bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secondary structure determines electron transport in peptides
Authors: Samajdar Rajarshi , Meigooni Moeen , Yang Hao , Li Jialing , Liu Xiaolin , Jackson Nicholas E. , Mosquera Martín A. , Tajkhorshid Emad , Schroeder Charles M. 
Published: February 2024

AbstractProteins play a key role in biological electron transport, but the structure-function relationships governing the electronic properties of peptides are not fully understood. Despite recent progress, understanding the link between peptide conformational flexibility, hierarchical structures, and electron transport pathways has been challenging. Here, we use single-molecule experiments, molecular dynamics (MD) simulations, non-equilibrium Green’s function-density functional theory (NEGF-DFT) calculations, and unsupervised machine learning to understand the role of primary amino acid sequence and secondary structure on charge transport in peptides. Our results reveal a two-state molecular conductance behavior for peptides across several different amino acid sequences. MD simulations and Gaussian mixture modeling are used to show that this two-state molecular conductance behavior arises due to the conformational flexibility of peptide backbones, with a high-conductance state arising due to a more defined secondary structure (beta turn) and a low-conductance state occurring for extended peptide structures. Conformer selection for the peptide structures is rationalized using principal component analysis (PCA) of intramolecular hydrogen bonding distances along peptide backbones. Molecular conformations from MD simulations are used to model charge transport in NEGF-DFT calculations, and the results are in reasonably good agreement with experiments. Projected density of states (PDOS) calculations and molecular orbital visualizations are further used to understand the role of amino acid side chains on transport. Overall, our results show that secondary structure plays a key role in electron transport in peptides, which provides new avenues for understanding the electronic properties of longer peptides or proteins.Significance StatementElectron transport in proteins serves as a biological power line that fuels cellular activities such as respiration and photosynthesis. Within cells, proteins act as conduits, shuttling electrons through a series of reactions and pathways to generate proton gradients and to fuel ATP synthesis. Despite recent progress, the mechanisms underlying the flow of energy in protein complexes are not fully understood. Here, we study electron transport in peptides at the single-molecule level by combining experiments and molecular modeling. Our results reveal two distinct molecular sub-populations underlying electron transport that arise due to the flexibility of peptide backbones and the ability to fold into compact structures. This work provides a basis for understanding energy flow in larger proteins or biomolecular assemblies.
Information structure of heterogeneous criticality in a fish school
Authors: Niizato Takayuki , Sakamoto Kotaro , Mototake Yoh-ichi , Murakami Hisashi , Tomaru Takenori 
Published: February 2024

ABSTRACTThe integrated information theory (IIT) measures the degree of consciousness in living organisms from an information-theoretic perspective. This theory can be extended to general systems such as those measuring criticality. Herein, we applied the IIT to actual collective behaviour (Plecoglossus altivelis). We found that the group integrity (i.e., Φ) could be maximised in the critical state and that several levels of criticalities existed in a group as subgroups. Furthermore, these fragmented critical groups coexisted with traditional criticality as a whole. The distribution of high-criticality subgroups was heterogeneous in terms of time and space. In particular, the core fish in the high-criticality group tended to be unaffected by internal and external stimulation, in contrast to those in the low-criticality group. The results of this study are consistent with previous interpretations of critical phenomena and provide a new interpretation of the detailed dynamics of an empirical critical state.
The Strongest Protein Binder is Surprisingly Labile
Authors: Fernandez-Calvo Alba , Reifs Antonio , Saa Laura , Cortajarena Aitziber L. , Sancho David De , Perez-Jimenez Raul 
Published: February 2024

