bluuebunny/crossref_metadata_2025 huggingface dataset:
The Neutrophil-to-Lymphocyte Ratio as a Prognostic Indicator in Head and Neck Cancer: A Systematic Review and Meta-Analysis
Authors: Tham Tristan , Bardash Yonatan , Herman Saori Wendy , Costantino Peter D.
Published: November 2017

Background

The aim of this systematic review and meta-analysis was to investigate the relationship between the Neutrophil-to-Lymphocyte Ratio (NLR) and prognosis in HNC.

Methods

Studies were identified from Pubmed, Embase, Scopus, and the Cochrane Library. A systematic review and meta-analysis were performed to generate the pooled hazard ratios (HR) for overall survival (OS), disease free survival (DFS), and progression free survival (PFS).

Results

Our analysis combined the results of over 6770 patients in 26 cohorts (25 studies). The pooled data demonstrated that an elevated NLR significantly predicted poorer OS, DFS, and PFS. Heterogeneity was found for OS, PFS, and marginally for DFS. Subgroup analysis in OS demonstrated that elevated NLR remained an indicator of poor prognosis.

Conclusions

Elevated pretreatment NLR is a prognostic marker for HNC. It represents a simple and easily obtained marker that could be used to stratify groups of high-risk patients that might benefit from adjuvant therapy.
Venous Thromboembolism Risk in Head and Neck Cancer: Significance of the Preoperative Platelet-to-Lymphocyte Ratio
Authors: Tham Tristan , Rahman Lauren , Persaud Christina , Costantino Peter
Published: November 2017

Abstract (250 limit)

Objective

We aimed to investigate the association between the preoperative platelet-to-lymphocyte ratio (PLR) and venous thromboembolism (VTE) in head and neck cancer (HNC) patients undergoing major surgery.

Study Design

Retrospective cohort study

Setting

Academic tertiary hospital from 2011 to 2017

Subjects and Methods

Patients with confirmed HNC undergoing major surgery were included in this study. The preoperative PLR was recorded for all patients. Known VTE risk factors, including age, sex, smoking, BMI, prior VTE, and anticoagulation were also recorded. Risk factors were screened in univariate analysis using Wilcoxon’s rank sum test and χ2 test (Bonferroni corrected). Significant covariates were subsequently included in a multivariate regression model. Bootstrap techniques were used to obtain credible confidence intervals (CI).

Results

There were 306 patients enrolled with 7 cases of VTE (6 DVTs and 1 PE). On univariate analysis, length of stay (p = 0.0026), length of surgery (p = 0.0029), and PLR (p = 0.0002) were founded to have significant associations with VTE. A Receiver Operator Characteristic (ROC) curve was constructed, that yielded an AUROC of 0.905 (95% CI: 0.82 - 0.98). Using an optimized cutoff, the multivariate model showed that length of surgery (β 95% CI: 0.0001 - 0.0006; p = 0.0056), and PLR (β 95% CI: 5.3256 - 5.3868; p < 0.0001) were significant independent predictors of VTE.

Conclusion

This exploratory pilot study has shown that PLR offers a potentially accurate risk stratification measure as an adjunct to current tools in VTE risk prediction, without additional cost to health systems.

Oral Presentation

This data was presented as an oral presentation at the Annual American Academy of Otolaryngology – Head and Neck Surgery (AAO-HNSF) Meeting, 13th September 2017
Analysis of ancient human mitochondrial DNA from Verteba Cave, Ukraine: insights into the origins and expansions of the Late Neolithic-Chalcolithic Cututeni-Tripolye Culture
Authors: Wakabayashi Ken , Schmidt Ryan W. , Gakuhari Takashi , Koganebuchi Kae , Ogawa Motoyuki , Karsten Jordan K. , Sokhatsky Mykhailo , Oota Hiroki
Published: November 2017

Background

The Eneolithic (~ 5,500 yrBP) site of Verteba Cave in Western Ukraine contains the largest collection of human skeletal remains associated with the archaeological Cucuteni-Tripolye Culture. Their subsistence economy is based largely on agro-pastoralism and had some of the largest and most dense settlement sites during the Middle Neolithic in all of Europe. To help understand the evolutionary history of the Tripolye people, we performed mtDNA analyses on ancient human remains excavated from several chambers within the cave.

Results

Burials at Verteba Cave are largely commingled and secondary in nature. A total of 68 individual bone specimens were analyzed. Most of these specimens were found in association with well-defined Tripolye artifacts. We determined 28 mtDNA D-Loop (368 bp) sequences and defined 8 sequence types, belonging to haplogroups H, HV, W, K, and T. These results do not suggest continuity with local pre-Eneolithic peoples, but rather complete population replacement. We constructed maximum parsimonious networks from the data and generated population genetic statistics. Nucleotide diversity (π) is low among all sequence types and our network analysis indicates highly similar mtDNA sequence types for samples in chamber G3. Using different sample sizes due to the uncertainly in number of individuals (11, 28, or 15), we found Tajima’s D statistic to vary. When all sequence types are included (11 or 28), we do not find a trend for demographic expansion (negative but not significantly different from zero); however, when only samples from Site 7 (peak occupation) are included, we find a significantly negative value, indicative of demographic expansion.

