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Plus nous étudions l'ARN, plus complexe il devient. En améliorant notre compréhension du paysage transcriptionnel, nous commençons à saisir que nous avons longtemps négligé un mécanisme génétique majeur en pathologie humaine. Le vaste répertoire de transcrits produits par le génome humain découle de mécanismes tels que l'épissage alternatif ou l'utilisation différentielle de promoteurs. Pour relever le nouveau défi d'interprétation à l'ère du séquençage haut débit, il est nécessaire d'améliorer la caractérisation des variations causales impactant l'ARN. Pour cela, plusieurs obstacles doivent être surmontés: ◗ prédire de manière sensible et précise l'impact des variants; ◗ obtenir des échantillons d'ARN pertinents et de bonne qualité; ◗ déployer les techniques adéquates pour évaluer qualitativement et quantitativement les transcrits. Ainsi, une véritable expertise est requise pour interpréter correctement ces données. The more we study RNA, the more complex it becomes. As we try to understand our large transcriptional landscape, we begin to grasp how we may have long overlooked a major genetic disease-causing mechanism. The vast repertoire of RNA transcripts arises from mechanisms such as alternative splicing or differential promoter usage. To address the new interpretation challenge we face in the era of next generation sequencing, we must improve the characterization of disease-causing genomic variations impacting RNA. To do so, several challenges must be overcome: ◗ predicting accurately splicing variations; ◗ obtaining relevant and good quality RNA samples; ◗ deploying the proper techniques to evaluate transcripts qualitatively and quantitatively. Therefore, in order to correctly interpret these data, expertise is required. [ABSTRACT FROM AUTHOR]

Dorper sheep is popular among farming enterprises with strong adaptability, disease resistance, and roughage tolerance, and an unique characteristic of natural shedding of wool. In a large number of observations on experimental sheep farms, it was found that the wool of some sheep still had not shed after May, thus manual shearing was required. Therefore, understanding the molecular mechanisms of normal hair follicles (HFs) development is crucial to revealing the improvement of sheep wool-related traits and mammalian skin-related traits. In this study, transcriptome analysis was performed on skin tissues of adult Dorper ewes in the shedding (S) and non-shedding (N) groups in September 2019, January 2020, and March 2020, respectively. The results identified 3,278 differentially expressed transcripts (DETs) in the three comparison groups within the S group, 720 DETs in the three comparison groups within the N group, and 1,342 DETs in the three comparison groups between the S- vs -N groups. Time-series expression analysis revealed 2 unique expression patterns in HF development, namely, elevated expression in the anagen phase (A pattern) and the telogen phase (T pattern). DETs with stage-specific expression had a significant presence in processes related to the hair cycle and skin development, and several classic signaling pathways involved in sheep HF development, such as Rap1, estrogen, PI3K-Akt, and MAPK, were detected. Combined analysis of DETs, time-series expression data, and weighted gene co-expression network analysis identified core genes and their transcripts influencing HF development, such as DBI , FZD3 , KRT17 , ZDHHC21 , TMEM79 , and HOXC13. Additionally, alternative splicing analysis predicted that the isoforms XM_004004383.4 and XM_012125926.3 of ZDHHC21 might play a crucial role in sheep HF development. This study is a valuable resource for explaining the morphology of normal growth and development of sheep HFs and the genetic foundation of mammalian skin-related traits. It also offers potential insights into factors influencing human hair advancement. [ABSTRACT FROM AUTHOR]

CASK (MIM#300172), encoding a calcium/calmodulin‐dependent serine protein kinase, is crucial for synaptic transmission and gene regulation during neural development. Pathogenic variants of CASK are known to cause several neurodevelopmental disorders, including X‐linked intellectual disability and microcephaly with pontine and cerebellar hypoplasia (MICPCH). This study introduces a novel, de novo synonymous CASK variant (NM_001367721.1: c.1737G>A, p.(Glu579=)), discovered in a male patient diagnosed with MICPCH, characterized by microcephaly, developmental delay, visual impairment, and myoclonic seizures. The variant disrupts a donor splice‐site at the end of exon 18. Transcriptomic analysis of blood identified 12 different CASK transcripts secondary to the synonymous variant. Nearly one third of these transcripts were predicted to result in nonsense mediated decay or protein degradation. Protein modeling revealed structural alterations in the PDZ functional domain of CASK, due to exon 18 deletion. Our findings highlight the utility of transcriptomic analysis in demonstrating the underlying disease mechanism in neurodevelopmental disorders. [ABSTRACT FROM AUTHOR]

Flesh firmness is an important quality of pear fruits. Breeding cultivars with suitably low flesh firmness is one of the popular pear breeding goals. At present, SNP markers related to pear flesh firmness and genes affecting flesh firmness are still uncertain. In this study, a QTL analysis was performed, and the result showed that the position of 139.857 cM in lineage group 14 (LG14) had the highest average logarithm of odds (3.41) over two years. This newly discovered locus was identified as a flesh firmness-related QTL (qFirmness-LG14). The 'C/T' SNP was found in corresponding Marker1512129. The 'C' genotype is the high-firmness genotype, which is a dominant trait. The average firmness of fruits with genotype C is 21.4% higher than genotype without the C genotype. Transcriptome profiling was obtained between 'Zaoshengxinshui' and 'Qiushui' at five time points. Three candidate genes in the interval of qFirmness-LG14 might affect firmness. A gene of xyloglucan endotransglucosylase 1 (PpXTH1) was upregulated in 'Qiushui' at all five time points. Two transcription factors (PpHY5 and PpERF113) were upregulated in 'Zaoshengxinshui', which might be negative regulatory genes for high flesh firmness. The transcriptome results also isolated a large number of cell wall-related genes (e.g., Pectate lyase, Pectin acetylesterase, Pectin methylesterase, and 4-coumarate-CoA ligase) and transcription factors (e.g., ERF, WRKY). These genes are all potential upstream and downstream genes related to flesh firmness. In conclusion, this study provides valuable insights into the QTLs and molecular mechanisms associated with fruit firmness in Pyrus pyrifolia. [ABSTRACT FROM AUTHOR]

In addition to printed books, Prekmurian Slovene language has a rich tradition of manuscripts (especially handwritten songbooks), which dates back to the 16th century. The preserved manuscript songbooks are mostly collections of religious, church songs; however, many mortuary songbooks can also be found. The first manuscript in Prekmurje was the socalled Prva Martjanska pesmarica (songbook), which was started by Protestants in the 16th century in the village of Martjanci (near Murska Sobota). The copyists included the songs from this songbook into their own manuscripts, and the songs spread everywhere between the Mura and the Raba. The tradition of songbooks continued in the 18th, 19th and 20th centuries. In the process of copying, various authors improved and added to the poems linguistically. Many of them were taken over by other authors in their printed prayer books and songbooks (e.g. Mikloš Kuzmič, Štefan Sijarto, Mihael Bakoš, Jožef Pustaj, Anton Števanec). Today some manuscripts are kept in archives or libraries, while others are still in private ownership. Several manuscripts were never recovered.

Abstract Background The APOE gene is the strongest genetic risk factor for late-onset Alzheimer’s Disease (LOAD). However, the gene regulatory mechanisms at this locus remain incompletely characterized. Methods To identify novel AD-linked functional elements within the APOE locus, we integrated SNP variants with multi-omics data from human postmortem brains including 2,179 RNA-seq samples from 3 brain regions and two ancestries (European and African), 667 DNA methylation samples, and ChIP-seq samples. Additionally, we plotted the expression trajectory of APOE transcripts in human brains during development. Results We identified an AD-linked APOE transcript (jxn1.2.2) particularly observed in the dorsolateral prefrontal cortex (DLPFC). The APOE jxn1.2.2 transcript is associated with brain neuropathological features, cognitive impairment, and the presence of the APOE4 allele in DLPFC. We prioritized two independent functional SNPs (rs157580 and rs439401) significantly associated with jxn1.2.2 transcript abundance and DNA methylation levels. These SNPs are located within active chromatin regions and affect brain-related transcription factor-binding affinities. The two SNPs shared effects on the jxn1.2.2 transcript between European and African ethnic groups. Conclusion The novel APOE functional elements provide potential therapeutic targets with mechanistic insight into the disease etiology.

