bluuebunny/crossref_metadata_2025 huggingface dataset:
The social field of international adjudication: Structures and practices of a conflictive professional universe
Authors: Soave Tommaso
Published: May 2023

The modern professional world of international adjudication bears little trace of the ‘invisible college’ theorized by Oscar Schachter 50 years go. Instead, it has become a social field marked by a fierce competition among actors possessing unequal skills and influence. Moving from these premises, this article unravels the socio-professional dynamics of the community of legal experts – judges, arbitrators, government agents, private counsel, court bureaucrats, specialized academics, etc. – dealing with the judicial settlement of international disputes on a daily basis. On the one hand, the community has developed a specific set of social structures, practices, and dispositions that distinguish it from the rest of the international legal profession and insulate its activities from outside interference. On the other, it is the site of an endless struggle among its participants, who deploy various forms of capital to consolidate their positions relative to one another. Having outlined the twofold structure of the community – externally autonomous and internally conflictive – the article reflects on how co-operation and competition affect the everyday unfolding of international judicial proceedings and the production of legal outcomes at the international level.
The dyadic effects of social support on anxiety among family members during COVID-19: The mediating role of perceived family resilience
Authors: Feng Li , Feng Jingyan , Li Xiaohui , An Yuanyuan
Published: May 2023

Families have been suffering from huge financial loss and psychological distress due to the COVID-19 pandemic. Most existing studies investigated the protective factors for anxiety at the individual level, while understandings from the perspective of family dyadic level were left unknown. Considering that social support could serve as a protective factor to reduce anxiety both at individual level and at dyadic level, the present study adopted dyadic data analysis approach to tackle this puzzle. In total, 2512 Chinese parent–adolescent dyads completed a survey with scales of anxiety, social support, and perceived family resilience on July 31 and August 1 of 2021. Results showed that: (1) adolescents’ perceived social support had significant actor and partner effects on their own and parents’ anxiety, whereas parents’ perceived social support only had a significant actor effect on their own anxiety and (2) the actor mediating effects of social support on anxiety via one’s own perceived family resilience were found in both adolescents and parents, and a partner mediating effect of adolescents’ social support was significantly associated with parents’ anxiety through parents’ perceived family resilience. Findings emphasize that interventions aiming at increasing adolescents’ support resources could generate a significant effect on reducing anxiety.
A pair degree condition for Hamiltonian cycles in 3-uniform hypergraphs
Authors: Schülke Bjarne
Published: May 2023

We prove a new sufficient pair degree condition for tight Hamiltonian cycles in
$3$
-uniform hypergraphs that (asymptotically) improves the best known pair degree condition due to Rödl, Ruciński, and Szemerédi. For graphs, Chvátal characterised all those sequences of integers for which every pointwise larger (or equal) degree sequence guarantees the existence of a Hamiltonian cycle. A step towards Chvátal’s theorem was taken by Pósa, who improved on Dirac’s tight minimum degree condition for Hamiltonian cycles by showing that a certain weaker condition on the degree sequence of a graph already yields a Hamiltonian cycle.

In this work, we take a similar step towards a full characterisation of all pair degree matrices that ensure the existence of tight Hamiltonian cycles in
$3$
-uniform hypergraphs by proving a
$3$
-uniform analogue of Pósa’s result. In particular, our result strengthens the asymptotic version of the result by Rödl, Ruciński, and Szemerédi.
A unique bizarre subtype of mixed total anomalous pulmonary venous connection
Authors: Öztürk Erkut , Bas Serap , Recep Berra Zümrün Tan , Tanıdır Ibrahim Cansaran , Hatemi Ali Can
Published: May 2023

Mixed total anomalous pulmonary venous connection is a rare CHD with a wide variation in pulmonary venous anatomy and drainage. We present a ten-day-old newborn with a rare bizarre subtype of mixed total anomalous pulmonary venous connection.
Inventing Ordinary Anarchy in Cold War Britain
Authors: Scott-Brown Sophie
Published: May 2023

When you think of 1960s anarchism, community playgrounds and financial planning for tenants’ associations may not spring to mind, yet these, along with similar topics, were Anarchy's (1961–1970) staple fare. The A5 monthly, edited by British journalist Colin Ward (1924–2010), maintained a steady output of ‘anarchist applications’ in the spheres of education, housing, and community development. Although published during the 1960s, the origins and ethos of the journal lay in the previous decade. Responding to this heightened Cold War “moment,” Ward developed an idiosyncratic radical pragmatism prioritizing the practice of popular democracy over the theory of it. In reconstructing Anarchy's intellectual formation, this article contributes to revisionist scholarship acknowledging a more experimental radical culture in 1950s Britain than is usually granted, one that prefigured aspects of the later counterculture but also differed from it in important respects.
Neural networks for quantile claim amount estimation: a quantile regression approach
Authors: Laporta Alessandro G. , Levantesi Susanna , Petrella Lea
Published: May 2023

