scholarly journals NFAT and AP1 are Essential for the Expression of a Glioblastoma Multiforme Related IL-13Ra2 Transcript

2010 ◽  
Vol 32 (5-6) ◽  
pp. 313-329
Author(s):  
Anhua Wu ◽  
Katya Ericson ◽  
Wang Chao ◽  
Walter C. Low
Keyword(s):  
Binding Assay ◽  
Regulatory Mechanisms ◽  
Soluble Form ◽  
Diagnostic Biomarker ◽  
Complex Mechanism ◽  
Flow Cytometry Analysis ◽  
Rt Pcr ◽  
High Level ◽  
Insight Into

Background: IL-13Ra2 is overexpressed by gliomas but not by normal tissue. However, the molecular basis for IL-13Ra2 overexpression in gliomas is unknown.Methods: In the present study we have investigated the regulatory mechanisms that are responsible for the expression of IL-13Ra2 with mutation analysis, quantitative RT-PCR, Flow cytometry analysis, transcription factor binding assay and Elisa.Results: Our results reveal a complex mechanism for regulating IL-13Ra2 expression that involves at least 2 promoters and 4 transcripts of human IL-13Ra2. Transcription factors NFAT and AP1 are necessary and essential for the expression of this GBM related transcript, and are responsible for the high level of expression of IL-13Ra2 in GBM. Most interestingly, we found that expression of this transcript results in the production of a secreted form of IL-13Ra2 and thus may have the potential to be used as a diagnostic biomarker for GBM patients and other cancer patients that express the soluble form of this receptor.Conclusions: This study is the first to characterize the role of NFAT and AP1 in the regulation of IL-13Ra2 expression, and provides insight into understanding the high levels of IL-13Ra2 expressed by GBM cells.

scholarly journals Benefit of Having Multiple ampD Genes for Acquiring β-Lactam Resistance without Losing Fitness and Virulence in Pseudomonas aeruginosa

2008 ◽  
Vol 52 (10) ◽  
pp. 3694-3700 ◽  
Author(s):  
Bartolomé Moya ◽  
Carlos Juan ◽  
Sebastián Albertí ◽  
José L. Pérez ◽  
Antonio Oliver
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Mouse Model ◽  
Resistance Mechanism ◽  
Systemic Infection ◽  
Triple Mutant ◽  
Biological Cost ◽  
Sequential Inactivation ◽  
High Level ◽  
Insight Into

ABSTRACT The inactivation of ampD in Pseudomonas aeruginosa leads to a partially derepressed phenotype, characterized by a moderately high level basal ampC expression that is still further inducible, due to the presence of two additional ampD genes in this species (ampDh2 and ampDh3). The sequential inactivation of the three ampD genes was shown to lead to a stepwise upregulation of ampC expression, reaching full derepression in the triple mutant. To gain insight into the biological role of P. aeruginosa AmpD multiplicity, we determined the effects of the inactivation of the ampD genes on fitness and virulence. We show that, in contrast to what was previously documented for Salmonella spp., the inactivation of ampD in P. aeruginosa does not affect fitness or virulence in a mouse model of systemic infection. This lack of effect was demonstrated to be dependent on the presence of the additional ampD genes (ampDh2 and ampDh3), since the double and the triple ampD mutants completely lost their biological competitiveness and virulence; full ampC derepression and disruption of the AmpD peptidoglycan recycling system itself are both found to cause a major biological cost. Furthermore, among the ampD genes, ampDh3 is found to be the most relevant for virulence in P. aeruginosa. Therefore, as a consequence of the presence of additional ampD genes, partial ampC derepression mediated by ampD inactivation confers a biologically efficient resistance mechanism on P. aeruginosa.

scholarly journals Reduced Progesterone Metabolites in Human Late Pregnancy

2011 ◽  
pp. 225-241 ◽  
Author(s):  
M. HILL ◽  
A. PAŘÍZEK ◽  
R. KANCHEVA ◽  
J. E. JIRÁSEK
Keyword(s):  
Sex Hormones ◽  
Gestational Age ◽  
Pain Perception ◽  
Late Pregnancy ◽  
Hypoxic Stress ◽  
Complex Mechanism ◽  
Human Pregnancy ◽  
Progesterone Metabolites ◽  
Insight Into

