bluuebunny/crossref_metadata_2025 huggingface dataset:
Calcification and ecological depth preferences of the planktonic foraminifer
Trilobatus trilobus
in the central Atlantic
Authors: Zarkogiannis Stergios D.
Published: December 2024

Understanding the controls behind the calcification and distribution of planktonic foraminifera in the modern ocean is important when these organisms are used for palaeoceanographic reconstructions. This study combines previously reported shell mass data with new shell geochemistry, light microscopy and X-ray micro-computed tomography analyses to dissect various parameters of
Trilobatus trilobus
shells from surface sediments, investigating the factors influencing their biometry. The goal is to understand which aspects of the marine environment are critical for the calcification and vertical distribution of this species.
Trilobatus trilobus
is found to produce larger, thinner and overall lighter shells in equatorial regions than in subtropical gyre regions, where the shells are up to 4% smaller, more than 60% thicker and approximately 45% heavier. The skeletal mass percentage together with other calcification metrics (shell weight and thickness) are found to depend primarily on ambient seawater salinity rather than carbonate chemistry. In line with their degree of calcification, on the basis of geochemically reconstructed apparent calcification depths, this group of organisms is found shallower in the water column at the Equator and the subtropical gyres, while its habitat deepens in between these regions at the extra-equatorial sites. Furthermore, it is demonstrated that in the (central) Atlantic, it occupies a density layer slightly below the salinity maximum isopycnal at various depths, presumably by adjusting its shell properties.
A real-time forecasting and estimating system of West Nile virus: a case study of the 2023 WNV outbreak in Colorado, USA
Authors: Yi Chunlin , Cohnstaedt Lee W. , Scoglio Caterina M.
Published: December 2024

West Nile virus (WNV) is a mosquito-borne arbovirus that remains a persistent public health challenge in the USA, with seasonal outbreaks that can lead to severe cases. In this study, we detail a real-time prediction system for WNV that incorporates an adapted compartment model to account for the transmission dynamics among birds, mosquitoes and humans, including asymptomatic cases and the influence of weather factors. Using data assimilation techniques, we generate weekly WNV case forecasts for Colorado in 2023, providing valuable insights for public health planning. Comparative analyses underscore the enhanced forecast accuracy achieved by integrating weather variables into our models.
Optimal COVID-19 vaccine prioritization by age depends critically on inter-group contacts and vaccination rates
Authors: Atienza-Diez Iker , Rodriguez-Maroto Gabriel , Ares Saúl , Manrubia Susanna
Published: December 2024

The limited availability of COVID-19 vaccines has prompted extensive research on optimal vaccination strategies. Previous studies have considered various non-pharmaceutical interventions, vaccine efficacy and distribution strategies. In this work, we address the combined effects of inter-group contacts and vaccination rates under contact reduction, analysing the Spanish population’s demographic and age group contact patterns and incorporating reinfection dynamics. We conduct an exhaustive analysis, evaluating 362 880 permutations of nine age groups across six vaccination rates and two distinct, empirically quantified scenarios for social contacts. Our results show that at intermediate-to-high vaccination rates with unrestricted social contacts, optimal age-based vaccination strategies only slightly deviate from older-to-younger prioritization, yielding marginal reductions in deaths and infections. However, when significant reductions in social contacts are enforced—similar to the lockdowns in 2020—there are substantial improvements, particularly at moderate vaccination rates. These restrictions lead to a transition where infection propagation is halted, a scenario that became achievable during the pandemic with the observed vaccination rates. Our findings emphasize the importance of combining appropriate social contact reductions with vaccination to optimize age-based vaccination strategies, underscoring the complex, nonlinear dynamics involved in pandemic dynamics and the necessity for tailored context-specific interventions.
The early Cambrian
Saccorhytus
is a non-feeding larva of a scalidophoran worm
Authors: Vannier Jean
Published: December 2024

With its bag-like appearance, spiny ornament and single opening,
Saccorhytus coronarius
is one of the most enigmatic animals of the early Cambrian Kuanchuanpu Formation (
ca
535 Ma) and has been at the heart of debates concerning the origin of two major animal lineages: the deuterostomes and the ecdysozoans. Although Ecdysozoa is now the most plausible option, key aspects of its palaeobiology have remained elusive. I suggest here that
Saccorhytus
was the possible larval stage of one of the numerous scalidophoran worms that co-existed with it in the Kuanchuanpu biota, especially those with bilateral pairs of broad-based sclerites such as
Eokinorhynchus
. This new interpretation is mainly based on the development of extant priapulid worms (Scalidophora). It would imply that
Saccorhytus
is a non-feeding larva and that its enigmatic single aperture with a pleated structure is not a mouth but more likely the opening through which the juvenile exited. Thus, the strange anatomy of
Saccorhytus
could be explained in a simple way without involving complex evolutionary processes (e.g. simplification, miniaturization, loss of anus, etc.). Instead of being a relatively basal member of the total group Ecdysozoa,
Saccorhytus
would find a more likely position among the total group Scalidophora.
Taking cues from ecological and evolutionary theories to expand the landscape of disgust
Authors: Love A. E. , Heckley A. M. , Webber Q. M. R.
Published: December 2024

