scholarly journals The microRNA cluster C19MC is deregulated in parathyroid tumours

2012 ◽  
Vol 49 (2) ◽  
pp. 115-124 ◽  
Author(s):  
Valentina Vaira ◽  
Francesca Elli ◽  
Irene Forno ◽  
Vito Guarnieri ◽  
Chiara Verdelli ◽  
...  
Keyword(s):  
Cell Biology ◽  
Molecular Mechanisms ◽  
Hierarchical Cluster ◽  
Unsupervised Hierarchical Cluster ◽  
Genomic Aberration ◽  
Expression Levels ◽  
Significant Difference ◽  
Mirna Clusters ◽  
Parathyroid Tumours ◽  
Almost All

A subset of over-expressed microRNAs (miRNAs) identified in parathyroid carcinomas (Ca) compared to normal glands belongs to C19MC, a cluster on chromosome 19q13.4 involved in stem cell biology and tumourigenesis. In this study, the expression of C19MC–MIR371–3 clusters and the molecular mechanisms presiding their modulation were investigated in a series of six normal parathyroids, 24 adenomas (Ad), 15 Ca and five matched metastases. The general expression levels of C19MC or MIR371–3 clusters in Ad lesions did not differ from normal glands, while they distinguished Ad from Ca at unsupervised hierarchical cluster analysis (P=0.0008). MIR517C showed the most significant difference in expression between Ca and Ad (P=0.0003) and it positively correlated with serum calcium, parathormone and tumour weight. In regard to the molecular mechanism determining C19MC cluster activation, we could detect C19MC copy number (CN) gain in ten Ca (67%) extending distal to the MIR371–3 cluster in almost all samples. Conversely, only four Ad (16%) showed C19MC amplification, with one case presenting distal genomic aberration to MIR371–3. Globally, CN variations of 19q13.4 loci were significantly associated with MIR517C up-regulation (P=0.006). Opposite to normal glands where C19MC promoter was methylated, hypomethylation occurred in 15 out of 30 analysed tumours. Though the epigenetic status did not correlate with C19MC miRNA expression levels, loss of C19MC promoter methylation was significantly associated with Ca and metastatic disease (P=0.01). In conclusion, C19MC cluster aberrations are a characteristic of Ca with respect to Ad. Altogether, these evidences point towards a role for 19q13.4 miRNA clusters as oncogenes in parathyroid tumourigenesis.

scholarly journals Changes of small non-coding RNAs by severe acute respiratory syndrome coronavirus 2 infection

2021 ◽  
Author(s):  
Wenzhe Wu ◽  
Eun-Jin Choi ◽  
Binbin Wang ◽  
Ke Zhang ◽  
Awadalkareem Adam ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Airway Epithelial Cells ◽  
Host Responses ◽  
Airway Epithelial ◽  
Global Public Health ◽  
Significant Difference ◽  
Non Coding Rnas ◽  
Almost All

The ongoing pandemic of coronavirus disease 2019 (COVID-19), which results from the rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a significant global public health threat, with molecular mechanisms underlying its pathogenesis largely unknown. Small non-coding RNAs (sncRNAs) are known to play important roles in almost all biological processes. In the context of viral infections, sncRNAs have been shown to regulate the host responses, viral replication, and host-virus interaction. Compared with other subfamilies of sncRNAs, including microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs), tRNA-derived RNA fragments (tRFs) are relatively new and emerge as a significant regulator of host-virus interactions. Using T4 PNK-RNA-seq, a modified next-generation sequencing (NGS), we recently found that nasopharyngeal swabs (NPS) samples from SARS-CoV-2 positive and negative subjects show a significant difference in sncRNA profiles. There are about 166 SARS-CoV-2-impacted sncRNAs. Among them, tRFs are the most significantly affected and almost all impacted tRFs are derived from the 5'-end of tRNAs (tRF5). Using a modified qRT-PCR, which was recently developed to specifically quantify tRF5s by isolating the tRF signals from its corresponding parent tRNA signals, we validated that tRF5s derived from tRNA GluCTC (tRF5-GluCTC), LysCTT (tRF5-LysCTT), ValCAC (tRF5-ValCAC), CysGCA (tRF5-CysGCA) and GlnCTG (tRF5-GlnCTG) are enhanced in NPS samples of SARS-CoV2 patients and SARS41 CoV2-infected airway epithelial cells. In addition to host-derived ncRNAs, we also identified several sncRNAs derived from the virus (svRNAs), among which a svRNA derived from CoV2 genomic site 346 to 382 (sv-CoV2-346) has the highest expression. The induction of both tRFs and sv-CoV2-346 has not been reported previously, as the lack of the 3'-OH ends of these sncRNAs prevents them to be detected by routine NGS. In summary, our studies demonstrated the involvement of tRFs in COVID-19 and revealed new CoV2 svRNAs.

