bluuebunny/crossref_metadata_2025_split huggingface dataset:
AnnoDUF: A Web-Based Tool for Annotating Functions of Proteins having Domains of Unknown Function (DUFs)
Authors: Vishwakarma Aman , Padmashali Namrata , Thiyagarajan Saravanamuthu 
Published: June 2024

ABSTRACTThe rapid expansion of biological sequence databases due to high-throughput genomic and proteomic sequencing methods has left a considerable number of identified protein sequences with unclear or incomplete functional annotations. DUFs are protein domains that lack functional annotations but are present in numerous proteins. To address the challenge of finding functional annotations for DUFs, we have developed a computational method, which efficiently identifies and annotates these enigmatic protein domains by utilizing PSI-BLAST and data mining techniques. Our pipeline identifies putative potential functionalities of DUFs, thereby decreasing the gap between known sequences and functions. The tool can also take user input sequences to annotate. We executed our pipeline on 4,775 unique DUF sequences obtained from Pfam, resulting in putative annotations for 1,971 of these. These annotations were subsequently incorporated into a comprehensive database and interfaced with a web-based server named ‘AnnoDUF’. AnnoDUF is freely accessible to both academic and industrial users, via World Wide Web at the linkhttp://bts.ibab.ac.in/annoduf.php.
The influence of basal CO2on neurofluid dynamics measured using resting-state BOLD fMRI
Authors: Zhong Xiaole Z. , Chang Catie , Chen J. Jean 
Published: June 2024

AbstractAn understanding of neurofluid dynamics has been gaining importance, in part given the link between neurofluid dynamics and glymphatic flow. As carbon dioxide (CO2) strongly modulates cerebral blood volume (CBV) and cerebrospinal fluid (CSF) flow, modulation of basal CO2 through different capnic conditions may offer insight into the mechanisms through which neurofluid dynamics are influenced. In this work, we report observations of neurofluid dynamics at normocapnia as well as during short-term hyper- and hypocapnia. We use the resting-state BOLD fMRI signal in neurofluid regions of interest (i.e. blood vessels, CSF compartments) as a surrogate of neurofluid dynamics. From these BOLD signals, we extract the power and central frequency of signal oscillations. We found that 1) Relative to a normocapnic steady state, both hypocapnic and hypercapnic steady states are associated with increased BOLD signal power and shifts in BOLD signal frequency in vascular ROIs in a band-dependent manner; 2) Relative to hypocapnia, hypercapnia is associated with both increased and decreased BOLD signal power in vascular ROIs, depending on the frequency band; 3) these trends are largely reproduced in the CSF ROIs and in the CSF velocity dynamics; 4) these power and frequency variations across capnic conditions are mostly driven by respiratory and heart-rate differences rather than by steady-state CO2and associated vascular-tone variations; 5) the cardiac and respiratory response functions differ substantially across capnic conditions. This work contributes to the establishment of the BOLD signal as a surrogate for neurofluid flow, and highlight the role of the autonomic nervous system (ANS) in linking vascular and CSF dynamics in the brain. The findings suggest that the ANS is also instrumental in the regulation of neurofluid flow in response to alterations of cerebral hemodynamic homeostasis. Furthermore, our findings suggest that this mechanism of ANS regulation differs across capnic states, or more broadly, across individuals with different basal capnic states.
Cold seeps are hotspots of deep-sea nitrogen-loss driven by microorganisms across 21 phyla
Authors: Jiang Qiuyun , Cao Lei , Han Yingchun , Li Shengjie , Zhao Rui , Zhang Xiaoli , Ruff S. Emil , Zhao Zhuoming , Peng Jiaxue , Liao Jing , Zhu Baoli , Wang Minxiao , Lin Xianbiao , Dong Xiyang 
Published: June 2024