In this paper, we discuss the estimation of conditional quantiles of aggregate claim amounts for non-life insurance embedding the problem in a quantile regression framework using the neural network approach. As the first step, we consider the quantile regression neural networks (QRNN) procedure to compute quantiles for the insurance ratemaking framework. As the second step, we propose a new quantile regression combined actuarial neural network (Quantile-CANN) combining the traditional quantile regression approach with a QRNN. In both cases, we adopt a two-part model scheme where we fit a logistic regression to estimate the probability of positive claims and the QRNN model or the Quantile-CANN for the positive outcomes. Through a case study based on a health insurance dataset, we highlight the overall better performances of the proposed models with respect to the classical quantile regression one. We then use the estimated quantiles to calculate a loaded premium following the quantile premium principle, showing that the proposed models provide a better risk differentiation.
A 1-bit reconfigurable intelligent metasurface-based antenna design for 5G application
Authors: Zhou Yajun , Chen Lianfeng , Zhang Qifei , Wang Hao , Guo Linyan
Published: May 2023

A 1-bit reconfigurable intelligent metasurface-based antenna for 5G application is proposed. The proposed antenna based on artificial electromagnetic metamaterial has the advantages of easy processing and low cost. This meets the requirements of future communication network development. This antenna shows that the unit cell has a stable 180° phase difference between the ON and OFF states by loading a PIN diode at 6.425–7.125 GHz. A 10 × 10 array antenna is constructed by using 2 × 2 meta-atoms to reduce the complexity of the control network. This proposed antenna can achieve ±40° beam scanning with a gain tolerance of 3 dB and a maximum gain of 18.7 dBi. In addition, beamforming performance, such as multi-beams, is also achieved. These properties ensure that the proposed antenna has great potential in wireless communication systems and microwave imaging systems.
Children’s Rights and Educational Psychology
Authors: Ziemes Johanna Fee , Gutzwiller-Helfenfinger Eveline
Published: May 2023

Abstract. Psychology aims to be descriptive but depends on norms and values to guide both research and practice. Educational psychology, as a sub-discipline and applied branch of psychology, focuses on describing processes of teaching, learning, and development. This article aims to connect notions of human and children’s rights with concepts of educational psychology to illustrate the interdependence of normative and descriptive frameworks. We use Martha Nussbaum’s capability approach as an operationalization to move from a normative legal framework toward concrete research topics and practices within educational and school psychology. According to the Convention on the Rights of the Child, children have the right to feel safe, learn, participate, and form an identity. We argue that educational psychology can help to specify these normative postulations of the CRC and aid the implementation of positive rights. The phenomenon of school bullying is introduced as a specific area where children’s rights are affected. After a brief characterization of its major features from an ecological-systemic perspective, we draw on research on bullying prevention and the creation of positive learning environments to illustrate the aptness of educational psychology for realizing children’s positive rights. We conclude that educational psychology is not only able to prevent human rights infringements but also to promote children’s rights and capabilities, especially in reference to competencies, participation, and identity.
Thermal Structure of the Paleo‐Continental Subduction Zone: Insights From Quantitatively Constrained Prograde P–T Paths of Exhumed LT/UHP Eclogites in the Dabie Orogen
Authors: Xia Mei , Zhang Qiang‐Qiang , Gao Xiao‐Ying
Published: May 2023

The discrepancy of geothermal gradients predicted by numerical modeling and recorded by peak metamorphic conditions of exhumed high/ultrahigh pressure (HP/UHP) metamorphic rocks triggers many uncertainties on the thermal structure of subduction zones, which is especially significant for continental subduction zones. Well‐constrained prograde P‒temperature (T) paths of HP/UHP rocks reflect the change in P–T conditions during continental subduction and are insusceptible to later processes, making them robust recorders of the thermal structure of subduction zones. To make a reliable estimation of the thermal structure of a continental subduction zone, the prograde P–T paths of three low (L)T‒UHP eclogites in the Dabie orogen were robustly constrained using a multiple thermobarometry method. The results demonstrate that these eclogites underwent three stages of metamorphic evolution during continental subduction from epidote amphibolite‐facies at ∼450°C–470°C/11–13 kbar, through amphibole eclogite‐facies at 585°C–600°C/17–19 kbar, to peak UHP eclogite‐facies at 600°C–630°C/27–29 kbar, indicating a low and continuously changing geothermal gradient from ∼12°C/km at lower crust depth (40 km) to 10°C/km at depth of 60 km and to ∼6°C/km at sub‐arc depth (100 km). The consistency of this result and the average thermal gradient recovered by peak metamorphic conditions of exhumed HP/UHP metamorphic rocks of continental origin suggests that the continental subduction zones may have a common thermal structure characterized by strongly concave upward geothermal gradient. A comparison of the results of this study and analytical models shows that shear heating may play a crucial role in the thermal evolution of continental subduction zones.
Seasonal Evolution of the Arctic Sea Ice Thickness Distribution
Authors: Toppaladoddi S. , Moon W. , Wettlaufer J. S.
Published: May 2023

