bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secondary metabolites produced during Aspergillus fumigatus and Pseudomonas aeruginosa biofilm formation
Authors: Bastos Rafael Wesley , Akiyama Daniel , Fernanda dos Reis Thaila , Colabardini Ana Cristina , Luperini Rafael Sanchez , Alves de Castro Patrícia , Baldini Regina Lúcia , Fill Taícia , Goldman Gustavo H. 
Published: May 2022

AbstractIn Cystic Fibrosis (CF), mucus plaques are formed in the patient’s lung, creating a hypoxic condition and a propitious environment for colonization and persistence of many microorganisms. There is clinical evidence showing that Aspergillus fumigatus can co-colonize CF patients with Pseudomonas aeruginosa, which has been associated with lung function decline. P. aeruginosa produces several compounds with inhibitory and anti-biofilm effects against A. fumigatus in vitro; however, little is known about the fungal compounds produced in counterattack. Here, we annotated fungal and bacterial secondary metabolites (SM) produced in mixed biofilms in normoxia and hypoxia conditions. We detected nine SMs produced by P. aeruginosa. Phenazines and different analogs of pyoverdin were the main compounds produced by P. aeruginosa, and their secretion were increased by the fungal presence. The roles of the two operons responsible for phenazines production (phzA1 and phzA2) were also investigated showing both mutants are able to produce partial sets of phenazines. We detected a total of 20 SMs secreted by A. fumigatus either in monoculture or in co-culture with P. aeruginosa. All these compounds are secreted during biofilm formation either in normoxia or hypoxia. However, only eight compounds (demethoxyfumitremorgin C, fumitremorgin, ferrichrome, ferricrocin, tricetylfusigen, gliotoxin, gliotoxin E, and pyripyropene A) were detected during the biofilm formation by the co-culture of A. fumigatus and P. aeruginosa upon both normoxia and hypoxia conditions. Overall, we showed how diverse is SM secretion during A. fumigatus and P. aeruginosa mixed culture and how this can affect biofilm formation both in normoxia and hypoxia.Author SummaryThe interaction between Pseudomonas aeruginosa and Aspergillus fumigatus has been well-characterized in vitro. In this scenario, the bacterium exerts a strong inhibitory effect against the fungus. However, little is known about the metabolites produced by the fungus to counterattack the bacteria. Our work aimed to annotate secondary metabolites (SM) secreted during co-culture between P. aeruginosa and A. fumigatus during biofilm formation in both normoxia and hypoxia. The bacterium produces several different types of phenazines and pyoverdins, in response to the fungus presence. In contrast, we were able to annotate 29 metabolites produced during A. fumigatus biofilm formation but only eight compounds were detected during biofilm formation by the co-culture of A. fumigatus and P. aeruginosa upon both normoxia and hypoxia. In conclusion, we have detected many SMs secreted during A. fumigatus and P. aeruginosa biofilm formation. This analysis can provide several opportunities to understand the interaction between these two species.
Relative abundance data can misrepresent heritability of the microbiome
Authors: Bruijning Marjolein , Ayroles Julien F. , Henry Lucas P. , Koskella Britt , Meyer Kyle M. , Metcalf C. Jessica E. 
Published: May 2022

AbstractHost genetics can shape microbiome composition, but to what extent it does, remains unclear. Like any other complex trait, this question can be addressed by estimating the heritability (h2) of the microbiome – the proportion of variance in the abundance of each taxon that is attributable to host genetic variation. However, unlike most complex traits, microbiome heritability is typically based on relative abundance data, where taxon-specific abundances are expressed as the proportion of the total microbial abundance in a sample. We derived an analytical approximation for the heritability that one obtains when using such relative abundances and we uncovered three problems: 1) The interdependency between taxa leads to imprecise heritability estimates. 2) Large sample size leads to high false discovery rates, overestimating the number of heritable taxa. 3) Microbial co-abundances lead to biased heritability estimates. We conclude that caution must be taken when interpreting heritability estimates and comparing values across studies.
Reducing CRISPR dark matter reveals a strong association between the bacterial membranome and CRISPR-Cas systems
Authors: Rubio Alejandro , Sprang Maximilian , Garzón Andrés , Pachón-Ibáñez Maria Eugenia , Pachón Jerónimo , Andrade-Navarro Miguel A. , Pérez-Pulido Antonio J. 
Published: May 2022

