Learner training for phonetic transcription of typical and/or disordered speech: A scoping review.

BACKGROUND: Phonetic transcription is a core skill of speech and language therapists/pathologists (SLT/Ps) for clinical assessment of speech sounds and/or errors, and linguists for investigation of phonetic phenomena in various languages; hence, it is included in the curriculum of the corresponding degree programme. Many experts and course instructors have discussed their opinions on different aspects of phonetic transcription teaching and/or reported their own training programmes. However, no review has systematically summarized the types of expert recommendations and training methodology reported in the literature. Such information is important for mapping the knowledge gaps, refining current teaching and planning further research. AIMS: To systematically summarize (1) the materials and procedures for delivering and evaluating phonetic transcription training programmes, and (2) the opinions from experts in phonetic transcription teaching regarding but not limited to the content, rationale(s), format and structure, and timing of teaching phonetic transcription of typical speech and/or disordered speech reported in the literature. METHODS & PROCEDURES: A scoping review was carried out by following the Joanna Briggs Institute methodology. PubMed, EBSCOhost and Web of Science were searched and citation searching of included papers was completed. The included papers were divided into training programme reports, of which data (e.g., type and number of speech stimuli used, type and number of learners, outcome measures) were charted, and expert opinion papers, analysed using content analysis. MAIN CONTRIBUTION: A total of 565 studies were retrieved. After excluding duplicates and irrelevant papers and merging two sources that reported the same training, a total of 23 sources on training programmes and six opinion papers were analysed. Most training were for English and for SLT/P students, with some for the linguistics students. There are variations in the training content (with phonetic transcription practice as the main procedure), delivery mode (some presented via websites or computer software), stimuli (audio recordings of typical adults and children with speech disorders were most used), feedback (mostly immediate feedback using answer keys) and outcome measures (mainly transcription accuracy of learners and user opinions). Content analysis of opinion papers determined five main categories: rationale for training; aspects of the delivery of training; transcription; problem areas noted; and strategies/resources. CONCLUSIONS & IMPLICATIONS: Implications and considerations for teaching are discussed, along with recommendations for research in the design of evidence-based training. The findings can contribute to the development of general guidelines about phonetic transcription training in educational programmes and the establishment of pre-registration competencies. WHAT THIS PAPER ADDS: What is already known on this subject Phonetic transcription is a core skill of SLT/Ps and linguists for clinical speech assessment and research, and it is an important component in the curriculum of the relevant degree programmes. Many experts and course instructors have discussed their opinions regarding phonetic transcription teaching and/or reported their own training programmes in various sources such as books and book chapters, research papers and conference proceedings. What this paper adds to the existing knowledge The paper reports a scoping review that systematically summarized the materials and procedures for delivering and evaluating phonetic transcription programmes and experts' opinions and recommendations for phonetic transcription teaching, reported in the literature. The data from these two types of sources allowed an integrated discussion of the various aspects of phonetic transcription training, such as content, format and structure, materials and timing of teaching and the evaluation of training efficacy. What are the potential or actual clinical implications of this work? The data synthesized and discussed provide a foundation for a review of current practice in phonetic transcription teaching in SLT education. The findings can contribute to the development of general guidelines about phonetic transcription training in educational programmes and the establishment of pre-registration competencies.

A review of the role of transcription factors in regulating adipogenesis and lipogenesis in beef cattle.

In the past few decades, genomic selection and other refined strategies have been used to increase the growth rate and lean meat production of beef cattle. Nevertheless, the fast growth rates of cattle breeds are often accompanied by a reduction in intramuscular fat (IMF) deposition, impairing meat quality. Transcription factors play vital roles in regulating adipogenesis and lipogenesis in beef cattle. Meanwhile, understanding the role of transcription factors in regulating adipogenesis and lipogenesis in beef cattle has gained significant attention to increase IMF deposition and meat quality. Therefore, the aim of this paper was to provide a comprehensive summary and valuable insight into the complex role of transcription factors in adipogenesis and lipogenesis in beef cattle. This review summarizes the contemporary studies in transcription factors in adipogenesis and lipogenesis, genome-wide analysis of transcription factors, epigenetic regulation of transcription factors, nutritional regulation of transcription factors, metabolic signalling pathways, functional genomics methods, transcriptomic profiling of adipose tissues, transcription factors and meat quality and comparative genomics with other livestock species. In conclusion, transcription factors play a crucial role in promoting adipocyte development and fatty acid biosynthesis in beef cattle. They control adipose tissue formation and metabolism, thereby improving meat quality and maintaining metabolic balance. Understanding the processes by which these transcription factors regulate adipose tissue deposition and lipid metabolism will simplify the development of marbling or IMF composition in beef cattle.

