bluuebunny/crossref_metadata_2025_split huggingface dataset:
Several phased siRNA annotation methods can frequently misidentify 24 nucleotide siRNA-dominated PHAS loci
Authors: Polydore Seth , Lunardon Alice , Axtell Michael J. 
Published: September 2018

AbstractSmall RNAs regulate key physiological functions in land plants. Small RNAs can be divided into two categories: microRNAs (miRNAs) and short interfering RNAs (siRNAs); siRNAs are further sub-divided into transposon/repetitive region-localized heterochromatic siRNAs and phased siRNAs (phasiRNAs). PhasiRNAs are produced from the miRNA-mediated cleavage of a Pol II RNA transcript; the miRNA cleavage site provides a defined starting point from which phasiRNAs are produced in a distinctly phased pattern. 21-22 nucleotide (nt)-dominated phasiRNA-producing loci (PHAS) are well represented in all land plants to date. In contrast, 24 nt-dominated PHAS loci are known to be encoded only in monocots and are generally restricted to male reproductive tissues. Currently, only one miRNA (miR2275) is known to trigger the production of these 24 nt-dominated PHAS loci. In this study, we use stringent methodologies in order to examine whether or not 24 nt-dominated PHAS loci also exist in Arabidopsis thaliana. We find that highly expressed heterochromatic siRNAs were consistently mis-identified as 24 nt-dominated PHAS loci using multiple PHAS-detecting algorithms. We also find that MIR2275 is not found in A. thaliana, and it seems to have been lost in the last common ancestor of Brassicales. Altogether, our research highlights the potential issues with widely used PHAS-detecting algorithms which may lead to false positives when trying to annotate new PHAS, especially 24 nt-dominated loci.
Visualisation and analysis of RNA-Seq assembly graphs
Authors: Nazarie Fahmi W. , Shih Barbara , Angus Tim , Barnett Mark W. , Chen Sz-Hau , Summers Kim M. , Klein Karsten , Faulkner Geoffrey J. , Saini Harpreet K. , Watson Mick , Dongen Stijn van , Enright Anton J. , Freeman Tom C. 
Published: September 2018

AbstractRNA-sequencing (RNA-Seq) is a powerful transcriptome profiling technology enabling transcript discovery and quantification. RNA-Seq data are large, and most commonly used as a source of genelevel quantification measurements, whilst the underlying assemblies of reads, if inspected, are usually viewed as sequence reads mapped on to a reference genome. Whilst sufficient for many needs, when the underlying transcript assemblies are complex, this visualisation approach can be limiting; errors in assembly can be difficult to spot and interpretation of splicing events is challenging.Here we report on the development of a graph-based visualisation method as a complementary approach to understanding transcript diversity and read assembly from short-read RNA-Seq data. Following the mapping of reads to the reference genome, read-to-read comparison is performed on all reads mapping to a given gene, producing a matrix of weighted similarity scores between reads. This is used to produce an RNA assembly graph where nodes represent reads derived from a cDNA and edges similarity scores between reads, above a defined threshold. Visualisation of resulting graphs is performed using Graphia Professional. This tool can render the often large and complex graph topologies that result from DNA/RNA sequence assembly in 3D space and supports info rmatio no verlay on to nodes, e.g. transcript models. We have also implemented an analysis pipeline for the creation of RNA assembly graphs with both a command-line and web-based interface that allows users to create and visualise these data. Here we demonstrate the utility of this approach on RNA-Seq data, including the unusual structure of these graphs and how they can be used to identify issues in assembly, repetitive sequences within transcripts and splice variants. We believe this approach has the potential to significantly improve our understanding of transcript complexity.
Automated EEG mega-analysis I: Spectral and amplitude characteristics across studies
Authors: Bigdely-Shamlo Nima , Touryan Jonathan , Ojeda Alejandro , Kothe Christian , Mullen Tim , Robbins Kay 
Published: September 2018

