bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of seven days’ fasting on physical performance and metabolic adaptation during exercise in humans
Authors: Kolnes Kristoffer J. , Nilsen Emelie T. F. , Brufladt Steffen , Meadows Allison M. , Jeppesen Per B. , Skattebo Øyvind , Johansen Egil I. , Birk Jesper B. , Højlund Kurt , Hingst Janne , Skålhegg Bjørn S. , Kjøbsted Rasmus , Griffin Julian L. , Kolnes Anders J. , O’Rahilly Stephen , Wojtaszewski Jørgen F. P. , Jensen Jørgen 
Published: January 2025

AbstractHumans have, throughout history, faced periods of starvation necessitating increased physical effort to gather food. To explore adaptations in muscle function, 13 participants (7 males and 6 females) fasted for seven days. They lost 4.6 ± 0.3 kg lean and 1.4 ± 0.1 kg fat mass. Maximal isometric and isokinetic strength remained unchanged, while peak oxygen uptake decreased by 13%. Muscle glycogen was halved, while expression of electron transport chain proteins was unchanged. Pyruvate dehydrogenase kinase 4 (PDK4) expression increased 13-fold, accompanied by inhibitory pyruvate dehydrogenase phosphorylation, reduced carbohydrate oxidation and decreased exercise endurance capacity. Fasting had no impact on 5’ AMP-activated protein kinase (AMPK) activity, challenging its proposed role in muscle protein degradation. The participants maintained muscle strength and oxidative enzymes in skeletal muscle during fasting but carbohydrate oxidation and high-intensity endurance capacity were reduced.
Carbon nitride caught in the act of artificial photosynthesis
Authors: Cruz Daniel , Żółtowska Sonia , Savateev Oleksandr , Antonietti Markus , Giusto Paolo 
Published: January 2025

AbstractCovalent semiconductors of the carbon nitride family are among the most promising systems to realize “artificial photosynthesis”, that is exploiting synthetic materials which use sunlight as an energy source to split water into its elements or converting CO2 into added value chemicals. However, the role of surface interactions and electronic properties on the reaction mechanism remain still elusive. Here, we use in-situ spectroscopic techniques that enable monitoring surface interactions in carbon nitride under artificial photosynthetic conditions. We show that the water adsorption and light illumination cause changes of the surface electron density, which activate the photocatalyst and enable the water splitting process. Our results reveal critical details on the photocatalytic mechanism, which proceeds through proton-coupled electron transfer, and provide key information to design more efficient photocatalyst for artificial photosynthesis.
In vivo spontaneous Ca2+ activity in the pre-hearing mammalian cochlea
Authors: De Faveri Francesca , Ceriani Federico , Marcotti Walter 
Published: January 2025

AbstractThe refinement of neural circuits towards mature function is driven during development by patterned spontaneous calcium-dependent electrical activity. In the auditory system, this sensory-independent activity arises in the pre-hearing cochlea and regulates the survival and refinement of the auditory pathway. However, the origin and interplay of calcium signals during cochlear development is unknown in vivo. Here we show how calcium dynamics in the cochlear neuroepithelium of live pre-hearing mice shape the activity of the inner hair cells (IHCs) and their afferent synapses. Both IHCs and supporting cells (SCs) generate spontaneous calcium-dependent activity. Calcium waves from SCs synchronise the activity of nearby IHCs, which then spreads longitudinally recruiting several additional IHCs via a calcium wave-independent mechanism. This synchronised IHC activity in vivo increases the probability of afferent terminal recruitment. Moreover, the modiolar-to-pillar segregation in sound sensitivity of mature auditory nerve fibres appears to be primed at pre-hearing ages.
Targeting pleuro-alveolar junctions reverses lung fibrosis in mice
Authors: Fischer Adrian , Han Wei , Hu Shaoping , Mück-Häusl Martin , Wannemacher Juliane , Kadri Safwen , Lin Yue , Dai Ruoxuan , Christ Simon , Su Yiqun , Dasgupta Bikram , Sardogan Aydan , Deisenhofer Christoph , Dutta Subhasree , Kadri Amal , Güney Tankut Gökhan , Correa-Gallegos Donovan , Mayr Christoph H. , Hatz Rudolf , Stoleriu Mircea Gabriel , Lindner Michael , Hilgendorff Anne , Adler Heiko , Machens Hans-Günther , Schiller Herbert B. , Hauck Stefanie M. , Rinkevich Yuval 
Published: January 2025

