bluuebunny/crossref_metadata_2025_split huggingface dataset:
PI(4,5)P2forms dynamic cortical structures and directs actin distribution and cell polarity in C. elegans embryos
Authors: Scholze Melina J. , Barbieux Kévin S. , De Simone Alessandro , Boumasmoud Mathilde , Süess Camille C. N. , Wang Ruijia , Gönczy Pierre 
Published: November 2017

AbstractAsymmetric division is crucial for embryonic development and stem cell lineages. In the one-cellC. elegansembryo, a contractile cortical actomyosin network contributes to anterior-posterior (A-P) polarity and asymmetric division by segregating PAR proteins to discrete cortical domains. Here, we discovered that the plasma membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) forms dynamic structures inC. eleganszygotes, distributing in a polarized and PAR-dependent manner along the A-P axis. PIP2cortical structures overlap with F-actin and coincide with the actin regulators RHO-1, CDC-42 and ECT-2. Particle image velocimetry analysis revealed that PIP2and F-actin cortical movements are coupled, with PIP2structures moving slightly ahead. Importantly, we established that PIP2cortical structures form in an actin-dependent manner and, conversely, that decreasing or increasing the level of PIP2results in severe F-actin disorganization, revealing the interdependence between these components. Furthermore, we uncovered that PIP2regulates the sizing of PAR cortical domains. Overall, our work establishes for the first time that a lipid membrane component, PIP2, is a critical modulator of actin organization and cell polarity inC. elegansembryos.Summary statementPI(4,5)P2is distributed in dynamic cortical structures and regulates asymmetric division by controlling actin organization and cell polarity in the one-cellC. elegansembryo.
White LED Lighting for Plants
Authors: Sharakshane Anton 
Published: November 2017

The highest intensity of photosynthesis is obtained under red light, but plants die or their growth gets disrupted if only red light is used. For example, Korean researchers [1] have shown that under pure red light the amount of the grown lettuce is greater than under a combination of red and blue light, but the leaves have a significantly smaller amount of chlorophyll, polyphenols and antioxidants. And the researchers at the Faculty of Biology of the Moscow State University [2] have found that the synthesis of sugars is reduced, growth is inhibited and no blossoming occurs in the leaves of Chinese cabbage under narrow-band red and blue light (as compared to a sodium lamp).What kind of lighting is needed to get a fully developed, large, fragrant and tasty plant with moderate energy consumption?
Automatic sorting system for large calcium imaging data
Authors: Takekawa Takashi , Asai Hirotaka , Ohkawa Noriaki , Nomoto Masanori , Okubo-Suzuki Reiko , Ghandour Khaled , Sato Masaaki , Hayashi Yasunori , Inokuchi Kaoru , Fukai Tomoki 
Published: November 2017

SUMMARYIt has become possible to observe neural activity in freely moving animals via calcium imaging using a microscope, which could not be observed previously. However, it remains difficult to extract the dynamics of nerve cells from the recorded imaging data. In this study, we greatly improved the stability, and robustness of the cell activity estimation method via non-negative matrix decomposition with shrinkage estimation of the baseline. In addition, by improving the initial state of the iterative algorithm using a newly proposed method to extract the shape of the cell via image processing, a solution could be obtained with a small number of iterations. These methods were applied to artificial and real data, and their effectiveness was confirmed.
Predicting Cancer Drug Response Using a Recommender System
Authors: Supahvilai Chayaporn , Bertrand Denis , Nagarajan Niranjan 
Published: November 2017