Common Gene Expression Changes in Matched Pretreatment and Relapse Samples from Eastern Cooperative Oncology Group Acute Promyelocytic Leukemia (APL) Patients Treated on the Chemotherapy (C) or All-Trans Retinoic Acid (ATRA)-Containing (A) Randomization Arms of Protocol E2491.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4311-4311
Author(s):  
Qingping Cui ◽  
Haesook Kim ◽  
Peter H. Wiernik ◽  
Martin S. Tallman ◽  
Robert E. Gallagher
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Transcriptional Control ◽  
Molecular Mechanisms ◽  
Eastern Cooperative Oncology Group ◽  
Hierarchical Cluster ◽  
Cesium Chloride ◽  
P Value ◽  
Unsupervised Hierarchical Cluster ◽  
Global Comparison

Abstract This study was based on the hypothesis that a global comparison of gene expression levels between APL cells before treatment and at relapse might provide crucial information about molecular mechanisms involved in the selection of relapse clones. Matched samples were derived from 7 patients treated on protocol E2491 (randomization of newly diagnosed patients to either C alone or ATRA for induction and then to maintenance ATRA or observation after consolidation), 4 on A arms and 3 on the C arm. Comparable levels of promyeloblasts were present in the low-density mononuclear cell fraction derived from bone marrow (BM) or peripheral blood (PB) with 1 exception (Patient 4). RNA was prepared by a guanidinium-cesium chloride gradient procedure, and gene expression analysis utilized the Affymetrix Human Genome U-133 Plus 2.0 chip. For unsupervised hierarchical cluster analysis, the normalized data were filtered by the following criteria: coefficient of variation across samples (standard deviation/mean) 〉0.7 and expression level ≥100 in at least 50% of samples. Although there was considerable heterogeneity, 1415 filtered genes clustered into three groups (UCG; see table): #1 with 6 pretreatment patients, #2 with 3 relapse patients (2 C and 1 A), and #3 with 1 pretreatment and 4 relapse patients (1 C and 3 A). Derivation of RNA from PB cells may have contributed to UCG #2 clustering. By supervised analysis, using the criteria of a mean difference of ≥100 between the pretreatment and relapse values and a p-value <.01 by paired t-tests, 443 genes were selected with a median false discovery rate of 13%. To further select a robust and consistent set of genes, an ad-hoc ‘leave-one paired sample-out’ analysis was performed. 139 genes were selected across all 7 subsets and, for 116 genes, the difference between pretreatment and relapse values was ≥1.5-fold--40 upregulated (U) and 76 downregulated (D). The relapse changes in expression of named genes included those affecting signal transduction via ras-related genes (RASA1, D; RASSF1, U; RAB1B&5C, U; ARF6, U; RGS10, U) and protein kinase A (AKAP11, D; PRKAR1A, D), apoptosis (MAP3K5/ASK1, D; CFLAR/FLIP, D; FAF1, U; UBE2D2, U), chromatin (SMARCA2, D; SMARCB1, U; HNRPH3, D), cell division (ANAPC4, D; CDC2L6, D; CENPJ, D), interferon activity (IRF7, U), and microRNA synthesis (DICER1, D). Gene expression changes (>2.5-fold) in the 443 gene set included: HGF, 3.6xD; APAF1, 3.4xD; IRF1, 2.6xU; FOSL1, 2.7xU; TGFB1, 2.9xU; RELB, 3.7xU; MAFF, 4.3xU. Although highly diverse, these findings point to potentially drug-targetable alterations of AP-1 and NFΚB transcriptional control in association with alterations in ras- and PKA-regulated signal transduction pathways and possibly to microRNA synthesis as common molecular processes in APL cells related to disease progression and relapse.

