bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution of DNA methylation inPapiobaboons
Authors: Vilgalys Tauras , Rogers Jeffrey , Jolly Clifford ,   Baboon Genome Analysis Consortium, Mukherjee Sayan , Tung Jenny 
Published: August 2018

AbstractChanges in gene regulation have long been thought to play an important role in primate evolution. However, although a number of studies have compared genome-wide gene expression patterns across primate species, fewer have investigated the gene regulatory mechanisms that underlie such patterns, or the relative contribution of drift versus selection. Here, we profiled genome-scale DNA methylation levels from five of the six extant species of the baboon genusPapio(4–14 individuals per species). This radiation presents the opportunity to investigate DNA methylation divergence at both shallow and deeper time scales (380,000 – 1.4 million years). In contrast to studies in human populations, but similar to studies in great apes, DNA methylation profiles clearly mirror genetic and geographic structure. Divergence in DNA methylation proceeds fastest in unannotated regions of the genome and slowest in regions of the genome that are likely more constrained at the sequence level (e.g., gene exons). Both heuristic approaches and Ornstein-Uhlenbeck models suggest that DNA methylation levels at a small set of sites have been affected by positive selection, and that this class is enriched in functionally relevant contexts, including promoters, enhancers, and CpG islands. Our results thus indicate that the rate and distribution of DNA methylation changes across the genome largely mirror genetic structure. However, at some CpG sites, DNA methylation levels themselves may have been a target of positive selection, pointing to loci that could be important in connecting sequence variation to fitness-related traits.
Species-Specific Root Microbiota Dynamics in Response to Plant-Available Phosphorus
Authors: Bodenhausen Natacha , Somerville Vincent , Desirò Alessandro , Walser Jean-Claude , Borghi Lorenzo , van der Heijden Marcel G.A. , Schlaeppi Klaus 
Published: August 2018

SummaryPhosphorus (P) is a limiting element for plant growth. Several root microbes, including arbuscular mycorrhizal fungi (AMF), have the capacity to improve plant nutrition and their abundance is known to depend on P fertility. However, how complex root-associated bacterial and fungal communities respond to changes in P availability remains ill-defined.We manipulated the availability of soil P in pots and compared the root microbiota of non-mycorrhizal Arabidopsis with mycorrhizal Petunia plants. Root bacteria and fungi were profiled using ribosomal operon gene fragment sequencing, we searched for P sensitive microbes and tested whether a P sensitive core microbiome could be identified.Root microbiota composition varied substantially by P availability. A P sensitive core microbiome was not identified as different bacterial and fungal groups responded to low-P conditions in Arabidopsis and Petunia. P sensitive microbes included Mortierellomycotina in Arabidopsis, while these were AMF and their symbiotic endobacteria in Petunia. Of note, their P-dependent root colonization was reliably quantified by sequencing.The species-specific root microbiota dynamics suggest that Arabidopsis and Petunia evolved different microbial associations under the selection pressure of low P availability. This implies that the development of microbial products that improve P availability requires the consideration of host-species specificity.
Toll-Like Receptor-4 Disruption Suppresses Adipose Tissue Remodeling and Increases Survival During Cancer Cachexia Syndrome
Authors: Henriques Felipe , Lopes Magno A. , Franco Felipe O. , Knobl Pamela , Santos Kaltinaitis B. , Bueno Luana L. , Correa Victor A. , Bedard Alexander H. , Guilherme Adilson , Birbrair Alexander , Peres Sidney B. , Farmer Stephen R. , Batista Miguel L. 
Published: August 2018

