Distinct Extracellular RNA Profiles in Different Plasma Components

Circulating extracellular RNAs (exRNAs) have great potential to serve as biomarkers for a wide range of diagnostic, therapeutic, and prognostic applications. So far, knowledge of the difference among different sources of exRNAs is limited. To address this issue, we performed a sequential physical and biochemical precipitation to collect four fractions (platelets and cell debris, the thrombin-induced precipitates, extracellular vesicles, and supernatant) from each of 10 plasma samples. From total RNAs of the 40 fractions, we prepared ligation-free libraries to profile full spectrum of all RNA species, without size selection and rRNA reduction. Due to complicated RNA composition in these libraries, we utilized a successive stepwise alignment strategy to map the RNA sequences to different RNA categories, including miRNAs, piwi-interacting RNAs, tRNAs, rRNAs, lincRNAs, snoRNAs, snRNAs, other ncRNAs, protein coding RNAs, and circRNAs. Our data showed that each plasma fraction had its own unique distribution of RNA species. Hierarchical cluster analyses using transcript abundance demonstrated similarities in the same plasma fraction and significant differences between different fractions. In addition, we observed various unique transcripts, and novel predicted miRNAs among these plasma fractions. These results demonstrate that the distribution of RNA species and functional RNA transcripts is plasma fraction-dependent. Appropriate plasma preparation and thorough inspection of different plasma fractions are necessary for an exRNA-based biomarker study.

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A-to-I editing in the miRNA seed region regulates target mRNA selection and silencing efficiency

Nucleic Acids Research ◽

10.1093/nar/gku662 ◽

2014 ◽

Vol 42 (15) ◽

pp. 10050-10060 ◽

Cited By ~ 35

Author(s):

Hideaki Kume ◽

Kimihiro Hino ◽

Josephine Galipon ◽

Kumiko Ui-Tei

Keyword(s):

Gene Expression Regulation ◽

Seed Region ◽

Rna Sequences ◽

Protein Coding ◽

Adenosine Deaminases ◽

Target Mrnas ◽

Non Coding Rna ◽

The Difference ◽

Mirna Seed

Abstract Hydrolytic deamination of adenosine to inosine (A-to-I) by adenosine deaminases acting on RNA (ADARs) is a post-transcriptional modification which results in a discrepancy between genomic DNA and the transcribed RNA sequence, thus contributing to the diversity of the transcriptome. Inosine preferentially base pairs with cytidine, meaning that A-to-I modifications in the mRNA sequences may be observed as A-to-G substitutions by the protein-coding machinery. Genome-wide studies have revealed that the majority of editing events occur in non-coding RNA sequences, but little is known about their functional meaning. MiRNAs are small non-coding RNAs that regulate the expression of target mRNAs with complementarities to their seed region. Here, we confirm that A-to-I editing in the miRNA seed duplex globally reassigns their target mRNAs in vivo, and reveal that miRNA containing inosine in the seed region exhibits a different degree of silencing efficiency compared to the corresponding miRNA with guanosine at the same position. The difference in base-pairing stability, deduced by melting temperature measurements, between seed-target duplexes containing either C:G or I:C pairs may account for the observed silencing efficiency. These findings unequivocally show that C:G and I:C pairs are biologically different in terms of gene expression regulation by miRNAs.

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Comparative Effects of High-Tech Visual Scene Displays and Low-Tech Isolated Picture Symbols on Engagement From Students With Multiple Disabilities

Language Speech and Hearing Services in Schools ◽

10.1044/2019_lshss-19-0007 ◽

2019 ◽

Vol 50 (4) ◽

pp. 693-702 ◽

Cited By ~ 1

Author(s):

Christine Holyfield ◽

Sydney Brooks ◽

Allison Schluterman

Keyword(s):