Comparison of intelligibility measures for children with velopharyngeal insufficiency: visual analog scale ratings, interval scales, and orthographic transcription (OT)-based measures.

Regardless of the underlying cause for speech impairment in speakers with cleft palate, a universal consequence of cleft palate is reduced speech intelligibility. Still, there is no standardised approach for measuring intelligibility for speakers with cleft speech. The current study aimed to determine the relationship between orthographic transcription (OT)-based measures, interval-scale ratings, and visual analog scale (VAS) ratings for perceptual judgements of intelligibility in speakers with cleft palate as judged by speech-language pathologists (SLPs). The speaker participants were six speakers with velopharyngeal insufficiency secondary to cleft palate. Four sets of sentences from the Hearing in Noise Test were recorded from each speaker. A total of 14 SLPs provided their intelligibility judgement on these speaker's recordings by word-by-word orthographic transcriptions, a visual analog scale (0-100), and a 5-point interval rating scale. A Spearman rank correlation test indicated a negative, strong correlation between OT-based measurements and VAS scores (r = -.94; p = 0.01) and between OT-based measurements and interval rating scores (r = -.77, p = 0.01). A strong, positive correlation was found between scores obtained from VAS and interval rating scales (r = .83, p = 0.05). The strong relationship between the objective measure of intelligibility (i.e. OT-based measure) and a subjective measure of intelligibility (i.e. VAS and interval scale) supports using a less time-consuming VAS as a substitute for orthographic transcription in measuring intelligibility in cleft palate speech.

Genome-wide and comparative phylogenetic analysis of senescence-associated NAC transcription factors in sunflower (Helianthus annuus).

BACKGROUND: Leaf senescence delay impacts positively in grain yield by maintaining the photosynthetic area during the reproductive stage and during grain filling. Therefore a comprehensive understanding of the gene families associated with leaf senescence is essential. NAC transcription factors (TF) form a large plant-specific gene family involved in regulating development, senescence, and responses to biotic and abiotic stresses. The main goal of this work was to identify sunflower NAC TF (HaNAC) and their association with senescence, studying their orthologous to understand possible functional relationships between genes of different species. RESULTS: To clarify the orthologous relationships, we used an in-depth comparative study of four divergent taxa, in dicots and monocots, with completely sequenced genomes (Arabidopsis thaliana, Vitis vinifera, Musa acuminata and Oryza sativa). These orthologous groups provide a curated resource for large scale protein sequence annotation of NAC TF. From the 151 HaNAC genes detected in the latest version of the sunflower genome, 50 genes were associated with senescence traits. These genes showed significant differential expression in two contrasting lines according to an RNAseq assay. An assessment of overexpressing the Arabidopsis line for HaNAC001 (a gene of the same orthologous group of Arabidopsis thaliana ORE1) revealed that this line displayed a significantly higher number of senescent leaves and a pronounced change in development rate. CONCLUSIONS: This finding suggests HaNAC001 as an interesting candidate to explore the molecular regulation of senescence in sunflower.

A host-pathogen interactome uncovers phytopathogenic strategies to manipulate plant ABA responses.

