bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genotyping by sequencing can reveal the complex mosaic genomes in gene pools resulting from reticulate evolution: a case study in diploid and polyploid citrus
Authors: Ahmed Dalel , Comte Aurore , Curk Franck , Costantino Gilles , Luro François , Dereeper Alexis , Mournet Pierre , Froelicher Yann , Ollitrault Patrick 
Published: February 2019

AbstractBackground and AimsReticulate evolution, coupled with reproductive features limiting further interspecific recombinations, results in admixed mosaics of large genomic fragments from the ancestral taxa. Whole-genome sequencing (WGS) data are powerful tools to decipher such complex genomes but still too costly to be used for large populations. The aim of this work was to develop an approach to infer phylogenomic structures in diploid, triploid and tetraploid individuals from sequencing data in reduced genome complexity libraries. The approach was applied to the cultivated Citrus gene pool resulting from reticulate evolution involving four ancestral taxa, C. maxima, C. medica, C. micrantha and C. reticulata.MethodsA genotyping by sequencing library was established with the restriction enzyme ApeKI applying one base (A) selection. Diagnostic single nucleotide polymorphisms (DSNPs) for the four ancestral taxa were mined in 29 representative varieties. A generic pipeline based on a maximum likelihood analysis of the number of read data was established to infer ancestral contributions along the genome of diploid, triploid and tetraploid individuals. The pipeline was applied to 48 diploid, four triploid and one tetraploid citrus accessions.Key ResultsAmong 43 598 mined SNPs, we identified a set of 15 946 DSNPs covering the whole genome with a distribution similar to that of gene sequences. The set efficiently inferred the phylogenomic karyotype of the 53 analysed accessions, providing patterns for common accessions very close to that previously established using WGS data. The complex phylogenomic karyotypes of 21 cultivated citrus, including bergamot, triploid and tetraploid limes, were revealed for the first time.ConclusionsThe pipeline, available online, efficiently inferred the phylogenomic structures of diploid, triploid and tetraploid citrus. It will be useful for any species whose reproductive behaviour resulted in an interspecific mosaic of large genomic fragments. It can also be used for the first generations of interspecific breeding schemes.
Researching the Intercultural: Intersubjectivity and the Problem with Postpositivism
Authors: Holliday Adrian , Macdonald Malcolm N 
Published: February 2019

AbstractIn intercultural communication studies, the positivist preoccupation with objectivist, essentialist, solid large cultures has been replaced by a postmodern recognition that the intercultural is liquid and ideologically constructed. However, a postpositivist resistance to this paradigm change, while recognizing the dangers of essentialism, continues to be objectivist and fails to address the intersubjective nature of the ideological construction of culture. This results in a soft essentialism. This methodological failure of postpositivism is driven by a neoliberal technicalized commodification of quantitative and qualitative methods that does not address the subjective implicatedness of researchers. It therefore prevents an understanding of the liquid nature of the intercultural and sustains the neo-racist implications of essentialism. An example of this is commodifying international students as culturally problematic to serve a quantifiable notion of intercultural competence. The methodological flaws of postpositivism can only be avoided by means of an approach to researching cultural groups in which large culture concepts such as nation are viewed as one of many possible, emergent, ideologically constructed variables rather than as the starting point for research.
Assessment of metagenomic assemblers based on hybrid reads of real and simulated metagenomic sequences
Authors: Wang Ziye , Wang Ying , Fuhrman Jed A , Sun Fengzhu , Zhu Shanfeng 
Published: February 2019

