bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tn-Core: context-specific reconstruction of core metabolic models using Tn-seq data
Authors: diCenzo George C , Mengoni Alessio , Fondi Marco 
Published: November 2017

ABSTRACTMotivationTn-seq (transposon mutagenesis and sequencing) and constraint-based metabolic modelling represent highly complementary approaches. They can be used to probe the core genetic and metabolic networks underlying a biological process, revealing invaluable information for synthetic biology engineering of microbial cell factories. However, while algorithms exist for integration of –omics data sets with metabolic models, no method has been explicitly developed for integration of Tn-seq data with metabolic reconstructions.ResultsWe report the development of Tn-Core, a Matlab toolbox designed to generate gene-centric, context-specific core reconstructions consistent with experimental Tn-seq data. Extensions of this algorithm allow: i) the generation of context-specific functional models through integration of both Tn-seq and RNA-seq data; ii) to visualize redundancy in core metabolic processes; and iii) to assist in curation ofde novodraft metabolic models. The utility of Tn-Core is demonstrated primarily using aSinorhizobium melilotimodel as a case study.Availability and implementationThe software can be downloaded fromhttps://github.com/diCenzo-GC/Tn-Core. All results presented in this work have been obtained with Tn-Core v. 1.0.Contactgeorgecolin.dicenzo@unifi.it,marco.fondi@unifi.itSupplementary informationSupplementary data are available at Bioinformatics online.
CRISPys: Optimal sgRNA design for editing multiple members of a gene family using the CRISPR system
Authors: Hyams Gal , Abadi Shiran , Avni Adi , Halperin Eran , Shani Eilon , Mayrose Itay 
Published: November 2017

AbstractThe discovery and development of the CRISPR-Cas9 system in the past few years has made eukaryotic genome editing, and specifically gene knockout for reverse genetics, a simpler, efficient, and effective task. The system is directed to the genomic target site by a programmed single-guide RNA (sgRNA) that base-pairs with the DNA target, subsequently leading to site-specific double-strand breaks. However, many gene families in eukaryotic genomes exhibit partially overlapping functions and, thus, the knockout of one gene might be concealed by the function of the other. In such cases, the reduced specificity of the CRISPR-Cas9 system, which may lead to the cleavage of genomic sites that are not identical to the sgRNA, can be harnessed for the simultaneous knockout of multiple homologous genes. Here, we introduce CRISPys, an algorithm for the optimal design of sgRNAs that would potentially target multiple members of a given gene family. CRISPys first clusters all the potential targets in the input sequences into a hierarchical tree structure that specifies the similarity among them. Then, sgRNAs are proposed in the internal nodes of the tree by embedding mismatches where needed, such that the cleavage efficiencies of the induced targets are maximized. We suggest several approaches for designing the optimal individual sgRNA, and an approach that provides a set of sgRNAs that also accounts for the homologous relationships among gene-family members. We further show by in-silico examination over all gene families in theSolanum lycopersicumgenome that our suggested approach outperforms simpler alignment-based techniques.Graphical abstractHighlightsMany genes in eukaryotic genomes exhibit partially overlapping functions. This imposes difficulties on reverse-genetics, as the knockout of one gene might be concealed by the function of the other.We present CRISPys, a graph-based algorithm for the optimal design of CRISPR systems given a set of redundant genes.CRISPys harnesses the lack of specificity of the CRISPR-Cas9 genome editing technique, providing researchers the ability to simultaneously mutate multiple genes.We show that CRISPys outperforms existing approaches that are based on simple alignment of the input gene family.
Hominin-specific NOTCH2 paralogs expand human cortical neurogenesis through regulation of Delta/Notch interactions
Authors: Suzuki Ikuo K. , Gacquer David , Van Heurck Roxane , Kumar Devesh , Wojno Marta , Bilheu Angéline , Herpoel Adèle , Chéron Julian , Polleux Franck , Detours Vincent , Vanderhaeghen Pierre 
Published: November 2017

