bluuebunny/crossref_metadata_2025_split huggingface dataset:
Geological degassing enhances microbial metabolism in the continental subsurface
Authors: Bornemann Till L.V. , Adam Panagiotis S. , Turzynski Victoria , Schreiber Ulrich , Figueroa-Gonzalez Perla Abigail , Rahlff Janina , Köster Daniel , Schmidt Torsten C. , Schunk Ralf , Krauthausen Bernhard , Probst Alexander J. 
Published: March 2020

AbstractMantle degassing provides a substantial amount of reduced and oxidized gases shaping microbial metabolism at volcanic sites across the globe, yet little is known about its impact on microbial life under non-thermal conditions. Here, we characterized deep subsurface fluids from a cold-water geyser driven by mantle degassing using genome-resolved metagenomics to investigate how the gases impact the metabolism and activity of indigenous microbes compared to non-impacted sites. While species-specific analyses of Altiarchaeota suggest site-specific adaptations and a particular biogeographic pattern, chemolithoautotrophic core features of the communities appeared to be conserved across 17 groundwater ecosystems between 5 and 3200 m depth. We identified a significant negative correlation between ecosystem depth and bacterial replication, except for samples impacted by high amounts of subsurface gases, which exhibited near-surface activity. Our results suggest that geological degassing leads to higher nutrient flows and microbial activity in the deep subsurface than previously estimated.
Characterization of fluorescent proteins with intramolecular photostabilization
Authors: Henrikus Sarah S. , Tassis Konstantinos , Zhang Lei , van der Velde Jasper H. M. , Gebhardt Christian , Herrmann Andreas , Jung Gregor , Cordes Thorben 
Published: March 2020

AbstractGenetically encodable fluorescent proteins have revolutionized biological imagingin vivoandin vitro. Since there are no other natural fluorescent tags with comparable features, the impact of fluorescent proteins for biological research cannot be overemphasized. Despite their importance, their photophysical properties, i.e., brightness, count-rate and photostability, are relatively poor compared to synthetic organic fluorophores or quantum dots. Intramolecular photostabilizers were recently rediscovered as an effective approach to improve photophysical properties. The approach uses direct conjugation of photostablizing compounds such as triplet-state quenchers or redox-active substances to an organic fluorophore, thereby creating high local concentrations of photostabilizer. Here, we introduce an experimental strategy to screen for the effects of covalently-linked photostabilizers on fluorescent proteins. We recombinantly produced a double cysteine mutant (A206C/L221C) of α-GFP for attachment of photostabilizer-maleimides on the ß-barrel in close proximity to the chromophore. Whereas labelling with photostabilizers such as Trolox, Nitrophenyl, and Cyclooctatetraene, which are often used for organic fluorophores, had no effect on α-GFP-photostability, a substantial increase of photostability was found upon conjugation of α-GFP to an azobenzene derivative. Although the mechanism of the photostabilizing effects remains to be elucidated, we speculate that the higher triplet-energy of azobenzene might be crucial for triplet-quenching of fluorophores in the near-UV and blue spectral range. Our study paves the way towards the development and design of a second generation of fluorescent proteins with photostabilizers placed directly in the protein barrel by methods such as unnatural amino acid incorporation.
Putative ligand binding sites of two functionally characterized bark beetle odorant receptors
Authors: Yuvaraj Jothi K. , Roberts Rebecca E. , Sonntag Yonathan , Hou Xiaoqing , Grosse-Wilde Ewald , Machara Aleš , Hansson Bill S. , Johanson Urban , Löfstedt Christer , Andersson Martin N. 
Published: March 2020

