bluuebunny/crossref_metadata_2025_split huggingface dataset:
Notch, β-catenin and MAPK signaling segregate endoderm and mesoderm in the diploblastNematostella vectensis
Authors: Haillot Emmanuel , Lebedeva Tatiana , Steger Julia , Genikhovich Grigory , Montenegro Juan D. , Cole Alison G. , Technau Ulrich 
Published: October 2024

SummaryCnidaria are typically considered diploblastic (i.e. consisting of two germ layers) in contrast to their triploblastic sister clade, the Bilateria. However, a recent study suggested that sea anemones and other cnidarians have three segregated germ layer identities, corresponding to the bilaterian germ layers1. Here, we investigated, how the three germ layer identities are specified during early development of the sea anemoneNematostella vectensis. First, the mesodermal territory is specified at the animal pole at 6 hours postfertilization, followed by the specification of a ring of endodermal territory between mesoderm and ectoderm. We then assessed the role of β-catenin, MAPK and Notch signaling pathways during mesoderm and endoderm formation. Our results show that the mesoderm is initiated by MAPK signaling and simultaneously restricted to the future oral side by mutually exclusive nuclear β-catenin signaling. The mesodermal cells then express the Delta ligand, while the ectodermal cells express the Notch receptor. Inhibition of Notch signaling as well as ectopic expression of the Notch intracellular domain showed that endodermal tissue identity is induced by Notch signaling at the boundary between mesoderm and ectoderm. We propose a new model that outlines the different steps leading to the segregation of mesoderm and endoderm identities inNematostella, confirming the presence of 3 distinct germ layer identities in this cnidarian. Notably, the observed crosstalk of MAPK, β-catenin and Notch signaling in the specification of three germ layers inNematostellais highly reminiscent to early stage gastrulae of sea urchins suggesting that triploblasty may predate the split of cnidarians and bilaterians.
NINJ1 is a restriction factor for HSV-1 in mouse macrophages
Authors: Hartenian Ella , Agustoni Magalie , Broz Petr 
Published: October 2024

AbstractRestriction factors block multiple stages of viral infection. Here we describe how NINJ1 controls HSV-1 infection of mouse macrophages, a key cell type during systemic and local acute infection. We observed thatNinj1−/–macrophages are more susceptible to infection than WT cells.Ninj1−/–macrophages exhibited earlier and stronger expression of all kinetic classes of viral proteins, resulting in higher production of infectious viral particles, with initial differences seen in the first few hours post infection. Given the important role of NINJ1 during cell death, we next investigated if NINJ1 restricts HSV-1 in a manner related to its role in cell death. However, infectedNinj1-deficient cells did not exhibit differences in cell death compared to WT controls at early time points in infection where we observe a difference in infection rates. Instead, the higher infection rate inNinj1−/–macrophages correlated to enhancement in the average numbers of viral particles entering each cell. Finally, we determined the consequences of the altered entry and found higher ISG RNA expression in infectedNinj1−/–cells, which we ascribe to both TLR signaling and STING-mediated recognition. Together, this indicates that the NINJ1 present on WT macrophages reduces HSV-1 entry, which has consequences for the inflammatory phenotype associated with HSV-1 infection.
Linking Pre- and Perinatal Risk Factors to a Multivariate Fusion of Child Cortical Structure
Authors: Lindseth Linn R. S. , Beck Dani , Westlye Lars T. , Tamnes Christian K. , Norbom Linn B. 
Published: October 2024

