bluuebunny/crossref_metadata_2025_split huggingface dataset:
Probing the evolutionary robustness of two repurposed drugs targeting iron uptake inPseudomonas aeruginosa
Authors: Rezzoagli Chiara , Wilson David , Weigert Michael , Wyder Stefan , Kümmerli Rolf 
Published: October 2017

AbstractBackground and objectivesTreatments that inhibit the expression or functioning of bacterial virulence factors hold great promise to be both effective and exert weaker selection for resistance than conventional antibiotics. However, the evolutionary robustness argument, based on the idea that anti-virulence treatments disarm rather than kill pathogens, is controversial. Here we probe the evolutionary robustness of two repurposed drugs, gallium and flucytosine, targeting the iron-scavenging pyoverdine of the opportunistic human pathogenPseudomonas aeruginosa.MethodologyWe subjected replicated cultures of bacteria to two concentrations of each drug for 20 consecutive days in human serum as an ex-vivo infection model. We screened evolved populations and clones for resistance phenotypes, including the restoration of growth and pyoverdine production, and the evolution of iron uptake by-passing mechanisms. We whole-genome sequenced evolved clones to identify the genetic basis of resistance.ResultsWe found that mutants resistant against anti-virulence treatments readily arose, but their selective spreading varied between treatments. Flucytosine resistance quickly spread in all populations due to disruptive mutations inupp, a gene encoding an enzyme required for flucytosine activation. Conversely, resistance against gallium arose only sporadically, and was based on mutations in transcriptional regulators, upregulating pyocyanin production, a redox-active molecule promoting siderophore-independent iron acquisition. The spread of gallium resistance could be hampered because pyocyanin-mediated iron delivery benefits resistant and susceptible cells alike.Conclusions and implicationsOur work highlights that anti-virulence treatments are not evolutionarily robustper se. Instead, evolutionary robustness is a relative measure, with specific treatments occupying different positions on a continuous scale.
Dissociable signatures of visual salience and behavioral relevance across attentional priority maps in human cortex
Authors: Sprague Thomas C. , Itthipuripat Sirawaj , Vo Vy A. , Serences John T. 
Published: October 2017

AbstractComputational models posit that visual attention is guided by activity within spatial maps that index the image-computable salience and the behavioral relevance of objects in the scene. However, the simultaneous influence of these factors on putative neural ‘attentional priority maps’ in human cortex is not well understood. We tested the hypothesis that visual salience and behavioral relevance independently impact the activation profile across retinotopically-organized cortical regions by quantifying attentional priority maps measured in human brains using functional MRI while participants attended one of two differentially-salient stimuli. We find that the topography of activation in priority maps, as reflected in the modulation of region-level patterns of population activity, independently indexed the physical salience and behavioral relevance of each scene element. Moreover, salience strongly impacted activation patterns in early visual areas, whereas later visual areas were dominated by relevance. This suggests that prioritizing spatial locations relies on distributed neural codes containing graded representations of salience and relevance across the visual hierarchy.Significance StatementOften, it is necessary to orient towards bright, unique, or sudden events in the environment – that is, salient stimuli. However, we can focus processing resources on less salient visual information if it is relevant to the task at hand. We tested a theory which supposes that we represent different scene elements according to both their salience and their relevance in a series of ‘priority maps’ by measuring fMRI activation patterns across the human brain and reconstructing spatial maps of the visual scene under different task conditions. We found that different regions indexed either the salience or the relevance of scene items, but not their interaction, suggesting an evolving representation of salience and relevance across different visual areas.
Dietary and Developmental Shifts in Butterfly-Associated Bacterial Communities
Authors: Phalnikar Kruttika , Kunte Krushnamegh , Agashe Deepa 
Published: October 2017