AbstractAntimicrobial resistance is widely recognized as a serious global public health problem. To combat this threat, a thorough understanding of bacterial genomes is necessary. The current wide availability of bacterial genomes provides us with an in-depth understanding of the great variability of dispensable genes and their relationship with antimicrobials. Some of these accessory genes are those involved in CRISPR-Cas systems, which are acquired immunity systems that are present in part of bacterial genomes. They prevent viral infections through small DNA fragments called spacers. But the vast majority of these spacers have not yet been associated with the virus they recognize, and this has been named CRISPR dark matter. By analyzing the spacers of tens of thousands of genomes from six bacterial species highly resistant to antibiotics, we have been able to reduce the CRISPR dark matter from 80-90% to as low as 15% in some of the species. In addition, we have observed that, when a genome presents CRISPR-Cas systems, this is accompanied by particular collections of membrane proteins. Our results suggest that when a bacterium presents membrane proteins that make it compete better in its environment, and these proteins are in turn receptors for specific phages, it would be forced to acquire CRISPR-Cas immunity systems to avoid infection by these phages.
Donor strand complementation, isopeptide bonds and glycosylation reinforce highly resilient archaeal thread filaments
Authors: Gaines Matthew C. , Isupov Michail N. , Sivabalasarma Shamphavi , Haque Risat Ul , McLaren Mathew , Tripp Patrick , Neuhaus Alexander , Gold Vicki , Albers Sonja-Verena , Daum Bertram 
Published: May 2022

AbstractPili are ubiquitous filamentous surface extensions that play crucial roles for bacterial and archaeal cellular processes such as adhesion, biofilm formation, motility, cell-cell communication, DNA uptake and horizontal gene transfer to name a few. Here we report on the discovery and structure of the archaeal thread – a remarkably stable archaeal pilus that belongs to a so-far largely unknown class of protein filaments. We find that the filament is highly glycosylated and interconnected via donor strand complementation, as well as isopeptide bonds, reminiscent of bacterial type I pili. Despite striking structural similarity with bacterial type-1 pili, archaeal threads appear to have evolved independently and are likely assembled by a markedly distinct mechanism.
Assessing pyrethroid resistance status in the Culex pipiens complex (Diptera: Culicidae) from the northwest suburbs of Chicago, Illinois using Cox regression of bottle bioassays and other detection tools
Authors: Burgess Edwin R. , Lopez Kristina , Irwin Patrick , Jaeger Collin P. , Estep Alden S. 
Published: May 2022

AbstractCulex pipiens complex is an important vector of epizootic and zoonotic pathogens, including West Nile virus. Chicago, Illinois and its suburbs have suffered high incidence of human West Nile virus infections in the past. This makes abatement programs in and around the Chicago area an essential service. The control of Cx. pipiens is often complicated by rapidly evolving resistance to pyrethroids, which are the most widely used chemical class in US mosquito abatement programs. The present study assessed Sumithrin® resistance in Cx. pipiens collected from five locations around Cook County, Illinois, neighboring the city limits of Chicago. According to CDC guidelines, samples from all five locations demonstrated some resistance to Sumithrin®. When assessed with Anvil®, a formulated product made of Sumithrin® synergized with piperonyl butoxide, susceptibility was rescued in mosquitoes from three out of the five locations, suggesting involvement of mixed-function oxidases and/or carboxylesterases in Sumithrin® resistance at these locations. Not all locations had susceptibility rescued by Anvil®, but these locations had relatively low knockdown resistance allele frequencies, suggesting that mechanisms other than knockdown resistance may be involved. Enzyme activities did not reveal any marked trends that could be related back to mortality in the bottle bioassays, which highlights the need for multiple types of assays to infer enzymatic involvement in resistance. Future directions in pyrethroid resistance management in Chicago area Cx. pipiens are discussed.
Mechanical confinement and DDR1 signalling synergise to regulate collagen-induced apoptosis in rhabdomyosarcoma cells
Authors: Gonzalez-Molina Jordi , Kirchhof Katharina Miria , Rathod Bhavik , Moyano-Galceran Lidia , Calvo-Noriega Maria , Kokaraki Georgia , Bjørkøy Astrid , Ehnman Monika , Carlson Joseph W. , Lehti Kaisa 
Published: May 2022

