bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spread of a single superclone drives insecticide resistance inAcyrthosiphon kondoiacross an invasive range
Authors: Thia Joshua A. , Hunt Benjamin J. , Wang Shuchao , Troczka Bartlomiej J , Brown Courtney J. , Arinanto Leonhard S. , Chirgwin Evatt , Stelmach Monica , Richardson Kelly , Joglekar Chinmayee , Dorai Ashritha P. S. , Yang Qiong , Babineau Marielle , Bass Chris , Hoffmann Ary A. , Umina Paul A. 
Published: December 2024

ABSTRACTPopulations under similar selection pressures may adapt via parallel evolution or dispersal of advantageous alleles. Here, we investigated insecticide resistance in the invasive blue-green aphid,Acyrthosiphon kondoi, which reproduces clonally in Australia and has rapidly developed resistance across geographic locations. Using genomic, transcriptomic, and experimental approaches, we explored the evolutionary origins and molecular mechanisms of resistance. We developed the first reference genome forA. kondoi(443.8 Mb, 28,405 annotated genes, BUSCO score 97.5%) and established isofemale strains from southern Australia with varying resistance statuses. All resistant strains shared a common ancestor, supporting the spread of a resistant ‘superclone’ distinct from susceptible strains. Resistance was associated with overexpression of an esterase gene homologous to the E4/FE4 esterases linked to multi-chemical resistance in other aphid pests. Functional experiments inDrosophila melanogasterconfirmed the causal role of this E4-like esterase in resistance to organophosphates, carbamates, and pyrethroids. These findings highlight how clonal dispersal and insecticide overuse can transform local adaptation into a widespread pest management issue. Our results suggest a parallel macroevolutionary response to insecticide selection inA. kondoiand other aphid species at the gene family level, but with a distinct regulatory mechanism inA. kondoi. Given the rapid spread of the resistant superclone, alternative management strategies, including expanded chemical control options and enhanced biological control, are urgently needed to mitigate this growing pest problem.
LPS stimulates dynamic changes in B cell metabolism to promote proliferation
Authors: Cheung Dana M.S. , Razsolkov Momchil , Bonacina Fabrizia , Andrews Stephen , Sumoreeah Megan , Sinclair Linda V. , Howden Andrew J.M. , Arthur J. Simon C. 
Published: December 2024

AbstractFollowing activation, naïve B cells exit quiescence and enter a proliferative phase before becoming mature antibody-producing or memory B cells. One method of activation is to use Lipopolysaccharide (LPS), a well-established B cell mitogen that can drive proliferationex vivo.Using quantitative proteomics, we identify an upregulation of proteins following LPS stimulation involved in metabolic pathways including amino acid uptake and cholesterol biosynthesis. We highlight the large, neutral amino acid transporter SLC7A5 as a target of LPS-induced activation, and by utilising SLC7A5 conditional knockout mice, we demonstrate the requirement of this transporter for B cell proliferationex vivo. LPS stimulation increased cellular cholesterol levels and inhibition of the rate-limiting enzymes HMG-CoA-reductase (HMGCR) and Squalene monooxygenase in the cholesterol biosynthesis pathway significantly reduced proliferation. The critical role of the cholesterol biosynthetic pathway was not limited to LPS. Stimulation via TLR7, TLR9, CD40 and the B Cell Receptor also increased cholesterol levels and inhibition of HMGCR reduced proliferation. Together these results suggest a common requirement for metabolic rewiring in B cells to allow proliferation in response to activation.
Modelling co-development between the somites and neural tube in human Trunk-like Structures (hTLS)
Authors: Makwana Komal , Tilley Louise , Chakravarty Probir , Thompson Jamie , Baillie-Benson Peter , Rodriguez-Polo Ignacio , Moris Naomi 
Published: December 2024

