bluuebunny/crossref_metadata_2025_split huggingface dataset:
Foster thy young: Enhanced prediction of orphan genes in assembled genomes
Authors: Li Jing , Singh Urminder , Bhandary Priyanka , Campbell Jacqueline , Arendsee Zebulun , Seetharam Arun S. , Wurtele Eve Syrkin 
Published: December 2019

ABSTRACTProteins encoded by newly-emerged genes (“orphan genes”) share no sequence similarity with proteins in any other species. They provide organisms with a reservoir of genetic elements to quickly respond to changing selection pressures. Here, we systematically assess the ability of five gene annotation pipelines to accurately predict genes in genomes according to phylostratal origin. BRAKER and MAKER are existing, popularab initiotools that infer gene structures by machine learning. Direct Inference is an evidence-based pipeline we developed to predict gene structures from alignments of RNA-Seq data. The BIND pipeline integratesab initiopredictions of BRAKER and Direct inference; MIND combines Direct Inference and MAKER predictions. We use highly-curated Arabidopsis and yeast annotations as gold-standard benchmarks, and cross-validate in rice. Each pipeline under-predicts orphan genes (as few as 11 percent, under one prediction scenario). Increasing RNA-Seq diversity greatly improves prediction efficacy. The combined methods (BIND and MIND) yield best predictions overall, BIND identifying 68% of annotated orphan genes and 99% of ancient genes in Arabidopsis. We provide a light weight, flexible, reproducible solution to improve gene prediction.
Molecular basis of differential parasitism between non-encapsulated and encapsulatedTrichinellarevealed by a high-quality genome assembly
Authors: Liu Xiaolei , Feng Yayan , Bai Xue , Wang Xuelin , Qin Rui , Tang Bin , Yu Xinxin , Yang Yong , Liu Mingyuan , Gao Fei 
Published: December 2019

AbstractUnderstanding roles of repetitive sequences in genomes of parasites could offer insights into their evolution, speciation, and parasitism. As a unique intracellular nematode,Trichinellaconsists of two clades, encapsulated and non-encapsulated. Genomic correlation to the distinct differences between the two clades is still unclear. Here we report an annotated draft reference genome of non-encapsulatedTrichinella,T. pseudospiralis, and performed comparative analyses with encapsulatedT. spiralis. Genome analysis revealed that, duringTrichinellaevolution, repetitive sequence insertions played an important role in gene family expansion in synergy with DNA methylation, especially for the DNase II members of the phospholipase D superfamily and Glutathione S-transferases. We further identify the genomic and epigenomic regulation of excretory/secretory products in relation to differences in parasitism, pathology and immunology between the two cladesTrichinella. The present study provided a foundation for further elucidation of mechanism of nurse cell formation and immunoevasion as well as identification of phamarcological and diagnostic targets of trichinellosis.
MACREL: antimicrobial peptide screening in genomes and metagenomes
Authors: Santos-Junior Célio Dias , Pan Shaojun , Zhao Xing-Ming , Coelho Luis Pedro 
Published: December 2019

ABSTRACTMotivationAntimicrobial peptides (AMPs) have the potential to tackle multidrug-resistant pathogens in both clinical and non-clinical contexts. The recent growth in the availability of genomes and metagenomes provides an opportunity forin silicoprediction of novel AMP molecules. However, due to the small size of these peptides, standard gene prospection methods cannot be applied in this domain and alternative approaches are necessary. In particular, standard gene prediction methods have low precision for short peptides, and functional classification by homology results in low recall.ResultsHere, we present Macrel (for metagenomic AMP classification and retrieval), which is an end-to-end pipeline for the prospection of high-quality AMP candidates from (meta)genomes. For this, we introduce a novel set of 22 peptide features. These were used to build classifiers which perform similarly to the state-of-the-art in the prediction of both antimicrobial and hemolytic activity of peptides, but with enhanced precision (using standard benchmarks as well as a stricter testing regime). We demonstrate that Macrel recovers high-quality AMP candidates using realistic simulations and real data.AvailabilityMacrel is implemented in Python 3. It is available as open source athttps://github.com/BigDataBiology/macreland through bioconda. Classification of peptides or prediction of AMPs in contigs can also be performed on the webserver:http://big-data-biology.org/software/macrel.
Different strategies to manageVarroa jacobsoniandTropilaelaps mercedesaein Papua New Guinea
Authors: Roberts John MK , Schouten Cooper N , Sengere Reuben W , Jave John , Lloyd David 
Published: December 2019