Conclusions

Our results suggest individuals buried at Verteba Cave had overall low mtDNA diversity, most likely due to increased conflict among sedentary farmers and nomadic pastoralists to the East and North. Early Farmers tend to show demographic expansion. We find different signatures of demographic expansion for the Tripolye people that may be caused by existing population structure or the spatiotemporal nature of ancient data. Regardless, peoples of the Tripolye Culture are more closely related to early European farmers and lack genetic continuity with Mesolithic hunter-gatherers or pre-Eneolithic groups in Ukraine.
Tn5Prime, a Tn5 based 5’ Capture Method for Single Cell RNA-seq
Authors: Cole Charles , Byrne Ashley , Beaudin Anna E. , Forsberg E. Camilla , Vollmers Christopher
Published: November 2017

RNA-seq is a powerful technique to investigate and quantify entire transcriptomes. Recent advances in the field have made it possible to explore the transcriptomes of single cells. However, most widely used RNA-seq protocols fail to provide crucial information regarding transcription start sites. Here we present a protocol, Tn5Prime, that takes advantage of the Tn5 transposase based Smartseq2 protocol to create RNA-seq libraries that capture the 5’ end of transcripts. The Tn5Prime method dramatically streamlines the 5’ capture process and is both cost effective and reliable. By applying Tn5Prime to bulk RNA and single cell samples we were able to define transcription start sites as well as quantify transcriptomes at high accuracy and reproducibility. Additionally, similar to 3’ end based high-throughput methods like Drop-Seq and 10X Genomics Chromium, the 5’ capture Tn5Prime method allows the introduction of cellular identifiers during reverse transcription, simplifying the analysis of large numbers of single cells. In contrast to 3’ end based methods, Tn5Prime also enables the assembly of the variable 5’ ends of antibody sequences present in single B-cell data. Therefore, Tn5Prime presents a robust tool for both basic and applied research into the adaptive immune system and beyond.
SgTiler: a fast method to design tiling sgRNAs for CRISPR/Cas9 mediated screening
Authors: Ahmed Musaddeque , He Housheng Hansen
Published: November 2017

Screening of genomic regions of interest using CRISPR/Cas9 is getting increasingly popular. The system requires designing of single guide RNAs (sgRNAs) that can efficiently guide the Cas9 endonuclease to the targeted region with minimal off-target effects. Tiling sgRNAs is the most effective way to perturb regulatory regions, such as promoters and enhancers. sgTiler is the first tool that provides a fast method for designing tiling sgRNAs.

Availability and Implementation

sgTiler is a command line tool that requires only one command to execute. Its source code is freely available on the web at https://github.com/HansenHeLab/sgTiler. sgTiler is implemented in Python and supported on any platform with Python and Bowtie.
Decoding the auditory brain with canonical component analysis
Authors: de Cheveigné Alain , Wong Daniel , Di Liberto Giovanni M. , Hjortkjaer Jens , Slaney Malcolm , Lalor Edmund
Published: November 2017

The relation between a stimulus and the evoked brain response can shed light on perceptual processes within the brain. Signals derived from this relation can also be harnessed to control external devices for Brain Computer Interface (BCI) appli-cations. While the classic event-related potential (ERP) is appropriate for isolated stimuli, more sophisticated “decoding” strategies are needed to address continuous stimuli such as speech, music or environmental sounds. Here we describe an approach based on Canonical Correlation Analysis (CCA) that finds the optimal transform to apply to both the stimulus and the response to reveal correlations between the two. Compared to prior methods based on forward or backward models for stimulus-response mapping, CCA finds significantly higher correlation scores, thus providing increased sensitivity to relatively small effects, and supports classifier schemes that yield higher classification scores. CCA strips the brain response of variance unrelated to the stimulus, and the stimulus representation of variance that does not affect the response, and thus improves observations of the relation between stimulus and response.
Transposable Element Expression Predicts Prognosis in Acute Myeloid Leukemia
Authors: Colombo Anthony , Triche Timothy , Ramsingh Giridharan
Published: November 2017

Over half of the human genome is comprised of transposable elements (TE). TE have been implicated in cancer pathogenesis. Despite large-scale studies of the transcriptome in cancer, a comprehensive look at TE expression investigating its relationship to various mutations and its role in predicting prognosis has not been performed. We characterized TE expression in 178 adult acute myeloid leukemia (AML) patients using transcriptome data from The Cancer Genome Atlas (TCGA). We identified significant dysregulation of TE, with distinct patterns of TE expression correlated to specific mutations and distinct coding gene networks. TP53 mutated AML had a unique TE expression signature and was associated with significantly suppressed expression of TE and various classes of non-coding RNA. We identified 17 candidate prognostic TE transcripts that can classify AML subtypes as either high or low risk. These 17 TE were able to further sub-stratify low risk AML (based on mutational profile and coding gene expression) into favorable and unfavorable prognostic categories. The expression signature of the 17 TE was able to predict prognosis in an independent cohort of 284 pediatric AML patients, and was also able to predict time to relapse in an independent dataset of relapsed adult cases. This first comprehensive study of TE expression in AML demonstrates that TE expression can be used as a biomarker for predicting prognosis in AML and also provides novel insights into the biology of TP53 mutated AML. Studies characterizing its role in other cancers are warranted.
Impaired perceptual learning in Fragile X syndrome is mediated by parvalbumin neuron dysfunction in V1 and is reversible
Authors: Goel Anubhuti , Cantu Daniel A. , Guilfoyle Janna , Chaudhari Gunvant R. , Newadkar Aditi , Todisco Barbara , de Alba Diego , Kourdougli Nazim , Schmitt Lauren M. , Pedapati Ernest , Erickson Craig A. , Portera-Cailliau Carlos
Published: November 2017

