bluuebunny/crossref_metadata_2025_split huggingface dataset:
A computational framework for systematic exploration of biosynthetic diversity from large-scale genomic data
Authors: Navarro-Muñoz Jorge C. , Selem-Mojica Nelly , Mullowney Michael W. , Kautsar Satria , Tryon James H. , Parkinson Elizabeth I. , De Los Santos Emmanuel L.C. , Yeong Marley , Cruz-Morales Pablo , Abubucker Sahar , Roeters Arne , Lokhorst Wouter , Fernandez-Guerra Antonio , Dias Cappelini Luciana Teresa , Thomson Regan J. , Metcalf William W. , Kelleher Neil L. , Barona-Gomez Francisco , Medema Marnix H. 
Published: October 2018

AbstractGenome mining has become a key technology to explore and exploit natural product diversity through the identification and analysis of biosynthetic gene clusters (BGCs). Initially, this was performed on a single-genome basis; currently, the process is being scaled up to large-scale mining of pan-genomes of entire genera, complete strain collections and metagenomic datasets from which thousands of bacterial genomes can be extracted at once. However, no bioinformatic framework is currently available for the effective analysis of datasets of this size and complexity. Here, we provide a streamlined computational workflow, tightly integrated with antiSMASH and MIBiG, that consists of two new software tools, BiG-SCAPE and CORASON. BiG-SCAPE facilitates rapid calculation and interactive visual exploration of BGC sequence similarity networks, grouping gene clusters at multiple hierarchical levels, and includes a ‘glocal’ alignment mode that accurately groups both complete and fragmented BGCs. CORASON employs a phylogenomic approach to elucidate the detailed evolutionary relationships between gene clusters by computing high-resolution multi-locus phylogenies of all BGCs within and across gene cluster families (GCFs), and allows researchers to comprehensively identify all genomic contexts in which particular biosynthetic gene cassettes are found. We validate BiG-SCAPE by correlating its GCF output to metabolomic data across 403 actinobacterial strains. Furthermore, we demonstrate the discovery potential of the platform by using CORASON to comprehensively map the phylogenetic diversity of the large detoxin/rimosamide gene cluster clan, prioritizing three new detoxin families for subsequent characterization of six new analogs using isotopic labeling and analysis of tandem mass spectrometric data.
methyl-ATAC-seq measures DNA methylation at accessible chromatin
Authors: Spektor R , Tippens ND , Mimoso CA , Soloway PD 
Published: October 2018

ABSTRACTChromatin features are characterized by genome-wide assays for nucleosome location, protein binding sites, 3-dimensional interactions, and modifications to histones and DNA. For example, Assay for Transposase Accessible Chromatin sequencing (ATAC-seq) identifies nucleosome-depleted (open) chromatin, which harbors potentially active gene regulatory sequences; and bisulfite sequencing (BS-seq) quantifies DNA methylation. When two distinct chromatin features like these are assayed separately in populations of cells, it is impossible to determine, with certainty, where the features are coincident in the genome by simply overlaying datasets. Here we describe methyl-ATAC-seq (mATAC-seq), which implements modifications to ATAC-seq, including subjecting the output to BS-seq. Merging these assays into a single protocol identifies the locations of open chromatin, and reveals, unambiguously, the DNA methylation state of the underlying DNA. Such combinatorial methods eliminate the need to perform assays independently and infer where features are coincident.
Dopaminergic medication reduces striatal sensitivity to negative outcomes in Parkinson’s disease
Authors: McCoy Brónagh , Jahfari Sara , Engels Gwenda , Knapen Tomas , Theeuwes Jan 
Published: October 2018

