring compliance, in conjunction with an appropriate control scheme, improves torque control, efficiency, output impedance, and disturbance rejection. However, springs add weight to the actuator and complexity to the control, which may have negative effects on the performance of the powered exoskeleton. Therefore, there is an unmet need for new SEA designs that are lighter and more efficient than available systems, as well as for control strategies that push the performance of SEA-based exoskeletons without requiring complex modeling and tuning. This article presents the design, development, and testing of a novel SEA with high force density for powered exoskeletons, as well as the use of a two degree-of-freedom (2DOF) PID system to improve output impedance and disturbance rejection. Benchtop testing results show reduced output impedance and damping values when using a 2DOF PID controller as compared to a 1DOF PID controller. Human experiments with three able-bodied subjects (N = 3) show improved torque tracking with reduced root-mean-square error by 45.2% and reduced peak error by 49.8% when using a 2DOF PID controller. Furthermore, EMG data shows a reduction in peak EMG value when using the exoskeleton in assistive mode compared to the exoskeleton operating in transparent mode.
Does Socioeconomic Status Moderate the Relation Between Cultural Wording of Recruitment Information and Organizational Attraction?
Authors: Stevenor Brent A. , Brooks Margaret E. , Den Houter Kate M. , Hirvo Alexis
Published: October 2023

Abstract: Strategies to increase socioeconomic status (SES) diversity within organizations have been given little attention. Research suggests that subtle characteristics of recruitment materials influence peoples’ perceptions of organizations. In this hybrid registered report, we examined whether SES moderates the relation between individualistic–collectivistic recruitment message wording and organizational attraction. Using a large sample ( N = 652), we found that people high in SES were more attracted to collectivistic-worded recruitment information than were people low in SES. People low in SES were more attracted to individualistic-worded recruitment information than collectivistic-worded recruitment information. The implications of our findings and directions for future research are discussed.
Fractal Distribution of Subduction‐Related Crack‐Seal Veins (Schistes Lustrés, W. Alps): Implications for Fluid Flow and Rupture Processes at the Downdip End of the Seismogenic Zone
Authors: Herviou Clément , Agard Philippe , Verlaguet Anne , Gyomlai Thomas , Bonnet Guillaume , Mendes Kevin , Plunder Alexis
Published: October 2023

In the Western Alps, oceanic lithosphere fragments recovered from subduction are exposed continuously across the Liguro‐Piemont domain. In this nappe‐stack, the Schistes Lustrés metasediments are volumetrically dominant and contain large amounts of high‐pressure lawsonite‐ and Fe‐Mg carpholite‐bearing veins. These veins formed close to peak burial conditions at 30–60 km depth where deep slow slips and tremors occur. In the 12 studied outcrops, vein thickness distribution fit power laws while vein spacings and clustering show significant deviations from power laws, interpreted as the result of truncation artifacts and, possibly, at least in part, of later ductile deformation. Vein distribution at the outcrop scale suggests that fluids mostly circulated pervasively through the rock rather than along major localized conduits, in agreement with geochemical studies. Through the study of vein textures at macroscopic and microscopic scales, we showed that these high‐pressure veins formed by an incremental crack‐seal mechanism under tensile and shear failure and possibly between extremely weak planes. The spacings between crack‐seal inclusion trails and bands, which is in the same order as slip increments for low frequency‐earthquakes, fit a power law for a small fractal range with a fractal exponent similar to those estimated for slow slip events and ordinary earthquakes. In addition, the shear stress drop estimated for these veins is consistent with those inferred for slow slips and tremors. Data suggest that these veins, formed at the downdip end of the seismogenic zone, may correspond to the record of successive low‐frequency earthquakes during subduction of the Liguro‐Piemont ocean.
Study of Urban Thermal Environment and Local Circulations of Guangdong‐Hong Kong‐Macao Greater Bay Area Using WRF and Local Climate Zones
Authors: Xin Rui , Li Xian‐Xiang , Shi Yurong , Li Lei , Zhang Yuejuan , Liu Chun‐Ho , Dai Yongjiu
Published: October 2023

