bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural variation in tetrapyrrole biosynthetic enzymes and their regulation modify the chlorophyll mutantOy1-N1989
Authors: Kaur Amanpreet , Khangura Rajdeep S. , Dilkes Brian P. 
Published: September 2024

AbstractTetrapyrroles are macrocyclic compounds present in and required for all life on Earth. Mutants with defects in tetrapyrrole pathway enzymes can be used to uncover natural variation in this pathway and study pathway regulation. We report here the effects of theOy1-N1989/+mutation, a semi-dominant allele of subunit I in the Mg-chelatase enzyme with reduced chlorophyll biosynthesis, on global gene expression and morphological traits. Coordinate regulation of the tetrapyrrole pathway was observed as transcriptional feedback regulation of genes in the tetrapyrrole pathway inOy1-N1898/+ mutants. Natural variation in the wild-type allele atoy1modulated the severity of the impact ofOy1-N1989/+on gene expression. We also studied the effects of previously identified cis-acting expression variation atoy1in wild-type plants. The seventy transcripts encoding biosynthetic enzymes in the tetrapyrrole pathway exhibited similar transcriptional co-regulation in response to cis-variation inoy1transcript accumulation in wild-type plants as observed in the RNAseq ofOy1-N1989/+ mutants. This demonstrated that the coordinate regulation of the pathway also occurs during physiologically-relevant variation in OY1 abundance. Cis variants at seven tetrapyrrole pathway genes were linked to variation in chlorophyll accumulation inOy1-N1989/+mutant or wild-type plants. Analysis of trans-acting transcriptional variation by eGWAS detected multiple transcriptional hotspots, which disproportionately affected the expression of a subset of tetrapyrrole pathway genes, indicating that some genes are repeated targets of transcriptional regulation. The trans-regulatory hotspots coordinately regulated this pathway and may work to limit the accumulation of phototoxic intermediates.Author SummaryThe mutant allele and interactions with the genetic background determine the severity of mutant phenotypes. We usedOy1-N1989/+mutants, affecting Mg-chelatase subunit I, to identify natural variants in the tetrapyrrole pathway affecting transcriptional regulation and variation in mutant traits. By integrating GWAS and transcriptomics, we identified similar feedback regulation of porphyrin and chlorophyll metabolism in mutants as well as in wild-type plants affected by natural variation. This is the first demonstration of natural variation affecting transcriptional feedback in the tetrapyrrole pathway under normal conditions. Using GWAS as a regulatory discovery tool, we identified unexplored regulatory mechanisms in a pathway that is critical for energy capture from the sun and chemical energy utilization in all living things and multiple human diseases.
Spatiotemporal, environmental, and behavioral predictors ofVarroamite intensity in managed honey bee apiaries
Authors: Boehm Vock Laura F. , Mossman Lauren M. , Rapti Zoi , Dolezal Adam G. , Clifton Sara M. 
Published: September 2024

AbstractHoney bees contribute substantially to the world economy through pollination services and honey production. In the U.S. alone, honey bee pollination is estimated to contribute at least $11 billion annually, primarily through the pollination of specialty crops. However, beekeepers lose about half of their hives every season due to disease, insecticides, and other environmental factors. Here, we explore and validate a spatiotemporal statistical model ofVarroa destructormite burden (in mites/300 bees) in managed honey bee colonies, exploring the impact of both environmental factors and beekeeper behaviors. We examine risk factors forVarroainfestation using apiary inspection data collected across the state of Illinois over 2018-19, and we test the models using inspection data from 2020-21. After accounting for spatial and temporal trends, we find that environmental factors (e.g., floral quality, insecticide load) are not predictive ofVarroaintensity, while several beekeeper behaviors (e.g., smaller colony density, supplemental feeding, and mite monitoring/treatment) are protective againstVarroa. Interestingly, while monitoringandtreating forVarroais protective, treatingwithoutmonitoring is no more effective than not treating at all. This is an important result supporting Integrated Pest Management (IPM) approaches.Author SummaryHoney bees contribute substantially to the world economy through pollination services and honey production. However, beekeepers lose about half of their hives every season due to disease, insecticides, and other environmental factors. Pathogens, such asVarroamites and the viruses they vector, are especially detrimental to colony health, and best practices for pest management remain contentious. In this study, we modelVarroa destructormite burden in managed honey bee colonies using apiary inspection data collected across the state of Illinois from 2018 – 2021. Our modelling approach accounts for both spatial and temporal trends, allowing us to investigate the marginal impacts of environmental factors and beekeeper interventions on mite burden. We show that treating forVarroamites has a protective effect only when accompanied by a monitoring strategy, important evidence in favor of Integrated Pest Management (IPM) approaches.
Pythia: Non-random DNA repair allows predictable CRISPR/Cas9 integration and gene editing
Authors: Naert Thomas , Yamamoto Taiyo , Han Shuting , Horn Melanie , Bethge Phillip , Vladimirov Nikita , Voigt Fabian F. , Figueiro-Silva Joana , Bachmann-Gagescu Ruxandra , Helmchen Fritjof , Lienkamp Soeren S. 
Published: September 2024