AbstractApiculture in the Pacific nation of Papua New Guinea (PNG) is under significant pressure from emerging parasitic mites,Varroa jacobsoniandTropilaelaps mercedesae. While numerous mite control products exist, beekeepers in Papua New Guinea have limited access and resources for these products and their effectiveness under local conditions is untested. Here we determined the effectiveness of two brood manipulation strategies – queen caging and queen removal – for managingV. jacobsoniandT. mercedesaein comparison to the chemical miticide Bayvarol®. Our results found Bayvarol®was the most effective control strategy forV. jacobsoni, maintaining high efficacy (>90%) over four months with significantly reduced mean numbers ofV. jacobsonicompared to untreated control hives. In contrast, mean numbers ofT. mercedesaewere significantly reduced by the brood manipulation strategies over two months, but not by Bayvarol®compared to the controls. These results highlight that a combination of different strategies is likely needed to effectively manage both mite pests in PNG. We discuss how these strategies could be optimised and adopted to achieve better mite management for PNG beekeepers.
UHRF1-SRA recognizes symmetric non-CG methylated DNA through dual-flip out of 5-methyl cytosines
Authors: Nakarakanti Naveen Kumar , Abhishek Suman , Deeksha Waghela , Rajakumara Eerappa 
Published: December 2019

AbstractNon-CG DNA methylation (non-mCG) is enriched in the genome of brain neurons and germline cells. Non-mCG is differentially distributed on neuronal X-chromosome in males and females. Accumulation of non-mCG during postnatal brain development correlates with reduced gene expression and inactivation of distal regulatory elements, and allele specific gene regulation. Recently, UHRF1 has been found to contribute tode novonon-CG methylation, however, whether UHRF1 could recognize non-mCG is not known. Here, we have demonstrated through calorimetric measurements that the SRA domain of UHRF1 can recognize mCH and fully-mCHG, types of non-mCG. Furthermore, our ITC binding analyses with methylated CG DNA (mCG) revealed 6-fold decrease in binding affinity for fully-mCG compared to hemi-mCG and, despite symmetrical 5mCs, stoichiometry of 1:1 for UHRF1 SRA binding to fully-mCG indicates UHRF1 may not form stable complex with fully-mCG DNA. In contrast, UHRF1 SRA recognizes fully-mCHG with a stoichiometry of 2:1 protein to DNA duplex, and has tighter binding compared to fully-mCG. Crystal structure of UHRF1 SRA bound to 5mC containing DNA in fully-mCHG context revealed dual flip-out mechanism of 5mC recognition. Altogether, this study indicates that UHRF1 SRA also recognizes non-mCG DNA, besides known hemi-mCG DNA and exhibits contrasting mechanisms for hemi-mCG and fully-mCHG DNA recognition. These findings may open a new window to investigate the biological function of non-CG methylation recognition by the UHRF1.
A high quality reference genome for the fish pathogenStreptococcus iniae
Authors: Alsheikh-Hussain Areej S. , Ben Zakour Nouri L. , Forde Brian M. , Silayeva Oleksandra , Barnes Andrew C. , Beatson Scott A. 
Published: December 2019

AbstractFish mortality caused byStreptococcus iniaeis a major economic problem in fish aquaculture in warm and temperate regions globally. There is also risk of zoonotic infection byS. iniaethrough handling of contaminated fish. In this study, we present the complete genome sequence ofS. iniaestrain QMA0248, isolated from farmed barramundi in South Australia. The 2.12 Mb genome ofS. iniaeQMA0248 carries a 32 Kb prophage, a 12 Kb genomic island, and 92 discrete insertion sequence (IS) elements. These include 9 novel IS types that belong mostly to the IS3family. Comparative and phylogenetic analysis betweenS. iniaeQMA0248 and publicly available completeS. iniaegenomes revealed discrepancies that are likely due to misassembly in the genomes of isolates ISET0901 and ISNO. We also determined by long-range PCR that a tandem duplication of an rRNA region in the PacBio assembly of QMA0248 was an assembly error. A similar rRNA duplication in the PacBio genome ofS. iniae89353 may also be a misassembly. Our study not only highlights assembly problems in existing genomes, but provides a high quality reference genome forS. iniaeQMA0248, including manually curated mobile genetic elements, that will assist futureS. iniaecomparative genomic and evolutionary studies.
A novel virus alters gene expression and vacuolar morphology inMalasseziacells and induces a TLR3-mediated inflammatory immune response
Authors: Park Minji , Cho Yong-Joon , Kim Donggyu , Yang Chul-Su , Lee Shi Mun , Dawson Thomas L. , Nakamizo Satoshi , Kabashima Kenji , Lee Yang Won , Jung Won Hee 
Published: December 2019