The Guangdong‐Hong Kong‐Macao Greater Bay Area (GBA), a cluster of world‐class cities, is undergoing rapid urbanization. However, the heterogeneity of the urban thermal environment resulting from the diversity of urban forms is not yet fully understood. This paper assesses the heterogeneity of the urban heat island (UHI) effect in the GBA using the coupled Weather Research and Forecasting (WRF) model/multi‐layer urban canopy and building energy model (BEP/BEM), with high‐resolution local climate zone (LCZ) map as urban land use/land cover data. The average UHI intensity is found to peak at 1.8 ± 0.4°C in the evening, when the average UHI intensity of LCZ 2 can reach a maximum of 2.4 ± 0.58°C. Properly setting air‐conditioning temperatures can effectively prevent the enhancement of the UHI phenomenon at night by the anthropogenic heat (AH) released from air‐conditioning. The UHI‐induced local circulations and enhanced surface roughness inhibit the penetration of sea breezes inland, and surface wind speed decreases in all LCZs, with a maximum change of more than 0.8 m s−1. However, the increased thermal difference between land and sea leads to enhanced sea breezes offshore, especially in the Pearl River estuary. In addition, a series of sensitivity experiments have been conducted in this paper on initial and boundary conditions, building drag coefficients and urban fractions, which paves the way for further analyzing urban climate in GBA using WRF model and LCZs.
The Mojave Section of the San Andreas Fault (California): 1. Shaping the Terrace Stratigraphy of Little Rock Creek Through the Competition Between Rapid Strike‐Slip Faulting and Lateral Stream Erosion Over the Last 40 k.y.
Authors: Moulin Adrien , Cowgill Eric , Scharer Katherine , McPhilipps Devin , Heimsath Arjun
Published: October 2023

To determine the post‐40 ka slip‐rate along the Mojave section of the San Andreas Fault (MSAF) we re‐analyze the sedimentary record preserved where Little Rock (LR) Creek flows across the fault. At this location, interaction between the northeast‐flowing stream and right‐lateral fault has resulted in the abandonment and preservation of 11 strath terraces and one paleo‐floodplain in the downstream trailing corner of the river, two of which are also preserved upstream to provide cross‐fault matches. A new model of fault‐induced river deflection, together with standard terrace riser restoration, yields strike‐slip displacements of 1,140 ± 160 m for the older terrace and 360 ± 70 m for the younger one. When combined with new 10Be dating and reinterpretation of prior measurements the displaced terraces yield right‐lateral slip‐rates of 27.7+6.9/−3.5 and 26.8+3.4/−3.0 mm/yr over the last 23 k.y. and last 40 k.y., where uncertainties are at 95% credible intervals. These new rate determinations are consistent with independent late Holocene estimates, indicating that the long‐term rate of strain accumulation along the MSAF is relatively fast and does not vary significantly when averaged over timescales of 15–20 k.y. Using our new model of stream deflection, we find that the fluvial sequence was emplaced in two distinct periods, each characterized by a temporally stable but markedly different deflected river geometry. Each period coincides with a distinct stage of erosive power along LR Creek determined from independent paleoclimate proxies. Importantly, application of the new river‐deflection model allows strike‐slip displacements to be determined in the absence of upstream piercing points.
Zones of Weakness Within the Juan de Fuca Plate Mapped From the Integration of Multiple Geophysical Data and Their Relation to Observed Seismicity
Authors: Ashraf Asif , Filina Irina
Published: October 2023

This study aims to explain the nonuniform earthquake pattern along the Cascadia Subduction Zone. In particular, we investigate the relationship between the tectonic features of the subducting oceanic Juan de Fuca slab and the onshore seismicity pattern. We have integrated multiple geophysical data sets toward three general objectives. The first study intends to study variations in physical properties along three 2‐dimensional models through regions of different seismicities that combine public gravity, magnetic, and seismic data sets. These models reveal multiple zones of decreased crustal density that we interpret as regions of weaker oceanic crust. The second objective is to delineate major tectonic features by performing spatial analysis of potential fields. The overall methodology comprises gravity and magnetic data filtering, followed by lineaments mapping and cross‐referencing interpretation with available seismic reflection data. This process allows delineating zones of crustal weakness by extrapolating outside our three 2‐D models. We also map multiple seamounts that appear to cluster along identified zones of weaker crust. Third, we investigate the relationship between the mapped tectonic elements, namely the zones of weak crust with accompanying seamounts, and the observed seismicity trends within the subducted slab. The alignment between those suggests that mapped weak crust zones and associated seamounts may have an influence on the overall subduction process. As more of these structures are heading toward the Washington portion of the margin than to the Oregon portion, more earthquakes are observed in the north than in the south.
TRAF7-targeted HOXA5 acts as a tumor suppressor in prostate cancer progression and stemness via transcriptionally activating SPRY2 and regulating MEK/ERK signaling
Authors: Ye Jianfeng , Liu Wangmin , Yu Xueyang , Wu Lina , Chen Zhengjie , Yu Yufei , Wang Jianfeng , Bai Song , Zhang Mo
Published: October 2023