AbstractPre- and perinatal factors such as maternal pregnancy and child birth complications affect child brain development, emphasizing the importance of early life exposures. While most previous studies have focused on a few variables in isolation, here, we investigated associations between a broad range of pregnancy- and birth-related variables and multivariate cortical brain MRI features. Our sample consisted of 8,396 children aged 8.9 to 11.1 years from the ABCD Study. Through multiple correspondence analysis and factor analysis of mixed data, we distilled numerous pre- and perinatal variables into four overarching dimensions; maternal pregnancy complications, maternal substance use, compromised fetal growth, and newborn birth complications. Vertex-wise measures of cortical thickness, surface area, and curvature were fused using linked independent component analysis. Linear mixed effects models showed that maternal pregnancy complications and compromised fetal growth, including low birth weight, being born preterm, or as a twin, were associated with smaller global surface area. Additionally, compromised fetal growth was associated with two regional patterns reflecting a complex combination of 1) smaller occipital, inferior frontal and insular cortex, larger fronto-temporal cortex, thinner pre- and post-central cortex, and thicker inferior frontal and insular cortex, and 2) smaller and thicker occipital and temporal lobe cortex, and larger and thinner insular cortex. In contrast, maternal substance use and newborn birth complications showed no associations with child cortical structure. By employing a multifactorial and multivariate morphometric fusion approach, we connected complications during pregnancy and fetal growth to global surface area and specific regional signatures across child cortical MRI features.Significance StatementEarly life stages, including the prenatal and perinatal periods, are critically important for a wide range of real-life outcomes. In this study, we linked maternal complications during pregnancy and compromised fetal growth to both globally reduced cortical surface area and complex cortical structural patterns later in late childhood. Our findings underscore the importance of providing support to mothers and children during these crucial phases, helping to ensure optimal conditions for healthy child development.
Investigating the effects of prednisolone on behavior in mouse models of Duchenne muscular dystrophy
Authors: Verhaeg M.A.T. , van de Vijver D. , Tanganyika-de Winter C.L. , van der Pijl E.M. , Mastenbroek L.J.M. , Leka U. , Stan T.L. , van Putten M. 
Published: October 2024

AbstractBackgroundNext to progressive muscle loss, Duchenne muscular dystrophy patients suffer from behavioral and cognitive problems. This is due to mutations in theDMDgene, that result in the lack of dystrophin in both the muscles and brain. As part of the standards of care, patients receive corticosteroids (prednisolone or deflazacort) to slow down muscle degeneration. The precise consequences of chronic corticosteroid usage on the behavior of DMD patients remain unclear, mainly due to challenges of recruiting corticosteroid naïve patients into clinical studies.ObjectiveThis study used DMD mouse models, representing mutations resulting in lack of one or more dystrophin isoforms, to analyze the effects of corticosteroid treatment on different behavioral domains.MethodsPrednisolone (PDN) or placebo was administered via a subcutaneous 60-day slow release pellet (66 µg/day) and mice were subjected to several behavioral tests.ResultsUnfortunately, the pellet only exposed mice to PDN for half of the intended duration. During the time of PDN exposure, we found a small amelioration in anxiety but were unable to find any differences in social interaction and spatial learning and memory.ConclusionsShort term exposure to PDN via a slow release pellet does not seem to negatively affect anxiety, social interaction or spatial learning and memory. We cannot rule out that a longer treatment period than 4 weeks would affect behavior in DMD mice.
Aging increases the distinctiveness of emotional brain states across rumination, worry, and positive thinking
Authors: Misaki Masaya , Tsuchiyagaito Aki , Guinjoan Salvador , Paulus Martin 
Published: October 2024

AbstractEmotional well-being improves with age, but how neural activity related to emotional brain states changes with aging remains unclear. This study examined individualized brain activation patterns for rumination, worry, and positive thinking to explore age-related variations in emotional state representation. Thirty-five participants (aged 18-64) recalled autobiographical events tied to these emotional states during fMRI scanning. Brain activity was analyzed using an individualized machine learning classifier. Results showed increased discriminability of rumination and worry with age, with older adults exhibiting heightened activation in cognitive control regions during rumination and reduced activation in the cingulate and temporoparietal junction during worry. No significant age-related changes were found for positive thinking, although increased discriminability between positive and negative states correlated with well- being (FDR < 0.05). These findings suggest that aging enhances cognitive control during rumination and reduces anxiety responses during worry, potentially contributing to improved emotional well-being in older adults.
How relevant is the prior? Bayesian causal inference for dynamic perception in volatile environments
Authors: Meijer David , Barumerli Roberto , Baumgartner Robert 
Published: October 2024

