bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA Replication-transcription conflicts do not significantly contribute to spontaneous mutations due to replication errors in Escherichia coli.
Authors: Foster Patricia L. , Niccum Brittany A. , Lee Heewook 
Published: August 2021

ABSTRACTEncounters between DNA replication and transcription can cause genomic disruption, particularly when the two meet head-on. Whether these conflicts produce point mutations is debated. This paper presents detailed analyses of a large collection of mutations generated during mutation accumulation experiments with mismatch-repair (MMR) defective Escherichia coli. With MMR absent, mutations are primarily due to DNA replication errors. Overall, there were no differences in the frequencies of base-pair substitutions or small indels (insertion and deletions ≤ 4 bp) in the coding sequences or promoters of genes oriented codirectionally versus head-on to replication. Among a subset of highly expressed genes there was a 2- to 3-fold bias for indels in genes oriented head-on to replication, but this difference was almost entirely due to the asymmetrical genomic locations of tRNA genes containing mononucleotide runs, which are hotspots for indels. No additional orientation bias in mutation frequencies occurred when MMR− strains were also defective for transcription-coupled repair (TCR). However, in contrast to other reports, loss of TCR slightly increased the overall mutation rate, meaning that TCR is antimutagenic. There was no orientation bias in mutation frequencies among the stress-response genes that are regulated by RpoS or induced by DNA damage. Thus, biases in the locations of mutational targets can account for most, if not all, apparent biases in mutation frequencies between genes oriented head-on versus co-directional to replication. In addition, the data revealed a strong correlation of the frequency of base-pair substitutions with gene length, but no correlation with gene expression levels.IMPORTANCEBecause DNA replication and transcription occur on the same DNA template, encounters between the two machines occur frequently. When these encounters are head-to-head, genomic disruption can occur. But, whether replication-transcription conflicts contribute to spontaneous mutations is debated. Analyzing in detail a large collection of mutations generated with mismatch repair defective Escherichia coli strains, we find that across the genome there are no significant differences in mutation frequencies between genes oriented co-directionally versus head-on to replication. Among a subset of highly expressed genes there was a 2- to 3-fold bias for small insertions and deletions in head-on oriented genes, but this difference was almost entirely due to the asymmetrical locations of tRNA genes containing mononucleotide runs, which are hotspots for these mutations. Thus, biases in the positions of mutational target sequences can account for most, if not all, apparent biases in mutation frequencies between genes oriented head-on and co-directionally to replication.
Landscaping the behavioural ecology of primate stone tool use
Authors: Almeida-Warren Katarina , Matsuzawa Tetsuro , Carvalho Susana 
Published: August 2021

AbstractEcology is fundamental to the development, transmission, and perpetuity of primate technology. Previous studies on tool site selection have addressed the relevance of targeted resources and raw materials for tools, but few have considered the broader foraging landscape. In this first landscape-scale study of the ecological contexts of wild chimpanzee (Pan troglodytes verus) tool-use, we investigate the conditions required for nut-cracking to occur and persist over time at discrete locations in Bossou (Guinea). We examine this at three levels: selection, frequency of use, and inactivity. We find that, further to the presence of a nut tree and availability of raw materials, abundance of food-providing trees as well as proximity to nest sites were significant predictors of nut-cracking occurrence. This suggests that the spatial distribution of nut-cracking sites is mediated by the broader behavioural landscape and is influenced by non-extractive foraging of predictable resources, as well as non-foraging activities. Additionally, the number of functional tools was greater at sites with higher frequency of nut-cracking and was negatively correlated with site inactivity. Our findings indicate that the technological landscape of the Bossou chimpanzees shares affinities with the ‘favoured places’ model of hominin site formation and provides new insights for reconstructing ancient patterns of landscape use.RésuméL’écologie est fondamentale pour le développement, la transmission et la pérennité de la technologie des primates. Des études antérieures ont identifié la disponibilité des ressources cibles ainsi que les matières premières pour les outils comme des facteurs influents dans la sélection des emplacements pour les activités technologiques. Cependant, il y a peu d’études qui abordent cette recherche à l’échelle du paysage et du comportement fourrager. Dans cette première étude paysagère sur l’utilisation d’outils par le chimpanzé sauvage (Pan troglodytes verus), nous recherchons les conditions écologiques qui influencent la sélection, l’utilisation et l’inactivité des emplacements utilisés pour le cassage des noix en Bossou, Guinée. Nos résultats montrent qu’en plus de la présence d’un noyer et de la disponibilité des matières premières, l’abondance d’arbres nourriciers ainsi que la proximité des sites de nidification étaient des prédicteurs significatifs de l’occurrence du cassage des noix. Cela suggère que la distribution spatiale des sites de cassage de noix est influencée par le paysage comportemental et est influencée par le fourrage non-extractive de ressources prévisibles, ainsi que par des activités non-fourragers. Nos résultats indiquent que le paysage technologique des chimpanzés de Bossou partage des affinités avec le modèle des « lieux favoris » de la formation des sites hominidés et fournit de nouvelles perspectives pour reconstruire les modes d’utilisation du paysage anciens.
Mining folded proteomes in the era of accurate structure prediction
Authors: Bayly-Jones Charles , Whisstock James 
Published: August 2021

