bluuebunny/crossref_metadata_2025 huggingface dataset:
Interacting stressors matter: diet quality and virus infection in honeybee health
Authors: Dolezal Adam G. , Carrillo-Tripp Jimena , Judd Timothy M. , Allen Miller W. , Bonning Bryony C. , Toth Amy L.
Published: February 2019

Honeybee population declines have been linked to multiple stressors, including reduced diet diversity and increased exposure to understudied viral pathogens. Despite interest in these factors, few experimental studies have explored the interaction between diet diversity and viral infection in honeybees. Here, we used a mixture of laboratory cage and small semi-field nucleus hive experiments to determine how these factors interact. In laboratory experiments, we found that high-quality diets (polyfloral pollen and high-quality single-source pollen) have the potential to reduce mortality in the face of infection with Israeli acute paralysis virus (IAPV). There was a significant interaction between diet and virus infection on mortality, even in the presence of high virus titres, suggesting that good diets can help bees tolerate virus infection. Further, we found that extreme stress in the form of pollen starvation in conjunction with IAPV infection increase exiting behaviour from small experimental hives. Finally, we showed that higher-quality pollen diets have significantly higher iron and calcium content, suggesting micronutrient deficiencies could be an under-explored area of bee nutrition.
Theoretical study of the molecular aspect of the suspected novichok agent A234 of the Skripal poisoning
Authors: Bhakhoa Hanusha , Rhyman Lydia , Ramasami Ponnadurai
Published: February 2019

Novichoks are the suspected nerve agents in the March 2018 Skripal poisoning. In this context, the novichok agent A234 (chemical structure proposed by Mirzayanov) was studied using computational methods to shed light on its molecular, electronic, spectroscopic, thermodynamic and toxicity parameters as well as on potential thermal and hydrolysis degradation pathways. The poisoning action and antidote of A234 were also investigated. Some of these parameters were compared to three common G- and V-series nerve agents, namely GB, VR and VX. The research findings should be useful towards the detection, development of antidotes and destruction of A234.
Molecular characterization of aldehydes and ketones in particle phase of mainstream and sidestream cigarette smoke
Authors: Chen Xiu , Shi Quan , Zhou Xibin , Liu Xuezheng
Published: February 2019

Aldehydes and ketones (AKs) in cigarette smoke are risk to humans and environment. Due to the complexity of itself and the interference of the smoke tar matrix, the aldehydes and ketones in particle phase (AKPs) of mainstream smoke (MSS) and sidestream smoke (SSS) have not been well investigated. In this study, the AKPs of MSS and SSS were derivatized into polar products by reaction with Girard T reagent. The derivatives were isolated rapidly by column chromatography and analysed by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Fifteen species of aldehydes and ketones were detected by positive ion electrospray ionization (ESI) FT-ICR MS: O
1–6
, N
1
O
1–4
, N
2
O
1–3
and N
3
O
2–3
. The total number of AKPs obtained by ESI FT-ICR MS in MSS and SSS is about 1100 and 970, respectively. After hydrolysis, the original AKPs were obtained and 63 carbonyls were identified and quantified by gas chromatography–mass spectrometry (GCMS). The nitrogen-containing and high-oxygen AKPs were further characterized by Orbitrap mass spectrometry. Structures of compounds with high relative abundance in the mass spectrum were speculated (e.g. a series of degradants of cembrenediol) by comparison with the results of GCMS.
Discovery of common chemical exposures across three continents using silicone wristbands
Authors: Dixon Holly M. , Armstrong Georgina , Barton Michael , Bergmann Alan J. , Bondy Melissa , Halbleib Mary L. , Hamilton Winifred , Haynes Erin , Herbstman Julie , Hoffman Peter , Jepson Paul , Kile Molly L. , Kincl Laurel , Laurienti Paul J. , North Paula , Paulik L. Blair , Petrosino Joe , Points Gary L. , Poutasse Carolyn M. , Rohlman Diana , Scott Richard P. , Smith Brian , Tidwell Lane G. , Walker Cheryl , Waters Katrina M. , Anderson Kim A.
Published: February 2019

To assess differences and trends in personal chemical exposure, volunteers from 14 communities in Africa (Senegal, South Africa), North America (United States (U.S.)) and South America (Peru) wore 262 silicone wristbands. We analysed wristband extracts for 1530 unique chemicals, resulting in 400 860 chemical data points. The number of chemical detections ranged from 4 to 43 per wristband, with 191 different chemicals detected, and 1339 chemicals were not detected in any wristband. No two wristbands had identical chemical detections. We detected 13 potential endocrine disrupting chemicals in over 50% of all wristbands and found 36 chemicals in common between chemicals detected in three geographical wristband groups (Africa, North America and South America). U.S. children (less than or equal to 11 years) had the highest percentage of flame retardant detections compared with all other participants. Wristbands worn in Texas post-Hurricane Harvey had the highest mean number of chemical detections (28) compared with other study locations (10–25). Consumer product-related chemicals and phthalates were a high percentage of chemical detections across all study locations (36–53% and 18–42%, respectively). Chemical exposures varied among individuals; however, many individuals were exposed to similar chemical mixtures. Our exploratory investigation uncovered personal chemical exposure trends that can help prioritize certain mixtures and chemical classes for future studies.
Structure and catalytic behaviour of CuO–CeO
2
prepared by high-energy ball milling
Authors: The Luong Nguyen , Okumura Hideyuki , Yamasue Eiji , Ishihara Keiichi N.
Published: February 2019