ABSTRACTCancer-induced cachexia, characterized by systemic inflammation, body weight loss, adipose tissue (AT) remodeling and muscle wasting, is a malignant metabolic syndrome with undefined etiology. Here, we show that Toll-like receptor 4 (TLR4) mediates AT remodeling, in particular, AT browning and inflammatory response in mice bearing Lewis lung carcinoma (LLC). LLC tumor-bearing (TB) TLR4−/− mice were spared from AT remodeling due to a reduced macrophage infiltration and adipocyte atrophy. TLR4−/− mice were also resistant to cold-induced browning of subcutaneous AT (scAT). Importantly, pharmacological inhibition of TLR4 reproduced the main protective effect against AT remodeling found in TLR4−/− TB mice. Moreover, the treatment was effective in prolonging the survival and attenuating tumor mass growth when compared to non-treated-TB animals. Further, tumor-induced elevation of circulating pro-inflammatory cytokines was similarly abolished in both genetic ablation and pharmacological inhibition of TLR4. These data suggest that TLR4 is a critical mediator and a promising therapeutic target for cancer-induced AT remodeling.HIGHLIGHTSGenetic ablation and pharmacological inhibition of TLR4 attenuate adipose tissue remodeling during cancer-associated cachexia;TLR4 suppression play an essential role in the browning phenotype induced by cachexia;Administration of TLR4 drug inhibitor increase survival and reduces tumor mass growth in tumor bearing mice;TLR4 pathway is a promising target for cancer-cachexia therapeutic intervention.
Effects of green seaweed extract onArabidopsisearly development suggest roles for hormone signalling in plant responses to algal fertilisers
Authors: Ghaderiardakani Fatemeh , Collas Ellen , Damiano Deborah Kohn , Tagg Katherine , Graham Neil S. , Coates Juliet C. 
Published: August 2018

AbstractThe growing population requires sustainable, environmentally-friendly crops. The plant growth-enhancing properties of algal extracts have suggested their use as biofertilisers. The mechanism(s) by which algal extracts affect plant growth are unknown.We examined the effects of extracts from the common green seaweedUlva intestinalison germination and root development in the model land plantArabidopsis thaliana.Ulvaextract concentrations above 0.1% inhibitedArabidopsisgermination and root growth.Ulvaextract <0.1% stimulated root growth. All concentrations ofUlvaextract inhibited lateral root formation. An abscisic-acid-insensitive mutant,abi1, showed altered sensitivity to germination- and root growth-inhibition inhibition. Ethylene- and cytokinin-insensitive mutants were partly insensitive to germination-inhibition. This suggests that different mechanisms mediate each effect ofUlvaextract on earlyArabidopsisdevelopment and that multiple hormones contribute to germination-inhibition.Elemental analysis showed thatUlvacontains high levels of Aluminium ions (Al3+). Ethylene and cytokinin have been suggested to function in Al3+-mediated root growth inhibition: our data suggest that ifUlvaAl3+levels inhibit root growth, this is via a novel mechanism. We suggest algal extracts should be used cautiously as fertilisers, as the inhibitory effects on early development may outweigh any benefits if the concentration of extract is too high.
Stability of host-parasite systems: you must differ to coevolve
Authors: Berezovskaya Faina , Karev Georgy P. , Katsnelson Mikhail I. , Wolf Yuri I. , Koonin Eugene V. 
Published: August 2018

AbstractBackgroundGenetic parasites are ubiquitous satellites of cellular life forms most of which host a variety of mobile genetic elements including transposons, plasmids and viruses. Theoretical considerations and computer simulations suggest that emergence of genetic parasites is intrinsic to evolving replicator systems.ResultsUsing methods of bifurcation analysis, we investigated the stability of simple models of replicator-parasite coevolution in a well-mixed environment. It is shown that the simplest imaginable system of this type, one in which the parasite evolves during the replication of the host genome through a minimal mutation that renders the genome of the emerging parasite incapable of producing the replicase but able to recognize and recruit it for its own replication, is unstable. In this model, there are only either trivial or “semi-trivial”, parasite-free equilibria: an inefficient parasite is outcompeted by the host and dies off whereas an efficient one pushes the host out of existence, which leads to the collapse of the entire system. We show that stable host-parasite coevolution (a non-trivial equilibrium) is possible in a modified model where the parasite is qualitatively distinct from the host replicator in that the replication of the parasite depends solely on the availability of the host but not on the carrying capacity of the environment.ConclusionsWe analytically determine the conditions for stable host-parasite coevolution in simple mathematical models and find that a parasite that initially evolves from the host through the loss of the ability to replicate autonomously must be substantially derived for a stable host-parasite coevolution regime to be established.
BEES: Bayesian Ensemble Estimation from SAS
Authors: Bowerman Samuel , Curtis Joseph E. , Clayton Joseph , Brookes Emre H. , Wereszczynski Jeff 
Published: August 2018

