bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Membrane-Bound Cytochrome EnablesMethanosarcina acetivoransto Conserve Energy to Support Growth from Extracellular Electron Transfer
Authors: Holmes Dawn E , Ueki Toshiyuki , Tang Hai-Yan , Zhou Jinjie , Smith Jessica A , Chaput Gina , Lovley Derek R 
Published: March 2019

AbstractConservation of energy to support growth solely from extracellular electron transfer was demonstrated for the first time in a methanogen.Methanosarcina acetivoransgrew with methanol as the sole electron donor and the extracellular electron acceptor anthraquione-2,6-disulfonate (AQDS) as the sole electron acceptor when methane production was inhibited with bromoethanesulfonate. Transcriptomics revealed that transcripts for the gene for the transmembrane, multi-heme,c-type cytochrome MmcA were 4-fold higher in AQDS-respiring cells versus methanogenic cells. A strain in which the gene for MmcA was deleted failed to grow via AQDS reduction whereas strains in which other cytochrome genes were deleted grew as well as the wild-type strain. The MmcA-deficient strain grew with the conversion of methanol or acetate to methane, suggesting that MmcA has a specialized role as a conduit for extracellular electron transfer. Enhanced expression of genes for methanol conversion to methyl-coenzyme M and components of the Rnf complex suggested that methanol is oxidized to carbon dioxide in AQDS-respiring cells through a pathway that is similar to methyl-coenezyme M oxidation in methanogenic cells. However, during AQDS respiration the Rnf complex and reduced methanophenazine probably transfer electrons to MmcA, which functions as the terminal reductase for AQDS reduction. Extracellular electron transfer may enable survival of methanogens in dynamic environments in which oxidized humic substances and Fe(III) oxides are intermittently available. The availability of tools for genetic manipulation ofM. acetivoransmakes it an excellent model microbe for evaluatingc-type cytochrome-dependent extracellular electron transfer in Archaea.ImportanceExtracellular electron exchange inMethanosarcinaspecies and closely related Archaea plays an important role in the global carbon cycle and can enhance the speed and stability of anaerobic digestion, an important bioenergy strategy. The potential importance ofc-type cytochromes for extracellular electron transfer to syntrophic bacterial partners and/or Fe(III) minerals in some Archaea has been suspected for some time, but the studies withMethanosarcina acetivoransreported here provide the first genetic evidence supporting this hypothesis. The results suggest parallels with Gram-negative bacteria, such asShewanellaandGeobacterspecies, in which outer-surfacec-type cytochromes are an essential component for electrical communication with the extracellular environment.M. acetivoransoffers an unprecedented opportunity to study mechanisms for energy conservation from the anaerobic oxidation of one-carbon organic compounds coupled to extracellular electron transfer in Archaea with implications not only for methanogens, but possibly also for anaerobic methane oxidation.
DEEPCON: Protein Contact Prediction using Dilated Convolutional Neural Networks with Dropout
Authors: Adhikari Badri 
Published: March 2019

AbstractBackgroundExciting new opportunities have arisen to solve the protein contact prediction problem from the progress in neural networks and the availability of a large number of homologous sequences through high-throughput sequencing. In this work, we study how deep convolutional neural network methods (ConvNets) may be best designed and developed to solve this long-standing problem.MethodWith publicly available datasets, we designed and trained various ConvNet architectures. We tested several recent deep learning techniques including wide residual networks, dropouts, and dilated convolutions. We studied the improvements in the precision of medium-range and long-range contacts, and compared the performance of our best architectures with the ones used in existing state-of-the-art methods.ResultsThe proposed ConvNet architectures predict contacts with significantly more precision than the architectures used in several state-of-the-art methods. When trained using the DeepCov dataset consisting of 3,456 proteins and tested on PSICOV dataset of 150 proteins, our architectures achieve up to 15% higher precision when L/2 long-range contacts are evaluated. Similarly, when trained using the DNCON2 dataset consisting of 1,426 proteins and tested on 84 protein domains in the CASP12 dataset, our single network achieves 4.8% higher precision than the ensembled DNCON2 method when top L long-range contacts are evaluated. DEEPCON will be made publicly available athttps://github.com/badriadhikari/DEEPCON/.
Functional genomics of a symbiotic community: shared traits in the olive fruit fly gut microbiota
Authors: Blow Frances , Gioti Anastasia , Goodhead Ian B. , Kalyva Maria , Kampouraki Anastasia , Vontas John , Darby Alistair C. 
Published: March 2019

