bluuebunny/crossref_metadata_2025_split huggingface dataset:
Germline DNA replication shapes the recombination landscape in mammals
Authors: Pratto Florencia , Brick Kevin , Cheng Gang , Lam Gabriel , Cloutier Jeffrey M. , Dahiya Daisy , Wellard Stephen R. , Jordan Philip W. , Camerini-Otero R. Daniel 
Published: September 2020

Summary:Genetic recombination generates novel trait combinations and understanding how recombination is distributed across the genome is key to modern genetics. The PRDM9 protein defines recombination hotspots, however megabase-scale recombination patterning is independent of PRDM9. The single round of DNA replication, which precedes recombination in meiosis, may establish these patterns, therefore we devised a novel approach to study meiotic replication that includes robust and sensitive mapping of replication origins. We find that meiotic DNA replication is distinct; reduced origin firing slows replication in meiosis and a distinctive replication pattern in human males underlies the sub-telomeric increase in recombination. We detected a robust correlation between replication and both contemporary and ancestral recombination and found that replication origin density coupled with chromosome size determines the recombination potential of individual chromosomes. Our findings and methods have far-reaching implications for understanding the mechanisms underlying DNA replication, genetic recombination, and the landscape of mammalian germline variation.
A proof of concept for neutralizing antibody-guided vaccine design against SARS-CoV-2
Authors: Zhang Li , Cao Lei , Gao Xing-Su , Zheng Bin-Yang , Deng Yong-Qiang , Li Jing-Xin , Feng Rui , Bian Qian , Guo Xi-Ling , Wang Nan , Qiu Hong-Ying , Wang Lei , Cui Zhen , Ye Qing , Chen Geng , Lu Kui-Kui , Chen Yin , Chen Yu-Tao , Pan Hong-Xing , Zhu Bao-Li , Qin Cheng-Feng , Wang Xiangxi , Zhu Feng-Cai 
Published: September 2020

AbstractMutations and transient conformational movements of receptor binding domain (RBD) that make neutralizing epitopes momentarily unavailable, present immune escape routes to SARS-CoV-2. To mitigate viral escape, we developed a cocktail of neutralizing antibodies (NAbs) targeting epitopes located on different domains of spike (S) protein. Screening of a library of monoclonal antibodies generated from peripheral blood mononuclear cells of COVID-19 convalescent patients yielded potent NAbs, targeting N-terminal domain (NTD) and RBD domain of S, effective atnMconcentrations. Remarkably, combination of RBD-targeting NAbs and NTD-binding NAb, FC05, dramatically enhanced the neutralization potency in cell-based assays and animal model. Results of competitive SPR assays and cryo-EM structures of Fabs bound to S unveil determinants of immunogenicity. Combinations of immunogens, identified in NTD and RBD of S, when immunized in rabbits elicited potent protective immune responses against SARS-CoV-2. These results provide a proof-of-concept for neutralization-based immunogen design targeting SARS-CoV-2 NTD and RBD.One sentence summaryImmunogens identified in the NTD and RBD of the SARS-CoV-2 spike protein using a cocktail of non-competing NAbs when injected in rabbits elicited a potent protective immune response against SARS-CoV-2.
A first-takes-all model of centriole copy number control
Authors: Dias Louro Marco António , Bettencourt-Dias Mónica , Carneiro Jorge 
Published: September 2020