Abstract
Lung fibrosis development utilizes alveolar macrophages, with mechanisms that are incompletely understood. Here, we fate map connective tissue during mouse lung fibrosis and observe disassembly and transfer of connective tissue macromolecules from pleuro-alveolar junctions (PAJs) into deep lung tissue, to activate fibroblasts and fibrosis. Disassembly and transfer of PAJ macromolecules into deep lung tissue occurs by alveolar macrophages, activating cysteine-type proteolysis on pleural mesothelium. The PAJ niche and the disassembly cascade is active in patient lung biopsies, persists in chronic fibrosis models, and wanes down in acute fibrosis models. Pleural-specific viral therapeutic carrying the cysteine protease inhibitor Cystatin A shuts down PAJ disassembly, reverses fibrosis and regenerates chronic fibrotic lungs. Targeting PAJ disassembly by targeting the pleura may provide a unique therapeutic avenue to treat lung fibrotic diseases.
Single-cell RNA sequencing identifies CXADR as a fate determinant of the placental exchange surface
Authors: Angelova Dafina M. , Tsolova Aleksandra , Prater Malwina , Ballasy Noura , Bacon Wendi , Hamilton Russell S. , Blackwell Danielle , Yu Ziyi , Li Xin , Liu Xin , Hemberger Myriam , Charnock-Jones D. Stephen 
Published: January 2025

AbstractThe placenta is the critical interface between mother and fetus, and consequently, placental dysfunction underlies many pregnancy complications. Placental formation requires an adequate expansion of trophoblast stem and progenitor cells followed by finely tuned lineage specification events. Here, using single-cell RNA sequencing of mouse trophoblast stem cells during the earliest phases of differentiation, we identify gatekeepers of the stem cell state, notably Nicol1, and uncover unsuspected trajectories of cell lineage diversification as well as regulators of lineage entry points. We show that junctional zone precursors and precursors of one of the two syncytial layers of the mouse placental labyrinth, the Syncytiotrophoblast-I lineage, initially share similar trajectories. Importantly, our functional analysis of one such lineage precursor marker, CXADR, demonstrates that this cell surface protein regulates the differentiation dynamics between the two syncytial layers of the mouse labyrinth, ensuring the correct establishment of the placental exchange surface. Deciphering the mechanisms underlying trophoblast lineage specification will inform our understanding of human pregnancy in health and disease.
Preservation of organic carbon in marine sediments sustained by sorption and transformation processes
Authors: Babakhani Peyman , Dale Andrew W. , Woulds Clare , Moore Oliver W. , Xiao Ke-Qing , Curti Lisa , Peacock Caroline L. 
Published: January 2025

Abstract
Controls on organic carbon preservation in marine sediments remain controversial but crucial for understanding past and future climate dynamics. Here we develop a conceptual-mathematical model to determine the key processes for the preservation of organic carbon. The model considers the major processes involved in the breakdown of organic carbon, including dissolved organic carbon hydrolysis, mixing, remineralization, mineral sorption and molecular transformation. This allows redefining of burial efficiency as preservation efficiency, which considers both particulate organic carbon and mineral-phase organic carbon. We show that preservation efficiency is almost three times higher than the conventionally defined burial efficiency and reconciles predictions with global field data. Kinetic sorption and transformation are the dominant controls on organic carbon preservation. We conclude that a synergistic effect between kinetic sorption and molecular transformation (geopolymerization) creates a mineral shuttle in which mineral-phase organic carbon is protected from remineralization in the surface sediment and released at depth. The results explain why transformed organic carbon persists over long timescales and increases with depth.
Bacteria use exogenous peptidoglycan as a danger signal to trigger biofilm formation
Authors: Vaidya Sanika , Saha Dibya , Rode Daniel K. H. , Torrens Gabriel , Hansen Mads F. , Singh Praveen K. , Jelli Eric , Nosho Kazuki , Jeckel Hannah , Göttig Stephan , Cava Felipe , Drescher Knut 
Published: January 2025