Malaria control relies on insecticides targeting the mosquito vector, but this is increasingly compromised by insecticide resistance, which can be achieved by elevated expression of detoxifying enzymes that metabolize the insecticide. In diploid organisms, gene expression is regulated both in cis, by regulatory sequences on the same chromosome, and by trans acting factors, affecting both alleles equally. Differing levels of transcription can be caused by mutations in cis-regulatory modules (CRM), but few of these have been identified in mosquitoes. We crossed bendiocarb-resistant and susceptible Anopheles gambiae strains to identify cis-regulated genes that might be responsible for the resistant phenotype using RNAseq, and CRM sequences controlling gene expression in insecticide resistance relevant tissues were predicted using machine learning. We found 115 genes showing allele-specific expression (ASE) in hybrids of insecticide susceptible and resistant strains, suggesting cis-regulation is an important mechanism of gene expression regulation in A. gambiae. The genes showing ASE included a higher proportion of Anopheles-specific genes on average younger than genes with balanced allelic expression. [ABSTRACT FROM AUTHOR]

Background: The APOE gene is the strongest genetic risk factor for late-onset Alzheimer's Disease (LOAD). However, the gene regulatory mechanisms at this locus remain incompletely characterized. Methods: To identify novel AD-linked functional elements within the APOE locus, we integrated SNP variants with multi-omics data from human postmortem brains including 2,179 RNA-seq samples from 3 brain regions and two ancestries (European and African), 667 DNA methylation samples, and ChIP-seq samples. Additionally, we plotted the expression trajectory of APOE transcripts in human brains during development. Results: We identified an AD-linked APOE transcript (jxn1.2.2) particularly observed in the dorsolateral prefrontal cortex (DLPFC). The APOE jxn1.2.2 transcript is associated with brain neuropathological features, cognitive impairment, and the presence of the APOE4 allele in DLPFC. We prioritized two independent functional SNPs (rs157580 and rs439401) significantly associated with jxn1.2.2 transcript abundance and DNA methylation levels. These SNPs are located within active chromatin regions and affect brain-related transcription factor-binding affinities. The two SNPs shared effects on the jxn1.2.2 transcript between European and African ethnic groups. Conclusion: The novel APOE functional elements provide potential therapeutic targets with mechanistic insight into the disease etiology. [ABSTRACT FROM AUTHOR]

Dorper sheep is popular among farming enterprises with strong adaptability, disease resistance, and roughage tolerance, and an unique characteristic of natural shedding of wool. In a large number of observations on experimental sheep farms, it was found that the wool of some sheep still had not shed after May, thus manual shearing was required. Therefore, understanding the molecular mechanisms of normal hair follicles (HFs) development is crucial to revealing the improvement of sheep wool-related traits and mammalian skin-related traits. In this study, transcriptome analysis was performed on skin tissues of adult Dorper ewes in the shedding (S) and non-shedding (N) groups in September 2019, January 2020, and March 2020, respectively. The results identified 3,278 differentially expressed transcripts (DETs) in the three comparison groups within the S group, 720 DETs in the three comparison groups within the N group, and 1,342 DETs in the three comparison groups between the S-vs-N groups. Time-series expression analysis revealed 2 unique expression patterns in HF development, namely, elevated expression in the anagen phase (A pattern) and the telogen phase (T pattern). DETs with stage-specific expression had a significant presence in processes related to the hair cycle and skin development, and several classic signaling pathways involved in sheep HF development, such as Rap1, estrogen, PI3K-Akt, and MAPK, were detected. Combined analysis of DETs, time-series expression data, and weighted gene co-expression network analysis identified core genes and their transcripts influencing HF development, such as DBI, FZD3, KRT17, ZDHHC21, TMEM79, and HOXC13. Additionally, alternative splicing analysis predicted that the isoforms XM_004004383.4 and XM_012125926.3 of ZDHHC21 might play a crucial role in sheep HF development. This study is a valuable resource for explaining the morphology of normal growth and development of sheep HFs and the genetic foundation of mammalian skin-related traits. It also offers potential insights into factors influencing human hair advancement.

Identification of pathogenic RB1 variants aids in the clinical management of families with retinoblastoma. We routinely screen DNA for RB1 variants, but transcript analysis can also be used for variant screening, and to help decide variant pathogenicity. DNA was screened by conformation analysis followed by Sanger sequencing. Large deletion/insertions were detected by polymorphism analysis, MLPA and quantitative-PCR. Methylation-specific PCR was used to detect hypermethylation. RNA screening was performed when a DNA pathogenic variant was missing, or to determine effects on splicing. Two hundred and thirteen small coding variants were predicted to affect splicing in 207 patients. Splice donor (sd) variants were nearly twice as frequent as splice acceptor (sa) with the most affected positions being sd + 1 and sa−1. Some missense and nonsense codons altered splicing, while some splice consensus variants did not. Large deletion/insertions can disrupt splicing, but RNA analysis showed that some of these are more complex than indicated by DNA testing. RNA screening found pathogenic variants in 53.8% of samples where DNA analysis did not. RB1 splicing is altered by changes at consensus splice sites, some missense and nonsense codons, deep intronic changes and large deletion/insertions. Common alternatively spliced transcripts may complicate analysis. An effective molecular screening strategy would include RNA analysis to help determine pathogenicity. [ABSTRACT FROM AUTHOR]

Mercury (Hg) methylation in mangrove sediments can result in the accumulation of neurotoxic methylmercury (MeHg). Identification of Hg methyltransferase gene hgcA provides the means to directly characterize the microbial Hg-methylating consortia in environments. Hitherto, the microbial Hg-methylating community in mangrove sediments was scarcely investigated. An effort to assess the diversity and abundance of hgcA genes and transcripts and link them to Hg and MeHg contents was made in the mangrove intertidal sediments along the urbanized Shenzhen Bay, China. The hgcA genes and transcripts associated with Thermodesulfobacteria [mainly Geobacteraceae, Syntrophorhabdaceae, Desulfobacterales, and Desulfarculales (these four lineages were previously classified into the Deltaproteobacteria taxon)], as well as Euryarchaeota (mainly Methanomicrobia and Theionarchaea) dominated the hgcA-harboring communities, while Chloroflexota, Nitrospirota, Planctomycetota, and Lentisphaerota-like hgcA sequences accounted for a small proportion. The hgcA genes appeared in greater abundance and diversity than their transcript counterparts in each sampling site. Correlation analysis demonstrated that the MeHg content rather than Hg content significantly correlated with the structure of the existent/active hgcA-harboring community and the abundance of hgcA genes/transcripts. These findings provide better insights into the microbial Hg methylation drivers in mangrove sediments, which could be helpful for understanding the MeHg biotransformation therein. [ABSTRACT FROM AUTHOR]

