bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multisystemic inflammatory disease in Pheasantshell (Unionidae,Actinonaias pectorosa) associated withYokenella regensburgeiinfection at sites experiencing seasonal mass mortality events
Authors: Da Silva Neto Jeronimo G. , Hardman Rebecca H. , Engman Augustin C. , Dinkins Gerald R. , Lane Timothy W. , Fry Michael M. , Rines Christian , Bisenieks Amber , Rajeev Sree , Dennis Michelle M. 
Published: March 2024

AbstractFreshwater mussels are integral components of riverine ecosystems, influencing water quality, nutrient cycling, and habitat characteristics. Enigmatic freshwater mussel declines, often characterized by sudden mass mortality events, pose significant challenges to conservation efforts. The Clinch River, a freshwater biodiversity hotspot, has experienced several enigmatic mass mortality events since 2016. Studies have reported bacteria associated with moribund Pheasantshell (Actinonaias pectorosa) during mortality events in the Clinch River, specificallyYokenella regensburgei. Despite reports of bacterial infection, little is known about their role as pathogens. Through a multiyear case-control study, combining in-situ experiments, field surveys, histology, bacterial isolation, and high-throughput sequencing, we assessed the role of bacteria in Pheasantshell (Actinonais pectorosa) mortality at two sites in the Clinch River. Between May 2021 and December 2023, we collected 29 wild moribund free-livingA. pectorosaand 68 hatchery-rearedA. pectorosamaintained in silos at the same sites and investigated differences in pathology and microbiology between groups. No silo mussels presented clinical signs of disease, or gross or microscopic lesions associated with pathological conditions leading to mortality. Our findings reveal a significant association betweenYokenella regensburgeiand severe multisystemic and multifocal infiltrative hemocytosis with necrosis, consistent with sepsis. Lesions associated with yokenellosis were of sufficient severity and physiological significance to explain mortality in infected hosts. Although our study does not explain the cause of these infections, it confirms that mussels at our study sites are ultimately dying from an infectious disease and thatY. regensburgeican be pathogenic in free-living mussels. Our results underscore the importance of considering bacterial diseases in wild mussel populations and emphasize the need for further research to elucidate the epidemiology and pathogenicity ofY. regensburgei. Overall, our study highlights the importance of integrated approaches combining pathology, microbiology, and epidemiology in freshwater mussel conservation efforts.
Postembryonic developmental roles of the ArabidopsisKEULEgene
Authors: Ruiz-Bayón Alejandro , Cara-Rodríguez Carolina , Sarmiento-Mañús Raquel , Muñoz-Viana Rafael , Lozano Francisca M. , Ponce María Rosa , Micol José Luis 
Published: March 2024

ABSTRACTCytokinesis in plant cells begins with the fusion of vesicles that transport cell wall materials at the center of the cell division plane, where the cell plate forms and expands radially until it fuses with the parental cell wall at the preprophase band. Vesicle fusion is facilitated bytrans-SNARE complexes, with assistance from Sec1/Munc18 (SM) proteins. The SNARE protein KNOLLE and the SM protein KEULE are required for membrane fusion at the cell plate. Due to the crucial function of KEULE, all Arabidopsis (Arabidopsis thaliana)keulemutants identified to date are seedling lethal. Here, we identified the Arabidopsisserrata4-1(sea4-1) andsea4-2mutants, which carry recessive, hypomorphic alleles ofKEULE. Homozygoussea4-1andsea4-2plants are viable and fertile but exhibit smaller rosettes and fewer leaves at bolting than the wild type. Their leaves are serrated, small, and undulated, with a complex venation pattern, develop necrotic patches, and undergo premature senescence. We established a likely relationship between these phenotypes and their defects in cytokinesis through reduced cell wall integrity and increased unfolded protein response. These findings shed light on the roles of KEULE in postembryonic development, particularly in the patterning of rosette leaves and leaf margins.
Subtle Visual Latency Can Profoundly Impair Implicit Sensorimotor Learning
Authors: Hadjiosif Alkis M. , Abraham George , Ranjan Tanvi , Smith Maurice A. 
Published: March 2024

