bluuebunny/crossref_metadata_2025_split huggingface dataset:
JNplots: an R package to visualize outputs from the Johnson-Neyman technique for categorical and continuous moderators, including options for phylogenetic regressions
Authors: Toyama Ken S. 
Published: May 2023

ABSTRACTThe analysis of two-way interactions in linear models is common in the fields of ecology and evolution, being often present in allometric, macroevolutionary, and experimental studies, among others. However, the interpretation of significant interactions can be incomplete when limited to the examination of model coefficients and significance tests. The Johnson-Neyman technique represents a step forward in the interpretation of significant two-way interactions, allowing the user to examine how changes in the moderator variable, it being categorical or continuous, affect the significance of the relationship between the dependent variable and the predictor. Despite its implementation in several software since its initial development, the available options to perform the method lack certain functionality aspects, including the visualization of regions of non-significance when the moderator is categorical, the implementation of phylogenetic corrections, and more intuitive graphical outputs. Here I present the R packageJNplots, which aims to fill gaps left by previous software regarding the calculation and visualization of regions of non-significance when fitting two-way interaction models.JNplotsincludes two basic functions which allow the user to investigate different types of interaction models, including cases where the moderator variable is categorical or continuous. The user can also specify whether the model to explore should be phylogenetically informed and choose a particular phylogenetic correlation structure to be used. Finally, the functions ofJNplotsproduce plots that are largely customizable and allow a more intuitive interpretation of the interaction term. Here I provide a walkthrough on the use ofJNplotsusing three different examples based on empirical data, each representing a different common scenario in which the package can be useful. Additionally, I present the different customization options for the graphical outputs ofJNplots.
Elevated HIV viral load is associated with higher recombination ratein vivo
Authors: Romero Elena V. , Feder Alison F. 
Published: May 2023

AbstractHIV’s exceptionally high recombination rate drives its intra-host diversification, enabling immune escape and multi-drug resistance within people living with HIV. While we know that HIV’s recombination rate varies by genomic position, we have little understanding of how recombination varies throughout infection or between individuals as a function of the rate of cellular coinfection. We hypothesize that denser intra-host populations may have higher rates of coinfection and therefore recombination. To test this hypothesis, we develop a new approach (Recombination Analysis via Time Series Linkage Decay, or RATS-LD) to quantify recombination using autocorrelation of linkage between mutations across time points. We validate RATS-LD on simulated data under short read sequencing conditions and then apply it to longitudinal, high-throughput intra-host viral sequencing data, stratifying populations by viral load (a proxy for density). Among sampled viral populations with the lowest viral loads (< 26,800 copies/mL), we estimate a recombination rate of 1.5×10−5events/bp/generation (95% CI: 7×10−6−2.9×10−5), similar to existing estimates. However, among samples with the highest viral loads (> 82,000 copies/mL), our median estimate is approximately 6 times higher. In addition to co-varying across individuals, we also find that recombination rate and viral load are associated within single individuals across different time points. Our findings suggest that rather than acting as a constant, uniform force, recombination can vary dynamically and drastically across intra-host viral populations and within them over time. More broadly, we hypothesize that this phenomenon may affect other facultatively asexual populations where spatial co-localization varies.
Lexical semantic content, not syntactic structure, is the main contributor to ANN-brain similarity of fMRI responses in the language network
Authors: Kauf Carina , Tuckute Greta , Levy Roger , Andreas Jacob , Fedorenko Evelina 
Published: May 2023