Atypical sensory processing is a core characteristic in autism spectrum disorders1 that negatively impacts virtually all activities of daily living. Sensory symptoms are predictive of the subsequent appearance of impaired social behavior and other autistic traits2, 3. Thus, a better understanding of the changes in neural circuitry that disrupt perceptual learning in autism could shed light into the mechanistic basis and potential therapeutic avenues for a range of autistic symptoms2. Likewise, the lack of directly comparable behavioral paradigms in both humans and animal models currently limits the translational potential of discoveries in the latter. We adopted a symptom-to-circuit approach to uncover the circuit-level alterations in the Fmr1-/- mouse model of Fragile X syndrome (FXS) that underlie atypical visual discrimination in this disorder4, 5. Using a go/no-go task and in vivo 2-photon calcium imaging in primary visual cortex (V1), we find that impaired discrimination in Fmr1-/- mice correlates with marked deficits in orientation tuning of principal neurons, and a decrease in the activity of parvalbumin (PV) interneurons in V1. Restoring visually evoked activity in PV cells in Fmr1-/- mice with a chemogenetic (DREADD) strategy was sufficient to rescue their behavioral performance. Finally, we found that human subjects with FXS exhibit strikingly similar impairments in visual discrimination as Fmr1-/- mice. We conclude that manipulating orientation tuning in autism could improve visually guided behaviors that are critical for playing sports, driving or judging emotions.
Efficient and accurate detection of splice junctions from RNAseq with Portcullis
Authors: Mapleson Daniel , Venturini Luca , Kaithakottil Gemy , Swarbreck David
Published: November 2017

Next generation sequencing (NGS) technologies enable rapid and cheap genome-wide transcriptome analysis, providing vital information about gene structure, transcript expression and alternative splicing. Key to this is the the accurate identification of exon-exon junctions from RNA sequenced (RNA-seq) reads. A number of RNA-seq aligners capable of splitting reads across these splice junctions (SJs) have been developed, however, it has been shown that while they correctly identify most genuine SJs available in a given sample, they also often produce large numbers of incorrect SJs. Herein we describe the extent of this problem using popular RNA-seq mapping tools, and present a new method, called Portcullis, to rapidly filter false SJs junctions from spliced alignments produced by any RNA-seq mapper capable of creating SAM/BAM files. We show that Portcullis distinguishes between genuine and false positive junctions to a high-degree of accuracy across different species, samples, expression levels, error profiles and read lengths. Portcullis makes efficient use of memory and threading and, to our knowledge, is currently the only SJ prediction tool that reliably scales for use with large RNAseq datasets and large highly fragmented genomes, whilst delivering highly accurate SJs.

Availability

Portcullis is available under the GPLv3 license at: http://maplesond.github.io/portcullis/

Contact

daniel.mapleson@earlham.ac.uk
Phytophthora methylomes modulated by expanded 6mA methyltransferases are associated with adaptive genome regions
Authors: Chen Han , Shu Haidong , Wang Liyuan , Zhang Fan , Li Xi , Ochola Sylvans Ochieng , Mao Fei , Ma Hongyu , Ye Wenwu , Gu Tingting , Jiang Lubing , Wu Yufeng , Wang Yuanchao , Kamoun Sophien , Dong Suomeng
Published: November 2017

Filamentous plant pathogen genomes often display a bipartite architecture with gene sparse, repeat-rich compartments serving as a cradle for adaptive evolution. However, the extent to which this “two-speed” genome architecture is associated with genome-wide epigenetic modifications is unknown. Here, we show that the oomycete plant pathogens Phytophthora infestans and Phytophthora sojae possess functional adenine N6- methylation (6mA) methyltransferases that modulate patterns of 6mA marks across the genome. In contrast, 5-methylcytosine (5mC) could not be detected in the two Phytophthora species. Methylated DNA IP Sequencing (MeDIP-seq) of each species revealed that 6mA is depleted around the transcriptional starting sites (TSS) and is associated with low expressed genes, particularly transposable elements. Remarkably, genes occupying the gene-sparse regions have higher levels of 6mA compared to the remainder of both genomes, possibly implicating the methylome in adaptive evolution of Phytophthora. Among three putative adenine methyltransferases, DAMT1 and DAMT3 displayed robust enzymatic activities. Surprisingly, single knockouts of each of the 6mA methyltransferases in P. sojae significantly reduced in vivo 6mA levels, indicating that the three enzymes are not fully redundant. MeDIP-seq of the damt3 mutant revealed uneven patterns of 6mA methylation across genes, suggesting that PsDAMT3 may have a preference for gene body methylation after the TSS. Our findings provide evidence that 6mA modification is an epigenetic mark of Phytophthora genomes and that complex patterns of 6mA methylation by the expanded 6mA methyltransferases may be associated with adaptive evolution in these important plant pathogens.
Mining the forest: uncovering biological mechanisms by interpreting Random Forests
Authors: de Ruiter Julian , Knijnenburg Theo , de Ridder Jeroen
Published: November 2017

Biological datasets are large and complex. Machine learning models are therefore essential to capture relationships in the data. Unfortunately, the inferred complex models are often difficult to understand and interpretation is limited to a list of features ranked on their importance in the model.

