bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell deformations generated by dynamic cortical actin waves drivein vivoswimming migration
Authors: Andrieu Cyril , Lee Bren Hunyi , Franz Anna 
Published: June 2024

AbstractAmoeboid cell migration drives many important developmental and disease-related processes including immune responses and cancer metastasis. Swimming cell migration is a subtype of amoeboid migration observed in cells in suspensionex vivo.However, the mechanism underlying swimming migrationin vivounder physiological conditions is unknown. UsingDrosophilafat body cells (FBCs) as a model, we show that FBCs actively swim to patrol the pupa. Their stop-and-go random walk is powered through the generation of oscillatory actomyosin waves, rather than persistent actin flows used by cells swimmingin vitro.These actomyosin waves exert peristaltic compressive forces as they move to the cell rear. This causes cell elongation towards the front to propel the cell forward. In addition, we demonstrate that, unlike in other types of amoeboid migration, all three RhoGTPases, RhoA, Cdc42 and Rac1, are required for FBC migration. They control actin wave formation by regulating actin polymerisation through the formin Dia. Furthermore, RhoA at the cell rear induces actomyosin contractions via Rho kinase and myosin II to generate cell deformations. Importantly, our work reveals that swimming migration is a novelin vivomigration mode for rapid and long-range cell dispersal, potentially also used by other cells such as immune cells and cancer cells when encountering an aqueous environment.
A generalized structured coalescent for purifying selection without recombination
Authors: Strütt Stefan , Excoffier Laurent , Peischl Stephan 
Published: June 2024

AbstractPurifying selection is a critical factor in shaping genetic diversity. Current theoretical models only address scenarios of either very weak or strong selection, leaving a significant gap in our knowledge. The effects of purifying selection on patterns of genomic diversity remain poorly understood when selection against deleterious mutations is weak to moderate, particularly when recombination is limited or absent. In this study, we extend an existing approach, the fitness-class coalescent, to incorporate arbitrary levels of purifying selection. This model offers a comprehensive framework for exploring the influence of purifying selection in a wide range of demographic scenarios. Moreover, our research reveals potential sources of qualitative and quantitative biases in demographic inference, highlighting the significant risk of attributing genetic patterns to past demographic events rather than purifying selection. This work expands our understanding of the complex interplay between selection, drift, and population dynamics, and how purifying selection distorts demographic inference.
Intrastromal graft of anterior lens capsule. A substitute for Bowman layer graft transplantation for keratoconus
Authors: Rodríguez-Barrientos Carlos A. , Translateur-Grynspan Amir , Zavala-Arcos Judith , Valdez Jorge E. , Santaella Gisella , Barraquer-Coll Carmen 
Published: June 2024

AbstractPurposeThe shortage of donor corneas limits Bowman layer transplantation for keratoconus. In this study, we evaluate the clinical outcome of anterior lens capsule xenograft transplantation in the corneal stroma of a rabbit model as substitute for Bowman layer graft that is used in stromal transplantation for advanced keratoconus.MethodsTransplantation of an anterior lens capsule in the corneal stroma was performed in four New Zealand white rabbits through the creation of a stromal pocket. Corneal transparency, central corneal thickness, and topographic characteristics of corneas were evaluated at different time points: pre- (0) and post- (7, 14, 21, and 28) operative days. Additionally, at the end of the study histopathological findings were evaluated.ResultsIn comparison to pre-operative day, transplantation of an anterior lens capsule preserved corneal transparency, central corneal thickness, and topographic characteristics remained constant throughout the study period. Histopathological analysis revealed the presence of the anterior lens capsule as a fully integrated lamellar graft without adverse effects in host stroma.ConclusionThe anterior lens capsule may be useful as a graft for intrastromal corneal trasplantation. Similarly to Bowman layer, anterior lens capsule has mechanical characteristics that facilitate corneal transplantation. In post-transplanted corneas the preservation of transparency, as well as the effect on corneal thickness, and topographic characteristics support the possibility of using anterior lens capsule as a substitute for Bowman layer graft.
Phenotypic analysis of the edible fruits ofLardizabala biternata, an endemic and monotypic vine from the Chilean biodiversity hotspot in South America
Authors: Herrera Jaime , Fernández Leonardo D. 
Published: June 2024