AbstractNitrogen bioavailability, governed by the balance of fixation and loss processes, is a key factor regulating oceanic productivity, ecosystem functions, and global biogeochemical cycles. The key nitrogen-loss organisms—denitrifiers and anaerobic ammonium-oxidizing (anammox) bacteria—are not well understood in marine seafloor environments, especially in deep-sea cold seeps. In this study, we combined geochemical measurements,15N stable isotope tracer analysis, metagenomics, metatranscriptomics, and three-dimensional protein structural simulations to investigate the diversity of denitrifying and anammox microbial communities and their biogeochemical roles in these habitats. Geochemical evidence from 301 sediment samples shows significantly higher nitrogen-loss rates in cold seeps compared to typical deep-sea sediments, with an estimated annual nitrogen loss of 6.16 Tg from seafloor surface sediments. Examination of a total of 147 million non-redundant genes reveals a high prevalence and active expression of nitrogen-loss genes, including nitrous-oxide reductase (NosZ; 6.88 genes per million or GPM on average), nitric oxide dismutase (Nod; 1.29 GPM), and hydrazine synthase (HzsA; 3.35 GPM) in surface sediments. Analysis of 3,164 metagenome-assembled genomes from this habitat has expanded the known diversity of nitrous-oxide reducers to six phyla and nitric oxide-dismutating organisms to one phylum and two new orders, while ten phyla host anammox bacteria going beyondPlanctomycetota. These microbes show diverse structural adaptations and complex gene cluster arrangements that potentially enable survival in the harsh conditions of cold seeps. These findings suggest that cold seeps, despite their low temperatures, are significant, previously underestimated hotspots of nitrogen loss, potentially contribute substantially to the global nitrogen cycle.
Strong dependence of demographic stochasticity on a small effective number of breeders in iteroparous species
Authors: Akita Tetsuya 
Published: June 2024

AbstractWe provided a theoretical basis for integrating the effective number of breeders (Nb) into the stochastic dynamics of the number of adults (N) for iteroparous species based on individual relationships between adult females and their offspring. Recruitment variation was partitioned into i) parental, ii) nonparental, and iii) environmental processes (including density-dependent effects). The first two processes, summarized byNb, magnified the contribution of the last process to recruitment variation. Assuming that there were no sex differences and an equal sex ratio, the relationship betweenNband the factor amplifying recruitment variation whenNb/N<0.1 was approximated to provide quantitative guidance for using onlyNb. For example,Nb<42 would have a non-negligible impact on population stochasticity in terms of amplifying the environmental impact by over 5%. The advantage of assessing recruitment variation usingNbalone is that only genetic information on samples from the same cohort is sufficient. Thus, the proposed method is applicable in data-limited situations (e.g. endangered species), where there is typically insufficient information on life-history parameters or current age/size structure. The study findings reveal the usefulness ofNbin the field of conservation biology and wildlife management.
Janus Mazebots and Cellbots Navigating Obstacles in Dense Mammalian Environment
Authors: Sokolich Max , Mallick Sudipta , Belta Calin , Weiss Ron , Das Sambeeta 
Published: June 2024

AbstractThe field of microrobotics has immensely grown in the last few decades, exhibiting several challenges as new features such as shapes, sizes, and actuation mechanisms are explored. Two of the biggest challenges faced in microrobotics are the development of a control system suited for precise microrobotic manipulation, and the ability to navigate microrobots in densely populated environments. In this paper, we fabricate the Mazebot microrobots using silica spheres and ferromagnetic coating, and we use them to create cellbots with genetically modified Chinese Hamster Ovary (CHO) cells. Subsequently, we navigate both the Mazebots and the cellbots through a dense environment populated by CHO cells. The Mazebots navigation is done with a control system that allows the Mazebots to swim on their own, or guide a specific cell from a given origin to a target location while avoiding cell obstacles. The control system operates in open and closed-loop modes, where the first one allows the microrobot to reorient the cell using self-induced fluid vortices, and the second one closely follows a predefined trajectory along the origin and destination. On the other hand, the cellbots navigation is done in closed-loop operation. This enables cell manipulation for potential applications in cell and tissue engineering when in a confined space. Biocompatibility of the Mazebots is confirmed through the exposure of CHO cells to the robots for 24 hours. Experimental results demonstrate the functionality of our algorithm and its potential for biomedical applications, showcasing our system as a powerful and efficient solution for precise cellular manipulation.
The what, how and why of trait-based analyses in ecology
Authors: Guillerme Thomas , Cardoso Pedro , Jørgensen Maria Wagner , Mammola Stefano , Matthews Thomas J. 
Published: June 2024

