bluuebunny/crossref_metadata_2025_split huggingface dataset:
Convergent evolution in silico reveals shape and dynamic principles of directed locomotion
Authors: Biazzi Renata B , Fujita André , Takahashi Daniel Y 
Published: November 2022

AbstractActive, directed locomotion on the ground is present in many phylogenetically distant species. Bilateral symmetry and modularity of the body are common traits often associated with improved directed locomotion. Nevertheless, both features result from natural selection, which is contingent (history-dependent) and multifactorial (several factors interact simultaneously). Based solely on the unique natural history on Earth, it is difficult to conclude that bilateral symmetry and modularity of the body are required traits for an improved locomotion ability as they can result from chance or be related to other body functions. As a way to avoid these caveats, we propose using physics-based simulations of 3D voxel-based soft robots evolved under different evolutionary scenarios to test the necessity of both traits for sustained and effective displacement on the ground. We found that an intermediate number of body modules (appendages) and high body symmetry are evolutionarily selected regardless of gravitational environments, robot sizes, and genotype encoding. Therefore, we conclude that both traits are strong candidates for universal principles related to improved directed locomotion.
Predicting Lifespan-Extending Chemical Compounds with Machine Learning and Biologically Interpretable Features
Authors: Ribeiro Caio , Farmer Christopher K. , de Magalhães João Pedro , Freitas Alex A. 
Published: November 2022

AbstractRecently, there has been a growing interest in the development of pharmacological interventions targeting ageing, as well as on the use of machine learning for analysing ageing-related data. In this work we use machine learning methods to analyse data from DrugAge, a database of chemical compounds (including drugs) modulating lifespan in model organisms. To this end, we created four datasets for predicting whether or not a compound extends the lifespan ofC. elegans(the most frequent model organism in DrugAge), using four different types of predictive biological features, based on compound-protein interactions, interactions between compounds and proteins encoded by ageing-related genes, and two types of terms annotated for proteins targeted by the compounds, namely Gene Ontology (GO) terms and physiology terms from the WormBase’s Phenotype Ontology. To analyse these datasets we used a combination of feature selection methods in a data pre-processing phase and the well-established random forest algorithm for learning predictive models from the selected features. The two best models were learned using GO terms and protein interactors as features, with predictive accuracies of about 82% and 80%, respectively. In addition, we interpreted the most important features in those two best models in light of the biology of ageing, and we also predicted the most promising novel compounds for extending lifespan from a list of previously unlabelled compounds.
Instantaneous antidepressant effect of lateral habenula deep brain stimulation in rats studied with functional magnetic resonance imaging
Authors: Li Gen , Bo Binshi , Wang Puxin , Qian Peixing , Li Mingzhe , Li Yuyan , Tong Chuanjun , Zhang Kaiwei , Zhang Baogui , Jiang Tianzi , Liang Zhifeng , Duan Xiaojie 
Published: November 2022

AbstractThe available treatments for depression have substantial limitations, including low response rates and substantial lag time before a response is achieved. We applied deep brain stimulation (DBS) to the lateral habenula (LHb) of two rat models of depression (Wistar Kyoto rats and lipopolysaccharide-treated rats) and observed an immediate (within seconds to minutes) alleviation of depressive-like symptoms with a high response rate. Simultaneous functional magnetic resonance imaging (fMRI) conducted on the same sets of depressive rats used in behavioral tests revealed DBS-induced activation of multiple regions in afferent and efferent circuitry of the LHb. The activation levels of brain regions connected to the medial LHb (M-LHb) was correlated with the extent of behavioral improvements. Rats with more medial stimulation sites in the LHb exhibited greater antidepressant effects than those with more lateral stimulation sites. These results indicated that the antidromic activation of the limbic system and orthodromic activation of the monoaminergic systems connected to the M-LHb played a critical role in the rapid antidepressant effects of LHb-DBS. This study indicates that M-LHb-DBS might act as a valuable, rapid-acting antidepressant therapeutic strategy for treatment-resistant depression and demonstrates the potential of using fMRI activation of specific brain regions as biomarkers to predict and evaluate antidepressant efficacy.
No evidence for an effect of chronic boat noise on the fitness of reared water fleas
Authors: Prosnier Loïc , Rojas Emilie , Médoc Vincent 
Published: November 2022

