bluuebunny/crossref_metadata_2025 huggingface dataset:
Sea Ice Dipole Around East Antarctica Induced by Remote Forcing From Indian Ocean
Authors: Ma Weihan , Li Xichen , Zhang Li , Hou Yurong , Man Kai
Published: January 2025

While the variability of West Antarctic sea ice, represented by the Antarctic Dipole (ADP), has been extensively investigated, the sea ice variability around East Antarctica has received relatively less attention. In this study, we identify significant dipole‐like sea ice variability over the Bellingshausen, Weddell, and King Hakon VII Seas during austral winter, which is comparable in magnitude to the ADP and is termed the East Antarctic sea ice Dipole (EAD). Our analysis shows that the EAD pattern is driven by local thermodynamic and dynamic processes associated with an anomalous low‐pressure system over the Weddell Sea, which is linked to a Rossby wave train triggered by tropical sea surface temperature variabilities, particularly those over the Indian Ocean. This teleconnection between the Indian Ocean and East Antarctica is further confirmed by numerical model experiments, with Indian Ocean warming identified as the main forcing. Our findings highlight the importance of this teleconnection in improving sea ice prediction models, especially in light of the projected acceleration of Indian Ocean warming in climate models.
Analysis of Electron Distribution Functions From the Magnetospheric Multiscale (MMS) Mission Using the Gaussian Mixture Model
Authors: Sanò Beniamino , Maes Anno Nathan N. , Newman David L. , Goldman Marty , Valentini Francesco , Perrone Denise , Lapenta Giovanni
Published: January 2025

Velocity distribution functions (VDFs) measured by the Magnetospheric Multiscale (MMS) mission are complex 3D data sets that can be represented as a superposition of multiple beams. Recent work proposed the use of the Gaussian Mixture Model (GMM) to identify different populations. Here we investigate the approach by considering first synthetic distributions made by synthetically creating beams of either Maxwellian distributions or kappa distributions with varying power law index. By varying the inter‐beam average difference and the beam standard deviation we evaluate the ability of the GMM in recognizing correctly the beam. We then apply the method systematically to MMS data in the tail and in the dayside of the Earth's magnetosphere. The approach relies on a GMM algorithm to detect and characterize the number of distinct clusters within a VDF, and a model selection approach based on the Bayesian Information Criterion to determine the optimal number of clusters. The conclusion of the analysis is that the GMM can estimate the complexity of a VDF in terms of the number of optimal beams provided by information theory criteria. By evaluating the complexity of VDFs, we can identify regions of interest within the plasma where significant physical phenomena may be present.
Evolution of Terrestrial Aridity and Dryland Since Pangea
Authors: Li Zhibo , Hu Yongyun , Fu Qiang , Bao Xiujuan , Zhang Jian , Li Xiang , Guo Jiaqi , Lin Qifan , Yuan Shuai , Lan Jiawenjing , Han Jing , Zhang Shiyan , Wei Qiang , Liu Yonggang , Yang Jun , Nie Ji , Guo Zhengtang
Published: January 2025

In the geological past, terrestrial aridity had critical influences on the evolution of life and ecosystems. Here, we combine climate simulations and geological records to investigate the evolution of terrestrial aridity since Pangea. Throughout this geological epoch, tectonics had led to the breakup and reassembly of landmasses, alongside climatic oscillations between hothouse and icehouse conditions. Our findings reveal a dynamic landscape of dryland coverage, encompassing approximately 56% of global land during Pangea, diminishing to about 32% in the Cretaceous, and subsequently rising to around 40% in the Cenozoic era. We identify continental configurations and surface temperatures as pivotal determinants of dryland distribution. Our analysis indicates that the evolution of dryland areas is predominantly influenced by the subtropical land area (79.5%) and global mean surface temperature (15.4%). Furthermore, our study highlights a significant expansion of the dryland area, particularly within semi‐arid regions, during periods of carbon dioxide‐induced warming, attributed chiefly to increased potential evapotranspiration.
Prediction and observation of topological modes in fractal nonlinear optics
Authors: Malomed Boris A.
Published: January 2025

This item from the News and Views (N&V) category aims to provide a summary of theoretical and experimental results recently published in ref. 24, which demonstrates the creation of corner modes in nonlinear optical waveguides of the higher-order topological insulator (HOTI) type. Actually, these are second-order HOTIs, in which the transverse dimension of the topologically protected edge modes is smaller than the bulk dimension (it is 2, in the case of optical waveguide) by 2, implying zero dimension of the protected modes, which are actually realized as corner or defect ones. Work24 reports the prediction and creation of various forms of the corner modes in a HOTI with a fractal transverse structure, represented by the Sierpiński gasket (SG). The self-focusing nonlinearity of the waveguide's material transforms the corner modes into corner solitons, almost all of which are stable. The solitons may be attached to external or internal corners created by the underlying SG. This N&V item offers an overview of these new findings reported in ref. 24 and other recent works, and a brief discussion of directions for further work on this topic.
Building a growing genomic repository for maternal and fetal health through the PING Consortium
Authors: Abdelmalek Clara M. , Singh Shriya , Fasil Blain , Horvath Allison R. , Mulkey Sarah B. , Curé Carlos , Campos Maribel , Cavalcanti Denise P. , Tong Van T. , Mercado Marcela , Daza Marcela , Benavides Mónica Marcela , Acosta Jacqueline , Gilboa Suzanne , Valencia Diana , Sancken Christina L. , Newton Suzanne , Scalabrin Deolinda M. F. , Mussi-Pinhata Marisa M. , Vasconcelos Zilton , Chakhtoura Nahida , Moye Jack , Leslie Elizabeth J. , Bulas Dorothy , Vezina Gilbert , Marques Fernanda J. P. , Leyser Marcio , Del Campo Miguel , Vilain Eric , DeBiasi Roberta L. , Wang Tongguang , Nath Avindra , Haydar Tarik , Muenke Max , Mansour Tamer A. , du Plessis Adre J. , Murray Jeffrey C. , Cordero José F. , Kousa Youssef A.
Published: January 2025

Background

Prenatally transmitted viruses can cause severe damage to the developing brain. There is unexplained variability in prenatal brain injury and postnatal neurodevelopmental outcomes, suggesting disease modifiers. Of note, prenatal Zika infection can cause a spectrum of neurodevelopmental disorders, including congenital Zika syndrome. Currently, there is no preventative treatment or cure. The Prenatal Infection and Neurodevelopmental Genetics (PING) Consortium aims to identify modulators of brain injury and adverse neurodevelopmental outcomes for Zika and other prenatal viral infections.