AbstractFunctional diversity is increasingly used alongside taxonomic diversity to describe populations and communities in ecology. Indeed, functional diversity metrics allow researchers to summarize complex occupancy patterns in space and/or time (what is changing?) that lead to changes in communities and/or populations (the process; how is it changing?) in response to some stressors (the mechanism; why is it changing?). However, as the diversity of functional diversity metrics and methods increases, it is often not directly clear which metric is more readily appropriate for which question. We studied the ability of different functional diversity metrics to recover patterns and signals from different processes linked to common assembly mechanisms (environmental filtering, competitive exclusion, equalizing fitness, and facilitation) in community ecology. Using both simulated data and an empirical dataset affected by more complex and nuanced mechanisms, we tested the effectiveness of different space occupancy metrics to recover the simulated or empirical changes. We show that different metrics perform better for different tasks, emphasizing the importance of not using a one-size-fits-all metric. Instead, researchers should carefully consider and test whether a particular metric will be effective in capturing a pattern of interest.
Genome-wide analysis of Smad and Schnurri transcription factors inC. elegansdemonstrates widespread interaction and a function in collagen secretion
Authors: Vora Mehul , Dietz Jonathan , Wing Zachary , George Karen , Liu Jun , Rongo Christopher , Savage-Dunn Cathy 
Published: June 2024

ABSTRACTSmads and their transcription factor partners mediate the transcriptional responses of target cells to secreted ligands of the Transforming Growth Factor-β (TGF-β) family, including those of the conserved bone morphogenetic protein (BMP) family, yet only a small number of direct target genes have been well characterized. InC. elegans,the BMP2/4 ortholog DBL-1 regulates multiple biological functions, including body size, via a canonical receptor-Smad signaling cascade. Here, we identify functional binding sites for SMA-3/Smad and its transcriptional partner SMA-9/Schnurri based on ChIP-seq peaks (identified by modEncode) and expression differences of nearby genes identified from RNA-seq analysis of corresponding mutants. We found that SMA-3 and SMA-9 have both overlapping and unique target genes. At a genome- wide scale, SMA-3/Smad acts as a transcriptional activator, whereas SMA-9/Schnurri direct targets include both activated and repressed genes. Mutations insma-9partially suppress the small body size phenotype ofsma-3,suggesting some level of antagonism between these factors and challenging the prevailing model for Schnurri function. Functional analysis of target genes revealed a novel role in body size for genes involved in one-carbon metabolism and in the endoplasmic reticulum (ER) secretory pathway, including the disulfide reductasedpy-11. Our findings indicate that Smads and SMA-9/Schnurri have previously unappreciated complex genetic and genomic regulatory interactions that in turn regulate the secretion of extracellular components like collagen into the cuticle to mediate body size regulation.
Longitudinal Associations Between MicroRNAs and Weight in the Diabetes Prevention Program
Authors: Flowers Elena , Stroebel Benjamin , Gong Xingyue , Lewis Kimberly , Aouizerat Bradley E. , Gadgil Meghana , Kanaya Alka M. , Zhang Li 
Published: June 2024

