bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sampling strategy optimization to increase statistical power in landscape genomics: a simulation-based approach
Authors: Selmoni Oliver , Vajana Elia , Guillaume Annie , Rochat Estelle , Joost Stéphane 
Published: April 2019

AbstractAn increasing number of studies are using landscape genomics to investigate local adaptation in wild and domestic populations. The implementation of this approach requires the sampling phase to consider the complexity of environmental settings and the burden of logistic constraints. These important aspects are often underestimated in the literature dedicated to sampling strategies.In this study, we computed simulated genomic datasets to run against actual environmental data in order to trial landscape genomics experiments under distinct sampling strategies. These strategies differed by design approach (to enhance environmental and/or geographic representativeness at study sites), number of sampling locations and sample sizes. We then evaluated how these elements affected statistical performances (power and false discoveries) under two antithetical demographic scenarios.Our results highlight the importance of selecting an appropriate sample size, which should be modified based on the demographic characteristics of the studied population. For species with limited dispersal, sample sizes above 200 units are generally sufficient to detect most adaptive signals, while in random mating populations this threshold should be increased to 400 units. Furthermore, we describe a design approach that maximizes both environmental and geographical representativeness of sampling sites and show how it systematically outperforms random or regular sampling schemes. Finally, we show that although having more sampling locations (between 40 and 50 sites) increase statistical power and reduce false discovery rate, similar results can be achieved with a moderate number of sites (20 sites). Overall, this study provides valuable guidelines for optimizing sampling strategies for landscape genomics experiments.
Traces of Meaning Itself: Encoding distributional word vectors in brain activity
Authors: Sassenhagen Jona , Fiebach Christian J. 
Published: April 2019

AbstractHow is semantic information stored in the human mind and brain? Some philosophers and cognitive scientists argue for vectorial representations of concepts, where the meaning of a word is represented as its position in a high-dimensional neural state space. At the intersection of natural language processing and artificial intelligence, a class of very successful distributional word vector models has developed that can account for classic EEG findings of language, i.e., the ease vs. difficulty of integrating a word with its sentence context. However, models of semantics have to account not only for context-based word processing, but should also describe how word meaning is represented. Here, we investigate whether distributional vector representations of word meaning can model brain activity induced by words presented without context. Using EEG activity (event-related brain potentials) collected while participants in two experiments (English, German) read isolated words, we encode and decode word vectors taken from the family of prediction-based word2vec algorithms. We find that, first, the position of a word in vector space allows the prediction of the pattern of corresponding neural activity over time, in particular during a time window of 300 to 500 ms after word onset. Second, distributional models perform better than a human-created taxonomic baseline model (WordNet), and this holds for several distinct vector-based models. Third, multiple latent semantic dimensions of word meaning can be decoded from brain activity. Combined, these results suggest that empiricist, prediction-based vectorial representations of meaning are a viable candidate for the representational architecture of human semantic knowledge.
Prevalence of Hepatitis C Virus Genotypes in the Southern Region, Saudi Arabia
Authors: AlKahtani Abdullah M , Alsultan Meaad N , Hakami Abdulrahim R , Alamri Mohammad 
Published: April 2019

ABSTRACTAimThe aim of this study was to investigate the prevalence of HCV genotypes in the Southern Region, Saudi Arabia.Materials & methodsA total of 76 HCV-positive individuals were selected for this study, including 34 males and 42 females, both acute and chronic patients. All HCV isolates were genotyped by direct sequencing of the 5’UTR region. The Chemistry profile, viral load and history of blood transfusion were collected from the hospital record.ResultsThe most common genotype was gt 4 (48.7%) followed by gt 1 (34.2%) and gt 3 (14.5%). Genotype 2 (2.6%) was only found in elderly male individuals. Patients with history of blood transfusion showed a high percentage of genotype 1 compared to the total number of all patients with genotype 1 (23% and 11% respectively). Biochemical assay showed high level of ALT particularly in genotype 4. No significant relationship was observed between HCV genotype and AST level between genotypes. The viral load was higher in HCV patients received blood transfusion than other genotypes.ConclusionThe prevalence of genotypes in this study confirmed the observation of other investigations, but no link was found between sex and genotype. There might be an association between blood donation in the past and infections with genotype 1.
Induced expression of Xerophyta viscosa XvSap1 gene greatly impacts tolerance to drought stress in transgenic sweetpotato
Authors: Mbinda Wilton , Dixelius Christina , Oduor Richard 
Published: April 2019

