bluuebunny/crossref_metadata_2025 huggingface dataset:
IMU as an input versus a measurement of the state in inertial-aided state estimation
Authors: Burnett Keenan , Schoellig Angela P. , Barfoot Timothy D.
Published: January 2025

Treating inertial measurement unit (IMU) measurements as inputs to a motion model and then preintegrating these measurements have almost become a de facto standard in many robotics applications. However, this approach has a few shortcomings. First, it conflates the IMU measurement noise with the underlying process noise. Second, it is unclear how the state will be propagated in the case of IMU measurement dropout. Third, it does not lend itself well to dealing with multiple high-rate sensors such as a lidar and an IMU or multiple asynchronous IMUs. In this paper, we compare treating an IMU as an input to a motion model against treating it as a measurement of the state in a continuous-time state estimation framework. We methodically compare the performance of these two approaches on a 1D simulation and show that they perform identically, assuming that each method’s hyperparameters have been tuned on a training set. We also provide results for our continuous-time lidar-inertial odometry in simulation and on the Newer College Dataset. In simulation, our approach exceeds the performance of an imu-as-input baseline during highly aggressive motion. On the Newer College Dataset, we demonstrate state-of-the art results. These results show that continuous-time techniques and the treatment of the IMU as a measurement of the state are promising areas of further research. Code for our lidar-inertial odometry can be found at: https://github.com/utiasASRL/steam_icp.
Spatial, occupational, and age-related effects on reported variation in colloquial German
Authors: Wirtz Mason A. , Pickl Simon , Niehaus Konstantin , Elspaß Stephan , Möller Robert
Published: January 2025

While dialectal variation is often investigated from a geographical angle, there exists substantial variation both within the community and individual. The aim of the present article is to investigate the extent to which spatial, occupational, and age-related factors are associated with the diversity of linguistic variants reported per informant at a given locality. Drawing on colloquial language data from the Atlas zur deutschen Alltagssprache ‘Atlas of Colloquial German,’ we found that informants from southeastern Germany and Austria reported familiarity with more variants. Moreover, we multifactorially operationalize occupational complexity, a variable that can capture the effects of different communicative, technical, and physical skills required in a job (via the Dictionary of Occupational Titles). Bayesian multilevel modeling revealed that informants in occupations involving physical precision work and communicative complexity reported less familiarity with variants, and that younger informants were familiar with a wider range of variants.
Measuring Adulthood – A Meta-Analysis of the Markers of Adulthood Scale
Authors: Wright Megan , Oxley Florence , von Stumm Sophie
Published: January 2025

Abstract: Adulthood is traditionally inferred from the socio-demographic milestones of marriage, parenthood, and having a stable, long-term career. Yet today these milestones are often delayed or unattainable for young people. We conducted a meta-analysis of studies using the Markers of Adulthood scale across the past three decades to assess (a) endorsement rates (%) of marriage, parenthood, and career as markers of adulthood, and (b) whether people think they have reached adulthood. Across 39 samples ( N = 17,465), marriage and parenthood were endorsed by a quarter of participants, whereas career was endorsed by 57%, suggesting that in today’s society career defines adult status more than marriage and parenthood. Furthermore, half of emerging adults (aged 18–29 years) considered themselves to have reached adulthood despite traditional milestones of adulthood occurring less frequently and later in life than ever before. Our findings have three main implications for measuring adult status including (1) deemphasise on the socio-demographic milestones of marriage and parenthood; (2) include wider age ranges in research; and (3) explore cultural differences. Reducing the focus on socio-demographic milestones and including more diverse samples will improve our understanding of adulthood and advance adults’ identity development.
Cracks, Gaps, and Holes in Validation Practice as Evidenced From a Validation Synthesis of the English Version of the Rosenberg Self-Esteem Scale
Authors: Hubley Anita M. , Ruddell Robert J. , Ma Zhu Sophie
Published: January 2025

Abstract: We conducted a validation synthesis of the English version of the Rosenberg Self-Esteem Scale. Twenty-eight studies met our criteria for inclusion. Using the 2014 Standards for Educational and Psychological Testing ( AERA, APA, & NCME, 2014 ) as a frame of reference, we examined the sources of validity and reliability evidence gathered; identified trends, gaps, and issues with this evidence; and made recommendations to guide future validation practice. None of the studies directly cited any edition of the Standards. Validity evidence has relied predominantly on internal structure, followed by relations to other variables, and little to no other sources of evidence. Reliability evidence was reported in most studies but consisted exclusively of internal consistency estimates. Increased awareness and use of the Standards and better training in measurement could help improve validation practice. Recommendations to researchers include becoming more familiar with modern validity theory, paying more attention to sources of validity evidence that address score meaning, presenting clear and explicit a priori expectations of the evidence needed to support the validity of intended inferences, and evaluating obtained evidence with a more critical eye to determine the degree to which theoretical rationales and the evidence support the meaning of test scores for a given use, sample, and context.
Decoupling of Magnetic Fabrics From Magnetic Remanences: Insights From Migmatites in Central Tianshan, NW China
Authors: Zhu Xin , Wang Bo , Dong Yunpeng , Chen Yan , Liu Hongsheng , Sun Shengsi , Xue Zhenhua , Zhong Lingling , He Zhiyuan
Published: January 2025

