bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep DNAshape: Predicting DNA shape considering extended flanking regions using a deep learning method
Authors: Li Jinsen , Chiu Tsu-Pei , Rohs Remo 
Published: October 2023

AbstractUnderstanding the mechanisms of protein-DNA binding is critical in comprehending gene regulation. Three-dimensional DNA shape plays a key role in these mechanisms. In this study, we present a deep learning-based method, Deep DNAshape, that fundamentally changes the currentk-mer based high-throughput prediction of DNA shape features by accurately accounting for the influence of extended flanking regions, without the need for extensive molecular simulations or structural biology experiments. By using the Deep DNAshape method, refined DNA shape features can be predicted for any length and number of DNA sequences in a high-throughput manner, providing a deeper understanding of the effects of flanking regions on DNA shape in a target region of a sequence. Deep DNAshape method provides access to the influence of distant flanking regions on a region of interest. Our findings reveal that DNA shape readout mechanisms of a core target are quantitatively affected by flanking regions, including extended flanking regions, providing valuable insights into the detailed structural readout mechanisms of protein-DNA binding. Furthermore, when incorporated in machine learning models, the features generated by Deep DNAshape improve the model prediction accuracy. Collectively, Deep DNAshape can serve as a versatile and powerful tool for diverse DNA structure-related studies.
Social tension in the aftermath of public conflicts: an ethological analysis in humans
Authors: Pallante Virginia , Norscia Ivan , Lindegaard Marie Rosenkrantz 
Published: October 2023

AbstractIn social mammals, conflicts are stressful events for the individuals involved. In the post-conflict context, it is possible to detect the emotional state of the former opponents through the expression of displacement activities and aggressive behaviours, which indicate an increase of social tension. In humans, stressful events also induce a physiological response which leads to increased social tension behaviours. However, the variation of such behaviours in the post-conflict conflict, has never been investigated. By conducting a video analysis of street fights recorded by Close Circuit Television cameras, we assessed the variation of behaviours associated with anxiety, aggression related anger and other behaviours possibly related to both anxiety and anger (body postures and talking with gestures) in human opponents. We compared the expression of social tension behaviours before and after the eruption of the conflict and found that displacement activities (related to anxiety), aggressive behaviours (related to anger) and talking with gestures (possibly related to anxiety/anger), but not body postures, increased in post-conflict context. Moreover, displacement activities and aggressive patterns showed a temporal variation, decreasing in the 10 minutes following the conflict. Finally, different from anger-related behaviours, the level of anxiety-related behaviours was more sensitive to aggression intensity, indicating that different social tension behaviours rely on different responses that might be separated. With our study we were able to highlight the importance of the ethological approach for the study of post-conflict social tension in humans, which show a variation in its expression as observed in nonhuman primates. Following a similar comparative approach, we encourage further studies to explore the role of social tension in affecting post-conflict social dynamics.
A Straightforward Approach for Living Biomembrane Printing onto Nanoparticle
Authors: Mizuta Ryosuke , Kanao Eisuke , Ukyo Keigo , Sawada Shin-ichi , Ishihama Yasushi , Sasaki Yoshihiro , Akiyoshi Kazunari 
Published: October 2023

AbstractBiomembrane coating technologies have increasingly been pursued to grant natural dynamic bio-interfaces onto synthetic nanomaterials. Herein, we report a one-step method to coat “living” biomembrane on nanoparticle surfaces in a non-destructive manner. In our method, nanoparticles were efficiently coated with cell membranes without losing the structural integrity by mechanically facilitating the passage of nanoparticles to a concentration layer of living cells with simple centrifugation. This was similar to the exosome-releasing process via endocytosis and exocytosis. The biomembrane originating from living Raw264.7 cells was coated onto the silica nanoparticle prepared by our method, and proteome profiling with nanoflow liquid chromatography-tandem mass spectrometry demonstrated that it was constructed with proteins derived from the membranous component. This proteome profile was not observed in silica nanoparticles prepared with dead cells. Finally, the hybridized cell membrane effectively suppressed the phagocytic activity of Raw264.7 cells to silica nanoparticles and improved the uptake efficiency into cancer cells. We believe our simple and efficient method to coat living biomembranes should be useful in developing medical and pharmaceutical applications involving nanoparticles.
Candidate Genes Associated with Parity Mode Evolution are Under Selection in Oviparous and Viviparous Snakes
Authors: Maggs X 
Published: October 2023