AbstractSignificant achievements have been made in the fMRI field by pooling statistical results from multiple studies (meta-analysis). More recently, fMRI standardization efforts have focused on enabling the joint analysis of raw fMRI data across studies (mega-analysis), with the hope of achieving more detailed insights. However, it has not been clear if such analyses in the EEG field are possible or equally fruitful. Here we present the results of a large-scale EEG mega-analysis using 18 studies from six sites representing several different experimental paradigms. We demonstrate that when meta-data are consistent across studies, both channel-level and source-level EEG mega-analysis are possible and can provide insights unavailable in single studies. The analysis uses a fully-automated processing pipeline to reduce line noise, interpolate noisy channels, perform robust referencing, remove eye-activity, and further identify outlier signals. We define several robust measures based on channel amplitude and dispersion to assess the comparability of data across studies and observe the effect of various processing steps on these measures. Using ICA-based dipolar sources, we also observe consistent differences in overall frequency baseline amplitudes across brain areas. For example, we observe higher alpha in posterior vs anterior regions and higher beta in temporal regions. We also detect consistent differences in the slope of the aperiodic portion of the EEG spectrum across brain areas. In a companion paper, we apply mega-analysis to assess commonalities in event-related EEG features across studies. The continuous raw and preprocessed data used in this analysis are available through the DataCatalog at https://cancta.net.
Flexible backbone assembly and refinement of symmetrical homomeric complexes
Authors: Roy Burman Shourya S. , Yovanno Remy A. , Gray Jeffrey J. 
Published: September 2018

SummarySymmetrical homomeric proteins are ubiquitous in every domain of life, and information about their structure is essential to decipher function. The size of these complexes often makes them intractable to high-resolution structure determination experiments. Computational docking algorithms offer a promising alternative for modeling large complexes with arbitrary symmetry. Accuracy of existing algorithms, however, is limited by backbone inaccuracies when using homology-modeled monomers. Here, we present Rosetta SymDock2 with a broad search of symmetrical conformational space using a six-dimensional coarse-grained score function followed by an all-atom flexible-backbone refinement, which we demonstrate to be essential for physically-realistic modeling of tightly packed complexes. In global docking of a benchmark set of complexes of different point symmetries — staring from homology-modeled monomers — we successfully dock (defined as predicting three near-native structures in the five top-scoring models) 19 out of 31 cyclic complexes and 5 out of 12 dihedral complexes.HighlightsSymDock2 is an algorithm to assemble symmetric protein structures from monomersCoarse-grained score function discriminates near-native conformationsFlexible backbone refinement is necessary to create realistic all-atom modelsResults improve six-fold and outperform other symmetric docking algorithmsGraphical Abstract
Comparison of null models for combination drug therapy reveals Hand model as biochemically most plausible
Authors: Sinzger Mark , Vanhoefer Jakob , Loos Carolin , Hasenauer Jan 
Published: September 2018

AbstractNull models for the effect of combination therapies are widely used to evaluate synergy and antagonism of drugs. Due to the relevance of null models, their suitability is continuously discussed. Here, we contribute to the discussion by investigating the properties of five null models. Our study includes the model proposed by David J. Hand, which we refer to asHand model. The Hand model has been introduced almost 20 years ago but hardly was used and studied. We show that the Hand model generalizes the principle of dose equivalence compared to the Loewe model and resolves the ambiguity of the Tallarida model. This provides a solution to the persisting conflict about the compatibility of two essential model properties: the sham combination principle and the principle of dose equivalence. By embedding several null models into a common framework, we shed light in their biochemical validity and provide indications that the Hand model is biochemically most plausible. We illustrate the practical implications and differences between null models by examining differences of null models on published data.
A versatile platform strain for high-fidelity multiplex genome editing
Authors: Egbert Robert G. , Rishi Harneet S. , Adler Benjamin A. , McCormick Dylan M. , Toro Esteban , Gill Ryan T. , Arkin Adam P. 
Published: September 2018