The Thorndike et al. (1975, https://doi.org/10.1029/jc080i033p04501) theory of the ice thickness distribution, g(h), treats the dynamic and thermodynamic aggregate properties of the ice pack in a novel and physically self‐consistent manner. Therefore, it has provided the conceptual basis of the treatment of sea‐ice thickness categories in climate models. The approach, however, is not mathematically closed due to the treatment of mechanical deformation using the redistribution function ψ, the authors noting “The present theory suffers from a burdensome and arbitrary redistribution function ψ.” Toppaladoddi and Wettlaufer (2015, https://doi.org/10.1103/physrevlett.115.148501) showed how ψ can be written in terms of g(h), thereby solving the mathematical closure problem and writing the theory in terms of a Fokker‐Planck equation, which they solved analytically to quantitatively reproduce the observed winter g(h). Here, we extend this approach to include open water by formulating a new boundary condition for their Fokker‐Planck equation, which is then coupled to the observationally consistent sea‐ice growth model of Semtner (1976, https://doi.org/10.1175/1520-0485(1976)006<0379:amfttg>2.0.co;2) to study the seasonal evolution of g(h). We find that as the ice thins, g(h) transitions from a single‐ to a double‐peaked distribution, which is in agreement with observations. To understand the cause of this transition, we construct a simpler description of the system using the equivalent Langevin equation formulation and solve the resulting stochastic ordinary differential equation numerically. Finally, we solve the Fokker‐Planck equation for g(h) under different climatological conditions to study the evolution of the open‐water fraction.
Estimating Net Retention Time of Solute in Storage Zones of a Stream
Authors: Kim Byunguk , Seo Il Won , Kwon Siyoon , Baek Donghae
Published: May 2023

Because of the influence of various storage zones, solute transport in a stream channel cannot be interpreted by advection and dispersion processes alone. Thus, in recent decades, various models that incorporate storage‐zone effects have been proposed to characterize anomalous storage mechanisms. The validity of these models has been predominantly demonstrated using tracer breakthrough curves measured in surface flow. However, the storage effect is usually less influential on the breakthrough curve behavior than in‐stream flow dynamics. Thus, for model validation, the tracer behavior within the storage zone should be investigated separately. The present study aims to quantify the time‐dependent storage effect, herein termed the net retention time distribution (NRTD), from tracer measurements in the flow zone using a deconvolution technique with manipulation in the Fourier domain. The results demonstrated that the deconvolved NRTDs successfully represented the temporal behavior of the tracer in the storage zones without significant distortion in the primary information of the observed breakthrough curves. Using estimates of NRTD, we evaluated the simulations of the transient storage model, and found that the storage effects were underestimated as much as an average 18.5% in this study. The deconvolved NRTDs were also utilized to predict the biodegradation losses of organic chemicals flowing along a stream at confidence intervals.
North‐West Europe Hottest Days Are Warming Twice as Fast as Mean Summer Days
Authors: Patterson Matthew
Published: May 2023

Europe has seen a rapid increase in the frequency and intensity of hot extremes in recent decades. In this study it is shown, using ERA5 reanalysis data 1960–2021, that the hottest summer days in North‐West Europe are warming approximately twice as fast as mean summer days. Moreover, this pattern stands out as relatively unusual across the Northern Hemisphere. It is also shown that comprehensive climate models fail to capture this difference in trends. A hypothesis is suggested to explain the differential rate of warming between the mean and hottest days, namely that the hottest days are often linked to warm advection from Iberia and North Africa, areas that are warming faster than North‐West Europe. This hypothesis can account for about 25% of the difference between ERA5 and a climate model ensemble and hence further research is needed to understand the drivers of the differing trends in mean and extreme temperature.
Atlantic Water Boundary Current Along the Southern Yermak Plateau, Arctic Ocean
Authors: Fer Ilker , Peterson Algot K. , Nilsen Frank
Published: May 2023

The major ocean current that carries heat into the Arctic Ocean splits into three main branches of Atlantic Water (AW) and recirculations when it encounters the Yermak Plateau (YP) located north of Svalbard. While the branches that cross the plateau and recirculations have been extensively studied, there has been limited observation of the transport and variability of the Yermak branch. In this study, we present year‐round observations from an array of three moorings that were deployed across the boundary current on the southern slope of the YP. The temporal‐averaged sections show a surface‐intensified AW core, which is strongest in winter but also persistent throughout the record within the upper 500 m. The volume transport of AW is highest in fall (1.4 ± 0.2 Sv; 1 Sv = 106 m3 s−1) and decreases to 0.8 ± 0.1 Sv in summer. Beneath a surface‐intensified core, the velocity profile has a minimum at middepth, gradually increasing toward the bottom. This cold, bottom‐intensified current is detectable in all seasons and reaches a maximum transport of 1.5 Sv in spring. The transport of AW is regulated by wind stress curl and coastal upwelling along the northwestern shelf of Svalbard. A positive wind stress curl increases the volume transport in the Yermak branch, thereby reducing the Svalbard branch transport. Eddy kinetic energy is surface‐intensified and decreases to negligible values below 500 m. In the upper 500 m, the average baroclinic conversion in winter and summer is about 1 × 10−5 W m−3, which is 4–10 times the barotropic conversion rates.
Bedding Scale Correlation on Mars in Western Arabia Terra
Authors: Annex A. M. , Lewis K. W. , Koeppel A. H. D. , Edwards C. S.
Published: May 2023