AbstractAmong the numerous questions about human impacts on ecosystems, there is a growing interest for acoustic pollution. First studies on underwater acoustic pollution focused, and showed effects, on vertebrates’ behaviours. Knowledge on the effects on invertebrates is more limited and there is a huge lack concerning zooplankton species, although widely used as bioindicators in chemical pollution. Consequently, it is critical to assess the impact of noise on zooplankton’s fitness (survival and fecundity). Here, isolated water fleas,Daphnia magna, were reared from birth to death in the presence or absence of motorboat noises. Effects on lifespan and clonal offspring production (e.g., clutch size, number of offspring produced along life) were assessed and chronic exposure to boat noise did not affectDaphnia’s fitness. The spectral and temporal features of the sounds could explain the results. This study highlights the importance of integrating noise pollution into ecotoxicological research to understand, and prevent, human impacts on communities.
Soil metatranscriptomics: An improved RNA extraction method toward functional analysis using nanopore direct RNA sequencing
Authors: Poursalavati Abdonaser , Javaran Vahid J. , Laforest-Lapointe Isabelle , Fall Mamadou L. 
Published: November 2022

AbstractSoil microbes play an undeniable role in sustainable agriculture, plant health, and soil management. A deeper understanding of soil microbial composition and function has been gained through next-generation sequencing. While soil metagenomics has provided valuable information about microbial diversity, issues stemming from RNA extraction, low RNA abundance in some microbial populations (e.g., viruses), and mRNA enrichment have slowed the progress of soil metatranscriptomics. A variety of soil RNA extraction methods have been developed so far. Yet none of the available protocols can obtain RNA with high quality, purity, and yield for third-generation sequencing. This latter requires RNA with high quality and large quantities (with no or low contamination, such as humic acids). Also, use of commercial kits for in-batch soil RNA extraction is quite expensive, and these commercial kits lack buffer composition details, which prevents the optimization of protocols for different soil types. An improved and cost-effective method for extracting RNAs from mineral and organic soils is presented in this paper. An acidic sodium acetate buffer and phosphate buffer with modifications to bead-beating and nucleic acid precipitation lead to higher RNA yields and quality. Using this method, we obtained almost DNA-free RNA. By using nanopore’s direct RNA sequencing, the extracted contamination-free RNAs were successfully sequenced. Lastly, taxonomic groups such as bacteria, fungi, archaea, and viruses were classified and profiled as well as functional annotation of the datasets was carried out using an in-house customized bioinformatics workflow.
Safety and immunogenicity of SARS-CoV-2 self-amplifying RNA vaccine expressing anchored RBD: a randomised, observer-blind, phase 1 study
Authors: Akahata Wataru , Sekida Takashi , Nogimori Takuto , Ode Hirotaka , Tamura Tomokazu , Kono Kaoru , Kazami Yoko , Washizaki Ayaka , Masuta Yuji , Suzuki Rigel , Matsuda Kenta , Komori Mai , Morey Amber , Ishimoto Keiko , Nakata Misako , Hasunuma Tomoko , Fukuhara Takasuke , Iwatani Yasumasa , Yamamoto Takuya , Smith Jonathan F , Sato Nobuaki 
Published: November 2022

