bluuebunny/crossref_metadata_2025_split huggingface dataset:
Species interactions and eco-evolutionary dynamics of dispersal: the diversity dependence of dispersal
Authors: Bonte Dries , Keith Sally , Fronhofer Emanuel A. 
Published: June 2024

Dispersal plays a pivotal role in the eco-evolutionary dynamics of spatially structured populations, communities and ecosystems. As an individual-based trait, dispersal is subject to both plasticity and evolution. Its dependence on conditions and context is well understood within single-species metapopulations. However, species do not exist in isolation; they interact locally through various horizontal and vertical interactions. While the significance of species interactions is recognized for species coexistence and food web functioning, our understanding of their influence on regional dynamics, such as their impact on spatial dynamics in metacommunities and meta-food webs, remains limited. Building upon insights from behavioural and community ecology, we aim to elucidate biodiversity as both a driver and an outcome of connectivity. By synthesizing conceptual, theoretical and empirical contributions from global experts in the field, we seek to explore how a more mechanistic understanding of diversity–dispersal relationships influences the distribution of species in spatially and temporally changing environments. Our findings highlight the importance of explicitly considering interspecific interactions as drivers of dispersal, thus reshaping our understanding of fundamental dynamics including species coexistence and the emergent dynamics of metacommunities and meta-ecosystems. We envision that this initiative will pave the way for advanced forecasting approaches to understanding biodiversity dynamics under the pressures of global change.
This article is part of the theme issue ‘Diversity-dependence of dispersal: interspecific interactions determine spatial dynamics’.
Dispersal evolution alters evolution-mediated priority effects in a metacommunity
Authors: Fajgenblat Maxime , De Meester Luc , Urban Mark C. 
Published: June 2024

Biologists have long sought to predict the distribution of species across landscapes to understand biodiversity patterns and dynamics. These efforts usually integrate ecological niche and dispersal dynamics, but evolution can also mediate these ecological dynamics. Species that disperse well and arrive early might adapt to local conditions, which creates an evolution-mediated priority effect that alters biodiversity patterns. Yet, dispersal is also a trait that can evolve and affect evolution-mediated priority effects. We developed an individual-based model where populations of competing species can adapt not only to local environments but also to different dispersal probabilities. We found that lower regional species diversity selects for populations with higher dispersal probabilities and stronger evolution-mediated priority effects. When all species evolved dispersal, they monopolized fewer patches and did so at the same rates. When only one of the species evolved dispersal, it evolved lower dispersal than highly dispersive species and monopolized habitats once freed from maladaptive gene flow. Overall, we demonstrate that dispersal evolution can shape evolution-mediated priority effects when provided with a greater ecological opportunity in species-poor communities. Dispersal- and evolution-mediated priority effects probably play greater roles in species-poor regions like the upper latitudes, isolated islands and in changing environments.
This article is part of the theme issue 'Diversity-dependence of dispersal: interspecific interactions determine spatial dynamics'.
Nucleolin acute degradation reveals novel functions in cell cycle progression and division in TNBC
Authors: Mills Joseph , Tessari Anna , Anastas Vollter , Kumar Damu Sunil , Rad Nastaran Samadi , Lamba Saranya , Cosentini Ilaria , Reers Ashley , Zhu Zirui , Miles Wayne O. , Coppola Vincenzo , Cocucci Emanuele , Magliery Thomas J. , Shive Heather , Davies Alexander E. , Rizzotto Lara , Croce Carlo M. , Palmieri Dario 
Published: June 2024