The phytopathogen Pseudomonas syringae delivers into host cells type III secreted effectors (T3SEs) that promote virulence. One virulence mechanism employed by T3SEs is to target hormone signaling pathways to perturb hormone homeostasis. The phytohormone abscisic acid (ABA) influences interactions between various phytopathogens and their plant hosts, and has been shown to be a target of P. syringae T3SEs. In order to provide insight into how T3SEs manipulate ABA responses, we generated an ABA-T3SE interactome network (ATIN) between P. syringae T3SEs and Arabidopsis proteins encoded by ABA-regulated genes. ATIN consists of 476 yeast-two-hybrid interactions between 97 Arabidopsis ABA-regulated proteins and 56 T3SEs from four pathovars of P. syringae. We demonstrate that T3SE interacting proteins are significantly enriched for proteins associated with transcription. In particular, the ETHYLENE RESPONSIVE FACTOR (ERF) family of transcription factors is highly represented. We show that ERF105 and ERF8 displayed a role in defense against P. syringae, supporting our overall observation that T3SEs of ATIN converge on proteins that influence plant immunity. In addition, we demonstrate that T3SEs that interact with a large number of ABA-regulated proteins can influence ABA responses. One of these T3SEs, HopF3Pph6 , inhibits the function of ERF8, which influences both ABA-responses and plant immunity. These results provide a potential mechanism for how HopF3Pph6 manipulates ABA-responses to promote P. syringae virulence, and also demonstrate the utility of ATIN as a resource to study the ABA-T3SE interface.

Oral feeding of Lactobacillus bulgaricus N45.10 inhibits the lung inflammation and airway remodeling in murine allergic asthma: Relevance to the Th1/Th2 cytokines and STAT6/T-bet.

Asthma is a chronic disease with impacts on public health. It affects the airways causing pulmonary inflammation mediated by CD4 T cells type Th2, eosinophilia, mucus hypersecretion, and elevated IgE. The unbalance between cytokines and transcription factors is an important feature in asthma. Probiotics has gaining highlight as a therapy for chronic diseases. Thus, we investigate the Lactobacillus bulgaricus (Lb) effect in murine allergic asthma. BALB/c-mice were sensitized to ovalbumin (OA) on days 0 and 7 and were challenged from day 14-28 with OA. Mice received Lb seven days prior to sensitization and it was kept until day 28. The Lb attenuated the eosinophils infiltration, mucus and collagen secretion, IgE production, pro-inflammatory cytokines, TLR4 expression, GATA3, STAT6 and RORγt in lung. Otherwise, Lb increased the anti-inflammatory cytokines, the T-bet and foxp3. Finally, Lb attenuated the allergic asthma-induced inflammation and airway remodeling by interfering on Th1/Th2 cytokines and STAT6/T-bet transcription factors.

Blood money: Harvey's De motu cordis (1628) as an exercise in accounting.

William Harvey's famous quantitative argument from De motu cordis (1628) about the circulation of blood explained how a small amount of blood could recirculate and nourish the entire body, upending the Galenic conception of the blood's motion. This paper argues that the quantitative argument drew on the calculative and rhetorical skills of merchants, including Harvey's own brothers. Modern translations of De motu cordis obscure the language of accountancy that Harvey himself used. Like a merchant accounting for credits and debits, intake and output, goods and moneys, Harvey treated venous and arterial blood as essentially commensurate, quantifiable and fungible. For Harvey, the circulation (and recirculation) of blood was an arithmetical necessity. The development of Harvey's circulatory model followed shifts in the epistemic value of mercantile forms of knowledge, including accounting and arithmetic, also drawing on an Aristotelian language of reciprocity and balance that Harvey shared with mercantile advisers to the royal court. This paper places Harvey's calculations in a previously underappreciated context of economic crisis, whose debates focused largely on questions of circulation.

Inhibitory effect of moschamine isolated from Carthamus tinctorius on LPS-induced inflammatory mediators via AP-1 and STAT1/3 inactivation in RAW 264.7 macrophages.