Methods

The Consortium pools information from eight multi-site studies conducted at 23 research centers in six countries to build a growing clinical and genomic repository, which is being mined for modifiers of virally induced brain injury. Partners include Children’s National Hospital (USA), Instituto Nacional de Salud (Colombia), the Natural History of Zika Virus Infection in Gestation program (Brazil), Zika Instituto Fernandes Figueira (Brazil), the Centers for Disease Control and Prevention, and the National Institutes of Health.

Results

We have enrolled 4102 mothers and 3877 infants with 3063 biological samples and clinical data covering over 80 phenotypic fields and 5000 variables. Thus far, we have performed whole exome sequencing on 1226 participants.

Conclusion

Here, we present the Consortium’s formation and overarching study design.

Impact

The PING Consortium brings together investigators and institutions to determine the causes of virally induced brain injury and neurological deficits. The clinical and genomic repository, with data from over 8000 patients, will serve as a foundation for a variety of basic and clinical studies.
Molecular and spatial analysis of tertiary lymphoid structures in Sjogren’s syndrome
Authors: Nayar Saba , Turner Jason D. , Asam Saba , Fennell Eanna , Pugh Matthew , Colafrancesco Serena , Berardicurti Onorina , Smith Charlotte G. , Flint Joe , Teodosio Ana , Iannizzotto Valentina , Gardner David H. , van Roon Joel , Korsunsky Ilya , Howdle Dawn ,   Roche Fibroblast Network Consortium, Brenner Michael , Coles Mark , Powrie Fiona M. , Raychaudhuri Soumya , Frei Andreas P. , Lassen Kara G. , Bowman Simon J. , Ng Wan-Fai , Croft Adam P. , Filer Andrew , Fisher Benjamin A. , Buckley Christopher D. , Barone Francesca
Published: January 2025

Tertiary lymphoid structures play important roles in autoimmune and non-autoimmune conditions. While many of the molecular mechanisms involved in tertiary lymphoid structure formation have been identified, the cellular sources and temporal and spatial relationship remain unknown. Here we use combine single-cell RNA-sequencing, spatial transcriptomics and proteomics of minor salivary glands of patients with Sjogren’s disease and Sicca Syndrome, with ex-vivo functional studies to construct a cellular and spatial map of key components involved in the formation and function of tertiary lymphoid structures. We confirm the presence of a fibroblast cell state and identify a pericyte/mural cell state with potential immunological functions. The identification of cellular properties associated with these structures and the molecular and functional interactions identified by this analysis may provide key therapeutic cues for tertiary lymphoid structures associated conditions in autoimmunity and cancer.
Monogamy relations for relativistically causal correlations
Authors: Weilenmann Mirjam
Published: January 2025

Non-signalling conditions encode minimal requirements that any (quantum) systems must satisfy in order to be consistent with special relativity. Recent works have argued that in scenarios involving more than two parties, correlations compatible with relativistic causality do not have to satisfy all possible non-signalling conditions but only a subset of them. Here we show that correlations satisfying only this subset of constraints have to satisfy highly non-local monogamy relations between the effects of space-like separated random variables. These monogamy relations take the form of entropic inequalities between the various systems and we give a general method to derive them. Using these monogamy relations, we refute previous suggestions for physical mechanisms that could lead to relativistically causal correlations, demonstrating that such mechanisms would lead to superluminal signalling.
Multiphase superconductivity in PdBi2
Authors: Powell Lewis , Kuang Wenjun , Hawkins-Pottier Gabriel , Jalil Rashid , Birkbeck John , Jiang Ziyi , Kim Minsoo , Zou Yichao , Komrakova Sofiia , Haigh Sarah , Timokhin Ivan , Balakrishnan Geetha , Geim Andre K. , Walet Niels , Principi Alessandro , Grigorieva Irina V.
Published: January 2025

Unconventional superconductivity, where electron pairing does not involve electron-phonon interactions, is often attributed to magnetic correlations in a material. Well known examples include high-Tc cuprates and uranium-based heavy fermion superconductors. Less explored are unconventional superconductors with strong spin-orbit coupling, where interactions between spin-polarised electrons and external magnetic field can result in multiple superconducting phases and field-induced transitions between them, a rare phenomenon in the superconducting state. Here we report a magnetic-field driven phase transition in β-PdBi2, a layered non-magnetic superconductor. Our tunnelling spectroscopy on thin PdBi2 monocrystals incorporated in planar superconductor-insulator-normal metal junctions reveals a marked discontinuity in the superconducting properties with increasing in-plane field, which is consistent with a transition from conventional (s-wave) to nodal pairing. Our theoretical analysis suggests that this phase transition may arise from spin polarisation and spin-momentum locking caused by locally broken inversion symmetry, with p-wave pairing becoming energetically favourable in high fields. Our findings also reconcile earlier predictions of unconventional multigap superconductivity in β-PdBi2 with previous experiments where only a single s-wave gap could be detected.
Complement factor H targeting antibody GT103 in refractory non-small cell lung cancer: a phase 1b dose escalation trial
Authors: Clarke Jeffrey M. , Simon George R. , Mamdani Hirva , Gu Lin , Herndon James E. , Stinchcombe Thomas E. , Ready Neal , Crawford Jeffrey , Sonpavde Guru , Balevic Stephen , Nixon Andrew B. , Campa Michael , Gottlin Elizabeth B. , Li Huihua , Saxena Ruchi , He You Wen , Antonia Scott , Patz Edward F.
Published: January 2025