AbstractThe olive fruit flyBactroceraoleae is a major pest of olives worldwide and houses a specialized gut microbiota dominated by the obligate symbiont “CandidatusErwinia dacicola”.Ca. E. dacicola is thought to supplement dietary nitrogen to the host, with only indirect evidence for this hypothesis so far. Here, we sought to investigate the contribution of the symbiosis to insect fitness and explore the ecology of the insect gut. For this purpose, we examined the composition of bacterial communities associated with Cretan olive fruit fly populations, and inspected several genome and transcriptome assemblies. We identified, and reconstructed the genome of, a novel component of the gut microbiota,Tatumellasp. TA1, which is stably associated with Mediterranean olive fruit fly populations. We also reconstructed a number of pathways related to nitrogen assimilation and interaction with the host. The results show that, despite variation in taxa composition of the gut microbial community, core functions related to the symbiosis are maintained. Functional redundancy between different microbial taxa was observed for genes allowing urea hydrolysis. The latter is encoded in the obligate symbiont genome by a conserved urease operon, likely acquired by horizontal gene transfer, based on phylogenetic evidence. A potential underlying mechanism is the action of mobile elements, especially abundant in theCa. E. dacicola genome. This finding, along with the identification, in the studied genomes, of extracellular surface structure components that may mediate interactions within the gut community, suggest that ongoing and past genetic exchanges between microbes may have shaped the symbiosis.
A Robust Model for Circadian Redox Oscillations
Authors: Olmo Marta del , Kramer Achim , Herzel Hanspeter 
Published: March 2019

AbstractThe circadian clock is an endogenous oscillator that controls daily rhythms in metabolism, physiology and behavior. Although the timekeeping components differ among species, a common design principle is a transcription-translation negative feedback loop. However, it is becoming clear that other mechanisms can contribute to the generation of 24 h rhythms. In mammalian adrenal gland, heart and brown adipose tissue, peroxiredoxins (Prx) exhibit 24 h rhythms in their redox state. Such rhythms are generated as a result of an inactivating hyperoxidation reaction that is reduced by coordinated import of the sulfiredoxin (Srx) into the mitochondria. However, a quantitative description of the Prx/Srx oscillating system is still missing. We investigate the basic principles that generate mitochondrial Prx/Srx rhythms using computational modeling. We observe that the previously described delay in mitochondrial Srx import, in combination with an appropriate separation of fast and slow reactions is sufficient to generate robust self-sustained relaxation-like oscillations. We find that our conceptual model can be regarded as a series of three consecutive phases and two temporal switches, highlighting the importance of delayed negative feedback and switches in the generation of oscillations.
Cultivatingin situtriggers growth of previously uncultivated microorganisms via a growth initiation factor in nature
Authors: Jung Dawoon , Machida Koshi , Nakao Yoichi , Kindaichi Tomonori , Ohashi Akiyoshi , Aoi Yoshiteru 
Published: March 2019