Seeds of Carthamus tinctorius L. (Compositae) have been used in Korean traditional medicines for the treatment of cardiovascular and bone diseases. In this study, we investigated the anti-inflammatory effects of known serotonin derivatives (1-9) isolated from the ethyl acetate (EtOAc) soluble fraction from the seeds of C. tinctorius. Compound 2, identified as moschamine, most potently inhibited lipopolysaccharide (LPS)-induced production of prostaglandin E2 (PGE2) and nitric oxide (NO) in RAW 264.7 macrophages. Moschamine concentration-dependently inhibited LPS-induced PGE2 and NO production in RAW 264.7 macrophages. Consistent with these findings, moschamine suppressed the protein and mRNA levels of cyclooxygenase-2 (COX-2), microsomal prostaglandin E2 synthase (mPGES)-1, and inducible NO synthase (iNOS), interleukin (IL)-6, and IL-1ß. In addition, pretreatment of moschamine significantly inhibited LPS-stimulated the transcriptional activity of activator protein-1 (AP-1) and the phosphorylation of signal transducer and activator of transcription (STAT)1/3 in RAW 264.7 macrophages. Moreover, moschamine inhibited LPS-induced the phosphorylation of p38 mitogen-activated protein kinase (p38) and extracellular signal-regulated kinase (ERK), but it had no effect on c-Jun N-terminal kinase (JNK). These results suggest that the mechanism of anti-inflammatory activity of moschamine is associated with the downregulation of COX-2, mPGES-1, iNOS, IL-6, and IL-1ß expression through the suppression of AP-1 and STAT1/3 activation in LPS-induced RAW 264.7 macrophages.

Surprisal analysis characterizes the free energy time course of cancer cells undergoing epithelial-to-mesenchymal transition.

The epithelial-to-mesenchymal transition (EMT) initiates the invasive and metastatic behavior of many epithelial cancers. Mechanisms underlying EMT are not fully known. Surprisal analysis of mRNA time course data from lung and pancreatic cancer cells stimulated to undergo TGF-ß1-induced EMT identifies two phenotypes. Examination of the time course for these phenotypes reveals that EMT reprogramming is a multistep process characterized by initiation, maturation, and stabilization stages that correlate with changes in cell metabolism. Surprisal analysis characterizes the free energy time course of the expression levels throughout the transition in terms of two state variables. The landscape of the free energy changes during the EMT for the lung cancer cells shows a stable intermediate state. Existing data suggest this is the previously proposed maturation stage. Using a single-cell ATP assay, we demonstrate that the TGF-ß1-induced EMT for lung cancer cells, particularly during the maturation stage, coincides with a metabolic shift resulting in increased cytosolic ATP levels. Surprisal analysis also characterizes the absolute expression levels of the mRNAs and thereby examines the homeostasis of the transcription system during EMT.

Endocrine Disruption of Propylparaben in the Male Mosquitofish (Gambusia affinis): Tissue Injuries and Abnormal Gene Expressions of Hypothalamic-Pituitary-Gonadal-Liver Axis.

Propylparaben (PrP) is a widely used preservative that is constantly detected in aquatic environments and poses a potential threat to aquatic ecosystems. In the present work, adult male mosquitofish were acutely (4d) and chronically (32d) exposed to environmentally and humanly realistic concentrations of PrP (0, 0.15, 6.00 and 240 µg/L), aimed to investigate the toxic effects, endocrine disruption and possible mechanisms of PrP. Histological analysis showed time- and dose-dependent manners in the morphological injuries of brain, liver and testes. Histopathological alterations in the liver were found in 4d and severe damage was identified in 32d, including hepatic sinus dilatation, cytoplasmic vacuolation, cytolysis and nuclear aggregation. Tissue impairments in the brain and testes were detected in 32d; cell cavitation, cytomorphosis and blurred cell boundaries appeared in the brain, while the testes lesions contained spermatogenic cell lesion, decreased mature seminal vesicle, sperm cells gathering, seminiferous tubules disorder and dilated intercellular space. Furthermore, delayed spermatogenesis had occurred. The transcriptional changes of 19 genes along the hypothalamus-pituitary-gonadal-liver (HPGL) axis were investigated across the three organs. The disrupted expression of genes such as Ers, Ars, Vtgs, cyp19a, star, hsd3b, hsd17b3 and shh indicated the possible abnormal steroidogenesis, estrogenic or antiandrogen effects of PrP. Overall, the present results provided evidences for the toxigenicity and endocrine disruptive effects on the male mosquitofish of chronic PrP exposure, which highlights the need for more investigations of its potential health risks.