SummaryThe human cerebral cortex has undergone rapid expansion and increased complexity during recent evolution. Hominid-specific gene duplications represent a major driving force of evolution, but their impact on human brain evolution remains unclear. Using tailored RNA sequencing (RNAseq), we profiled the spatial and temporal expression of Hominid-specific duplicated (HS) genes in the human fetal cortex, leading to the identification of a repertoire of 36 HS genes displaying robust and dynamic patterns during cortical neurogenesis. Among these we focused on NOTCH2NL, previously uncharacterized HS paralogs of NOTCH2. NOTCH2NL promote the clonal expansion of human cortical progenitors by increasing self-renewal, ultimately leading to higher neuronal output. NOTCH2NL function by activating the Notch pathway, through inhibition of Delta/Notch interactions. Our study uncovers a large repertoire of recently evolved genes linking genomic evolution to human brain development, and reveals how hominin-specific NOTCH paralogs may have contributed to the expansion of the human cortex.
Giant flagellins form thick flagellar filaments in two species of marine γ-proteobacteria
Authors: Thomson Nicholas M. , Ferreira Josie L. , Matthews-Palmer Teige R. , Beeby Morgan , Pallen Mark J. 
Published: November 2017

AbstractFlagella, the primary means of motility in bacteria, are helical filaments that function as microscopic propellers composed of thousands of copies of the protein flagellin. Here, we show that many bacteria encode “giant” flagellins, greater than a thousand amino acids in length, and that two species that encode giant flagellins, the marine γ- proteobacteria Bermanella marisrubri and Oleibacter marinus, produce monopolar flagellar filaments considerably thicker than filaments composed of shorter flagellin monomers. We confirm that the flagellum from B. marisrubri is built from its giant flagellin. Phylogenetic analysis reveals that the mechanism of evolution of giant flagellins has followed a stepwise process involving an internal domain duplication followed by insertion of an additional novel insert. This work illustrates how “the” bacterial flagellum should not be seen as a single, idealised structure, but as a continuum of evolved machines adapted to a range of niches.
Synaptic m6A Epitranscriptome Reveals Functional Partitioning of Localized Transcripts for Dynamic Tripartite Synapse Modulation
Authors: Merkurjev Daria , Hong Wan-Ting , lida Kei , Goldie Belinda J , Yamaguti Hitoshi , Oomoto Ikumi , Ohara Takayuki , Kawaguchi Shin-ya , Hirano Tomoo , Martin Kelsey C , Pellegrini Matteo , Wang Dan Ohtan 
Published: November 2017

AbstractA localized transcriptome at the synapse facilitates synapse-, stimulus-, and transcript-specific synthesis of the local proteome in response to neuronal activity. While enzyme-mediated mRNA modifications have been shown to regulate cellular mRNA turnover and translation, the role of these modifications in regulating synaptic RNA has not been studied. We established low-input m6A-seq of synaptosomal RNA to determine the chemically modified local transcriptome in healthy adult mouse forebrain and identified 4,329 selectively enriched m6A RNA peaks in 2,987 genes, which we refer to as the synaptic m6A epitranscriptome (SME). SME is functionally enriched in synthesis and modulation of tripartite synapses, and in pathways implicated in neurodevelopmental and neuropsychiatric diseases. Interrupting m6A-mediated regulation via knockdown of reader YTHDF1 in hippocampal neurons alters expression of SME member Apc, and causes synaptic malfunctions manifesting immature spine morphology and dampened excitatory synaptic transmission concomitant with decreased PSD-95 clustering and GluA1 surface expression. Our findings indicate that chemical modifications of synaptic mRNAs critically contribute to synaptic function.
Partitioning of semisynthetic lipidated N-Ras in lipid raft nanodomains determined by FRET to lipid domain markers
Authors: Shishina Anna K. , Kovrigina Elizaveta A. , Galiakhmetov Azamat R. , Rathore Rajendra , Kovrigin Evgenii L. 
Published: November 2017

