bluuebunny/crossref_metadata_2025 huggingface dataset:
nf-core/taxprofiler: highly parallelised and flexible pipeline for metagenomic taxonomic classification and profiling
Authors: Stamouli Sofia , Beber Moritz E. , Normark Tanja , Christensen Thomas A. , Andersson-Li Lili , Borry Maxime , Jamy Mahwash ,   nf-core community, Fellows Yates James A.
Published: October 2023

1 Abstract

Metagenomic classification tackles the problem of characterising the taxonomic source of all DNA sequencing reads in a sample. A common approach to address the differences and biases between the many different taxonomic classification tools is to run metagenomic data through multiple classification tools and databases. This, however, is a very time-consuming task when performed manually - particularly when combined with the appropriate preprocessing of sequencing reads before the classification.

Here we present nf-core/taxprofiler, a highly parallelised read-processing and taxonomic classification pipeline. It is designed for the automated and simultaneous classification and/or profiling of both short- and long-read metagenomic sequencing libraries against a 11 taxonomic classifiers and profilers as well as databases within a single pipeline run. Implemented in Nextflow and as part of the nf-core initiative, the pipeline benefits from high levels of scalability and portability, accommodating from small to extremely large projects on a wide range of computing infrastructure. It has been developed following best-practise software development practises and community support to ensure longevity and adaptability of the pipeline, to help keep it up to date with the field of metagenomics.
Synergistic phenotypic shifts during domestication promote plankton-to-biofilm transition in purple sulfur bacteriumChromatium okenii
Authors: Di Nezio Francesco , Ong Irvine Lian Hao , Riedel René , Goshal Arkajyoti , Dhar Jayabrata , Roman Samuele , Storelli Nicola , Sengupta Anupam
Published: October 2023

The ability to isolate microorganisms from natural environments to pure cultures under optimized laboratory settings has markedly improved our understanding of microbial ecology. Laboratory-induced artificial growth conditions often diverge from those in natural ecosystems, forcing wild isolates into selective pressures which are distinct compared to those in nature. Consequently, fresh isolates undergo diverse eco-physiological adaptations mediated by modification of key phenotypic traits. For motile microorganisms, we still lack a biophysical understanding of the relevant traits which emerge during domestication, and possible mechanistic interrelations between them which could ultimately drive short-to-long term microbial adaptation under laboratory conditions. Here, using microfluidics, atomic force microscopy (AFM), quantitative imaging, and mathematical modelling, we study phenotypic adaptation of natural isolates ofChromatium okenii, a motile phototrophic purple sulfur bacterium (PSB) common to meromictic settings, grown under ecologically-relevant laboratory conditions over multiple generations. Our results indicate that the naturally planktonicC. okeniipopulations leverage synergistic shifts in cell-surface adhesive interactions, together with changes in their cell morphology, mass density, and distribution of intracellular sulfur globules, to supress their swimming traits, ultimately switching to a sessile lifeform under laboratory conditions. A computational model of cell mechanics confirms the role of the synergistic phenotypic shifts in suppressing the planktonic lifeform. Over longer domestication periods (∼10 generations), the switch from planktonic to sessile lifeform is driven by loss of flagella and enhanced adhesion. By investigating key phenotypic traits across different physiological stages of lab-grownC. okenii, we uncover a progressive loss of motility via synergistic phenotypic shifts during the early stages of domestication, which is followed by concomitant deflagellation and enhanced surface attachment that ultimately drive the transition of motile sulphur bacteria to a sessile biofilm state. Our results establish a mechanistic link between suppression of motility and surface attachment via synergistic phenotypic changes, underscoring the emergence of adaptive fitness under felicitous laboratory conditions that comes at a cost of lost ecophysiological traits tailored for natural environments.