Exploring Practical Metrics to Support Automatic Speech Recognition Evaluations.

Recent studies into the evaluation of automatic speech recognition for its quality of output in the form of text have shown that using word error rate to see how many mistakes exist in English does not necessarily help the developer of automatic transcriptions or captions. Confidence levels as to the type of errors being made remain low because mistranslations from speech to text are not always captured with a note that details the reason for the error. There have been situations in higher education where students requiring captions and transcriptions have found that some academic lecture results are littered with word errors which means that comprehension levels drop and those with cognitive, physical and sensory disabilities are particularly affected. Despite the incredible improvements in general understanding of conversational automatic speech recognition, academic situations tend to include numerous domain specific terms and the lecturers may be non-native speakers, coping with recording technology in noisy situations. This paper aims to discuss the way additional metrics are used to capture issues and feedback into the machine learning process to enable enhanced quality of output and more inclusive practices for those using virtual conferencing systems. The process goes beyond what is expressed and examines paralinguistic aspects such as timing, intonation, voice quality and speech understanding.

Towards Universally Designed Communication: Opportunities and Challenges in the Use of Automatic Speech Recognition Systems to Support Access, Understanding and Use of Information in Communicative Settings.

Unlike physical barriers, communication barriers do not have an easy solution: people speak or sign in different languages and may have wide-ranging proficiency levels in the languages they understand and produce. Universal Design (UD) principles in the domain of language and communication have guided the production of multimodal (audio, visual, written) information. For example, UD guidelines encourage websites to provide information in alternative formats (for example, a video with captions; a sign language version). The same UD for Learning principles apply in the classroom, and instructors are encouraged to prepare content to be presented multimodally, making use of increasingly available technology. In this chapter, I will address some of the opportunities and challenges offered by automatic speech recognition (ASR) systems. These systems have many strengths, and the most evident is the time they employ to convert speech sounds into a written form, faster than the time human transcribers need to perform the same process. These systems also present weaknesses, for example, a higher rate of errors when compared to human-generated transcriptions. It is essential to weigh the strengths and weaknesses of technology when choosing which device(s) to use in a universally designed environment to enhance access to information and communication. It is equally imperative to understand which tools are most appropriate for diverse populations. Therefore, researchers should continue investigating how people process information in a multimodal format, and how technology can be improved based on this knowledge and users' needs and feedback.

The interactive effects of ethinylestradiol and progesterone on transcriptional expression of genes along the hypothalamus-pituitary-thyroid axis in embryonic zebrafish (Danio rerio).

Progestins and estrogens are widespread in various aquatic environments and their potential endocrine disruption effects to aquatic organisms have drawn growing concern. However, their combined effects in aquatic organisms remain elusive. The aim of the present study was to assess the effects of the binary mixtures of gestodene (GES) and 17α-ethinylestradiol (EE2) on the hypothalamic-pituitary-thyroid (HPT) axis of zebrafish (Danio rerio) using the eleuthero-embryos. Embryos were exposed to GES and EE2 alone or in combination at concentrations ranging from 41 to 5329 ng L-1 (nominal ones from 50 to 5000 ng L-1) for 48 h, 96 h and 144 h post fertilization (hpf). The results showed that the transcripts of the genes along the HPT axis displayed pronounced alterations. There was no clear pattern in the change of the transcripts of these genes over time and with concentrations. However, in general, the transcripts of the genes were inversely affected by EE2 (increase 0.5 to 4.2-folds) and GES (inhibition 0.4 to 4.9-folds), and their mixtures showed interactive effects in embryonic zebrafish. In addition, physiological data (mortality, malformation, body length and heart rate etc.) denoted higher toxicity of the two chemicals in combination than alone based on the developmental toxicity and neurotoxicity (locomotor behavior). These results indicated that the interactive effects of these two chemicals might be different between at the transcriptional level and at the whole organismal level. In summary, GES and EE2 affect the HPT axis (related genes expression and thyroid hormones (THs) levels) and exhibit developmental toxicity and neurotoxicity.

