Gene disruption of medaka (Oryzias latipes) orthologue for mammalian tissue-type transglutaminase (TG2) causes movement retardation

2020 ◽  
Vol 168 (3) ◽  
pp. 213-222
Author(s):  
Yuko Watanabe ◽  
Kazuho Okuya ◽  
Yuki Takada ◽  
Masato Kinoshita ◽  
Saori Yokoi ◽  
...  

Abstract Transglutaminases are an enzyme family that catalyses protein cross-linking essential for several biological functions. In the previous studies, we characterized the orthologues of the mammalian transglutaminase family in medaka (Oryzias latipes), an established fish model. Among the human isozymes, tissue-type transglutaminase (TG2) has multiple functions that are involved in several biological phenomena. In this study, we established medaka mutants deficient for the orthologue of human TG2 using the CRISPR/Cas9 and transcription activator-like effector nucleases systems. Although apparent morphological changes in the phenotype were not observed, movement retardation was found in the mutant fish when evaluated by a tank-diving test. Furthermore, comparative immunohistochemistry analysis using in this fish model revealed that orthologue of human TG2 was expressed at the periventricular layer of the optic tectum. Our findings provide novel insight for the relationship between tissue-type transglutaminase and the nervous system and the associated behaviour.

2020 ◽  
Vol 26 ◽  
Author(s):  
Yujie Shen ◽  
Yexiang Lin ◽  
Kai Liu ◽  
Jinlan Chen ◽  
Juanjuan Zhong ◽  
...  

Background: A number of studies have proposed that lncRNA XIST plays a role in the development and chemosensitivity of NSCLC. Besides, XIST may become a potential therapeutic target for NSCLC patients. The aim of this review is to reveal the biological functions and exact mechanisms of XIST in NSCLC. Methods: In this review, relevant researches involving in the relationship between XIST and NSCLC are collected through systematic retrieval of PubMed Results: XIST is an oncogene in NSCLC and is abnormally upregulated in NSCLC tissues. Considerable evidence has shown that XIST exerts a critical role in the proliferation, invasion, migration, apoptosis and chemosensitivity of NSCLC cells. XIST mainly functions as a ceRNA in NSCLC process, while XIST also functions at transcriptional levels. Conclusion: LncRNA XIST has potential to become a novel biomolecular marker of NSCLC and a therapeutic target for NSCLC.


2020 ◽  
Vol 5 (1) ◽  
pp. 11-14
Author(s):  
Seyed Mohammad Azizi ◽  
Mehrdad Hashemi ◽  
Sarvenaz Falsafi ◽  
Seyedeh Mina Azizi ◽  
Reza Shirkoohi

Aim and Background: Gastric cancer is the fourth most common cancer in the world and the second leading cause of cancer-related deaths. The metastatic invasive cells of tumor tissue are the main cause of mortality. Numerous biological phenomena are involved in organizing the metastatic process. The Epithelial to Mesenchymal Transition is one of the major mechanisms modulating malignant phenotypes by gastric epithelial cells. Specific cell signals are responsible for epithelial or mesenchymal maintenance of the cells in the tissue. These signals are evaluated by measuring the expression of epithelial and mesenchymal biomarkers in that tissue. Villin is an actin-binding protein mainly expressed in the brush border of epithelium which preserves the shape of the cell and its adhesion to the tissue. The aim of the present research is to study the expression of Villin in the cells as a feasible epithelial biomarker in order to evaluate the cross-sectional situation of the cells. Materials and Methods: 38 patients with gastric cancer that were admitted to the Cancer Institute of Imam Khomeini in a period of 6 months were chosen randomly. two samples were collected from each individual; one from the tumoral tissue and one from normal margin of the tumorous tissue. These samples were evaluated after obtaining informed consent from the patients. RNA was extracted from the samples and used as template for cDNA synthesis. The Villin expression was then measured through Real-Time PCR and statistical data according to tissue type and different grades were collected. Results: The expression of Villin in tumor tissue of the patients with gastric cancer was significantly lower than the normal tissue. Conclusion: As it appears decreased expression of Villin can act as an effective factor toward loss of epithelial nature of the cell and occurring Epithelial to Mesenchymal Transition followed by metastasis.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lee Curtin ◽  
Paula Whitmire ◽  
Haylye White ◽  
Kamila M. Bond ◽  
Maciej M. Mrugala ◽  
...  

