An incoherent feedforward loop formed by SirA/BarA, HilE and HilD is involved in controlling the growth cost of virulence factor expression by Salmonella Typhimurium

An intricate regulatory network controls the expression of Salmonella virulence genes. The transcriptional regulator HilD plays a central role in this network by controlling the expression of tens of genes mainly required for intestinal colonization. Accordingly, the expression of HilD is highly regulated by multiple factors, such as the SirA/BarA two-component system and the Hcp-like protein HilE. SirA/BarA positively regulates translation of hilD mRNA through a regulatory cascade involving the small RNAs CsrB and CsrC, and the RNA-binding protein CsrA, whereas HilE inhibits HilD activity by protein-protein interaction. In this study, we show that SirA/BarA also positively regulates translation of hilE mRNA through the same mentioned regulatory cascade. Thus, our results reveal a paradoxical regulation exerted by SirA/BarA-Csr on HilD, which involves simultaneous opposite effects, direct positive control and indirect negative control through HilE. This kind of regulation is called an incoherent type-1 feedforward loop (I1-FFL), which is a motif present in certain regulatory networks and represents a complex biological problem to decipher. Interestingly, our results, together with those from a previous study, indicate that HilE, the repressor component of the I1-FFL reported here (I1-FFLSirA/BarA-HilE-HilD), is required to reduce the growth cost imposed by the expression of the genes regulated by HilD. Moreover, we and others found that HilE is necessary for successful intestinal colonization by Salmonella. Thus, these findings support that I1-FFLSirA/BarA-HilE-HilD cooperates to control the precise amount and activity of HilD, for an appropriate balance between the growth cost and the virulence benefit generated by the expression of the genes induced by this regulator. I1-FFLSirA/BarA-HilE-HilD represents a complex regulatory I1-FFL that involves multiple regulators acting at distinct levels of gene expression, as well as showing different connections to the rest of the regulatory network governing Salmonella virulence.

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Multi-omic regulatory networks capture downstream effects of kinase inhibition in Mycobacterium tuberculosis

npj Systems Biology and Applications ◽

10.1038/s41540-020-00164-4 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Albert T. Young ◽

Xavier Carette ◽

Michaela Helmel ◽

Hanno Steen ◽

Robert N. Husson ◽

...

Keyword(s):

Transcription Factor ◽

Mycobacterium Tuberculosis ◽

Regulatory Network ◽

Regulatory Networks ◽

Protein Interaction Data ◽

Kinase Inhibition ◽

Protein Protein Interaction ◽

Downstream Effects ◽

Regulate Cell Growth ◽

Regulatory Effects

AbstractThe ability of Mycobacterium tuberculosis (Mtb) to adapt to diverse stresses in its host environment is crucial for pathogenesis. Two essential Mtb serine/threonine protein kinases, PknA and PknB, regulate cell growth in response to environmental stimuli, but little is known about their downstream effects. By combining RNA-Seq data, following treatment with either an inhibitor of both PknA and PknB or an inactive control, with publicly available ChIP-Seq and protein–protein interaction data for transcription factors, we show that the Mtb transcription factor (TF) regulatory network propagates the effects of kinase inhibition and leads to widespread changes in regulatory programs involved in cell wall integrity, stress response, and energy production, among others. We also observe that changes in TF regulatory activity correlate with kinase-specific phosphorylation of those TFs. In addition to characterizing the downstream regulatory effects of PknA/PknB inhibition, this demonstrates the need for regulatory network approaches that can incorporate signal-driven transcription factor modifications.

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HOTAIRM1 regulates neuronal differentiation by modulating NEUROGENIN 2 and the downstream neurogenic cascade

Cell Death and Disease ◽

10.1038/s41419-020-02738-w ◽

2020 ◽

Vol 11 (7) ◽

Cited By ~ 1

Author(s):

Jessica Rea ◽

Valentina Menci ◽

Paolo Tollis ◽

Tiziana Santini ◽

Alexandros Armaos ◽

...