Abstract
For any organism, survival is enhanced by the ability to sense and respond to threats in advance. For bacteria, danger sensing among kin cells has been observed, but the presence or impacts of general danger signals are poorly understood. Here we show that different bacterial species use exogenous peptidoglycan fragments, which are released by nearby kin or non-kin cell lysis, as a general danger signal. Using microscopy and gene expression profiling of Vibrio cholerae, we find that even brief signal exposure results in a regulatory response that causes three-dimensional biofilm formation, which protects cells from a broad range of stresses, including bacteriophage predation. A diverse set of species (Pseudomonas aeruginosa, Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecalis) also respond to exogenous peptidoglycan by forming biofilms. As peptidoglycan from different Gram-negative and Gram-positive species triggered three-dimensional biofilm formation, we propose that this danger signal and danger response are conserved among bacteria.
Interfacial water confers transcription factors with dinucleotide specificity
Authors: Morgunova Ekaterina , Nagy Gabor , Yin Yimeng , Zhu Fangjie , Nayak Sonali Priyadarshini , Xiao Tianyi , Sokolov Ilya , Popov Alexander , Laughton Charles , Grubmuller Helmut , Taipale Jussi 
Published: January 2025

AbstractTranscription factors (TFs) recognize specific bases within their DNA-binding motifs, with each base contributing nearly independently to total binding energy. However, the energetic contributions of particular dinucleotides can deviate strongly from the additive approximation, indicating that some TFs can specifically recognize DNA dinucleotides. Here we solved high-resolution (<1 Å) structures of MYF5 and BARHL2 bound to DNAs containing sets of dinucleotides that have different affinities to the proteins. The dinucleotides were recognized either enthalpically, by an extensive water network that connects the adjacent bases to the TF, or entropically, by a hydrophobic patch that maintained interfacial water mobility. This mechanism confers differential temperature sensitivity to the optimal sites, with implications for thermal regulation of gene expression. Our results uncover the enigma of how TFs can recognize more complex local features than mononucleotides and demonstrate that water-mediated recognition is important for predicting affinities of macromolecules from their sequence.
Biological, environmental, and psychological stress and the human gut microbiome in healthy adults
Authors: Delgadillo Desiree R. , Borelli Jessica L. , Mayer Emeran A. , Labus Jennifer S. , Cross Marie P. , Pressman Sarah D. 
Published: January 2025

AbstractEmerging research suggests that the gut microbiome plays a crucial role in stress. We assess stress-microbiome associations in two samples of healthy adults across three stress domains (perceived stress, stressful life events, and biological stress /Respiratory Sinus Arrhythmia; RSA). Study 1 (n = 62; mean-age = 37.3 years; 68% female) and Study 2 (n = 74; mean-age = 41.6 years; female only) measured RSA during laboratory stressors and used 16S rRNA pyrosequencing to classify gut microbial composition from fecal samples. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States was used to predict functional pathways of metagenomes. Results showed differences in beta diversity between high and low stressful life events groups across both studies. Study 1 revealed differences in beta diversity between high and low RSA groups. In Study 1, the low perceived stress group was higher in alpha diversity than the high perceived stress group. Levels of Clostridium were negatively associated with RSA in Study 1 and levels Escherichia/Shigella were positively associated with perceived stress in Study 2. Associations between microbial functional pathways (L-lysine production and formaldehyde absorption) and RSA are discussed. Findings suggest that certain features of the gut microbiome are differentially associated with each stress domain.
Addressing inter individual variability in CSF levels of brain derived proteins across neurodegenerative diseases
Authors: Mravinacová Sára , Bergström Sofia , Olofsson Jennie , de San José Nerea Gómez , Anderl-Straub Sarah , Diehl-Schmid Janine , Fassbender Klaus , Fliessbach Klaus , Jahn Holger , Kornhuber Johannes , Landwehrmeyer G. Bernhard , Lauer Martin , Levin Johannes , Ludolph Albert C. , Prudlo Johannes , Schneider Anja , Schroeter Matthias L. , Wiltfang Jens , Steinacker Petra ,   FTLD Consortium, Otto Markus , Nilsson Peter , Månberg Anna 
Published: January 2025