AbstractReduced levels of dopamine in Parkinson’s disease (PD) contribute to changes in learning, resulting from the loss of midbrain dopamine neurons that transmit a teaching signal to the striatum. Dopamine medication used by PD patients has previously been linked to either behavioral changes during learning itself or adjustments in approach and avoidance behavior after learning. To date, however, very little is known about the specific relationship between dopaminergic medication-driven differences during learning and subsequent changes in approach/avoidance tendencies in individual patients. We assessed 24 PD patients on and off dopaminergic medication and 24 healthy controls (HC) performing a probabilistic reinforcement learning task, while undergoing functional magnetic resonance imaging. During learning, medication in PD reduced an overemphasis on negative outcomes. When patients were on medication, learning rates were lower for negative (but not positive) outcomes and concurrent striatal BOLD responses showed reduced prediction error sensitivity. Medication-induced shifts in negative learning rates were predictive of changes in approach/avoidance choice patterns after learning, and these changes were accompanied by striatal BOLD response alterations. These findings highlight dopamine-driven learning differences in PD and provide new insight into how changes in learning impact the transfer of learned value to approach/avoidance responses in novel contexts.
Synergistic interactions between confinement and macromolecular crowding spatially order transcription and translation in cell-free expression
Authors: Elizabeth Norred S. , Dabbs Rosemary M. , Chauhan Gaurav , Caveney Patrick M. , Collier C. Patrick , Abel Steven M. , Simpson Michael L. 
Published: October 2018

ABSTRACTSynergistic interactions between macromolecular crowding and confinement spatially organize transcription and translation in cells. Yet, reproducing such spatial ordering in cell-free expression platforms has proven to be elusive. Here we report crowding- and confinement-driven spatial self-organization of cell-free expression that mimics expression behavior within and around the nucleoid of prokaryotes. These experiments use Ficoll-70 to approximate cellular macromolecular crowding conditions within cell-size lipid vesicles. Intriguingly, there was an abrupt change in transcriptional dynamics when crowding reached physiologically relevant levels. Imaging experiments revealed that this change in transcriptional dynamics was coincident with localization of plasmid DNA and mRNA at the vesicle wall. Computer simulations demonstrated that crowding leads to an entropically induced attraction between plasmid DNA and the wall, causing localization of DNA near the wall at sufficiently high crowding levels. The experiments demonstrate cell-like spatial organization of translation, where translational activity is controlled by chromosomally-templated positioning of mRNA. This cell-free system provides a flexible experimental platform to probe the underlying mechanisms of self-organization of membrane-less structures in cells and the spatial control of gene expression.
GAL4 drivers specific for Type Ib and Type Is motor neurons inDrosophila
Authors: Perez-Moreno Juan J. , O’Kane Cahir J. 
Published: October 2018

ABSTRACTTheDrosophilalarval neuromuscular system is extensively used by researchers to study neuronal cell biology, andDrosophilaglutamatergic motor neurons (MNs) have become a major model system. There are two main Types of glutamatergic MNs, Ib and Is, with different structural and physiological properties at synaptic level at the neuromuscular junction. To generate genetic tools to identify and manipulate MNs of each Type, we screened forGAL4driver lines for this purpose. Here we describeGAL4drivers specific for examples of neurons within each Type, Ib or Is. These drivers showed high expression levels and were expressed in only few MNs, making them amenable tools for specific studies of both axonal and synapse biology in identified Type I MNs.
TADs pair homologous chromosomes to promote interchromosomal gene regulation
Authors: Viets Kayla , Sauria Michael , Chernoff Chaim , Anderson Caitlin , Tran Sang , Dove Abigail , Goyal Raghav , Voortman Lukas , Gordus Andrew , Taylor James , Johnston Robert J. 
Published: October 2018

AbstractHomologous chromosomes colocalize to regulate gene expression in processes including genomic imprinting and X-inactivation, but the mechanisms driving these interactions are poorly understood. InDrosophila, homologous chromosomes pair throughout development, promoting an interchromosomal gene regulatory mechanism called transvection. Despite over a century of study, the molecular features that facilitate chromosome-wide pairing are unknown. The “button” model of pairing proposes that specific regions along chromosomes pair with a higher affinity than their surrounding regions, but only a handful of DNA elements that drive homologous pairing between chromosomes have been described. Here, we identify button loci interspersed across the fly genome that have the ability to pair with their homologous sequences. Buttons are characterized by topologically associated domains (TADs), which drive pairing with their endogenous loci from multiple locations in the genome. Fragments of TADs do not pair, suggesting a model in which combinations of elements interspersed along the full length of a TAD are required for pairing. Though DNA-binding insulator proteins are not associated with pairing, buttons are enriched for insulator cofactors, suggesting that these proteins may mediate higher order interactions between homologous TADs. Using a TAD spanning thespinelessdgene as a paradigm, we find that pairing is necessary but not sufficient for transvection.spinelesspairing and transvection are cell-type-specific, suggesting that local buttoning and unbuttoning regulates transvection efficiency between cell types. Together, our data support a model in which specialized TADs button homologous chromosomes together to facilitate cell-type-specific interchromosomal gene regulation.
Quantitative Analysis of Interactive Behavior of Mitochondria and Lysosomes Using Structured Illumination Microscopy
Authors: Chen Qixin , Shao Xintian , Hao Mingang , Tian Zhiqi , Wang Chenran , Liu Fei , Zang Kai , Wang Fengshan , Ling Peixue , Guan Jun-Lin , Diao Jiajie 
Published: October 2018

