bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid cyclic stretching induces a synthetic, proinflammatory phenotype in cultured human intestinal smooth muscle, with the potential to alter signaling to adjacent bowel cells
Authors: Wolfson Sharon M. , Beigel Katherine , Anderson Sierra E. , Deal Brooke , Weiner Molly , Lee Se-Hwan , Taylor Deanne , Heo Su Chin , Heuckeroth Robert O. , Hashmi Sohaib K. 
Published: October 2024

AbstractBackground and AimsBowel smooth muscle experiences mechanical stress constantly during normal function, and pathologic mechanical stressors in disease states. We tested the hypothesis that pathologic mechanical stress could alter transcription to induce smooth muscle phenotypic class switching.MethodsPrimary human intestinal smooth muscle cells (HISMCs), seeded on electrospun aligned poly-ε-caprolactone nano-fibrous scaffolds, were subjected to pathologic, high frequency (1 Hz) uniaxial 3% cyclic stretch (loaded) or kept unloaded in culture for 6 hours. Total RNA sequencing, qRT-PCR, and quantitative immunohistochemistry defined loading-induced changes in gene expression. NicheNet predicted how differentially expressed genes might impact HISMCs and other bowel cells.ResultsLoading induced differential expression of 4537 genes in HISMCs. Loaded HISMCs had a less contractile phenotype, with increased expression of synthetic SMC genes, proinflammatory cytokines, and altered expression of axon guidance molecules, growth factors and morphogens. Many differentially expressed genes encode secreted ligands that could act cell-autonomously on smooth muscle and on other cells in the bowel wall.DiscussionHISMCs demonstrate remarkably rapid phenotypic plasticity in response to mechanical stress that may convert contractile HISMCs into proliferative, fibroblast-like cells or proinflammatory cells. These mechanical stress-induced changes in HISMC gene expression may be relevant for human bowel disease.
Biotic interactions and environmental filtering both determine earthworm alpha and beta diversity in tropical rainforests
Authors: Goulpeau Arnaud , Hedde Mickaël , Ganault Pierre , Lapied Emmanuel , Maggia Marie-Eugénie , Marcon Eric , Decaëns Thibaud 
Published: October 2024

AbstractUnderstanding the relative importance of biotic interactions, multiple environmental drivers, and neutral processes in shaping community diversity and composition is a central question for both theoretical and applied ecology.We analysed a dataset describing 125 earthworm communities sampled in 10 localities in French Guiana. DNA barcodes were used to delimit operational taxonomic units (OTUs) that we considered as species surrogates to avoid the taxonomic deficit and calculate community-scale species richness and pair-wise Sørensen beta-diversity. We used log-ratio and generalised linear models to highlight the effects of biotic interactions and environment as drivers of alpha diversity, and generalised dissimilarity models to figure out the relative contribution of space and environment to beta-diversity at different spatial extents.Community-scale alpha diversity was mainly explained by habitat filtering (soil texture) and interspecific competition that limit the number of locally co-existing species.Beta diversity between pairs of communities was mainly explained by distance when comparing communities in similar habitats, by topography and available soil phosphorus when comparing communities in different habitats, and by distance, elevation and climate when comparing all possible pairs of communities.While community composition is determined locally by neutral processes and environmental filtering, biogeographic processes linked to dispersal limitation and adaptation to local environment are the most influential on a regional scale. This highlights the complex interplay of dispersal limitation, biotic interactions and environmental filtering during the process of community assembly.
Wild Florida Mottled Ducks demonstrate strong heterogeneity in their humoral innate immune response
Authors: Ayala Andrea J. , Cheng Matthew , Hellinger Thomas A. , Mark McBride K. , Webb Jonathan , Fanning Andrew , Snyder Paul , Ferragamo Margherita , Garcia Samantha C. , Sterner Nyah , Bischoff Karyn L. , Moreno Salvador-Almagro , Ogbunugafor C. Brandon 
Published: October 2024