AbstractShort sub-100ms visual feedback latencies are common in many types of human-computer interactions yet are known to markedly reduce performance in a wide variety of motor tasks from simple pointing to operating surgical robotics. These latencies are also present in the computer-based experiments used to study the sensorimotor learning that underlies the acquisition of motor performance. Inspired by neurophysiological findings showing that cerebellar LTD and cortical LTP would both be disrupted by sub-100ms latencies, we hypothesized that implicit sensorimotor learning may be particularly sensitive to these short latencies. Remarkably, we find that improving latency by just 60ms, from 85 to 25ms in latency-optimized experiments, increases implicit learning by 50% and proportionally decreases explicit learning, resulting in a dramatic reorganization of sensorimotor memory. We go on to show that implicit sensorimotor learning is considerably more sensitive to latencies in the sub-100ms range than at higher latencies, in line with the latency-specific neural plasticity that has been observed. This suggests a clear benefit for latency reduction in computer-based training that involves implicit sensorimotor learning and that across-study differences in implicit motor learning might often be explained by disparities in feedback latency.
MetaDIA: A Novel Database Reduction Strategy for DIA Human Gut Metaproteomics
Authors: Duan Haonan , Ning Zhibin , Sun Zhongzhi , Guo Tiannan , Sun Yingying , Figeys Daniel 
Published: March 2024

AbstractBackgroundMicrobiomes, especially within the gut, are complex and may comprise hundreds of species. The identification of peptides in metaproteomics presents a significant challenge, as it involves matching peptides to mass spectra within an enormous search space for complex and unknown samples. This poses difficulties for both the accuracy and the speed of identification. Specifically, analysis of data-independent acquisition (DIA) datasets has relied on libraries constructed from prior data-dependent acquisition (DDA) results. This approach requires running the samples in DDA mode to construct a library from the identified results, which can then be used for the DIA data. However, this method is resource-intensive, consumes samples, and limits identification to peptides previously identified by DDA. These limitations restrict the application of DIA in metaproteomics research.ResultsWe introduced a novel strategy to reduce the search space by utilizing species abundance and functional abundance information from the microbiome to score each peptide and prioritize those most likely to be detected. Employing this strategy, we have developed and optimized a workflow called MetaDIA for analysis of microbiome DIA data, which operates independently of DDA assistance. Our method demonstrated strong consistency with the traditional DDA-based library approach at both protein and functional levels.ConclusionOur approach successfully created a smaller, yet sufficient database for DIA data search requirements in metaproteomics, showing high consistency with results from the conventional DDA-based library. We believe this method can facilitate the application of DIA in metaproteomics.
Microglia contact cerebral vasculature through gaps between astrocyte endfeet
Authors: Morris Gary P. , Foster Catherine G. , Sutherland Brad A. , Grubb Søren 
Published: March 2024

AbstractThe close spatial relationship between microglia and cerebral blood vessels implicates microglia in vascular development, homeostasis and disease. In this study we used the publicly available Cortical MM^3 electron microscopy dataset to systematically investigate microglial interactions with the vasculature. Our analysis revealed that approximately 20% of microglia formed direct contacts with blood vessels through gaps between adjacent astrocyte endfeet. We termed these contact points “plugs”. Plug-forming microglia exhibited closer proximity to blood vessels than non-plug forming microglia and formed multiple plugs, predominantly near the soma, ranging in surface area from ∼0.01 μm2to ∼15 μm2. Plugs were enriched at the venule end of the vascular tree and displayed a preference for contacting endothelial cells over pericytes at a ratio of 3:1. In summary, we provide novel insights into the ultrastructural relationship between microglia and the vasculature, laying a foundation for understanding how these contacts contribute to the functional cross-talk between microglia and cells of the vasculature in health and disease.
A Novel ex-vivo platform for personalized treatment in metastatic ovarian cancer
Authors: Valdivia Alain , Adefolaju Adebimpe , Thang Morrent , Cuaboy Luz Andrea , John Catherine , Mann Breanna , Satterlee Andrew , Bae-Jump Victoria L , Hingtgen Shawn 
Published: March 2024

