bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Y178C rhodopsin mutation causes aggregation and comparatively severe retinal degeneration
Authors: Vasudevan Sreelakshmi , Park Paul S.–H. 
Published: January 2025

Abstract
Rhodopsin is the light-activated G protein-coupled receptor that initiates vision in photoreceptor cells of the retina. Numerous mutations in rhodopsin promote receptor misfolding and aggregation, causing autosomal dominant retinitis pigmentosa, a progressive retinal degenerative disease. The mechanism by which these mutations cause photoreceptor cell death, and the role aggregation plays in this process is still unclear. We recently demonstrated with the P23H and G188R rhodopsin mutants that the severity of aggregation observed in vitro is also reflected in vivo and impacts the rate of retinal degeneration. A Y178C rhodopsin mutant was investigated here to determine if this relationship applies broadly among mutations that cause misfolding and aggregation of the receptor. In vitro characterization indicated the Y178C rhodopsin mutant exhibits similar properties to the more severely aggregating G188R rhodopsin mutant, where the mutant is mislocalized to the endoplasmic reticulum in HEK293 cells and form aggregates that cannot be rescued by treatment with the retinoid 9-cis retinal. Despite these similarities in vitro, the Y178C rhodopsin mutant promoted a more severe retinal degeneration compared to the G188R mutant in vivo in mice. Aggregates of the Y178C rhodopsin mutant labeled by the dye PROTEOSTAT were morphologically similar to those formed by both the P23H and G188R rhodopsin mutants. There was, however, significantly greater photoreceptor cell death occurring independently of PROTEOSTAT-labeled aggregates in mice expressing the Y178C rhodopsin mutant compared to those expressing either the P23H or G188R rhodopsin mutants. Here, we demonstrate that PROTEOSTAT-labeled aggregates are not the sole cause of photoreceptor cell death promoted by the Y178C rhodopsin mutation in vivo, and there may be alternate aggregate forms contributing to cell death in these mice.
Single cell profiling of circulating autoreactive CD4 T cells from patients with autoimmune liver diseases suggests tissue imprinting
Authors: Cardon Anaïs , Guinebretière Thomas , Dong Chuang , Gil Laurine , Ado Sakina , Gavlovsky Pierre-jean , Braud Martin , Danger Richard , Schultheiß Christoph , Doméné Aurélie , Paul-Gilloteaux Perrine , Chevalier Caroline , Bernier Laura , Judor Jean-Paul , Fourgeux Cynthia , Imbert Astrid , Khaldi Marion , Bardou-Jacquet Edouard , Elkrief Laure , Lannes Adrien , Silvain Christine , Schnee Matthieu , Tanne Florence , Vavasseur Fabienne , Brusselle Lucas , Brouard Sophie , Kwok William W. , Mosnier Jean-François , Lohse Ansgar W. , Poschmann Jeremie , Binder Mascha , Gournay Jérôme , Conchon Sophie , Milpied Pierre , Renand Amédée 
Published: January 2025

Abstract
Autoimmune liver diseases (AILD) involve dysregulated CD4 T cell responses against liver self-antigens, but how these autoreactive T cells relate to liver tissue pathology remains unclear. Here we perform single-cell transcriptomic and T cell receptor analyses of circulating, self-antigen-specific CD4 T cells from patients with AILD and identify a subset of liver-autoreactive CD4 T cells with a distinct B-helper transcriptional profile characterized by PD-1, TIGIT and HLA-DR expression. These cells share clonal relationships with expanded intrahepatic T cells and exhibit transcriptional signatures overlapping with tissue-resident T cells in chronically inflamed environments. Using a mouse model, we demonstrate that, following antigen recognition in the liver, CD4 T cells acquire an exhausted phenotype, play a crucial role in liver damage, and are controlled by immune checkpoint pathways. Our findings thus suggest that circulating autoreactive CD4 T cells in AILD are imprinted by chronic antigen exposure to promote liver inflammation, thereby serving as a potential target for developing biomarkers and therapies for AILD.
Biological correlates associated with high-risk breast cancer patients identified using a computational method
Authors: Oh Jung Hun , Pareja Fresia , Elkin Rena , Xu Kaiming , Norton Larry , Deasy Joseph O. 
Published: January 2025

