bluuebunny/crossref_metadata_2025_split huggingface dataset:
The microbiome as a biosensor: functional profiles elucidate hidden stress in hosts
Authors: Zolti Avihai , Green Stefan J. , Sela Noa , Hadar Yitzhak , Minz Dror 
Published: September 2019

AbstractMicrobial communities are highly responsive to environmental cues, and both their structure and activity can be altered in response to changing conditions. We hypothesized that host-associated microbial communities, particularly those colonizing host surfaces, can serve asin situsensors to reveal environmental conditions experienced by both microorganisms and the host. For a proof-of-concept, we studied a model plant-soil system and employed a non-deterministic gene-centric approach. A holistic analysis was performed using plants of two species and irrigation with water of low quality to induce host stress. Our analyses examined the genetic potential (DNA) and gene expression patterns (RNA) of plant-associated microbial communities, as well as transcriptional profiling of host plants. Transcriptional analysis of plants irrigated with treated wastewater revealed significant enrichment of general stress-associated root transcripts relative to plants irrigated with fresh water. Metagenomic analysis of root-associated microbial communities in treated wastewater-irrigated plants, however, revealed enrichment of more specific stress-associated genes relating to high levels of salt, high pH and lower levels of oxygen. Meta-analysis of these differentially abundant genes obtained from other metagenome studies provided evidence of the link between environmental factors such as pH and oxygen and these genes. Analysis of microbial transcriptional response demonstrated that enriched gene content was actively expressed, which implies contemporary response to elevated levels of pH and salt. We demonstrate here that microbial profiling can elucidate stress signals that cannot be observed even through interrogation of host transcriptome, leading to an alternate mechanism for evaluatingin situconditions experienced by host organisms.Significance StatementThis study examines the potential for microbial communities to provide insight into stresses experienced by their eukaryotic host organisms, through profiling of metagenomes and metatranscriptomes. Our study uses plant host-associated microorganisms as anin vivoandin situmicrosensor to identify environmental stresses experienced by the microbial community and by the plant. Transcriptionally active host-associated microbial communities are responsive in a highly specific manner to environmental conditions. Conversely, host transcriptome sequencing provides only a very general stress response. This study is a proof-of-concept for the use of microbial communities as microsensors, with a great potential for interrogation of a wide range of host systems.
Gradual decrease in the inter-population diversity of HIV-1 Env among group M lineages worldwide
Authors: Han Changze , Johnson Jacklyn , Dong Rentian , Kandula Raghavendranath , Kort Alexa J. , Wong Maria , Yang Tianbao , Breheny Patrick J. , Brown Grant D. , Haim Hillel 
Published: September 2019

AbstractHIV-1 group M was transmitted to humans nearly one century ago. The virus has since diversified to form distinct clades, which spread to multiple regions worldwide. Of the different proteins encoded by HIV-1, the envelope glycoproteins (Envs) have diversified most rapidly in all infected populations. We compared the range of variants that emerged during the AIDS pandemic in diverse HIV-1 clades and distinct geographic regions. Our analyses focused on two components of Env that contain multiple epitopes of broadly-neutralizing antibodies: the glycan shield and apex domain. Interestingly, at each Env position, the amino acid in the inferred clade ancestor was replaced by a unique combination of emerging variants. Key antigenic sites and genetic signatures of vaccine protection have gradually evolved toward conserved frequency distributions (FDs) of all amino acids. FDs are specific for position and clade and are highly conserved in populations from different regions. Remarkably, founder effects of Env mutations in distinct clades and recently-infected regions were significantly reduced during the epidemic by evolution of each site toward the position-specific FD. These findings suggest that the selective pressures that guide evolution of Env are conserved in different populations. They are sufficiently strong to reduce founder effects at the clade and regional levels and have significantly altered the distribution of Env forms that circulate worldwide. Consequently, the intra-population diversity of the Env protein continues to increase whereas the inter-population diversity is gradually decreasing.ImportanceThe Env protein of HIV-1 is the primary target in AIDS vaccine design. Due to frequent mutations, new Env variants continuously emerge in the population. The increasing number of Env forms and apparent randomness of the changes limit our ability to design broadly-effective vaccines. We examined the populations-level changes that occurred in Env during the AIDS epidemic. Each position of the molecule has evolved toward a specific combination of amino acids. Similar changes occurred in different HIV-1 subtypes and geographic regions toward the same sets of forms, often from distinct ancestral sequences. Such conserved patterns of evolution define a new framework for designing vaccines that are tailored to the unique combination of Env variants expected to circulate in each population.
Visualizing in vitro-in vivo correlation of miktoarm copolymer nanomicelles in cancer cellular uptake and trafficking
Authors: Cui Zheng , Zhang Xiaofei , Zhang Xiaojin , He Suna , Gao Wei , He Bing , Wang Xueqing , Zhang Hua , Zhong Zhenlin , Zhang Qiang 
Published: September 2019