Graphical abstract
Local sleep in songbirds: Different simultaneous sleep states across the avian pallium
Authors: Yeganegi Hamed , Ondracek Janie M.
Published: October 2023

Wakefulness and sleep have often been treated as distinct and global brain states. However, an emerging body of evidence on the local regulation of sleep stages challenges this conventional view. Apart from unihemispheric sleep, the current data that support local variations of neural oscillations during sleep are focused on the homeostatic regulation of local sleep, i.e., the role preceding awake activity. Here, to examine local differences in brain activity during natural sleep, we recorded the electroencephalogram (EEG) and the local field potential (LFP) across multiple sites within the avian pallium of zebra finches without perturbing the previous awake state. We scored the sleep stages independently in each pallial site and found that the sleep stages are not pallium-wide phenomena but rather deviate widely across electrode sites. Importantly, deeper electrode sites had a dominant role in defining the temporal aspects of sleep state congruence. Altogether, these findings show that local regulation of sleep oscillations also occurs in the avian brain without prior awake recruitment of specific pallial circuits and in the absence of mammalian cortical neural architecture.
Conformations of a highly expressed Z19 α-zein studied with AlphaFold2 and MD simulations
Authors: Christensen Niels Johan
Published: October 2023

α-zeins are amphiphilic maize proteins with interesting material properties suitable for numerous applications, e.g., in renewable plastics, foods, therapeutics and additive manufacturing (3D-printing). To exploit their full potential, molecular-level insights are essential. Since α-zeins have resisted experimental atomic-resolution characterization, molecular models have been central to elucidating their structure, but deep-learning α-zein models are largely unexplored. Therefore, this work studies an AlphaFold2 model of a highly expressed zein with molecular dynamics (MD) simulations. The mature protein sequence of the α-zein cZ19C2 gave a loosely packed model with 7 α-helical segments connected by turns/loops and 68% total α-helicity. Compact tertiary structure was limited to a C-terminal bundle of three α-helices, each aligning well with the published repeat sequence NPAAYLQQQQLLPFNQLA(V/A)(L/A). The model was subjected to MD simulations in water containing 0, 3, 23, 50, and 100 mol% ethanol for 400 ns, with extension of selected simulations to the μs timescale. Although the simulations gave structurally diverse endpoints, several patterns were observed: In water and ≤ 2 mol% ethanol, the model rapidly formed compact globular structures, largely preserving the C-terminal bundle. At ≥ 50 mol% ethanol, extended conformations prevailed, consistent with previous SAXS studies. Tertiary structure was partially stabilized in water and in 2 mol% and 23 mol% ethanol, but was disrupted in ≥ 50 mol% ethanol. Averaged results indicated slightly increased helicity with ethanol concentration. Multiple copies of a globular model conformation rapidly formed branched aggregates in aqueous all-atom and coarse-grained MD simulations. β-sheet content was typically <1% across all simulations. In aqueous simulations with glycidyl methacrylate (GMA), 55% of GMA was found within 4 Å of the model. Pre-reaction complexes for methacrylation were indicated by GMA epoxide carbons within 2.9 – 3.3 Å of side chain hydroxyl oxygens, suggesting accessibility of reactive sites in compact α-zein conformations.
A dynamic humidity arena to explore humidity related behaviours in insects
Authors: Giri Ganesh , Nagloo Nicolas , Enjin Anders
Published: October 2023

Humidity is a critical environmental factor influencing the behaviour of terrestrial organisms. Despite its significance, the neural mechanisms and behavioural algorithms governing humidity sensation in insects remain elusive. In this study, we introduce a novel dynamic humidity arena to investigate humidity-guided behaviour in the vinegar flyDrosophila melanogaster. The arena allows precise humidity control, low error rates, and fast settling times, making it a robust tool for studying humidity-related behaviours. Our results reveal that desiccated and starved flies (DS flies) search for higher relative humidity environments (65-75%) while sated flies tend to stay within their initial environments. In contrast, Ionotropic receptor (Ir)93a mutant flies with impaired humidity sensing show no preference to relative humidity. The search for higher humidity in DS flies is reflected in their relatively high displacement and walking speed compared to control and mutant flies. Our novel method manipulates humidity cues to create complex humidity landscapes that respond in real-time to insect movement. This will help us shed light on how humidity shapes behaviour and offers a foundation for further research in the field of hygrosensation.
Cysteine hyperoxidation rewires communication pathways in the nucleosome and destabilizes the dyad
Authors: Karami Yasaman , Bignon Emmanuelle
Published: October 2023

