bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ideotype for drought tolerance in bioenergyPopulus nigra
Authors: Smith Hazel K , Puértolas Jaime , Douthe Cyril , Emiliani Giovanni , Giovannelli Alessio , Rowland Libby S , Allwright Mike , Bailey-Bale Jack H , Valdes-Fragoso Pili M , Larsen Elisabeth K , Alberti Giorgio , Zaldei Alessandro , Hirons Andrew D , Alasia Franco , Ribas-Carbo Miquel , Flexas Jaume , Dodd Ian C , Davies William J , Taylor Gail 
Published: February 2024

AbstractFast-growing perennial trees such as Populus nigra L. are important species for wood, plywood, pulp, and bioenergy feedstock production, yet tree vigor in a changing climate is poorly understood. This research aimed to identify breeding targets for yield in water-limited environments, alongside unraveling the relationship between drought, yield, and glucose release in P. nigra. A diversity panel of 20 P. nigra genotypes, selected from a wide natural association population, was grown at three divergent European sites. Through extensive phenotyping of physiological and morphological productivity and water-use traits, under irrigated conditions and when exposed to a progressive drought, we elucidated the adaptive and plastic drivers underlying tree productivity. We have identified the underpinning traits for drought tolerance, whereby high yields can be maintained under water deficit, in this key species. This highlighted the importance of examining the yield stress index (YSI) over the drought resistance index (DRI) to assess genotypes for performance under moderate drought. In this way, we found genotypes with high hydraulic capacity, and large leaves made up of many cells to be best suited to multiple European environments, with contrasting water availability. Moreover, we identified genotypes that combine yield and water use efficiency, with good glucose release potential, which will be important traits for the future of poplar as a bioenergy crop. Vigorous poplar genotypes, which are adapted to wet climates showed high environmental plasticity. However, in European drought scenarios, these trees outperform drought resistant genotypes, and some exhibit good glucose release. These trees are a valuable resource for the future.
Cyclin-dependent kinase 5 (Cdk5) activity is modulated by light and gates rapid phase shifts of the circadian clock
Authors: Brenna Andrea , Borsa Micaela , Saro Gabriella , Ripperger Jürgen A. , Glauser Dominique A. , Yang Zhihong , Adamantidis Antoine , Albrecht Urs 
Published: February 2024

AbstractThe circadian clock enables organisms to synchronize biochemical and physiological processes over a 24-hour period. Natural changes in lighting conditions, as well as artificial disruptions like jet lag or shift work, can advance or delay the clock phase to align physiology with the environment. Within the suprachiasmatic nucleus (SCN) of the hypothalamus, circadian timekeeping and resetting rely on both membrane depolarization and intracellular second-messenger signaling. Voltage-gated calcium channels (VGCCs) facilitate calcium influx in both processes, activating intracellular signaling pathways that triggerPeriod(Per) gene expression. However, the precise mechanism by which these processes are concertedly gated remains unknown.Our study demonstrates that cyclin-dependent kinase 5 (Cdk5) activity is modulated by light and regulates phase shifts of the circadian clock. We observed that knocking down Cdk5 in the SCN of mice affects phase delays but not phase advances. This is linked to uncontrolled calcium influx into SCN neurons and an unregulated protein kinase A (PKA) – calcium/calmodulin-dependent kinase (CaMK) – cAMP response element-binding protein (CREB) signaling pathway. Consequently, genes such asPer1are not induced by light in the SCN of Cdk5 knock-down mice. Our experiments identified Cdk5 as a crucial light-modulated kinase that influences rapid clock phase adaptation. This finding elucidates how light responsiveness and clock phase coordination adapt activity onset to seasonal changes, jet lag, and shift work.
Biomechanical Implications of Spinopelvic Alignment on Femoral Head Cartilage and the Proximal Femoral Physis in Slipped Capital Femoral Epiphysis: A Theoretical Finite Element Analysis
Authors: Kumaran Yogesh , Mumtaz Muzammil , Quatman Carmen , Balch-Samora Julie , Soehnlen Sophia , Hoffman Brett , Tripathi Sudharshan , Nishida Norihiro , Goel Vijay K. 
Published: February 2024

