bluuebunny/crossref_metadata_2025_split huggingface dataset:
IGF1 Signaling in Temporomandibular Joint Fibrocartilage Stem Cells Regulates Cartilage Growth and Homeostasis in Mice
Authors: Bi Ruiye , Luo Xueting , Li Qianli , Li Peiran , Fan Yi , Ying Binbin , Zhu Songsong 
Published: November 2021

AbstractObjectiveInvestigate functional roles of Igf1 in fibrocartilage stem cell (FCSC) for temporomandibular joint (TMJ) cartilage growth and homeostasis.MethodsGli1-CreER+; RosaTdTomato mice were used for validating FCSCs lineage labeling efficiency. In Gli1-/Col2-CreER+; Igf1fl/fl mice, TMJ cartilage morphological and functional changes were characterized at 4 weeks and 5 months after Igf1 deletion. H&E, Safranine O and immuno-histochemistry staining were performed. FCSCs specificity were characterized using EdU and TUNEL staining. A unilateral anterior crossbite (UAC) mouse model was generated for mimicking TMJ osteoarthritis status.ResultsIn Gli1-CreER+; RosaTdTomato mice, RFP labeled FCSCs showed favorable proliferative capacity. 4 weeks after Igf1 deletion, Gli1+ and Col2+ cell lineages led to distinct pathological changes of TMJ cartilage morphology. A more serious reduction of cartilage thickness and cell density were found in the superficial layers in Gli1-CreER+; Igf1fl/fl mice. 5 months after Igf1 deletion, more severe disordered cell arrangement in TMJ cartilage were found in both groups with Gli1+ and Col2+ specific deletion of Igf1. Immunostaining showed that PI3K/Akt signaling pathway was blocked in the superficial layers of TMJ in Gli1-CreER+; RosaTdTomato mice. Finally, deletion of Igf1 in FCSCs significantly aggravated osteoarthritis (OA) phenotypic changes in TMJ in UAC mice model, characterized in decreased cartilage thickness, cell numbers and loss of extracellular matrix secretion.ConclusionIgf1 deletion disrupted stem cell functions of FCSCs, leading to disordered cell distribution during TMJ growth, as well as exaggerated the OA process in TMJ under pathological condition. In TMJ cartilage, Igf1 expression in FCSCs is critical for PI3K/Akt activation, which may be involved in regulating FCSCs self-renewal and differentiation.
Nonmetric ANOVA: a generic framework for analysis of variance on dissimilarity measures
Authors: Malyutina Alina , Tang Jing , Amiryousefi Ali 
Published: November 2021

Classic Analysis of Variance (ANOVA; cA) tests the explanatory power of a partitioning on a set of objects. Nonparametric ANOVA (npA) extends to a case where instead of the object values themselves, their mutual distances are available. While considerably widening the applicability of the cA, the npA does not provide a statistical framework for the cases where the mutual dissimilarity measurements between objects are nonmetric. Based on the central limit theorem (CLT), we introduce nonmetric ANOVA (nmA) as an extension of the cA and npA models where metric properties (identity, symmetry, and subadditivity) are relaxed. Our model allows any dissimilarity measures to be defined between objects where a distinctiveness of a specific partitioning imposed on those are of interest. This derivation accommodates an ANOVA-like framework of judgment, indicative of significant dispersion of the partitioned outputs in nonmetric space. We present a statistic which under the null hypothesis of no differences between the mean of the imposed partitioning, follows an exactF-distribution allowing to obtain the consequentialp-value. Three biological examples are provided and the performance of our method in relation to the cA and npA is discussed.Significance StatementThe Nonmetric Analysis of Variance (nmANOVA) conveys a framework that allows a compatible type of ANOVA for the cases where the proper metric measurements between objects are either lost, unknown or however inaccessible. While classic ANOVA is based on the measurements of the data from a base datum, the nmANOVA is formulated on the dissimilarity outputs (not necessarily metric) defined between all objects. As the main goal of ANOVA in providing a statistical test for assessing the significance of a considered partitioning on the data, the nmANOVA is yielding a paralleled scheme of inference with 1) accommodating the outcomes dissimilarities intowithinandbetweengroups statistics, 2) assessing their respective divergence with a parametric distribution, and 3) providing a resultantp-value indicative of evidences fore rejecting the null hypothesis.
Enhancer and super-enhancer landscape in polycystic kidney disease
Authors: Lakhia Ronak , Mishra Abheepsa , Biggers Laurence , Malladi Venkat , Cobo-Stark Patricia , Hajarnis Sachin , Patel Vishal 
Published: November 2021