AbstractMost microorganisms resist cultivation under standard laboratory conditions. On the other hand, to cultivate microbes in a membrane-bound device incubated in nature (in situcultivation) is an effective approach. In the present study, we appliedin situcultivation to isolate diverse previously uncultivated marine sponge-associated microbes and comparatively analyzed this method’s efficiencies with those of the conventional method. Then, we attempted to clarify the key and unknown mechanism ofin situcultivation by focusing on growth triggering via growth initiation factor. We hypothesized that majority of environmental microorganisms are in nongrowing state and requiring “growth initiation factor” for the recovery and that can be provided from environments. Consequently, significantly more novel and diverse microbial types were isolated viain situcultivation than by standard direct plating (SDP). Next, the effect of the sponge extract on starvation recovery was compared between strains derived fromin situand SDP cultivation. Adding small amounts of the sponge extracts to the medium elevated the colony-formation efficiencies of thein situstrains at the starvation recovery step, while it showed no positive effect on that of SDP strains. Conversely, specific growth rates or carrying capacities of all tested strains were not positively affected. These results indicate that, 1) the sponge extract contains chemical compounds that facilitate starvation recovery, these substances selectively worked on thein situstrains, and 2) growth initiation factor in the sponge extract did not continuously promote growth activity but worked as triggers for regrowth (resuscitation from dormancy).ImportanceMost microbial species resist cultivation under laboratory condition. This is critical impediment for both academic and applied microbiology, and thus clarification of the mechanism of microbial uncultivability is highly demanded. Several evidences have been reported that to cultivate microbes in a membrane-bound device incubated in nature (in situcultivation) is an effective approach. However, the mechanism behind this approach has not been clarified. The present study shows the evidence that 1) initiating growth is a key for cultivating previously uncultivated microbes rather than simple growth promotion, and 2) growth initiation factor (signaling-like compounds) in natural environments stimulate microbial resuscitation from a nongrowing state. Since no study has focused on growth initiation for cultivation of previously uncultivated microorganisms, the discovery shown in the present study provides a new insight into microorganisms previously considered uncultivable and a microbial growth controlling system in nature.
Minimisation of surface energy drives apical epithelial organisation and gives rise to Lewis’ law
Authors: Kokic Marco , Iannini Antonella , Villa-Fombuena Gema , Casares Fernando , Iber Dagmar 
Published: March 2019

ABSTRACTThe packing of cells in epithelia exhibits striking regularities, regardless of the organism and organ. One of these regularities is expressed in Lewis’ law, which states that the average apical cell area is linearly related to the number of neighbours, such that cells with larger apical area have on average more neighbours. The driving forces behind the almost 100-year old Lewis’ law have remained elusive. We now provide evidence that the observed apical epithelial packing minimizes surface energy at the intercellular apical adhesion belt. Lewis’ law emerges because the apical cell surfaces then assume the most regular polygonal shapes within a contiguous lattice, thus minimising the average perimeter per cell, and thereby surface energy. We predict that the linear Lewis’ law generalizes to a quadratic law if the variability in apical areas is increased beyond what is normally found in epithelia. We confirm this prediction experimentally by generating heterogeneity in cell growth inDrosophilaepithelia. Our discovery provides a link between epithelial organisation, cell division and growth and has implications for the general understanding of epithelial dynamics.
Enhancer-promoter association determines Sox2 transcription regulation in mouse pluripotent cells
Authors: Huang Lei , Li Qing , Huang Qitong , Kong Siyuan , Zhu Xiusheng , Peng Yanling , Zhang Yubo 
Published: March 2019

AbstractDistal enhancer-promoter associations are essential for transcription control and emerging as a common epigenetic way to determine gene expression in eukaryotes. However, it remains as an uncultivated land on how their diversity influences gene transcription during development. In this study, we select three defined Sox2 associated enhancers (E1, E2 and E3), representing different distal interaction categories, to further explore their biological effects. We construct three enhancer-knockout cells via CRISPR/Cas9 system in mouse embryonic stem cells. Results show that these associations carry out various biological features. Embryonic stem cell specific association (E1) speeds up cell cycle and involves in cardiac development, which has been validated in vivo. In contrast, the indirect one (E2) restrains nerve differentiation and has potential effect on lipid metabolism. The common one (E3) promotes nerve differentiation and inhibits oxidation-reduction process. Together, these different associations determine Sox2 transcription and function specificity in mouse embryonic stem cells. Our study will enable a way for exploring miscellaneous spatiotemporal gene transcription control and advancing quantitative knowledge by utilizing three-dimensional genomic information.Summary statementSox2 transcription is complicated in mouse embryonic stem cells. It involves in heavily enhancer-promoter associations, which might make it a suitable model for phase-separation study. To decompose this cooperative regulation, diverse interactions are investigated. The biological effects have been explored in multiple perspectives. This may represent a quantitative way to explore and a potential new strategy to transcription control study.
Substantial genetic mixing among sexual and androgenetic lineages within the clam genus Corbicula
Authors: Martin Vastrade , Emilie Etoundi , Thibaut Bournonville , Mathilde Colinet , Nicolas Debortoli , Hedtke Shannon M. , Emilien Nicolas , Lise-Marie Pigneur , Julie Virgo , Jean-François Flot , Jonathan Marescaux , Karine Van Doninck 
Published: March 2019