AbstractOver 100 divergent lineages of squamates are viviparous (live-bearing) while others are oviparous (egg-laying). Estimated origins of oviparity and viviparity across the squamate phylogeny are a subject of scientific debate. Identifying genomic changes that influence parity mode evolution can provide insights on the adaptive nature of both parity modes. Using BUSTED in the HyPhy suite and whole genomes of 27 species of snakes, I test for gene-wide episodic diversifying selection (EDS) in 1,587 candidate genes. The genomes represent 14 viviparous and 13 oviparous species across four families (Viperidae, Elapidae, Natricidae, and Pythonidae), including eight new genomes fromLachesis muta, Lachesis stenophrys, Agkistrodon contortrix, Trimeresurus albolabris, Gloydius halys, Ophryacus undulatus, Ovophis monticola, andCalloselasma rhodostoma. Candidate genes were chosen based on evidence for their involvement of seven physiological processes expected to change during evolutionary transitions between parity modes. EDS was measured across candidate gene trees under different foreground branch tests: 1) all viviparous branches, 2) viviparous Viperidae branches, 3) viviparous Elapidae and Natricidae branches, 4) all oviparous branches, and 5) oviparous Viperidae branches (estimated reversals). Over 16% of tests found evidence for EDS, translating to 533 genes with EDS associated with parity mode. Some genes had significant EDS in multiple tests. However, the ‘all oviparous’ test identified a 2.8 to 5.9-fold increase in the number of unique genes with EDS compared to other foreground tests. These results suggest that EDS may influence the evolution of both oviparity and viviparity. Future research using population-level data from snakes may further elucidate the role of selection in parity mode evolution.
Comparison of phage and plasmid populations present in the gut microbiota of Parkinson’s disease patients
Authors: Lecomte Alexandre , Duru Ilhan Cem , Laine Pia , Shishido Tânia Keiko , Suppula Joni , Paulin Lars , Scheperjans Filip , Pereira Pedro , Auvinen Petri 
Published: October 2023

AbstractThe aging population worldwide is on the rise, leading to a higher number of Parkinson’s disease (PD) cases each year. PD is presently the second most prevalent neurodegenerative disease, affecting an estimated 7-10 million individuals globally. This research aimed to identify mobile genetic elements in human fecal samples using a shotgun metagenomics approach. We found over 44,000 plasmid contigs and compared plasmid populations between PD patients (n = 68) and healthy controls (n = 68). Significant associations emerged between Body Mass Index (BMI) and plasmid alpha diversity. Moreover, the gene populations present on plasmids displayed marked differences in alpha and beta diversity between PD patients and healthy controls. We identified a considerable number of phage contigs that were differentially abundant in the two groups. Moreover, we improved the continuity and identification of the protein coding regions of the phage contigs by implementing alternative genetic codes. We built a classification system based on a selection of the phages differentially abundant in the groups. A machine learning approach based on phage abundances allowed a classification of the subjects into the PD or control group with an area under curve (AUC) of 0.969.
A bioactive peptide from the pearl has dual roles in resisting SARS-CoV-2 infection and its complications
Authors: Liu Xiaojun , Wang Yayu , Yin Zehui , Wang Qin , Chen Xinjiani , Li Bailei , Yao Liping , Zhang Zhen , Zhang Rongqing 
Published: October 2023

AbstractAngiotensin-converting enzyme 2 (ACE2) is a critical receptor for the entry of the SARS-CoV-2 virus into cells. Moreover, a decrease in ACE2 level and its activity due to SARS-CoV-2 infection is considered a crucial reason for the development of Covid-19-associated complications. Here, we report a bioactive peptide derived from the seawater pearl oysterPinctada fucata, named SCOL polypeptide, which binds strongly to ACE2 and effectively inhibits 65% of the binding of the SARS-CoV-2 S protein to ACE2; thus, this peptide can be used as a blocker to enable cells to resist SARS-CoV-2 infection. The SCOL polypeptide also increases ACE2 enzyme activity by 3.76 times. Previous studies have shown that ACE2 deficiency is associated with inflammation, pain, cardiovascular diseases, insulin resistance, and nervous system injury. Therefore, the SCOL polypeptide can be used to treat or alleviate complications such as lung inflammation, pain, diabetes, cardiovascular diseases, and loss of taste or smell caused by SARS-CoV-2 infection. Thus, the SCOL polypeptide can play a dual role in resisting SARS-CoV-2 infection.
LET-381/FoxF and UNC-30/Pitx2 control the development ofC. elegansmesodermal glia that regulate motor behavior
Authors: Stefanakis Nikolaos , Jiang Jessica , Liang Yupu , Shaham Shai 
Published: October 2023