Layered rocks in the Arabia Terra region of Mars preserve a record of the planet's ancient climate. However, the exact formation mechanism of these rhythmically layered deposits is currently unknown. We previously proposed two distinct regionally correlative units of the Arabia Terra layered deposits based on their bedding thicknesses, orientation, and morphology from High Resolution Imaging Science Experiment stereo observations. For this work, we selected two adjacent craters in Arabia Terra, Sera and Jiji, for further study to test the proposed stratigraphic correlation. We constructed vertical stratigraphic sections of the deposits from dip‐corrected bed thickness measurements and local stratigraphic correlations. We found that individual beds maintain a consistent thickness over kilometer scales but are somewhat variable at the basin scale. Each crater exhibited strata with a thinning‐upward trend that terminated at terraces with inconsistent bedding, possibly indicating an equilibrium elevation for the formation mechanism. We also identified a probable stratigraphic correlation between basins using the similarities in bedding characteristics and patterns of measurable differences in bed‐to‐bed thicknesses, indicating synchronous strata. The planar bedding and uniform thickness of the beds within the deposits are consistent with airfall deposition over a prolonged geologic period. This process likely occurred under comparably dry conditions relative to the previously proposed depositional and diagenetic formation mechanisms.
Aβ1-6A2V(D) peptide, effective on Aβ aggregation, inhibits tau misfolding and protects the brain after traumatic brain injury
Authors: Diomede Luisa , Zanier Elisa R. , Moro Federico , Vegliante Gloria , Colombo Laura , Russo Luca , Cagnotto Alfredo , Natale Carmina , Xodo Federica Marta , De Luigi Ada , Mosconi Michele , Beeg Marten , Catania Marcella , Rossi Giacomina , Tagliavini Fabrizio , Di Fede Giuseppe , Salmona Mario
Published: May 2023

Alzheimer’s disease (AD), the leading cause of dementia in older adults, is a double proteinopathy characterized by amyloid-β (Aβ) and tau pathology. Despite enormous efforts that have been spent in the last decades to find effective therapies, late pharmacological interventions along the course of the disease, inaccurate clinical methodologies in the enrollment of patients, and inadequate biomarkers for evaluating drug efficacy have not allowed the development of an effective therapeutic strategy. The approaches followed so far for developing drugs or antibodies focused solely on targeting Aβ or tau protein. This paper explores the potential therapeutic capacity of an all-D-isomer synthetic peptide limited to the first six amino acids of the N-terminal sequence of the A2V-mutated Aβ, Aβ1-6A2V(D), that was developed following the observation of a clinical case that provided the background for its development. We first performed an in-depth biochemical characterization documenting the capacity of Aβ1-6A2V(D) to interfere with the aggregation and stability of tau protein. To tackle Aβ1-6A2V(D) in vivo effects against a neurological decline in genetically predisposed or acquired high AD risk mice, we tested its effects in triple transgenic animals harboring human PS1(M146 V), APP(SW), and MAPT(P301L) transgenes and aged wild-type mice exposed to experimental traumatic brain injury (TBI), a recognized risk factor for AD. We found that Aβ1-6A2V(D) treatment in TBI mice improved neurological outcomes and reduced blood markers of axonal damage. Exploiting the C. elegans model as a biosensor of amyloidogenic proteins’ toxicity, we observed a rescue of locomotor defects in nematodes exposed to the brain homogenates from TBI mice treated with Aβ1-6A2V(D) compared to TBI controls. By this integrated approach, we demonstrate that Aβ1-6A2V(D) not only impedes tau aggregation but also favors its degradation by tissue proteases, confirming that this peptide interferes with both Aβ and tau aggregation propensity and proteotoxicity.
Targeting metabolism by B-raf inhibitors and diclofenac restrains the viability of BRAF-mutated thyroid carcinomas with Hif-1α-mediated glycolytic phenotype
Authors: Aprile Marianna , Cataldi Simona , Perfetto Caterina , Federico Antonio , Ciccodicola Alfredo , Costa Valerio
Published: May 2023

Background

B-raf inhibitors (BRAFi) are effective for BRAF-mutated papillary (PTC) and anaplastic (ATC) thyroid carcinomas, although acquired resistance impairs tumour cells’ sensitivity and/or limits drug efficacy. Targeting metabolic vulnerabilities is emerging as powerful approach in cancer.

Methods

In silico analyses identified metabolic gene signatures and Hif-1α as glycolysis regulator in PTC. BRAF-mutated PTC, ATC and control thyroid cell lines were exposed to HIF1A siRNAs or chemical/drug treatments (CoCl2, EGF, HGF, BRAFi, MEKi and diclofenac). Genes/proteins expression, glucose uptake, lactate quantification and viability assays were used to investigate the metabolic vulnerability of BRAF-mutated cells.

Results

A specific metabolic gene signature was identified as a hallmark of BRAF-mutated tumours, which display a glycolytic phenotype, characterised by enhanced glucose uptake, lactate efflux and increased expression of Hif-1α-modulated glycolytic genes. Indeed, Hif-1α stabilisation counteracts the inhibitory effects of BRAFi on these genes and on cell viability. Interestingly, targeting metabolic routes with BRAFi and diclofenac combination we could restrain the glycolytic phenotype and synergistically reduce tumour cells’ viability.