AbstractIn metagenomic studies of microbial communities, the short reads come from mixtures of genomes. Read assembly is usually an essential first step for the follow-up studies in metagenomic research. Understanding the power and limitations of various read assembly programs in practice is important for researchers to choose which programs to use in their investigations. Many studies evaluating different assembly programs used either simulated metagenomes or real metagenomes with unknown genome compositions. However, the simulated datasets may not reflect the real complexities of metagenomic samples and the estimated assembly accuracy could be misleading due to the unknown genomes in real metagenomes. Therefore, hybrid strategies are required to evaluate the various read assemblers for metagenomic studies. In this paper, we benchmark the metagenomic read assemblers by mixing reads from real metagenomic datasets with reads from known genomes and evaluating the integrity, contiguity and accuracy of the assembly using the reads from the known genomes. We selected four advanced metagenome assemblers, MEGAHIT, MetaSPAdes, IDBA-UD and Faucet, for evaluation. We showed the strengths and weaknesses of these assemblers in terms of integrity, contiguity and accuracy for different variables, including the genetic difference of the real genomes with the genome sequences in the real metagenomic datasets and the sequencing depth of the simulated datasets. Overall, MetaSPAdes performs best in terms of integrity and continuity at the species-level, followed by MEGAHIT. Faucet performs best in terms of accuracy at the cost of worst integrity and continuity, especially at low sequencing depth. MEGAHIT has the highest genome fractions at the strain-level and MetaSPAdes has the overall best performance at the strain-level. MEGAHIT is the most efficient in our experiments. Availability: The source code is available at https://github.com/ziyewang/MetaAssemblyEval.
NFPws: a web server for delineating broadly neutralizing antibody specificities from serum HIV-1 neutralization data
Authors: Raju Nagarajan , Setliff Ian , Georgiev Ivelin S 
Published: February 2019

Abstract

Motivation
A better understanding of antibody responses to HIV-1 infection in humans can provide novel insights for the development of an effective HIV-1 vaccine. Neutralization fingerprinting (NFP) is an efficient and accurate algorithm for delineating the epitope specificities found in polyclonal antibody responses to HIV-1 infection. Here, we report the development of NFPws, a web server implementation of the NFP algorithm. The server takes as input serum neutralization data for a set of diverse viral strains, and uses a mathematical model to identify similarities between the serum neutralization pattern and the patterns for known broadly neutralizing monoclonal antibodies (bNAbs), in order to predict the prevalence of bNAb epitope specificities in the given serum. In addition, NFPws also computes and displays a number of estimates related to prediction confidence, as well as the likelihood of presence of novel, previously uncharacterized, antibody specificities in a given serum. NFPws also implements a JSmol viewer for molecular structure visualization of the prediction results. Overall, the NFPws server will be an important tool for the identification and analysis of epitope specificities of bNAb responses against HIV-1.

Availability and implementation
NFPws is freely available to access at (http://iglab.accre.vanderbilt.edu/NFPws). The webserver is developed using html, CSS, javascript and perl CGI scripts. The NFP algorithm is implemented with scripts written in octave, linux shell and perl. JSmol is implemented to visualize the prediction results on a representative 3D structure of an HIV-1 antigen.
Inter-Modular Linkers play a crucial role in governing the biosynthesis of non-ribosomal peptides
Authors: Farag Sherif , Bleich Rachel M , Shank Elizabeth A , Isayev Olexandr , Bowers Albert A , Tropsha Alexander 
Published: February 2019

Abstract

Motivation
Non-ribosomal peptide synthetases (NRPSs) are modular enzymatic machines that catalyze the ribosome-independent production of structurally complex small peptides, many of which have important clinical applications as antibiotics, antifungals and anti-cancer agents. Several groups have tried to expand natural product diversity by intermixing different NRPS modules to create synthetic peptides. This approach has not been as successful as anticipated, suggesting that these modules are not fully interchangeable.

Results
We explored whether Inter-Modular Linkers (IMLs) impact the ability of NRPS modules to communicate during the synthesis of NRPs. We developed a parser to extract 39 804 IMLs from both well annotated and putative NRPS biosynthetic gene clusters from 39 232 bacterial genomes and established the first IMLs database. We analyzed these IMLs and identified a striking relationship between IMLs and the amino acid substrates of their adjacent modules. More than 92% of the identified IMLs connect modules that activate a particular pair of substrates, suggesting that significant specificity is embedded within these sequences. We therefore propose that incorporating the correct IML is critical when attempting combinatorial biosynthesis of novel NRPS.

Availability and implementation
The IMLs database as well as the NRPS-Parser have been made available on the web at https://nrps-linker.unc.edu. The entire source code of the project is hosted in GitHub repository (https://github.com/SWFarag/nrps-linker).