ABSTRACTSuper-resolution optical microscopy has extended the spatial resolution of cell biology from the cellular level to the nanoscale, enabling the observation of the interactive behavior of single mitochondria and lysosomes. Quantitative parametrization of interaction between mitochondria and lysosomes under super-resolution optical microscopy, however, is currently unavailable, which has severely limited our understanding of the molecular machinery underlying mitochondrial functionality. Here, we introduce an M-value to quantitatively investigate mitochondria and lysosome contact (MLC) and mitophagy under structured illumination microscopy. We found that the M-value for an MLC is typically less than 0.4, whereas in mitophagy it ranges from 0.5 to 1.0. This system permits further investigation of the detailed molecular mechanism governing the interactive behavior of mitochondria and lysosomes.
Using long-read sequencing to detect imprinted DNA methylation
Authors: Gigante Scott , Gouil Quentin , Lucattini Alexis , Keniry Andrew , Beck Tamara , Tinning Matthew , Gordon Lavinia , Woodruff Chris , Speed Terence P. , Blewitt Marnie E. , Ritchie Matthew E. 
Published: October 2018

Systematic variation in the methylation of cytosines at CpG sites plays a critical role in early development of humans and other mammals. Of particular interest are regions of differential methylation between parental alleles, as these often dictate monoallelic gene expression, resulting in parent of origin specific control of the embryonic transcriptome and subsequent development, in a phenomenon known as genomic imprinting. Using long-read nanopore sequencing we show that, with an average genomic coverage of approximately ten, it is possible to determine both the level of methylation of CpG sites and the haplotype from which each read arises. The long-read property is exploited to characterise, using novel methods, both methylation and haplotype for reads that have reduced basecalling precision compared to Sanger sequencing. We validate the analysis both through comparison of nanopore-derived methylation patterns with those from Reduced Representation Bisulfite Sequencing data and through comparison with previously reported data.Our analysis successfully identifies known imprinting control regions as well as some novel differentially methylated regions which, due to their proximity to hitherto unknown monoallelically expressed genes, may represent new imprinting control regions.
Nuclear actin interactome analysis links actin to KAT14 histone acetyl transferase and mRNA splicing
Authors: Viita Tiina , Kyheröinen Salla , Prajapati Bina , Virtanen Jori , Varjosalo Markku , Vartiainen Maria K. 
Published: October 2018

AbstractIn addition to its essential functions within the cytoskeleton, actin also localizes to the cell nucleus, where it is linked to many important nuclear processes from gene expression to maintenance of genomic integrity. However, the molecular mechanisms by which actin operates in the nucleus remain poorly understood. Here we have used two complementary mass spectrometry (MS) techniques, AP-MS and BioID-MS, to identify binding partners for nuclear actin. Common high-confidence interactions highlight the role of actin in chromatin remodeling complexes and identify the hATAC histone modifier as a novel actin-containing nuclear complex. Further analysis demonstrates that actin binds directly to the hATAC subunit KAT14, and modulates its histone acetyl transferase activity in vitro and in cells. BioID-MS, which can detect also transient interactions, links actin to several steps of transcription as well as to RNA processing. Alterations in nuclear actin levels disturb alternative exon skipping of the SMN2 minigene, suggesting also a functional role for actin in RNA splicing. This interactome analysis thus identifies both novel direct binding partners and functional roles for nuclear actin, as well as forms a platform for further mechanistic studies on how actin operates during essential nuclear processes.
A two-step mechanism for the inactivation of microtubule organizing center function at the centrosome
Authors: Magescas Jérémy , Zonka Jennifer C. , Feldman Jessica L. 
Published: October 2018

