bluuebunny/crossref_metadata_2025_split huggingface dataset:
The origin of the odorant receptor gene family in insects
Authors: Brand Philipp , Robertson Hugh M. , Lin Wei , Pothula Ratnasri , Klingeman William E. , Jurat-Fuentes Juan Luis , Johnson Brian R. 
Published: February 2018

AbstractThe sense of smell enables the detection and discrimination of airborne chemicals via chemosensory receptors that have evolved independently multiple times throughout the tree of life. In insects, the odorant receptor (OR) gene family is the major chemosensory gene family involved in olfaction and its origin has been hypothesized to coincide with the evolution of a terrestrial lifestyle in hexapods. Missbach et al. (2014) challenged this view and suggested that ORs evolved with an ancestral OR co-receptor (Orco) after the origin of terrestriality, hypothesizing that the OR/Orco system is an adaptation to winged flight in insects instead. Building upon this work, we investigated the genomes of basal hexapod and insect lineages including Collembola, Diplura, Archaeognatha, Zygentoma, Odonata, and Ephemeroptera in an effort to identify the origin of the insect OR gene family. While absent from all non-insect hexapod lineages analyzed, ORs are present in all insect genomes. Orco is absent only in the most ancient insect lineage Archaeognatha. A fully functional OR/Orco system was present in our newly generated genome data of the Zygentoma Thermobia domestica. We suggest that ORs did evolve as adaptation to a terrestrial lifestyle outside high-humidity habitats, and not winged flight, representing a key evolutionary novelty in the ancestor of all insects. The OR family is therefore the first known molecular synapomorphy for the Class Insecta.
Laminin heparin-binding peptides promiscuously bind growth factors and enhance diabetic wound healing
Authors: Ishihara Jun , Ishihara Ako , Fukunaga Kazuto , Briquez Priscilla S. , Hubbell Jeffrey A. 
Published: February 2018

AbstractLaminin, as a key component of the basement membrane extracellular matrix (ECM), regulates tissue morphogenesis. We show that multiple laminin isoforms promiscuously bind to growth factors (GFs) with high affinity, through their heparin binding domains (HBDs) located in the a chain LG domains. Interestingly, these domains also bind to syndecan cell-surface receptors, promoting attachment of fibroblasts and endothelial cells. We next explore application of these multifunctional laminin HBDs in skin healing in the type 2 diabetic mouse. We demonstrate that covalent incorporation of laminin HBDs into fibrin matrix enables the slow-release of GFs. Incorporation of the α33043-3067 laminin HBD significantly enhances in vivo wound-healing efficacy of vascular endothelial cell growth factor (VEGF)-A165 and platelet-derived growth factor (PDGF)-BB, under conditions where the GFs alone in fibrin are inefficacious. This laminin HBD peptide may be clinically useful by improving biomaterials as both GF reservoirs and cell scaffolds, leading to effective tissue regeneration.
Temperature drives Zika virus transmission: evidence from empirical and mathematical models
Authors: Tesla Blanka , Demakovsky Leah R. , Mordecai Erin A. , Ryan Sadie J. , Bonds Matthew H. , Ngonghala Calistus N. , Brindley Melinda A. , Murdock Courtney C. 
Published: February 2018

AbstractTemperature is a strong driver of vector-borne disease transmission. Yet, for emerging arboviruses we lack fundamental knowledge on the relationship between transmission and temperature. Current models rely on the untested assumption that Zika virus responds similarly to dengue virus, potentially limiting our ability to accurately predict the spread of Zika. We conducted experiments to estimate the thermal performance of Zika virus (ZIKV) in field-derived Aedes aegypti across eight constant temperatures. We observed strong, unimodal effects of temperature on vector competence, extrinsic incubation period, and mosquito survival. We used thermal responses of these traits to update an existing temperature-dependent model to infer temperature effects on ZIKV transmission. ZIKV transmission was optimized at 29°C, and had a thermal range of 22.7°C - 34.7°C. Thus, as temperatures move toward the predicted thermal optimum (29°C) due to climate change, urbanization, or seasonally, Zika could expand north and into longer seasons. In contrast, areas that are near the thermal optimum were predicted to experience a decrease in overall environmental suitability. We also demonstrate that the predicted thermal minimum for Zika transmission is 5°C warmer than that of dengue, and current global estimates on the environmental suitability for Zika are greatly over-predicting its possible range.
Kaptive Web: user-friendly capsule and lipopolysaccharide serotype prediction forKlebsiellagenomes
Authors: Wick Ryan R , Heinz Eva , Holt Kathryn E , Wyres Kelly L 
Published: February 2018

