bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting primary production in the southern California Current Ecosystem from chlorophyll, nutrient concentrations, and irradiance
Authors: Stukel Michael R. , Goericke Ralf , Landry Michael R. 
Published: March 2019

AbstractWe investigated the processes driving variability in primary productivity in the California Current Ecosystem (CCE) in order to develop an algorithm for predicting primary productivity from in situ irradiance, nutrient, and chlorophyll (chl) measurements. Primary productivity data from seven process cruises of the CCE Long-Term Ecological Research (CCE LTER) program were used to parameterize the algorithm. An initial algorithm was developed using only irradiance to predict chl-specific productivity was found to have model-data misfit that was correlated with NH4+ concentrations. We thus found that the best estimates of primary productivity were obtained using an equation including NH4+ and irradiance: PP/Chl = V0m×(1-exp(−α×PAR/V0m)×NH4/(NH4+KS), where PP/Chl is chlorophyll-specific primary production in units of mg C d−1 / mg Chl, PAR is photosynthetically active radiation (units of μEi m−2 s−1), NH4+ is in units of μmol L−1, V0m = 66.5 mg C d−1 / mg Chl, α = 1.5, and KS = 0.025 μmol L−1. We then used this algorithm to compute primary productivity rates for the CCE-P1706 cruise on which in situ primary productivity samples were not available. We compared these estimates to independent productivity estimates derived from protistan grazing dilution experiments and found excellent agreement.
Statistical Analysis of Variability in TnSeq Data Across Conditions Using Zero-Inflated Negative Binomial Regression
Authors: Subramaniyam Siddharth , Zaveri Anisha , DeJesus Michael A. , Smith Clare , Baker Richard E. , Ehrt Sabine , Schnappinger Dirk , Sassetti Christopher M. , Ioerger Thomas R. 
Published: March 2019

AbstractDeep sequencing of transposon mutant libraries (or TnSeq) is a powerful method for probing essentiality of genomic loci under different environmental conditions. Various analytical methods have been described for identifying conditionally essential genes whose tolerance for insertions varies between two conditions. However, for large-scale experiments involving many conditions, a method is needed for identifying genes that exhibit significant variability in insertions across multiple conditions. In this paper, we introduce a novel statistical method for identifying genes with significant variability of insertion counts across multiple conditions based on Zero-Inflated Negative Binomial (ZINB) regression. Using likelihood ratio tests, we show that the ZINB fits TnSeq data better than either ANOVA or a Negative Binomial (in a generalized linear model). We use ZINB regression to identify genes required for infection ofM. tuberculosisH37Rv in C57BL/6 mice. We also use ZINB to perform a retrospective analysis of genes conditionally essential in H37Rv cultures exposed to multiple antibiotics. Our results show that, not only does ZINB generally identify most of the genes found by pairwise resampling (and vastly out-performs ANOVA), but it also identifies additional genes where variability is detectable only when the magnitudes of insertion counts are treated separately from local differences in saturation, as in the ZINB model.
Phase space characterization for gene circuit design
Authors: Muñoz Silva Macarena A. , Matute Tamara , Nuñez Isaac , Valdes Ambrosio , Ruiz Carlos A. , Vidal Peña Gonzalo A. , Federici Fernán , Rudge Timothy J. 
Published: March 2019

ABSTRACTGenetic circuit design requires characterization of the dynamics of synthetic gene expression. This is a difficult problem since gene expression varies in complex ways over time and across different contexts. Here we present a novel method for characterizing the dynamics of gene expression with a few parameters that account for changes in cellular context (host cell physiology) and compositional context (adjacent genes). The dynamics of gene circuits were characterized by a trajectory through a multi-dimensional phase space parameterized by the expression levels of each of their constituent transcriptional units (TU). These trajectories followed piecewise linear dynamics, with each dynamical regime corresponding to different growth regimes, or cellular contexts. Thus relative expression rates were changed by transitions between growth regimes, but were constant in each regime. We present a plausible two-factor mathematical model for this behavior based on resource consumption. By analyzing different combinations of TUs, we then showed that relative expression rates were significantly affected by the neighboring TU (compositional context), but maintained piecewise linear dynamics across cellular and compositional contexts. Taken together these results show that TU expression dynamics could be predicted by a reference TU up to a context dependent scaling factor. This model provides a framework for design of genetic circuits composed of TUs. A common sharable reference TU may be chosen and measured in the cellular contexts of interest. The output of each TU in the circuit may then be predicted from a simple function of the output of the reference TU in the given cellular context. This will aid in genetic circuit design by providing simple models for the dynamics of gene circuits and their constituent TUs.
A sound-sensitive source of alpha oscillations in human non-primary auditory cortex
Authors: Billig Alexander J. , Herrmann Björn , Rhone Ariane E. , Gander Phillip E. , Nourski Kirill V. , Snoad Beau F. , Kovach Christopher K. , Kawasaki Hiroto , Howard Matthew A. , Johnsrude Ingrid S. 
Published: March 2019