Acetylcholine is the endogenous agonist for the neuronal nicotinic acetylcholine receptor (nAChR) system, which is involved in attention, memory, affective behaviours and substance use disorders. Brain nAChRs are highly diverse with 11 different subunits that can form multiple receptor subtypes, each with distinct receptor and pharmacological properties. Different neuronal cell types can also express different nAChR subtypes, resulting in highly complex cholinergic signalling. Identifying which nAChR subunit transcripts are expressed in cell types can provide an indication of which nAChR combinations are possible and which receptor subtypes may be most pharmacologically relevant to target. In addition to differences in expression across cell types, nAChRs also undergo changes in expression levels from adolescence to adulthood. In this study, we used fluorescent in situ hybridization to identify and quantify the expression of α4, α5, α6, β2 and β3 nAChR subunit transcripts in dopaminergic, GABAergic, glutamatergic and noradrenergic neurons and astrocytes in the ventral tegmental area (VTA) and locus coeruleus (LC) in adult and adolescent, male and female C57BL/6J mice. There were distinct differences in the pattern of nAChR subunit transcript expression between the two brain regions. LC noradrenergic neurons had high prevalence of α6, β2 and β3 expression, with very low expression of α4, suggesting the α6(non‐α4)β2β3 receptor as a main subtype in these neurons. VTA astrocytes from adult mice showed greater prevalence of α5, α6, β2 and β3 transcript compared with adolescent mice. These data highlight the complex nAChR expression patterns across brain region and cell type. [ABSTRACT FROM AUTHOR]

Background: Dementia is a cognitive decline that leads to the progressive deterioration of an individual's ability to perform daily activities independently. As a result, a considerable amount of time and resources are spent on caretaking. Early detection of dementia can significantly reduce the effort and resources needed for caretaking. Aims: This research proposes an approach for assessing cognitive decline by analysing speech data, specifically focusing on speech relevance as a crucial indicator for memory recall. Methods & Procedures: This is a cross‐sectional, online, self‐administered. The proposed method used deep learning architecture based on transformers, with BERT (Bidirectional Encoder Representations from Transformers) and Sentence‐Transformer to derive encoded representations of speech transcripts. These representations provide contextually descriptive information that is used to analyse the relevance of sentences in their respective contexts. The encoded information is then compared using cosine similarity metrics to measure the relevance of uttered sequences of sentences. The study uses the Pitt Corpus Dementia dataset for experimentation, which consists of speech data from individuals with and without dementia. The accuracy of the proposed multi‐QA‐MPNet (Multi‐Query Maximum Inner Product Search Pretraining) model is compared with other pretrained transformer models of Sentence‐Transformer. Outcomes & Results: The results show that the proposed approach outperforms the other models in capturing context level information, particularly semantic memory. Additionally, the study explores the suitability of different similarity measures to evaluate the relevance of uttered sequences of sentences. The experimentation reveals that cosine similarity is the most appropriate measure for this task. Conclusions & Implications: This finding has significant implications for the early warning signs of dementia, as it suggests that cosine similarity metrics can effectively capture the semantic relevance of spoken language. The persistent cognitive decline over time acts as one of the indicators for prevalence of dementia. Additionally early dementia could be recognised by analysis on other modalities like speech and brain images. WHAT THIS PAPER ADDS: What is already known on this subject: It is already known that speech‐ and language‐based detection methods can be useful for dementia diagnosis, as language difficulties are often early signs of the disease. Additionally, deep learning algorithms have shown promise in detecting and diagnosing dementia through analysing large datasets, particularly in speech‐ and language‐based detection methods. However, further research is needed to validate the performance of these algorithms on larger and more diverse datasets and to address potential biases and limitations. What this paper adds to existing knowledge: This study presents a unique and effective approach for cognitive decline assessment through analysing speech data. The study provides valuable insights into the importance of context and semantic memory in accurately detecting the potential in dementia and demonstrates the applicability of deep learning models for this purpose. The findings of this study have important clinical implications and can inform future research and development in the field of dementia detection and care. What are the potential or actual clinical implications of this work?: The proposed approach for cognitive decline assessment using speech data and deep learning models has significant clinical implications. It has the potential to improve the accuracy and efficiency of dementia diagnosis, leading to earlier detection and more effective treatments, which can improve patient outcomes and quality of life. [ABSTRACT FROM AUTHOR]

Ticks, blood-sucking ectoparasites, spread diseases to humans and animals. Haemaphysalis longicornis is a significant vector for tick-borne diseases in medical and veterinary contexts. Identifying protective antigens in H. longicornis for an anti-tick vaccine is a key tick control strategy. Enolase, a multifunctional protein, significantly converts D-2-phosphoglycerate and phosphoenolpyruvate in glycolysis and gluconeogenesis in cell cytoplasm. This study cloned a complete open reading frame (ORF) of enolase from the H. longicornis tick and characterized its transcriptional and silencing effect. We amplified the full-length cDNA of the enolase gene using rapid amplification of cDNA ends. The complete cDNA, with an ORF of 1,297 nucleotides, encoded a 432-amino acid polypeptide. Enolase of the Jeju strain H. longicornis exhibited the highest sequence similarity with H. flava (98%), followed by Dermacentor silvarum (82%). The enolase motifs identified included N-terminal and C-terminal regions, magnesium binding sites, and several phosphorylation sites. Reverse transcription-polymerase chain reaction (RT-PCR) analysis indicated that enolase mRNA transcripts were expressed across all developmental stages of ticks and organs such as salivary gland and midgut. RT-PCR showed higher transcript levels in syn-ganglia, suggesting that synganglion nerves influence enolase's role in tick salivary glands. We injected enolase double-stranded RNA into adult unfed female ticks, after which they were subsequently fed with normal unfed males until they spontaneously dropped off. RNA interference significantly (P<0.05) reduced feeding and reproduction, along with abnormalities in eggs (no embryos) and hatching. These findings suggest enolase is a promising target for future tick control strategies. [ABSTRACT FROM AUTHOR]

Importance: Haemaphysalis longicornis is an obligate blood-sucking ectoparasite that has gained attention due its role of transmitting medically and veterinary significant pathogens and it is the most common tick species in Republic of Korea. The preferred strategy for controlling ticks is a multi-antigenic vaccination. Testing the efficiency of a combination antigen is a promising method for creating a tick vaccine. Objective: The aim of the current research was to analyze the role of subolesin and enolase in feeding and reproduction of H. longicornis by gene silencing. Methods: In this study, we used RNA interference to silence salivary enolase and subolesin in H. longicornis. Unfed female ticks injected with double-stranded RNA targeting subolesin and enolase were attached and fed normally on the rabbit's ear. Real-time polymerase chain reaction was used to confirm the extent of knockdown. Results: Ticks in the subolesin or enolase dsRNA groups showed knockdown rates of 80% and 60% respectively. Ticks in the combination dsRNA (subolesin and enolase) group showed an 80% knockdown. Knockdown of subolesin and enolase resulted in significant depletion in feeding, blood engorgement weight, attachment rate, and egg laying. Silencing of both resulted in a significant (p < 0.05) reduction in tick engorgement, egg laying, egg hatching (15%), and reproduction. Conclusions and Relevance: Our results suggest that subolesin and enolase are an exciting target for future tick control strategies. [ABSTRACT FROM AUTHOR]