AbstractInterpreting sensory prediction errors can be challenging in volatile environments because they can be caused by stochastic noise or by outdated predictions. Noisy signals should be integrated with prior beliefs to improve precision, but the two should be segregated when environmental changes render prior beliefs irrelevant. Bayesian causal inference provides a statistically optimal solution to deal with uncertainty about the causes of prediction errors. However, the method quickly becomes memory intensive and computationally intractable when applied sequentially.Here, we systematically evaluate the predictive performance of Bayesian causal inference for perceptual decisions in a spatial prediction task based on noisy audiovisual sequences with occasional changepoints. We elucidate the simplifying assumptions of a previously proposed reduced Bayesian observer model, and we compare it to an extensive set of models based on alternative simplification strategies.Model-free analyses revealed the hallmarks of Bayesian causal inference: participants seem to have integrated sensory evidence with prior beliefs to improve accuracy when prediction errors were small, but prior influence decreased gradually as prediction errors increased, signalling probable irrelevance of the priors due to changepoints. Model comparison results indicated that participants computed probability-weighted averages over the causal options (noise or changepoint), akin to the reduced Bayesian observer model. However, participants’ reliance on prior beliefs was systematically smaller than expected, and this was best explained by individually fitting lower-than-optimal parameters for the a-priori probability of prior relevance.We conclude that perceptual decision makers utilize priors flexibly to the extent that they are deemed relevant, though also conservatively with a lower tendency to bind than ideal observers. Simplified consecutive Bayesian causal inference predicts key characteristics of belief updating in changepoint environments and forms a suitable foundation for modelling dynamic perception in a changing world.
A co-transcriptional mechanism for tightly controlling RNA homeostasis in yeast
Authors: Esteban-Serna Sofia , Widén Tove , Gwynne Mags , Farquhar Iseabail , Duchen Michael R , Swain Peter S , Granneman Sander 
Published: October 2024

SummaryTranscription termination by the Nrd1-Nab3-Sen1 (NNS) complex is key in repressing pervasive transcription inSaccharomyces cerevisiae. Counterintuitively, during starvation, multiple mRNAs that are upregulated are also increasingly bound and prematurely terminated and degraded via NNS. Here we demonstrate that this NNS-mediated attenuation is important for controlling the expression and protein concentration of an evolutionarily conserved mitochondrial transporter, Pic2. Strikingly, we find that even a modest increase in Pic2 protein levels caused by defective NNS regulation has major phenotypical consequences, increasing cell volume and intracellular stress, prolonging cell cycle and decreasing growth rate. Disrupting Nab3 binding toPIC2globally redistributed Nrd1 binding, changing the levels of other NNS-regulated transcripts. We propose that imbalances in the availability of the subunits constituting the NNS complex underlie the cell volume and cycle anomalies. Collectively our results illustrate that even subtle changes in how RNA-binding proteins interact with a single RNA substrate can cause global defects and they emphasise the crucial role of the NNS complex in preserving microbial fitness during stress.HighlightsNNS regulates the expression and protein concentration of a stress-response protein-coding gene (PIC2), improving cell fitness and adaptability to environmental challenges.Creating an imbalance in RNA binding of Nab3 and Nrd1 forPIC2mRNA disturbs the homeostasis of co-regulated transcripts.Even a modest defect in NNS regulation ofPIC2elicits severe defects in cell growth, increases cell size and intracellular stress, and prolongs the cell cycle.
Unveiling the Functional Fate of Duplicated Genes Through Expression Profiling and Structural Analysis
Authors: Vesztrocy Alex Warwick , Glover Natasha , Thomas Paul D. , Dessimoz Christophe , Julca Irene 
Published: October 2024