AbstractAs whole genome sequencing becomes an established component of the microbiologist’s toolbox, it is imperative that researchers, clinical microbiologists and public health professionals have access to genomic analysis tools for rapid extraction of epidemiologically and clinically relevant information. For the gram-negative hospital pathogens such asKlebsiella pneumoniae, initial efforts have focused on detection and surveillance of antimicrobial resistance genes and clones. However, with the resurgence of interest in alternative infection control strategies targetingKlebsiellasurface polysaccharides, the ability to extract information about these antigens is increasingly important.Here we present Kaptive Web, an online tool for rapid typing ofKlebsiellaK and O loci, which encode the polysaccharide capsule and lipopolysaccharide O antigen, respectively. Kaptive Web enables users to upload and analyse genome assemblies in a web browser. Results can be downloaded in tabular format or explored in detail via the graphical interface, making it accessible for users at all levels of computational expertise.We demonstrate Kaptive Web’s utility by analysis of >500K. pneumoniaegenomes. We identify extensive K and O locus diversity among 201 genomes belonging to the carbapenemase- associated clonal group 258 (25 K and six O loci). Characterisation of a further 309 genomes indicates that such diversity is common among the multi-drug resistant clones and that these loci represent useful epidemiological markers for strain subtyping. These findings reinforce the need for rapid, reliable and accessible typing methods such as Kaptive Web.Kaptive Web is available for use at kaptive.holtlab.net and source code is available at github.com/kelwyres/Kaptive-Web.
Metabolic pairing of aerobic and anaerobic production in a one-pot batch cultivation
Authors: Salmela Milla , Lehtinen Tapio , Efimova Elena , Santala Suvi , Mangayil Rahul 
Published: February 2018

AbstractBackgroundThe versatility of microbial metabolic pathways enables their utilization in vast number of applications. However, the electron and carbon recovery rates, essentially constrained by limitations of cell energetics, are often too low in terms of process feasibility. Cocultivation of divergent microbial species in a single process broadens the metabolic landscape and thus, the possibilities for more complete carbon and energy utilization.ResultsIn this study, we integrated the metabolisms of two bacteria, an obligate anaerobeClostridium butyricumand an obligate aerobeAcinetobacter baylyiADP1. In the process, a glucose-negative mutant ofA. baylyiADP1 first deoxidized the culture allowingC. butyricumto grow and produce hydrogen from glucose. In the next phase, ADP1 produced long chain alkyl esters utilizing the by-products ofC. butyricum, namely acetate and butyrate.ConclusionsThe cocultivation of strictly anaerobic and aerobic bacteria allowed the production of both hydrogen gas and long-chain alkyl esters in a simple one-pot batch process. The study demonstrates the potential of ‘metabolic pairing’ using designed microbial consortia for optimal electron and carbon recovery.
Modulation of defence and iron homeostasis genes in rice roots by the diazotrophic endophyte: Herbaspirillum seropedicae
Authors: Brusamarello-Santos L. C. C , Alberton D. , Valdameri G. , Camilios-Neto D. , Covre R. , Lopes K. , Tadra-Sfeir M. Z. , Faoro H. , Monteiro R. A. , Silva A. B. , Broughton W. J. , Pedrosa F. O. , Wassem R. , Souza E. M. 
Published: February 2018