AbstractThe Florida Mottled Duck (Anas fulvigula fulvigula) is a unique subspecies of waterfowl whose range is limited to peninsular Florida, USA. As an endemic species, Florida Mottled Ducks face numerous conservation stressors, such as habitat conversion and hybridization with non-native Mallards (Anas platyrhynchos). In addition to these numerous stressors, Mottled Ducks are also contending with emerging and/or geographically expanding waterborne pathogens such asVibriospp., due to the effects of climate change. However, even given their conservation needs, little is known with respect to the health, physiology and the immunity of wild Mottled Ducks in Florida. Given this lack of data, we performed health assessments of Mottled Ducks in the Central Florida area.Specifically, we examined the humoral innate immune system, i.e., plasma, of Mottled Ducks in response to a common, but extraneous pathogen,Escherichia colistrain ATCC number 8739. We utilized a bactericidal assay (BKA) commonly used in eco-immunology, to provide insight into the bactericidal capacities of captured Florida Mottled Ducks. We statistically tested the BKA capacity of 23 Mottled Ducks in response to age and whole blood lead levels (Pb). We found that there was no statistically significant relationship between the covariates we measured and Mottled Duck BKA capacity againstE. coli. However, the variability we observed in the BKA capacity of this subspecies warrants further research into additional physiological and ecological covariates coupled with potential immune stressors that Florida Mottled Ducks may be contending with.
MSFragger-DDA+ Enhances Peptide Identification Sensitivity with Full Isolation Window Search
Authors: Yu Fengchao , Deng Yamei , Nesvizhskii Alexey I. 
Published: October 2024

AbstractLiquid chromatography-mass spectrometry (LC-MS) based proteomics, particularly in the bottom-up approach, relies on the digestion of proteins into peptides for subsequent separation and analysis. The most prevalent method for identifying peptides from data-dependent acquisition (DDA) mass spectrometry data is database search. Traditional tools typically focus on identifying a single peptide per tandem mass spectrum (MS2), often neglecting the frequent occurrence of peptide co-fragmentations leading to chimeric spectra. Here, we introduce MSFragger-DDA+, a novel database search algorithm that enhances peptide identification by detecting co-fragmented peptides with high sensitivity and speed. Utilizing MSFragger’s fragment ion indexing algorithm, MSFragger-DDA+ performs a comprehensive search within the full isolation window for each MS2, followed by robust feature detection, filtering, and rescoring procedures to refine search results. Evaluation against established tools across diverse datasets demonstrated that, integrated within the FragPipe computational platform, MSFragger-DDA+ significantly increases identification sensitivity while maintaining stringent false discovery rate (FDR) control. It is also uniquely suited for wide-window acquisition (WWA) data. MSFragger-DDA+ provides an efficient and accurate solution for peptide identification, enhancing the detection of low-abundance co-fragmented peptides. Coupled with the FragPipe platform, MSFragger-DDA+ enables more comprehensive and accurate analysis of proteomics data.
Heterologous expression and optimization of fermentation conditions for recombinant ikarugamycin production
Authors: Evers Julia K. , Glöckle Anna , Wiegand Monique , Schuler Sebastian , Einsiedler Manuel , Gulder Tobias A. M. 
Published: October 2024

AbstractIkarugamycin is a member of the natural product family of the polycyclic tetramate macrolactams (PoTeMs). The compound exhibits a diverse range of biological activities, including antimicrobial, antiprotozoal, anti-leukemic, and anti-inflammatory properties. In addition, it interferes with several crucial cellular functions, such as oxidized low-density lipoprotein uptake in macrophages, Nef-induced CD4 cell surface downregulation, and mechanisms of endocytosis. It is therefore used as a tool compound to study diverse biological processes. However, ikarugamycin commercial prices are very high, with up to 1300 € per 1 mg, thus limiting its application. We therefore set out to develop a high-yielding recombinant production platform of ikarugamycin by screening different expression vectors, recombinant host strains, and cultivation conditions. Overall, this has led to overproduction levels of more than 100 mg/L, which, together with a straightforward purification protocol, establishes biotechnological access to affordable ikarugamycin enabling its increased use in biomedical research in the future.
Assembloid model to study loop circuits of the human nervous system
Authors: Miura Yuki , Kim Ji-il , Jurjuț Ovidiu , Kelley Kevin W. , Yang Xiao , Chen Xiaoyu , Thete Mayuri Vijay , Revah Omer , Cui Bianxiao , Pachitariu Marius , Pașca Sergiu P. 
Published: October 2024