AbstractBacterial adhesins are cell-surface proteins that anchor to the cell wall of the host, thus initiating infection. The initial step in infection is precisely the binding to fibrinogen (Fg) from human tissue, after which bacteria can colonize the heart valves by the formation of biofilms. The study of this family of proteins is hence essential to develop new strategies to fight bacterial infections. In the case ofStaphylococcus aureus, there exists a type of adhesins known as Microbial Surface Components Recognizing Adhesive Matrix Molecules (MSCRAMMs). Here, we focus on one of them, the Clumping Factor A (ClfA), which has been found to bind Fg through the dock-lock-latch (DLL) mechanism. Interestingly, it has recently been discovered that MSCRAMMs proteins employ a catch-bond to withstand forces exceeding 2 nN, making this type of interaction as mechanically strong as a covalent bond. However, whether this strength is an evolved feature characteristic of the bacterial protein or is typical only of the interaction with its partner is not known. Here we combine single-molecule force spectroscopy (smFS), biophysical binding assays and molecular simulations to study the intrinsic mechanical strength of ClfA. We find that despite the extremely high forces required to break its interactions with Fg, ClfA is not by itself particularly strong, in the absence of its human target. Integrating the results from both theory and experiments we dissect contributions to the mechanical stability of this protein.
Guidelines for QSM phantom production and evaluation of candidate phantom materials
Authors: Hooper Padriac , Jin Jin , O’Brien Kieran , Tourell Monique , Robinson Simon Daniel , Barth Markus 
Published: February 2024

AbstractPurposeQuantitative susceptibility mapping (QSM) is an MR technique that depicts and precisely quantifies spatial biodistributions from MR phase images. Recently, QSM has gained much uptake as method for mapping iron and identifying calcium. However, QSM as a quantitative method needs an objective reference to assess its accuracy. Here we present guidelines for reproducible workflows for QSM phantom design and production to help standardization efforts and provide characterizations and recommendations for iron- and calcium-based materials given the repeatability and reproducibility.Methods5 concentrations of 4 materials (USPIO, ferritin, calcium chloride, calcium carbonate) were imaged with a multi-echo gradient-echo acquisition at 3 and 7 Tesla. Magnetic susceptibility and R2* relaxivity as well as intra-session, inter-session repeatability, inter-scanner reproducibility and molar susceptibility by QSM were quantified.ResultsThe QSM measurements of USPIO had a moderate to good inter-session repeatability. The molar susceptibility was approximately 2.45 times larger at 3 T compared to 7 T. The QSM measurements of ferritin had excellent inter-session repeatability. The molar susceptibility was approximately 4 % larger at 3 T compared to 7 T. The QSM measurements of calcium chloride had excellent inter-session repeatability and excellent inter-scanner reproducibility. The QSM measurements of calcium carbonate had a good to excellent inter-session repeatability and an excellent inter-scanner reproducibility.ConclusionThis work reveals ferritin and calcium chloride to be the most repeatable and reproducible iron-and calcium-based materials for QSM, respectively. A detailed methodology for phantom production, concentration ranges, visual analysis and statistical analysis are provided.
Transcriptome sequencing and bioinformatics analysis of kidney tissue in a tree shrew model of calcium oxalate nephrolithiasis
Authors: Wang Guang , Huang Ziye , Wu Yuyun , Xu Rui , Li Jiongming 
Published: February 2024

AbstractBackgroundKidney stones, predominantly composed of calcium oxalate, are a prevalent and recurrent urological condition. Given their high incidence and recurrence rates, understanding their pathogenesis and identifying effective treatment strategies are imperative.MethodsIn this study, we established a calcium oxalate nephrolithiasis model using tree shrews, a primate-like animal species. When compared to commonly used rodent models (rats and mice), the tree shrew model demonstrated superior reproducibility and relevance. And leveraging transcriptome sequencing and comprehensive bioinformatics analysis.Resultswe identified 1,927 differentially expressed genes, including 1,450 upregulated and 476 downregulated genes. Furthermore, we annotated these genes to 41 KEGG enriched pathways and 1,413 GO enrichments, encompassing 1276 Biological Processes, 72 Cellular Components, and Molecular Functions. Notably, we prioritized the top 50 core genes that could potentially underlie the pathogenesis of calcium oxalate nephrolithiasis.ConclusionsOur findings establish the tree shrew as a relevant model for studying kidney stone formation and provide valuable insights into the underlying molecular mechanisms. These insights hold promise for the development of novel therapeutic strategies to address this significant health burden.
QM/MM simulations of EFGR with afatinib reveal the role of theβ-dimethylaminomethyl substitution
Authors: Ma Shuhua , Patel Heeral , Peeples Craig A. , Shen Jana 
Published: February 2024

