bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metachronal rowing provides robust propulsive performance across four orders of magnitude variation in Reynolds number
Authors: Ford Mitchell P. , Santhanakrishnan Arvind 
Published: November 2024

AbstractMetachronal rowing of multiple propulsors (paddles) is a swimming strategy used by numerous organisms across various phyla, with body sizes ranging from 0.01 mm to 100 mm. This size range corresponds to a huge variation in flow regimes characterized by Reynolds number (Re) ranging on the orders of 10−2(viscosity dominated) to 104(inertially dominated). Though the rhythmic and coordinated stroking of paddles is conserved across species and developmental stages, the hydrodynamic scalability of metachronal rowing has not been examined across this broadRerange. We used a self-propelled metachronal paddling robot to examine how swimming performance changes across four orders of variation inRe(21 to 54,724) relevant to most aquatic crustaceans. We found that the Strouhal number (St), characterizing momentum transfer from paddles to the wake, was unchanging atSt≈ 0.26 forRe >42 and within the reportedStof various flying and swimming animals. Peak dimensionless strength (circulation) of paddle tip vortices linearly increased withReand was mostly unaffected by changing fluid viscosity. Our findings show that the swimming performance of metachronal rowing is conserved across widely varying flow regimes, with dimensionless swimming speed scaling linearly withReacross the entire tested range.
Mora-ERP-based RNN-Transformer for decoding single-trial EEGs during silent Japanese speeches
Authors: Yamazaki Toshimasa , Kudo Saori , Kamata Sei-Ichiro , Fujii Satoshi , Tsukiyama Sho , Yata Tetsushi , Aoki Shunsuke 
Published: November 2024

AbstractWe developed a method for decoding single-trial electroencephalography (EEG) during silent Japanese speeches. In order to cope with problems that there would be always noises in single-trial EEGs, a recurrent neural network (RNN) was used which could reproduce signals under noises. Each of silent-mora-related potentials and the single-trial EEG minus the event-related potential (ERP) were assigned to the signal and the noise, respectively, with reference to the averaging principle. Next, in our Transformer, dot product between the RNN output and the single-trial EEG after positional encoding then Softmax with Loss yielded probabilities of moras, each of which consists of silent Japanese words, phrases or part of sentences. The present decoding was completed by tracing the maximal probability at each block representing time. Average mora error rates (MERs) on pretrained and validated performances for the patient was as low as 1.5 % and 0 %, respectively. The performance for the testing would be refined by many single-trial EEGs during silent Japanese speeches obtained by EEG Web interfaces. This method might be applied to other “mora” languages.
In SituIntegration of Porous Polyethylene Nanomembrane with Wound Exudates for Scarless Healing
Authors: Yuan Shijie , Gu Qiao , Guo Xingchen , Tang Xuanxuan , Qiu Jiawen , Shang Linkuo , Lin Julie Qiaojin , Weng Lu-Tao , Gao Ping 
Published: November 2024

AbstractAchieving scarless wound repair through innovative material designs, such as hydrogels infused with growth factors and cells, has been extensively explored. In this study, we introduce a scarless healing material called pgPE, which is based on a porous and biologically inert ultra-high molecular weight polyethylene (UHMWPE) nanomembrane. This highly flexible nanomembrane conforms closely to the wound site and effectively absorbs wound-associated species into its nanopores, forming pgPEin situ. The resulting pgPE creates an ideal environment that fosters physiological metabolism while acting as a barrier against pathogens. Our findings demonstrate that pgPE facilitates complete skin reconstruction, including the regeneration of hair follicles. Additionally, we characterized the immune microenvironment and hypoxic conditions, revealing that pgPE alleviates hypoxia and modulates immune responses, thereby promoting healing towards a scar-free outcome. The integration of wound-associated species within pgPE has been evidenced through three-dimensional Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) analysis of postmortem samples. This study highlights the potential of personalized solutions that align with physiological systems for enhanced wound healing.
Tissue Context Drives Regional Differences in Trophoblast Differentiation in Fetal Membranes and Chorionic Villi
Authors: Yang Liheng (Henry) , Caldwell Allyson , Coyne Carolyn B. 
Published: November 2024