AbstractIntroductionLardizabala biternatais a vine endemic to Chile, distributed between 32°S and 40°S. Its sweet edible fruits have historically been harvested by hand from the wild as there are no productive systems for this vine. Herein, we conducted the first phenotypic analysis ofL. biternatafruits, which includes qualitative and quantitative analyses of morphological and morphometric traits. This phenotypic analysis is the baseline for the development of production systems that could reduce anthropogenic pressure on wild populations and favour theex-situconservation of this vine.Materials and methodsWe collected 282 fruits from two geographically distant populations during four fruiting seasons. In all of them we recorded 14 morphological attributes, including total weight, length, width, height, diameter, volume, edible pulp content, seed number weight and individual seed weight. We investigated morphometric differences between populations and seasons by analysis of variance (ANOVAs), phenotypic correlations by regressions and associations between traits by principal component analysis (PCA).ResultsOn overage, fruits weighed 20.8 g (3.0 – 44.6 g) and measured 54 mm in length (20.1 – 83.4 mm) and 23.7 mm in diameter. Edible pulp contributed around 44.4% of total fruit weight. Observed traits displayed significant variations between seasons and among traits (length vs width vs height). Fruit weight showed a high correlation with edible pulp weight, fruit length, seed weight, seed number, and others.Discussion and conclusionsOur study represents the first phenotypic analysis of the fruits of this wild, endemic, and rare plant. We comprehensively describe the morphological and morphometric characteristics of its fruits. The characteristics ofL. biternatafruits show significant morphometric variation between populations and seasons. However, the edible pulp consistently remains the main component of the fresh fruit weight. Like other domesticated members of the Lardizabalaceae, the fruits of this wild plant have the potential for cultivation through the development of sustainable production systems. The information we provide serves as a baseline for the development of such systems through selection and genetic improvement of the plant.
Optimizing Fed-Batch Processes with Dynamic Control Flux Balance Analysis
Authors: Gotsmy Mathias , Giannari Dafni , Mahadevan Radhakrishnan , Zanghellini Jürgen 
Published: June 2024

AbstractFed-batch processes are prevalent in biotechnological industries, but design of experiments often results in sub-optimal conditions due to incomplete solution space characterization. We employ a single-level dynamic control (DC) algorithm for dynamic flux balance analysis (dFBA), enhancing efficiency by reducing Karush-Kuhn-Tucker (KKT) condition constraints and adapting the algorithm for predicting optimal process length. In a growth-decoupled plasmid DNA production case study, we predict the optimal feeding profile and switching time between growth and production phase. Comparing our algorithm to its predecessor shows a speed-up of at least a factor of four. When the process length is part of the objective function the speed-up becomes considerably larger.
Transcriptomic analysis ofPicea abiestissue culture reveals the impact of culture conditions and the presence of glucuronoxylan on extracellular lignin production
Authors: Sapouna Ioanna , Sivan Pramod , Vilaplana Francisco , Srivastava Vaibhav , McKee Lauren Sara 
Published: June 2024

AbstractTissue cultures are an important study model for woody plant tissue and can be used to study lignin biosynthesis. The greatest disadvantage of protocols based on extraction of lignin from wood biomass is the almost inevitable alteration of the native structure of lignin. Using a Norway spruce tissue culture with the ability to secrete monolignols into a liquid culture medium, fundamental aspects of lignin have been studied in the past, such as its structure, the enzyme activity related to its polymerization, and its interactions with a secondary cell wall hemicellulose. In this study, parameters that can induce monolignol production and secretion in the tissue culture are investigated via gene expression analysis. The impact of the composition of the solid growth medium, which was in some cases supplemented with xylan, was studied in depth through transcriptomic investigation. We find that the state (i.e. liquid or solid) and the xylan content of the medium can impact gene expression, although microscopic analysis suggests that cellular morphology is consistent. Extracellular lignin was collected from a formulation of liquid medium with the same composition as that used for cellular growth, which was previously presumed to be “non-inducing” of lignin biosynthesis. Chemical analysis of this lignin was performed using nuclear magnetic resonance spectroscopy and size exclusion chromatography, which revealed changes in its structure compared to the polymer produced in the previously developed “inducing” liquid medium. These experiments show that there is still much we do not understand about an oft-used tissue culture system, but show the way to a deeper understanding of the genetic control of lignin biosynthesis.
Differences in fMRI-based functional connectivity during abstinence or interventions between heroin-dependent individuals and healthy controls
Authors: Kurtin Danielle L. , Prabhu Anusha M. , Groen Alissa , Amer Matthew J. , Lingford-Hughes Anne , Paterson Louise M. 
Published: June 2024