In this review, we focused on the intersection between steroid metabolomics, obstetrics and steroid neurophysiology to give a comprehensive insight into the role of sex hormones and neuroactive steroids (NAS) in the mechanism controlling pregnancy sustaining. The data in the literature including our studies show that there is a complex mechanism providing synthesis of either pregnancy sustaining or parturition provoking steroids. This mechanism includes the boosting placental synthesis of CRH with approaching parturition inducing the excessive synthesis of 3β-hydroxy-5-ene steroid sulfates serving primarily as precursors for placental synthesis of progestogens, estrogens and NAS. The distribution and changing activities of placental oxidoreductases are responsible for the activation or inactivation of the aforementioned steroids, which is compartment-specific (maternal and fetal compartments) and dependent on gestational age, with a tendency to shift the production from the pregnancy-sustaining steroids to the parturition provoking ones with an increasing gestational age. The fetal and maternal livers catabolize part of the bioactive steroids and also convert some precursors to bioactive steroids. Besides the progesterone, a variety of its 5α/β-reduced metabolites may significantly influence the maintenance of human pregnancy, provide protection against excitotoxicity following acute hypoxic stress, and might also affect the pain perception in mother and fetus.

scholarly journals Translational inhibition and phase separation primes the epigenetic silencing of transposons

2020 ◽  
Author(s):  
Eun Yu Kim ◽  
Ling Wang ◽  
Zhen Lei ◽  
Hui Li ◽  
Wenwen Fan ◽  
...  
Keyword(s):  
Phase Separation ◽  
Epigenetic Silencing ◽  
Regulatory Mechanisms ◽  
Genome Integrity ◽  
Liquid Droplets ◽  
Ribosome Stalling ◽  
Insight Into ◽  
Liquid Liquid Phase Separation

AbstractTransposons are mobile DNAs that can cause fatal mutations. To counteract these genome invaders, the host genomes deploy small interfering (si) RNAs to initiate and establish the epigenetic silencing. However, the regulatory mechanisms for the selective recognition of transposons by the host genomes remain still elusive. Here we show that plant transposon RNAs undergo frequent ribosome stalling caused by their inherently unfavourable codon sequence usage. The ribosome stalling then causes the RNA truncation and the localization to siRNA bodies, which are both critical prerequisites for the siRNA processing. In addition, SGS3, the key protein in the siRNA biogenesis pathway, forms liquid droplets in vitro through its prion-like domains implicating the role of liquid-liquid phase separation in the formation of the siRNA bodies. Our study provides a novel insight into the regulatory mechanisms for the recognition of invasive genetic elements which is essential for the maintenance of genome integrity.

scholarly journals Fruit ripening: dynamics and integrated analysis of carotenoids and anthocyanins

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Leepica Kapoor ◽  
Andrew J. Simkin ◽  
C. George Priya Doss ◽  
Ramamoorthy Siva
Keyword(s):  
Fruit Ripening ◽  
Nutritive Value ◽  
Color Change ◽  
Regulatory Mechanisms ◽  
Carbon Gain ◽  
Integrated Analysis ◽  
Great Utility ◽  
Genetic And Environmental Factors ◽  
Insight Into

Abstract Background Fruits are vital food resources as they are loaded with bioactive compounds varying with different stages of ripening. As the fruit ripens, a dynamic color change is observed from green to yellow to red due to the biosynthesis of pigments like chlorophyll, carotenoids, and anthocyanins. Apart from making the fruit attractive and being a visual indicator of the ripening status, pigments add value to a ripened fruit by making them a source of nutraceuticals and industrial products. As the fruit matures, it undergoes biochemical changes which alter the pigment composition of fruits. Results The synthesis, degradation and retention pathways of fruit pigments are mediated by hormonal, genetic, and environmental factors. Manipulation of the underlying regulatory mechanisms during fruit ripening suggests ways to enhance the desired pigments in fruits by biotechnological interventions. Here we report, in-depth insight into the dynamics of a pigment change in ripening and the regulatory mechanisms in action. Conclusions This review emphasizes the role of pigments as an asset to a ripened fruit as they augment the nutritive value, antioxidant levels and the net carbon gain of fruits; pigments are a source for fruit biofortification have tremendous industrial value along with being a tool to predict the harvest. This report will be of great utility to the harvesters, traders, consumers, and natural product divisions to extract the leading nutraceutical and industrial potential of preferred pigments biosynthesized at different fruit ripening stages.