We propose a computational approach, called Foresight, that enables interpretation of the patterns uncovered by Random Forest models trained on biological datasets. Foresight exploits the correlation structure in the data to uncover relevant groups of features and the interactions between them. This facilitates interpretation of the computational model and can provide more detailed insight in the underlying biological relationships than simply ranking features. We demonstrate Foresight on both an artificial dataset and a large gene expression dataset of breast cancer patients. Using the latter dataset we show that our approach retrieves biologically relevant features and provides a rich description of the interactions and correlation structure between these features.
The Block Object Storage Service (bossDB): A Cloud-Native Approach for Petascale Neuroscience Discovery
Authors: Hider Robert , Kleissas Dean M. , Pryor Derek , Gion Timothy , Rodriguez Luis , Matelsky Jordan , Gray-Roncal William , Wester Brock
Published: November 2017

Large volumetric neuroimaging datasets have grown in size over the past ten years from gigabytes to terabytes, with petascale data becoming available and more common over the next few years. Current approaches to store and analyze these emerging datasets are insufficient in their ability to scale in both cost-effectiveness and performance. Additionally, enabling large-scale processing and annotation is critical as these data grow too large for manual inspection. We provide a new cloud-native managed service for large and multi-modal experiments, with support for data ingest, storage, visualization, and sharing through a RESTful Application Programming Interface (API) and web-based user interface. Our project is open source and can be easily and cost-effectively used for a variety of modalities and applications.
A genome-wide association study finds novel genetic associations with broadly-defined headache in UK Biobank (N = 223,773)
Authors: Meng Weihua , Adams Mark J , Hebert Harry L , Deary Ian J , McIntosh Andrew M , Smith Blair H
Published: November 2017

Headache is the most common neurological symptom and a leading cause of years lived with disability. We sought to identify the genetic variants associated with a broadly-defined headache phenotype in 223,773 subjects from the UK Biobank cohort. We defined headache based on a specific question answered by the UK Biobank participants. We performed a genome-wide association study of headache as a single entity, using 74,461 cases and 149,312 controls. We identified 3,343 SNPs which reached the genome-wide significance level of P < 5 × 10−8. The SNPs were located in 28 loci, with the top SNP of rs11172113 in the LRP1 gene having a P value of 4.92 × 10−47. Of the 28 loci, 14 have previously been associated with migraine. Among 14 new loci, rs77804065 with a P value of 5.87 × 10−15 in the LINC02210-CRHR1 gene was the top SNP.

Positive relationships (P < 0.001) between multiple brain tissues and genetic associations were identified through tissue expression analysis, whereas no vascular related tissues showed significant relationships. We identified several significant positive genetic correlations between headache and other psychological traits including neuroticism, depressive symptoms, insomnia, and major depressive disorder.

Our results suggest that brain function is closely related to broadly-defined headache. In addition, we also found that many psychological traits have genetic correlations with headache.
Adaptive dynamics of unstable cancer populations: the canonical equation
Authors: Aguadé-Gorgorió Guim , Solé Ricard
Published: November 2017

In most instances of tumour development, genetic instability plays a role in allowing cancer cell populations to respond to selection barriers, such as physical constraints or immune responses, and rapidly adapt to an always changing environment. Modelling instability is a nontrivial task, since by definition evolving changing instability leads to changes in the underlying landscape. In this paper we explore mathematically a simple version of unstable tumor progression using the formalism of Adaptive Dynamics (AD) where selection and mutation are explicitly coupled. Using a set of basic fitness landscapes, the so called canonical equation for the evolution of genetic instability on a minimal scenario associated to a population of unstable cells is derived. The implications and potential extensions of this model are discussed.
Mesoscale turbulence in the hippocampus
Authors: Sheremet A. , Qin Y. , Kennedy J.P. , Maurer A.P.
Published: November 2017

Wave turbulence provides a powerful stochastic description for nonlinear collective neural activity in the hippocampus. Recent studies that show theta waves propagating across the hippocampus suggest that turbulence is a natural description for collective neural activity. We formulate the fundamental principles of a turbulence model and demonstrate turbulent behavior by analyzing rat hippocampal LFP traces. LFP spectra and bispectra exhibit fundamental turbulent properties: weak nonlinear coupling, energy cascade, and stationary spectra of the Kolmogorov-Zakharov type (power-law). Weak turbulence holds the promise of quantitative physical models of hippocampal dynamics, in the service of understanding the mechanisms of multi-scale integration of brain activity to cognition.
Dynamics of human telomerase recruitment depend on template-telomere base-pairing
Authors: Schmidt Jens C. , Zaug Arthur J. , Kufer Regina , Cech Thomas R.
Published: November 2017