The aim of this study is to prepare CuO–CeO
2
composite by means of mechanical milling and to investigate its characteristics as a catalyst. The structural and morphological features of milled samples are observed by X-ray diffractometry and scanning electron microscopy. The redox property and total OSC (oxygen storage capacity) of the milled sample were measured by using GC-TCD and TG-DTA, which are important parameters to indicate the effectiveness of catalysts. Interestingly, reduction of CuO is repeatedly observed when milling of CuO–CeO
2
powder mixture is processed in air. The redox property of milled CuO–CeO
2
sample is investigated by H
2
-TPR, where three reduction peaks are observed for 0 h milling and only one broad peak for various other milling times. The total OSC of mechanically driven CuO–CeO
2
catalyst is much higher than that of the CeO
2
–ZrO
2
traditional catalyst system at low temperatures.
Effect of lignin structure on adsorbable organic halogens formation in chlorine dioxide bleaching
Authors: Shi Lisheng , Ge Jiayan , Nie Shuangxi , Qin Chengrong , Yao Shuangquan
Published: February 2019

Adsorbable organic halogens (AOX) are formed in pulp bleaching as a result of the reaction of residual lignin with chlorine dioxide. The natural structure of lignin is very complex and it tends to be damaged by various extraction methods. All the factors can affect the study about the mechanism of AOX formation in the reaction of lignin with chlorine dioxide. Lignin model compounds, with certain structures, can be used to study the role of different lignin structures on AOX formation. The effect of lignin structure on AOX formation was determined by reacting phenolic and non-phenolic lignin model compound with a chlorine dioxide solution. Vanillyl alcohol (VA) and veratryl alcohol (VE) were selected for the phenolic and non-phenolic lignin model compound, respectively. The pattern consumption of lignin model compounds suggests that both VA and VE began reacting with chlorine dioxide within 10 min and then gradually steadied. The volume of AOX produced by VE was significantly higher than that produced by VA for a given initial lignin model compound concentration. In a solution containing a combination of VA and VE in chlorine dioxide, VE was the dominant producer of AOX. This result indicates that the non-phenolic lignin structure was more easily chlorinated, while the phenolic lignin structure was mainly oxidized. In addition, AOX content produced in the combined experiments exceeded the total content of the two separate experiments. It suggested that the combination of phenolic and non-phenolic lignin structure can promote AOX formation.
High-order asymptotics for the spin-weighted spheroidal equation at large real frequency
Authors: Casals Marc , Ottewill Adrian C. , Warburton Niels
Published: February 2019

The spin-weighted spheroidal eigenvalues and eigenfunctions arise in the separation by variables of spin-field perturbations of Kerr black holes. We derive a large, real-frequency asymptotic expansion of the spin-weighted spheroidal eigenvalues and eigenfunctions to high order. This expansion corrects and extends existing results in the literature and we validate it via a high-precision numerical calculation.
Future climate change is predicted to affect the microbiome and condition of habitat-forming kelp
Authors: Qiu Zhiguang , Coleman Melinda A. , Provost Euan , Campbell Alexandra H. , Kelaher Brendan P. , Dalton Steven J. , Thomas Torsten , Steinberg Peter D. , Marzinelli Ezequiel M.
Published: February 2019

Climate change is driving global declines of marine habitat-forming species through physiological effects and through changes to ecological interactions, with projected trajectories for ocean warming and acidification likely to exacerbate such impacts in coming decades. Interactions between habitat-formers and their microbiomes are fundamental for host functioning and resilience, but how such relationships will change in future conditions is largely unknown. We investigated independent and interactive effects of warming and acidification on a large brown seaweed, the kelp
Ecklonia radiata
, and its associated microbiome in experimental mesocosms. Microbial communities were affected by warming and, during the first week, by acidification. During the second week, kelp developed disease-like symptoms previously observed in the field. The tissue of some kelp blistered, bleached and eventually degraded, particularly under the acidification treatments, affecting photosynthetic efficiency. Microbial communities differed between blistered and healthy kelp for all treatments, except for those under future conditions of warming and acidification, which after two weeks resembled assemblages associated with healthy hosts. This indicates that changes in the microbiome were not easily predictable as the severity of future climate scenarios increased. Future ocean conditions can change kelp microbiomes and may lead to host disease, with potentially cascading impacts on associated ecosystems.
Maternal longevity and offspring sex in wild ungulates
Authors: Douhard Mathieu , Festa-Bianchet Marco , Hamel Sandra , Nussey Daniel H. , Côté Steeve D. , Pemberton Josephine M. , Pelletier Fanie
Published: February 2019