The coupling of magnetic fabrics and magnetic remanences is critical in interpreting paleomagnetic data. To estimate whether primary magnetic fabrics imply primary magnetic remanences, and to assess the practicability of metamorphic rocks in magnetic study, we carried out petrographic, geochronological, rock magnetic investigations, and analyses in anisotropy of magnetic susceptibility and paleomagnetism on migmatites in the Central Tianshan, NW China. Petrological observations indicate no significant dynamic recrystallization post to the migmatization. In‐situ monazite U‐Pb dating suggests that the migmatization happened during ∼314–297 Ma. Rock magnetic results reveal that the magnetic properties of migmatites are dominated by biotites with minor titanomagnetites. Despite the structural and compositional complexities of migmatites, a simple magnetic fabric pattern is observed with concentrated magnetic foliations and dispersed magnetic lineations. The anisotropy degree and shape parameter significantly change from leucosomes, mesosomes to melanosomes, suggesting that the magnetic fabrics should have been acquired during the migmatization. Characteristic remanent magnetization directions were isolated from a quarter of samples with anomalous shallow magnetic inclination. Combined with available geochronological and paleomagnetic results from the Central Tianshan and neighboring blocks, the magnetic remanences preserved in the migmatites were suggested to be obtained at ∼314–303 Ma, later than the acquisition of magnetic fabrics, probably due to thermal remagnetization or resulted from long‐term progressive magnetization during tectonic exhumation of migmatites. This study provides an important yet rarely reported example to manifest the decoupling of magnetic fabrics from magnetic remanences. Meanwhile, migmatites are found to be operable materials for magnetic fabric and paleomagnetic studies.
Improving Earthquake Early Warning Access for the Deaf Community
Authors: van Deelen Grace
Published: January 2025

Earthquake early warning systems are rarely accessible to people who are deaf or hard of hearing. A group of scientists is working to change that.
Watching a Solar Event from All Angles
Authors: Blinder Collin
Published: January 2025

A fleet of spacecraft captured unprecedented details of the major solar outbursts in May and June 2024.
Myosteatosis is associated with adiposity, metabolic derangements and mortality in patients with chronic kidney disease
Authors: Sabatino Alice , Cordeiro Antonio C. , Prado Carla M. , Lindholm Bengt , Stenvinkel Peter , Avesani Carla Maria
Published: January 2025

Background/Objectives

Myosteatosis has been associated with sarcopenia, and increased mortality risk in patients on hemodialysis. We aimed to explore the associations between myosteatosis, as assessed by computed tomography (CT), with demographic parameters, body composition metrics, muscle strength, metabolic parameters and mortality in patients with chronic kidney disease (CKD).

Subjects/Methods

We enrolled 216 patients (age 60.3 ± 10.6 years, 63% men) with CKD stages 3–5. Abdominal CT scans at the third lumbar vertebra (L3) were used to assess body composition. Abdominal obesity was determined by abdominal adipose tissue (AT), sarcopenia by low skeletal muscle area (SMA) and low handgrip strength. Myosteatosis was evaluated by two parameters using CT scans at L3: mean muscle attenuation and percentage of intermuscular adipose tissue (%IMAT) within SMA. We evaluated the correlation between parameters of myosteatosis with demographic, clinical and metabolic variables. To determine independent predictors of myosteatosis, a multiple linear regression model was fitted. Mortality risk was evaluated with Cox-regression analysis.

Results

Both parameters of myosteatosis were independently associated with age, metabolic syndrome, abdominal AT and SMA in the multiple linear regression analysis (adjusted R2 for multiple linear regression: muscle attenuation model 0.535, P < 0.001; %IMAT model 0.462, P < 0.001). Moreover, higher %IMAT and lower attenuation were associated with a higher mortality risk.

Conclusion

In patients with CKD, increased myosteatosis, as assessed by abdominal CT, was associated with old age, adiposity, metabolic dysfunction, and higher mortality risk.
A tiered strategy to identify relevant genetic variants in familial pulmonary fibrosis: a proof of concept for the clinical practice
Authors: Alonso-González Aitana , Véliz-Flores Ibrahim , Tosco-Herrera Eva , González-Barbuzano Silvia , Mendoza-Alvarez Alejandro , Galván-Fernández Helena , Sastre Leandro , Fernández-Varas Beatriz , Corrales Almudena , Rubio-Rodríguez Luis A. , Jáspez David , Lorenzo-Salazar José M. , Molina-Molina Maria , Rodríguez-de-Castro Felipe , González-Montelongo Rafaela , Flores Carlos
Published: January 2025

Idiopathic pulmonary fibrosis (IPF) is a progressive, late-onset disease marked by lung scarring and irreversible loss of lung function. Genetic factors significantly contribute to both familial and sporadic cases, yet there are scarce evidence-based studies highlighting the benefits of integrating genetics into the management of IPF patients. In this study, we performed whole-exome sequencing and telomere length (TL) measurements on IPF patients and their relatives. We then identified rare deleterious variants using three virtual gene panels encompassing IPF or TL genes with varying levels of evidence supporting their potential relationship with the disease. We identified 10 candidate variants in well-established disease genes, and these results were validated using two automatic prioritization tools (Exomiser and Franklin). Pathogenic variants were found in two telomere-related genes (RTEL1 and NAF1), and both were associated with severe TL shortening. Our results suggest that this tiered virtual panel strategy is sufficiently robust and serves as a viable solution in clinical practice. It generates valuable genetic data which can be interpreted and validated with the expertise of a multidisciplinary team.
Paracrine role of endothelial IGF-1 receptor in depot-specific adipose tissue adaptation in male mice
Authors: Luk Cheukyau , Bridge Katherine I. , Warmke Nele , Simmons Katie J. , Drozd Michael , Moran Amy , MacCannell Amanda D. V. , Cheng Chew W. , Straw Sam , Scragg Jason L. , Smith Jessica , Ozber Claire H. , Wilkinson Chloe G. , Skromna Anna , Makava Natallia , Prag Hiran A. , Simon Futers T. , Brown Oliver I. , Bruns Alexander-Francisco , Walker Andrew MN , Watt Nicole T. , Mughal Romana , Griffin Kathryn J. , Yuldasheva Nadira Y. , Limumpornpetch Sunti , Viswambharan Hema , Sukumar Piruthivi , Beech David J. , Vidal-Puig Antonio , Witte Klaus K. , Murphy Michael P. , Hartley Richard C. , Wheatcroft Stephen B. , Cubbon Richard M. , Roberts Lee D. , Kearney Mark T. , Haywood Natalie J.
Published: January 2025