AbstractMotivationAs we move towards an era of precision medicine, the ability to predict patient-specific drug responses in cancer based on molecular information such as gene expression data represents both an opportunity and a challenge. In particular, methods are needed that can accommodate the high-dimensionality of data to learn interpretable models capturing drug response mechanisms, as well as providing robust predictions across datasets.ResultsWe propose a method based on ideas from “recommender systems” (CaDRReS) that predicts cancer drug responses for unseen cell-lines/patients based on learning projections for drugs and cell-lines into a latent “pharmacogenomic” space. Comparisons with other proposed approaches for this problem based on large public datasets (CCLE, GDSC) shows that CaDRReS provides consistently good models and robust predictions even across unseen patient-derived cell-line datasets. Analysis of the pharmacogenomic spaces inferred by CaDRReS also suggests that they can be used to understand drug mechanisms, identify cellular subtypes, and further characterize drug-pathway associations.AvailabilitySource code and datasets are available athttps://github.com/CSB5/CaDRReSContactnagarajann@gis.a-star.edu.sgSupplementary informationSupplementary data are available online.
Stoichiometry and compositional plasticity of the yeast nuclear pore complex revealed by quantitative fluorescence microscopy
Authors: Rajoo Sasikumar , Vallotton Pascal , Onischenko Evgeny , Weis Karsten 
Published: November 2017

AbstractThe nuclear pore complex (NPC) is an 8-fold symmetrical channel providing selective transport of biomolecules across the nuclear envelope. Each NPC consists of ~30 different nuclear pore proteins (Nups) all present in multiple copies per NPC. Significant progress has recently been made in the characterization of the vertebrate NPC structure, however, because of the estimated size differences between the vertebrate and yeast NPC, it has been unclear whether the NPC architecture is conserved between species. Here, we have developed a quantitative image analysis pipeline, termed Nuclear Rim Intensity Measurement or NuRIM, to precisely determine copy numbers for almost all Nups within native NPCs of budding yeast cells. Our analysis demonstrates that the majority of yeast Nups are present at most in 16 copies per NPC. This reveals a dramatic difference to the stoichiometry determined for the human NPC suggesting that despite a high degree of individual Nup conservation, the yeast and human NPC architecture is significantly different. Furthermore, using NuRIM we examined the effects of mutations on NPC stoichiometry. We demonstrate for two paralog pairs of key scaffold Nups, Nup170/Nup157 and Nup192/Nup188 that their altered expression leads to significant changes in Nup stoichiometry inducing either voids in the NPC structure or substitution of one paralog by the other. Thus, our results not only provide accurate stoichiometry information for the intact yeast NPC but also reveal an intriguing compositional plasticity of the NPC architecture, which may explain how differences in NPC composition could arise in the course of evolution.SignificanceThe nuclear pore complex (NPC) is one of the largest protein complexes in eukaryotes comprising over 500 nucleoporin subunits. The NPC is essential for transport of biomolecules across the nuclear envelope, however, due to its enormous size, it has been a challenge to characterize its molecular architecture. Herein, we have developed a novel, widely applicable imaging pipeline to determine the absolute nucleoporin abundances in native yeast NPCs. This reveals that the NPC composition dramatically differs between yeast and human despite an overall conservation of individual subunits. We also applied our imaging pipeline to examine yeast mutants revealing a remarkable compositional plasticity of NPCs. Our stoichiometry analyses provide an important resource for the generation of high-resolution structure models of the NPC.
The Long and the Short of Serotonergic Stimulation: Optogenetic activation of dorsal raphe serotonergic neurons changes the learning rate for rewards
Authors: Iigaya Kiyohito , Fonseca Madalena S. , Murakami Masayoshi , Mainen Zachary F. , Dayan Peter 
Published: November 2017

AbstractSerotonin plays an influential, but computationally obscure, modulatory role in many aspects of normal and dysfunctional learning and cognition. Here, we studied the impact of optogenetic stimulation of dorsal raphe serotonin neurons in mice performing a non-stationary, reward-driven, foraging task. We report that activation of serotonin neurons significantly boosted learning rates for choices following long inter-trial-intervals that were driven by the recent history of reinforcement.
The genome sequence of the wild tomatoSolanum pimpinellifoliumprovides insights into salinity tolerance
Authors: Razali Rozaimi , Bougouffa Salim , Morton Mitchell J. L. , Lightfoot Damien J. , Alam Intikhab , Essack Magbubah , Arold Stefan T. , Kamau Allan , Schmöckel Sandra M. , Pailles Yveline , Shahid Mohammed , Michell Craig T. , Al-Babili Salim , Ho Yung Shwen , Tester Mark , Bajic Vladimir B. , Negrão Sónia 
Published: November 2017