Behavioural avoidance of parasites in the environment generates what is known as the ‘landscape of disgust’ (analogous to the predator-induced ‘landscape of fear’). Despite the potential for improving our inference of host–parasite dynamics, three limitations of the landscape of disgust restrict the insight that is gained from current research: (i) many host–parasite systems will not be appropriate for invoking the landscape of disgust framework; (ii) existing research has primarily focused on immediate choices made by hosts on small scales, limiting predictive power, generalizability, and the value of the insight obtained; and (iii) relevant ecological and evolutionary theory has yet to be integrated into the framework, challenging our ability to interpret the landscape of disgust within the context of most host–parasite systems. In this review, we explore the specific requirements for implementing a landscape of disgust framework in empirical systems. We also propose greater integration of habitat selection and evolutionary theories, aiming to generate novel insight, by exploring how the landscape of disgust varies within and across generations, presenting opportunities for future research. Despite interest in the impacts of parasitism on animal movement and behaviour, many unanswered questions remain.
Context-dependent rhythmicity in chimpanzee displays
Authors: van der Vleuten B. J. R. , Hovenkamp V. A. , Varkevisser J. M. , Spierings M. J.
Published: December 2024

Rhythm is an important component of human language and music production. Rhythms such as isochrony (intervals spaced equally in time) are also present in vocalizations of certain non-human species, including several birds and mammals. This study aimed to identify rhythmic patterns with music-based methods within the display behaviour of chimpanzees (
Pan troglodytes
), humans’ closest living relatives. Behavioural observations were conducted on individuals from two zoo-housed colonies. We found isochronous rhythms in vocal (e.g. pants, grunts and hoots) as well as in motoric (e.g. swaying and stomping) behavioural sequences. Among individuals, variation was found in the duration between onsets of behavioural elements, resulting in individual-specific tempi. Despite this variation in individual tempi, display sequences were consistently structured with stable, isochronous rhythms. Overall, directed displays targeted at specific individuals were less isochronous than undirected displays. The presence of rhythmic patterns across two independent colonies of chimpanzees suggests that underlying mechanisms for rhythm production may be shared between humans and non-human primates. This shared mechanism indicates that the cognitive requirements for rhythm production potentially preceded human music and language evolution.
Nucleotide GPT: Sequence-Based Deep Learning Prediction of Nuclear Subcompartment-Associated Genome Architecture
Authors: Mclaughlin Shae M. , Ahanger Sajad H. , Lim Daniel A.
Published: December 2024

The spatial organization of the genome within the nucleus is partially determined by its interactions with distinct nuclear subcompartments, such as the nuclear lamina and nuclear speckles, which play key roles in gene regulation during development. However, whether these genome-nuclear subcompartment interactions are encoded in the underlying DNA sequence remains poorly understood. The mechanisms for gene regulation are primarily encoded in noncoding DNA sequences, but deciphering how these sequence features control gene expression remains a significant challenge in genomics. Here, we present Nucleotide GPT, a transformer-based model that predicts genomic associations with spatially distinct, physical nuclear subcompartments from DNA sequence alone. Pre-trained on a diverse set of multi-species genomes, we demonstrate Nucleotide GPT’s genomic understanding through evaluation on diverse prediction tasks, including histone modifications, promoter detection, and transcription factor binding sites. When finetuned to predict genome interactions with two separate nuclear subcompartments – the lamina of the inner nuclear membrane and nuclear speckles that lie more interior – Nucleotide GPT achieves an average accuracy of 73.6% for lamina-associated domains (LADs) and 79.4% accuracy for speckle-associated domains (SPADs), averaged across three cortical development cell types. Analysis of the model’s learned representations through Uniform Manifold Approximation and Projection (UMAP) reveals that Nucleotide GPT develops internal embeddings that effectively distinguish LADs from inter-LADs, with predicted probabilities closely corresponding to experimentally determined LAD classifications. When examining these representations in the context of cell type-invariant constitutive LADs (cLADs) compared to cell type-specific LADs, the model assigns lower confidence scores to cell type-specific LADs compared to cLADs that are conserved across neuronal differentiation, suggesting sequence features may play a stronger role in maintaining cLAD associations. Examination of the model’s attention patterns at correctly classified regions suggests that specific sequence elements govern model decision making about nuclear subcompartment associations. Our results demonstrate the utility of transformer architectures for studying three-dimensional (3D) genome organization and substantiate a role for DNA sequence in determining nuclear subcompartment associations.
Two distinct durable human class-switched memory B cell populations are induced by vaccination and infection
Authors: Perugino Cory A. , Liu Hang , Feldman Jared , Marbourg Jess , Guy Thomas V. , Hui Anson , Ingram Nicole , Liebaert Julian , Chaudhary Neha , Tao Weiyang , Jacob-Dolan Catherine , Hauser Blake M. , Mian Zayd , Nathan Anusha , Zhao Zezhou , Kaseke Clarety , Tano-Menka Rhoda , Getz Matthew A. , Senjobe Fernando , Berrios Cristhian , Ofoman Onosereme , Manickas-Hill Zachary , Wesemann Duane R. , Lemieux Jacob E. , Goldberg Marcia B. , Nündel Kerstin , Moormann Ann , Marshak-Rothstein Ann , Larocque Regina C. , Ryan Edward T. , Iafrate John A. , Lingwood Daniel , Gaiha Gaurav , Charles Richelle , Balazs Alejandro B. , Pandit Aridaman , Naranbhai Vivek , Schmidt Aaaron G. , Pillai Shiv
Published: December 2024