AbstractThe functional organization of human auditory cortex can be probed by characterizing responses to various classes of sound at different anatomical locations. Along with histological studies this approach has revealed a primary field in posteromedial Heschl’s gyrus (HG) with pronounced induced high-frequency (70-150 Hz) activity and short-latency responses that phase-lock to rapid transient sounds. Low-frequency neural oscillations are also relevant to stimulus processing and information flow, however their distribution within auditory cortex has not been established. Alpha activity (7-14 Hz) in particular has been associated with processes that may differentially engage earlier versus later levels of the cortical hierarchy, including functional inhibition and the communication of sensory predictions. These theories derive largely from the study of occipitoparietal sources readily detectable in scalp electroencephalography. To characterize the anatomical basis and functional significance of less accessible temporal-lobe alpha activity we analyzed responses to sentences in seven human adults (four female) with epilepsy who had been implanted with electrodes in superior temporal cortex. In contrast to primary cortex in posteromedial HG, a non-primary field in anterolateral HG was characterized by high spontaneous alpha activity that was strongly suppressed during auditory stimulation. Alpha-power suppression decreased with distance from anterolateral HG throughout superior temporal cortex, and was more pronounced for clear compared to degraded speech. This suppression could not be accounted for solely by a change in the slope of the power spectrum. The differential manifestation and stimulus-sensitivity of alpha oscillations across auditory fields should be accounted for in theories of their generation and function.Significance StatementTo understand how auditory cortex is organized in support of perception, we recorded from patients implanted with electrodes for clinical reasons. This allowed measurement of activity in brain regions at different levels of sensory processing. Oscillations in the alpha range (7-14 Hz) have been associated with functions including sensory prediction and inhibition of regions handling irrelevant information, but their distribution within auditory cortex is not known. A key finding was that these oscillations dominated in one particular non-primary field, anterolateral Heschl’s gyrus, and were suppressed when subjects listened to sentences. These results build on our knowledge of the functional organization of auditory cortex and provide anatomical constraints on theories of the generation and function of alpha oscillations.
Mechanisms of Economic Decisions under Sequential Offers
Authors: Ballesta Sébastien , Padoa-Schioppa Camillo 
Published: March 2019

AbstractBinary choices between goods are thought to take place in orbitofrontal cortex (OFC). However, current notions emerged mostly from studies where two offers were presented simultaneously, and other work suggested that choices under sequential offers rely on fundamentally different mechanisms. Here we recorded from the OFC of macaques choosing between two juices offered sequentially. Analyzing neuronal responses across time windows, we discovered different groups of neurons that closely resemble those identified under simultaneous offers, suggesting that decisions in the two modalities are formed in the same neural circuit. Building on this result, we examined four hypotheses on the decision mechanisms. OFC neurons encoded goods and values in a juice-based representation (labeled lines). Contrary to previous assessments, decisions did not involve mutual inhibition between pools of offer value cells. Instead, decisions involved mechanisms of circuit inhibition, whereby each offer value indirectly inhibits neurons encoding the opposite choice outcome. These results reconcile disparate findings and provide a unitary account for the neuronal mechanisms underlying economic decisions.
Structure of a Tc holotoxin pore provides insights into the translocation mechanism
Authors: Roderer Daniel , Hofnagel Oliver , Benz Roland , Raunser Stefan 
Published: March 2019

AbstractTc toxins are modular toxin systems that are composed of a pentameric membrane translocator (TcA) and a cocoon (TcB and TcC) encapsulating the toxic enzyme. Binding of Tcs to target cells and a pH shift trigger the conformational transition from the soluble prepore state to the membrane-embedded pore. Subsequently, the toxic enzyme is translocated and released into the cytoplasm. Here, we show in atomic detail an assembled Tc toxin complex fromP. luminescensin the membrane. We find that the five TcA protomers conformationally adapt to fit around the cocoon during prepore-to-pore transition. The architecture of the Tc toxin complex also allows TcB-TcC to bind to an already membrane-embedded TcA pore to form a holotoxin. Mammalian lipids with zwitterionic head groups are preferred over other lipids for Tc toxin integration. The translocated toxic enzyme, which can be partially visualized, transiently interacts with alternating negative charges and hydrophobic stretches.
Deep convolutional neural networks for predicting the quality of single protein structural models
Authors: Hou Jie , Cao Renzhi , Cheng Jianlin 
Published: March 2019