Abstract
Using a novel unsupervised method to integrate multi-omic data, we previously identified a breast cancer group with a poor prognosis. In the current study, we characterize the biological features of this subgroup, defined as the high-risk group, using various data sources. Assessment of three published hypoxia signatures showed that the high-risk group exhibited higher hypoxia scores (p < 0.0001 in all three signatures), compared to the low-risk group. Our analysis of the immune cell composition using CIBERSORT and leukocyte fraction showed significant differences between the high and low-risk groups across the entire cohort, as well as within PAM50 subtypes. Within the basal subtype, the low-risk group had a statistically significantly higher spatial fraction of tumor-infiltrating lymphocytes (TILs) compared to the high-risk group (p = 0.0362). Our findings indicate that this subgroup with poor prognosis is driven by a distinct biological signature with high activation of hypoxia-related genes as well as a low number of TILs.
The Ronne Ice Shelf survived the last interglacial
Authors: Wolff Eric W. , Mulvaney Robert , Grieman Mackenzie M. , Hoffmann Helene M. , Humby Jack , Nehrbass-Ahles Christoph , Rhodes Rachael H. , Rowell Isobel F. , Sime Louise C. , Fischer Hubertus , Stocker Thomas F. , Landais Amaelle , Parrenin Frédéric , Steig Eric J. , Dütsch Marina , Golledge Nicholas R. 
Published: January 2025

Abstract
The fate of the West Antarctic Ice Sheet (WAIS)1 is the largest cause of uncertainty in long-term sea-level projections. In the last interglacial (LIG) around 125,000 years ago, data suggest that sea level was several metres higher than today2–4, and required a significant contribution from Antarctic ice loss, with WAIS usually implicated. Antarctica and the Southern Ocean were warmer than today5–8, by amounts comparable to those expected by 2100 under moderate to high future warming scenarios. However, direct evidence about the size of WAIS in the LIG is sparse. Here we use sea salt data from an ice core from Skytrain Ice Rise, adjacent to WAIS, to show that, during most of the LIG, the Ronne Ice Shelf was still in place, and close to its current extent. Water isotope data are consistent with a retreat of WAIS9, but seem inconsistent with more dramatic model realizations10 in which both WAIS and the large Antarctic ice shelves were lost. This new constraint calls for a reappraisal of other elements of the LIG sea-level budget. It also weakens the observational basis that motivated model simulations projecting the highest end of projections for future rates of sea-level rise to 2300 and beyond.
AAV capsid prioritization in normal and steatotic human livers maintained by machine perfusion
Authors: Kim Jae-Jun , Kurial Simone N. T. , Choksi Pervinder K. , Nunez Miguel , Lunow-Luke Tyler , Bartel Jan , Driscoll Julia , Her Chris L. , Dhillon Simaron , Yue William , Murti Abhishek , Mao Tin , Ramos Julian N. , Tiyaboonchai Amita , Grompe Markus , Mattis Aras N. , Syed Shareef M. , Wang Bruce M. , Maher Jacquelyn J. , Roll Garrett R. , Willenbring Holger 
Published: January 2025

Abstract
Therapeutic efficacy and safety of adeno-associated virus (AAV) liver gene therapy depend on capsid choice. To predict AAV capsid performance under near-clinical conditions, we established side-by-side comparison at single-cell resolution in human livers maintained by normothermic machine perfusion. AAV-LK03 transduced hepatocytes much more efficiently and specifically than AAV5, AAV8 and AAV6, which are most commonly used clinically, and AAV-NP59, which is better at transducing human hepatocytes engrafted in immune-deficient mice. AAV-LK03 preferentially transduced periportal hepatocytes in normal liver, whereas AAV5 targeted pericentral hepatocytes in steatotic liver. AAV5 and AAV8 transduced liver sinusoidal endothelial cells as efficiently as hepatocytes. AAV capsid and steatosis influenced vector episome formation, which determines gene therapy durability, with AAV5 delaying concatemerization. Our findings inform capsid choice in clinical AAV liver gene therapy, including consideration of disease-relevant hepatocyte zonation and effects of steatosis, and facilitate the development of AAV capsids that transduce hepatocytes or other therapeutically relevant cell types in the human liver with maximum efficiency and specificity.
Variable stressor exposure shapes fitness within and across generations
Authors: Lee Marcus 
Published: January 2025