AbstractBackgroundSlipped capital femoral epiphysis (SCFE) is a prevalent pediatric hip disorder. Recent studies suggest the spine’s sagittal profile may influence the proximal femoral growth plate’s slippage, an aspect not extensively explored. This study utilizes finite element analysis to investigate how different spinopelvic alignments affect shear stress and potential slippage at the growth plate.MethodsA finite element model was developed from CT scans of a healthy adult male lumbar spine, pelvis, and femurs. The model was subjected to various sagittal alignments through rotational boundary conditions. Simulations of two-leg stance, one-leg stance, walking heel strike, ascending stairs heel strike, and descending stairs heel strike were conducted. Parameters measured included hip joint contact area, stress, and maximum Tresca (shear) stress on the growth plate.FindingsPosterior pelvic tilt cases indicated larger shear stresses compared to the anterior pelvic tilt variants except in two leg stance. Two leg stance resulted in decreases in the posterior tilted pelvi variants compared to anterior tilted pelvi, however a combination of posterior pelvic tilt and high pelvic incidence indicated larger shear stresses on the growth plate. One leg stance and heal strike resulted in higher shear stress on the growth plate in posterior pelvic tilt variants compared to anterior pelvic tilt, with a combination of posterior pelvic tilt and high pelvic incidence resulting in the largest shear stress.InterpretationOur findings suggest that posterior pelvic tilt and high pelvic incidence can lead to increased shear stress at the growth plate. Activities performed in patients with these alignments may predispose to biomechanical loading that shears the growth plate, potentially causing slippage.
A live cell imaging-based assay for tracking particle uptake by clathrin-mediated endocytosis
Authors: Ashby Grant , Keng Kayla E. , Hayden Carl C. , Stachowiak Jeanne C. 
Published: February 2024

ABSTRACTA popular strategy for therapeutic delivery to cells and tissues is to encapsulate therapeutics inside particles that cells internalize via endocytosis. The efficacy of particle uptake by endocytosis is often studied in bulk using flow cytometry and Western blot analysis and confirmed using confocal microscopy. However, these techniques do not reveal the detailed dynamics of particle internalization and how the inherent heterogeneity of many types of particles may impact their endocytic uptake. Toward addressing these gaps, here we present a live-cell imaging-based method that utilizes total internal reflection fluorescence (TIRF) microscopy to track the uptake of a large ensemble of individual particles in parallel, as they interact with the cellular endocytic machinery. To analyze the resulting data, we employ an open-source tracking algorithm in combination with custom data filters. This analysis reveals the dynamic interactions between particles and endocytic structures, which determine the probability of particle uptake. In particular, our approach can be used to examine how variations in the physical properties of particles (size, targeting, rigidity), as well as heterogeneity within the particle population, impact endocytic uptake. These data impact the design of particles toward more selective and efficient delivery of therapeutics to cells.
Augmented-reality-based multi-person exercise has more beneficial effects on mood state and oxytocin secretion than standard solitary exercise
Authors: Shima Takeru , Iijima Junpei , Sutoh Hirotaka , Terashima Chiho , Matsuura Yuki 
Published: February 2024