AbstractNucleoli are large nuclear sub-compartments where vital processes, such as ribosome assembly, take place. Technical obstacles still limit our understanding of the biological functions of nucleolar proteins in cell homeostasis and cancer pathogenesis. Since most nucleolar proteins are essential, their abrogation cannot be achieved through conventional approaches. Additionally, the biological activities of many nucleolar proteins are connected to their physiological concentration. Thus, artificial overexpression might not fully recapitulate their endogenous functions.Proteolysis-based approaches, such as the Auxin Inducible Degron (AID) system paired with CRISPR/Cas9 knock-in gene-editing, have the potential to overcome these limitations, providing unprecedented characterization of the biological activities of endogenous nucleolar proteins.We applied this system to endogenous nucleolin (NCL), one of the most abundant nucleolar proteins, and characterized the impact of its acute depletion on Triple-Negative Breast Cancer (TNBC) cell behavior.Abrogation of endogenous NCL reduced proliferation and caused defective cytokinesis, resulting in bi-nucleated tetraploid cells. Bioinformatic analysis of patient data, and quantitative proteomics using our experimental NCL-depleted model, indicated that NCL levels are correlated with the abundance of proteins involved in chromosomal segregation. In conjunction with its effects on sister chromatid dynamics, NCL abrogation enhanced the anti-proliferative effects of chemical inhibitors of mitotic modulators such as the Anaphase Promoting Complex.In summary, using the AID system in combination with CRISPR/Cas9 for endogenous gene editing, our findings indicate a novel role for NCL in supporting the completion of the cell division in TNBC models, and that its abrogation could enhance the therapeutic activity of mitotic-progression inhibitors.
Long-term single molecule localization microscopy uncovers dynamic co-assembly of Lrp6 and Ror2 into Wnt-signalosomes
Authors: Philippi Michael , Dohle Julia , Watrinet Isabelle , Holtmannspötter Michael , Li Jinye , Birkholz Oliver , Miao Yi , Rothbauer Ulrich , Christopher Garcia K. , Kurre Rainer , Piehler Jacob , You Changjiang 
Published: June 2024

AbstractThe conserved Wnt signaling has been classified as two categories of canonical and noncanonical Wnt signaling. With a high promiscuity of Wnt signaling, how receptors from the two distinct pathways re-arrange in multi-protein signalosomes remains elusive. We here developed single-molecule tracking and localization microscopy based on labeling with reversibly binding nanobodies (rbTALM) for imaging receptor dynamics in the plasma membrane for extended time periods. To this end, we engineered nanobody-tag pairs with fine-tuned binding stabilities ensuring single-molecule tracking with high fidelity, yet continuous exchange of photobleached labels. Multicolor rbTALM imaging enabled simultaneous tracking and super-resolution imaging of three different Wnt co-receptors in the same cell for more than one hour at video rate. Time-lapse correlation analyses uncovered cooperative association of canonical and noncanonical Wnt co-receptors into a common, hybrid Wnt signalosome, demonstrating the exciting possibilities of rbTALM imaging for exploring nanoscale dynamics across millisecond to hour timescales.
Cell of origin alters myeloid-mediated immunosuppression in lung adenocarcinoma
Authors: Yang Minxiao , Shulkin Noah , Gonzalez Edgar , Castillo Jonathan , Yan Chunli , Zhang Keqiang , Arvanitis Leonidas , Borok Zea , Wallace W. Dean , Raz Dan , Torres Evanthia T. Roussos , Marconett Crystal N. 
Published: June 2024

SUMMARYSolid carcinomas are often highly heterogenous cancers, arising from multiple epithelial cells of origin. Yet, how the cell of origin influences the response of the tumor microenvironment is poorly understood. Lung adenocarcinoma (LUAD) arises in the distal alveolar epithelium which is populated primarily by alveolar epithelial type I (AT1) and type II (AT2) cells. It has been previously reported thatGramd2+AT1 cells can give rise to a histologically-defined LUAD that is distinct in pathology and transcriptomic identity from that arising fromSftpc+AT2 cells1,2. To determine how cells of origin influence the tumor immune microenvironment (TIME) landscape, we comprehensively characterized transcriptomic, molecular, and cellular states within the TIME ofGramd2+AT1 andSftpc+AT2-derived LUAD using KRASG12Doncogenic driver mouse models. Myeloid cells within theGramd2+AT1-derived LUAD TIME were increased, specifically, immunoreactive monocytes and tumor associated macrophages (TAMs). In contrast, theSftpc+AT2 LUAD TIME was enriched for Arginase-1+myeloid derived suppressor cells (MDSC) and TAMs expressing profiles suggestive of immunosuppressive function. Validation of immune infiltration was performed using flow cytometry, and intercellular interaction analysis between the cells of origin and major myeloid cell populations indicated that cell-type specific markers SFTPD in AT2 cells and CAV1 in AT1 cells mediated unique interactions with myeloid cells of the differential immunosuppressive states within each cell of origin mouse model. Taken together,Gramd2+AT1-derived LUAD presents with an anti-tumor, immunoreactive TIME, while the TIME ofSftpc+AT2-derived LUAD has hallmarks of immunosuppression. This study suggests that LUAD cell of origin influences the composition and suppression status of the TIME landscape and may hold critical implications for patient response to immunotherapy.
Modeling the dietary effects on bat viral shedding and potential consequences for pathogen spillover
Authors: Vanalli Chiara , Falvo Caylee , Crowley Dan , Schwarz Benjamin , Plowright Raina , Hudson Peter J. , Rynda-Apple Agnieszka , Cattadori Isabella M. 
Published: June 2024

