bluuebunny/crossref_metadata_2025_split huggingface dataset:
Topological constraints and finite-size effects in quantitative polymer models of chromatin organization
Authors: Abdulla Amith Z. , Tortora Maxime M. C. , Vaillant Cédric , Jost Daniel 
Published: June 2023

AbstractPolymer physics simulations have provided a versatile framework to quantitatively explore the complex mechanisms driving chromosome organization. However, simulating whole chromosomes over biologically-relevant timescales at high resolution often constitutes a computationally-intensive task — while genes or other regions of biological interest may typically only span a small fraction of the full chromosome length. Conversely, only simulating the sub-chromosomal region of interest might provide an over-simplistic or even wrong description of the mechanism controlling the 3D organization. In this work, we characterize what should be the minimal length of chromosome to be simulated in order to correctly capture the properties of a given restricted region. In particular, since the physics of long, topologically-constrained polymers may significantly deviate from those of shorter chains, we theoretically investigate how chromosomes being a long polymer quantitatively affects the structure and dynamics of its sub-segments. We show that increasing the total polymer length impacts on the topological constraints acting on the system and thus affects the compaction and mobility of sub-chains. Depending on the entanglement properties of the system, we derive a phenomenological relation defining the minimal total length to account for to maintain a correct topological regime. We finally detail the implications of these conclusions in the case of several specific biological systems.Abstract Figure
Septin organization is regulated by the Gpa1 Ubiquitination Domain and Endocytic Machinery during the yeast pheromone response
Authors: Johnson Cory P. , Shrestha Sudati , Hart Andrew , Jarvis Katherine F. , Genrich Loren E. , Latario Sarah G. , Leclerc Nicholas , Systuk Tetiana , Scandura Matthew , Geohegan Remi P. , Khalil André , Kelley Joshua B. 
Published: June 2023

AbstractThe septin cytoskeleton plays a key role in the morphogenesis of the yeast mating projection, forming structures at the base of the projection. The yeast mating response uses the G-protein coupled receptor (GPCR), Ste2, to detect mating pheromone and initiate mating projection morphogenesis. Desensitization of the Gα, Gpa1, by the Regulator of G-protein Signaling (RGS), Sst2, is required for proper septin organization and morphogenesis. We hypothesized that Gpa1 would utilize known septin regulators to control septin organization. We found that single deletions of the septin chaperone Gic1, the Cdc42 GAP Bem3, and the endocytic adaptor proteins Ent1 and Ent2 rescued the polar cap accumulation of septins in the hyperactive Gα. We hypothesized that hyperactive Gα might increase the rate of endocytosis of a pheromone-responsive cargo, thereby altering where septins are localized. Mathematical modeling predicted that changes in endocytosis could explain the septin organizations we find in WT and mutant cells. Our results show that Gpa1-induced disorganization of septins requires clathrin-mediated endocytosis. Both the GPCR and the Gα are known to be internalized by clathrin-mediated endocytosis during the pheromone response. Deletion of the GPCR C-terminus to block internalization partially rescued septin organization. However, deleting the Gpa1 ubiquitination domain required for its endocytosis completely abrogated septin accumulation at the polarity site. Our data support a model where the location of endocytosis serves as a spatial mark for septin structure assembly and that desensitization of the Gα delays its endocytosis sufficiently that septins are placed peripheral to the site of Cdc42 polarity.
Proinsulin degradation and presentation of a proinsulin B-chain autoantigen involves ER-associated protein degradation (ERAD)-enzyme UBE2G2
Authors: Cremer Tom , Hoelen Hanneke , van de Weijer Michael L. , Janssen George M , Costa Ana. I. , van Veelen Peter A. , Lebbink Robert Jan , Wiertz Emmanuel J.H.J. 
Published: June 2023