The reverse transcriptase telomerase adds telomeric repeats to chromosome ends to counteract telomere shortening and thereby assures genomic stability in dividing human cells. Key variables in telomere homeostasis are the frequency with which telomerase engages the chromosome end and the number of telomeric repeats it adds during each association event. To study telomere elongation in vivo we have established a live-cell imaging assay to track individual telomerase RNPs in HeLa cells. Using this assay and the drug imetelstat, which is a competitive inhibitor of telomeric DNA binding, we demonstrate that stable association of telomerase with the single-stranded overhang of the chromosome end requires telomerase-DNA base-pairing. Furthermore, we show that telomerase processivity contributes to telomere elongation in vivo. Together, these findings provide new insight into the dynamics of telomerase recruitment and the importance of processivity in maintaining telomere length in human cancer cells.
Polymerase pausing induced by sequence-specific RNA binding protein drives heterochromatin assembly
Authors: Parsa Jahan-Yar , Boudoukha Selim , Burke Jordan , Homer Christina , Madhani Hiten D.
Published: November 2017

Packaging of pericentromeric DNA into heterochromatin is crucial for genome stability, development and health, yet its endogenous triggers remain poorly understood1. A defining feature of pericentromeric heterochromatin is histone H3 lysine 9 methylation (H3K9me)2–4. In S. pombe, transcripts derived from the pericentromeric dg and dh repeat during S phase5–7 promote heterochromatin formation through two pathways: an RNAi-dependent mechanism involving recruitment of the Clr4 H3K9 methyltransferase complex (CLR-C) via the RITS complex8–13, and RNAi-independent mechanism involving an RNAPII-associated RNA-binding protein Seb1, the repressor complex SHREC, and RNA processing activities14–19. We show here that Seb1 promotes long-lived RNAPII pausing. Pause sites associated with sequence-specific Seb1 RNA binding events are significantly enriched in pericentromeric repeat regions and their presence correlates with the heterochromatin-triggering activities of the corresponding dg and dh DNA fragments. Remarkably, globally increasing RNAPII stalling by other means induces the formation of novel large ectopic heterochromatin domains. Such ectopic heterochromatin occurs even in cells lacking functional RITS, demonstrating that RNAPII pausing can be sufficient to trigger de novo heterochromatin independently of RNAi. These results uncover Seb1-mediated polymerase stalling as a new signal for nucleating heterochromatin assembly in repetitive DNA.
White Matter Connectivity Reflects Success in Musical Improvisation
Authors: Zeng Tima , Przysinda Emily , Pfeifer Charles , Arkin Cameron , Loui Psyche
Published: November 2017

Creativity is the ability to produce work that is novel, high in quality, and appropriate to an audience. One domain of creativity comes from musical improvisation, in which individuals spontaneously create novel auditory-motor sequences that are aesthetically rewarding. Here we test the hypothesis that individual differences in creative behavior are subserved by mesial and lateral differences in white matter connectivity. We compare jazz improvising musicians against classical (non-improvising) musicians and non-musician control subjects in musical performance and diffusion tensor imaging. Subjects improvised on short musical motifs and underwent DTI. Statistical measures of fluency and entropy for musical performances predicted expert ratings of creativity for each performance. Tract-Based Spatial Statistics (TBSS) showed higher Fractional Anisotropy (FA) in the cingulate cortex and corpus callosum in jazz musicians. FA in the cingulate also correlated with entropy. Probabilistic tractography from these mesial regions to lateral seed regions of the arcuate fasciculus, a pathway known to be involved in sound perception and production, showed mesial-to-lateral connectivity that correlated with improvisation training. Results suggest that white matter connectivity between lateral and mesial structures may integrate domain-general and domain-specific components of creativity.
Laccaria bicolor MiSSP8 is a small-secreted protein decisive for the establishment of the ectomycorrhizal symbiosis
Authors: Pellegrin Clément , Daguerre Yohann , Ruytinx Joske , Guinet Frédéric , Kemppainen Minna , Frei dit Frey Nicolas , Puech-Pagès Virginie , Hecker Arnaud , Pardo Alejandro G. , Martin Francis M. , Veneault-Fourrey Claire
Published: November 2017

The ectomycorrhizal symbiosis is a predominant tree-microbe interaction in forest ecosystems sustaining tree growth and health. Its establishment and functioning implies a long-term and intimate relationship between the soil-borne fungi and the roots of trees. Mycorrhiza-induced Small Secreted Proteins (MiSSPs) are hypothesized as keystone symbiotic proteins, required to set up the symbiosis by modifying the host metabolism and/or building the symbiotic interfaces.

L. bicolor MiSSP8 is the third most highly induced MiSSPs in symbiotic tissues and it is also expressed in fruiting bodies. The MiSSP8-RNAi knockdown mutants are strongly impaired in their mycorrhization ability with Populus, with the lack of fungal mantle and Hartig net development due to a lack of hyphal aggregation. MiSSP8 C-terminus displays a repetitive motif containing a kexin cleavage site, recognized by KEX2 in vitro. This suggests MiSSP8 protein might be cleaved into small peptides. Moreover, the MiSSP8 repetitive motif is found in other proteins predicted secreted by both saprotrophic and ectomycorrhizal fungi. Thus, our data indicate that MiSSP8 is a small-secreted protein involved at early stages of ectomycorrhizal symbiosis, likely by regulating hyphal aggregation and pseudoparenchyma formation.
Using Optimal F-Measure and Random Resampling in Gene Ontology Enrichment Calculations
Authors: Ge Weihao , Fazal Zeeshan , Jakobsson Eric
Published: November 2017

Background

A central question in bioinformatics is how to minimize arbitrariness and bias in analysis of patterns of enrichment in data. A prime example of such a question is enrichment of gene ontology (GO) classes in lists of genes. Our paper deals with two issues within this larger question. One is how to calculate the false discovery rate (FDR) within a set of apparently enriched ontologies, and the second how to set that FDR within the context of assessing significance for addressing biological questions, to answer these questions we compare a random resampling method with a commonly used method for assessing FDR, the Benjamini-Hochberg (BH) method. We further develop a heuristic method for evaluating Type II (false negative) errors to enable utilization of F-Measure binary classification theory for distinguishing “significant” from “non-significant” degrees of enrichment.