AbstractBark beetle behavior is to a large extent mediated via olfaction. Targeting the odorant receptors (ORs) may thus provide avenues towards improved pest control during outbreaks. Such an approach requires information on the function of receptors and their interactions with ligands. Hence, we annotated 73 ORs from an antennal transcriptome of the spruce bark beetleIps typographusand report the functional characterization of two ORs (ItypOR46 and ItypOR49), which are selective for single enantiomers of the common bark beetle pheromone compounds ipsenol and ipsdienol, respectively. We use homology modeling and molecular docking to predict their binding sites. The importance of residues Tyr84 and Thr205 in ItypOR46 in the activation by ipsenol is experimentally supported, and hydrogen bonding appears key in pheromone binding. The biological significance of the characterized ORs positions them as prime targets for pest control and use in biosensors to detect bark beetle infestations.
Elevated temperatures impose transcriptional constraints on coffee genotypes and elicit intraspecific differences in thermoregulation
Authors: de Oliveira Raphael Ricon , Cherubino Ribeiro Thales Henrique , Cardon Carlos Henrique , Fedenia Lauren , Maia Vinicius Andrade , Ferrara Barbosa Barbara Castanheira , Caldeira Cecílio Frois , Klein Patricia E. , Chalfun-Junior Antonio 
Published: March 2020

ABSTRACTThe projected impact of global warming on coffee production may require the heat-adapted genotypes in the next decades. To identify thermotolerance cellular strategies, we compared the effect of elevated temperature on two commercialCoffea arabicaL. genotypes exploring leaf physiology, transcriptome and carbohydrate/protein composition. Growth temperatures were 23/19°C (day/night), as optimal condition (OpT), and 30/26°C (day/night) as a possible warmer scenario (WaT). The cv. Acauã showed lower levels of leaf temperature under both conditions compared to cv. Catuaí, whereas slightly or no differences for other leaf physiological parameters. Therefore, to explore thermoregulatory pathways the leaf transcriptome was examined using RNAseq. Genotypes showed a marked number of differentially-expressed genes (DEGs) under OpT, however DEGs strongly decrease in both at WaT condition indicating a transcriptional constraint. DEGs responsive to WaT revealed shared and genotype-specific genes mostly related to carbohydrate metabolism. Under OpT, leaf starch content was greater in cv. Acauã although the levels of leaf starch, sucrose, and leaf protein decreased in both genotypes as WaT was imposed. These findings indicate that genotypes with a greater capacity to maintain carbohydrate homeostasis under temperature fluctuations could be more thermotolerant and which may be useful in breeding for a changing climate.HIGHLIGHTIn response to warming, transcriptional differences decrease in coffee genotypes hampering breeding programs. Differences in gene expression and sugar levels confirm intraspecific variation associating thermotolerance to maintenance of energetic homeostasis.
User guide to the red blood cell model (RCM), a multiplatform JAVA-based model of human red blood cell homeostasis
Authors: Rogers Simon , Lew Virgilio L. 
Published: March 2020

AbstractWe introduce here a new multiplatform JAVA-based mathematical-computational model of RBC homeostasis for investigating the dynamics of changes in RBC homeostasis in health and disease. We provide a brief overview on the homeostasis of human RBCs and on the general biophysical principles guiding the modelling design. By way of a detailed tutorial we apply the model to investigate in depth the multiple effects associated with RBC dehydration induced by potassium permeabilization, a necessary preliminary for understanding the pathophysiology of a wide group of inherited haemolytic anaemias, a subject of intense current research and clinical interest. Using the red cell model (RCM), we design and run in silico representations of experimental protocols to study global RBC responses to calcium and potassium permeabilization covering a wide range of experimental, physiological and pathological conditions. Model outputs report the evolution in time of all the homeostatic variables in the system allowing, for the first time, a detailed and comprehensive account of the complex processes shaping global cell responses. Analysis of the results explains the mechanisms by which the entangled operation of all the RBC components link cell dehydration and protein crowding to cell acidification and to the generation of hypertonic, alkaline effluents. Open access to the RCM in a GitHub repository, together with the tutorial primed for a specific investigation pave the way for researchers and clinicians to apply the model on many different aspects of RBC physiology and pathology.
Integration of anatomy ontology data with protein-protein interaction networks improves the candidate gene prediction accuracy for anatomical entities
Authors: Fernando Pasan Chinthana , Mabee Paula M , Zeng Erliang 
Published: March 2020