AbstractHow cells control the numbers of its subcellular components is a fundamental question in biology. Given that biosynthetic processes are fundamentally stochastic it is utterly puzzling that some structures display no copy number variation within a cell population. Centriole biogenesis, with each centriole being duplicated once and only once per cell cycle, stands out due to its remarkable fidelity. This is a highly controlled process, which depends on low-abundance rate-limiting factors. How can exactly one centriole copy be produced given the natural variation in the concentration of these key players? Hitherto, tentative explanations of this control evoked lateral inhibition-or phase separation-like mechanisms emerging from the dynamics of these rate-limiting factors, but how centriole number is regulated remains unclear. Here, we propose a novel solution to centriole copy number control based on the assembly of a centriolar scaffold, the cartwheel. We hypothesise that once the first cartwheel is formed it continues to elongate by stacking the intermediate cartwheel building blocks that would otherwise form supernumerary structures. Using probability theory and computer simulations, we show that this mechanism may ensure formation of one and only one cartwheel over a wide range of parameter values at physiologically relevant conditions. By comparison to alternative models, we conclude that the key signatures of this novel mechanism are an increasing assembly time with cartwheel numbers and that stochasticity in cartwheel building blocks should be converted into variation in cartwheel numbers or length, both of which can be tested experimentally.Author summaryCentriole duplication stands out as a biosynthetic process of exquisite fidelity in the noisy world of the cell. Each centriole duplicates exactly once per cell cycle, such that the number of centrioles per cell shows no variance across cells, in contrast with most cellular components that show broadly distributed copy numbers. We propose a new solution to the number control problem. We show that elongation of the first cartwheel, a core centriolar structure, may sequester the building blocks necessary to assemble supernumerary centrioles. As a corollary, the variation in regulatory kinases and cartwheel components across the cell population is predicted to translate into cartwheel length variation instead of copy number variation, which is an intriguing overlooked possibility.
PspA adopts an ESCRT-III-like fold and remodels bacterial membranes
Authors: Junglas Benedikt , Huber Stefan T. , Heidler Thomas , Schlösser Lukas , Mann Daniel , Hennig Raoul , Clarke Mairi , Hellmann Nadja , Schneider Dirk , Sachse Carsten 
Published: September 2020

SummaryPspA is the main effector of the phage shock protein (Psp) system and preserves the bacterial inner membrane integrity and function. Here, we present the 3.6 Å resolution cryo-EM structure of PspA assembled in helical rods. PspA monomers adopt a canonical ESCRT-III fold in an extended open conformation. PspA rods are capable of enclosing lipids and generate positive membrane curvature. Using cryo-EM we visualized how PspA remodels membrane vesicles into μm-sized structures and how it mediates the formation of internalized vesicular structures. Hot spots of these activities are zones derived from PspA assemblies, serving as lipid transfer platforms and linking previously separated lipid structures. These membrane fusion and fission activities are in line with the described functional properties of bacterial PspA/IM30/LiaH proteins. Our structural and functional analyses reveal that bacterial PspA belongs to the evolutionary ancestry of ESCRT-III proteins involved in membrane remodeling.
Co-Citation Percentile Rank and JYUcite: a new network-standardized output-level citation influence metric and its implementation using Dimensions API
Authors: Seppänen Janne-Tuomas , Värri Hanna , Ylönen Irene 
Published: September 2020

AbstractJudging value of scholarly outputs quantitatively remains a difficult but unavoidable challenge. Most of the proposed solutions suffer from three fundamental shortcomings: they involve i) the concept of journal, in one way or another, ii) calculating arithmetic averages from extremely skewed distributions, and iii) binning data by calendar year. Here, we introduce a new metric Co-citation Percentile Rank (CPR), that relates the current citation rate of the target output taken at resolution of days since first citable, to the distribution of current citation rates of outputs in its co-citation set, as its percentile rank in that set. We explore some of its properties with an example dataset of all scholarly outputs from University of Jyväskylä spanning multiple years and disciplines. We also demonstrate how CPR can be efficiently implemented with Dimensions database API, and provide a publicly available web resource JYUcite, allowing anyone to retrieve CPR value for any output that has a DOI and is indexed in the Dimensions database. Finally, we discuss how CPR remedies failures of the Relative Citation Ratio (RCR), and remaining issues in situations where CPR too could potentially lead to biased judgement of value.
Genetic variation, environment and demography intersect to shape Arabidopsis defense metabolite variation across Europe
Authors: Katz Ella , Bagaza Clement , Holden Samuel , Angelovici Ruthie , Kliebenstein Daniel J. 
Published: September 2020