Results

The results show the preferability and feasibility of random resampling assessment of FDR over the analytical methods with which we compare it. They also show that the reasonableness of any arbitrary threshold depends strongly on the structure of the dataset being tested, suggesting that the less arbitrary method of F-measure optimization to determine significance threshold is preferable.

Conclusion

Therefore, we suggest using F-measure optimization instead of placing an arbitrary threshold to evaluate the significance of Gene Ontology Enrichment results, and using resampling to replace analytical methods
AQMM: Enabling Absolute Quantification of Metagenome and Metatranscriptome
Authors: Jiang Xiao-Tao , Yu Ke , Li Li-Guan , Yin Xiao-Le , Li An-Dong , Zhang Tong
Published: November 2017

Metatranscriptome has become increasingly important along with the application of next generation sequencing in the studies of microbial functional gene activity in environmental samples. However, the quantification of target active gene is hindered by the current relative quantification methods, especially when tracking the sharp environmental change. Great needs are here for an easy-to-perform method to obtain the absolute quantification. By borrowing information from the parallel metagenome, an absolute quantification method for both metagenomic and metatranscriptomic data to per gene/cell/volume/gram level was developed. The effectiveness of AQMM was validated by simulated experiments and was demonstrated with a real experimental design of comparing activated sludge with and without foaming. Our method provides a novel bioinformatic approach to fast and accurately conduct absolute quantification of metagenome and metatranscriptome in environmental samples. The AQMM can be accessed from https://github.com/biofuture/aqmm.
A semi-quantitative analysis of lupus arthritis using contrasted high-field MRI
Authors: Zollars Eric S , Chapin Russell
Published: November 2017

Objective

Arthritis in systemic lupus erythematosus is poorly described and there is no objective measure for quantification of the arthritis. We aim to develop MRI as a research tool for the quantification of lupus arthritis.

Methods

Patients were eligible for entry into the study if they were evaluated at the MUSC Lupus Center and determined by their treating physician to have active hand arthritis due to SLE. Standard of care lupus activity measures were collected along with a detailed physical exam. MRI images were obtained using standard musculoskeletal sequences with gadolinium contrast. Semi-quantitative scoring of the images used the OMERACT RAMRIS system.

Results

RAMRIS demonstrates large amounts of synovitis, tenosynovitis, bone marrow edema and erosive disease in only a minority of patients. Some patients were not scored as having any synovitis or tenosynovits. We describe potential features of lupus arthritis that are not captured in the RAMRIS scores and may be contributing to symptoms.

Conclusion

Lupus arthritis is an entity separate from rheumatoid arthritis and requires the development of new quantitative methods to describe it. MRI findings suggest the inadequacy of a typical lupus musculoskeletal measures and even swollen/tender joint counts to assess the level of disease activity.
BayCount: A Bayesian Decomposition Method for Inferring Tumor Heterogeneity using RNA-Seq Counts
Authors: Xie Fangzheng , Zhou Mingyuan , Xu Yanxun
Published: November 2017

Tumors are heterogeneous - a tumor sample usually consists of a set of subclones with distinct transcriptional profiles and potentially different degrees of aggressiveness and responses to drugs. Understanding tumor heterogeneity is therefore critical for precise cancer prognosis and treatment. In this paper, we introduce BayCount, a Bayesian decomposition method to infer tumor heterogeneity with highly over-dispersed RNA sequencing count data. Using negative binomial factor analysis, BayCount takes into account both the between-sample and gene-specific random effects on raw counts of sequencing reads mapped to each gene. For the posterior inference, we develop an efficient compound Poisson based blocked Gibbs sampler. Simulation studies show that BayCount is able to accurately estimate the subclonal inference, including number of subclones, the proportions of these subclones in each tumor sample, and the gene expression profiles in each subclone. For real-world data examples, we apply BayCount to The Cancer Genome Atlas lung cancer and kidney cancer RNA sequencing count data and obtain biologically interpretable results. Our method represents the first effort in characterizing tumor heterogeneity using RNA sequencing count data that simultaneously removes the need of normalizing the counts, achieves statistical robustness, and obtains biologically/clinically meaningful insights. The R package BayCount implementing our model and algorithm is available for download.
Deregulation of TGF-β1 signaling induces glycolysis by chromatin remodeling in pathogenic TH17 cells
Authors: Yu Xiang , Wang Li , Han Zhijun , Yao Chao , Qiu Rong , Cui Yange , Dai Dai , Jin Wenfei , Shen Nan
Published: November 2017