Gene activity is tightly controlled by reversible chemical modifications called epigenetic marks, which are of various types and modulate gene accessibility without affecting the DNA sequence. Despite an increasing body of evidence demonstrating the role of oxidative-type modifications of histones in gene expression regulation, there remains a complete absence of structural data at the atomistic level to understand the molecular mechanisms behind their regulatory action. Owing toμs time-scale MD simulations and protein communication networks analysis, we describe the impact of histone H3 hyperoxidation (i.e., S-sulfonylation) on the nucleosome dynamics. Our results reveal the atomic-scale details of the intrinsic structural networks within the canonical histone core and their perturbation by hyperoxidation of the histone H3 C110. We show that this modification involves local rearrangement of the communication networks and destabilizes the dyad, which could be important for nucleosome disassembly.
Novel diagnosis- and progression-related microRNA signatures in melanoma
Authors: Gómez-Martínez Helena , Gómez-Cabañes Borja , Galiana-Roselló Cristina , Morales Alejandro Virués , Rabinad Beatriz Dolader , Rey Díez Natalia del , López Adolfo , Hernando Eva , García-García Francisco
Published: October 2023

Melanoma, an aggressive form of skin cancer with a high mortality rate, has recently experienced an increase in incidence. Consequently, the search for biomarkers, such as microRNAs (miRNAs), to facilitate the early detection and management of cancer patients represents a significant current concern.

To identify these potential biomarkers, we developed a novel and integrative strategy. This involved conducting a systematic review of melanoma studies in accordance with PRISMA guidelines, followed by the performance of exploratory analysis and data normalization. Subsequently, individual analyses were conducted for each study, followed by a meta-analysis of miRNAs that integrated all results while considering patient information.

In the diagnostic scenario, we identified twenty-four differentially expressed miRNAs, with eleven being upregulated and thirteen being downregulated. In the severity scenario, a total of twenty-three differentially expressed miRNAs were identified, comprising seven that were upregulated and sixteen that were downregulated. An extensive functional characterization of these miRNA signatures was conducted, providing insight into their biological role and impact on melanoma diagnosis and prognosis.

Our findings contribute to a more comprehensive understanding of the molecular mechanisms and developmental processes involved in melanoma, particularly in early-stage development and ulceration. This, in turn, provides a foundation for the development of novel resources for the precise detection and treatment of melanoma.
Socioecological drivers of injuries in female and male rhesus macaques (Macaca mulatta)
Authors: Pavez-Fox Melissa A. , Siracusa Erin R. , Ellis Samuel , Kimock Clare M. , Rivera-Barreto Nahiri , Negron-Del Valle Josue E. , Phillips Daniel , Ruiz-Lambides Angelina , Snyder-Mackler Noah , Higham James P. , Brent Lauren J.N. , De Moor Delphine
Published: October 2023

Competition over access to resources, such as food and mates, is believed to be one of the major costs associated with group living. Two socioecological factors suggested to predict the intensity of competition are group size and the relative abundance of sexually active individuals. However, empirical evidence linking these factors to injuries and survival costs is scarce. Here, we leveraged 10 years of data from free-ranging rhesus macaques where injuries inflicted by conspecifics are associated with a high mortality risk. We tested if group size and adult sex ratio predicted the occurrence of injuries and used data on physical aggression to contextualise these results. We found that males were less likely to be injured when living in larger groups, potentially due to advantages in intergroup encounters. Females, instead, had higher injury risk when living in larger groups but this was not explained by within-group aggression among females. Further, male-biased sex ratios predicted a weak increase in injury risk in females and were positively related to male-female aggression, indicating that male coercion during mating competition may be a cause of injuries in females. Overall, our results provide insights into sex differences in the fitness-related costs of competition and empirical evidence for long-standing predictions on the evolution of group living.
Matrix architecture and mechanics regulate myofibril organization, costamere assembly, and contractility of engineered myocardial microtissues
Authors: DePalma Samuel J. , Jillberto Javiera , Stis Austin E. , Huang Darcy D. , Lo Jason , Davidson Christopher D. , Chowdhury Aamilah , Jewett Maggie E. , Kobeissi Hiba , Chen Christopher S. , Lejeune Emma , Helms Adam S. , Nordsletten David A. , Baker Brendon M.
Published: October 2023