Human stem cell-based embryo models have opened new avenues of research in development by providing experimentally amenablein vitrosystems. One of the features of embryo models is their multilineage differentiation, which allows the co-development of, and interactions between, tissues. Here, we utilise a human Trunk-like Structure (hTLS) model to explore trunk development. We show that hTLS have morphologically organised somites and a neural tube that form through self-organised, endogenous signalling including anteroposterior FGF, Wnt and Retinoic Acid (RA) gradients that modulate the fate of neuromesodermal progenitors. Comparison to an existing dataset from organogenesis-stage human embryos shows that hTLS cells approximate Carnegie Stage 13-14 (28-35 days post-fertilisation). The absence of a notochord leads to a dorsal identity, but exogenous exposure to smoothened agonist (promoting Sonic Hedgehog signalling) progressively ventralises both somites and neural tube in a dose-dependent manner. Furthermore, we identify endogenous signalling from the neural tube to the somites, which leads to medially localisedALDH1A2,and subsequent RA signalling from the somites to the neural tube, which leads to spontaneous neural progenitor patterning andPAX6expression. Together, our data highlight the value of modularity in embryo models which we leverage to explore human trunk co-development.SummaryUsing a 3D, stem cell-based model of human embryonic trunk development, we examine the interactions across somitic and neural tissues to better understand the dynamics of human trunk co-development.
Sotalol dose optimization for fetal tachycardia: a pregnancy physiologically based pharmacokinetic model study
Authors: van Hove Hedwig , van der Heijden Joyce E.M. , van Uden Anne , Gijsen Violette M.G.J. , Greupink Rick , de Wildt Saskia N. , van Drongelen Joris 
Published: December 2024

AbstractObjectiveTo establish an optimized sotalol dosing strategy for fetal tachycardia by using a pregnancy computational model for dose simulations.MethodsA physiologically-based computational model, including pregnancy-related changes and placental transfer values, was established and verified. Simulations of the current dosing advises and prospective dosing scenarios were performed. To avoid maternal dose-related toxicity (QT-prolongation) we aimed for maternal concentrations <2.5 mg/L. Based on neonatal concentration-effect data, we aimed for a fetal Ctroughconcentrations of 0.4 – 1.0 mg/L.ResultsThe pregnancy physiologically-based pharmacokinetic model accurately predicted maternal and fetal exposures. Predictions indicate that almost 16% of maternal plasma concentrations exceed the toxic level of 2.5 mg/L at the maximum oral daily dose of 480 milligram, while 90% of fetuses have a Ctroughconcentration within the therapeutic window. When lowering the maximum daily dose to 400 mg, 0.1% of maternal plasma concentrations exceed 2.5 mg/L, while 87% of the fetal plasma concentrations remain in the therapeutic window. Additionally dosing 480 mg in three times daily reduces the risk of high maternal plasma exposure to 0.3%, while maintaining effective fetal Ctroughconcentrations in 95% of fetuses.ConclusionPregnancy computational modeling can be used to adequately predict maternal and fetal sotalol exposures. Our simulations suggest that daily doses should not exceed 400 milligram and that dividing the oral daily dose over three doses improves the balance between high maternal plasma exposure and effective fetal concentrations.FundingThis publication is based on research funded by the Bill & Melinda Gates Foundation (INV-023795).
Diminished functional gradient of the precuneus during altered states of consciousness
Authors: Lyu Dian , Adapa Ram , Carhart-Harris Robin L. , Roseman Leor , Owen Adrian M. , Naci Lorina , Menon David K. , Stamatakis Emmanuel A. 
Published: December 2024

AbstractThe relationship between the default mode network (DMN) and task-positive networks, such as the frontoparietal control network (FPCN), is a prominent feature of functional connectivity (FC) in the human brain. This relationship is primarily anticorrelated at rest in healthy brains and is disrupted in altered states of consciousness. Although the DMN and FPCN seem to perform distinct and even opposing roles, they are anatomically adjacent and exhibit ambiguous boundaries. To test the hypothesis that the DMN-FPCN distinction manifests probabilistically rather than having absolute anatomical boundaries, we examined the differences in FC along the dorsal-ventral (d-v) axis in the posterior precuneus (PCu), which serves a convergence zone between the DMN and FPCN. Our findings indicate that the connectivity differences along this axis are continuous as characterized by linear slopes. Notably, these linear relationships (i.e., functional gradients of the precuneus/FGp) are present only within the territories of the DMN and FPCN, respectively associating with positive and negative slopes. Furthermore, the gradient is functionally relevant, as its spatial configurations change in specific ways in altered states of consciousness (ASC): the magnitude of FGp is similarly impaired across different types of ASC, while the spatial entropy of FGp differs between psychedelic and sedative states. These results suggest that the DMN and FPCN, while appearing distinct, may originate from a single, integrated mechanism.Significance StatementThis research provides new insights into the brain’s functional organization underlying human conscious states by examining the relationship between two large-scale networks: the default mode network (DMN) and the frontoparietal control network (FPCN). These networks, which are attuned to handle internal and external information respectively, are often viewed as oppositional. However, our findings indicate they form an integrated system with continuous connectivity. We identified the posterior precuneus as a key convergence point, revealing a gradient of connectivity between the two networks. This gradient flattens during altered states of consciousness induced by psychedelics or sedatives, showing a loss of functional differentiation between the DMN and FPCN.
Keeping Your Eye, Head, and Hand on the Ball: Rapidly Orchestrated Visuomotor Behavior in a Continuous Action Task
Authors: Schroeger Anna , Goettker Alexander , Braun Doris I. , Gegenfurtner Karl R. 
Published: December 2024