AbstractPredicting the global quality and local (residual-specific) quality of a single protein structural model is important for protein structure prediction and application. In this work, we developed a deep one-dimensional convolutional neural network (1DCNN) that predicts the absolute local quality of a single protein model as well as two 1DCNNs to predict both local and global quality simultaneously through a novel multi-task learning framework. The networks accept sequential and structural features (i.e. amino acid sequence, agreement of secondary structure and solvent accessibilities, residual disorder properties and Rosetta energies) of a protein model of any size as input to predict its quality, which is different from existing methods using a fixed number of hand-crafted features as input. Our three methods (InteractQA-net, JointQA-net and LocalQA-net) were trained on the structural models of the single-domain protein targets of CASP8, 9, 10 and evaluated on the models of CASP11 and CASP12 targets. The results show that the performance of our deep learning methods is comparable to the state-of-the-art quality assessment methods. Our study also demonstrates that combining local and global quality predictions together improves the global quality prediction accuracy. The source code and executable of our methods are available at:https://github.com/multicom-toolbox/DeepCovQA
Gene content of the fish-hunting cone snail Conus consors
Authors: Andreson Reidar , Roosaare Märt , Kaplinski Lauris , Laht Silja , Kõressaar Triinu , Lepamets Maarja , Brauer Age , Kukuškina Viktorija , Remm Maido 
Published: March 2019

AbstractBackgroundConus consors is a fish-hunting cone snail that lives in the tropical waters of the Indo-Pacific region. Cone snails have attracted scientific interest for the amazing potency of their venom, which consists of a complex mixture of small proteins known as conopeptides, many of which act as ion channel and receptor modulators with high selectivity.ResultsWe have analysed publicly available transcriptomic sequences from 8 tissues of Conus consors and complemented the transcriptome data with the data from genomic DNA reads. We identified 17,715 full-length protein sequences from the transcriptome. In addition, we predicted 168 full-length or partial conopeptide sequences and characterized gene structures of several conopeptide superfamilies.
Replicated anthropogenic hybridisations reveal parallel patterns of admixture in marine mussels
Authors: Simon Alexis , Arbiol Christine , Nielsen Einar Eg , Couteau Jérôme , Sussarellu Rossana , Burgeot Thierry , Bernard Ismaël , Coolen Joop W.P. , Lamy Jean-Baptiste , Robert Stéphane , Skazina Maria , Strelkov Petr , Queiroga Henrique , Cancio Ibon , Welch John J. , Viard Frédérique , Bierne Nicolas 
Published: March 2019

AbstractHuman-mediated transport creates secondary contacts between genetically differentiated lineages, bringing new opportunities for gene exchange. When similar introductions occur in different places, they provide informally replicated experiments for studying hybridisation. We here examined 4279Mytilusmussels, sampled in Europe and genotyped with 77 ancestry informative markers. We identified a type of introduced mussels, called ‘dock mussels’, associated with port habitats and displaying a particular genetic signal of admixture betweenM. edulisand the Mediterranean lineage ofM. galloprovincialis. These mussels exhibit similarities in their ancestry compositions, regardless of the local native genetic backgrounds and the distance separating colonised ports. We observed fine-scale genetic shifts at the port entrance, at scales below natural dispersal distance. Such sharp clines do not fit with migration-selection tension zone models, and instead suggest habitat choice and early stage adaptation to the port environment, possibly coupled with connectivity barriers. Variations in the spread and admixture patterns of dock mussels seem to be influenced by the local native genetic backgrounds encountered. We next examined departures from the average admixture rate at different loci, and compared human-mediated admixture events, to naturally admixed populations and experimental crosses. When the sameM. galloprovincialisbackground was involved, positive correlations in the departures of loci across locations were found; but when different backgrounds were involved, no or negative correlations were observed. While some observed positive correlations might be best explained by a shared history and saltatory colonisation, others are likely produced by parallel selective events. Altogether, genome-wide effect of admixture seems repeatable, and more dependent on genetic background than environmental context. Our results pave the way towards further genomic analyses of admixture, and monitoring of the spread of dock mussels both at large and fine spacial scales.
Cryo-EM of dynein microtubule-binding domains shows how an axonemal dynein distorts the microtubule
Authors: Lacey Samuel E. , He Shaoda , Scheres Sjors H. W. , Carter Andrew P. 
Published: March 2019