AbstractProtein structure fundamentally underpins the function and processes of numerous biological systems. Fold recognition algorithms offer a sensitive and robust tool to detect structural, and thereby functional, similarities between distantly related homologs. In the era of accurate structure prediction owing to advances in machine learning techniques, previously curated sequence databases have become a rich source of biological information. Here, we use bioinformatic fold recognition algorithms to scan the entire AlphaFold structure database to identify novel protein family members, infer function and group predicted protein structures. As an example of the utility of this approach, we identify novel, previously unknown members of various pore-forming protein families, including MACPFs, GSDMs and aerolysin-like proteins. Further, we explore the use of structure-based mining for functional inference.
Detection and phylogeny ofWolbachiain field-collectedAedes albopictusandAedes aegyptifrom Manila City, Philippines
Authors: Regilme Maria Angenica F. , Inukai Tatsuya , Watanabe Kozo 
Published: August 2021

AbstractBackgroundWolbachiais the most common bacterial endosymbiont of arthropods, such as the medically importantAedes albopictusand recent reports also detected inAedes aegypti. Our study showed additional support for the presence of wolbachia inAe. albopictusandAe. aegyptiusing Wolbachia specific markers,wsp, and 16S.Main textThis study collected 12 adultAe. albopictusand 359Ae. aegyptifrom 183 households in a dengue-prone area, Manila, Philippines, between June and September 2017.Aedeslarvae (n = 509) were also collected from 17 water containers from 11 households. The DNA of theAedeslarvae and adults were screened for the presence ofWolbachiausing thewspand 16S markers, following optimized polymerase chain reaction (PCR) conditions, and sequenced. Our results showed that 3 out of 359 (0.84%) adultAe. aegyptiand 12 out of 12 (100%) adultAe. albopictuswereWolbachiapositive, whereas all larvae tested negative forWolbachia(0/509; 0%). Thewspmarker revealed sixWolbachia-positiveAe. albopictus, whereas the 16S marker showedWolbachiain threeAe. aegyptiand tenAe. albopictusConclusionOur results suggest that the utilization of two Wolbachia specific markers,wspand16Sdemonstrated Wolbachia presence in individualAe. albopictusandAe. aegypti. The results of the Wolbachia infection inAe. albopictusshowed that the detected strains were from either supergroups A and B. Despite the low infection rate of Wolbachia inAe. aegypti,our results demonstrated the presence of Wolbachia in field-collectedAe. aegyptisupporting previous studies.
Long-read and chromosome-scale assembly of the hexaploid wheat genome achieves high resolution for research and breeding
Authors: Aury Jean-Marc , Engelen Stefan , Istace Benjamin , Monat Cécile , Lasserre-Zuber Pauline , Belser Caroline , Cruaud Corinne , Rimbert Hélène , Leroy Philippe , Arribat Sandrine , Dufau Isabelle , Bellec Arnaud , Grimbichler David , Papon Nathan , Paux Etienne , Ranoux Marion , Alberti Adriana , Wincker Patrick , Choulet Frédéric 
Published: August 2021