ABSTRACTPrecision genome editing accelerates the discovery of the genetic determinants of phenotype and the engineering of novel behaviors in organisms. Advances in DNA synthesis and recombineering have enabled high-throughput engineering of genetic circuits and biosynthetic pathways via directed mutagenesis of bacterial chromosomes. However, the highest recombination efficiencies have to date been reported in persistent mutator strains, which suffer from reduced genomic fidelity. The absence of inducible transcriptional regulators in these strains also prevents concurrent control of genome engineering tools and engineered functions. Here, we introduce a new recombineering platform strain, BioDesignER, which incorporates (1) a refactored λ-Red recombination system that reduces toxicity and accelerates multi-cycle recombination, (2) genetic modifications that boost recombination efficiency, and (3) four independent inducible regulators to control engineered functions. These modifications resulted in single-cycle recombineering efficiencies of up to 25% with a seven-fold increase in recombineering fidelity compared to the widely used recombineering strain EcNR2. To facilitate genome engineering in BioDesignER, we have curated eight context-neutral genomic loci, termed Safe Sites, for stable gene expression and consistent recombination efficiency. BioDesignER is a platform to develop and optimize engineered cellular functions and can serve as a model to implement comparable recombination and regulatory systems in other bacteria.
An essential checkpoint for TLR9 signaling is release from Unc93b1 in endosomes
Authors: Majer Olivia , Woo Brian J , Liu Bo , Dis Erik Van , Barton Gregory M 
Published: September 2018

Abstract:Nucleic acid-sensing Toll-like receptors (TLRs) are subject to complex regulation to facilitate recognition of microbial DNA and RNA while limiting recognition of self-nucleic acids1. Failure to properly regulate nucleic acid-sensing TLRs can lead to autoimmune and autoinflammatory disease2-6. Intracellular localization of these receptors is thought to be critical for self vs. non-self discrimination7, yet the molecular mechanisms that reinforce compartmentalized activation of intracellular TLRs remain poorly understood. Here we describe a new mechanism that prevents TLR9 activation from locations other than endosomes. This control is achieved through the regulated release of TLR9 from its trafficking chaperone Unc93b1, which only occurs within endosomes and is required for ligand binding and signal transduction. Mutations in Unc93b1 that increase affinity for TLR9 impair release and result in defective signaling. The release is specific to TLR9, as TLR7 does not dissociate from Unc93b1 in endosomes. This work defines a novel checkpoint that reinforces self vs. non-self discrimination by TLR9 and provides a mechanism by which TLR9 and TLR7 activation can be distinctly regulated.
Spatial neglect is causally linked to an attention-related area in macaque temporal cortex
Authors: Bogadhi Amarender R. , Bollimunta Anil , Leopold David A. , Krauzlis Richard J. 
Published: September 2018

SummarySpatial neglect is a common clinical syndrome involving disruption of the brain’s attention-related circuitry, including the dorsocaudal temporal cortex. While neglect is readily modeled in macaques, the absence of evidence for temporal cortex involvement has suggested a fundamental difference from humans. To map the neurological expression of spatial neglect in macaques, we measured attention-related fMRI activity across the cerebral cortex during experimental induction of neglect through reversible inactivation of the superior colliculus. During inactivation, monkeys exhibited hallmark attentional deficits of neglect in tasks using either moving or static stimuli. The behavioral deficits were accompanied by marked reductions in fMRI attentional modulation that were strongest in a small region on the floor of the superior temporal sulcus. Notably, direct inactivation of this mid-STS cortical region caused similar neglect-like spatial attention deficits. These results identify a putative macaque homolog to temporal cortex structures known to play a central role in human neglect.HighlightsDuring neglect the mid-STS cortex shows largest reduction in attentional modulationThe mid-STS cortex is selectively affected with static as well as dynamic stimuliMid-STS cortex is affected during neglect caused by SC or FEF inactivationInactivation of mid-STS cortex itself causes neglect without eye movement deficitsIn BriefUsing fMRI in macaques performing attention tasks combined with reversible inactivations, Bogadhi et al. provide causal evidence that a region on the floor of the superior temporal sulcus is a crucial node in the cortical control of covert selective attention and a putative homolog to temporal cortex regions in humans implicated in spatial neglect.
Microglia limit lesion expansion and promote functional recovery after spinal cord injury in mice
Authors: Brennan Faith H. , Hall Jodie C.E. , Guan Zhen , Popovich Phillip G. 
Published: September 2018