AbstractThe lack of functional precision models that recapitulate the pathology and structure/function relationship of advanced ovarian cancer (OC) within an appropriate anatomic setting constitutes a hurdle on the path to developing more reliable therapies and matching those therapies with the right patients. Here, we developed and characterized an Organotypic Mesentery Membrane Culture (OMMC) model as a novel ex-vivo platform where freshly resected human patient OC tumor tissue or established cell lines are seeded directly atop living intact rat mesenteric membranes, rapidly engraft, and enable functional assessment of treatment response to FDA-approved standard care of treatment as single and combination drug therapies within just five days. This study showed successful survival of dissected mesentery tissue, survival and engraftment of tumor cells and patient tumor tissue seeded on OMMCs, mesentery-tumor cell interaction, and quantification of tumor response to treatment and off-target toxicity. Summarized “drug sensitivity scores”, using a multi-parametric algorithm, were also calculated for each patient’s treatment response, enabling us to suggest the most effective therapeutic option. Finally, we compared drug sensitivity results from patient tumor tissue on OMMCs to matched outcomes of individual patients in the clinic and identified positive correlations in drug sensitivity, beginning to validate the functionality of OMMCs as a functional predictor of treatment response.Summary sentenceWe have successfully developed and characterized a novel ex-vivo platform for personalized treatment of metastatic ovarian cancer.
Cancer Stemness Online: A resource for investigating cancer stemness and associations with immune response
Authors: Zhou Weiwei , Su Minghai , Jiang Tiantongfei , Xie Yunjin , Shi Jingyi , Ma Yingying , Xu Kang , Xu Gang , Li Yongsheng , Xu Juan 
Published: March 2024

AbstractCancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features, which are potential culprit in immunotherapy resistance. Although the state-of-art predictive computational methods have facilitated predicting the cancer stemness, currently there is no efficient resource that can meet various requirements of usage. Here, we presented the Cancer Stemness Online, an integrated resource for efficiently scoring cancer stemness potential at bulk and single-cell level. The resource integrates 8 robust predictive algorithms as well as 27 signature gene sets associated with cancer stemness for predicting the stemness scores. Downstream analyses were performed from five different aspects, including identifying the signature genes of cancer stemness, exploring the association with cancer hallmarks, cellular states, immune response and communication with immune cells, investigating the contributions for patient survival and the robustness analysis of cancer stemness among different methods. Moreover, the pre-calculated cancer stemness atlas for more than 40 cancer types can be accessed by users. Both the tables and diverse visualization for the analytical results are available for download. Together, Cancer Stemness Online is a powerful resource for scoring cancer stemness and going deeper and wider in the downstream functional interpretation, including immune response as well as cancer hallmark. Cancer Stemness Online is freely accessible athttp://bio-bigdata.hrbmu.edu.cn/CancerStemnessOnline.
BayesianSSA: a Bayesian statistical model based on structural sensitivity analysis for predicting responses to enzyme perturbations in metabolic networks
Authors: Hosoda Shion , Iwata Hisashi , Miura Takuya , Tanabe Maiko , Okada Takashi , Mochizuki Atsushi , Sato Miwa 
Published: March 2024

AbstractBackgroundChemical bioproduction has attracted attention as a key technology in a decarbonized society. In computational design for chemical bioproduction, it is necessary to predict changes in metabolic fluxes when up-/down-regulating enzymatic reactions, that is, responses of the system to enzyme perturbations. Structural sensitivity analysis (SSA) was previously developed as a method to predict qualitative responses to enzyme perturbations on the basis of the structural information of the reaction network. However, the network structural information can sometimes be insufficient to predict qualitative responses unambiguously, which is a practical issue in bioproduction applications. To address this, in this study, we propose BayesianSSA, a Bayesian statistical model based on SSA. BayesianSSA extracts environmental information from perturbation datasets collected in environments of interest and integrates it into SSA predictions.ResultsWe applied BayesianSSA to synthetic and real datasets of the central metabolic pathway ofEscherichia coli. Our result demonstrates that BayesianSSA can successfully integrate environmental information extracted from perturbation data into SSA predictions. In addition, the posterior distribution estimated by BayesianSSA can be associated with the known pathway reported to enhance succinate export flux in previous studies.ConclusionsWe believe that BayesianSSA will accelerate the chemical bioproduction process and contribute to advancements in the field.
High-fidelity enhanced AsCas12a knock-in mice for efficient multiplexed gene editing, disease modeling and orthogonal immunogenetics
Authors: Tang Kaiyuan , Zhou Xiaoyu , Fang Shao-Yu , Vandenbulcke Erica , Du Andrew , Shen Johanna , Cao Hanbing , Zhou Jerry , Chen Krista , Xin Shan , Zhou Liqun , Lin Shawn H. , Majety Medha , Ling Xingyu , Lam Stanley Z. , Chow Ryan , Bai Suxia , Nottoli Timothy , Booth Carmen , Liu Chen , Dong Matthew B. , Chen Sidi 
Published: March 2024