AbstractExercise is known to have positive effects on psychological well-being, with team sports often associated with superior mental health compared to individual sports. Augmented reality (AR) technology has the potential to convert solitary exercise into multi-person exercise. Given the role of oxytocin in mediating the psychological benefits of exercise and sports, this study aimed to investigate the impact of AR-based multi-person exercise on mood and salivary oxytocin levels. Fourteen participants underwent three distinct regimens: non-exercise (Rest), standard solitary cycling exercise (Ex), and AR-based multi-person cycling exercise (Ex+AR). In both exercise conditions (Ex and Ex+AR), participants engaged in cycling at a self-regulated pace to maintain a Rating of Perceived Exertion of 10. In the Ex+AR condition, participants’ avatars were projected onto a tablet screen, allowing them to cycle alongside ten other virtual avatars in an AR environment. Mood states (assessed using POMS2) and saliva samples were collected before and immediately after each 10-minute regimen. Subsequently, the levels of salivary oxytocin were measured. Participants exhibited higher cycling speeds during Ex+AR compared to Ex, despite comparable levels of self-reported fatigue between the two groups. Notably, only the Ex+AR condition significantly improved mood states associated with depression-dejection and exhibited a trend toward suppressing anger-hostility in participants. Moreover, the Ex+AR condition led to a significant elevation in salivary oxytocin levels, while the Ex condition showed a trend toward an increase. However, changes in salivary oxytocin did not show a significant correlation with changes in mood states. These findings suggest that Ex+AR enhances mood states and promotes oxytocin release. AR-based multi-person exercise may offer greater psychological benefits compared to standard solitary exercise, although the relationship between oxytocin and mood changes remains inconclusive.HighlightsExercise, especially team sports, has positive effects on mood state, and oxytocin partially supports these effects.Augmented reality (AR) technology can potentially convert standard solitary exercise into multi-person exercise.AR-based multi-person exercise (Ex+AR) significantly ameliorated depression-dejection and increased salivary oxytocin levels, but standard solitary exercise did not.Ex+AR may provide more significant psychological benefits than standard solitary exercise.
The RNA demethylases ALKBH5 and FTO regulate translation of the ATF4 mRNA in sorafenib-treated hepatocarcinoma cells
Authors: Adjibade Pauline , Mazroui Rachid 
Published: February 2024

AbstractTranslation is one of the main gene expression steps targeted by cellular stress, commonly refereed as translational stress, which includes treatment with anticancer drugs. While translational stress blocks translation initiation of bulk mRNAs, it allows translation of a specific set of mRNAs known as short upstream open reading frames (uORFs)-mRNAs. Among these, ATF4 mRNA encodes a transcription factor that reprograms gene expression during various cellular stress towards functions required for cell response to stress. Stress-induced ATF4 mRNA translation occurs via a specialised mode that relies on the presence of uORFs upstream to the main ATF4 ORF. However, mechanisms regulating ATF4 mRNA translation, particularly towards chemoresistance, remained limited. Here, we report a role of both ALKBH5 and FTO, the two RNA demethylating enzymes in promoting translation of ATF4 mRNA in liver cancer Hep3B cells treated with sorafenib, a stress inducer used in chemotherapy. Depletion experiments confirmed that both enzymes are required for inducing ATF4 mRNA translation, while polyribosome assays coupled to RT-qPCR indicated that this induction of ATF4 mRNA translation occurs at its initiation step. Usingin vitromethylation assays, we found that ALKBH5 is required for the inhibition of the methylation of a reporter ATF4 mRNA at a conserved adenosine (A235) site located at its uORF2, suggesting that ALKBH5-mediated translation of ATF4 mRNA involves demethylation of its A235. Preventing methylation of A235 by introducing an A/G mutation into the ATF4 mRNA reporter renders that reporter insensitive to ALKBH5 depletion, supporting the role of ALKBH5 demethylation activity in translation. Finally, targeting either ALKBH5 or FTO sensitizes Hep3B to sorafenib-induced cell death, contributing to their resistance. We concluded that ALKBH5 and FTO are novel factors that promote resistance to sorafenib treatment, in part by mediating translation of ATF4 mRNA.
navigate: an open-source platform for smart light-sheet microscopy
Authors: Marin Zach , Wang Xiaoding , Collison Dax W. , McFadden Conor , Lin Jinlong , Borges Hazel , Chen Bingying , Mehra Dushyant , Shen Qionghua , Galecki Seweryn , Daetwyler Stephan , Fiolka Reto , Dean Kevin M. 
Published: February 2024