SummaryBACKGROUNDVLPCOV-01 is a lipid nanoparticle-encapsulated self-amplifying RNA (saRNA) vaccine that expresses a membrane-anchored receptor-binding domain (RBD) derived from the SARS-CoV-2 spike protein.METHODSA phase 1 study of VLPCOV-01 was conducted at Medical Corporation Heishinkai OPHAC Hospital, Japan. Participants aged 18 to 55 or ≥65 years who had completed two doses of the BNT162b2 mRNA vaccine 6 to 12 months previously were randomised to receive one intramuscular vaccination of 0·3, 1·0, or 3·0 μg VLPCOV-01, 30 μg BNT162b2, or placebo between February 16, 2022, and March 17, 2022. Solicited adverse events were collected up to 6 days post-administration. Interim immunogenicity analyses included SARS-CoV-2 IgG and neutralising antibody titres. Follow-up for safety and immunogenicity evaluation is ongoing. (The trial is registered: jRCT2051210164).FINDINGS92 healthy adults were enrolled, with 60 participants receiving VLPCOV-01. No serious adverse events were reported up to 26 weeks, and no prespecified trial-halting events were met. VLPCOV-01 induced robust IgG titres against SARS-CoV-2 RBD protein that were maintained up to 26 weeks in non-elderly participants, with geometric means ranging from 5037 (95% CI 1272–19,940) at 0·3 μg to 12,873 (95% CI 937–17,686) at 3 μg, in comparison to 3166 (95% CI 1619–6191) with 30 μg BNT162b2. Among elderly participants, IgG titres at 26 weeks post-vaccination with 3 μg VLPCOV-01 were 9865 (95% CI 4396–22138) compared to 4183 (95% CI 1436–12180) following vaccination with 30 μg BNT162b2. Pseudovirus neutralising antibody responses were observed against multiple SARS-CoV-2 variants and strongly correlated with anti-SARS-CoV-2 IgG (r=0·950, p<0·001).INTERPRETATIONVLPCOV-01 is immunogenic following low dose administration, with anti-SARS-CoV-2 immune responses comparable to BNT162b2. These findings support further development of VLPCOV-01 as a COVID-19 booster vaccine and the potential for saRNA vectors as a vaccine platform.FUNDINGSupported by AMED, Grant No. JP21nf0101627.
Is anxiety a pathway to Alcohol Use Disorders? A phenome-wide association study of theGABRA2coding variant rs279858
Authors: Merikangas Alison K. , Kember Rachel L. , Plawecki Martin H. , Kamarajan Chella , Chan Grace , Bauer Lance , Meyers Jacquelyn L. , Nurnberger John I. , Kramer John , Porjesz Bernice , Edenberg Howard J. , Almasy Laura 
Published: November 2022

AbstractAlcohol use disorders (AUDs) and related electrophysiological endophenotypes have been associated with theGABRA2gene. However, the causal variants inGABRA2and their mechanisms of influence on AUD and its correlates have not been established. Here we investigate the phenotypic spectrum of aGABRA2coding variant (rs279858) through a phenome-wide association study (PheWAS) in two open-source datasets.We applied the PheWAS approach to identify a broad range of phenotypes associated with rs279858 in the MRC IEU OpenGWAS PheWAS and the Open Targets Genetics Portal. These databases extend the array of phenotypes beyond those available in electronic health records (EHR) to include numerous non-medical phenotypes and traits. We then followed up the results from those exploratory associations by examining the genetic correlations between our “top hits” and alcohol- and smoking-related phenotypes.In both data sources, rs279858 (C effect allele) was associated with anxiety-related phenotypes, including reduced risk-taking behavior and an increase in nervous feelings, as well as reduced number of lifetime sexual partners. Follow-up analyses revealed that these phenotypes were genetically correlated with each other and with alcohol- and smoking-related phenotypes.This work illustrates the utility of the PheWAS approach, particularly for phenotypes that extend beyond those that are typically captured in EHR data. In fact, the associations described here are all behavioral rather than clinical phenotypes. We postulate that these traits may be related to anxiety or behavioral inhibition that has been identified as a risk factor for AUD, and may represent pathophysiological intermediaries betweenGABRA2and AUD.
The Bidirectional Relationship Between Head Injuries and Conduct Problems: Longitudinal Modelling of a Population-Based Birth Cohort Study
Authors: Carr Hannah R. , Hall James E. , Eisenbarth Hedwig , Brandt Valerie C. 
Published: November 2022