AbstractRice is staple food of nearly half the world’s population. Rice yields must therefore increase to feed ever larger populations. By colonising rice and other plants,Herbaspirillumspp. stimulate plant growth and productivity. However the molecular factors involved are largely unknown. To further explore this interaction, the transcription profiles of Nipponbare rice roots inoculated withHerbaspirillum seropedicaewere determined by RNA-seq. Mapping the 104 million reads against theOryza sativacv. Nipponbare genome produced 65 million unique mapped reads that represented 13,840 transcripts each with at least two-times coverage. About 7.4 % (1,019) genes were differentially regulated and of these 256 changed expression levels more than two times. Several of the modulated genes encoded proteins related to plant defence (e.g. a putative probenazole inducible protein), plant disease resistance as well as enzymes involved in flavonoid and isoprenoid synthesis. Genes related to the synthesis and efflux of phytosiderophores (PS) and transport of PS-iron complexes were also induced by the bacteria. These data suggest that the bacterium represses the rice defence system while concomitantly activating iron uptake. Transcripts ofH. seropedicaewere also detected amongst which genes involved in nitrogen fixation, cell motility and cell wall synthesis were the most expressed.HighlightsRNASeq ofH. seropedicaecolonised rice roots showed remarkable regulation of defence, metal transport, stress and signalling genes. Fe-uptake genes were highly induced with implications in plant nutrition and immunity.
Selective increases in inter-individual variability in response to environmental enrichment
Authors: Körholz Julia , Zocher Sara , Grzyb Anna N. , Morisse Benjamin , Poetzsch Alexandra , Ehret Fanny , Schmied Christopher , Kempermann Gerd 
Published: February 2018

AbstractOne manifestation of individualization is a progressively differential response of individuals to the non-shared components of the same environment. Individualization has practical implications in clinical setting, where subtle differences between patients are often decisive for the success of an intervention, yet there has been no suitable animal model to study its underlying biological mechanisms. Here we show that enriched environment (ENR) can serve as a model of brain individualization. We kept 40 isogenic mice for 3 months in ENR and compared the effects on a wide range of phenotypes on both mean and variance to an equally sized group of standard-housed control animals. While ENR influenced multiple parameters and restructured correlation patterns between them, it only increased differences among individuals in traits related to brain and behavior (adult hippocampal neurogenesis, motor cortex thickness, open field and object exploration, rotarod performance), in agreement with the hypothesis of a specific activity-dependent development of brain individuality.
Molecular Typing with COI - DNA Barcode of mosquitoes with medical importance from rural area of La Pintada, Antioquia, Colombia
Authors: Hoyos-López Richard 
Published: February 2018

SummaryDNA barcode is a methodology that allows the identification of species using a short fragment of cytochrome oxidase I and library sequences stored in the barcode of life database (bold>), make up an alternative tool for mosquito identification in areas epidemiologically active for arboviruses, protozoa and bacteria. In our study, we collected 114 adult mosquitoes in a rural area in the municipality of La Pintada (Antioquia, Colombia), and were separate for genus and species using morphological keys. Two Legs were taken of specimens mounted, and these were used for DNA extraction, amplification of COI-Barcode through PCR and sequencing. 38 sequences were characterized of seven mosquito species and used in bold> for molecular identification, subsequent characterization of genetic distances intra/interspecies, and MOTUs grouping by neighbor-joining analyses. Seven MOTUs were separate corresponding to seven species identify by morphological keys. bold> was able to identify five species, and two were identified to the genre. The following medically important mosquitoes were recorded in the rural area from La Pintada(Antioquia): Aedes aegypti, Anopheles triannulatus, Coquillettidia nigricans, Mansonia titillans, Ochlerotatus angustivitatus, Psorophora ferox and Psorophora (Grabhamia)sp.
Structure and mutagenic analysis of the lipid II flippase MurJ from Escherichia coli
Authors: Zheng Sanduo , Sham Lok-To , Rubino Frederick A. , Brock Kelly , Robins William P. , Mekelanos John J. , Marks Debora S. , Bernhardt Thomas G. , Kruse Andrew C. 
Published: February 2018

