bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is whole-brain functional connectivity a neuromarker of sustained attention? Comment on Rosenberg & al. (2016)
Authors: Kristensen Simon Bang , Sandberg Kristian 
Published: November 2017

AbstractIdentification of neuromarkers accurately predicting cognitive characteristics from a single, standardised MRI scan could be tremendously useful in basic psychology and clinical practise. In a recent article, Rosenberg et al. (Nat Neurosci, 19, 165-171, 2016) argue that whole-brain functional network strength is a broadly applicable neuromarker of sustained attention. They claim that this marker accurately predicts performance from task related as well as resting state activity. Here, we discuss the applicability and generalizability in the context of three methodological concerns: Simulations show that the statistical methods for the 1) initial validation analyses as well as 2) internal validation using leave-one-out cross validation, are biased towards significance; 3) simple and complex models are compared suboptimally. Overall, we find that the article of Rosenberg et al. provides sufficient proof that network strength is associated with attentional capacity that it is not possible to say to which extent, and for this reason we argue that it cannot be concluded that the network is a broadly applicable neuromarker.
Structure of the eukaryotic cytoplasmic pre-40S ribosomal subunit
Authors: Scaiola Alain , Peña Cohue , Weisser Melanie , Böhringer Daniel , Leibundgut Marc , Klingauf-Nerurkar Purnima , Gerhardy Stefan , Panse Vikram Govind , Ban Nenad 
Published: November 2017

AbstractFinal maturation of eukaryotic ribosomes occurs in the cytoplasm and requires the sequential removal of associated assembly factors and processing of the immature 20S pre-RNA. Using cryo-electron microscopy (cryo-EM), we have determined the structure of a cytoplasmic pre-40S particle poised to initiate final maturation at a resolution of 3.4 Å. The structure reveals the extent of conformational rearrangements of the 3’ major and 3’ minor domains of the ribosomal RNA that take place during maturation, as well as the roles of the assembly factors Enp1, Ltv1, Rio2, Tsr1, and Pno1 in the process. Altogether, we provide a structural framework for the coordination of the final maturation events that drive a pre-40S particle towards the mature form capable of engaging in translation.
Structural centrosome aberrations promote non-cell-autonomous invasiveness
Authors: Ganier Olivier , Schnerch Dominik , Oertle Philipp , Lim Roderick Y. H. , Plodinec Marija , Nigg Erich A. 
Published: November 2017

AbstractCentrosomes are the main microtubules organizing centers of animal cells. Although centrosome aberrations are common in tumors, their consequences remain subject to debate. Here, we studied the impact of structural centrosome aberrations, induced by deregulated expression of Ninein-like protein (NLP), on epithelial spheres grown in Matrigel matrices. We demonstrate that NLP-induced structural centrosome aberrations trigger the escape (’budding’) of living cells from epithelia. Remarkably, all cells disseminating into the matrix were undergoing mitosis. This invasive behavior reflects a novel mechanism that depends on the acquisition of two distinct properties. First, NLP-induced centrosome aberrations trigger a re-organization of the cytoskeleton, which stabilizes microtubules and weakens E-cadherin junctions during mitosis. Second, atomic force microscopy reveals that cells harboring these centrosome aberrations display increased stiffness. As a consequence, mitotic cells are pushed out of mosaic epithelia, particularly if they lack centrosome aberrations. We conclude that centrosome aberrations can trigger cell dissemination through a novel, non-cell autonomous mechanism, raising the prospect that centrosome aberrations contribute to the dissemination of metastatic cells harboring normal centrosomes.
The unconventional kinetoplastid kinetochore protein KKT4 tracks with dynamic microtubule tips
Authors: Llauró Aida , Hayashi Hanako , Bailey Megan E. , Wilson Alex , Ludzia Patryk , Asbury Charles L. , Akiyoshi Bungo 
Published: November 2017

AbstractKinetochores are multiprotein machines that drive chromosome segregation in all eukaryotes by maintaining persistent, load-bearing linkages between the chromosomes and the tips of dynamic spindle microtubules. Kinetochores in commonly studied eukaryotes are assembled from widely conserved components like the Ndc80 complex that directly binds microtubules. However, in evolutionarily-divergent kinetoplastid species such as Trypanosoma brucei, which causes sleeping sickness, the kinetochores assemble from a unique set of proteins lacking homology to any known microtubule-binding domains. Here we show that a kinetochore protein from T. brucei called KKT4 binds directly to microtubules, diffuses along the microtubule lattice, and tracks with disassembling microtubule tips. The protein localizes both to kinetochores and to spindle microtubules in vivo, and its depletion causes defects in chromosome segregation. We define a minimal microtubule-binding domain within KKT4 and identify several charged residues important for its microtubule-binding activity. Laser trapping experiments show that KKT4 can maintain load-bearing attachments to both growing and shortening microtubule tips. Thus, despite its lack of similarity to other known microtubule-binding proteins, KKT4 has key functions required for harnessing microtubule dynamics to drive chromosome segregation. We propose that it represents a primary element of the kinetochore-microtubule interface in kinetoplastids.
Cyclic-di-adenosine monophosphate (c-di-AMP) is required for osmotic regulation inStaphylococcus aureusbut dispensable for viability in anaerobic conditions
Authors: Zeden Merve S. , Schuster Christopher F. , Bowman Lisa , Zhong Qiyun , Williams Huw D. , Gründling Angelika 
Published: November 2017