Waterborne exposure to microcystin-LR alters thyroid hormone levels, iodothyronine deiodinase activities, and gene transcriptions in juvenile zebrafish (Danio rerio).

This study investigated the effects of microcystin (MC) on the regulation of thyroid hormone (TH) metabolism in juvenile zebrafish exposed to MC-LR. The results showed that acute MC-LR exposure at concentrations ranging from 50 µg/L to 400 µg/L led to significant reductions in thyroxine (T4) and triiodothyronine (T3) levels in juvenile zebrafish. The transcription levels of genes involved in TH synthesis, such as corticotropin-releasing hormone (crh), thyroid-stimulating hormone (tsh), thyroid peroxidase (tpo) and transthyretin (ttr), were significantly decreased followed by an increase after MC-LR exposure. Transcription of the TH nuclear receptors (tr-α and tr-ß) was significantly reduced during the exposure period. Moreover, the activities of iodothyronine deiodinase type Ⅰ (ID1) and iodothyronine deiodinase type Ⅱ (ID2) showed initially decreased and then increased trend, while the activity of iodothyronine deiodinase type Ⅲ (ID3) significantly decreased during MC-LR exposure. In addition, the effect of MC-LR on deiodinase activities and T4 contents were important causes of the decreased T3 at the early exposure stage. These results indicated that acute MC-LR exposure significantly interfered with the transcription of genes related to TH synthesis, transport and metabolism, and affected normal function of the thyroid which leads to decrease of T4 and T3 in juvenile zebrafish. Therefore, the thyroid function is susceptible to interference by MC-LR, and it may cause adverse effects on the growth and development of juvenile zebrafish.

Insights into the genes involved in the ethylene biosynthesis pathway in Arabidopsis thaliana and Oryza sativa.

BACKGROUND: Ethylene is a gaseous plant hormone that acts as a requisite role in many aspects of the plant life cycle, and it is also a regulator of plant responses to abiotic and biotic stresses. In this study, we attempt to provide comprehensive information through analyses of existing data using bioinformatics tools to compare the identified ethylene biosynthesis genes between Arabidopsis (as dicotyledonous) and rice (as monocotyledonous). RESULTS: The results exposed that the Arabidopsis proteins of the ethylene biosynthesis pathway had more potential glycosylation sites than rice, and 1-aminocyclopropane-1-carboxylate oxidase proteins were less phosphorylated than 1-aminocyclopropane-1-carboxylate synthase and S-adenosylmethionine proteins. According to the gene expression patterns, S-adenosylmethionine genes were more involved in the rice-ripening stage while in Arabidopsis, ACS2, and 1-aminocyclopropane-1-carboxylate oxidase genes were contributed to seed maturity. Furthermore, the result of miRNA targeting the transcript sequences showed that ath-miR843 and osa-miR1858 play a key role to regulate the post-transcription modification of S-adenosylmethionine genes in Arabidopsis and rice, respectively. The discovered cis- motifs in the promoter site of all the ethylene biosynthesis genes of A. thaliana genes were engaged to light-induced response in the cotyledon and root genes, sulfur-responsive element, dehydration, cell cycle phase-independent activation, and salicylic acid. The ACS4 protein prediction demonstrated strong protein-protein interaction in Arabidopsis, as well as, SAM2, Os04T0578000, Os01T0192900, and Os03T0727600 predicted strong protein-protein interactions in rice. CONCLUSION: In the current study, the complex between miRNAs with transcript sequences of ethylene biosynthesis genes in A. thaliana and O. sativa were identified, which could be helpful to understand the gene expression regulation after the transcription process. The binding sites of common transcription factors such as MYB, WRKY, and ABRE that control target genes in abiotic and biotic stresses were generally distributed in promoter sites of ethylene biosynthesis genes of A. thaliana. This was the first time to wide explore the ethylene biosynthesis pathway using bioinformatics tools that markedly showed the capability of the in silico study to integrate existing data and knowledge and furnish novel insights into the understanding of underlying ethylene biosynthesis pathway genes that will be helpful for more dissection.