Conclusion

The identification of a metabolic vulnerability of BRAF-mutated carcinomas and the capacity BRAFi and diclofenac combination to target metabolism open new therapeutic perspectives in maximising drug efficacy and reducing the onset of secondary resistance and drug-related toxicity.
Unifying speed limit, thermodynamic uncertainty relation and Heisenberg principle via bulk-boundary correspondence
Authors: Hasegawa Yoshihiko
Published: May 2023

The bulk-boundary correspondence provides a guiding principle for tackling strongly correlated and coupled systems. In the present work, we apply the concept of the bulk-boundary correspondence to thermodynamic bounds described by classical and quantum Markov processes. Using the continuous matrix product state, we convert a Markov process to a quantum field, such that jump events in the Markov process are represented by the creation of particles in the quantum field. Introducing the time evolution of the continuous matrix product state, we apply the geometric bound to its time evolution. We find that the geometric bound reduces to the speed limit relation when we represent the bound in terms of the system quantity, whereas the same bound reduces to the thermodynamic uncertainty relation when expressed based on quantities of the quantum field. Our results show that the speed limits and thermodynamic uncertainty relations are two aspects of the same geometric bound.
Quality control of protein synthesis in the early elongation stage
Authors: Nagao Asuteka , Nakanishi Yui , Yamaguchi Yutaro , Mishina Yoshifumi , Karoji Minami , Toya Takafumi , Fujita Tomoya , Iwasaki Shintaro , Miyauchi Kenjyo , Sakaguchi Yuriko , Suzuki Tsutomu
Published: May 2023

In the early stage of bacterial translation, peptidyl-tRNAs frequently dissociate from the ribosome (pep-tRNA drop-off) and are recycled by peptidyl-tRNA hydrolase. Here, we establish a highly sensitive method for profiling of pep-tRNAs using mass spectrometry, and successfully detect a large number of nascent peptides from pep-tRNAs accumulated in Escherichia coli pthts strain. Based on molecular mass analysis, we found about 20% of the peptides bear single amino-acid substitutions of the N-terminal sequences of E. coli ORFs. Detailed analysis of individual pep-tRNAs and reporter assay revealed that most of the substitutions take place at the C-terminal drop-off site and that the miscoded pep-tRNAs rarely participate in the next round of elongation but dissociate from the ribosome. These findings suggest that pep-tRNA drop-off is an active mechanism by which the ribosome rejects miscoded pep-tRNAs in the early elongation, thereby contributing to quality control of protein synthesis after peptide bond formation.
Enabling accurate and early detection of recently emerged SARS-CoV-2 variants of concern in wastewater
Authors: Sapoval Nicolae , Liu Yunxi , Lou Esther G. , Hopkins Loren , Ensor Katherine B. , Schneider Rebecca , Stadler Lauren B. , Treangen Todd J.
Published: May 2023

As clinical testing declines, wastewater monitoring can provide crucial surveillance on the emergence of SARS-CoV-2 variant of concerns (VoCs) in communities. In this paper we present QuaID, a novel bioinformatics tool for VoC detection based on quasi-unique mutations. The benefits of QuaID are three-fold: (i) provides up to 3-week earlier VoC detection, (ii) accurate VoC detection (>95% precision on simulated benchmarks), and (iii) leverages all mutational signatures (including insertions & deletions).
Ultralong 100 ns spin relaxation time in graphite at room temperature
Authors: Márkus B. G. , Gmitra M. , Dóra B. , Csősz G. , Fehér T. , Szirmai P. , Náfrádi B. , Zólyomi V. , Forró L. , Fabian J. , Simon F.
Published: May 2023

Graphite has been intensively studied, yet its electron spins dynamics remains an unresolved problem even 70 years after the first experiments. The central quantities, the longitudinal (T1) and transverse (T2) relaxation times were postulated to be equal, mirroring standard metals, but T1 has never been measured for graphite. Here, based on a detailed band structure calculation including spin-orbit coupling, we predict an unexpected behavior of the relaxation times. We find, based on saturation ESR measurements, that T1 is markedly different from T2. Spins injected with perpendicular polarization with respect to the graphene plane have an extraordinarily long lifetime of 100 ns at room temperature. This is ten times more than in the best graphene samples. The spin diffusion length across graphite planes is thus expected to be ultralong, on the scale of ~ 70 μm, suggesting that thin films of graphite — or multilayer AB graphene stacks — can be excellent platforms for spintronics applications compatible with 2D van der Waals technologies. Finally, we provide a qualitative account of the observed spin relaxation based on the anisotropic spin admixture of the Bloch states in graphite obtained from density functional theory calculations.
Small-sample learning reveals propionylation in determining global protein homeostasis
Authors: Shui Ke , Wang Chenwei , Zhang Xuedi , Ma Shanshan , Li Qinyu , Ning Wanshan , Zhang Weizhi , Chen Miaomiao , Peng Di , Hu Hui , Fang Zheng , Guo Anyuan , Gao Guanjun , Ye Mingliang , Zhang Luoying , Xue Yu
Published: May 2023

Proteostasis is fundamental for maintaining organismal health. However, the mechanisms underlying its dynamic regulation and how its disruptions lead to diseases are largely unclear. Here, we conduct in-depth propionylomic profiling in Drosophila, and develop a small-sample learning framework to prioritize the propionylation at lysine 17 of H2B (H2BK17pr) to be functionally important. Mutating H2BK17 which eliminates propionylation leads to elevated total protein level in vivo. Further analyses reveal that H2BK17pr modulates the expression of 14.7–16.3% of genes in the proteostasis network, and determines global protein level by regulating the expression of genes involved in the ubiquitin-proteasome system. In addition, H2BK17pr exhibits daily oscillation, mediating the influences of feeding/fasting cycles to drive rhythmic expression of proteasomal genes. Our study not only reveals a role of lysine propionylation in regulating proteostasis, but also implements a generally applicable method which can be extended to other issues with little prior knowledge.
PRMT1 mediated methylation of cGAS suppresses anti-tumor immunity
Authors: Liu Jing , Bu Xia , Chu Chen , Dai Xiaoming , Asara John M. , Sicinski Piotr , Freeman Gordon J. , Wei Wenyi
Published: May 2023