AbstractChanges in the quality and quantity of food resources can affect individuals’ health, the way they control infections and consequently the likelihood of onward transmission of pathogens. Dietary shifts have been proposed as one of the factors driving spillovers of zoonotic viruses from bats through a bridging host to humans. While there is a general understanding of the relationship between nutrition and infection in model systems, how diet affects pathogen shedding and the risk of spillover from bats is lacking. We used a data-driven mathematical modeling approach to disentangle the relation between diet, immunity, and viral shedding of Jamaican fruit bats infected with H18N11 and fed different dietary regimes. Model selection indicates that the synergistic interaction between the metabolite citrulline and the cytokine TNFα controls viral shedding in a diet-dependent manner. Bats on a sub-optimal fat diet are more successful in terminating shedding than bats on an optimal or sub-optimal sugar diet. However, when bat foraging behavior is considered, bats on the optimal diet show a lower spillover hazard, probably because of a feeding behavior less conducive to transmission. This study provides novel insights into the diet-driven mechanisms of viral shedding and how they can potentially contribute to spillover events.
Recovery after human bone marrow mesenchymal stem cells (hBM-MSCs)-derived extracellular vesicles (EVs) treatment in post-MCAO rats requires handling associated with repeated behavioral testing
Authors: Gomez-Galvez Yolanda , Gupta Malvika , Kaur Mandeep , Fusco Salvatore , Podda Maria Vittoria , Grassi Claudio , Srivastava Amit , Iacovitti Lorraine , Blanco-Suarez Elena 
Published: June 2024

ABSTRACTRehabilitation is the only current intervention that improves sensorimotor function in ischemic stroke patients, similar to task-specific intensive training in animal models of stroke. Bone marrow mesenchymal stem cells (BM-MSCs)-derived extracellular vesicles (EVs) are promising in restoring brain damage and function in stroke models. Additionally, the non-invasive intranasal route allows EVs to reach the brain and target specific ischemic regions. Yet unclear is how handling might enhance recovery or influence other therapies such as EVs after stroke. We used the transient middle cerebral artery occlusion (MCAO) model of stroke in rats to assess how intensive handling alone, in the form of sensorimotor behavioral tests, or in combination with an intranasal multidose or single dose of EVs restored neurological function and ischemic damage. Handled rats were exposed to a battery of sensorimotor tests, including the modified Neurological Severity Score (mNSS), beam balance, corner, grid walking, forelimb placement, and cylinder tests, together with Magnetic Resonance Imaging (MRI) at 2, 7, 14, 21, and 28 days post-stroke (dps). Handled MCAO rats were also exposed to an intranasal multidose of EVs (8 doses in total across four weeks, each dose containing 0.8 × 109EVs in 120 µl) or a single dose of EVs (2.4 × 109EVs in 200 µl) at 2 dps. Non-handled rats were evaluated only by mNSS and MRI at 2, 28, and 56 dps and were treated with a single intranasal dose of EVs. Our results showed that handling animals after MCAO is necessary for EVs to work and that a single cumulative dose of EVs further improves the neurological function recovered during handling without affecting ischemic damage. These results show the importance of rehabilitation in combination with other treatments and highlight how intensive behavioral testing might influence functional recovery after stroke, especially when other treatments are also given.
Optimized Biomechanical Design of a Pulsatile Fontan Conduit for Congenital Heart Palliation
Authors: Emuna Nir , Marsden Alison L. , Humphrey Jay D. 
Published: June 2024