ABSTRACTBacterial communities associated with insects can substantially influence host ecology, evolution and behavior. Host diet is a key factor that shapes bacterial communities, but the impact of dietary transitions across insect development is poorly understood. We analyzed bacterial communities of 12 butterfly species across different development stages, using 16S rDNA amplicon sequencing. Butterfly larvae typically consume leaves of a single host plant, whereas adults are more generalist nectar feeders. Thus, we expected bacterial communities to vary substantially across butterfly development. Surprisingly, very few species showed significant developmental transitions in bacterial communities, suggesting weak impacts of dietary transitions across butterfly development. On the other hand, bacterial communities were strongly influenced by butterfly species identity and dietary variation across species. Larvae of most butterfly species largely mirrored bacterial community composition of their diets, suggesting passive acquisition rather than active selection. Overall, our results suggest that although butterflies harbor distinct microbiomes across taxonomic groups and dietary guilds, the dramatic dietary shifts that occur during development do not impose strong selection to maintain distinct bacterial communities.
Enter the matrix: factorization uncovers knowledge from omics Names/Affiliations
Authors: Stein-O’Brien Genevieve L. , Arora Raman , Culhane Aedin C. , Favorov Alexander V. , Garmire Lana X. , Greene Casey S. , Goff Loyal A. , Li Yifeng , Ngom Aloune , Ochs Michael F. , Xu Yanxun , Fertig Elana J. 
Published: October 2017

AbstractOmics data contains signal from the molecular, physical, and kinetic inter- and intra-cellular interactions that control biological systems. Matrix factorization techniques can reveal low-dimensional structure from high-dimensional data that reflect these interactions. These techniques can uncover new biological knowledge from diverse high-throughput omics data in topics ranging from pathway discovery to time course analysis. We review exemplary applications of matrix factorization for systems-level analyses. We discuss appropriate application of these methods, their limitations, and focus on analysis of results to facilitate optimal biological interpretation. The inference of biologically relevant features with matrix factorization enables discovery from high-throughput data beyond the limits of current biological knowledge—answering questions from high-dimensional data that we have not yet thought to ask.
Neural data science: accelerating the experiment-analysis-theory cycle in large-scale neuroscience
Authors: Paninski L , Cunningham J.P 
Published: October 2017

AbstractModern large - scale multineuronal recording methodologies, including multielectrode arrays, calcium imaging, and optogenetic techniques, produce single - neuron resolution data of a magnitude and precision that were the realm of science fiction twenty years ago. The major bottlenecks in systems and circuit neuroscience no longer lie in simply collecting data from large neural populations, but also in understanding this data: developing novel scientific questions, with corresponding analysis techniques and experimental designs to fully harness these new capabilities and meaningfully interrogate these questions. Advances in methods for signal processing, network analysis, dimensionality reduction, and optimal control – developed in lockstep with advances in experimental neurotechnology - - promise major breakthroughs in multiple fundamental neuroscience problems. These trends are clear in a broad array of subfields of modern neuroscience; this review focuses on recent advances in methods for analyzing neural time - series data with single - neuronal precision.
Figure 1.The central role of data science in modern large - scale neuroscience.Topics reviewed herein are indicated in black.
Directed evolution of TurboID for efficient proximity labeling in living cells and organisms
Authors: Branon Tess C. , Bosch Justin A. , Sanchez Ariana D. , Udeshi Namrata D. , Svinkina Tanya , Carr Steven A. , Feldman Jessica L. , Perrimon Norbert , Ting Alice Y. 
Published: October 2017

AbstractProtein interaction networks and protein compartmentation underlie every signaling process and regulatory mechanism in cells. Recently, proximity labeling (PL) has emerged as a new approach to study the spatial and interaction characteristics of proteins in living cells. However, the two enzymes commonly used for PL come with tradeoffs – BioID is slow, requiring tagging times of 18-24 hours, while APEX peroxidase uses substrates that have limited cell permeability and high toxicity. To address these problems, we used yeast display-based directed evolution to engineer two mutants of biotin ligase, TurboID and miniTurbo, with much greater catalytic efficiency than BioID, and the ability to carry out PL in cells in much shorter time windows (as little as 10 minutes) with non-toxic and easily deliverable biotin. In addition to shortening PL time by 100-fold and increasing PL yield in cell culture, TurboID enabled biotin-based PL in new settings, including yeast,Drosophila, andC. elegans.
A simple and powerful analysis of lateral subdiffusion using single particle tracking
Authors: Renner Marianne , Wang Lili , Levi Sabine , Hennekinne Laetitia , Triller Antoine 
Published: October 2017

