bluuebunny/crossref_metadata_2025_split huggingface dataset:
Energy allocation explains how protozoan phenotypic traits adapt to temperature and nutrient supply
Authors: Perna Andrea , Rivoli Enrico S. , Reiss Julia , Perkins Daniel M. 
Published: July 2023

AbstractTo survive and reproduce, living organisms need to maintain an efficient balance between energy intake and energy expenditure. When the environment changes, a previously efficient energy allocation strategy may become inefficient in the new environment, and organisms are required to change their physiology, morphology, and behaviour. However, how multiple phenotypic traits interact with each other and with the characteristics of the environment to determine energy allocation is poorly understood. To address this knowledge gap, we develop a predictive framework, based on energetic and biophysical principles, to characterise phenotype-environment interactions. We tested this by adapting axenic populations of the ciliateTetrahymena pyriformisto different environmental conditions of temperature and resource levels, and measured population growth, cell size, respiration, and movement. Movement speed and respiration rate increased with acute changes in environmental temperature in a way that could be predicted from simple physical scaling relations such as the Boltzmann-Arrhenius equation and the ‘viscous drag’ impacting movement. Based on theoretical arguments, we argue that these short-term changes of metabolic rate and movement speed introduce a mismatch between energy intake and energy expenditure and are not sustainable on the long-term. In fact, by around 3.5 days after the introduction ofTetrahymenainto a novel environment, all measured quantities were further modulated in a direction that likely restored the energy allocation balance of the cells. Changes in cell size played a substantial role in mediating these adaptations, by simultaneously affecting multiple phenotypic traits, such as metabolic rate and the energetic costs of movement. In a small microbial consumer likeTetrahymena, size changes can happen over rapid timescales, relative to the timescales of ecological changes and of seasonal environmental fluctuations. Changes in body size can therefore be effectively leveraged – alongside physiological and biochemical regulations – to cope with environmental changes.
Mechanical Hand Synergies during Dynamic Hand Movements are Mostly Controlled in a Non-Synergistic Way by Spinal Motor Neurons
Authors: Oßwald Marius , Cakici Andre L. , Oliveira Daniela Souza de , Braun Dominik I. , Vecchio Alessandro Del 
Published: July 2023

AbstractPrecise control of spinal motor neurons is crucial for voluntary hand and digit movements. However, the specific mechanisms by which motor unit ensembles govern dynamic synergistic and individual digit tasks remain poorly understood. We recorded synchronized 3D hand kinematics and high-density surface EMG (HD-sEMG) data from extrinsic hand muscles of twelve participants during 13 dynamic hand and digit movement tasks, consisting of single-digit flexion/extension and mechanically synergistic grasping tasks.We extracted single motor unit (MU) activity and identified identical MUs across tasks. We extracted 7.8 ± 1.8 MUs per task and participant and found 182 out of 554 total MUs active during multiple movements. Analysis of the MU discharge patterns revealed two groups of motor units that were categorized intoprime mover MUs, showing strong correlation between firing rate modulation and digit kinematics, andpostural MUswith little modulated activity. We found these motor units could switch between the two modes, showing either postural or movement encoding activation depending on the task. However, MUs acted as prime mover only for one specific digit. We further observed highly task specific recruitment ofprime moverMUs. Across participants, we found only 9 ± 8.2 % ofprime moverMUs active during a grasp task and any single digit task involved in the grasp motion.We draw three conclusions: (1) Single digits are controlled by distinct groups of MUs. (2) Unexpectedly, mechanically synergistic grasp movements are mostly controlled in a non-synergistic way by distinct groups of MUs. 3) Multiple manifolds construct the movement of the human hand, and each motor unit can flexibly switch between postural and dynamic modes.Significance StatementWe investigated the neural control of motor unit ensembles during single-digit and synergistic grasping tasks in dynamic conditions. We found that motor units exhibited strong movement-correlated activity only for one specific digit. We further observed highly task specific recruitment of motor units during mechanically synergistic grasp movements, showing that on a motor unit level, mechanically synergistic movements are controlled in a non-synergistic way. The findings extend the knowledge of motor unit recruitment strategies in natural movements and have strong implications in the field of neurorehabilitation and control of assistive devices.
EPINEST, an agent-based model to simulate epidemic dynamics in large-scale poultry production and distribution networks
Authors: Pinotti Francesco , Lourenço José , Gupta Sunetra , Das Gupta Suman , Henning Joerg , Blake Damer , Tomley Fiona , Barnett Tony , Pfeiffer Dirk , Hoque Md. Ahasanul , Fournié Guillaume 
Published: July 2023