Abstract
Environmental variation has long been considered a key driver of evolutionary change, predicted to shape different strategies, such as genetic specialization, plasticity, or bet-hedging to maintain fitness. However, little evidence is available with regards to how the periodicity of stressors may impact fitness across generations. To address this gap, I conducted a reciprocal split-brood experiment using the freshwater crustacean, Daphnia magna, and an ecologically relevant environmental stressor, ultraviolet radiation (UVR). I exposed one group to constant and another group to fluctuating UVR conditions. Despite receiving the same dose of UVR, the first experimental generation displayed significant treatment-by-genotype interactions with respect to survival and reproductive output, as well as a delayed reproductive maturity under fluctuating UVR conditions. In the following experimental generation individuals exposed to fluctuating UVR exhibited higher fitness than those in a constant UVR regime. The ancestral conditions, i.e., maternal environment, however affected the survival probability and reproductive output, but did not significantly influence the maturation date. Overall, I demonstrate that the delivery of a stressor, not just its intensity, can have profound fitness consequences across generations, with important implications for seasonal succession of genotype–phenotype patterns in natural environments.
Evaluation of the Digital Ventilated Cage® system for circadian phenotyping
Authors: Tir Selma , Foster Russell G. , Peirson Stuart N. 
Published: January 2025

Abstract
The study of circadian rhythms has been critically dependent upon analysing mouse home cage activity, typically employing wheel running activity under different lighting conditions. Here we assess a novel method, the Digital Ventilated Cage (DVC®, Tecniplast SpA, Italy), for circadian phenotyping. Based upon capacitive sensors mounted under black individually ventilated cages with inbuilt LED lighting, each cage becomes an independent light-controlled chamber. Home cage activity in C57BL/6J mice was recorded under a range of lighting conditions, along with circadian clock-deficient cryptochrome-deficient mice (Cry1

−/−
, Cry2

−/−
double knockout). C57BL/6J mice exhibited a 24 h period under light/dark conditions, with a free-running period of 23.5 h under constant dark, and period lengthening under constant light. Animals displayed expected phase shifting responses to jet-lag and nocturnal light pulses. Sex differences in circadian parameters and phase shifting responses were also observed. Cryptochrome-deficient mice showed subtle changes in activity under light/dark conditions and were arrhythmic under constant dark, as expected. Our results show the suitability of the DVC system for circadian behavioural screens, accurately detecting circadian period, circadian disruption, phase shifts and mice with clock defects. We provide an evaluation of the strengths and limitations of this method, highlighting how the use of the DVC for studying circadian rhythms depends upon the research requirements of the end user.
Chemical- and photo-activation of protein-protein thiol-ene coupling for protein profiling
Authors: Campaniҫo André , Baran Marcin , Bowie Andrew G. , Longley Daniel B. , Harrison Timothy , McGouran Joanna F. 
Published: January 2025

Abstract
The thiol-ene reaction between an alkene and a thiol can be exploited for selective labelling of cysteine residues in protein profiling applications. Here, we explore thiol-ene activation in systems from chemical models to complex cellular milieus, using UV, visible wavelength and redox initiators. Initial studies in chemical models required an oxygen-free environment for efficient coupling and showed very poor activation when using a redox initiator. When thiol-ene activation was performed in protein and cell lysate models, all three initiation methods were successful. Faster thiol-ene reaction was observed as the cysteine and alkene were brought into proximity by a binding event prior to activation, leading to quicker adduct formation in the protein model system than the chemical models. Furthermore, in the protein-protein coupling, none of the activators required an oxygen-free environment. Taken together, these observations demonstrate the broad potential for thiol-ene coupling to be used in protein profiling.
Spatially resolved transcriptomics and graph-based deep learning improve accuracy of routine CNS tumor diagnostics
Authors: Ritter Michael , Blume Christina , Tang Yiheng , Patel Areeba , Patel Bhuvic , Berghaus Natalie , Kada Benotmane Jasim , Kueckelhaus Jan , Yabo Yahaya , Zhang Junyi , Grabis Elena , Villa Giulia , Zimmer David Niklas , Khriesh Amir , Sievers Philipp , Seferbekova Zaira , Hinz Felix , Ravi Vidhya M. , Seiz-Rosenhagen Marcel , Ratliff Miriam , Herold-Mende Christel , Schnell Oliver , Beck Juergen , Wick Wolfgang , von Deimling Andreas , Gerstung Moritz , Heiland Dieter Henrik , Sahm Felix 
Published: January 2025