Keyword(s):

Neuronal Differentiation ◽

Cell Fate ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Regulatory Networks ◽

Rna Binding ◽

Rna Binding Proteins ◽

Regulatory Cascade ◽

Expression Control ◽

Gene Expression Control

Abstract Neuronal differentiation is a timely and spatially regulated process, relying on precisely orchestrated gene expression control. The sequential activation/repression of genes driving cell fate specification is achieved by complex regulatory networks, where transcription factors and noncoding RNAs work in a coordinated manner. Herein, we identify the long noncoding RNA HOTAIRM1 (HOXA Transcript Antisense RNA, Myeloid-Specific 1) as a new player in neuronal differentiation. We demonstrate that the neuronal-enriched HOTAIRM1 isoform epigenetically controls the expression of the proneural transcription factor NEUROGENIN 2 that is key to neuronal fate commitment and critical for brain development. We also show that HOTAIRM1 activity impacts on NEUROGENIN 2 downstream regulatory cascade, thus contributing to the achievement of proper neuronal differentiation timing. Finally, we identify the RNA-binding proteins HNRNPK and FUS as regulators of HOTAIRM1 biogenesis and metabolism. Our findings uncover a new regulatory layer underlying NEUROGENIN 2 transitory expression in neuronal differentiation and reveal a previously unidentified function for the neuronal-induced long noncoding RNA HOTAIRM1.

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Positive Control of Swarming, Rhamnolipid Synthesis, and Lipase Production by the Posttranscriptional RsmA/RsmZ System in Pseudomonas aeruginosa PAO1

Journal of Bacteriology ◽

10.1128/jb.186.10.2936-2945.2004 ◽

2004 ◽

Vol 186 (10) ◽

pp. 2936-2945 ◽

Cited By ~ 184

Author(s):

Karin Heurlier ◽

Faye Williams ◽

Stephan Heeb ◽

Corinne Dormond ◽

Gabriella Pessi ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Target Genes ◽

Rna Binding ◽

Regulatory Protein ◽

Lipase Production ◽

Positive Control ◽

Negative Control ◽

Control Element ◽

Signal Molecules ◽

Positive Effects

ABSTRACT In Pseudomonas aeruginosa, the small RNA-binding, regulatory protein RsmA is a negative control element in the formation of several extracellular products (e.g., pyocyanin, hydrogen cyanide, PA-IL lectin) as well as in the production of N-acylhomoserine lactone quorum-sensing signal molecules. RsmA was found to control positively the ability to swarm and to produce extracellular rhamnolipids and lipase, i.e., functions contributing to niche colonization by P. aeruginosa. An rsmA null mutant was entirely devoid of swarming but produced detectable amounts of rhamnolipids, suggesting that factors in addition to rhamnolipids influence the swarming ability of P. aeruginosa. A small regulatory RNA, rsmZ, which antagonized the effects of RsmA, was identified in P. aeruginosa. Expression of the rsmZ gene was dependent on both the global regulator GacA and RsmA, increased with cell density, and was subject to negative autoregulation. Overexpression of rsmZ and a null mutation in rsmA resulted in quantitatively similar, negative or positive effects on target genes, in agreement with a model that postulates titration of RsmA protein by RsmZ RNA.

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Identifying miRNA-TF-mRNA Regulatory Network for Aortic Valve Calcification Diseases Through Bioinformatics Analysis

10.21203/rs.3.rs-877964/v1 ◽

2021 ◽

Author(s):

Mingdong Zhang ◽

Zhexin Lu ◽

Yongliang Fan ◽

Hongbing Gu ◽

Sheng Shi ◽

...

Keyword(s):

Transcription Factors ◽

Aortic Valve ◽

Regulatory Network ◽

Aortic Valve Disease ◽

Regulatory Networks ◽

R Package ◽

Gene Expression Omnibus ◽

Valve Disease ◽

Protein Protein Interaction ◽

New Treatment

Abstract Background:Calcareous aortic valve disease(CAVD) is widespread in society, and its incidence seems to increase with the age of the global population. However, the specific pathogenesis of calcareous aortic valve disease remains unclear. The purpose of the research is to construct miRNA-TF-mRNA regulatory networks and find the key genes, microRNAs (miRNAs) and transcription factors (TFs) to clarify the pathogenesis of CAVD and provide new treatment methods for CAVD.Methods:GSE51472, GSE87885 and GSE12644 datasets were downloaded from Gene Expression Omnibus (GEO) database. Differentailly expressed genes (DEGs) and differentially expressed miRNAs(DEMs) were identified through integrative analysis by R software. Moreover, KEGG pathway analysis and Gene Ontology (GO) analysis were performed using the clusterProfiler R package. Then, STRING database, Cytoscape and Cytohubba were applied to construct the protein-protein interaction (PPI) network and screen hub genes. Finally, a miRNA-TF-mRNA network was constructed based on bioinformatics data based on the TRRUST, miRWalk and miRtarbase database. And through the verification of dataset GSE12644, we have determined the key regulatory factors.Results:We have established a regulatory network of miRNA-TF-mRNA includes 17 genes,17 miRNAs and 12 TFs. In the miRNA-TF-mRNA network, genes VCAM1, ITGB2, CD86, transcription factors HIF1A, KLF2 are identified as key regulators.Conclusions: Our study has constructed a regulatory network of miRNA-TF-mRNA in CAVD, which may provide new insights about the interaction between genes, miRNAs and TFs in the pathogenesis of CAVD, and identify potential biomarkers or therapeutic targets for CAVD, which may reveal promising approaches for CAVD diagnosis and therapy.