Supplementary information
Supplementary data are available at Bioinformatics online.
Unbiased approximations of products of expectations
Authors: Lee A , Tiberi S , Zanella G 
Published: February 2019

SummaryWe consider the problem of approximating the product of $n$ expectations with respect to a common probability distribution $\mu$. Such products routinely arise in statistics as values of the likelihood in latent variable models. Motivated by pseudo-marginal Markov chain Monte Carlo schemes, we focus on unbiased estimators of such products. The standard approach is to sample $N$ particles from $\mu$ and assign each particle to one of the expectations; this is wasteful and typically requires the number of particles to grow quadratically with the number of expectations. We propose an alternative estimator that approximates each expectation using most of the particles while preserving unbiasedness, which is computationally more efficient when the cost of simulations greatly exceeds the cost of likelihood evaluations. We carefully study the properties of our proposed estimator, showing that in latent variable contexts it needs only ${O} (n)$ particles to match the performance of the standard approach with ${O}(n^{2})$ particles. We demonstrate the procedure on two latent variable examples from approximate Bayesian computation and single-cell gene expression analysis, observing computational gains by factors of about 25 and 450, respectively.
Focal TLR4 activation mediates disturbed flow-induced endothelial inflammation
Authors: Qu Dan , Wang Li , Huo Mingyu , Song Wencong , Lau Chi-Wai , Xu Jian , Xu Aimin , Yao Xiaoqiang , Chiu Jeng-Jiann , Tian Xiao Yu , Huang Yu 
Published: February 2019

Abstract

Aims
Disturbed blood flow at arterial branches and curvatures modulates endothelial function and predisposes the region to endothelial inflammation and subsequent development of atherosclerotic lesions. Activation of the endothelial Toll-like receptors (TLRs), in particular TLR4, contributes to vascular inflammation. Therefore, we investigate whether TLR4 can sense disturbed flow (DF) to mediate the subsequent endothelial inflammation.

Methods and results
En face staining of endothelium revealed that TLR4 expression, activation, and its downstream inflammatory markers were elevated in mouse aortic arch compared with thoracic aorta, which were absent in Tlr4mut mice. Similar results were observed in the partial carotid ligation model where TLR4 signalling was activated in response to ligation-induced flow disturbance in mouse carotid arteries, and such effect was attenuated in Tlr4mut mice. DF in vitro increased TLR4 expression and activation in human endothelial cells (ECs) and promoted monocyte-EC adhesion, which were inhibited in TLR4-knockdown ECs. Among endogenous TLR4 ligands examined as candidate mediators of DF-induced TLR4 activation, fibronectin containing the extra domain A (FN-EDA) expressed by ECs was increased by DF and was revealed to directly interact with and activate TLR4.

Conclusion
Our findings demonstrate the indispensable role of TLR4 in DF-induced endothelial inflammation and pinpoint FN-EDA as the endogenous TLR4 activator in this scenario. This novel mechanism of vascular inflammation under DF condition may serve as a critical initiating step in atherogenesis.
Is small cusp size a limitation for aortic valve repair?†
Authors: Komiya Tatsuhiko , Shimamoto Takeshi , Nonaka Michihito , Matsuo Takehiko 
Published: February 2019

Abstract

OBJECTIVES
We sought to investigate cusp size limitations for valve repair in patients with aortic regurgitation (AR).

METHODS
Preoperative computed tomography was performed in 105 patients. Cusp geometric height (GH) and annulus size were measured. Mean patient age was 60.7 ± 13.7 years. Mean GH of 3 cusps was used in the analysis. Annulus cusp mismatch was graded using predicted coaptation length. Patients were categorized by mean GH into group S (GH <16 mm; n = 35) or L (GH ≥16 mm; n = 70).

RESULTS
Preoperative mean GH was 17.1 ± 2.3 mm. GH and body height were significantly correlated (r = 0.61). Intraoperative mean GH (18.8 ± 2.2 mm) was larger than preoperative mean GH (P < 0.0001). However, postoperative (17.1 ± 2.0 mm) and preoperative mean GH did not differ. Moderate AR was not present on predischarge echocardiography. Mild AR was observed in 51% and 17% of patients in groups S and L, respectively (P = 0.006). During follow-up, moderate or severe AR was observed in 14% and 10% of patients in groups S and L, respectively (P = 0.74). Two patients in group S required reoperation for a regurgitant valve. Twenty (83%) and 15 (21%) patients in groups S and L, respectively, had severe annulus cusp mismatch before surgery. Annulus cusp mismatch resolved in most patients in group L postoperatively, whereas more than half the patients in group S still had severe mismatch.

