bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the equivalence between agent-based and continuum models for cell population modeling. Application to glioblastoma evolution in microfluidic devices
Authors: Arroyo-Vázquez Raquel B. , Pérez-Aliacar Marina , Ayensa-Jiménez Jacobo , Doblaré Manuel 
Published: September 2024

AbstractMathematical models are invaluable tools for understanding the mechanisms and interactions that control the behavior of complex systems. Modeling a problem as cancer evolution includes many coupled phenomena being therefore impossible to obtain sufficient experimental results to fully evaluate all possible conditions. In this work, we focus on Agent-Based Models (ABMs), as these models allow to obtain more complete and interpretable information at the individual level than other types ofin silicomodels. However, ABMs, need many parameters, requiring more information at the cellular and environmental levels to be calibrated. To overcome this problem we propose a complementary approach to traditional calibration methods. We used existent continuum models able to reproduce experimental data, validated and with fitted parameters, to establish relationships between parameters of both, continuum and agent-based models, to simplify and improve the process of adjusting the parameters of the ABM. With this approach, it is possible to bridge the gap between both kinds of models, allowing to work with them simultaneously and take advantage of the benefits of each of them.To illustrate this methodology, the evolution of glioblastoma (GB) is modeled as an example of application. The resulting ABM obtains very similar results to those previously obtained with the continuum model, replicating the main histopathological features (the formation of necrotic cores and pseudopalisades) appearing in several different in vitro experiments in microfluidic devices, as we previously obtained with continuum models. However, ABMs have additional advantages: since they also incorporates the inherent random effects present in Biology, providing a more natural explanation and a deeper understanding of biological processes. Moreover, additional relevant phenomena can be easily incorporated, such as the mechanical interaction between cells or with the environment, angiogenic processes and cell concentrations far from the continuum requirement as happens, for intance, with immune cells.
RepeatParam: Algorithm for Parameterising Repeat Proteins and Analysis of Repeat Protein Architectures
Authors: Pretorius Daniella , Murray James W. 
Published: September 2024

AbstractMotivationTandem repeat proteins consist of repetitive sequence and structure motifs and have diverse roles in Nature for molecular recognition and signalling. The architecture of repeat proteins can be described using simple helical parameters. Understanding these structural features can inform both the function of these proteins and be used to parametrically design new proteins. Despite their importance, no existing program is capable of completely parameterising repeat proteins.ResultsHere we describe a novel repeat protein parameterisation algorithm, RepeatParam, and a comprehensive repeat protein dataset. RepeatParam determines a helix that defines the global protein architecture and a superhelix that describes the relationship between consecutive repeats. We analyse the relationships between helical parameters and families of different repeat proteins.Availabilityhttps://github.com/dpretorius/repeat-protein-parameterisation
Expression, purification, and characterization of diacylated Lipo-YcjN fromEscherichia coli
Authors: Treviño Matthew A. , Amankwah Kofi , Fernandez Daniel , Weston Scott , Stewart Claire J. , Gallardo Jaime Morales , Shahgholi Mona , Sharaf Naima G. 
Published: September 2024

AbstractYcjN is a putative substrate-binding protein expressed from a cluster of genes involved in carbohydrate import and metabolism inEscherichia coli. Here, we determine the crystal structure of YcjN to a resolution of 1.95 Å, revealing that its three-dimensional structure is similar to substrate binding proteins in subcluster D-I, which includes the well-characterized maltose binding protein (MBP). Furthermore, we found that recombinant overexpression of YcjN results in the formation of a lipidated form of YcjN that is posttranslationally diacylated at cysteine 21. Comparisons of size-exclusion chromatography profiles and dynamic light scattering measurements of lipidated and non-lipidated YcjN proteins suggest that lipidated YcjN aggregates in solution via its lipid moiety. Additionally, bioinformatic analysis indicates that YcjN-like proteins may exist in both Bacteria and Archaea, potentially in both lipidated and non-lipidated forms. Together, our results provide a better understanding of the aggregation properties of recombinantly expressed bacterial lipoproteins in solution and establish a foundation for future studies that aim to elucidate the role of these proteins in bacterial physiology.
Modeling of Non-invasive Cell Membrane Potential Measurement: LTSpice Simulation and Machine Learning Analysis
Authors: Ma Xiaofeng 
Published: September 2024