During recent decades, changes in lifestyle have led to widespread nutritional obesity and its related complications. Remodelling adipose tissue as a therapeutic goal for obesity and its complications has attracted much attention and continues to be actively explored. The endothelium lines all blood vessels and is close to all cells, including adipocytes. The endothelium has been suggested to act as a paracrine organ. We explore the role of endothelial insulin-like growth factor-1 receptor (IGF-1R), as a paracrine modulator of white adipose phenotype. We show that a reduction in endothelial IGF-1R expression in the presence of high-fat feeding in male mice leads to depot-specific beneficial white adipose tissue remodelling, increases whole-body energy expenditure and enhances insulin sensitivity via a non-cell-autonomous paracrine mechanism. We demonstrate that increased endothelial malonate may be contributory and that malonate prodrugs have potentially therapeutically relevant properties in the treatment of obesity-related metabolic disease.
A soft thermal sensor for the continuous assessment of flow in vascular access
Authors: Deng Yujun , Arafa Hany M. , Yang Tianyu , Albadawi Hassan , Fowl Richard J. , Zhang Zefu , Kandula Viswajit , Ramesh Ashvita , Correia Chase , Huang Yonggang , Oklu Rahmi , Rogers John A. , Carlini Andrea S.
Published: January 2025

Hemodialysis for chronic kidney disease (CKD) relies on vascular access (VA) devices, such as arteriovenous fistulas (AVF), grafts (AVG), or catheters, to maintain blood flow. Nonetheless, unpredictable progressive vascular stenosis due to neointimal formation or complete occlusion from acute thrombosis remains the primary cause of mature VA failure. Despite emergent surgical intervention efforts, the lack of a reliable early detection tool significantly reduces patient outcomes and survival rates. This study introduces a soft, wearable device that continuously monitors blood flow for early detection of VA failure. Using thermal anemometry, integrated sensors noninvasively measure flow changes in large vessels. Bench testing with AVF and AVG models shows agreement with finite element analysis (FEA) simulations, while human and preclinical swine trials demonstrate the device’s sensitivity. Wireless adaptation could enable at-home monitoring, improving detection of VA-related complications and survival in CKD patients.
Distinct roles of dentate gyrus and medial entorhinal cortex inputs for phase precession and temporal correlations in the hippocampal CA3 area
Authors: Ahmadi Siavash , Sasaki Takuya , Sabariego Marta , Leibold Christian , Leutgeb Stefan , Leutgeb Jill K.
Published: January 2025

The hippocampal CA3 subregion is a densely connected recurrent circuit that supports memory by generating and storing sequential neuronal activity patterns that reflect recent experience. While theta phase precession is thought to be critical for generating sequential activity during memory encoding, the circuit mechanisms that support this computation across hippocampal subregions are unknown. By analyzing CA3 network activity in the absence of each of its theta-modulated external excitatory inputs, we show necessary and unique contributions of the dentate gyrus (DG) and the medial entorhinal cortex (MEC) to phase precession. DG inputs are essential for preferential spiking of CA3 cells during late theta phases and for organizing the temporal order of neuronal firing, while MEC inputs sharpen the temporal precision throughout the theta cycle. A computational model that accounts for empirical findings suggests that the unique contribution of DG inputs to theta-related spike timing is supported by targeting precisely timed inhibitory oscillations. Our results thus identify a novel and unique functional role of the DG for sequence coding in the CA3 circuit.
Pantothenate kinase 4 controls skeletal muscle substrate metabolism
Authors: Miranda-Cervantes Adriana , Fritzen Andreas M. , Raun Steffen H. , Hodek Ondřej , Møller Lisbeth L. V. , Johann Kornelia , Deisen Luisa , Gregorevic Paul , Gudiksen Anders , Artati Anna , Adamski Jerzy , Andersen Nicoline R. , Sigvardsen Casper M. , Carl Christian S. , Voldstedlund Christian T. , Kjøbsted Rasmus , Hauck Stefanie M. , Schjerling Peter , Jensen Thomas E. , Cebrian-Serrano Alberto , Jähnert Markus , Gottmann Pascal , Burtscher Ingo , Lickert Heiko , Pilegaard Henriette , Schürmann Annette , Tschöp Matthias H. , Moritz Thomas , Müller Timo D. , Sylow Lykke , Kiens Bente , Richter Erik A. , Kleinert Maximilian
Published: January 2025