CONCLUSIONS
Small cusp size (GH <16 mm) is not necessarily a contraindication in aortic valve repair. However, most patients in this group had annulus cusp mismatch. Root replacement or secure annulus plication is mandatory to correct annulus cusp mismatch.
Cost–utility analysis of minimally invasive surgery for lung cancer: a randomized controlled trial
Authors: Bendixen Morten , Kronborg Christian , Jørgensen Ole Dan , Andersen Claus , Licht Peter Bjørn 
Published: February 2019

AbstractOBJECTIVES:Minimally invasive video-assisted thoracic surgery (VATS) was first introduced in the early 1990s. For decades, numerous non-randomized studies demonstrated advantages of VATS over thoracotomy with lower morbidity and shorter hospital stay, but only recently did a randomized trial document that VATS results in lower pain scores and better quality of life. Opposing arguments for VATS have always been increased costs and concerns about oncological adequacy. In this paper, we aim to investigate the cost-effectiveness of VATS.METHODS:The study was designed as a cost–utility analysis of the first 12 months following surgery and was performed together with a clinical randomized controlled trial of VATS versus thoracotomy for lobectomy of stage 1 lung cancer during a 6-year period (2008–2014). All health-related expenses were retrieved from a national database (Statistics Denmark) including hospital readmissions, outpatient clinic visits, prescription medication costs, consultations with general practitioners, specialists, physiotherapists, psychologists and chiropractors.RESULTS:One hundred and three VATS patients and 103 thoracotomy patients were randomized. Mean costs per patient operated by VATS were 103 108 Danish Kroner (Dkr) (€13 818) and 134 945 Dkr (€18 085) by thoracotomy, making the costs for VATS 31 837 Dkr (€4267) lower than thoracotomy (P < 0.001). The difference in quality-adjusted life years gained over 52 weeks of follow-up was 0.021 (P = 0.048, 95% confidence interval −0.04 to −0.00015) in favour of VATS. The median duration of the surgical procedure was shorter after thoracotomy (79 vs 100 min; P < 0.001). The mean length of hospitalization was shorter following VATS (4.8 vs 6.7 days; P = 0.027). The use of other resources was not significantly different between groups. The costs of resources were lower in the VATS group. This difference was primarily due to reduced costs of readmissions (VATS 29 247 Dkr vs thoracotomy 51 734 Dkr; P < 0.001) and costs of outpatient visits (VATS 51 412 Dkr vs thoracotomy 61 575 Dkr; P = 0.012).CONCLUSIONS:VATS is a cost-effective alternative to thoracotomy following lobectomy for stage 1 lung cancer. Economical outcomes as measured by quality-adjusted life years were significantly better and overall costs were lower for VATS.Clinical Trial Registration Number:NCT01278888.
The Effects of Recognition of Foreign Education for Newly Arrived Immigrants
Authors: Tibajev Andrey , Hellgren Carina 
Published: February 2019

AbstractWe analyze the effects of formal recognition of foreign higher education on employment probabilities and earnings for newly arrived immigrants in Sweden. Prior research has found that immigrants have lower returns on education if it was acquired in the country of origin than if it was acquired in the host country. One reason for this is that foreign credentials work poorly as productivity signals and risk-averse employers avoid employees with credentials they do not fully understand. A formal recognition statement can help overcome this problem by providing credible information about the foreign education, thus reducing uncertainty. Data consists of immigrants who, within the first ten years of residence in Sweden, had their foreign degree formally recognized during 2007–2011. Using fixed effects regressions, we estimate the treatment effect of official recognition to be 4.4 percentage points higher probability of being employed, and 13.9 log points higher wage for those with employment. We also find considerable treatment effect heterogeneity across subcategories of immigrants from different regions of origin, with different reasons for immigration and who obtained recognition during different economic conditions. Our conclusions are that the mechanism of employer uncertainty is real, and that recognition does reduce it. But as the signal of foreign education becomes better, other mechanisms such as human capital transferability problems and quality differences, and the ability to use foreign human capital, become more salient, leading to heterogeneous effects.
Increase of internalized mental health symptoms among adolescents during the last three decades
Authors: Blomqvist Ida , Henje Blom Eva , Hägglöf Bruno , Hammarström Anne 
Published: February 2019