GT103 is a first-in-class, fully human, IgG3 monoclonal antibody targeting complement factor H that kills tumor cells and promotes anti-cancer immunity in preclinical models. We conducted a first-in-human phase 1b study dose escalation trial of GT103 in refractory non-small cell lung cancer to assess the safety of GT103 (NCT04314089). Dose escalation was performed using a “3 + 3” schema with primary objectives of determining safety, tolerability, PK profile and maximum tolerated dose (MTD) of GT103. Secondary objectives included describing objective response rate, progression-free survival and overall survival. Dose escalation cohorts included GT103 given intravenously at 0.3, 1, 3, 10, and 15 mg/kg every 3 weeks, and 10 mg/kg every 2 weeks. Thirty one patients were enrolled across 3 institutions. Two dose-limiting adverse events were reported: grade 3 acute kidney injury (0.3 mg/kg) and grade 2 colitis (1 mg/kg). No dose-limiting toxicities were noted at the highest dose levels and the MTD was not reached. No objective responses were seen. Stable disease occurred in 9 patients (29%) and the median overall survival was 25.7 weeks (95% confidence interval [CI], 19.1–30.6). Pharmacokinetic analysis confirmed an estimated half life of 6.5 days. The recommended phase 2 dose of GT103 was 10 mg/kg every 3 weeks, however further dose optimization is needed given the absence of an MTD. The study achieved its primary objective of demonstrating safety and tolerability of GT103 in refractory NSCLC.
Tumor cell-based liquid biopsy using high-throughput microfluidic enrichment of entire leukapheresis product
Authors: Mishra Avanish , Huang Shih-Bo , Dubash Taronish , Burr Risa , Edd Jon F. , Wittner Ben S. , Cunneely Quinn E. , Putaturo Victor R. , Deshpande Akansha , Antmen Ezgi , Gopinathan Kaustav A. , Otani Keisuke , Miyazawa Yoshiyuki , Kwak Ji Eun , Guay Sara Y. , Kelly Justin , Walsh John , Nieman Linda T. , Galler Isabella , Chan PuiYee , Lawrence Michael S. , Sullivan Ryan J. , Bardia Aditya , Micalizzi Douglas S. , Sequist Lecia V. , Lee Richard J. , Franses Joseph W. , Ting David T. , Brunker Patricia A. R. , Maheswaran Shyamala , Miyamoto David T. , Haber Daniel A. , Toner Mehmet
Published: January 2025

Circulating Tumor Cells (CTCs) in blood encompass DNA, RNA, and protein biomarkers, but clinical utility is limited by their rarity. To enable tumor epitope-agnostic interrogation of large blood volumes, we developed a high-throughput microfluidic device, depleting hematopoietic cells through high-flow channels and force-amplifying magnetic lenses. Here, we apply this technology to analyze patient-derived leukapheresis products, interrogating a mean blood volume of 5.83 liters from seven patients with metastatic cancer. High CTC yields (mean 10,057 CTCs per patient; range 100 to 58,125) reveal considerable intra-patient heterogeneity. CTC size varies within patients, with 67% overlapping in diameter with WBCs. Paired single-cell DNA and RNA sequencing identifies subclonal patterns of aneuploidy and distinct signaling pathways within CTCs. In prostate cancers, a subpopulation of small aneuploid cells lacking epithelial markers is enriched for neuroendocrine signatures. Pooling of CNV-confirmed CTCs enables whole exome sequencing with high mutant allele fractions. High-throughput CTC enrichment thus enables cell-based liquid biopsy for comprehensive monitoring of cancer.
Machine learning derived retinal pigment score from ophthalmic imaging shows ethnicity is not biology
Authors: Rajesh Anand E. , Olvera-Barrios Abraham , Warwick Alasdair N. , Wu Yue , Stuart Kelsey V. , Biradar Mahantesh I. , Ung Chuin Ying , Khawaja Anthony P. , Luben Robert , Foster Paul J. , Cleland Charles R. , Makupa William U. , Denniston Alastair K. , Burton Matthew J. , Bastawrous Andrew , Keane Pearse A. , Chia Mark A. , Turner Angus W. , Lee Cecilia S. , Tufail Adnan , Lee Aaron Y. , Egan Catherine ,   UK Biobank Eye and Vision Consortium, Allen Naomi , Aslam Tariq , Atan Denize , Balaskas Konstantinos , Barman Sarah , Barrett Jenny , Bishop Paul , Black Graeme , Braithwaite Tasanee , Carare Roxana , Chakravarthy Usha , Chan Michelle , Chua Sharon , Day Alexander , Desai Parul , Dhillon Baljean , Dick Andrew , Doney Alexander , Ennis Sarah , Gallacher John , Garway-Heath David Ted , Gibson Jane , Guggenheim Jeremy , Hammond Chris , Hardcastle Alison , Harding Simon , Hogg Ruth , Hysi Pirro , Lascaratos Gerassimos , Littlejohns Thomas , Lotery Andrew , Luthert Phil , MacGillivray Tom , Mackie Sarah , Madhusudhan Savita , McGuinness Bernadette , McKay Gareth , McKibbin Martin , Moore Tony , Morgan James , O’Sullivan Eoin , Oram Richard , Owen Chris , Patel Praveen , Paterson Euan , Peto Tunde , Petzold Axel , Pontikos Nikolas , Rahi Jugnoo , Rudnicka Alicja , Sattar Naveed , Self Jay , Sergouniotis Panagiotis , Sivaprasad Sobha , Steel David , Stratton Irene , Strouthidis Nicholas , Sudlow Cathie , Sun Zihan , Tapp Robyn , Thomas Dhanes , Trucco Emanuele , Viswanathan Ananth , Vitart Veronique , Weedon Mike , Williams Katie , Williams Cathy , Woodside Jayne , Yates Max , Zheng Yalin
Published: January 2025

