Carvedilol Induces Changes In Gene Expression In The Wild-Type Rat Heart

2012 ◽  
Author(s):  
Jennifer I. Drake ◽  
Ramesh Natarajan ◽  
Harm J. Bogaard ◽  
Donatas Kraskauskas ◽  
Norbert F. Voelkel
Keyword(s):  
Gene Expression ◽  
Rat Heart ◽  
Wild Type ◽  
In The Wild

scholarly journals Role of Sigma Factors in Controlling Global Gene Expression in Light/Dark Transitions in the Cyanobacterium Synechocystis sp. Strain PCC 6803

2007 ◽  
Vol 189 (21) ◽  
pp. 7829-7840 ◽  
Author(s):  
Tina C. Summerfield ◽  
Louis A. Sherman
Keyword(s):  
Gene Expression ◽  
Global Gene Expression ◽  
Growth Conditions ◽  
Day Length ◽  
Regulation Of Transcription ◽  
Wild Type ◽  
Protein Levels ◽  
In The Wild ◽  
Altered Gene ◽  
Pcc 6803

ABSTRACT We report on differential gene expression in the cyanobacterium Synechocystis sp. strain PCC 6803 after light-dark transitions in wild-type, ΔsigB, and ΔsigD strains. We also studied the effect of day length in the presence of glucose on a ΔsigB ΔsigE mutant. Our results indicated that the absence of SigB or SigD predominately altered gene expression in the dark or in the light, respectively. In the light, approximately 350 genes displayed transcript levels in the ΔsigD strain that were different from those of the wild type, with over 200 of these up-regulated in the mutant. In the dark, removal of SigB altered more than 150 genes, and the levels of 136 of these were increased in the mutant compared to those in the wild type. The removal of both SigB and SigE had a major impact on gene expression under mixotrophic growth conditions and resulted in the inability of cells to grow in the presence of glucose with 8-h light and 16-h dark cycles. Our results indicated the importance of group II σ factors in the global regulation of transcription in this organism and are best explained by using the σ cycle paradigm with the stochastic release model described previously (R. A. Mooney, S. A. Darst, and R. Landick, Mol. Cell 20:335-345, 2005). We combined our results with the total protein levels of the σ factors in the light and dark as calculated previously (S. Imamura, S. Yoshihara, S. Nakano, N. Shiozaki, A. Yamada, K. Tanaka, H. Takahashi, M. Asayama, and M. Shirai, J. Mol. Biol. 325:857-872, 2003; S. Imamura, M. Asayama, H. Takahashi, K. Tanaka, H. Takahashi, and M. Shirai, FEBS Lett. 554:357-362, 2003). Thus, we concluded that the control of global transcription is based on the amount of the various σ factors present and able to bind RNA polymerase.

scholarly journals Effect of Metallothionein-III on Mercury-Induced Chemokine Gene Expression

Toxics ◽  
2018 ◽  
Vol 6 (3) ◽  
pp. 48 ◽  
Author(s):  
Jin-Yong Lee ◽  
Maki Tokumoto ◽  
Gi-Wook Hwang ◽  
Min-Seok Kim ◽  
Tsutomu Takahashi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Mercury Vapor ◽  
Brain Diseases ◽  
Wild Type ◽  
Chemokine Gene ◽  
Mercury Compounds ◽  
In The Wild ◽  
The Brain ◽  
Chemokine Gene Expression