ABSTRACTCyclic di-adenosine monophosphate (c-di-AMP) is a recently discovered signaling molecule important for the survival of Firmicutes, a large bacterial group that includes notable pathogens such asStaphylococcus aureus. However, the exact role of this molecule has not been identified.dacA, theS. aureusgene encoding the diadenylate cyclase enzyme required for c-di-AMP production, cannot be deleted when bacterial cells are grown in rich medium, indicating that c-di-AMP is required for growth in this condition. Here, we report that anS. aureus dacAmutant can be generated in chemically defined medium. Consistent with previous findings, this mutant had a severe growth defect when cultured in rich medium. Using this growth defect in rich medium, we selected for suppressor strains with improved growth to identify c-di-AMP-requiring pathways. Mutations bypassing the essentiality ofdacAwere identified inalsTandopuD, encoding a predicted amino acid and osmolyte transporter, the latter of which we show here to be the main glycine betaine-uptake system inS. aureus. Inactivation of these transporters likely prevents the excessive osmolyte and amino acid accumulation in the cell, providing further evidence for a key role of c-di-AMP in osmotic regulation. Suppressor mutations were also obtained inhepS, hemB, ctaAandqoxB, coding for proteins required for respiration. Furthermore, we show thatdacAis dispensable for growth in anaerobic conditions. Together, these finding reveal an essential role for the c-di-AMP signaling network in aerobic, but not anaerobic, respiration inS. aureus.
A hyperthermophilic phage decoration protein suggests common evolutionary origin with Herpesvirus Triplex proteins and an anti-CRISPR protein
Authors: Stone Nicholas P. , Hilbert Brendan J. , Hidalgo Daniel , Halloran Kevin T. , Kelch Brian A. 
Published: November 2017

AbstractVirus capsid proteins reproducibly self-assemble into regularly-shaped, stable shells that protect the viral genome from external environmental assaults, while maintaining the high internal pressure of the tightly packaged viral genome. To elucidate how capsids maintain stability under harsh conditions, we investigated the capsid components of a hyperthermophilic virus, phage P74-26. We determined the structure of a capsid protein gp87 and show that it has the same fold as trimeric decoration proteins that enhance the structural stability of capsids in many other phage, despite lacking significant sequence homology. We also find that gp87 is significantly more stable than its mesophilic homologs, reflecting the high temperature environment in which phage P74-26 thrives. Our analysis of the gp87 structure reveals that the core domain of the decoration protein is conserved in trimeric capsid components across numerous dsDNA viruses, including human pathogens such as Herpesviruses. Moreover, this core β-barrel domain is found in the anti-CRISPR protein AcrIIC1, which suggests a mechanism for the evolution of this broad spectrum Cas9 inhibitor. Our work illustrates the principles for increased stability of a thermophilic decoration protein, and extends the evolutionary reach of the core trimeric decoration protein fold.
The distance decay of similarity in tropical rainforests. A spatial point processes analytical formulation
Authors: Tovo Anna , Favretti Marco 
Published: November 2017

AbstractIn this paper we are concerned with the analytical description of the change in floristic composition (species turnover) with the distance between two plots of a tropical rainforest due to the clustering of the individuals of the different species. We describe the plant arrangement by a superposition of spatial point processes and in this framework we introduce an analytical function which represents the average spatial density of the Sørensen similarity between two infinitesimal plots at distancer. We see that the decay in similarity with the distance is essentially described by the pair correlation function of the superposed process and that it is governed by the most abundant species. We test our analytical model with empirical data obtained for the Barro Colorado Island and Pasoh rainforests. To this end we adopt the statistical estimator for the pair correlation function in [1] and we design a novel one for the Sørensen similarity. Furthermore, we test our analytical formula by modelling the forest study area with Neyman-Scott point processes. We conclude comparing the advantages of our approach with other ones existing in literature.
Muscarinic Lateral Excitation Contributes to Visual Object Segmentation during Collision Avoidance
Authors: Zhu Ying , Dewell Richard B. , Wang Hongxia , Gabbiani Fabrizio 
Published: November 2017