Homeobox A5 (HOXA5), a homeodomain transcription factor, is considered a tumor suppressor in cancer progression; however, its function in prostate cancer (PCa) remains unclear. This study focused on the relevance of HOXA5 in PCa progression. We identified the downregulation of HOXA5 in PCa tissues based on the TCGA database and further verified in 30-paired PCa and adjacent normal tissues. Functional studies revealed that HOXA5 upregulation impaired the stem-like characteristics and malignant behaviors of PCa cells in vitro and in vivo. Mechanistically, HOXA5 was found to be regulated by tumor necrosis factor receptor-associated factor 7 (TRAF7), a putative E3-ubiquitin ligase. We observed that TRAF7 was overexpressed in PCa and subsequently enhanced the degradation of HOXA5 protein via its ubiquitin ligase activity, contributing to the acquisition of an aggressive PCa phenotype. For its downstream mechanism, we demonstrated that sprouty RTK signaling antagonist 2 (SPRY2) served as a downstream target of HOXA5. HOXA5 could directly bind to the SPRY2 promoter, thereby regulating the SPRY2-mediated MEK/ERK signaling pathway. Silencing SPRY2 largely compromised the tumor-suppressive effect of HOXA5 in PCa progression and cancer stemness. Our findings highlight the previously-underappreciated signaling axis of TRAF7–HOXA5–SPRY2, which provides a novel prognostic and therapeutic target for PCa treatment.
Initial conditions combine with sensory evidence to induce decision-related dynamics in premotor cortex
Authors: Boucher Pierre O. , Wang Tian , Carceroni Laura , Kane Gary , Shenoy Krishna V. , Chandrasekaran Chandramouli
Published: October 2023

We used a dynamical systems perspective to understand decision-related neural activity, a fundamentally unresolved problem. This perspective posits that time-varying neural activity is described by a state equation with an initial condition and evolves in time by combining at each time step, recurrent activity and inputs. We hypothesized various dynamical mechanisms of decisions, simulated them in models to derive predictions, and evaluated these predictions by examining firing rates of neurons in the dorsal premotor cortex (PMd) of monkeys performing a perceptual decision-making task. Prestimulus neural activity (i.e., the initial condition) predicted poststimulus neural trajectories, covaried with RT and the outcome of the previous trial, but not with choice. Poststimulus dynamics depended on both the sensory evidence and initial condition, with easier stimuli and fast initial conditions leading to the fastest choice-related dynamics. Together, these results suggest that initial conditions combine with sensory evidence to induce decision-related dynamics in PMd.
Soluble organic matter Molecular atlas of Ryugu reveals cold hydrothermalism on C-type asteroid parent body
Authors: Schmitt-Kopplin Philippe , Hertkorn Norbert , Harir Mourad , Moritz Franco , Lucio Marianna , Bonal Lydie , Quirico Eric , Takano Yoshinori , Dworkin Jason P. , Naraoka Hiroshi , Tachibana Shogo , Nakamura Tomoki , Noguchi Takaaki , Okazaki Ryuji , Yabuta Hikaru , Yurimoto Hisayoshi , Sakamoto Kanako , Yada Toru , Nishimura Masahiro , Nakato Aiko , Miyazaki Akiko , Yogata Kasumi , Abe Masanao , Usui Tomohiro , Yoshikawa Makoto , Saiki Takanao , Tanaka Satoshi , Terui Fuyuto , Nakazawa Satoru , Okada Tatsuaki , Watanabe Sei-ichiro , Tsuda Yuichi ,   Hayabusa2-initial-analysis SOM team, Hamase Kenji , Furusho Aogu , Hashiguchi Minako , Fukushima Kazuhiko , Aoki Dan , Aponte José C. , Parker Eric T. , Glavin Daniel P. , McLain Hannah L. , Elsila Jamie E. , Graham Heather V. , Eiler John M. , Ruf Alexander , Orthous-Daunay Francois-Regis , Isa Junko , Vuitton Véronique , Thissen Roland , Ogawa Nanako O. , Sakai Saburo , Yoshimura Toshihiro , Koga Toshiki , Sugahara Haruna , Ohkouchi Naohiko , Mita Hajime , Furukawa Yoshihiro , Oba Yasuhiro
Published: October 2023