1AbstractMany biomolecular complexes exist in a flexible ensemble of states in solution which are necessary to perform their biological function. Small angle scattering (SAS) measurements are a popular method for characterizing these flexible molecules due to their relative ease of use and ability to simultaneously probe the full ensemble of states. However, SAS data is typically low-dimensional and difficult to interpret without the assistance of additional structural models. In theory, experimental SAS curves can be reconstituted from a linear combination of theoretical models, although this procedure carries significant risk of overfitting the inherently low-dimensional SAS data. Previously, we developed a Bayesian-based method for fitting ensembles of model structures to experimental SAS data that rigorously avoids overfitting. However, we have found that these methods can be difficult to incorporate into typical SAS modeling workflows, especially for users that are not experts in computational modeling. To this end, we present the “Bayesian Ensemble Estimation from SAS” (BEES) program. Two forks of BEES are available, the primary one existing as module for the SASSIE webserver and a developmental version that is a standalone python program. BEES allows users to exhaustively sample ensemble models constructed from a library of theoretical states and to interactively analyze and compare each model’s performance. The fitting routine also allows for secondary data sets to be supplied, thereby simultaneously fitting models to both SAS data as well as orthogonal information. The flexible ensemble of K63-linked ubiquitin trimers is presented as an example of BEES’ capabilities.
A Bayesian Approach to Restricted Latent Class Models for Scientifically-Structured Clustering of Multivariate Binary Outcomes
Authors: Wu Zhenke , Casciola-Rosen Livia , Rosen Antony , Zeger Scott L. 
Published: August 2018

SummaryThis paper presents a model-based method for clustering multivariate binary observations that incorporates constraints consistent with the scientific context. The approach is motivated by the precision medicine problem of identifying autoimmune disease patient subsets or classes who may require different treatments. We start with a family of restricted latent class models or RLCMs (e.g., Xu and Shang, 2018). However, in the motivating example and many others like it, the unknown number of classes and the definition of classes using binary states are among the targets of inference. We use a Bayesian approach to RCLMs in order to use informative prior assumptions on the number and definitions of latent classes to be consistent with scientific knowledge so that the posterior distribution tends to concentrate on smaller numbers of clusters and sparser binary patterns. The paper derives a posterior sampling algorithm based on Markov chain Monte Carlo with split-merge updates to efficiently explore the space of clustering allocations. Through simulations under the assumed model and realistic deviations from it, we demonstrate greater interpretability of results and superior finite-sample clustering performance for our method compared to common alternatives. The methods are illustrated with an analysis of protein data to detect clusters representing autoantibody classes among scleroderma patients.
Assessing 16S marker gene survey data analysis methods using mixtures of human stool sample DNA extracts
Authors: Olson Nathan D , Kumar M. Senthil , Li Shan , Hao Stephanie , Timp Winston , Salit Marc L. , Stine O.Colin , Bravo Hector Corrada 
Published: August 2018

AbstractBackgroundAnalysis of 16S rRNA marker-gene surveys, used to characterize prokaryotic microbial communities, may be performed by numerous bioinformatic pipelines and downstream analysis methods. However, there is limited guidance on how to decide between methods, appropriate data sets and statistics for assessing these methods are needed. We developed a mixture dataset with real data complexity and an expected value for assessing 16S rRNA bioinformatic pipelines and downstream analysis methods. We generate an assessment dataset using a two-sample titration mixture design. The sequencing data were processed using multiple bioinformatic pipelines, i) DADA2 a sequence inference method, ii) Mothur a de novo clustering method, and iii) QIIME with open-reference clustering. The mixture dataset was used to qualitatively and quantitatively assess count tables generated using the pipelines.ResultsThe qualitative assessment was used to evalute features only present in unmixed samples and titrations. The abundance of Mothur and QIIME features specific to unmixed samples and titrations were explained by sampling alone. However, for DADA2 over a third of the unmixed sample and titration specific feature abundance could not be explained by sampling alone. The quantitative assessment evaluated pipeline performance by comparing observed to expected relative and differential abundance values. Overall the observed relative abundance and differential abundance values were consistent with the expected values. Though outlier features were observed across all pipelines.ConclusionsUsing a novel mixture dataset and assessment methods we quantitatively and qualitatively evaluated count tables generated using three bioinformatic pipelines. The dataset and methods developed for this study will serve as a valuable community resource for assessing 16S rRNA marker-gene survey bioinformatic methods.
Functional and Comparative Genomics of Niche-Specific Adapted ActinomycetesKocuria rhizophilaStrain D2 Isolated from Healthy Human Gut
Authors: Ghattargi Vikas C. , Nimonkar Yogesh S. , Sape Kamala , Prakash Om , Suryavanshi Mangesh V. , Shouche Yogesh S. , Meti Bharati S. , Pawar Shrikant P. 
Published: August 2018