In species with sexual size dimorphism, the offspring of the larger sex usually have greater energy requirements and may lead to greater fitness costs for parents. The effects of offspring sex on maternal longevity, however, have only been tested in humans. Human studies produced mixed results and considerable debate mainly owing to the difficulty of distinguishing the effects of sexual dimorphism from sociocultural factors. To advance this debate, we examined how the relative number of sons influenced maternal longevity in four species of free-living ungulates (Soay sheep
Ovis aries
; bighorn sheep,
Ovis canadensis
; red deer,
Cervus elaphus
; mountain goat,
Oreamnos americanus
), with high male-biased sexual size dimorphism but without complicating sociocultural variables. We found no evidence for a higher cumulative cost of sons than of daughters on maternal longevity. For a given number of offspring, most females with many sons in all four populations lived longer than females with few sons. The higher cost of sons over daughters on maternal lifespan reported by some human studies may be the exception rather than the rule in long-lived iteroparous species.
Phylogenetic investigation of skin sloughing rates in frogs: relationships with skin characteristics and disease-driven declines
Authors: Ohmer Michel E. B. , Cramp Rebecca L. , White Craig R. , Harlow Peter S. , McFadden Michael S. , Merino-Viteri Andrés , Pessier Allan P. , Wu Nicholas C. , Bishop Phillip J. , Franklin Craig E.
Published: February 2019

Amphibian skin is highly variable in structure and function across anurans, and plays an important role in physiological homeostasis and immune defence. For example, skin sloughing has been shown to reduce pathogen loads on the skin, such as the lethal fungusBatrachochytrium dendrobatidis(Bd), but interspecific variation in sloughing frequency is largely unknown. Using phylogenetic linear mixed models, we assessed the relationship between skin turnover rate, skin morphology, ecological traits and overall evidence ofBd-driven declines. We examined skin sloughing rates in 21 frog species from three continents, as well as structural skin characteristics measured from preserved specimens. We found that sloughing rate varies significantly with phylogenetic group, but was not associated with evidence ofBd-driven declines, or other skin characteristics examined. This is the first comparison of sloughing rate across a wide range of amphibian species, and creates the first database of amphibian sloughing behaviour. Given the strong phylogenetic signal observed in sloughing rate, approximate sloughing rates of related species may be predicted based on phylogenetic position. While not related to available evidence of declines, understanding variation in sloughing rate may help explain differences in the severity of infection in genera with relatively slow skin turnover rates (e.g.Atelopus).
Adaptation to drought is coupled with slow growth in marginal silver fir (Abies albaMill.) populations
Authors: Csilléry Katalin , Buchmann Nina , Fady Bruno
Published: February 2019

Drought is increasingly considered as the most important selection pressure for forest trees in the context of climate change. We studied adaptation to drought in marginal populations of silver fir (Abies albaMill.) from the French Mediterranean Alps. Drought tolerance was assessed using proxies both from seedlings and adult trees. We measured water stress response, growth and bud break of seedlings originating from 16 populations in a greenhouse common garden experiment (N=8199) and water use efficiency viaδ13Cof adult trees of the source populationsin-situ(N=315). Further, 357 single nucleotide polymorphisms (SNPs) were used to uncover the demographic history of the populations. Demographic distances between populations were used to generate a null expectation for trait divergence, thereby detect the signature of natural selection. We found evidence for adaptive population divergence in drought tolerance across life stages. Seedlings originating from source populations with low soil water capacity resisted better to water stress in the greenhouse, and additionally, adult trees from these populations had a higher water use efficiency. Seedling growth showed an evolutionary trade-off with drought tolerance: seedlings with fast growth and high stature came from populations that had lower drought tolerance. In contrast, population divergence in bud break showed only a weak signal of adaptation, which was independent of that in drought tolerance. Variation in phenology between populations was associated with variance in temperature and drought frequency and severity at the source populations. Our results highlight the adaptive value of marginal populations, advance our understanding of the different processes that have allowed silver fir to cope with drought stress under a warming climate, and contribute to our knowledge to advise assisted migration programs.
Chemosymbiotic bivalves contribute to the nitrogen budget of seagrass ecosystems
Authors: Cardini Ulisse , Bartoli Marco , Lee Raymond , Lücker Sebastian , Mooshammer Maria , Polzin Julia , Weber Miriam , Petersen Jillian M.
Published: February 2019

In many seagrass sediments, lucinid bivalves and their sulfur-oxidizing symbionts are thought to underpin key ecosystem functions, but little is known about their role in nutrient cycles, particularly nitrogen. We used natural stable isotopes, elemental analyses, and stable isotope probing to study the ecological stoichiometry of a lucinid symbiosis in spring and fall. Chemoautotrophy appeared to dominate in fall, when chemoautotrophic carbon fixation rates were up to one order of magnitude higher as compared to the spring, suggesting a flexible nutritional mutualism. In fall, an isotope pool dilution experiment revealed carbon limitation of the symbiosis and ammonium excretion rates up to 10-fold higher compared to fluxes reported for non-symbiotic marine bivalves. These results provide evidence that lucinid bivalves can contribute substantial amounts of ammonium to the ecosystem. Given the preference of seagrasses for this nitrogen source, lucinid bivalves’ contribution may boost productivity of these important blue carbon ecosystems.
Deep protein methylation profiling by combined chemical and immunoaffinity approaches reveals novel PRMT1 targets
Authors: Hartel Nicolas G. , Chew Brandon , Qin Jian , Xu Jian , Graham Nicholas A.
Published: February 2019