Memory lymphocytes are durable cells that persist in the absence of antigen, but few human B cell subsets have been characterized in terms of durability. The relative durability of eight non-overlapping human B cell sub-populations covering 100% of all human class-switched B cells was interrogated. Only two long-lived B cell populations persisted in the relative absence of antigen. In addition to canonical germinal center-derived switched-memory B cells with an IgD-CD27+CXCR5+phenotype, a second, non-canonical, but distinct memory population of IgD-CD27-CXCR5+DN1 B cells was also durable, exhibited a uniqueTP63-linked transcriptional and anti-apoptotic signature, had low levels of somatic hypermutation, but was more clonally expanded than canonical switched-memory B cells. DN1 B cells likely evolved to preserve immunological breadth and may represent the human counterparts of rodent extrafollicular memory B cells that, unlike canonical memory B cells, can enter germinal centers and facilitate B cell and antibody evolution.

Graphical Abstract
Galectin-9 binding to HLA-DR in dendritic cells controls immune synapse formation and T cell proliferation
Authors: Rodgers Furones Andrea , Brands Thijs , Fedorova Kristina , Wijfjes Zacharias , Classens René , Kroese Lona , Verdoes Martijn , van Mierlo Guido , van Spriel Annemiek B , Querol Cano Laia
Published: December 2024

To initiate T cell-mediated immunity, dendritic cells (DCs) present antigens to specific T cells through the establishment of an immune synapse (IS). While the molecular mechanisms behind the formation of the IS on the T cell side are well understood, how IS components are organized at the DC membrane remain ill-defined. Galectins, a family of β-galactoside binding proteins, modulate immune cell function via the establishment of specific glycan-dependent or independent interactions. Nonetheless, the molecular mechanisms that underlie galectin function are poorly described and very little is known regarding their contribution to DC-mediated T cell activation. Here, we demonstrate that intracellular galectin-9 (gal9) in DCs is required for T cell activation. Murine and human DCs lacking gal9 showed impaired induction of CD4+, but not CD8+, T cell proliferation, suggesting a conserved function for gal9 in modulating DC–T cell interactions. Live-cell imaging revealed that galectin-9-depleted DCs fail to establish stable ISs with T cells, resulting in reduced T cell activation and proliferation. Unbiased co-immunoprecipitation and mass spectrometry identified HLA-II as a gal9 binding partner in DCs, and we observed a marked reduction of HLA-II recruitment to the immune synapse in DCs lacking gal9. Conditional gal9 knockout in DCs led to enhanced tumor growthin vivo, compared to their wild-type (WT) counterparts, underscoring a role for gal9 in T cell-dependent anti-tumor immunity. Collectively, this study provides the first detailed account of gal9-mediated HLA-II organization at the synaptic site of DCs, revealing a novel mechanism by which galectins orchestrate immune receptor positioning from within the cytoplasm to enhance CD4+T cell activation.
Single cell transcriptomics reveal mast cell heterogeneity in the human gut
Authors: Hussein Hind , Modave Elodie , Stakenborg Nathalie , Delfini Marcello , Vandereyken Katy , Sifrim Alejandro , Voet Thierry , Boeckxstaens Guy E.
Published: December 2024

Gut mast cells are key players in infection and inflammation, as well as in homeostasis. Mast cells regulate gastrointestinal (GI) function by controlling vascular and epithelial permeability, and interacting with the immune system and the enteric nervous system. Mucosal (MCT) and connective tissue (MCTC) mast cells coexist in the gastrointestinal tract, but are located in distinct microanatomical niches. However, little is known about the transcriptional heterogeneity of human intestinal mast cells. Additionally, whether distinct microanatomical niches instruct mast cell phenotypes in the human gut is currently unknown. We therefore performed 10x single cell RNA sequencing on healthy rectal biopsies and on dissected layers of human sigmoid colon. We identified five transcriptionally distinct mast cell subsets (MC1-5) which exhibited a layer-specific distribution in the healthy human colon and distinct cytokine, chemokine, protease, and transcription factor profiles, and were associated with putative immune and neuro-immune functions. This study provides a framework for the integration of mast cell heterogeneity in the study of gastrointestinal disease mechanisms in humans.
Global patterns of species diversity and distribution in the biomedically and biotechnologically important fungal genusAspergillus
Authors: Riedling Olivia L. , David Kyle T. , Rokas Antonis
Published: December 2024