AbstractThis paper presents a novel simulation approach using electric pulses to measure cell membrane potential. The primary objective was to develop a non-invasive method for accurately assessing membrane potential without altering the cell membrane or its internal components. Traditional techniques, such as voltage-sensitive dyes, often require cell incubation, which can affect membrane properties and reduce measurement accuracy. To overcome these limitations, we modeled the cell as two series-connected capacitors with a negative potential between them. By manipulating this negative potential and analyzing the charge and discharge characteristics, simulations conducted with LTspice demonstrated the feasibility of predicting membrane potential based on these characteristics.We tested 202 groups with various capacitor combinations and measured four key parameters related to charge and discharge currents: maximum current, minimum current, total charge time, and total discharge time. Using the XGBRegressor model, we achieved a strong fit with an R2score of 0.9. This indicates a robust correlation between the measured charge and discharge characteristics and the internal potential of the cell. Our findings suggest that accurate measurement of cell membrane potential is possible by attaching an electrode to the cell without disrupting membrane integrity. Thus, this simulation-based approach offers a promising and non-invasive alternative for measuring cell membrane potential.
Mechanisms of traditional Chinese medicine in modulating cardiac microvascular endothelial cells in various injury models: A comprehensive systematic review
Authors: Zhou Huiwen , Liu Hongxu , Li Xiang , Shang Juju , Chen Jiaping , Zong Huiqi 
Published: September 2024

AbstractBackgroundThe structural and functional failure of cardiac microvascular endothelial cells (CMECs) is a primary contributor to coronary microvascular dysfunction (CMD). Traditional Chinese medicine (TCM) has been identified as a potential therapeutic approach for preserving CMECs and mitigating CMD.ObjectiveThis systematic review aims to present the latest evidence on TCM intervention mechanisms in CMECs under diverse injury models.MethodsThis systematic review was performed following the parameters of the PRISMA statement (Preferred Reporting Items for Systematic Reviews and Meta-Analysis). A comprehensive literature search was conducted using PubMed, Embase, Web of Science, Scopus, China National Knowledge Infrastructure and China Biology Medicine disc. Reference lists of selected articles were reviewed to identify relevant studies. The search was not limited by year and was conducted solely in English. Eligible studies comprised publications describing in vitro studies that presented the latest evidence on TCM intervention mechanisms in CMECs under diverse injury models.ResultsA total of 63 papers were included in this study. According to the cell processing approach, 19 studies on ischemia or hypoxic injury models, 16 studies on Ischemia/reperfusion (I/R) or hypoxia/reoxygenation (H/R) injury models, 10 studies on inflammatory injury models, 5 studies on metabolic injury models, 3 studies on angiotensin II injury models, and 10 studies on other models. TCM exhibits structural and functional intervention capabilities in diverse damage conditions of CMECs. Its mechanism of action involves antioxidant, anti-apoptotic, anti-inflammatory effects, as well as regulation of energy metabolism through signaling pathways such as HIF-1α/VEGF, PI3K/AKT, MAPK, and NF-κB.ConclusionsThe CCM and its constituents modulate CMECs through multiple signaling pathways in response to various injury models, thereby conferring protection on the coronary microcirculation.Graphical Abstract
A novel mechanism for the uptake of enterobactin-chelated ferric ions by the mitochondria and subsequent reduction to ferrous ions inside
Authors: Dutta Abeg , Parthasarathy Anutthaman , Ganesh Pandian Namasivayam 
Published: September 2024

