bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interpretable variational encoding of genotypes identifies comprehensive clonality and lineages in single cells geometrically
Authors: Chung Hoi Man , Huang Yuanhua 
Published: July 2024

AbstractClone assignment in single-cell genomics remains a challenge due to its diverse mutation macrostructures and many missing signals. Existing statistical methods, for the sake of numerical convergence, pose strong constraints on the form of predicted mutation patterns, so they easily identify sub-optimally fitted clones that overlook weak and rare mutations. To solve this problem, we developed SNPmanifold, a Python package that learns flexible mutation patterns using a shallow binomial variational autoencoder. The latent space of SNPmanifold can effectively represent and visualize complex mutations of SNPs (single-nucleotide polymorphisms) in the form of geometrical manifolds. Based on nuclear or mitochondrial SNPs, we demonstrated that SNPmanifold can effectively identify a large number of multiplexed donors of origin (k = 18) that all existing unsupervised methods fail and lineages of somatic clones with promising biological interpretation. Therefore, SNPmanifold can reveal insights into single-cell SNPs more comprehensively than other existing methods, especially in complex datasets.
Fish predation induces drifting and emergence in an experimental stream mesocosm system
Authors: Vermiert Anna-Maria , Pimentel Iris Madge , Rehsen Philipp M. , Meisner Jonathan , Horstmann Martin , Beermann Arne J. , Leese Florian , Weiss Linda C. , Tollrian Ralph 
Published: July 2024

AbstractPredator-prey interactions are important drivers of adaptation in aquatic communities, shaping the behaviour of invertebrates with cascading effects on community dynamics. Behavioural responses, such as moving with the downstream current (drift) or altering the timing of emergence, can be initiated and reduces the risk of encountering predators. This study aimed to examine the effects of indirect and direct predation pressure on drift behaviour and emergence patterns of aquatic invertebrates. Using an experimental mesocosm setup (ExStream), we analysed how the number of drifting and emerging invertebrates changed with elevated levels of chemical cues from fish (indirect predation,Gasterosteus aculeatusandCottus rhenanus) and subsequent additional direct predation byCottus rhenanusover a 9-day period. Our findings show that most of the analysed invertebrate groups displayed noticeable responses to either indirect, direct, or both forms of predation. Furthermore, our study revealed a significant impact of predation on emergence patterns, reducing the number and the size of emergent invertebrates. Given the importance of drift and emergence in dispersion and in facilitating resource flows into terrestrial systems, our findings indicate a strong effect of predation on the communities.
Behavioral and neural correlates of social hierarchy formation in a sex-changing fish
Authors: Quertermous Haylee M , Kamstra Kaj , van der Burg Chloé A , Muncaster Simon , Todd Erica V , Jasoni Christine L , Brown Culum , Gemmell Neil J 
Published: July 2024

AbstractSocial hierarchies in sex-changing fish determine which fish will change sex, yet little is known about how these hierarchies are formed at the neurobehavioral level. Here, we investigate the formation of social hierarchies within groups of the New Zealand spotty wrasse (spotty), integrating both behavioral observations of social activity with neural activation patterns upon social disruption. We find that dominance hierarchies form rapidly and linearly based on size, with larger fish displaying more aggressive or dominant behaviors (such as monopolizing the shelter) and smaller fish displaying more submissive behaviors (such as escape behavior). Disruption of the social hierarchy induced rapid behavioral changes, particularly in the second-ranked fish, highlighting that second ranked spotty will opportunistically adopt a dominant position in the hierarchy upon removal of the most dominant fish. Neural activation patterns reveal that the social decision-making network is deeply involved in the establishment of dominance, with the fish attaining dominance showing significant differences to all other ranked fish. This study underscores the complexity of social relationships and their neural underpinnings in the spotty wrasse, providing a foundation for further research into the cellular and molecular mechanisms of socially-controlled sex change. Overall, we demonstrate that disruption of social hierarchy triggers rapid changes in behavior and brain regions associated with social decision-making.
Age-related differences in working memory subprocesses decomposed by the reference-back paradigm
Authors: Gaál Zsófia Anna , Nagy Boglárka , Czigler István , Csizmadia Petra , Petró Béla , Kojouharova Petia 
Published: July 2024