ABSTRACTIncidences of infection and occurrence ofKocuria rhizophilain human gut are prominent but certainly no reports on the species ability to withstand human gastrointestinal dynamics.Kocuria rhizophilastrain D2 isolated from healthy human gut was comprehensively characterized. The functional analysis revealed the ability to produce various gastric enzymes and sensitive to major clinical antibiotics. It also exhibited tolerance to acidic pH and bile salts. Strain D2 displayed bile-salt hydrolytic (BSH) activity, strong cell surface traits such as hydrophobicity, auto-aggregation capacity and adherence to human HT-29 cell line. Prominently, it showed no hemolytic activity and was susceptible to the human serum. Exploration of the genome led to the discovery of the genes for the above said properties and has ability to produce various essential amino acids and vitamins. Further, comparative genomics have identified core, accessory and unique genetic features. The core genome has given insights into the phylogeny while the accessory and unique genes has led to the identification of niche specific genes. Bacteriophage, virulence factors and biofilm formation genes were absent with this species. Housing CRISPR and antibiotic resistance gene was strain specific. The integrated approach of functional, genomic and comparative analysis denotes the niche specific adaption to gut dynamics of strain D2. Moreover the study has comprehensively characterized genome sequence of each strain to know the genetic difference and intern recognize the effects of on phenotype and functionality complexity. The evolutionary relationship among strains along and adaptation strategies has been included in this study.SignificanceReports of Kocuria rhizophila isolation from various sources have been reported but the few disease outbreaks in humans and fishes have been prominent, but no supportive evidence about the survival ability of Kocuria spp. within human GIT. Here, we report the gut adaption potential of K. rhizophila strain D2 by functional and genomic analysis. Further; comparative genomics reveals this adaption to be strain specific (Gluten degradation). Genetic difference, evolutionary relationship and adaptation strategies have been including in this study.
Identification of a cis-acting determinant limiting expression of sphingomyelinase genesph2inLeptospira interroganswith agfpreporter plasmid
Authors: Matsunaga James , Haake David A. 
Published: August 2018

ABSTRACTMany Pomona strains of the spirocheteLeptospira interrogansexpress the osmotically-inducible sphingomyelinase gene,sph2, at much higher levels than non-Pomona strains. We developed a new green fluorescent protein (GFP) reporter plasmid to examinesph2gene expression determinants. The vector allows fusion of the test promoter to the ribosome-binding site and coding region ofgfp. We fused thesph2promoters from the serovar Lai strain 56601 and from the serovar Pomona strain LC82-25 togfpto examine the molecular determinants of differentialsph2expression between the two strains. Similar to what is observed with the nativesph2genes, introduction of the plasmids into the Lai 56601 strain resulted in near background levels ofgfpexpression from the Laisph2promoter, while expression from the Pomonasph2promoter was high. Expression from both fusions increased at physiologic levels of osmolarity achieved by addition of sodium chloride to the culture medium. We examined the role of a 17 bp upstream element found in allL. interrogansstrains expressing low basal levels ofsph2and missing from Pomona strains that expresssph2at high levels. When the 17 bp sequence present upstream of the Laisph2promoter was deleted or scrambled, fusion expression increased substantially. Conversely, insertion of the 17 bp sequence upstream of the Pomonasph2promoter diminished fusion expression. In contrast, removal of an insertion sequence-like element that is found only in the Pomonasph2upstream sequence had no effect on expression from the Pomonasph2fusion in the Lai strain. These findings demonstrate the utility of thegfpreporter plasmid in analyzing gene expression inL. interrogans.IMPORTANCEGenetic tools are needed to examine gene expression in the pathogenLeptospira interrogans. We developed a reporter plasmid that replicates inL. interroganswith green fluorescent protein (GFP) as the read out of promoter activity. We demonstrated an application of the new reporter plasmid by identifying an upstream element responsible for the poor basal expression of thesph2sphingomyelinase gene in a serovar Lai strain ofL. interrogans. This new tool is useful for discovery of the molecular determinants ofL. interrogansgene expression.
Onychomycosis caused by Aspergillus subramanianii
Authors: Hirose Miki , Noguchi Hiromitsu , Yaguchi Takashi , Matsumoto Tadahiko , Hiruma Masataro , Fukushima Satoshi , Ihn Hironobu 
Published: August 2018