CIRCE element evolved for the coordinated transcriptional regulation of bacterial duplicate groELs.

Chaperonin groEL genes are duplicated in approximately 20% of bacteria, and the duplicates are differentially transcribed due to their divergent functions. The coordinated regulation of this differential transcription is as yet undetermined. In this study, we reported that the controlling inverted repeat of chaperone expression (CIRCE) element (the HrcA-binding site located upstream of the promoter) evolved for the transcriptional regulation of duplicate groELs. CIRCE composition and locations were found to be phylogenetically conserved in bacterial taxa. Myxococcus xanthus DK1622 has two CIRCE elements (CIRCE1groESL1 and CIRCE2groESL1) in the promoter region of groESL1 and one CIRCE element (CIRCEgroEL2) before groEL2. We also found that negative HrcA and positive ?32 regulators coordinated the transcription of duplicate groELs, and that the double deletion in DK1622 eliminated transcriptional differences and reduced the heat-shock responses of groELs. In vitro binding assays showed that HrcA protein binding was biased towards CIRCE1groESL1, followed by CIRCEgroEL2, but that HrcA proteins failed to bind with CIRCE2groESL1. Mutation experiments revealed that single-nucleotide mutations in the inverted repeat regions changed the HrcA-binding abilities of CIRCEs. We constructed an in vivo transcription-regulation system in Escherichia coli to pair each of the regulators with a groEL promoter. The results indicated that the transcriptional regulation performed by HrcA and ?32 was biased towards the groEL2 and groEL1 promoters, respectively. Based on promoter-sequence characteristics, we proposed a model of the coordinated regulation of the transcription of duplicate groELs in M. xanthus DK1622.

A Positive Feedback Amplifier Circuit That Regulates Interferon (IFN)-Stimulated Gene Expression and Controls Type I and Type II IFN Responses.

Interferon (IFN)-I and IFN-II both induce IFN-stimulated gene (ISG) expression through Janus kinase (JAK)-dependent phosphorylation of signal transducer and activator of transcription (STAT) 1 and STAT2. STAT1 homodimers, known as γ-activated factor (GAF), activate transcription in response to all types of IFNs by direct binding to IFN-II activation site (γ-activated sequence)-containing genes. Association of interferon regulatory factor (IRF) 9 with STAT1-STAT2 heterodimers [known as interferon-stimulated gene factor 3 (ISGF3)] or with STAT2 homodimers (STAT2/IRF9) in response to IFN-I, redirects these complexes to a distinct group of target genes harboring the interferon-stimulated response element (ISRE). Similarly, IRF1 regulates expression of ISGs in response to IFN-I and IFN-II by directly binding the ISRE or IRF-responsive element. In addition, evidence is accumulating for an IFN-independent and -dependent role of unphosphorylated STAT1 and STAT2, with or without IRF9, and IRF1 in basal as well as long-term ISG expression. This review provides insight into the existence of an intracellular amplifier circuit regulating ISG expression and controlling long-term cellular responsiveness to IFN-I and IFN-II. The exact timely steps that take place during IFN-activated feedback regulation and the control of ISG transcription and long-term cellular responsiveness to IFN-I and IFN-II is currently not clear. Based on existing literature and our novel data, we predict the existence of a multifaceted intracellular amplifier circuit that depends on unphosphorylated and phosphorylated ISGF3 and GAF complexes and IRF1. In a combinatorial and timely fashion, these complexes mediate prolonged ISG expression and control cellular responsiveness to IFN-I and IFN-II. This proposed intracellular amplifier circuit also provides a molecular explanation for the existing overlap between IFN-I and IFN-II activated ISG expression.

Effect of diterpenoid kaurenoic acid on genotoxicity and cell cycle progression in gastric cancer cell lines.