ABSTRACTThe evolution of palliative surgical procedures for children born with congenital heart defects has proven remarkably successful in extending life, but the resulting non-physiological circulation predisposes to myriad sequelae that compromise quality of life and overall life span. Among these procedures, standard-of-care Fontan completion surgery bypasses the nonfunctional ventricle and provides steady flow of deoxygenated blood to the lungs via a synthetic conduit that typically connects the inferior vena cava to a pulmonary artery. This altered circulation reduces cardiac output, elevates central venous pressures, and possibly contributes to adverse remodeling of the pulmonary vessels. There is, therefore, strong motivation to develop a next generation Fontan conduit capable of serving as a sub-pulmonic pulsatile pump, and there are now several reports of initial attempts. None of these studies have been driven by biomechanical considerations, however, and none have achieved the desired functionality. We thus present a novel analytical framework to improve design and guide fabrication by focusing on the microstructure and material properties of the contractile myofibers and associated passive matrix. Our optimized designs simultaneously ensure desired levels of stroke volume, ejection fraction, and pressure generation given constraints on Frank-Starling myofiber contraction and the limited space within the thoracic cavity of a three-to four-year-old child. This analysis also highlights the need to minimize any associated axial force or torque generation that a pulsatile conduit could transmit to the host vessels at the requisite anastomoses.
From Cardiac Myosin to the Beta Receptor: Autoantibodies Promote a Fibrotic Transcriptome and Reduced Ventricular Recovery in Human Myocarditis
Authors: Myers Jennifer M. , Sandel Clayton , Alvarez Kathy , Garman Lori , Wiley Graham , Montgomery Courtney , Gaffney Patrick , Stavrakis Stavros , Fairweather DeLisa , Bruno Katelyn A. , Zhao Yan Daniel , Cooper Leslie T. , Cunningham Madeleine W. 
Published: June 2024

AbstractBackgroundMyocarditis leads to dilated cardiomyopathy (DCM) with one-third failing to recover normal ejection fraction (EF50%), and there is a critical need for prognostic biomarkers to assess risk of nonrecovery. Cardiac myosin (CM) autoantibodies (AAbs) cross-reactive with the β−adrenergic receptor (βAR) are associated with myocarditis/DCM, but their potential for prognosis and functional relevance is not fully understood.MethodsCM AAbs and myocarditis-derived human monoclonal antibodies (mAbs) were investigated to define pathogenic mechanisms and CM epitopes of nonrecovery. Myocarditis patients who do not recover ejection fraction (EF<50%) by one year were studied in a longitudinal (n=41) cohort. Sera IgG and human mAbs were investigated for autoreactivity with CM and CM peptides by ELISA, protein kinase A (PKA) activation, and transcriptomic analysis in H9c2 heart cell line.ResultsCM AAbs were significantly elevated in nonrecovered compared to recovered patients and correlated with reduced EF (<50%). CM epitopes specific to nonrecovery were identified. Transcriptomic analysis revealed serum IgG and mAb 2C.4 induced fibrosis/apoptosis pathwaysin vitrosimilar to isoproterenol treated cells. Sera IgG and 2C.4 activated PKA in an IgG and βAR-dependent manner. Endomyocardial biopsies from myocarditis/DCM revealed IgG+ trichrome+ tissues.ConclusionsCM AAbs were significantly elevated in nonrecovered patients, suggesting novel prognostic relevance. CM AAbs correlated with lower EF, and Ab-induced fibrosis/apoptosis pathways suggested a role for CM AAbs in patients who do not recover and develop irreversible heart failure. Homology between CM and βARs supports mechanisms related to cross-reactivity of CM AAbs with the βAR, a potential AAb target in nonrecovery.
Individual variation in meiotic crossover positioning, rate and interference are associated with distinct genetic processes in domestic pigs
Authors: Brekke Cathrine , Gjuvsland Arne B. , Berg Peer , Johnston Susan E. 
Published: June 2024

AbstractMeiotic crossovers are essential for proper chromosome segregation, and provide an important mechanism for adaptation through linking beneficial alleles and purging deleterious mutations. However, crossovers can also break apart beneficial alleles and are themselves a source of new mutations within the genome. The rate and distribution of crossovers shows huge variation both within and between chromosomes, individuals and species, yet the molecular and evolutionary causes and consequences of this variation remain poorly understood. A key step in understanding this variation is to understand the genetic architecture of how many crossovers occur, where they occur, and how they interfere, as this allows us to identify the degree to which these factors are governed by common or distinct genetic processes. Here, we investigate individual variation in crossover count, crossover interference (ν), and crossover positioning measured as both intra-chromosomal allelic shuffling and distance to telomere (Mb), in a large genotyped breeding population of domestic pigs. Using measures from 82,474 gametes from 4,704 mothers and 271 fathers, we show that crossover traits are heritable within each sex (h2= 0.03 - 0.11), with the exception of male crossover interference. Crossover count and interference have a strongly shared genetic architecture in females, mostly driven by variants atRNF212. Female crossover positioning is mediated by variants atMEI4,PRDM9, andSYCP2. We also identify tentative associations at genomic regions corresponding toCTCFandREC114/REC8/CCNB1IP1(crossover count), andZCWPW1andZCWPW2(crossover positioning). Our results show that crossover count and crossover positioning in female pigs have the capacity to evolve somewhat independently in our dataset.
Nonlinear compliance of NompC gating spring and its implication in mechanotransduction
Authors: Wang Yukun , Jin Peng , Kumar Avinash , Jan Lily , Cheng Yifan , Jan Yuh-Nung , Zhang Yongli 
Published: June 2024