ABSTRACTFibrillar collagens promote cell proliferation, migration, and survival in various epithelial cancers and are generally associated with tumour aggressiveness. However, the impact of fibrillar collagens on soft tissue sarcoma behaviour remains poorly understood.Unexpectedly, we find here that fibrillar collagen-related gene expression is associated with favourable patient prognosis in rhabdomyosarcoma. By developing and using collagen matrices with distinct stiffness and in vivo-like microarchitectures, we uncover that the activation of DDR1 has pro-apoptotic and integrin β1 pro-survival function, specifically in 3D rhabdomyosarcoma cell cultures. We demonstrate that rhabdomyosarcoma cell-intrinsic or extrinsic matrix remodelling promotes cell survival. Mechanistically, we find that the 3D-specific collagen-induced apoptosis results from a dual DDR1-independent and a synergistic DDR1-dependent TRPV4-mediated response to mechanical confinement. Altogether, our results indicate that dense microfibrillar collagen-rich microenvironments are detrimental to rhabdomyosarcoma cells through an apoptotic response orchestrated by the induction of DDR1 signalling and mechanical confinement. This mechanism helps to explain the preference of rhabdomyosarcoma cells to grow in and metastasise to low fibrillar collagen microenvironments such as the lung.
A cocktail containing two synergetic antibodies broadly neutralizes SARS-CoV-2 and its variants including Omicron BA.1 and BA.2
Authors: Zhang Xinghai , Luo Feiyang , Zhang huajun , Guo Hangtian , Zhou Junhui , Li Tingting , Chen Shaohong , Song Shuyi , Shen Meiying , Wu Yan , Gao Yan , Han Xiaojian , Wang Yingming , Hu Chao , Lu Yuchi , Wang Wei , Wang Kai , Tang Ni , Jin Tengchuan , Yang Chengyong , Cheng Guofeng , Yang Haitao , Jin Aishun , Ji Xiaoyun , Gong Rui , Chiu Sandra , Huang Ailong 
Published: May 2022

AbstractNeutralizing antibodies (NAbs) can prevent and treat infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, continuously emerging variants, such as Omicron, have significantly reduced the potency of most known NAbs. The selection of NAbs with broad neutralizing activities and the identification of conserved critical epitopes are still urgently needed. Here, we identified an extremely potent antibody (55A8) by single B-cell sorting from convalescent SARS-CoV-2-infected patients that recognized the receptor-binding domain (RBD) in the SARS-CoV-2 spike (S) protein. 55A8 could bind to wild-type SARS-CoV-2, Omicron BA.1 and Omicron BA.2 simultaneously with 58G6, a NAb previously identified by our group. Importantly, an antibody cocktail containing 55A8 and 58G6 (2-cocktail) showed synergetic neutralizing activity with a half-maximal inhibitory concentration (IC50) in the picomolar range in vitro and prophylactic efficacy in hamsters challenged with Omicron (BA.1) through intranasal delivery at an extraordinarily low dosage (25 μg of each antibody daily) at 3 days post-infection. Structural analysis by cryo-electron microscopy (cryo-EM) revealed that 55A8 is a Class III NAb that recognizes a highly conserved epitope. It could block angiotensin-converting enzyme 2 (ACE2) binding to the RBD in the S protein trimer via steric hindrance. The epitopes in the RBD recognized by 55A8 and 58G6 were found to be different and complementary, which could explain the synergetic mechanism of these two NAbs. Our findings not only provide a potential antibody cocktail for clinical use against infection with current SARS-CoV-2 strains and future variants but also identify critical epitope information for the development of better antiviral agents.
Achieving improved accuracy for imputation of ancient DNA
Authors: Ausmees Kristiina , Nettelblad Carl 
Published: May 2022

