bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rational design of hepatitis C virus E2 core nanoparticle vaccines
Authors: He Linling , Tzarum Netanel , Lin Xiaohe , Shapero Benjamin , Sou Cindy , Mann Colin J. , Stano Armando , Zhang Lei , Nagy Kenna , Giang Erick , Law Mansun , Wilson Ian A. , Zhu Jiang 
Published: July 2019

ABSTRACTHepatitis C virus (HCV) envelope glycoproteins E1 and E2 are critical for cell entry with E2 being the major target of neutralizing antibodies (NAbs). Here, we present a comprehensive strategy for B cell-based HCV vaccine development through E2 optimization and nanoparticle display. We redesigned variable region 2 in a truncated form (tVR2) on E2 cores derived from genotypes 1a and 6a, resulting in improved stability and antigenicity. Crystal structures of three optimized E2 cores with human cross-genotype NAbs (AR3s) revealed how the modified tVR2 stabilizes E2 without altering key neutralizing epitopes. We then displayed these E2 cores on 24- and 60-meric nanoparticles and achieved high yield, high purity, and enhanced antigenicity. In mice, these nanoparticles elicited more effective NAb responses than soluble E2 cores. Next-generation sequencing (NGS) defined distinct B-cell patterns associated with nanoparticle-induced antibody responses, which cross-neutralized HCV by targeting the conserved neutralizing epitopes on E2.One Sentence SummaryAn HCV vaccine strategy is presented that displays redesigned E2 cores on nanoparticles as vaccine candidates for eliciting a broadly neutralizing B-cell response.
Dormancy dampens the microbial distance-decay relationship
Authors: Locey KJ , Muscarella ME , Larsen ML , Bray SR , Jones SE , Lennon JT 
Published: July 2019

ABSTRACTMuch of Earth’s biodiversity has the capacity to engage in dormancy whereby individuals enter a reversible state of reduced metabolic activity. By increasing resilience to unfavorable conditions, dormancy leads to the accumulation of “seed banks” that should diminish the influence of environmental filtering, while allowing passive dispersers to colonize new habitats. Although prevalent among single-celled organisms, evidence that dormancy influences patterns of microbial biodiversity and biogeography is lacking. We constructed geographical and environmental distance-decay relationships (DDRs) using 16S rRNA sequencing to characterize the total (DNA) and the active (RNA) bacterial communities in a regional survey of 49 forested ponds. As expected, the total community harbored greater diversity and exhibited weaker DDRs than the active portion of the community. These empirical observations were robust to different measures of community similarity and random resampling tests. Furthermore, findings from the field survey were reproduced by models that included aspects of dormancy along with the geographical coordinates and environmental characteristics of our study system. In addition to maintaining local diversity, our results support recent theoretical predictions that dormancy shapes geographical patterns of biodiversity.
Termite mounds contain distinct methanotroph communities that are kinetically adapted to elevated methane concentrations
Authors: Chiri Eleonora , Greening Chris , Arndt Stefan K. , Nauer Philipp A. 
Published: July 2019

AbstractTermite mounds have recently been confirmed to mitigate approximately half of termite methane (CH4) emissions, but the aerobic methane-oxidizing bacteria (methanotrophs) responsible for this consumption have not been resolved. Here we describe the abundance, composition, and kinetics of the methanotroph communities in the mounds of three distinct termite species. We show that methanotrophs are rare members of the termite mound biosphere and have a comparable abundance, but distinct composition, to those of adjoining soil samples. Across all mounds, the most abundant and prevalent particulate methane monooxygenase sequences detected were affiliated with Upland Soil Cluster α (USCα), with sequences homologous toMethylocystisand Tropical Upland Soil Cluster also detected. The Michaelis-Menten kinetics of CH4oxidation in mounds were estimated fromin situreaction rates. The apparent CH4affinities of the communities were in the low micromolar range, which is one to two orders of magnitude higher than those of upland soils, but significantly lower than those measured in soils with a large CH4source such as landfill-cover soils. The rate constant of CH4oxidation, as well as the porosity of the mound material, were significantly positively correlated with the abundance of methanotroph communities of termite mounds. We conclude that termite-derived CH4emissions have selected for unique methanotroph communities that are kinetically adapted to elevated CH4concentrations. However, factors other than substrate concentration appear to limit methanotroph abundance and hence these bacteria only partially mitigate termite-derived CH4emissions. Our results also highlight the predominant role of USCα in an environment with elevated CH4concentrations and suggest a higher functional diversity within this group than previously recognised.
Role for Merlin/NF2 in transcription elongation through interaction with the PAF complex
Authors: Roehrig Anne E. , Klupsch Kristina , Oses-Prieto Juan A. , Chaib Selim , Henderson Stephen , Emmett Warren , Young Lucy C. , Surinova Silvia , Blees Andreas , Pfeiffer Anett , Tijani Maha , Brunk Fabian , Hartig Nicole , Muñoz-Alegre Marta , Hergovich Alexander , Jennings Barbara H. , Burlingame Alma L. , Rodriguez-Viciana Pablo 
Published: July 2019