The sample from the near-Earth carbonaceous asteroid (162173) Ryugu is analyzed in the context of carbonaceous meteorites soluble organic matter. The analysis of soluble molecules of samples collected by the Hayabusa2 spacecraft shines light on an extremely high molecular diversity on the C-type asteroid. Sequential solvent extracts of increasing polarity of Ryugu samples are analyzed using mass spectrometry with complementary ionization methods and structural information confirmed by nuclear magnetic resonance spectroscopy. Here we show a continuum in the molecular size and polarity, and no organomagnesium molecules are detected, reflecting a low temperature and water-rich environment on the parent body approving earlier mineralogical and chemical data. High abundance of sulfidic and nitrogen rich compounds as well as high abundance of ammonium ions confirm the water processing. Polycyclic aromatic hydrocarbons are also detected in a structural continuum of carbon saturations and oxidations, implying multiple origins of the observed organic complexity, thus involving generic processes such as earlier carbonization and serpentinization with successive low temperature aqueous alteration.
Upcycling fish scales through heating for steganography and Rhodamine B adsorption application
Authors: Sow Malcolm Miao Geng , Zhang Zheng , Sow Chorng Haur , Lim Sharon Xiaodai
Published: October 2023

With increasing population and limited resources, a potential route for improving sustainability is increased reuse of waste materials. By re-looking at wastes, interesting properties and multifunctionalities can be discovered in materials previously explored. Despite years of research on bio-compatible fish scales, there is limited study on the fluorescence property of this abundant waste material. Controlled denaturation of collagen and introduction of defects can serve as a means to transform the fluorescence property of these fish scale wastes while providing more adsorption sites for pollutant removal, turning multifunctional fish scales into a natural steganographic material for transmitting text and images at both the macroscopic and microscopic levels and effectively removing Rhodamine B pollutants (91 % removal) within a short contact time (10 minutes). Our work offers a glimpse into the realm of engineering defects-induced fluorescence in natural material with potential as bio-compatible fluorescence probes while encouraging multidimensional applicability to be established in otherwise overlooked waste resources.
Structural basis of dimerization of chemokine receptors CCR5 and CXCR4
Authors: Di Marino Daniele , Conflitti Paolo , Motta Stefano , Limongelli Vittorio
Published: October 2023

G protein-coupled receptors (GPCRs) are prominent drug targets responsible for extracellular-to-intracellular signal transduction. GPCRs can form functional dimers that have been poorly characterized so far. Here, we show the dimerization mechanism of the chemokine receptors CCR5 and CXCR4 by means of an advanced free-energy technique named coarse-grained metadynamics. Our results reproduce binding events between the GPCRs occurring in the minute timescale, revealing a symmetric and an asymmetric dimeric structure for each of the three investigated systems, CCR5/CCR5, CXCR4/CXCR4, and CCR5/CXCR4. The transmembrane helices TM4-TM5 and TM6-TM7 are the preferred binding interfaces for CCR5 and CXCR4, respectively. The identified dimeric states differ in the access to the binding sites of the ligand and G protein, indicating that dimerization may represent a fine allosteric mechanism to regulate receptor activity. Our study offers structural basis for the design of ligands able to modulate the formation of CCR5 and CXCR4 dimers and in turn their activity, with therapeutic potential against HIV, cancer, and immune-inflammatory diseases.
Redundancy and the role of protein copy numbers in the cell polarization machinery of budding yeast
Authors: Brauns Fridtjof , Iñigo de la Cruz Leila , Daalman Werner K.-G. , de Bruin Ilse , Halatek Jacob , Laan Liedewij , Frey Erwin
Published: October 2023

How can a self-organized cellular function evolve, adapt to perturbations, and acquire new sub-functions? To make progress in answering these basic questions of evolutionary cell biology, we analyze, as a concrete example, the cell polarity machinery of Saccharomyces cerevisiae. This cellular module exhibits an intriguing resilience: it remains operational under genetic perturbations and recovers quickly and reproducibly from the deletion of one of its key components. Using a combination of modeling, conceptual theory, and experiments, we propose that multiple, redundant self-organization mechanisms coexist within the protein network underlying cell polarization and are responsible for the module’s resilience and adaptability. Based on our mechanistic understanding of polarity establishment, we hypothesize that scaffold proteins, by introducing new connections in the existing network, can increase the redundancy of mechanisms and thus increase the evolvability of other network components. Moreover, our work gives a perspective on how a complex, redundant cellular module might have evolved from a more rudimental ancestral form.
A single nanobody neutralizes multiple epochally evolving human noroviruses by modulating capsid plasticity
Authors: Salmen Wilhelm , Hu Liya , Bok Marina , Chaimongkol Natthawan , Ettayebi Khalil , Sosnovtsev Stanislav V. , Soni Kaundal , Ayyar B. Vijayalakshmi , Shanker Sreejesh , Neill Frederick H. , Sankaran Banumathi , Atmar Robert L. , Estes Mary K. , Green Kim Y. , Parreño Viviana , Prasad B. V. Venkataram
Published: October 2023