Background: The associations of high-density lipoprotein (HDL) level and functionality with lipid metabolism, inflammation, and innate immunity in coronary artery disease (CAD) remain controversial. The differential expression of a set of genes related to HDL metabolism (24 genes) and atherogenesis (41 genes) in peripheral blood mononuclear cells (PBMC) from CAD and control patients with varied HDL cholesterol (HDL-C) levels was compared. Methods: 76 male patients 40–60 years old with CAD diagnosed by angiography and 63 control patients were divided into three groups with low, normal (1.0–1.4 mM), and increased HDL-C levels. Transcript levels were measured by real-time PCR. The differentially expressed genes (DEGs) and associated metabolic pathways were analyzed for three groups, with prevalent CAD as an outcome. Results: The common feature was the increased odds ratio values for liver X receptor (LXR) gene expression for three patient groups. CAD patients with low HDL-C possessed 24 DEGs with lower expression of genes involved in cholesterol efflux, and down-regulated SREBF1 and ABCG1 are suggested as gene signatures. CAD patients with normal HDL-C possessed nine DEGs with down-regulated ITGAM and ALB as gene signatures. CAD patients with increased HDL-C possessed 19 DEGs with down-regulated APOA1 and HMGCR as gene signatures. With gene expression signatures, one standard deviation higher average gene expressions were associated with 5.1-, 48.8-, and 38.9-fold fewer CAD cases for three patient groups. As HDL-C increased in CAD patients, the expression of ABCG1, CUBN, and HDLBP genes increased, while the expression of HMGCR and NPC2 genes, involved in cholesterol synthesis and trafficking, decreased. The expression of CD14, CD36, S100A8, S100A9, S100A12, TLR5, TLR8, and VEGFA genes, involved in angiogenesis and inflammation mainly via nuclear factor-κB (NF-κB), decreased. Conclusions: The increased accumulation of cholesteryl ester in PBMC from patients with low HDL-C was suggested. This assumption contrasts with the suggested accumulation of free cholesterol in PBMC from patients with increased HDL-C, concomitant with suppression of cholesterol synthesis and traffic to the plasma membrane, and with an inflammatory state controlled by depressed CD36-mediated and upregulated apoE-mediated immunometabolic signaling. Gene signatures may be used for the diagnosis, prognosis, and treatment of CAD in dependence on HDL-C levels.

Introduction: Proinflammatory cytokines are implicated in pancreatic ß cell failure in type 1 and type 2 diabetes and are known to stimulate alternative RNA splicing and the expression of nonsense-mediated RNA decay (NMD) components. Here, we investigate whether cytokines regulate NMD activity and identify transcript isoforms targeted in ß cells. Methods: A luciferase-based NMD reporter transiently expressed in rat INS1(832/13), human-derived EndoC-ßH3, or dispersed human islet cells is used to examine the effect of proinflammatory cytokines (Cyt) on NMD activity. The gain- or loss-of-function of two key NMD components, UPF3B and UPF2, is used to reveal the effect of cytokines on cell viability and function. RNA-sequencing and siRNA-mediated silencing are deployed using standard techniques. Results: Cyt attenuate NMD activity in insulin-producing cell lines and primary human ß cells. These effects are found to involve ER stress and are associated with the downregulation of UPF3B. Increases or decreases in NMD activity achieved by UPF3B overexpression (OE) or UPF2 silencing raise or lower Cyt-induced cell death, respectively, in EndoC-ßH3 cells and are associated with decreased or increased insulin content, respectively. No effects of these manipulations are observed on glucose-stimulated insulin secretion. Transcriptomic analysis reveals that Cyt increases alternative splicing (AS)-induced exon skipping in the transcript isoforms, and this is potentiated by UPF2 silencing. Gene enrichment analysis identifies transcripts regulated by UPF2 silencing whose proteins are localized and/or functional in the extracellular matrix (ECM), including the serine protease inhibitor SERPINA1/α-1-antitrypsin, whose silencing sensitizes ß-cells to Cyt cytotoxicity. Cytokines suppress NMD activity via UPR signaling, potentially serving as a protective response against Cyt-induced NMD component expression. Conclusion: Our findings highlight the central importance of RNA turnover in ß cell responses to inflammatory stress. [ABSTRACT FROM AUTHOR]

To investigate the functional differences of angiopoietin-related protein 4 (ANGPTL4) transcripts in hepatocellular carcinoma (HCC) cells. By transfecting ANGPTL4-Transcript 1 and ANGPTL4-Transcript 3 overexpression vectors into HepG2 and Huh7 cell lines with ANGPTL4 knockdown, the effects of overexpression of two transcripts on cell viability, invasion, migration, and apoptosis were analyzed. The expression of two transcripts was compared in human liver cancer tissue, and their effects on tumor development were validated in vivo experiments in mice. Compared with control, the overexpression of ANGPTL4-Transcript 1 had no significant effect on viability, invasion, healing, and apoptosis of HepG2 and Huh7 cells. However, these two cell lines overexpressing ANGPTL4-Transcript 3 showed remarkably enhanced cell viability, invasive and healing ability, and decreased apoptosis ability. Furthermore, the mRNA level of ANGPTL4-Transcript 3 was significantly increased in human HCC tissues and promoted tumor growth compared with Transcript 1. Different transcripts of gene ANGPTL4 have distinct effects on HCC. The abnormally elevated Transcript 3 with the specific ability of promoting HCC proliferation, infiltration, and migration is expected to become a new biological marker and more precise intervention target for HCC. [ABSTRACT FROM AUTHOR]

Sally Snyder conducted ethnographic field research in the Skagit region of the Pacific Northwest in the 1950s. She focused on ethnopsychology as reflected in folktales and mythology. While still a graduate student, the Swinomish Indian Tribal Community asked her to orient her field work on Tribal lands lost in the Point Elliott Treaty of 1855. She adapted her study to include cultural geography and genealogy. She created a set of Field Notes and Exhibits to support her testimony during the Indian Claims Case hearings in 1953 and 1955. In the 1970s, she resumed her work as expert anthropologist during the United States of America v. State of Washington proceedings regarding Tribal claims to traditional fishing territory. She served as ethnographic consultant for Tribal governments and on cultural resource assessment projects. Snyder’s work in the legal realm reveals the importance of her role in this nonacademic context. The ethnographic information contained in her expert reports, depositions, testimony, and exhibits is of significance to Pacific Northwest history. [ABSTRACT FROM AUTHOR]

During the remote 2024 Spring Business Meeting of the Visual Resources Association, the VRA president highlighted the accomplishments and challenges of the Association in a State of the Association address. This article provides the transcript. [ABSTRACT FROM AUTHOR]

This study is an empirical inquiry into the re-election of elected assembly members and investigates whether incumbents' general participation in legislative sessions is a determinant of the outcome of their re-election efforts. This study measures legislative participation based on the amount of speech on the plenary session floor during the immediately preceding term, which is tabulated from published local assembly transcripts. The data for the analysis come from 41 prefecture assemblies in Japan that held elections on the same day in April 2015. This sample enables us to test whether legislative participation has a positive electoral impact across different localities. The empirical analysis of the re-election outcomes of elected officials suggests that floor speech is a factor contributing to electoral success for assembly members. In addition, this speech effect diminishes as incumbents accumulate terms, and it is the first term legislators who benefit most from the positive re-election effect of speech. [ABSTRACT FROM AUTHOR]

Differential expression of genes (DEGs) in coronary artery disease (CAD) and the association between transcript level and high-density lipoprotein cholesterol (HDL-C) were studied with 76 male patients with CAD and 63 control patients. The transcript level of genes related to HDL metabolism (24 genes) and atherosclerosis-prone (41 genes) in RNA isolated from peripheral blood mononuclear cells was measured by real-time RT-PCR. Twenty-eight DEGs were identified. The expression of cholesterol transporters, ALB, APOA1, and LCAT was down-regulated, while the expression of AMN, APOE, LDLR, LPL, PLTP, PRKACA, and CETP was up-regulated. The systemic inflammation in CAD is evidenced by the up-regulation of IL1B, TLR8, CXCL5, and TNFRSF1A. For the controls, TLR8 and SOAT1 were negative predictors of the HDL-C level. For CAD patients, PRKACG, PRKCQ, and SREBF1 were positive predictors, while PRKACB, LCAT, and S100A8 were negative predictors. For CAD patients, the efficiency of reverse cholesterol transport is 73–79%, and intracellular free cholesterol seems to accumulate at hyperalphalipoproteinemia. Both atheroprotective (via S100A8) and proatherogenic (via SREBF1, LCAT, PRKACG, PRKACB, and PRKCQ) associations of gene expression with HDL-C determine HDL functionality in CAD patients. The selected key genes and involved pathways may represent HDL-specific targets for the diagnosis and treatment of CAD and atherosclerosis.