SummaryDuring mitosis, the centrosome acts as a microtubule organizing center (MTOC), orchestrating microtubules into the mitotic spindle through its pericentriolar material (PCM). This activity is biphasic, cycling through assembly and disassembly during the cell cycle. Although hyperactive centrosomal MTOC activity is a hallmark of some cancers, little is known about how the centrosome is inactivated as an MTOC. Analysis of endogenous PCM proteins inC. elegansrevealed that the PCM is composed of distinct protein territories that are removed from the centrosome at different rates and using different behaviors. Inhibition of PP2A phosphatases stabilized the PCM and perturbation of cortical pulling forces altered the timing and behavior by which proteins were removed from the centrosome. These data indicate that PCM disassembly is a two-step process, beginning with a phosphatase-dependent dissolution of PCM proteins followed by the ejection of ruptured PCM by cortical forces, ultimately inactivating MTOC function at the centrosome.
Single-Cell Transcriptomics Unveils Gene Regulatory Network Plasticity
Authors: Iacono Giovanni , Massoni-Badosa Ramon , Heyn Holger 
Published: October 2018

SUMMARYSingle-cell RNA sequencing (scRNA-seq) plays a pivotal role in our understanding of cellular heterogeneity. Current analytical workflows are driven by categorizing principles that consider cells as individual entities and classify them into complex taxonomies. We have devised a conceptually different computational framework based on a holistic view, where single-cell datasets are used to infer global, large-scale regulatory networks. We developed correlation metrics that are specifically tailored to single-cell data, and then generated, validated and interpreted single-cell-derived regulatory networks from organs and perturbed systems, such as diabetes and Alzheimer’s disease. Using advanced tools from graph theory, we computed an unbiased quantification of a gene’s biological relevance, and accurately pinpointed key players in organ function and drivers of diseases. Our approach detected multiple latent regulatory changes that are invisible to single-cell workflows based on clustering or differential expression analysis. In summary, we have established the feasibility and value of regulatory network analysis using scRNA-seq datasets, which significantly broadens the biological insights that can be obtained with this leading technology.
Stepwise evolution and convergent recombination underlie the global dissemination of carbapenemase-producingEscherichia coli
Authors: Patiño-Navarrete Rafael , Rosinski-Chupin Isabelle , Cabanel Nicolas , Gauthier Lauraine , Takissian Julie , Madec Jean-Yves , Hamze Monzer , Bonnin Remy A. , Naas Thierry , Glaser Philippe 
Published: October 2018

AbstractCarbapenem-resistantEnterobacteriaceaeare considered by WHO as “critical” priority pathogens for which novel antibiotics are urgently needed. The dissemination of carbapenemase-producingEscherichia coli(CP-Ec) in the community is a major public health concern. However, the global molecular epidemiology of CP-Ecisolates, as well as the genetic bases for the emergence and global dissemination of specific lineages, remain largely unknown. Here, by combining a thorough genomic and evolutionary analysis ofEcST410 isolates with a broad analysis of 12,584E. coli and Shigellagenomes, we showed that the fixation of carbapenemase genes depends largely on a combination of mutations inftsIencoding the penicillin binding protein 3 and in the porin genesompCandompF. MutatedftsIgenes and a specificompCallele inducing reduced susceptibility to diverse β-lactams spread across the species by recombination. The selection of CP-Eclineages able to disseminate is more complex than the mere acquisition of carbapenemase genes.
The winner takes it all: how semelparous insects can become periodical
Authors: Diekmann Odo , Planqué Robert 
Published: October 2018