Metabolic flexibility in skeletal muscle is essential for maintaining healthy glucose and lipid metabolism, and its dysfunction is closely linked to metabolic diseases. Exercise enhances metabolic flexibility, making it an important tool for discovering mechanisms that promote metabolic health. Here we show that pantothenate kinase 4 (PanK4) is a new conserved exercise target with high abundance in muscle. Muscle-specific deletion of PanK4 impairs fatty acid oxidation which is related to higher intramuscular acetyl-CoA and malonyl-CoA levels. Elevated acetyl-CoA levels persist regardless of feeding state and are associated with whole-body glucose intolerance, reduced insulin-stimulated glucose uptake in glycolytic muscle, and impaired glucose uptake during exercise. Conversely, increasing PanK4 levels in glycolytic muscle lowers acetyl-CoA and enhances glucose uptake. Our findings highlight PanK4 as an important regulator of acetyl-CoA levels, playing a key role in both muscle lipid and glucose metabolism.
Emergence of ferroelectricity in Sn-based perovskite semiconductor films by iminazole molecular reconfiguration
Authors: Liu Yu , Yang Shuzhang , Hua Lina , Yang Xiaomin , Li Enlong , Wen Jincheng , Wu Yanqiu , Zhu Liping , Yang Yingguo , Zhao Yan , An Zhenghua , Chu Junhao , Li Wenwu
Published: January 2025

Ferroelectric semiconductors have the advantages of switchable polarization ferroelectric field regulation and semiconductor transport characteristics, which are highly promising in ferroelectric transistors and nonvolatile memory. However, it is difficult to prepare a Sn-based perovskite film with both robust ferroelectric and semiconductor properties. Here, by doping with 2-methylbenzimidazole, Sn-based perovskite [93.3 mol% (FA0.86Cs0.14)SnI3 and 6.7 mol% PEA2SnI4] semiconductor films are transformed into ferroelectric semiconductor films, owing to molecular reconfiguration. The reconfigured ferroelectric semiconductors exhibit a high remanent polarization (Pr) of 23.2 μC/cm2. The emergence of ferroelectricity can be ascribed to the hydrogen bond enhancement after imidazole molecular doping, and then the spatial symmetry breaks causing the positive and negative charge centers to become non-coincident. Remarkably, the transistors based on perovskite ferroelectric semiconductors have a low subthreshold swing of 67 mv/dec, which further substantiates the superiority of introducing ferroelectricity. This work has developed a method to realize Sn-based ferroelectric semiconductor films for electronic device applications.
Essential and dual effects of Notch activity on a natural transdifferentiation event
Authors: Daniele Thomas , Cury Jeanne , Morin Marie-Charlotte , Ahier Arnaud , Isaia Davide , Jarriault Sophie
Published: January 2025

Cell identity can be reprogrammed, naturally or experimentally, albeit with low frequency. Why some cells, but not their neighbours, undergo a cell identity conversion remains unclear. We find that Notch signalling plays a key role to promote natural transdifferentiation in C. elegans hermaphrodites. Endogenous Notch signalling endows a cell with the competence to transdifferentiate by promoting plasticity factors expression (hlh-16/Olig and sem-4/Sall). Strikingly, ectopic Notch can trigger additional transdifferentiation in vivo. However, Notch signalling can both promote and block transdifferentiation depending on its activation timing. Notch only promotes transdifferentiation during an early precise window of opportunity and signal duration must be tightly controlled in time. Our findings emphasise the importance of temporality and dynamics of the underlying molecular events preceding the initiation of natural cell reprogramming. Finally, our results support a model where both an extrinsic signal and the intrinsic cellular context combine to empower a cell with the competence to transdifferentiate.
Genomic and phenotypic stability of fusion-driven pediatric sarcoma cell lines
Authors: Kasan Merve , Geyer Florian H. , Siebenlist Jana , Sill Martin , Öllinger Rupert , Faehling Tobias , de Álava Enrique , Surdez Didier , Dirksen Uta , Oehme Ina , Scotlandi Katia , Delattre Olivier , Müller-Nurasyid Martina , Rad Roland , Strauch Konstantin , Grünewald Thomas G. P. , Cidre-Aranaz Florencia
Published: January 2025

Human cancer cell lines are the mainstay of cancer research. Recent reports showed that highly mutated adult carcinoma cell lines (mainly HeLa and MCF-7) present striking diversity across laboratories and that long-term continuous culturing results in genomic/transcriptomic heterogeneity with strong phenotypical implications. Here, we hypothesize that oligomutated pediatric sarcoma cell lines mainly driven by a fusion transcription factor, such as Ewing sarcoma (EwS), are genetically and phenotypically more stable than the previously investigated adult carcinoma cell lines. A comprehensive molecular and phenotypic characterization of multiple EwS cell line strains, together with a simultaneous analysis during 12 months of continuous cell culture show that fusion-driven pediatric sarcoma cell line strains are genomically more stable than adult carcinoma strains, display remarkably stable and homogenous transcriptomes, and exhibit uniform and stable drug response. Additionally, the analysis of multiple EwS cell lines subjected to long-term continuous culture reveals that variable degrees of genomic/transcriptomic/phenotypic changes among fusion-driven cell lines, further exemplifying that the potential for reproducibility of in vitro scientific results may be rather understood as a spectrum, even within the same tumor entity.
Design principles for engineering bacteria to maximise chemical production from batch cultures
Authors: Mannan Ahmad A. , Darlington Alexander P. S. , Tanaka Reiko J. , Bates Declan G.
Published: January 2025