Few metrics exist to describe phenotypic diversity within ophthalmic imaging datasets, with researchers often using ethnicity as a surrogate marker for biological variability. We derived a continuous, measured metric, the retinal pigment score (RPS), that quantifies the degree of pigmentation from a colour fundus photograph of the eye. RPS was validated using two large epidemiological studies with demographic and genetic data (UK Biobank and EPIC-Norfolk Study) and reproduced in a Tanzanian, an Australian, and a Chinese dataset. A genome-wide association study (GWAS) of RPS from UK Biobank identified 20 loci with known associations with skin, iris and hair pigmentation, of which eight were replicated in the EPIC-Norfolk cohort. There was a strong association between RPS and ethnicity, however, there was substantial overlap between each ethnicity and the respective distributions of RPS scores. RPS decouples traditional demographic variables from clinical imaging characteristics. RPS may serve as a useful metric to quantify the diversity of the training, validation, and testing datasets used in the development of AI algorithms to ensure adequate inclusion and explainability of the model performance, critical in evaluating all currently deployed AI models. The code to derive RPS is publicly available at: https://github.com/uw-biomedical-ml/retinal-pigmentation-score.
STAT1 regulates immune-mediated intestinal stem cell proliferation and epithelial regeneration
Authors: Takashima Shuichiro , Sharma Roshan , Chang Winston , Calafiore Marco , Fu Ya-Yuan , Jansen Suze A. , Ito Takahiro , Egorova Anastasiya , Kuttiyara Jason , Arnhold Viktor , Sharrock Jessica , Santosa Endi , Chaudhary Ojasvi , Geiger Heather , Iwasaki Hiromi , Liu Chen , Sun Joseph , Robine Nicolas , Mazutis Linas , Lindemans Caroline A. , Hanash Alan M.
Published: January 2025

The role of the immune system in regulating tissue stem cells remains poorly understood, as does the relationship between immune-mediated tissue damage and regeneration. Graft vs. host disease (GVHD) occurring after allogeneic bone marrow transplantation (allo-BMT) involves immune-mediated damage to the intestinal epithelium and its stem cell compartment. To assess impacts of T-cell-driven injury on distinct epithelial constituents, we have performed single cell RNA sequencing on intestinal crypts following experimental BMT. Intestinal stem cells (ISCs) from GVHD mice have exhibited global transcriptomic changes associated with a substantial Interferon-γ response and upregulation of STAT1. To determine its role in crypt function, STAT1 has been deleted within murine intestinal epithelium. Following allo-BMT, STAT1 deficiency has resulted in reduced epithelial proliferation and impaired ISC recovery. Similarly, epithelial Interferon-γ receptor deletion has also attenuated proliferation and ISC recovery post-transplant. Investigating the mechanistic basis underlying this epithelial response, ISC STAT1 expression in GVHD has been found to correlate with upregulation of ISC c-Myc. Furthermore, activated T cells have stimulated Interferon-γ-dependent epithelial regeneration in co-cultured organoids, and Interferon-γ has directly induced STAT1-dependent c-Myc expression and ISC proliferation. These findings illustrate immunologic regulation of a core tissue stem cell program after damage and support a role for Interferon-γ as a direct contributor to epithelial regeneration.
Structural and electronic features enabling delocalized charge-carriers in CuSbSe2
Authors: Fu Yuchen , Lohan Hugh , Righetto Marcello , Huang Yi-Teng , Kavanagh Seán R. , Cho Chang-Woo , Zelewski Szymon J. , Woo Young Won , Demetriou Harry , McLachlan Martyn A. , Heutz Sandrine , Piot Benjamin A. , Scanlon David O. , Rao Akshay , Herz Laura M. , Walsh Aron , Hoye Robert L. Z.
Published: January 2025

Inorganic semiconductors based on heavy pnictogen cations (Sb3+ and Bi3+) have gained significant attention as potential nontoxic and stable alternatives to lead-halide perovskites for solar cell applications. A limitation of these novel materials, which is being increasingly commonly found, is carrier localization, which substantially reduces mobilities and diffusion lengths. Herein, CuSbSe2 is investigated and discovered to have delocalized free carriers, as shown through optical pump terahertz probe spectroscopy and temperature-dependent mobility measurements. Using a combination of theory and experiment, the critical enabling factors are found to be: 1) having a layered structure, which allows distortions to the unit cell during the propagation of an acoustic wave to be relaxed in the interlayer gaps, with minimal changes in bond length, thus limiting deformation potentials; 2) favourable quasi-bonding interactions across the interlayer gap giving rise to higher electronic dimensionality; 3) Born effective charges not being anomalously high, which, combined with the small bandgap ($$\le$$
≤
1.2 eV), result in a low ionic contribution to the dielectric constant compared to the electronic contribution, thus reducing the strength of Fröhlich coupling. These insights can drive forward the rational discovery of perovskite-inspired materials that can avoid carrier localization.
Deep learning-based aberration compensation improves contrast and resolution in fluorescence microscopy
Authors: Guo Min , Wu Yicong , Hobson Chad M. , Su Yijun , Qian Shuhao , Krueger Eric , Christensen Ryan , Kroeschell Grant , Bui Johnny , Chaw Matthew , Zhang Lixia , Liu Jiamin , Hou Xuekai , Han Xiaofei , Lu Zhiye , Ma Xuefei , Zhovmer Alexander , Combs Christian , Moyle Mark , Yemini Eviatar , Liu Huafeng , Liu Zhiyi , Benedetto Alexandre , La Riviere Patrick , Colón-Ramos Daniel , Shroff Hari
Published: January 2025