ABSTRACTOBJECTIVECirculating microRNAs show cross-sectional associations with overweight and obesity. Few studies provided data to differentiate between a snapshot perspective on these associations versus how microRNAs characterize prodromal risk from disease pathology and complications. This study assessed longitudinal relationships between circulating microRNAs and weight at multiple time-points in the Diabetes Prevention Program trial.RESEARCH DESIGN AND METHODSA subset of participants (n=150) from the Diabetes Prevention Program were included. MicroRNAs were measured from banked plasma using a Fireplex Assay. We used generalized linear mixed models to evaluate relationships between microRNAs and changes in weight at baseline, year-1, and year-2. Logistic regression was used to evaluate whether microRNAs at baseline were associated with weight change after 2 years.RESULTSIn fully adjusted models that included relevant covariates, seven miRs (i.e., miR-126, miR-15a, miR-192, miR-23a, and miR-27a) were statistically associated with weight over 2 years. MiR-197 and miR-320a remained significant after adjustment for multiple comparisons. Baseline levels of let-7f, miR-17, and miR-320c were significantly associated with 3% weight loss after 2 years in fully adjusted models.DISCUSSIONThis study provided evidence for longitudinal relationships between circulating microRNAs and weight. Because microRNAs characterize the combined effects of genetic determinants and responses to behavioral determinants, they may provide insights about the etiology of overweight and obesity in the context or risk for common, complex diseases. Additional studies are needed to validate the potential genes and biological pathways that might be targeted by these microRNA biomarkers and have mechanistic implications for weight loss and disease prevention.
An Infusible Extracellular Matrix Biomaterial Improves Survival in a Model of Severe Systemic Inflammation
Authors: Karkanitsa Maria , Wang Raymond M. , Lyons Anne C. , Mesfin Joshua M. , Chen Alexander , Spang Martin T. , Quintero Filiberto , Sadtler Kaitlyn , Hepokoski Mark , Christman Karen L. 
Published: June 2024

ABSTRACTExcess systemic inflammation can often be lethal in septic and trauma patients due to onset of multiple organ dysfunction syndrome (MODS). As of right now, there are no effective immunomodulatory therapeutics that can promote survival within this patient population. Pro-regenerative extracellular matrix (ECM) biomaterials have shown success for treatment of local inflammation but have not been fully explored for treating systemic inflammation. Here, we demonstrate efficacy of an intravenously delivered infusible ECM (iECM) material, which promotes increased survival in a murine model of MODS by decreasing systemic mediators of inflammation. Lung and kidney failure are associated with higher mortality in MODS compared to other organ failures, and we demonstrate that iECM localizes primarily to kidney and lung tissues during systemic inflammation induced by endotoxin. iECM successfully lowered vascular permeability within lung tissue and lowered levels of inflammatory cytokine signaling such as IL-6, verified via ELISA and gene expression analyses. We also demonstrated that immune cell infiltration into lung tissue was modulated with iECM treatment, with an increase in neutrophil retention in the lung and decreases in pro-inflammatory macrophage presence. In summation, iECM improves survival from severe systemic inflammation by decreasing the local and systemic inflammatory signaling pathways that contribute to MODS. These results provide a strong rationale for translational studies of iECM treatment in systemic inflammatory syndromes, including sepsis and trauma.
Development and Utilization of 3D Anatomy Education Content using Metaverse and XR for Remote Telemedicine Education
Authors: Choi Dong Hyeok , Choi Seo Yi , Ahn So Hyun , Lee Rena , Cho Sung Ho , Han Seung Ho 
Published: June 2024

AbstractThe objective of this study is to explore innovative integration within the field of anatomy education by leveraging HoloLens 2 Augmented Reality Head-Mounted Display (AR HMD) technology and real-time cloud rendering. Initial 3D datasets, comprising extensive anatomical information for each bone, were obtained through the 3D scanning of a full-body cadaver of Korean male origin. Subsequently, these datasets underwent refinement processes aimed at enhancing visual fidelity and optimizing polygon counts, utilizing Blender software. Unity was employed for the development of the Metaverse platform, incorporating tailored 3D User Experience (UX) and User Interface (UI) components to facilitate interactive anatomy education via imported cadaver models. Integration with real-time remote rendering cloud servers, such as Azure, was implemented to augment the performance and rendering capabilities of the HoloLens 2 AR HMD. The extended reality (XR) content uses the Photon Cloud network for real-time data synchronization and HoloLens 2 voice functionality. The metaverse platform supports user interaction through room creation and joining, with various tools for bone manipulation, color differentiation, and surface output. Collaboration features enable sharing and synchronization of model states. The study highlights the importance of technological innovation in anatomy education for future medical professionals. The proposed content aims to address limitations of traditional methods and enhance learning experiences. Continued efforts in developing and improving such technologies are crucial to equip learners with essential skills for adaptation in the evolving healthcare landscape. keyword: Metaverse, Anatomy, Cadaver, Extended Reality(XR), Virtual Reality(VR)
Active enhancement of synapse driven depolarization of perisynaptic astrocytic processes
Authors: Nakatani Ryo J. , De Schutter Erik 
Published: June 2024