SUMMARYSolanum pimpinellifolium, a wild relative of cultivated tomato, offers a wealth of breeding potential for several desirable traits such as tolerance to abiotic and biotic stresses. Here, we report the genome and annotation ofS. pimpinellifolium‘LA0480’. The ‘LA0480’ genome size (811 Mb) and the number of annotated genes (25,970) are within the range observed for other sequenced tomato species. We developed and utilized the Dragon Eukaryotic Analyses Platform (DEAP) to functionally annotate the ‘LA0480’ protein-coding genes. Additionally, we used DEAP to compare protein function betweenS. pimpinellifoliumand cultivated tomato. Our data suggest enrichment in genes involved in biotic and abiotic stress responses. Moreover, we present phenotypic data from one field experiment that demonstrate a greater salinity tolerance for fruit-and yield-related traits inS. pimpinellifoliumcompared with cultivated tomato. To understand the genomic basis for these differences inS. pimpinellifoliumandS. lycopersicum, we analyzed 15 genes that have previously been shown to mediate salinity tolerance in plants. We show thatS. pimpinellifoliumhas a higher copy number of the inositol-3-phosphate synthase and phosphatase genes, which are both key enzymes in the production of inositol and its derivatives. Moreover, our analysis indicates that changes occurring in the inositol phosphate pathway may contribute to the observed higher salinity tolerance in ‘LA0480’. Altogether, our work provides essential resources to understand and unlock the genetic and breeding potential ofS. pimpinellifolium, and to discover the genomic basis underlying its environmental robustness.
DHX36 binding at G-rich sites in mRNA untranslated regions promotes translation
Authors: Sauer Markus , Juranek Stefan , Kazemier Hinke G. , Benhalevy Daniel , Wang Xiantao , Hafner Markus , Paeschke Katrin 
Published: November 2017

ABSTRACTTranslation efficiency can be affected by mRNA stability and secondary structures, including so-called G-quadruplex (G4) structures. The highly conserved and essential DEAH-box helicase DHX36/RHAU is able to resolve G4 structures on DNA and RNA in vitro, however a system-wide analysis of DHX36 targets and function is lacking. We globally mapped DHX36 occupancy in human cell lines and found that it preferentially binds to G-rich sequences in the coding sequences (CDS) and 5' and 3' untranslated regions (UTR) of more than 4,500 mRNAs. Functional analyses, including RNA sequencing, ribosome footprinting, and quantitative mass spectrometry revealed that DHX36 decreased target mRNA stability. However, target mRNA accumulation in DHX36 KO cells did not lead to a significant increase in ribosome footprints or protein output indicating that they were translationally incompetent. We hypothesize that DHX36 resolves G4 and other structures that interfere with efficient translation initiation.
Efficient CRISPR/Cas-mediated homologous recombination in the model diatomThalassiosira pseudonana
Authors: Belshaw Nigel , Grouneva Irina , Aram Lior , Gal Assaf , Hopes Amanda , Mock Thomas 
Published: November 2017

AbstractCRISPR/Cas enables targeted genome editing in many different plant and algal species including the model diatomThalassiosira pseudonana. However, efficient gene targeting by homologous recombination (HR) to date is only reported for photosynthetic organisms in their haploid life-cycle phase and there are no examples of efficient nuclease-meditated HR in any photosynthetic organism. Here, a CRISPR/Cas construct, assembled using Golden Gate cloning, enabled highly efficient HR for the first time in a diploid photosynthetic organism. HR was induced inT. pseudonanaby means of sequence specific CRISPR/Cas, paired with a donor matrix, generating substitution of the silacidin gene by a resistance cassette (FCP:NAT). Approximately 85% of NAT resistantT. pseudonanacolonies screened positive for HR using a nested PCR approach and confirmed by sequencing of the PCR products. The knockout of the silacidin gene inT. pseudonanacaused a significant increase in cell size, confirming the role of this gene for cell-size regulation in centric diatoms. Highly efficient gene targeting by HR makesT. pseudonanaas genetically tractable asNannochloropsisandPhyscomitrella, hence rapidly advancing functional diatom biology, bionanotechnology and any biotechnological application targeted on harnessing the metabolic potential of diatoms.
A bacterial effector directly targets Arabidopsis Argonaute 1 to suppress Pattern-triggered immunity and cause disease
Authors: Thiébeauld Odon , Charvin Magali , Singla-Rastogi Meenu , Perez-Quintero Alvaro L , Yang Fan , Pontier Dominique , Barraud Pierre , Pouzet Cécile , Bapaume Laure , Amesefe Delase , Li Guangyong , Deslandes Laurent , Lagrange Thierry , Alfano James R. , Navarro Lionel 
Published: November 2017