AbstractWe used a data-driven approach to study the electrophysiological correlates of the working memory subprocesses revealed by the reference-back paradigm. In the absence of prior research, we focused on how aging affects the four subprocesses:updating,substitution,gate opening, andgate closing.We conducted our experiment with 25 younger adults (M=20.17±1.47) and 23 older adults (M=67.35±4.01) using the reference-back paradigm. Significant reaction time costs were observed for all four subprocesses, but age-related differences were found only insubstitution, which was larger in older than younger adults, indicating it as being the most vulnerable subprocess in aging.Using difference waves, we identified event-related potential components that characterize the subprocesses we studied. Regardingupdating:three occipital negativities between 80-180 ms, 300-400 ms, and 400-1,000 ms were observed, with only the latter range showing age group differences. Source analysis showed larger activity differences in the right frontal and temporal areas for younger adults. Regardingsubstitution: a frontal positivity between 250-600 ms emerged in younger adults, while a posterior positivity between 550-750 ms was found in older adults indicating different underlying processes supported by sLORETA results. Regardinggate opening:three parieto-occipital components were identified: a negativity between 150-250 ms, a positivity between 300-500 ms, and a positivity between 500-700 ms, all showing age-related differences. Regardinggate closing: we found an occipital negativity between 150-300 ms and a frontal positivity between 300-600 ms, neither of which changed between the age groups.From our findings, we conclude that the process of protecting information (gate closing) remains stable with age, despite older adults’ sensitivity to interference. Conversely,gate openingis sensitive to age-related changes, likely to be resulting in different brain activity patterns duringsubstitutionbeing the updating of working memory with new information.
Differentiation Success of Reprogrammed Cells is HeterogenousIn Vivoand Modulated by Somatic Cell Identity Memory
Authors: Zikmund Tomas , Fiorentino Jonathan , Penfold Chris , Stock Marco , Shpudeiko Polina , Agarwal Gaurav , Langfeld Larissa , Petrova Kseniya , Peshkin Leonid , Hamperl Stephan , Scialdone Antonio , Hoermanseder Eva 
Published: July 2024

SummaryNuclear reprogramming can change cellular fates. Yet, reprogramming efficiency is low and the resulting cell types are often not functional. Here, we used nuclear transfer to eggs to follow single cells during reprogrammingin vivo. We show that the differentiation success of reprogrammed cells varies across cell types and depends on the expression of genes specific to the previous cellular identity. We find subsets of reprogramming resistant cells that fail to form functional cell types, undergo cell death, or disrupt normal body patterning. Reducing expression levels of genes specific to the cell-type of origin leads to better reprogramming and improved differentiation trajectories. Thus, our work demonstrates that failing to reprogramin vivois cell-type specific and emphasises the necessity of minimising aberrant transcripts of the previous somatic identity for improving reprogramming.
Structured neural fluctuations can generate noise invariance and inter-areal gating at distinct timescales
Authors: Montijn Jorrit S. , Heimel J. Alexander 
Published: July 2024

AbstractThe brain processes, computes, and categorizes sensory input. But even in sensory brain areas, the relationship between input signals and neuronal spiking activity is complex and non-linear. Fast subsecond fluctuations in neuronal population responses dominate the temporal dynamics of neural circuits. Traditional approaches have treated this activity as “noise” that can be averaged away by taking the mean spiking rate over wide time bins or over multiple trial repetitions, but this ignores much of the temporal dynamics that naturally occur in neural systems. We find that subsecond flares of increased population activity are layer– and cell-type specific, and large-scale computational modelling suggests they may serve as an inter-areal gating mechanism. Moreover, we find that most of the neural variability is restricted to a population-gain axis. This observation explains why neural systems can function in the presence of excessive variability: population-level spiking dynamics generate invariance to the majority of neural noise.
Physiologically refined cell culture conditions uncover oncogene-dependent metabolic signatures in Ewing sarcoma spheroids
Authors: Ceranski A. Katharina , Carreño-Gonzalez Martha J. , Ehlers Anna C. , Kolodynska Zuzanna , Vinca Endrit , Faehling Tobias , Hanssen Kimberley M. , Poeller Philipp , Ohmura Shunya , Cidre-Aranaz Florencia , Schulze Almut , Grünewald Thomas G. P. 
Published: July 2024