AbstractRepresentations from artificial neural network (ANN) language models have been shown to predict human brain activity in the language network. To understand what aspects of linguistic stimuli contribute to ANN-to-brain similarity, we used an fMRI dataset of responses to n=627 naturalistic English sentences (Pereira et al., 2018) and systematically manipulated the stimuli for which ANN representations were extracted. In particular, we i) perturbed sentences’ word order, ii) removed different subsets of words, or iii) replaced sentences with other sentences of varying semantic similarity. We found that the lexical semantic content of the sentence (largely carried by content words) rather than the sentence’s syntactic form (conveyed via word order or function words) is primarily responsible for the ANN-to-brain similarity. In follow-up analyses, we found that perturbation manipulations that adversely affect brain predictivity also lead to more divergent representations in the ANN’s embedding space and decrease the ANN’s ability to predict upcoming tokens in those stimuli. Further, results are robust to whether the mapping model is trained on intact or perturbed stimuli, and whether the ANN sentence representations are conditioned on the same linguistic context that humans saw. The critical result—that lexical- semantic content is the main contributor to the similarity between ANN representations and neural ones—aligns with the idea that the goal of the human language system is to extract meaning from linguistic strings. Finally, this work highlights the strength of systematic experimental manipulations for evaluating how close we are to accurate and generalizable models of the human language network.
Calcium-triggered DNA-mediated membrane fusion in synthetic cells
Authors: Hsu Yen-Yu , Samuel J. Chen , Bernal-Chanchavac Julio , Sharma Bineet , Moghimianavval Hossein , Stephanopoulos Nicholas , Liu Allen P. 
Published: May 2023

AbstractIn cells, membrane fusion is mediated by SNARE proteins, whose activities are calcium-dependent. While several non-native membrane fusion mechanisms have been demonstrated, few can respond to external stimuli. Here, we develop a calcium-triggered DNA-mediated membrane fusion strategy where fusion is regulated using surface-bound PEG chains that are cleavable by the calcium-activated protease calpain-1.
Low circulating choline, a modifiable dietary factor, is associated with the pathological progression and metabolome dysfunction in Alzheimer’s disease
Authors: Judd Jessica M. , Jasbi Paniz , Winslow Wendy , Serrano Geidy E. , Beach Thomas G. , Klein-Seetharaman Judith , Velazquez Ramon 
Published: May 2023

AbstractMost Americans (∼90%) are deficient in dietary choline, an essential nutrient. Associations between circulating choline and pathological progression in Alzheimer’s disease (AD) remain unknown. Here, we examined these associations and performed a metabolomic analysis in blood serum from severe AD, moderate AD, and healthy controls. Additionally, to gain mechanistic insight, we assessed the effects of dietary choline deficiency (Ch-) in 3xTg-AD mice and choline supplementation (Ch+) in APP/PS1 mice. In humans, we found AD-associated reductions in choline, it’s derivative acetylcholine (ACh), and elevated pro-inflammatory cytokine TNFα. Choline and ACh were negatively correlated with Plaque density, Braak stage, and TNFα, but positively correlated with MMSE and brain weight. Metabolites L-Valine, 4-Hydroxyphenylpyruvic, Methylmalonic, and Ferulic acids were associated with choline levels. In mice, Ch-paralleled AD severe, but Ch+ was protective. In conclusion, low circulating choline is associated with AD-neuropathological progression, illustrating the importance of dietary choline consumption to offset disease.
Evolution in response to an abiotic stress shapes species coexistence
Authors: Fragata Inês , Godinho Diogo P. , Rodrigues Leonor R. , Cruz Miguel A. , Zélé Flore , Godoy Oscar , Magalhães Sara 
Published: May 2023

AbstractAdaptation to abiotic stresses is pervasive and generally relies on traits that are not independent from those affecting species interactions. Still, how such evolution affects species coexistence remains elusive. We addressed this using populations of two herbivorous spider mite species (Tetranychus urticaeandT. evansi) evolving separately on tomato plants hyper-accumulating cadmium, a stressful environment for the mites, or on control plants with no-cadmium. Combinations of phenotypic analyses with structural stability theory predicted that adaptation of both species to cadmium allow them to coexist in that environment, whereas for cadmium-naïve mite populations the most likely outcome is competitive exclusion. The shift from exclusion to coexistence was due to an increase in structural niche differences caused by a simultaneous increase in intra and a decrease in interspecific competition. However, adaptation to cadmium did not affect species interactions and competitive outcomes in the cadmium-free environment, indicating that such evolutionary changes were environment-specific. Experimental outcomes of population dynamics with populations of the two species from each selection regime in each environment were fully compatible with model predictions. Therefore, evolution of single species in a new environment, even in absence of interspecific competitors, shapes species coexistence. Hence, population shifts to novel environments may have unforeseen evolutionary consequences for community composition and the maintenance of species diversity.Significance StatementThe evolutionary consequences of strong selective pressures imposed by environmental changes on species interactions and their subsequent coexistence remain largely unknown. To fill this knowledge gap, we combined the power of experimental evolution and structural stability to analyze how evolution of two spider mite species on plants with or without cadmium affected their ability to coexist. We found that evolution in the high cadmium environment led to changes in growth rates, but also in the strength of intra-and interspecific competition, such that coexistence became possible, but only when the two species evolved in the new environment. Our study highlights that evolution under high pollutant concentrations, even in the absence of competitors, can shape long-term coexistence between species.
The tryptophan catabolite or kynurenine pathway in autism spectrum disorder; a systematic review and meta-analysis
Authors: Almulla Abbas F. , Thipakorn Yanin , Tunvirachaisakul Chavit , Maes Michael 
Published: May 2023