SummaryCRISPR-based genome engineering holds enormous promise for basic science and therapeutic applications. Integrating and editing DNA sequences is still challenging in many cellular contexts, largely due to insufficient control of the repair process. We find that repair at the genome-cargo interface is predictable by deep-learning models and adheres to sequence context specific rules. Based onin silicopredictions, we devised a strategy of triplet base-pair repeat repair arms that correspond to microhomologies at double-strand breaks (trimologies), which facilitated integration of large cargo (>2 kb) and protected the targeted locus and transgene from excessive damage. Successful integrations occurred in >30 loci in human cells and inin vivomodels. Germline transmissible transgene integration inXenopus, and endogenous tagging of tubulin in adult mice brains demonstrated integration during early embryonic cleavage and in non-dividing differentiated cells. Further, optimal repair arms for single- or double nucleotide edits were predictable, and facilitated small editsin vitroandin vivousing oligonucleotide templates.We provide a design-tool (Pythia,pythia-editing.org) to optimize custom integration, tagging or editing strategies. Pythia will facilitate genomic integration and editing for experimental and therapeutic purposes for a wider range of target cell types and applications.
An annotated reference library for supporting DNA metabarcoding analysis of aquatic macroinvertebrates in French freshwater environments
Authors: Gauvin Paula , Eme David , Domaizon Isabelle , Rimet Frédéric 
Published: September 2024

AbstractFreshwater ecosystems are increasingly threatened by human activities, leading to biodiversity loss and ecosystem degradation. Effective biodiversity monitoring, particularly through the use of aquatic macroinvertebrates as bioindicators, is crucial for assessing ecological health. While traditional morphological methods face limitations, DNA metabarcoding offers higher accuracy and efficiency in species identification using environmental DNA. However, the success of metabarcoding is contingent on the quality of reference libraries, which are often incomplete or biased. This study aimed to construct a comprehensive COI-based DNA barcode library for freshwater macroinvertebrates in France, specifically targeting short gene regions amplified with fwhF2/fwhR2N primers, suitable for degraded DNA. A list of species occurring in French freshwater ecosystems was established from official national checklists and Alpine lake surveys. The resulting library was analyzed for taxonomic completeness, barcode coverage and genetic diversity. The checklist consisted of 2,841 species across 10 phyla, for which 56% had at least one COI-5P sequences available in the Barcode of Life Data System (BOLD). Alignment challenges with the primers were identified for certain taxa, particularly among Coleoptera, Diptera, and Malacostraca. The genetic diversity approached by the number of haplotypes per species highlighted that most of the species have limited diversity, with only 3 species having more than 100 haplotypes. Finally, this study showed that a total of 57 haplotypes were shared among 116 distinct species. This work emphasized the need for expanded sequencing efforts to improve barcode coverage and highlighted the pitfalls associated with the use of these primers for further biodiversity assessment of macroinvertebrates with degraded DNA.
Bifidobacterium pseudocatenulatumcapsular exopolysaccharide enhances systemic anti-tumour immunity in pre-clinical breast cancer
Authors: Price Christopher A. , Nicklin Alicia , Kujawska Magdalena , Koev Todor T. , Ilker Nilda , Fowler Wesley J. , McKee Alastair M. , Mitchell Luke , Rowe Mitchel , Taylor James A.G.E. , Benwell Christopher J. , Dreger Sally A. , Mueller Julia , Hall Lindsay J. , Robinson Stephen D. 
Published: September 2024