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Multi-omic regulatory networks capture downstream effects of kinase inhibition in Mycobacterium tuberculosis

10.1101/584177 ◽

2019 ◽

Cited By ~ 1

Author(s):

Albert T. Young ◽

Xavier Carette ◽

Michaela Helmel ◽

Hanno Steen ◽

Robert N Husson ◽

...

Keyword(s):

Transcription Factor ◽

Mycobacterium Tuberculosis ◽

Regulatory Network ◽

Regulatory Networks ◽

Protein Interaction Data ◽

Kinase Inhibition ◽

Protein Protein Interaction ◽

Regulate Cell Growth ◽

Regulatory Effects ◽

Network Approaches

The ability of Mycobacterium tuberculosis (Mtb) to adapt to diverse stresses in its host environment is crucial for pathogenesis. Two essential Mtb serine/threonine protein kinases, PknA and PknB, regulate cell growth in response to environmental stimuli, but little is known about their downstream ef-fects. By combining RNA-Seq data, following treatment with either a PknA/PknB inhibitor or an inactive control, with publicly available ChIP-Seq and protein-protein interaction data, we show that the Mtb transcription factor (TF) regulatory network propagates the effects of kinase inhibition and leads to widespread changes in regulatory programs involved in cell wall integrity, stress response, and energy production, among others. We also observe that changes in TF regulatory activity correlate with kinase-specific phosphorylation of those TFs. In addition to characterizing the downstream regulatory effects of PknA/PknB inhibition, this demonstrates the need for regulatory network approaches that can incorporate signal-driven transcription factor modifications.

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New insights into the regulatory networks of paralogous genes in bacteria

Microbiology ◽

10.1099/mic.0.033266-0 ◽

2010 ◽

Vol 156 (1) ◽

pp. 14-22 ◽

Cited By ~ 26

Author(s):

Mario A. Martínez-Núñez ◽

Ernesto Pérez-Rueda ◽

Rosa María Gutiérrez-Ríos ◽

Enrique Merino

Keyword(s):

Gene Duplication ◽

Regulatory Network ◽

Regulatory Networks ◽

Rna Binding ◽

Rna Binding Proteins ◽

Selection Process ◽

Dna Supercoiling ◽

Model Organisms ◽

Paralogous Genes ◽

Pubmed Database

Extensive genomic studies on gene duplication in model organisms such as Escherichia coli and Saccharomyces cerevisiae have recently been undertaken. In these models, it is commonly considered that a duplication event may include a transcription factor (TF), a target gene, or both. Following a gene duplication episode, varying scenarios have been postulated to describe the evolution of the regulatory network. However, in most of these, the TFs have emerged as the most important and in some cases the only factor shaping the regulatory network as the organism responds to a natural selection process, in order to fulfil its metabolic needs. Recent findings concerning the regulatory role played by elements other than TFs have indicated the need to reassess these early models. Thus, we performed an exhaustive review of paralogous gene regulation in E. coli and Bacillus subtilis based on published information, available in the NCBI PubMed database and in well-established regulatory databases. Our survey reinforces the notion that despite TFs being the most prominent components shaping the regulatory networks, other elements are also important. These include small RNAs, riboswitches, RNA-binding proteins, sigma factors, protein–protein interactions and DNA supercoiling, which modulate the expression of genes involved in particular metabolic processes or induce a more complex response in terms of the regulatory networks of paralogous genes in an integrated interplay with TFs.

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Aktivitas Antifungi Air Perasan Bawang Merah (Allium ascalonicum L.) Terhadap Candida albicans Secara In Vitro

Jurnal Ilmu Kedokteran ◽

10.26891/jik.v9i2.2015.71-77 ◽

2017 ◽

Vol 9 (2) ◽

pp. 71

Author(s):

Nurhasanah Nurhasanah ◽

Fauzia Andrini ◽

Yulis Hamidy

Keyword(s):