Activation of the cGAS/STING innate immunity pathway is essential and effective for anti-tumor immunotherapy. However, it remains largely elusive how tumor-intrinsic cGAS signaling is suppressed to facilitate tumorigenesis by escaping immune surveillance. Here, we report that the protein arginine methyltransferase, PRMT1, methylates cGAS at the conserved Arg133 residue, which prevents cGAS dimerization and suppresses the cGAS/STING signaling in cancer cells. Notably, genetic or pharmaceutical ablation of PRMT1 leads to activation of cGAS/STING-dependent DNA sensing signaling, and robustly elevates the transcription of type I and II interferon response genes. As such, PRMT1 inhibition elevates tumor-infiltrating lymphocytes in a cGAS-dependent manner, and promotes tumoral PD-L1 expression. Thus, combination therapy of PRMT1 inhibitor with anti-PD-1 antibody augments the anti-tumor therapeutic efficacy in vivo. Our study therefore defines the PRMT1/cGAS/PD-L1 regulatory axis as a critical factor in determining immune surveillance efficacy, which serves as a promising therapeutic target for boosting tumor immunity.
The thioesterase APT1 is a bidirectional-adjustment redox sensor
Authors: Ji Tuo , Zheng Lihua , Wu Jiale , Duan Mei , Liu Qianwen , Liu Peng , Shen Chen , Liu Jinling , Ye Qinyi , Wen Jiangqi , Dong Jiangli , Wang Tao
Published: May 2023

The adjustment of cellular redox homeostasis is essential in when responding to environmental perturbations, and the mechanism by which cells distinguish between normal and oxidized states through sensors is also important. In this study, we found that acyl-protein thioesterase 1 (APT1) is a redox sensor. Under normal physiological conditions, APT1 exists as a monomer through S-glutathionylation at C20, C22 and C37, which inhibits its enzymatic activity. Under oxidative conditions, APT1 senses the oxidative signal and is tetramerized, which makes it functional. Tetrameric APT1 depalmitoylates S-acetylated NAC (NACsa), and NACsa relocates to the nucleus, increases the cellular glutathione/oxidized glutathione (GSH/GSSG) ratio through the upregulation of glyoxalase I expression, and resists oxidative stress. When oxidative stress is alleviated, APT1 is found in monomeric form. Here, we describe a mechanism through which APT1 mediates a fine-tuned and balanced intracellular redox system in plant defence responses to biotic and abiotic stresses and provide insights into the design of stress-resistant crops.
Aqueous phase conversion of CO2 into acetic acid over thermally transformed MIL-88B catalyst
Authors: Ahmad Waqar , Koley Paramita , Dwivedi Swarit , Lakshman Rajan , Shin Yun Kyung , van Duin Adri C. T. , Shrotri Abhijit , Tanksale Akshat
Published: May 2023

Sustainable production of acetic acid is a high priority due to its high global manufacturing capacity and numerous applications. Currently, it is predominantly synthesized via carbonylation of methanol, in which both the reactants are fossil-derived. Carbon dioxide transformation into acetic acid is highly desirable to achieve net zero carbon emissions, but significant challenges remain to achieve this efficiently. Herein, we report a heterogeneous catalyst, thermally transformed MIL-88B with Fe0 and Fe3O4 dual active sites, for highly selective acetic acid formation via methanol hydrocarboxylation. ReaxFF molecular simulation, and X-ray characterisation results show a thermally transformed MIL-88B catalyst consisting of highly dispersed Fe0/Fe(II)-oxide nanoparticles in a carbonaceous matrix. This efficient catalyst showed a high acetic acid yield (590.1 mmol/gcat.L) with 81.7% selectivity at 150 °C in the aqueous phase using LiI as a co-catalyst. Here we present a plausible reaction pathway for acetic acid formation reaction via a formic acid intermediate. No significant difference in acetic acid yield and selectivity were noticed during the catalyst recycling study up to five cycles. This work is scalable and industrially relevant for carbon dioxide utilisation to reduce carbon emissions, especially when green methanol and green hydrogen are readily available in future.
Electron diffraction of deeply supercooled water in no man’s land
Authors: Krüger Constantin R. , Mowry Nathan J. , Bongiovanni Gabriele , Drabbels Marcel , Lorenz Ulrich J.
Published: May 2023

A generally accepted understanding of the anomalous properties of water will only emerge if it becomes possible to systematically characterize water in the deeply supercooled regime, from where the anomalies appear to emanate. This has largely remained elusive because water crystallizes rapidly between 160 K and 232 K. Here, we present an experimental approach to rapidly prepare deeply supercooled water at a well-defined temperature and probe it with electron diffraction before crystallization occurs. We show that as water is cooled from room temperature to cryogenic temperature, its structure evolves smoothly, approaching that of amorphous ice just below 200 K. Our experiments narrow down the range of possible explanations for the origin of the water anomalies and open up new avenues for studying supercooled water.
Distinct genomic routes underlie transitions to specialised symbiotic lifestyles in deep-sea annelid worms
Authors: Moggioli Giacomo , Panossian Balig , Sun Yanan , Thiel Daniel , Martín-Zamora Francisco M. , Tran Martin , Clifford Alexander M. , Goffredi Shana K. , Rimskaya-Korsakova Nadezhda , Jékely Gáspár , Tresguerres Martin , Qian Pei-Yuan , Qiu Jian-Wen , Rouse Greg W. , Henry Lee M. , Martín-Durán José M.
Published: May 2023