SUMMARYPseudomonas syringaetype III effectors were previously shown to suppress the Arabidopsis microRNA (miRNA) pathway through unknown mechanisms. Here, we first show that the HopT1-1 effector promotes bacterial growth by suppressing the Arabidopsis Argonaute 1 (AGO1)-dependent miRNA pathway. We further demonstrate that HopT1-1 interacts with Arabidopsis AGO1 through conserved glycine/tryptophan (GW) motifs, and in turn suppresses miRNA function. This process is not associated with a general decrease in miRNA accumulation. Instead, HopT1-1 reduces the level of AGO1-associated miRNAs in a GW-dependent manner. Therefore, HopT1-1 alters AGO1-miRISC activity, rather than miRNA biogenesis or stability. In addition, we show that the AGO1-binding platform of HopT1-1 is essential to suppress the production of reactive oxygen species (ROS) and of callose deposits during Pattern-triggered immunity (PTI). These data imply that the RNA silencing suppression activity of HopT1-1 is intimately coupled with its virulence function. Overall, these findings provide sound evidence that a bacterial effector has evolved to directly target a plant AGO protein to suppress PTI and cause disease.
Centromeric DNA destabilizes H3 nucleosomes to promote CENP-A deposition during the cell cycle
Authors: Shukla Manu , Pin Tong , White Sharon A. , Singh Puneet P. , Reid Angus M. , Sandra Catania , Pidoux Alison L. , Allshire Robin C. 
Published: November 2017

SummaryActive centromeres are defined by the presence of nucleosomes containing CENP-A, a histone H3 variant, which alone is sufficient to direct kinetochore assembly. Once assembled at a location CENP-A chromatin and kinetochores are maintained at that location though a positive feedback loop where kinetochore proteins recruited by CENP-A itself promote deposition of new CENP-A following replication. Although CENP-A chromatin itself is a heritable entity, it is normally associated with specific sequences. Intrinsic properties of centromeric DNA may favour the assembly of CENP-A rather than H3 nucleosomes. Here we investigate histone dynamics on centromeric DNA. We show that during S-phase histone H3 is deposited as a placeholder at fission yeast centromeres and is subsequently evicted in G2 when we detect deposition of the majority of new CENP-ACnp1. We also find that centromeric DNA has an innate property of driving high rates of turnover of H3 containing nucleosomes resulting in low nucleosome occupancy. When placed at an ectopic chromosomal location in the absence of any CENP-ACnp1assembly, centromeric DNA retains its ability to impose S-phase deposition and G2 eviction of H3, suggesting that features within this DNA program H3 dynamics. As RNAPII occupancy on this centromere DNA coincides with H3 eviction in G2, we propose a model in which RNAPII-coupled chromatin remodelling promotes replacement of H3 with CENP-ACnp1nucleosomes.
Mannan molecular sub-structures control nanoscale glucan exposure in Candida
Authors: Graus Matthew S. , Wester Michael J. , Lowman Douglas W. , Williams David L. , Kruppa Michael D. , Young Jesse M. , Pappas Harry C. , Lidke Keith A. , Neumann Aaron K. 
Published: November 2017