AbstractBackgroundIdentification of genes responsible for anatomical entities is a major requirement in many fields including developmental biology, medicine, and agriculture. Current wet-lab techniques used for this purpose, such as gene knockout, are high in resource and time consumption. Protein-protein interaction (PPI) networks are frequently used to predict disease genes for humans and gene candidates for molecular functions, but they are rarely used to predict genes for anatomical entities. This is because PPI networks suffer from network quality issues, which can be a limitation for their usage in predicting candidate genes for anatomical entities. We developed an integrative framework to predict candidate genes for anatomical entities by combining existing experimental knowledge about gene-anatomy relationships with PPI networks using anatomy ontology annotations. We expected this integration to improve the quality of the PPI networks and be better optimized to predict candidate genes for anatomical entities. We used existing Uberon anatomy entity annotations for zebrafish and mouse genes to construct gene networks by calculating semantic similarity between the genes. These ‘anatomy-based gene networks’ are semantic networks, as they are constructed based on the Uberon anatomy ontology annotations that are obtained from the experimental data in the literature. We integrated these anatomy-based gene networks with mouse and zebrafish PPI networks retrieved from the STRING database, and we compared the performance of their network-based candidate gene predictions.ResultsAccording to candidate gene prediction performance evaluations tested under four different semantic similarity calculation methods (Lin, Resnik, Schlicker, and Wang), the integrated networks showed better receiver operating characteristic (ROC) and precision-recall curve performances than PPI networks for both zebrafish and mouse.ConclusionIntegration of existing experimental knowledge about gene-anatomical entity relationships with PPI networksviaanatomy ontology improves the network quality, which makes them better optimized for predicting candidate genes for anatomical entities.
The circulatory physiopathology of human red blood cells investigated with a multiplatform model of cellular homeostasis. III. Senescence changes during the full circulatory lifespan
Authors: Rogers Simon , Lew Virgilio L. 
Published: March 2020

AbstractHuman red blood cells (RBCs) have a circulatory lifespan of about four months. Under constant oxidative and mechanical stress, but devoid of organelles and deprived of biosynthetic capacity for protein renewal, RBCs undergo substantial homeostatic changes, progressive densification followed by late density reversal among others, changes assumed to have been harnessed by evolution to sustain the rheological competence of the RBCs for as long as possible. The unknown mechanisms by which this is achieved are the subject of this investigation. Each RBC traverses capillaries between 1000 and 2000 times per day, roughly one transit per minute, a total of about 2•105transits during their lifespan. A dedicated Lifespan model of RBC homeostasis was developed as an extension of the RCM introduced in the first paper of this series to explore the cumulative patterns predicted for repetitive capillary transits over a standardized lifespan period of 120 days, using experimental data to constrain the parameter space. Capillary transits were simulated by periods of elevated cell/medium volume ratios and by transient deformation-induced permeability changes attributed to PIEZO1 channel mediation as outlined in the second paper of this series. The first unexpected finding was that quantal changes generated during single capillary transits cease accumulating after a few days and cannot account for the observed progressive densification of RBCs on their own, thus ruling out the quantal hypothesis. The second unexpected finding was that the documented patterns of RBC densification and late reversal could only be emulated by the implementation of a strict time-course of decay in the activities of the calcium and Na/K pumps, but only in addition to the quantal changes. These results showed that both quantal changes and pump-decay regimes were necessary to account for the documented lifespan pattern, neither sufficient on their own. They also suggested a strong selective component in the pump decay sequence. A third finding was that RBCs exposed to levels of calcium permeation above certain thresholds in the circulation could develop a pattern of late or early hyperdense collapse followed by delayed density reversal. When tested over much reduced lifespan periods the results emulated the known circulatory fate of irreversible sickle cells, the cell subpopulation responsible for vaso-occlusion and for most of the clinical manifestations of sickle cell disease. Analysis of the results provided an insightful new understanding of the mechanisms driving the changes in RBC homeostasis during circulatory aging in health and disease.
Structural basis for targeting human cancer antigen STEAP1 with antibodies
Authors: Oosterheert Wout , Gros Piet 
Published: March 2020