ABSTRACTCellular membranes are heterogeneous planar lipid bilayers displaying lateral phase separation with the nanometer-scale liquid-ordered phase (aka “lipid rafts” or Lo) surrounded by the liquid-disordered phase (Ld). Many membrane-associated proteins were found to stably integrate in the rafts, which is critical for their biological function. Isoforms H and N of Ras GTPase possess a unique ability to switch their lipid domain preference depending on the type of bound guanine nucleotide (GDP or GTP). This behavior, however, has never been reproducedin vitroin model bilayers with recombinant proteins, and therefore has been attributed to action of other proteins binding Ras at the membrane surface. In this paper, we report the observation of the nucleotide-dependent switch of lipid domain preferences of the semisynthetic lipidated N-Ras in raft lipid vesiclesin the absence of other proteins. To detect segregation of Ras molecules in raft and disordered lipid domains, we measured Förster Resonance Energy Transfer (FRET) between the donor fluorophore, mant, attached to the protein-bound guanine nucleotides, and the acceptor, rhodamine-conjugated lipid, localized to the liquid-disordered domains. We demonstrated that N-Ras preferentially populated raft domains when bound to mant-GDP, while losing preference for rafts when it was associated with a GTP mimic, mant-GppNHp. At the same time, the isolated lipidated C-terminal peptide of N-Ras was found localized outside of the liquid-ordered rafts, most likely—in the bulk disordered lipid.
Evolution at the edge of expanding populations
Authors: Deforet Maxime , Carmona-Fontaine Carlos , Korolev Kirill S. , Xavier Joao B. 
Published: November 2017

AbstractPredicting evolution of expanding populations is critical to control biological threats such as invasive species and cancer metastasis. Expansion is primarily driven by reproduction and dispersal, but nature abounds with examples of evolution where organisms pay a reproductive cost to disperse faster. When does selection favor this ‘survival of the fastest?’ We searched for a simple rule, motivated by evolution experiments where swarming bacteria evolved into an hy-perswarmer mutant which disperses∼100% faster but pays a growth cost of ∼ 10% to make many copies of its flagellum. We analyzed a two-species model based on the Fisher equation to explain this observation: the population expansion rate (v) results from an interplay of growth (r) and dispersal (D) and is independent of the carrying capacity:. A mutant can take over the edge only if its expansion rate (v2) exceeds the expansion rate of the established species’ (v1); this simple condition (v2>v1) determines the maximum cost in slower growth that a faster mutant can pay and still be able to take over. Numerical simulations and time-course experiments where we tracked evolution by imaging bacteria suggest that our findings are general: less favorable conditions delay but do not entirely prevent the success of the fastest. Thus, the expansion rate defines a traveling wave fitness, which could be combined with trade-offs to predict evolution of expanding populations.
A de novo approach to disentangle partner identity and function in holobiont systems
Authors: Meng Arnaud , Marchet Camille , Corre Erwan , Peterlongo Pierre , Alberti Adriana , Da Silva Corinne , Wincker Patrick , Pelletier Eric , Probert Ian , Decelle Johan , Le Crom Stéphane , Not Fabrice , Bittner Lucie 
Published: November 2017

AbstractBackgroundStudy of meta-transcriptomic datasets involving non-model organisms represents bioinformatic challenges. The production of chimeric sequences and our inability to distinguish the taxonomic origins of the sequences produced are inherent and recurrent difficulties in de novo assembly analyses. The study of holobiont transcriptomes shares similarities with meta-transcriptomic, and hence, is also affected by challenges invoked above. Here we propose an innovative approach to tackle such difficulties which was applied to the study of marine holobiont models as a proof of concept.ResultsWe considered three holobionts models, of which two transcriptomes were previously assembled and published, and a yet unpublished transcriptome, to analyze their raw reads and assign them to the host and/or to the symbiont(s) using Short Read Connector, a k-mer based similarity method. We were able to define four distinct categories of reads for each holobiont transcriptome: host reads, symbiont reads, shared reads and unassigned reads. The result of the independent assemblies for each category within a transcriptome led to a significant diminution of de novo assembled chimeras compared to classical assembly methods. Combining independent functional and taxonomic annotations of each partner’s transcriptome is particularly convenient to explore the functional diversity of an holobiont. Finally, our strategy allowed to propose new functional annotations for two well-studied holobionts and a first transcriptome from a planktonic Radiolaria-Dinophyta system forming widespread symbiotic association for which our knowledge is limited. ConclusionsIn contrast to classical assembly approaches, our bioinformatic strategy not only allows biologists to studying separately host and symbiont data from a holobiont mixture, but also generates improved transcriptome assemblies. The use of Short Read Connector has proven to be an effective way to tackle meta-transcriptomic challenges to study holobiont systems composed of either well-studied or poorly characterized symbiotic lineages such as the newly sequenced marine plankton Radiolaria-Dinophyta symbiosis and ultimately expand our knowledge about these marine symbiotic associations.
Diel predator activity drives a dynamic landscape of fear
Authors: Kohl Michel T. , Stahler Daniel R. , Metz Matthew C. , Forester James D. , Kauffman Matthew J. , Varley Nathan , White P.J. , Smith Douglas W. , MacNulty Daniel R. 
Published: November 2017

