bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extended fractional-polynomial generalizations of diffusion and Fisher-KPP equations on directed networks: Modeling neurodegenerative progression
Authors: Rahimabadi Arsalan , Benali Habib 
Published: February 2023

AbstractIn a variety of practical applications, there is a need to investigate diffusion or reaction-diffusion processes on complex structures, including brain networks, that can be modeled as weighted undirected and directed graphs. As an instance, the celebrated Fisher-Kolmogorov-Petrovsky-Piskunov (Fisher-KPP) reaction-diffusion equation are becoming increasingly popular for use in graph frameworks by substituting the standard graph Laplacian operator for the continuous one to study the progression of neurodegenerative diseases such as tauopathies including Alzheimer’s disease (AD). However, due to the porous structure of neuronal fibers, the spreading of toxic species can be governed by an anomalous diffusion process rather than a normal one, and if this is the case, the standard graph Laplacian cannot adequately describe the dynamics of the spreading process. To capture such more complicated dynamics, we propose a diffusion equation with a nonlinear Laplacian operator and a generalization of the Fisher-KPP reaction-diffusion equation on undirected and directed networks using extensions of fractional polynomial (FP) functions. A complete analysis is also provided for the extended FP diffusion equation, including existence, uniqueness, and convergence of solutions, as well as stability of equilibria. Moreover, for the extended FP Fisher-KPP reaction-diffusion equation, we derive a family of positively invariant sets allowing us to establish existence, uniqueness, and boundedness of solutions. Finally, we conclude by investigating nonlinear diffusion on a directed one-dimensional lattice and then modeling tauopathy progression in the mouse brain to gain a deeper understanding of the potential applications of the proposed extended FP equations.
Vaccinia virus induces EMT-like transformation and RhoA-mediated mesenchymal migration
Authors: Liu Wei , Lu Jia-Yin , Wang Ya-Jun , Xu Xin-Xin , Chen Yu-Chen , Yu Sai-Xi , Xiang Xiao-Wei , Chen Xue-Zhu , Jiu Yaming , Gao Hai , Sheng Mengyao , Chen Zheng-Jun , Hu Xinyao , Li Dong , Maiuri Paolo , Huang Xinxin , Ying Tianlei , Xu Guo-Liang , Pang Dai-Wen , Zhang Zhi-Ling , Liu Baohong , Liu Yan-Jun 
Published: February 2023

AbstractThe emerging outbreak of monkeypox is closely associated with the viral infection and spreading, threatening global public health. Virus-induced cell migration facilitates viral transmission. However, high-resolution dynamics and mechanisms underlying this type of cell migration remain unclear. Here, we investigate the motility of cells infected by vaccinia virus (VACV), a close relative of monkeypox, through combining multi-omics analyses and high-resolution live-cell imaging. We find that, upon VACV infection, the epithelial cells undergo EMT-like transformation, during which they lose intercellular junctions and acquire the migratory capacity to promote viral spreading. After transformation, VACV-induced mesenchymal migration is highly dependent on the actin cytoskeleton and RhoA signaling, which is responsible for the depolymerization of robust actin stress fibers, the leading-edge protrusion formation, and the rear-edge recontraction. Our study reveals how poxviruses alter the epithelial phenotype and regulate RhoA signaling to induce fast migration, providing a unique perspective to understand the pathogenesis of poxviruses.
Network-based molecular subtyping of acral melanoma
Authors: Mingzhu Yin , Zhang Yiding , Wang Wenhua , Zhao Shuang , Su Juan , Li Shao , Chen Xiang 
Published: February 2023