AbstractSix-transmembrane epithelial antigen of the prostate (STEAP1) is an integral membrane protein that is highly upregulated on the cell surface of several human cancers, making it a promising therapeutic target. It shares sequence homology with three enzymes (STEAP2-4) that catalyze the NADPH-dependent reduction of iron(III). However, STEAP1 lacks an intracellular NADPH-binding domain and does not exhibit cellular ferric-reductase activity. Thus, both the molecular function of STEAP1 and its role in cancer progression remain elusive. Here, we present a ~3.0 Å cryo-electron microscopy structure of trimeric human STEAP1 bound to three Fab-fragments of the clinically employed antibody mAb120.545. STEAP1 adopts a reductase-like conformation and interacts with the Fabs through its extracellular helices. Enzymatic assays in human cells reveal that STEAP1 promotes iron(III) reduction when fused to the intracellular NADPH-binding domain of its family member STEAP4, implicating STEAP1 as a functional ferric reductase in STEAP hetero-trimers. Our work provides a foundation for deciphering the molecular mechanisms of STEAP1 and will be instrumental in the design of new therapeutic strategies to target STEAP1 in cancer.
Landscape drivers and effectiveness of pest control by insectivorous birds in a landscape-dominant woody crop
Authors: Martínez-Núñez Carlos , Rey Pedro J. , Manzaneda Antonio J. , García Daniel , Tarifa Rubén , Molina José L. , Salido Teresa 
Published: March 2020

AbstractAvian-mediated pest control is a significant ecosystem service with important economic implications. However, there is an overall paucity of experimental information about how landscape simplification affect its current level. Information on pest control by birds is missing in some permanent agroecosystems of worldwide importance, like olive orchards, that dominate vast areas in the Mediterranean region.We assess the effectiveness of insectivorous birds for controlling the two main pest insects in olive orchards and explore the effects of landscape complexity and distance to semi-natural patches on avian insectivore abundance and pest control. For this, we combine bird surveys with field experiments (branch exclusions and pest plasticine models) at the regional scale.Landscape heterogeneity increased the abundance and richness of insectivorous birds, which were also more abundant and diverse in semi-natural patches, compared to the farm olive matrix. Experiments evidenced that pest control by birds (measured as attack rates to plasticine models and pest damage) in the studied olive orchards is negligible, while pests were overall abundant and pest damage was high on most farms. This raises alarms about the status of avian pest control in this agroecosystem.Although landscape heterogeneity increased the abundance/richness of insectivorous birds, and favored some forest species, insectivorous bird abundance seems diluted in relation to prey availability in all landscapes. Thus, pest control by birds seems currently unsuccessful in olive orchards. Our results might be evidencing the loss of an ecosystem service due to a generalized massive decline of common and forest insectivorous birds.Key messageOlive orchards dominate extensive areas causing important landscape simplification.Insectivorous birds are more abundant in semi-natural patches within olive farms.Field experiments show a low impact of birds on olive pests and damage.Avian-mediated pest biocontrol seems diluted by limited suitable habitat for birds.Agri-environmental measures should focus on increasing landscape complexity.
Loss of genetic variation in the two-locus multiallelic haploid model
Authors: Pontz Martin , Feldman Marcus W. 
Published: March 2020

AbstractIn the evolutionary biology literature, it is generally assumed that in deterministic haploid selection models, in the absence of variation-generating mechanisms such as mutation, no polymorphic equilibrium can be stable. However, results corroborating this claim are scarce and almost always depend upon additional assumptions. Using ideas from game theory, we establish a condition on the fitness parameters of haplotypes formed by two loci such that a monomorphism is a global attractor. Further, we show that no isolated equilibrium exists, at which an unequal number of alleles from two loci is present. Under the assumption of convergence of trajectories to equilirium points, we settle the two-locus three-allele case for a fitness scheme formally equivalent to the classical symmetric viability model.
The lupus autoantigen La is anXist-binding protein involved inXistfolding and cloud formation
Authors: Ha Norbert , Ding Nan , Hong Ru , Liu Rubing , Roca Xavier , Luo Yingyuan , Duan Xiaowei , Wang Xiao , Ni Peiling , Zhang Li-Feng , Chen Lingyi 
Published: March 2020