AbstractThe sequencing of the wheat (Triticum aestivum) genome has been a methodological challenge for many years due to its large size (15.5 Gb), repeat content, and hexaploidy. Many initiatives aiming at obtaining a reference genome of cultivar Chinese Spring have been launched in the past years and it was achieved in 2018 as the result of a huge effort to combine short-read sequencing with many other resources. Reference-quality genome assemblies were then produced for other accessions but the rapid evolution of sequencing technologies offers opportunities to reach high-quality standards at lower cost. Here, we report on an optimized procedure based on long-reads produced on the ONT (Oxford Nanopore Technology) PromethION device to assemble the genome of the French bread wheat cultivar Renan. We provide the most contiguous and complete chromosome-scale assembly of a bread wheat genome to date. Coupled with an annotation based on RNA-Seq data, this resource will be valuable for the crop community and will facilitate the rapid selection of agronomically important traits. We also provide a framework to generate high-quality assemblies of complex genomes using ONT.
Key Drivers of Ecological Assembly in the Hindgut of Atlantic Cod (Gadus morhua) when Fed with a Macroalgal Supplemented diet – How Robust Is the Gut to Taxonomic Perturbation?
Authors: Keating C. , Bolton-Warberg M. , Hinchcliffe J. , Davies R. , Whelan S. , Wan A. H. L. , Fitzgerald R. D. , Davies S. J. , Smith C. J. , Ijaz U. Z. 
Published: August 2021

AbstractThe microbiota in the gastrointestinal tract of any species is shaped by internal and external cues in addition to random events which can be difficult to disentangle from a range of interacting variables. Estimating ecological assembly processes can help elucidate these factors. In our study, farmed Atlantic cod (Gadus morhua) were fed a diet of 10% macroalgae supplement (Ulva rigida species [ULVA] or Ascophyllum nodosum [ASCO] or a non-amended control diet [CTRL]) over a 12-week period and the ecological assembly processes quantified. The CTRL samples showed selection (variable selection - divergence in communities related to selective environmental conditions) as a key assembly process, while dispersal limitation (limited movement results in divergent communities through stochastic processes) was a driver of the gut microbiome for fish fed the macroalgae supplemented diet at Week 12 (i.e., ASCO and ULVA). Fish from the ASCO grouping diverged into ASCO_N (normal) and ASCO_LG (lower growth), where ASCO_LG individuals found the diet unpalatable. The recruitment of new taxa over time was altered in the ASCO_LG fish, with the gut microbiome showing phylogenetic under dispersion (nepotistic recruitment of species). Finally, the gut microbiome (CTRL and ULVA only) showed increasing robustness to taxonomic disturbance over time and an increase in functional redundancy. This study advances our understanding of the ecological assembly and succession in the hindgut of juvenile Atlantic cod across dietary regimes. Understanding the processes driving ecological assembly in the gut microbiome, in fish research specifically, could allow us to manipulate the microbiome for improved health or resilience to disease for improved aquaculture production.
A yeast model of the ALS protein Matrin3 uncovers Hsp90 and its co-chaperone Sti1 as modifiers of misfolding and toxicity
Authors: Di Gregorio Sonja E. , Esmaeili Mohammad , Salem Ahmed , Duennwald Martin L. 
Published: August 2021

AbstractThe MATR3 gene encoding the protein Matrin3 is implicated in the pathogenesis of the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Matrin3 forms neuronal cytoplasmic and nuclear inclusions in ALS-affected neurons. Additionally, 13 heterozygous missense mutations in MATR3 are identified in ALS patients. To further explore Matrin3 misfolding and toxicity, we established and characterized a yeast model. We demonstrate that wild type Matrin3 and the ALS-associated variant F115C are toxic and form inclusions in yeast. Our further characterization uncovers substantial modification of Matrin3 toxicity and inclusion formation by Hsp90 and its co-chaperones, specifically Sti1. Thus, our study demonstrates how specific branches of cellular protein quality control regulate the misfolding and toxicity of Matrin3.Summary StatementWe established and characterized a yeast model expressing human Matrin3, a protein implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Using this yeast model and mammalian neuronal cells, we showed that Matrin3 mislocalizes and forms inclusions, is cytotoxic, and increases sensitivity to cellular stress. We also uncovered that Hsp90 and particularly its co-chaperone Sti1 alter Matrin3 toxicity.
Multi-omics investigation of Clostridioides difficile-colonized patients reveals protective commensal carbohydrate metabolism
Authors: Fishbein Skye R. S. , Robinson John I. , Hink Tiffany , Reske Kimberly A. , Newcomer Erin P. , Burnham Carey-Ann D. , Henderson Jeffrey P. , Dubberke Erik R. , Dantas Gautam 
Published: August 2021