Abstract
The diagnostic landscape of brain tumors integrates comprehensive molecular markers alongside traditional histopathological evaluation. DNA methylation and next-generation sequencing (NGS) have become a cornerstone in central nervous system (CNS) tumor classification. A limiting requirement for NGS and methylation profiling is sufficient DNA quality and quantity, which restrict its feasibility. Here we demonstrate NePSTA (neuropathology spatial transcriptomic analysis) for comprehensive morphological and molecular neuropathological diagnostics from single 5-µm tissue sections. NePSTA uses spatial transcriptomics with graph neural networks for automated histological and molecular evaluations. Trained and evaluated across 130 participants with CNS malignancies and healthy donors across four medical centers, NePSTA predicts tissue histology and methylation-based subclasses with high accuracy. We demonstrate the ability to reconstruct immunohistochemistry and genotype profiling on tissue with minimal requirements, inadequate for conventional molecular diagnostics, demonstrating the potential to enhance tumor subtype identification with implications for fast and precise diagnostic workup.
Warning people that they are being microtargeted fails to eliminate persuasive advantage
Authors: Carrella Fabio , Simchon Almog , Edwards Matthew , Lewandowsky Stephan 
Published: January 2025

Abstract
The practice of microtargeting in politics, involving tailoring persuasive messages to individuals based on personal vulnerabilities, has raised manipulation concerns. As microtargeting’s persuasive benefits are well-established and its use facilitated by AI tools and personality-inference models, ethical and regulatory concerns are magnified. Here, we explore countering microtargeting effects by creating a warning signal deployed when users encounter personality-tailored political ads. Three studies evaluated the effectiveness of warning “popups” against potential microtargeting by comparing persuasiveness of targeted vs. non-targeted messages with and without popups. Using within subject-designs, Studies 1 (N = 666), 2a (N = 432), and 2b (N = 669) reveal a targeting effect, with targeted ads deemed more persuasive than non-targeted ones. More important, the presence of a warning popup had no meaningful impact on persuasiveness. Overall, across the three studies, personality-targeted ads were significantly more persuasive than non-targeted ones, and this advantage persisted despite warnings. Given the focus on transparency in initiatives like the EU’s AI Act, our finding that warnings have little effect has potential policy implications.
Efficient oxidative coupling of amines to imines under natural sunlight using a benzothiadiazole-based molecular photocatalyst
Authors: Singh Ajeet , Das Bidisa , Ray Saumi 
Published: January 2025

A donor–acceptor-type small organic molecular photocatalyst (SOMP) with benzothiadiazole is utilized for oxidative coupling of amines to imines which under natural sunlight converts >99% amine with >98% selectivity within 2 hours.
Auditory Global–Local Processing Under Tonal Language Background: Effect of Attention and Autistic Traits
Authors: Chen Yu , Wang Ting , Tang Enze , Ding Hongwei 
Published: January 2025

Purpose:
Neurotypical individuals show a robust “global precedence effect (GPE)” when processing hierarchically structured visual information. However, the auditory domain remains understudied. The current research serves to fill the knowledge gap on auditory global–local processing across the broader autism phenotype under the tonal language background.

Method:

This study examined auditory global–local processing styles in 37 Mandarin-speaking young adults (age:
M
= 20.35,
SD
= 2.32; 19 males) with varying autistic traits. The participants were required to judge global and local pitch structures in nine-tone melodies with both congruent and incongruent conditions under both directed attention and divided attention modes.

Results:
We found that GPE persisted independent of the attention modes during hierarchical processing. Autistic traits were among the potential contributors that reshaped GPE in auditory global–local processing under a tonal language background.

Conclusions:
Our study provides an initial investigation into auditory global–local processing among Mandarin-speaking individuals across a range of autistic traits, revealing the presence of the GPE effect during hierarchical pitch structure processing. The advantage of global processing versus local processing expanded with increasing autistic traits, providing further support for the notion that auditory global processing may remain intact in autism and the broader phenotype. We highlight that GPE is a process of coarse-to-fine integration of sensory perception and cognitive feedback iteration, which both top-down and bottom-up processes wield influence on. These findings have implications for the study of atypical auditory processing in autism and may help to refine the early diagnosis and auditory-based intervention for autism.