ABSTRACTWhile most CNS glia arise from neuroectodermal progenitors, some, like microglia, are mesodermally derived. To understand mesodermal glia development and function, we investigatedC. elegansGLR glia, which ensheath the brain neuropil and separate it from the circulatory-system cavity. Transcriptome analysis suggests GLR glia merge astrocytic and endothelial characteristics relegated to separate cell types in vertebrates. Combined fate acquisition is orchestrated by LET-381/FoxF, a fate-specification/maintenance transcription factor expressed in glia and endothelia of other animals. Among LET-381/FoxF targets, UNC-30/Pitx2 transcription factor controls GLR glia morphology and represses alternative mesodermal fates. LET-381 and UNC-30 co-expression in naïve cells is sufficient for GLR glia gene expression. GLR glia inactivation by ablation orlet-381mutation disrupts locomotory behavior and induces salt hypersensitivity, suggesting brain-neuropil activity dysregulation. Our studies uncover mechanisms of mesodermal glia development and show that like neurons, glia differentiation requires autoregulatory terminal selector genes that define and maintain the glial fate.
Graded changes in local functional connectivity of the cerebral cortex in young people with depression
Authors: Jamieson Alec J. , Davey Christopher G. , Pujol Jesus , Blanco-Hinojo Laura , Harrison Ben J. 
Published: October 2023

AbstractMajor depressive disorder (MDD) is marked by significant changes to the coupling of spontaneous neural activity within various brain regions. However, many methods for assessing this local connectivity use fixed or arbitrary neighborhood sizes, resulting in a decreased capacity to capture smooth changes to the spatial gradient of local correlations. A newly developed method sensitive to classical anatomo-functional boundaries, Iso-Distant Average Correlation (IDAC), was therefore used to examine depression associated alterations to the local functional connectivity of the brain. One-hundred and forty-five adolescents and young adults with MDD and 95 healthy controls underwent a resting-state fMRI scan. Whole-brain functional connectivity maps of intracortical neural activity within iso-distant local areas (5-10mm, 15-20mm, and 25-30mm) were generated to characterize local fMRI signal similarities. Across all spatial distances, MDD participants demonstrated greater local functional connectivity of the bilateral posterior hippocampus, retrosplenial cortex, dorsal insula, fusiform gyrus, and supplementary motor area. Additionally, in the short and medium range connections there were depression associated alterations in the midcingulate (15-20mm and 25-30mm) and subgenual anterior cingulate (15-20mm). Our study identified increased synchrony of the neural activity in several regions commonly implicated in the neurobiology of depression; however, a subset of identified effects was dependent on the spatial distance under consideration. Longitudinal examination of these effects will clarify whether these differences are also found in other age groups and if this synchrony is additionally altered by continued disease progression.
Geranylgeranyl Isoprenoids and Hepatic Rap1a Regulate Basal and Statin-Induced Expression of PCSK9
Authors: Wang Yating , Tinsley Brea , Spolitu Stefano , Zadroga John A , Agarwal Heena , Sarecha Amesh K , Ozcan Lale 
Published: October 2023

AbstractLow-density lipoprotein cholesterol (LDL-C) lowering is the main goal of atherosclerotic cardiovascular disease prevention, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition is now a validated therapeutic strategy that lowers serum LDL-C and reduces coronary events. Ironically, the most widely used medicine to lower cholesterol, statins, has been shown to increase circulating PCSK9 levels, which limits their efficacy. Here, we show that geranylgeranyl isoprenoids and hepatic Rap1a regulate both basal and statin induced expression of PCSK9 and contribute to LDL-C homeostasis. Rap1a prenylation and activity is inhibited upon statin treatment, and statin mediated PCSK9 induction is dependent on geranylgeranyl synthesis and hepatic Rap1a. Accordingly, treatment of mice with a small molecule activator of Rap1a lowered PCSK9 protein and plasma cholesterol and inhibited statin mediated PCSK9 induction in hepatocytes. The mechanism involves inhibition of the downstream RhoA-ROCK pathway and regulation of PCSK9 at the post transcriptional level. These data further identify Rap1a as a novel regulator of PCSK9 protein and show that blocking Rap1a prenylation through lowering geranylgeranyl levels contributes to statin-mediated induction of PCSK9.
Comparison of alternative solvents forin situextraction of hydrocarbons from the colonial green algaBotryococcus brauniirace B (Showa)
Authors: Ozawa-Uyeda Takehiro A. , Overmans Sebastian , de Freitas Bárbara Bastos , Lozoya-Gloria Edmundo , Lauersen Kyle J. 
Published: October 2023