scholarly journals Early Phenotypes in Girls at Risk for PCOS Replicate Metabolic and Reproductive Subtypes: An Unsupervised Clustering Analysis

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A739-A739
Author(s):  
Laura Christine Torchen ◽  
Ryan Sisk ◽  
Sarayu Ratnam ◽  
Andrea Elizabeth Dunaif
Keyword(s):  
At Risk ◽  
Longitudinal Studies ◽  
Quantitative Traits ◽  
Hierarchical Cluster ◽  
Unsupervised Hierarchical Cluster ◽  
Adult Women ◽  
Gonadotropin Secretion ◽  
Insulin Levels ◽  
Increased Risk ◽  
Significant Difference

Abstract Both daughters of women with PCOS (PCOS-d) and overweight girls (OW-g) are proposed to be at increased risk of PCOS because they have peripubertal increases in testosterone (T) levels, a cardinal feature of PCOS. We are testing this hypothesis by performing longitudinal studies in these girls after menarche. In adult women with PCOS, we have recently identified reproductive and metabolic subtypes using unsupervised cluster analyses. These subtypes were associated with novel PCOS susceptibility genetic loci suggesting that the subtypes reflect biologically discrete entities. We performed similar analyses in our cohort of early postmenarchal PCOS-d and OW-g to test the hypothesis that these subtypes are present in girls at risk for PCOS. Fifteen PCOS-d and 10 OW-g aged 11-16 years and with postmenarchal age less than 2 years were studied. Mothers of PCOS-d fulfilled NIH criteria for PCOS, mothers of OW-g were reproductively normal with no history of irregular menses or clinical hyperandrogenism. OW-g had a BMI above the 85th percentile for age. There was no BMI inclusion criterion for PCOS-d; four PCOS-d had a BMI above the 85th percentile. The girls were of comparable age, post-menarchal age and BMI z score. A fasting morning blood sample was drawn for T, SHBG, DHEAS, glucose and insulin. Leuprolide 10 mcg/kg SC was administered. LH and FSH levels were measured at baseline, 30 min, and 60 min following leuprolide. Unsupervised hierarchical cluster analysis adjusted for age was performed on quantitative traits including BMI, T, fasting insulin, fasting glucose, DHEAS, SHBG, and LH and FSH. These are the same quantitative traits used for clustering in adult PCOS. The clustering revealed 2 distinct PCOS subtypes: a reproductive group (41%), characterized by higher SHBG levels, LH and FSH with relatively low BMI and insulin levels, and a metabolic group (41%), characterized by higher BMI and insulin levels and lower SHBG, LH, and FSH. Jaccard coefficients indicated cluster stability (0.70 reproductive, 0.69 metabolic). There was a significant difference in the distribution of the two subgroups in PCOS-d and OW-g: PCOS-d 60% reproductive, 13% metabolic, 27% indeterminate; OW-g 25% reproductive, 50% metabolic, 25% indeterminate (Chi Sq P=0.05). We found that early postmenarchal PCOS-d and OW-g demonstrate reproductive and metabolic subtypes similar to those identified in adult women with PCOS. The majority of PCOS-d had the reproductive subtype. These findings suggest that this subtype, which is characterized by disordered gonadotropin secretion, is an early harbinger of PCOS. Longitudinal studies are ongoing to test this hypothesis.

