bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neural correlates of phenomenological attitude toward perceptual experience
Authors: Nishida Satoshi , Hamada Hiro Taiyo , Niikawa Takuya , Miyahara Katsunori 
Published: July 2024

AbstractPhenomenology is one of the most promising approaches to study conscious experience. It holds that a rigorous study of conscious experience requires a transition in the subject from the “natural attitude” (NA) to the “phenomenological attitude” (PA). NA describes our ordinary stance, in which our attention is directed at external objects and events. PA is a distinctive, reflective stance in which our attention is directed at our conscious experience itself. Despite its theoretical importance in philosophy and science of consciousness, the neural mechanisms underlying PA remain unknown. To clarify this point, we developed a novel behavioral task in which participants alternate between NA and PA in relation to their stimulus-evoked subjective experiences. Participants are presented with two sentences and requested to identify the one that best captures their experience. These sentences are designed to induce either NA or PA. We found that participants had lower error rates but slower reaction times in the PA condition compared to the NA condition, suggesting a difference beyond task difficulty. Using fMRI, we also found that multivoxel activation patterns in the premotor cortex, posterior parietal cortex, supplementary motor area, and cerebellum successfully classified the task conditions. Furthermore, the activation strength in these regions was lower in the PA condition, indicating that PA depends on neural processes that suppress action-related information. These findings provide the first evidence for the neural signature of PA, contributing to a better understanding of phenomenological method and its underlying neural mechanisms.Significance statementPhenomenology is one of the most promising approaches to study conscious experience. A key step is a transition from the natural attitude (NA)—where our attention is directed at external objects and events—to the phenomenological attitude (PA)—where our attention is directed toward our conscious experience itself. However, the neural processes underlying PA remain unclear. This study aimed to clarify this point by analyzing fMRI signals measured during a cognitive task that forced participants to repeatedly alternate between NA and PA. We observed that multiple action-related brain regions exhibited different activation patterns between NA and PA. Our findings provide the first neuroscientific evidence that illuminates the core process of the phenomenological method.
Computational simulations ofPachycrocutabite damage based on a ∼1.2 Ma ravaged hippopotamus femur from Fuente Nueva 3 (Orce, Granada, Spain)
Authors: Courtenay Lloyd A. , Serrano-Ramos Alexia , Barsky Deborah , Jiménez-Arenas Juan-Manuel , Yravedra José 
Published: July 2024

AbstractUnderstanding the behaviour and interactions of extinct carnivoran species present a significant challenge in archaeological and palaeontological research, often limited by numerous constraints in the fossil record. Here we analyse a hippopotamus femur consumed by an extinct species of giant hyena, recovered from the open-air site Fuente Nueva 3 (∼1.2 Ma, Orce, Granada, Spain). Leveraging the use of advanced microscopic techniques to digitise the tooth marks observed on this specimen in three dimensions, the present study utilises artificially intelligent algorithms to then simulate the possible morphological variability of this carnivoran. This allows us to characterisePachycrocuta brevirostristooth pit morphology, so as to construct a diagnostic reference sample of this species. Our findings underscore the importance tooth mark size has on identifying the activity ofPachycrocuta, revealing the giant hyena to have produced remarkably large, deep, and circular tooth pits on dense cortical bone.
Hotspot of Exotic Benthic Marine Invertebrates Discovered in the Tropical East Atlantic: DNA Barcoding Insights from the Bijagós Archipelago, Guinea-Bissau
Authors: Moura Carlos J. , Wirtz Peter , Nhanquê Filipe T. , Barbosa Castro , Serrão Ester 
Published: July 2024