ABSTRACTType 1 diabetes (T1D) is characterized by HLA class I-mediated presentation of autoantigens on the surface of pancreatic β-cells. Recognition of these autoantigens by CD8+T cells results in the destruction of pancreatic β-cells and, consequently, insulin deficiency. Most epitopes presented at the surface of β-cells derive from the insulin precursor molecule proinsulin. The intracellular processing pathway(s) involved in the generation of these peptides are poorly defined. In this study, we show that a proinsulin B-chain antigen (PPIB5-14) originates from proinsulin molecules that are processed by ER-associated protein degradation (ERAD) and thus originate from ER-resident proteins. Furthermore, screening genes encoding for E2 ubiquitin conjugating enzymes, we identified UBE2G2 to be involved in proinsulin degradation. These results indicate that insulin-derived peptides, presented by HLA-class I molecules at the cell surface, originate from ER-resident proinsulin that has been dislocated to the cytosol for subsequent degradation. These insights into the pathway involved in the generation of insulin-derived peptides emphasize the importance of proinsulin processing in the ER to T1D pathogenesis and identify novel targets for future therapies that may cure or even prevent T1D.Graphical abstract
Differentially abundant bacteria drive the N2-fixation of a widespread moss in the forest-tundra transition zone
Authors: Escolástico-Ortiz Dennis Alejandro , Blasi Charlotte , Bellenger Jean-Philippe , Derome Nicolas , Villarreal-A Juan Carlos 
Published: June 2023

ABSTRACTBryophytes maintain symbiosis with epiphytic bacteria influencing the local nutrient budget. Moss bacterial communities are composed of a core microbiome and bacteria recruited from environmental sources. Notably, symbiotic N2-fixing bacteria contribute to the N budget in northern ecosystems through biological nitrogen fixation. This process may be affected by the abundance of diazotrophs and moss nutrient content. We used the abundant mossRacomitrium lanuginosumin a forest tundra and shrub tundra in Northern Quebec, Canada, to investigate the bacterial and diazotrophic communities associated with habitat type using amplicon sequencing of the bacterial 16S rRNA andnifHgenes and test whether the moss core microbiome has recruitment from the soil bacteria community. ThenifHamplicons and element analysis were used to test the effect of diazotrophic abundance and moss nutrient content on N2-fixation activity estimated by acetylene reduction assays. Moss microbial communities between tundra types hosted similar bacterial diversity but differentially abundant groups. The core microbiome ofR. lanuginosumis composed of bacteria strongly associated with northern mosses with no significant recruitment from the soil. The relative abundances of dominant diazotrophs are significantly correlated with acetylene reduction rates. In contrast, the moss nutrient content did not significantly drive N2-fixation. The proteobacterial generaAzorhizobiumandRhodomicrobiumrepresent newly reported bacteria associated with N2-fixation rates in the tundra. We identified critical bacterial groups related to moss-bacterial symbiosis and N2-fixation in the forest-tundra transition zone, a changing environment susceptible to climate warming.
Efficient Sex Separation by Exploiting Differential Alternative Splicing of a Dominant Marker inAedes aegypti
Authors: Weng Shih-Che , Antoshechkin Igor , Marois Eric , Akbari Omar S. 
Published: June 2023

AbstractOnly female mosquitoes consume blood and transmit deadly human pathogens. Therefore, it is critical to remove females before conducting releases for genetic biocontrol interventions. Here we describe a robust sex-sorting approach termed SEPARATOR (SexingElementProduced byAlternativeRNA-splicing ofATransgenicObservableReporter) that exploits sex-specific alternative splicing of an innocuous reporter to ensure exclusive dominant male-specific expression. Using SEPARATOR, we demonstrate reliable sex selection from larval and pupal stages inAedes aegypti, and use a Complex Object Parametric Analyzer and Sorter (COPAS®) to demonstrate scalable high-throughput sex-selection of first instar larvae. Additionally, we use this approach to sequence the transcriptomes of early larval males and females and find several genes that are sex-specifically expressed in males. SEPARATOR can simplify mass production of males for release programs and is designed to be cross-species portable and should be instrumental for genetic biocontrol interventions.
RAMAN DEVELOPMENTAL MARKERS IN ROOT CELL WALLS ARE ASSOCIATED WITH LODGING TENDENCY IN TEF
Authors: Diehn Sabrina , Kirby Noa , Ben-Zeev Shiran , Alemu Muluken Demelie , Saranga Yehoshua , Elbaum Rivka 
Published: June 2023