scholarly journals Genomic and Transcriptomic Profiling of Brain Metastases

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5598
Author(s):  
Christopher P. Wardell ◽  
Emilie Darrigues ◽  
Annick De Loose ◽  
Madison P. Lee ◽  
Murat Gokden ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Molecular Mechanisms ◽  
Prognostic Significance ◽  
Hierarchical Cluster ◽  
Molecular Characteristics ◽  
Unsupervised Hierarchical Cluster ◽  
Metastatic Progression ◽  
Poor Survival ◽  
Mutational Signatures ◽  
Black Race

Brain metastases (BM) are the most common brain tumors in adults occurring in up to 40% of all cancer patients. Multi-omics approaches allow for understanding molecular mechanisms and identification of markers with prognostic significance. In this study, we profile 130 BM using genomics and transcriptomics and correlate molecular characteristics to clinical parameters. The most common tumor origins for BM were lung (40%) followed by melanoma (21%) and breast (15%). Melanoma and lung BMs contained more deleterious mutations than other subtypes (p < 0.001). Mutational signatures suggested that the bulk of the mutations were gained before metastasis. A novel copy number event centered around the MCL1 gene was found in 75% of all samples, suggesting a broader role in promoting metastasis. Unsupervised hierarchical cluster analysis of transcriptional signatures available in 65 samples based on the hallmarks of cancer revealed four distinct clusters. Melanoma samples formed a distinctive cluster in comparison to other BM subtypes. Characteristics of molecular profiles did not correlate with survival. However, patients with self-identified black race or those who did not receive radiation correlated with poor survival. These data identify potential new drivers of brain metastatic progression. Our data also suggest further investigation of sociodemographic and clinical features is needed in BM cohorts.

scholarly journals RBL1/p107 Expression Levels Are Modulated by Multiple Signaling Pathways

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 5025
Author(s):  
Elisa Ventura ◽  
Carmelina Antonella Iannuzzi ◽  
Francesca Pentimalli ◽  
Antonio Giordano ◽  
Andrea Morrione
Keyword(s):  
Cell Cycle ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Oncogenic Signaling ◽  
Expression Levels ◽  
Close Family Member ◽  
Calcium Calmodulin Dependent ◽  
Cycle Arrest ◽  
Significant Difference ◽  
Multiple Signaling

The members of the retinoblastoma (RB) protein family, RB1/p105, retinoblastoma-like (RBL)1/p107 and RBL2/p130 are critical modulators of the cell cycle and their dysregulation has been associated with tumor initiation and progression. The activity of RB proteins is regulated by numerous pathways including oncogenic signaling, but the molecular mechanisms of these functional interactions are not fully defined. We previously demonstrated that RBL2/p130 is a direct target of AKT and it is a key mediator of the apoptotic process induced by AKT inhibition. Here we demonstrated that RBL1/p107 levels are only minorly modulated by the AKT signaling pathway. In contrast, we discovered that RBL1/p107 levels are regulated by multiple pathways linked directly or indirectly to Ca2+-dependent signaling. Inhibition of the multifunctional calcium/calmodulin-dependent kinases (CaMKs) significantly reduced RBL1/p107 expression levels and phosphorylation, increased RBL1/p107 nuclear localization and led to cell cycle arrest in G0/G1. Targeting the Ca2+-dependent endopeptidase calpain stabilized RBL1/p107 levels and counteracted the reduction of RBL1/p107 levels associated with CaMKs inhibition. Thus, these novel observations suggest a complex regulation of RBL1/p107 expression involving different components of signaling pathways controlled by Ca2+ levels, including CaMKs and calpain, pointing out a significant difference with the mechanisms modulating the close family member RBL2/p130.

