bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic evolution of pyranopterin-dependent biochemistry
Authors: Goldford Joshua E. , Murali Ranjani , Valentine Joan Selverstone , Fischer Woodward W. 
Published: September 2023

AbstractMolybdenum (Mo)-dependent biochemistry is essential for many key metabolic pathways. However, theory and geological evidence suggests that its solubility during long intervals with low dioxygen would have limited its availability on early Earth. We developed models of metabolic evolution and found that reactions employing tungsten (W)-dependent biochemistry likely preceded Mo-dependent reactions, where Mo-usage increased dramatically after the production of dioxygen. Consistent with this finding, we analyzed genomes from over 65,000 phylogenetically diverse microbes and metagenomes from an environmental dataset, and we observed that dioxygen-utilizing prokaryotes living in aerobic niches are enriched with Mo-dependent enzymes as compared to anaerobic microbes. As an independent evaluation of this hypothesis, we combined protein language models, machine learning, and phylogenomic analysis to build a classifier for W- or Mo-pterin dependence in the DMSO reductase superfamily, and we found that W-pterin-dependent enzymes cluster near the root of the tree and that a subset of late-evolving aldehyde oxidoreductases (AORs) from aerobes are predicted to rely on Mo instead of W. Overall, our combination of metabolic modeling, phenotypic analysis, machine learning, and phylogenomic analysis suggest that Mo-pterin-dependent biochemistry likely derived from W-pterin-dependent biochemistry, and that Mo-usage increased drastically after the rise of oxygen.
3Dmapper: A Command Line Tool For BioBank-scale Mapping Of Variants To Protein Structures
Authors: Ruiz-Serra Victoria , Valentini Samuel , Madroñero Sergi , Valencia Alfonso , Porta-Pardo Eduard 
Published: September 2023

ABSTRACTThe interpretation of genomic data is crucial to understand the molecular mechanisms of biological processes. Protein structures play a vital role in facilitating this interpretation by providing functional context to genetic coding variants. However, mapping genes to proteins is a tedious and error-prone task due to inconsistencies in data formats. Over the past two decades, numerous tools and databases have been developed to automatically map annotated positions and variants to protein structures. However, most of these tools are web-based and not well-suited for large-scale genomic data analysis. To address this issue, we introduce 3Dmapper, a standalone command-line tool developed in Python and R. It systematically maps annotated protein positions and variants to protein structures, providing a solution that is both efficient and reliable. 3Dmapper is freely available on GitHub athttps://github.com/vicruiser/3Dmapper.
Antigenicity and infectivity characterization of SARS-CoV-2 BA.2.86
Authors: Yang Sijie , Yu Yuanling , Jian Fanchong , Song Weiliang , Yisimayi Ayijiang , Chen Xiaosu , Xu Yanli , Wang Peng , Wang Jing , Yu Lingling , Niu Xiao , Wang Jing , Xiao Tianhe , An Ran , Wang Yao , Gu Qingqing , Shao Fei , Jin Ronghua , Shen Zhongyang , Wang Youchun , Cao Yunlong 
Published: September 2023

AbstractThe recently identified SARS-CoV-2 variant, BA.2.86, which carries a substantial number of Spike mutations, has raised a global alarm. An immediate assessment of its antigenic properties and infectivity is necessary. Here, we reveal the distinct antigenicity of BA.2.86 compared with previous variants including XBB.1.5. BA.2.86 significantly evades convalescent plasma from XBB breakthrough infection (BTI) and reinfections. Key mutations that mediate the enhanced resistance include N450D, K356T, L452W, A484K, V483del, and V445H on the RBD, while BA.2.86’s NTD mutations and E554K on SD1 also largely contribute. However, we found that BA.2.86 pseudovirus exhibits compromised efficiency of infecting HEK293T-hACE2 cells compared to XBB.1.5 and EG.5, which may be caused by K356T, V483del, and E554K, and could potentially limit BA.2.86’s transmissibility. In sum, it appears that BA.2.86 has traded its infectivity for higher immune evasion during long-term host-viral evolution. Close attention should be paid to monitoring additional mutations that could improve BA.2.86’s infectivity.
Prosocial Decision-Making and Human Brain: A Graph Theory Analysis on Resting-State Functional Magnetic Resonance Image
Authors: Xu Jinwei , Sun Delin 
Published: September 2023