Abstractnavigateis a turnkey, open-source software solution designed to enhance light-sheet fluorescence microscopy (LSFM) by integrating smart microscopy techniques into a user-friendly framework. It enables automated, intelligent imaging with a Python-based control system that supports GUI-reconfigurable acquisition routines and the integration of diverse hardware sets. As a comprehensive package, navigate democratizes access to advanced LSFM capabilities, facilitating the development and implementation of smart microscopy workflows without requiring deep programming knowledge or specialized expertise in light-sheet microscopy.
Accurate Assembly of Circular RNAs with TERRACE
Authors: Zahin Tasfia , Shi Qian , Zang Xiaofei Carl , Shao Mingfu 
Published: February 2024

AbstractCircular RNA (circRNA) is a class of RNA molecules that forms a closed loop with its 5’ and 3’ ends covalently bonded. Due to this specific structure circRNAs are more stable than linear RNAs, admit distinct biological properties and functions, and have been proven to be promising biomarkers. Circular RNAs were severely overlooked previously owing to the biases in the RNA-seq protocols and in the detection algorithms, but recently gained tremendous attentions in both aspects. However, most existing methods for assembling circRNAs heavily rely on the annotated transcriptomes, and hence exhibit unsatisfactory accuracy when a high-quality transcriptome is unavailable. Here we present TERRACE, a new algorithm for full-length assembly of circRNAs from paired-end total RNA-seq data. TERRACE uses the splice graph as the underlying data structure to organize the splicing and coverage information. We transform the problem of assembling circRNAs into finding two paths that “bridge” the three fragments in the splice graph induced by back-spliced reads. To solve this formulation, we adopted a definition for optimal bridging paths and a dynamic programming algorithm to calculate such paths, an approach that was proven useful for assembling linear RNAs. TERRACE features an efficient algorithm to detect back-spliced reads that are missed by RNA-seq aligners, contributing to its much improved sensitivity. It also incorporates a new machine-learning approach that is trained to assign a confidence score to each assembled circRNA, which is shown superior to using abundance for scoring. TERRACE is compared with leading circRNA detection methods on both simulations and biological datasets. Our method consistently outperforms by a large margin in sensitivity while maintaining better or comparable precision. In particular, when the annotations are not provided, TERRACE can assemble 123%-412% more correct circRNAs than state-of-the-art methods on human tissues. TERRACE presents a major leap on assembling full-length circRNAs from RNA-seq data, and we expect it to be widely used in the downstream research on circRNAs.
Expression of Most Retrotransposons in Human Blood Correlates with Biological Aging
Authors: Tsai Yi-Ting , Seymen Nogayhan , Thompson I. Richard , Zou Xinchen , Mumtaz Warisha , Gerlevik Sila , Mufti Ghulam J. , Karimi Mohammad M. 
Published: February 2024

AbstractRetrotransposons (RTEs) have been postulated to reactivate with age and contribute to aging through activated innate immune response and inflammation. Here, we analyzed the relationship between RTE expression and aging using published transcriptomic and methylomic datasets of human blood. Despite no observed correlation between RTE activity and chronological age, the expression of most RTE classes and families except short interspersed nuclear elements (SINEs) correlated with biological age-associated gene signature scores. Strikingly, we found that the expression of SINEs was linked to upregulated DNA repair pathways in multiple cohorts. We also observed DNA hypomethylation with aging and significant increase in RTE expression level in hypomethylated RTEs except for SINEs. Additionally, our single-cell transcriptomic analysis suggested a role for plasma cells in aging mediated by RTEs. Altogether, our multi-omics analysis of large human cohorts highlights the role of RTEs in biological aging and suggests possible mechanisms and cell populations for future investigations.
PuMA: PubMed Gene-Celltype-Relation Atlas
Authors: Bickmann Lucas , Sandmann Sarah , Walter Carolin , Varghese Julian 
Published: February 2024