AbstractA ‘landscape of fear’ (LOF) is a map that describes continuous spatial variation in an animal’s perception of predation risk. The relief on this map reflects, for example, places that an animal avoids to minimize risk. Although the LOF concept is a potential unifying theme in ecology that is often invoked to explain the ecological and conservation significance of fear, quantified examples of a LOF over large spatial scales are lacking as is knowledge about the daily dynamics of a LOF. Despite theory and data to the contrary, investigators often assume, implicitly or explicitly, that a LOF is a static consequence of a predator’s mere presence. We tested the prediction that a LOF in a large-scale, free-living system is a highly-dynamic map with ‘peaks’ and ‘valleys’ that alternate across the diel (24-hour) cycle in response to daily lulls in predator activity. We did so with extensive data from the case study of Yellowstone elk(Cervus elaphus)and wolves(Canis lupus)that was the original basis for the LOF concept. We quantified the elk LOF, defined here as spatial allocation of time away from risky places and times, across nearly 1000-km2of northern Yellowstone National Park and found that it fluctuated with the crepuscular activity pattern of wolves, enabling elk to use risky places during wolf downtimes. This may help explain evidence that wolf predation risk has no effect on elk stress levels, body condition, pregnancy, or herbivory. The ability of free-living animals to adaptively allocate habitat use across periods of high and low predator activity within the diel cycle is an underappreciated aspect of animal behavior that helps explain why strong antipredator responses may trigger weak ecological effects, and why a LOF may have less conceptual and practical importance than direct killing.
Stoichiometric homeostasis of wetland vegetation along a nutrient gradient in a subtropical wetland. Understanding stoichiometric mechanisms of nutrient retention in wetland macrophytes
Authors: Julian Paul , Gerber Stefan , Bhomia Rupesh K. , King Jill , Osborne Todd Z. , Wright Alan L. 
Published: November 2017

AbstractNutrient homeostasis relates ambient stoichiometric conditions in an environment to the stoichiometry of living entities of the ecosystem. In wetland ecosystems, vegetation can be a large, highly variable and dynamic sink of nutrients. This study investigated stoichiometric homeostasis of dominant emergent and submerged aquatic vegetation (EAV and SAV, respectively) within two treatment flow-ways (FW) of Everglades Stormwater Treatment Area 2 (STA-2). These FW encompass a large gradient in plant nutrient availability. The hypotheses of this study is that wetland vegetation is non-homeostatic relative to ambient nutrients and consequently nutrient resorption will not vary along the nutrient gradient. We developed a framework to investigate how vegetation uptake and resorption of nutrients contribute separately to homeostasis. Overall, the wetland vegetation in this study was non-homeostatic with respect to differential uptake of nitrogen (N) vs. phosphorus (P). Resorption evaluated for EAV was high for P and moderate for N, resorption efficiency did not significantly vary along the gradient and therefore did not affect overall homeostatic status. Nutrient addition experiments may help to compensate for some of the limitation of our study, especially with respect to resolving the primary nutrient source (organic vs. inorganic sources, water vs. soil compartment) and nutrient utilization rates.
Insights into platypus population structure and history from whole-genome sequencing
Authors: Martin Hilary C. , Batty Elizabeth M. , Hussin Julie , Westall Portia , Daish Tasman , Kolomyjec Stephen , Piazza Paolo , Bowden Rory , Hawkins Margaret , Grant Tom , Moritz Craig , Grutzner Frank , Gongora Jaime , Donnelly Peter 
Published: November 2017