Language Learning ◽

Augmentative And Alternative Communication ◽

Visual Analysis ◽

Multiple Disabilities ◽

Visual Scene ◽

Future Research ◽

High Tech ◽

Single Subject ◽

Wide Range ◽

The Difference

Purpose Augmentative and alternative communication (AAC) is an intervention approach that can promote communication and language in children with multiple disabilities who are beginning communicators. While a wide range of AAC technologies are available, little is known about the comparative effects of specific technology options. Given that engagement can be low for beginning communicators with multiple disabilities, the current study provides initial information about the comparative effects of 2 AAC technology options—high-tech visual scene displays (VSDs) and low-tech isolated picture symbols—on engagement. Method Three elementary-age beginning communicators with multiple disabilities participated. The study used a single-subject, alternating treatment design with each technology serving as a condition. Participants interacted with their school speech-language pathologists using each of the 2 technologies across 5 sessions in a block randomized order. Results According to visual analysis and nonoverlap of all pairs calculations, all 3 participants demonstrated more engagement with the high-tech VSDs than the low-tech isolated picture symbols as measured by their seconds of gaze toward each technology option. Despite the difference in engagement observed, there was no clear difference across the 2 conditions in engagement toward the communication partner or use of the AAC. Conclusions Clinicians can consider measuring engagement when evaluating AAC technology options for children with multiple disabilities and should consider evaluating high-tech VSDs as 1 technology option for them. Future research must explore the extent to which differences in engagement to particular AAC technologies result in differences in communication and language learning over time as might be expected.

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COMBINATORIAL POLYNOMIALLY COMPUTABLE CHARACTERISTICS OF SUBSTITUTIONS AND THEIR PROPERTIES

Computational nanotechnology ◽

10.33693/2313-223x-2020-7-2-34-41 ◽

2020 ◽

Vol 7 (2) ◽

pp. 34-41

Author(s):

VLADIMIR NIKONOV ◽

◽

ANTON ZOBOV ◽

Keyword(s):

Mathematical Expectation ◽

Point Of View ◽

Small Range ◽

Computational Point ◽

Wide Range ◽

Bijective Function ◽

The Difference ◽

Element Base ◽

Selection Of

The construction and selection of a suitable bijective function, that is, substitution, is now becoming an important applied task, particularly for building block encryption systems. Many articles have suggested using different approaches to determining the quality of substitution, but most of them are highly computationally complex. The solution of this problem will significantly expand the range of methods for constructing and analyzing scheme in information protection systems. The purpose of research is to find easily measurable characteristics of substitutions, allowing to evaluate their quality, and also measures of the proximity of a particular substitutions to a random one, or its distance from it. For this purpose, several characteristics were proposed in this work: difference and polynomial, and their mathematical expectation was found, as well as variance for the difference characteristic. This allows us to make a conclusion about its quality by comparing the result of calculating the characteristic for a particular substitution with the calculated mathematical expectation. From a computational point of view, the thesises of the article are of exceptional interest due to the simplicity of the algorithm for quantifying the quality of bijective function substitutions. By its nature, the operation of calculating the difference characteristic carries out a simple summation of integer terms in a fixed and small range. Such an operation, both in the modern and in the prospective element base, is embedded in the logic of a wide range of functional elements, especially when implementing computational actions in the optical range, or on other carriers related to the field of nanotechnology.

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Generalized Heterodyne Configurations for Photo-induced Force Microscopy

10.26434/chemrxiv.9633407 ◽

2019 ◽

Author(s):

Le Wang ◽

Devon Jakob ◽

Haomin Wang ◽

Alexis Apostolos ◽

Marcos M. Pires ◽

...

Keyword(s):