AbstractNeural circuits connecting the cerebral cortex, the basal ganglia and the thalamus are fundamental networks for sensorimotor processing and their dysfunction has been consistently implicated in neuropsychiatric disorders1-9. These recursive, loop circuits have been investigated in animal models and by clinical neuroimaging, however, direct functional access to developing human neurons forming these networks has been limited. Here, we use human pluripotent stem cells to reconstruct anin vitrocortico-striatal-thalamic-cortical circuit by creating a four-part loop assembloid. More specifically, we generate regionalized neural organoids that resemble the key elements of the cortico-striatal-thalamic-cortical circuit, and functionally integrate them into loop assembloids using custom 3D-printed biocompatible wells. Volumetric and mesoscale calcium imaging, as well as extracellular recordings from individual parts of these assembloids reveal the emergence of synchronized patterns of neuronal activity. In addition, a multi–step rabies retrograde tracing approach demonstrate the formation of neuronal connectivity across the network in loop assembloids. Lastly, we apply this system to study heterozygous loss ofASH1Lgene associated with autism spectrum disorder and Tourette syndrome and discover aberrant synchronized activity in disease model assembloids. Taken together, this human multi-cellular platform will facilitate functional investigations of the cortico-striatal-thalamic-cortical circuit in the context of early human development and in disease conditions.
Insights into a clock’s fidelity through vesicular encapsulation
Authors: Tu Li Alexander Zhan , LiWang Andy , Subramaniam Anand Bala 
Published: October 2024

ABSTRACTThe single-celled cyanobacterium,Synechococcus elongatus, generates circadian rhythms with exceptional fidelity and synchrony despite their femtoliter volumes. Here, we explore the mechanistic aspects of this fidelity, by reconstituting the KaiABC post-translational oscillator (PTO) in cell-mimetic giant vesicles (GUVs) under well-defined conditionsin vitro. PTO proteins were encapsulated with a coefficient of variation that closely matched protein variations observed in live cells. Using fluorescently labeled KaiB and confocal microscopy, we were able to measure circadian rhythms generated by thousands of encapsulated PTOs at the single-vesicle level for several days as a function of protein concentration and GUV size. We find that PTO fidelity decreased with decreasing levels of encapsulated PTO proteins and in smaller GUVs. We also observed that in encapsulated PTOs, a significant fraction of KaiB localized to GUV membranes like it does in cyanobacteria. A mathematical model that uses empirical bulk concentration and stoichiometry limitations suggests that cyanobacteria overcome challenges to fidelity by expressing high levels of PTO proteins along with the CikA and SasA proteins, which buffer stochastic variations in the levels of KaiA and KaiB, respectively. Further, the model suggests that the transcription-translation feedback loop (TTFL) contributes at most a small percentage to the overall fidelity of the cyanobacterial circadian clock under constant conditions but is essential for maintaining phase synchrony. Our results are the first experimental demonstration of populations of synthetic cells that can autonomously keep circadian time. Additionally, the approach of using bulk relationships to understand complex phenomena in cell-like systems could be useful for understanding other collective behavior important in biology, such as liquid-liquid phase separation.
An intracellular calcium sensory complex CPKs/ECA1 controls cytosolic calcium homeostasis for plant osmosensitivity
Authors: Liang Xiaoju , Zhou Yeling , Xu Weifeng , Liang Jiansheng 
Published: October 2024