Acute gastroenteritis caused by human noroviruses (HuNoVs) is a significant global health and economic burden and is without licensed vaccines or antiviral drugs. The GII.4 HuNoV causes most epidemics worldwide. This virus undergoes epochal evolution with periodic emergence of variants with new antigenic profiles and altered specificity for histo-blood group antigens (HBGA), the determinants of cell attachment and susceptibility, hampering the development of immunotherapeutics. Here, we show that a llama-derived nanobody M4 neutralizes multiple GII.4 variants with high potency in human intestinal enteroids. The crystal structure of M4 complexed with the protruding domain of the GII.4 capsid protein VP1 revealed a conserved epitope, away from the HBGA binding site, fully accessible only when VP1 transitions to a “raised” conformation in the capsid. Together with dynamic light scattering and electron microscopy of the GII.4 VLPs, our studies suggest a mechanism in which M4 accesses the epitope by altering the conformational dynamics of the capsid and triggering its disassembly to neutralize GII.4 infection.
MANF stimulates autophagy and restores mitochondrial homeostasis to treat autosomal dominant tubulointerstitial kidney disease in mice
Authors: Kim Yeawon , Li Chuang , Gu Chenjian , Fang Yili , Tycksen Eric , Puri Anuradhika , Pietka Terri A. , Sivapackiam Jothilingam , Kidd Kendrah , Park Sun-Ji , Johnson Bryce G. , Kmoch Stanislav , Duffield Jeremy S. , Bleyer Anthony J. , Jackrel Meredith E. , Urano Fumihiko , Sharma Vijay , Lindahl Maria , Chen Ying Maggie
Published: October 2023

Misfolded protein aggregates may cause toxic proteinopathy, including autosomal dominant tubulointerstitial kidney disease due to uromodulin mutations (ADTKD-UMOD), a leading hereditary kidney disease. There are no targeted therapies. In our generated mouse model recapitulating human ADTKD-UMOD carrying a leading UMOD mutation, we show that autophagy/mitophagy and mitochondrial biogenesis are impaired, leading to cGAS-STING activation and tubular injury. Moreover, we demonstrate that inducible tubular overexpression of mesencephalic astrocyte-derived neurotrophic factor (MANF), a secreted endoplasmic reticulum protein, after the onset of disease stimulates autophagy/mitophagy, clears mutant UMOD, and promotes mitochondrial biogenesis through p-AMPK enhancement, thus protecting kidney function in our ADTKD mouse model. Conversely, genetic ablation of MANF in the mutant thick ascending limb tubular cells worsens autophagy suppression and kidney fibrosis. Together, we have discovered MANF as a biotherapeutic protein and elucidated previously unknown mechanisms of MANF in the regulation of organelle homeostasis, which may have broad therapeutic applications to treat various proteinopathies.
A human lung alveolus-on-a-chip model of acute radiation-induced lung injury
Authors: Dasgupta Queeny , Jiang Amanda , Wen Amy M. , Mannix Robert J. , Man Yuncheng , Hall Sean , Javorsky Emilia , Ingber Donald E.
Published: October 2023