AbstractWhile many studies on eye movements focus on highly controlled, repetitive conditions, we expanded this approach by measuring eye, head, and hand movements of participants playing an iPad-based version of the classic computer game Pong. This allowed us to capture more natural sequential behavior while maintaining the benefits of experimental control. Participants intercepted a moving ball by sliding a paddle at the bottom of the screen so that the ball bounced back and moved toward the computerized opponent. We tested i) how participants adapted their eye, hand, and head movements to this dynamic, continuous task, ii) whether these adaptations are related to interception performance, and iii) how their behavior changed under different conditions and over time. We found that eye, hand, and head movements are largely shaped towards participant’s action (and lesser so towards the opponent’s action). Movements that reduce or destabilize visual input, like saccades, blinks and head movements, are reduced during critical periods of interception. Instead, participants increase the frequency of pursuit eye movements, ensuring that they closely track the ball when their action comes closer. This pursuit strategy is associated with better game performance. Our results demonstrate an orchestration of eye, head, and hand movement patterns, which is rapidly established and finely adjusted to meet the evolving demands of impending actions and task demands.
Comparative transcriptomics reveal contrasting fungal strategies in a plant pathogen versus an endophyte during initial host colonization
Authors: Moonjely Soumya , Trail Frances 
Published: December 2024

ABSTRACTConidial germination marks the beginning of the fungal life cycle on the host plant, leading to disease or mutually beneficial relationships. Here, we use comparative transcriptomics to unravel the transcriptional similarities and differences during conidial germination and initial colony establishment of the plant pathogenFusarium graminearum,and the endophyteMetarhizium anisopliae. Our comparison crosses four stages from fresh conidia to polar growth, hyphal extension, ending in either first hyphal branching (on medium) or appressorium formation (on barley).F. graminearumexhibited a higher number of upregulated genes for CAZymes, specialized metabolites and effectors compared toM. anisopliaeduring the interaction with the host, particularly during the appressorium stage, reflecting its pathogenic nature. The formation of appressoria byM. anisopliaeconidia during germination on barley roots has not been documented previously and includes both morphological characteristics and gene expression patterns that regulate appressorium development. Our analysis reveals reduced transcript levels of CAZyme and specialized metabolite genes inM. anisopliaecompared toF. graminearum, reflecting a less aggressive host penetration approach. The candidate genes associated with indole-3-acetic acid synthesis were upregulated inM. anisopliaeduring the appressorium stage, supporting its endophytic lifestyle, and suggesting that the fungus uses a phytohormone based strategy to interact with plant hosts. Collectively, our findings expand the transcriptome resources and provide valuable insights into the gene networks involved in conidial germination and initiation of infection in pathogenic versus endophytic fungi, as well as documenting appressorium formation for the first time, in the endophytic life cycle ofM. anisopliae.IMPORTANCEConidial germination is the initial step for fungal colonization in diverse environments. Here we examine the transcriptional similarities and differences in conidial germination and colony establishment ofFusarium graminearumandMetarhizium anisopliae, two fungal species belongs to the Order Hypocreales with distinct lifestyles.F. graminearumis a plant pathogen and the causal agent of Fusarium head blight on cereal crops, whereasM. anisopliaeis an insect pathogen and root endophyte which forms beneficial associations with plants. We compared the transcriptome profiles of these species under two nutrient conditions across four stages of conidial germination. Our study shows that the expression profile of the genes encoding carbohydrate-active enzymes, specialized metabolites, and putative effectors varies betweenF. graminearumandM. anisopliae. The results of this study provide insights into gene networks associated with spore germination stages on the host in a pathogenic versus an endophytic fungus.
Priestia megateriumILBB592 based biofertilizer increases the efficiency of phosphorus fertilization, positively affects soybean nutrition and yield and modifies the rhizospheric bacterial community
Authors: Torres Pablo , Fresia Pablo , Beyhaut Elena , Cuitiño María José , Altier Nora , Abreo Eduardo 
Published: December 2024