ABSTRACTWidespread aberrant gene expression is pathological hallmark of polycystic kidney disease (PKD). Numerous pathogenic signaling cascades, including c-Myc, Fos, and Jun are transactivated. However, the underlying epigenetic regulators are poorly defined. Here we show that H3K27ac, a histone modification that marks active enhancers, is elevated in mouse and human ADPKD samples. Using comparative H3K27ac ChIP-Seq analysis, we mapped >16000 active intronic and intergenic enhancer elements in Pkd1-mutant mouse kidneys. We find that the cystic kidney epigenetic landscape resembles that of a developing kidney, and >90% of upregulated genes in Pkd1-mutant kidneys are co-housed with activated enhancers in the same topologically associated domains. Furthermore, we identify an evolutionarily-conserved enhancer cluster downstream of the c-Myc gene and super-enhancers flanking both Jun and Fos loci in mouse and human ADPKD models. Deleting these regulatory elements reduces c-Myc, Jun, or Fos abundance and suppresses proliferation and 3D cyst growth of Pkd1-mutant cells. Finally, inhibiting glycolysis and glutaminolysis or activating Ppara in Pkd1-mutant cells lowers global H3K27ac levels and on c-Myc enhancers. Thus, our work suggests that epigenetic rewiring mediates the transcriptomic dysregulation in PKD, and the regulatory elements can be targeted to slow cyst growth.
The sperm protein Spaca6 is essential for fertilization in zebrafish
Authors: Binner Mirjam I. , Kogan Anna , Panser Karin , Schleiffer Alexander , Deneke Victoria E. , Pauli Andrea 
Published: November 2021

AbstractFertilization is a key process in all sexually reproducing species, yet the molecular mechanisms that underlie this event remain unclear. To date, only a few proteins have been shown to be essential for sperm-egg binding and fusion in mice, and only some are conserved across vertebrates. One of these conserved, testis-expressed factors is SPACA6, yet its function has not been investigated outside of mammals. Here we show that zebrafish spaca6 encodes for a sperm membrane protein which is essential for fertilization. Zebrafish spaca6 knockout males are sterile. Furthermore, Spaca6-deficient sperm have normal morphology, are motile, and can approach the egg, but fail to bind to the egg and therefore cannot complete fertilization. Interestingly, sperm lacking Spaca6 have decreased levels of another essential and conserved sperm fertility factor, Dcst2, revealing a previously unknown dependence of Dcst2 expression on Spaca6. Together, our results show that zebrafish Spaca6 regulates Dcst2 levels and is required for binding between the sperm membrane and the oolemma. This is in contrast to murine SPACA6, which was reported not to be required for sperm-egg membrane binding but necessary for fusion. These findings demonstrate that Spaca6 is essential for zebrafish fertilization and is a conserved sperm factor in vertebrate reproduction.
Characterization and simulation of metagenomic nanopore sequencing data with Meta-NanoSim
Authors: Yang Chen , Lo Theodora , Nip Ka Ming , Hafezqorani Saber , Warren Rene L , Birol Inanc 
Published: November 2021

ABSTRACTNanopore sequencing is crucial to metagenomic studies as its kilobase-long reads can contribute to resolving genomic structural differences among microbes. However, platform-specific challenges, including high base-call error rate, non-uniform read lengths, and the presence of chimeric artifacts, necessitate specifically designed analytical tools. Here, we present Meta-NanoSim, a fast and versatile utility that characterizes and simulates the unique properties of nanopore metagenomic reads. Further, Meta-NanoSim improves upon state-of-the-art methods on microbial abundance estimation through a base-level quantification algorithm. We demonstrate that Meta-NanoSim simulated data can facilitate the development of metagenomic algorithms and guide experimental design through a metagenomic assembly benchmarking task.
Human-Plant Coevolution: A modelling framework for theory-building on the origins of agriculture
Authors: Angourakis Andreas , Alcaina-Mateos Jonas , Madella Marco , Zurro Debora 
Published: November 2021