Candida Albicans ◽

Antifungal Activity ◽

Allium Sativum ◽

Fungicidal Activity ◽

Positive Control ◽

Negative Control ◽

Randomized Design ◽

Significant Difference ◽

Completely Randomized Design

Shallot (Allium ascalonicum L.) has been known as traditional medicine. Shallot which has same genus with garlic(Allium sativum L.) contains allicin that is also found in garlic and has been suspected has fungicidal activity toCandida albicans. It is supported by several researches. Therefore, shallot is suspected has antifungal activity too.The aim of this research was to know antifungal activity of shallot’s water extortion againsts Candida albicans invitro. This was a laboratory experimental research which used completely randomized design, with diffusion method.Shallot’s water extortion was devided into three concentrations, there were 50%, 100% and 200%. Ketoconazole 2%was positive control and aquadest was negative control. The result of this research based on analysis of varians(Anova), there was significant difference between several treatments and was confirmed with Duncan New MultipleRange Test (DNMRT) p<0,05, there was significant difference between 100% shallot’s water extortion with othertreatments, but there was no significant difference between 50% shallot’s water extortion with 200% shallot’s. Theconclusion was shallot’s water extortion had antifungal activity againsts Candida albicans with the best concentration100%, but it was lower than ketoconazole 2%.

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The Comparison of Ostecyte in the Pressure area and Tension area on Tooth Movement Because of Hyperbaric Oxygen Therapy

DENTA ◽

10.30649/denta.v12i1.162 ◽

2018 ◽

Vol 12 (1) ◽

pp. 34

Author(s):

Arya Barahmanta ◽

Muhammad Faizal Winaris ◽

Pambudi Raharjo

Keyword(s):

Hyperbaric Oxygen ◽

Oxygen Therapy ◽

Tooth Movement ◽

Bone Remodelling ◽

Orthodontic Tooth Movement ◽

Negative Control Group ◽

Positive Control ◽

Negative Control ◽

Control Group ◽

Pressure Area

Background: Orthodontic tooth movement is a interaction prosess of resorption and deposition of bone remodeling. Orthodontic tooth movement by mechanical strength causes changes in alveolar bone. Osteocyte is an essential cell to respond bone remodelling. Hyperbaric Oxygen Therapy affects production of osteocyte because it can release Reactive Oxygen Species (ROS) and Nitrid Oxide (NO). Purpose: To determine the difference number of osteocyte in pressure and tension area during tooth movement by adjuvant of Hyperbaric Oxygen 2,4 ATA during 7 days starting on day 8 to day 14. Materials and Methods: This research used Completery Randomized Control Group Post Test Only Design. 36 cavia cobaya (male) were divided into 3 groups randomly : the negative control groups, positive control group, and treatment group. Preparat staining used Hematoxylin Eosin (HE) and calculated on microscop 1000x with 20 field of view. Data analyses used one way ANOVA and LSD test then compared each area by using paired T test. Result: The data showed that the treatment group (P=10,67) tension area has the highest number of osteocyte than negative control group (K-=3,67), positive control (K+=7,42). In the pressure area showed that negative control group (K-=5,00) has the highest than positive control group (K+=3,83) and treatment (P=3,25). Conclusion: Therapy HBO 2,4 ATA 7 days starting on day 8 to day 14 is could increase osteocyte in the tissue to stimulate process of bone remodelling.<pre> </pre>Keywords: Hyperbaric Oxygen, Tooth movement, Bone remodeling, Osteocyte Correspondence: Arya Brahmanta, Department of Orthodonty, Faculty of Dentistry, Hang Tuah University, Arif Rahman Hakim 150, Surabaya, Phone 031-5945864, Email: <a href="mailto:[email protected]">arya.brahmanta@hangtuah.ac.id</a>

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UJI AKTIVITAS HEPATOPROTEKTOR KOMBINASI EKSTRAK ETANOL DAUN PANDAN WANGI (Pandanus amaryllifolius roxb) DAN KAYU MANIS (Cinnamomum burmanii) TERHADAP KADAR MDA YANG DIINDUKSI PARASETAMOL

Jurnal Kesehatan Kusuma Husada ◽

10.34035/jk.v12i1.580 ◽

2020 ◽

pp. 68-73

Author(s):

Yuni Asri Mulatsih Agami ◽

Eka Wisnu Kusuma

Keyword(s):