AbstractKey message Drought stress in sweetpotato could be overcome by introducing XvSap1 gene from Xerophyta viscosa.Drought stress often leads to reduced yields and is perilous delimiter for expanded cultivation and increased productivity of sweetpotato. Cell wall stabilization proteins have been identified to play a pivotal role in mechanical stabilization during desiccation stress mitigation. They are involved in myriad cellular processes that modify the cell wall properties to tolerate the mechanical stress during dehydration in plants. This provides a possible approach to engineer crops for enhanced stable yields under adverse climatic conditions. In this study, we introduced the XvSap1 gene isolated from Xerophyta viscosa, a resurrection plant into sweetpotato by Agrobacterium-mediated transformation. Detection of the transgene by PCR coupled with Southern blot revealed the integration of XvSap1 in the three independent events. Sweetpotato plants expressing the XvSap1 gene exhibited superior growth performance such as shoot length, number of leaves and yield than the wild type plants under drought stress. Quantitative real time-PCR results confirmed higher expression of the XvSap1 gene in XSP1 transgenic plants imposed with drought stress. In addition, the transgenic plants had increased levels of chlorophyll, free proline and relative water content but malonaldehyde content was decreased under drought stress compared to wild type plants. Conjointly, our findings show that XvSap1 can enhance drought resilience without causing deleterious phenotypic and yield changes, thus providing a promising candidate target for improving the drought tolerance of sweetpotato cultivars through genetic engineering. The transgenic drought tolerant sweetpotato line provides a valuable resource as drought tolerant crop on arid lands of the world.
Tissue-specific changes in the RNA structurome mediate salinity response inArabidopsis
Authors: Tack David C. , Su Zhao , Yu Yunqing , Bevilacqua Philip C. , Assmann Sarah M. 
Published: April 2019

AbstractRNA structures are influenced by their physico-chemical environment. Few studies have assessed genome-wide impacts of abiotic stresses onin vivoRNA structure, however, and none have investigated tissue-specificity. We applied our Structure-seq method to assessin vivomRNA secondary structure in Arabidopsis shoots and roots under control and salt stress conditions. Structure-seq utilizes dimethyl sulfate (DMS) forin vivotranscriptome-wide covalent modification of accessible As and Cs, i.e. those lacking base pairing and protection. Tissue type was a strong determinant of DMS reactivity, indicating tissue-specificity of RNA structuromes. Both tissues exhibited a significant inverse correlation between salt stress-induced changes in transcript reactivity and changes in transcript abundance, implicating changes in RNA structure and accessibility in transcriptome regulation. In mRNAs wherein the 5’UTR, CDS and 3’UTR concertedly increased or decreased in mean reactivity under salinity, this inverse correlation was more pronounced, suggesting that concordant structural changes across the mRNA have the greatest impact on abundance. Transcripts with the greatest and least salt stress-induced changes in DMS reactivity were enriched in genes encoding stress-related functions and included housekeeping functions, respectively. We conclude that secondary structure regulates mRNA abundance, thereby contributing to tissue specificity of the transcriptome and its dynamic adjustment under stress.One Sentence Summary:Transcriptome-wide methods reveal dynamic tissue-specific and salt stress-dependent modulation of mRNA accessibility and structure, and correlated mRNA abundance changes.
Drosophilaadult muscle precursor cells contribute to motor axon pathfinding and proper innervation of embryonic muscles
Authors: Lavergne Guillaume , Jagla Krzysztof 
Published: April 2019