AbstractAcrylamides are the most commonly used warheads of targeted covalent inhibitors (TCIs) directed at cysteines; however, the reaction mechanisms of acrylamides in proteins remain controversial, particularly for those involving protonated or unreactive cysteines. Using the combined semiempirical quantum mechanics (QM)/molecular mechanics (MM) free energy simulations, we investigated the reaction between afatinib, the first TCI drug for cancer treatment, and Cys797 in the EGFR kinase. Afatinib contains aβ-dimethylaminomethyl (β-DMAM) substitution which has been shown to enhance the intrinsic reactivity and potency against EGFR for related inhibitors. Two hypothesized reaction mechanisms were tested. Our data suggest that Cys797 becomes deprotonated in the presence of afatinib and the reaction proceeds via a classical Michael addition mechanism, with Asp800 stabilizing the ion-pair reactant stateβ-DMAM+/C797−and the transition state of the nucleophilic attack. Our work elucidates an important structure-activity relationship of acrylamides in proteins.
Human lymphoid-neutrophil/monocyte restriction co-ordinately activates increased proliferation despite parallel heterogeneity in transcriptional changes
Authors: Wang Fangwu , Gonzalez Laura , Hammond Colin , Hirst Martin , Simons Benjamin D. , Eaves Connie 
Published: February 2024

AbstractRecent studies indicate the human lympho-myeloid restriction process to be a different and more heterogeneous one than historically inferred. Here we describe the development of bulk and clonal culture systems that efficiently support early B-lymphoid differentiation and their use to identify biological and molecular changes that accompany their initial restriction from subsets of CD34+ human cord blood cells with lympho-myeloid-limited potential. Analyses of the changes observed revealed the acquisition of B-lymphoid- and neutrophil/monocyte (NM)-restricted properties are accompanied by a concomitantly accelerated and lineage-shared cell cycling activity and loss of self-renewal properties. Parallel, single-cell transcriptome analysis identified reduced expression of multiple self-renewal-associated genes and an accompanying heterogeneous activation of lineage-regulatory modules during the production of B, NM and dendritic cell precursors. These results uncover a connected regulation of lineage-shared proliferation control with persistent heterogeneity in the biological and transcriptional changes in the same cells undergoing B and NM lineage restriction.
Personalized composite scaffolds for accelerated cell- and growth factor-free craniofacial bone regeneration
Authors: Kim Mirae , Collins Caralyn P. , Liu Yugang , Tsal Hsiu-Ming , Ahn Yujin , Wang Xinlong , Song Joseph W. , Duan Chongwen , Sun Cheng , Yi Zhu , He Tong-Chuan , Reid Russell R. , Ameer Guillermo A. 
Published: February 2024

AbstractApproaches to regenerating bone often rely on the integration of biomaterials and biological signals in the form of cells or cytokines. However, from a translational point of view, these approaches face challenges due to the sourcing and quality of the biologic, unpredictable immune responses, complex regulatory paths, and high costs. We describe a simple manufacturing process and a material-centric 3D-printed composite scaffold system (CSS) that offers distinct advantages for clinical translation. The CSS comprises a 3D-printed porous polydiolcitrate-hydroxyapatite composite elastomer infused with a polydiolcitrate-graphene oxide hydrogel composite. Using a continuous liquid interface production 3D printer, we fabricate a precise porous ceramic scaffold with 60% hydroxyapatite content resembling natural bone. The resulting scaffold integrates with a thermoresponsive hydrogel composite, customizablein situto fit the defect. This hybrid phasic porous CSS mimics the bone microenvironment (inorganic and organic) while allowing independent control of each material phase (rigid and soft). The CSS stimulates osteogenic differentiationin vitroandin vivo. Moreover, it promotes M2 polarization and blood vessel ingrowth, which are crucial for supporting bone formation. Our comprehensive micro-CT analysis revealed that within 4 weeks in a critical-size defect model, the CSS accelerated ECM deposition (8-fold) and mineralized osteoid (69-fold) compared to the untreated. Our material-centric approach delivers impressive osteogenic properties and streamlined manufacturing advantages, potentially expediting clinical application for bone reconstruction surgeries.
Investigating the use of odour and colour foraging cues by rosy-faced lovebirds (Agapornis roseicollis) using deep-learning based behavioural analysis
Authors: Wai Tsang Winson King , Kei Poon Emily Shui , Newman Chris , Buesching Christina D. , Sin Simon Yung Wa 
Published: February 2024