AbstractTrophoblasts within the fetal membrane primarily serve as protective barriers, shielding the developing fetus from the external environment, while those in chorionic villi facilitate interactions between the maternal and fetal compartments. Although these distinct trophoblast populations perform specialized roles based on their placental location, the mechanisms governing their development and differentiation remain largely unknown. In this study, we derived trophoblast organoids from both the smooth chorion of fetal membranes and chorionic villi from matched human placentas to create parallelin vitromodels of these distinct trophoblast populations. Using comparative transcriptional profiling with both bulk and single-cell RNA sequencing, we identified subtle transcriptional variations, while overall gene expression patterns and cellular composition remained highly conserved. Comparative single-cell RNA sequencing and differentiation trajectory analysis of organoids derived from chorion and villous tissues, along with their respective tissue counterparts, revealed region-specific gene expression patterns that were only partially conserved in organoids. The similarity between thesein vitromodels suggests that regional differences in trophoblast expression observedin vivoare driven by environmental and regional cues. These findings highlight the critical role of local environmental factors in shaping trophoblast function and offer insights into the conserved mechanisms that support placental integrity and fetal development, while emphasizing the influence of region-specific cuesin vivo.
Nerpa 2: linking biosynthetic gene clusters to nonribosomal peptide structures
Authors: Olkhovskii Ilia , Kushnareva Aleksandra , Tagirdzhanov Azat , Gurevich Alexey 
Published: November 2024

AbstractSummaryHere, we introduce Nerpa 2, a tool for linking computationally-predicted biosynthetic gene clusters of nonribosomal peptides (NRPs) to their putative products. Nerpa 2 is based on our previous tool, Nerpa, but outperforms it in accuracy and sensitivity thanks to the software and algorithmic updates, including a wholly revised scoring function and extension of the training dataset. Nerpa 2 handles a variety of NRP biosynthesis use cases not supported by the original tool, is purely cross-platform, and provides output results in convenient HTML reports.Availability and implementationNerpa 2 is available athttps://github.com/gurevichlab/nerpa.
Phytoplankton Photophysiology Reveals Depth Specific Zooplankton Grazing
Authors: Graff Jason R. , Maas Amy E. 
Published: November 2024

AbstractMarine particle forensics frequently uncover information on composition, age, size, and ecological history. Zooplankton fecal pellets are also studied for process-related data, such as grazing rates and carbon sequestration potential. Here, flow cytometric analyses of fecal pellet contents revealed intact phytoplankton with photophysiological characteristics mirroring those of free-living cells. Mapping the cytometrically derived properties of cells inside fecal pellets onto vertical profiles from free-living cells revealed the potential to estimate depth specific grazing by individual zooplankton. An experiment conducted at sea confirmed that the photophysiological characteristics of free-living phytoplankton from multiple depths, consumed by zooplankton, and excreted within fecal pellets are retained for at least 24 hours after grazing is initiated. These results have implications for high resolution modeling of individual or group specific zooplankton grazing dynamics that are critical for accurately linking zooplankton grazing in the surface ocean with the mesopelagic and deep ocean food webs and carbon export.Scientific Significance StatementFecal pellet forensics have provided significant contributions to the study of zooplankton grazing and the marine carbon cycle. Gaps in knowledge about these processes remain, and continued investigations into fecal pellet contents and their fate are important for assessing connections between the surface and deeper ocean ecosystems. We describe a study conducted in the North Atlantic in the Spring of 2021 using flow cytometry to investigate fecal pellets contents. Observations that intact phytoplankton within the pellets had similar photophysiological properties to the free-living community led to a series of sample collections and experiments which provided a path forward for determining depth specific grazing by zooplankton community members. Phytoplankton survival after passing through zooplankton guts and being packaged into fecal pellets, with their potential for release far below the surface mixed layer, support prior observations of healthy phytoplankton communities at depth and validate this mechanism for the rapid transport of freshly fixed carbon to deep ocean systems. The results should be of interest to plankton ecologists and carbon cycle scientists connecting surface and deep ocean ecosystems as application of this approach at a broader scale will provide opportunities for high resolution modeling of individual and group specific zooplankton behaviors.
Gaia: A Context-Aware Sequence Search and Discovery Tool for Microbial Proteins
Authors: Jha Nishant , Kravitz Joshua , West-Roberts Jacob , Camargo Antonio , Roux Simon , Cornman Andre , Hwang Yunha 
Published: November 2024