Mercury compounds are known to cause central nervous system disorders; however the detailed molecular mechanisms of their actions remain unclear. Methylmercury increases the expression of several chemokine genes, specifically in the brain, while metallothionein-III (MT-III) has a protective role against various brain diseases. In this study, we investigated the involvement of MT-III in chemokine gene expression changes in response to methylmercury and mercury vapor in the cerebrum and cerebellum of wild-type mice and MT-III null mice. No difference in mercury concentration was observed between the wild-type mice and MT-III null mice in any brain tissue examined. The expression of Ccl3 in the cerebrum and of Cxcl10 in the cerebellum was increased by methylmercury in the MT-III null but not the wild-type mice. The expression of Ccl7 in the cerebellum was increased by mercury vapor in the MT-III null mice but not the wild-type mice. However, the expression of Ccl12 and Cxcl12 was increased in the cerebrum by methylmercury only in the wild-type mice and the expression of Ccl3 in the cerebellum was increased by mercury vapor only in the wild-type mice. These results indicate that MT-III does not affect mercury accumulation in the brain, but that it affects the expression of some chemokine genes in response to mercury compounds.

scholarly journals Time course of neuropathological events in hyperhomocysteinemic amyloid depositing mice reveals early neuroinflammatory changes that precede amyloid changes and cerebrovascular events

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Erica M. Weekman ◽  
Tiffany L. Sudduth ◽  
Brittani R. Price ◽  
Abigail E. Woolums ◽  
Danielle Hawthorne ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
Time Course ◽  
Control Diet ◽  
Interleukin 1 ◽  
Amyloid Deposition ◽  
Wild Type ◽  
Necrosis Factor Alpha ◽  
Co Morbidity ◽  
In The Wild

Abstract Background Vascular contributions to cognitive impairment and dementia (VCID) are the second leading cause of dementia behind only Alzheimer’s disease (AD); however, VCID is commonly found as a co-morbidity with sporadic AD. We have previously established a mouse model of VCID by inducing hyperhomocysteinemia in both wild-type and amyloid depositing mice. While we have shown the time course of neuropathological events in the wild-type mice with hyperhomocysteinemia, the effect of amyloid deposition on this time course remains unknown; therefore, in this study, we determined the time course of neuropathological changes in our mouse model of hyperhomocysteinemia-induced VCID in amyloid depositing mice. Methods APP/PS1 mice were placed on either a diet deficient in folate and vitamins B6 and B12 and enriched in methionine to induce hyperhomocysteinemia or a control diet for 2, 6, 10, 14, or 18 weeks. Immunohistochemistry and gene expression analysis were used to determine neuroinflammatory changes. Microhemorrhages and amyloid deposition were analyzed using histology and, finally, behavior was assessed using the 2-day radial arm water maze. Results Neuroinflammation, specifically a pro-inflammatory phenotype, was the first pathological change to occur. Specifically, we see a significant increase in gene expression of tumor necrosis factor alpha, interleukin 1 beta, interleukin 6, and interleukin 12a by 6 weeks. This was followed by cognitive deficits starting at 10 weeks. Finally, there is a significant increase in the number of microhemorrhages at 14 weeks on diet as well as redistribution of amyloid from the parenchyma to the vasculature. Conclusions The time course of these pathologies points to neuroinflammation as the initial, key player in homocysteine-induced VCID co-morbid with amyloid deposition and provides a possible therapeutic target and time points.

scholarly journals Listeria monocytogenes σB Regulates Stress Response and Virulence Functions

2003 ◽  
Vol 185 (19) ◽  
pp. 5722-5734 ◽  
Author(s):  
Mark J. Kazmierczak ◽  
Sharon C. Mithoe ◽  
Kathryn J. Boor ◽  
Martin Wiedmann
Keyword(s):  
Gene Expression ◽  
Listeria Monocytogenes ◽  
Stress Response ◽  
Consensus Sequence ◽  
Virulence Gene ◽  
Wild Type ◽  
Promoter Regions ◽  
Virulence Gene Expression ◽  
Stress Response Genes ◽  
In The Wild