SUMMARYThe PAF complex (PAFC) coordinates transcription elongation and mRNA processing events and its CDC73/parafibromin subunit functions as a tumour suppressor. The NF2/Merlin tumour suppressor functions at the cell cortex and nucleus and is a key mediator of contact inhibition. Here we provide a direct link between nuclear Merlin and transcription elongation controlled by cell-cell adhesion. Merlin interacts with the PAFC in a cell density-dependent manner and tumour-derived inactivating mutations in both Merlin and CDC73 mutually disrupt their interaction. Growth suppression by Merlin requires CDC73 and Merlin regulates PAFC association with chromatin in a subset of genes. We also identify by CDC73 affinity-proteomics a role for FAT cadherins in regulating the Merlin-PAFC interaction. Our results suggest that in addition to its function within the Hippo pathway, nuclear Merlin is part of a tumour suppressor network which coordinates postinitiation steps of the transcription cycle of genes mediating in contact inhibition.
Human footprint differentially impacts genetic connectivity of four wide-ranging mammals in a fragmented landscape
Authors: Thatte Prachi , Chandramouli Anuradha , Tyagi Abhinav , Patel Kaushal , Baro Phulmani , Chhattani Himanshu , Ramakrishnan Uma 
Published: July 2019

AbstractAimMaintaining connectivity is critical for long-term persistence of wild carnivores in landscapes fragmented due to anthropogenic activity. We examined spatial genetic structure and the impact of landscape features on connectivity in four wide-spread species- jungle cat (Felis chaus), leopard (Panthera pardus), sloth bear (Melursus ursinus) and tiger (Panthera tigris). Location Our study was carried out in the central Indian landscape, a stronghold in terms of distribution and abundance of large mammals. The landscape comprises fragmented forests embedded in a heterogeneous matrix of multiple land-use types.MethodsMicrosatellite data from non-invasively sampled individuals (90 jungle cats, 82 leopards, 104 sloth bears and 117 tigers) were used to investigate genetic differentiation. Impact of landscape features on gene flow was inferred using a multi-model landscape resistance optimization approach.ResultsAll four study species revealed significant isolation by distance (IBD). The correlation between genetic and geographic distance was significant only over a short distance for jungle cat, followed by longer distances for sloth bear, leopard and tiger. Overall, human footprint had a high negative impact on geneflow in tigers, followed by leopards, sloth bears and the least on jungle cats. Individual landscape variables- land-use, human population density, density of linear features and roads- impacted the study species differently. Although land-use was found to be an important variable explaining genetic connectivity for all four species, the amount of variation explained, the optimum spatial resolution and the resistance offered by different land-use classes varied.Main conclusionsAs expected from theory, but rarely demonstrated using empirical data, the pattern of spatial autocorrelation of genetic variation scaled with dispersal ability and density of the study species. Landscape genetic analyses revealed species-specific impact of landscape features and provided insights into interactions between species biology and landscape structure. Our results emphasize the need for incorporating functional connectivity data from multiple species for landscape-level conservation planning.
Interactions between social groups of colobus monkeys (Colobus vellerosus) explain similarities in their gut microbiomes
Authors: Wikberg Eva , Christie Diana , Sicotte Pascale , Ting Nelson 
Published: July 2019