AbstractWe describe a case of a 23‐year‐old female patient with no apparent underlying diseases. She showed a discoloration of the proximal portion of the left big toenail with paronychia. Direct microscopy revealed septate hyphae with conidiophores, and a periodic acid–Schiff‐stained nail specimen revealed septate hyphae branching at angles of approximately 45°. On the basis of phylogenetic analysis, we finally arrived at the diagnosis of ungual aspergillosis caused by Aspergillus subramanianii. After p.o. administration of terbinafine and topical application of 10% efinaconazole solution, the disease resolved in 6 months. A. subramanianii is one of the new species in the genus Aspergillus section Circumdati. Reported clinical isolates have been isolated from lung tissue, wounds and feet. This is the first documented case of onychomycosis caused by A. subramanianii. Onychomycosis due to Aspergillus species is uncommon. We summarized the reported cases of ungual aspergillosis in Japan.
Immunological dysfunction in chronic arsenic exposure: From subclinical condition to skin cancer
Authors: Yu Sebastian , Liao Wei‐Ting , Lee Chih‐Hung , Chai Chee‐Yin , Yu Chia‐Li , Yu Hsin‐Su 
Published: August 2018

AbstractExposure to arsenic is a global health issue. Long‐term arsenic exposure may associate with various cancers and many other pathological effects. Over 100 million people worldwide are exposed to arsenic particularly in countries such as Bangladesh, Chile, China, India, Mexico, Taiwan and the USA. Drinking of water contaminated with arsenic is the major route of human exposure. Skin lesions are considered to be the most common adverse effects associated with chronic arsenic exposure. Skin lesions usually develop with the latency period spanning more than 20 years from first exposure. Arsenic‐induced Bowen's disease, the most frequently encountered carcinoma in situ resulting from chronic arsenic exposure, is characterized by multiple and recrudescent lesions. Long‐term arsenic exposure results in impaired immunity in susceptible individuals. In the prenatal stage, enhanced placental inflammatory responses and reduced placental T cells by arsenic may result in decreased thymic size and functions in newborns. In childhood, arsenic exposure may reduce peripheral CD4+ cells and interleukin‐2 secretion which leads to susceptibility to opportunistic infections. There was an impairment of macrophage function and oxidative DNA damage of peripheral polymorphonuclear leukocytes in adults with skin lesions. In arsenic‐induced Bowen's disease lesions, a decrease in the number and functions of Langerhans cells and, in parallel, a selective CD4+ cell apoptosis was noticed. These findings provide scientific evidence for understanding the phenomenon of arsenic‐induced immune escape in the early stage of carcinogenesis and a reasonable explanation for multiple and recrudescent arsenic cancers in the skin.
England, Englishness and the Labour Party
Authors: Denham John , Devine Daniel 
Published: August 2018

AbstractRecent research has indicated that English identity was a strong predictor for a Leave vote in the referendum on membership of the European Union, and that it is an identity that is increasingly playing a role in British politics. In this paper, we explore whether Englishness affects even left‐right positioning of parties. Focusing on Labour, we find that it does, even controlling for other attitudinal and demographic variables. Alongside age and perceptions of the party leader, perceptions of immigration change and perceived lack of political efficacy also play a significant role. Given the potential electoral significance of this, we reflect on and propose a range of policy options that Labour could utilise to address this gap between English‐identifiers and the party.