ABSTRACT While the stress-responsive alternative sigma factor σB has been identified in different species of Bacillus, Listeria, and Staphylococcus, theσ B regulon has been extensively characterized only in B. subtilis. We combined biocomputing and microarray-based strategies to identify σB-dependent genes in the facultative intracellular pathogen Listeria monocytogenes. Hidden Markov model (HMM)-based searches identified 170 candidateσ B-dependent promoter sequences in the strain EGD-e genome sequence. These data were used to develop a specialized, 208-gene microarray, which included 166 genes downstream of HMM-predicted σB-dependent promoters as well as selected virulence and stress response genes. RNA for the microarray experiments was isolated from both wild-type and ΔsigB null mutant L. monocytogenes cells grown to stationary phase or exposed to osmotic stress (0.5 M KCl). Microarray analyses identified a total of 55 genes with statistically significantσ B-dependent expression under the conditions used in these experiments, with at least 1.5-fold-higher expression in the wild type over the sigB mutant under either stress condition (51 genes showed at least 2.0-fold-higher expression in the wild type). Of the 55 genes exhibiting σB-dependent expression, 54 were preceded by a sequence resembling the σB promoter consensus sequence. Rapid amplification of cDNA ends-PCR was used to confirm the σB-dependent nature of a subset of eight selected promoter regions. Notably, theσ B-dependent L. monocytogenes genes identified through this HMM/microarray strategy included both stress response genes (e.g., gadB, ctc, and the glutathione reductase gene lmo1433) and virulence genes (e.g., inlA, inlB, and bsh). Our data demonstrate that, in addition to regulating expression of genes important for survival under environmental stress conditions, σB also contributes to regulation of virulence gene expression in L. monocytogenes. These findings strongly suggest thatσ B contributes to L. monocytogenes gene expression during infection.

Rescue of Erythropoietin-Deficient Mice From Anemia by Complementation with BAC Transgene.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3614-3614
Author(s):  
Shun Yamazaki ◽  
Norio Suzuki ◽  
Naoshi Obara ◽  
Xiaoqing Pan ◽  
Ikuo Hirano ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fetal Liver ◽  
Pcr Analysis ◽  
Wild Type ◽  
Bac Clone ◽  
Oxygen Homeostasis ◽  
In The Wild ◽  
Liver And Kidney ◽  
Bac Transgene ◽  
Definitive Erythropoiesis

Abstract Abstract 3614 Poster Board III-550 To maintain tissue oxygen homeostasis, erythropoietin (Epo) regulates the erythropoiesis. During embryonic development Epo is produced in the liver, but after birth and throughout adulthood Epo is produced and secreted from the kidney and support definitive erythropoiesis in the bone marrow. Anemia or hypoxic stress provokes transcription of the Epo gene and the mechanisms how the Epo gene expression is activated in a tissue-specific and hypoxia-inducible manner are one of the research topics of the molecular biology or gene regulation study. Since Epo-null mice die in utero of definitive erythropoiesis failure in the fetal liver, physiological significance of the Epo production for the adult erythropoiesis remains to be clarified. We have found that transgenic reporter gene expression driven by a BAC clone containing 180-kb mouse Epo gene locus recapitulates the Epo gene expression in the liver and kidney. To examine whether the Epo gene transcriptional activity within the 180-kb BAC is sufficient to recapitulate physiological Epo production, we attempted to rescue Epo-null mice from embryonic lethality with a BAC transgene harboring a floxed allele of the Epo gene. We found that transgene-derived Epo recovered the erythropoiesis in the fetal liver of Epo-null mice and Epo-null mice with the BAC transgene were born showing a Mendelian ratio. The rescued mice showed no hematological abnormality and were fertile. In the rescued mice bleeding anemia transiently increased plasma Epo level and after recovery from anemia plasma Epo level declined similarly to wild-type mice. In an RT-PCR analysis Epo production in the liver and kidney of the rescued mice was practically equivalent to that in the wild-type counterpart, while other tissues produced only marginal amount of Epo. These results thus demonstrate that the BAC transgene contains the Epo gene regulatory domain region sufficient to fully recapitulate the endogenous Epo gene expression and to compensate for the Epo-deficiency. We also found that the Epo gene deletion from the BAC transgene by general deletor-Cre transgene provoked the Epo-null phenotype, demonstrating that conditional inactivation of the Epo gene is attained in the BAC-rescued mice. The latter system will be a precious tool to investigate adult stage-specific roles of Epo. Disclosures: Yamamoto: Chugai Pharmaceutical, Co., Ltd. : Research Funding.