AbstractThe gut microbiome is structured by social groups in a variety of host taxa. Whether this pattern is driven by relatedness, similar diets, or shared social environments is under debate because few studies have had access to the data necessary to disentangle these factors in wild populations. We investigated whether diet, relatedness, or the 1-meter proximity network best explains differences in the gut microbiome among 45 female colobus monkeys in 8 social groups residing at Boabeng-Fiema, Ghana. We combined demographic and behavioural data collected May-August 2007 and October 2008-April 2009 with 16S rRNA sequencing of faecal samples collected during the latter part of each observation period. Social group identity explained a large percentage of the variation in gut microbiome beta-diversity. When comparing the predictive power of dietary dissimilarity, relatedness, and connectedness in the 1-meter proximity network, the models with social connectedness received the strongest support, even in our analyses that excluded within-group dyads. This novel finding indicates that microbes may be transmitted during intergroup encounters, which could occur either indirectly via shared environments or directly via social contact. Lastly, some of the gut microbial taxa that appear to be transmitted via 1-meter proximity are associated with digestion of plant material, but further research is needed to investigate whether this type of gut microbe transmission yields health benefits, which could provide an incentive for the formation and maintenance of social bonds within and between social groups.
Nicotianamine synthase 2 is required for symbiotic nitrogen fixation inMedicago truncatulanodules
Authors: Escudero Viviana , Abreu Isidro , del Sastre Eric , Tejada-Jiménez Manuel , Larue Camile , Novoa-Aponte Lorena , Wen Jiangqi , Mysore Kirankumar S. , Abadía Javier , Argüello José M. , Castillo-Michel Hiram , Álvarez-Fernández Ana , Imperial Juan , González-Guerrero Manuel 
Published: July 2019

SUMMARYSymbiotic nitrogen fixation carried out by the interaction between legumes and diazotrophic bacteria known as rhizobia requires of relatively large levels of transition metals. These elements act as cofactors of many key enzymes involved in this process. Metallic micronutrients are obtained from soil by the roots and directed to sink organs by the vasculature, in a process participated by a number of metal transporters and small organic molecules that mediate metal delivery in the plant fluids. Among the later, nicotianamine is one of the most important. Synthesized by nicotianamine synthases (NAS), this non-proteinogenic amino acid forms metal complexes participating in intracellular metal homeostasis and long-distance metal trafficking. Here we characterized theNAS2gene from model legumeMedicago truncatula. MtNAS2 is located in the root vasculature and in all nodule tissues in the infection and fixation zones. Symbiotic nitrogen fixation requires ofMtNAS2function, as indicated by the loss of nitrogenase activity in the insertional mutantnas2-1, a phenotype reverted by reintroduction of a wild-type copy ofMtNAS2. This would be the result of the altered iron distribution innas2-1nodules, as indicated by X-ray fluorescence studies. Moreover, iron speciation is also affected in these nodules. These data suggest a role of nicotianamine in iron delivery for symbiotic nitrogen fixation.Significance StatementNicotianamine synthesis mediated by MtNAS2 is important for iron allocation for symbiotic nitrogen fixation by rhizobia inMedicago truncatularoot nodules.
Neural signatures of model-free learning when avoiding harm to self and other
Authors: Lockwood Patricia L. , Klein-Flügge Miriam , Abdurahman Ayat , Crockett Molly J. 
Published: July 2019

AbstractMoral behaviour requires learning how our actions help or harm others. Theoretical accounts of learning propose a key division between ‘model-free’ algorithms that efficiently cache outcome values in actions and ‘model-based’ algorithms that prospectively map actions to outcomes, a distinction that may be critical for moral learning. Here, we tested the engagement of these learning mechanisms and their neural basis as participants learned to avoid painful electric shocks for themselves and a stranger. We found that model-free learning was prioritized when avoiding harm to others compared to oneself. Model-free prediction errors for others relative to self were tracked in the thalamus/caudate at the time of the outcome. At the time of choice, a signature of model-free moral learning was associated with responses in subgenual anterior cingulate cortex (sgACC), and resisting this model-free influence was predicted by stronger connectivity between sgACC and dorsolateral prefrontal cortex. Finally, multiple behavioural and neural correlates of model-free moral learning varied with individual differences in moral judgment. Our findings suggest moral learning favours efficiency over flexibility and is underpinned by specific neural mechanisms.
Characterization of clostridium botulinum neurotoxin serotype A (BoNT/A) and fibroblast growth factor receptor interactions using a novel receptor dimerization assay
Authors: James Nicholas G. , Malik Shiazah , Sanstrum Bethany J. , Rheaume Catherine , Broide Ron S. , Jameson David M. , Brideau-Andersen Amy , Jacky Birgitte 
Published: July 2019