AbstractBackgroundAutism spectrum disorder (ASD) is a neurodevelopment disorder characterized by impaired social communication and interaction, as well as rigid and unchanging interests and behaviors. In ASD, studies show activated immune-inflammatory and nitro-oxidative pathways which are accompanied by depletion of plasma tryptophan (TRP), increased competing amino acids (CAAs) and activation of the TRP catabolite (TRYCAT) pathway.ObjectivesThis study aims to systematically review and meta-analyze data on peripheral TRP, CAAs, TRYCAT pathway activity, and individual TRYCATs, including kynurenine (KYN) and kynurenic acid (KA) levels, in blood and urine of ASD patients.MethodsAfter searching PubMed, Google Scholar, and SciFinder extensively, a total of 25 full-text papers were included in the analysis, with a total of 6653 participants (3,557 people with ASD and 30,96 healthy controls).ResultsBlood TRP and the TRP/CAAs ratio were not significantly different between ASD patients and controls (standardized mean difference, SMD= −0.227, 95% confidence interval, CI: −0.540; 0.085 and SMD= 0.158, 95%CI: −0.042; 0.359) respectively. The KYN/TRP ratio showed no significant difference between ASD and controls (SMD= 0.001, 95%CI: −0.169; 0.171). Blood KYN and KA levels were not significantly changed in ASD. Moreover, there were no significant differences in urine TRP, KYN and KA levels between ASD and controls. We could not establish increases in neurotoxic TRYCATs in ASD.ConclusionsOur study demonstrates that there are no abnormalities in peripheral blood TRP metabolism, IDO activity, and TRYCAT production in ASD. Reduced TRP availability and elevated neurotoxic TRYCAT levels are not substantial contributors to ASD’s pathophysiology.
Neural mechanisms of sequential dependence in time perception: The impact of prior task and memory processing
Authors: Cheng (程思) Si , Chen (陈思佚) Siyi , Glasauer Stefan , Keeser Daniel , Shi (施壮华) Zhuanghua 
Published: May 2023

AbstractOur perception and decision-making are susceptible to prior context. Such sequential dependence has been extensively studied in the visual domain, but less is known about its impact on time perception. Moreover, there are ongoing debates about whether these sequential biases occur at the perceptual stage or during subsequent post-perceptual processing. Using functional Magnetic Resonance Imaging (fMRI), we investigated neural mechanisms underlying temporal sequential dependence and the role of action in time judgments across trials. Participants performed a timing task where they had to remember the duration of green coherent motion and were cued to either actively reproduce its duration or simply view it passively. We found that sequential biases in time perception were only evident when the preceding task involved active duration reproduction. Merely encoding a prior duration without reproduction failed to induce such biases. Neurally, we observed activation in networks associated with timing, such as striato-thalamo-cortical circuits, and performance monitoring networks, particularly when a “Response” trial was anticipated. Importantly, the hippocampus showed sensitivity to these sequential biases, and its activation negatively correlated with the individual’s sequential bias following active reproduction trials. These findings highlight the significant role of memory networks in shaping time-related sequential biases at the post-perceptual stages.Significance StatementOur study explores the neural mechanisms of sequential dependence in time perception and reveals that active reproduction of time duration in the previous trial can bias subsequent estimates, resulting in a sequential dependence effect. In contrast, passive viewing of a stimulus without reproducing its duration does not produce this effect. At the neural level, we observed increased activity in memory regions like the hippocampus when sequential biases were reduced. Furthermore, we found a negative correlation between hippocampal activation and sequential bias following active reproduction trials, suggesting that the involvement of memory networks mediates how we are influenced by past experiences when judging time.
An algorithm for drug discovery based on deep learning with an example of developing a drug for the treatment of lung cancer
Authors: Chebanov Dmitrii K. , Misyurin Vsevolod A. , Shubina Irina Zh. 
Published: May 2023