AbstractThe advancement of CRISPR gene editing technology, especially the development of Cas9 knock-in mice, has significantly boosted the functional discovery of various genetics factors in diverse fields including genetics, genomics, immunology, and the biology of cancer. However, the pleiotropic effects on human disease and the complex nature of gene interaction networks require a knock-in mouse model capable of simultaneous multiplexed gene perturbation. Here, we present the generation and applications of Cre-dependent conditional and constitutive high-fidelity, enhanced AsCas12a (enAsCas12a-HF1) Rosa26-knock-in mice in the C57BL/6 background. With these mouse strains, we demonstrate highly efficient and multiplexedin vivoandex vivogenome engineering as applied to lipid nanoparticle (LNP)-RNA-based liver protein targeting, AAV-based tumor modeling, and retrovirus-based immune cell engineering. By integrating with a dCas9-SPH CRISPR activation transgenic strain, we establish a simultaneous dual gene activation and knockout (DAKO) system that showcases the modular potential of these enAsCas12a-HF1 mice. Importantly, constitutive expression of enAsCas12a-HF1 does not lead to any discernable pathological differences as compared to the C57BL/6 background strain. These knock-in mice and the accompanying delivery methods would empower the deconvolution of complex gene interaction networks in broad areas of research.
Thoracic epidural blockade after myocardial infarction benefits from anti-arrhythmic pathways mediated in part by parasympathetic modulation
Authors: Hoang Jonathan D , van Weperen Valerie YH , Kang Ki-Woon , Jani Neil R , Swid Mohammed A , Chan Christopher A , Lokhandwala Zulfiqar Ali , Lux Robert L , Vaseghi Marmar 
Published: March 2024

ABSTRACTBackgroundThoracic epidural anesthesia (TEA) has been shown to reduce the burden of ventricular tachyarrhythmias (VT) in small case-series of patients with refractory VT and cardiomyopathy. However, its electrophysiological and autonomic effects in diseased hearts remain unclear and its use after myocardial infarction (MI) is limited by concerns for potential RV dysfunction.MethodsMI was created in Yorkshire pigs (N=22) by LAD occlusion. Six weeks post-MI, an epidural catheter was placed at the C7-T1 vertebral level for injection of 2% lidocaine. RV and LV hemodynamics were recorded using Millar pressure-conductance catheters, and ventricular activation-recovery intervals (ARIs), a surrogate of action potential durations, by a 56-electrode sock and 64-electrode basket catheter. Hemodynamics and ARIs, baroreflex sensitivity (BRS) and intrinsic cardiac neural activity, and ventricular effective refractory periods (ERP) and slope of restitution (Smax) were assessed before and after TEA. VT/VF inducibility was assessed by programmed electrical stimulation.ResultsTEA reduced inducibility of VT/VF by 70%. TEA did not affect RV-systolic pressure or contractility, although LV-systolic pressure and contractility decreased modestly. Global and regional ventricular ARIs increased, including in scar and border zone regions post-TEA. TEA reduced ARI dispersion specifically in border zone regions. Ventricular ERPs prolonged significantly at critical sites of arrhythmogenesis, and Smaxwas reduced. Interestingly, TEA significantly improved cardiac vagal function, as measured by both BRS and intrinsic cardiac neural activity.ConclusionTEA does not compromise RV function in infarcted hearts. Its anti-arrhythmic mechanisms are mediated by increases in ventricular ERP and ARIs, decreases in Smax, and reductions in border zone heterogeneity. TEA improves parasympathetic function, which may independently underlie some of its observed anti-arrhythmic mechanisms. This study provides novel insights into the anti-arrhythmic mechanisms of TEA, while highlighting its applicability to the clinical setting.Abstract IllustrationMyocardial infarction is known to cause cardiac autonomic dysfunction characterized by sympathoexcitation coupled with reduced vagal tone. This pathological remodeling collectively predisposes to ventricular arrhythmia. Thoracic epidural anesthesia not only blocks central efferent sympathetic outflow, but by also blocking ascending projections of sympathetic afferents, relieving central inhibition of vagal function. These complementary autonomic effects of thoracic epidural anesthesia may thus restore autonomic balance, thereby improving ventricular electrical stability and suppressing arrhythmogenesis. DRG=dorsal root ganglion, SG=stellate ganglion.
Helical Twists and β-Turns in Structures at Serine–Proline Sequences: Stabilization of cis-Proline and type VI β-turns via C–H/O interactions
Authors: Oven Harrison C. , Yap Glenn P. A. , Zondlo Neal J. 
Published: March 2024