AbstractClostridioides difficile infection (CDI) imposes a substantial burden on the health care system in the United States. Understanding the biological basis for the spectrum of C. difficile-related disease manifestations is imperative to improving treatment and prevention of CDI. Here, we investigate the correlates of asymptomatic C. difficile colonization using a multi-omics approach, comparing the fecal microbiome and metabolome profiles of patients with CDI versus asymptomatically-colonized patients. We find that microbiomes of asymptomatic patients are significantly enriched for species in the class Clostridia relative to those of symptomatic patients. Asymptomatic patient microbiomes were enriched with fucose, rhamnose, and sucrose degradation pathways relative to CDI patient microbiomes. Fecal metabolomics corroborates this result: we identify carbohydrate compounds enriched in asymptomatic patients relative to CDI patients, and correlated with a number of commensal Clostridia. Further, we reveal that across C. difficile isolates, the carbohydrates rhamnose and lactulose do not serve as robust growth substrates in vitro, corroborating their enriched detection in our metagenomic and metabolite profiling of asymptomatic individuals. We conclude that in asymptomatically-colonized individuals, carbohydrate metabolism by other commensal Clostridia may prevent CDI by inhibiting C. difficile proliferation. These insights into C. difficile colonization and putative commensal competition suggest novel avenues to develop probiotic or prebiotic therapeutics against CDI.
New insights into the evolution of SPX gene family from algae to legumes; a focus on soybean
Authors: Chegini Mahnaz Nezamivand , Ebrahimie Esmaeil , Tahmasebi Ahmad , Moghadam Ali , Eshghi Saied , Mohammadi-Dehchesmeh Manijeh , Kopriva Stanislav , Niazi Ali 
Published: August 2021

AbstractBackgroundSPX-containing proteins have been known as key players in phosphate signaling and homeostasis. In Arabidopsis and rice, functions of some SPXs have been characterized, but little is known about their function in other plants, especially in the legumes.ResultsWe analyzed SPX gene family evolution in legumes and in a number of key species from algae to angiosperms. We found that SPX harboring proteins showed fluctuations in domain fusions from algae to the angiosperms with, finally, four classes appearing and being retained in the land plants. Despite these fluctuations, Lysine Surface Cluster (KSC), and the third residue of Phosphate Binding Sites (PBS) showed complete conservation in almost all of SPXs except few proteins in Selaginella moellendorffii and Papaver sumniferum, suggesting they might have different ligand preferences. In addition, we found that the WGD/segmentally or dispersed duplication types were the most frequent contributors to the SPX expansion, and that there is a positive correlation between the amount of WGD contribution to the SPX expansion in individual species and its number of EXS genes. We could also reveal that except SPX class genes, other classes lost the collinearity relationships among Arabidopsis and legume genomes. The sub- or neo-functionalization of the duplicated genes in the legumes makes it difficult to find the functional orthologous genes. Therefore, we used two different methods to identify functional orthologs in soybean and Medicago. High variance in the dynamic and spatial expression pattern of GmSPXs proved the new or sub-functionalization in the paralogs.ConclusionThis comprehensive analysis revealed how SPX gene family evolved from algae to legumes and also discovered several new domains fused to SPX domain in algae. In addition, we hypothesized that there different phosphate sensing mechanisms might occur in S. moellendorffii and P. sumniferum. Finally, we predicted putative functional orthologs of AtSPXs in the legumes, especially, orthologs of AtPHO1 and AtPHO1;H1, involved in long-distance Pi transportation. These findings help to understand evolution of phosphate signaling and might underpin development of new legume varieties with improved phosphate use efficiency.
Gene Expression Risk Scores for COVID-19 Illness Severity
Authors: Peterson Derick R , Baran Andrea M , Bhattacharya Soumyaroop , Branche Angela R , Croft Daniel P , Corbett Anthony M , Walsh Edward E , Falsey Ann R , Mariani Thomas J 
Published: August 2021