Supplemental Material:

https://doi.org/10.23641/asha.28114118
A new method for determining the onset times of solar energetic particles and their uncertainties: Poisson-CUSUM bootstrap hybrid method
Authors: Palmroos C. , Dresing N. , Gieseler J. , Gutiérrez C. P. , Vainio R. 
Published: January 2025

Context. Solar energetic particle (SEP) events are a type of space weather phenomena in which highly energetic charged particles are released from the Sun into interplanetary space by violent and eruptive phenomena, such as solar flares and coronal mass ejections. In order to assess the origin of SEPs, an accurate timing of their arrival at spacecraft is of utmost importance. Several methods for determining the starting time of an SEP event at an observer exist, but the uncertainty of this starting time is not assessed in a systematic way by the vast majority of studies.
Aims. Employing a newly developed hybrid method of Poisson-CUSUM combined with bootstrapping, we show that the uncertainty related to the onset of an event in any particular energy range is often more than the mere time resolution of the measuring apparatus, and furthermore, it is not necessarily symmetric with respect to the past and future of the determined onset. In addition, we provide a software tool to the scientific community that applies the presented method and automates the determination of SEP event onset times and their related uncertainties, and it finally allows one to easily perform a velocity dispersion analysis.
Methods. By applying the Poisson-CUSUM method coupled with statistical bootstrapping to SEP event observations, we demonstrate the effectiveness of the method on synthetic and real data, and we compare them to an analysis conducted using a classical approach in which the uncertainty is assumed based on the time resolution of the data.
Results. In the example case, the inferred SEP path length and injection time related to the event, acquired by the velocity dispersion analysis, differ from what is obtained without properly assessing the uncertainty related to the onset times in varying energies. We also present the software package, PyOnset, that automates many steps of the method along with providing powerful data-visualization methods and analysis tools. We release the code to the scientific community as open-source software.
Constrained optimization approach for magnetohydrostatic equilibria on the solar atmosphere
Authors: Jafarpour M. H. , Nasiri S. 
Published: January 2025

Context. The magnetic field plays an essential role in the evolution of structures and the description of events in the solar atmosphere. Several models have been developed to reconstruct the magnetic field, due to the impossibility of its direct measurement in the solar corona. The model proposed here extrapolates the photospheric magnetogram data up to the corona using a constrained optimization method. In the upper photosphere and chromosphere, both the magnetic and nonmagnetic forces must be taken into account, and the magnetic field reconstruction must be done considering the plasma pressure and density. This is done by applying the Lagrange multiplier technique, as the constrained optimization method, to compute the magnetic field, plasma pressure, and density in magnetohydrostatic equilibria.
Aims. This approach has previously been introduced to reconstruct a nonlinear force-free magnetic field. For this work we extended it to a more realistic issue to reconstruct the magnetic field and calculate the plasma pressure and density in a magnetohydrostatic environment.
Methods. Our approach was to use the constrained optimization method, which is computationally more efficient and easy to implement. The Lagrange multiplier technique is a powerful mathematical tool that has been successfully applied to many areas of physics. We sought to minimize a Lagrangian, which minimizes the divergence term subject to the constraint magnetohydrostatic equilibrium equation. The plasma parameters and magnetic field were eventually computed following the iteration scheme along with appropriate boundary data.
Results. In our previous work, we applied Lagrange multiplier techniques to reconstruct a force-free magnetic field for the solar atmosphere. For this wok, we extended the same optimization technique to extrapolate magnetic field and plasma parameters in magnetohydrostatic equilibria. The results for the magnetic field and plasma parameters were calculated and compared with those obtained by other models in the magnetohydrostatic equilibrium environment as well as the semi-analytical solution as a reference model.
Conclusions. A force-free magnetic field and a suitable distribution for pressure and density were used as the initial input for their corresponding evolution equations. After 20 000 iterations, the convergence of the Lagrangian in our model was slightly better than that of the comparison model. The indicators such as the relative magnetic energy and magnetic field lines were investigated, which are in agreement with the reference model compared to the comparison model.