AbstractTraumatic spinal cord injury (SCI) elicits a robust intraspinal inflammatory reaction that is dominated by at least two major subpopulations of macrophages, i.e., those derived from resident microglia and another from monocytes that infiltrate the injury site from the circulation. Previously, we implicated monocyte-derived macrophages (MDMs) as effectors of acute post-injury pathology after SCI; however, it is still unclear whether microglia also contribute to lesion pathology. Assigning distinct functional roles to microglia and MDMs in vivo has been difficult because these CNS macrophage subsets are morphologically and phenotypically similar. Here, to characterize the role that microglia play in experimental models of thoracic spinal contusion or lumbar crush injury, mice were fed vehicle chow or chow laced with a CSF1R receptor antagonist, PLX5622. Feeding PLX5622 depletes microglia. In both groups, spontaneous recovery of hindlimb motor function was evaluated for up to 8 weeks post-SCI using open-field and horizontal ladder tests. Histopathological assessment of intraspinal pathology was assessed in 8 week post-injury tissues. In both SCI models, microglia depletion exacerbated lesion pathology and impaired spontaneous recovery of hind limb function. Notably, the loss of microglia prevented astroglial encapsulation of the lesion core, which was associated with larger lesions, enhanced demyelination and neuron loss and a larger inflammatory response that was dominated by monocyte-derived macrophages. The neuroprotective and healing properties of microglia become obvious in the subacute phases of recovery; microglia depletion up to 7 days post-injury (dpi) had no apparent effect on recovery while delayed depletion from 8-28dpi exacerbated lesion pathology and significantly impaired functional recovery. These data suggest that microglia have essential tissue repair functions after SCI. Selective enhancement of microglial activities may be a novel strategy to preserve tissue and promote recovery of function after neurotrauma.
Identification of miRNAs and associated pathways regulated by Leukemia Inhibitory Factor in trophoblastic cell lines
Authors: Morales-Prieto Diana M. , Barth Emanuel , Murrieta-Coxca Jose Martín , Favaro Rodolfo R. , Gutiérrez-Samudio Ruby N. , Chaiwangyen Wittaya , Ospina-Prieto Stephanie , Gruhn Bernd , Schleußner Ekkehard , Marz Manja , Markert Udo R. 
Published: September 2018

ABSTRACTIntroductionLeukemia Inhibitory Factor (LIF) regulates behavior of trophoblast cells and their interaction with immune and endothelial cells.In vitro, trophoblast cell response to LIF may vary depending on the cell model. Reported differences in the miRNA profile of trophoblastic cells may be responsible for these observations. Therefore, miRNA expression was investigated in four trophoblastic cell lines under LIF stimulation followed byin silicoanalysis of altered miRNAs and their associated pathways.MethodsLow density TaqMan miRNA assays were used to quantify levels of 762 mature miRNAs under LIF stimulation in three choriocarcinoma-derived (JEG-3, ACH-3P and AC1-M59) and a trophoblast immortalized (HTR-8/SVneo) cell lines. Expression of selected miRNAs was confirmed in primary trophoblast cells and cell lines by qPCR. Targets and associated pathways of the differentially expressed miRNAs were inferred from the miRTarBase followed by a KEGG Pathway Enrichment Analysis. HTR-8/SVneo and JEG-3 cells were transfected with miR-21-mimics and expression of miR-21 targets was assessed by qPCR.ResultsA similar number of miRNAs changed in each tested cell line upon LIF stimulation, however, low coincidence of individual miRNA species was observed and occurred more often among choriocarcinoma-derived cells (complete data set athttp://www.ncbi.nlm.nih.gov/geo/under GEO accession number GSE130489). Altered miRNAs were categorized into pathways involved in human diseases, cellular processes and signal transduction. Six cascades were identified as significantly enriched, including JAK/STAT and TGFB-SMAD. Upregulation of miR-21-3p was validated in all cell lines and primary cells and STAT3 was confirmed as its target.DiscussionDissimilar miRNA responses may be involved in differences of LIF effects on trophoblastic cell lines.
Special interests and inclusive academic learning: an autistic perspective
Authors: Boven Frederik 
Published: September 2018