Bacteria can be engineered to manufacture chemicals, but it is unclear how to optimally engineer a single cell to maximise production performance from batch cultures. Moreover, the performance of engineered production pathways is affected by competition for the host’s native resources. Here, using a ‘host-aware’ computational framework which captures competition for both metabolic and gene expression resources, we uncover design principles for engineering the expression of host and production enzymes at the cell level which maximise volumetric productivity and yield from batch cultures. However, this does not break the fundamental growth-synthesis trade-off which limits production performance. We show that engineering genetic circuits to switch cells to a high synthesis-low growth state after first growing to a large population can further improve performance. By analysing different circuit topologies, we show that highest performance is achieved by circuits that inhibit host metabolism to redirect it to product synthesis. Our results should facilitate construction of microbial cell factories with high and efficient production capabilities.
Overcoming optical losses in thin metal-based recombination layers for efficient n-i-p perovskite-organic tandem solar cells
Authors: Tian Jingjing , Liu Chao , Forberich Karen , Barabash Anastasia , Xie Zhiqiang , Qiu Shudi , Byun Jiwon , Peng Zijian , Zhang Kaicheng , Du Tian , Sathasivam Sanjayan , Macdonald Thomas J. , Dong Lirong , Li Chaohui , Zhang Jiyun , Halik Marcus , Le Corre Vincent M. , Osvet Andres , Heumüller Thomas , Li Ning , Zhou Yinhua , Lüer Larry , Brabec Christoph J.
Published: January 2025

Perovskite-organic tandem solar cells (P-O-TSCs) hold substantial potential to surpass the theoretical efficiency limits of single-junction solar cells. However, their performance is hampered by non-ideal interconnection layers (ICLs). Especially in n-i-p configurations, the incorporation of metal nanoparticles negatively introduces serious parasitic absorption, which alleviates photon utilization in organic rear cell and decisively constrains the maximum photocurrent matching with front cell. Here, we demonstrate an efficient strategy to mitigate optical losses in Au-embedded ICLs by tailoring the shape and size distribution of Au nanoparticles via manipulating the underlying surface property. Achieving fewer, smaller, and more uniformly spherical Au nanoparticles significantly minimizes localized surface plasmon resonance absorption, while maintaining efficient electron-hole recombination within ICLs. Consequently, optimized P-O-TSCs combining CsPbI2Br with various organic cells benefit from a substantial current gain of >1.5 mA/cm2 in organic rear cells, achieving a champion efficiency of 25.34%. Meanwhile, optimized ICLs contribute to improved long-term device stability.
Single-neuron spiking variability in hippocampus dynamically tracks sensory content during memory formation in humans
Authors: Waschke Leonhard , Kamp Fabian , van den Elzen Evi , Krishna Suresh , Lindenberger Ulman , Rutishauser Ueli , Garrett Douglas D.
Published: January 2025

During memory formation, the hippocampus is presumed to represent the content of stimuli, but how it does so is unknown. Using computational modelling and human single-neuron recordings, we show that the more precisely hippocampal spiking variability tracks the composite features of each individual stimulus, the better those stimuli are later remembered. We propose that moment-to-moment spiking variability may provide a new window into how the hippocampus constructs memories from the building blocks of our sensory world.
E4F1 coordinates pyruvate metabolism and the activity of the elongator complex to ensure translation fidelity during brain development
Authors: Di Michele Michela , Attina Aurore , Roux Pierre-François , Tabet Imène , Laguesse Sophie , Florido Javier , Houdeville Morane , Choquet Armelle , Encislai Betty , Arena Giuseppe , De Blasio Carlo , Wendling Olivia , Frenois François-Xavier , Papon Laura , Stuani Lucille , Fuentes Maryse , Jahannault Talignani Céline , Rousseau Mélanie , Guégan Justine , Buscail Yoan , Dupré Pierrick , Michaud Henri-Alexandre , Rodier Geneviève , Bellvert Floriant , Kulyk Hanna , Ferraro Peyret Carole , Mathieu Hugo , Close Pierre , Rapino Francesca , Chaveroux Cédric , Pirot Nelly , Rubio Lucie , Torro Adeline , Sorg Tania , Ango Fabrice , Hirtz Christophe , Compan Vincent , Lebigot Elise , Legati Andrea , Ghezzi Daniele , Nguyen Laurent , David Alexandre , Sardet Claude , Lacroix Matthieu , Le Cam Laurent
Published: January 2025

Pyruvate metabolism defects lead to severe neuropathies such as the Leigh syndrome (LS) but the molecular mechanisms underlying neuronal cell death remain poorly understood. Here, we unravel a connection between pyruvate metabolism and the regulation of the epitranscriptome that plays an essential role during brain development. Using genetically engineered mouse model and primary neuronal cells, we identify the transcription factor E4F1 as a key coordinator of AcetylCoenzyme A (AcCoA) production by the pyruvate dehydrogenase complex (PDC) and its utilization as an essential co-factor by the Elongator complex to acetylate tRNAs at the wobble position uridine 34 (U34). E4F1-mediated direct transcriptional regulation of Dlat and Elp3, two genes encoding key subunits of the PDC and of the Elongator complex, respectively, ensures proper translation fidelity and cell survival in the central nervous system (CNS) during mouse embryonic development. Furthermore, analysis of PDH-deficient cells highlight a crosstalk linking the PDC to ELP3 expression that is perturbed in LS patients.
diaTracer enables spectrum-centric analysis of diaPASEF proteomics data
Authors: Li Kai , Teo Guo Ci , Yang Kevin L. , Yu Fengchao , Nesvizhskii Alexey I.
Published: January 2025