AbstractIntracellular Ca2+controls various cellular functions and local Ca2+dynamics is tightly regulated upon environmental cues. Maintaining cellular Ca2+balance is essential for plant survival. Here we report a calcium-dependent protein kinases (CPKs)-mediated signaling pathway, in conjunction with the ER membrane-resident Ca2+-ATPase ECA1, acts influentially for cytosolic Ca2+homeostasis and osmotic stress tolerance. We show that targeting cytosolic Ca2+efflux via specific inhibitors oreca1mutation results in augmented [Ca2+]cyt spikes, elevated cytoplasmic ABA ([ABA]cyt) level and ultimately hypersensitive to osmotic stress. Screening ofArabidopsisCPKs revealed direct binding of CPK2/6/11 to ECA1. Moreover, CPK2/6/11 phosphorylate the N-terminal of ECA1 at Ser5, thereby enhancing its activity for cytosolic Ca2+efflux into ER and subsequently lower [ABA]cyt. The cumulative effect of ECA1 and CPKs mutation onArabidopsisplant sensitivity to osmotic stress further illustrates that CPKs/ECA1 acts an intracellular sensory module for plant stress tolerance via regulating [Ca2+]cyt and [ABA]cyt homeostasis.One-sentence summary:CPKs/ECA1 acts an intracellular sensory module for plant osmotic stress tolerance via regulating cytosolic Ca2+and ABA homeostasis.
Targeting ZNF638 activates antiviral immune responses and potentiates immune checkpoint inhibition in glioblastoma
Authors: Seetharam Deepa , Chandar Jay , Ramsoomair Christian K. , Desgraves Jelisah F. , Medina Alexandra Alvarado , Hudson Anna Jane , Amidei Ava , Castro Jesus R. , Govindarajan Vaidya , Wang Sarah , Zhang Yong , Sonabend Adam M. , Valdez Mynor J. Mendez , Maric Dragan , Govindarajan Vasundara , Rivas Sarah R. , Lu Victor M. , Tiwari Ritika , Sharifi Nima , Thomas Emmanuel , Alexander Marcus , DeMarino Catherine , Johnson Kory , De La Fuente Macarena I , Nasany Ruham Alshiekh , Noviello Teresa Maria Rosaria , Ivan Michael E. , Komotar Ricardo J. , Iavarone Antonio , Nath Avindra , Heiss John , Ceccarelli Michele , Chiappinelli Katherine B. , Figueroa Maria E. , Bayik Defne , Shah Ashish H. 
Published: October 2024

AbstractViral mimicry refers to the activation of innate anti-viral immune responses due to the induction of endogenous retroelement (RE) expression. Viral mimicry has been previously described to augment anti-tumor immune responses and sensitize solid tumors to immunotherapy including colorectal cancer, melanoma, and clear renal cell carcinoma. Here, we found that targeting a novel, master epigenetic regulator, Zinc Finger Protein 638 (ZNF638), induces viral mimicry in glioblastoma (GBM) preclinical models and potentiates immune checkpoint inhibition (ICI). ZNF638 recruits the HUSH complex, which precipitates repressive H3K9me3 marks on endogenous REs. In GBM, ZNF638 is associated with marked locoregional immunosuppressive transcriptional signatures, reduced endogenous RE expression and poor immune cell infiltration (CD8+T-cells, dendritic cells). ZNF638 knockdown decreased H3K9-trimethylation, increased cytosolic dsRNA and activated intracellular dsRNA-signaling cascades (RIG-I, MDA5 and IRF3). Furthermore, ZNF638 knockdown upregulated antiviral immune programs and significantly increased PD-L1 immune checkpoint expression in patient-derived GBM neurospheres and diverse murine models. Importantly, targeting ZNF638 sensitized mice to ICI in syngeneic murine orthotopic models through innate interferon signaling. This response was recapitulated in recurrent GBM (rGBM) samples with radiographic responses to checkpoint inhibition with widely increased expression of dsRNA, PD-L1 and perivascular CD8 cell infiltration, suggesting dsRNA-signaling may mediate response to immunotherapy. Finally, we showed that low ZNF638 expression was a biomarker of clinical response to ICI and improved survival in rGBM patients and melanoma patients. Our findings suggest that ZNF638 could serve as a target to potentiate immunotherapy in gliomas.
Heterosis in crosses between remnant populations of a rare prairie forb: implications for restoration genetics
Authors: Oakley Christopher G. , Turner Isabelle A. , Rojas-Gutierrez Juan Diego , Easter Bob 
Published: October 2024