scholarly journals TheS. cerevisiaeHAP Complex, a Key Regulator of Mitochondrial Function, Coordinates Nuclear and Mitochondrial Gene Expression

2003 ◽  
Vol 4 (1) ◽  
pp. 37-46 ◽  
Author(s):  
S. Buschlen ◽  
J-M Amillet ◽  
B. Guiard ◽  
A. Fournier ◽  
C. Marcireau ◽  
...  
Keyword(s):  
Gene Expression ◽  
Respiratory Chain ◽  
Mitochondrial Gene ◽  
Nuclear Gene ◽  
Negative Control ◽  
Nuclear Genes ◽  
Wild Type ◽  
Mitochondrial Translation ◽  
Respiratory Chain Complexes ◽  
In The Wild

We have comparedSaccharomyces cerevisiaeglobal gene expression in wild-type and mutants (Δhap2 and Δhap4) of the HAP transcriptional complex, which has been shown to be necessary for growth on respiratory substrates. Several hundred ORFs are under positive or negative control of this complex and we analyse here in detail the effect of HAP on mitochondria. We found that most of the genes upregulated in the wild-type strain were involved in organelle functions, but practically none of the downregulated ones. Nuclear genes encoding the different subunits of the respiratory chain complexes figure in the genes more expressed in the wild-type than in the mutants, as expected, but in this group we also found key components of the mitochondrial translation apparatus. This control of mitochondrial translation may be one of the means of coordinating mitochondrial and nuclear gene expression in elaborating the respiratory chain. In addition, HAP controls the nuclear genes involved in several other mitochondrial processes (import, mitochondrial division) that define the metabolic state of the cell, but not mitochondrial DNA replication and transcription. In most cases, a putative CCAAT-binding site is present upstream of the ORF, while in others no such sites are present, suggesting the control to be indirect. The large number of genes regulated by the HAP complex, as well as the fact that HAP also regulates some putative transcriptional activators of unknown function, place this complex at a hierarchically high position in the global transcriptional regulation of the cell.

scholarly journals Neurofilament deficiency in quail caused by nonsense mutation in neurofilament-L gene.

1993 ◽  
Vol 121 (2) ◽  
pp. 387-395 ◽  
Author(s):  
O Ohara ◽  
Y Gahara ◽  
T Miyake ◽  
H Teraoka ◽  
T Kitamura
Keyword(s):  
Gene Expression ◽  
Amino Acid ◽  
Japanese Quail ◽  
Nonsense Mutation ◽  
Trace Amount ◽  
Molecular Mechanisms ◽  
Deficient Mutant ◽  
Wild Type ◽  
In The Wild ◽  
Genetic Events

The existence of a neurofilament-deficient mutant of Japanese quail was recently documented (Yamasaki, H., C. Itakura, and M. Mizutani. 1991. Acta Neuropathol. 82:427-434), but the genetic events leading to the neurofilament deficiency have yet to be determined. Our molecular biological analyses revealed that the expression of neurofilament-L (NF-L) gene was specifically repressed in neurons of this mutant. To search for mutation(s) responsible for the shutdown of this gene expression, we cloned and sequenced the NF-L genes in the wild-type and mutant quails. It is eventually found that the NF-L gene in the mutant includes a nonsense mutation at the deduced amino acid residue 114, indicating that the mutant is incapable of producing even a trace amount of polymerization-competent NF-L protein at any situation. The identification of this nonsense mutation provides us with a solid basis on which molecular mechanisms underlying the alteration in the neuronal cytoskeletal architecture in the mutant should be interpreted.