AbstractBackgroundPrevious studies suggest an overall increase of adolescent mental health symptoms globally since the 1980s until today, especially an increase of internalizing symptoms in girls. Due to methodological limitations of these studies, further studies are warranted to obtain a more solid knowledgebase.MethodsThis study was cross-sectional and compared two separate but geographically identical groups of adolescents in a middle-sized industrial municipality in Northern Sweden at two time-points [(i) 1981, n = 1083, (505 girls, 577 boys), response rate 99.7%; (ii) 2014, n = 682, (338 girls, 344 boys), response rate 98.3%]. All students in their last year of compulsory school were included. The same self-report questionnaire, consisting of four sub-scales (functional somatic-, anxiety-, depressive symptoms and conduct problems), was used at both occasions. Data were analyzed with descriptive statistics, two-way ANOVA and general linear model.ResultsSymptoms of anxiety and depression and functional somatic symptoms, increased among both boys and girls from 1981 until 2014 (P < 0.001 for all subscales), and the increase of these symptoms was higher in girls. Conduct problems were significantly higher in boys in 1981 and decreased over time so that in 2014 there was no longer a significant difference between boys and girls regarding conduct problems (P = 0.286).ConclusionIn this population-based study spanning over 30 years, both girls and boys showed increasing internalizing problems, while conduct problems decreased. To halt this trend, we need a deeper understanding of the impact of the major societal changes that have occurred during the last three decades.
Development and genomic elucidation of hybrid yeast with improved glucose-xylose co-fermentation at high temperature
Authors: Lin Yuping , Cai Yanqing , Guo Yufeng , Li Xin , Qi Xianni , Qi Qi , Wang Qinhong 
Published: February 2019

ABSTRACT
Enhanced capability of co-fermenting glucose and xylose at high temperature is highly desirable for yeast application in second-generation bioethanol production. Here, we obtained hybrid strains with improved glucose-xylose co-fermentation properties at high temperature by combining genome shuffling and adaptive evolution. Genome resequencing of these strains suggested predominantly inherited genetic information from one parental strain Spathaspora passalidarum SP rather than the other parental strain Saccharomyces cerevisiae ScY01, possibly due to that the CUG codon system of S. passalidarum might have systematically eliminated most of the functional proteins from S. cerevisiae through misfolding. Compared to SP, one-copy loss of a 146-kb fragment was found in the hybrid strain and regained after being evolved for a while, whereas one-copy loss of an 11-kb fragment was only found after being evolved for a longer time. Besides, the genes affected by nonsynonymous variants were also identified, especially the mutation S540F in the endoplasmic reticulum chaperon Kar2. Structural prediction indicated that S540F might change the substrate binding activity of Kar2, and thus play a role in preventing protein aggregation in yeast at high temperature. Our results illustrated genomic alterations during this process and revealed some genomic factors that might be involved to determine yeast thermotolerance.
FSH3 mediated cell death is dependent on NUC1 in Saccharomyces cerevisiae
Authors: Gowsalya Ramachandran , Ravi Chidambaram , Kannan Muthukumar , Nachiappan Vasanthi 
Published: February 2019

ABSTRACT
Family of Serine Hydrolases (FSH) members FSH1, FSH2 and FSH3 in Saccharomyces cerevisiae share conserved sequences with the human candidate tumor suppressor OVCA2. In this study, hydrogen peroxide (H2O2) exposure increased the expression of both mRNA and protein levels of FSH3 in wild-type (WT) yeast cells. The deletion of FSH3 improved the yeast growth rate under H2O2-induction as compared to WT control cells. The overexpression of FSH3 in WT yeast cells caused an apoptotic phenotype, including accumulation of reaction oxygen species, decreased cell viability and cell death. The double deletions fsh1Δ fsh2Δ, fsh1Δ fsh3Δ and fsh2Δ fsh3Δ displayed increased growth compared to WT cells. However, the overexpression of FSH3 effectively inhibited cell growth in all double deletions. Moreover, the overexpression of FSH3 in cells lacking NUC1 did not cause any growth defect in the presence or absence of H2O2. Our results suggest that FSH3 induced apoptosis of yeast in a NUC1 dependent manner.