AbstractIn biological membranes many factors such as cytoskeleton, lipid composition, crowding and molecular interactions deviate lateral diffusion from the expected random walks. These factors have different effects on diffusion but act simultaneously so the observed diffusion is a complex mixture of diffusive behaviors (directed, >Brownian, anomalous or confined). Therefore commonly used approaches to quantify diffusion based on averaging of the displacements, such as the mean square displacement, are not adapted to the analysis of this heterogeneity. We introduce a new parameter, the packing coefficientPc, which gives an estimate of the degree of free movement that a molecule displays in a period of time independently of its global diffusivity. Applying this approach to two different situations (diffusion of a lipid probe and trapping of receptors at synapses), we show thatPcdetected and localized temporary changes of diffusive behavior both in time and in space. More importantly, it allowed the detection of periods with very high confinement (~immobility), their frequency and duration, and thus it can be used to calculate the effectivekonandkoffof scaffolding interactions such those that immobilize receptors at synapses.
Inhibition of mitochondrial fission preserves photoreceptors after retinal detachment
Authors: She Xiangjun , Lu Xinmin , Li Tong , Sun Junran , Liang Jian , Zhai Yuanqi , Yang Shiqi , Gu Qing , Wei Fang , Zhu Hong , Wang Fenghua , Luo Xueting , Sun Xiaodong 
Published: October 2017

AbstractPhotoreceptor degeneration is a leading cause of visual impairment worldwide. Separation of neurosensory retina from the underlying retinal pigment epithelium is a prominent feature preceding photoreceptor degeneration in a variety of retinal diseases. Although ophthalmic surgeries have been well developed to restore retinal structures, post-op patients usually experience progressive photoreceptor degeneration and irreversible vision loss that is incurable at present. Previous studies point to a critical role of mitochondria-mediated apoptotic pathway in photoreceptor degeneration, but the upstream triggers remain largely unexplored. In this study, we show that after experimental RD induction, photoreceptors activate dynamin-related protein 1 (Drp1)-dependent mitochondrial fission pathway and subsequent apoptotic cascades. Mechanistically, endogenous ROS is necessary for Drp1 activation in vivo and exogenous ROS insult is sufficient to activate Drp1-dependent mitochondrial fission in cultured photoreceptors. Accordingly, inhibition of Drp1 activity effectively preserves mitochondrial integrity and rescues photoreceptors. Collectively, our data delineates a ROS-Drp1-mitochondria axis that promotes photoreceptor degeneration in retinal diseased models.
MreB Filaments Create Rod Shape By Aligning Along Principal Membrane Curvature
Authors: Hussain Saman , Wivagg Carl N. , Szwedziak Piotr , Wong Felix , Schaefer Kaitlin , Izoré Thierry , Renner Lars D. , Sun Yingjie , Bisson Filho Alexandre W. , Walker Suzanne , Amir Ariel , Löwe Jan , Garner Ethan C. 
Published: October 2017

AbstractMreB is essential for rod shape in many bacteria. Membrane-associated MreB filaments move around the rod circumference, helping to insert cell wall in the radial direction to reinforce rod shape. To understand how oriented MreB motion arises, we altered the shape ofBacillus subtilis.MreB motion is isotropic in round cells, and orientation is restored when rod shape is externally imposed. Stationary filaments orient within protoplasts, and purified MreB tubulates liposomesin vitro,orienting within tubes. Together, this demonstrates MreB orients along the greatest principal membrane curvature, a conclusion supported with biophysical modeling. We observed that spherical cells regenerate into rods in a local, self-reinforcing manner: rapidly propagating rods emerge from small bulges, exhibiting oriented MreB motion and increased glycan crosslinking. We propose that the coupling of MreB filament alignment to shape-reinforcing peptidoglycan synthesis creates a locally-acting, self-organizing mechanism allowing the rapid establishment and stable maintenance of emergent rod shape.
Biomechanics of the peafowl’s crest reveals frequencies tuned to social displays
Authors: Kane Suzanne Amador , Beveren Daniel Van , Dakin Roslyn 
Published: October 2017