Optical aberrations hinder fluorescence microscopy of thick samples, reducing image signal, contrast, and resolution. Here we introduce a deep learning-based strategy for aberration compensation, improving image quality without slowing image acquisition, applying additional dose, or introducing more optics. Our method (i) introduces synthetic aberrations to images acquired on the shallow side of image stacks, making them resemble those acquired deeper into the volume and (ii) trains neural networks to reverse the effect of these aberrations. We use simulations and experiments to show that applying the trained ‘de-aberration’ networks outperforms alternative methods, providing restoration on par with adaptive optics techniques; and subsequently apply the networks to diverse datasets captured with confocal, light-sheet, multi-photon, and super-resolution microscopy. In all cases, the improved quality of the restored data facilitates qualitative image inspection and improves downstream image quantitation, including orientational analysis of blood vessels in mouse tissue and improved membrane and nuclear segmentation in C. elegans embryos.
SOX2+ sustentacular cells are stem cells of the postnatal adrenal medulla
Authors: Santambrogio Alice , Kemkem Yasmine , Willis Thea L. , Berger Ilona , Kastriti Maria Eleni , Faure Louis , Russell John P. , Lodge Emily J. , Yianni Val , Kövér Bence , Oakey Rebecca J. , Altieri Barbara , Bornstein Stefan R. , Steenblock Charlotte , Adameyko Igor , Andoniadou Cynthia L.
Published: January 2025

Renewal of the catecholamine-secreting chromaffin cell population of the adrenal medulla is necessary for physiological homeostasis throughout life. Definitive evidence for the presence or absence of an adrenomedullary stem cell has been enigmatic. In this work, we demonstrate that a subset of sustentacular cells endowed with a support role, are in fact adrenomedullary stem cells. Through genetic tracing and comprehensive transcriptomic data of the mouse adrenal medulla, we show that cells expressing Sox2/SOX2 specialise as a unique postnatal population from embryonic Schwann Cell Precursors and are also present in the normal adult human adrenal medulla. Postnatal SOX2+ cells give rise to chromaffin cells of both the adrenaline and noradrenaline lineages in vivo and in vitro. We reveal that SOX2+ stem cells have a second, paracrine role in maintaining adrenal chromaffin cell homeostasis, where they promote proliferation through paracrine secretion of WNT6. This work identifies SOX2+ cells as a true stem cell for catecholamine-secreting chromaffin cells.
Verifiable measurement-based quantum random sampling with trapped ions
Authors: Ringbauer Martin , Hinsche Marcel , Feldker Thomas , Faehrmann Paul K. , Bermejo-Vega Juani , Edmunds Claire L. , Postler Lukas , Stricker Roman , Marciniak Christian D. , Meth Michael , Pogorelov Ivan , Blatt Rainer , Schindler Philipp , Eisert Jens , Monz Thomas , Hangleiter Dominik
Published: January 2025

Quantum computers are now on the brink of outperforming their classical counterparts. One way to demonstrate the advantage of quantum computation is through quantum random sampling performed on quantum computing devices. However, existing tools for verifying that a quantum device indeed performed the classically intractable sampling task are either impractical or not scalable to the quantum advantage regime. The verification problem thus remains an outstanding challenge. Here, we experimentally demonstrate efficiently verifiable quantum random sampling in the measurement-based model of quantum computation on a trapped-ion quantum processor. We create and sample from random cluster states, which are at the heart of measurement-based computing, up to a size of 4 × 4 qubits. By exploiting the structure of these states, we are able to recycle qubits during the computation to sample from entangled cluster states that are larger than the qubit register. We then efficiently estimate the fidelity to verify the prepared states—in single instances and on average—and compare our results to cross-entropy benchmarking. Finally, we study the effect of experimental noise on the certificates. Our results and techniques provide a feasible path toward a verified demonstration of a quantum advantage.
An integrated photonic engine for programmable atomic control
Authors: Christen Ian , Propson Thomas , Sutula Madison , Sattari Hamed , Choong Gregory , Panuski Christopher , Melville Alexander , Mallek Justin , Brabec Cole , Hamilton Scott , Dixon P. Benjamin , Menssen Adrian J. , Braje Danielle , Ghadimi Amir H. , Englund Dirk
Published: January 2025

Solutions for scalable, high-performance optical control are important for the development of scaled atom-based quantum technologies. Modulation of many individual optical beams is central to applying arbitrary gate and control sequences on arrays of atoms or atom-like systems. At telecom wavelengths, miniaturization of optical components via photonic integration has pushed the scale and performance of classical and quantum optics far beyond the limitations of bulk devices. However, material platforms for high-speed telecom integrated photonics lack transparency at the short wavelengths required by leading atomic systems. Here, we propose and implement a scalable and reconfigurable photonic control architecture using integrated, visible-light modulators based on thin-film lithium niobate. We combine this system with techniques in free-space optics and holography to demonstrate multi-channel, gigahertz-rate visible beamshaping. When applied to silicon-vacancy artificial atoms, our system enables the spatial and spectral addressing of a dynamically-selectable set of these stochastically-positioned point emitters.
Banning new gas boilers as a no-regret mitigation option
Authors: Escribe Célia , Vivier Lucas
Published: January 2025