Aspergillusfungi are key producers of pharmaceuticals, enzymes, and food products and exhibit diverse lifestyles, ranging from saprophytes to opportunistic pathogens. To improve understanding ofAspergillusspecies diversity, identify key environmental factors influencing their geographic distributions, and estimate the impact of future climate change, we trained a random forest machine learning classifier on 30,542 terrestrial occurrence records for 176 species (∼40% of known species in the genus) and 96 environmental variables. We found that regions with high species diversity are concentrated in temperate forests, which suggests that areas with mild seasonal variation may serve as diversity hotspots. Species range estimates revealed extensive variability, both within and across taxonomic sections; while some species are cosmopolitan, others have more restricted ranges. Furthermore, range overlap between species is generally low. The top predictors of mean species richness were the index of cumulative human impact and five bioclimatic factors, such as temperature and temperate vs non-temperate ecoregions. Our future climate analyses revealed considerable variation in species range estimates in response to changing climates; some species ranges are predicted to expand (e.g., the food spoilage and mycotoxin-producingAspergillus versicolor), and others are predicted to contract or remain stable. Notably, the predicted range of the major pathogenAspergillus fumigatuswas predicted to decrease in response to climate change, whereas the range of the major pathogenAspergillus flavuswas predicted to increase and gradually decrease. Our findings reveal how both natural and human factors influenceAspergillusspecies ranges and highlight their ecological diversity, including the diversity of their responses to changing climates, which is of relevance to pathogen and mycotoxin risk assessment.
Disentangling cell type and state transcriptional programs
Authors: Wang Jiayi , Crowell Helena L. , Robinson Mark D.
Published: December 2024

Single-cell omics approaches profile molecular constituents of individual cells. Replicated multi-condition experiments in particular aim at studying how the molecular makeup and composition of cell subpopulations changes at the sample-level. Two main approaches have been proposed for these tasks: firstly, cluster-based methods that group cells into (non-overlapping) subpopulations based on their molecular profiles and, secondly, cluster-free but neighborhood-based methods that identify (overlapping) groups of cells in consideration of cross-condition changes. In either approach, discrete cell groups are subjected to differential testing across conditions; and, a low-dimensional cell embedding, which is in turn derived from a subset of selected features, is required to delineate subpopulations or neighborhoods.

We hypothesized that decoupling differences in cell type (i.e., between subpopulations) and cell state (i.e., between conditions) for feature selection would yield an embedding space that captures different aspects of cellular heterogeneity. And, that type-not-state embeddings would arrive at differential testing results that are comparable between clusterand neighborhood-based differential testing approaches. Our study leverages a simulation framework with competing type and state effects, as well as an experimental dataset, to evaluate a set of feature scoring and selection strategies, and to compare results from downstream differential analyses.
Accurate sample deconvolution of pooled snRNA-seq using sex-dependent gene expression patterns
Authors: Twa Guy M. , Phillips Robert A. , Robinson Nathaniel J. , Day Jeremy J.
Published: December 2024

Single nucleus RNA sequencing (snRNA-seq) technology offers unprecedented resolution for studying cell type-specific gene expression patterns. However, snRNA-seq poses high costs and technical limitations, often requiring the pooling of independent biological samples and loss of individual sample-level data. Deconvolution of sample identity using inherent features would enable the incorporation of pooled barcoding and sequencing protocols, thereby increasing data throughput and analytical sample size without requiring increases in experimental sample size and sequencing costs. In this study, we demonstrate a proof of concept that sex-dependent gene expression patterns can be leveraged for the deconvolution of pooled snRNA-seq data. Using previously published snRNA-seq data from the rat ventral tegmental area, we trained a range of machine learning models to classify cell sex using genes differentially expressed in cells from male and female rats. Models that used sex-dependent gene expression predicted cell sex with high accuracy (90-92%) and outperformed simple classification models using only sex chromosome gene expression (69-89%). The generalizability of these models to other brain regions was assessed using an additional published data set from the rat nucleus accumbens. Within this data set, model performance remained highly accurate in cell sex classification (89-90% accuracy) with no additional re-training. This work provides a model for future snRNA-seq studies to perform sample deconvolution using a two-sex pooled sample sequencing design and benchmarks the performance of various machine learning approaches to deconvolve sample identification from inherent sample features.
Optimal treatment for drug-induced cancer persisters involves release periods and intermediate drug doses
Authors: Corigliano Mattia , Di Bernardo Arianna , Cosentino Lagomarsino Marco , Pompei Simone
Published: December 2024