AbstractFeathers act as vibrotactile sensors that can detect mechanical stimuli during avian flight and tactile navigation, suggesting that they may also detect stimuli during social displays. In this study, we present the first measurements of the biomechanical properties of the feather crests found on the heads of birds, with an emphasis on those from the Indian peafowl (Pavo cristatus). We show that in peafowl these crest feathers are coupled to filoplumes, small feathers known to function as mechanosensors. We also determined that airborne stimuli with the frequencies used during peafowl courtship and social displays couple efficiently via resonance to the vibrational response of their feather crests. Specifically, vibrational measurements showed that although different types of feathers have a wide range of fundamental resonant frequencies, peafowl crests are driven near-optimally by the shaking frequencies used by peacocks performing train-rattling displays. Peafowl crests were also driven to vibrate near resonance in a playback experiment that mimicked the effect of these mechanical sounds in the acoustic very near-field, reproducing the way peafowl displays are experienced at distances ≤ 1.5min vivo. When peacock wing-shaking courtship behaviour was simulated in the laboratory, the resulting airflow excited measurable vibrations of crest feathers. These results demonstrate that peafowl crests have mechanical properties that allow them to respond to airborne stimuli at the frequencies typical of this species’ social displays. This suggests a new hypothesis that mechanosensory stimuli could complement acoustic and visual perception and/or proprioception of social displays in peafowl and other bird species. We suggest behavioral studies to explore these ideas and their functional implications.
Control of Thiol-Maleimide Reaction Kinetics in PEG Hydrogel Networks
Authors: Jansen Lauren E. , Negrón-Piñeiro Lenny J. , Galarza Sualyneth , Peyton Shelly R. 
Published: October 2017

AbstractMichael-type addition reactions are widely used to polymerize biocompatible hydrogels. The thiol-maleimide modality achieves the highest macromer coupling efficiency of the reported Michael-type pairs, but the resulting hydrogel networks are heterogeneous, because polymerization is faster than the individual components can be manually mixed. The reactivity of the thiol dictates the overall reaction speed, which can be slowed in organic solvents and acidic buffers. Since these modifications also reduce the biocompatibility of resulting hydrogels, we investigated a series of biocompatible buffers and crosslinkers to decelerate gelation while maintaining high cell viability. We found that lowering the polymer weight percentage (wt%), buffer concentration, and pH slowed gelation kinetics, but crosslinking with an electronegative peptide was optimal for both kinetics and cell viability. Slowing the speed of polymerization resulted in more uniform hydrogels, both in terms of visual inspection and the diffusion of small molecules through the network. However, reactions that were too slow resulted in non-uniform particle dispersion due to settling, thus there is a trade-off in hydrogel network uniformity versus cell distribution in the hydrogels when using these networks in cell applications.
Transcriptome dynamics at theArabidopsisgraft junction reveal an inter-tissue recognition mechanism that activates vascular regeneration
Authors: Melnyk Charles W , Gabel Alexander , Hardcastle Thomas J , Robinson Sarah , Miyashima Shunsuke , Grosse Ivo , Meyerowitz Elliot M 
Published: October 2017

ABSTRACTThe ability for cut tissues to join together and form a chimeric organism is a remarkable property of many plants, however, grafting is poorly characterized at the molecular level. To better understand this process we monitored genome-wide temporal and spatial gene expression changes in graftedArabidopsis thalianahypocotyls. Tissues above and below the graft rapidly developed an asymmetry such that many genes were more highly expressed on one side than the other. This asymmetry correlated with sugar responsive genes and we observed an accumulation of starch above the graft that decreased along with asymmetry once the sugar-transporting vascular tissues reconnected. Despite the initial starvation response below the graft, many genes associated with vascular formation were rapidly activated in grafted tissues but not in cut and separated tissues indicating that a recognition mechanism activated that was independent of functional vascular connections. Auxin which is transported cell-to-cell, had a rapidly elevated response that was symmetric, suggesting that auxin was perceived by the root within hours of tissue attachment to activate the vascular regeneration process. A subset of genes were expressed only in grafted tissues, indicating that wound healing proceeded via different mechanisms depending on the presence or absence of adjoining tissues. Such a recognition process could have broader relevance for tissue regeneration, inter-tissue communication and tissue fusion events.
Molecular function limits divergent protein evolution on planetary timescales
Authors: Konaté Mariam M. , Plata Germán , Park Jimin , Usmanova Dinara R. , Wang Harris H. , Vitkup Dennis 
Published: October 2017