AbstractN-linked mannans (N-mannans) in the cell wall of Candida albicans are thought to mask β-(1,3)-glucan from recognition by Dectin-1, contributing to innate immune evasion. Lateral cell wall exposures of glucan on Candida albicans are predominantly single receptor-ligand interaction sites and are restricted to nanoscale geometries. Candida species exhibit a range of basal glucan exposures and their mannans also vary in size and complexity at the molecular level. We used super resolution fluorescence imaging and a series of protein mannosylation mutants in C. albicans and C. glabrata to investigate the role of specific N-mannan features in regulating the nanoscale geometry of glucan exposure. Decreasing acid labile mannan abundance and α-(1,6)-mannan backbone length correlated most strongly with increased density and nanoscopic size of glucan exposures in C. albicans and C. glabrata, respectively. Additionally, a C. albicans clinical isolate with high glucan exposure produced similarly perturbed N-mannan structures and exhibited similar changes to nanoscopic glucan exposure geometry. We conclude that acid labile N-mannan controls glucan exposure geometry at the nanoscale. Furthermore, variations in glucan nanoexposure characteristics are clinically relevant and are likely to impact the nature of the pathogenic surface presented to innate immunocytes at dimensions relevant to receptor engagement, aggregation and signaling.
Prefrontal cortex regulates amygdala response to threat in trait anxiety
Authors: Ironside Maria. , Browning Michael. , Ansari Tahereh L. , Harvey Christopher J. , Sekyi-Djan Mama N. , Bishop Sonia J. , Harmer Catherine J. , O’Shea Jacinta 
Published: November 2017

AbstractBackgroundHighly co-morbid mood and anxiety disorders are associated with aberrant fronto-limbic signalling during emotional processing. Animal models suggest that hypoactive prefrontal cortex weakens top-down control of limbic structures, causing heightened limbic and behavioural reactivity to negative information. Here we tested for this causal mechanism in human trait anxiety. We reasoned that if dorsolateral prefrontal cortex controls amygdala response to affective information, then stimulation of that brain region should reduce the hyperactive amygdala threat responsivity seen in trait anxiety.MethodsUsing a within-subjects design, sixteen high-trait anxious females received active and sham transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex, in counterbalanced order, with sessions timed to be at least one month apart. Each session was followed immediately by a functional magnetic resonance imaging (fMRI) scan during which participants performed an attentional task with threat-related distractors.ResultsAs predicted, compared to sham stimulation, active prefrontal cortex stimulation reduced amygdala threat reactivity and simultaneously increased activity in cortical regions associated with attentional control and improved task accuracy.ConclusionsThese results demonstrate a causal role for impoverished frontal regulation of amygdaloid function in attentional capture by threat in trait anxiety. The finding that prefrontal stimulation reduces amygdala threat reactivity acutely indicates a neurocognitive mechanism that could contribute to tDCS treatment effects in affective disorders.
Accurate Reconstruction of Microbial Strains from Metagenomic Sequencing Using Representative Reference Genomes
Authors: Zhou Zhemin , Luhmann Nina , Alikhan Nabil-Fareed , Quince Christopher , Achtman Mark 
Published: November 2017

AbstractExploring the genetic diversity of microbes within the environment through metagenomic sequencing first requires classifying these reads into taxonomic groups. Current methods compare these sequencing data with existing biased and limited reference databases. Several recent evaluation studies demonstrate that current methods either lack sufficient sensitivity for species-level assignments or suffer from false positives, overestimating the number of species in the metagenome. Both are especially problematic for the identification of low-abundance microbial species, e. g. detecting pathogens in ancient metagenomic samples. We present a new method, SPARSE, which improves taxonomic assignments of metagenomic reads. SPARSE balances existing biased reference databases by grouping reference genomes into similarity-based hierarchical clusters, implemented as an efficient incremental data structure. SPARSE assigns reads to these clusters using a probabilistic model, which specifically penalizes non-specific mappings of reads from unknown sources and hence reduces false-positive assignments. Our evaluation on simulated datasets from two recent evaluation studies demonstrated the improved precision of SPARSE in comparison to other methods for species-level classification. In a third simulation, our method successfully differentiated multiple co-existing Escherichia coli strains from the same sample. In real archaeological datasets, SPARSE identified ancient pathogens with ≤ 0.02% abundance, consistent with published findings that required additional sequencing data. In these datasets, other methods either missed targeted pathogens or reported non-existent ones. SPARSE and all evaluation scripts are available at https://github.com/zheminzhou/SPARSE.