AbstractStructures at serine-proline sites in proteins were analyzed using a combination of peptide synthesis with structural methods and bioinformatics analysis of the PDB. Dipeptides were synthesized with the proline derivative (2S,4S)-(4-iodophenyl)hydroxyproline [hyp(4-I-Ph)]. The crystal structure of Boc-Ser-hyp(4-I-Ph)-OMe had two molecules in the unit cell. One molecule exhibitedcis-proline and a type VIa2 β-turn (BcisD). Thecis-proline conformation was stabilized by a C–H/O interaction between Pro C–Hαand the Ser side-chain oxygen. NMR data were consistent with stabilization ofcis-proline by a C–H/O interaction in solution. The other crystallographically observed molecule hadtrans-Pro and both residues in the PPII conformation. Two conformations were observed in the crystal structure of Ac-Ser-hyp(4-I-Ph)-OMe, with Ser adopting PPII in one and the β conformation in the other, each with Pro in the δ conformation andtrans-Pro. Structures at Ser-Pro sequences were further examined via bioinformatics analysis of the PDB and via DFT calculations. Ser–ProversusAla-Pro sequences were compared to identify bases for Ser stabilization of local structures. C–H/O interactions between the Ser side-chain Oγand Pro C–Hαwere observed in 45% of structures with Ser-cis- Pro in the PDB, with nearly all Ser-cis-Pro structures adopting a type VI β-turn. 53% of Ser-trans-Pro sequences exhibited main-chain C=Oi•••H–Ni+3or C=Oi•••H–Ni+4hydrogen bonds, with Ser as theiresidue and Pro as thei+1 residue. These structures were overwhelmingly either type I β-turns or N-terminal capping motifs on α-helices or a 310-helices. These results indicate that Ser-Pro sequences are particularly potent in favoring these structures. In each, Ser is in either the PPII or β conformation, with the Ser Oγcapable of engaging in a hydrogen bond with the amide N–H of thei+2 (type I β-turn or 3 -helix; Serχ1t) ori+3 (α-helix; Serχ1g+) residue. Non-prolinecisamide bonds can also be stabilized by C–H/O interactions.Abstract FigureGraphical Table of Contents
DNA barcoding and species delimitation based on four Chloroplast loci to identify species within the Elaeocarpaceae family
Authors: Khushwaha Jyotsana , Joshi Alpana , Das Subrata K. 
Published: March 2024

AbstractDNA barcoding is an indispensable taxonomic tool for plant species identification. The present research successfully amplified the four coding regions of plastid namely;matK,rpoB,ndhJ, andaccD, sequenced, and submitted it to NCBI Genbank after verification. This study evaluated the significance of single (matK,rpoB,ndhJ, andaccD) and two-locus plastid loci (rpoB+matK,ndhJ+matK,accD+matK) and examined their abilities for species identification and phylogenetic construction of Elaeocarpaceae plants. The average aligned length formatK,rpoB,ndhJ,accD,ndhJ+matK,rpoB+matK, andaccD+matKwas 395 bp, 538 bp, 477 bp, 254 bp, 872 bp, 937 bp, and 649 bp, respectively. The highest substitution rate was recorded in therpoB(18.47%), followed byndhJ(17.38%),accD(14.00%), andmatK(11.23%). The number of variable sites, segregating sites (S), nucleotide diversity (Pi), and mutations (Eta) were observed to be highest in thematKregion. Evolutionary relationship based on the Neighbor-joining method demonstrated that candidate barcode sequences were competent for identifyingCrinodendron,Elaeocarpus,Sloanea, andValleaspecies. A significant barcoding gap was identified in two barcoding regions (matKandndhJ+matK). The species-specific barcodes for the genusElaeocarpuswere generated based on Single Nucleotide Polymorphism (SNP) analysis. This study offers novel strategies for effectively identifying species within Elaeocarpaceae and lays the foundation for germplasm conservation and utilization.