Targeted cancer therapies often induce a reversible drug-tolerant state in subpopulations of cells, akin to bacterial persistence. Precise characterization of these “cancer persisters” may inform the design of more effective treatment strategies. A previous investigation into the transition to persistence of colorectal cancer cell lines has revealed a distinct dependence on drug presence and concentration, not typical of bacterial systems. Leveraging these findings, this study uses mathematical modeling to explore intermittent treatment protocols aimed at diminishing the long-term fitness of the treated population, thereby enhancing therapeutic efficacy. We adapt a mathematical model originally designed for bacteria to describe colorectal cancer population dynamics in response to a series of treatment and release cycles. The model predicts the long-term increase or reduction of a treated population, as well as its asymptotic composition, leading us to identify success and failure regions within a clinically accessible parameter space, also in combination with hypothetical drugs that act on persisters. Strikingly, our analysis suggests, perhaps counter-intuitively, that optimal treatment outcomes may be achieved in correspondence of non-zero recovery periods and lower than currently administered in the clinics drug concentrations. Furthermore, by incorporating patient drug pharmacokinetics in the model, we demonstrate that intermittent dosing strategies currently explored in clinical trials can be optimized to potentially rival the efficacy of continuous dosing regimens. These findings underscore the potential of mathematical models in guiding the design of optimal treatment protocols by fine-tuning non-trivial decisional trade-offs.
DNA methylation and gene expression trajectories of human postprandial metabolism
Authors: Costeira Ricardo , Ruiz Lidia Daimiel , Gehrmann Thies , Bogaards Fatih , Villicaña Sergio , Sinke Lucy , Raza Yasrab , Tomlinson Max , Christiansen Colette , Heijmans Bastiaan T , Slagboom P Eline , Spector Tim D , Small Kerrin S , Alcala-Diaz Juan F , Rangel-Zuñiga Oriol , López-Miranda Jose , Waldenberger Melanie , Berry Sarah E , Ordovás José M , Bell Jordana T
Published: December 2024

Human postprandial metabolism is characterised by a highly individualised response to food that is predictive of cardiometabolic health and underexplored at the molecular level. We profiled blood DNA methylation (DNAm) and gene expression trajectories before and after a test meal in 225 European participants. We identify DNAm changes at fasting, 30 minutes and 4 hours after meal challenge, including in metabolically relevant genesINPP4A, GHRL, ASIPandABCG1, with changes observed as early as 30mins postprandially. Gene expression trajectories also changed postprandially predominantly at 4 hours, with replication of lipid metabolism (CPT1A)and circadian rhythm (PER1)genes. Genetic variants affect postprandial molecular trajectories at genes linked to obesity (PDE9A)and glucose response (GPT2). Multiple signals associated with postprandial glucose and triglyceride levels, with replication ofCPT1Amethylation. The postprandial DNAm and expression trajectories target metabolically relevant genes, giving insights towards mechanisms underlying inter-individual response to food and cardiometabolic disease risk.
Enhanced data collection in the Canadian Arctic for seabird bycatch information yields highly variable results
Authors: Provencher Jennifer F. , Morrill André , Mallory Mark L.
Published: December 2024

Incidental catch of seabirds (bycatch) in fisheries has been identified as a major threat to the conservation of seabird populations globally. Acquiring accurate, detailed data on seabird bycatch is an ongoing challenge to effective integrated ecosystem management of commercial fisheries. This is especially true in the Arctic region where different countries have highly variable reporting and data systems to track and understand seabird bycatch in fisheries. To collect detailed data on seabird bycatch in the Greenland halibut (Reinhardtius hippoglossoides) fishery in northern Canada, we applied two methods that asked for more information than standardly reported in the fishery as a voluntary effort with industry partners. We found that the amount of bird bycatch reported in both enhanced datasheets completed by at-sea observers (ASO) and carcass collections yielded different results when compared to the typical seabird bycatch reporting in the fisheries ASO database. Across three years of data collection (2016, 2018, and 2019), the number of seabirds reported using the enhanced data collection methods were 0.5-11-fold the number from typical ASO database values. In a fourth year of observations (2023), enhanced datasheets from the ASO reported no bycaught fulmars (gulls and terns were reported), but the accompanying photographs showed northern fulmars as bycatch, further supporting that seabird identification is hampering accurate reporting. We then used these data to model how the differences between data sources may fluctuate across years. These large discrepancies between the methods highlight the challenges with obtaining accurate and precise seabird bycatch data needed to implement a meaningful ecosystem approach to the management of the fisheries. Future modelling efforts need to take these differing data sources and variability into account to fully understand the potential population level impacts of fisheries on seabird populations.
Wideband Tuning and Deep-Tissue Spectral Detection of Indium Phosphide Nano-Laser Particles
Authors: Cho Sangyeon , Moon Wonjoon , Martino Nicola , Yun Seok Hyun
Published: December 2024

Laser particles (LPs) emitting narrowband spectra across wide spectral ranges are highly promising for high-multiplex optical barcoding. Here, we present LPs based on indium phosphide (InP) nanodisks, operating in the near-infrared wavelength range of 740-970 nm. Utilizing low-order whispering gallery resonance modes in size-tuned nanodisks, we achieved an ultrawide color palette with 27% bandwidth utilization and nanometer-scale linewidth. The minimum laser size was 430 nm in air and 560 nm within the cytoplasm, operating at mode order 4 or 5. We further demonstrated spectral detection of laser peaks with high signal-to-background ratios in highly-scattering media, including 1-cm-thick chicken breast tissue and blood vessels in live mice.
Emotional content effects the precision of visual working memory
Authors: Haghian Zeinab , Vahabie Abdol-Hossein , Rezayat Ehsan
Published: December 2024

Objectives

Our working memory (WM) is susceptible to errors influenced by various sources. Recent research has illuminated the intricate relationship between emotional valence and working memory performance. This study aims to comprehensively investigate memory recall biases across different emotional categories.