AbstractLacunarity, a quantitative morphological measure of how shapes fill space, and fractal dimension, a morphological measure of the complexity of pixel arrangement, have shown relationships with outcome across a variety of cancers. However, the application of these metrics to glioblastoma (GBM), a very aggressive primary brain tumor, has not been fully explored. In this project, we computed lacunarity and fractal dimension values for GBM-induced abnormalities on clinically standard magnetic resonance imaging (MRI). In our patient cohort (n = 402), we connect these morphological metrics calculated on pretreatment MRI with the survival of patients with GBM. We calculated lacunarity and fractal dimension on necrotic regions (n = 390), all abnormalities present on T1Gd MRI (n = 402), and abnormalities present on T2/FLAIR MRI (n = 257). We also explored the relationship between these metrics and age at diagnosis, as well as abnormality volume. We found statistically significant relationships to outcome for all three imaging regions that we tested, with the shape of T2/FLAIR abnormalities that are typically associated with edema showing the strongest relationship with overall survival. This link between morphological and survival metrics could be driven by underlying biological phenomena, tumor location or microenvironmental factors that should be further explored.


2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Francisco Vassiliepe Sousa Arruda ◽  
Arthur Alves Melo ◽  
Mayron Alves Vasconcelos ◽  
Romulo Farias Carneiro ◽  
Ito Liberato Barroso-Neto ◽  
...  

Lectins are sugar-binding proteins widely distributed in nature with many biological functions. Although many lectins have a remarkable biotechnological potential, some of them can be cytotoxic. Thus, the aim of this study was to assess the toxicity of five lectins, purified from seeds of different species ofCanavaliagenus. In order to determine the toxicity, assays withArtemianauplii were performed. In addition, a fluorescence assay was carried out to evaluate the binding of lectins toArtemianauplii. In order to verify the relationship between the structure of lectins and their cytotoxic effect, structural analysis was carried out to evaluate the volume of the carbohydrate recognition domain (CRD) of each lectin. The results showed that all lectins exhibited different toxicities and bound to a similar area in the digestive tract ofArtemianauplii. Concerning the structural analysis, differences in spatial arrangement and volume of CRD may explain the variation of the toxicity exhibited by each lectin. To this date, this is the first study that establishes a link between toxicity and structure of CRD from Diocleinae lectins.


2002 ◽  
Vol 87 (2) ◽  
pp. 448-452 ◽  
Author(s):  
Pairunyar Sawathiparnich ◽  
Sandeep Kumar ◽  
Douglas E. Vaughan ◽  
Nancy J. Brown

Recent studies have defined a link between the renin-angiotensin-aldosterone system and fibrinolysis. The present study tests the hypothesis that endogenous aldosterone regulates plasminogen activator inhibitor-1 (PAI-1) production in humans. Hemodynamic parameters, PAI-1 and tissue-type plasminogen activator (t-PA) antigen, potassium, PRA, angiotensin II, and aldosterone were measured in nine male hypertensive subjects after a 3-wk washout, after 2 wk of hydrochlorothiazide (HCTZ; 25 mg plus 20 mmol KCl/d), and after 2 wk of spironolactone (100 mg/d plus KCl placebo). Spironolactone (P = 0.04), but not HCTZ (P = 0.57 vs. baseline; P = 0.1 vs. spironolactone), significantly lowered systolic blood pressure. Angiotensin II increased from baseline during both HCTZ (P = 0.02) and spironolactone (P = 0.02 vs. baseline; P = 0.19 vs. HCTZ) treatments. Although both HCTZ (P = 0.004) and spironolactone (P < 0.001 vs. baseline) increased aldosterone, the effect was greater with spironolactone (P < 0.001 vs. HCTZ). HCTZ increased PAI-1 antigen (P = 0.02), but did not alter t-PA antigen. In contrast, there was no effect of spironolactone on PAI-1 antigen (P = 0.28), whereas t-PA antigen was increased (P = 0.01). There was a significant correlation between PAI-1 antigen and serum aldosterone during both baseline and HCTZ study days (r2 = 0.57; P = 0.0003); however, treatment with spironolactone abolished this correlation (r2 = 0.13; P = 0.33). This study provides evidence that endogenous aldosterone influences PAI-1 production in humans.