AbstractGut microbes have merged as powerful regulators of cancer responses, withBifidobacteriumspecies and strains playing a key role in promoting anti-tumour immunity. While they represent promising candidates for cancer therapeutics, the specific underlying microbial mechanisms driving their efficacy remains poorly understood. In this study, we demonstrate the broad potential ofBifidobacteriumspecies to inhibit breast cancer progression across multiple pre-clinical mouse models. We identify a novel strain,Bifidobacterium pseudocatenulatum210, which induces systemic anti-tumour immunity and enhances responses to standard-of-care therapies via its cell surface capsular exopolysaccharide (EPS).B. pseudocatenulatum210 EPS promotes dendritic cell activation and increases systemic cDC1 infiltration, leading to robust CD8+T cell-mediated anti-tumour activity. Our findings positionBifidobacteriumEPS as a novel class of therapeutic compounds with significant potential for cancer treatment.
Targeting the host transcription factor HSF1 prevents human cytomegalovirus replication in vitro and in vivo
Authors: Akter Dilruba , Biswas Juthi , Miller Michael J. , Thiele Dennis J. , Murphy Eain A. , O’Connor Christine M. , Moffat Jennifer F. , Chan Gary C. 
Published: September 2024

AbstractFDA-approved antivirals against HCMV have several limitations, including only targeting the later stages of the viral replication cycle, adverse side effects, and the emergence of drug-resistant strains. Antivirals targeting host factors specifically activated within infected cells and necessary for viral replication could address the current drawbacks of anti-HCMV standard-of-care drugs. In this study, we found HCMV infection stimulated the activation of the stress response transcription factor heat shock transcription factor 1 (HSF1). HCMV entry into fibroblasts rapidly increased HSF1 activity and subsequent relocalization from the cytoplasm to the nucleus, which was maintained throughout viral replication and in contrast to the transient burst of activity induced by canonical heat shock. Prophylactic pharmacological inhibition or genetic depletion of HSF1 prior to HCMV infection attenuated the expression of all classes of viral genes, including immediate early (IE) genes, and virus production, suggesting HSF1 promotes the earliest stages of the viral replication cycle. Therapeutic treatment with SISU-102, an HSF1 inhibitor tool compound, after IE expression also reduced the levels of L proteins and progeny production, suggesting HSF1 regulates multiple steps along the HCMV replication cycle. Leveraging a newly developed human skin xenograft transplant murine model, we found prophylactic treatment with SISU-102 significantly attenuated viral replication in transplanted human skin xenografts as well as viral dissemination to distal sites. These data demonstrate HCMV infection rapidly activates and relocalizes HSF1 to the nucleus to promote viral replication, which can be exploited as a host-directed antiviral strategy.One Sentence SummaryInhibiting of HSF1 as a host-directed antiviral therapy attenuates HCMV replication in vitro and in vivo.
AKT-mediated phosphorylation of TSC2 controls stimulus- and tissue-specific mTORC1 signaling and organ growth
Authors: Cormerais Yann , Lapp Samuel C. , Kalafut Krystle C. , Cissé Madi Y. , Shin Jong , Stefadu Benjamin , Personnaz Jean , Schrotter Sandra , D’Amore Angelica , Martin Emma R. , Salussolia Catherine L. , Sahin Mustafa , Menon Suchithra , Byles Vanessa , Manning Brendan D. 
Published: September 2024