SummaryPhosphorus (P) is needed by soybean plants to form vital molecules like ATP and nucleotides and perform plant functions like photosynthesis and Nitrogen biological fixation at nodules. Because P concentration in the soil solution is naturally low, P fertilization is applied to satisfy soybean requirements in high yielding crops. However, a small portion of added P is readily available to the plants, while most is retained by the soil matrix and eventually made available or lost through erosion and run-off to water bodies, where it promotes eutrophication. Therefore, technologies that enhance P uptake by crops could lead to lower P inputs and outputs from soybean cropping systems, improving sustainability. Priestia megaterium ILBB592 and Bacillus pumilus ILBB44 are two PGPR with P mobilization features that were single formulated as biofertilizers and co-inoculated with Bradyrhizobium elkanii on seeds of soybean Genesis 5602 in two consecutive years in the field, with and without P fertilization. Co-inoculation with ILBB592 improved plant P uptake, along with N and K, with and without P fertilization. Diversity was increased by co-inoculation with ILBB44 and ILBB592, and predicted genes related with P cycling in the rhizospheric soils were also augmented after co-inoculation with ILBB592, mostly with P fertilization. Shoot dry weight and yield were also improved although effect on yield was not statistically significant. P fertilization alone had no effect in the first year but showed some effect on nodules dry weight, P uptake and yield on the second year, suggesting a sufficient P level was obtained after repeated fertilizations. ILBB592 biofertilizer showed a positive effect on most plant parameters, including nodulation and P uptake in both years and both P fertilization regimes and is therefore considered as a useful technology to reduce P fertilization without jeopardizing plant performance.
Architecture of the UBR4 complex, a giant E4 ligase central to eukaryotic protein quality control
Authors: Grabarczyk Daniel B , Ehrmann Julian F , Murphy Paul , Kurzbauer Robert , Bell Lillie E , Deszcz Luiza , Neuhold Jana , Schleiffer Alexander , Shulkina Alexandra , Versteeg Gijs A , Meinhart Anton , Zavodszky Eszter , Hegde Ramanujan S , Clausen Tim 
Published: December 2024

SummaryEukaryotic cells have evolved sophisticated quality control mechanisms to eliminate aggregation-prone proteins that compromise cellular health. Central to this defense is the ubiquitin-proteasome system, where UBR4 acts as essential E4 ubiquitin ligase, amplifying degradation marks on defective proteins. Our cryo-EM analysis of UBR4 in complex with its cofactors KCMF1 and CALM1 reveals a massive 1.3 MDa ring structure, featuring a central substrate-binding arena and flexibly attached catalytic units. Structural data illustrate how UBR4 binds substrate and extends K48-specific ubiquitin chains. Importantly, efficient substrate targeting depends on both pre-ubiquitination and specific N-degrons, with KCMF1 acting as key substrate filter. Furthermore, we show that the architecture of the E4 megacomplex is conserved across eukaryotes but with species specific adaptations, allowing UBR4 to perform its precisely tuned quality-control function in diverse cellular environments.
Mother-to-infant plasmid transmission in early postpartum and its association with dominant gut bacteria
Authors: Kuriyama Yuki , Suganuma Natsuki , Ito Kohei 
Published: December 2024