Purpose
Many people with an autistic spectrum condition have one or more “special interests” which is more restricted, and which they pursue with more than average intensity. The purpose of this paper is to offer a first-person perspective on inclusion of special interests in academic learning. The paper describes examples of special interests of university students and offers recommendations for university teachers.

Design/methodology/approach
The author combines the emerging strategy of using his own autobiographical material as research object with the more establish method of conceptual analysis.

Findings
The author finds that special interests can be a source of academic strength, but can also interfere with learning. The paper argues that including special interests in academic learning is an effective way of including students with autism in higher education, but requires some special provisions.

Originality/value
Existing research has focused either on the special interests of persons with autism or on their inclusion in education, but the combination of these two issues has rarely been considered. The paper addresses this neglected topic from the inside perspective of a former student with autism who, after completing a research master’s in philosophy, was diagnosed with Asperger’s syndrome at age 34. The author combines this inside perspective with knowledge of the theory and history of autism.
Effects of different roughness elements on friction and pressure drop of laminar flow in microchannels
Authors: Lalegani Fakhrodin , Saffarian Mohammad Reza , Moradi Ahmadreza , Tavousi Ebrahim 
Published: September 2018

Purpose
According to very small dimensions of the microchannels, producing a microchannel with smooth surfaces is approximately impossible. The surface roughness can have a specific effect on microchannel performances. This paper aims to investigate the changes in friction and pressure drop in the microchannels by considering the different roughness elements on microchannel wall and changes in elementary geometry and flow conditions. Results show a significant effect of roughness on the pressure drop and friction.

Design/methodology/approach
Two-dimensional fluid flow in the rough microchannels is analyzed using FLUENT. Microchannels have a height of 50 µm. Water at room temperature (25°C) has been used as working fluid. The Reynolds numbers are considered in laminar flow range and from 50 to 300.

Findings
The results show that the value of friction factor reduces nonlinearly with an increase in Reynolds number. But, the pressure drops and the Poiseuille number in the microchannels increase with an increase in Reynolds number. The values of the pressure drop and the friction factor increase by increasing the height and size of the roughness elements, but these values reduce with an increase in the distance of roughness elements.

Originality/value
The roughness elements types in this research are rectangular, trapezoidal, elliptical, triangular and complex (composed of multiple types of roughness elements). The effects of the Reynolds number, roughness height, roughness distance and roughness size on the pressure drop and friction in the rough microchannels are investigated and discussed. Furthermore, differences between the effects of five types of roughness elements are identified.
New services development: a study in the context of a health organization
Authors: Eberle Luciene , Milan Gabriel Sperandio , De Toni Deonir , Lazzari Fernanda 
Published: September 2018

PurposeThe purpose of this study is to highlight the understanding of the consequent factors of new services development (NSD) in the literature owing to the impact on organizational competitiveness, especially in professional services, such as that investigated by health plan operators in the present study.Design/methodology/approachThe sample (customer of family health plans) consisted of 255 valid cases. For the analysis of the data, multivariate statistical techniques were used through the modeling of structural equations.FindingsThe results found evidence of the significant relationships between the NSD considering the constructs, client orientation, reputation, professional competences and customer retention, as consequences of the NSD, which impact on the success of the new services launched by the health plan operator from the perception of the customer.Practical implicationsThis implies that health plan operators need to develop new customer-oriented services by investing in new technologies and having more trained and qualified staff so that they can deliver superior services and, as a consequence, have a more profitable relationship with customers.Originality/valueThe new services may result in greater organizational performance and greater competitiveness for health service providers.