AbstractAcral melanoma is more biologically aggressive with a worse prognosis compared with other melanoma subtypes. However, the molecular basis underlying the biological and clinical behavior of this cancer is still unclear. Here, using the combination of multi-omics data analysis and network-based disease gene prediction algorithm, we first demonstrate the existence of two acral melanoma subtypes which greatly differed in clinical performance, cellular and molecular mechanisms, and discovered a biomarker panel (EREG, VSIG4, FCGR3A, RAB20) that accurately distinguished these two subtypes with the AUC of 0.946, which has been verified by clinical samples. Subtype I has thinner Breslow with a better prognosis. On the contrary, subtype II is a high-risk subtype that is easier to invade the dermis. We further analyzes the intrinsic biological mechanism of the two subtypes from the cellular level, and reveals the important role of macrophages subgroups in the molecular typing of acral melanoma. Feature genes of subtype I are enriched in FCN1+ macrophages that promote inflammatory and immune responses. In contrast, feature genes of subtype II are enriched in SPP1+ macrophages which ha the greatest impact on tumor cells. The identification of the two subtypes opens up important biological and clinical perspectives for acral melanoma.
High-Quality Nuclei Isolation from Postmortem Human Heart Muscle Tissues for Single-Cell Studies
Authors: Araten Sarah , Mathieu Ronald , Jetly Anushka , Shin Hoon , Hilal Nazia , Zhang Bo , Morillo Katherine , Nandan Deepa , Sivankutty Indu , Chen Ming Hui , Choudhury Sangita 
Published: February 2023

AbstractSingle-cell approaches have become an increasingly popular way of understanding the genetic factors behind disease. Isolation of DNA and RNA from human tissues is necessary to analyze multi-omic data sets, providing information on the single-cell genome, transcriptome, and epigenome. Here, we isolated high-quality single-nuclei from postmortem human heart tissues for DNA and RNA analysis. Postmortem human tissues were obtained from 106 individuals, 33 with a history of myocardial disease, diabetes, or smoking, and 73 controls without heart disease. We demonstrated that the Qiagen EZ1 instrument and kit consistently isolated genomic DNA of high yield, which can be used for checking DNA quality before conducting single-cell experiments. Here, we provide a method for single-nuclei isolation from cardiac tissue, otherwise known as the SoNIC method, which allows for the isolation of single cardiomyocyte nuclei from postmortem tissue by nuclear ploidy status. We also provide a detailed quality control measure for single-nuclei whole genome amplification and a pre-amplification method for confirming genomic integrity.
Nomadic ungulate movements under threat: Declining mobility of Mongolian gazelles in the Eastern Steppe
Authors: Mendgen Philipp , Dejid Nandintsetseg , Olson Kirk , Buuveibaatar Bayarbaatar , Calabrese Justin M. , Chimeddorj Buyanaa , Dalannast Munkhnast , Fagan William F. , Leimgruber Peter , Müller Thomas 
Published: February 2023

AbstractIncreasing habitat fragmentation and disturbance threaten long distance movements of ungulates. While the effects of impermeable barriers on ungulate migrations have been well researched, quantitative evidence for gradual and long-term changes of mobility in response to anthropogenic disturbance remains relatively rare.We investigated changes in movement behavior of Mongolian gazelleProcapra gutturosa, a nomadic ungulate species native to the Mongolian steppe. Using GPS tracking data collected from 62 gazelle individuals between 2007 and 2021, we quantified 16-day displacement distances for each individual as a metric for long-distance movements. We used generalized linear mixed models, generalized additive models and additive quantile mixed models to assess how anthropogenic and environmental factors affected gazelle movement behavior.Long distance 16-day movements decreased significantly by up to 36 %, from 142 km in 2007 to 92 km in 2021. Changes in gazelle mobility were affected by the increasing number of vehicles in Mongolia, but could not be explained by concurrent changes in other environmental factors like temperature, precipitation or vegetation greenness that often drive ungulate migration behavior. Moreover, we found that gazelle movement decreased close to roads, and that gazelles stayed further away from roads during the snow-free season, when vehicular traffic likely is most intense.Conserving landscape permeability is essential for maintaining populations of highly mobile species. Our study provides evidence for a gradual decline in gazelle mobility over fifteen years as a response to increasing anthropogenic impact. To date, the transportation infrastructure permeating the Eastern Steppe does not pose physical barriers, yet our findings suggest that increasing traffic volume may create semipermeable barriers to gazelle movement. As human activity is increasing throughout the Eastern Steppe, interactions between ungulates and vehicle traffic need to be closely monitored in order to identify, localize, and mitigate semipermeable barrier effects before landscape permeability is severely altered.
Interactive Bioacoustic Playback as a Tool for Detecting and Exploring Nonhuman Intelligence: “Conversing” with an Alaskan Humpback Whale
Authors: McCowan Brenda , Hubbard Josephine , Walker Lisa , Sharpe Fred , Frediani Jodi , Doyle Laurance 
Published: February 2023