The mechanical function of the myocardium is defined by cardiomyocyte contractility and the biomechanics of the extracellular matrix (ECM). Understanding this relationship remains an important unmet challenge due to limitations in existing approaches for engineering myocardial tissue. Here, we established arrays of cardiac microtissues with tunable mechanics and architecture by integrating ECM-mimetic synthetic, fiber matrices and induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), enabling real-time contractility readouts, in-depth structural assessment, and tissue-specific computational modeling. We find that the stiffness and alignment of matrix fibers distinctly affect the structural development and contractile function of pure iPSC-CM tissues. Further examination into the impact of fibrous matrix stiffness enabled by computational models and quantitative immunofluorescence implicates cell-ECM interactions in myofibril assembly and notably costamere assembly, which correlates with improved contractile function of tissues. These results highlight how iPSC-CM tissue models with controllable architecture and mechanics can inform the design of translatable regenerative cardiac therapies.
Personalised metabolic whole-body models for newborns and infants predict growth and biomarkers of inherited metabolic diseases
Authors: Zaunseder Elaine , Mütze Ulrike , Okun Jürgen G. , Hoffmann Georg F. , Kölker Stefan , Heuveline Vincent , Thiele Ines
Published: October 2023

Extensive whole-body models (WBMs) accounting for organ-specific dynamics have been developed to simulate adult metabolism. However, there is currently a lack of models representing infant metabolism taking into consideration its special requirements in energy balance, nutrition, and growth. Here, we present a resource of organ-resolved, sex-specific, anatomically accurate models of newborn and infant metabolism, referred to as infant-whole-body models (infant-WBMs), spanning the first 180 days of life. These infant-WBMs were parameterised to represent the distinct metabolic characteristics of newborns and infants accurately. In particular, we adjusted the changes in organ weights, the energy requirements of brain development, heart function, and thermoregulation, as well as dietary requirements and energy requirements for physical activity. Subsequently, we validated the accuracy of the infant-WBMs by showing that the predicted neonatal and infant growth was consistent with the recommended growth by the World Health Organisation. We assessed the infant-WBMs’ reliability and capabilities for personalisation by simulating 10,000 newborn models, personalised with blood concentration measurements from newborn screening and birth weight. Moreover, we demonstrate that the models can accurately predict changes over time in known blood biomarkers in inherited metabolic diseases. By this, the infant-WBM resource can provide valuable insights into infant metabolism on an organ-resolved level and enable a holistic view of the metabolic processes occurring in infants, considering the unique energy and dietary requirements as well as growth patterns specific to this population. As such, the infant-WBM resource holds promise for personalised medicine, as the infant-WBMs could be a first step to digital metabolic twins for newborn and infant metabolism for personalised systematic simulations and treatment planning.
Do bed bugs transmit human viruses, or do humans transmit bed bug viruses? A worldwide survey of the bed bug RNA virosphere
Authors: Walt Hunter K. , King Jonas G. , Sheele Johnathan M. , Meyer Florencia , Pietri Jose E. , Hoffmann Federico G.
Published: October 2023

Bed bugs (Hemiptera:Cimicidae) are a globally distributed hematophagous pest that routinely feed on humans. Unlike many blood-sucking arthropods, they have never been linked to disease transmission in a natural setting, and despite interest in their role as disease vectors, little is known about the viruses that bed bugs naturally harbor. Here, we present a global-scale survey of the bed bug RNA virosphere. We sequenced the metatranscriptomes of 22 individual bed bugs (Cimex lectulariusandCimex hemipterus) from 8 locations around the world. We detected sequences from two known bed bug viruses (Shuangao bedbug virus 1 and Shuangao bedbug virus 2) which extends their geographical range and the host range of Shuangao bedbug virus 1 toCimex lectularius. We identified three novel bed bug virus sequences from a tenui-like virus (Bunyavirales), a toti-like virus (Ghabrivirales), and a luteo-like virus (Tolivirales).