The low uptake of low-carbon heating systems across Europe has prompted authorities to consider more ambitious measures, including a complete ban on the installation of new fossil fuel boilers. In this analysis, we simulate the impacts of introducing this ban in France under 11,664 scenarios covering major uncertainties. We find that the ban induces major changes in the energy system, leading to efficiency gains. Additionally, we find that the ban increases the likelihood of reaching carbon neutrality while reducing total system cost in over 75% of scenarios. Finally, we show that the implementation of the ban, when coupled with the existing subsidy framework, mitigates inequalities among owner-occupied households but generates adverse effects for those in privately rented homes.
Engineering ultra-strong electron-phonon coupling and nonclassical electron transport in crystalline gold with nanoscale interfaces
Authors: Kumbhakar Shreya , Maji Tuhin Kumar , Tongbram Binita , Mandal Shinjan , Soundararaj Shri Hari , Debnath Banashree , T Phanindra Sai , Jain Manish , Krishnamurthy H. R. , Pandey Anshu , Ghosh Arindam
Published: January 2025

Electrical resistivity in good metals, particularly noble metals such as gold (Au), silver (Ag), or copper, increases linearly with temperature (T) for T > ΘD, where ΘD is the Debye temperature. This is because the coupling (λ) between the electrons and the lattice vibrations, or phonons, in these metals is weak, with λ ~ 0.1−0.2. In this work, we outline a nanostructuring strategy of crystalline Au where this concept of metallic transport breaks down. We show that by embedding a distributed network of ultra-small Ag nanoparticles (AgNPs) of radius ~ 1–2 nm inside a crystalline Au shell, the electron-phonon interaction can be enhanced, with an effective λ as high as  ≈ 20. With increasing AgNP density, the electrical resistivity deviates from T-linearity and approaches a saturation to the Mott-Ioffe-Regel scale ρMIR ~ ha/e2 for both disorder (T → 0) and phonon (T ≫ ΘD)-dependent components of resistivity (here, a = 0.3 nm, is the lattice constant of Au).
Harnessing orbital Hall effect in spin-orbit torque MRAM
Authors: Gupta Rahul , Bouard Chloé , Kammerbauer Fabian , Ledesma-Martin J. Omar , Bose Arnab , Kononenko Iryna , Martin Sylvain , Usé Perrine , Jakob Gerhard , Drouard Marc , Kläui Mathias
Published: January 2025

Spin-Orbit Torque (SOT) Magnetic Random-Access Memory (MRAM) devices offer improved power efficiency, nonvolatility, and performance compared to static RAM, making them ideal, for instance, for cache memory applications. Efficient magnetization switching, long data retention, and high-density integration in SOT MRAM require ferromagnets (FM) with perpendicular magnetic anisotropy (PMA) combined with large torques enhanced by Orbital Hall Effect (OHE). We have engineered a PMA [Co/Ni]3 FM on selected OHE layers (Ru, Nb, Cr) and investigated the potential of theoretically predicted larger orbital Hall conductivity (OHC) to quantify the torque and switching current in OHE/[Co/Ni]3 stacks. Our results demonstrate a  ~30% enhancement in damping-like torque efficiency with a positive sign for the Ru OHE layer compared to a pure Pt layer, accompanied by a  ~20% reduction in switching current for Ru compared to pure Pt across more than 250 devices, leading to more than a 60% reduction in switching power. These findings validate the application of Ru in devices relevant to industrial contexts, supporting theoretical predictions regarding its superior OHC. This investigation highlights the potential of enhanced orbital torques to improve the performance of orbital-assisted SOT-MRAM, paving the way for next-generation memory technology.
Fam102a translocates Runx2 and Rbpjl to facilitate Osterix expression and bone formation
Authors: Yamashita Yu , Hayashi Mikihito , Liu Anhao , Sasaki Fumiyuki , Tsuchiya Yosuke , Takayanagi Hiroshi , Saito Mitsuru , Nakashima Tomoki
Published: January 2025

Bone remodeling maintains the robustness of the bone tissue by balancing bone resorption by osteoclasts and bone formation by osteoblasts. Although these cells together play a crucial role in bone remodeling, only a few reports are available on the common factors involved in the differentiation of the two types of cells. Here, we show family with sequence similarity 102 member A (Fam102a) as a bone-remodeling factor that positively regulates both osteoclast and osteoblast differentiation. Fam102a regulates osteoblast differentiation by controlling recombination signal binding protein for immunoglobulin κ J region-like (Rbpjl). The Fam102a-Rbpjl axis promotes the nuclear translocation of transcription factors and enhances the expression of Osterix, a transcription factor essential for osteoblast differentiation. The deletion of Fam102a or a functional mutation in Rbpjl leads to osteopenia accompanied by reduced osteoblastic bone formation. Thus, the Fam102a-Rbpjl axis plays an important role in osteoblasts and this finding provides insights into bone remodeling.
Universal, untargeted detection of bacteria in tissues using metabolomics workflows
Authors: Chen Wei , Qiu Min , Paizs Petra , Sadowski Miriam , Ramonaite Toma , Zborovsky Lieby , Mejias-Luque Raquel , Janßen Klaus-Peter , Kinross James , Goldin Robert D. , Rebec Monica , Liebeke Manuel , Takats Zoltan , McKenzie James S. , Strittmatter Nicole
Published: January 2025