GATA2 May Contribute with EVI1 to the Leukemogenic Mechanism in Patients with 3q21q26 Rearrangements.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2852-2852
Author(s):  
Iria Vazquez ◽  
Idoya Lahortiga ◽  
Nerea Marcotegui ◽  
Maria Jose Larrayoz ◽  
Carmen Vicente ◽  
...  
Keyword(s):  
Real Time ◽  
Expression Profile ◽  
Poor Prognosis ◽  
Taqman Assay ◽  
Fish Analysis ◽  
Complex Mechanism ◽  
Rt Pcr ◽  
Normal Bone ◽  
Normal Human

Abstract Patients with 3q21q26 rearrangements seem to share similar clinicopathologic features and a common molecular mechanism, leading to MDS or AML. The overexpression of EVI1 (3q26) has been implicated in the dysplasia that characterizes this subset of myeloid neoplasias with poor prognosis. However, EVI1 overexpression had been detected in 9% of AML cases without 3q26 abnormalities; and several 3q21q26 cases with no EVI1 overexpression had been reported. Our aim was to characterize different subgroups in 3q rearrangements, and to define the gene expression profile of these groups, specially in the group with 3q21q26 rearrangements. We analyzed 44 samples (6 cell lines and 38 samples of patients) with 3q rearrangements at G-band level, 36 had AML and 8 MDS. As a control, we analyzed 6 samples of patients with 3q rearrangements and lymphoid neoplasias, a cDNA panel of normal human tissues (Clontech), and 10 normal bone marrow samples. FISH analysis was performed using six BACs: PR11-390G14, RP11-475N22 (GATA2), RP11-689D3 (RPN1) on 3q21; RP11-82C9 (EVI1), RP11-115B16 (MDS1) and RP11-196F13 (TRAIL) on 3q26; and a centromere probe. Expression of GATA2, MDS1-EVI1, and EVI1 was measured by a quantitative real-time RT-PCR (Taqman) assay (Applied Biosystems). Samples were first classified attending at the G-banding. FISH analysis showed the heterogeneity of breakpoints in these cases, and the samples were grouped as 3q21 (5 cases), 3q26 (11 cases), 3q21q26 (16 cases) and other 3q rearrangements (12 cases). Real time RT-PCR showed overexpression (OE) of EVI1 and/or GATA2 in 75% of all the cases (33/44), suggesting the important role of these genes in patients with 3q rearrangements and myeloid neoplasias. In patients with lymphoid neoplasias and 3q rearrangements no genes were found to be OE. A different expression profile was found in the groups analyzed (Table 1). In the 3q21 group, 40% of the patients had GATA2 OE, but no EVI1 or MDS1-EVI1 OE was found. Our data show that EVI1 OE could be specific of the groups 3q26 (64%) and 3q21q26 (69%). The number of cases with EVI1 OE was significantly higher in patients with 3q rearrangements than in those with complex karyotype (data not show). In the group with 3q21q26, EVI1 and/or GATA2 were overexpressed in 87.5% of the cases (14/16). In conclusion, we have detected a different expression profile of the genes analyzed among samples with different 3q rearrangements. Our results suggest a more complex mechanism in patients with 3q21q26 rearrangements, in which GATA2 overexpression may contribute with EVI1 to the leukemogenic progress. Further molecular studies are in progress to analyze the different EVI1 transcripts. Table 1: Incidence of the overexpression of EVI1, GATA2 and MDS1-EVI1 in 32 patients with 3q21 and/or 3q26 rearrangements. Frequency & Percentage EVI1 GATA2 MDS1-EVI1 3q21 0% (0/5) 40% (2/5) 0% (0/5) 3q26 64% (7/11) 73% (8/11) 36% (4/11) 3q21q26 75% (12/16) 69% (11/16) 13% (2/16)

scholarly journals Direct, gabapentin-insensitive interaction of a soluble form of the calcium channel subunit α2δ-1 with thrombospondin-4