2018 ◽  
Vol 30 (2) ◽  
pp. 402-407 ◽  
Author(s):  
Kyle M Benowitz ◽  
Elizabeth C McKinney ◽  
Christopher B Cunningham ◽  
Allen J Moore

AbstractDifferential gene expression has been associated with transitions between behavioral states for a wide variety of organisms and behaviors. Heterochrony, genetic toolkits, and predictable pathways underlying behavioral transitions have been hypothesized to explain the relationship between transcription and behavioral changes. Less studied is how variation in transcription is related to variation within a behavior, and if the genes that are associated with this variation are predictable. Here, we adopt an evolutionary systems biology perspective to address 2 hypotheses relating differential expression to changes within and between behavior. We predicted fewer genes will be associated with variation within a behavior than with transitions between states, and the genes underlying variation within a behavior will represent a narrower set of biological functions. We tested for associations with parenting variation within a state with a set of genes known a priori to be differentially expressed (DE) between parenting states in the burying beetle Nicrophorus vespilloides. As predicted, we found that far fewer genes are DE related to variation within parenting. Moreover, these were not randomly distributed among categories or pathways in the gene set we tested and primarily involved genes associated with neurotransmission. We suggest that this means candidate genes will be easier to identify for associations within a behavior, as descriptions of behavioral state may include more than a single phenotype.


2019 ◽  
Vol 1 (4) ◽  
pp. 471-488 ◽  
Author(s):  
Shailesh Kumar ◽  
Kirklin R. Smith ◽  
Yazmin L. Serrano Negron ◽  
Susan T. Harbison

Although sleep is heritable and conserved across species, sleep duration varies from individual to individual. A shared genetic architecture between sleep duration and other evolutionarily important traits could explain this variability. Learning and memory are critical traits sharing a genetic architecture with sleep. We wanted to know whether learning and memory would be altered in extreme long or short sleepers. We therefore assessed the short-term learning and memory ability of flies from the Sleep Inbred Panel (SIP), a collection of 39 extreme long- and short-sleeping inbred lines of Drosophila. Neither long nor short sleepers had appreciable learning, in contrast to a moderate-sleeping control. We also examined the response of long and short sleepers to enriched social conditions, a paradigm previously shown to induce morphological changes in the brain. While moderate-sleeping control flies had increased daytime sleep and quantifiable increases in brain structures under enriched social conditions, flies of the Sleep Inbred Panel did not display these changes. The SIP thus emerges as an important model for the relationship between sleep and learning and memory.


Author(s):  
Daniel C. McFarland ◽  
Jimmie Holland

The relationship between depression and cancer has long captured the imagination of clinicians and the lay population. Therefore, the science behind this putative relationship is paramount to determine reality from myth. This chapter begins with a historical and relevant clinical overview from within the context of psycho-oncology and psychoneuroimmunology. An exploration of the association between cancer and depression follows by reviewing cancer initiation and progression data in the context of depression. Biological correlates of the stress response in depression, inflammation, and its effects on cancer are presented. Social attributes to these biological phenomena are also evaluated through the putative mechanisms of epigenetics and the stress response. The strongest data for the relationship between depression and cancer fall into four distinct areas: (1) the cytokine hypothesis of depression; (2) dysregulation of the HPA, glucocorticoids, and diurnal circadian rhythms; (3) enhanced sympathetic nervous system activity; and (4) alterations in DNA protein transcription/epigenetics.


2020 ◽  
Vol 60 (5) ◽  
pp. 1330-1345 ◽  
Author(s):  
Shannon M Buttimer ◽  
Natasha Stepanova ◽  
Molly C Womack

Abstract Anurans (frogs and toads) have a unique pelvic and hind limb skeleton among tetrapods. Although their distinct body plan is primarily associated with saltation, anuran species vary in their primary locomotor mode (e.g., walkers, hoppers, jumpers, and swimmers) and are found in a wide array of microhabitats (e.g., burrowing, terrestrial, arboreal, and aquatic) with varying functional demands. Given their largely conserved body plan, morphological adaptation to these diverse niches likely results from more fine-scale morphological change. Our study determines how shape differences in Anura’s unique pelvic and hind limb skeletal structures vary with microhabitat, locomotor mode, and jumping ability. Using microCT scans of preserved specimens from museum collections, we added 3D landmarks to the pelvic and hind limb skeleton of 230 anuran species. In addition, we compiled microhabitat and locomotor data from the literature for these species that span 52 of the 55 families of frogs and ∼210 million years of anuran evolution. Using this robust dataset, we examine the relationship between pelvic and hind limb morphology and phylogenetic history, allometry, microhabitat, and locomotor mode. We find pelvic and hind limb changes associated with shifts in microhabitat (“ecomorphs”) and locomotor mode (“locomorphs”) and directly relate those morphological changes to the jumping ability of individual species. We also reveal how individual bones vary in evolutionary rate and their association with phylogeny, body size, microhabitat, and locomotor mode. Our findings uncover previously undocumented morphological variation related to anuran ecological and locomotor diversification and link that variation to differences in jumping ability among species.


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