AbstractGenotype imputation has the potential to increase the amount of information that can be gained from the often limited biological material available in ancient samples. As many widely used tools have been developed with modern data in mind, their design is not necessarily reflective of the requirements in studies of ancient DNA. Here, we investigate if an imputation method based on the full probabilistic Li and Stephens model of haplotype frequencies might be beneficial for the particular challenges posed by ancient data. We present an implementation called prophaser, and compare imputation performance to two alternative pipelines that have been used in the ancient DNA community based on the Beagle software. Considering empirical ancient data downsampled to lower coverages as well as present-day samples with artificially thinned genotypes, we show that the proposed method is advantageous at lower coverages, where it yields improved accuracy and ability to capture rare variation. The software prophaser is optimized for running in a massively parallel manner and achieved reasonable runtimes on the experiments performed when executed on a GPU.
Approximating Solutions of the Chemical Master Equation using Neural Networks
Authors: Sukys Augustinas , Öcal Kaan , Grima Ramon 
Published: May 2022

AbstractThe Chemical Master Equation (CME) provides an accurate description of stochastic biochemical reaction networks in well-mixed conditions, but it cannot be solved analytically for most systems of practical interest. While Monte Carlo methods provide a principled means to probe the system dynamics, their high computational cost can render the estimation of molecule number distributions and other numerical tasks infeasible due to the large number of repeated simulations typically required. In this paper we aim to leverage the representational power of neural networks to approximate the solutions of the CME and propose a framework for Neural Estimation of Stochastic Simulations for Inference and Exploration (Nessie). Our approach is based on training a neural network to learn the distributions predicted by the CME from a relatively small number of stochastic simulations, thereby accelerating computationally intensive tasks such as parameter exploration and inference. We show on biologically relevant examples that simple neural networks with one hidden layer are able to capture highly complex distributions across parameter space. We provide a detailed discussion of the neural network implementation and code for easy reproducibility.
Investigating the impact of database choice on the accuracy of metagenomic read classification for the rumen microbiome
Authors: Smith Rebecca H. , Glendinning Laura , Walker Alan W. , Watson Mick 
Published: May 2022

AbstractMicrobiome analysis is quickly moving towards high-throughput methods such as metagenomic sequencing. Accurate taxonomic classification of metagenomic data relies on reference sequence databases, and their associated taxonomy. However, for understudied environments such as the rumen microbiome many sequences will be derived from novel or uncultured microbes that are not present in reference databases. As a result, taxonomic classification of metagenomic data from understudied environments may be inaccurate. To assess the accuracy of taxonomic read classification, this study classified metagenomic data that had been simulated from cultured rumen microbial genomes from the Hungate collection. To assess the impact of reference databases on the accuracy of taxonomic classification, the data was classified with Kraken 2 using several reference databases. We found that the choice and composition of reference database significantly impacted on taxonomic classification results, and accuracy. In particular, NCBI RefSeq proved to be a poor choice of database. Our results indicate that inaccurate read classification is likely to be a significant problem, affecting all studies that use insufficient reference databases. We observe that adding cultured reference genomes from the rumen to the reference database greatly improves classification rate and accuracy. We also demonstrate that metagenome-assembled genomes (MAGs) have the potential to further enhance classification accuracy by representing uncultivated microbes, sequences of which would otherwise be unclassified or incorrectly classified. However, classification accuracy was strongly dependent on the taxonomic labels assigned to these MAGs. We therefore highlight the importance of accurate reference taxonomic information and suggest that, with formal taxonomic lineages, MAGs have the potential to improve classification rate and accuracy, particularly in environments such as the rumen that are understudied or contain many novel genomes.
Trimethylamine N-oxide (TMAO) enhances substrate mechanical stability probed by single molecule magnetic tweezers
Authors: Chaudhuri Deep , Chowdhury Debojyoti , Chakraborty Soham , Dutta Akashdeep , Mistry Ayush , Haldar Shubhasis 
Published: May 2022