AbstractMost fungal viruses have been identified in plant pathogens, whereas the presence of viral particles in human pathogenic fungi is less well studied. In the present study, we observed extrachromosomal double-stranded RNA (dsRNA) segments in various clinical isolates ofMalasseziaspecies.Malasseziais the most dominant fungal genus on the human skin surface, and species in this group are considered etiological factors of various skin diseases including dandruff, seborrheic dermatitis, and atopic dermatitis. We identified novel dsRNA segments, and our sequencing results revealed that the virus, named MrV40, belongs to the Totiviridae family and contains an additional satellite dsRNA segment encoding a novel protein. The transcriptome of virus-infectedMalassezia restrictacells was compared to that of virus-cured cells, and the results showed that transcripts involved in ribosomal biosynthesis were downregulated and those involved in energy production and programmed cell death were upregulated. Moreover, transmission electron microscopy revealed significantly larger vacuoles in virus-infectedM. restrictacells, indicating that MrV40 infection dramatically alteredM. restrictaphysiology. Our analysis also revealed that viral nucleic acid from MrV40 induced a TLR3-mediated inflammatory immune response in bone marrow-derived dendritic cells, suggesting that a viral element contributes to the pathogenicity ofMalassezia.ImportanceMalasseziais the most dominant fungal genus on the human skin surface and is associated with various skin diseases including dandruff and seborrheic dermatitis. AmongMalasseziaspecies,Malassezia restrictais the most widely observed species on the human skin. In the current study, we identified a novel dsRNA virus, named MrV40, inM. restrictaand characterized the sequence and structure of the viral genome along with an independent satellite dsRNA viral segment. Moreover, expression of genes involved in ribosomal synthesis and programmed cell death was altered, indicating that virus infection affected the physiology of the fungal host cells. Our data also showed that the viral nucleic acid from MrV40 induces a TLR3-mediated inflammatory immune response in bone marrow-derived dendritic cells, indicating that a viral element likely contributes to the pathogenicity ofMalassezia. This is the first study to identify and characterize a novel mycovirus inMalassezia.
Using force data to self-pace an instrumented treadmill and measure self-selected walking speed
Authors: Song Seungmoon , Choi HoJung , Collins Steven H. 
Published: December 2019

AbstractBackgroundSelf-selected speed is an important functional index of walking. A self-pacing controller that reliably matches walking speed without additional hardware can be useful for measuring self-selected speed in a treadmill-based laboratory.MethodsWe adapted a previously proposed self-pacing controller for force-instrumented treadmills and validated its use for measuring self-selected speeds. We first evaluated the controller’s estimation of subject speed and position from the force-plates by comparing it to those from motion capture data. We then compared five tests of self-selected speed. Ten healthy adults completed a standard 10-meter walk test, a 150-meter walk test, a commonly used manual treadmill speed selection test, a two-minute self-paced treadmill test, and a 150-meter self-paced treadmill test. In each case, subjects were instructed to walk at or select their comfortable speed. We also assessed the time taken for a trial and a survey on comfort and ease of choosing a speed in all the tests.ResultsThe self-pacing algorithm estimated subject speed and position accurately, with root mean square differences compared to motion capture of 0.023 m s−1and 0.014 m, respectively. Self-selected speeds from both self-paced treadmill tests correlated well with those from the 10-meter walk test (R> 0.93,p< 1 × 10−13). Subjects walked slower on average in the self-paced treadmill tests (1.23 ± 0.27 m s−1) than in the 10-meter walk test (1.32 ± 0.18 m s−1) but the speed differences within subjects were consistent. These correlations and walking speeds are comparable to those from the manual treadmill speed selection test (R= 0.89,p= 3 × 10−11; 1.18 ± 0.24 m s−1). Comfort and ease of speed selection were similar in the self-paced tests and the manual speed selection test, but the self-paced tests required only about a third of the time to complete. Our results demonstrate that these self-paced treadmill tests can be a strong alternative to the commonly used manual treadmill speed selection test.ConclusionsThe self-paced force-instrumented treadmill well adapts to subject walking speed and reliably measures self-selected walking speeds. We provide the self-pacing software to facilitate use by gait researchers and clinicians.
The Ty1 integrase nuclear localization signal is necessary and sufficient for retrotransposon targeting to tRNA genes
Authors: Asif-Laidin Amna , Conesa Christine , Bonnet Amandine , Grison Camille , Adhya Indranil , Menouni Rachid , Fayol Hélène , Palmic Noé , Acker Joël , Lesage Pascale 
Published: December 2019