ABSTRACTHere we report on a rare and opportunistic acoustic “conversation” with an adult female humpback whale, known as Twain, in Southeast Alaska. Post hoc acoustic and statistical analyses of a 20-minute acoustic exchange between the broadcast of a recorded contact call, known as a ‘whup/throp’, with call responses by Twain revealed an intentional human-whale acoustic (and behavioral) interaction. Our results show that Twain participated both physically and acoustically in three phases of interaction (Phase 1: Engagement, Phase 2: Agitation, Phase 3: Disengagement), independently determined by blind observers reporting on surface behavior and respiratory activity of the interacting whale. A close examination of both changes to the latency between Twain’s calls and the temporal matching to the latency of the exemplar across phases indicated that Twain was actively engaged in the exchange during Phase 1 (Engagement), less so during Phase 2 (Agitation), and disengaged during Phase 3 (Disengagement). These results, while preliminary, point to several key considerations for effective playback design, namely the importance of salient, dynamic and adaptive playbacks, that should be utilized in experimentation with whales and other intelligent nonhuman species.
A novel lethal cuticular structural protein, AaCPR100A and its upstream interaction protein, G12-like, function in cuticle and egg shell formation in the yellow fever mosquito,Aedes aegypti
Authors: Chen Jing , Wu Yuchen , Lu Haoran , Cheng Gong , Tu Zhijian Jake , Liao Chenghong , Han Qian 
Published: February 2023

AbstractAaCPR100A is a structural protein, found in the soft cuticle ofAe. Aegypti. RNAi ofAaCPR100Aresulted in high mortality inAe. Aegyptiand abnormal egg development in the surviving mosquitoes. Over thirty proteins that could interact with AaCPR100A were screened out by yeast two-hybrid assay, and subsequently, further verification by hybrid and GST pull-down assays identified that G12-like had the strongest interaction with AaCPR100A. RNAi ofG12-likesuggested it may be related to larva development. Interestingly, the adults in which theG12-likegenewasknocked down were sensitive to low temperature, and their egg shell formation, production, and hatching were affected.G12-likehas the opposite effect in the upstream expression ofAaCPR100A, promotingAaCPR100Afunction in the larval stage and inhibitingAaCPR100Ain the adult stage. In all, functional studies of AaCPR100A and its interaction protein G12-like provide insight into its involvement in cuticle development and formation and egg shell formation.
Nano-structured Hydrotrope-Caged Cytochrome c with Boosted Stability in Harsh Environments: A Molecular Insight
Authors: Bharadwaj Pranav , Sarkar Dheeraj Kumar , Bisht Meena , Shet Sachin M. , Kotrappanavar Nataraj Sanna , Lokesh Veeresh , Franklin Gregory , Brezovsky Jan , Mondal Dibyendu 
Published: February 2023