AbstractCytoskeleton-tethered mechanosensitive channels (MSCs) utilize compliant proteins or protein domains called gating springs to convert mechanical stimuli into electric signals, enabling sound and touch sensation and proprioception. The mechanical properties of these gating springs, however, remain elusive. Here, we explored the mechanical properties of the homotetrameric NompC complex containing long ankyrin-repeat domains (ARDs). We developed a toehold-mediated strand displacement approach to tether single membrane proteins, allowing us to exert force on them and precisely measure their absolute extension using optical tweezers. Our findings revealed that each ARD has a low stiffness of ∼0.7 pN/nm and begins to unfold stepwise at ∼7 pN, leading to nonlinear compliance. Our calculations indicate that this nonlinear compliance may help regulate NompC’s sensitivity, dynamic range, and kinetics to detect mechanical stimuli. Overall, our research highlights the importance of a compliant and unfolding-refolding gating spring in facilitating a graded response of MSC ion transduction across a wide spectrum of mechanical stimuli.
Altered connectome topology in newborns at risk for cognitive developmental delay: a cross-etiologic study
Authors: Speckert Anna , Payette Kelly , Knirsch Walter , von Rhein Michael , Grehten Patrice , Kottke Raimund , Hagmann Cornelia , Natalucci Giancarlo , Moehrlen Ueli , Mazzone Luca , Ochsenbein-Kölble Nicole , Padden Beth ,   SPINA BIFIDA STUDY GROUP ZURICH, Latal Beatrice , Jakab Andras 
Published: June 2024

AbstractThe human brain connectome is characterized by the duality of highly modular structure and efficient integration, supporting information processing. Newborns with congenital heart disease (CHD), prematurity, or spina bifida aperta (SBA) constitute a population at risk for altered brain development and developmental delay (DD). We hypothesize that, independent of etiology, alterations of connectomic organization reflect neural circuitry impairments in cognitive DD. Our study aim is to address this knowledge gap by using a multi-etiologic neonatal dataset to reveal potential commonalities and distinctions in the structural brain connectome and their associations with DD. We used diffusion tensor imaging (DTI) of 187 newborns (42 controls, 51 with CHD, 51 with prematurity, and 43 with SBA). Structural weighted connectomes were constructed using constrained spherical deconvolution based probabilistic tractography and the Edinburgh Neonatal Atlas. Assessment of brain network topology encompassed the analysis of global graph features, network-based statistics, and low-dimensional representation of global and local graph features. The Cognitive Composite Score of the Bayley Scales of Infant and Toddler Development 3rdedition was used as outcome measure at corrected 2 years for the preterm born individuals and SBA patients, and at 1 year for the healthy controls and CHD.We revealed differences in the connectomic structure of newborns across the four groups after visualizing the connectomes in a two-dimensional space defined by network integration and segregation. Further, ANCOVA analyses revealed differences in global efficiency (p < 0.0001), modularity (p < 0.0001), mean rich club coefficient (p = 0.017) and small-worldness (p = 0.016) between groups after adjustment for postmenstrual age at scan and gestational age at birth. Moreover, small-worldness was significantly associated with poorer cognitive outcome, specifically in the CHD cohort (r = -0.41, p = 0.005).Our cross-etiologic study identified divergent structural brain connectome profiles linked to deviations from optimal network integration and segregation in newborns at risk for DD. Small-worldness emerges as a key feature, associating with early cognitive outcomes, especially within the CHD cohort, emphasizing small-worldness’ crucial role in shaping neurodevelopmental trajectories. Neonatal connectomic alterations associated with DD may serve as a marker identifying newborns at-risk for DD and provide early therapeutic interventions.