AbstractProtein sequence similarity search is fundamental to genomics research, but current methods are typically not able to consider crucial genomic context information that can be indicative of protein function, especially in microbial systems. Here we present Gaia (Genomic AI Annotator), a sequence annotation platform that enables rapid, context-aware protein sequence search across genomic datasets. Gaia leverages gLM2, a mixed-modality genomic language model trained on both amino acid sequences and their genomic neighborhoods to generate embeddings that integrate sequence-structure-context information. This approach allows for the identification of functionally related genes that are found in conserved genomic contexts, which may be missed by traditional sequence- or structure-based search alone. Gaia enables real-time search of a curated database comprising over 85M protein clusters (defined at 90% sequence identity) from 131,744 microbial genomes. We compare the sequence, structure and context sensitivity of gLM2 embedding-based search against existing tools like MMseqs2 and Foldseek. We showcase Gaia-enabled discoveries of phage tail proteins and siderophore synthesis loci that were previously difficult to annotate with traditional tools. Gaia search is freely available athttps://gaia.tatta.bio.
Controlling human stem cell-derived islet composition using magnetic sorting
Authors: Kelley Allison B. , Shunkarova Mira , Maestas Marlie M. , Gale Sarah E. , Hogrebe Nathaniel J. , Millman Jeffrey R. 
Published: November 2024

ABSTRACTStem cell-derived islets (SC-islets) consists of multiple hormone-producing cell types and offer a promising therapeutic avenue for treating type 1 diabetes (T1D). Currently, the composition of cell types generated within these SC-islets currently cannot be controlled via soluble factors during this differentiation process and consist of off-target cell types. In this study, we devised a magnetic-activated cell sorting (MACS) protocol to enrich SC-islets for CD49a, a marker associated with functional insulin-producing β cells. SC-islets were generated from human pluripotent stem cells (hPSCs) using an adherent differentiation protocol and then sorted and aggregated into islet-like clusters to produce CD49a-enriched, CD49a-depleted, and unsorted SC-islets. Single-cell RNA sequencing (scRNA-seq) and immunostaining revealed that CD49a-enriched SC-islets had higher proportions of β cells and improved transcriptional identity compared to other cell types. Functional assays demonstrated that CD49a-enriched SC-islets exhibited enhanced glucose-stimulated insulin secretion bothin vitroandin vivofollowing transplantation into diabetic mice. These findings suggest that CD49a-based sorting significantly improves β cell identity and the overall function of SC-islets, improving their effectiveness for T1D cell replacement therapies.
Mechanism of Nucleotide-Dependent Allosteric Regulation inEscherichia coliAspartate Transcarbamoylase
Authors: Miller Robert C. , Patterson Michael G. , Bhatt Neti , Pei Xiaokun , Ando Nozomi 
Published: November 2024

AbstractDiscovered nearly 70 years ago, the allosteric regulation ofEscherichia coliaspartate transcarbamoylase (ATCase) is discussed in every biochemistry textbook. ATCase catalyzes the first step in pyrimidine bio-synthesis. Despite extensive research, the mechanism by which this enzyme is regulated by pyrimidine and purine nucleotides has remained elusive. Here, we present a detailed analysis ofE. coliATCase using a combination of biochemical assays, small-angle X-ray scattering (SAXS), cryo-electron microscopy (cryo-EM), and X-ray crystallography, revealing the mechanism of allosteric communication between nucleotide-binding sites and active sites. We show how the pyrimidine pair, CTP and UTP, synergistically inhibit the enzyme by inducing a quaternary structure that enforces active-site cooperativity. Additionally, we provide the first evidence of how the purine pair, ATP and GTP, drive the enzyme into its most active state by promoting an expanded conformation that allows independent function of the active sites. Our findings resolve longstanding questions in the literature and uncover a novel mechanism by whichE. coliATCase regulates the balance of pyrimidines and purines.
Metabolic Divergence Between Healthy and Conditional Presenilin-1/2 knockout Dementia Model Mice under Chronic Nicotine exposure
Authors: Si Youwen , Qiu Shuai , Wang Lina , Meng Bo , Qi Feiyan 
Published: November 2024