AbstractThe domestication of plants and the origin of agricultural societies has been the focus of much theoretical discussion on why, how, when, and where these happened. The ‘when’ and ‘where’ have been substantially addressed by bioarchaeology, thanks to advances in methodology and the broadening of the geographical and chronological scope of evidence. However, the ‘why’ and ‘how’ have lagged behind, holding on to relatively old models with limited explanatory power. Armed with the evidence now available, we can return to theory by revisiting the mechanisms allegedly involved, disentangling their connection to the diversity of trajectories, and identifying the weight and role of the parameters involved. We present the Human-Plant Coevolution (HPC) model, which represents the dynamics of coevolution between a human and a plant population. The model consists of an ecological positive feedback system (mutualism), which can be reinforced by positive evolutionary feedback (coevolution). The model formulation is the result of wiring together relatively simple simulation models of population ecology and evolution, through a computational implementation in R. The HPC model captures a variety of potential scenarios, though which conditions are linked to the degree and timing of population change and the intensity of selective pressures. Our results confirm that the possible trajectories leading to neolithisation are diverse and involve multiple factors. However, simulations also show how some of those factors are entangled, what are their effects on human and plant populations under different conditions, and what might be the main causes fostering agriculture and domestication.
Robust Identification of Temporal Biomarkers in Longitudinal Omics Studies
Authors: Metwally Ahmed A. , Zhang Tom , Wu Si , Kellogg Ryan , Zhou Wenyu , Tang Hua , Snyder Michael 
Published: November 2021

AbstractLongitudinal studies increasingly collect rich ‘omics’ data sampled frequently over time and across large cohorts to capture dynamic health fluctuations and disease transitions. However, the generation of longitudinal omics data has preceded the development of analysis tools that can efficiently extract insights from such data. In particular, there is a need for statistical frameworks that can identify not only which omics features are differentially regulated between groups but also over what time intervals. Additionally, longitudinal omics data may have inconsistencies, including nonuniform sampling intervals, missing data points, subject dropout, and differing numbers of samples per subject. In this work, we developed a statistical method that provides robust identification of time intervals of temporal omics biomarkers. The proposed method is based on a semi-parametric approach, in which we use smoothing splines to model longitudinal data and infer significant time intervals of omics features based on an empirical distribution constructed through a permutation procedure. We benchmarked the proposed method on five simulated datasets with diverse temporal patterns, and the method showed specificity greater than 0.99 and sensitivity greater than 0.72. Applying the proposed method to the Integrative Personal Omics Profiling (iPOP) cohort revealed temporal patterns of amino acids, lipids, and hormone metabolites that are differentially regulated in male versus female subjects following a respiratory infection. In addition, we applied the longitudinal multi-omics dataset of pregnant women with and without preeclampsia, and the method identified potential lipid markers that are temporally significantly different between the two groups. We provide an open-source R package, OmicsLonDA (Omics Longitudinal Differential Analysis): https://bioconductor.org/packages/OmicsLonDA to enable widespread use.
WWOX-Mediated Degradation of AMOTp130 Negatively Affects Egress of Filovirus VP40 VLPs
Authors: Liang Jingjing , Ruthel Gordon , Freedman Bruce D. , Harty Ronald N. 
Published: November 2021