AbstractClostridium botulinum neurotoxin serotype A (BoNT/A) is a potent neurotoxin that also serves as an effective therapeutic for a variety of neuromuscular and glandular diseases and disorders. The observed pharmacological effect of BoNT/A is due to specific targeting and entry into motor nerve terminals within muscles followed by cleavage of the SNARE protein, SNAP-25, inducing a block in neurotransmission and temporary muscular paralysis. Specific binding and internalization of BoNT/A into neuronal cells are mediated by its binding domain (HC/A), which binds to GT1b ganglioside and protein cell surface receptors. Previously, fibroblast growth factor receptor 3 (FGFR3) was identified as a BoNT/A receptor, in addition to synaptic vesicle protein (SV2). To further study BoNT/A interactions with FGFRs, an FCS & TIRF receptor dimerization assay was developed to measure dimerization of FGFRs in live cells, as FGFR dimerization can be considered an indirect measure for receptor-ligand binding interaction and downstream signaling. The ability of HC/A to facilitate dimerization of three FGFR subtypes (FGFR1-3) was assessed. Recombinant HC/A (rHC/A) was shown to dimerize FGFR subtypes in the rank order FGFR3c > FGFR2b > FGFR1c. With potencies (EC50 values) defined as the concentration of ligand required to dimerize 50% of the receptors, wild type rHC/A dimerized FGFR3c with an EC50 of 24 nM, similar to FGF9, a native FGFR3c ligand, which had an EC50 of 15 nM, while FGFR1c and FGFR2b required higher rHC/A concentrations (≥100 nM and 68 nM, respectively). Furthermore, addition of the GT1b ganglioside to the culture media resulted in increased dimerization, whereas a ganglioside mutant variant of HC/A (rHC/A W1266L;Y1267S) showed decreased dimerization. Interestingly, reduced dimerization was also observed with an SV2 mutant variant of HC/A (rHC/A T1145A;T1146A). These results support a model wherein BoNT/A interacts with FGFRs, gangliosides, and SV2 on the cell surface to facilitate cell uptake.
Automated recognition of functional compound-protein relationships in literature
Authors: Döring Kersten , Qaseem Ammar , Telukunta Kiran K , Becer Michael , Thomas Philippe , Günther Stefan 
Published: July 2019

AbstractMotivationMuch effort has been invested in the identification of protein-protein interactions using text mining and machine learning methods. The extraction of functional relationships between chemical compounds and proteins from literature has received much less attention, and no ready-to-use open-source software is so far available for this task.MethodWe created a new benchmark dataset of 2,753 sentences from abstracts containing annotations of proteins, small molecules, and their relationships. Two kernel methods were applied to classify these relationships as functional or non-functional, named shallow linguistic and all-paths graph kernel. Furthermore, the benefit of interaction verbs in sentences was evaluated.ResultsThe cross-validation of the all-paths graph kernel (AUC value: 84.2%, F1 score: 81.8%) shows slightly better results than the shallow linguistic kernel (AUC value: 81.6%, F1 score: 79.7%) on our benchmark dataset. Both models achieve state-of-the-art performance in the research area of relation extraction. Furthermore, the combination of shallow linguistic and all-paths graph kernel could further increase the overall performance. We used each of the two kernels to identify functional relationships in all PubMed abstracts (28 million) and provide the results, including recorded processing time.AvailabilityThe software for the tested kernels, the benchmark, the processed 28 million PubMed abstracts, all evaluation scripts, as well as the scripts for processing the complete PubMed database are freely available at https://github.com/KerstenDoering/CPI-Pipeline.Author summaryText mining aims at organizing large sets of unstructured text data to provide efficient information extraction. Particularly in the area of drug discovery, the knowledge about small molecules and their interactions with proteins is of crucial importance to understand the drug effects on cells, tissues, and organisms. This data is normally hidden in written articles, which are published in journals with a focus on life sciences. In this publication, we show how text mining methods can be used to extract data about functional interactions between small molecules and proteins from texts. We created a new dataset with annotated sentences of scientific abstracts for the purpose of training two diverse machine learning methods (kernels), and successfully classified compound-protein pairs as functional and non-functional relations, i.e. no interactions. Our newly developed benchmark dataset and the pipeline for information extraction are freely available for download. Furthermore, we show that the software can be easily up-scaled to process large datasets by applying the approach to 28 million abstracts.
Myco- and photobiont associations in crustose lichens in the McMurdo Dry Valleys (Antarctica) reveal high differentiation along an elevational gradient
Authors: Wagner Monika , Bathke Arne C. , Cary Craig , Junker Robert R. , Trutschnig Wolfgang , Ruprecht Ulrike 
Published: July 2019