SummaryVisual neurons specialized in tracking objects on a collision course are often finely tuned to their target stimuli as this is critical for survival. The presynaptic neural networks converging on these neurons and their role in tuning them remains poorly understood. We took advantage of well-known characteristics of one such neuron to investigate the properties of its presynaptic input network. We find a structure more complex than hitherto realized. In addition to dynamic lateral inhibition used to filter out background motion, presynaptic circuits include normalizing inhibition and short-range lateral excitatory interactions mediated by muscarinic acetylcholine receptors. These interactions preferentially boost responses to coherently expanding visual stimuli generated by colliding objects, as opposed to spatially incoherent controls, helping implement object segmentation. Hence, in addition to active dendritic conductances within collision detecting neurons, multiple layers of both inhibitory and excitatory presynaptic connections are needed to finely tune neural circuits for collision detection.
Which line to follow? The utility of different line-fitting methods to capture the mechanism of morphological scaling
Authors: Shingleton Alexander W. 
Published: November 2017

AbstractBivariate morphological scaling relationships describe how the size of two traits co-varies among adults in a population. In as much as body shape is reflected by the relative size of various traits within the body, morphological scaling relationships capture how body shape varies with size, and therefore have been used widely as descriptors of morphological variation within and among species. Despite their extensive use, there is continuing discussion over which line-fitting method should be used to describe linear morphological scaling relationships. Here I argue that the ‘best’ line-fitting method is the one that most accurately captures the proximate developmental mechanisms that generate scaling relationships. Using mathematical modeling, I show that the ‘best’ line-fitting method depends on the pattern of variation among individuals in the developmental mechanisms that regulate trait size, and the morphological variation this pattern of developmental variation produces. For Drosophila traits, this pattern of variation indicates that major axis regression is the best line-fitting method. For morphological traits in other animals, however, other line-fitting methods may be more accurate. I provide a simple web-based application for researchers to explore how different line-fitting methods perform on their own morphological data.
Leveraging multiple transcriptome assembly methods for improved gene structure annotation
Authors: Venturini Luca , Caim Shabhonam , Kaithakottil Gemy G , Mapleson Daniel L , Swarbreck David 
Published: November 2017

AbstractThe performance of RNA-Seq aligners and assemblers varies greatly across different organisms and experiments, and often the optimal approach is not known beforehand. Here we show that the accuracy of transcript reconstruction can be boosted by combining multiple methods, and we present a novel algorithm to integrate multiple RNA-Seq assemblies into a coherent transcript annotation. Our algorithm can remove redundancies and select the best transcript models according to user-specified metrics, while solving common artefacts such as erroneous transcript chimerisms. We have implemented this method in an open-source Python3 and Cython program, Mikado, available at https://github.com/lucventurini/Mikado.
The affinity of the S9.6 antibody for double-stranded RNAs impacts the mapping of R-loops in fission yeast
Authors: Hartono Stella R. , Malapert Amélie , Legros Pénélope , Bernard Pascal , Chédin Frédéric , Vanoosthuyse Vincent 
Published: November 2017

ABSTRACTR-loops, which result from the formation of stable DNA:RNA hybrids, can both threaten genome integrity and act as physiological regulators of gene expression and chromatin patterning. To characterize R-loops in fission yeast, we used the S9.6 antibody-based DRIPc-seq method to sequence the RNA strand of R-loops and obtain strand-specific R-loop maps at near nucleotide resolution. Surprisingly, preliminary DRIPc-seq experiments identified mostly RNase H-resistant but exosome-sensitive RNAs that mapped to both DNA strands and resembled RNA:RNA hybrids (dsRNAs), suggesting that dsRNAs form widely in fission yeast. We confirmed in vitro that S9.6 can immuno-precipitate dsRNAs and provide evidence that dsRNAs can interfere with its binding to R-loops. dsRNA elimination by RNase III treatment prior to DRIPc-seq allowed the genome-wide and strand-specific identification of genuine R-loops that responded in vivo to RNase H levels and displayed classical features associated with R-loop formation. We also found that most transcripts whose levels were altered by in vivo manipulation of RNase H levels did not form detectable R-loops, suggesting that prolonged manipulation of R-loop levels could indirectly alter the transcriptome. We discuss the implications of our work in the design of experimental strategies to probe R-loop functions.
Glutathione levels influence chronological life span ofSaccharomyces cerevisiaein a glucose-dependent manner
Authors: Tello-Padilla Mayra Fabiola , Perez-Gonzalez Alejandra Yudid , Canizal-García Melina , González-Hernández Juan Carlos , Cortes-Rojo Christian , Olivares-Marin Ivanna Karina , Madrigal-Perez Luis Alberto 
Published: November 2017