Method

To explore this relationship, we designed and implemented a delayed-reproduction facial emotion n-back task. Participants were tasked with recalling the emotional valence of target faces across various n-back conditions, selecting their responses from a continuum of 19 morphed faces ranging from sad to happy.

Results

Our findings indicate that participants generally exhibit a negativity bias, struggling more with happy faces. Interestingly, they also perceive happy faces as less happy and sad faces as less sad, suggesting both positive and negative reappraisal in their emotional valence perception. This underscores the complex interplay between emotional valence and cognitive performance. Notably, recall of neutral images remained stable and was unaffected by preceding emotional contexts.

Conclusion

These findings demonstrate that emotional content in working memory significantly impacts errors during WM tasks, with more emotionally charged faces leading to a greater drift toward the lower valence axis. This highlights the need for further exploration of how emotional factors influence cognitive processes in working memory.
A gene co-expression network-based analysis of mesenchymal stromal cells reveals novel genes and molecular pathways underlying heterotopic ossification
Authors: Yang Meiling , Shi Yongpeng , Shen Shichao , Yan Bin , Yang Lei , Li Liuxun
Published: December 2024

Background

Heterotopic ossification (HO) represents a frequently seen refractory disease second to musculoskeletal injury, in which bone tissue ectopically exists within soft tissue, resulting in serious extremity loss-of-function. This work focused on identifying regulating factors and gene network associated with HO pathology.

Material and Methods

We randomized the heterotopic ossification dataset GSE94683 as HO and NON-HO group. Weighted gene co-expression network analysis (WGCNA) was applied in identifying HO related modules. We discovered differentially expressed genes (DEGs) between the two groups. Then, we integrated protein-protein interaction (PPI) network, co-expression network, enrichment analysis, gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) for identifying the HO-related pathways. We also employed GSE126118 test set to investigate hub genes related to HO. Eventually, potential therapeutics for reversing abnormal hub gene levels were predict by DGIdb.

Results

We discovered twelve HO status modules and 1,483 DEGs in HO samples compared with NON-HO counterparts. Four hub genes were obtained from the overlap of HO related PPI and coexpression networks. Training and test sets were adopted for verification, and three abnormally high hub gene expression in HO were obtained. Functional enrichment of DEGs indicated that these genes were involved in the stem cell pluripotency regulatory pathways, cytokine-cytokine receptor interaction, as well as rap1 pathway. Based on the results from GSEA and GSVA, many hub gene sets were mainly enriched in immune responses.

Conclusion

We identified a gene coexpression network associated with regulatory factors in HO, which provided a new perspective on the pathogenesis and provided potential biomarkers or therapeutic targets.
Study design and the sampling of deleterious rare variants in biobank-scale datasets
Authors: Steiner Margaret C. , Rice Daniel P. , Biddanda Arjun , Ianni-Ravn Mariadaria K. , Porras Christian , Novembre John
Published: December 2024

One key component of study design in population genetics is the “geographic breadth” of a sample (i.e., how broad a region across which individuals are sampled). How the geographic breadth of a sample impacts observations of rare, deleterious variants is unclear, even though such variants are of particular interest for biomedical and evolutionary applications. Here, in order to gain insight into the effects of sample design on ascertained genetic variants, we formulate a stochastic model of dispersal, genetic drift, selection, mutation, and geographically concentrated sampling. We use this model to understand the effects of the geographic breadth of sampling effort on the discovery of negatively selected variants. We find that samples which are more geographically broad will discover a greater number variants as compared geographically narrow samples (an effect we label “discovery”); though the variants will be detected at lower average frequency than in narrow samples (e.g. as singletons, an effect we label “dilution”). Importantly, these effects are amplified for larger sample sizes and moderated by the magnitude of fitness effects. We validate these results using both population genetic simulations and empirical analyses in the UK Biobank. Our results are particularly important in two contexts: the association of large-effect rare variants with particular phenotypes and the inference of negative selection from allele frequency data. Overall, our findings emphasize the importance of considering geographic breadth when designing and carrying out genetic studies, especially at biobank scale.

Significance

As genetic studies grow, researchers are increasingly seeking to identify rare genetic variants with large impacts on traits. In this paper, we combine theoretical methods and data analysis to show how differences in sampling with respect to geographic location can influence the number and frequency of genetic variants that are found. Our results suggest that geographically broad samples will include more distinct genetic variants, though each variant will be found at a lower frequency, as compared to geographically narrow samples. Our results can help researchers to consider the implications of study design on expected results when constructing new genetic samples.
Early-life adversity alters adult nucleus incertus neurons: implications for neuronal mechanisms of increased stress and compulsive behavior vulnerability
Authors: Gugula Anna , Sambak Patryk , Trenk Aleksandra , Drabik Sylwia , Nogaj Aleksandra , Soltys Zbigniew , Gundlach Andrew L. , Blasiak Anna
Published: December 2024

BACKGROUND

Early-life stress (ELS) arising from physical and emotional abuse disrupts normal brain development and impairs hypothalamic-pituitary-adrenal axis function, increasing the risk of psychopathological disorders and compulsive behaviors in adulthood. However, the underlying neural mechanisms remain unclear. The brainstem nucleus incertus (NI) is a highly stress-sensitive locus, involved in behavioral activation and stress-induced reward (food/alcohol) seeking, but its sensitivity to ELS remains unexplored.