AbstractNicotine, a primary bioactive compound in tobacco, influences a wide range of metabolic pathways, with potential implications for neurodegenerative diseases such as Alzheimer’s disease (AD). This study investigates the metabolic effects of chronic nicotine administration in presenilin-1/2 double knockout (DKO) mice and wild-type (WT) control mice. Eight-month-old DKO and WT mice underwent a three-month oral nicotine administration which did not significantly affect body weight or spontaneous locomotor activity in either DKO or WT mice, as measured by weekly body weight measurement and open field test.The metabolomic analyses were performed using untargeted LC-MS and GC-MS techniques. The results revealed distinct metabolic profiles between DKO and WT mice under nicotine exposure. In DKO mice, nicotine exacerbated deficits in purine and nicotinamide metabolism, further highlighting dysregulation in energy homeostasis. Key findings include reduced adenosine and elevated dopamine levels in DKO serum, alongside increased cotinine concentrations, suggesting altered nicotine metabolism. WT mice showed significant changes in energy and lipid metabolism pathways, though with less pronounced alterations compared to DKO mice. Enrichment analyses identified significant pathway disruptions, particularly in choline metabolism, amino acid metabolism, and central carbon metabolism, with genotype-dependent responses to nicotine.This study highlights the intrinsic metabolic alterations in DKO mice, such as disruptions in purine and nicotinamide metabolism, which contribute to their neurodegenerative pathology and unique responses to nicotine. By revealing the differential metabolic impacts of nicotine on healthy and neurodegenerative states, the findings provide valuable insights into its dual therapeutic and pathological roles. These results may guide future research into the metabolic underpinnings of neurodegeneration and the potential for nicotine as a targeted therapeutic intervention.
A divide-and-conquer approach based on deep learning for long RNA secondary structure prediction: focus on pseudoknots identification
Authors: Loïc Omnes , Eric Angel , Pierre Bartet , François Radvanyi , Fariza Tahi 
Published: November 2024

AbstractThe accurate prediction of RNA secondary structure, and pseudoknots in particular, is of great importance in understanding the functions of RNAs since they give insights into their folding in three-dimensional space. However, existing approaches often face computational challenges or lack precision when dealing with long RNA sequences and/or pseudoknots. To address this, we propose a divide-and-conquer method based on deep learning, called DivideFold, for predicting the secondary structures including pseudoknots of long RNAs. Our approach is able to scale to long RNAs by recursively partitioning sequences into smaller fragments until they can be managed by an existing model able to predict RNA secondary structure including pseudoknots. We show that our approach exhibits superior performance compared to state-of-the-art methods for pseudoknots prediction and secondary structure prediction including pseudoknots for long RNAs. The source code of DivideFold, along with all the datasets used in this study, is accessible athttps://evryrna.ibisc.univ-evry.fr/evryrna/dividefold/home.
Complex regulation of Cav2.2 N-type Ca2+channels by Ca2+and G-proteins Short title: Cav2.2 modulation by Ca2+and G-proteins
Authors: Thomas Jessica R. , Sun Jinglang , De la Rosa Vazquez Juan , Lee Amy 
Published: November 2024

ABSTRACTG-protein coupled receptors inhibit Cav2.2 N-type Ca2+channels by a fast, voltage-dependent pathway mediated by Gαi/ Gβγ and a slow, voltage-independent pathway mediated by Gαq−dependent reductions in phosphatidylinositol 4,5-bisphosphate (PIP2) or increases in arachidonic acid. Studies of these forms of regulation generally employ Ba2+as the permeant ion, despite that Ca2+-dependent pathways may impinge upon G-protein modulation. To address this possibility, we compared tonic G-protein inhibition of currents carried by Ba2+(IBa) and Ca2+(ICa) in HEK293T cells transfected with Cav2.2. BothIBaandICaexhibited voltage-dependent facilitation (VDF), consistent with Gβγ unbinding from the channel. Compared to that forIBa, VDF ofICawas less sensitive to an inhibitor of Gα proteins (GDP-β-S) and an inhibitor of Gβγ (C-terminal construct of G-protein coupled receptor kinase 2). While insensitive to high intracellular Ca2+buffering, VDF ofICathat remained in GDP-β-S was blunted by reductions in PIP2. We propose that when G-proteins are inhibited, Ca2+influx through Cav2.2 promotes a form of VDF that involves PIP2. Our results highlight the complexity whereby Cav2.2 channels integrate G-protein signaling pathways, which may enrich the information encoding potential of chemical synapses in the nervous system.
Modelling the influence of changes in vaccination timing, timeliness and coverage on the example of measles outbreaks in the UK between 2010-19
Authors: Suffel Anne M , Warren-Gash Charlotte , McDonald Helen I , Kucharski Adam , Robert Alexis 
Published: November 2024