SUMMARYEwing sarcoma (EwS) cell line culture largely relies on standard techniques, which do not recapitulate physiological conditions. Here, we report on a physiologically improved, feasible, and cost-efficient EwS cell culture technique employing an advanced medium composition, reduced fetal calf serum, and spheroidal growth. Functionalin vitroassays and transcriptome profiling demonstrated that these refined conditions better recapitulate proliferation rates of patient tumors as well as hypoxic conditions relevant for EwS pathophysiology. Moreover, transcriptional signatures associated with the oncogenic activity of the EwS-specific FET::ETS fusion transcription factors in the refined culture conditions were shifted from proliferative towards metabolic gene signatures. The herein presented optimized physiological EwS cell culture technique provides a broadly applicable approach for enhancedin vitromodeling relevant to advancing EwS research and the validity of experimental results.MOTIVATIONCell culture remains the main platform to model EwS for research purposes. Yet, concerns exist about the limitations of standardin vitrotechniques to adequately reflect physiological conditions. In this study, we refined EwS cell culture methods to increase modeling capacity while ensuring a practical and cost-effective handling, thereby broadening their applicability within the scientific community.
Combinations of Insecticide-Treated Nets and Indoor Residual Spraying for Insecticide Resistance Management: A Modelling Exploration
Authors: Hobbs Neil Philip , Hastings Ian Michael 
Published: July 2024

AbstractInsecticides are heavily used for the control of vectors of disease. Malaria control has been reliant on insecticide treated nets (ITNs) and indoor residual spraying (IRS). There are concerns insecticide resistance will impede malaria control. The use of insecticide resistance management (IRM) strategies is recommended. One proposed IRM strategy is the combination of ITNs and IRS. Using a mathematical model of polygenic insecticide resistance evolution, this combination strategy is evaluated. First, combinations are evaluated against ITNs alone to determine if and when combinations may be beneficial in slowing resistance evolution to the pyrethroid on the ITN. Second combinations where multiple IRS insecticides are available are compared against full-dose mixture ITNs. Results of the simulations indicate the addition of IRS to ITNs may be beneficial, providing coverage of both interventions is high. The greater number IRS insecticides available for rotation the better, however even when combinations rotate three different IRS insecticides this is still a less potent IRM strategy than deploying full-dose mixtures. In conclusion the combination of ITNs and IRS appears to offer limited benefit over full-dose mixture ITNs for an IRM perspective
Gut microbiota regulates food intake in a rodent model of binge-eating disorder
Authors: Demangeat Thomas , Loison Léa , Huré Marion , Jean-Luc do Rego , Déchelotte Pierre , Achamrah Najate , Coëffier Moïse , Ribet David 
Published: July 2024