AbstractConventional knowledge of mitochondrial iron metabolism talks about the export of iron in its doubly charged state once it is reduced inside the cell until it reaches the mitochondria. At physiological oxygen tension and pH 7.4, the comparatively soluble Fe(II) is easily available. Fe(III) hydrolyses to generate insoluble ferric hydroxides. Iron must be regularly chaperoned because of its near insolubility and potential toxicity due to redox activity. All tissues pick up iron through the binding of transferrin (Tf) to the transferrin receptor 1 (TfR1), followed by the complex’s internalisation through receptor-mediated endocytosis. The low pH created by the operation of a proton pump within the endosome reduces Tf’s affinity for iron. Importantly, the TfR1 promotes iron escape from Tf in the pH range (pH 5-5.5) reached by the endosome. A "trap," such as pyrophosphate, is neededin vitrofor iron release from Tf. However, a physiological chelator that can play this role has not yet been discovered. Fe(III) is hypothesised to be reduced to Fe(II) in erythroid cells by a ferrireductase known as the six-transmembrane epithelial antigen of the prostate 3 in the endosomal membrane after being released from Tf in the endosome. Following this, the divalent metal transporter-1 (DMT1) transports Fe(II) through the endosomal membrane and, it is generally accepted that this generates the cytosolic labile or chelatable iron pool. This reservoir of iron is believed to provide the metal for metabolic requirements, including as iron intake by the mitochondrion for haem and ISC synthesis, as well as storage in the cytosolic protein ferritin. The possibility of Fe(III) entering the mitochondria has not been explored before. A series of dockings shows that binding of the alpha subunit to a complex of Fe(III) with enterobactin is as stable as the binding with of the same chelator with Fe(II). Enterobactin is a bacterial iron chelator thought to play an integral role in host iron metabolism. Our results suggest an interesting possibility of iron being trafficked to the mitochondria as Fe(III). We propose a potential mechanism of Fe(III) trafficking and subsequent reduction to Fe(II) inside the mitochondria.
Telomere-to-telomere African wild rice (Oryza longistaminata) reference genome reveals segmental and structural variation
Authors: Guang Xuanmin , Yang Jingnan , Zhang Shilai , Guo Fei , Li Linzhou , Lian Xiaoping , Zeng Tao , Cai Chongyang , Liu Fushu , Li Zhihao , Hu Yangzi , Fang Dongming , He Weiming , Sahu Sunil Kumar , Li Wangsheng , Lu Haorong , Li Yuxiang , Liu Huan , Xu Xun , Gu Ying , Hu Fengyi , Dong Yuliang , Wei Tong 
Published: September 2024

AbstractRice (Oryza sativa) is one of the most important staple food crops worldwide, and its wild relatives serve as an important gene pool in its breeding. Compared with cultivated rice species, African wild rice (Oryza longistaminata) has several advantageous traits, such as resistance to increased biomass production, clonal propagation via rhizomes, and biotic stresses. However, previousO. longistaminatagenome assemblies have been hampered by gaps and incompleteness, restricting detailed investigations into their genomes. To streamline breeding endeavors and facilitate functional genomics studies, we generated a 343-Mb telomere-to-telomere (T2T) genome assembly for this species, covering all telomeres and centromeres across the 12 chromosomes. This newly assembled genome has markedly improved over previous versions. Comparative analysis revealed a high degree of synteny with previously published genomes. A large number of structural variations were identified between theO. longistaminataandO. sativa. A total of 2,466 segmentally duplicated genes were identified and enriched in cellular amino acid metabolic processes. We detected a slight expansion of some subfamilies of resistance genes and transcription factors. This newly assembled T2T genome ofO. longistaminataprovides a valuable resource for the exploration and exploitation of beneficial alleles present in wild relative species of cultivated rice.
Efficiently Constructing Complete Genomes with CycloneSEQ to Fill Gaps in Bacterial Draft Assemblies
Authors: Liang Hewei , Wang Mengmeng , Hu Tongyuan , Wang Haoyu , He Wenxin , Ju Yanmei , Guo Ruijin , Chen Junyi , Guo Fei , Zeng Tao , Dong Yuliang , Wang Bo , Liu Chuanyu , Jin Xin , Zhang Wenwei , Zou Yuanqiang , Xu Xun , Xiao Liang 
Published: September 2024