AbstractThe colony-forming, green microalgaBotryococcus brauniisecretes petroleum-like hydrocarbons, which enables the non-destructive continuousin situextraction, ‘milking’, of these extracellular products during culture growth without cell lysis. This work compares the suitability of 15 different solvents, including alkanes, halogenated solvents, and green solvents, forin situextraction ofB. brauniirace B (Showa strain) hydrocarbons after acclimation to moderate salinity stress. After 24 h of extraction, bio-based terpene ‘green’ solvents such as ɣ-terpinene showed the highest hydrocarbon recovery, around 10-fold greater than with conventional alkane solvents. Brominated alkanes and liquid perfluorocarbons (FCs) formed a lower phase to algal cultures rather than an upper phase as with other solvents, but only bromodecane effectively captured extracellular hydrocarbons similar to conventional alkane solvents. However, bromodecane and all green solvents were too toxic for two-phase continuous culture contact hydrocarbon milking, leading to 33–100% chlorophyll content loss. To overcome the biologically adverse effects of these solvents with suitable hydrocarbon recovery, future research should focus on their application in short-term extraction period ‘milking’ systems to minimize algal-solvent contact and enable continuous extraction.Abstract FigureGraphical Abstract
Fine-tuning TrailMap: The utility of transfer learning to improve the performance of deep learning in axon segmentation of light-sheet microscopy images
Authors: Oostrom Marjolein , Muniak Michael A. , Eichler West Rogene M. , Akers Sarah , Pande Paritosh , Obiri Moses , Wang Wei , Bowyer Kasey , Wu Zhuhao , Bramer Lisa M. , Mao Tianyi , Webb-Robertson Bobbie Jo 
Published: October 2023

AbstractLight-sheet microscopy has made possible the 3D imaging of both fixed and live biological tissue, with samples as large as the entire mouse brain. However, segmentation and quantification of that data remains a time-consuming manual undertaking. Machine learning methods promise the possibility of automating this process. This study seeks to advance the performance of prior models through optimizing transfer learning. We fine-tuned the existing TrailMap model using expert-labeled data from noradrenergic axonal structures in the mouse brain. By fine-tuning the final two layers of the neural network at a lower learning rate of the TrailMap model, we demonstrate an improved recall and an occasionally improved adjusted F1- score within our test dataset over using the originally trained TrailMap model.Availability and implementation: The software and data are freely available athttps://github.com/pnnl/brain_ohsuandhttps://data.pnl.gov/group/204/nodes/dataset/35673, respectively.
Bicyclomycin generates ROS and blocks cell division inEscherichia coli
Authors: Prakash Anand , Dutta Dipak 
Published: October 2023

AbstractThe role of reactive oxygen species (ROS) in the killing exerted by antibiotics on bacteria is debated. Evidences attribute the part of toxicity of many antibiotics to their ability to generate ROS by interfering with cellular metabolism, but some studies dismiss the role of ROS. Bicyclomycin (BCM) is a broad-spectrum antibiotic that is the only known compound to inhibitE. colitranscription terminator factor Rho with no known other cellular targets. In the present study, we addressed this question by checking whether the induction of oxidative stress could explain the increased sensitivity to Bicyclomycin in thehnsdeleted strain even in Δkilbackground inE. coli. BCM evoked the generation of ROS inE. colicells. BCM is known to cause the cell filamentation phenotype inE. coli.Performing fluorescence microscopic analysis, we show that bicyclomycin-dependent cell filamentation is associated with SOS response. RecA- GFP filaments were found to colocalize with the damaged DNA sites in the cell. Further analyzes revealed that the genomic DNA was partitioned but the cell septum formation was severely affected under BCM treatment. Furthermore, we observed biofilm formation byE. coliafter BCM treatment. We hypothesize that ROS production after BCM treatment could lead to cell filamentation in bacteria. A better understanding of the mode of toxicity of BCM will help us in designing better antibiotic treatment regimes for clinical practices, including combinatorial drug therapies. The cell filamentation phenotype observed after BCM treatment makes this antibiotic a promising drug for PAS therapy.
Phylogenetic diversity of the carbon monoxide-utilizing prokaryotes and their divergent carbon monoxide metabolisms in the human gut microbiome
Authors: Katayama Yuka Adachi , Kamikawa Ryoma , Yoshida Takashi 
Published: October 2023