AbstractProsocial behavior is the cornerstone of a harmonious society. However, the functional organization of the brain underlying prosocial decision-making needs to be further explored. Here, we used graph theory analysis to investigate the brain functional connectivity derived from functional magnetic resonance imaging (fMRI) scans during rest in 55 female Chinese university students. The behavioral responses were collected in another fMRI scan during which participants completed an economic exchange game task by making multiple choices between a prosocial and a selfish option against either human counterparts (i.e., social environment) or robot counterparts (i.e., non-social environment). We found that making more prosocial decisions is accompanied by a longer path length in the right anterior superior temporal gyrus (aSTG), higher degree centrality in the posterior cingulate cortex (PCC), and higher betweenness centrality in the left aSTG. Our results suggest that human prosocial decisions are associated with greater inter-regional collaborations that are dominated by a few core nodes within the brain network ofTheory of Mind(ToM). Moreover, an individual’s preference for making prosocial decisions could be uncovered by graph theory analysis of the functional brain network even without explicit task requirements.
The anterior cingulate cortex is involved in intero-exteroceptive integration for spatial image transformation of the self-body
Authors: Sasaoka Takafumi , Hirose Kenji , Maekawa Toru , Inui Toshio , Yamawaki Shigeto 
Published: September 2023

AbstractSpatial image transformation of the self-body is a fundamental function of visual perspective-taking. Recent research underscores the significance of integration of intero-exteroceptive information to construct representations of our embodied self. This raises the intriguing hypothesis that interoceptive processing might be involved in the spatial image transformation of our self-body. To test this hypothesis, the present study used functional magnetic resonance imaging to measure brain activity during an arm laterality judgment (ALJ) task. In this task, participants were tasked with discerning whether the outstretched arm of a human figure, viewed from the front or back, was the right or left hand. The reaction times for the ALJ task proved longer when the stimulus presented orientations of 0°, 90°, and 270° relative to the upright orientation, and when the front view presented as compared to the back view. Corresponding to the increased reaction time, increased brain activity was manifested in a cluster centered on the dorsal anterior cingulate cortex (ACC). Furthermore, this cluster of brain activity exhibited overlap with regions where the difference in activation between the front and back views positively correlated with the participants’ interoceptive sensitivity, as assessed through the heartbeat detection task, within the pregenual ACC. These results suggest that the ACC plays an important role in integrating intero-exteroceptive cues for the purpose of spatially transforming the image of our self-body.
Tropical montane gradients elucidate the contributions of functional traits to competitive and environmental fitness
Authors: Mungee Mansi , Pandit Rohan , Athreya Ramana 
Published: September 2023

AbstractFunctional traits can be classified as alpha or beta, based on their relative importance in determining a species’ competitive and environmental fitness, respectively. However, the link between a trait and its contribution to a particular aspect of fitness is not always straight-forward. We investigated phylogenetic and functional diversity for bird communities along a 200-2800 m elevational transect in the eastern Himalayas. We hypothesized that beta traits, associated with environmental tolerances, would exhibit a directional change in mean values, while alpha traits, linked to competitive strategies, would show a decrease in dispersion with elevation. Our findings showed that most functional traits exhibited a decrease in dispersion with elevation. However, surprisingly, the mean values of these traits also exhibited a significant relationship with elevation, suggesting their involvement in both competitive and environmental fitness. Furthermore, we observed that morphological traits, traditionally considered beta traits associated with environmental tolerance, were influenced more strongly by resource availability and habitat structure rather than aspects of temperature or air density. These results challenge the simplistic classification of traits as either alpha or beta. We suggest that future studies should carefully analyze the variation in mean values and dispersion of individual traits before assigning them solely to a particular category of fitness. The results contribute to a broader understanding of the complex interactions between functional traits, fitness, and environmental conditions in Himalayan bird communities.
The CNS Microenvironment Promotes Leukemia Cell Survival by Disrupting Tumor Suppression and Cell Cycle Regulation in Pediatric T-cell Acute Lymphoblastic Leukemia
Authors: Enlund Sabina , Sinha Indranil , Neofytou Christina , Amor Amanda Ramilo , Papadakis Konstantinos , Nilsson Anna , Jiang Qingfei , Hermanson Ola , Holm Frida 
Published: September 2023