AbstractBackgroundCurrent microbial sequencing relies on short-read platforms like Illumina and DNBSEQ, favored for their low cost and high accuracy. However, these methods often produce fragmented draft genomes, hindering comprehensive bacterial function analysis. CycloneSEQ, a novel long-read sequencing platform developed by BGI-Research, its sequencing performance and assembly improvements has been evaluated.FindingsUsing CycloneSEQ long-read sequencing, the type strain produced long reads with an average length of 11.6 kbp and an average quality score of 14.4. After hybrid assembly with short reads data, the assembled genome exhibited an error rate of only 0.04 mismatches and 0.08 indels per 100 kbp compared to the reference genome. This method was validated across 9 diverse species, successfully assembling complete circular genomes. Hybrid assembly significantly enhances genome completeness by using long reads to fill gaps and accurately assemble multi-copy rRNA genes, which unable be achieved by short reads solely. Through data subsampling, we found that over 500 Mbp of short-read data combined with 100 Mbp of long-read data can result in a high-quality circular assembly. Additionally, using CycloneSEQ long reads effectively improves the assembly of circular complete genomes from mixed microbial communities.ConclusionsCycloneSEQ’s read length is sufficient for circular bacterial genomes, but its base quality needs improvement. Integrating DNBSEQ short reads improved accuracy, resulting in complete and accurate assemblies. This efficient approach can be widely applied in microbial sequencing.
In Vivo Optical Clearing of Mammalian Brain
Authors: Franzesi Giovanni Talei , Gupta Ishan , Hu Ming , Piatkevich Kiryl , Yildirim Murat , Zhao Jian-Ping , Eom Minho , Han Seungjae , Park Demian , Andaraarachchi Himashi , Li Zhaohan , Greenhagen Jesse , Islam Amirul Muhammad , Vashishtha Parth , Yaqoob Zahid , Pak Nikita , Wissner-Gross Alexander D , Martin-Alarcon Daniel A. , Veinot Jonathan J. , So Peter T. C. , Kortshagen Uwe , Yoon Young-Gyu , Sur Mriganka , Boyden Edward S. 
Published: September 2024

ABSTRACTEstablished methods for imaging the living mammalian brain have, to date, taken the brain’s optical properties as fixed; we here demonstrate that it is possible to modify the optical properties of the brain itself to significantly enhance at-depth imaging while preserving native physiology. Using a small amount of any of several biocompatible materials to raise the refractive index of solutions superfusing the brain prior to imaging, we could increase several-fold the signals from the deepest cells normally visible and, under both one-photon and two-photon imaging, visualize cells previously too dim to see. The enhancement was observed for both anatomical and functional fluorescent reporters across a broad range of emission wavelengths. Importantly, visual tuning properties of cortical neurons in awake mice, and electrophysiological properties of neurons assessedex vivo, were not altered by this procedure.
DDGemb: predicting protein stability change upon single- and multi-point variations with embeddings and deep learning
Authors: Savojardo Castrense , Manfredi Matteo , Martelli Pier Luigi , Casadio Rita 
Published: September 2024

AbstractThe knowledge of protein stability upon residue variation is an important step for functional protein design and for understanding how protein variants can promote disease onset. Computational methods are important to complement experimental approaches and allow a fast screening of large datasets of variations. In this work we present DDGemb, a novel method combining protein language model embeddings and transformer architectures to predict protein ΔΔG upon both single- and multi-point variations. DDGemb has been trained on a high-quality dataset derived from literature and tested on available benchmark datasets of single- and multi-point variations. DDGemb performs at the state of the art in both single- and multi-point variations.
Connecting crowns: Analyzing morphological covariation in the modern human postcanine dentition
Authors: Šimková Petra G. , Krenn Viktoria A. , Fornai Cinzia , Wurm Lisa , Halász Vanda , Lidinsky Dominika , Weber Gerhard W. 
Published: September 2024