Spatial Resolution ◽

Repetition Rate ◽

Modulation Frequency ◽

High Harmonic ◽

Chemical Imaging ◽

Heterodyne Detection ◽

Force Microscopy ◽

Wide Range ◽

The Difference ◽

Afm Cantilever

<div>Infrared chemical microscopy through mechanical probing of light-matter interactions by atomic force microscopy (AFM) bypasses the diffraction limit. One increasingly popular technique is photo-induced force microscopy (PiFM), which utilizes the mechanical heterodyne signal detection between cantilever mechanical resonant oscillations and the photo induced force from light-matter interaction. So far, photo induced force microscopy has been operated in only one heterodyne configuration. In this article, we generalize heterodyne configurations of photoinduced force microscopy by introducing two new schemes: harmonic heterodyne detection and sequential heterodyne detection. In harmonic heterodyne detection, the laser repetition rate matches integer fractions of the difference between the two mechanical resonant modes of the AFM cantilever. The high harmonic of the beating from the photothermal expansion mixes with the AFM cantilever oscillation to provide PiFM signal. In sequential heterodyne detection, the combination of the repetition rate of laser pulses and polarization modulation frequency matches the difference between two AFM mechanical modes, leading to detectable PiFM signals. These two generalized heterodyne configurations for photo induced force microscopy deliver new avenues for chemical imaging and broadband spectroscopy at ~10 nm spatial resolution. They are suitable for a wide range of heterogeneous materials across various disciplines: from structured polymer film, polaritonic boron nitride materials, to isolated bacterial peptidoglycan cell walls. The generalized heterodyne configurations introduce flexibility for the implementation of PiFM and related tapping mode AFM-IR, and provide possibilities for additional modulation channel in PiFM for targeted signal extraction with nanoscale spatial resolution.</div>

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BloodGen3Module: Blood transcriptional module repertoire analysis and visualization using R

Bioinformatics ◽

10.1093/bioinformatics/btab121 ◽

2021 ◽

Author(s):

Darawan Rinchai ◽

Jessica Roelands ◽

Mohammed Toufiq ◽

Wouter Hendrickx ◽

Matthew C Altman ◽

...

Keyword(s):

Transcript Abundance ◽

R Package ◽

Supplementary Information ◽

Illustrative Case ◽

Bioinformatic Tools ◽

Transcriptional Module ◽

Wide Range ◽

Downstream Analysis ◽

Computing Module ◽

Parallel Workflow

Abstract Motivation We previously described the construction and characterization of generic and reusable blood transcriptional module repertoires. More recently we released a third iteration (“BloodGen3” module repertoire) that comprises 382 functionally annotated gene sets (modules) and encompasses 14,168 transcripts. Custom bioinformatic tools are needed to support downstream analysis, visualization and interpretation relying on such fixed module repertoires. Results We have developed and describe here a R package, BloodGen3Module. The functions of our package permit group comparison analyses to be performed at the module-level, and to display the results as annotated fingerprint grid plots. A parallel workflow for computing module repertoire changes for individual samples rather than groups of samples is also available; these results are displayed as fingerprint heatmaps. An illustrative case is used to demonstrate the steps involved in generating blood transcriptome repertoire fingerprints of septic patients. Taken together, this resource could facilitate the analysis and interpretation of changes in blood transcript abundance observed across a wide range of pathological and physiological states. Availability The BloodGen3Module package and documentation are freely available from Github: https://github.com/Drinchai/BloodGen3Module Supplementary information Supplementary data are available at Bioinformatics online.

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Transdiagnostic comparison of visual working memory capacity in bipolar disorder and schizophrenia

International Journal of Bipolar Disorders ◽

10.1186/s40345-020-00217-x ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Catherine V. Barnes-Scheufler ◽

Caroline Passow ◽

Lara Rösler ◽

Jutta S. Mayer ◽

Viola Oertel ◽

...

Keyword(s):