AbstractGene duplication is a major evolutionary source of functional innovation. Following duplication events, gene copies (paralogues) may undergo various fates, including retention with functional modifications (such as silencing, sub-functionalisation, or neo-functionalisation) or loss. When paralogues are retained, this results in complex orthology relationships, including one-to-many or many-to-many. In such cases, determining which one-to-one pair is more likely to have conserved functions, can be challenging. It has been proposed that, following gene duplication, the copy that diverges more slowly in sequence is more likely to maintain the ancestral function – referred to here as “the least diverged orthologue (LDO) conjecture”. This study explores this conjecture, using a novel method to identify asymmetric evolution of paralogues and apply it to all gene families across the Tree of Life in the PANTHER database. Structural data for over 1 million proteins and expression data for 16 animals and 20 plants were then used to investigate functional divergence following duplication. This analysis, the most comprehensive to date, revealed that whilst the majority of paralogues display similar rates of sequence evolution, significant differences in branch lengths following gene duplication can be correlated with functional divergence. Overall, the results support the least diverged orthologue conjecture, suggesting that the least diverged orthologue (LDO) tends to retain the ancestral function, whilst the most diverged orthologue (MDO) may acquire a new, potentially specialised, role.
Altricial brains and the evolution of infant vocal learning
Authors: Biazzi Renata B. , Takahashi Daniel Y. , Ghazanfar Asif A. 
Published: October 2024

AbstractHuman infant vocal development is strongly influenced by interactions with caregivers who reinforce more speech-like sounds. This trajectory of vocal development in humans is radically different from those of our close phylogenetic relatives, Old World monkeys and apes. In these primates most closely related to humans on the evolutionary tree, social feedback plays no significant role in their vocal development. Oddly, infant marmoset monkeys, a more distantly related New World primate, do exhibit socially guided vocal learning. To explore what developmental mechanism could have evolved to account for these behavioral differences, we hypothesized that the evolution of human and marmoset vocal learning in early infancy in both species is because they are born neurally altricial relative to other primate and in a cooperative breeding social environment. Our analysis found that, indeed, human and marmoset brain are growing faster at birth when compared with chimpanzees and rhesus macaques, making them altricial relative to these primates. We formalized our hypothesis using a logistic growth model showing that the maturation of a system dependent on the rate of brain growth and the amount of social stimuli benefits from an altricial brain and a cooperative breeding environment. Our data suggest that in primates, the evolution of socially guided vocal learning during early infancy in humans and marmosets was afforded by infants with a relatively altricial brain and behavior, sustained and stimulated by cooperative breeding environments.Significance statementHumans rely on social feedback from caregivers to learn how to produce species-typical sounds, whereas other primates like macaque monkeys or chimpanzees do not. What accounts for this difference in developmental strategies? We tested the hypothesis that being born with a more immature (thus more plastic) brain may be the reason by using marmoset monkeys. This species is more distantly related to humans but exhibit the same type of vocal learning and who have a similar socially rich infant care environment. We found that, indeed, human and marmoset brain are growing faster at birth when compared with chimpanzees and rhesus macaques, making them altricial relative to these primates and this explains their similar vocal developmental strategies.
Overcoming Challenges of Reproducibility and Variability for theClostridioides difficiletypification
Authors: Antón Lucía Bravo , Guerrero-López Alejandro , Schmidt-Santiago Lucía , Sevilla-Salcedo Carlos , Blázquez-Sánchez Mario , Rodríguez-Temporal David , Rodríguez-Sánchez Belén , Gómez-Verdejo Vanessa 
Published: October 2024