ABSTRACTA major obstacle in improving survival in pediatric T-cell acute lymphoblastic leukemia is understanding how to predict and treat leukemia relapse in the CNS. Leukemia cells are capable of infiltrating and residing within the CNS, where they interact with the microenvironment and remain sheltered from systemic treatment. These cells can survive in the CNS niche, by hijacking the microenvironment and disrupting normal functions, thus promoting malignant transformation. While the protective effects of the bone marrow niche have been widely studied, the mechanisms behind leukemia infiltration into the CNS and the role of the CNS niche in leukemia cell survival remain unknown.We have identified a dysregulated gene expression profile in CNS infiltrated T-ALL and CNS relapse, promoting cell survival, chemoresistance and disease progression. Furthermore, we discovered that interactions between leukemia cells and CNS microenvironment induce epigenetic alterations, such as changes in gene regulation and histone modifications, including H3K36me3 levels.These findings can be utilized to predict CNS infiltration and CNS relapse, therefore avoiding overtreatment and adverse effects caused by CNS directed therapy. Additionally, the identified genetic drivers of disease progression can serve as a first step towards identifying therapeutic targets, to sensitize the CNS niche to current therapeutic strategies.
Evaluation of Bayesian Linear Regression Models as a Fine Mapping tool
Authors: Shrestha Merina , Bai Zhonghao , Gholipourshahraki Tahereh , Hjelholt Astrid J. , Hu Sile , Kjølby Mads , Rohde Palle D. , Sørensen Peter 
Published: September 2023

AbstractOur aim was to evaluate Bayesian Linear Regression (BLR) models with BayesC and BayesR priors as a fine mapping tool and compare them to the state-of-the-art external models: FINEMAP, SuSIE-RSS, SuSIE-Inf and FINEMAP-Inf. Based on extensive simulations, we evaluated the different models based on F1classification score. The different models were applied on quantitative and binary UK Biobank (UKB) phenotypes and evaluated based upon predictive accuracy and features of credible sets (CSs). We used over 533K genotyped and 6.6 million imputed single nucleotide polymorphisms (SNPs) for simulations and UKB phenotypes respectively, from over 335K UKB White British Unrelated samples. We simulated phenotypes from low (GA1) to moderate (GA2) polygenicity, heritability (h2) of 10% and 30%, causal SNPs (π) of 0.1% and 1% sampled genome-wide, and disease prevalence (PV) of 5% and 15%. Single marker summary statistics and in-sample linkage disequilibrium were used to fit models in regions defined by lead SNPs. BayesR improved the F1score, averaged across all simulations, between 27.26% and 13.32% relative to the external models. Predictive accuracy quantified as variance explained (R2), averaged across all the UKB quantitative phenotypes, with BayesR was decreased by 5.32% (SuSIE-Inf) and 3.71% (FINEMAP-Inf), and was increased by 7.93% (SuSIE-RSS) and 8.3% (BayesC). Area under the receiver operating characteristic curve averaged across all the UKB binary phenotypes, with BayesR was increased between 0.40% and 0.05% relative to the external models. SuSIE-RSS and BayesR, demonstrated the highest number of CSs, with BayesC and BayesR exhibiting the smallest average median size CSs in the UKB phenotypes. The BLR models performed similar to the external models. Specifically, BayesR’s performance closely aligned with SuSIE-Inf and FINEMAP-Inf models. Collectively, our findings from both simulations and application of the models in the UKB phenotypes support that the BLR models are efficient fine mapping tools.
Galvanic vs. Pulsatile Effects on Decision-Making Networks: Reshaping the Neural Activation Landscape
Authors: Adkisson Paul , Steinhardt Cynthia R. , Fridman Gene Y. 
Published: September 2023