Protein methylation has been implicated in many important biological contexts including signaling, metabolism, and transcriptional control. Despite the importance of this post-translational modification, the global analysis of protein methylation by mass spectrometry-based proteomics has not been extensively studied due to the lack of robust, well-characterized techniques for methyl peptide enrichment. Here, to better investigate protein methylation, we optimized and compared two methods for methyl peptide enrichment: immunoaffinity purification (IAP) and high pH strong cation exchange (SCX). Comparison of these methods revealed that they are largely orthogonal for monomethyl arginine (MMA), suggesting that the usage of both techniques is required to provide a global view of protein methylation. Using both IAP and SCX, we investigated changes in protein methylation downstream of protein arginine methyltransferase 1 (PRMT1) and quantified ∼1,000 methylation sites on 407 proteins. Of these methylation sites, PRMT1 knockdown resulted in significant changes to 97 arginine methylation sites on 59 proteins. In contrast, zero lysine methylation sites were significantly changed upon PRMT1 knockdown. In PRMT1 knockdown cells, 84 MMA sites were either significantly downregulated or upregulated. PRMT1 knockdown also induced significant changes in both asymmetric dimethyl arginine (ADMA) and symmetric dimethyl arginine (SDMA), suggesting that loss of PRMT1 activity allows scavenging of PRMT1 substrates by other PRMTs. Using neutral loss fragmentation ions unique to ADMA and SDMA, we annotated dimethylarginines as either ADMA or SDMA. Through integrative analysis of methyl forms, we identified 12 high confidence PRMT1 substrates, 43 putative PRMT1 substrates, and 17 methylation sites that are scavenged by other non-PRMT1 arginine methyltransferases in the absence of PRMT1 activity. Taken together, our results suggest that deep protein methylation profiling by mass spectrometry requires orthogonal enrichment techniques to identify novel PRMT1 methylation targets and highlight the dynamic interplay between methyltransferases in mammalian cells.
The length of the expressed 3’ UTR is an intermediate molecular phenotype linking genetic variants to complex diseases
Authors: Mariella Elisa , Marotta Federico , Grassi Elena , Gilotto Stefano , Provero Paolo
Published: February 2019

In the last decades, genome wide association studies (GWAS) have uncovered tens of thousands of associations between common genetic variants and complex diseases. However, these statistical associations can rarely be interpreted functionally and mechanistically. As the majority of the disease-associated variants are located far from coding sequences, even the relevant gene is often unclear. A way to gain insight into the relevant mechanisms is to study the genetic determinants of intermediate molecular phenotypes, such as gene expression and transcript structure. We propose a computational strategy to discover genetic variants affecting the relative expression of alternative 3’ untranslated region (UTR) isoforms, generated through alternative polyadenylation, a widespread post-transcriptional regulatory mechanism known to have relevant functional consequences. When applied to a large dataset in which whole genome and RNA sequencing data are available for 373 European individuals, 2,530 genes with alternative polyadenylation quantitative trait loci (apaQTL) were identified. We analyze and discuss possible mechanisms of action of these variants, and we show that they are significantly enriched in GWAS hits, in particular those concerning immune-related and neurological disorders. Our results point to an important role for genetically determined alternative polyadenylation in affecting predisposition to complex diseases, and suggest new ways to extract functional information from GWAS data.
Large scale automated phylogenomical analysis of bacterial whole-genome isolates and the Evergreen platform
Authors: Szarvas Judit , Ahrenfeldt Johanne , Bellod Cisneros Jose Luis , Frølund Thomsen Martin Christen , Aarestrup Frank M. , Lund Ole
Published: February 2019

Public health authorities whole-genome sequence thousands of pathogenic isolates each month for microbial diagnostics and surveillance of pathogenic bacteria. The computational methods have not kept up with the deluge of data and need for real-time results.

We have therefore created a bioinformatics pipeline for rapid subtyping and continuous phylogenomic analysis of bacterial samples, suited for large-scale surveillance. To decrease the computational burden, a two level clustering strategy is employed. The data is first divided into sets by matching each isolate to a closely related reference genome. The reads then are aligned to the reference to gain a consensus sequence and SNP based genetic distance is calculated between the sequences in each set. Isolates are clustered together with a threshold of 10 SNPs. Finally, phylogenetic trees are inferred from the non-redundant sequences and the clustered isolates are placed on a clade with the cluster representative sequence. The method was benchmarked and found to be accurate in grouping outbreak strains together, while discriminating from non-outbreak strains.

The pipeline was applied in Evergreen Online, which processes publicly available sequencing data from foodborne bacterial pathogens on a daily basis, updating the phylogenetic trees as needed. It has so far placed more than 100,000 isolates into phylogenies, and has been able to keep up with the daily release of data. The trees are continuously published on https://cge.cbs.dtu.dk/services/Evergreen
Link Your Sites (LYS) Scripts: Automated search of protein structures and mapping of sites under positive selection detected by PAML
Authors: Moreta Lys Sanz , da Fonseca Rute R.
Published: February 2019

The visualization of the molecular context of an amino acid mutation in a protein structure is crucial for the assessment of its functional impact and to understand its evolutionary implications. Currently, searches for fast evolving amino acid positions using codon substitution models like those implemented in PAML [1] are done in almost complete proteomes, generating large numbers of candidate proteins that require individual structural analyses. Here we present two python wrapper scripts as the package Link Your Sites (LYS). The first one i) mines the RCSB database [10] using the blast alignment tool to find the best matching homologous sequences, ii) fetches their domain positions by using Prosites [3,8,9], iii) parses the output of PAML extracting the positional information of fast-evolving sites and transform them into the coordinate system of the protein structure, iv) outputs a file per gene with the positions correlations to its homologous sequence. The second script uses the output of the first one to generate the protein’s graphical assessment. LYS can therefore generate figures to be used in publication highlighting the positively selected sites mapped on regions that are known to have functional relevance and/or be used to reduce the number of targets that will be further analyzed by providing a list of those for which structural information can be retrieved.