Data-independent acquisition has become a widely used strategy for peptide and protein quantification in liquid chromatography-tandem mass spectrometry-based proteomics studies. The integration of ion mobility separation into data-independent acquisition analysis, such as the diaPASEF technology available on Bruker’s timsTOF platform, further improves the quantification accuracy and protein depth achievable using data-independent acquisition. We introduce diaTracer, a spectrum-centric computational tool optimized for diaPASEF data. diaTracer performs three-dimensional (mass to charge ratio, retention time, ion mobility) peak tracing and feature detection to generate precursor-resolved “pseudo-tandem mass spectra”, facilitating direct (“spectral-library free”) peptide identification and quantification from diaPASEF data. diaTracer is available as a stand-alone tool and is fully integrated into the widely used FragPipe computational platform. We demonstrate the performance of diaTracer and FragPipe using diaPASEF data from triple-negative breast cancer, cerebrospinal fluid, and plasma samples, data from phosphoproteomics and human leukocyte antigens immunopeptidomics experiments, and low-input data from a spatial proteomics study. We also show that diaTracer enables unrestricted identification of post-translational modifications from diaPASEF data using open/mass-offset searches.
Compound electron acceleration at planetary foreshocks
Authors: Shi Xiaofei , Artemyev Anton , Angelopoulos Vassilis , Liu Terry , Wilson III Lynn B.
Published: January 2025

Shock waves, the interface of supersonic and subsonic plasma flows, are the primary region for charged particle acceleration in multiple space plasma systems, including Earth’s bow shock, which is readily accessible for in-situ measurements. Spacecraft frequently observe relativistic electron populations within this region, characterized by energy levels surpassing those of solar wind electrons by a factor of 10,000 or more. However, mechanisms of such strong acceleration remain elusive. Here we use observations of electrons with energies up to 200 kiloelectron volts and a data-constrained model to reproduce the observed power-law electron spectrum and demonstrate that the acceleration by more than 4 orders of magnitude is a compound process including a complex, multi-step interaction between more commonly known mechanisms and resonant scattering by several distinct plasma wave modes. The proposed model of electron acceleration addresses a decades-long issue of the generation of energetic (and relativistic) electrons at planetary plasma shocks. This work may further guide numerical simulations of even more effective electron acceleration in astrophysical shocks.
MCM2-7 ring closure involves the Mcm5 C-terminus and triggers Mcm4 ATP hydrolysis
Authors: Faull Sarah V. , Barbon Marta , Mossler Audrey , Yuan Zuanning , Bai Lin , Reuter L. Maximilian , Riera Alberto , Winkler Christian , Magdalou Indiana , Peach Matthew , Li Huilin , Speck Christian
Published: January 2025

The eukaryotic helicase MCM2-7, is loaded by ORC, Cdc6 and Cdt1 as a double-hexamer onto replication origins. The insertion of DNA into the helicase leads to partial MCM2-7 ring closure, while ATP hydrolysis is essential for consecutive steps in pre-replicative complex (pre-RC) assembly. Currently it is unknown how MCM2-7 ring closure and ATP-hydrolysis are controlled. A cryo-EM structure of an ORC-Cdc6-Cdt1-MCM2-7 intermediate shows a remodelled, fully-closed Mcm2/Mcm5 interface. The Mcm5 C-terminus (C5) contacts Orc3 and specifically recognises this closed ring. Interestingly, we found that normal helicase loading triggers Mcm4 ATP-hydrolysis, which in turn leads to reorganisation of the MCM2-7 complex and Cdt1 release. However, defective MCM2-7 ring closure, due to mutations at the Mcm2/Mcm5 interface, leads to MCM2-7 ring splitting and complex disassembly. As such we identify Mcm4 as the key ATPase in regulating pre-RC formation. Crucially, a stable Mcm2/Mcm5 interface is essential for productive ATP-hydrolysis-dependent remodelling of the helicase.
Generalized cue reactivity in rat dopamine neurons after opioids
Authors: Lehmann Collin M. , Miller Nora E. , Nair Varun S. , Costa Kauê M. , Schoenbaum Geoffrey , Moussawi Khaled
Published: January 2025

Cue reactivity is the maladaptive neurobiological and behavioral response upon exposure to drug cues and is a major driver of relapse. A widely accepted assumption is that drugs of abuse result in disparate dopamine responses to cues that predict drug vs. natural rewards. The leading hypothesis is that drug-induced dopamine release represents a persistently positive reward prediction error that causes runaway enhancement of dopamine responses to drug cues, leading to their pathological overvaluation. However, this hypothesis has not been directly tested. Here, we develop Pavlovian and operant procedures in male rats to measure firing responses within the same dopamine neurons to drug versus natural reward cues, which we find to be similarly enhanced compared to cues predicting natural rewards in drug-naive controls. This enhancement is associated with increased behavioral reactivity to the drug cue, suggesting that dopamine neuronal activity may still be relevant to cue reactivity, albeit not as previously hypothesized. These results challenge the prevailing hypothesis of cue reactivity, warranting revised models of dopaminergic function in opioid addiction, and provide insights into the neurobiology of cue reactivity with potential implications for relapse prevention.
Feshbach hypothesis of high-Tc superconductivity in cuprates
Authors: Homeier Lukas , Lange Hannah , Demler Eugene , Bohrdt Annabelle , Grusdt Fabian
Published: January 2025