AbstractThe implementation of Matrix-Assisted Laser Desorption Ionization–Time of Flight (MALDI-TOF) mass spectrometry has had a profound impact on clinical microbiology, facilitating rapid bacterial identification through protein profile analysis. However, the application of this technique is limited by challenges related to the reproducibility and variability of spectra, particularly in distinguishing closely related bacterial strains, as exemplified by the differentiation ofClostridioides difficileribotypes. This study evaluates the integration of Machine Learning algorithms to enhance the robustness and accuracy of MALDI-TOF spectra analysis. For this purpose, we compared traditional classifiers to gain insight into how spectral variability affects their performance in bacterial typing. Furthermore, specific Data Augmentation techniques for MALDI-TOF spectra were designed to reduce the inherent variability in MALDI-TOF spectra, and to address the issue of limited sample sizes. The results demonstrate that these methods can significantly enhance the accuracy of classification ofC. difficilestrains especially when facing variability in the sample acquisition process. This highlights that the combination of domain adaptation with machine learning (ML) could make MALDI-TOF a more versatile and reliable tool in clinical diagnostics.
Skin bacterial community dynamics of hands and forearms before and after military field exercise
Authors: Glenna Susanne , Birkeland Einar E. , Orr Russell J. S. , Gilfillan Gregor D. , Dalland Marianne , Økstad Ole Andreas , Voie Øyvind A. , Rounge Trine B. 
Published: October 2024

AbstractThe human skin microbiome is crucial for skin health and immunity, especially in the context of extreme conditions faced by military personnel. Soldiers encounter unique stressors and hygienic challenges that can impact the microbial composition of their skin during field exercises and in regular occupational settings. In this study, we aimed to investigate the impact of a military field exercise on the diversity and composition of the skin bacterial microbiota using 16S rRNA sequencing. We conducted a longitudinal study during the NATO exerciseCold Response 2022, involving Norwegian soldiers (n= 19) engaged in outdoor training operations. Skin swabs were taken from soldiers’ hands and forearms directly before and after the 10-day winter field exercise, and following a 3-week post-exercise leave. Our results reveal hand and forearm-specific shifts in bacterial populations associated with the exercise, likely influenced by environmental exposure, reduced hygiene, and heightened social contact. Alpha diversity increased on forearms while remaining stable on hands, which appeared more resilient to perturbations. Both sites exhibited temporal changes in composition, with soil- and water-associated bacteria enriched post-exercise; most being transient on hands but more sustained on forearms. The soldiers’ microbiomes became more similar during the exercise, followed by divergence in the leave period. Neither skin site returned to original composition at follow-up, indicating that field exercises may have lasting effects on the microbiome. Our findings highlight the impact of outdoor exposure on microbial communities and suggest that resilience and stability differ between skin sites.ImportanceOptimizing soldier health and resilience is critical for maintaining military readiness and operational effectiveness. The skin, as the body’s first line of defense, is subjected to numerous challenges in military environments. Unique environmental and hygiene challenges can disrupt the skin microbiome and increase susceptibility to skin and soft tissue infections. This longitudinal research provides valuable insights into the effects of military service on the bacterial dynamics of the skin microbiome, but can also inform hygiene management and disease prevention in comparable situations.
Innovating for sustainability in food and beverage companies: the role of governance and environmental factors in climate change mitigation
Authors: Quiñoá-Piñeiro Lara , López-Cabarcos M. Ángeles , Piñeiro-Chousa Juan 
Published: October 2024

PurposeFocusing on the food and beverage (F&B) sectors, this study aims to identify combinations of external environmental factors (natural disasters and water stress) and internal corporate governance factors (corporate social responsibility [CSR] sustainability committee, board gender diversity and stakeholder engagement) that lead to the integration of climate change mitigation innovation and technologies.Design/methodology/approachA fuzzy set qualitative comparative analysis (fsQCA) was conducted on a global sample of 262 listed companies in the F&B sectors. Two additional analyses were performed for European and Asian companies.FindingsIn the three models, the presence of CSR sustainability committees and stakeholder engagement was crucial for achieving the integration of climate change mitigation innovation and technologies. The relevance of board gender diversity differs between the European and Asian models, highlighting potential regional influences on corporate climate innovation decisions. The combination of external and internal factors is the key to justifying different approaches to achieving climate innovation.Originality/valueThis study offers insights into the factors driving the integration of climate change mitigation innovation and technologies into company strategies. Related strategies must combine external and internal factors to enhance the climate resilience and competitiveness of F&B companies while reducing their environmental impact.