AbstractMechanistic target of rapamycin (mTOR) complex 1 (mTORC1) integrates diverse intracellular and extracellular growth signals to regulate cell and tissue growth. How the molecular mechanisms regulating mTORC1 signaling established through biochemical and cell biological studies function under physiological states in specific mammalian tissues are unknown. Here, we characterize a genetic mouse model lacking the 5 phosphorylation sites on the tuberous sclerosis complex 2 (TSC2) protein through which the growth factor-stimulated protein kinase AKT can active mTORC1 signaling in cell culture models. These phospho-mutant mice (TSC2-5A) are developmentally normal but exhibit reduced body weight and the weight of specific organs, such as brain and skeletal muscle, associated with cell intrinsic decreases in growth factor-stimulated mTORC1 signaling. The TSC2-5A mouse model demonstrates that TSC2 phosphorylation is a primary mechanism of mTORC1 activation in some, but not all, tissues and provides a genetic tool to facilitate studies on the physiological regulation of mTORC1.
Evolutionary trajectories of β-lactam resistance inEnterococcus faecalisstrains
Authors: Ugalde Silva Paul , Desbonnet Charlene , Rice Louis B , García-Solache Mónica 
Published: September 2024

AbstractResistance to ampicillin and imipenem inEnterococcus faecalisis infrequent. However, the evolution of resistance can occur through prolonged antibiotic exposure during the treatment of chronic infections. In this study, we conducted a Long-Term Evolution Experiment (LTEE) using four genetically diverse strains ofE. faecaliswith varying susceptibilities to ampicillin and imipenem. Each strain was subjected to increasing concentrations of either ampicillin or imipenem over 200 days, with three independent replicates for each strain.Selective pressure from imipenem led to the rapid selection of highly resistant lineages across all genetic backgrounds, compared to ampicillin. In addition to high resistance, we describe, for the first time, the evolution of a β-lactam dependent phenotype observed in lineages from all backgrounds. WGS and bioinformatic analysis revealed mutations in three main functional classes: genes involved in cell wall synthesis and degradation, genes in the walK/R two-component system, and genes in the c-di-AMP pathway. Our analysis identified new mutations in genes known to be involved in resistance as well as novel genes potentially associated with resistance.Furthermore, the newly described β-lactam dependent phenotype was correlated with the inactivation of c-di-AMP degradation, resulting in high levels of this second messenger. Together, these data highlight the diverse genetic mechanisms underlying resistance to ampicillin and imipenem inE. faecalis. The emergence of high resistance levels and β-lactam dependency underscores the importance of understanding evolutionary dynamics in the development of antibiotic resistance.ImportanceE. faecalisis a major human pathogen, and treatment is frequently compromised by poor response to first-line antibiotics such ampicillin. Understanding the factors that play a role in susceptibility/resistance to these drugs will help guide the development of much needed treatments.
Chemical signatures of social information in Barbary macaques
Authors: Weiß Brigitte M. , Birkemeyer Claudia , Kücklich Marlen , Widdig Anja 
Published: September 2024

AbstractPrimates are well-known for their complex social lives and intricate social relationships, which requires them to obtain and update social knowledge about conspecifics. The sense of smell may provide access to social information that is unavailable in other sensory domains or enhance the precision and reliability of other sensory cues. However, the cognition of social information in catarrhine primates has been studied primarily in the visual and auditory domain. We assessed the social information content of body odor in a catarrhine primate, the Barbary macaque (Macaca sylvanus), in three semi-free ranging groups at Affenberg Salem, Germany. In particular, we related socially relevant attributes (identity, genetic relatedness, rank, sex, age, group membership) to chemical profiles of body odor. We applied non-invasive active sampling via thermal desorption tubes and analyzed samples by gas chromatography–mass spectrometry. We found robust evidence for individual odor signatures and limited support for kin signatures. Chemical profiles were also related to group membership, but little to rank, sex or age. The detected associations between chemical profiles and socially relevant attributes form the theoretical foundations for olfactory information transfer, highlighting the potential of body odor to provide valuable social information in this highly visually oriented primate.
How neural network structure alters the brain’s self-organized criticality
Authors: Sugimoto Yoshiki A. , Yadohisa Hiroshi , Abe Masato S. 
Published: September 2024