AbstractTef (Eragrostis tef(Zucc.) Trotter) is an important staple crop in Ethiopia and Eritrea. Its grains are gluten-free and protein rich, so it is considered as a “super-food”. Adapting tef to modern farming practices could allow its intensive growth in other regions and enable larger communities to gain from its nutritional values. However, high lodging susceptibility prevents the application of mechanical harvest and causes significant yield losses. Lodging describes the displacement of roots (root lodging) or fracture of culms (stem lodging), forcing plants to bend or fall from their vertical position. Lodging is facilitated by various abiotic and biotic factors, and the lodging severity is increased in overpopulated fields. In this study, we aimed to understand the microstructural properties of crown roots, underlining tef tolerance/susceptibility to lodging. We analyzed plants at 5 and 10 weeks after emergence and compared trellised to lodged plants. Root cross sections from different tef genotypes were characterized by scanning electron microscopy, micro computed tomography and Raman micro spectroscopy. Lodging susceptible genotypes exhibited early tissue maturation, including developed aerenchyma, intensive lignification, and lignin with high levels of crosslinks. A comparison between trellised and lodged plants suggested that lodging itself does not affect the histology of root tissue. Furthermore, cell wall composition along plant maturation was typical to each of the tested genotypes independently of trellising. Our results suggest that it is possible to select lines that exhibit slow maturation of crown roots. Such lines are predicted to show reduction in lodging and facilitate mechanical harvest.
An Experimental Platform for Stochastic Analyses of Single Serotonergic Fibers in the Mouse Brain
Authors: Mays Kasie C. , Haiman Justin H. , Janušonis Skirmantas 
Published: June 2023

ABSTRACTThe self-organization of the serotonergic matrix, a massive axon meshwork in all vertebrate brains, is driven by the structural and dynamical properties of its constitutive elements. Each of these elements, a single serotonergic axon (fiber), has a unique trajectory and can be supported by a soma that executes one of many available transcriptional programs. It necessitates the development of specialized methods for single-fiber analyses, both at the experimental and theoretical levels. We developed an integrated system that facilitates experimental isolation of single serotonergic fibers in brain tissue, including regions with high fiber densities, and demonstrated the potential of their quantitative analyses based on stochastic modeling. Single fibers were visualized using two transgenic mouse models, one of which is the first implementation of the Brainbow toolbox in this system. The trajectories of serotonergic fibers were automatically traced in the three spatial dimensions with a novel algorithm, and their properties were captured with a single parameter associated with the directional von Mises-Fisher probability distribution. The system represents an end-to-end workflow that can be imported into various studies, including those investigating serotonergic dysfunction in brain disorders. It also supports new research directions inspired by single-fiber analyses in the serotonergic matrix, including supercomputing simulations and modeling in physics.
Anthropogenic nest material use correlates with human landscape modifications in a global sample of birds
Authors: Sheard Catherine , Stott Lucy , Street Sally E. , Healy Susan D. , Sugasawa Shoko , Lala Kevin N. 
Published: June 2023

AbstractAs humans increasingly modify the natural world, many animals have responded by changing their behaviour. Predicting the extent of these responses is a key step in conserving these species. For example, the tendency for some species of birds to incorporate anthropogenic items – particularly plastic material – into their nests is of increasing concern, as in some cases this behaviour has harmful effects on both adults and young. Studies of this phenomenon, however, have to date been limited in geographic and taxonomic scope. To investigate the global correlates of anthropogenic (including plastic) nest material use, we used Bayesian phylogenetic mixed models and a dataset of recorded nest materials in 6,147 species of birds. We find that after controlling for research effort, anthropogenic nest material use is correlated with proximity to human landscape modification, synanthropic (artificial) nesting locations, breeding environment, and the number of materials that has been recorded within the species’ nest. We also demonstrate that anthropogenic nest material use is unrelated to body mass, range size, or conservation status. These results indicate that anthropogenic materials are more likely to be included in nests when they are more readily available, as well as potentially by species who have more flexibility in nest material choice.
CRISPR screens in iPSC-derived neurons reveal principles of tau proteostasis
Authors: Samelson Avi J. , Ariqat Nabeela , McKetney Justin , Rohanitazangi Gita , Parra Bravo Celeste , Bose Rudra , Travaglini Kyle J. , Lam Victor L. , Goodness Darrin , Dixon Gary , Marzette Emily , Jin Julianne , Tian Ruilin , Tse Eric , Abskharon Romany , Pan Henry , Carroll Emma C. , Lawrence Rosalie E. , Gestwicki Jason E. , Eisenberg David , Kanaan Nicholas M. , Southworth Daniel R. , Gross John D. , Gan Li , Swaney Danielle L. , Kampmann Martin 
Published: June 2023