IntroductionProinflammatory cytokines are implicated in pancreatic ß cell failure in type 1 and type 2 diabetes and are known to stimulate alternative RNA splicing and the expression of nonsense-mediated RNA decay (NMD) components. Here, we investigate whether cytokines regulate NMD activity and identify transcript isoforms targeted in ß cells.MethodsA luciferase-based NMD reporter transiently expressed in rat INS1(832/13), human-derived EndoC-ßH3, or dispersed human islet cells is used to examine the effect of proinflammatory cytokines (Cyt) on NMD activity. The gain- or loss-of-function of two key NMD components, UPF3B and UPF2, is used to reveal the effect of cytokines on cell viability and function. RNA-sequencing and siRNA-mediated silencing are deployed using standard techniques.ResultsCyt attenuate NMD activity in insulin-producing cell lines and primary human ß cells. These effects are found to involve ER stress and are associated with the downregulation of UPF3B. Increases or decreases in NMD activity achieved by UPF3B overexpression (OE) or UPF2 silencing raise or lower Cyt-induced cell death, respectively, in EndoC-ßH3 cells and are associated with decreased or increased insulin content, respectively. No effects of these manipulations are observed on glucose-stimulated insulin secretion. Transcriptomic analysis reveals that Cyt increases alternative splicing (AS)-induced exon skipping in the transcript isoforms, and this is potentiated by UPF2 silencing. Gene enrichment analysis identifies transcripts regulated by UPF2 silencing whose proteins are localized and/or functional in the extracellular matrix (ECM), including the serine protease inhibitor SERPINA1/α-1-antitrypsin, whose silencing sensitizes ß-cells to Cyt cytotoxicity. Cytokines suppress NMD activity via UPR signaling, potentially serving as a protective response against Cyt-induced NMD component expression.ConclusionOur findings highlight the central importance of RNA turnover in ß cell responses to inflammatory stress.

The COVID-19 pandemic has caused people to rely more and more on online communication tools, which has resulted in an astounding amount of data from virtual meetings and discussions across various platforms such as Zoom, Slack, Microsoft Teams, Discord, and others. The increase in online interactions has led to a massive information overload, which makes it difficult for people to efficiently sift through lengthy meeting transcripts in order to extract important insights. Meeting summarizers have become essential tools providing a simplified answer as a result of the realization of how important it is to deal with this information overload. These summarizing tools save users the tiresome job of reading through lengthy transcripts by providing an effective way to extract relevant information from dense meeting recordings. However, there aren't many thorough studies available on meeting summarizers. This research paper aims to provide important insights and a thorough understanding of the current landscape by conducting an in-depth analysis of speech-to-text meeting summarization methods. This will pave the way for future advancements and improvements in the field of meeting summarization technology. In this research paper, we aim to clarify the features and complexities of speech-to-text meeting summarizers, highlighting their potential for recording spoken material into written form, highlighting important points, and producing short and informative summaries. In addition, our objective is to examine the effectiveness and constraints of these instruments in managing a range of meeting configurations, language variations, and contextual details. Through this detailed exploration, our goal is to make a substantial contribution and promote a thorough knowledge of speech-to-text meeting summarizing techniques. [ABSTRACT FROM AUTHOR]

Secondary development is a key biological characteristic of woody plants and the basis of wood formation. Exogenous nitrogen can affect the secondary growth of poplar, and some regulatory mechanisms have been found in the secondary xylem. However, the effect of nitrogen on cambium has not been reported. Herein, we investigated the effects of different nitrogen concentrations on cambium development using combined transcriptome and metabolome analysis. The results show that, compared with 1 mM NH4NO3 (M), the layers of hybrid poplar cambium cells decreased under the 0.15 mM NH4NO3 (L) and 0.3 mM NH4NO3 (LM) treatments. However, there was no difference in the layers of hybrid poplar cambium cells under the 3 mM NH4NO3 (HM) and 5 mM NH4NO3 (H) treatments. Totals of 2365, 824, 649 and 398 DEGs were identified in the M versus (vs.) L, M vs. LM, M vs. HM and M vs. H groups, respectively. Expression profile analysis of the DEGs showed that exogenous nitrogen affected the gene expression involved in plant hormone signal transduction, phenylpropanoid biosynthesis, the starch and sucrose metabolism pathway and the ubiquitin-mediated proteolysis pathway. In M vs. L, M vs. LM, M vs. HM and M vs. H, differential metabolites were enriched in flavonoids, lignans, coumarins and saccharides. The combined analysis of the transcriptome and metabolome showed that some genes and metabolites in plant hormone signal transduction, phenylpropanoid biosynthesis and starch and sucrose metabolism pathways may be involved in nitrogen regulation in cambium development, whose functions need to be verified. In this study, from the point of view that nitrogen influences cambium development to regulate wood formation, the network analysis of the transcriptome and metabolomics of cambium under different nitrogen supply levels was studied for the first time, revealing the potential regulatory and metabolic mechanisms involved in this process and providing new insights into the effects of nitrogen on wood development. [ABSTRACT FROM AUTHOR]

Background: Medical documentation plays a crucial role in clinical practice, facilitating accurate patient management and communication among health care professionals. However, inaccuracies in medical notes can lead to miscommunication and diagnostic errors. Additionally, the demands of documentation contribute to physician burnout. Although intermediaries like medical scribes and speech recognition software have been used to ease this burden, they have limitations in terms of accuracy and addressing provider-specific metrics. The integration of ambient artificial intelligence (AI)–powered solutions offers a promising way to improve documentation while fitting seamlessly into existing workflows. Objective: This study aims to assess the accuracy and quality of Subjective, Objective, Assessment, and Plan (SOAP) notes generated by ChatGPT-4, an AI model, using established transcripts of History and Physical Examination as the gold standard. We seek to identify potential errors and evaluate the model's performance across different categories. Methods: We conducted simulated patient-provider encounters representing various ambulatory specialties and transcribed the audio files. Key reportable elements were identified, and ChatGPT-4 was used to generate SOAP notes based on these transcripts. Three versions of each note were created and compared to the gold standard via chart review; errors generated from the comparison were categorized as omissions, incorrect information, or additions. We compared the accuracy of data elements across versions, transcript length, and data categories. Additionally, we assessed note quality using the Physician Documentation Quality Instrument (PDQI) scoring system. Results: Although ChatGPT-4 consistently generated SOAP-style notes, there were, on average, 23.6 errors per clinical case, with errors of omission (86%) being the most common, followed by addition errors (10.5%) and inclusion of incorrect facts (3.2%). There was significant variance between replicates of the same case, with only 52.9% of data elements reported correctly across all 3 replicates. The accuracy of data elements varied across cases, with the highest accuracy observed in the "Objective" section. Consequently, the measure of note quality, assessed by PDQI, demonstrated intra- and intercase variance. Finally, the accuracy of ChatGPT-4 was inversely correlated to both the transcript length (P =.05) and the number of scorable data elements (P =.05). Conclusions: Our study reveals substantial variability in errors, accuracy, and note quality generated by ChatGPT-4. Errors were not limited to specific sections, and the inconsistency in error types across replicates complicated predictability. Transcript length and data complexity were inversely correlated with note accuracy, raising concerns about the model's effectiveness in handling complex medical cases. The quality and reliability of clinical notes produced by ChatGPT-4 do not meet the standards required for clinical use. Although AI holds promise in health care, caution should be exercised before widespread adoption. Further research is needed to address accuracy, variability, and potential errors. ChatGPT-4, while valuable in various applications, should not be considered a safe alternative to human-generated clinical documentation at this time. [ABSTRACT FROM AUTHOR]