AbstractElectrophysiological properties underlie the fundamental mechanisms of the brain. Although astrocytes have typically been considered not electrically excitable, recent studies have shown depolarization of astrocytes induced by local extracellular potassium changes caused by neuronal activity. Interestingly, astro-cytic depolarization is only induced within the periphery of the astrocyte, where astrocytes contact neurons. This depolarization affects the brain’s information processing, as depolarization alters astrocyte functionality and neurotransmit-ter dynamics. However, specific mechanisms causing astrocytic depolarization have remained unknown due to the limitations of experimental techniques. Here, we construct a computational whole-cell astrocyte model containing experimen-tally verified astrocytic channels relevant to depolarization. Using our model, we suggest that previously reported potassium channels alone are insufficient for astrocyte depolarization and additional mechanisms are required. Our sim-ulations show that NMDARs contribute to this depolarization by cooperating with Kir 4.1 to actively enhance extracellular potassium concentration and, thus, sustain depolarization.
Effect of Circadian Rhythm Modulated Blood Flow on Nanoparticle based Targeted Drug Delivery in VirtualIn VivoArterial Geometries
Authors: Goraya Shoaib A. , Ding Shengzhe , Arif Mariam K. , Kong Hyunjoon , Masud Arif 
Published: June 2024

AbstractDelivery of drug using nanocarriers tethered with vasculature-targeting epitopes aims to maximize the therapeutic efficacy of the drug while minimizing the drug side effects. Circadian rhythm which is governed by the central nervous system has implications for targeted drug delivery due to sleep-wake cycle changes in blood flow dynamics. This paper presents an advanced fluid dynamics modeling method that is based on viscous incompressible shear-rate fluid (blood) coupled with an advection-diffusion equation to simulate the formation of drug concentration gradients in the blood stream and buildup of concentration at the targeted site. The method is equipped with an experimentally calibrated nanoparticle-endothelial cell adhesion model that employs Robin boundary conditions to describe nanoparticle retention based on probability of adhesion, a friction model accounting for surface roughness of endothelial cell layer, and a dispersion model based on Taylor-Aris expression for effective diffusion in the boundary layer. The computational model is first experimentally validated and then tested on engineered bifurcating arterial systems where impedance boundary conditions are applied at the outflow to account for the downstream resistance at each outlet. It is then applied to a virtual geometric model of anin vivoarterial tree developed through MRI-based image processing techniques. These simulations highlight the potential of the computational model for drug transport, adhesion, and retention at multiple sites in virtualin vivomodels. The model provides a virtual platform for exploring circadian rhythm modulated blood flow for targeted drug delivery while minimizing thein vivoexperimentation.Statement of SignificanceA novel integration of nanoparticle-based drug delivery framework with shear-rate dependent blood flow model is presented. The framework is comprised of a unique combination of mechanics-based dispersion model, an asperity model for endothelium surface roughness, and a stochastic nanoparticle-endothelial cell adhesion model. Simulations of MRI basedin vivocarotid artery system showcase the effects of vessel geometry on nanoparticle adhesion and retention at the targeted site. Vessel geometry and target site location impact nanoparticle adhesion; curved and bifurcating regions favor local accumulation of drug. It is also shown that aligning drug administration with circadian rhythm and sleep cycle can enhance the efficacy of drug delivery processes. These simulations highlight the potential of the computational modeling for exploring circadian rhythm modulated blood flow for targeted drug delivery while minimizing thein vivoexperimentation.