AbstractAlthough the production of toxic CO within the human body has been detected, only a few CO-utilizing prokaryotes (CO utilizers) have been reported in the human gut, and their phylogenetic and physiological diversity remains unclear. Here, we unveiled more than thousand representative genomes originating from previously unexplored potential CO-utilizing prokaryotes, which contain CO dehydrogenase (CODH) genes. More than half of CODH-bearing prokaryotes possess genes for the autotrophic Wood–Ljungdahl pathway (WLP). However, 79% of these prokaryotes commonly lack a key gene for WLP, which encodes enzyme that synthesizes formate from CO2and reductants such as H2, suggesting that they share a degenerated WLP. Instead, many were predicted to possess an alternative way of synthesizing formate from pyruvate, which is a product of glycolysis. In addition to degenerated WLP, seven genes neighboring the CODH gene were found, which may reflect diverse utilization of CO in the human gut. Our findings reveal the unique and diverse nature of CO metabolism in the human gut microbiome, suggesting its potential contribution to CO consumption and gut homeostasis.Impact statementCarbon monoxide (CO)-utilizing prokaryotes mitigate the toxic impact of CO by consuming it as energy and/or carbon sources. In addition to various environments, CO is also produced via multiple routes, such as heme degradation, in the human body and accumulates in the gut. Revealing CO-utilizing prokaryotes and their CO metabolisms in the human gut would contribute to gaining insight into how microbial community functions are involved in maintaining human gut homeostasis. Nevertheless, the limited number of CO utilizers in the human gut microbiome have been reported. In our study, a significant proportion of human gut microbial genomes belonging to diverse phyla were revealed to be of potential CO-utilizing prokaryotes. Additionally, the majority of CO-utilizing prokaryote genomes in the human gut have potentially remodeled the Wood– Ljungdahl pathway (WLP), one of the most well-known autotrophic pathways, to the degenerated, heterotrophic form. Moreover, there were seven other genes neighboring CODH in the human gut CO-utilizers, suggesting various CO utilization. Our findings would pave the way for future explorations into microbial metabolic adaptations and their implications for human health.Data summaryThe human gut prokaryote genomes were downloaded from HumGut database (Hiseni et al. 2021;https://arken.nmbu.no/~larssn/humgut/). The accession numbers of CODH/ACS-bearing genomes from environments without host-association (Inoueet al., 2022) are listed in Table S1. Metatranscriptomic datasets were downloaded from the NCBI Sequence Read Archive (SRA) under the Bioproject accession numbers PRJNA354235 and PRJNA707065 and their accession IDs are listed in Table S2.
Data-driven regularisation lowers the size barrier of cryo-EM structure determination
Authors: Kimanius Dari , Jamali Kiarash , Wilkinson Max E , Lövestam Sofia , Velazhahan Vaithish , Nakane Takanori , Scheres Sjors H.W. 
Published: October 2023

AbstractMacromolecular structure determination by electron cryo-microscopy (cryo-EM) is limited by the alignment of noisy images of individual particles. Because smaller particles have weaker signals, alignment errors impose size limitations on its applicability. Here, we explore how image alignment is improved by the application of deep-learning to exploit prior knowledge about biological macromolecular structures that would otherwise be difficult to express mathematically. We train a denoising convolutional neural network on pairs of half-set reconstructions from the electron microscopy data bank (EMDB) and use this denoiser as an alternative to a commonly used smoothness prior. We demonstrate that this approach, which we call Blush regularisation, yields better reconstructions than existing algorithms, in particular for data with low signal-to-noise ratios. The reconstruction of a protein-nucleic acid complex with a molecular weight of 40 kDa, which was previously intractable, illustrates that regularisation through denoising will expand the applicability of cryo-EM structure determination for a wide range of biological macromolecules.