It is well known that some pathogenic cells have enhanced glycolysis, the regulatory network leading to increased glycolysis are not well characterized. Here, we show that pathogenic TH17 cells specifically upregulate glycolytic pathway genes compared to homeostatic TH17 cells. Bioenergetic assay and metabolomics analyses indicate that pathogenic TH17 cells are highly glycolytic compared to nonpathogenic TH17 cells. Chromatin landscape analyses demonstrate TH17 cells in vivo show distinct chromatin states, and pathogenic TH17 cells show enhanced chromatin accessibility at glycolytic genes with NF-kB binding sites. Mechanistic studies reveal that TGF-β1 signaling induces TH17 cell chromatin remodeling and represses c-Rel-mediated glycolysis. A miR-21-Peli1-c-Rel loop was further identified to be essential for glycolysis of pathogenic TH17 cells. These findings extend our understanding of the regulation TH17 cell glycolysis in vivo and provide insights for future therapeutic intervention to TH17 cell mediated autoimmune diseases.
MapZ forms a stable ring structure that acts as a nano-track for FtsZ treadmilling inStreptococcus mutans
Authors: Li Yongliang , Shao Shipeng , Xu Xiao , Su Xiaodong , Sun Yujie , Wei Shicheng
Published: November 2017

Bacterial binary division requires the accurate placement of the division machinery. FtsZ, the vital component of the division machinery, can assemble into filaments and self-organize into a ring structure (Z-ring) at the proper site for cell division. Thus, understanding how bacteria control the spatiotemporal formation of the FtsZ ring is crucial for small molecule and nanoparticle antibacterial drug discovery. MapZ, a recently identified FtsZ regulator inStreptococcaceae,has been found to localize at the mid-cell and position the FtsZ ring. However, the mechanism is still unclear. Here, by using total internal reflection fluorescence microscopy, super-resolution imaging, and single molecule tracking, we investigated the mechanism by which MapZ regulates the FtsZ ring position. The results show that FtsZ exhibites dynamic treadmilling motion in S.mutans.Importantly, depletion of MapZ leads to an unconstrained movement of treadmilling FtsZ filaments and a shorter lifetime of the constricting FtsZ ring. Furthermore, by revealing that MapZ forms an immobile ring-like nanostructure at the division site, our study suggests that MapZ forms a stable ring that acts as a nanotrack to guide and restrict treadmilling FtsZ filaments in S.mutans, representing a novel way in which bacteria control the division.
Comparing miRNA structure of mirtrons and non-mirtrons
Authors: Titov Igor I. , Vorozheykin Pavel S.
Published: November 2017

Background

MicroRNAs proceeds through the different canonical and non-canonical pathways; the most frequent of the non-canonical ones is the splicing-dependent biogenesis of mirtrons. We compare the mirtrons and non-mirtrons of human and mouse to explore how their maturation appears in the precursor structure around the miRNA.

Results

We found the coherence of the overhang lengths what indicates the dependence between the cleavage sites. To explain this dependence we suggest the 2-lever model of the Dicer structure that couples the imprecisions in Drosha and Dicer. Considering the secondary structure of all animal pre-miRNAs we confirmed that single-stranded nucleotides tend to be located near the miRNA boundaries and in its center and are characterized by a higher mutation rate. The 5′ end of the canonical 5′ miRNA approaches the nearest single-stranded nucleotides what suggests the extension of the loop-counting rule from the Dicer to the Drosha cleavage site. A typical structure of the annotated mirtron pre-miRNAs differs from the canonical pre-miRNA structure and possesses the 1- and 2nt hanging ends at the hairpin base. Together with the excessive variability of the mirtron Dicer cleavage site (that could be partially explained by guanine at its ends inherited from splicing) this is one more evidence for the 2-lever model. In contrast with the canonical miRNAs the mirtrons have higher snp densities and their pre-miRNAs are inversely associated with diseases. Therefore we supported the view that mirtrons are under positive selection while canonical miRNAs are under negative one and we suggested that mirtrons are an intrinsic source of silencing variability which produces the disease-promoting variants. Finally, we considered the interference of the pre-miRNA structure and the U2snRNA:pre-mRNA basepairing. We analyzed the location of the branchpoints and found that mirtron structure tends to expose the branchpoint site what suggests that the mirtrons can readily evolve from occasional hairpins in the immediate neighbourhood of the 3′ splice site.

Conclusion

The miRNA biogenesis manifests itself in the footprints of the secondary structure. Close inspection of these structural properties can help to uncover new pathways of miRNA biogenesis and to refine the known miRNA data, in particular, new non-canonical miRNAs may be predicted or the known miRNAs can be re-classified.
CDC20B is required for deuterosome-mediated centriole production in multiciliated cells
Authors: Revinski Diego R. , Zaragosi Laure-Emmanuelle , Boutin Camille , Ruiz-Garcia Sandra , Deprez Marie , Thomé Virginie , Rosnet Olivier , Gay Anne-Sophie , Mercey Olivier , Paquet Agnès , Pons Nicolas , Ponzio Gilles , Marcet Brice , Kodjabachian Laurent , Barbry Pascal
Published: November 2017