AbstractAggregation of the protein tau defines tauopathies, which include Alzheimer’s disease and frontotemporal dementia. Specific neuronal subtypes are selectively vulnerable to tau aggregation and subsequent dysfunction and death, but the underlying mechanisms are unknown. To systematically uncover the cellular factors controlling the accumulation of tau aggregates in human neurons, we conducted a genome-wide CRISPRi-based modifier screen in iPSC-derived neurons. The screen uncovered expected pathways, including autophagy, but also unexpected pathways, including UFMylation and GPI anchor synthesis. We discover that the E3 ubiquitin ligase CUL5SOCS4is a potent modifier of tau levels in human neurons, ubiquitinates tau, and is a correlated with vulnerability to tauopathies in mouse and human. Disruption of mitochondrial function promotes proteasomal misprocessing of tau, which generates tau proteolytic fragments like those in disease and changes tau aggregationin vitro. These results reveal new principles of tau proteostasis in human neurons and pinpoint potential therapeutic targets for tauopathies.
Deficiency of the lipid flippase ATP10A causes diet-induced dyslipidemia in female mice
Authors: Norris Adriana C. , Yazlovitskaya Eugenia M. , Zhu Lin , Rose Bailey S. , May Jody C. , Gibson-Corley Katherine N. , McLean John A. , Stafford John M. , Graham Todd R. 
Published: June 2023

AbstractGenetic association studies have linked ATP10A and closely related type IV P-type ATPases (P4-ATPases) to insulin resistance and vascular complications, such as atherosclerosis. ATP10A translocates phosphatidylcholine and glucosylceramide across cell membranes, and these lipids or their metabolites play important roles in signal transduction pathways regulating metabolism. However, the influence of ATP10A on lipid metabolism in mice has not been explored. Here, we generated gene-specificAtp10Aknockout mice and show thatAtp10A-/-mice fed a high-fat diet did not gain excess weight relative to wild-type littermates. However,Atp10A-/-mice displayed female-specific dyslipidemia characterized by elevated plasma triglycerides, free fatty acids and cholesterol, as well as altered VLDL and HDL properties. We also observed increased circulating levels of several sphingolipid species along with reduced levels of eicosanoids and bile acids. TheAtp10A-/-mice also displayed hepatic insulin resistance without perturbations to whole-body glucose homeostasis. Thus, ATP10A has a sex-specific role in regulating plasma lipid composition and maintaining hepatic liver insulin sensitivity in mice.
Hypervirulent pneumococci display high levels of nasopharyngeal shedding and rapid onward transmission
Authors: Baltazar Murielle , Jacques Laura C. , Audshasai Teerawit , Yang Marie , Kadioglu Aras 
Published: June 2023

AbstractStreptococcus pneumoniaeserotype 1 is a major cause of invasive pneumococcal disease. Despite its high attack rate, serotype 1 exhibits a low carriage prevalence within the population, which raises important questions about the relationship between carriage and transmission of hypervirulent pneumococcal strains between individuals. We compared the transmission dynamics of serotype 1 sequence type ST217 to serotype 2 strain D39 using a novel model of transmission in young adult mice. Donor index mice were intranasally infected with ST217, D39 or isogenic pneumolysin-deficient mutants and co-housed with recipient naive contact mice. Three days later, all mice were infected with influenza A virus (IAV). Pneumococcal transmission was analysed during colonisation alone and co-infection with IAV by quantification of shedding and nasal colonisation in index and contact mice. The role of the toxin pneumolysin in shedding, transmission and colonisation, and the host nasopharyngeal immune response were investigated. We show that ST217 was shed in index mice at significantly greater levels compared to D39. Upon viral co-infection, ST217 was shed and transmitted at a faster rate to contact mice and displayed higher transmission levels compared to D39. Interestingly, the toxin pneumolysin did not play a role in shedding. However, upon acquisition by contact mice, pneumolysin-dependent macrophage recruitment was observed in the nasopharynx. Our results show that the rapid and high transmission rate of serotype 1 is a key factor in its ability to disseminate quickly within the population and cause disease outbreaks.
Diversification of Nucleoside Analogues as Potent Antiviral Drug Leads
Authors: Scheeff Stephan , Wang Yan , Lyu Mao-Yun , Nasiri Ahmadabadi Behzad , Hau Sam Chun Kit , Hui Tony K. C. , Zhang Yufeng , Zuo Zhong , Chan Renee Wan Yi , Ng Billy Wai-Lung 
Published: June 2023