Acute exposure to high-dose gamma radiation due to radiological disasters or cancer radiotherapy can result in radiation-induced lung injury (RILI), characterized by acute pneumonitis and subsequent lung fibrosis. A microfluidic organ-on-a-chip lined by human lung alveolar epithelium interfaced with pulmonary endothelium (Lung Alveolus Chip) is used to model acute RILI in vitro. Both lung epithelium and endothelium exhibit DNA damage, cellular hypertrophy, upregulation of inflammatory cytokines, and loss of barrier function within 6 h of radiation exposure, although greater damage is observed in the endothelium. The radiation dose sensitivity observed on-chip is more like the human lung than animal preclinical models. The Alveolus Chip is also used to evaluate the potential ability of two drugs - lovastatin and prednisolone - to suppress the effects of acute RILI. These data demonstrate that the Lung Alveolus Chip provides a human relevant alternative for studying the molecular basis of acute RILI and may be useful for evaluation of new radiation countermeasure therapeutics.
Spatial and temporal dynamics of West Nile virus between Africa and Europe
Authors: Mencattelli Giulia , Ndione Marie Henriette Dior , Silverj Andrea , Diagne Moussa Moise , Curini Valentina , Teodori Liana , Di Domenico Marco , Mbaye Rassoul , Leone Alessandra , Marcacci Maurilia , Gaye Alioune , Ndiaye ElHadji , Diallo Diawo , Ancora Massimo , Secondini Barbara , Di Lollo Valeria , Mangone Iolanda , Bucciacchio Andrea , Polci Andrea , Marini Giovanni , Rosà Roberto , Segata Nicola , Fall Gamou , Cammà Cesare , Monaco Federica , Diallo Mawlouth , Rota-Stabelli Omar , Faye Oumar , Rizzoli Annapaola , Savini Giovanni
Published: October 2023

It is unclear whether West Nile virus (WNV) circulates between Africa and Europe, despite numerous studies supporting an African origin and high transmission in Europe. We integrated genomic data with geographic observations and phylogenetic and phylogeographic inferences to uncover the spatial and temporal viral dynamics of WNV between these two continents. We focused our analysis towards WNV lineages 1 (L1) and 2 (L2), the most spatially widespread and pathogenic WNV lineages. Our study shows a Northern-Western African origin of L1, with back-and-forth exchanges between West Africa and Southern-Western Europe; and a Southern African origin of L2, with one main introduction from South Africa to Europe, and no back introductions observed. We also noticed a potential overlap between L1 and L2 Eastern and Western phylogeography and two Afro-Palearctic bird migratory flyways. Future studies linking avian and mosquito species susceptibility, migratory connectivity patterns, and phylogeographic inference are suggested to elucidate the dynamics of emerging viruses.
Fibrocystin/Polyductin releases a C-terminal fragment that translocates into mitochondria and suppresses cystogenesis
Authors: Walker Rebecca V , Yao Qin , Xu Hangxue , Maranto Anthony , Swaney Kristen F , Ramachandran Sreekumar , Li Rong , Cassina Laura , Polster Brian M , Outeda Patricia , Boletta Alessandra , Watnick Terry , Qian Feng
Published: October 2023

Fibrocystin/Polyductin (FPC), encoded by PKHD1, is associated with autosomal recessive polycystic kidney disease (ARPKD), yet its precise role in cystogenesis remains unclear. Here we show that FPC undergoes complex proteolytic processing in developing kidneys, generating three soluble C-terminal fragments (ICDs). Notably, ICD15, contains a novel mitochondrial targeting sequence at its N-terminus, facilitating its translocation into mitochondria. This enhances mitochondrial respiration in renal epithelial cells, partially restoring impaired mitochondrial function caused by FPC loss. FPC inactivation leads to abnormal ultrastructural morphology of mitochondria in kidney tubules without cyst formation. Moreover, FPC inactivation significantly exacerbates renal cystogenesis and triggers severe pancreatic cystogenesis in a Pkd1 mouse mutant Pkd1V/V in which cleavage of Pkd1-encoded Polycystin-1 at the GPCR Proteolysis Site is blocked. Deleting ICD15 enhances renal cystogenesis without inducing pancreatic cysts in Pkd1V/V mice. These findings reveal a direct link between FPC and a mitochondrial pathway through ICD15 cleavage, crucial for cystogenesis mechanisms.
Expanding PROTACtable genome universe of E3 ligases
Authors: Liu Yuan , Yang Jingwen , Wang Tianlu , Luo Mei , Chen Yamei , Chen Chengxuan , Ronai Ze’ev , Zhou Yubin , Ruppin Eytan , Han Leng
Published: October 2023