AbstractOlfaction and vision can play important roles in optimizing foraging decisions of birds, enabling them to maximize their net rate of energy intake while searching for, handling, and consuming food. Parrots have been used extensively in avian cognition research, and some species use olfactory cues to find food. Here we pioneered machine learning analysis and pose-estimation with convolutional neural networks (CNNs) to elucidate the relative importance of visual and olfactory cues for informing foraging decisions in the rosy-faced lovebird (Agapornis roseicollis) as a non-typical model species. In a binary choice experiment, we used markerless body pose tracking to analyse bird response behaviours. Rosy-faced lovebirds quickly learnt to discriminate the feeder provisioned with food by forming an association with visual (red/green papers) but not olfactory (banana/almond odour) cues. When visual cues indicated the provisioned and empty feeders, feeder choice was more successful, choice latency shorter, and interest in the empty feeder significantly lower. This demonstrates that visual cues alone are sufficient to inform lovebird foraging decisions without needing to use olfactory cues, suggesting that selection has not driven olfactory-based foraging in lovebird evolution.
A Novel Support Vector Machine-Based One-Day, Single-Dose Prediction Model of Genotoxic Hepatocarcinogenicity in Rats
Authors: Gi Min , Suzuki Shugo , Kanki Masayuki , Yokohira Masanao , Tsukamoto Tetsuya , Fujioka Masaki , Vachiraarunwong Arpamas , Qiu Guiyu , Guo Runjie , Wanibuchi Hideki 
Published: February 2024

AbstractThe development of a rapid and accurate model for determining the genotoxicity and carcinogenicity of chemicals is crucial for effective cancer risk assessment, and it also contributes to cancer prevention. This study aims to develop a one-day, single-dose model for identifying genotoxic hepatocarcinogens (GHCs) in rats. Microarray gene expression data from the livers of rats administered a single dose of 58 compounds, including 5 GHCs, was obtained from the Open TG-GATEs database and used for the identification of marker genes and the construction of a predictive classifier to identify GHCs in rats. We identified 10 gene markers commonly responsive to all 5 GHCs and used them to construct a support vector machine-based predictive classifier. This classifier effectively distinguishes GHCs from other compounds, demonstrating 100% sensitivity and over 96% specificity. To further assess the model’s effectiveness and reliability, we conducted multi-institutional one-day single oral administration studies on rats. These studies examined 64 compounds, including 23 GHCs, with gene expression data of the marker genes obtained via quantitative PCR (qPCR) 24 hours after a single oral administration. Our results demonstrate that qPCR analysis is an effective alternative to microarray analysis. The GHC predictive model showed high accuracy and reliability, achieving a sensitivity of 91% (21/23) and a specificity of 93% (38/41) across multiple validation studies in three institutions. In conclusion, the present one-day single oral administration model proves to be a reliable and highly sensitive tool for identifying GHCs and is anticipated to be a valuable tool in identifying and screening potential GHCs.
YAP promotes chromosomal instability by transcriptionally activating AJUBA through its super enhancer in breast cancer
Authors: Huang Qingwen , Zhang Rui , Meng Weijian , Dong Hongliang , Qi Zhihong , Chen Zhuo , Liu Liang , Shen Jie , Xie Daxing 
Published: February 2024