SUMMARYIntegration of transposable elements into the genome is mutagenic. Mechanisms that target integration into relatively safe locations and minimize deleterious consequences for cell fitness have emerged during evolution. In budding yeast, the integration of the Ty1 LTR retrotransposon upstream of RNA polymerase III (Pol III)-transcribed genes requires the interaction between the AC40 subunit of Pol III and Ty1 integrase (IN1). Here we show that the IN1-AC40 interaction involves a short linker sequence in the bipartite nuclear localization signal (bNLS) of IN1. Mutations in this sequence do not impact the frequency of Ty1 retromobility, instead they decrease the recruitment of IN1 to Pol III-transcribed genes and the subsequent integration of Ty1 at these loci. The replacement of Ty5 retrotransposon targeting sequence by the IN1 bNLS induces Ty5 integration into Pol III-transcribed genes. Therefore, the IN1 bNLS is both necessary and sufficient to confer integration site specificity on Ty1 and Ty5 retrotransposons.
Imputed Genomic Data Reveals a Moderate Effect of Low Frequency Variants to the Heritability of Complex Human Traits
Authors: Hartman Kevin A , Rashkin Sara R , Witte John S , Hernandez Ryan D 
Published: December 2019

AbstractThe genetic architecture of complex human traits remains largely unknown. The distribution of heritability across the minor allele frequency (MAF) spectrum for a trait will be a function of the MAF of its causal variants and their effect sizes. Assumptions about these relationships underpin the tools used to estimate heritability. We examine the performance of two widely used tools, Haseman-Elston (HE) Regression and genomic-relatedness-based restricted maximum-likelihood (GREML). Our simulations show that HE is less biased than GREML under a wide variety of models and that the estimated standard error for HE tends to be substantially overestimated. We then applied HE Regression to infer the heritability of 72 quantitative biomedical traits from up to 50,000 individuals with genotype and imputation data from the UK Biobank. We found that adding each individuals’ geolocation as covariates corrected for population stratification that could not be accounted for by principal components alone (particularly for rare variants). The biomedical traits we analyzed had an average heritability of 0.27, with low frequency variants (MAF≤0.05) explaining an average of 47.7% of the total heritability (and lower frequency variants with MAF≤0.02 explaining a majority of our increased heritability over previous estimates). Variants in regions of low linkage disequilibrium (LD) accounted for 3.3-fold more heritability than the variants in regions of high LD, an effect primarily driven by low frequency variants. These findings suggest a moderate action of negative selection on the causal variants of these traits.
A MUC5B polymorphism associated with Idiopathic Pulmonary Fibrosis mediates overexpression through decreased CpG methylation and C/EBPβ transcriptional activation
Authors: Armesto-Jimenez Amaranta U. , Arason Ari J. , Stefansson Olafur A. , Gudmundsson Gunnar , Gudjonsson Thorarinn , Magnusson Magnus K. 
Published: December 2019

AbstractIdiopathic pulmonary fibrosis is a progressive and fatal lung disease of unknown aetiology. The strongest genetic risk factor associated with IPF development is aMUC5Bpromoter polymorphism (rs35705950). However, the mechanism underlying its effects remains unknown. In this study we have focused on the molecular consequences of the polymorphism on the regulation of MUC5B expression. We have identified a combined mechanism involving both methylation and direct transcriptional regulation mediated by the polymorphic variant on MUC5B overexpression. Our results demonstrate that the minor allele (T) associated withrs35705950disturbs a DNA methylation site, directly increasing MUC5B expression. Furthermore, this same variant also creates a novel binding site for the transcription factor C/EBPβ leading to transcriptional activation ofMUC5B. Our findings provide a novel insight into the regulatory effects of the IPF risk allele,rs35705950and identifies C/EBPβ as an important regulatory factor in the development of IPF.
Multi-genomic analysis of the Cation Diffusion Facilitator transporters from algae
Authors: Ibuot Aniefon , Dean Andrew P. , Pittman Jon K. 
Published: December 2019