I.SUMMARYPrimarily due to safety concerns, biphasic pulsatile stimulation is the present standard for electrical excitation of neural tissue with a diverse set of applications. While pulses have been shown to be effective to achieve functional outcomes, they have well-known deficits. Due to recent technical advances, galvanic stimulation, delivery of current for extended periods of time (>1s), has re-emerged as an alternative to pulsatile stimulation. In this paper, we use a winner-take-all decision-making cortical network model to investigate differences between pulsatile and galvanic stimulation in the context of a perceptual decision-making task. Based on previous work, we hypothesized that galvanic stimulation would produce more spatiotemporally distributed, network-sensitive neural responses, while pulsatile stimulation would produce highly synchronized activation of a limited group of neurons. Our resultsin-silicosupport these hypotheses for low-amplitude galvanic stimulation but deviate when galvanic amplitudes are large enough to directly activate or block nearby neurons. We conclude that with careful parametrization, galvanic stimulation could overcome some limitations of pulsatile stimulation to deliver more naturalistic firing patterns in the group of targeted neurons.
New tree shrew Parkinson’s model: a cost-effective alternative to monkey models
Authors: Li Hao , Mei Leyi , Nie Xiupeng , Wu Liping , Ren Xiaofeng , Lv Longbao , Yang Jitong , Cao Haonan , Wu Jing , Zhang Yuhua , Hu Yingzhou , Wang Wenchao , Turck Christoph W. , Shi Bingyin , Li Jiali , Xu Lin , Hu Xintian 
Published: September 2023

AbstractThe surge in demand for experimental monkeys has led to a rapid increase in their associated costs. Consequently, there is a growing need for the development of a cost-effective model for Parkinson’s disease (PD) that exhibits all core clinical and pathological phenotypes of PD. Evolutionarily, tree shrews (Tupaia belangeri) are much closer to primates in comparison to rodents and share more similar PD-related brain structures and movement ability with monkeys. As such, tree shrews represent an ideal small animal species for modeling PD. To develop a tree shrew PD model, we used the 1-Methyl-4-phenylpyridinium (MPP+) metabolite, derived from the well-established PD modeling drug 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), to induce lesions in the dopaminergic neurons of the unilateral substantia nigra. After determining the optimal modeling dosage, the tree shrews consistently exhibited and maintained all classic clinical manifestations of PD for a 5-month period. The symptoms closely resembled the ones observed in PD monkeys and included bradykinesia, rest tremor, postural instability, and apomorphine-induced rotations, a classic phenotype of unilateral PD models. Immunostaining showed a significant loss of dopaminergic neurons (approximately 95%) in the substantia nigra on the lesioned side of the brain, a crucial pathological marker of PD. Further cytomorphological analysis revealed that the size of nigral dopaminergic neurons in tree shrews exceeded that of rodents and more closely approximated that of macaques. Based on the principle that structure determines function, the morphological similarity between tree shrews and monkeys may be an important structural basis for the manifestation of the highly similar phenotypes between monkey and tree shrew PD models. Collectively, this study successfully developed a PD model in a small animal species that faithfully recapitulated the classical clinical symptoms and key pathological indicators of PD monkeys. In addition to the well-recognized monkey models, the tree shrew model provides a novel avenue for the evaluation of PD treatments and underlying mechanisms.
A molecular atlas of plastid and mitochondrial evolution from algae to angiosperms
Authors: Raval Parth K. , MacLeod Alexander I. , Gould Sven B. 
Published: September 2023