SummaryAdult Muscle Precursors (AMPs), theDrosophilamuscle stem cells, arise from the asymmetric cell divisions of a subset of muscle progenitors ([1]) and are characterized by the persistent expression of the myogenic transcription factor Twist ([2]) and activation of the Notch pathway ([3]; [4]). They occupy stereotyped positions in the vicinity of developing body wall muscles, stay quiescent and undifferentiated during embryonic life and are reactivated during second larval instar ([5]; [6]) to generate muscles of the adult fly. Strikingly, AMPs are also located in the path of intersegmental (ISN) and segmental (SN) motor neuron branches ([2]; [7]). However, their role and interactions with the motor neurons have not yet been analyzed in details. Here, using AMP sensor line revealing cell membrane extensions we show that the navigating ISN first contacts the dorso-lateral (DL-AMPs) and then the dorsal AMP (D-AMP) marking the end of its trajectory. In parallel, the segmental nerve SNa innervating lateral muscles targets the lateral AMPs (L-AMPs).In vivoanalyses of AMPs behavior highlight an active filopodial dynamic of AMPs toward the ISN and SNa suggesting they could guide motor axons and contribute to muscle innervations. Indeed, our data show that loss or mispositioning of L-AMPs affect the SNa motor axons pathfinding and branching, leading to loss or aberrant muscle innervation. The finding of a transient expression of the guidance molecule Sidestep in L-AMPs suggests its implication in this process. Thus, proper muscle innervation does not only rely on the dialogue between the motor neurons and the muscles, but also on the AMP cells. AMPs represent spatial landmarks for navigating motor neurons and their positioning is critical for the muscles innervation in the lateral region.
B cells suppress medullary granulopoiesis by an extracellular glycosylation-dependent mechanism
Authors: Irons Eric E. , Lee-Sundlov Melissa M. , Hoffmeister Karin M. , Lau Joseph T.Y. 
Published: April 2019

AbstractThe immune response relies on the timely integration of cell-intrinsic processes with cell-extrinsic cues. During infection, B cells vacate the bone marrow for the emergency generation of granulocytes. However, it is unclear if cross-talk between B cells and neutrophils also encourages the return to homeostasis. Here, we report that B cells remodel glycans on hematopoietic progenitors to suppress granulopoiesis. Human B cells secrete active ST6Gal-1 sialyltransferase to modify the sialylation and Gr-1 expression of co-cultured hematopoietic progenitors. After adoptive transfer, total hematopoietic and B cells modified the sialylation of non-self cells and elevated blood ST6Gal-1. Mature IgD+ B cells co-localized with megakaryocytes to sialylated bone marrow niches, suggesting their role in medullary extrinsic sialylation. Finally, ST6Gal-1 expression in multiple myeloma cells negatively correlated with neutrophil abundance in human patients. Our results highlight the growing significance of extracellular glycoslytransferases as mediators of a novel glycan-dependent interaction between B cells and granulocytes.
RNA polymerases as moving barriers to condensin loop extrusion
Authors: Brandão Hugo B. , Wang Xindan , Paul Payel , van den Berg Aafke A. , Rudner David Z. , Mirny Leonid A. 
Published: April 2019

AbstractTo separate replicated sister chromatids during mitosis, eukaryotes and prokaryotes have structural maintenance of chromosome (SMC) condensin complexes that were recently shown to organize chromosomes by a process known as DNA loop extrusion. In rapidly dividing bacterial cells, the process of separating sister chromatids occurs concomitantly with ongoing transcription. How transcription interferes with the condensin loop extrusion process is largely unexplored, but recent experiments show that sites of high transcription may directionally affect condensin loop extrusion. We quantitatively investigate different mechanisms of interaction between condensin and elongating RNA polymerases (RNAP) and find that RNAPs are likely steric barriers that can push and interact with condensins. Supported by new Hi-C and ChIP-seq data for cells after transcription inhibition and RNAP degradation, we argue that translocating condensins must bypass transcribing RNAPs within ~2 seconds of an encounter at rRNA genes and within ~10 seconds at protein coding genes. Thus, while individual RNAPs have little effect on the progress of loop extrusion, long, highly transcribed operons can significantly impede the extrusion process. Our data and quantitative models further suggest that bacterial condensin loop extrusion occurs by two independent, uncoupled motor activities; the motors translocate on DNA in opposing directions and function together to enlarge chromosomal loops, each independently bypassing steric barriers in their path. Our study provides a quantitative link between transcription and 3D genome organization and proposes a mechanism of interactions between SMC complexes and elongating transcription machinery relevant from bacteria to higher eukaryotes.
Transcription amplification by nuclear speckle association
Authors: Kim Jiah , Khanna Nimish , Belmont Andrew S. 
Published: April 2019