AbstractNucleoside analogues are potent antiviral agents, but the continuous emergence of pathogenic viruses demands novel and diverse structures. Herein, we have created a diversified library of highly bioactive and non-cytotoxic nucleoside analogues featuring an unprecedented carbobicyclic core that mimics natural ribonucleoside conformation. These regio- and stereo-divergent analogues exhibit up to 16-fold greater antiviral efficacy than the FDA-approved antiviral, ribavirin. Importantly, the carbobicyclic core structure is critical for the potent antiviral efficacy, thus opening up ample opportunities for further lead optimization and mechanistic investigations.Abstract Figure
Resilient performance on construction projects in the post-pandemic era: an organizational perspective
Authors: Tonetto Mirela Schramm , Formoso Carlos Torres , Saurin Tarcisio Abreu , Bonesi De Luca Fabiana , Lora Fernanda Pavan , Lantelme Elvira 
Published: June 2023

PurposeThe COVID-19 pandemic offered a unique glimpse into the resilience of construction projects, shedding light on several learning opportunities. The purpose of this paper is to develop propositions for the improvement of resilient performance in construction in the post-pandemic era.Design/methodology/approachThe propositions were developed based on an empirical study in Brazil. Data collection involved the analysis of regulations, interviews with health experts, managers, and workers, in addition to non-participant observations of the use of 37 control practices in 39 construction sites comparing the work-as-imagined and the work-as-done. The practices were classified in a hierarchy of controls.FindingsSeven propositions for the improvement of resilient performance were developed, addressing collaboration between construction companies, slack resources, new health and safety practices, production planning and control, digital technologies, visual management, and organizational culture. These propositions emphasize organizational support for resilience. This is in contrast to the nature of most observed practices (57%) that relied on administrative controls and personal protective equipment, which are measures dependent on behaviors that resemble resilience at the individual level.Originality/valueAlthough much has been studied on COVID-19 implications for construction projects, previous empirical studies have not adopted the organizational resilience perspective as the main theoretical background.
Discard the false and retain the true: the effect of hypocrisy on the cognitive legitimacy of social enterprises
Authors: Zhang Kun , Zhang Xiu-e , Xu Xuejiao 
Published: June 2023

PurposeHypocrisy often observed in the social responsibility practices of commercial enterprises is more likely to occur in social enterprises. However, this issue has received little research attention. This study explores, from a consumer perspective, the formation of perceived hypocrisy and its impact on the cognitive legitimacy of social enterprises.Design/methodology/approachThis research conducted two experiments, and data were collected from 515 subjects in China to test the proposed hypotheses.FindingsBehavioral inconsistency in social enterprises leads to consumers' perceived hypocrisy. The higher the perceived hypocrisy towards social enterprises, the weaker their cognitive legitimacy of social enterprises. At a lower level of inconsistency, the perceived hypocrisy of social enterprises was lower than that of commercial enterprises. Egoistic attribution to prosocial behavior moderated the negative effect of perceived hypocrisy on cognitive legitimacy. The stronger the egoistic attribution, the greater is the negative effect of perceived hypocrisy on the cognitive legitimacy of social enterprises.Practical implicationsSocial entrepreneurs should be acutely aware of the harmful effects of hypocrisy on social enterprises. Social enterprises should not exaggerate their propaganda or be consistent with their words and actions.Originality/valueThis study innovatively analyzes the damage to the cognitive legitimacy of social enterprises caused by the hypocrisy that tends to occur in commercial enterprises and argues from the consumer viewpoint. These findings enrich the perspective on exploring social enterprise legitimacy.