Bacterial symbioses allow annelids to colonise extreme ecological niches, such as hydrothermal vents and whale falls. Yet, the genetic principles sustaining these symbioses remain unclear. Here, we show that different genomic adaptations underpin the symbioses of phylogenetically related annelids with distinct nutritional strategies. Genome compaction and extensive gene losses distinguish the heterotrophic symbiosis of the bone-eating worm Osedax frankpressi from the chemoautotrophic symbiosis of deep-sea Vestimentifera. Osedax’s endosymbionts complement many of the host’s metabolic deficiencies, including the loss of pathways to recycle nitrogen and synthesise some amino acids. Osedax’s endosymbionts possess the glyoxylate cycle, which could allow more efficient catabolism of bone-derived nutrients and the production of carbohydrates from fatty acids. Unlike in most Vestimentifera, innate immunity genes are reduced in O. frankpressi, which, however, has an expansion of matrix metalloproteases to digest collagen. Our study supports that distinct nutritional interactions influence host genome evolution differently in highly specialised symbioses.
Construction of 3D copper-chitosan-gas diffusion layer electrode for highly efficient CO2 electrolysis to C2+ alcohols
Authors: Bi Jiahui , Li Pengsong , Liu Jiyuan , Jia Shuaiqiang , Wang Yong , Zhu Qinggong , Liu Zhimin , Han Buxing
Published: May 2023

High-rate electrolysis of CO2to C2+alcohols is of particular interest, but the performance remains far from the desired values to be economically feasible. Coupling gas diffusion electrode (GDE) and 3D nanostructured catalysts may improve the efficiency in a flow cell of CO2electrolysis. Herein, we propose a route to prepare 3D Cu-chitosan (CS)-GDL electrode. The CS acts as a “transition layer” between Cu catalyst and the GDL. The highly interconnected network induces growth of 3D Cu film, and the as-prepared integrated structure facilitates rapid electrons transport and mitigates mass diffusion limitations in the electrolysis. At optimum conditions, the C2+Faradaic efficiency (FE) can reach 88.2% with a current density (geometrically normalized) as high as 900 mA cm−2at the potential of −0.87 V vs. reversible hydrogen electrode (RHE), of which the C2+alcohols selectivity is 51.4% with a partial current density of 462.6 mA cm−2, which is very efficient for C2+alcohols production. Experimental and theoretical study indicates that CS induces growth of 3D hexagonal prismatic Cu microrods with abundant Cu (111)/Cu (200) crystal faces, which are favorable for the alcohol pathway. Our work represents a novel example to design efficient GDEs for electrocatalytic CO2reduction (CO2RR).
Higher-order epistasis shapes natural variation in germ stem cell niche activity
Authors: Fausett Sarah R. , Sandjak Asma , Billard Bénédicte , Braendle Christian
Published: May 2023

To study how natural allelic variation explains quantitative developmental system variation, we characterized natural differences in germ stem cell niche activity, measured as progenitor zone (PZ) size, between twoCaenorhabditis elegansisolates. Linkage mapping yielded candidate loci on chromosomes II and V, and we found that the isolate with a smaller PZ size harbours a 148 bp promoter deletion in the Notch ligand,lag-2/Delta, a central signal promoting germ stem cell fate. As predicted, introducing this deletion into the isolate with a large PZ resulted in a smaller PZ size. Unexpectedly, restoring the deleted ancestral sequence in the isolate with a smaller PZ did not increase—but instead further reduced—PZ size. These seemingly contradictory phenotypic effects are explained by epistatic interactions between thelag-2/Deltapromoter, the chromosome II locus, and additional background loci. These results provide first insights into the quantitative genetic architecture regulating an animal stem cell system.
Self-wavelength shifting in two-dimensional perovskite for sensitive and fast gamma-ray detection
Authors: Jin Tong , Liu Zheng , Luo Jiajun , Yuan Jun-Hui , Wang Hanqi , Xie Zuoxiang , Pan Weicheng , Wu Haodi , Xue Kan-Hao , Liu Linyue , Hu Zhanli , Zheng Zhiping , Tang Jiang , Niu Guangda
Published: May 2023

Lead halide perovskites have recently emerged as promising X/γ-ray scintillators. However, the small Stokes shift of exciton luminescence in perovskite scintillators creates problems for the light extraction efficiency and severely impedes their applications in hard X/γ-ray detection. Dopants have been used to shift the emission wavelength, but the radioluminescence lifetime has also been unwantedly extended. Herein, we demonstrate the intrinsic strain in 2D perovskite crystals as a general phenomenon, which could be utilized as self-wavelength shifting to reduce the self-absorption effect without sacrificing the radiation response speed. Furthermore, we successfully demonstrated the first imaging reconstruction by perovskites for application of positron emission tomography. The coincidence time resolution for the optimized perovskite single crystals (4 × 4 × 0.8 mm3) reached 119 ± 3 ps. This work provides a new paradigm for suppressing the self-absorption effect in scintillators and may facilitate the application of perovskite scintillators in practical hard X/γ-ray detections.
Computational pathology improves risk stratification of a multi-gene assay for early stage ER+ breast cancer
Authors: Chen Yuli , Li Haojia , Janowczyk Andrew , Toro Paula , Corredor Germán , Whitney Jon , Lu Cheng , Koyuncu Can F. , Mokhtari Mojgan , Buzzy Christina , Ganesan Shridar , Feldman Michael D. , Fu Pingfu , Corbin Haley , Harbhajanka Aparna , Gilmore Hannah , Goldstein Lori J. , Davidson Nancy E. , Desai Sangeeta , Parmar Vani , Madabhushi Anant
Published: May 2023