scholarly journals Control of morphogenesis, protease secretion and gene expression in Candida albicans by the preferred nitrogen source ammonium

Microbiology ◽  
2014 ◽  
Vol 160 (8) ◽  
pp. 1599-1608 ◽  
Author(s):  
Nico Dunkel ◽  
Kajal Biswas ◽  
Ekkehard Hiller ◽  
Kurt Fellenberg ◽  
Somisetty V. Satheesh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Candida Albicans ◽  
Nitrogen Source ◽  
Expression Profiles ◽  
Filamentous Growth ◽  
Ammonium Uptake ◽  
Wild Type ◽  
Pathogenic Yeast ◽  
In The Wild ◽  
Protease Secretion

Micro-organisms sense the availability of nutrients in their environment to control cellular behaviour and the expression of transporters and enzymes that are required for the utilization of these nutrients. In the pathogenic yeast Candida albicans, the preferred nitrogen source ammonium suppresses the switch from yeast to filamentous growth in response to certain stimuli, and it also represses the secretion of proteases, which are required for the utilization of proteins as an alternative nitrogen source. To investigate whether C. albicans senses the availability of ammonium in the extracellular environment or if ammonium uptake into the cell is required to regulate morphogenesis and gene expression, we compared the behaviour of wild-type cells and ammonium uptake-deficient mutants in the presence and absence of extracellular ammonium. Arginine-induced filamentous growth was suppressed by ammonium in the wild-type, but not in mutants lacking the ammonium permeases Mep1 and Mep2. Similarly, ammonium suppressed protease secretion and extracellular protein degradation in the wild-type, but not in mutants lacking the ammonium transporters. By comparing the gene expression profiles of C. albicans grown in the presence of low or high ammonium concentrations, we identified a set of genes whose expression is controlled by nitrogen availability. The repression of genes involved in the utilization of alternative nitrogen sources, which occurred under ammonium-replete conditions in the wild-type, was abrogated in mep1Δ mep2Δ mutants. These results demonstrate that C. albicans does not respond to the presence of sufficient amounts of the preferred nitrogen source ammonium by sensing its availability in the environment. Instead, ammonium has to be taken up into the cell to control morphogenesis, protease secretion and gene expression.

scholarly journals BMP4 and PHLDA1 are plausible drug-targetable candidate genes for KRAS G12A-, G12D-, and G12V-driven colorectal cancer

2021 ◽  
Author(s):  
Shumpei Ohnami ◽  
Kouji Maruyama ◽  
Kai Chen ◽  
Yu Takahashi ◽  
Keiichi Hatakeyama ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Clinical Practice ◽  
Driver Mutations ◽  
Wild Type ◽  
Promising Candidate ◽  
Transfected Cells ◽  
Effector Molecules ◽  
Novel Treatments ◽  
In The Wild

AbstractDespite the frequent detection of KRAS driver mutations in patients with colorectal cancer (CRC), no effective treatments that target mutant KRAS proteins have been introduced into clinical practice. In this study, we identified potential effector molecules, based on differences in gene expression between CRC patients carrying wild-type KRAS (n = 390) and those carrying KRAS mutations in codon 12 (n = 240). CRC patients with wild-type KRAS harboring mutations in HRAS, NRAS, PIK3CA, PIK3CD, PIK3CG, RALGDS, BRAF, or ARAF were excluded from the analysis. At least 11 promising candidate molecules showed greater than two-fold change between the KRAS G12 mutant and wild-type and had a Benjamini-Hochberg-adjusted P value of less than 1E-08, evidence of significantly differential expression between these two groups. Among these 11 genes examined in cell lines transfected with KRAS G12 mutants, BMP4, PHLDA1, and GJB5 showed significantly higher expression level in KRAS G12A, G12D, and G12V transfected cells than in the wild-type transfected cells. We expect that this study will lead to the development of novel treatments that target signaling molecules functioning with KRAS G12-driven CRC.

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