ABSTRACTBackground and AimsA major goal in both basic and applied evolutionary genetics is understanding the role of drift in shaping genetic variation with fitness consequences. For organisms amenable to controlled crosses, the increased fitness of progeny from between-relative to within-population crosses (heterosis) provides a useful tool to infer historical fixation of partly recessive deleterious alleles by drift and/or bottlenecks. Additionally, heterosis may also provide a unique benefit in regional admixture provenancing for restorations of rare plant species, but empirical data to directly test this idea is lacking.MethodsWe quantified heterosis in crosses between small remnant populations of a rare prairie forb (Silene regiaSims). We measured early fitness components (seed number per fruit, germination, and juvenile survival) in a controlled environment. Adult fitness components (survival and reproduction) were quantified over two flowering seasons in two different environments, a field common garden simulating the initial stages of a restoration, and a greenhouse. To our knowledge, our study is the first to estimate cumulative fitness for a rare species in conditions of a newly established restoration in the field. Additionally, we provide a unique comparison of heterosis estimated under controlled vs. field conditions.Key ResultsThe consequences of between-population crosses for cumulative fitness in the field were strongly positive in two of the populations (132-292% heterosis) and neutral in a third. Heterosis was generally stronger when measured under field conditions and was more likely to be detected for adult fitness components.ConclusionsRegional admixture provenancing in restorations should be beneficial for this species. We advocate for more research on heterosis in rare species, particularly in restorations. Such restorations can be opportunities for experimental genetics in addition to reestablishing important ecosystem services.
Inhibition Resolves Simon Conflict: Evidence from EEG Decoding
Authors: Lee Yoon Seo , Bae Gi-Yeul , Cho Yang Seok 
Published: October 2024

AbstractThe congruency sequence effect (CSE), a hypothesized marker of top-down cognitive control, refers to a reduced congruency effect after incongruent trials compared to congruent trials. Although this effect has been observed across various distractor interference tasks, the nature of the control processes underlying the CSE remains a topic of active debate. It has been suggested that cognitive control may resolve conflicts in information processing either by (a) enhancing the representation of goal information and/or (b) suppressing the representation of distractor information. The present study aimed to identify the conflict resolution processes within the context of the color Simon task by decoding the goal and distracting information from human scalp EEG signals. For the decoding analysis, models were trained separately for color and location attributes corresponding to goal and distractor information. Additionally, decoding accuracy was calculated in different frequency bands: theta (4-8 Hz), alpha (8-12 Hz), low beta (12-20 Hz), and high beta (20-30 Hz). Results showed that decoding accuracy for distractor information was reduced when cognitive control was activated and this pattern was only observed in the high beta-frequency band (20-30 Hz). In contrast, no such difference was observed for target information. These findings suggest that cognitive control regulates Simon conflict by inhibiting distractor representation in the brain, thereby preventing unwanted distraction-driven behaviors.
Comparative evaluation of methodologies for estimating the effectiveness of non-pharmaceutical interventions in the context of COVID-19: a simulation study
Authors: Ganser Iris , Paireau Juliette , Buckeridge David L , Cauchemez Simon , Thiebaut Rodolphe , Prague Mélanie 
Published: October 2024

AbstractNumerous studies assessing the effectiveness of non-pharmaceutical interventions (NPIs) against COVID-19 have produced conflicting results, partly due to methodological differences. This study aims to clarify these discrepancies by comparing two frequently used approaches in terms of parameter bias and confidence interval coverage of NPI effectiveness parameters. We compared two-step approaches, where NPI effects are regressed on by-products of a first analysis, such as the effective reproduction numberℛt, with more integrated models that jointly estimate NPI effects and transmission rates in a single-step approach. We simulated datasets with mechanistic and an agent-based models and analyzed them with both mechanistic models and a two-step regression procedure. In the latter,ℛtwas estimated first and then used as the outcome in a linear regression with NPI variables as predictors. Mechanistic models consistently outperformed two-step regressions, exhibiting minimal bias (0-5%) and accurate confidence interval coverage. Conversely, the two-step regression showed up to 25% bias, with significantly lower-than-nominal confidence interval coverage, reflecting challenges in uncertainty propagation. We identified additional challenges in the two-step regression method, such high depletion of susceptibles and time lags in observational data. Our findings suggest caution when using two-step regression methods for estimating NPI effectiveness.
Examining the causal genetic effects of substance use on aging
Authors: Balbona Jared V. , Jeffries Paul , Gorelik Aaron J. , Nelson Elliot C. , Bogdan Ryan , Agrawal Arpana , Johnson Emma C. 
Published: October 2024

AbstractSubstance use shortens lifespan, impedes health, and accelerates the biological aging process. We found widespread genetic correlations between alcohol, tobacco, cannabis, and opioid use and use disorders with indices of aging across the lifespan. There was evidence of tobacco and alcohol use and use disorders causally impacting physical, cognitive, and biological aging, with the effects of alcohol being more dependent on quantity of consumption; evidence of reverse causality was scant.