Bipolar Disorder ◽

Working Memory ◽

Visual Working Memory ◽

Effect Size ◽

Working Memory Capacity ◽

Memory Capacity ◽

Medium Effect ◽

Full Spectrum ◽

Small Effect Size ◽

The Difference

Abstract Background Impaired working memory is a core cognitive deficit in both bipolar disorder and schizophrenia. Its study might yield crucial insights into the underpinnings of both disorders on the cognitive and neurophysiological level. Visual working memory capacity is a particularly promising construct for such translational studies. However, it has not yet been investigated across the full spectrum of both disorders. The aim of our study was to compare the degree of reductions of visual working memory capacity in patients with bipolar disorder (PBD) and patients with schizophrenia (PSZ) using a paradigm well established in cognitive neuroscience. Methods 62 PBD, 64 PSZ, and 70 healthy controls (HC) completed a canonical visual change detection task. Participants had to encode the color of four circles and indicate after a short delay whether the color of one of the circles had changed or not. We estimated working memory capacity using Pashler’s K. Results Working memory capacity was significantly reduced in both PBD and PSZ compared to HC. We observed a small effect size (r = .202) for the difference between HC and PBD and a medium effect size (r = .370) for the difference between HC and PSZ. Working memory capacity in PSZ was also significantly reduced compared to PBD with a small effect size (r = .201). Thus, PBD showed an intermediate level of impairment. Conclusions These findings provide evidence for a gradient of reduced working memory capacity in bipolar disorder and schizophrenia, with PSZ showing the strongest degree of impairment. This underscores the importance of disturbed information processing for both bipolar disorder and schizophrenia. Our results are compatible with the cognitive manifestation of a neurodevelopmental gradient affecting bipolar disorder to a lesser degree than schizophrenia. They also highlight the relevance of visual working memory capacity for the development of both behavior- and brain-based transdiagnostic biomarkers.

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Role of Transposable Elements in Gene Regulation in the Human Genome

Life ◽

10.3390/life11020118 ◽

2021 ◽

Vol 11 (2) ◽

pp. 118

Author(s):

Arsala Ali ◽

Kyudong Han ◽

Ping Liang

Keyword(s):

Gene Regulation ◽

Transposable Elements ◽

Regulatory Sequences ◽

Rna Sequences ◽

Expression Of Genes ◽

Wide Range ◽

Lineage Specificity ◽

Regulatory Rnas ◽

Potential Factors ◽

Interspersed Repeats

Transposable elements (TEs), also known as mobile elements (MEs), are interspersed repeats that constitute a major fraction of the genomes of higher organisms. As one of their important functional impacts on gene function and genome evolution, TEs participate in regulating the expression of genes nearby and even far away at transcriptional and post-transcriptional levels. There are two known principal ways by which TEs regulate the expression of genes. First, TEs provide cis-regulatory sequences in the genome with their intrinsic regulatory properties for their own expression, making them potential factors for regulating the expression of the host genes. TE-derived cis-regulatory sites are found in promoter and enhancer elements, providing binding sites for a wide range of trans-acting factors. Second, TEs encode for regulatory RNAs with their sequences showed to be present in a substantial fraction of miRNAs and long non-coding RNAs (lncRNAs), indicating the TE origin of these RNAs. Furthermore, TEs sequences were found to be critical for regulatory functions of these RNAs, including binding to the target mRNA. TEs thus provide crucial regulatory roles by being part of cis-regulatory and regulatory RNA sequences. Moreover, both TE-derived cis-regulatory sequences and TE-derived regulatory RNAs have been implicated in providing evolutionary novelty to gene regulation. These TE-derived regulatory mechanisms also tend to function in a tissue-specific fashion. In this review, we aim to comprehensively cover the studies regarding these two aspects of TE-mediated gene regulation, mainly focusing on the mechanisms, contribution of different types of TEs, differential roles among tissue types, and lineage-specificity, based on data mostly in humans.

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The draft genome sequence of the grove snail Cepaea nemoralis

G3 Genes|Genome|Genetics ◽

10.1093/g3journal/jkaa071 ◽

2021 ◽

Vol 11 (2) ◽

Author(s):

Suzanne V Saenko ◽

Dick S J Groenenberg ◽

Angus Davison ◽

Menno Schilthuizen

Keyword(s):