Motivation

Automatizing the search for protein structures to assess the functional impact of sites found to be under positive selection by codeml, implemented in PAML [1]. Building publication-quality figures highlighting the sites on a protein structure model that are within and outside functional domains. reduces the workload associated with selecting proteins for which a functional assessment of the impact of mutations can be done using a protein structure. This is especially relevant when analyzing almost complete proteomes which is the case of large comparative genomic studies.

Software

LYS scripts are executed in the command line. They automatically search for homologous proteins at the RSCB database [10], determine the functional domain locations and correlate the positions pointed by the M8 model [1], and output a data frame that can be used as the input by PyMOL [7] to generate a visualization of the results.

Availability

LYS is easy to install and implement and they are available at https://github.com/LysSanzMoreta/LYSAutomaticSearch
Cranial anatomy of the predatory actinopterygianBrazilichthys macrognathusfrom the Permian (Cisuralian) Pedra de Fogo Formation, Parnaíba Basin, Brazil
Authors: Figueroa Rodrigo T. , Friedman Matt , Gallo Valéria
Published: February 2019

Brazilichthys macrognathusis the only named actinopterygian from the Permain (Cisuralian) Pedra de Fogo Formation of northeastern Brazil, where it is represented by a single three-dimensionally preserved but incompletely described skull of unclear systematic placement. We used X-ray computed microtomography (μ-CT) to better document its anatomy and phylogenetic affinities. μ-CT reveals parts of the internal skeleton. We correct errors in original description, including the number of infraorbital bones and the misidentification of the dermosphenotic as sclerotic ossifications. These reinterpretations of external anatomy are joined by new data on internal structure, including the palate, parasphenoid, and branchial and hyoid arches. A maximum parsimony analysis of anatomical data resolvesBrazilichthysas a stem actinopterygian, crownward of all Devonian species. This placement is supported by the absence of a dermosphenotic posterior ramus and the presence of opercular process of the hyomandibula. A similar placement is suggested by a Bayesian analysis of this same dataset, although relationships throughout the tree are less resolved. Our results reject previous interpretations ofBrazilichthysas a relative of Birgeriidae, a Triassic group consistently placed within the actinopterygian crown. AlthoughAcrolepisis too poorly known to be included in our analysis, we also reject a close relationship between this taxon andBrazilichthys, as their only shared similarities appear to be broadly distributed among early actinopterygians.
Sex biased expression and co-expression networks in development, using the hymenopteran Nasonia vitripennis
Authors: Rago Alfredo , Werren John (Jack) H , Colbourne John K
Published: February 2019

Sexual dimorphism requires gene expression regulation in developing organisms. Differential expression, alternative splicing and transcript-transcript interactions all contribute to developmental differences between the sexes. However, few studies have described how these processes change across developmental stages, or how they interact to form co-expression networks. We compare the dynamics of all three regulatory processes in the sexual development of the model parasitoid wasp Nasonia vitripennis, a system that permits genome wide analysis of sex bias from early embryos to adults. We find relatively little sex-bias in embryos and larvae at the whole-gene level, but several sub-networks show sex-biased transcript-transcript interactions in early developmental stages. These provide new candidates for hymenopteran sex determination, including histone modification genes. In contrast, sex-bias in pupae and adults is driven by whole-gene differential expression. We observe sex-biased splicing consistently across development, but mostly in genes that are already biased at the whole-gene level. Finally, we discover that sex-biased networks are enriched by genes specific to the Nasonia clade, and that those genes possess the topological properties of key regulators. These findings suggest that regulators in sex-biased networks evolve more rapidly than regulators of other developmental networks.
Sulfur-oxidizing symbionts without canonical genes for autotrophic CO2fixation
Authors: Seah Brandon K. B. , Antony Chakkiath Paul , Huettel Bruno , Zarzycki Jan , Borzyskowski Lennart Schada von , Erb Tobias J. , Kouris Angela , Kleiner Manuel , Liebeke Manuel , Dubilier Nicole , Gruber-Vodicka Harald R.
Published: February 2019

Since the discovery of symbioses between sulfur-oxidizing (thiotrophic) bacteria and invertebrates at hydrothermal vents over 40 years ago, it has been assumed that autotrophic fixation of CO2by the symbionts drives these nutritional associations. In this study, we investigatedCandidatusKentron, the clade of symbionts hosted byKentrophoros, a diverse genus of ciliates which are found in marine coastal sediments around the world. Despite being the main food source for their hosts, Kentron lack the key canonical genes for any of the known pathways for autotrophic fixation, and have a carbon stable isotope fingerprint unlike other thiotrophic symbionts from similar habitats. Our genomic and transcriptomic analyses instead found metabolic features consistent with growth on organic carbon, especially organic and amino acids, for which they have abundant uptake transporters. All known thiotrophic symbionts have converged on using reduced sulfur to generate energy lithotrophically, but they are diverse in their carbon sources. Some clades are obligate autotrophs, while many are mixotrophs that can supplement autotrophic carbon fixation with heterotrophic capabilities similar to those in Kentron. We have shown that Kentron are the only thiotrophic symbionts that appear to be entirely heterotrophic, unlike all other thiotrophic symbionts studied to date, which possess either the Calvin-Benson-Bassham or reverse tricarboxylic acid cycles for autotrophy.