AbstractIn this study, a clear correlation between the in vitro and in vivo cellular uptake and trafficking was discovered by delivering miktoarm copolymer nanomicelles (MCNs) to cancer cells and tumor tissues. To monitor this process, two different FRET pairs, DiO and DiI, DiD and DiR, were loaded into MCNs to monitor the Förster resonance energy transfer (FRET) efficiency. The change in FRET efficiency in vitro and in vivo demonstrated a similar sequence of events for the transport of MCNs: hyperbranched block PCL inserted into cytomembrane, while the loaded hydrophobic fluorescence probes were released and followed by time-dependent intracellular clustering within endocytic vesicles. Additionally, uptake of loaded fluorescence probes with successively increasing ratios of copolymers suggested that with the increase of mass ratio of copolymer to fluorescence probes, cellular uptake of probes significantly decreased. This result was also consistent with the uptake behavior in cancer tissues. Collectively, the interaction between MCNs and cellular membrane dictated the uptake and trafficking of core-loaded hydrophobic probes. This concept paves a new way to analyze in vitro-in vivo correlation of other nanocarriers for endocytosis mechanism studies as well as further novel copolymers design in biomedical applications.
Dynamic oligopeptide acquisition by the RagAB transporter fromPorphyromonas gingivalis
Authors: Madej Mariusz , White Joshua B. R. , Nowakowska Zuzanna , Rawson Shaun , Scavenius Carsten , Enghild Jan J. , Bereta Grzegorz P. , Pothula Karunakar , Kleinekathoefer Ulrich , Baslé Arnaud , Ranson Neil , Potempa Jan , van den Berg Bert 
Published: September 2019

AbstractPorphyromonas gingivalis, an asaccharolyticBacteroidetes, is a keystone pathogen in human periodontitis that may also contribute to the development of other chronic inflammatory diseases, such as rheumatoid arthritis, cardiovascular disease and Alzheimer’s disease.P. gingivalisutilizes protease-generated peptides derived from extracellular proteins for growth, but how those peptides enter the cell is not clear. Here we identify RagAB as the outer membrane importer for peptides. X-ray crystal structures show that the transporter forms a dimeric RagA2B2complex with the RagB substrate binding surface-anchored lipoprotein forming a closed lid on the TonB-dependent transporter RagA. Cryo-electron microscopy structures reveal the opening of the RagB lid and thus provide direct evidence for a “pedal bin” nutrient uptake mechanism. Together with mutagenesis, peptide binding studies and RagAB peptidomics, our work identifies RagAB as a dynamic OM oligopeptide acquisition machine with considerable substrate selectivity that is essential for the efficient utilisation of proteinaceous nutrients byP. gingivalis.
Large-scale Phenomic and Genomic Analysis of Brain Asymmetrical Skew
Authors: Kong Xiang-Zhen , Postema Merel , Carrión Castillo Amaia , Pepe Antonietta , Crivello Fabrice , Joliot Marc , Mazoyer Bernard , Fisher Simon E. , Francks Clyde 
Published: September 2019