AbstractThe rapid intensification of poultry production raises important concerns about the associated risks of zoonotic infections. Here, we introduce EPINEST (EPI-demic NEtwork Simulation in poultry Transportation systems): an agent-based modelling designed to simulate pathogen transmission within realistic poultry production and distribution networks. The modular structure of the model allows for easy parameterization to suit specific countries and system configurations. Moreover, the framework enables the replication of a wide range of eco-epidemiological scenarios by incorporating diverse pathogen life-history traits, modes of transmission and interactions between multiple strains and/or pathogens. EPINEST was developed in the context of an interdisciplinary multicentre study conducted in Bangladesh, India, Vietnam and Sri Lanka, and will facilitate the investigation of the spreading patterns of various health hazards such as avian influenza,Campylobacter, Salmonellaand antimicrobial resistance in these countries. Furthermore, this modelling framework holds potential for broader application in veterinary epidemiology and One Health research, extending its relevance beyond poultry to encompass other livestock species and disease systems.
Influenza A virus infection alters lipid packing and surface electrostatic potential of the host plasma membrane
Authors: Petrich Annett , Chiantia Salvatore 
Published: July 2023

AbstractThe pathogenesis of influenza A viruses (IAVs) is influenced by several factors, including IAV strain origin and reassortment, tissue tropism and host type. While such factors were mostly investigated in the context of virus entry, fusion and replication, little is known about the viral-induced changes to the host lipid membranes which might be relevant in the context of virion assembly. In this work, we applied several biophysical fluorescence microscope techniques (i.e., Förster energy resonance transfer, generalized polarization imaging and scanning fluorescence correlation spectroscopy) to quantify the effect of infection by two IAV strains of different origin on the plasma membrane (PM) of avian and human cell lines. We found that IAV infection affects the membrane charge of the inner leaflet of the PM. Moreover, we showed that IAV infection impacts lipid-lipid interactions by decreasing membrane fluidity and increasing lipid packing. Because of such alterations, diffusive dynamics of membrane-associated proteins are hindered. Taken to-gether, our results indicate that the infection of avian and human cell lines with IAV strains of different origins had similar effects on the biophysical properties of the PM.
Dynamic Changes in Lymphocyte Populations Establish Zebrafish as a Thymic Involution Model
Authors: Hasan Ameera , Macias Jose J. , Wood Brashé , Malone-Perez Megan , Park Gilseung , Foster Clay A. , Frazer J. Kimble 
Published: July 2023

AbstractThe thymus is the site of T lymphocyte development and T cell education to recognize foreign, but not self, antigens. B cells also reside and develop in the thymus, although their functions are less clear. During ‘thymic involution,’ a process of lymphoid atrophy and adipose replacement linked to sexual maturation, thymocytes decline. However, thymic B cells decrease far less than T cells, such that B cells comprise ∼1% of human neonatal thymocytes, but up to ∼10% in adults. All jawed vertebrates possess a thymus, and we and others have shown zebrafish (Danio rerio) also have thymic B cells. Here, we investigated the precise identities of zebrafish thymic T and B cells and how they change with involution. We assessed the timing and specific details of zebrafish thymic involution using multiple lymphocyte-specific, fluorophore-labeled transgenic lines, quantifying the changes in thymic T- and B-lymphocytes pre- vs. post-involution. Our results prove that, as in humans, zebrafish thymic B cells increase relative to T cells post-involution. We also performed RNA sequencing (RNA-seq) onD. reriothymic and marrow lymphocytes of four novel double-transgenic lines, identifying distinct populations of immature T and B cells. Collectively, this is the first comprehensive analysis of zebrafish thymic involution, demonstrating its similarity to human involution, and establishing the highly genetically- manipulatable zebrafish model as a template for involution studies.
Calcineurin contributes to RNAi-mediated transgene silencing and small interfering RNA production in the human fungal pathogenCryptococcus neoformans
Authors: Yadav Vikas , Mohan Riya , Sun Sheng , Heitman Joseph 
Published: July 2023