AbstractBackgroundThe gut microbiome plays a crucial role in human health, and it is known that the microbiome is transmitted from mother to infant at birth and has profound effects on an individual’s health. Although extensive research has been conducted on mother-to-infant microbiome transmission, little is known about plasmid transmission and its effects on the infant microbiome. Plasmids are considered important contributors to early development of the gut microbiome due to their functions, such as antibiotic resistance, and their ability to be transferred between a wide range of host bacteria.MethodsIn this study, we assembled plasmid sequences from longitudinal fecal data of 65 mother-infant pairs and analyzed plasmid sharing between mothers and infants during the first year of life. After identifying shared plasmids, we investigated the relationship between plasmid sharing and delivery mode. We also characterized the functions and host range of shared plasmids.ResultsWe found that the number of plasmids was lower in infants than in mothers, probably reflecting the lower overall diversity of the infant microbiome. Additionally, we detected shared plasmids between mothers and infants, marking the first discovery of mother-to-infant plasmid transmission. Our findings revealed that plasmids are more likely to be transmitted from mother to infant immediately after birth, with the likelihood of transmission decreasing as infants age. This underscores the critical role of the maternal microbiome in shaping early development of the gut microbiome. Moreover, plasmids from dominant bacteria in mother-to-infant microbiome transmission, such asBacteroides, were frequently transmitted to infants and carried specific functional traits. In particular, plasmid genes such asmbpA, mbpB, and mbpCwere frequently shared between mothers and infants. Each of these genes encodes a protein of a specific size and plays an important role in plasmid mobilization, or the transfer of plasmids to other bacteria. Plasmids improve the fitness and environmental adaptability of host bacteria, which may contribute to the development of a healthy gut microbiome in infants.ConclusionsThis study revealed that mother-to-infant plasmid transmission likely occurs during the early postpartum period and is influenced by dominant gut bacteria. These findings provide new insights into the mother’s role in shaping the infant’s gut microbiome development.
C. elegansnucleolar RG repeats are sufficient for nucleolar accumulation but insufficient for sub-nucleolar compartmentalization
Authors: Spaulding Emily L. , Updike Dustin L. 
Published: December 2024

ABSTRACTIntrinsically disordered arginine-glycine (RG) repeat domains are enriched in multilayered biomolecular condensates such as the nucleolus.C. elegansnucleolar RG repeats are dispensable for nucleolar accumulation and instead contribute to the organization of sub-nucleolar compartments. The sufficiency of RG repeats to facilitate sub-nucleolar compartmentalization is unclear. In this study, we drive expression of full-length RG repeats in theC. elegansgermline to test their ability to localize to nucleoli and organize into nucleolar sub-compartmentsin vivo. We find that repeats accumulate within germ cell nucleoli but do not enrich in the correct sub-compartment. Our results suggest RG repeats may indirectly influence nucleolar organization by creating an environment favorable for sub-nucleolar compartmentalization of proteins primarily based on their function within the nucleolus.
DNAJC13 localization to endosomes is opposed by its J domain and its disordered C- terminal tail
Authors: Adoff Hayden , Novy Brandon , Holland Emily , Lobingier Braden T 
Published: December 2024

AbstractEndosomes are a central sorting hub for membrane cargos. DNAJC13/RME-8 plays a critical role in endosomal trafficking by regulating the endosomal recycling or degradative pathways. DNAJC13 localizes to endosomes through its N-terminal Plekstrin Homology (PH)-like domain, which directly binds endosomal phosphoinositol-3-phosphate (PI(3)P). However, little is known about how DNAJC13 localization is regulated. Here, we show that two regions within DNAJC13, its J domain and disordered C-terminal tail, act as negative regulators of its PH-like domain. Using a structure-function approach combined with quantitative proteomics, we mapped these control points to a conserved YLT motif in the C-terminal tail as well as the catalytic HPD triad in its J domain. Mutation of either motif enhanced DNAJC13 endosomal localization in cells and increased binding to PI(3)Pin vitro. Further, these effects required the N-terminal PH-like domain. We show that, similar to other PI(3)P binding domains, the N-terminal PH-like domain binds PI(3)P weakly in isolation and requires oligomerization for efficient PI(3)P binding and endosomal localization. Together, these results demonstrate that interaction between DNAJC13 and PI(3)P serves as a molecular control point for regulating DNAJC13 localization to endosomes.Significance StatementDNAJC13 controls endosomal sorting by regulating proteins which mediate the endosomal recycling and degradative subdomains.Here we show that subcellular localization of DNAJC13 is regulated through the coordinated action of three of its domains: the PH-like domain which has low affinity for PI(3)P, the J domain, and a YLT motif in its disordered C-terminus.This study defines a novel mechanism by which DNAJC13 function is regulated.