METHODS

We used neonatal maternal separation stress in rats as a model for ELS and examined its impact on stress-related mRNA and neuropeptide expression in the NI, using fluorescentin situhybridization and immunohistochemistry, respectively. Using whole-cell, patch-clamp recordings we determined the influence of ELS on the synaptic activity, excitability, and electrophysiological properties of NI neurons. Using c-Fos protein expression we also assessed the impact of ELS on the sensitivity of NI neurons to acute restraint stress in adulthood.

RESULTS

ELS weakened the acute stress responsiveness of NI neurons, and caused dendritic shrinkage, impaired synaptic transmission and altered electrophysiological properties of NI neurons in a cell-type-specific manner. Additionally, ELS increased the expression of mRNA encoding corticotropin-releasing hormone receptor type 1 and the nerve-growth factor receptor, TrkA in adult NI.

CONCLUSIONS

The multiple, cell-type specific changes in the expression of neuropeptides and molecules associated with stress and substance abuse in the NI, as well as impairments in NI neuron morphology and electrophysiology caused by early-life stress and observed in the adult brain, may contribute to the increased susceptibility to stress and compulsive behaviors observed in individuals with a history of ELS.
Effect of network structure and adaptive foraging on pollination services of species-rich plant-pollinator communities
Authors: Valdovinos Fernanda S.
Published: December 2024

Network science has had a great impact on ecology by providing tools to characterize the structure of species interactions in communities and evaluate the effect of such network structure on community dynamics. This has been particularly the case for the study of plant-pollinator communities, which has experienced a tremendous growth with the adoption of network analyses. Here, I build on such body of research to evaluate how network structure and adaptive foraging of pollinators affect ecosystem services of plant-pollinator communities. Specifically, I quantify — using model simulations — pollen deposition in networks that exhibit structures like the ones of empirical networks (hereafter empirically connected networks) and those with higher connectance and lower nestedness than empirical networks, for scenarios where pollinators are fixed foragers and scenarios where they are adaptive foragers. I found that empirically connected networks with adaptive foraging exhibit the highest pollen deposition rate. Increased network connectance reduces pollen deposition as increased number of interactions lead to greater conspecific pollen dilution in the absence of other mechanisms such as pollinator floral constancy. High nestedness in moderately connected networks increases the proportion of pollinators visiting only one or two plant species, which are associated with the highest quality visits. Adaptive foraging allows pollinators to quantitatively specialize on specialist plant species which increases conspecific pollen deposition. This research advances pollination biology by elucidating how population dynamics, consumer-resource interactions, adaptive foraging, and network structure affects pollen deposition in a network context.
Anapc5andAnapc7as genetic modifiers of KIF18A function in fertility and mitotic progression
Authors: Nesbit Carleigh , Martin Whitney , Czechanski Anne , Byers Candice , Raghupathy Narayanan , Ferraj Ardian , Stumpff Jason , Reinholdt Laura
Published: December 2024

The kinesin family member 18A (KIF18A) is an essential regulator of microtubule dynamics and chromosome alignment during mitosis. Functional dependency on KIF18A varies by cell type and genetic context but the heritable factors that influence this dependency remain unknown. To address this, we took advantage of the variable penetrance observed in different mouse strain backgrounds to screen for loci that modulate germ cell depletion in the absence of KIF18A. We found a significant association at a Chr5 locus where anaphase promoting complex subunits 5 (Anapc5) and 7 (Anapc7) were the top candidate genes. We found that both genes were differentially expressed in a sensitive strain background when compared to resistant strain background at key timepoints in gonadal development. We also identified a novel retroviral insertion inAnapc7that may in part explain the observed expression differences. In cell line models, we found that depletion of KIF18A induced mitotic arrest, which was partially rescued by co-depletion of ANAPC7 (APC7) and exacerbated by co-depletion of ANAPC5 (APC5). These findings suggest that differential expression and activity ofAnapc5andAnapc7may influence sensitivity to KIF18A depletion in germ cells and CIN cells, with potential implications for optimizing antineoplastic therapies.
Pirin does not bind to p65 or regulate NFκB-dependent gene expression but does modulate cellular quercetin levels
Authors: Meschkewitz Melissa , Lisabeth Erika M , Cab-Gomez A. Denaly , Leipprandt Jeffrey , Neubig Richard R
Published: December 2024