AbstractMorphological covariation within the modern human postcanine dentition remains an open field of study. Analysis of covariation patterns of the three-dimensional (3D) shape between different tooth types has been seldom conducted, but it is relevant for the advancement of human biology and evolution, as well as dental anthropology, phylogeny, and medicine. Here, we analysed 3D shape covariation of the postcanine dentition (excluding third molars), both within and between dental arches using geometric morphometrics (GM). Based on high-resolution (µCT) scans of 526 teeth from 136 individuals we found high pairwise correlation in tooth pairs within the dental arches (lower P3 and P4, r1= 0.89; upper P3 and P4, r1= 0.81; upper M1 and M2, r1= 0.86). The correlation values between antagonists varied notably from the highest value detected between upper and lower M1s (r = 0.9), to the lowest between upper P4s and lower M1s (r = 0.58). Of all analysed tooth types, only the upper M1s showed moderate to high correlation in every pair analysis. Noticeably, unusually high covariation was detected between some of the tooth type pairs that do not articulate in a normal dentition (e.g., lower P3 and upper M2, r1= 0.88). Furthermore, a relatively high covariation was found in the pairs of lower P4s and M1s (r1= 0.79), and upper P4s and M1s (r1= 0.77), which are the only tooth type pairs of the postcanine dentition belonging to different tooth classes (premolars and molars, respectively) and still serving similar masticatory functions.This study points to the fact that higher morphological integration seems to characterize teeth within the same dental arch rather than between antagonistic teeth. With this study, we provided an overview of pairwise correlations and strength of covariation between different tooth types. This information might inform future studies aimed at understanding developmental, phylogenetic, and functional aspects of the human postcanine dentition, including possible phenotype-genotype associations. However, with this study being the first one performed on a 3D sample of this size, we also report on obstacles and peculiarities that have been determined.
Virus-like particle-based vaccines targeting theAnophelesmosquito salivary protein, TRIO
Authors: Francian Alexandra , Flores-Garcia Yevel , Powell John R. , Petrovsky Nikolai , Zavala Fidel , Chackerian Bryce 
Published: September 2024

ABSTRACTMalaria is a highly lethal infectious disease caused byPlasmodiumparasites. These parasites are transmitted to vertebrate hosts when mosquitoes of theAnophelesgenus probe for a blood meal. Sporozoites, the infectious stage ofPlasmodium, transit to the liver within hours of injection into the dermis. Vaccine efforts are hindered by the complexity of the parasite’s lifecycle and the speed at which the infection is established in the liver. In an effort to enhance immunity againstPlasmodium, we produced a virus-like particle (VLP)-based vaccine displaying an epitope of TRIO, anAnophelessalivary protein which has been shown to enhance mobility and dispersal of sporozoites in the dermis. Previous work demonstrated that passive immunization with TRIO offered protection from liver infection and acted synergistically with aPlasmodiumtargeted vaccine. Immunization of mice with TRIO VLPs resulted in high-titer and long-lasting antibody responses that did not significantly drop for over 18 months post-immunization. TRIO VLPs were similarly immunogenic when combined with an anti-malaria vaccine targeting the L9 epitope of thePlasmodium falciparumcircumsporozoite protein.However, when used in a malaria challenge mouse model, TRIO VLPs only provided modest protection from infection and did not boost the protection provided by L9 VLPs.
The Nuclear and Mitochondrial Genomes ofAmoebophryasp. exKarlodinium veneficum
Authors: DeMontigny Wesley , Bachvaroff Tsvetan 
Published: September 2024

AbstractDinoflagellates are a diverse group of microplankton that include free-living, symbiotic, and parasitic species.Amoebophrya, a basal lineage of parasitic dinoflagellates, infects a variety of marine microorganisms, including harmful-bloom-forming algae. Although there are currently three publishedAmoebophryagenomes, this genus has considerable genomic diversity. We add to the growing genomic data forAmoebophryawith an annotated genome assembly forAmoebophryasp. exKarlodinium veneficum. This species appears to translate all three canonical stop codons contextually. Stop codons are present in the open reading frames of about half of the predicted gene models, including genes essential for cellular function. The in-frame stop codons are likely translated by suppressor tRNAs that were identified in the assembly. We also assembled the mitochondrial genome, which has remained elusive in the previousAmoebophryagenome assemblies. The mitochondrial genome assembly consists of many fragments with high sequence identity in the genes but low sequence identity in intergenic regions. Nuclear and mitochondrially-encoded proteins indicate thatAmoebophryasp. exK. veneficumdoes not have a bipartite electron transport chain, unlike previously analyzedAmoebophryaspecies. This study highlights the importance of analyzing multiple genomes from highly diverse genera such asAmoebophrya.SummaryThis new long-read assembly demonstrates the remarkable diversity found withinAmoebophrya. Despite being assigned the rank of genus, the available genome assemblies indicate significant variation in gene content, AT content, genetic codes, and potentially mitochondrial biology. Furthermore, this study contributes to the expanding list of organisms that contextually translate all three canonical stop codons. Although the mechanisms underlying such a genetic code remain elusive, the relative ease of culturingAmoebophryasuggests it may be useful as a model organism for future research on this subject.