AbstractAlgae and plants carry two organelles of endosymbiotic origin that have been co-evolving in their host cells for more than a billion years. The biology of plastids and mitochondria can differ significantly across major lineages and organelle changes likely accompanied the adaptation to new ecological niches such as the terrestrial habitat. Based on organelle proteome data and the genomes of 168 phototrophic (Archaeplastida) versus a broad range of 518 non-phototrophic eukaryotes, we screened for changes in plastid and mitochondrial biology across one billion years of evolution. Taking into account 331,571 protein families (or orthogroups), we identify 31,625 protein families that are unique to primary plastid-bearing eukaryotes. 1906 and 825 protein families are predicted to operate in plastids and mitochondria, respectively. Tracing the evolutionary history of these protein families through evolutionary time uncovers the significant remodeling the organelles experienced from algae to land plants. The analyses of gained orthogroups identifies molecular adaptations of organelle biology that connect to the diversification of major lineages and facilitated major transitions from chlorophytes en route to the global greening and origin of angiosperms.
Eavesdropping and audience effect in fighting fruit flies reveal feedback between social information use and production
Authors: Hutchins Marina , Saltz Julia 
Published: September 2023

AbstractSocial information use and production occur simultaneously during social learning events; however, these two processes are often studied independently. We propose that social information use and production represent a feedback loop: eavesdroppers influence the behaviors of those being observed, which then alters the eavesdroppers’ social decisions. Here, we usedDrosophila melanogasterto investigate the relationship between social information use and production in an aggressive context. We tested whether paired males altered their aggression when they were observed by (i) a male; (ii) a female, or; (iii) no one. Next, we allowed each individual eavesdropper to interact with the paired males that they just observed, and measured their social behaviors. In addition, we tested how naïve flies responded when interacting with paired males. We found that paired males reduced their aggression when observed by a male, representing a change in social information production. In response, male eavesdroppers were overall less aggressive towards the more aggressive of the paired males they had observed, but their response to social information was also modulated by their genotype. In contrast, female eavesdroppers did not elicit changes to the behavior of the paired males, nor did we find evidence that they used the social information collected to make mating decisions. Overall, we found support for the feedback loop in males, but not females: information was exchanged bi-directionally during eavesdropping events, resulting in the modification of behavior by all parties. Utilizing the social information feedback framework can contribute to a better understanding of how social behaviors and animal communication are expressed and evolve.Competing InterestsNoneSignificance StatementAnimals often observe the social interactions that occur between others, but the effects of both watching and being watched on behavior are rarely studied together. Using a novel approach, we studied how an audience influenced and learned from an aggressive contest in fruit flies. A male audience caused contest participants to decrease their aggression, and the male who was watching later showed decreased aggression toward the contest winner. Surprisingly, we did not see any effect of a female audience on male-male aggression, and females’ later behavior was not altered by observing a contest. Together, these results show how observing a fight led to changes in both the behavior of the contest participants and the male audience, thus suppressing group levels of aggressive behavior. Accounting for this interaction between social information use and production is necessary to understand social behaviors.
STAT3 is a genetic modifier of TGF-beta induced EMT in KRAS mutant pancreatic cancer
Authors: D’Amico Stephen , Kirillov Varvara , Petrenko Oleksi , Reich Nancy C. 
Published: September 2023

AbstractOncogenic mutations in KRAS are among the most common in cancer. Classical models suggest that loss of epithelial characteristics and the acquisition of mesenchymal traits are associated with cancer aggressiveness and therapy resistance. However, the mechanistic link between these phenotypes and mutant KRAS biology remains to be established. Here we identify STAT3 as a genetic modifier of TGF-beta-induced epithelial to mesenchymal transition. Gene expression profiling of pancreatic cancer cells identifies more than 200 genes commonly regulated by STAT3 and oncogenic KRAS. Functional classification of STAT3 responsive program reveals its major role in tumor maintenance and epithelial homeostasis. The signatures of STAT3-activated cell states can be projected onto human KRAS mutant tumors, suggesting that they faithfully reflect characteristics of human disease. These observations have implications for therapeutic intervention and tumor aggressiveness.SignificanceThe identification of the molecular and genetic characteristics of tumors is essential for understanding disease progression and aggressiveness. KRAS mutations are the most frequent oncogenic drivers in human cancer. In this study we demonstrate that the ubiquitously expressed transcription factor STAT3 is a genetic modifier of TGF-beta-induced EMT, and thereby oncogenic KRAS dependency. Bothin vitroandin vivostudies demonstrate that STAT3 responsive program is an inherent part of oncogenic KRAS outcome.