AbstractThe human cerebral hemispheres show a left-right asymmetrical torque pattern, which has been claimed to be absent in chimpanzees. The functional significance and developmental mechanisms are unknown. Here we carried out the largest-ever analysis of global brain shape asymmetry in magnetic resonance imaging data. Three population datasets were used, the UK Biobank (N = 39,678), Human Connectome Project (N = 1,113) and BIL&GIN (N = 453). At the population level, there was an anterior and dorsal skew of the right hemisphere, relative to the left. Both skews were associated independently with handedness, and various regional grey and white matter metrics oppositely in the two hemispheres, as well as other variables related to cognitive functions, sociodemographic factors, and physical and mental health. The two skews showed SNP-based heritabilities of 4-13%, but also substantial polygenicity in causal mixture model analysis, and no individually significant loci were found in GWAS for either skew. There was evidence for a significant genetic correlation (rg=−0.40, p=0.0075) between horizontal brain skew and Autism Spectrum Disorder. These results provide the first large-scale description of population-average brain skews and their inter-individual variations, their replicable associations with handedness, and insights into biological and other factors which associate with human brain asymmetry.
The genetic landscape of Ethiopia: diversity, intermixing and the association with culture
Authors: López Saioa , Tarekegn Ayele , Band Gavin , van Dorp Lucy , Bird Nancy , Morris Sam , Oljira Tamiru , Mekonnen Ephrem , Bekele Endashaw , Blench Roger , Thomas Mark G. , Bradman Neil , Hellenthal Garrett 
Published: September 2019

SummaryThe rich linguistic, ethnic and cultural diversity of Ethiopia provides an unprecedented opportunity to understand the level to which cultural factors correlate with -- and shape -- genetic structure in human populations. Using primarily novel genetic variation data covering 1,214 Ethiopians representing 68 different ethnic groups, together with information on individuals’ birthplaces, linguistic/religious practices and 31 cultural practices, we disentangle the effects of geographic distance, elevation, and social factors upon shaping the genetic structure of Ethiopians today. We provide evidence of associations between social behaviours and increased genetic differences among present-day peoples. We show that genetic similarity is broadly associated with linguistic classifications, but indicate pronounced genetic similarity among groups from disparate language classifications that may in part be attributable to recent intermixing. We also illustrate how groups reporting the same culture traits are more genetically similar on average and show evidence of recent intermixing, suggesting how shared cultural traits may promote admixture. In addition to providing insights into the genetic structure and history of Ethiopia, these results identify the most important cultural and geographic proxies for genetic differentiation and provide a resource for designing sampling protocols for future genetic studies involving Ethiopians.
The key miRNAs for metastasis and survival of colon adenocarcinoma
Authors: Yu Mengxi , Li Wei , Zhang Chuang , Xie Feng , He Chengyan 
Published: September 2019

AbstractWGCNA (weighted gene co-expression network analysis) can provide a system-level insight into molecular interaction. To understand the co-expression pattern of miRNA in the progress of colon cancer development, this study constructed the WGCNA co-expression network to find the key microRNA of clinical significance and therefor provide possible personalized treatment targets. The miRNA expression data and clinical follow-up information of 442 valid colon cancer samples were obtained from TCGA. After the co-expression network was constructed, we found the turquoise module has the strongest correlation with stage IV. The miRNAs of the key module are enriched by GO and analyzed by KEGG, and the HUB-miRNAs are screened out through the network node degree. For clinical significance validation, data of 65 cases of colon cancer in GES29623 were analyzed by Cox regression and Kaplan-Meier, in 9 HUB-miRNAs, 2 miRNAs associated with overall survival rate were screened out. They can divide patients into high-risk group and low-risk group. Conclusion: has-miR-126-3p and has-miR-137 are the key miRNAs of COAD metastasis, they are of prognostic value in COAD.
Single-cell transcriptomic landscape of cardiac neural crest cell derivatives during embryonic and neonatal development
Authors: Liu Xuanyu , Chen Wen , Li Wenke , Zeng Ziyi , Priest James R. , Zhou Zhou 
Published: September 2019

