scholarly journals Sensitivity to expression levels underlies differential dominance of a putative null allele of the Drosophila tßh gene in behavioral phenotypes

PLoS Biology ◽  
2021 ◽  
Vol 19 (5) ◽  
pp. e3001228
Author(s):  
Christine Damrau ◽  
Julien Colomb ◽  
Björn Brembs
Keyword(s):  
Null Allele ◽  
Walking Speed ◽  
Fruit Fly ◽  
Complex Interaction ◽  
Differential Sensitivity ◽  
Wild Type ◽  
Behavioral Measures ◽  
Expression Levels ◽  
Proboscis Extension ◽  
Gene Expression Levels

The biogenic amine octopamine (OA) and its precursor tyramine (TA) are involved in controlling a plethora of different physiological and behavioral processes. The tyramine-ß-hydroxylase (tßh) gene encodes the enzyme catalyzing the last synthesis step from TA to OA. Here, we report differential dominance (from recessive to overdominant) of the putative null tßhnM18 allele in 2 behavioral measures in Buridan’s paradigm (walking speed and stripe deviation) and in proboscis extension (sugar sensitivity) in the fruit fly Drosophila melanogaster. The behavioral analysis of transgenic tßh expression experiments in mutant and wild-type flies as well as of OA and TA receptor mutants revealed a complex interaction of both aminergic systems. Our analysis suggests that the different neuronal networks responsible for the 3 phenotypes show differential sensitivity to tßh gene expression levels. The evidence suggests that this sensitivity is brought about by a TA/OA opponent system modulating the involved neuronal circuits. This conclusion has important implications for standard transgenic techniques commonly used in functional genetics.

scholarly journals Differential dominance of an allele of theDrosophila tßhgene challenges standard genetic techniques

2018 ◽  
Author(s):  
Christine Damrau ◽  
Anders Eriksson ◽  
Julien Colomb ◽  
Björn Brembs
Keyword(s):  
Walking Speed ◽  
Gene Dosage ◽  
Fruit Fly ◽  
Complex Interaction ◽  
Wild Type ◽  
Behavioral Measures ◽  
Functional Genetics ◽  
Proboscis Extension ◽  
Genetic Techniques ◽  
Aminergic Systems

AbstractThe biogenic amine octopamine (OA) and its precursor tyramine (TA) are involved in controlling a plethora of different physiological and behavioral processes. The tyramine-ß-hydroxylase (tßh) gene encodes the enzyme catalyzing the last synthesis step from TA to OA. Here, we report differential dominance (from recessive to overdominant) of the putative nulltßhnM18allele in two behavioral measures in Buridan’s paradigm (walking speed and stripe deviation) and a proboscis extension assay in the fruit flyDrosophila melanogaster. The behavioral analysis of transgenictßhexpression experiments in mutant and wild type flies as well as of OA- and TA-receptor mutants revealed a complex interaction of both aminergic systems. Our analysis suggests that the different neuronal networks responsible for the three phenotypes show different sensitivity totßhgene dosage. This conclusion entails important implications for standard transgenic techniques, commonly used in functional genetics.

High epiregulin (EREG) gene expression plus K-ras wild-type (WT) status as predictors of cetuximab benefit in the treatment of advanced colorectal cancer (ACRC): Results from NCIC CTG CO.17—A phase III trial of cetuximab versus best supportive care (BSC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4016-4016 ◽  
Author(s):  
D. J. Jonker ◽  
C. Karapetis ◽  
C. Harbison ◽  
C. J. O’Callaghan ◽  
D. Tu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cox Model ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Wild Type ◽  
Total Study Population ◽  
Positive Group ◽  
Expression Levels ◽  
Gene Expression Levels