AbstractPlants face a variety of challenges within their ever-changing environment. Diverse metabolites are central to the plants ability to overcome these challenges. Understanding the environmental and genetic factors influencing the variation in specialized metabolites is the key to understand how plants survive and develop under changing environments. Here we measure the variation in specialized metabolites across a population of 797 naturalArabidopsis thalianaaccessions. We show a combination of geography, environmental parameters, demography, and different genetic processes that creates a specific pattern in their accumulation and distribution. By identifying and tracking causal polymorphisms at multiple loci controlling metabolites variation we show that each locus displays extensive allelic heterogeneity with signatures of both parallel and convergent evolutionary processes. These loci combine epistatically and show differing relationships to environmental parameters leading to different distributions. This provides a detailed perspective about the complexity of the forces and mechanisms that shape the accumulation and distribution of a family of specialized metabolites critical for plant fitness.
Heteroplasmy and repeat expansion in the plant-like mitochondrial genome of a bivalve mollusc
Authors: Calcino Andrew , Baranyi Christian , Wanninger Andreas 
Published: September 2020

AbstractBackgroundAnimal mitochondrial genomes are typically circular, 14-20 kb in length, maternally inherited, contain 13 coding genes, two ribosomal genes and are homoplasmic. In contrast, plant mitogenomes display frequent gene rearrangements, often contain greatly expanded repetitive regions, encode various open reading frames of unknown function and may be heteroplasmic due to differential repeat expansions between molecules. Error correction by recombination is common in plant mitochondria and has been proposed as the driver behind the rearrangements and repeat expansions that are often observed. In contrast, most animal mitochondria never or only very seldomly recombine and their utilisation of other repair mechanisms for mitochondrial genome error correction is a potential driver of their non-coding DNA reduction.ResultsUsing PacBio long reads for genome assembly and structural variant detection, we identify evidence of heteroplasmy in the form of variable repeat lengths within two blocks of repetitive DNA within the expanded 46 kb mitochondrial genome of the bivalve mollusc, quagga mussel,Dreissena rostriformis. The quagga mussel also has a greatly expanded repertoire of coding genes in comparison to most animals which includes an additional nine open reading frames (ORFs) encoding predicted transmembrane peptides of unknown orthology.ConclusionsThe genome size, repeat content and coding gene repertoire of the quagga mussel mitogenome closely resemble those of plants and the identification of repeat-associated heteroplasmy is consistent with the utilisation of plant-like recombination-based error correction mechanisms. Given the frequency of mitochondrial repeat expansions within the Bivalvia, recombination may be an underappreciated mechanism for mitogenomic error correction within this and other animal lineages.Significance StatementUnlike most animals, the mitochondrial genomes of many bivalve molluscs are often greatly expanded and contain large non-coding regions and additional predicted genes of unknown function. While these features are uncommon in other animal groups, they are common features of plant mitochondrial genomes. Here we show that the mitochondrial genome of the bivalve mollusc, the quagga mussel, displays many plant-like features and additionally, shows evidence of variability in the repeat lengths between mitochondrial molecules within an individual mussel. We propose that similar error correction mechanisms in plants and bivalves may play a role in these observed commonalities.
Cross kingdom analysis of putative quadruplex-forming sequences in fungal genomes: novel antifungal targets to ameliorate fungal pathogenicity?
Authors: Warner Emily F. , Bohálová Natália , Brázda Václav , Waller Zoë A. E. , Bidula Stefan 
Published: September 2020

AbstractFungi contribute to upwards of 1.5 million human deaths annually, are involved in the spoilage of up to a third of food crops, and have a devastating effect on plant and animal biodiversity. Moreover, this already significant issue is exacerbated by a rise in antifungal resistance and a critical requirement for novel drug targets. Quadruplexes are four-stranded secondary structures in nucleic acids which can regulate processes such as transcription, translation, replication, and recombination. They are also found in genes linked to virulence in microbes, and quadruplex-binding ligands have been demonstrated to eliminate drug resistant pathogens. Using a computational approach, we identified putative quadruplex-forming sequences (PQS) in 1362 genomes across the fungal kingdom and explored their potential involvement in virulence, drug resistance, and pathogenicity. Here we present the largest analysis of PQS in fungi and identified significant heterogeneity of these sequences throughout phyla, genera, and species. Moreover, PQS were genetically conserved. Notably, loss of PQS in cryptococci and aspergilli was associated with pathogenicity. PQS in the clinically important pathogensAspergillus fumigatus, Cryptococcus neoformans, andCandida albicanswere located within genes (particularly coding regions), mRNA, repeat regions, mobile elements, tRNA, ncRNA, rRNA, and the centromere. Genes containing PQS in these organisms were found to be primarily associated with metabolism, nucleic acid binding, transporter activity, and protein modification. Finally, PQS were found in over 100 genes associated with virulence, drug resistance, or key biological processes in these pathogenic fungi and were found in genes which were highly upregulated during germination, hypoxia, oxidative stress, iron limitation, and in biofilms. Taken together, quadruplexes in fungi could present interesting novel targets to ameliorate fungal virulence and overcome drug resistance.
Correlating the structure and activity ofY. pestisAil in a bacterial cell envelope
Authors: Kent J. E. , Fujimoto L. M. , Shin K. , Singh C. , Yao Y. , Park S. , Opella S. J. , Plano G. V. , Marassi F. M. 
Published: September 2020