The role of tetraspanin CD81 in malignant transformation is best studied in colorectal cancer, and it appears that other transcripts beside the fully coding mRNA may also be dysregulated in malignant cells. Recent data from a comprehensive pan‐cancer transcriptome analysis demonstrated differential activity of two alternative CD81 gene promoters in malignant versus nonmalignant gut mucosa. The promoter active in gut mucosa gives rise to transcripts CD81‐203 and CD81‐213, while the promoter active in colon and rectal cancer gives rise to transcripts CD81‐205 and CD81‐215. Our study aimed to explore the biomarker potential of the transcripts from the alternative CD81 gene promoters in colon cancer, as well as to investigate their structure and potential function using in silico tools. The analysis of the transcripts' expression in several colon cell lines cultivated in 2D and 3D and a set of colon cancer and healthy gut mucosa samples by qPCR and RNA sequencing suggested their low expression and stromal origin. Expression patterns in tumor and nontumor tissue along with in silico data suppose that the transcript CD81‐215 may be a noncoding RNA of stromal origin with possible involvement in signaling related to malignant transformation. Significance statement: Elements of the noncoding transcriptome are increasingly being accepted as the factors contributing to the complexity of the genome, but their role remains unexplored in spite of demonstrated relevance for many diseases, including cancer. Noncoding transcripts harbor vast potential for application in personalized medicine, both as prospective therapeutics and therapeutic targets. The differential expression of the transcript CD81‐215 in tumor and nontumor tissue, along with in silico predictions of its structure, localization, and interaction partners, point to the possible involvement of this molecule in colorectal carcinogenesis and its biomarker potential. [ABSTRACT FROM AUTHOR]

Misfolded α-synuclein (α-syn) is believed to contribute to neurodegeneration in Lewy body disease (LBD) based on considerable evidence including a gene-dosage effect observed in relation to point mutations and multiplication of SNCA in familial Parkinson's disease. A contradictory concept proposes early loss of the physiological α-syn as the major driver of neurodegeneration. There is a paucity of data on SNCA transcripts in various α-syn immunoreactive cytopathologies. Here, the total cell body, nuclear, and cytoplasmic area density of SNCA transcripts in neurons without and with various α-syn immunoreactive cytopathologies in the substantia nigra and amygdala in autopsy cases of LBD (n = 5) were evaluated using RNAscope combined with immunofluorescence for disease-associated α-syn. Single-nucleus RNA sequencing was performed to elucidate cell-type specific SNCA expression in non-diseased frontal cortex (n = 3). SNCA transcripts were observed in the neuronal nucleus and cytoplasm in neurons without α-syn, those containing punctate α-syn immunoreactivity, irregular-shaped compact inclusion, and brainstem-type and cortical-type LBs. However, SNCA transcripts were only rarely found in the α-syn immunoreactive LB areas. The total cell body SNCA transcript area densities in neurons with punctate α-syn immunoreactivity were preserved but were significantly reduced in neurons with compact α-syn inclusions both in the substantia nigra and amygdala. This reduction was also observed in the cytoplasm but not in the nucleus. Only single SNCA transcripts were detected in astrocytes with or without disease-associated α-syn immunoreactivity in the amygdala. Single-nucleus RNA sequencing revealed that excitatory and inhibitory neurons, oligodendrocyte progenitor cells, oligodendrocytes, and homeostatic microglia expressed SNCA transcripts, while expression was largely absent in astrocytes and microglia. The preserved cellular SNCA expression in the more abundant non-Lewy body type α-syn cytopathologies might provide a pool for local protein production that can aggregate and serve as a seed for misfolded α-syn. Successful segregation of disease-associated α-syn is associated with the exhaustion of SNCA production in the terminal cytopathology, the Lewy body. Our observations inform therapy development focusing on targeting SNCA transcription in LBD. [ABSTRACT FROM AUTHOR]

Mercury (Hg) methylation in mangrove sediments can result in the accumulation of neurotoxic methylmercury (MeHg). Identification of Hg methyltransferase gene hgcA provides the means to directly characterize the microbial Hg-methylating consortia in environments. Hitherto, the microbial Hg-methylating community in mangrove sediments was scarcely investigated. An effort to assess the diversity and abundance of hgcA genes and transcripts and link them to Hg and MeHg contents was made in the mangrove intertidal sediments along the urbanized Shenzhen Bay, China. The hgcA genes and transcripts associated with Thermodesulfobacteria [mainly Geobacteraceae, Syntrophorhabdaceae, Desulfobacterales, and Desulfarculales (these four lineages were previously classified into the Deltaproteobacteria taxon)], as well as Euryarchaeota (mainly Methanomicrobia and Theionarchaea) dominated the hgcA-harboring communities, while Chloroflexota, Nitrospirota, Planctomycetota, and Lentisphaerota-like hgcA sequences accounted for a small proportion. The hgcA genes appeared in greater abundance and diversity than their transcript counterparts in each sampling site. Correlation analysis demonstrated that the MeHg content rather than Hg content significantly correlated with the structure of the existent/active hgcA-harboring community and the abundance of hgcA genes/transcripts. These findings provide better insights into the microbial Hg methylation drivers in mangrove sediments, which could be helpful for understanding the MeHg biotransformation therein.

The present issue (vol. 3, no. 2) of the transcript: An e-Journal of Literary and Cultural Studies is a themed one with special focus on Disability Studies. With this aim in view, the issue comprises four articles and one book-review on various aspects of the area chosen for analysis. The subjects explored range from locating female experiences of disability and sexuality, followed by an analysis on the politics of subjugating female bodies to power structures, and then comprising two genre-based studies—one on Graphic novels and the other on cinema—thereby enabling the development of a truly multimedial perspective on Disability Studies. In her article on the twin issues of sexuality and violence, and their joint interface with women with disabilities, Dr. Mukul Chaturvedi analyses select narratives of such women, including a few court cases, and studies how violence inflicted upon them is often examined without due cognisance of the sexuality of the victims concerned. This engagement with the disciplinary rigours of repressive structures continues in the article by Rishiraj Sen & Shweta Jha which deals with a select lesserexplored short stories of Chughtai to show how regimes of surveillance, norms, and punishment are deployed to construct desexualised female bodies amenable to the unjust strictures of patriarchy. Mushrifa Rahim, in her article, examines the efficacy of the Graphic novels with its visual dynamics as a medium of expressing the intricate experiential dynamics of disability and also enabling newer orientations on the subject-matter explored through its medium. Roy Jreijiry & Carla Dreij continue this “medial” engagement with the representation of disability through an analysis of Lebanese cinema comprising characters played by actors with both assumed and reallife disabilities. The authors also shed light on the problematic consequences of normalising disability at the cost of trivialising or making light of the special needs of the persons with disabilities. The book-review by Dr. Krishna Kumar S examines Andrew Leland’s The Country of the Blind: A Memoir at the End of Sight as a work that looks at blindness both as a lived experience and a subject of historical inquiry, and shows how writing as an activity could ultimately prove to be an enabling experience and a faculty for “sightedness” thereby effectively countering the limitations of blindness. As the issue editor (2023–2024), I would like to thank the contributors of this special issue for bringing out various dimensions of Disability Studies to the fore, and, by extension, also opening up fresh possibilities for developing a multidisciplinary approach to the subject. They deserve our sincere gratitude for the timely submission of their articles and also for their prompt response during the subsequent phases of reviewing and revision. We owe the anonymous reviewers a special note of acknowledgement for their incisive and constructive feedback to the articles compiled in this issue. The forthcoming issue (vol. 4, no. 1) will be an ix https://doi.org/10.53034/Transcript.2023.v03.n02.000 open-themed issue; however, we would welcome articles specifically dealing with the literatures of North-East India. The detailed CFP will be out soon in our website https://thetranscript.in along with the guidelines for the submission of articles.