Multiciliated cells (MCCs) harbour dozens to hundreds of motile cilia, which beat in a synchronized and directional manner, thus generating hydrodynamic forces important in animal physiology. In vertebrates, MCC differentiation critically depends on the synthesis and release of numerous centrioles by specialized structures called deuterosomes. Little is known about the composition, organization and regulation of deuterosomes. Here, single-cell RNA sequencing reveals that human deuterosome-stage MCCs are characterized by the expression of many cell cycle-related genes. We further investigated the uncharacterized vertebrate-specificcell division cycle 20B(CDC20B) gene, the host gene of microRNA-449abc. We show that the CDC20B protein associates to deuterosomes and is required for the release of centrioles and the subsequent production of cilia in mouse andXenopusMCCs. CDC20B interacts with PLK1, which has been shown to coordinate centriole disengagement with the protease Separase in mitotic cells. Strikingly, over-expression of Separase rescued centriole disengagement and cilia production in CDC20B-deficient MCCs. This work reveals the shaping of a new biological function, deuterosome-mediated centriole production in vertebrate MCCs, by adaptation of canonical and recently evolved cell cycle-related molecules.
Detecting pathogen exposure during the non-symptomatic incubation period using physiological data
Authors: Milechin Lauren , Davis Shakti , Patel Tejash , Hernandez Mark , Ciccarelli Greg , Schwartz Steven , Samsi Siddharth , Hensley Lisa , Goff Arthur , Trefry John , Johnston Sara , Purcell Bret , Cabrera Catherine , Fleischman Jack , Reuther Albert , Rossi Franco , Honko Anna , Pratt William , Swiston Albert
Published: November 2017

Early pathogen exposure detection allows better patient care and faster implementation of public health measures (patient isolation, contact tracing). Existing exposure detection most frequently relies on overt clinical symptoms, namely fever, during the infectious prodromal period. We have developed a robust machine learning based method to better detect asymptomatic states during the incubation period using subtle, sub-clinical physiological markers. Starting with high-resolution physiological waveform data from non-human primate studies of viral (Ebola, Marburg, Lassa, and Nipah viruses) and bacterial (Y. pestis) exposure, we processed the data to reduce short-term variability and normalize diurnal variations, then provided these to a supervised random forest classification algorithm and post-classifier declaration logic step to reduce false alarms. In most subjects detection is achieved well before the onset of fever; subject cross-validation across exposure studies (varying viruses, exposure routes, animal species, and target dose) lead to 51h mean early detection (at 0.93 area under the receiver-operating characteristic curve [AUCROC]). Evaluating the algorithm against entirely independent datasets for Lassa, Nipah, andY. pestisexposures un-used in algorithm training and development yields a mean 51h early warning time (at AUCROC=0.95). We discuss which physiological indicators are most informative for early detection and options for extending this capability to limited datasets such as those available from wearable, non-invasive, ECG-based sensors.
LINE-2 transposable elements are a source for functional human microRNAs and target sites
Authors: Petri Rebecca , Brattås Per Ludvik , Sharma Yogita , Jönsson Marie E , Pircs Karolina , Bengzon Johan , Jakobsson Johan
Published: November 2017

Transposable elements (TEs) are dynamically expressed at high levels in multiple human tissues, but the function of TE-derived transcripts remains largely unknown. In this study, we identify numerous TE-derived microRNAs (miRNAs) by conducting Argonaute2 RNA Immunoprecipitation followed by small RNA sequencing (AGO2 RIP-seq) on human brain tissue. Many of these miRNAs originated from LINE-2 (L2) elements, which entered the human genome around 100-300 million years ago. We found that L2-miRNAs derive from the 3’ end of the L2 consensus sequence and thus share very similar sequences, indicating that they could target transcripts with L2s in their 3’UTR. In line with this, we found that many protein-coding genes carry fragments of L2-derived sequences in their 3’UTR, which serve as target sites for L2-miRNAs. L2-miRNAs and targets were generally ubiquitously expressed at low levels in multiple human tissues, suggesting a role for this network in buffering transcriptional levels of housekeeping genes. Interestingly, we also found evidence that this network is perturbed in glioblastoma. In summary, our findings uncover a TE-based post-transcriptional network that shapes transcriptional regulation in human cells.
A new optimal design of surface mounted permanent magnet synchronous motors with integral slot per pole
Authors: Rezaeealam Behrooz , Rezaee-Alam Farhad
Published: November 2017

Purpose

The purpose of this paper is to present a new optimal design for integral slot permanent magnet synchronous motors (PMSMs) to shape the air-gap magnetic field in sinusoidal and to reduce the cogging torque, simultaneously.

Design/methodology/approach

For obtaining this new optimal design, the influence of different magnetizations of permanent magnets (PMs), including radial, parallel and halbach magnetization is investigated on the performance of one typical PMSM by using the conformal mapping (CM) method. To reduce the cogging torque even more, the technique of slot opening shift is also implemented on the stator slots of analyzed PMSM without reduction in the main performance, including the air-gap magnetic field, the average torque and back-electromotive force (back-EMF).

Findings

Finally, an optimal configuration including the Hat-type magnet poles with halbach magnetization on the rotor and shifted slot openings on the stator is obtained through the CM method, which shows the main reduction in cogging torque and the harmonic content of air-gap magnetic field.

Practical implications

The obtained optimal design is completely practical and is validated by comparing with the corresponding results obtained through finite element method.

Originality/value

This paper presents a new optimal design for integral slot PMSMs, which can include different design considerations, such as the reduction of cogging torque and the total harmonic distortion of air-gap magnetic field by using the CM method.