AbstractThe brain criticality hypothesis has been a central research topic in theoretical neuroscience for two decades. This hypothesis suggests that the brain operates near the critical point at the boundary between order and disorder, where it acquires its information-processing capabilities. The mechanism that maintains this critical state has been proposed as a feedback system known as self-organized criticality (SOC); brain parameters, such as synaptic plasticity, are regulated internally without external adjustment. Therefore, clarifying how SOC occurs can help us to understand the mechanisms that maintain brain function and cause brain disorders. From the standpoint of neural network structures, the topology of neural circuits also plays a crucial role in information processing, with healthy neural networks exhibiting small-world, scale-free, and modular characteristics. However, how these network structures affect SOC remains poorly understood. In this study, we numerically investigated the possibility that the structure of neural networks contributes to the brain’s critical state and dysfunction using a mathematical model. Our results reveal that the time scales at which synaptic plasticity operates to achieve a critical state differ depending on the network structure. Additionally, we observed Dragon king phenomena associated with abnormal neural activity, depending on the network structure and synaptic plasticity time scales. Notably, Dragon king was observed over a wide range of synaptic plasticity time scales in scale-free networks with high-degree hub nodes. This study emphasizes the importance of neural network topology in neuroscience from the perspective of SOC.
Modularity of the Schur index, modular differential equations, and high-temperature asymptotics
Authors: Pan Yiwen , Yang Peihe 
Published: September 2024

In this paper we analytically explore the modularity of the flavored Schur index of 4d N=2 superconformal field theories. We focus on the A1 theories of class-S and N=4 theories with SU(N) gauge group. We work out the modular orbit of the flavored index and defect index, compute the dimension of the space spanned by the orbit, and provide complete basis for computing modular transformation matrices. The dimension obtained from the flavored analysis predicts the minimal order of the unflavored modular differential equation satisfied by the unflavored Schur index. With the help of modularity, we also study analytically the high temperature asymptotics of the Schur index. In the high temperature limit τ→+i0, we identified the (defect) Schur index of the genus-zero A1 theories of class S with the S3 partition function of the SU(2)×U(1)n star-shaped quiver (with Wilson line insertion). In the identification, we observe an interesting relation between the linear-independence of defect indices and the convergence of the Wilson line partition functions.

Published by the American Physical Society
2024
Climate change as fake news. Positive attribute framing as a tactic against corporate reputation damage from the evaluations of sceptical, right-wing audiences
Authors: Chmiel Michal , Fatima Sania , Ingold Ciara , Reisten Jana , Tejada Catalina 
Published: September 2024

PurposeThe paper aims to examine whether CSR communication about a company’s support for climate change created using different content framing categories (positive vs negative) can lead climate change-sceptical audiences to positively influence their evaluations of the credibility of CSR communication, of a company and its actions, and lead to higher purchase intentions.Design/methodology/approachThe paper used an experimental design. About 266 respondents recruited via the Prolific platform were invited to participate in an online study. A between-subject design was used, and data was analysed using the bootstrapping technique, allowing to identify moderators of the relationship between CSR communication framing and different evaluations of a company.FindingsThe paper provides empirical support for the role of political preferences and climate change beliefs in predicting the preference for positive attribute framing among climate change sceptical audiences. It is argued that climate change sceptics are still in the process of deliberation about whether climate change is occurring.Research limitations/implicationsThe research findings may not be generalizable to countries where support for climate change is low, and a technique like attribute framing may not lead to noticeable differences in message reception.Practical implicationsThe paper underscores the impact of the type of attribute framing in CSR communication on different aspects of company evaluations depending on beliefs in climate change. Commercial communicators should additionally invest in climate change education to address the climate change challenge.Social implications Addressing climate change effectively requires support from companies to communicate their CSR efforts purposefully and to address climate change sceptical audiences.Originality/valueThe paper identifies beliefs in climate change as an important moderator of CSR communication attribute framing effectiveness.