AbstractGreen and nano-structured catalytic media are vital for bio-catalysis to attenuate the denaturation tendency of biocata-lysts under severe reaction conditions. Hydrotropes with multi-faceted physiochemical properties represent promising systems for sustainable protein packaging. Herein, the suitability of adenosine-5’-triphosphate (ATP) and cholinium sa-licylate ([Cho][Sal]) ionic liquid (IL) to form nano-structures and to nano-confine Cytochrome c (Cyt c) were demonstrat-ed to enhance the stability and activity under multiple stressors. Experimental and computational analyses were under-taken to explain the nano-structured phenomenon of ATP and IL, structural organizations of nano-confined Cyt c, and site-specific interactions that stabilize the protein structure. Both ATP and IL form nano-structures in aqueous media and could cage Cyt c via multiple nonspecific soft interactions. Remarkably, the engineered molecular nano-cages of ATP (5-10 mM), IL (300 mg/mL), and ATP+IL surrounding Cyt c resulted in 9-to-72-fold higher peroxidase activity than native Cyt c with exceptionally high thermal tolerance (110oC). The polar interactions with the cardiolipin binding site of Cyt c, mediated by hydrotropes, were well correlated with the increased peroxidase activity. Furthermore, higher activity trends were observed in the presence of urea, GuHCl, and trypsin without any protein degradation. Specific binding of hy-drotropes in highly mobile regions of Cyt c (Ω 40-54 residues) and enhanced H-bonding with Lys and Arg offered excel-lent stability under extreme conditions. Additionally, ATP effectively counteracted reactive oxygen species (ROS)-induced denaturation of Cyt c, which was enhanced by the [Sal] counterpart of IL. Overall, this study explored the robustness of nano-structured hydrotropes to have a higher potential for protein packaging with improved stability and activity under extreme conditions. Thus, the present work highlights a novel strategy for real-time industrial bio-catalysis to protect mitochondrial cells from ROS-instigated apoptosis.SummarySuitability of ATP and [Cho][Sal] ionic liquid to form nanostructured hydrotropes and their utility in protein packaging in extreme conditions are discussed. Both ATP and IL form nanostructures in aqueous media and could cage Cyt c via multiple nonspecific soft interactions. The engineered molecular nanocages surrounding Cyt c resulted in 9-to-72-fold higher peroxidase activity than native Cyt c with exceptionally high thermal tolerance (110°C) and stability in the presence of urea, GuHCl, and trypsin without any protein degradation.
Differential expression of some termite neuropeptides and insulin/IGF-related hormones and their plausible functions in growth, reproduction and caste determination
Authors: Veenstra Jan A. 
Published: February 2023

AbstractBackgroundInsulin-like growth factor (IGF) and other Insulin-like peptides (ilps) are important hormones regulating growth and development in animals. Whereas most animals have a single female and male adult phenotype, in some insect species the same genome may lead to different final forms. Perhaps the best known example is the honeybee where females can either develop into queens or workers. More extreme forms of such polyphenism occur in termites, where queens, kings, workers and soldiers coexist. Both juvenile hormone and insulin-like peptides are known to regulate growth and reproduction as well as polyphenism. In termites the role of juvenile hormone in reproduction and the induction of the soldier caste is well known, but the role of IGF and other ilps in these processes remains largely unknown. Here the various termite ilps are identified and hypotheses regarding their functions suggested.MethodsGenome assemblies and transcriptome short read archives (SRAs) were used to identify insulin-like peptides and neuropeptides in termites and to determine their expression in different species, tissues and castes.Results and DiscussionTermites have seven different ilps,i.e. gonadulin, IGF and an ortholog ofDrosophilainsulin-like peptide 7 (dilp7), which are commonly present in insects, and four smaller peptides, that have collectively been called short IGF-related peptides (sirps) and individually atirpin, birpin, cirpin and brovirpin. Gonadulin is lost from the higher termites which have however amplified the brovirpin gene, of which they often have two or three paralogs. Based on differential expression of these genes it seems likely that IGF is a growth hormone and atirpin an autocrine tissue factor that is released when a tissue faces metabolic stress. Birpin seems to be responsible for growth and in the absence of juvenile hormone this may lead to reproductive adults or, when juvenile hormone is present, to soldiers. Brovirpin is expressed both by the brain and the ovary and likely stimulates vitellogenesis, while the function of cirpin is less clear.
Neutral models ofde novogene emergence suggest that gene evolution has a preferred trajectory
Authors: Iyengar Bharat Ravi , Bornberg-Bauer Erich 
Published: February 2023

AbstractNew protein coding genes can emerge from genomic regions that previously did not contain any genes, via a process calledde novogene emergence. To synthesize a protein, DNA must be transcribed as well as translated. Both processes need certain DNA sequence features. Stable transcription requires promoters and a polydenylation signal, while translation requires at least an open reading frame (ORF). We develop mathematical models based on mutation probabilities, and the assumption of neutral evolution, to find out how quickly genes emerge and are lost. We also investigate the effect of the order by which DNA features evolve, and if sequence composition is biased by mutation rate. We rationalize how genes are lost much more rapidly than they emerge, and how genes with long ORFs preferentially arise in regions that are already transcribed. Our study not only answers some fundamental questions on the topic ofde novoemergence but also provides a modeling framework for future studies.
DiscoTope-3.0 - Improved B-cell epitope prediction using AlphaFold2 modeling and inverse folding latent representations
Authors: Høie Magnus Haraldson , Gade Frederik Steensgaard , Johansen Julie Maria , Würtzen Charlotte , Winther Ole , Nielsen Morten , Marcatili Paolo 
Published: February 2023