AbstractAccurate diagnosis and monitoring of neurodegenerative diseases require reliable biomarkers. Cerebrospinal fluid (CSF) proteins are promising candidates for reflecting brain pathology; however, their diagnostic utility may be compromised by natural variability between individuals, weakening their association with disease. Here, we measured the levels of 69 pre-selected proteins in cerebrospinal fluid using antibody-based suspension bead array technology in a multi-disease cohort of 499 individuals with neurodegenerative disorders including Alzheimer’s disease (AD), behavioral variant frontotemporal dementia, primary progressive aphasias, amyotrophic lateral sclerosis (ALS), corticobasal syndrome, primary supranuclear palsy, along with healthy controls. We identify significant inter-individual variability in overall CSF levels of brain-derived proteins, which could not be attributed to specific disease associations. Using linear modelling, we show that adjusting for median CSF levels of brain-derived proteins increases the diagnostic accuracy of proteins previously identified as altered in CSF in the context of neurodegenerative disorders. We further demonstrate a simplified approach for the adjustment using pairs of correlated proteins with opposite alteration in the diseases. With this approach, the proteins adjust for each other and further increase the biomarker performance through additive effect. When comparing the diseases, two proteins—neurofilament medium and myelin basic protein—showed increased levels in ALS compared to other diseases, and neurogranin showed a specific increase in AD. Several other proteins showed similar trends across the studied diseases, indicating that these proteins likely reflect shared processes related to neurodegeneration. Overall, our findings suggest that accounting for inter-individual variability is crucial in future studies to improve the identification and performance of relevant biomarkers. Importantly, we highlight the need for multi-disease studies to identify disease-specific biomarkers.
Temporal ablation of the ciliary protein IFT88 alters normal brainwave patterns
Authors: Strobel Matthew R. , Zhou Yuxin , Qiu Liyan , Hofer Aldebaran M. , Chen Xuanmao 
Published: January 2025

AbstractThe primary cilium is a hair-like organelle that hosts molecular machinery for various developmental and homeostatic signaling pathways. Its alteration can cause rare ciliopathies such as the Bardet-Biedl and Joubert syndromes, but is also linked to Alzheimer’s disease, clinical depression, and autism spectrum disorder. These afflictions are caused by disturbances in a wide variety of genes but a common phenotype amongst them is cognitive impairment. While cilia-mediated neural function has been widely examined in early neurodevelopment, their function in the adult brain is not well understood. To help elucidate the role of cilia in neural activity, we temporally induced the ablation of IFT88, a gene encoding the intraflagellar transport 88 protein which is neccessary for ciliogenesis, in adult mice before performing memory-related behavioral assays and electroencephalogram/electromyogram (EEG/EMG) recordings. Inducible IFT88 KO mice exhibited severe learning deficits in trace fear conditioning and Morris water maze tests. They had strongly affected brainwave activity both under isoflurane induced anesthesia and during normal activity. And additionally, inducible IFT88 KO mice had altered sleep architecture and attenuated phase-amplitude coupling, a process that underlies learning and memory formation. These results highlight the growing significance of primary cilia for healthy neural function in the adult brain.
Crowd counting in domain generalization based on multi-scale attention and hierarchy level enhancement
Authors: Zhou Jiarui , Zhang Jianming , Gui Yan 
Published: January 2025

AbstractIn order to solve the problem of weak single domain generalization ability in existing crowd counting methods, this study proposes a new crowd counting framework called Multi-scale Attention and Hierarchy level Enhancement (MAHE). Firstly, the model can focus on both the detailed features and the macro information of structural position changes through the fusion of channel attention and spatial attention. Secondly, the addition of multi-head attention feature module facilitates the model’s capacity to effectively capture complex dependency relationships between sequence elements. In addition, the three-stage encoding and decoding processing mode enables the model to effectively represent crowd density information. Finally, the fusion of multi-scale features derived from different receptive fields is further enhanced through multi-scale hierarchy level feature fusion, thereby enabling the model to learn high-level semantic information and low-level multi-scale visual field feature information. This method enhances the model’s capacity to capture key feature information, even in highly differentiated datasets, thereby improving the model’s generalization ability on a single domain. The model has demonstrated strong generalization capabilities through extensive experiments on different datasets. This study not only improves the accuracy of crowd counting, but also introduces a new research approach for single domain generalization of crowd counting.
The appropriate nutrient conditions for methicillin-resistant Staphylococcus aureus and Candida albicans dual-species biofilm formation in vitro
Authors: Vávrová Pavlína , Janďourek Ondřej , Diepoltová Adéla , Nachtigal Petr , Konečná Klára 
Published: January 2025