Significance Statement

Many animals and protists depend on symbiotic sulfur-oxidizing bacteria as their main food source. These bacteria use energy from oxidizing inorganic sulfur compounds to make biomass autotrophically from CO2, serving as primary producers for their hosts. Here we describe apparently non-autotrophic sulfur symbionts called Kentron, associated with marine ciliates. They lack genes for known autotrophic pathways, and have a carbon stable isotope fingerprint heavier than other symbionts from similar habitats. Instead they have the potential to oxidize sulfur to fuel the uptake of organic compounds for heterotrophic growth, a metabolic mode called chemolithoheterotrophy that is not found in other symbioses. Although several symbionts have heterotrophic features to supplement primary production, in Kentron they appear to supplant it entirely.
Intraspecific Variation in Microsatellite Mutation Profiles in Daphnia magna
Authors: Ho Eddie K. H. , Macrae Fenner , Latta Leigh C. , Benner Maia J. , Sun Cheng , Ebert Dieter , Schaack Sarah
Published: February 2019

Microsatellite loci (tandem repeats of short nucleotide motifs) are highly abundant in eukaryotic genomes and are often used as genetic markers because they can exhibit variation both within and between populations. Although widely recognized for their mutability and utility, the mutation rates of microsatellites have only been empirically estimated in a few species and have rarely been compared across genotypes and populations and intraspecific differences in overall microsatellite content have rarely been explored. To investigate the accumulation of microsatellite DNA over long-and short-time periods, we quantified the abundance and genome-wide mutation rates in whole-genome sequences of 47 mutation accumulation (MA) lines and 12 non-MA lines derived from six different genotypes of the crustacean Daphnia magna collected from three populations (Finland, Germany, and Israel). Each genotype possessed a distinctive microsatellite profile and clustered according to their population of origin. During the period of mutation accumulation, we observed very high microsatellite mutation rates (a net change of −0.19 to 0.33 per copy per generation), which surpass rates reported from a closely-related congener, D. pulex, by an order of magnitude. Rates vary between microsatellite motifs and among genotypes, with those starting with high microsatellite content exhibiting greater losses and those with low microsatellite content exhibiting greater gains. Our results show that microsatellite mutation rates depend both on characteristics of the microsatellites and the genomic background. These context-dependent mutation dynamics may, in conjunction with other evolutionary forces that may differ among populations, explain the differential accumulation of repeat content in the genome over long time periods.
Deciphering the Genetics of Major End-Use Quality Traits in Wheat
Authors: Naraghi Sepehr Mohajeri , Simsek Senay , Kumar Ajay , Rabbi S.M. Hisam Al , Alamri Mohammed S. , Elias Elias M. , Mergoum Mohamed
Published: February 2019

Improving the end-use quality traits is one of the primary objectives in wheat breeding programs. In the current study, a population of 127 recombinant inbred lines (RILs) derived from a cross between Glenn (PI-639273) and Traverse (PI-642780) was developed and used to identify quantitative trait loci (QTL) for 16 end-use quality traits in wheat. The phenotyping of these 16 traits was performed in nine environments in North Dakota, USA. The genotyping for the RIL population was conducted using the wheat Illumina iSelect 90K SNP assay. A high-density genetic linkage map consisting of 7,963 SNP markers identified a total of 76 additive QTL (A-QTL) and 73 digenic epistatic QTL (DE-QTL) associated with these traits. Overall, 12 stable major A-QTL and three stable DE-QTL were identified for these traits, suggesting that both A-QTL and DE-QTL played an important role in controlling end-use quality traits in wheat. The most significant A-QTL (AQ.MMLPT.ndsu.1B) was detected on chromosome 1B for mixograph middle line peak time. TheAQ.MMLPT.ndsu.1BA-QTL was located very close to the position of the Glu-B1 gene encoding for a subunit of high molecular weight glutenin and explained up to 24.43% of phenotypic variation for mixograph MID line peak time. A total of 23 co-localized QTL loci were detected, suggesting the possibility of the simultaneous improvement of the end-use quality traits through selection procedures in wheat breeding programs. Overall, the information provided in this study could be used in marker-assisted selection to increase selection efficiency and to improve the end-use quality in wheat.
Characterization of prevalence and health consequences of uniparental disomy in four million individuals from the general population
Authors: Nakka Priyanka , Smith Samuel Pattillo , O’Donnell-Luria Anne H. , McManus Kimberly F. ,   23andMe Research Team, Mountain Joanna L. , Ramachandran Sohini , Sathirapongsasuti J. Fah
Published: February 2019