Proteolysis-targeting chimera (PROTAC) and other targeted protein degradation (TPD) molecules that induce degradation by the ubiquitin-proteasome system (UPS) offer new opportunities to engage targets that remain challenging to be inhibited by conventional small molecules. One fundamental element in the degradation process is the E3 ligase. However, less than 2% amongst hundreds of E3 ligases in the human genome have been engaged in current studies in the TPD field, calling for the recruiting of additional ones to further enhance the therapeutic potential of TPD. To accelerate the development of PROTACs utilizing under-explored E3 ligases, we systematically characterize E3 ligases from seven different aspects, including chemical ligandability, expression patterns, protein-protein interactions (PPI), structure availability, functional essentiality, cellular location, and PPI interface by analyzing 30 large-scale data sets. Our analysis uncovers several E3 ligases as promising extant PROTACs. In total, combining confidence score, ligandability, expression pattern, and PPI, we identified 76 E3 ligases as PROTAC-interacting candidates. We develop a user-friendly and flexible web portal (https://hanlaboratory.com/E3Atlas/) aimed at assisting researchers to rapidly identify E3 ligases with promising TPD activities against specifically desired targets, facilitating the development of these therapies in cancer and beyond.
Controlling the selectivity of the hydrogenolysis of polyamides catalysed by ceria-supported metal nanoparticles
Authors: Wu XinBang , Lee Wei-Tse , Turnell-Ritson Roland C. , Delannoi Pauline C. L. , Lin Kun-Han , Dyson Paul J.
Published: October 2023

Catalytic hydrogenolysis is a promising approach to transform waste plastic into valuable chemicals. However, the transformation of N-containing polymers, such as polyamides (i.e. nylon), remains under-investigated, particularly by heterogeneous catalysis. Here, we demonstrate the hydrogenolysis of various polyamides catalysed by platinum-group metal nanoparticles supported on CeO2. Ru/CeO2 and Pt/CeO2 are both highly active but display different selectivity; Ru/CeO2 is selective for the conversion of all polyamides into water, ammonia, and methane, whereas Pt/CeO2 yields hydrocarbons retaining the carbon backbone of the parent polyamide. Density functional theory computations illustrate that Pt nanoparticles require higher activation energy for carbon−carbon bond cleavage than Ru nanoparticles, rationalising the observed selectivity. The high activity and product selectivity of both catalysts was maintained when converting real-world polyamide products, such as fishing net. This study provides a mechanistic basis for heterogeneously catalysed polyamide hydrogenolysis, and a new approach to the valorisation of polyamide containing waste.
Controls of thermal response of temperate lakes to atmospheric warming
Authors: Zhou Jian , Leavitt Peter R. , Rose Kevin C. , Wang Xiwen , Zhang Yibo , Shi Kun , Qin Boqiang
Published: October 2023

Atmospheric warming heats lakes, but the causes of variation among basins are poorly understood. Here, multi-decadal profiles of water temperatures, trophic state, and local climate from 345 temperate lakes are combined with data on lake geomorphology and watershed characteristics to identify controls of the relative rates of temperature change in water (WT) and air (AT) during summer. We show that differences in local climate (AT, wind speed, humidity, irradiance), land cover (forest, urban, agriculture), geomorphology (elevation, area/depth ratio), and water transparency explain >30% of the difference in rate of lake heating compared to that of the atmosphere. Importantly, the rate of lake heating slows as air warms (P < 0.001). Clear, cold, and deep lakes, especially at high elevation and in undisturbed catchments, are particularly responsive to changes in atmospheric temperature. We suggest that rates of surface water warming may decline relative to the atmosphere in a warmer future, particularly in sites already experiencing terrestrial development or eutrophication.
Photoelectrochemical oxidative C(sp3)−H borylation of unactivated hydrocarbons
Authors: Zhong Ping-Fu , Tu Jia-Lin , Zhao Yating , Zhong Nan , Yang Chao , Guo Lin , Xia Wujiong
Published: October 2023

Organoboron compounds are of high significance in organic synthesis due to the unique versatility of boryl substituents to access further modifications. The high demand for the incorporation of boryl moieties into molecular structures has witnessed significant progress, particularly in the C(sp3)−H borylation of hydrocarbons. Taking advantage of special characteristics of photo/electrochemistry, we herein describe the development of an oxidative C(sp3)−H borylation reaction under metal- and oxidant-free conditions, enabled by photoelectrochemical strategy. The reaction exhibits broad substrate scope (>57 examples), and includes the use of simple alkanes, halides, silanes, ketones, esters and nitriles as viable substrates. Notably, unconventional regioselectivity of C(sp3)−H borylation is achieved, with the coupling site of C(sp3)−H borylation selectively located in the distal methyl group. Our method is operationally simple and easily scalable, and offers a feasible approach for the one-step synthesis of high-value organoboron building blocks from simple hydrocarbons, which would provide ample opportunities for drug discovery.
Genome-wide analysis of the interplay between chromatin-associated RNA and 3D genome organization in human cells
Authors: Calandrelli Riccardo , Wen Xingzhao , Charles Richard John Lalith , Luo Zhifei , Nguyen Tri C. , Chen Chien-Ju , Qi Zhijie , Xue Shuanghong , Chen Weizhong , Yan Zhangming , Wu Weixin , Zaleta-Rivera Kathia , Hu Rong , Yu Miao , Wang Yuchuan , Li Wenbo , Ma Jian , Ren Bing , Zhong Sheng
Published: October 2023