AbstractTrimethylamine N-oxide (TMAO) is a well-known osmolyte to stabilize the folded proteins through a variety of mechanisms. Since mechanical strength of proteins is a critical determinant of its stabilization, TMAO might play a relevant role by favoring its folding dynamics or by enhancing its mechanical stability. To address this question, we have performed the single-molecule magnetic tweezers experiment to explore the TMAO effect on two structurally distinct substrates-protein L and talin. We observed that TMAO increases the mechanical stability of these proteins through increasing their unfolding force. Additionally, we are able to demonstrate that TMAO retards the unfolding kinetics, while accelerating the refolding kinetics under force; which eventually tilts the energy landscape towards the folded state. Interestingly, this TMAO-enhanced protein folding generates mechanical work output upto ∼67 zJ, allowing the protein folding under higher force regime. Overall this TMAO-enhanced mechanical stability provides a significant implication to folding-induced structural stability of proteins.
On the Prediction of non-CG DNA Methylation
Authors: Sereshki Saleh , Omirou Michalis , Fasoula Dionysia , Lonardi Stefano 
Published: May 2022

AbstractDNA cytosine methylation is an epigenetic modification that has a critical role in gene regulation and genome stability. DNA methylation can be detected and measured using sequencing instruments after sodium bisulfite conversion, but experiments can be expensive for large eukaryotic genomes. Sequencing non-uniformity and mapping biases can leave parts of the genome with low or no coverage, thus hampering the ability of obtaining DNA methylation levels for all cytosines. To address these limitations, several computational methods have been proposed that can predict DNA methylation from the DNA sequence around the cytosine, or from the methylation level of nearby cytosines. Most of these methods are, however, entirely focused on CG methylation in humans and other mammals. In this work, we study for the first time the problem of predicting cytosine methylation for CG, CHG, and CHH contexts on five plant species, either from the DNA primary sequence around the cytosine or the methylation levels of neighboring cytosines. In this framework, we also study (1) the cross-species prediction problem, i.e., the classification performance when training on one species and testing on another species, and the (2) the cross-context prediction problem, i.e., the classification performance when training on one context and testing on another context (within the same species). Finally, we show that providing the classifier with gene annotation information allows our classifier to outperform the prediction accuracy of state-of-the-art methods.
Action initiation and punishment learning differ from childhood to adolescence while reward learning remains stable
Authors: Pauli Ruth , Brazil Inti , Kohls Gregor , Klein-Flügge Miriam C. , Rogers Jack C. , Dikeos Dimitris , Dochnal Roberta , Fairchild Graeme , Fernández-Rivas Aranzazu , Herpertz-Dahlmann Beate , Hervas Amaia , Konrad Kerstin , Popma Arne , Stadler Christina , Freitag Christine M. , De Brito Stephane A. , Lockwood Patricia L. 
Published: May 2022

AbstractTheoretical and empirical accounts suggest that adolescence is associated with heightened reward learning and impulsivity. Experimental tasks and computational models that can dissociate reward learning from the tendency to initiate actions impulsively (action initiation bias) are thus critical to characterise the mechanisms that drive developmental differences. However, existing work has rarely quantified both learning ability and action initiation, or it has tested small samples. Here, using computational modelling of a learning task collected from a large sample (N=742, 9-18 years, 11 countries), we tested differences in reward and punishment learning and action initiation from childhood to adolescence. Computational modelling revealed that whilst punishment learning rates increased with age, reward learning remained stable. In parallel, action initiation biases decreased with age. Results were similar when considering pubertal stage instead of chronological age. We conclude that heightened reward responsivity in adolescence can reflect differences in action initiation rather than enhanced reward learning.