AbstractA significant fraction of active chromosome regions and genes reproducibly position near nuclear speckles, but the functional significance of this positioning is unknown. Here we show that Hsp70 BAC transgenes and endogenous genes turn on 2-4 mins after heat shock irrespective of their distance to nuclear speckles. However, we observe 12-56-fold and 3-7-fold higher transcription levels for speckle-associated Hsp70 transgenes and endogenous genes, respectively, after 1-2 hrs heat shock. Several fold higher transcription levels for several genes flanking the Hsp70 locus also correlate with speckle-association at 37 °C. Live-cell imaging reveals this modulation of Hsp70 transcription temporally correlates with speckle association/disassociation. Our results demonstrate stochastic gene expression dependent on positioning relative to a liquid-droplet nuclear compartment through a “transcriptional amplification” mechanism distinct from transcriptional bursting.
Anex vivocystic fibrosis model recapitulates key clinical aspects of chronicStaphylococcus aureusinfection
Authors: Sweeney Esther , Hassan Marwa M. , Harrington Niamh E. , Smyth Alan R. , Hurley Matthew N. , Tormo-Mas María Ángeles , Harrison Freya 
Published: April 2019

AbstractStaphylococcus aureusis one of the most prevalent organisms isolated from the airways of people with cystic fibrosis (CF), predominantly early in life. Yet its role in the pathology of lung disease is poorly understood. Clinical studies are limited in scope by age and health of participants andin vitrostudies are not always able to accurately recapitulate chronic disease characteristics such as the development of small colony variants. Further, animal models also do not fully represent features of clinical disease: in particular, mice are not readily colonized byS. aureusand when infection is established it leads to the formation of abscesses, a phenomenon almost never observed in the human CF lung. Here, we present details of the development of an existingex vivopig lung model of CF infection to investigate the growth ofS. aureus. We show thatS. aureusis able to establish infection and demonstrates clinically significant characteristics including small colony variant phenotype, increased antibiotic tolerance and preferential localisation in mucus. Tissue invasion and the formation of abscesses were not observed, in line with clinical data.
Transcriptome Surveys in Silverfish Suggest a Multistep Origin of the Insect Odorant Receptor Gene Family
Authors: Thoma Michael , Missbach Christine , Jordan Melissa D. , Grosse-Wilde Ewald , Newcomb Richard D. , Hansson Bill S. 
Published: April 2019

AbstractThe insect odorant receptor (Or) gene family is among the largest multigene families in insect genomes, but its evolutionary origin and mode of expansion is still a matter of debate. We performed transcriptomic surveys of two wingless insect species, the silverfishLepisma saccharinaandTricholepidion gertschi, and identified multiple Or gene family members in both species. A phylogenetic analysis suggests that the silverfish Ors do not fall into the clade comprised of more derived flying insect ligand-binding Ors, but, along with bristletail, firebrat and some mayfly Ors, are consistently resolved as a distinct set of genes that may constitute an evolutionary intermediate between gustatory receptors and the more derived Ors of flying insects. We propose to consider these “primitive Ors” separately from higher insect Ors until their cellular expression patterns and function are resolved and suggest a multistep evolutionary scenario ultimately leading to the highly sensitive, rapidly evolving and physiologically diverse Or gene family observed in higher insects.
tagPAINT: covalent labelling of genetically encoded protein tags for DNA-PAINT imaging
Authors: Nieves Daniel J. , Hilzenrat Geva , Tran Jason , Yang Zhengmin , MacRae Hugh H. , Baker Matthew A. B. , Gooding J Justin , Gaus Katharina 
Published: April 2019