AbstractThe aim of this short note is to give a simple explanation for the remarkable periodicity of Magicicada species, which appear as adults only every 13 or 17 years, depending on the region. We show that a combination of two types of density dependence may drive, for large classes of initial conditions, all but one year class to extinction. Competition for food leads to negative density dependence in the form of a uniform (i.e., affecting all age classes in the same way) reduction of the survival probability. Satiation of predators leads to positive density dependence within the reproducing age class. The analysis focuses on the full life cycle map derived by iteration of a semelparous Leslie matrix.
Neural G0: a quiescent-like state found in neuroepithelial-derived cells and glioma
Authors: Feldman Heather M. , Toledo Chad M. , Arora Sonali , Hoellerbauer Pia , Corrin Philip , Carter Lucas , Kufeld Megan , Bolouri Hamid , Basom Ryan , Delrow Jeffrey , McFaline-Figueroa José L. , Trapnell Cole , Pollard Steven M. , Patel Anoop , Plaisier Christopher L. , Paddison Patrick J. 
Published: October 2018

AbstractSingle cell RNA-seq has emerged as a powerful tool for resolving cellular states associated with normal and maligned developmental processes. Here, we used scRNA-seq to examine the cell cycle states of expanding human neural stem cells (hNSCs). From this data, we created a cell cycle classifier, which, in addition to traditional cell cycle phases, also identifies a putative quiescent-like state in neuroepithelial-derived cell types during mammalian neurogenesis and in gliomas. This state, Neural G0, is enriched for expression of quiescent NSC genes and other neurodevelopmental markers found in non-dividing neural progenitors. For gliomas, Neural G0 cell populations and gene expression is significantly associated with less aggressive tumors and extended patient survival. Genetic screens to identify modulators of Neural G0 revealed that knockout of genes associated with the Hippo/Yap and p53 pathways diminished Neural G0in vitro, resulting in faster G1 transit, down regulation of quiescence-associated markers, and loss of Neural G0 gene expression. Thus, Neural G0 represents a dynamic quiescent-like state found in neuro-epithelial derived cells and gliomas.
High stretchability, strength and toughness of living cells enabled by hyperelastic vimentin network
Authors: Hu Jiliang , Li Yiwei , Hao Yukun , Zheng Tianqi , Parada German Alberto , Wu Huayin , Lin Shaoting , Wang Shida , Zhao Xuanhe , Goldman Robert D. , Cai Shengqiang , Guo Ming 
Published: October 2018

AbstractIn many normal and abnormal physiological processes, including cellular migration during normal development and invasion in cancer metastasis, cells are required to withstand severe deformations. The structural integrity of eukaryotic cells under small deformations has been known to depend on the cytoskeleton including actin filaments (F-actin), microtubules and intermediate filaments (IFs). However, it remains unclear how cells resist severe deformations since both F-actin and microtubules fluidize or disassemble under moderate strains. Here, we demonstrate that vimentin intermediate filaments (VIFs), a marker of mesenchymal cells, dominate cytoplasmic mechanics at large deformations. Our results show that cytoskeletal VIFs form a stretchable, hyperelastic network. This network works synergistically with other dissipative cytoplasmic components, substantially enhancing the strength, stretchability, resilience and toughness of the living cytoplasm.
Knowledge-based aircraft fuel system integration
Authors: Munjulury Raghu Chaitanya , Staack Ingo , Sabaté López Adrián , Krus Petter 
Published: October 2018

Purpose
This paper aims to present a knowledge-based fuel system, implementation and application, oriented towards its use in aircraft conceptual design.

Design/methodology/approach
Methodology and software tools oriented to knowledge-based engineering applications (MOKA) is used as a foundation for the implementation and integration of fuel systems.

Findings
Including fuel systems earlier in the design process creates an opportunity to optimize it and obtain better solutions by allocating suitable locations in an aircraft, thereby reflecting on the centre of gravity of the aircraft.

Research limitations/implications
All geometries are symbolic, representing a space allocation inside the aircraft for the fuel system. A realistic representation of the real components could be realized in detail design.

Practical implications
Fuel weight is a significant part of take-off weight and decisive in aircraft sizing and range estimations. The three-dimensional geometry provides a better estimation of the volume that is available to allocate the necessary entities. It also provides fast measures for weight and balance, fuel capacity, relative tank positions and a first estimation of piping length.

Originality/value
Fuel systems appear early in the design process, as they are involved in several first estimations. By using a knowledge-based engineering approach, several alternatives can be visualized and estimated in the conceptual design process. Furthermore, using the weights and centre of gravity at different angles of pitch and roll of each fuel tank, the aircraft could be optimized for handling qualities by using automatically generated system simulation models.