AbstractFunctional conservation is known to constrain protein evolution. Nevertheless, the long-term divergence patterns of proteins maintaining the same molecular function and the possible limits of this divergence have not been explored in detail. We investigate these fundamental questions by characterizing the divergence between ancient protein orthologs with conserved molecular function. Our results demonstrate that the decline of sequence and structural similarities between such orthologs significantly slows down after ~1-2 billion years of independent evolution. As a result, their sequence and structural similarities have not substantially decreased for the past billion years. The effective divergence limit (>25% sequence identity) is not primarily due to protein sites universally conserved in all linages. Instead, less than four amino acid types are accepted, on average, per site in orthologs strictly conserving their molecular function. Our analysis also reveals different divergence patterns for protein sites with experimentally determined small and large fitness effects of mutations.
Grid cell co-activity patterns during sleep reflect spatial overlap of grid fields during active behaviors
Authors: Trettel Sean G. , Trimper John B. , Hwaun Ernie , Fiete Ila R. , Colgin Laura Lee 
Published: October 2017

ABSTRACTContinuous attractor network models of grid formation posit that recurrent connectivity between grid cells controls their patterns of co-activation. Grid cells from a common module exhibit stable offsets in their periodic spatial tuning curves across environments, which may reflect recurrent connectivity or correlated sensory inputs. Here we explore whether cell-cell relationships predicted by attractor models persist during sleep states in which spatially informative sensory inputs are absent. We recorded ensembles of grid cells in superficial layers of medial entorhinal cortex during active exploratory behaviors and overnight sleep. Per pair and collectively, we found preserved patterns of spike-time correlations across waking, REM, and non-REM sleep, which reflected the spatial tuning offsets between these cells during active exploration. The preservation of cell-cell relationships across states was not explained by theta oscillations or CA1 activity. These results suggest that recurrent connectivity within the grid cell network drives grid cell activity across behavioral states.
Cell Cycle Control by Nuclear Sequestration ofCDC20andCDH1mRNA in Plant Stem Cells
Authors: Yang Weibing , Wightman Raymond , Meyerowitz Elliot M. 
Published: October 2017

AbstractIn eukaryotic cells, most RNA molecules are exported into the cytoplasm after being transcribed in the nucleus. Long noncoding RNAs (lncRNAs) have been found to reside and function primarily inside the nucleus, but nuclear localization of protein-coding messenger RNAs (mRNAs) has been considered rare in both animals and plants. Here we show that two mRNAs, transcribed from theCDC20andCCS52B(plant orthologue ofCDH1) genes, are specifically sequestered inside the nucleus during the cell cycle. CDC20 and CDH1 both function as coactivators of the anaphase-promoting complex or cyclosome (APC/C) E3 ligase to trigger cyclin B (C YCB) destruction. In theArabidopsis thalianashoot apical meristem (SAM), we findCDC20andCCS52Bare co-expressed withCYCBsin mitotic cells.CYCBtranscripts can be exported and translated, whereasCDC20andCCS52BmRNAs are strictly confined to the nucleus at prophase and the cognate proteins are not translated until the redistribution of the mRNAs to the cytoplasm after nuclear envelope breakdown (NEBD) at prometaphase. The 5’ untranslated region (UTR) is necessary and sufficient forCDC20mRNA nuclear localization as well as protein translation. Mitotic enrichment ofCDC20andCCS52Btranscripts enables the timely and rapid activation of APC/C, while their nuclear sequestration at prophase appears to protect cyclins from precocious degradation.