ABSTRACTEbola (EBOV) and Marburg (MARV) viruses continue to emerge and cause severe hemorrhagic disease in humans. A comprehensive understanding of the filovirus-host interplay will be crucial for identifying and developing antiviral strategies. The filoviral VP40 matrix protein drives virion assembly and egress, in part by recruiting specific WW-domain-containing host interactors via its conserved PPxY Late (L) domain motif to positively regulate virus egress and spread. In contrast to these positive regulators of virus budding, a growing list of WW-domain-containing interactors that negatively regulate virus egress and spread have been identified, including BAG3, YAP/TAZ and WWOX. In addition to host WW-domain regulators of virus budding, host PPxY-containing proteins also contribute to regulating this late stage of filovirus replication. For example, angiomotin (AMOT) is a multi-PPxY-containing host protein that functionally interacts with many of the same WW-domain-containing proteins that regulate virus egress and spread. In this report, we demonstrate that host WWOX, which negatively regulates egress of VP40 VLPs and recombinant VSV-M40 virus, interacts with and suppresses the expression of AMOT. We found that WWOX disrupts AMOT’s scaffold-like tubular distribution and reduces AMOT localization at the plasma membrane via lysosomal degradation. In sum, our findings reveal an indirect and novel mechanism by which modular PPxY/WW-domain interactions between AMOT and WWOX regulate PPxY-mediated egress of filovirus VP40 VLPs. A better understanding of this modular network and competitive nature of protein-protein interactions will help to identify new antiviral targets and therapeutic strategies.IMPORTANCEFiloviruses (Ebola [EBOV] and Marburg [MARV]) are zoonotic, emerging pathogens that cause outbreaks of severe hemorrhagic fever in humans. A fundamental understanding of the virus-host interface is critical for understanding the biology of these viruses and for developing future strategies for therapeutic intervention. Here, we reveal a novel mechanism by which host proteins WWOX and AMOTp130 interact with each other and with the EBOV matrix protein VP40 to regulate VP40-mediated egress of virus like particles (VLPs). Our results highlight the biological impact of competitive interplay of modular virus-host interactions on both the virus lifecycle and the host cell.
Transcriptome and fatty-acid signatures of adipocyte hypertrophy and its non-invasive MR-based characterization in human adipose tissue
Authors: Honecker Julius , Ruschke Stefan , Seeliger Claudine , Laber Samantha , Strobel Sophie , Pröll Priska , Nellaker Christoffer , Lindgren Cecilia M. , Kulozik Ulrich , Ecker Josef , Karampinos Dimitrios C. , Claussnitzer Melina , Hauner Hans 
Published: November 2021

ABSTRACTAdipose tissue is an organ with great plasticity and its hypertrophic expansion is associated with adipocyte dysfunction. How changes in adipocyte morphology are linked to gene expression and which cellular functions are affected remains elusive. We show that adipocyte hypertrophy is associated with transcriptomic changes using RNA-Seq data obtained from adipose tissue and size-separated adipocytes. Genes involved in oxidative phosphorylation, protein biosynthesis and fatty acid metabolism were down-regulated in large adipocytes while genes involved in inflammation were upregulated. For mitochondrial function, a reduction in the expression of thermogenesis related genes and estimated brown/beige adipocyte content was observed in individuals with large adipocytes. As a novel finding the total adipose tissue fatty acid composition was dependent on cell size and depot. MR spectroscopy methods for clinical scanning were developed to characterize adipocyte size and fatty acid composition in a fast and non-invasive manner. Together, the present data provides mechanistic insights on how adipocyte hypertrophy contributes to the manifestation of metabolic disease at the molecular and cellular level. MR spectroscopy was identified as a promising technique for an in-parallel assessment of adipose morphology and fatty acid composition allowing to translate our findings into an improved, non-invasive phenotyping of adipose tissue.
ME-ACP: Multi-view Neural Networks with Ensemble Model for Identification of Anticancer Peptides
Authors: Feng Guanwen , Yao Hang , Li Chaoneng , Liu Ruyi , Huang Rungen , Fan Xiaopeng , Ge Ruiquan , Miao Qiguang 
Published: November 2021

AbstractCancer remains one of the most threatening diseases, which kills millions of lives every year. As a promising perspective for cancer treatments, anticancer peptides (ACPs) overcome a lot of disadvantages of traditional treatments. However, it is time-consuming and expensive to identify ACPs through conventional experiments. Hence, it is urgent and necessary to develop highly effective approaches to accurately identify ACPs in large amounts of protein sequences. In this work, we proposed a novel and effective method named ME-ACP which employed multi-view neural networks with ensemble model to identify ACPs. Firstly, we employed residue level and peptide level features preliminarily with ensemble models based on lightGBMs. Then, the outputs of lightGBM classifiers were fed into a hybrid deep neural network (HDNN) to identify ACPs. The experiments on independent test datasets demonstrated that ME-ACP achieved competitive performance on common evaluation metrics.
Insights from systematic literature review of supply chain resilience and disruption
Authors: Agrawal Nishant , Jain Rajesh Kumar 
Published: November 2021