FLT3-ITD Confers Resistance to Bortezomib By Protecting the mTOR/4EBP1 Pathway through Activation of STAT5 and Induction of Pim-1 Expression

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1270-1270
Author(s):  
Ayako Nogami ◽  
Keigo Okada ◽  
Gaku Oshikawa ◽  
Shinya Ishida ◽  
Hiroki Akiyama ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Kinase Inhibitor ◽  
Conflicts Of Interest ◽  
Expression Level ◽  
Apoptotic Pathway ◽  
Expression Levels ◽  
Combined Use ◽  
Significant Difference ◽  
Induced Apoptosis ◽  
Novel Therapeutic Strategies

Abstract FLT3-ITD and FLT3-TKD are the most frequent tyrosine kinase mutations in AML, with the former strongly associated with a poor prognosis. We have recently revealed that FLT3-ITD confers resistance to the PI3K/AKT pathway inhibitors by protecting the mTOR/4EBP1/Mcl-1 pathway through STAT5 activation in AML. The proteasomal inhibitor bortezomib (BZM) has recently been reported as a promising agent for treatment of AML. We examine here the molecular mechanisms involved in induction of apoptosis by BZM in hematopoietic cells, including AML cells, and evaluate the effects of FLT3-ITD and TKD on these mechanisms and on the sensitivity of cells to BZM-induced apoptosis. We first comparatively examined the effect of BZM on survival of hematopoietic 32D cells and human leukemic UT7 cells driven by FLT3-ITD (32D/ITD and UT7/ITD) or FLT3-D835Y (32D/TKD and UT7/TKD). BZM induced activation of Bax, decline in mitochondrial membrane potential, and activation of caspase-9, thus leading to apoptosis, more conspicuously in cells driven by FLT3-ITD than FLT3-TKD. These results indicate that FLT3-ITD, as compared with FLT3-TKD, conferred resistance to apoptosis induced by BZM through the intrinsic pathway in these cells. To elucidate the molecular mechanisms involved in BZM-induced apoptosis in these cells, we next examined the effect of BZM on expression levels of FLT3 in these cells as well as in human leukemic MV4-11 cells expressing FLT3-ITD. Intriguingly, treatment of these cells with BZM conspicuously reduced expression levels of FLT3. It was further reveled that BZM further facilitated the decline in FLT3-ITD expression in MV4-11 cells treated with actinomycin D to shut down the transcriptional activity. Furthermore, BZM significantly retarded the recovery of FLT3-ITD expression in MV4-11 cells washed out from the translation inhibitor cycloheximide. These results suggest that BZM may downregulate the FLT3-ITD expression mainly at the translational level. However, we did not observe any significant difference in extent of the BZM-induced decline in expression levels between FLT3-ITD and FLT3-TKD. We next examined the effect of BZM on the mTOR/4EBP1 pathway, which we have shown to play important roles in regulation of apoptosis downstream of FLT3-ITD. It was found that BZM downregulated this pathway more significantly in 32D/TKD cells than in 32D/ITD cells. Because we have also previously found that STAT5 activated robustly by FLT3-ITD plays an important role in modulation of the mTOR/4EBP1 pathway, we examined the effects of BZM on 32D/TKD cells forced to express the constitutively activated STAT5 mutant, STAT5A1*6. As expected, STAT5A1*6 conferred resistance to BZM-induced downregulation of the mTOR/4EBP1 pathway as well as apoptosis in 32D/TKD cells. Consistent with this, the STAT5 inhibitor pimozide, clinically in use for neuropsychiatric disorders, abrogated the resistance of 32D/ITD, UT7/ITD, and MV4-11 cells to BZM-induced inhibition of the mTOR/4EBP1 pathway and apoptosis. We finally examined the possible involvement of the STAT5 target gene product Pim-1 in acquisition of resistance to BZM by cells expressing FLT3-ITD. We fist confirmed that Pim-1 was expressed at a higher level in 32D/ITD cells than in 32D/TKD cells and that STAT5A1*6 increased the expression level of Pim-1 in 32D/TKD cells. We then examined the effects of a specific Pim kinase inhibitor, AZD-1208, and found that it synergistically downregulated the mTOR/4EBP1 pathway and induced apoptosis with BZM in 32D/ITD cells as well as 32D/TKD cells expressing STAT5A1*6. We also examined the effects of a BET bromodomain inhibitor, JQ1, which has recently been shown to inhibit the STAT5 activity and to reduce specifically the expression level of Pim-1 as well as c-Myc in MV4-11 cells. As expected, pretreatment of 32D/ITD or MV4-11 cells with JQ1 conspicuously sensitized these cells to BZM-induced apoptosis. These results suggest that BZM downregulates FLT3 expression and the mTOR/4EBP1 pathway to activate the intrinsic apoptotic pathway and that robust STAT5 activation by FLT3-ITD confers resistance to BZM on AML cells through protection of the mTOR/4EBP1 pathway at least partly by inducing Pim-1 expression. The present study may contribute to development of novel therapeutic strategies against FLT3-ITD-positive AML by combined use of BZM and the STAT5/Pim-1 pathway inhibitors. Disclosures No relevant conflicts of interest to declare.