AbstractAdaptation to external environmental challenges at the cellular level requires rapid responses and involves relay of information to the nucleus to drive key gene expression changes through downstream transcription factors. Here, we describe an alternative route of adaptation through a direct role for cellular signaling components in governing gene expression via RNA interference-mediated small RNA production. Calcium-calcineurin signaling is a highly conserved signaling cascade that plays central roles in stress adaptation and virulence of eukaryotic pathogens, including the human fungal pathogenCryptococcus neoformans. Upon activation inC. neoformans, calcineurin localizes to P-bodies, membrane-less organelles that are also the site for RNA processing. Here, we studied the role of calcineurin and its substrates in RNAi-mediated transgene silencing. Our results reveal that calcineurin regulates both the onset and the reversion of transgene silencing. We found that some calcineurin substrates that localize to P-bodies also regulate transgene silencing but in opposing directions. Small RNA sequencing in mutants lacking calcineurin or its targets revealed a role for calcineurin in small RNA production. Interestingly, the impact of calcineurin and its substrates was found to be different in genome-wide analysis, suggesting that calcineurin may regulate small RNA production inC. neoformansthrough additional pathways. Overall, these findings define a mechanism by which signaling machinery induced by external stimuli can directly alter gene expression to accelerate adaptative responses and contribute to genome defense.Article summarySignaling cascades primarily drive responses to external stimuli through gene expression changes via transcription factors that localize to the nucleus and bind to DNA. Our study identifies an alternative mechanism whereby calcineurin, a key and direct downstream effector of calcium signaling, is involved in post-transcriptional regulation of gene expression through RNAi-mediated small RNA production. We propose that such signaling allows cells to bypass the requirement for communication to the nucleus and rapidly drive stress responses in a reversible fashion.
YAP and TAZ differentially regulate postnatal cortical progenitor proliferation and astrocyte differentiation
Authors: Chen Jessie , Tsai Yung-Hsu , Linden Anne , Kessler John A , Peng Chian-Yu 
Published: July 2023

AbstractWW domain-containing transcription regulator 1 (TAZ) and Yes-associated protein (YAP) are transcriptional co-activators traditionally studied together as a part of the Hippo pathway and best known for their roles in stem cell proliferation and differentiation. Despite their similarities, TAZ and YAP can exert divergent cellular effects by differentially interacting with other signaling pathways that regulate stem cell maintenance or differentiation. In the developing central nervous system, In this study, we show that TAZ regulates astrocytic differentiation and maturation of postnatal neural stem and progenitor cells (NPCs), and that TAZ mediates some but not all of the effects of bone morphogenetic protein (BMP) signaling on astrocytic development. By contrast, TAZ and YAP both mediate effects on NPC fate of β1-integrin and integrin-linked kinase (ILK) signaling, and these effects are dependent on extracellular matrix (ECM) cues. These findings demonstrate that TAZ and YAP perform divergent functions in the regulation of astrocyte differentiation, where YAP regulates cell cycle states of astrocytic progenitors and TAZ regulates differentiation and maturation from astrocytic progenitors into astrocytes.Summary StatementAstrocytes are accounts for nearly half of the cells in the central nervous system, where they perform a diverse array of physiological functions. During development, astrocytes are primarily generated after neuronal differentiation in a stepwise manner from multiple glial committed progenitor subtypes. How gliogenic progenitors maintain proliferative properties versus differentiate into astrocytes is not fully understood. This work aims to elucidate how environmental signals utilizes molecularly similar intracellular components to achieve distinct developmental outcomes. In addition, many of the cell types that are involved in glial development are also present in brain tumors including glioblastoma. Knowledge on mechanisms regulating proliferation and differentiation of glial progenitors will provide insights into differences and similarities between normal and malignant cells.
Experimental infection of elk (Cervus canadensis) and mule deer (Odocoileus hemionus) with SARS-CoV-2
Authors: Porter Stephanie M. , Hartwig Airn E. , Bielefeldt-Ohmann Helle , Root J. Jeffrey , Bosco-Lauth Angela M. 
Published: July 2023