AbstractThe platypus is an egg-laying mammal which, alongside the echidna, occupies a unique place in the mammalian phylogenetic tree. Despite widespread interest in its unusual biology, little is known about its population structure or recent evolutionary history. To provide new insights into the dispersal and demographic history of this iconic species, we sequenced the genomes of 57 platypuses from across the whole species range in eastern mainland Australia and Tasmania. Using a highly-improved reference genome, we called over 6.7M SNPs, providing an informative genetic data set for population analyses. Our results show very strong population structure in the platypus, with our sampling locations corresponding to discrete groupings between which there is no evidence for recent gene flow. Genome-wide data allowed us to establish that 28 of the 57 sampled individuals had at least a third-degree relative amongst other samples from the same river, often taken at different times. Taking advantage of a sampled family quartet, we estimated thede novomutation rate in the platypus at 7.0×10−9/bp/generation (95% CI 4.1×10−9− 1.2×10−8/bp/generation). We estimated effective population sizes of ancestral populations and haplotype sharing between current groupings, and found evidence for bottlenecks and long-term population decline in multiple regions, and early divergence between populations in different regions. This study demonstrates the power of whole-genome sequencing for studying natural populations of an evolutionarily important species.
Simple statistical identification and removal of contaminant sequences in marker-gene and metagenomics data
Authors: Davis Nicole M. , Proctor Diana M. , Holmes Susan P. , Relman David A. , Callahan Benjamin J. 
Published: November 2017

AbstractBackgroundThe accuracy of microbial community surveys based on marker-gene and metagenomic sequencing (MGS) suffers from the presence of contaminants — DNA sequences not truly present in the sample. Contaminants come from various sources, including reagents. Appropriate laboratory practices can reduce contamination, but do not eliminate it. Here we introduce decontam (https://github.com/benjjneb/decontam), an open-source R package that implements a statistical classification procedure that identifies contaminants in MGS data based on two widely reproduced patterns: contaminants appear at higher frequencies in low-concentration samples, and are often found in negative controls.Resultsdecontam classified amplicon sequence variants (ASVs) in a human oral dataset consistently with prior microscopic observations of the microbial taxa inhabiting that environment and previous reports of contaminant taxa. In metagenomics and marker-gene measurements of a dilution series, decontam substantially reduced technical variation arising from different sequencing protocols. The application of decontam to two recently published datasets corroborated and extended their conclusions that little evidence existed for an indigenous placenta microbiome, and that some low-frequency taxa seemingly associated with preterm birth were contaminants.Conclusionsdecontam improves the quality of metagenomic and marker-gene sequencing by identifying and removing contaminant DNA sequences. decontam integrates easily with existing MGS workflows, and allows researchers to generate more accurate profiles of microbial communities at little to no additional cost.
The relationship between varicella (chickenpox) and scarlet fever in contemporary Hong Kong
Authors: Coleman S. 
Published: November 2017

AbstractScarlet fever epidemics have reemerged in China, the UK, and Hong Kong. This research tests whether scarlet fever epidemics in Hong Kong are linked to varicella epidemics. Varicella infection is a known risk for invasive Group A Streptococcal infections, and historical research shows a connection between varicella and scarlet fever. This analysis examines the relationship between these two disease in Hong Kong from 2011 to 2015 and compares varicella rates before and after the reintroduction of scarlet fever. Analysis shows that scarlet fever and varicella have synchronous annual epidemic cycles, and a mathematical model of the relationship between scarlet fever and varicella is estimated. Varicella rates were unchanged by the return of scarlet fever, but annual varicella cycles may have influenced the size and timing of scarlet fever outbreaks. Vaccination policies for varicella may need to be adjusted to limit scarlet fever epidemics.