AbstractThe climate conditions of the McMurdo Dry Valleys (78° S) are characterized by low temperatures and low precipitation. The annual temperatures at the valley bottoms have a mean range from −30 °C to −15 °C and decrease with elevation. Precipitation occurs mostly in form of snow (3-50 mm a−1water equivalent) and, liquid water is rare across much of the landscape for most of the year and represents the primary limitation to biological activity. Snow delivered off the polar plateau by drainage winds, dew and humidity provided by clouds and fog are important water sources for rock inhibiting crustose lichens. In addition, the combination of the extremely low humidity and drying caused by foehn winds, confined to lower areas of the valleys, with colder and moister air at higher altitudes creates a strongly improving water availability gradient with elevation.We investigated the diversity and interaction specificity of myco-/photobiont associations of a total of 232 crustose lichen specimens, collected along an elevational gradient (171-959 m a.s.l.) within the McMurdo Dry Valleys with regard to the spatial distribution caused by climatological and geographical factors. For the identification of the mycobiont and photobiont species three markers each were amplified (nrITS, mtSSU, RPB1 and nrITS, psbJ-L, COX2, respectivley). Elevation, associated with a water availability gradient, turned out to be the key factor explaining most of the distribution patterns of the mycobionts. Pairwise comparisons showedLecidea cancriformisandRhizoplaca macleaniito be significantly more common at higher, andCarbonea vorticosaandLecidea polypycnidophoraat lower, elevations. Lichen photobionts were dominated by the globally distributedTrebouxiaOTU,Tr_A02 which occurred at all habitats. Network specialization resulting from mycobiont-photobiont bipartite network structure varied with elevation and associated abiotic factors.Along an elevational gradient, the spatial distribution, diversity and genetic variability of the lichen symbionts appear to be mainly influenced by improved water relations at higher altitudes.
A dynamic regression panel approach to the determinants of monetary policy and economic growth
Authors: Olamide Ebenezer Gbenga , Maredza Andrew 
Published: July 2019

PurposeEmpirically, the purpose of this paper is to investigate policy variables that determine monetary policy and economic growth of some selected countries within the economic bloc of Southern Africa Development Community (SADC). The selected countries are Botswana, Democratic Republic of Congo, Lesotho, Madagascar, Malawi, Mozambique, Namibia, South Africa, Swaziland, Zambia and Zimbabwe.Design/methodology/approachAnnual time series data for a panel of 11 Southern African countries spanning 1980–2015 were employed in the study. The major instrument of estimation is the dynamic regression panel model. In order to conform to econometric principles, robustness checks were carried out on the variables of interest so as to avoid spurious results. An estimation of impulse response and variance decomposition analyses were to complement the approach to the study.FindingsThe result of the long-run dynamic panel regression reveals that GDP growth rate, inflation rate, exchange rate, money supply and oil and commodity prices do have profound impact on monetary policy within SADC. It was further revealed from the study that commodity price shock is the major exogenous determinant of monetary policy dynamics and the effect is transmitted via exchange rate channel to macroeconomics of the region; with inflation rate and money supply playing a major role in the transmission mechanism as it affects the economies of the countries in this region.Practical implicationsThe policy implication is that inflation is seen as a major challenge to the countries under review. Among other things, a hybrid of inflation and monetary targeting should be adopted to complement each other as policy combination within the region.Originality/valueThe study accounts for the determinants of monetary policyvis-à-visgrowth potentials of some selected countries in SADC, using a combination of dynamic regression panel approach and SVAR elements.