Pirin is a non-heme iron binding protein with a variety of proposed functions including serving as a co-activator of p65 NFκB and quercetinase activity. We report here, failure to confirm pirin’s primary proposed mechanism, binding of Fe(III)-pirin and p65. Analytical size exclusion chromatography (SEC) and fluorescence polarization (FP) studies did not detect an interaction. We also found no effects of pirin on TNFα-activated p65-regulated gene transcription using mouse embryonic fibroblasts (MEFs) from a pirin knockout mouse and a pirin knockdown NIH3T3 fibroblast cell line. TNFα - activated p65 response gene mRNA was neither increased nor decreased in cells with loss of pirin compared to wildtype cells. Furthermore, pirin immunofluorescence in NIH3T3 fibroblasts showed primarily a cytoplasmic localization, not nuclear as in most previous studies. This was confirmed by cell fractionation analysis. Pirin did show colocalization with the endoplasmic reticulum (ER) marker protein disulfide-isomerase (PDI) as well as cyotoplasmic labeling. We confirmed pirin’s quercetinase activity in biochemical assays and demonstrated competitive inhibition by the pirin inhibitor CCG-257081. Cellular quercetin levels in cells exposed to quercetinin vitrowere increased by knockdown of pirin or by treatment with pirin inhibitors. Since pirin is localized to ER and flavanols are protective of ER stress, we investigated whether pirin knockdown altered ER stress signaling but did not find any effect of pirin knockdown on ER stress response genes. Our results challenge the dominant model of pirin’s function (NFκB regulation) but confirm its quercetinase activity with implications for the mechanisms of pirin binding small molecules.

Significance Statement

Pirin has multiple proposed functions and plays an important role in cancer (melanoma, colon, and breast) and inflammatory diseases. Small molecule pirin-binding compounds have been identified but pirin’s functional mechanism remains poorly understood. We raise doubts about the primary description of pirin as a nuclear regulator of p65 NFκB function but validate pirin’s role as a quercetinase. We show that pirin-binding compounds can raise cellular quercetin levels. Further studies will be required to fully understand pirin’s biological mechanisms.
Regulated resource reallocation is transcriptionally hard wired into the yeast stress response
Authors: Kocik Rachel A. , Gasch Audrey P.
Published: December 2024

Many organisms maintain generalized stress responses activated by adverse conditions. Although details vary, a common theme is the redirection of transcriptional and translational capacity away from growth-promoting genes and toward defense genes. Yet the precise roles of these coupled programs are difficult to dissect. Here we investigatedSaccharomyces cerevisiaeresponding to salt as a model stressor. We used molecular, genomic, and single-cell microfluidic methods to examine the interplay between transcription factors Msn2 and Msn4 that induce stress-defense genes and Dot6 and Tod6 that transiently repress growth-promoting genes during stress. Surprisingly, loss of Dot6/Tod6 led to slower acclimation to salt, whereas loss of Msn2/4 produced faster growth during stress. This supports a model where transient repression of growth-promoting genes accelerates the Msn2/4 response, which is essential for acquisition of subsequent peroxide tolerance. Remarkably, we find that Msn2/4 regulateDOT6mRNA production, influence Dot6 activation dynamics, and are required for full repression of growth-promoting genes. Thus, Msn2/4 directly regulate resource reallocation needed to mount their own response. We discuss broader implications for common stress responses across organisms.

SYNOPSIS

This study investigates how genes induced and repressed in the yeast Environmental Stress Response contribute to stress tolerance, growth rate, and resource allocation. The work uses molecular, genomic, and systems biology approaches to present new insights into eukaryotic responses to acute stress.

HIGHLIGHTS

Cells lacking stress-activated transcription factors have a faster post-stress growth rate

Cells lacking repressors of growth-promoting genes have a slower post-stress growth rate

Stress-defense factors control the induction of growth-promoting gene repressors, thereby coordinating the resource re-allocation needed for the response
Chemically Induced Nuclear Pore Complex Protein Degradation via E3 Ligase TRIM21
Authors: Li Xiaomei , Wang Qingyang , Guo Anping , Qiu Yaping , Chen Qiuxia , Li You , Zhang Lanjun , Guo Yaxin , Meng Xiaoyun , Li Shiqian , Liu Guizhi , Zhang Liyun , Liu Jian , Li Xianyang , Cai Longying , Cheng Xuemin , Liu Chuan , Wang Xiaotao , Wood Andrew , Murray James , Liu Guansai , Li Jin , Huang Xiaodong , Dou Dengfeng
Published: December 2024

Despite the exciting progress of the bifunctional degrader molecules, also known as proteolysis-targeting chimeras (PROTACs), the rapidly expanding field is still significantly hampered by the lacking of available E3 ligase ligands. Our research bridges this gap by uncovering a series of small-molecule ligands to the E3 ligase TRIM21 through DNA-Encoded Library (DEL) technology. We confirmed their interaction with TRIM21 using crystallography and demonstrated their anti-proliferative effects across various cancer cell types. Furthermore, proteomic studies identified that the mRNA Export Factor GLE1, and the Nuclear Pore Complex Protein NUP155, were significantly down-regulated upon TRIM21 ligand treatment. This degradation required TRIM21 and was ubiquitin-proteasome-dependent. More specifically, NUP155 was the primary target for the TRIM21 ligands, while GLE1 was considered a passenger target upon the initial degradation of NUP155. Using immunofluorescence techniques, we further demonstrated that the degradation of GLE1 and NUP155 proteins impaired the integrity of the nuclear envelope, leading to cell death. Highlighted by this research, a novel mode of action has been discovered for the TRIM21 E3 ligase ligand, acting as a monovalent degrader that triggers de novo interaction with functional complex proteins and induces their degradation.