Genome Sequence ◽

Draft Genome ◽

Agricultural Pests ◽

Shell Color ◽

Protein Coding ◽

Cepaea Nemoralis ◽

Edible Species ◽

Wide Range ◽

In Captivity ◽

Long Read

Abstract Studies on the shell color and banding polymorphism of the grove snail Cepaea nemoralis and the sister taxon Cepaea hortensis have provided compelling evidence for the fundamental role of natural selection in promoting and maintaining intraspecific variation. More recently, Cepaea has been the focus of citizen science projects on shell color evolution in relation to climate change and urbanization. C. nemoralis is particularly useful for studies on the genetics of shell polymorphism and the evolution of “supergenes,” as well as evo-devo studies of shell biomineralization, because it is relatively easily maintained in captivity. However, an absence of genomic resources for C. nemoralis has generally hindered detailed genetic and molecular investigations. We therefore generated ∼23× coverage long-read data for the ∼3.5 Gb genome, and produced a draft assembly composed of 28,537 contigs with the N50 length of 333 kb. Genome completeness, estimated by BUSCO using the metazoa dataset, was 91%. Repetitive regions cover over 77% of the genome. A total of 43,519 protein-coding genes were predicted in the assembled genome, and 97.3% of these were functionally annotated from either sequence homology or protein signature searches. This first assembled and annotated genome sequence for a helicoid snail, a large group that includes edible species, agricultural pests, and parasite hosts, will be a core resource for identifying the loci that determine the shell polymorphism, as well as in a wide range of analyses in evolutionary and developmental biology, and snail biology in general.

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Natural Science and Supernatural Thought Experiments

Religions ◽

10.3390/rel10060389 ◽

2019 ◽

Vol 10 (6) ◽

pp. 389

Author(s):

James Robert Brown

Keyword(s):

Natural Science ◽

Thought Experiment ◽

Thought Experiments ◽

The Other ◽

Space And Time ◽

Wide Range ◽

The Difference ◽

Theological Thought

Religious notions have long played a role in epistemology. Theological thought experiments, in particular, have been effective in a wide range of situations in the sciences. Some of these are merely picturesque, others have been heuristically important, and still others, as I will argue, have played a role that could be called essential. I will illustrate the difference between heuristic and essential with two examples. One of these stems from the Newton–Leibniz debate over the nature of space and time; the other is a thought experiment of my own constructed with the aim of making a case for a more liberal view of evidence in mathematics.

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Sequence Variation in Two Protein-Coding Genes Correlates with Mycelial Compatibility Groupings in Sclerotium rolfsii

Phytopathology ◽

10.1094/phyto-07-12-0151-r ◽

2013 ◽

Vol 103 (5) ◽

pp. 479-487 ◽

Cited By ~ 6

Author(s):

Efrén Remesal ◽

Blanca B. Landa ◽

María del Mar Jiménez-Gasco ◽

Juan A. Navas-Cortés

Keyword(s):

Rna Polymerase Ii ◽

Sequence Variation ◽

Geographic Origin ◽

Sclerotium Rolfsii ◽

Nuclear Ribosomal Dna ◽

Causal Organism ◽

Protein Coding ◽

Protein Coding Genes ◽

Wide Range ◽

Mycelial Compatibility

Populations of Sclerotium rolfsii, the causal organism of Sclerotium root-rot on a wide range of hosts, can be placed into mycelial compatibility groups (MCGs). In this study, we evaluated three different molecular approaches to unequivocally identify each of 12 previously identified MCGs. These included restriction fragment length polymorphism (RFLP) patterns of the internal transcribed spacer (ITS) region of nuclear ribosomal DNA (rDNA) and sequence analysis of two protein-coding genes: translation elongation factor 1α (EF1α) and RNA polymerase II subunit two (RPB2). A collection of 238 single-sclerotial isolates representing 12 MCGs of S. rolfsii were obtained from diseased sugar beet plants from Chile, Italy, Portugal, and Spain. ITS-RFLP analysis using four restriction enzymes (AluI, HpaII, RsaI, and MboI) displayed a low degree of variability among MCGs. Only three different restriction profiles were identified among S. rolfsii isolates, with no correlation to MCG or to geographic origin. Based on nucleotide polymorphisms, the RPB2 gene was more variable among MCGs compared with the EF1α gene. Thus, 10 of 12 MCGs could be characterized utilizing the RPB2 region only, while the EF1α region resolved 7 MCGs. However, the analysis of combined partial sequences of EF1α and RPB2 genes allowed discrimination among each of the 12 MCGs. All isolates belonging to the same MCG showed identical nucleotide sequences that differed by at least in one nucleotide from a different MCG. The consistency of our results to identify the MCG of a given S. rolfsii isolate using the combined sequences of EF1α and RPB2 genes was confirmed using blind trials. Our study demonstrates that sequence variation in the protein-coding genes EF1α and RPB2 may be exploited as a diagnostic tool for MCG typing in S. rolfsii as well as to identify previously undescribed MCGs.

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