AbstractRecently, DNA-PAINT single molecule localisation microscopy (SMLM) has shown great promise for quantitative imaging. However, labelling strategies so far have relied on approaches that are multivalent or affinity-based. Here, we demonstrate tagPAINT - the covalent labelling of expressed protein tags (SNAP tag and Halo tag) with single DNA docking strands for single molecule localisation microscopy via DNA-PAINT. We utilised tagPAINT for T-cell receptor signalling proteins at the immune synapse as a proof of principle.
CRISPR/Cas9 Treatment Causes Extended TP53-Dependent Cell Cycle Arrest In Human Cells
Authors: Geisinger Jonathan M. , Stearns Tim 
Published: April 2019

ABSTRACTWhile the mechanism of CRISPR/Cas9 cleavage is understood, the large variation in mutant recovery for a given target sequence between cell lines is much less clear. We hypothesized that this variation may be due to differences in how the DNA damage response affects cell cycle progression. We used incorporation of EdU as a marker of cell cycle progression to analyze the response of several human cell lines to CRISPR/Cas9 treatment with a single guide directed to a unique locus. Cell lines with functionally wild-type TP53 exhibited higher levels of cell cycle arrest compared to lines without. Chemical inhibition of TP53 protein combined with TP53 and RB1 transcript silencing alleviated induced arrest in TP53+/+ cells. This arrest is driven in part by Cas9 binding to DNA. Additionally, wild-type Cas9 induced fewer 53BP1 foci in TP53+/+ cells compared to TP53−/− cells, suggesting that differences in break sensing are responsible for cell cycle arrest variation. We conclude that CRISPR/Cas9 treatment induces a cell cycle arrest dependent on functional TP53 as well as Cas9 DNA binding and cleavage. Our findings suggest that transient inhibition of TP53 may increase genome editing efficiency in primary and TP53+/+ cell lines.
Pentamycin biosynthesis in PhilippineStreptomycessp. S816: Cytochrome P450-catalysed installation of the C-14 hydroxyl group
Authors: Zhou Shanshan , Song Lijiang , Masschelein Joleen , Sumang Felaine A.M. , Papa Irene A. , Zulaybar Teofila O. , Custodio Aileen B. , Zabala Daniel , Alcantara Edwin P. , de los Santos Emmanuel L.C. , Challis Gregory L. 
Published: April 2019

ABSTRACTPentamycin is a polyene antibiotic, registered in Switzerland for the treatment of vaginal candidiasis, trichomo-niasis and mixed infections. Chemical instability has hindered its wide-spread application and development as a drug. Here we report the identification ofStreptomycessp. S816, isolated from Philippine mangrove soil, as a pentamycin producer. Genome sequence analysis identified the putative pentamycin biosynthetic gene cluster, which shows a high degree of similarity to the gene cluster responsible for filipin III biosynthesis. TheptnJgene, which is absent from the filipin III biosynthetic gene cluster, was shown to encode a cytochrome P450 capable of converting filipin III to pentamycin. This confirms that the cluster directs pentamycin biosynthesis, paving the way for biosynthetic engineering approaches to the production of pentamycin analogues. Several otherStreptomycesgenomes were found to containptnJorthologues clustered with genes encoding polyketide synthases that appear to have similar architectures to those responsible for the assembly of filipin III and pentamycin, suggesting pentamycin production may be common inStreptomycesspecies.
Vulnerable species interactions are important for the stability of mutualistic networks
Authors: Simmons Benno I. , Wauchope Hannah S. , Amano Tatsuya , Dicks Lynn V. , Sutherland William J. , Dakos Vasilis 
Published: April 2019

AbstractSpecies are central to ecology and conservation. However, it is the interactions between species that generate the functions on which ecosystems and humans depend. Despite the importance of interactions, we lack an understanding of the risk that their loss poses to ecological communities. Here, we quantify risk as a function of the vulnerability (likelihood of loss) and importance (contribution to network stability in terms of species coexistence) of 4330 mutualistic interactions from 41 empirical pollination and seed dispersal networks across six continents. Remarkably, we find that more vulnerable interactions are also more important: the interactions that contribute most to network stability are those that are most likely to be lost. Furthermore, most interactions tend to have more similar vulnerability and importance across networks than expected by chance, suggesting that vulnerability and importance may be intrinsic properties of interactions, rather than only a function of ecological context. These results provide a starting point for prioritising interactions for conservation in species interaction networks and, in areas lacking network data, could allow interaction properties to be inferred from taxonomy alone.