Meiotic nondisjunction and resulting aneuploidy can lead to severe health consequences in humans. Aneuploidy rescue can restore euploidy but may result in uniparental disomy (UPD), the inheritance of both homologs of a chromosome from one parent with no representative copy from the other. Current understanding of UPD is limited to ~3,300 cases for which UPD was associated with clinical presentation due to imprinting disorders or recessive diseases. Thus, the prevalence of UPD and its phenotypic consequences in the general population are unknown. We searched for instances of UPD in over four million consented research participants from the personal genetics company 23andMe, Inc., and 431,094 UK Biobank participants. Using computationally detected DNA segments identical-by-descent (IBD) and runs of homozygosity (ROH), we identified 675 instances of UPD across both databases. Here we present the first characterization of UPD prevalence in the general population, a machine-learning framework to detect UPD using ROH, and a novel association between autism and UPD of chromosome 22.
Integrating Biomedical Research and Electronic Health Records to Create Knowledge Based Biologically Meaningful Machine Readable Embeddings
Authors: Nelson Charlotte A. , Butte Atul J. , Baranzini Sergio E.
Published: February 2019

In order to advance precision medicine, detailed clinical features ought to be described in a way that leverages current knowledge. Although data collected from biomedical research is expanding at an almost exponential rate, our ability to transform that information into patient care has not kept at pace. A major barrier preventing this transformation is that multi-dimensional data collection and analysis is usually carried out without much understanding of the underlying knowledge structure. In an effort to bridge this gap, Electronic Health Records (EHRs) of individual patients were connected to a heterogeneous knowledge network called Scalable Precision Medicine Oriented Knowledge Engine (SPOKE). Then an unsupervised machine-learning algorithm was used to create Propagated SPOKE Entry Vectors (PSEVs) that encode the importance of each SPOKE node for any code in the EHRs. We argue that these results, alongside the natural integration of PSEVs into any EHR machine-learning platform, provide a key step toward precision medicine.
Fingerprinting Adiposity and Metabolic Function in the Brains of Overweight and Obese Humans
Authors: Farruggia Michael C. , Van Kooten Maria J. , Burke Mary V. , Scheinost Dustin , Todd Constable R. , Small Dana M.
Published: February 2019

The brain plays a central role in the pathophysiology of obesity. Connectome-based Predictive Modeling (CPM) is a newly developed, data-driven approach that exploits whole-brain functional connectivity to predict a behavior or trait that varies across individuals. We used CPM to determine whether brain “fingerprints” evoked during milkshake consumption could be isolated for common measures of adiposity in 67 overweight and obese adults. We found that a CPM could be identified for waist circumference, but not percent body fat or BMI, the most frequently used measures to assess brain correlates of obesity. In an exploratory analysis, we were also able to derive a largely distinct CPM predicting fasting blood insulin. These findings demonstrate that brain network patterns are more tightly coupled to waist circumference than BMI or percent body fat and that adiposity and glucose tolerance are associated with distinct maps, pointing to dissociable central pathophysiological phenotypes for obesity and diabetes.
Immunization with recombinant enolase ofSporothrixspp (rSsEno) confers effective protection against sporotrichosis in mice
Authors: Fuentes Deivys Leandro Portuondo , Dores-Silva Paulo Roberto , Ferreira Lucas Souza , Téllez-Martínez Damiana , Marcos Caroline Maria , de Aguiar Loesch Maria Luiza , Quimbayo Fanny Guzmán , Borges Júlio César , Batista-Duharte Alexander , Carlos Iracilda Zeppone
Published: February 2019

In recent years, research has focused on the immunoreactive components of theS. schenckiicell wall that can be relevant targets for preventive and therapeutic vaccines against sporotrichosis, an emergent worldwide mycosis. In previous studies, we identified a 47-kDa enolase as an immunodominant antigen in mice vaccinated with purified fungal wall proteins and adjuvants. In this study, the immunolocalization of this immunogen in the cell wall ofS. schenckiiandS. brasiliensisis shown for the first time. In addition, a recombinant enolase ofSporothrixspp (rSsEno) was studied with the adjuvant Montanide Pet-GelA (PGA) as a vaccine candidate. The rSsEno was produced with high purity. In addition, mice immunized with rSsEno plus PGA showed increased antibody titers against enolase and increased median survival time comparedto nonimmunized or rSsEno-immunized mice. Enolase immunization induced a predominant T-helper-1 (Th1) cytokine pattern in splenic cells after in vitro stimulation with rSsEno. Elevated production of interferon-γ (IFN-γ) and interleukin-2 (IL-2) was observed with other cytokines involved in the innate immune defense, such as TNF-alpha, IL-6, and IL-4, which are necessary for antibody production. These results suggest that we should continue testing this antigen as a potential vaccine candidate against sporotrichosis.
Domain-relevant auditory expertise modulates the additivity of neural mismatch responses in humans
Authors: Hansen Niels Chr. , Højlund Andreas , Møller Cecilie , Pearce Marcus , Vuust Peter
Published: February 2019