AbstractWe have designed an algorithm implemented in a software platform for the development of new anti-tumor drugs in the form of small molecules. Several molecules were generated for the treatment of patients with lung cancer as an example. At the initial stage, we identified the targets for the therapy. Firstly, we evaluated the expression profile of the genes most associated with poor clinical outcome in patients with lung cancer using deep learning. Additional patients’ data were gained by generative adversarial neural networks (GAN) technology. As a result, a set of genes was successfully selected, which expression was associated with poor prognosis. We identified the genes that could distinguish normal tissue from tumor tissue using another deep learning model that was trained to predict normal and tumor tissue based on gene expression. The other genes were considered as targets for targeted lung cancer therapy. After that, a module was developed that predicts the interactions of inhibitors with proteins. For this purpose, the amino acid sequences of proteins were represented in vector form, as well as formulas of chemical compounds interacting with proteins. In addition, a deep learning-based module was developed that predicts the IC50 in experiments on cell lines. Virtual pre-clinical trials with the selected inhibitors were performed to identify relevant cell lines for laboratory experiments. As a result, the study obtained formulas of several molecules with the predicted binding to certain proteins.
Prior flavivirus immunity skews the yellow fever vaccine response to expand cross-reactive antibodies with increased risk of antibody dependent enhancement of Zika and dengue virus infection
Authors: Santos-Peral Antonio , Luppa Fabian , Goresch Sebastian , Nikolova Elena , Zaucha Magdalena , Lehmann Lisa , Dahlstroem Frank , Karimzadeh Hadi , Kummerer Beate M , Thorn-Seshold Julia , Winheim Elena , Dobler Gerhard , Hoelscher Michael , Endres Stefan , Krug Anne B , Pritsch Michael , Barba-Spaeth Giovanna , Rothenfusser Simon 
Published: May 2023

AbstractHuman pathogenic flaviviruses pose a significant health concern and vaccination is the most effective instrument to control their circulation. How pre-existing immunity to antigenically related viruses modulates immunization outcome remains poorly understood. In this study, we evaluated the effect of vaccination against tick-borne encephalitis virus (TBEV) on the epitope immunodominance and immunogenicity of the yellow fever 17D vaccine (YF17D) in a cohort of 250 human vaccinees.Following YF17D vaccination, all study participants seroconverted and generated protective neutralizing antibody titers. At day 28, TBEV pre-immunity did not affect the polyclonal neutralizing response which largely depended on the IgM fraction. We found that sera from TBEV-immunized individuals enhanced YF17D vaccine virus infection via antibody-dependent enhancement (ADE). Upon vaccination, individuals with TBEV pre-immunity had higher concentrations of cross-reactive IgG antibodies with limited neutralizing capacity against YF17D whereas vaccinees without prior flavivirus exposure showed a non-cross-reacting response. Using a set of recombinant YF17D envelope protein mutants displaying different epitopes, we identified quaternary epitopes as the primary target of neutralizing antibodies. Sequential immunizations redirected the IgG response towards the pan-flavivirus fusion loop epitope (FLE) with the potential to mediate enhancement of dengue and Zika virus infections whereas TBEV naïve individuals elicited an IgG response directed towards neutralizing epitopes without an enhancing effect.We propose that the YF17D vaccine effectively conceals the FLE and primes a neutralizing IgG response in individuals with no prior flavivirus exposure. In contrast, the response in TBEV-experienced recipients favors weakly-neutralizing, cross-reactive epitopes potentially increasing the risk of severe dengue and Zika disease due to ADE.
SHORT-TERM CALORIC RESTRICTION IN MICE PROMOTES RESOLUTION OF ATHEROSCLEROSIS, WHILE WEIGHT REGAIN ACCELERATES ITS PROGRESSION
Authors: Scolaro Bianca , Brown Emily J. , Krautter Franziska , Petitjean Marie , Donahoe Casey , Pena Stephanie , Garabedian Michela L. , Nikain Cyrus A. , Laskou Maria , Tufanli Ozlem , Hannemann Carmen , Aouadi Myriam , Weinstock Ada , Fisher Edward A. 
Published: May 2023