AbstractRapid extraction and visualization of cell-specific gene expression is important for automatic celltype annotation, e.g. in single cell analysis. There is an emerging field in which tools such as curated databases or Machine Learning methods are used to support celltype annotation. However, complementing approaches to efficiently incorporate latest knowledge of free-text articles from literature databases, such as PubMed are understudied. This work introduces the PubMed Gene/Celltype-Relation Atlas (PuMA) which provides a local, easy-to-use web-interface to facilitate automatic celltype annotation. It utilizes pretrained large language models in order to extract gene and celltype concepts from Pub-Med and links biomedical ontologies to suggest gene to celltype relations. It includes a search tool for genes and cells, additionally providing an interactive graph visualization for exploring cross-relations. Each result is fully traceable by linking the relevant PubMed articles. The software framework is freely available and enables regular article imports for incremental knowledge updates. GitLab:imigitlab.uni-muenster.de/published/PuMA
Asymmetric representation of symmetric semantic information in the human brain
Authors: Wang Jiaxin , Kawahata Kiichi , Blanc Antoine , Maeda Naoya , Nishimoto Shinji , Nishida Satoshi 
Published: February 2024

AbstractSpecific pairs of semantic entities have symmetric relationships, such as word pairs with opposite meanings (e.g., “intelligent” and “stupid”; “human” and “mechanical”). Such semantic symmetry is a key feature of semantic information. However, the representation of symmetric semantic information in the brain is not yet understood. Additionally, it is unclear whether symmetric pairs of semantic information do have symmetric representations in the brain? We addressed this question in a data-driven manner by using the voxelwise modeling of movie-evoked cortical response measured by functional magnetic resonance imaging. In this modeling, response in each voxel was predicted from semantic labels designated for each movie scene. The semantic labels consisted of 30 different items, including 15 pairs of semantically symmetric items. Each item was manually evaluated using a 5-point scale. By localizing the semantic representation associated with each item based on the voxelwise accuracy of brain-response predictions, we found that semantic representations of symmetric item pairs are broadly distributed but with little overlap in the cortex. Additionally, the weight of voxelwise models revealed highly complex, various patterns of cortical representations for each item pair. These results suggest that symmetric semantic information is rather asymmetric and heterogeneous representations in the human brain.Significance statementThis study aimed to investigate if symmetric pairs of semantic information have symmetric representations in the human brain using statistical modeling of functional magnetic resonance imaging signals evoked by naturalistic movies. We built a model based on movie labeling of symmetric semantic items to quantify the cortical representations of symmetric semantic entities. These findings showed that symmetric pairs of semantic entities are represented in widespread cortical regions; however, still exhibit little overlap in localization and heterogeneous representations. These results offer significant insights into the cortical representations of semantic symmetry and advance the understanding of representational structure of semantic information in the human brain.
Dose escalation pre-clinical trial of novel DOK7-AAV in mouse model of DOK7 congenital myasthenia
Authors: Cossins Judith , Kozma Imre , Canzonetta Claudia , Hawkins Al , Beeson David , Sepulveda Patricio , Dong Yin 
Published: February 2024

AbstractCongenital myasthenic syndromes (CMS) are a group of inherited disorders characterised by defective neuromuscular transmission and fatigable muscle weakness. Mutations inDOK7, a gene encoding a post-synaptic protein crucial in the formation and stabilisation of the neuromuscular junction (NMJ), rank among the leading three prevalent causes of CMS in diverse populations globally. The majority of DOK7 CMS patients experience varying degrees of disability despite receiving optimised treatment, necessitating the development of improved therapeutic approaches. Here we executed a dose escalation pre-clinical trial using a DOK7-CMS mouse model to assess the efficacy of Amp-101, an innovative AAV gene replacement therapy. Amp-101 is based on AAVrh74 and contains human DOK7 cDNA under the control of a muscle-restricted promoter. We show that at doses 6x1013vg/kg and 1x1014vg/kg, Amp-101 generated enlarged NMJs and rescued the very severe phenotype of the model. Treated mice became at least as strong as WT littermates and the diaphragm and tibialis anterior muscles displayed robust expression of DOK7. This data suggests that Amp-101 is a promising candidate to move forward to clinic trials.