AbstractAimThis study aimed to explore and document putative exotic marine benthic invertebrate species in the Bijagós Archipelago, Guinea-Bissau, to enhance understanding of marine biodiversity and address the extent of marine species introductions.LocationThe research was conducted in the Bijagós Archipelago, a UNESCO Biosphere Reserve located in Guinea-Bissau.MethodsThe study involved the region’s first scuba-diving survey of marine biodiversity. DNA barcoding was employed to assist in the identification of benthic invertebrate species. Molecular phylogenetic analyses were conducted with the available DNA barcodes to ensure accurate taxonomic assignments, detect cryptic species, and investigate the phylogeography of the taxa.ResultsThe survey resulted in the discovery of 28 new species records for the Bijagós Archipelago, including octocorals, scleractinians, hydroids, bryozoans, barnacles, and ascidians. Among these, seven species were documented for the first time in the East Atlantic:Stragulum bicolor,Tubastraea tagusensis,Nemalecium lighti,Diphasiasp.,Amathia alternata,A. distans, andSymplegma rubra. Molecular analyses revealed pervasive cryptic diversity within species previously listed as exotic, suggesting that some, such as the hydroidsPlumularia setacea,Obelia geniculata, andDynamena disticha, are not exotic due to their restricted biogeographic distributions. Many other species reported as introduced present only a few genetic lineages capable of long-distance dispersal due to human activities.Main ConclusionsThe study highlights considerable gaps in the knowledge of West African marine biodiversity and suggests a substantial underestimation of the anthropogenic trade in exotic marine species between the Tropical East Atlantic and the Americas, and between the Indo-Pacific and West Africa. Detailed taxonomic and genomic analyses are necessary for understanding marine exotic species’ biogeography and adaptive traits. Our findings challenge current classifications of exotic species and underscore the need for improved monitoring and management to prevent the spread of non-native marine species.
Accelerated Missense Mutation Identification in Intrinsically Disordered Proteins using Deep Learning
Authors: Seth Swarnadeep , Bhattacharya Aniket 
Published: July 2024

ABSTRACTWe use a combination of Brownian dynamics (BD) simulation results and Deep Learning (DL) strategies for rapid identification of large structural changes caused by missense mutations in intrinsically disordered proteins (IDPs). 2000 IDP sequences from DisProt database of length 20 −300 are used to obtain gyration radii from BD simulation on a coarse-grained single bead amino acid model (HPS model) used by us and others [Sethet al. J. Chem. Phys.160, 014902 (2024), Dignonet al. PLOS Comp. Biology, 14, 2018, Teseiet al. PNAS, 118, 2021] to generate the training sets for the DL algorithm. Using the gyration radii ⟨Rg⟩ of the simulated IDPs as the training set, we develop a multilayer perceptron neural net (NN) architecture that predicts the gyration radii of 33 IDPs previously studied using BD simulation with 95% accuracy from the sequence and the corresponding parameters from the HPS model. We now utilize this NN to predict gyration radii of every permutation of missense mutations in IDPs. Our approach successfully identifies mutation-prone regions that induce significant alterations in the radius of gyration when compared to the wild-type IDP sequence. We further validate the prediction by running BD simulations on the subset of identified mutants. The neural network yields a (104− 105)-fold faster computation in the search space for potentially harmful mutations. Our findings have substantial implications for rapid identification and understanding diseases related to missense mutations in IDPs and for the development of potential therapeutic interventions. The method can be extended to accurate predictions of other mutation effects in disordered proteins.
Synchronous assembly of peptide anisosome
Authors: Zhou Laicheng , Zhu Longcheng , Wang Cong , Xu Tengyan , Wang Jing , Zhang Bin , Zhang Xin , Wang Huaimin 
Published: July 2024

AbstractBiomolecular condensates, formed by liquid-liquid phase separation (LLPS) of proteins or the complex of protein and nucleic acids, play key roles in regulating physiological events in biological system. However, the formation of mono-component yet inhomogeneous condensates is limited, and the underlying mechanism remains unclear. Here, we report the symmetrical core-shell structural biomolecular condensates formed through the LLPS by programming a tetra-peptide library. Mechanistic studies reveal that the tryptophan (W) is critical for the formation of core-shell structure because of its stronger homotypical π-π interaction compared with other amino acids, which endow us to modulate the droplets from core-shell to homogeneous structures by encoding the amino acid composition. Using molecular dynamics (MD) simulation and molecular engineering, we find that the inner core of LLPS is composed of dynamic and reversible fibers surrounded by liquid-like shells, resulting in a stable core-shell LLPS. Furthermore, we could control the multiphasic droplet formation by an intrinsic redox reaction or post-translational modification of peptide through phosphorylation, which facilitates the rational design of synthetic LLPS with various applications on demand.
Dihydromyricetin alleviated the damage of hypoxia-induced mouse neurons by reducing ROS levels and inhibiting the expression of PAR and γH2AX
Authors: Du Xueping , Guo Yanjun , Yang Junzheng 
Published: July 2024