AbstractThe substantial personal, societal, and economic impacts of opioid addiction drive research investigating how opioid addiction affects the brain, and whether therapies attenuate addiction-related metrics of brain function. One useful approach to characterise the effects of opioid addiction on the brain is functional connectivity (FC). FC assesses the pairwise relationship of brain region function over time. This work is a systematic narrative review of studies investigating the effect of abstinence or interventions on FC in people who are dependent on heroin (HD) and healthy controls (HC). We found that HD typically showed weaker FC between three functional networks: the Executive Control Network, Default Mode Network, and the Salience Network. Abstinence and Transcranial Magnetic Stimulation (TMS) both attenuated differences in FC between HD and HC, often by increasing FC in HD. We critically assessed the clinical relevance of these results and the impact of study methods on the robustness of study results. We concluded with practical suggestions to improve the translational potential of neuromodulatory interventions (e.g., noninvasive brain stimulation) targeting the neural correlates of opioid addiction.HighlightsFunctional connectivity (FC) informs how neural resources are organised.FC is weaker in people with heroin dependence (HD) vs healthy controls (HC)Weaker FC is observed among resting, reward, cognitive, and attentional networks.Abstinence and brain stimulation strengthen FC and reduce craving/relapse in HD.FC may be a biomarker for developing therapies for HD.
Contribution of the neuron-specific ATP1A3 to embryonic spinal circuit emergence
Authors: Dinvaut Sarah , Calvet Sophie , Comte Jean-Christophe , Gury Raphael , Pascual Olivier , André Maelys , Ferrigno Rosaria , Honnorat Jérôme , Moret Frédéric , Marcy Guillaume , Falk Julien , Castellani Valérie 
Published: June 2024

AbstractThe early neurodevelopmental contributions of ion pumps remain poorly characterized. Combining analysis of public human embryo single-cell transcriptomic datasets and an embryonic chicken model, we found a conserved differentiation sequence whereby spinal cord neurons switch on neuron-specific alpha3 subunit (ATP1A3) of Na+/K+ATPases. In the chicken model, ATP1A3 is distributed along axons and growth cones. Its knockdown alters axon pathfinding of dorsal interneurons (DIN) that wire spinocerebellar circuits. In mirror of reported electric field (EF)-driven cell migration, we found that DIN axons align in EFs, which was abolished by Na+/K+ATPase inhibitor Ouabain and ATP1A3 knockdown. We recorded an embryonic trans-neural-epithelial potential generating EF whose pharmacological and surgical manipulation mimicked ATP1A3 knock-down-induced altered DIN axon pathfinding. Using DINs transplantation paradigm, we found that ATP1A3 is required cell-autonomously for EF-mediated long-range guidance. Finally, dominant-negative ATP1A3 mutation causing an early ATP1A3 childhood disease disrupts this fundamental developmental process, revealing unexpected pathogenic mechanisms.
Ferroptosis regulates hemolysis in stored murine and human red blood cells
Authors: D’Alessandro Angelo , Keele Gregory R. , Hay Ariel , Nemkov Travis , Earley Eric J. , Stephenson Daniel , Vincent Matthew , Deng Xutao , Stone Mars , Dzieciatkowska Monika , Hansen Kirk C. , Kleinman Steve , Spitalnik Steven L , Roubinian Nareg H. , Norris Philip J , Busch Michael P. , Page Grier P , Stockwell Brent R. , Churchill Gary A. , Zimring James C 
Published: June 2024