ABSTRACTRationaleCardiac neural crest cells (CNCCs) contribute greatly to cardiovascular development. A thorough understanding of the cell lineages, transcriptomic states and regulatory networks of CNCC derivatives during normal development is essential for deciphering the pathogenesis of CNCC-associated congenital anomalies. However, the transcriptomic landscape of CNCC derivatives during development has not yet been examined at a single-cell resolution.ObjectiveWe sought to systematically characterize the cell lineages, define the developmental chronology and elucidate the transcriptomic dynamics of CNCC derivatives during embryonic and neonatal development.Methods and ResultsWe performed single-cell transcriptomic sequencing of 34,131 CNCC-derived cells in mouse hearts from eight developmental stages between E10.5 and P7. Through single-cell analyses and single-molecule fluorescencein situhybridization, we confirmed the presence of CNCC-derived mural cells. Furthermore, we found the transition from CNCC-derived pericytes to microvascular smooth muscle cells, and identified the genes that were significantly regulated during this transition through pseudo-temporal analysis. CNCC-derived neurons first appeared at E10.5, which was earlier than previously recognized. In addition, the CNCC derivatives switched from a proliferative to a quiescent state with the progression of development. Gradual loss of the neural crest molecular signature with development was also observed in the CNCC derivatives. Our data suggested that many CNCC-derivatives had already committed or differentiated to a specific lineage when migrating to the heart. Finally, we characterized some previously unknown subpopulations of CNCC derivatives during development. For example, we found thatPenk+ cells, which were mainly localized in outflow tract cushions, were all derived from CNCCs.ConclusionsOur study provides novel insights into the cell lineages, molecular signatures, developmental chronology and state change dynamics of CNCC derivatives during embryonic and neonatal development. Our dataset constitutes a valuable resource that will facilitate future efforts in exploring the role of CNCC derivatives in development and disease.
Who predicts dollar-rupee volatility better? A tale of two options markets
Authors: Bhat Aparna Prasad 
Published: September 2019

PurposeThe purpose of this paper is to examine whether volatility implied from dollar-rupee options is an unbiased and efficient predictor ofex postvolatility, and to determine which options market is a better predictor of future realized volatility and to ascertain whether the model-free measure of implied volatility outperforms the traditional measure derived from the Black–Scholes–Merton model.Design/methodology/approachThe information content of exchange-traded implied volatility and that of quoted implied volatility for OTC options is compared with that of historical volatility and a GARCH(1, 1)-based volatility. Ordinary least squares regression is used to examine the unbiasedness and informational efficiency of implied volatility. Robustness of the results is tested by using two specifications of implied volatility and realized volatility and comparison across two markets.FindingsImplied volatility from both OTC and exchange-traded options is found to contain significant information for predictingex postvolatility, but is neither unbiased nor informationally efficient. The implied volatility of at-the-money options derived using the Black–Scholes–Merton model is found to outperform the model-free implied volatility (MFIV) across both markets. MFIV from OTC options is found to be a better predictor of realized volatility than MFIV from exchange-traded options.Practical implicationsThis study throws light on the predictive power of currency options in India and has strong practical implications for market practitioners. Efficient currency option markets can serve as effective vehicles both for hedging and speculation and can convey useful information to the regulators regarding the market participants’ expectations of future volatility.Originality/valueThis study is a comprehensive study of the informational efficiency of options on an emerging currency such as the Indian rupee. To the author’s knowledge, this is one of the first studies to compare the predictive ability of the exchange-traded and OTC markets and also to compare traditional model-dependent volatility with MFIV.
Effects of mummy consumption on fitness and oviposition site selection on Harmonia axyridis
Authors: Yu Xing‐Lin , Feng Yi , Feng Zhu‐Jun , Chana Phongsakorn , Zhu Guan‐Xiong , Xia Peng‐Liang , Liu Tong‐Xian 
Published: September 2019