AbstractObjectiveTo investigate the effect of dihydromyricetin on hypoxia-induced neurons, to understand the effect of dihydromyricetin on hypoxic-ischemic encephalopathy (HIE).MethodsCortical neurons were isolated from C57BL/6j mice (24 hour-year old), cultured, and subjected to 4h hypoxia and 20h reoxygenation to mimic the neonatal hypoxic-ischemic encephalopathy. After dihydromyricetin (20μmol/L) treatment of hypoxia-induced neurons for 2h, CCK-8 assay was used to analyze the neuronal viability, Hoechst33342/PI double staining assay was used to analyze the neuronal death, Western blotting was used to analyze the expression of Poly ADP-ribose (PAR) polymer protein andγH2AX, comet assay was used to detect DNA damage, immunofluorescence staining was used to observe the nuclear translocation of apoptosis inducing factor, and 2’,7’-dichlorodihydrofluorescein diacetate was used to detect the expression of reactive oxygen species (ROS).ResultsCompared with the control groups, hypoxia-treated neurons exhibited significantly lower activity, higher neuronal death rate and the high expressions of PAR andγH2AX, hypoxia could also induce AIF nuclear translocation, increase tail DNA content and tail length, increase the expression of ROS in neurons; after dihydromyricetin treatment, neuronal activity were significantly increased, neuronal death rate, ROS levels, and the expressions of PAR andγH2AX were also decreased, AIF nuclear translocation was inhibited, the tail DNA content and tail length were also decreased.ConclusionDihydromyricetin could alleviate the damage of hypoxia-induced neurons through decreasing the levels of ROS and inhibiting the expressions of PAR andγH2AX, suggesting that dihydromyricetin may have the protective effect on HIE.
Identification of the sequences responsible for maternalH19-ICR hypermethylation with Beckwith-Wiedemann syndrome-like overgrowth in mice
Authors: Hara Satoshi , Matsuhisa Fumikazu , Kitajima Shuji , Yatsuki Hitomi , Kubiura-Ichimaru Musashi , Soejima Hidenobu 
Published: July 2024

AbstractBeckwith-Wiedemann syndrome (BWS) is caused by a gain of methylation (GOM) at the imprinting control region within theIgf2-H19domain on the maternal allele (H19-ICR GOM). Mutations in the binding sites of several transcription factors are involved inH19-ICR GOM and BWS. However, the responsible sequence(s) forH19-ICR GOM with BWS-like overgrowth has not been identified in mice. Here, we report that a mutation in the SOX-OCT binding site (SOBS) causes partialH19-ICR GOM, which does not extend beyond CTCF binding site 3 (CTS3). Moreover, simultaneously mutating both SOBS and CTS3 causes complete GOM of the entireH19-ICR, leading to the misexpression of the imprinted genes, and frequent BWS-like overgrowth. In addition, CTS3 is critical for CTCF/cohesin-mediated chromatin conformation. These results indicate that SOBS and CTS3 are the sequences responsible forH19-ICR GOM leading to BWS-like overgrowth and are essential for maintaining the unmethylated state of maternalH19-ICR.
Hippocampal-prefrontal communication subspaces align with behavioral and network patterns in a spatial memory task
Authors: Young Ryan A. , Shin Justin D. , Guo Ziyi , Jadhav Shantanu P. 
Published: July 2024

ABSTRACTRhythmic network states have been theorized to facilitate communication between brain regions, but how these oscillations influence communication subspaces, i.e, the low-dimensional neural activity patterns that mediate inter-regional communication, and in turn how subspaces impact behavior remains unclear. Using a spatial memory task in rats, we simultaneously recorded ensembles from hippocampal CA1 and the prefrontal cortex (PFC) to address this question. We found that task behaviors best aligned with low-dimensional, shared subspaces between these regions, rather than local activity in either region. Critically, both network oscillations and speed modulated the structure and performance of this communication subspace. Contrary to expectations, theta coherence did not better predict CA1-PFC shared activity, while theta power played a more significant role. To understand the communication space, we visualized shared CA1-PFC communication geometry using manifold techniques and found ring-like structures. We hypothesize that these shared activity manifolds are utilized to mediate the task behavior. These findings suggest that memory-guided behaviors are driven by shared CA1-PFC interactions that are dynamically modulated by oscillatory states, offering a novel perspective on the interplay between rhythms and behaviorally relevant neural communication.
Elucidating Interactome Dynamics of the A2A Adenosine Receptor
Authors: Lee Wonseok , Son Ahrum , Kim Woojin , Park Jongham , Cho Ja-Young , Kim Ju-Won , Kim Young-Ok , Kong Hee Jeong , Kim Hyunsoo 
Published: July 2024