AbstractObjectiveBinge-eating disorder is characterized by recurrent episodes of consumption of large amounts of food within a short period of time, without compensatory behaviours. This disease is a major public health issue since it decreases patients quality of life and is associated with numerous comorbidities, encompassing anxiety, depression and complications associated with obesity. The pathophysiology of binge-eating disorder is complex and involves both endogenous, environmental and sociocultural factors. The gut microbiota has been proposed to be an important player in the onset or maintenance of eating disorders. Here, we aim to better delineate the potential role of the gut microbiota in binge-eating disorder.MethodWe used a model of binge-eating disorder where eight-weeks-old C57Bl/6 female mice had access during 2 hours, every 2 days over a 10-day period, to a highly palatable and high-calorie diet. Half of the animals received antibiotics to deplete their gut microbiota. Eating behaviour and other behavioural parameters were compared between groups.ResultsWe observed an increase in food intake in mouse exposed to high-fat high-sucrose diet, as well as tachyphagia and craving for food during binge-eating episodes. We demonstrate the gut microbiota depletion further increases food intake, specifically during binge-eating episodes.DiscussionThese results show that the gut microbiota is involved in the control of food intake during episodes of binge-eating. This strengthens the potential role of the gut bacteria in binge-eating disorder and open the way for future therapeutic strategies aiming at targeting patients’ gut microbiota.
Unbiased multiplex antigen screening of Cerebrospinal Fluid detects microbial and autoantigenic epitopes associated with Multiple Sclerosis
Authors: Barton Nathaniel J. , Tran Khanh , Olson Meagan N. , Deshpande Mugdha , Radu Irina , Francis Nimmy , Kurban Mariana , Orszulak Adrian R. , Chigas Samantha M. , Sundstrom Jonathan , Dawes Pepper , Murray Liam F. , Ionete Carolina , Lim Elaine T. , Hemond Christopher C. , Chan Yingleong 
Published: July 2024

AbstractTo comprehensively investigate the intrathecal antibody profile of multiple sclerosis (MS), we examined the cerebrospinal fluid of 195 patients (92 MS and 103 non-MS) for antibodies using a multiplex unbiased bacteria peptide library. We first tested against Epstein-Barr nuclear antigen 1 (EBNA1) for epitope sites enriched in MS and found a significant enrichment at position 407-419. We then used the data to perform a high-throughput screen against a library of 129 viruses known to infect humans. We discovered several additional epitopes from viruses such as Hantaan virus, Human Herpesvirus 6A and Human respiratory syncytial virus B associated with MS. Besides viral epitopes, we also screened for potential autoantigens of the central nervous system (CNS). We discovered several autoantigenic epitopes in proteins such as ADRB3, HTR3A and MPO that were significantly enriched for MS. Because of previous associations of Toxoplasma gondii infection with MS, we also performed a Toxoplasma gondii specific analysis and discovered additional epitopes enriched for MS. We further assessed epitope-epitope correlations within the patient samples and found distinct patterns of association between these microbial and autoantigenic epitopes. Finally, we performed machine-learning to determine if these epitopes are predictive for MS and found that the model incorporating all the epitopes could most effectively discriminate between MS and non-MS (ROC-AUC score = 0.91). Our results demonstrate the effectiveness of multiplex unbiased screens to detect the identity of potentially cross-reactive antibodies targeting MS CNS epitopes and they can also be used as effective biomarkers for MS.One Sentence SummaryWe performed an unbiased multiplex bacteria peptide antibody library screen on cerebrospinal fluid samples of patients with multiple sclerosis (MS) as well as non-MS controls and detected multiple viral and autoantigenic epitopes that are significantly enriched in MS patient samples.
Activation of two noncanonical R proteins by an insect effector confers plant immunity to aphid infestation
Authors: Lei Kang , Tian Dong , Shao Yutao , Wang Faming , Chang Jinhua , Char Si Nian , Li Guangwei , Dong Zhenying , Zhang Jianping , Cui Jiang-Hui , Zhao Songmin , Li Jingjing , Liu Hua , Liu Guo-Qing , Lv Peng , Wei Mingshu , Jin Xiaohuan , Song Qisheng , Yang Bing , Zhang Kunpu , Wu Di , Wang Dao Wen 
Published: July 2024