AbstractBackgroundThe Measles-Mumps-Rubella vaccine is given as a two-dose course in childhood, but the schedule of the second dose varies between countries. England recommended bringing forward the second dose from three years and four months to 18 months by 2025. We aim to quantify how changing the vaccine schedule could impact measles transmission dynamics.MethodsWe used a mathematical model stratified by age group and region to generate stochastic outbreaks with different vaccine schedules. We used detailed information on vaccine uptake for different age groups by region and year from electronic health records and modelled alternative scenarios changing the timing of the second MMR dose or changing uptake of either dose. We simulated measles incidence between 2010 and 2019 and compared the number of cases in each scenario.Results and discussionDelivering the second MMR vaccine at younger age resulted in a lower number of cases than in the reference set of simulations with 16% (IQR: 1.93– 28.48%) cases averted when the second dose was given at 18 months. The number of cases decreased even if the coverage of the second dose decreased by up to 3% (median reduction 15.94%; IQR: 0.41 −28.21%). The impact on case numbers was equivalent to increasing first dose coverage by 0.5% every year between 2010 and 2019 (16.38 % reduction, IQR:1.90 - 28.45), more cases could be avoided (28.60%, IQR: 17.08 - 38.05) if the first dose coverage was increased by 1% every year.Our data highlighted how patterns of vaccination uptake translate into outbreak risk. Although increasing coverage of the first MMR dose led to the best results, this may be challenging to achieve requiring substantial resources with already high coverage of the first dose. Hence, an earlier second MMR dose presents a good alternative for mitigating the risk of measles outbreaks.
Optimisation of DNA extraction from nasal lining fluid to assess the nasal microbiome using third-generation sequencing
Authors: Montgomery Samuel T. , Carr Phoebe G. , Caparrós-Martín Jose A. 
Published: November 2024

AbstractBackgroundSampling nasal lining fluid (NLF) via nasosorption is minimally invasive and well tolerated, but the feasibility of assessing the nasal microbiome using this technique is unknown. However, low biomass makes airway samples particularly susceptible to issues related to contaminant DNA. In this study, we evaluated the suitability of DNA isolated using methodologies for low-biomass respiratory samples and assessed how well lining fluid collected via nasosorption captures the nasal microbial diversity and composition compared to the traditional swab sampling approach.MethodsNasal swabs and NLF were collected from adult volunteers. DNA was extracted from a mock microbial community and NLF using a column-based kit (ZymoBIOMICS), a precipitation-based kit (Qiagen), or a previously published precipitation-based method. Quality and quantity of DNA was assessed and short-read16S rRNAsequencing performed to assess feasibility and extraction bias. An optimised extraction methodology was then used to extract DNA from NLF and nasal swabs, and full-length16S rRNAsequencing performed to compare microbial profiles between NLF and nasal swabs. Taxonomy was assigned using the nf-core/ampliseq pipeline, the PacificBiosciences/pb-16S-nf pipeline, or the software Emu, and downstream analyses were performed using R packages phyloseq and mixOmics.ResultsAll extraction methods recovered DNA from the mock community, but only precipitation-based methods yielded sufficient DNA from NLF. Extraction methodologies significantly affected microbial profiles, with mechanical lysis needed to minimize bias against specific genera. Profiles obtained from NLF and swabs were comparable with long-read sequencing.ConclusionsOur findings demonstrate the feasibility of profiling the nasal microbiome using NLF collected via nasosorption and validated two extraction methodologies as suitable for full-length16S rRNAsequencing of low-biomass respiratory samples. Our data demonstrate the importance of unbiased DNA extraction methodologies in low-biomass respiratory samples, and the subsequent impact of DNA extraction on observed microbial profiles. Additionally, we demonstrated NLF may be an appropriate surrogate samples for nasal swabs to assess the nasal microbiome using16S rRNAsequencing.