AbstractPolydeoxyribonucleotide (PDRN) is a tissue regeneration substance that resembles human DNA and is present in human cells, mullets, salmons, and flatfish. It stimulates physiological regeneration and metabolic activity. The regenerative and metabolic effects of PDRN are attributed to the activation of Adenosine A2A receptors (ADORA2A), which increases the production of angiogenesis factors and growth factors. Activation of ADORA2A leads to the activation of ADORA2A-interacting proteins with similar functions. To investigate the changes and dynamics of proteins in the presence of PDRN, we conducted selected reaction monitoring-mass spectrometry (SRM-MS) to quantify 491 proteins, 3,852 peptides. Through peptide-level analysis, we founded 374 proteins and 1,193 peptides demonstrating both up-regulation and down-regulation in expression. We conducted gene ontology (GO) analysis and physical network analysis and discovered a novel network of proteins related to neuronal differentiation among the ADORA2A-interacting protein. Based on network analysis, we found indirect interactions with MAPK1 and MP2K1, which are known to influence neuronal cell differentiation and suggest the formation of a network involving MAPK signaling transduction. Finally, using AlphaFold multimer, we were able to predict interaction sites among ADORA2A-interacting proteins in the network associated with neuronal cell differentiation. Specifically, we predicted five interaction sites between ADORA2A and NTRK1 (which interacts with ADORA2A), forming the edge. Thus, we provided indicators for further research using ADORA2A present in robust network and highlighted the potential of PDRN to impact neuronal differentiation.
50 years of antibody numbering schemes: a statistical and structural evaluation reveals key differences and limitations
Authors: Zhu Zirui , Olson Katherine S. , Magliery Thomas J. 
Published: July 2024

ABSTRACTThe complementarity determining region (CDR) of antibodies represents the most diverse region both in terms of sequence and structural characteristics, playing the most critical role in antibody recognition and binding for immune responses. Over the past decades, several numbering schemes have been introduced to define CDRs based on sequence. However, the existence of diverse numbering schemes has led to potential confusion, and a comprehensive evaluation of these schemes is lacking. We employ statistical analyses to quantify the diversity of CDRs compared to the framework regions. Comparative analyses across different numbering schemes demonstrates notable variations in CDR definitions. The Kabat and AbM numbering schemes tend to incorporate more conserved residues into their CDR definitions, whereas CDRs defined by the Chothia and IMGT numbering schemes display greater diversity, sometimes missing certain loop residues. Notably, we identify a critical residue, L29, within the kappa light chain CDR1, which appears to act as a pivotal structural point within the loop. In contrast, most numbering schemes designate the topological equivalent point in the lambda light chain as L30, suggesting the need for further refinement in the current numbering schemes. These findings shed light on regional sequence and structural conservation within antibody sequence databases while also highlighting discrepancies stemming from different numbering schemes. These insights yield valuable guidelines for the precise delineation of antibody CDRs and the strategic design of antibody repertoires, with practical implications in developing innovative antibody-based therapeutics and diagnostics.GRAPHIC ABSTRACTHIGHLIGHTSAmino acid distribution analysis conducted on 124,317 sequences archived in the abYsis database showed lower conservation among CDR residues, as defined by Kabat numbering, compared to the framework region.Both LCDR3 and HCDR3 exhibited particularly high levels of diversity compared to the other four CDR loops, highlighting additional functional roles of the CDR3 loops relative to the others.Two distinct residues, L29 and H30, displayed highly conserved hydrophobic side chain characteristics and played unique conformational roles within the CDR1 loop, contributing to the formation of an ‘M-shaped’ structure. This residue divides the C-terminus CDR1 loop, which was observed to be less conserved and have greater length diversity, and the N-terminus CRD1 loop.The Kabat numbering scheme appears to overestimate the LCDR2 and HCDR2 loops and underestimate HCDR1, only encompassing the C-terminal loop of the ‘M-shaped’ CDR1 loop.Structural analysis revealed that a residue within LCDR1 was numbered differently in the two subtypes (kappa and lambda) of the variable light domain. This discrepancy suggests the need for further refinement in the current major numbering schemes.
Large Language Models in Pathology: A Comparative Study of ChatGPT and Bard with Pathology Trainees on Multiple-Choice Questions
Authors: Du Wei , Jin Xueting , Harris Jaryse Carol , Brunetti Alessandro , Johnson Erika , Leung Olivia , Li Xingchen , Walle Selemon , Yu Qing , Zhou Xiao , Bian Fang , McKenzie Kajanna , Kanathanavanich Manita , Ozcelik Yusuf , El-Sharkawy Farah , Koga Shunsuke 
Published: July 2024