AbstractAccurate computational identification of B-cell epitopes is crucial for the development of vaccines, therapies, and diagnostic tools. However, current structure-based prediction methods face limitations due to the dependency on experimentally solved structures. Here, we introduce DiscoTope-3.0, a markedly improved B-cell epitope prediction tool that innovatively employs inverse folding structure representations and a positive-unlabelled learning strategy, and is explicitly adapted for both solved and predicted structures. Our tool demonstrates a considerable improvement in performance over existing methods, accurately predicting linear and conformational epitopes across multiple independent datasets. Most notably, DiscoTope-3.0 maintains high predictive performance across solved, relaxed and predicted structures, alleviating the need for experimental validation and extending the general applicability of accurate B-cell epitope prediction by more than 3 orders of magnitude. DiscoTope-3.0 is made widely accessible on two web servers, processing over 100 structures per submission, and as a downloadable package. In addition, the servers interface with RCSB and AlphaFoldDB, facilitating large-scale prediction across over 200 million cataloged proteins. DiscoTope-3.0 is available at:https://services.healthtech.dtu.dk/service.php?DiscoTope-3.0
Improving selection efficiency inC. americana×C. avellanainterspecific hybrids through the development of an indel-based genetic map
Authors: Brainard S.H. , Fischbach J.A. , Braun L.C. , Dawson J.C. 
Published: February 2023

AbstractThis study reports a genetic map created using a progeny family descended from the interspecific hazelnut crossCorylus avellana×Corylus americana. This research represents a critical step in the development of genomic tools that enable the deployment of next-generation sequencing methods in the breeding of hazelnut, specifically the improvement of well-adapted Midwestern hazelnut varieties. To produce this map, we first developed high-density molecular markers using short-read Illumina sequencing of genotype-by-sequencing libraries. By aligning reads to a newly assembled reference genome forC. americana, we were able to identify over 75,000 high-quality indel-based polymorphisms across an F1experimental population. These markers exhibited both high allele depth coverage, and low linkage disequilibrium, making them well-suited to genetic map development. We constructed such a map using 95 individuals from a single F1 family, demonstrating the utility of next-generation sequencing to efficiently and accurately generate high-density genetic maps. This research will improve the efficiency of breeding efforts, both through the validation of specific molecular markers that are associated with agronomically-relevant traits in breeding populations of interest.
Implicit auditory memory in older listeners: from encoding to 6-month retention
Authors: Bianco Roberta , Hall Edward T. R. , Pearce Marcus. T. , Chait Maria 
Published: February 2023

AbstractAny listening task, from sound recognition to sound-based communication, rests on auditory memory which is known to decline in healthy ageing. However, how this decline maps onto multiple components and stages of auditory memory remains poorly characterised. In an online unsupervised longitudinal study, we tested ageing effects on implicit auditory memory for rapid tone patterns. The test required participants (younger, aged 20-30, and older adults aged 60-70) to quickly respond to rapid regularly repeating patterns emerging from random sequences. Patterns were novel in most trials (REGn), but unbeknownst to the participants, a few distinct patterns reoccurred identically throughout the sessions (REGr). After correcting for processing speed, the response times (RT) to REGn should reflect the information held in echoic and short-term memory before detecting the pattern; long-term memory formation and retention should be reflected by the RT advantage (RTA) to REGr vs REGn which is expected to grow with exposure. Older participants were slower than younger adults in detecting REGn and exhibited a smaller RTA to REGr. Computational simulations using a model of auditory sequence memory indicated that these effects reflect age-related limitations both in early and long-term memory stages. In contrast to ageing-related accelerated forgetting of verbal material, here older adults maintained stable memory traces for REGr patterns up to 6 months after the first exposure. The results demonstrate that ageing is associated with reduced short-term memory and long-term memory formation for tone patterns, but not with forgetting, even over surprisingly long timescales.