scholarly journals Molecular regulation of Snai2 in development and disease

2019 ◽  
Vol 132 (23) ◽  
Author(s):  
Wenhui Zhou ◽  
Kayla M. Gross ◽  
Charlotte Kuperwasser
Keyword(s):  
Transcription Factor ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Zinc Finger Protein ◽  
Main Role ◽  
Biological Processes ◽  
Developmental Defects ◽  
Mesenchymal Transition ◽  
Damage Repair

ABSTRACT The transcription factor Snai2, encoded by the SNAI2 gene, is an evolutionarily conserved C2H2 zinc finger protein that orchestrates biological processes critical to tissue development and tumorigenesis. Initially characterized as a prototypical epithelial-to-mesenchymal transition (EMT) transcription factor, Snai2 has been shown more recently to participate in a wider variety of biological processes, including tumor metastasis, stem and/or progenitor cell biology, cellular differentiation, vascular remodeling and DNA damage repair. The main role of Snai2 in controlling such processes involves facilitating the epigenetic regulation of transcriptional programs, and, as such, its dysregulation manifests in developmental defects, disruption of tissue homeostasis, and other disease conditions. Here, we discuss our current understanding of the molecular mechanisms regulating Snai2 expression, abundance and activity. In addition, we outline how these mechanisms contribute to disease phenotypes or how they may impact rational therapeutic targeting of Snai2 dysregulation in human disease.

scholarly journals Physical Exercise and Cardiac Repair: The Potential Role of Nitric Oxide in Boosting Stem Cell Regenerative Biology

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1002
Author(s):  
Fabiola Marino ◽  
Mariangela Scalise ◽  
Eleonora Cianflone ◽  
Luca Salerno ◽  
Donato Cappetta ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Stem Cell ◽  
Physical Exercise ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Heart Function ◽  
Stem Cell Biology ◽  
Myocardial Repair ◽  
Beneficial Effects

Over the years strong evidence has been accumulated showing that aerobic physical exercise exerts beneficial effects on the prevention and reduction of cardiovascular risk. Exercise in healthy subjects fosters physiological remodeling of the adult heart. Concurrently, physical training can significantly slow-down or even reverse the maladaptive pathologic cardiac remodeling in cardiac diseases, improving heart function. The underlying cellular and molecular mechanisms of the beneficial effects of physical exercise on the heart are still a subject of intensive study. Aerobic activity increases cardiovascular nitric oxide (NO) released mainly through nitric oxidase synthase 3 activity, promoting endothelium-dependent vasodilation, reducing vascular resistance, and lowering blood pressure. On the reverse, an imbalance between increasing free radical production and decreased NO generation characterizes pathologic remodeling, which has been termed the “nitroso-redox imbalance”. Besides these classical evidence on the role of NO in cardiac physiology and pathology, accumulating data show that NO regulate different aspects of stem cell biology, including survival, proliferation, migration, differentiation, and secretion of pro-regenerative factors. Concurrently, it has been shown that physical exercise generates physiological remodeling while antagonizes pathologic remodeling also by fostering cardiac regeneration, including new cardiomyocyte formation. This review is therefore focused on the possible link between physical exercise, NO, and stem cell biology in the cardiac regenerative/reparative response to physiological or pathological load. Cellular and molecular mechanisms that generate an exercise-induced cardioprotective phenotype are discussed in regards with myocardial repair and regeneration. Aerobic training can benefit cells implicated in cardiovascular homeostasis and response to damage by NO-mediated pathways that protect stem cells in the hostile environment, enhance their activation and differentiation and, in turn, translate to more efficient myocardial tissue regeneration. Moreover, stem cell preconditioning by and/or local potentiation of NO signaling can be envisioned as promising approaches to improve the post-transplantation stem cell survival and the efficacy of cardiac stem cell therapy.