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ehab El-Awaad ◽  
Galyna Pryymachuk ◽  
Cora Fried ◽  
Jan Matthes ◽  
Jörg Isensee ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Potential Role ◽  
Binding Assay ◽  
Molecular Level ◽  
Biochemical Properties ◽  
Matrix Proteins ◽  
Soluble Form ◽  
Voltage Gated Calcium Channels ◽  
Thrombospondin 4

Abstract The α2δ‐1 subunit of voltage-gated calcium channels binds to gabapentin and pregabalin, mediating the analgesic action of these drugs against neuropathic pain. Extracellular matrix proteins from the thrombospondin (TSP) family have been identified as ligands of α2δ‐1 in the CNS. This interaction was found to be crucial for excitatory synaptogenesis and neuronal sensitisation which in turn can be inhibited by gabapentin, suggesting a potential role in the pathogenesis of neuropathic pain. Here, we provide information on the biochemical properties of the direct TSP/α2δ-1 interaction using an ELISA-style ligand binding assay. Our data reveal that full-length pentameric TSP-4, but neither TSP-5/COMP of the pentamer-forming subgroup B nor TSP-2 of the trimer-forming subgroup A directly interact with a soluble variant of α2δ-1 (α2δ-1S). Interestingly, this interaction is not inhibited by gabapentin on a molecular level and is not detectable on the surface of HEK293-EBNA cells over-expressing α2δ‐1 protein. These results provide biochemical evidence that supports a specific role of TSP-4 among the TSPs in mediating the binding to neuronal α2δ‐1 and suggest that gabapentin does not directly target TSP/α2δ-1 interaction to alleviate neuropathic pain.

scholarly journals Mvda is required for zebrafish early development

2021 ◽  
Vol 54 (1) ◽  
Author(s):  
Wenghong Wong ◽  
Yike Huang ◽  
Zhuanbin Wu ◽  
Yu Kong ◽  
Jing Luan ◽  
...  
Keyword(s):  
Early Development ◽  
Biological Function ◽  
Gene Mutations ◽  
Loss Of Function ◽  
Rt Pcr ◽  
Acridine Orange Staining ◽  
Transmission Electron ◽  
Insight Into

Abstract Background The MVD gene mutations are identified in porokeratosis, which is considered a skin-specific autoinflammatory keratinization disease. However, the biological function of MVD gene remains largely unknown. Therefore, we analyzed the function of mvda gene, orthologous to the human MVD gene, in developing zebrafish. Methods Morpholino antisense oligonucleotide technique was used to generate mvda loss-of-function phenotypes. Knockdown of mvda was confirmed by RT-PCR and Sanger sequencing. Scanning and transmission electron microscopy were performed to analyze the morphology of the epidermis. Angiogenesis study was presented using the Tg(fli1a:EGFP)y1 transgenic strain. In addition, acridine orange staining was used to examine the apoptotic cells in vivo. Results As expected, the mvda morphants showed abnormal morphology of the epidermis. Moreover, we observed ectopic sprouts in trunk angiogenesis and impaired formation of the caudal vein plexus in the mvda-deficient zebrafish. Besides, increased apoptosis was found throughout the tail, heart, and eyes in mvda zebrafish morphants. Conclusions These findings indicated the essential role of mvda in the early development of zebrafish. This was the first in vivo knockdown study of the zebrafish mvda gene, which might offer insight into the biological function of the human MVD gene.

scholarly journals The role of transcriptional regulation in maintaining the availability of mycobacterial adenylate cyclases

2013 ◽  
Author(s):  
Sarah J Casey ◽  
Mica J Ford ◽  
Michaela Gazdik
Keyword(s):  
Transcriptional Regulation ◽  
Mycobacterium Smegmatis ◽  
Mrna Level ◽  
Mycobacterium Species ◽  
Rt Pcr ◽  
Promoter Fusion ◽  
Low Levels ◽  
High Level ◽  
Starvation Conditions