4016 Background: Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR), improves overall survival (OS) and progression free survival (PFS) in patients with K-ras WT chemotherapy refractory ACRC. Gene expression of the EGFR ligand epiregulin (EREG) may further predict benefit from cetuximab. Methods: CRC tumour samples were analyzed from a phase III clinical trial of cetuximab plus BSC vs BSC alone (NEJM 2007; 357(20)). EREG gene expression was detected in tumour-derived genomic RNA blinded to clinical outcome by quantitative real time-PCR. Using a pre-specified threshold for “high” EREG derived from a prior study (CA225–045), the predictive effect of (1) high vs low EREG among K-ras WT and (2) high EREG/K-ras WT status (“Combimarker”) versus all other patients on OS and PFS was examined using a Cox model with tests for treatment-biomarker interaction. Results: Both EREG gene expression levels and K-ras mutation status were ascertained in 385 (67%) of the total study population (193 cetuximab, 192 BSC). In the K-ras WT subset, OS was better for cetuximab than BSC among patients with high EREG (HR 0.43; p<0.0001) but not for low EREG patients (HR 0.77, p=0.28). The test for interaction showed a non-significantly larger treatment effect in the high EREG group (HR 0.62, p=0.13). High EREG AND K-ras WT status (“Combimarker”) was present in 139 (36%). Within the Combimarker positive group the median PFS was 5.4 vs 1.9 months (HR, 0.31; p<0.0001), and median OS 9.8 vs 5.1 months (HR, 0.43; p<0.001) in the cetuximab vs BSC arms, respectively. In the rest (n=246, 64%) cetuximab was not associated with improved PFS (HR, 0.82; p=0.12) or OS (HR, 0.90; p=0.45). The test for treatment-Combimarker interaction showed a larger cetuximab effect on OS (HR 0.52; p=0.007) and PFS (HR 0.49; p=0.001) in the Combimarker positive group. Conclusions: In the setting of pre-treated ACRC, patients with both high EREG gene expression and K-ras wild- type status may benefit from cetuximab therapy. Determination of EREG gene expression levels should be prospectively evaluated in patient selection for EGFR targeted therapy. [Table: see text]

scholarly journals The impact of preserved Klotho gene expression on antioxidative stress activity in healthy kidney

2018 ◽  
Vol 315 (2) ◽  
pp. F345-F352 ◽  
Author(s):  
Takaaki Kimura ◽  
Kazuhiro Shiizaki ◽  
Tetsu Akimoto ◽  
Takahiro Shinzato ◽  
Toshihiro Shimizu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Renal Function ◽  
Human Kidney ◽  
Wild Type ◽  
Healthy Human ◽  
Expression Levels ◽  
Klotho Gene ◽  
Antioxidative Stress ◽  
Deficient Mice ◽  
Gene Expression Levels

Klotho, which was originally identified as an antiaging gene, forms a complex with fibroblast growth factor 23 receptor in the kidney, with subsequent signaling that regulates mineral metabolism. Other biological activities of Klotho, including antiaging effects such as protection from various types of cellular stress, have been shown; however, the precise mechanism of these effects of Klotho gene in the healthy human kidney is not well understood. In this study, we examined the relationships of Klotho and antioxidative stress gene expression levels in zero-hour biopsy specimens from 44 donors in kidney transplantation and verified them in animal models whose Klotho gene expression levels were varied. The nitrotyrosine expression level in the kidney was evaluated in these animal models. Expression levels of Klotho gene were positively correlated with the p53 gene and antioxidant enzyme genes such as catalase, superoxide dismutase 1 (SOD1), SOD2, peroxiredoxin 3 (PRDX3), and glutathione peroxidase 1 (GPX1) but not clinical parameters such as age and renal function or pathological features such as glomerulosclerosis and interstitial fibrosis tubular atrophy. The expression levels of all genes were significantly higher in mice with Klotho overexpression than in wild-type mice, and those except for catalase, PRDX3, and GPX1 were significantly lower in Klotho-deficient mice than in wild-type littermate mice. Nitrotyrosine-positive bands of various sizes were observed in kidney from Klotho-deficient mice only. The preservation of Klotho gene expression might induce the antioxidative stress mechanism for homeostasis of healthy human kidney independently of its general condition, including age, renal function, and histological findings.

scholarly journals Igf2 Gene Expression Levels in Wild-Type and Mutant Mice

2017 ◽  
Vol 2 (4) ◽  
Author(s):  
Giang Van Tran ◽  
Dung Quoc Tran ◽  
Pham Thanh ◽  
Nguyen Ty ◽  
Pham Quang Chinh
Keyword(s):  
Growth Factor ◽  
Placental Tissue ◽  
The Other ◽  
Mutant Mice ◽  
Parental Origin ◽  
Wild Type ◽  
Igf2 Gene ◽  
Expression Levels ◽  
Low Expression ◽  
Gene Expression Levels