Interestingly, some of the bed bug viruses branch near to insect-transmitted plant-infecting viruses, opening questions regarding the evolution of plant virus infection. When we analyzed the putative viral sequences by their host’s collection location, we found unexpected patterns of geographical diversity that may reflect humans’ role in bed bug dispersal. Additionally, we investigated the effect thatWolbachia,the primary bed bug endosymbiont, may have on viral abundance and found thatWolbachiainfection neither promotes nor inhibits viral infection. Finally, our results provide no evidence that bed bugs transmit any known human pathogenic viruses.
Y chromosome damage underlies testicular abnormalities in ATR-X syndrome
Authors: Carlos Nayla Leon , Le Thanh Nha Uyen , Garvie Andrew , Wong Lee H , Bagheri-Fam Stefan , Harley Vincent R
Published: October 2023

ATR-X (alphathalassemia,mentalretardation,X-linked) syndrome is a severe developmental disorder affecting males caused by mutations in the chromatin remodelling geneATRX. Genital abnormalities in affected boys include hypospadias and ambiguous genitalia, and patients show small poorly formed testes with only a few seminiferous tubules. Our mouse model recapitulated these testicular defects whenAtrxwas specifically deleted in Sertoli cells (ScAtrxKO). ScAtrxKO mice develop small testes with fewer and discontinuous tubules due to G2/M arrest and apoptosis of Sertoli cells.

Here, we investigated the mechanism underlying the Sertoli cell defects in ATR-X syndrome. In healthy male control mice, Sertoli cell nuclei contain a single novel “GATA4 PML nuclear body (NB)” that strongly expresses the transcription factor GATA4, as well as ATRX and its binding partner DAXX. The GATA4 PML NB co-localizes with heterochromatin protein HP1α and PH3 (a marker of chromosome condensation), and with the short arm of the Y chromosome (Yp). In contrast, ScAtrxKO Sertoli cells contain a single giant GATA4 PML NB, frequently associated with DNA double-strand breaks in G2/M-arrested Sertoli cells that underwent apoptosis. HP1α and PH3 were absent from the giant GATA4 foci suggesting a local failure in heterochromatin formation and chromosome condensation. Our data indicate that in Sertoli cells, ATRX protects a chromosomal region of Yp from DNA damage, probably during replication stress, and thus protects Sertoli cells from cell death. We discuss Y chromosome damage as a novel mechanism for testicular failure and the potential role of GATA4 during this process.

Disclosure Summary

The authors have nothing to disclose.
Changes in total charge on spike protein of SARS-CoV-2 in emerging lineages
Authors: Bozic Anze , Podgornik Rudolf
Published: October 2023

Motivation: Charged amino acid residues on the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been shown to influence its binding to different cell surface receptors, its non-specific electrostatic interactions with the environment, and its structural stability and conformation. It is therefore important to obtain a good understanding of amino acid mutations that affect the total charge on the spike protein which have arisen across different SARS-CoV-2 lineages during the course of the virus' evolution. Results: We analyse the change in the number of ionizable amino acids and the corresponding total charge on the spike proteins of almost 2200 SARS-CoV-2 lineages that have emerged over the span of the pandemic. Our results show that the previously observed trend toward an increase in the positive charge on the spike protein of SARS-CoV-2 variants of concern has essentially stopped with the emergence of the early omicron variants. Furthermore, recently emerged lineages show a greater diversity in terms of their composition of ionizable amino acids. We also demonstrate that the patterns of change in the number of ionizable amino acids on the spike protein are characteristic of related lineages within the broader clade division of the SARS-CoV-2 phylogenetic tree. Due to the ubiquity of electrostatic interactions in the biological environment, our findings are relevant for a broad range of studies dealing with the structural stability of SARS-CoV-2 and its interactions with the environment. Availability: The data underlying the article are available in the online Supplementary Material.
A 50-gene high-risk profile predictive of COVID-19 and Idiopathic Pulmonary Fibrosis mortality originates from a genomic imbalance in monocyte and T-cell subsets that reverses in survivors with post-COVID-19 Interstitial Lung Disease
Authors: Tourki Bochra , Jia Minxue , Karampitsakos Theodoros , Vera Iset M , Arsenault Alyssa , Marlin Krystin , Perrot Carole Y , Allen Dylan , Farsaei Forouzandeh , Rutenberg David , Bandyopadhyay Debabrata , Restrepo Ricardo , Qureshi Muhammad R. , Patel Kapilkumar , Tzouvelekis Argyrios , Kapetanaki Maria , Juan-Guardela Brenda , Kim Kami , Benos Panayiotis V , Herazo-Maya Jose D.
Published: October 2023

Background

We aim to study the source of circulating immune cells expressing a 50-gene signature predictive of COVID-19 and IPF mortality.