Transformative Learning in Mastery-Oriented CS0 Course

2021 ◽  
pp. 234763112110072
Author(s):  
Srinivasan Lakshminarayanan ◽  
N. J. Rao ◽  
G. K. Meghana
Keyword(s):  
Transformative Learning ◽  
First Year ◽  
Guided Discovery ◽  
Engineering Programs ◽  
Transformative Experiences ◽  
Significant Difference ◽  
Cognitive Levels ◽  
Almost All ◽  
Core Course

The introductory programming course, commonly known as CS1 and offered as a core course in the first year in all engineering programs in India, is unique because it can address higher cognitive levels, metacognition and some aspects of the affective domain. It can provide much needed transformative experiences to students coming from a system of school education that is dominantly performance-driven. Unfortunately, the CS1 course, as practiced in almost all engineering programs, is also performance-driven because of a variety of compulsions. This paper suggests that the inclusion of a course CS0 can bring about transformative learning that can potentially make a significant difference in the quality of learning in all subsequent engineering courses. The suggested instruction design of this course takes the advantage of the unique features of a course in programming. The proposed CS0 course uses “extreme apprenticeship” and “guided discovery” methods of instruction. The effectiveness of these instruction methods was established through the use of the thematic analysis, a well-known qualitative research method, and the associated coding of transformative learning experiences and instruction components.

scholarly journals The expression of the GATA6 gene in oral carcinoma cell lines

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Cheng-Lin Xu ◽  
Wei-Qun Guan ◽  
Xue-Ying Wang
Keyword(s):  
Cell Lines ◽  
Carcinoma Cell ◽  
Carcinoma Cells ◽  
Expression Levels ◽  
Carcinoma Cell Lines ◽  
Human Tongue ◽  
Adenoid Cystic ◽  
Significant Difference ◽  
Oral Epithelial ◽  
Gata6 Gene

Abstract Background This study aimed to investigate the expression level of the GATA6 gene in different oral cancer cells. Methods In this study, we sub-cultured normal oral epithelial cell lines HOK, human tongue squamous cell carcinoma cell lines CAL-27 and SCC-4, and human salivary gland adenoid cystic carcinoma cell lines SACC-LM and SACC-83. Subsequently, we used reverse transcription-polymerase chain reaction RT-PCR and Western blot methods to detect the mRNA and the protein expressions of GATA6 in normal oral epithelial cells, human tongue squamous cell carcinoma cells, and human salivary gland adenoid cystic carcinoma cells. Results The results of this study showed that the mRNA expression levels of GATA6 in CAL-27, SCC-4, and SACC-LM cells were significantly increased when compared with the HOK cells. However, the mRNA expression level of GATA6 in the SACC-83 cells had no significant difference compared with the HOK cells. The protein expression levels of GATA6 in the SCC-4 and SACC-LM cells were, however, significantly increased whereas the protein expression levels of GATA6 in the CAL-27 and SACC-83 cells had no significant difference when compared with the HOK cells. Conclusion The GATA6 gene may be related to the occurrence and progression of certain oral cancers.

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