AbstractIntraguild predation (IGP) has been commonly reported between predators and parasitoids used as biological control agents as predators consuming parasitoids within their hosts. However, the effect of parasitoid–mummy consumption on the fitness of the predator and subsequent oviposition site selection have not been well studied. In our study, we conducted two laboratory experiments to examine the influence of Aphidius gifuensis Ashmead (Hymenoptera: Braconidae) mummies as prey on fitness and subsequently oviposition site selection of Harmonia axyridis (Pallas) (Coleoptera: Coccinellidae). Results indicate that when H. axyridis was reared on A. gifuensis mummies only, its larval development was prolonged, and body weight of the 4th instar larvae and newly emerged adults, and fecundity decreased. Moreover, H. axyridis did not exhibit oviposition preference on plants infested with unparasitized aphids or aphids parasitized for shorter than 9 days. However, compared with plants with mummies (parasitized ≥9 days), H. axyridis laid more eggs on plants with unparasitized aphids. In contrast, H. axyridis previously fed with A. gifuensis mummies did not show a significant oviposition preference between plants with unparasitized aphids and those with mummies (parasitized ≥9 days). Overall, our results suggest that mummy consumption reduced the fitness of H. axyridis. Although H. axyridis avoided laying eggs on plants with A. gifuensis mummies, prior feeding experience on A. gifuensis mummies could alter the oviposition site preference. Thus, in biological control practice, prior feeding experience of H. axyridis should be carefully considered for reduction of IGP and increase of fitness of H. axyridis on A. gifuensis.
Preliminary report of knockdown resistance in Culex pipiens pallens and Aedes koreicus from Korea
Authors: Ryu Jihun , Hwang Do Un , Bae Yeon Jae , Lee Si Hyeock , Kim Young Ho , Lee Seung‐Yeol , Jung Hee‐Young , Choi Kwang Shik 
Published: September 2019

AbstractPyrethroid insecticides have been effective and powerful for controlling mosquitoes. However, abuse of these insecticides increases the number of resistant mosquitoes. In this study, Culex pipiens pallens and Aedes koreicus were collected from an artificial reservoir in the vicinity of a populated area in Korea, which is also a migratory bird catchment area. To monitor resistance to pyrethroid insecticides in mosquitoes, genomic DNA from the collected mosquitoes was sequenced for the kdr mutation in the voltage‐gated sodium channel (VGSC) gene. As a result, three samples with homozygous resistance (17.6%) and one with heterozygous resistance (5.9%) were found among 17 Cx. pipiens pallens specimens. One of the samples had a unique sequence at the amplified VGSC region. Of the 15 Ae. koreicus, no insecticide resistant individuals were found. In Korea, this is the first report of kdr genetic traits in Ae. koreicus and Cx. pipiens pallens and of a unique VGSC allele in Cx. pipiens pallens. Further investigation is needed to monitor the kdr resistance of these species in Korea and to determine how the unique sequence found in Cx. pipiens pallens is related to insecticide resistance.
The effect of apatinib combined with chemotherapy or targeted therapy on non‐small cell lung cancer in vitro and vivo
Authors: Liu Mingtao , Wang Xiuxiu , Li Hui , Xu Lisheng , Jing Lijun , Jiang Peng , Liu Baoyi , Li Yu 
Published: September 2019

BackgroundThe aim of this study was to investigate the feasibility of using a combination of apatinib in the treatment of non‐small cell lung cancer. Apatinib is a tyrosine kinase inhibitor which selectivelyacts on vascular endothelial growth factor receptor 2 (VEGFR‐2) and has shown good efficacy in a variety of malignancies, but the drug resistance is fast in single drug therapy.MethodsThe inhibitory effect of apatinib and other drugs on lung cancer cells was determined by CCK‐8 test in vitro, and the IC50 value was determined. To establish a nude mouse xenograft model, observe the inhibitory effect of apatinib combined with other drugs on lung cancer xenografts in nude mice; immunohistochemical staining of tumor microvessel density and Ki67 expression in transplanted tumor tissues; Western blot analysis of related signaling pathways expression; immunohistochemistry was used to detect tumor microvessel density in other organs and to observe its safety.ResultsIn this study, we found apatinib combined with pemetrexed, the first and third generation of epidermal growth factor receptor tyrosine kinase inhibitor, could synergistically inhibit the proliferation of non‐small cell lung cancer cell (NSCLC) lines, reduce the microvessel density and Ki67 protein levels of three non‐small cell lung cancer xenografts, and enhance anti‐tumor activity by synergistically inhibiting the MAPK‐ERK and PI3K‐AKT‐mTOR signaling pathway. Furthermore, there were no pathological abnormalities in the heart, brain, liver and kidney of each group.ConclusionsThe efficacy of apatinib combination is better than that of monotherapy, and there is no significant difference in toxicity of important organs, which suggests the feasibility of a combination of apatinib in the treatment of non‐small cell lung cancer.