SummaryChromosomal instability (CIN) has been proven to be a fundamental property of cancer and a key underlying mechanism of tumorigenesis and progression. Still, relatively few studies have revealed the mechanism of this process. In this research, we identified the core Hippo component, YAP, played a crucial role in CIN formation in breast cancer. Using public ChIP-seq data and bioinformatic analysis, we found YAP could transcriptionally induce spindle assembly checkpoint, AJUBA, via TEAD, then activate AJUBA-AURKA signaling. Abolish AJUBA-AURKA axis could reverse YAP-induced CIN formation and aberrant mitosis. Mechanically, YAP/TEAD complex could accumulate to the super enhancer region of AJUBA, thus significantly induced its expression, and subsequently promoted AURKA auto-phosphorylating. These findings revealed a novel cross-talk between Hippo and AJUBA-AURKA signaling, and provided a new insight in CIN formation in breast cancer.
Chromosomal inversions harbour excess mutational load in the coral,Acropora kenti,on the Great Barrier Reef
Authors: Zhang Jia , Schneller Nadja M. , Field Matt A. , Chan Cheong Xin , Miller David J. , Strugnell Jan M. , Riginos Cynthia , Bay Line , Cooke Ira 
Published: February 2024

AbstractThe future survival of coral reefs in the Anthropocene depends on the capacity of corals to adapt as oceans warm and extreme weather events become more frequent. Targeted interventions designed to assist evolutionary processes in corals require a comprehensive understanding of the distribution and structure of standing variation, however, efforts to map genomic variation in corals have so far focussed almost exclusively on SNPs, overlooking structural variants that have been shown to drive adaptive processes in other taxa. Here we show that the reef-building coral,Acropora kenti(syn. tenuis) harbors at least five large, highly polymorphic structural variants, all of which exhibit signatures of strongly suppressed recombination in heterokaryotypes, a feature commonly associated with chromosomal inversions.Based on their high minor allele frequency, uniform distribution across habitats, and elevated genetic load, we propose that these inversions inA. kentiare likely to be under balancing selection. An excess of SNPs with high impact on protein coding genes within these loci elevates their importance both as potential targets for adaptive selection and as contributors to genetic decline if coral populations become fragmented or inbred in future.
Effects of tenascin-C on dental pulp tissue in micein vivoand on the proliferation and differentiation of dental pulp stem cells into odontoblasts and calcificationin vitro
Authors: Kojima Kentaro , Akashi Yoshihiko , Nakajima Kei , Kokubun Katsutoshi , Shintani Seikou , Matsuzaka Kenichi 
Published: February 2024

AbstractThis study aimed to investigate the effects of tenascin-C (TN-C) on dental pulp tissue and on dental pulp stem cells (DPSCs). In in vivo studies, A collagen sponge with phosphate-buffered saline (PBS) for the control group or with TN-C for the experimental group was placed over the dental pulp of mice. The root pulp was excised at 7 and 21 days postoperatively and was observed microscopically using HE staining and immunohistochemistry. Inflammatory cells were found in the entire pulp tissue in the control group but no inflammatory cells were identified in the pulp tissue in the TN-C-treated experimental group. Further, nestin-positive cells at 7 days and dentin sialophosphoprotein (DSPP)-positive cells at 21 days were seen in the experimental group. In in vitro studies, DPSCs were cultured in a medium with or without TN-C, after which the proliferation rate of DPSCs was measured mRNA expression levels were examined using quantitative reverse transcription polymerase chain reaction (qRT-PCR), and the formation of calcified nodules was investigated using alizarin red staining. The cell proliferation rate was not significantly different between the experimental and control groups. The expression of nestin mRNA on day 7 was significantly higher in the experimental group than in the control group (P<0.05), but the expression of osteocalcin (OCN) mRNA was significantly higher in the control group than in the experimental group (P<0.05). More calcified nodules formed in the control group than in the experimental group. These results suggest that TN-C regulates inflammation during the healing process in the dental pulp and induces the differentiation of dental pulp into odontoblast-like cells. Further, TN-C promotes the early differentiation of DPSCs into odontoblast-like cells, which suggests that TN-C may further contribute to the inhibition of excessive dentin formation.