AbstractDiet plays a key role in determining the longevity of the organisms since it has been demonstrated that glucose restriction increases lifespan whereas a high-glucose diet decreases it. However, the molecular basis of how diet leads to the aging process is currently unknown. We propose that the quantity of glucose that fuels respiration influences ROS generation and glutathione levels, and both chemical species impact in the aging process. Herein, we provide evidence that mutation of the geneGSH1diminishes glutathione levels. Moreover, glutathione levels were higher with 0.5% than in 10% glucose in thegsh1Δand WT strains. Interestingly, the chronological life span (CLS) was lowered in thegsh1Δstrain cultured with 10% glucose but not under dietary restriction. Thegsh1Δstrain also showed an inhibition of the mitochondrial respiration in 0.5 and 10% of glucose but only increased the H2O2levels under dietary restriction. These results correlate well with the GSH/GSSG ratio, which showed a decrease ingsh1Δstrain cultured with 0.5% glucose. Altogether these data indicate that glutathione has a major role in the function of electron transport chain (ETC) and is essential to maintain life span ofSaccharomyces cerevisiaein 10% glucose.
Deep2Full: Predictive model for complementing phenotypic outcomes in a deep mutational scan using protein sequence and structure information
Authors: Sruthi C. K. , Prakash Meher K. 
Published: November 2017

AbstractLarge scale mutagenesis experiments are becoming possible owing to the advancement in the sequencing technologies and high throughput screening. Deep mutational scans perform exhaustive single-point muta-tions on a protein and probe their phenotypic effects. Performing a full scan with site-directed mutations of all the amino acid residues in a protein may not be practical, and may not even be required, especially if predictive computational models can be developed. Computational models are however naive to cellular response in the myriads of assay-conditions. In order to develop the realistic paradigm of assay context-aware predictive hybrid models, we combine minimal deep mutational studies with computational models and pre-dict the phenotypic outcomes quantitatively. Structural, sequence and co-evolutionary information along with partial deep mutational scan data was included to capture the phenotypic relevance of the mutations to the specific screening criterion. The model reliably predicts the fitness outcomes of hundreds of randomly selected amino acid mutations in β-lactamase, when the phenotypic fitness data from as few as 15% of the full mutation is available. Interestingly, the predictive capabilities are better with a random set of mutations rather than with a systematic substitution of all amino acids to alanine, asparagine and histidine (ANH). The model can potentially be extended for predicting the phenotypic outcomes at other concentrations of the stressor by carefully analyzing the dose-response curves of a representative set of mutations.Author SummaryMutations are the minor changes in protein sequences, with incommensurately high consequences for their function. Many severe diseases can occur with simple single point mutations. An interesting way of studying these mutations is not to isolate the protein from its natural conditions, but rather study how the fitness of the cell improves or decreases in response to these mutations. Whether it is for understanding disease biology or for bio-engineering applications it is important to quantify the impact of mutations on the cellular fitness. An experimental paradigm has evolved which has improved the ability to sample several hundred thousands of mutation-fitness relations using high throughput screening. However, since these are very specialized experiments, the question is if the number of such experiments required can be minimized, by using computer models to complement the rest of the fitness predictions. In this work we introduce this new paradigm which uses computer model trained on a partial deep mutation scan data, to predict the fitness variations in a full mutations scan that could also be repeated under multiple experimental conditions like drug concentrations.
Chronic ethanol ingestion impairs Drosophila melanogaster health in a microbiome-dependent manner
Authors: Chandler James Angus , Innocent Lina Victoria , Huang Isaac L. , Yang Jane L. , Eisen Michael B. , Ludington William B. 
Published: November 2017

SummaryEthanol is one of the worlds most abused drugs yet the impacts of chronic ethanol consumption are debated. Ethanol is a prevalent component in the diets of diverse animals and can act as a nutritional source, behavior modulator, and a toxin. The source of ethanol is microbes, which can both produce and degrade ethanol, and the gut microbiome has been associated with differential health outcomes in chronic alcoholism. To disentangle the various and potentially interacting roles of bacteria and ethanol on host health, we developed a model for chronic ethanol ingestion in the adult fruit fly, Drosophila melanogaster, which naturally consumes a diet between 0 and 5% ethanol. We took advantage of the tractability of the fly microbiome, which can be experimentally removed to separate the direct and indirect effects of commensal microbes. We found that moderate to heavy ethanol ingestion decreased lifespan and reproduction, without causing inebriation. These effects were more pronounced in flies lacking a microbiome, but could not be explained by simple bacterial degradation of ethanol. However, moderate ethanol ingestion increased reproduction in bacterially-colonized flies, relative to bacteria-free flies. Ethanol decreased intestinal stem cell turnover in bacterially-colonized flies and decreased intestinal barrier failure and increased fat content in all flies, regardless of microbiome status. Analysis of host gene expression finds that ethanol triggers the innate immune response, but only in flies colonized with bacteria. Taken together we show that, chronic ethanol ingestion negatively impacts fly health in a microbiome-dependent manner.