Resonant interactions associated with the emergence of a bound state constitute one of the cornerstones of modern many-body physics. Here we present a Feshbach perspective on the origin of strong pairing in Fermi-Hubbard type models. We perform a theoretical analysis of interactions between spin-polaron charge carriers in doped Mott insulators, modeled by a near-resonant two-channel scattering problem, and report evidence for Feshbach-type interactions in the $${d}_{{x}^{2}-{y}^{2}}$$

d

x

2

−

y

2

channel, consistent with the established phenomenology of cuprates. Existing experimental and numerical results on hole-doped cuprates lead us to conjecture the existence of a light, long-lived, low-energy excited state of two holes, which enables near-resonant interactions. To put our theory to a test we suggest to use coincidence angle-resolved photoemission spectroscopy (cARPES), pair-tunneling measurements or pump-probe experiments. The emergent Feshbach resonance among spin-polarons could also underlie superconductivity in other doped antiferromagnetic Mott insulators highlighting its potential as a unifying strong-coupling pairing mechanism rooted in quantum magnetism.
High-entropy alloys catalyzing polymeric transformation of water pollutants with remarkably improved electron utilization efficiency
Authors: Yao Ziwei , Chen Yidi , Wang Xiaodan , Hu Kunsheng , Ren Shiying , Zhang Jinqiang , Song Zhao , Ren Nanqi , Duan Xiaoguang
Published: January 2025

High-entropy alloy nanoparticles (HEA-NPs) exhibit favorable properties in catalytic processes, as their multi-metallic sites ensure both high intrinsic activity and atomic efficiency. However, controlled synthesis of uniform multi-metallic ensembles at the atomic level remains challenging. This study successfully loads HEA-NPs onto a nitrogen-doped carbon carrier (HEAs) and pioneers the application in peroxymonosulfate (PMS) activation to drive Fenton-like oxidation. The HEAs-PMS system achieves ultrafast pollutant removal across a wide pH range with strong resistance to real-world water interferences. Furthermore, the nonradical HEAs-PMS system selectively transforms phenolics into high-molecular-weight products via a polymerization pathway. The unique non-mineralization regime remarkably reduces PMS consumption and achieves a high electron utilization efficiency of up to 213.4%. Further DFT calculations and experimental analysis reveal that Fe and Co in HEA-NPs act as the primary catalytic sites to complex with PMS for activation, while Ni, Cu, and Pd serve as charge mediators to facilitate electron transfer. The resulting PMS* complexes on HEAs possess a high redox potential, which drives spatially separated phenol oxidation on nitrogen-doped graphene support to form phenoxyl radicals, subsequently triggering the formation of high-molecule polymeric products via polymerization reactions. This study offers engineered HEAs catalysts for water treatment with low oxidant consumption and emissions.
NHSL3 controls single and collective cell migration through two distinct mechanisms
Authors: Novikov Nikita M. , Gao Jinmei , Fokin Artem I. , Rocques Nathalie , Chiappetta Giovanni , Rysenkova Karina D. , Zea Diego Javier , Polesskaya Anna , Vinh Joelle , Guerois Raphael , Gautreau Alexis M.
Published: January 2025

The molecular mechanisms underlying cell migration remain incompletely understood. Here, we show that knock-out cells for NHSL3, the most recently identified member of the Nance-Horan Syndrome family, are more persistent than parental cells in single cell migration, but that, in wound healing, follower cells are impaired in their ability to follow leader cells. The NHSL3 locus encodes several isoforms. We identify the partner repertoire of each isoform using proteomics and predict direct partners and their binding sites using an AlphaFold2-based pipeline. Rescue with specific isoforms, and lack of rescue when relevant binding sites are mutated, establish that the interaction of a long isoform with MENA/VASP proteins is critical at cell-cell junctions for collective migration, while the interaction of a short one with 14-3-3θ in lamellipodia is critical for single cell migration. Taken together, these results demonstrate that NHSL3 regulates single and collective cell migration through distinct mechanisms.
Neurophysiological gradient in the Parkinsonian subthalamic nucleus as a marker for motor symptoms and apathy
Authors: Bernasconi Elena , Amstutz Deborah , Averna Alberto , Fischer Petra , Sousa Mario , Debove Ines , Petermann Katrin , Alva Laura , Magalhães Andreia D. , Lachenmayer M. Lenard , Nguyen Thuy-Anh K. , Schuepbach Michael , Nowacki Andreas , Pollo Claudio , Krack Paul , Tinkhauser Gerd
Published: January 2025

Sensing-based deep brain stimulation should optimally consider both the motor and neuropsychiatric domain to maximize quality of life of Parkinson’s disease (PD) patients. Here we characterize the neurophysiological properties of the subthalamic nucleus (STN) in 69 PD patients using a newly established neurophysiological gradient metric and contextualize it with motor symptoms and apathy. We could evidence a STN power gradient that holds most of the spectral information between 5 and 30 Hz spanning along the dorsal-ventral axis. It shows elevated power in the sub-beta range (8-12 Hz) toward the ventral STN, and elevated dorsal beta power (16–24 Hz) indicative for the hemispheres contralateral to the more affected hemi-body side. The rigidity response to DBS was highest dorsally on the axis. Importantly, apathetic symptoms can be related to reduced ventral alpha power. In conclusion, the STN spectral gradient may inform about the motor and neuropsychiatric domain, supporting integrative closed-loop strategies.
Chemical versus physical pressure effects on the structure transition of bilayer nickelates
Authors: Wang Gang , Wang Ningning , Lu Tenglong , Calder Stuart , Yan Jiaqiang , Shi Lifen , Hou Jun , Ma Liang , Zhang Lili , Sun Jianping , Wang Bosen , Meng Sheng , Liu Miao , Cheng Jinguang
Published: January 2025