Abstract“Occasional” sexuality occurs when a species combines clonal reproduction and genetic mixing. This strategy is predicted to combine the advantages of both asexuality and sexuality, but its actual consequences on the genetic diversity and species longevity are poorly understood. Androgenesis, a reproductive mode in which the offspring inherits its entire nuclear genome from the father, is often reported as a strictly clonal reproductive mode. Androgenesis is the predominant reproductive mode within the hermaphroditic, invasive lineages of the mollusk genus Corbicula. Their ability to reproduce clonally through androgenesis has been determinant in their invasive success, having colonized during the 20th century American and European freshwater systems, where they became notorious invaders with a widespread, global distribution. However, in androgenetic Corbicula clams, occasional genetic mixing between distinct lineages has also been observed when the sperm of one lineage fertilizes the oocyte of another one. Because of these occasional introgressions, the genetic relationships between Corbicula species remained unclear, and the biogeographic origins of the invasive androgenetic lineages have been challenging to identify. To address these issues, we analyzed the patterns of allele sharing for several nuclear and mitochondrial molecular markers among Corbicula individuals collected across both the native and invasive range. Our results show the occurrence of an allelic pool encompassing all Corbicula freshwater species worldwide, including sexual and androgenetic ones, which highlights the substantial genetic mixing within this genus. However, the differences in allele sharing patterns between invasive lineages, and the low diversity within each lineage, suggest recent, distinct biogeographic origins of invasive Corbicula androgenetic lineages. Finally, the polyploidy, high heterozygosity, and hybrid phenotypes and genotypes found in our study probably originated from hybridization events following egg parasitism between distinct Corbicula lineages. This extensive cross-lineage mixing found in Corbicula may generate nuclear diversity in an otherwise asexually reproducing species.
Short term memory properties of sensory neural architectures
Authors: Dubreuil Alexis M. 
Published: March 2019

AbstractA functional role of the cerebral cortex is to form and hold representations of the sensory world for behavioral purposes. This is achieved by a sheet of neurons, organized in modules called cortical columns, that receives inputs in a peculiar manner, with only a few neurons driven by sensory inputs through thalamic projections, and a vast majority of neurons receiving mainly cortical inputs. How should cortical modules be organized, with respect to sensory inputs, in order for the cortex to efficiently hold sensory representations in memory? To address this question we investigate the memory performance of trees of recurrent networks (TRN) that are composed of recurrent networks, modeling cortical columns, connected with each others through a tree-shaped feed-forward backbone of connections, with sensory stimuli injected at the root of the tree. On these sensory architectures two types of short-term memory (STM) mechanisms can be implemented, STM via transient dynamics on the feed-forward tree, and STM via reverberating activity on the recurrent connectivity inside modules. We derive equations describing the dynamics of such networks, which allow us to thoroughly explore the space of possible architectures and quantify their memory performance. By varying the divergence ratio of the tree, we show that serial architectures, where sensory inputs are successively processed in different modules, are better suited to implement STM via transient dynamics, while parallel architectures, where sensory inputs are simultaneously processed by all modules, are better suited to implement STM via reverberating dynamics.
PrankWeb: web server for ligand binding-site prediction and visualization
Authors: Jendele Lukas , Krivak Radoslav , Skoda Petr , Novotny Marian , Hoksza David 
Published: March 2019

ABSTRACTPrankWeb is an online resource providing an interface to P2Rank, a state-of-the-art ligand binding site prediction method. P2Rank is a template-free machine learning method which is based on the prediction of ligandability of local chemical neighborhoods centered on points placed on a solvent accessible surface of a protein. Points with high ligandability score are then clustered to form the resulting ligand binding sites. On top of that, PrankWeb then provides a web interface enabling users to easily carry out the prediction and visually inspect the predicted binding sites via an integrated sequence-structure view. Moreover, PrankWeb can determine sequence conservation for the input molecule and use it in both the prediction and results visualization steps. Alongside its online visualization options, PrankWeb also offers the possibility to export the results as a PyMOL script for offline visualization. The web frontend communicates with the serer side via a REST API. Therefore, in high-throughput scenarios users can utilize the server API directly, bypassing the need for a webbased front end or installation of the P2Rank application. PrankWeb is available at http://prankweb.cz/. The source code of the web application and the P2Rank method can be accessed at https://github.com/jendelel/PrankWebApp and https://github.com/rdk/p2rank, respectively.
Rapid and iterative genome editing in the zoonotic malaria parasitePlasmodium knowlesi: New tools forP. vivaxresearch
Authors: Mohring Franziska , Hart Melissa N. , Rawlinson Thomas A. , Henrici Ryan , Charleston James A. , Benavente Ernest Diez , Patel Avnish , Hall Joanna , Almond Neil , Campino Susana , Clark Taane G. , Sutherland Colin J. , Baker David A. , Draper Simon J. , Moon Robert W. 
Published: March 2019