Genomic imprinting occurs where only one allele of a gene is expressed depending on its parental origin. The imprinted Igf2 gene (Insulin-like growth factor 2) is encoding a growth factor, which play an important role in embryonic development and formation of the placenta. The regulation and expression of Igf2 is carried out by different promoters. Promoter expression is extremely complex in wild-type mice during development and is altered in several mutant mice bearing deletions at the Igf2/H19 locus. In this work, we analyzed the Igf2 RNA expression of the placenta-specific P0 promoter in placental tissue (embryonic day 17) of both wild-type and mutant mice. For all the other promoters, we used RNA extracted from liver tissues (postnatal day 7.5). All these RNAs were reverse transcribed to cDNA before quantifying expression levels of the promoters by quantitative PCR (qPCR).Our results show that transcriptions of Igf2 P2 and P3 promoters are the highest in all mice analyzed, except in ΔU2/Dom mutant mice where P0 and P1 promoters were highly expressed, while they display low expression in all the other mice strains analyzed. Furthermore, all promoters were stably expressed at high levels in wild-type and ΔU2/Dom mutation, but at a low level in Δ3/Dom

scholarly journals A Sparse and Low-Rank Regression Model for Identifying the Relationships Between DNA Methylation and Gene Expression Levels in Gastric Cancer and the Prediction of Prognosis

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 854
Author(s):  
Yishu Wang ◽  
Lingyun Xu ◽  
Dongmei Ai
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Dna Methylation ◽  
Regression Model ◽  
The Cancer Genome Atlas ◽  
Low Rank ◽  
Expression Levels ◽  
Rank Regression ◽  
Prediction Of Prognosis ◽  
Gene Expression Levels

DNA methylation is an important regulator of gene expression that can influence tumor heterogeneity and shows weak and varying expression levels among different genes. Gastric cancer (GC) is a highly heterogeneous cancer of the digestive system with a high mortality rate worldwide. The heterogeneous subtypes of GC lead to different prognoses. In this study, we explored the relationships between DNA methylation and gene expression levels by introducing a sparse low-rank regression model based on a GC dataset with 375 tumor samples and 32 normal samples from The Cancer Genome Atlas database. Differences in the DNA methylation levels and sites were found to be associated with differences in the expressed genes related to GC development. Overall, 29 methylation-driven genes were found to be related to the GC subtypes, and in the prognostic model, we explored five prognoses related to the methylation sites. Finally, based on a low-rank matrix, seven subgroups were identified with different methylation statuses. These specific classifications based on DNA methylation levels may help to account for heterogeneity and aid in personalized treatments.

scholarly journals Transcriptome Analysis Provides Insights into the Mechanism of Astaxanthin Enrichment in a Mutant of the Ridgetail White Prawn Exopalaemon carinicauda

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 618
Author(s):  
Yue Jin ◽  
Shihao Li ◽  
Yang Yu ◽  
Chengsong Zhang ◽  
Xiaojun Zhang ◽  
...  
Keyword(s):  
Transcriptome Analysis ◽  
Underlying Mechanism ◽  
Biological Processes ◽  
Wild Type ◽  
Expression Levels ◽  
In The Wild ◽  
Cuticle Proteins ◽  
Apolipoprotein D ◽  
High Level ◽  
Lower Expression

A mutant of the ridgetail white prawn, which exhibited rare orange-red body color with a higher level of free astaxanthin (ASTX) concentration than that in the wild-type prawn, was obtained in our lab. In order to understand the underlying mechanism for the existence of a high level of free astaxanthin, transcriptome analysis was performed to identify the differentially expressed genes (DEGs) between the mutant and wild-type prawns. A total of 78,224 unigenes were obtained, and 1863 were identified as DEGs, in which 902 unigenes showed higher expression levels, while 961 unigenes presented lower expression levels in the mutant in comparison with the wild-type prawns. Based on Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes analysis, as well as further investigation of annotated DEGs, we found that the biological processes related to astaxanthin binding, transport, and metabolism presented significant differences between the mutant and the wild-type prawns. Some genes related to these processes, including crustacyanin, apolipoprotein D (ApoD), cathepsin, and cuticle proteins, were identified as DEGs between the two types of prawns. These data may provide important information for us to understand the molecular mechanism of the existence of a high level of free astaxanthin in the prawn.