Bovine herpesvirus type 1 (BoHV-1) is an important agricultural pathogen that infects cattle and other ruminants worldwide. Though it was first sequenced and annotated over twenty years ago, the Cooper strain, used in this study, was sequenced as recently as 2012 and is currently said to encode 72 unique proteins. However, tandem mass spectrometry has identified several peptides produced during active infection that align with the BoHV-1 genome in unannotated regions. One of these abundant peptides, "ORF M", aligned antisense to the DNA helicase/primase protein UL5. This study characterizes the novel transcript and its protein product and provides evidence to support the existence of homolog protein-coding genes in other Herpesviruses. [ABSTRACT FROM AUTHOR]

ntroduction: Serum hepatitis B virus (HBV) RNA is a promising new biomarker to manage and predict clinical outcomes of chronic hepatitis B (CHB) infection. However, the HBV serum transcriptome within encapsidated particles, which is the biomarker analyte measured in serum, remains poorly characterized. This study aimed to evaluate serum HBV RNA transcript composition and proportionality by PCR-cDNA nanopore sequencing of samples from CHB patients having varied HBV genotype (gt, A to F) and HBeAg status. Methods: Longitudinal specimens from 3 individuals during and following pregnancy (approximately 7 months between time points) were also investigated. HBV RNA extracted from 16 serum samples obtained from 13 patients (73.3% female, 84.6% Asian) was sequenced and serum HBV RNA isoform detection and quantification were performed using three bioinformatic workflows; FLAIR, RATTLE, and a GraphMap-based workflow within the Galaxy application. A spikein RNA variant (SIRV) control mix was used to assess run quality and coverage. The proportionality of transcript isoforms was based on total HBV reads determined by each workflow. Results: All chosen isoform detection workflows showed high agreement in transcript proportionality and composition for most samples. HBV pregenomic RNA (pgRNA) was the most frequently observed transcript isoform (93.8% of patient samples), while other detected transcripts included pgRNA spliced variants, 3′ truncated variants and HBx mRNA, depending on the isoform detection method. Spliced variants of pgRNA were primarily observed in HBV gtB, C, E, or F-infected patients, with the Sp1 spliced variant detected most frequently. Twelve other pgRNA spliced variant transcripts were identified, including 3 previously unidentified transcripts, although spliced isoform identification was very dependent on the workflow used to analyze sequence data. Longitudinal sampling among pregnant and post-partum antiviral-treated individuals showed increasing proportions of 3′ truncated pgRNA variants over time. Conclusions: This study demonstrated long-read sequencing as a promising tool for the characterization of the serum HBV transcriptome. However, further studies are needed to better understand how serum HBV RNA isoform type and proportion are linked to CHB disease progression and antiviral treatment response [ABSTRACT FROM AUTHOR]

Objective To establish RH gene mRNA sequencing method based on nanopores sequencing and to explore the RHD and RHCE mRNA transcripts in D positive and Del individuals. Methods From March 2021 to May 2022, 5 RhD positive samples and 5 Del samples screened out by hospitals in Chengdu were sent to our laboratory for futher examination. The erythrocytes and buff coat were isolated, then DNA and RNA were extracted.All 10 samples were genotyped by PCR-SSP. After the mRNA was reversely transcribed into cDNA, the full-length mRNA of RHD and RHCE genes were simultaneously amplified by a pair of primers. Sanger sequencing and third-generation sequencing technology based on Nanopore were used to sequence the amplified products, and the types and expressions of different splices of RHD and RHCE gene mRNA transcripts were analyzed. Results The method established in this study can simultaneously amplify the full length transcripts of RHD and RHCE. Ten different RHD gene mRNA transcripts and nine RHCE gene mRNA transcripts were detected in 10 samples. RHD full-length transcript (RHD-201) can be detected in RhD Del type, but the expression amount was significantly lower than that in RhD positive samples. The expression amount of transcript RHD-207 (Del789) in Del samples was significantly higher than that in RhD positive samples. The transcript RHD-208 (Del8910+ 213) was only detected in RhD Del type individuals, and no significant difference was found between other RHD transcripts and all RHCE transcripts in the two phenotypes. Conclusion In this study, an analytical method for sequencing full-length transcript isomers of RHD and RHCE mRNA via the third generation was successfully established, and complex alternative splicing patterns were found in RHD and RHCE genes, providing a new method for the study of alternative splicing of blood group gene variants mRNA.

The “For the Record” project (FTR) is a collaboration between a team of linguistic researchers and police in the England & Wales jurisdiction (E&W). The aim of the project is to apply insights from linguistics to improve evidential consistency in police interview transcripts, which are routinely produced by transcribers employed by the police. The research described in this short report is intended as a pilot study, before extension nationally. For this part of the project, we analysed several types of data, including interview audio and transcripts provided by one force. This identified key areas where current transcription practise could be improved and enhanced, and a series of recommendations were made to that force. This pilot study indicates that there are three core components of quality transcription production in this context: Consistency, Accuracy, and Neutrality. We propose that the most effective way to address the issues identified is through developing new training and guidance for police interview transcribers.

This research suggests utilizing natural language processing to summarize the YouTube video transcript in a way that preserves important details. Around one-third of YouTube users in India who view videos on their mobile devices spend more than 48 hours each month on the platform, according to a Google study. It has gotten tougher to sit through these films, some of which may go longer than they should. Our efforts can even be in naught if we can't find the information we need in them. It can take a lot of time and effort to find movies that provide the information we are really seeking for. There are a lot of online videos, for instance, where the speaker wants to capture the audience's attention, but we won't understand the message unless we watch the entire video. The built-in model accepts links to YouTube videos and creates summaries for each one. It also gives the user the ability to choose the algorithm and the percentage of summaries they want to create. Another feature that the user has access to is the ability to transform the generated summary from text to speech and to translate it into the Hindi language. [ABSTRACT FROM AUTHOR]

Copyright of Croatian Annual of Criminal Sciences & Practice / Hrvatski Ljetopis za Kaznene Znanosti i Praksu is the property of Hrvatsko Udruzenje za Kaznene Znanosti i Praksu and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Bipolar disorder (BD) is a severe chronic disorder that represents one of the main causes of disability among young people. To date, no reliable biomarkers are available to inform the diagnosis of BD or clinical response to pharmacological treatment. Studies focused on coding and noncoding transcripts may provide information complementary to genome-wide association studies, allowing to correlate the dynamic evolution of different types of RNAs based on specific cell types and developmental stage with disease development or clinical course. In this narrative review, we summarize findings from human studies that evaluated the potential utility of messenger RNAs and noncoding transcripts, such as microRNAs, circular RNAs and long noncoding RNAs, as peripheral markers of BD and/or response to lithium and other mood stabilizers. The majority of available studies investigated specific targets or pathways, with large heterogeneity in the included type of cells or biofluids. However, a growing number of studies are using hypothesis-free designs, with some studies also integrating data on coding and noncoding RNAs measured in the same participants. Finally, studies conducted in neurons derived from induced-pluripotent stem cells or in brain organoids provide promising preliminary findings supporting the power and utility of these cellular models to investigate the molecular determinants of BD and clinical response. [ABSTRACT FROM AUTHOR]