ABSTRACTUnderstanding microbe-host interactions at the molecular level is a major goal of fundamental biology and therapeutic drug development. Structural biology strives to capture biomolecular structures in action, but the samples are often highly simplified versions of the complex native environment. Here we present anE. colimodel system that allows us to probe the structure and function of Ail, the major surface protein of the deadly pathogenYersinia pestis.We show that cell surface expression of Ail producesY. pestisvirulence phenotypes inE. coli,including resistance to human serum, co-sedimentation of human vitronectin and pellicle formation. Moreover, isolated bacterial cell envelopes, encompassing inner and outer membranes, yield high-resolution solid-state nuclear magnetic resonance (NMR) spectra that reflect the structure of Ail and reveal Ail sites that are sensitive to the bacterial membrane environment and involved in the interactions with human serum components. The data capture the structure and function of Ail in a bacterial outer membrane and set the stage for probing its interactions with the complex milieu of immune response proteins present in human serum.SIGNIFICANCEAil is a critical virulence factor ofY. pestis,and its interactions with human serum are central for promoting the immune resistance of bacteria to the human host defenses. Here we capture the action of Ail in a functional bacterial environment and set the stage for probing its interactions with the complex milieu of immune response proteins present in human serum. The development of anE. colimodel system ofY. pestisfor biophysical studies is new and biologically important. Finally, the work extends the rangein-situNMR spectroscopy to include models of microbial infection.
Glycine acylation and trafficking of a new class of bacterial lipoprotein by a composite secretion system
Authors: Icke Christopher , Hodges Freya J. , Puella Karthik , McKeand Samantha A. , Bryant Jack A. , Cunningham Adam F. , Cole Jeff A. , Henderson Ian R. 
Published: September 2020

AbstractProtein acylation is critical for many cellular functions including signal transduction, cell division and development. In bacteria, such lipoproteins have important roles in virulence and are therefore potential targets for the development of novel antimicrobials and vaccines. To date, all known bacterial lipoproteins are secreted from the cytosol via the Sec pathway, acylated on an N-terminal cysteine residue through the action of Lgt, Lsp and Lnt, and then targeted to the appropriate cellular location. In the case of Gram-negative bacteria, the lipoprotein trafficking Lol pathway transports the lipoproteins to the outer membrane where most substrate molecules are retained within the cell. Here we identify a new secretion pathway that displays the substrate lipoprotein on the cell surface. We demonstrate that the previously identifiedE. coliAat secretion system is a composite system that shares similarity with type I secretion systems and elements of the Lol pathway. Remarkably, during secretion by the Aat system, the AatD subunit acylates the substrate CexE on a highly conserved N-terminal glycine residue (rather than the canonical cysteine). Mutations in AatD or CexE that disrupt glycine acylation interfere with membrane incorporation and trafficking. Our data suggest that CexE is the first member of a new class of glycine-acylated bacterial lipoprotein, while Aat represents a new secretion system that we propose be defined as a lipoprotein secretion system (LSS).
Highly pathogenic avian influenza (H5N1) landscape suitability varies by wetland habitats and the degree of interface between wild waterfowl and poultry in India
Authors: Walsh Michael G. , Mor Siobhan M. , Hossain Shah 
Published: September 2020