AbstractElk (Cervus canadensis) and mule deer (Odocoileus hemionus) were experimentally evaluated for susceptibility to SARS-CoV-2. Elk did not shed infectious virus but produced low-level serological responses. Mule deer shed and transmitted virus in addition to mounting pronounced serological responses; they could therefore play a role in the epidemiology of SARS-CoV-2.Article Summary LineExperimental infection of elk (Cervus canadensis) and mule deer (Odocoileus hemionus) with SARS-CoV-2 revealed that while elk are minimally susceptible to infection, mule deer become infected, shed infectious virus, and can infect naïve contacts.
Mechanical control of cell proliferation patterns in growing tissues
Authors: Carpenter Logan C. , Pérez-Verdugo Fernanda , Banerjee Shiladitya 
Published: July 2023

ABSTRACTCell proliferation plays a crucial role in regulating tissue homeostasis and development. However, our understanding of how cell proliferation is controlled in densely packed tissues is limited. Here we develop a computational framework to predict the patterns of cell proliferation in growing tissues, connecting single-cell behaviors and cell-cell interactions to tissue-level growth. Our model incorporates probabilistic rules governing cell growth, division, and elimination, while also taking into account their feedback with tissue mechanics. In particular, cell growth is suppressed and apoptosis is enhanced in regions of high cell density. With these rules and model parameters calibrated using experimental data, we predict how tissue confinement influences cell size and proliferation dynamics, and how single-cell physical properties influence the spatiotemporal patterns of tissue growth. Our findings indicate that mechanical feedback between tissue confinement and cell growth leads to enhanced cell proliferation at tissue boundaries, whereas cell growth in the bulk is arrested. By tuning cellular elasticity and contact inhibition of proliferation we can regulate the emergent patterns of cell proliferation, ranging from uniform growth at low contact inhibition to localized growth at higher contact inhibition. Furthermore, mechanical state of the tissue governs the dynamics of tissue growth, with cellular parameters affecting tissue pressure playing a significant role in determining the overall growth rate. Our computational study thus underscores the impact of cell mechanical properties on the spatiotemporal patterns of cell proliferation in growing tissues.
A comparison of convolutional neural networks and few-shot learning in classifying long-tailed distributed tropical bird songs
Authors: Zhong Ming , LeBien Jack , Campos-Cerqueira Marconi , Aide T. Mitchell , Dodhia Rahul , Lavista Ferres Juan 
Published: July 2023

AbstractBiodiversity monitoring depends on reliable species identification, but it can often be difficult due to detectability or survey constraints, especially for rare and endangered species. Advances in bioacoustic monitoring and AI-assisted classification are improving our ability to carry out long-term studies, of a large proportion of the fauna, even in challenging environments, such as remote tropical rainforests. AI classifiers need training data, and this can be a challenge when working with tropical animal communities, which are characterized by high species richness but only a few common species and a long tail of rare species. Here we compare species identification results using two approaches: convolutional neural networks (CNN) and Siamese Neural Networks (SNN), a few-shot learning approach. The goal is to develop methodology that accurately identifies both common and rare species. To do this we collected more than 600 hours of audio recordings from Barro Colorado Island (BCI), Panama and we manually annotated calls from 101 bird species to create the training data set. More than 40% of the species had less than 100 annotated calls and some species had less than 10. The results showed that Siamese Networks outperformed the more widely used convolutional neural networks (CNN), especially when the number of annotated calls is low.
14-3-3 protein augments the protein stability of phosphorylated spastin and promotes the recovery of spinal cord injury through its agonist intervention
Authors: Liu Qiuling , Yang Hua , Luo Jianxian , Peng Cheng , Wang Ke , Zhang Guowei , Ji Zhisheng , Lin Hongsheng 
Published: July 2023