scholarly journals Elevated Expression of SLC6A4 Encoding the Serotonin Transporter (SERT) in Gilles de la Tourette Syndrome

Genes ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 86
Author(s):  
Mathis Hildonen ◽  
Amanda M. Levy ◽  
Christina Dahl ◽  
Victoria A. Bjerregaard ◽  
Lisbeth Birk Møller ◽  
...  
Keyword(s):  
Tourette Syndrome ◽  
Serotonin Transporter ◽  
Neurodevelopmental Disorder ◽  
Control Group ◽  
Obsessive Compulsive ◽  
Expression Levels ◽  
Compulsive Disorder ◽  
Hyperactivity Disorder ◽  
Elevated Expression ◽  
Gene Expression Levels

Gilles de la Tourette syndrome (GTS) is a complex neurodevelopmental disorder characterized by motor and vocal tics. Most of the GTS individuals have comorbid diagnoses, of which obsessive-compulsive disorder (OCD) and attention deficit-hyperactivity disorder (ADHD) are the most common. Several neurotransmitter systems have been implicated in disease pathogenesis, and amongst these, the dopaminergic and the serotonergic pathways are the most widely studied. In this study, we aimed to investigate whether the serotonin transporter (SERT) gene (SLC6A4) was differentially expressed among GTS individuals compared to healthy controls, and whether DNA variants (the SERT-linked polymorphic region 5-HTTLPR, together with the associated rs25531 and rs25532 variants, and the rare Ile425Val variant) or promoter methylation of SLC6A4 were associated with gene expression levels or with the presence of OCD as comorbidity. We observed that SLC6A4 expression is upregulated in GTS individuals compared to controls. Although no specific genotype, allele or haplotype was overrepresented in GTS individuals compared to controls, we observed that the LAC/LAC genotype of the 5-HTTLPR/rs25531/rs25532 three-locus haplotype was associated with higher SLC6A4 mRNA expression levels in GTS individuals, but not in the control group.

scholarly journals Mutations of folC cause increased susceptibility to sulfamethoxazole in Mycobacterium tuberculosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ruiqi Wang ◽  
Kun Li ◽  
Jifang Yu ◽  
Jiaoyu Deng ◽  
Yaokai Chen
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Type Strain ◽  
Wild Type Strain ◽  
Clinical Isolates ◽  
Aminobenzoic Acid ◽  
Wild Type ◽  
Dihydropteroate Synthase ◽  
Expression Levels ◽  
Encoding Gene ◽  
Increased Susceptibility

AbstractPrevious studies showed that mutation of folC caused decreased expression of the dihydropteroate synthase encoding gene folP2 in Mycobacterium tuberculosis (M. tuberculosis). We speculated that mutation of folC in M. tuberculosis might affect the susceptibility to sulfamethoxazole (SMX). To prove this, 53 clinical isolates with folC mutations were selected and two folC mutants (I43A, I43T) were constructed based on M. tuberculosis H37Ra. The results showed that 42 of the 53 clinical isolates (79.2%) and the two lab-constructed folC mutants were more sensitive to SMX. To probe the mechanism by which folC mutations make M. tuberculosis more sensitive to SMX, folP2 was deleted in H37Ra, and expression levels of folP2 were compared between H37Ra and the two folC mutants. Although deletion of folP2 resulted in increased susceptibility to SMX, no difference in folP2 expression was observed. Furthermore, production levels of para-aminobenzoic acid (pABA) were compared between the folC mutants and the wild-type strain, and results showed that folC mutation resulted in decreased production of pABA. Taken together, we show that folC mutation leads to decreased production of pABA in M. tuberculosis and thus affects its susceptibility to SMX, which broadens our understanding of mechanisms of susceptibilities to antifolates in this bacterium.

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