ABSTRACTWhile weight loss is highly recommended for those with obesity, >60% will regain their lost weight. This weight cycling is associated with elevated risk of cardiovascular disease, relative to never having lost weight. How weight loss/regaindirectlyinfluence atherosclerotic inflammation is unknown. Thus, we studied short-term caloric restriction (stCR) in obese hypercholesterolemic mice, without confounding effects from changes in diet composition. Weight loss was found to promote atherosclerosis resolution independent of plasma cholesterol. From single-cell RNA-sequencing and subsequent mechanistic studies, this can be partly attributed to a unique subset of macrophages accumulating with stCR in epididymal adipose tissue (eWAT) and atherosclerotic plaques. These macrophages, distinguished by high expression ofFcgr4, help to clear necrotic cores in atherosclerotic plaques. Conversely, weight regain (WR) following stCR accelerated atherosclerosis progression with disappearance of Fcgr4+ macrophages from eWAT and plaques. Furthermore, WR caused reprogramming of immune progenitors, sustaining hyper-inflammatory responsiveness. In summary, we have developed a model to investigate the inflammatory effects of weight cycling on atherosclerosis and the interplay between adipose tissue, bone marrow, and plaques. The findings suggest potential approaches to promote atherosclerotic plaque resolution in obesity and weight cycling through induction of Fcgr4+ macrophages and inhibition of immune progenitor reprogramming.Graphical abstract
Local haplotype visualization for trait association analysis with crosshap
Authors: Marsh Jacob I. , Petereit Jakob , Johnston Brady A. , Bayer Philipp E. , Fernandez Cassandria G. Tay , Al-Mamun Hawlader A. , Batley Jacqueline , Edwards David 
Published: May 2023

AbstractSummaryGWAS excels at harnessing dense genomic variant datasets to identify candidate regions responsible for producing a given phenotype. However, GWAS and traditional fine-mapping methods do not provide insight into the complex local landscape of linkage that contains and has been shaped by the causal variant(s). Here, we present ‘crosshap’, an R package that performs robust density-based clustering of variants based on their linkage profiles to capture haplotype structures in a local genomic region of interest. Following this, ‘crosshap’ is equipped with visualization tools for choosing optimal clustering parameters (ε) before producing an intuitive figure that provides an overview of the complex relationships between linked variants, haplotype combinations, phenotypic traits and metadata.Availability and implementationThe ‘crosshap’ package is freely available under the MIT license and can be downloaded directly from CRAN with R>4.0.0. The development version is available on GitHub alongside issue support (https://github.com/jacobimarsh/crosshap). Tutorial vignettes and documentation are available (https://jacobimarsh.github.io/crosshap/).
Bacterial Cytochrome P450-catalyzed Post-translational Macrocyclization
Authors: He Bei-Bei , Cheng Zhuo , Liu Jing , Liu Runze , Zhong Zheng , Gao Ying , Liu Hongyan , Li Yong-Xin 
Published: May 2023

AbstractBacterial cytochrome P450s represent an emerging enzyme family that can modify ribosomally synthesized peptides to generate structurally complex macrocyclic skeletons. However, the functional sequence space of this type of enzyme is largely unexplored. In this study, we conduct a systematic genome mining of small ribosomal peptide-tailoring P450s from genomes of actinobacteria via a precursor-centric, primary sequence-, and structure-guided strategy. We uncovered 1,957 putative P450s, prioritized two representative families for functional study, and characterized two P450 enzymes that can respectively catalyze Tyrosine-to-Tryptophan and Tryptophan-to-Tryptophan crosslinks to form 3-mer or 4-mer macrocycle. These two P450 enzymes exhibit broad substrate selectivity, suggesting a promising starting template for engineering unnatural cyclic peptide construction. Our work expanded the enzymatic catalysis of P450s and could inspire the community to discover hidden peptide-modifying enzymes.