AbstractAxon regeneration is abortive in the central nervous system following injury. Orchestrating microtubule dynamics has emerged as a promising approach to improve axonal regeneration. The microtubule severing enzyme spastin is essential for axonal development and regeneration through remodeling of microtubule arrangement. To date, however, little is known regarding the mechanisms underlying spastin action in neural regeneration after spinal cord injury. Here, we use glutathione transferase pulldown and immunoprecipitation assays to demonstrate that 14-3-3 interacts with spastin, bothin vivoandin vitro,via spastin Ser233 phosphorylation. Moreover, we show that 14-3-3 protects spastin from degradation by inhibiting the ubiquitination pathway and upregulates the spastin-dependent severing ability. Furthermore, the 14-3-3 agonist Fusicoccin (FC-A) promotes neurite outgrowth and regenerationin vitrowhich needs spastin activation. Western blot and immunofluorescence results revealed that 14-3-3 protein is upregulated in the neuronal compartment after spinal cord injuryin vivo. In addition, administration of FC-A not only promotes locomotor recovery, but also nerve regeneration following spinal cord injury in both contusion and lateral hemisection models; however, application of spastin inhibitor spastazoline successfully reverses these phenomena. Taken together, these results indicate that 14-3-3 is a molecular switch that regulates spastin protein levels, and the small molecule 14-3-3 agonist FC-A effectively mediates the recovery of spinal cord injury in mice which requires spastin participation.HighlightsThe formation of the 14-3-3 and spastin protein complex requires phosphorylation of spastin at the S233 site.14-3-3 is involved in the phosphorylation-ubiquitination crosstalk of spastin, thus impacting the protein stability.14-3-3 agonists Fusicoccin-A can facilitate the repair of spinal cord injury in mice.Activation of spastin function is a prerequisite for nerve regeneration and recovery of spinal cord injury in mice.Graphical Abstract
PTEN loss in glioma cell lines leads to increased extracellular vesicles biogenesis and PD-L1 cargo in a PI3K-dependent manner
Authors: Sanchez Julio C. , Pierpont Timothy M. , Argueta-Zamora Dariana , Wilson Kristin , August Avery , Cerione Richard A. 
Published: July 2023

AbstractPhosphatase and Tensin Homologue (PTEN) is one of the most frequently lost tumor suppressors in cancer and the predominant negative regulator of the PI3K/AKT signaling axis. A growing body of evidence has highlighted the loss of PTEN with immuno-modulatory functions including the upregulation of the programmed death ligand-1 (PD-L1), an altered tumor derived secretome that drives an immunosuppressive tumor immune microenvironment (TIME), and resistance to certain immunotherapies. Given their roles in immunosuppression and tumor growth, we examined whether the loss of PTEN would impact the biogenesis, cargo, and function of extracellular vesicles (EVs) in the context of the anti-tumor associated cytokine interferon-γ (IFN-γ). Through genetic and pharmacological approaches, we show that PD-L1 expression is regulated by JAK/STAT signaling, not PI3K signaling. Instead, we observe that PTEN loss positively upregulates cell surface levels of PD-L1 and enhances the biogenesis of EVs enriched with PD-L1 in a PI3K-dependent manner. We demonstrate that because of these changes, EVs derived from glioma cells lacking PTEN have a greater ability to suppress T cell receptor (TCR) signaling. Taken together, these findings provide important new insights into how the loss of PTEN can contribute to an immunosuppressive TIME, facilitate immune evasion, and highlight a novel role for PI3K signaling in the regulation of EV biogenesis and the cargo they contain.