AbstractMetal transport processes are relatively poorly understood in algae in comparison to higher plants and other eukaryotes. A screen of genomes from 33 taxonomically diverse algal species was conducted to identify members of the Cation Diffusion Facilitator (CDF) family of metal ion transporter. All algal genomes contained at least one CDF gene with four species having >10 CDF genes (median of 5 genes per genome), further confirming that this is a ubiquitous gene family. Phylogenetic analysis suggested a CDF gene organisation of five groups, which includes Zn-CDF, Fe/Zn-CDF and Mn-CDF groups, consistent with previous phylogenetic analyses, and two functionally undefined groups. One of these undefined groups was algal specific although excluded chlorophyte and rhodophyte sequences. The majority of sequences (22 out of 26 sequences) from this group had a putative ion binding site motif within transmembrane domain 2 and 5 that was distinct from other CDF proteins, such that alanine or serine replaced the conserved histidine residue. The phylogenetic grouping was supported by sequence cluster analysis. Yeast heterologous expression of CDF proteins from Chlamydomonas reinhardtii indicated Zn2+ and Co2+ transport function by CrMTP1, and Mn2+ transport function by CrMTP2, CrMTP3 and CrMTP4, which validated the phylogenetic prediction. However, the Mn-CDF protein CrMTP3 was also able to provide zinc and cobalt tolerance to the Zn- and Co-sensitive zrc1cot1 yeast strain. There is wide diversity of CDF transporters within the algae lineage, and some of these genes may be attractive targets for future applications of metal content engineering in plants or microorganisms.
Ubiquitin Links Smoothened to Intraflagellar Transport to Regulate Hedgehog Signaling
Authors: Desai Paurav B. , Stuck Michael W. , Lv Bo , Pazour Gregory J. 
Published: December 2019

AbstractIn the absence of hedgehog ligand, patched-1 (Ptch1) localizes to cilia and prevents ciliary accumulation and activation of smoothened (Smo). Upon ligand binding, Ptch1 is removed from cilia, Smo is derepressed and accumulates in cilia where it activates signaling. The mechanisms regulating these dynamic movements are not well understood but defects in intraflagellar transport components including Ift27 and the BBSome cause Smo to accumulate in cilia without pathway activation. We find that in the absence of ligand-induced pathway activation, Smo is ubiquitinated and removed from cilia, and this process is dependent on Ift27 and BBSome components. Activation of hedgehog signaling decreases Smo ubiquitination, and ciliary removal, resulting in its accumulation. Blocking ubiquitination of Smo by an E1 ligase inhibitor or by mutating two lysine residues in intracellular loop three cause Smo to aberrantly accumulate in cilia without pathway activation. These data provide a mechanism to control Smo’s ciliary level during hedgehog signaling by regulating the ubiquitination state of the receptor.SummaryHedgehog signaling involves the dynamic movement of receptors and effectors in and out of cilia. We find that the dynamics of Smo is regulated by ubiquitination, which regulates its interaction with the intraflagellar transport system to control ciliary levels of this receptor.
Identification of Six novel missense single nucleotide polymorphisms in the MAOA gene predisposing to aggressive behavior. Bioinformatics study
Authors: Abdelmoenim Abdelrahman H. , Mustafa Mujahed I. , Murshed Naseem S. , Omer Nosiba S. , Mohammed Alaa I. , Abdulmajed Rania A. , Dawoud Enas dk. , Makhawi Abdelrafie M. 
Published: December 2019

AbstractBackgroundAn astonishing observation is that aggressive behavior is actually a highly heritable. Recent experimental work and behavior research has linked individual variation in a functional polymorphism of the monoamine oxidase-A gene (MAOA) to the occurrence of anger-driven aggression. Aggressive antisocial and violent behavior has become a regularly debated topic in the scientific community; the impending question is what is the source of aggressive behavior, is it genetic or environmental or is it just an individual choice. This study aims to analyses the SNPs found in MAOA gene and it is possible association to aggressive behavior.MethodVarious bioinformatics software (SIFT, PolyPhen-2, PROVEAN, SNAP22, SNP&GO and PMut)is used to analyses the SNPs within the MAOA gene to study the structural and functional implication on the associated protein, which is further clarified using chimera software. Then gene-gene interaction is studied with geneMANIA software. Furthermore, conservation and annotation studies were done through the ConSurf server and Variant Effect Predictor (VEP) respectively.ResultSix missense SNPs were found to affect the structural and functional prospect of MAOA protein.ConclusionGenetic mutation within MAOA is likely to be associated with aggressive behavior; this will enrich future management and screening possibilities for this behavior.