ABSTRACTUsing the programmable RNA-sequence binding domain of the Pumilio protein, we FLAG-taggedXist(inactivatedXchromosomespecific transcript) in live cells. Affinity pulldown coupled to mass spectrometry was employed to identify a list of 138 candidateXist-binding proteins, from which, the lupus autoantigen La (encoding geneSsb) was validated as a protein functionally critical for X chromosome inactivation (XCI). Extensive XCI defects were detected inSsbknockdown cells, including chromatin compaction, death of female ES cells duringin vitrodifferentiation and chromosome-wide monoallelic gene expression pattern. Live-cell imaging ofXistRNA reveals the defining XCI defect:Xistcloud formation. La is a ubiquitous and versatile RNA-binding protein with RNA chaperone and RNA helicase activities. Functional dissection of La shows that the RNA chaperone domain and/or the ATP binding motif play critical roles in XCI. In mutant cells,Xisttranscripts are unstable and misfolded. These results show that La is critically involved in XCI, possibly as a protein regulating the in-cell structure ofXist.
Correlation of drug resistance with Single Nucleotide Variations through genome analysis and experimental validation in a multi-drug resistant clinical isolate ofM.tuberculosis
Authors: Bhattacharyya Kausik , Nemaysh Vishal , Joon Monika , Pratap Ramendra , Varma-Basil Mandira , Bose Mridula , Brahmachari Vani 
Published: March 2020

AbstractBackgroundGenome sequencing and genetic polymorphism analysis of clinical isolates ofM.tuberculosisis carried out to gain further insight into molecular pathogenesis and host-pathogen interaction. Therefore the functional evaluation of the effect of single nucleotide variation (SNV) is essential. At the same time, the identification of invariant sequences unique toM.tuberculosiscontributes to infection detection by sensitive methods. In the present study, genome analysis is accompanied by evaluation of the functional implication of the SNVs in a MDR clinical isolate VPCI591.ResultBy sequencing and comparative analysis of VPCI591 genome with 1553 global clinical isolates ofM.tuberculosis, we identified 143 unique strain specific SNVs. A novel intergenic variation in VPCI591 in the putative promoter/regulatory region mapping betweenembC (Rv3793)andembA(Rv3794) genes was found to enhance the expression ofembAB, which correlates with the high resistance of the VPCI591 to ethambutol. Similarly, the unique combination of three genic SNVs in RNA polymerase β gene (rpoB) in VPCI591 was evaluated for its effect on rifampicin resistance through molecular docking analysis. The comparative genomics also showed that along with variations, there are genes that remain invariant. 173 such genes were identified in our analysis.ConclusionWe have demonstrated that SNVs are not always benign and can also have functional effect. We show that variations bring about quantitative changes in transcription. Our results show the collective effect of SNVs on the structure of protein, impacting the interaction between the target protein and the drug molecule, withrpoBas an example.
Epigenetic Potential and DNA Methylation in an Ongoing House Sparrow (Passer domesticus) Range Expansion
Authors: Hanson Haley E. , Wang Chengqi , Schrey Aaron W. , Liebl Andrea L. , Jiang Rays H. Y. , Martin Lynn B. 
Published: March 2020

AbstractDuring range expansions, epigenetic mechanisms may mediate phenotypic responses to environmental cues, enabling organisms to adjust to novel conditions at novel sites. Here, we predicted that the number of CpG sites within the genome, one form of epigenetic potential, would be important for success during range expansions because DNA methylation can modulate gene expression and hence facilitate adaptive plasticity. Previously, we found that this same form of epigenetic potential was higher in introduced compared to native populations of house sparrows (Passer domesticus) for two immune genes (Toll-like receptors2Aand4). Here, we took a reduced-representation sequencing approach (ddRadSeq and EpiRadSeq) to investigate how CpG site number, as well as resultant DNA methylation, varied across five sites in the ∼70 year-old Kenyan house sparrow range expansion. We found that the number of CpG sites increased towards the vanguard of the invasion, even when accounting for variation in genetic diversity among sites. This pattern was driven by more losses of CpG sites towards the core of the invasion (the initial site of introduction). Across all sequenced loci, DNA methylation decreased but became more variable towards the range-edge. However, in the subset CpG sites proximal to mutated CpG sites, DNA methylation increased and variation declined. These results indicate that epigenetic potential influenced the Kenyan house sparrow range expansion, likely by providing greater phenotypic plasticity which is genetically assimilated as populations adapt to local conditions. Similar mechanisms might underlie the successes and failures of other natural and anthropogenic range expansions.