SummaryRed blood cell (RBC) metabolism regulates hemolysis during aging in vivo and in the blood bank. Here, we leveraged a diversity outbred mouse population to map the genetic drivers of fresh/stored RBC metabolism and extravascular hemolysis upon storage and transfusion in 350 mice. We identify the ferrireductase Steap3 as a critical regulator of a ferroptosis-like process of lipid peroxidation. Steap3 polymorphisms were associated with RBC iron content, in vitro hemolysis, and in vivo extravascular hemolysis both in mice and 13,091 blood donors from the Recipient Epidemiology and Donor evaluation Study. Using metabolite Quantitative Trait Loci analyses, we identified a network of gene products (FADS1/2, EPHX2 and LPCAT3) - enriched in donors of African descent - associated with oxylipin metabolism in stored human RBCs and related to Steap3 or its transcriptional regulator, the tumor protein TP53. Genetic variants were associated with lower in vivo hemolysis in thousands of single-unit transfusion recipients.HighlightsSteap3 regulates lipid peroxidation and extravascular hemolysis in 350 diversity outbred miceSteap3 SNPs are linked to RBC iron, hemolysis, vesiculation in 13,091 blood donorsmQTL analyses of oxylipins identified ferroptosis-related gene products FADS1/2, EPHX2, LPCAT3Ferroptosis markers are linked to hemoglobin increments in transfusion recipientsGraphical abstract
Chromogranin A (CgA) Deficiency Attenuates Tauopathy by Altering Epinephrine–Alpha-Adrenergic Receptor Signaling
Authors: Jati Suborno , Munoz-Mayorga Daniel , Shahabi Shandy , Tang Kechun , Tao Yuren , Dickson Dennis W. , Litvan Irene , Ghosh Gourisankar , Mahata Sushil K. , Chen Xu 
Published: June 2024

SummaryOur previous studies have indicated that insulin resistance, hyperglycemia, and hypertension in aged wild-type (WT) mice can be reversed in mice lacking chromogranin-A (CgA-KO mice). These health conditions are associated with a higher risk of Alzheimer’s disease (AD). CgA, a neuroendocrine secretory protein has been detected in protein aggregates in the brains of AD patients. Here, we determined the role of CgA in tauopathies, including AD (secondary tauopathy) and corticobasal degeneration (CBD, primary tauopathy). We found elevated levels of CgA in both AD and CBD brains, which were positively correlated with increased phosphorylated tau in the frontal cortex. Furthermore, CgA ablation in a human P301S tau (hTau) transgenic mice (CgA-KO/hTau) exhibited reduced tau aggregation, resistance to tau spreading, and an extended lifespan, coupled with improved cognitive function. Transcriptomic analysis of mice cortices highlighted altered levels of alpha-adrenergic receptors (Adra) in hTau mice compared to WT mice, akin to AD patients. Since CgA regulates the release of the Adra ligands epinephrine (EPI) and norepinephrine (NE), we determined their levels and found elevated EPI levels in the cortices of hTau mice, AD and CBD patients. CgA-KO/hTau mice exhibited reversal of EPI levels in the cortex and the expression of several affected genes, including Adra1 and 2, nearly returning them to WT levels. Treatment of hippocampal slice cultures with EPI or an Adra1 agonist intensified, while an Adra1 antagonist inhibited, tau hyperphosphorylation and aggregation. These findings reveal a critical role of CgA in regulation of tau pathogenesis via the EPI-Adra signaling axis.
Organ-Specific Microbiomes ofBiomphalariaSnails
Authors: Carruthers Lauren V. , Nordmeyer Stephanie C. , Anderson Timothy JC. , Chevalier Frédéric D. , Le Clec’h Winka 
Published: June 2024