It is unknown whether domain-relevant expertise is associated with more independent or more dependent predictive processing of acoustic features. Here, mismatch negativity (MMNm) was recorded with magnetoencephalography (MEG) from 25 musicians and 25 non-musicians, exposed to complex musical multi-feature and simple oddball control paradigms. Deviants differed in frequency (F), intensity (I), perceived location (L), or any combination of these (FI, IL, LF, FIL). Neural processing overlap was assessed through MMNm additivity by comparing double- and triple-deviant MMNms (“empirical”) to summed constituent single-deviant MMNms (“modelled”). Significantly greater subadditivity was present in musicians compared to non-musicians, specifically for frequency-related deviants in complex contexts. Despite using identical sounds, expertise effects were absent from the simple paradigm. This novel finding supports thedependent processing hypothesiswhereby experts recruit overlapping neural resources facilitating more integrative representations of domain-relevant stimuli. Such specialized predictive processing may enable experts such as musicians to capitalise on complex acoustic cues.
Performance of normative and approximate evidence accumulation on the dynamic clicks task
Authors: Radillo Adrian E. , Veliz-Cuba Alan , Josić Krešimir , Kilpatrick Zachary P.
Published: February 2019

The aim of a number of psychophysics tasks is to uncover how mammals make decisions in a world that is in flux. Here we examine the characteristics of ideal and near–ideal observers in a task of this type. We ask when and how performance depends on task parameters and design, and, in turn, what observer performance tells us about their decision-making process. In the dynamic clicks task subjects hear two streams (left and right) of Poisson clicks with different rates. Subjects are rewarded when they correctly identify the side with the higher rate, as this side switches unpredictably. We show that a reduced set of task parameters defines regions in parameter space in which optimal, but not near-optimal observers, maintain constant response accuracy. We also show that for a range of task parameters an approximate normative model must be finely tuned to reach near-optimal performance, illustrating a potential way to distinguish between normative models and their approximations. In addition, we show that using the negative log-likelihood and the 0/1-loss functions to fit these types of models is not equivalent: the 0/1-loss leads to a bias in parameter recovery that increases with sensory noise. These findings suggest ways to tease apart models that are hard to distinguish when tuned exactly, and point to general pitfalls in experimental design, model fitting, and interpretation of the resulting data.
Luliconazole, a New Antifungal, vs Amphotericin B, Voriconazole, Posaconazole and Caspofungin against Clinical and EnvironmentalAspergillusNigri Complex
Authors: Hivary Sahar , Fatahinia Mahnaz , Halvaeezadeh Marzieh , Mahmoudabadi Ali Zarei
Published: February 2019

Black Aspergilli are,the most causes of aspergillosis andAspergillus niger and A. tubingensis are two more frequently isolates. Although, amphotericin B was a gold standard for the treatment of invasive fungal infection for several decades, it replaced by several new antifungals. Furthermore, a novel antifungal, luliconazole, appears to offer the potential for improved therapy for aspergillosis. The aim of the present study was to compare the effect of a novel antifungal agent, luliconazole, with classical antifungalagainst clinical and environmental strains of black Aspergilli. Sixty seven strains of black Aspergilli were identified using morphological and molecular tests (β-Tubulin gene). Antifungal susceptibility test was applied according to CLSI M38 A2. The results were reported as MIC range, MIC50, MIC90and MICGM. In the present study,A. nigerwas the common isolate followed by,A. tubingensisand 54.1% (clinical) and 30% (environmental) of isolates were resistant to caspofungin. The highest resistant rate was found in amphotericin B for both clinical (86.5%) and environmental (96.7%) strains. Clinical strains ofAspergilluswere more sensitive to voriconazole (86.7%) than environmental strains (70.3%). On the other hand, 83.8% of clinical and 70% of environmental isolates were resistant to posaconazole, respectively. It is found that the lowest MIC range, MIC50, MIC90, and MICGMwas attributed to luliconazole in clinical strains. In conclusion, luliconazole vs. routine antifungal is a potent antifungal forA. nigercomplexin vitro. The MIC range, MIC50, MIC90and MICGMof luliconazole against black Aspergilli were the lowest among the representative tested antifungals.
Selectivity of Guanine Nucleotide Exchange Factor-mediated Cdc42 activation in primary human endothelial cells
Authors: Reinhard Nathalie R. , der Niet Sanne van , Chertkova Anna , Postma Marten , Hordijk Peter L. , Gadella Theodorus W.J. , Goedhart Joachim
Published: February 2019

The Rho GTPase family is involved in actin dynamics and regulates the barrier function of the endothelium. One of the main barrier-promoting Rho GTPases is Cdc42, also known as cell division control protein 42 homolog. Currently, regulation of Cdc42-based signaling networks in endothelial cells (ECs) lack molecular details. To examine these, we focused on a subset of 15 Rho guanine nucleotide exchange factors (GEFs), which are expressed in the endothelium. By performing single cell FRET measurements with Rho GTPase biosensors in primary human ECs, we monitored GEF efficiency towards Cdc42 and Rac1. A new, single cell-based analysis was developed and used to enable the quantitative comparison of cellular activities of the full-length GEFs. Our data reveal a specific GEF dependent activation profile, with most efficient Cdc42 activation induced by PLEKHG2, FGD1, PLEKHG1 and pRex1 and the highest selectivity for FGD1. Additionally, we generated truncated GEF constructs that comprise only the catalytic dbl homology (DH) domain or together with the adjacent pleckstrin homology domain (DHPH). The DH domain by itself did not activate Cdc42, whereas the DHPH domain of ITSN1, ITSN2 and PLEKHG1 showed activity towards Cdc42. Together, our study characterized endothelial GEFs that may activate Cdc42, which will be of great value for the field of vascular biology.

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Graphical Abstract