The interphase genome is dynamically organized in the nucleus and decorated with chromatin-associated RNA (caRNA). It remains unclear whether the genome architecture modulates the spatial distribution of caRNA and vice versa. Here, we generate a resource of genome-wide RNA-DNA and DNA-DNA contact maps in human cells. These maps reveal the chromosomal domains demarcated by locally transcribed RNA, hereafter termed RNA-defined chromosomal domains. Further, the spreading of caRNA is constrained by the boundaries of topologically associating domains (TADs), demonstrating the role of the 3D genome structure in modulating the spatial distribution of RNA. Conversely, stopping transcription or acute depletion of RNA induces thousands of chromatin loops genome-wide. Activation or suppression of the transcription of specific genes suppresses or creates chromatin loops straddling these genes. Deletion of a specific caRNA-producing genomic sequence promotes chromatin loops that straddle the interchromosomal target sequences of this caRNA. These data suggest a feedback loop where the 3D genome modulates the spatial distribution of RNA, which in turn affects the dynamic 3D genome organization.
Methylphosphonate-driven methane formation and its link to primary production in the oligotrophic North Atlantic
Authors: von Arx Jan N. , Kidane Abiel T. , Philippi Miriam , Mohr Wiebke , Lavik Gaute , Schorn Sina , Kuypers Marcel M. M. , Milucka Jana
Published: October 2023

Methylphosphonate is an organic phosphorus compound used by microorganisms when phosphate, a key nutrient limiting growth in most marine surface waters, becomes unavailable. Microbial methylphosphonate use can result in the formation of methane, a potent greenhouse gas, in oxic waters where methane production is traditionally unexpected. The extent and controlling factors of such aerobic methane formation remain underexplored. Here, we show high potential net rates of methylphosphonate-driven methane formation (median 0.4 nmol methane L−1 d−1) in the upper water column of the western tropical North Atlantic. The rates are repressed but still quantifiable in the presence of in-situ or added phosphate, suggesting that some methylphosphonate-driven methane formation persists in phosphate-replete waters. The genetic potential for methylphosphonate utilisation is present in and transcribed by key photo- and heterotrophic microbial taxa, such as Pelagibacterales, SAR116, and Trichodesmium. While the large cyanobacterial nitrogen-fixers dominate in the surface layer, phosphonate utilisation by Alphaproteobacteria appears to become more important in deeper depths. We estimate that at our study site, a substantial part (median 11%) of the measured surface carbon fixation can be sustained by phosphorus liberated from phosphonate utilisation, highlighting the ecological importance of phosphonates in the carbon cycle of the oligotrophic ocean.
Electrochemically induced crystalline-to-amorphization transformation in sodium samarium silicate solid electrolyte for long-lasting sodium metal batteries
Authors: Sun Ge , Lou Chenjie , Yi Boqian , Jia Wanqing , Wei Zhixuan , Yao Shiyu , Lu Ziheng , Chen Gang , Shen Zexiang , Tang Mingxue , Du Fei
Published: October 2023

Exploiting solid electrolyte (SE) materials with high ionic conductivity, good interfacial compatibility, and conformal contact with electrodes is essential for solid-state sodium metal batteries (SSBs). Here we report a crystalline Na5SmSi4O12 SE which features high room-temperature ionic conductivity of 2.9 × 10−3 S cm−1 and a low activation energy of 0.15 eV. All-solid-state symmetric cell with Na5SmSi4O12 delivers excellent cycling life over 800 h at 0.15 mA h cm−2 and a high critical current density of 1.4 mA cm−2. Such excellent electrochemical performance is attributed to an electrochemically induced in-situ crystalline-to-amorphous (CTA) transformation propagating from the interface to the bulk during repeated deposition and stripping of sodium, which leads to faster ionic transport and superior interfacial properties. Impressively, the Na|Na5SmSi4O12|Na3V2(PO4)3 sodium metal batteries achieve a remarkable cycling performance over 4000 cycles (6 months) with no capacity loss. These results not only identify Na5SmSi4O12 as a promising SE but also emphasize the potential of the CTA transition as a promising mechanism towards long-lasting SSBs.