Mycobacterium species have a complex cAMP regulatory network indicated by the high number of adenylate cyclases annotated in their genomes. However the need for a high level of redundancy in adenylate cyclase genes remains unknown. We have used semiquantitiative RT-PCR to examine the expression of the eight Mycobacterium smegmatis cyclases with orthologs in the human pathogen Mycobacterium tuberculosis, where cAMP has recently been shown to be important for virulence. All eight cyclases were transcribed in the cell in all environments tested, and only four demonstrated environmental-mediated changes in transcription. M. smegmatis genes MSMEG_0545 and MSMEG_4279 were upregulated during starvation conditions while MSMEG_0545 and MSMEG_4924 were downregulated in H2O2 and MSMEG_3780 was downregulated in low pH. Promoter fusion constructs containing M. tuberculosis H37Rv promoters showed consistent regulation compared to their M. smegmatis orthologs. Overall our findings indicate that while low levels of transcriptional regulation occur, regulation at the mRNA level does not play a major role in controlling cellular cyclase availability in a given environment.

scholarly journals Strategija repozicioniranja: posljedica neuspjeha ili nastavak priče o uspjehu

2017 ◽  
Vol 7 (1) ◽  
pp. 28
Author(s):  
Ivona Mikulandra Volić ◽  
Ina Relja ◽  
Mate Brković
Keyword(s):  
Strategic Change ◽  
Core Business ◽  
The Core ◽  
Successful Business ◽  
High Level ◽  
The Impact ◽  
A Company ◽  
Insight Into

The issue of disinvesting and the exiting of a company from a business regardless of their performance is of a critical importance for its further activities. The attention of researchers is more focused on the buyer’s side of the story than the seller since the acquisition implies a growth that is equated with success, and sales are usually perceived as a failure without noticing the potential positive consequences for the seller. Exiting the core business by implementing a repositioning strategy can bring a significant strategic change for the enterprise, as well as being a continuation for the enterprise as well as for the entrepreneur of the previous successful business. By presenting a case study this paper analyses the possible causes and questions the justification for the implementation of the repositioning strategy in three selected Croatian companies (Adris Group d.d., Lura Group d.o.o. and Jolly Jbs d.o.o.) that through the process of mergers and acquisitions appear in the role of sellers, and by doing that they exited their core business that helped them gain a high level of customer recognition and business reputation among competitors and associates. The analysis provides insight into a seldom-analyzed application of the repositioning strategy of Croatian companies and it contributes to a better understanding of disinvestment and the impact of the repositioning strategy on the company's performance.

scholarly journals APPLICATION OF SYSTEM ARCHETYPES IN PRACTICE: AN UNDERUTILISED PATHWAY TO BETTER MANAGERIAL PERFORMANCE

2016 ◽  
Vol 17 (6) ◽  
pp. 1081-1096 ◽  
Author(s):  
Vladimír BUREŠ ◽  
Fridrich RACZ
Keyword(s):  
Qualitative Research ◽  
Final Section ◽  
Business Environment ◽  
Organisational Performance ◽  
Managerial Performance ◽  
Current State ◽  
High Level ◽  
System Archetypes ◽  
Insight Into

Current dynamic business environment forces managers to apply various tools in order to improve organisational performance and effectiveness. System archetypes enable to cope with complexity and make appropriate decisions. This study is theoretically grounded in the field of economic cybernetics and system archetype analysis. It applies qualitative research on the sample of 54 managers with the high level of seniority. The aim is to reveal whether system archetypes are effectively used in practice. Two hypotheses focused on both knowledge about and application of system archetypes are tested. The results prove that there are inconsistencies tied to forms of system archetypes insight and knowledge. Moreover, there is an inadequate level of attention identified in investigated organisations. Results imply various potential research pathways that are outlined in the final section of the paper. Hence, the manuscript offers a unique insight into the current state of practical system archetypes utilisation and contributes to the explanation of the role of system archetypes in the economic cybernetics framework.

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