ABSTRACTBackgroundThe microbiome is increasingly recognized to shape many aspects of its host biology and is a key determinant of health and disease. The microbiome may influence transmission of pathogens by their vectors, such as mosquitoes or aquatic snails. We previously sequenced the V4 region of the bacterial 16S rRNA gene from the hemolymph (blood) ofBiomphalariaspp. snails, vectors of the human blood fluke schistosome. We showed that snail hemolymph harbored an abundant and diverse microbiome. This microbiome is distinct from the water environment and can discriminate snail species and populations. As hemolymph bathes snail organs, we then investigated the heterogeneity of the microbiome in these organs.ResultsWe dissected ten snails for each of two different species (B. alexandrinaandB. glabrata) and collected their hemolymph and organs (ovotestis, hepatopancreas, gut, and stomach). We also ground in liquid nitrogen four whole snails of each species. We sampled the water in which the snails were living (environmental controls). Sequencing the 16S rRNA gene revealed organ-specific microbiomes. These microbiomes harbored a lower diversity than the hemolymph microbiome, and the whole-snail microbiome. The organ microbiomes tend to cluster by physiological function. In addition, we showed that the whole-snail microbiome is more similar to hemolymph microbiome.ConclusionsThese results are critical for future work on snail microbiomes and show the necessity of sampling individual organ microbiomes to provide a complete description of snail microbiomes.
A massively parallelin vivoassay of TdT mutants yields variants with altered nucleotide insertion biases
Authors: Carlson Courtney K. , Loveless Theresa B. , Milisavljevic Marija , Kelly Patrick I. , Mills Jeremy H. , Tyo Keith E. J. , Liu Chang C. 
Published: June 2024

AbstractTerminal deoxynucleotidyl transferase (TdT) is a unique DNA polymerase capable of template-independent extension of DNA with random nucleotides. TdT’sde novoDNA synthesis ability has found utility in DNA recording, DNA data storage, oligonucleotide synthesis, and nucleic acid labeling, but TdT’s intrinsic nucleotide biases limit its versatility in such applications. Here, we describe a multiplexed assay for profiling and engineering the bias and overall activity of TdT variants in high throughput. In our assay, a library of TdTs is encoded next to a CRISPR-Cas9 target site in HEK293T cells. Upon transfection of Cas9 and sgRNA, the target site is cut, allowing TdT to intercept the double strand break and add nucleotides. Each resulting insertion is sequenced alongside the identity of the TdT variant that generated it. Using this assay, 25,623 unique TdT variants, constructed by site-saturation mutagenesis at strategic positions, were profiled. This resulted in the isolation of several altered-bias TdTs that expanded the capabilities of our TdT-based DNA recording system, Cell History Recording by Ordered Insertion (CHYRON), by increasing the information density of recording through an unbiased TdT and achieving dual-channel recording of two distinct inducers (hypoxia and Wnt) through two differently biased TdTs. Select TdT variants were also testedin vitro, revealing concordance between each variant’sin vitrobias and thein vivobias determined from the multiplexed high throughput assay. Overall, our work, and the multiplex assay it features, should support the continued development of TdT-based DNA recorders,in vitroapplications of TdT, and further study of the biology of TdT.
The first interneuron of the mouse visual system is tailored to the natural environment through morphology and electrical coupling
Authors: Spinelli Matteo , Acevedo H. Alejandra , Block Christoph T. , Lindenthal Lucia , Schuhmann Fabian , Greschner Martin , Janssen-Bienhold Ulrike , Dedek Karin , Puller Christian 
Published: June 2024

SummaryThe topographic complexity of the mouse retina has long been underestimated, as obvious specializations, like a fovea or visual streak, are absent. However, anatomical and functional gradients exist. It was recently shown that receptive fields of retinal ganglion cells change their shape along the dorso-ventral retinal axis. These variations likely reflect the non-uniform statistics of the visual environment which vary dramatically from ground to sky. Horizontal cells are the first visual interneurons and dictate the synaptic signaling between photoreceptors and bipolar cells by lateral interactions, thereby shaping the receptive fields of down-stream neurons. Thus, we asked whether regional specializations are present at this earliest stage of synaptic circuitry, i.e. at the level of horizontal cells. We analyzed horizontal cell density distributions, morphological properties, localization of gap junction proteins, and the spatial extent of horizontal cell electrical coupling across complete retinas. All of these horizontal cell key features were asymmetrically organized along the dorso-ventral axis. Dorsal horizontal cells were less densely distributed, had larger dendritic trees, and electrical coupling was more extensive than in their ventral counterparts. The steepest change along this gradient occurred at the opsin transition zone of photoreceptors, i.e. the mouse visual horizon. Therefore, our results show that the cellular and synaptic organization of the mouse visual system are adapted to the visual environment at the earliest possible level, and that horizontal cells are well suited to form the cellular substrate for the global gradient previously described for the receptive field structures of retinal ganglion cells.