Fast and reliable identification of bacteria directly in clinical samples is a critical factor in clinical microbiological diagnostics. Current approaches require time-consuming bacterial isolation and enrichment procedures, delaying stratified treatment. Here, we describe a biomarker-based strategy that utilises bacterial small molecular metabolites and lipids for direct detection of bacteria in complex samples using mass spectrometry (MS). A spectral metabolic library of 233 bacterial species is mined for markers showing specificity at different phylogenetic levels. Using a univariate statistical analysis method, we determine 359 so-called taxon-specific markers (TSMs). We apply these TSMs to the in situ detection of bacteria using healthy and cancerous gastrointestinal tissues as well as faecal samples. To demonstrate the MS method-agnostic nature, samples are analysed using spatial metabolomics and traditional bulk-based metabolomics approaches. In this work, TSMs are found in >90% of samples, suggesting the general applicability of this workflow to detect bacterial presence with standard MS-based analytical methods.
Generic residue numbering of the GAIN domain of adhesion GPCRs
Authors: Seufert Florian , Pérez-Hernández Guillermo , Pándy-Szekeres Gáspár , Guixà-González Ramon , Langenhan Tobias , Gloriam David E. , Hildebrand Peter W.
Published: January 2025

The GPCR autoproteolysis inducing (GAIN) domain is an ancient protein fold ubiquitous in adhesion G protein-coupled receptors (aGPCR). It contains a tethered agonist necessary and sufficient for receptor activation. The GAIN domain is a hotspot for pathological mutations. However, the low primary sequence conservation of GAIN domains has thus far hindered the knowledge transfer across different GAIN domains in human receptors as well as species orthologs. Here, we present a scheme for generic residue numbering of GAIN domains, based on structural alignments of over 14,000 modeled GAIN domain structures. This scheme is implemented in the GPCR database (GPCRdb) and elucidates the domain topology across different aGPCRs and their homologs in a large panel of species. We identify conservation hotspots and statistically cancer-enriched positions in human aGPCRs and show the transferability of positional and structural information between GAIN domain homologs. The GAIN-GRN scheme provides a robust strategy to allocate structural homologies at the primary and secondary levels also to GAIN domains of polycystic kidney disease 1/PKD1-like proteins, which now renders positions in both GAIN domain types comparable to one another. In summary, our work enables researchers to generate hypothesis and rationalize experiments related to GAIN domain function and pathology.
Multipocket synergy towards high thermoelectric performance in topological semimetal TaAs2
Authors: Hu Haihua , Feng Xiaolong , Pan Yu , Hasse Vicky , Wang Honghui , He Bin , Felser Claudia
Published: January 2025

Charge-carrier compensation in topological semimetals amplifies the Nernst signal and simultaneously degrades the Seebeck coefficient. In this study, we report the simultaneous achievement of both a large Nernst signal and an unsaturating magneto-Seebeck coefficient in a topological nodal-line semimetal TaAs2 single crystal. The unique dual-high transverse and longitudinal thermopowers are attributed to multipocket synergy effects: the combination of a strong phonon-drag effect and the two overlapping highly dispersive conduction and valence bands with electron–hole compensation and high mobility, promising a large Nernst effect; the third Dirac band causes a large magneto-Seebeck effect. High transverse and longitudinal power factors of ~3100 and ~50 μW cm−1 K−2, respectively, are achieved, surpassing those of other topological semimetals and mainstream semiconductors. Our study presents a feasible approach for optimizing the longitudinal and transverse thermopowers in topological semimetals simultaneously and demonstrates the potential of TaAs2 for low temperature solid-state cooling.
Rational engineering of minimally immunogenic nucleases for gene therapy
Authors: Raghavan Rumya , Friedrich Mirco J. , King Indigo , Chau-Duy-Tam Vo Samuel , Strebinger Daniel , Lash Blake , Kilian Michael , Platten Michael , Macrae Rhiannon K. , Song Yifan , Nivon Lucas , Zhang Feng
Published: January 2025

Genome editing using CRISPR-Cas systems is a promising avenue for the treatment of genetic diseases. However, cellular and humoral immunogenicity of genome editing tools, which originate from bacteria, complicates their clinical use. Here we report reduced immunogenicity (Red)(i)-variants of two clinically relevant nucleases, SaCas9 and AsCas12a. Through MHC-associated peptide proteomics (MAPPs) analysis, we identify putative immunogenic epitopes on each nuclease. Using computational modeling, we rationally design these proteins to evade the immune response. SaCas9 and AsCas12a Redi variants are substantially less recognized by adaptive immune components, including reduced binding affinity to MHC molecules and attenuated generation of cytotoxic T cell responses, yet maintain wild-type levels of activity and specificity. In vivo editing of PCSK9 with SaCas9.Redi.1 is comparable in efficiency to wild-type SaCas9, but significantly reduces undesired immune responses. This demonstrates the utility of this approach in engineering proteins to evade immune detection.
Next generation thiazolyl ketone inhibitors of cytosolic phospholipase A2 α for targeted cancer therapy
Authors: Ashcroft Felicity J. , Bourboula Asimina , Mahammad Nur , Barbayianni Efrosini , Feuerherm Astrid J. , Nguyen Thanh Thuy , Hayashi Daiki , Kokotou Maroula G. , Alevizopoulos Konstantinos , Dennis Edward A. , Kokotos George , Johansen Berit
Published: January 2025

Eicosanoids are key players in inflammatory diseases and cancer. Targeting their production by inhibiting Group IVA cytosolic phospholipase A2 (cPLA2α) offers a promising approach for cancer therapy. In this study, we synthesize a second generation of thiazolyl ketone inhibitors of cPLA2α starting with compound GK470 (AVX235) and test their in vitro and cellular activities. We identify a more potent and selective lead molecule, GK420 (AVX420), which we test in parallel with AVX235 and a structurally unrelated compound, AVX002 for inhibition of cell viability across a panel of cancer cell lines. From this, we show that activity of polycomb group repressive complex 2 is a key molecular determinant of sensitivity to cPLA2α inhibition, while resistance depends on antioxidant response pathways. Consistent with these results, we show that elevated intracellular reactive oxygen species and activating transcription factor 4 target gene expression precede cell death in AVX420-sensitive T-cell acute lymphoblastic leukemia cells. Our findings imply cPLA2α may support cancer by mitigating oxidative stress and inhibiting tumor suppressor expression and suggest that AVX420 has potential for treating acute leukemias and other cancers that are susceptible to oxidative cell death.
TransLeish: Identification of membrane transporters essential for survival of intracellular Leishmania parasites in a systematic gene deletion screen
Authors: Albuquerque-Wendt Andreia , McCoy Ciaran , Neish Rachel , Dobramysl Ulrich , Alagöz Çağla , Beneke Tom , Cowley Sally A. , Crouch Kathryn , Wheeler Richard J. , Mottram Jeremy C. , Gluenz Eva
Published: January 2025