IntroductionSerum hepatitis B virus (HBV) RNA is a promising new biomarker to manage and predict clinical outcomes of chronic hepatitis B (CHB) infection. However, the HBV serum transcriptome within encapsidated particles, which is the biomarker analyte measured in serum, remains poorly characterized. This study aimed to evaluate serum HBV RNA transcript composition and proportionality by PCR-cDNA nanopore sequencing of samples from CHB patients having varied HBV genotype (gt, A to F) and HBeAg status.MethodsLongitudinal specimens from 3 individuals during and following pregnancy (approximately 7 months between time points) were also investigated. HBV RNA extracted from 16 serum samples obtained from 13 patients (73.3% female, 84.6% Asian) was sequenced and serum HBV RNA isoform detection and quantification were performed using three bioinformatic workflows; FLAIR, RATTLE, and a GraphMap-based workflow within the Galaxy application. A spike-in RNA variant (SIRV) control mix was used to assess run quality and coverage. The proportionality of transcript isoforms was based on total HBV reads determined by each workflow.ResultsAll chosen isoform detection workflows showed high agreement in transcript proportionality and composition for most samples. HBV pregenomic RNA (pgRNA) was the most frequently observed transcript isoform (93.8% of patient samples), while other detected transcripts included pgRNA spliced variants, 3′ truncated variants and HBx mRNA, depending on the isoform detection method. Spliced variants of pgRNA were primarily observed in HBV gtB, C, E, or F-infected patients, with the Sp1 spliced variant detected most frequently. Twelve other pgRNA spliced variant transcripts were identified, including 3 previously unidentified transcripts, although spliced isoform identification was very dependent on the workflow used to analyze sequence data. Longitudinal sampling among pregnant and post-partum antiviral-treated individuals showed increasing proportions of 3′ truncated pgRNA variants over time.ConclusionsThis study demonstrated long-read sequencing as a promising tool for the characterization of the serum HBV transcriptome. However, further studies are needed to better understand how serum HBV RNA isoform type and proportion are linked to CHB disease progression and antiviral treatment response.

Abstract Background Paraoxonase 2 (PON2) is an intracellular antioxidant enzyme located at the inner mitochondrial membrane. Previous studies have found PON2 to be an important antioxidant in a variety of cellular systems, such as the cardiovascular and renal system. Recent work has also suggested that PON2 plays an important role in the central nervous system (CNS), as decreased PON2 expression in the CNS leads to higher oxidative stress and subsequent cell toxicity. However, the precise role of PON2 in the CNS is still largely unknown, and what role it may play in specific regions of the brain remains unexamined. Dopamine metabolism generates considerable oxidative stress and antioxidant function is critical to the survival of dopaminergic neurons, providing a potential mechanism for PON2 in the dopaminergic system. Methods In this study, we investigated the role of PON2 in the dopaminergic system of the mouse brain by comparing transcript and protein expression of dopaminergic-related genes in wildtype (WT) and PON2 deficient (PON2-def) mouse striatum, and exposing WT cultured primary neurons to dopamine receptor agonists. Results We found alterations in multiple key dopaminergic genes at the transcript level, however many of these changes were not observed at the protein level. In cultured neurons, PON2 mRNA and protein were increased upon exposure to quinpirole, a dopamine receptor 2/3 (DRD2/3) agonist, but not fenoldopam, a dopamine receptor 1/5 (DRD1/5) agonist, suggesting a receptor-specific role in dopamine signaling. Conclusions Our findings suggest PON2 deficiency significantly impacts the dopaminergic system at the transcript level and may play a role in mitigating oxidative stress in this system further downstream through dopamine receptor signaling.

ABSTRACT Newcastle disease virus (NDV) is an avian paramyxovirus that causes major economic losses to the poultry industry around the world, with NDV pathogenicity varying due to strain virulence differences. However, the impacts of intracellular viral replication and the heterogeneity of host responses among cell types are unknown. Here, we investigated the heterogeneity of lung tissue cells in response to NDV infection in vivo and that of the chicken embryo fibroblast cell line DF-1 in response to NDV infection in vitro using single-cell RNA sequencing. We characterized the NDV target cell types in the chicken lung at the single-cell transcriptome level and classified cells into five known and two unknown cell types. The five known cell types are the targets of NDV in the lungs with virus RNA detected. Different paths of infection in the putative trajectories of NDV infection were distinguished between in vivo and in vitro, or between virulent Herts/33 strain and nonvirulent LaSota strain. Gene expression patterns and the interferon (IFN) response in different putative trajectories were demonstrated. IFN responses were elevated in vivo, especially in myeloid and endothelial cells. We distinguished the virus-infected and non-infected cells, and the Toll-like receptor signaling pathway was the main pathway after virus infection. Cell-cell communication analysis revealed the potential cell surface receptor-ligand of NDV. Our data provide a rich resource for understanding NDV pathogenesis and open the way to interventions specifically targeting infected cells. IMPORTANCE Newcastle disease virus (NDV) is an avian paramyxovirus that causes major economic losses to the poultry industry around the world, with NDV pathogenicity varying due to strain virulence differences. However, the impacts of intracellular viral replication and the heterogeneity of host responses among cell types are unknown. Here, we investigated the heterogeneity of lung tissue cells in response to NDV infection in vivo and that of the chicken embryo fibroblast cell line DF-1 in response to NDV infection in vitro using single-cell RNA sequencing. Our results open the way to interventions specifically targeting infected cells, suggest principles of virus-host interactions applicable to NDV and other similar pathogens, and highlight the potential for simultaneous single-cell measurements of both host and viral transcriptomes for delineating a comprehensive map of infection in vitro and in vivo. Therefore, this study can be a useful resource for the further investigation and understanding of NDV.

Sugar content is an important trait of fruits. The genetic background of fruits can affect their sugar content in different cultivars. The quantitative trait loci and genes related to sugar content during fruit ripening remain unclear. In this study, we performed quantitative trait locus (QTL) mapping of sugar content. Two QTLs (qSugar-LG6-Chr7 and qSugar-LG12-Chr3) were identified based on their total sugar contents. A total of 577 and 519 genes were annotated around these two QTL loci. The contents of fructose, sorbitol, glucose, and sucrose were measured at six time points in four cultivars before fruit maturation, including two sweet cultivars (“Zaoshengxinshui” and “ZQ65”) and two general cultivars (“Qiushui” and “ZQ82”). In sweet cultivars, sucrose and fructose accumulate substantially, and sorbitol content decreases significantly during fruit ripening. A transcriptome analysis identified 125 upregulated and 222 downregulated differentially expressed genes (DEGs) in sweet cultivars. Two sucrose transport genes (PpSUT, LOC103964096, and LOC103940043) were negatively correlated with sugar content. A weighted gene co-expression network analysis showed that two genes, sorbitol dehydrogenase (PpSDH, LOC103960512 and LOC103960513), around the locus of qSugar-LG6-Chr7 were negatively coexpressed with the total sugar content, which was downregulated in the sweet cultivars. PpSDH and PpSUT may play important roles in regulating sugar content during pear ripening. Transcriptome analysis also revealed that some DEGs were related to sugars (PpS6PDH and ATP-PpPFK), hormones (PpARG7), and transcription factors (PpEMB1444, PpCYP734A1, and PpWRKY50). In conclusion, this study provides new insights into the molecular mechanisms associated with sugar content in the fruit ripening of Pyrus pyrifolia. [ABSTRACT FROM AUTHOR]