SUMMARYMolecular characterization of resistance genes is crucial for efficiently understanding and fortifying plant immunity against insect herbivores. Here we report that RMES1A and RMES1B proteins confer resistance to the sorghum aphidMelanaphis sorghiwhen activated by an insect effector MsEF1. Map-based cloning plus genetic analysis of knockout mutants confirm that RMES1A and RMES1B are both required for aphid resistance. Upon aphid attack, RMES1A and RMES1B expression is elevated in the sclerenchyma cells and vascular bundles of leaves; the two proteins interact with MsEF1 in the exocysts, thus upregulating key defense processes such as reactive oxygen species burst. Structural modeling predicts that RMES1A and RMES1B each carry an ATP binding site and two leucine-rich-repeat domains but lack coiled-coil or Toll/Interleukin-1 receptor/resistance domain, thus likely representing a new type of resistance controlling proteins in plants. Our work reveals new genes and mechanisms for further deciphering and improving plant immunity to insect pests.
Antimicrobial mechanism ofin-situplasma activated water treatment of pathogenicEscherichia coliandStaphylococcus aureusbiofilms
Authors: Xia Binbin , Vyas Heema Kumari Nilesh , Rice Scott A. , Newsome Timothy P. , Cullen Patrick J. , Mai-Prochnow Anne 
Published: July 2024

AbstractAimsThis study investigated the efficacy and mechanisms of inactivation of againstEscherichia coliUTI89 andStaphylococcus aureusNCTC8325 through anin-situplasma-activated water (PAW) treatment.Methods and ResultsPAW was prepared by discharging atmospheric pressure cold plasma beneath the surface of sterile distilled water. The study investigated the inactivation of biofilm cells and biofilm matrix. A complete killing of biofilm cells was achieved on both ofE. coli(6.76 ± 0.01 log CFU/mL) andS. aureus(6.82 ± 0.02 log CFU/mL). This process happened earlier inS. aureus. Simultaneously, PAW treatment disrupted the biofilm structure, inducing a significant reduction in general biofilm biomass and extracellular polymer substances (EPS) matrix. With the disruption of EPS, PAW was enabled to further interact with the bacterial membrane, causing a significant increase in membrane permeability and disrupted membrane structure. Finally, PAW treatment led to a significant accumulation of intracellular reactive oxygen and nitrogen species within the biofilm cells.ConclusionsCollectively, these findings indicate that PAW effectively inactivates biofilms by mechanically targeting the biofilm EPS matrix and biofilm cells in both gram-negative and gram-positive bacteria.Impact statementThis study contributes novel insights into plasma-activated water’s mechanisms of action, particularly its impact on the biofilm extracellular polymeric substances matrix (exopolysaccharides, extracellular DNA, and protein), cell membrane permeability, depolarization, and intracellular ROS and RNS accumulation in both of Gram-positive and Gram-negative species. These findings highlight PAW-based treatments against biofilm-related challenges in antimicrobial development and water system decontamination.
Genome-wide mapping of autonomously replicating sequences in the marine diatomPhaeodactylum tricornutum
Authors: Yun Hyun-Sik , Yoneda Kohei , Sugasawa Takehito , Suzuki Iwane , Maeda Yoshiaki 
Published: July 2024

AbstractAutonomously replicating sequences (ARSs) are important accessories in episomal vectors that allow them to be replicated and stably maintained within transformants. Despite their importance, no information on ARSs in diatoms have been reported. Therefore, we attempted to identify ARS candidates in the model diatom,Phaeodactylum tricornutum, via chromatin immunoprecipitation sequencing. In this study, subunits of the origin recognition complex (ORC), ORC2 and ORC4, were used to screen for ARS candidates. ORC2 and ORC4 bound to 355 sites on theP. tricornutumgenome, of which 69 were constantly screened after multiple attempts. The screened ARS candidates had an AT-richness of approximately 50% (44.39–52.92%) and did not have conserved sequences. In addition, ARS candidates were distributed randomly but had a dense distribution pattern at several sites. Their positions tended to overlap with those of the genetic region (73.91%). Compared to the ARSs of several other eukaryotic organisms, the characteristics of the screened ARS candidates are complex. Thus, our findings suggest that the diatom has a distinct and unique native ARSs.