AbstractDyneins are motor proteins responsible for transport in the cytoplasm and the beating of the axoneme in cilia and flagella. They bind and release microtubules via a compact microtubule-binding domain (MTBD) at the end of a long coiled-coil stalk. Here we address how cytoplasmic and axonemal dynein MTBDs bind microtubules at near atomic resolution. We decorated microtubules with MTBDs of cytoplasmic dynein-1 and axonemal dynein DNAH7 and determined their cryo-EM structures using the stand-alone Relion package. We show the majority of the MTBD is remarkably rigid upon binding, with the transition to the high affinity state controlled by the movement of a single helix at the MTBD interface. In addition DNAH7 contains an 18-residue insertion, found in many axonemal dyneins, that reaches over and contacts the adjacent protofilament. Unexpectedly we observe that DNAH7, but not dynein-1, induces large distortions in the microtubule cross-sectional curvature. This raises the possibility that dynein coordination in axonemes is mediated via conformational changes in the microtubule.
A Synergistic Anti-Cancer FAK and HDAC Inhibitor Combination Discovered by a Novel Chemical-Genetic High-Content Phenotypic Screen
Authors: Dawson John C. , Serrels Bryan , Byron Adam , Muir Morwenna , Makda Ashraff , García-Muñoz Amaya , von Kriegsheim Alex , Carragher Neil O. , Frame Margaret C. 
Published: March 2019

AbstractWe mutated the Focal Adhesion Kinase (FAK) catalytic domain to inhibit binding of the chaperone, Cdc37 and ATP, mimicking the actions of a FAK kinase inhibitor. We re-expressed mutant and wild-type FAK in squamous cell carcinoma (SCC) cells from which endogenous FAK had been deleted, genetically fixing one axis of a FAK inhibitor combination high-content phenotypic screen to discover drugs that may synergize with FAK inhibitors. HDAC inhibitors represented the major class of compounds that potently induced multi-parametric phenotypic changes when FAK was rendered kinase-defective, or inhibited pharmacologically in SCC cells. Indeed, combined FAK and HDAC inhibitors arrest proliferation and induce apoptosis in a sub-set of cancer cell lines in vitro and efficiently inhibits tumor growth in vivo. Mechanistically, HDAC inhibitors potentiate inhibitor-induced FAK inactivation and reverses FAK-associated nuclear YAP in sensitive cancer cell lines. Here we report the discovery of a new clinically actionable synergistic combination between FAK and HDAC inhibitors.SignificanceWe describe a chemical-genetic, high-content phenotypic screening approach to discover effective anti-cancer combinations of targeted therapeutics through which we identified a novel, synergistic and clinically actionable, combination of FAK and HDAC inhibitors.
Feedback control promotes synchronisation of the cell-cycle across a population of yeast cells
Authors: Perrino Giansimone , Fiore Davide , Napolitano Sara , Galdi Francesca , Regina Antonella La , di Bernardo Mario , di Bernardo Diego 
Published: March 2019

AbstractThe periodic process of cell replication by division, known as cell-cycle, is a natural phenomenon occurring asynchronously in any cell population. Here, we consider the problem of synchronising cell-cycles across a population of yeast cells grown in a microfluidics device. Cells were engineered to reset their cell-cycle in response to low methionine levels. Automated syringes enable changing methionine levels (control input) in the microfluidics device. However, the control input resets only those cells that are in a specific phase of the cell-cycle (G1 phase), while the others continue to cycle unperturbed. We devised a simplified dynamical model of the cell-cycle, inferred its parameters from experimental data and then designed two control strategies: (i) an open-loop controller based on the application of periodic stimuli; (ii) a closed-loop model predictive controller (MPC) that selects the sequence of control stimuli which maximises a synchronisation index. Both the proposed control strategies were validated in-silico, together with experimental validation of the open-loop strategy.
Mechanisms of motor-independent membrane remodeling driven by dynamic microtubules
Authors: Rodríguez-García Ruddi , Volkov Vladimir A. , Chen Chiung-Yi , Katrukha Eugene A. , Olieric Natacha , Aher Amol , Grigoriev Ilya , López Magdalena Preciado , Steinmetz Michel O. , Kapitein Lukas C. , Koenderink Gijsje , Dogterom Marileen , Akhmanova Anna 
Published: March 2019

AbstractMicrotubule-dependent organization of membranous organelles, such as the endoplasmic reticulum, occurs through motor-based pulling and by coupling microtubule dynamics to membrane remodeling. How highly transient protein-protein interactions occurring at growing microtubule tips can induce load-bearing processive motion is currently unclear. Here, we reconstituted membrane tubulation in a minimal system with giant unilamellar vesicles, dynamic microtubules, End-Binding (EB) proteins and a membrane-targeted protein that interacts with EBs and microtubules. We showed that these components are sufficient to drive membrane remodeling by three mechanisms: membrane tubulation by growing microtubule ends, motor-independent membrane sliding along microtubule shafts and pulling by shrinking microtubules. Experiments and modeling demonstrated that the first two mechanisms can be explained by adhesion-driven biased membrane spreading on microtubules. Force spectroscopy revealed that attachments to growing and shrinking microtubule ends can sustain forces of ∼0.5 and ∼5 pN, respectively. Rapidly exchanging molecules that connect membranes to dynamic microtubules can thus bear sufficient load to induce membrane deformation and motility.