The observation of high-Tc superconductivity (HTSC) in concomitant with pressure-induced orthorhombic-tetragonal structural transition in bilayer La3Ni2O7 has sparked hopes of achieving HTSC by stabilizing the tetragonal phase at ambient pressure. Chemical pressure, introduced by replacing La3+ with smaller rare-earth R3+ has been considered as a potential route. However, our experimental and theoretical investigation reveals that such substitutions, despite causing lattice contraction, actually produce stronger orthorhombic distortions, requiring higher pressures for the structural transition. A linear extrapolation of Pc versus the average size of A-site cations (), yields a putative critical value of c ≈ 1.23 Å for Pc ≈ 1 bar. The negative correlation between Pc and  indicates that replacing La3+ with smaller R3+ ions is unlikely to reduce Pc to ambient pressure. Instead, substituting La3+ with larger cations like Sr2+ or Ba2+ might be a feasible approach. Our results provide guidance for realizing ambient-pressure HTSC in bilayer nickelates.
Efficient micromirror confinement of sub-teraelectronvolt cosmic rays in galaxy clusters
Authors: Reichherzer Patrick , Bott Archie F. A. , Ewart Robert J. , Gregori Gianluca , Kempski Philipp , Kunz Matthew W. , Schekochihin Alexander A.
Published: January 2025

Cosmic rays (CRs) play a pivotal role in shaping the thermal and dynamical properties of astrophysical environments, such as galaxies and galaxy clusters. Recent observations suggest a stronger confinement of CRs in certain astrophysical systems than predicted by current CR-transport theories. Here, we show that the incorporation of microscale physics into CR-transport models can account for this enhanced CR confinement. We develop a theoretical description of the effect of magnetic microscale fluctuations originating from the mirror instability on macroscopic CR diffusion. We confirm our theory with large-dynamical-range simulations of CR transport in the intracluster medium (ICM) of galaxy clusters and kinetic simulations of CR transport in micromirror fields. We conclude that sub-teraelectronvolt CR confinement in the ICM is far more effective than previously anticipated on the basis of Galactic-transport extrapolations. The transformative impact of micromirrors on CR diffusion provides insights into how microphysics can reciprocally affect macroscopic dynamics and observable structures across a range of astrophysical scales.
Analysis of multi-condition single-cell data with latent embedding multivariate regression
Authors: Ahlmann-Eltze Constantin , Huber Wolfgang
Published: January 2025

Identifying gene expression differences in heterogeneous tissues across conditions is a fundamental biological task, enabled by multi-condition single-cell RNA sequencing (RNA-seq). Current data analysis approaches divide the constituent cells into clusters meant to represent cell types, but such discrete categorization tends to be an unsatisfactory model of the underlying biology. Here, we introduce latent embedding multivariate regression (LEMUR), a model that operates without, or before, commitment to discrete categorization. LEMUR (1) integrates data from different conditions, (2) predicts each cell’s gene expression changes as a function of the conditions and its position in latent space and (3) for each gene, identifies a compact neighborhood of cells with consistent differential expression. We apply LEMUR to cancer, zebrafish development and spatial gradients in Alzheimer’s disease, demonstrating its broad applicability.
Evaluating generalizability of oncology trial results to real-world patients using machine learning-based trial emulations
Authors: Orcutt Xavier , Chen Kan , Mamtani Ronac , Long Qi , Parikh Ravi B.
Published: January 2025

Randomized controlled trials (RCTs) evaluating anti-cancer agents often lack generalizability to real-world oncology patients. Although restrictive eligibility criteria contribute to this issue, the role of selection bias related to prognostic risk remains unclear. In this study, we developed TrialTranslator, a framework designed to systematically evaluate the generalizability of RCTs for oncology therapies. Using a nationwide database of electronic health records from Flatiron Health, this framework emulates RCTs across three prognostic phenotypes identified through machine learning models. We applied this approach to 11 landmark RCTs that investigated anti-cancer regimens considered standard of care for the four most prevalent advanced solid malignancies. Our analyses reveal that patients in low-risk and medium-risk phenotypes exhibit survival times and treatment-associated survival benefits similar to those observed in RCTs. In contrast, high-risk phenotypes show significantly lower survival times and treatment-associated survival benefits compared to RCTs. Our results were corroborated by a comprehensive robustness assessment, including examinations of specific patient subgroups, holdout validation and semi-synthetic data simulation. These findings suggest that the prognostic heterogeneity among real-world oncology patients plays a substantial role in the limited generalizability of RCT results. Machine learning frameworks may facilitate individual patient-level decision support and estimation of real-world treatment benefits to guide trial design.
Orthology inference at scale with FastOMA
Authors: Majidian Sina , Nevers Yannis , Yazdizadeh Kharrazi Ali , Warwick Vesztrocy Alex , Pascarelli Stefano , Moi David , Glover Natasha , Altenhoff Adrian M. , Dessimoz Christophe
Published: January 2025

The surge in genome data, with ongoing efforts aiming to sequence 1.5 M eukaryotes in a decade, could revolutionize genomics, revealing the origins, evolution and genetic innovations of biological processes. Yet, traditional genomics methods scale poorly with such large datasets. Here, addressing this, ‘FastOMA’ provides linear scalability for orthology inference, enabling the processing of thousands of eukaryotic genomes within a day. FastOMA maintains the high accuracy and resolution of the well-established Orthologous Matrix (OMA) approach in benchmarks. FastOMA is available via GitHub at https://github.com/DessimozLab/FastOMA/.