PurposeThe study of supply chain disruption (SCD) and supply chain resilience (SCR) remains to be studied deeply in the field of business management. The purpose of this paper is to showcase a framework of SCR strategies to reduce the adverse effects of SCD using systematic literature review and data visualization.Design/methodology/approachUsing a systematic literature review approach, the paper explores the concepts of supply chain disruption and supply chain resilience. Through rigorous systematic screening, authors studied papers on both the concepts and have proposed a framework for the same. The authors also have used data visualization and network diagram approaches for better understanding of the topic.FindingsThe systematic literature review of both the concepts brings out some exciting results which give a new direction to supply chain field. The outcome of this research also outlines numerous future research direction, which will be useful for the research community.Practical implicationsThe numerous strategies of SCR should be implemented by manufacturing as well as a service organization. The framework reported in this research help academician and practitioners to understand SCR and to easily overcome any level of disruption. Supply chain managers must also formulate strategies accordingly and make plans to continually expand the system.Originality/valueThis research is the first such attempt to showcase a formal systematic framework and co-occurrence networks as well as overlay networks of SCR and SCD.
A cell-based smoothed finite element method for incompressible turbulent flows
Authors: Liu Mingyang , Gao Guangjun , Zhu Huifen , Jiang Chen 
Published: November 2021

PurposeThe purpose of this paper is to investigate the feasibility of solving turbulent flows based on smoothed finite element method (S-FEM). Then, the differences between S-FEM and finite element method (FEM) in dealing with turbulent flows are compared.Design/methodology/approachThe stabilization scheme, the streamline-upwind/Petrov-Galerkin stabilization is coupled with stabilized pressure gradient projection in the fractional step framework. The Reynolds-averaged Navier-Stokes equations with standard k-epsilon model are selected to solve turbulent flows based on S-FEM and FEM. Standard wall functions are applied to predict boundary layer profiles.FindingsThis paper explores a completely new application of S-FEM on turbulent flows. The adopted stabilization scheme presents a good performance on stabilizing the flows, especially for very high Reynolds numbers flows. An advantage of S-FEM is found in applying wall functions comparing with FEM. The differences between S-FEM and FEM have been investigated.Research limitations/implicationsThe research in this work is limited to the two-dimensional incompressible turbulent flow.Practical implicationsThe verification and validation of a new combination are conducted by several numerical examples. The new combination could be used to deal with more complicated turbulent flows.Social implicationsThe applications of the new combination to study basic and complex turbulent flow are also presented, which demonstrates its potential to solve more turbulent flows in nature and engineering.Originality/valueThis work carries out a great extension of S-FEM in simulations of fluid dynamics. The new combination is verified to be very effective in handling turbulent flows. The performances of S-FEM and FEM on turbulent flows were analyzed by several numerical examples. Superior results were found compared with existing results and experiments. Meanwhile, S-FEM has an advantage of accuracy in predicting boundary layer profile.
Conceptualizing the supplier switching process: an example from public procurement
Authors: Holma Anne-Maria , Bask Anu , Laakso Antti , Andersson Dan 
Published: November 2021

Purpose
This paper aims to develop a framework for switching a service supplier in a supply network.

Design/methodology/approach
The study builds on existing literature in the field of purchasing and supply management, public procurement (PP) and the Industrial Marketing and Purchasing approach, as well as on an illustrative example case, from the PP context, of a supplier switch in a service delivery process.

Findings
During a switching process, the buyer must simultaneously manage the ending of a relationship with the incumbent supplier and the beginning of a relationship with a new supplier. Collaboration with the focal suppliers to develop a service process with standardized components prevents disruptions in the service processes and reduces the impact of the switch on the wider network.

Research limitations/implications
The conceptualization suggested in this paper needs to be further explored in different empirical contexts to assess its practical adequacy.

Practical implications
Practitioners responsible for service procurement can use the findings to develop collaboration with suppliers, both when it comes to service process development and to the switching process. Furthermore, the authors highlight the importance of ending competencies and the development of an exit plan to conduct a “beautiful exit.”

Originality/value
The paper integrates relationship initiation and ending studies, as well as procurement process models to develop a refined switching process framework. Many PPs rely on short-term relationships due to the legal obligation to frequently invite suppliers to tender, thus understanding the supplier switching process is important both for private and public sector actors.