AbstractChildhood head injuries and conduct problems increase the risk of aggression and criminality and are well-known correlates. However, the direction and timing of their association and the role of their demographic risk factors remain unclear. This study investigates the bidirectional links between both from 3 to 17 years while revealing common and unique demographic risks.A total of 7,140 participants (51% female; 83.9% White ethnicity) from the Millennium Cohort Study were analysed at 6 timepoints from age 3 to 17. Conduct problems were parent-reported for ages 3 to 17 using the Strengths and Difficulties Questionnaire (SDQ) and head injuries at ages 3 to 14. A cross-lagged path model estimated the longitudinal bidirectional effects between the two whilst salient demographic risks were modelled cumulatively at three ecological levels (child, mother, and household).Conduct problems at age 7 promoted head injuries between 7 and 11 (Z= .07;SE= .03; 95% CI, .01-.12), and head injuries then promoted conduct problems at age 14 (ß= .07;SE= .03; 95% CI, .01-.12). Head injuries were associated with direct child-level risk until 7 years, whereas conduct problems were associated with direct risks from all ecological levels up until 17 years.The findings suggest a sensitive period at 7 to 11 years for the bidirectional relationship shared between head injuries and conduct problems. They suggest that demographic risks for increased head injuries play an earlier role than they do for conduct problems. Both findings have implications for intervention timing.
Discovery and biosynthetic assessment ofStreptomyces ortussp nov. isolated from a deep-sea sponge
Authors: Williams Sam E. , Back Catherine R. , Best Eleanor , Mantell Judith , Stach James E. M. , Williams Tom A. , Race Paul R. , Curnow Paul 
Published: November 2022

AbstractThe deep sea is known to host novel bacteria with the potential to produce a diverse array of undiscovered natural products. Understanding these bacteria is thus of broad interest in ecology and could also underpin applied drug discovery, specifically in the area of antimicrobials. Here, we isolate a new strain ofStreptomycesfrom the tissue of the deep-sea spongePolymastia corticatacollected at a depth of 1869 m from the Gramberg seamount in the Atlantic Ocean. This strain, which was given the initial designation A15ISP2-DRY2T, has a genome size of 9.29 Mb with a GC content of 70.83%. Phylogenomics determined that A15ISP2-DRY2Trepresents a novel species within the genusStreptomycesas part of theStreptomyces aurantiacusclade. The biosynthetic potential of A15ISP2-DRY2Twas assessed relative to other members of theaurantiacusclade via comparative gene cluster family (GCF) analysis. This revealed a clear congruent relationship between phylogeny and GCF content. A15ISP2-DRY2Tcontains six unique GCFs absent elsewhere in the clade. Culture-based assays were used to demonstrate the antibacterial activity of A15ISP2-DRY2Tagainst two drug-resistant human pathogens. We thus determine A15ISP2-DRY2Tto be a novel bacterial species with considerable biosynthetic potential and propose the systematic nameStreptomyces ortussp. nov.Impact StatementTheStreptomycesgenus has contributed more to our antibiotic arsenal than any other group of bacteria or fungi. Despite decades of exploration, global analysis has suggested they still possess more undiscovered biosynthetic diversity than any other bacterial group. Isolating novel species ofStreptomycesis therefore a priority for antibiotic discovery. Here we isolate a novel strain from a deep-sea sponge and use comparative cluster analysis to identify six biosynthetic clusters unique to our deep-sea strain. This work demonstrates the utility of continuing to isolate novelStreptomycesstrains for antibiotic discovery and, for the first time, we used species tree-gene cluster tree reconciliation to assess the contribution of vertical evolution on the biosynthetic gene cluster content ofStreptomyces.
Improving orthologous signal and model fit in datasets addressing the root of the animal phylogeny
Authors: McCarthy Charley GP , Mulhair Peter O , Siu-Ting Karen , Creevey Christopher J , O’Connell Mary J 
Published: November 2022