AbstractPolymicrobial biofilms, the reason for most chronic wound infections, play a significant role in increasing antibiotic resistance. The in vivo effectiveness of the new anti-biofilm therapy is conditioned by the profound evaluation using appropriate in vitro biofilm models. Since nutrient availability is crucial for in vitro biofilm formation, this study is focused on the impact of four selected cultivation media on the properties of methicillin-resistant Staphylococcus aureus and Candida albicans dual-species biofilms. To reflect the wound environment, Tryptic soy broth, RPMI 1640 with and without glucose, and Lubbock medium were supplemented with different amounts of host effector molecules present in human plasma or sheep red blood cells. The study demonstrates that the Lubbock medium provided the most appropriate amount of nutrients regarding the biomass structure and the highest degree of tolerance to selected antimicrobials with the evident contribution of the biofilm matrix. Our results allow the rational employment of nutrition conditions within methicillin-resistant Staphylococcus aureus and Candida albicans dual-species biofilm formation in vitro for preclinical research. Additionally, one of the potential targets of a complex antibiofilm strategy, carbohydrates, was revealed since they are prevailing molecules in the matrices regardless of the cultivation media.
Trabecular meshwork ultrastructural changes in primary and secondary glaucoma
Authors: Rao Aparna , Rao Tirupathi , Banka Nagapriya , Senthil Sirisha , Jaketi Saumya 
Published: January 2025

AbstractTo examine ultrastructural changes in the trabecular meshwork (TM) in patients with primary and secondary glaucoma using scanning electron microscopy (SEM). This was a qualitative descriptive hospital-based study on the ultrastructure of the TM. Pure TM samples were collected after microincisional trabeculectomy from 26 patients with primary or secondary glaucoma and 10 control samples from eye bank donor corneas. SEM was used to analyze structural changes in the TM beams, corneoscleral meshwork (CSM), and juxtacanalicular (JCT) regions. Morphological features were compared between groups and correlated with histopathological findings. SEM revealed flattened and broadened TM beams in the JCT, resembling controls, often with a dumbbell configuration. Histopathological examination (HPE) and SEM showed rounded TM beams with considerable thinning, especially in primary angle-closure glaucoma (PACG), compared to primary open-angle (POAG) and pseudoexfoliation glaucoma (XFG). Maximum thinning in all primary glaucoma occurred in the CSM region, with minimal changes in the JCT region despite a reduction in cellularity in both regions. In steroid glaucoma, amorphous, glistening material was found on the TM beams in the JCT and CSM. XFG eyes displayed vesicular bodies adjacent to fibrillar material scattered diffusely over the TM beams, particularly in the CSM, differing from the platelet clumps seen in regular blood clots. TM beam thinning in primary glaucoma primarily affects the CSM region, sparing the JCT region. Amorphous deposits or vesicular bodies, seen only in steroid-induced glaucoma and XFG, suggest different mechanisms of TM damage in these glaucoma types.
Patterns of object play behaviour and its functional implications in free-flying common ravens
Authors: Bapat Awani , Kempf Anna E. , Friry Salomé , Boucherie Palmyre H. , Bugnyar Thomas 
Published: January 2025

AbstractObject play has been proposed to provide individuals with information about their environment, facilitating foraging skills and tool use. In species where object play co-occurs with locomotor or social play, it may have additional functional implications, such as facilitating the evaluation of peers or forming social bonds. For instance, ravens judge others’ competitiveness via play caching and engage in social play by exchanging objects. However, most raven studies were conducted on a restricted number of individuals and under controlled captive settings. To validate these findings and to gauge the functional scope of object play under field conditions, we investigated the patterns and characteristics of object play in individually marked free-flying ravens in the Austrian Alps. Using two large data sets, we show a decrease in object play with age and a preference for playing longer with novel objects, supporting findings from captivity. We also find adults occasionally playing with objects and no difference in the duration of social or non-social object play bouts across age classes. Taken together, our findings are in line with the assumption that raven object play likely has more than one function and serves to gain information about the individual’s physical and social environment.