AbstractThe peptidoglycan cell wall provides an essential protective barrier in almost all bacteria, defining cellular morphology and conferring resistance to osmotic stress and other environmental hazards. The precursor to peptidoglycan, lipid II, is assembled on the inner leaflet of the plasma membrane. However, peptidoglycan polymerization occurs on the outer face of the plasma membrane, and lipid II must be flipped across the membrane by the MurJ protein prior to its use in peptidoglycan synthesis. Due to its central role in cell wall assembly, MurJ is of fundamental importance in microbial cell biology and is a prime target for novel antibiotic development. However, relatively little is known regarding the mechanisms of MurJ function, and structural data are only available for MurJ from the extremophile Thermosipho africanus. Here, we report the crystal structure of substrate-free MurJ from the Gram-negative model organism Escherichia coli, revealing an inward-open conformation. Taking advantage of the genetic tractability of E. coli, we performed high-throughput mutagenesis and next-generation sequencing to assess mutational tolerance at every amino acid in the protein, providing a detailed functional and structural map for the enzyme and identifying sites for inhibitor development. Finally, through the use of sequence co-evolution analysis we identify functionally important interactions in the outward-open state of the protein, supporting a rocker-switch model for lipid II transport.
Protein-ligand interfaces are polarized: Discovery of a strong trend for intermolecular hydrogen bonds to favor donors on the protein side with implications for predicting and designing ligand complexes
Authors: Raschka Sebastian , Wolf Alex J. , Bemister-Buffington Joseph , Kuhn Leslie A. 
Published: February 2018

AbstractUnderstanding how proteins encode ligand specificity is fascinating and similar in importance to deciphering the genetic code. For protein-ligand recognition, the combination of an almost infinite variety of interfacial shapes and patterns of chemical groups makes the problem especially challenging. Here we analyze data across non-homologous proteins in complex with small biological ligands to address observations made in our inhibitor discovery projects: that proteins favor donating H-bonds to ligands and avoid using groups with both H-bond donor and acceptor capacity. The resulting clear and significant chemical group matching preferences elucidate the code for protein-native ligand binding, similar to the dominant patterns found in nucleic acid base-pairing. On average, 90% of the keto and carboxylate oxygens occurring in the biological ligands formed direct H-bonds to the protein. A two-fold preference was found for protein atoms to act as H-bond donors and ligand atoms to act as acceptors, and 76% of all intermolecular H-bonds involved an amine donor. Together, the tight chemical and geometric constraints associated with satisfying donor groups generate a hydrogen-bonding lock that can be matched only by ligands bearing the right acceptor-rich key. Measuring an index of H-bond preference based on the observed chemical trends proved sufficient to predict other protein-ligand complexes and can be used to guide molecular design. The resulting Hbind and Protein Recognition Index software packages are being made available for rigorously defining intermolecular H-bonds and measuring the extent to which H-bonding patterns in a given complex match the preference key.Abbreviations3Dthree-dimensionalCATHClass Architecture Topology Homologous superfamilyH-bondshydrogen bondsMMFF94Merck Molecular Force FieldPDBProtein Data BankPRIProtein Recognition Index
A proteolytic complex targets multiple cell wall hydrolases inPseudomonas aeruginosa
Authors: Srivastava Disha , Seo Jin , Rimal Binayak , Kim Sung Joon , Darwin Andrew J. 
Published: February 2018

ABSTRACTCarboxy-terminal processing proteases (CTPs) occur in all three domains of life. In bacteria some of them have been associated with virulence. However, the precise roles of bacterial CTPs are poorly understood and few direct proteolytic substrates have been identified. One bacterial CTP is the CtpA protease ofPseudomonas aeruginosa, which is required for type III secretion system function, and for virulence in a mouse model of acute pneumonia. Here, we have investigated the function of CtpA inP. aeruginosaand identified some of the proteins it cleaves. We discovered that CtpA forms a complex with a previously uncharacterized protein, which we have named LbcA (lipoproteinbinding partner ofCtpA). LbcA is required for CtpA activityin vivoand promotes its activityin vitro. We have also identified four proteolytic substrates of CtpA, all of which are uncharacterized proteins predicted to cleave the peptide cross-links within peptidoglycan. Consistent with this, actpAnull mutant was found to have fewer peptidoglycan cross-links than the wild type and grew slowly in salt-free medium. Intriguingly, the accumulation of just one of the CtpA substrates was required for some ΔctpAmutant phenotypes, including the defective T3SS. We propose that LbcA•CtpA is a proteolytic complex in theP. aeruginosacell envelope, which controls the activity of several peptidoglycan cross-link hydrolases by degrading them. Furthermore, based on these and other findings we suggest that many bacterial CTPs might be similarly controlled by partner proteins as part of a widespread mechanism to control peptidoglycan hydrolase activity.IMPORTANCEBacterial carboxy-terminal processing proteases (CTPs) are widely conserved and have been associated with the virulence of several species. However, their roles are poorly understood and few direct substrates have been identified in any species.Pseudomonas aeruginosais an important human pathogen in which one CTP, known as CtpA, is required for type III secretion system function, and for virulence. This work provides an important advance by showing that CtpA works with a previously uncharacterized binding partner to degrade four substrates. These substrates are all predicted to hydrolyze peptidoglycan cross-links, suggesting that the CtpA complex is an important control mechanism for peptidoglycan hydrolysis. This is likely to emerge as a widespread mechanism used by diverse bacteria to control some of their peptidoglycan hydrolases. This is significant, given the links between CTPs and virulence in several pathogens, and the importance of peptidoglycan remodeling to almost all bacterial cells.
Behaviors of individual microtubules and microtubule populations relative to critical concentrations: Dynamic instability occurs when critical concentrations are driven apart by nucleotide hydrolysis
Authors: Jonasson Erin M. , Mauro Ava J. , Li Chunlei , Norby Ellen C. , Mahserejian Shant M. , Scripture Jared P. , Gregoretti Ivan V. , Alber Mark S. , Goodson Holly V. 
Published: February 2018