AbstractLarge language models (LLMs), such as ChatGPT and Bard, have shown potential in various medical applications. This study aimed to evaluate the performance of LLMs, specifically ChatGPT and Bard, in pathology by comparing their performance with those of pathology trainees, and to assess the consistency of their responses. We selected 150 multiple-choice questions from 15 subspecialties, excluding those with images. Both ChatGPT and Bard were tested on these questions across three separate sessions between June 2023 and January January 2024, and their responses were compared with those of 14 pathology trainees (8 junior and 6 senior) from two hospitals. Questions were categorized into easy, intermediate, and difficult based on trainee performance. Consistency and variability in LLM responses were analyzed across three evaluation sessions. ChatGPT significantly outperformed Bard and trainees, achieving an average total score of 82.2% compared to Bard’s 49.5%, junior trainees’ 45.1%, and senior trainees’ 58.3%. ChatGPT’s performance was notably stronger in difficult questions (61.8%-70.6%) compared to Bard (29.4%-32.4%) and trainees (5.9%-44.1%). For easy questions, ChatGPT (88.9%-94.4%) and trainees (75.0%-100.0%) showed similar high scores. Consistency analysis revealed that ChatGPT showed a high consistency rate of 80%-85% across three tests, whereas Bard exhibited greater variability with consistency rates of 54%-61%. ChatGPT consistently outperformed Bard and trainees, especially on difficult questions. While LLMs show significant promise in pathology education and practice, continued development and human oversight are crucial for reliable clinical application.
Genomic characterization of Dengue virus circulation in Ethiopia
Authors: Abera Adugna , Tegally Houriiyah , Tasew Geremew , Wilkinson Eduan , Ali Abraham , Regasa Feyisa , Bitew Molalegne , Chabuka Lucious , Mwanyika Gaspary , Tshiabuila Derek , Giandhari Jennifer , Pillay Sureshnee , Poogavanan Jenicca , Moir Monika , Kraemer Moritz U.G. , Khan Kamran , Huber Carmen , Tollera Getachew , Wit Tobias F. Rinke de , Baxter Cheryl , Lessells Richard , Wolday Dawit , Beyene Dereje , de Oliveira Tulio ,   CLIMADE Consortium
Published: July 2024

ABSTRACTIn Ethiopia, dengue virus (DENV) infections have been reported in several regions, however, little is known about the circulating genetic diversity. Here, we conducted clinical surveillance for DENV during the 2023 nationwide outbreak and sequenced DENV whole genomes for the first time in Ethiopia. We enrolled patients at three sentinel hospital sites. Using RT-PCR, we screened serum samples for three arboviruses followed by serotyping and sequencing for DENV-positive samples (10.4% of samples). We detected two DENV serotypes (DENV1 and DENV3). Phylogenetic analysis identified one transmission cluster of DENV1 (genotype III major lineage A), and two clusters of DENV3 (genotype III major lineage B). The first showed close evolutionary relationship to the 2023 Italian outbreak and the second cluster to Indian isolates. Co-circulation of DENV1 and DENV3 in some regions of Ethiopia highlights the potential for severe dengue. Intensified surveillance and coordinated public health response are needed to address the threat of severe dengue outbreaks.