For the protozoan parasite Leishmania, completion of its life cycle requires sequential adaptation of cellular physiology and nutrient scavenging mechanisms to the different environments of a sand fly alimentary tract and the acidic mammalian host cell phagolysosome. Transmembrane transporters are the gatekeepers of intracellular environments, controlling the flux of solutes and ions across membranes. To discover which transporters are vital for survival as intracellular amastigote forms, we carried out a systematic loss-of-function screen of the L. mexicana transportome. A total of 312 protein components of small molecule carriers, ion channels and pumps were identified and targeted in a CRISPR-Cas9 gene deletion screen in the promastigote form, yielding 188 viable null mutants. Forty transporter deletions caused significant loss of fitness in macrophage and mouse infections. A striking example is the Vacuolar H+ ATPase (V-ATPase), which, unexpectedly, was dispensable for promastigote growth in vitro but essential for survival of the disease-causing amastigotes.
Structural insights into the regulation of monomeric and dimeric apelin receptor
Authors: Yue Yang , Liu Lier , Wu Lijie , Xu Chanjuan , Na Man , Liu Shenhui , Liu Yuxuan , Li Fei , Liu Junlin , Shi Songting , Lei Hui , Zhao Minxuan , Yang Tianjie , Ji Wei , Wang Arthur , Hanson Michael A. , Stevens Raymond C. , Liu Jianfeng , Xu Fei
Published: January 2025

The apelin receptor (APJR) emerges as a promising drug target for cardiovascular health and muscle regeneration. While prior research unveiled the structural versatility of APJR in coupling to Gi proteins as a monomer or dimer, the dynamic regulation within the APJR dimer during activation remains poorly understood. In this study, we present the structures of the APJR dimer and monomer complexed with its endogenous ligand apelin-13. In the dimeric structure, apelin-13 binds exclusively to one protomer that is coupled with Gi proteins, revealing a distinct ligand-binding behavior within APJR homodimers. Furthermore, binding of an antagonistic antibody induces a more compact dimerization by engaging both protomers. Notably, structural analyses of the APJR dimer complexed with an agonistic antibody, with or without Gi proteins, suggest that G protein coupling may promote the dissociation of the APJR dimer during activation. These findings underscore the intricate interplay between ligands, dimerization, and G protein coupling in regulating APJR signaling pathways.
Surface remodeling and inversion of cell-matrix interactions underlie community recognition and dispersal in Vibrio cholerae biofilms
Authors: Moreau Alexis , Nguyen Danh T. , Hinbest Alexander J. , Zamora Anthony , Weerasekera Ranjuna , Matej Katherine , Zhou Xuening , Sanchez Sandra , Rodriguez Brenes Ignacio , Tai Jung-Shen Benny , Nadell Carey D. , Ng Wai-Leung , Gordon Vernita , Komarova Natalia L. , Olson Rich , Li Ying , Yan Jing
Published: January 2025

Biofilms are ubiquitous surface-associated bacterial communities embedded in an extracellular matrix. It is commonly assumed that biofilm cells are glued together by the matrix; however, how the specific biochemistry of matrix components affects the cell-matrix interactions and how these interactions vary during biofilm growth remain unclear. Here, we investigate cell-matrix interactions in Vibrio cholerae, the causative agent of cholera. We combine genetics, microscopy, simulations, and biochemical analyses to show that V. cholerae cells are not attracted to the main matrix component (Vibrio polysaccharide, VPS), but can be attached to each other and to the VPS network through surface-associated VPS and crosslinks formed by the protein Bap1. Downregulation of VPS production and surface trimming by the polysaccharide lyase RbmB cause surface remodeling as biofilms age, shifting the nature of cell-matrix interactions from attractive to repulsive and facilitating cell dispersal as aggregated groups. Our results shed light on the dynamics of diverse cell-matrix interactions as drivers of biofilm development.
2.5-dimensional covalent organic frameworks
Authors: Kitano Tomoki , Goto Syunto , Wang Xiaohan , Kamihara Takayuki , Sei Yoshihisa , Kondo Yukihito , Sannomiya Takumi , Uekusa Hidehiro , Murakami Yoichi
Published: January 2025

Covalently bonded crystalline substances with micropores have broad applications. Covalent organic frameworks (COFs) are representative of such substances. They have so far been classified into two-dimensional (2D) and three-dimensional (3D) COFs. 2D-COFs have planar shapes useful for broad purposes, but obtaining good crystals of 2D-COFs with sizes larger than 10 μm is significantly challenging, whereas yielding 3D-COFs with high crystallinity and larger sizes is easier. Here, we show COFs with 2.5-dimensional (2.5D) skeletons, which are microscopically constructed with 3D bonds but have macroscopically 2D planar shapes. The 2.5D-COFs shown herein achieve large single-crystal sizes above 0.1 mm and ultrahigh-density primary amines regularly allocated on and pointing perpendicular to the covalently-bonded network plane. Owing to the latter nature, the COFs are promising as CO2 adsorbents that can simultaneously achieve high CO2/N2 selectivity and low heat of adsorption, which are usually in a mutually exclusive relationship. 2.5D-COFs are expected to broaden the frontier and application of covalently bonded microporous crystalline systems.