ABSTRACTThe concept of critical concentration (CC) is central to understanding behaviors of microtubules and other cytoskeletal polymers. Traditionally, these polymers are understood to have one CC, measured multiple ways and assumed to be the subunit concentration necessary for polymer assembly. However, this framework does not incorporate dynamic instability (DI), and there is work indicating that microtubules have two CCs. We use our previously established simulations to confirm that microtubules have (at least) two experimentally relevant CCs and to clarify the behaviors of individuals and populations relative to the CCs. At free subunit concentrations above the lower CC (CCIndGrow), growth phases of individual filaments can occurtransiently; above the higher CC (CCPopGrow), the population’s polymer mass will increasepersistently. Our results demonstrate that most experimental CC measurements correspond to CCPopGrow, meaning “typical” DI occurs below the concentration traditionally considered necessary for polymer assembly. We report that [free tubulin] at steady state does not equal CCPopGrow, but instead approaches CCPopGrowasymptotically as [total tubulin] increases and depends on the number of stable microtubule seeds. We show that the degree of separation between CCIndGrowand CCPopGrowdepends on the rate of nucleotide hydrolysis. This clarified framework helps explain and unify many experimental observations.
Phylogeny Recapitulates Learning: Self-Optimization of Genetic Code
Authors: Attie Oliver , Sulkow Brian , Di Chong , Qiu Wei-Gang 
Published: February 2018

AbstractLearning algorithms have been proposed as a non-selective mechanism capable of creating complex adaptive systems in life. Evolutionary learning however has not been demonstrated to be a plausible cause for the origin of a specific molecular system. Here we show that genetic codes as optimal as the Standard Genetic Code (SGC) emerge readily by following a molecular analog of the Hebb’s rule (“neurons fire together, wire together”). Specifically, error-minimizing genetic codes are obtained by maximizing the number of physio-chemically similar amino acids assigned to evolutionarily similar codons. Formulating genetic code as a Traveling Salesman Problem (TSP) with amino acids as “cities” and codons as “tour positions” and implemented with a Hopfield neural network, the unsupervised learning algorithm efficiently finds an abundance of genetic codes that are more error-minimizing than SGC. Drawing evidence from molecular phylogenies of contemporary tRNAs and aminoacyl-tRNA synthetases, we show that co-diversification between gene sequences and gene functions, which cumulatively captures functional differences with sequence differences and creates a genomic “memory” of the living environment, provides the biological basis for the Hebbian learning algorithm. Like the Hebb’s rule, the locally acting phylogenetic learning rule, which may simply be stated as increasing phylogenetic divergence for increasing functional difference, could lead to complex and robust life systems. Natural selection, while essential for maintaining gene function, is not necessary to act at system levels. For molecular systems that are self-organizing through phylogenetic learning, the TSP model and its Hopfield network solution offer a promising framework for simulating emerging behavior, forecasting evolutionary trajectories, and designing optimal synthetic systems.