AbstractBackgroundThe correlates of COVID-19 illness severity following infection with SARS-Coronavirus 2 (SARS-CoV-2) are incompletely understood.MethodsWe assessed peripheral blood gene expression in 53 adults with confirmed SARS-CoV-2-infection clinically adjudicated as having mild, moderate or severe disease. Supervised principal components analysis was used to build a weighted gene expression risk score (WGERS) to discriminate between severe and non-severe COVID.ResultsGene expression patterns in participants with mild and moderate illness were similar, but significantly different from severe illness. When comparing severe versus non-severe illness, we identified >4000 genes differentially expressed (FDR<0.05). Biological pathways increased in severe COVID-19 were associated with platelet activation and coagulation, and those significantly decreased with T cell signaling and differentiation. A WGERS based on 18 genes distinguished severe illness in our training cohort (cross-validated ROC-AUC=0.98), and need for intensive care in an independent cohort (ROC-AUC=0.85). Dichotomizing the WGERS yielded 100% sensitivity and 85% specificity for classifying severe illness in our training cohort, and 84% sensitivity and 74% specificity for defining the need for intensive care in the validation cohort.ConclusionThese data suggest that gene expression classifiers may provide clinical utility as predictors of COVID-19 illness severity.
Calpain DEK1 acts as a developmental switch gatekeeping cell fate transitions
Authors: Demko Viktor , Belova Tatiana , Messerer Maxim , Hvidsten Torgeir R. , Perroud Pierre-François , Ako Ako Eugene , Johansen Wenche , Mayer Klaus F.X. , Olsen Odd-Arne , Lang Daniel 
Published: August 2021

SummaryCalpains are cysteine proteases that control cell fate transitions. Although calpains are viewed as modulatory proteases displaying severe, pleiotropic phenotypes in eukaryotes, human calpain targets are also directed to the N-end rule degradatory pathway. Several of these destabilized targets are transcription factors, hinting at a gene regulatory role. Here, we analyze the gene regulatory networks of Physcomitrium patens and characterize the regulons that are deregulated in DEK1 calpain mutants. Predicted cleavage patterns of regulatory hierarchies in the five DEK1-controlled subnetworks are consistent with the gene’s pleiotropy and the regulatory role in cell fate transitions targeting a broad spectrum of functions. Network structure suggests DEK1-gated sequential transition between cell fates in 2D to 3D development. We anticipate that both our method combining phenotyping, transcriptomics and data science to dissect phenotypic traits and our model explaining the calpain’s role as a switch gatekeeping cell fate transitions will inform biology beyond plant development.
Synthesis and characterization of a range of antimony(I/III) N,N′-bis(2,6-diisopropylphenyl)formamidinate complexes
Authors: Al-Dabbagh Areej , Guo Zhifang , Junk Peter , Wang Jun 
Published: August 2021

Formamidinatoantimony(I/III) complexes have been successfully synthesized as monomers or dimers in the solid state featuring a variety of coordination geometries and have also been comprehensively characterized. The antimony(I) formamidinate complex bis[μ-N,N′-bis(2,6-diisopropylphenyl)formamidinato]diantimony(I)(2 Sb—Sb) tetrahydrofuran heptasolvate, [Sb2(C25H35N2)2]·7C4H8O or [Sb2(DippForm)2]·7THF, (1), was obtained by a metathesis reaction between sodium bis(trimethylsilyl)amide [NaN(SiMe3)2] and N,N′-bis(2,6-diisopropylphenyl)formamidine (DippFormH), followed by SbCl3. A range of trivalent haloformamidinatoantimony(III) complexes, namely, bis[N,N′-bis(2,6-diisopropylphenyl)formamidinato]chloridoantimony(III), [Sb(C25H35N2)2Cl] or [Sb(DippForm)2Cl], (2), bis[N,N′-bis(2,6-diisopropylphenyl)formamidinato]bromidoantimony(III), [SbBr(C25H35N2)2] or [SbBr(DippForm)2], (3), bis[N,N′-bis(2,6-diisopropylphenyl)formamidinato]iodidoantimony(III), [Sb(C25H35N2)2I] or [Sb(DippForm)2I], (4), [N,N′-bis(2,6-diisopropylphenyl)formamidinato]dibromidoantimony(III), [SbBr2(C25H35N2)] or [SbBr2(DippForm)], (5), and [N,N′-bis(2,6-diisopropylphenyl)formamidinato]diiodidoantimony(III), [Sb(C25H35N2)I2] or [Sb(DippForm)I2], (6), were also synthesized by adding DippFormH and MN(SiMe3)2 (M = Li or Na) to the corresponding antimony halides SbX
3 (X = Cl, Br or I) in differing ratios. The complexes were all stable to rearrangement.