AbstractThere is conflicting evidence as to whether Porifera (sponges) or Ctenophora (comb jellies) comprise the root of the animal phylogeny. Support for either a Porifera-sister or Ctenophore-sister tree has been extensively examined in the context of model selection, taxon sampling and outgroup selection. The influence of dataset construction is comparatively understudied. We re-examine five animal phylogeny datasets that have supported either root hypothesis using an approach designed to enrich orthologous signal in phylogenomic datasets. We find that many component orthogroups in animal datasets fail to recover major animal lineages as monophyletic with the exception of Ctenophora, regardless of the supported root. Enriching these datasets to retain orthogroups recovering ≥3 major lineages reduces dataset size by up to 50% while retaining underlying phylogenetic information and taxon sampling. Site- heterogeneous phylogenomic analysis of these enriched datasets recovers both Porifera-sister and Ctenophora-sister positions, even with additional constraints on outgroup sampling. Two datasets which previously supported Ctenophora-sister support Porifera-sister upon enrichment. All enriched datasets display improved model fitness under posterior predictive analysis. While not conclusively rooting animals at either Porifera or Ctenophora, our results indicate that dataset size and construction as well as model fit influence animal root inference.
BIOLOGICAL DIAGNOSTICS OF THE ECOLOGICAL STATE OF URBAN ECOSYSTEMS
Authors: Galaktionova L.V. , Terekhova N.A. , Vedeneeva N.G. 
Published: November 2022

AnnotationThe processes of urbanization and the development of industrial production entail active environmental pollution with pollutants of various nature. The existing analytical methods for their determination in natural media make it possible to reveal their concentration. But in conditions of complex soil pollution, this approach does not give a complete picture of their total impact on living organisms. In the course of the study, an assessment was made of the ecological state of soils in large administrative and industrial centers of the Southern Urals (the cities of Orenburg and Mednogorsk) in terms of their phytotoxicity and enzymatic activity. On the territory of the objects of study, soil samples were taken from a layer of 0-20 cm in various functional zones. Phytotoxicity was assessed using a wheat test culture, and indicators of urease and catalase activity were used to assess biological activity. The calculation of the integral indicator of the ecological state on their basis showed the development of processes of degradation of the soil cover of cities under the influence of urbanization.
Does AlphaFold predict the spatial structure of a protein from physics or recognize it (its main parts and their association) using databases?
Authors: Finkelstein Alexei V. 
Published: November 2022

ABSTRACTThe great success of the AlphaFold programs poses the following questions: (i) What is the main reason for this success? (ii) What exactly do AlphaFolds do:predictionof the 3D protein structure based on its amino acid sequence and knowledge of the protein physics orrecognitionof this 3D structure, based on the similarity between some parts of its amino acid sequence and parts of sequences with already known 3D structures? The answers given in this paper are: The main reason for the tremendous success of the AlphaFold is (i) the usage of huge protein databases, which already cover all or almost all of the protein superfamilies existing in nature; (ii) using these databases and the resulting multiple sequence alignments and coevolutionary information (like correlations in pairs and especially in triplets of amino acid residues in the contacting chain regions), AlphaFoldrecognizesa 3D structure of the examined amino acid sequence by a similarity of this sequence (or its parts) to related sequences with already known 3D structures. Concluding, I have to emphasize that this paper does not diminish the merit and utility of AlphaFold; it only explains the basis of its success.
Tetraspanner-based nanodomains modulate BAR domain-induced membrane curvature
Authors: Haase Daniel , Rasch Christiane , Keller Ulrike , Elting Annegret , Wittmar Julia , Janning Annette , Kahms Martin , Schuberth Christian , Klingauf Jürgen , Wedlich-Söldner Roland 
Published: November 2022

AbstractTopography is a critical feature driving formation and dynamics of protein and lipid domains within biological membranes. The yeast plasma membrane (PM) has provided a powerful model system to study lateral domain formation, including characteristic BAR domain-induced PM furrows. Currently, it is not clear how the components involved in the establishment of these furrows cooperate to precisely regulate local PM topography. Here we report opposing functions for the Sur7 and Nce102 families of tetraspanner proteins in modulating membrane curvature and domain topography. Using STED nanoscopy and freeze-fracture EM we found that Sur7 tetraspanners form multimeric strands at the upper edges of PM furrows, which counteract the forces exerted by BAR domain proteins and prevent membrane tubulation. In contrast, Nce102 tetraspanners are located basal to the Sur7 proteins and promote BAR domain-induced curvature. The segregation of the two tetraspanner-based nanodomains is further supported by differential distribution of ergosterol to the upper edge of furrows and PIP2 lipids at the furrow base. These findings suggest a general role of tetraspanner proteins in sculpting local membrane domains.