AbstractTackling relapsingPlasmodium vivaxand zoonoticPlasmodium knowlesiinfections is critical to reducing malaria incidence and mortality worldwide. Understanding the biology of these important and related parasites was previously constrained by the lack of robust molecular and genetic approaches. Here, we establish CRISPR-Cas9 genome editing in a culture-adaptedP. knowlesistrain and define parameters for optimal homology-driven repair. We establish a scalable protocol for the production of repair templates by PCR and demonstrate the flexibility of the system by tagging proteins with distinct cellular localisations. Using iterative rounds of genome-editing we generate a transgenic line expressingP. vivaxDuffy binding protein (PvDBP), a lead vaccine candidate. We demonstrate that PvDBP plays no role in reticulocyte restriction but can alter the macaque/human host cell tropism ofP. knowlesi. Critically, antibodies raised against theP. vivaxantigen potently inhibit proliferation of this strain, providing an invaluable tool to support vaccine development.
MASST: A Web-based Basic Mass Spectrometry Search Tool for Molecules to Search Public Data
Authors: Wang Mingxun , Jarmusch Alan K. , Vargas Fernando , Aksenov Alexander A. , Gauglitz Julia M. , Weldon Kelly , Petras Daniel , Silva Ricardo da , Quinn Robby , Melnik Alexey V. , van der Hooft Justin J.J. , Caraballo Rodríguez Andrés Mauricio , Nothias Louis Felix , Aceves Christine M. , Panitchpakdi Morgan , Brown Elizabeth , Di Ottavio Francesca , Sikora Nicole , Elijah Emmanuel O. , Labarta-Bajo Lara , Gentry Emily C. , Shalapour Shabnam , Kyle Kathleen E. , Puckett Sara P. , Watrous Jeramie D. , Carpenter Carolina S. , Bouslimani Amina , Ernst Madeleine , Swafford Austin D. , Zúñiga Elina I. , Balunas Marcy J. , Klassen Jonathan L. , Loomba Rohit , Knight Rob , Bandeira Nuno , Dorrestein Pieter C. 
Published: March 2019

CorrespondenceWe introduce a web-enabled small-molecule mass spectrometry (MS) search engine. To date, no tool can query all the public small-molecule tandem MS data in metabolomics repositories, greatly limiting the utility of these resources in clinical, environmental and natural product applications. Therefore, we introduce aMassSpectrometrySearchTool (MASST) (https://proteosafe-extensions.ucsd.edu/masst/), that enables the discovery of molecular relationships among accessible public metabolomics and natural product tandem mass spectrometry data (MS/MS).
Differential Expression of the T cell Inhibitor TIGIT in Glioblastoma and Multiple Sclerosis
Authors: Lucca Liliana E. , Lerner Benjamin A. , DeBartolo Danielle , Park Calvin , Ponath Gerald , Raddassi Khadir , Hafler David A. , Pitt David 
Published: March 2019

AbstractTo identify co-inhibitory immune pathways important in the brain, we hypothesized that comparison of T cells in lesions from patients with MS with tumor infiltrating T cells (TILs) from patients with GBM may reveal novel targets for immunotherapy. Focusing on PD-1 and TIGIT, we found that TIGIT and its ligand CD155 were highly expressed on GBM TILs but were near-absent in MS lesions, while lymphocytic expression of PD-1/PDL-1 was comparable. TIGIT was also upregulated in peripheral lymphocytes in GBM, suggesting recirculation of TILs. These data raise the possibility that anti-TIGIT therapy may be beneficial for patients with glioblastoma.