Prognostic markers currently utilized in clinical practice for estrogen receptor-positive (ER+) and lymph node-negative (LN−) invasive breast cancer (IBC) patients include the Nottingham grading system and Oncotype Dx (ODx). However, these biomarkers are not always optimal and remain subject to inter-/intra-observer variability and high cost. In this study, we evaluated the association between computationally derived image features from H&E images and disease-free survival (DFS) in ER+ and LN− IBC. H&E images from a total ofn = 321 patients with ER+ and LN− IBC from three cohorts were employed for this study (Training set: D1 (n = 116), Validation sets: D2 (n = 121) and D3 (n = 84)). A total of 343 features relating to nuclear morphology, mitotic activity, and tubule formation were computationally extracted from each slide image. A Cox regression model (IbRiS) was trained to identify significant predictors of DFS and predict a high/low-risk category using D1 and was validated on independent testing sets D2 and D3 as well as within each ODx risk category. IbRiS was significantly prognostic of DFS with a hazard ratio (HR) of 2.33 (95% confidence interval (95% CI) = 1.02–5.32,p = 0.045) on D2 and a HR of 2.94 (95% CI = 1.18–7.35,p = 0.0208) on D3. In addition, IbRiS yielded significant risk stratification within high ODx risk categories (D1 + D2: HR = 10.35, 95% CI = 1.20–89.18,p = 0.0106; D1:p = 0.0238; D2:p = 0.0389), potentially providing more granular risk stratification than offered by ODx alone.
Religion and educational mobility in Africa
Authors: Alesina Alberto , Hohmann Sebastian , Michalopoulos Stelios , Papaioannou Elias
Published: May 2023

The African people and leaders1,2 have long seen education as a driving force of development and liberation, a view shared by international institutions3,4, as schooling has large economic and non-economic returns, particularly in low-income settings5. In this study, we examine the educational progress across faiths throughout postcolonial Africa, home to some of the world’s largest Christian and Muslim communities. We construct comprehensive religion-specific measures of intergenerational mobility in education using census data from 2,286 districts in 21 countries and document the following. First, Christians have better mobility outcomes than Traditionalists and Muslims. Second, differences in intergenerational mobility between Christians and Muslims persist among those residing in the same district, in households with comparable economic and family backgrounds. Third, although Muslims benefit as much as Christians when they move early in life to high-mobility regions, they are less likely to do so. Their low internal mobility accentuates the educational deficit, as Muslims reside on average in areas that are less urbanized and more remote with limited infrastructure. Fourth, the Christian–Muslim gap is most prominent in areas with large Muslim communities, where the latter also register the lowest emigration rates. As African governments and international organizations invest heavily in educational programmes, our findings highlight the need to understand better the private and social returns to schooling across faiths in religiously segregated communities and to carefully think about religious inequalities in the take-up of educational policies6.
ERα-associated translocations underlie oncogene amplifications in breast cancer
Authors: Lee Jake June-Koo , Jung Youngsook Lucy , Cheong Taek-Chin , Espejo Valle-Inclan Jose , Chu Chong , Gulhan Doga C. , Ljungström Viktor , Jin Hu , Viswanadham Vinayak V. , Watson Emma V. , Cortés-Ciriano Isidro , Elledge Stephen J. , Chiarle Roberto , Pellman David , Park Peter J.
Published: May 2023

Focal copy-number amplification is an oncogenic event. Although recent studies have revealed the complex structure1–3 and the evolutionary trajectories4 of oncogene amplicons, their origin remains poorly understood. Here we show that focal amplifications in breast cancer frequently derive from a mechanism—which we term translocation–bridge amplification—involving inter-chromosomal translocations that lead to dicentric chromosome bridge formation and breakage. In 780 breast cancer genomes, we observe that focal amplifications are frequently connected to each other by inter-chromosomal translocations at their boundaries. Subsequent analysis indicates the following model: the oncogene neighbourhood is translocated in G1 creating a dicentric chromosome, the dicentric chromosome is replicated, and as dicentric sister chromosomes segregate during mitosis, a chromosome bridge is formed and then broken, with fragments often being circularized in extrachromosomal DNAs. This model explains the amplifications of key oncogenes, including ERBB2 and CCND1. Recurrent amplification boundaries and rearrangement hotspots correlate with oestrogen receptor binding in breast cancer cells. Experimentally, oestrogen treatment induces DNA double-strand breaks in the oestrogen receptor target regions that are repaired by translocations, suggesting a role of oestrogen in generating the initial translocations. A pan-cancer analysis reveals tissue-specific biases in mechanisms initiating focal amplifications, with the breakage–fusion–bridge cycle prevalent in some and the translocation–bridge amplification in others, probably owing to the different timing of DNA break repair. Our results identify a common mode of oncogene amplification and propose oestrogen as its mechanistic origin in breast cancer.