The goal of our study was to evaluate the effect of kaurenoic acid, obtained from copaiba oil resin, in gastric cancer (GC) and a normal mucosa of stomach (MNP01) cell lines. The compound was tested at concentrations of 2.5, 5, 10, 30 and 60µg/mL. Comet and micronucleus assays were used to access its potential genotoxicity in vitro. Moreover, we evaluated the effect of kaurenoic acid in cell cycle progression and in the transcription of genes involved in the control of the cell cycle: MYC, CCND1, BCL2, CASP3, ATM, CHK2 and TP53. Kaurenoic acid induced an increase on cell DNA damage or micronucleus frequencies on GC cell lines in a dose-dependent manner. The GC and MNP01 cell lines entering DNA synthesis and mitosis decreased significantly with kaurenoic acid treatment, and had an increased growth phase compared with non-treated cells. The treatment induced apoptosis (or necrosis) even at a concentration of 2.5µg/mL in relation to non-treated cells. GC cell lines presented reduced MYC, CCND1, BCL2 and CASP3 transcription while ATM, CHK2 and TP53 increased in transcription in relation to non-treated cells, especially at a concentration above 10µg/mL. The gene transcription in the MNP01 (non-treated non-cancer cell line) was designated as a calibrator for all the GC cell lines. In conclusion, our results showed that kaurenoic acid obtained from Copaifera induces DNA damage and increases the micronuclei frequency in a dose-dependent manner in GC cells, with a significant genotoxicity observed above the concentration of 5µg/mL. Moreover, this compound seems to be able to induce cell cycle arrest and apoptosis in GC cells.

Interplay between Janus Kinase/Signal Transducer and Activator of Transcription Signaling Activated by Type I Interferons and Viral Antagonism.

Interferons (IFNs), which were discovered a half century ago, are a group of secreted proteins that play key roles in innate immunity against viral infection. The major signaling pathway activated by IFNs is the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, which leads to the expression of IFN-stimulated genes (ISGs), including many antiviral effectors. Viruses have evolved various strategies with which to antagonize the JAK/STAT pathway to influence viral virulence and pathogenesis. In recent years, notable progress has been made to better understand the JAK/STAT pathway activated by IFNs and antagonized by viruses. In this review, recent progress in research of the JAK/STAT pathway activated by type I IFNs, non-canonical STAT activation, viral antagonism of the JAK/STAT pathway, removing of the JAK/STAT antagonist from viral genome for attenuation, and the potential pathogenesis roles of tyrosine phosphorylation-independent non-canonical STATs activation during virus infection are discussed in detail. We expect that this review will provide new insight into the understanding the complexity of the interplay between JAK/STAT signaling and viral antagonism.

Dietary Selenium Status Regulates the Transcriptions of Selenoproteome and Activities of Selenoenzymes in Chicken Kidney at Low or Super-nutritional Levels.

To determine dietary selenium (Se) status regulates the transcriptions of selenoproteome and activities of selenoenzymes in chicken kidney, 1-day-old chickens received low Se (0.028 mg Se per kg of diet) or super-nutritional Se (3.0 or 5.0 mg Se per kg of diet) in their diets for 8 weeks. It was observed that dietary low or super-nutritional Se did not make renal appearance pathological changes in chicken. Low Se significantly reduced total antioxidant capability (T-AOC), glutathione (GSH) content, but malondialdehyde (MDA) content in the kidney increased and decreased glutathione peroxidase (Gpx) and thioredoxin reductase (TrxR) activity with changes in their mRNA levels. Super-nutritional Se (3.0 mg/kg) increased T-AOC and GSH contents then made them reduce, but it reduced MDA content significantly, elevated then reduced Gpx activity, and decreased TrxR activity with changes in their mRNA levels. Dietary low Se downregulated the mRNA expressions of Gpx1-4, Txnrd3, Sepn1, Selw, Sepx1, Selh, and SEPSECS. At super-nutritional Se, most selenoproteins were upregulated in chicken kidney, but Sepp2 and Sep15 was only upregulated in Se excess (5.0 mg/kg) bird. These results indicated that dietary Se status stabilizes normal renal physiology function via regulation of the selenoprotemic transcriptions and selenoenzyme activities in avian.