AbstractHighly pathogenic avian influenza (HPAI), subtype H5N1, constitutes one of the world’s most important health and economic concerns given the catastrophic impact of epizootics on the poultry industry, the high mortality attending spillover in humans, and its potential as a source subtype for a future pandemic. Nevertheless, we still lack an adequate understanding of HPAI H5N1 epidemiology and infection ecology. The nature of the wild waterfowl-poultry interface, and the sharing of diverse wetland habitat among these birds, currently underscore important knowledge gaps. India has emerged as a global hotspot for HPAI H5N1, while also providing critical wintering habitat for many species of migratory waterfowl and year-round habitat for several resident waterfowl species. The current study sought to examine the extent to which the wild waterfowl-poultry interface, varied wetland habitat, and climate influence HPAI H5N1 epizootics in poultry in India. Using World Organisation for Animal Health reported outbreaks, this study showed that the wild waterfowl-poultry interface and lacustrine, riparian, and coastal marsh wetland systems were strongly associated with landscape suitability, and these realtionships varied by scale. Although increasing poultry density was associated with increasing risk, this was only the case in the absence of wild waterfowl habitat, and only at local scale. In landscapes increasingly shared between wild waterfowl and poultry, suitability was greater among lower density poultry, again at local scale only. These findings provide further insight into the occurrence of HPAI H5N1 in India and suggest important landscape targets for blocking the waterfowl-poultry interface to interrupt virus transmission and prevent future outbreaks.
Evaluation method of ecosystem service value under complex ecological environment: A case study of Gansu Province, China
Authors: Zhao Xiaojiong , Wang Jian , Su Junde , Sun Wei 
Published: September 2020

AbstractScientific assessment of regional ecosystem service value (ESV) is helpful to make scientific ecological protection plan and compensation policy. The evaluation method has not been established that is adapted to the complex and diverse characteristics of the ecological environment. This paper takes Gansu Province as an example, on the basis of fully considering the regional differences of ecosystem service function, the five correction index of value equivalent factor per unit area were constructed in the provincial scale, and the regional difference adjustment index of 11 kinds of ES was constructed in regional scale, in the way, the value evaluation model based on regional difference was established. The results show that in 2015, the total ESV reached 2239.555 billion Yuan in Gansu Province, ESV gradually increased from the northeast to the southwest, and the high-value areas of service function located in Qilian Mountain and Longnan Mountain, of which the forest and grassland ecosystem contributed the most to the value. From the perspective of value composition, local climate regulation and biodiversity maintenance function are the main service functions of Gansu Province. From 2000 to 2015, ESV increased by 3.426 billion Yuan in Gansu Province, the value of forest and urban ecosystem continued increasing, while the value of cultivated land ecosystem continue decreasing. From the spatial characteristics of service value change, the area of value reduction gradually moved from the central part of Gansu Province to the surrounding area. In general, although this study needs further improvement, the constructed evaluation method provides a relatively comprehensive evaluation scheme for the spatiotemporal dynamic evaluation of ESV in Gansu Province. This study provided a more overall research idea for the evaluation of ESV under complex ecological environment.
Neural correlates of auditory pattern learning in the auditory cortex
Authors: Kang H. , Auksztulewicz R. , An H. J. , Abichacra N. , Sutter M. L. , Schnupp J. W. H. 
Published: September 2020

AbstractLearning of new auditory stimuli requires repetitive exposure to the stimulus. Fast and implicit learning of sounds presented at random times enables efficient auditory perception. However, it is unclear how such sensory encoding is processed on a neural level. We investigated neural responses that are developed from a passive, repetitive exposure to a specific sound in the auditory cortex of anesthetized rats, using electrocorticography. We presented a series of random sequences that are generated afresh each time, except for a specific reference sequence that remains constant and re-appears at random times across trials. We compared induced activity amplitudes between reference and fresh sequences. Neural responses from both primary and non-primary auditory cortical regions showed significantly decreased induced activity amplitudes for reference sequences compared to fresh sequences, especially in the beta band. This is the first study showing that neural correlates of auditory pattern learning can be evoked even in anesthetized, passive listening animal models.