Oxidative Stress ◽

Ethanol Extract ◽

Optimal Dose ◽

Experimental Methods ◽

Positive Control ◽

Negative Control ◽

Male Rats ◽

Negative Group ◽

Ic50 Value ◽

Dose Combination

Kasus penyakit hati semakin meningkat seiring penggunaan senyawa hepatotoksin salah satunya karena penggunaan parasetamol dengan dosis berlebih. Hal tersebut dapat meningkatkan produksi radikal bebas sehingga memicu terjadinya stress oksidatif yang dapat menimbulkan kerusakan jaringan yang ditandai dengan peningkatan kadar Malondialdehyde (MDA). Stress oksidatif dapat diatasi dengan antioksidan dari berbagai tanaman. Kulit kayu manis memiliki aktivitas antioksidan dengan nilai IC50 53ppm dan daun pandan wangi 39,7% Penelitian ini bertujuan untuk mengetahui aktivitas kombinasi ekstrak etanol daun pandan wangi dan kayu manis dalam menurunkan kadar MDA. tikus yang diinduksi parasetamol. Penelitian menggunakan metode eksperimental, dilakukan selama 9 hari dengan 30 ekor tikus jantan dibagi menjadi 6 Kelompok, yaitu: Normal diberi aquadest, Kontrol Positif diberi silimarin 100 mg/kgBB, Kontrol Negatif diberi CMC-Na 0,05%, serta 3 kelompok lainnya diberi kombinasi ekstrak daun pandan wangi:kayu manis berturut-turut dosis I (25:75), dosis II (50:50), dosis III (75:25). Semua kelompok diinduksi parasetamol 2,5 g/kgBB pada hari ke-7 setelah 30 menit perlakuan, kecuali kelompok normal. Pada hari ke 9 dilakukan pengukuran kadar MDA dengan metode TBARs menggunakan spektrofotometri. Pemberian kombinasi ekstrak etanol daun pandan wangi dan kayu manis dapat menurunkan kadar MDA dengan kombinasi dosis yang paling optimal adalah 75:25 berdasarkan statistik dengan nilai signifikan 0,000<0,05 dibandingkan dengan kelompok negatif. Cases of liver disease have increased with the use of hepatotoxin compounds, one of which is due to the use of paracetamol with excessive doses. This can increase the production of free radicals so that it triggers oxidative stress which can cause tissue damage which is characterized by increased levels of Malondialdehyde (MDA). Oxidative stress can be overcome with antioxidants from various plants. Cinnamomum burmanii has antioxidant activity with IC50 value of 53ppm and Pandanus amarrylifolius 39.7%. This study aims to determine the combined activity of ethanol extract of Pandanus amarrylifolius and Cinnamomum burmanii in reducing MDA levels. Paracetamol-induced rats. Research using experimental methods, conducted for 9 days with 30 male rats divided into 6 groups, namely: Normal given aquadest, Positive Control were given silimarin 100 mg / kgBB, Negative Control was given CMC-Na 0.05%, and 3 other groups were given a combination of Pandanus amarrylifolius extract: Cinnamomum burmanii dose I (25:75), dose II (50:50), dose III (75:25). All groups induced paracetamol 2.5 g / kgBB on the 7th day after 30 minutes of treatment, except the normal group. On the 9th day MDA levels were measured using the TBARs method using spectrophotometry. Giving a combination of Pandanus amarrylifolius and Cinnamomum burmanii ethanol extract can reduce MDA levels with the most optimal dose combination is 75:25 based on statistics with a significant value of 0,000<0.05 compared with the negative group.

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UJI IMUNOMODULATOR DARI EKSTRAK ETANOL DAUN WARU (HIBISCUS TILIACEUS) DENGAN METODE HIPERSENSITIVITAS TIPE LAMBAT

Jurnal Penelitian Farmasi & Herbal ◽

10.36656/jpfh.v1i2.103 ◽

2019 ◽

Vol 1 (2) ◽

pp. 11-16

Author(s):

Yanna Rotua Sihombing ◽

Debi Dinha Sitepu

Keyword(s):

Treatment Group ◽

Leaf Extract ◽

Positive Control ◽

Negative Control ◽

Delayed Type Hypersensitivity ◽

Hypersensitivity Response ◽

Delayed Type Hypersensitivity Response

Immunomodulator is a compound that can increaase the imuno system. One of the plants that have immunomodulator’s activity is Waru Leaf (Hibiscus tiliaceus). the purpose of this research was to test the effect of immunomodulator by extract of Waru Leaf ethanol on rat male. The activity of immunomodulator was determined by using digital pletysmometer by measuring the differences between the last leg swelling’s volume and the first leg swelling’s volume. The treatment group were divided into 5 groups. Each group consistof 5 rats CMC-Na 0,5% (negative control), Stimuno® 32,5 mg/kgBW (positive control), dose of EEDW 50, 100 and 200 mg/kgBW, and bacteria E.coli as antigen. The results slowed that distribution of EEDW dose 200 mg/kgBW can give the effect of immunostimulant by swelling enthancement compared by CMC-Na 0,5 %. EEDW 200 mg/kgBW that have activity comparable with Stimuno® 32,5 mg/kgBW. Thus, it is concluded that of Waru Leaf extract has immunomodulator effects on delayed-type hypersensitivity response of rat male.

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