Methods

Whole blood and Peripheral Blood Mononuclear cells (PBMC) were obtained from 231 subjects with COVID-19, post-COVID-19-ILD, IPF and controls. We measured the 50-gene signature (nCounter, Nanostring), interleukin 6 (IL6), interferon γ-induced protein (IP10), secreted phosphoprotein 1 (SPP1) and transforming growth factor beta (TGF-β) by Luminex. PCR was used to validate COVID-19 endotypes. For single-cell RNA sequencing (scRNA-seq) we used Chromium Controller (10X Genomics). For analysis we used the Scoring Algorithm of Molecular Subphenotypes (SAMS), Cell Ranger, Seurat, Propeller, Kaplan-Meier curves, CoxPH models, Two-way ANOVA, T-test, and Fisher’s exact.

Results

We identified three genomic risk profiles based on the 50-gene signature, and a subset of seven genes, associated with low, intermediate, or high-risk of mortality in COVID-19 with significant differences in IL6, IP10, SPP1 and TGFβ-1. scRNA-seq identified Monocytic-Myeloid-Derived Suppressive cells (M-MDSCs) expressing CD14+HLA DRlowCD163+and high levels of the 7-gene signature (7Gene-M-MDSC) in COVID-19. These cells were not observed in post-COVID-19-ILD or IPF. The 43-gene signature was mostly expressed in CD4 T and CD8 T cell subsets. Increased expression of the 43 gene signature was seen in T cell subsets from survivors with post-COVID-19-ILD. The expression of these genes remained low in IPF.

Conclusion

A 50-gene, high-risk profile in COVID-19 is characterized by a genomic imbalance in monocyte and T-cell subsets that reverses in survivors with post-COVID-19 Interstitial Lung Disease
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

Understanding 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

In 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

Biomembrane 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

Over 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

The 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.
Nonspecific membrane bilayer perturbations by ivermectin underlie SARS-CoV-2 in vitro activity
Authors: Eastman Richard T , Rusinova Radda , Herold Karl F , Huang Xi-Ping , Dranchak Patricia , Voss Ty C , Rana Sandeep , Shrimp Jonathan H , White Alex D , Hemmings Hugh C , Roth Bryan L , Inglese James , Andersen Olaf S , Dahlin Jayme L
Published: October 2023

Since it was proposed as a potential host-directed antiviral agent for SARS-CoV-2, the antiparasitic drug ivermectin has been investigated thoroughly in clinical trials, which have provided insufficient support for its clinical efficacy. To examine the potential for ivermectin to be repurposed as an antiviral agent, we therefore undertook a series of preclinical studies. Consistent with early reports, ivermectin decreased SARS-CoV-2 viral burden in in vitro models at low micromolar concentrations, five- to ten-fold higher than the reported toxic clinical concentration. At similar concentrations, ivermectin also decreased cell viability and increased biomarkers of cytotoxicity and apoptosis. Further mechanistic and profiling studies revealed that ivermectin nonspecifically perturbs membrane bilayers at the same concentrations where it decreases the SARS-CoV-2 viral burden, resulting in nonspecific modulation of membrane-based targets such as G-protein coupled receptors and ion channels. These results suggest that a primary molecular mechanism for the in vitro antiviral activity of ivermectin may be nonspecific membrane perturbation, indicating that ivermectin is unlikely to be translatable into a safe and effective antiviral agent. These results and experimental workflow provide a useful paradigm for performing preclinical studies on (pandemic-related) drug repurposing candidates.
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

Angiotensin-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

While 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

Major 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

Low-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

The 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.

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Graphical 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

Light-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

The 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.