TouR-Mediated Effector-Independent Growth Phase-Dependent Activation of the σ54 Ptou Promoter of Pseudomonas stutzeri OX1

ABSTRACT Transcription of the catabolic touABCDEF operon, encoding the toluene-o-xylene monooxygenase of Pseudomonas stutzeri OX1, is driven by the σ54-dependent Ptou promoter, whose activity is controlled by the phenol-responsive NtrC-like activator TouR. In this paper we describe for the first time a peculiar characteristic of this system, namely, that Ptou transcription is activated in a growth phase-dependent manner in the absence of genuine effectors of the cognate TouR regulator. This phenomenon, which we named gratuitous activation, was observed in the native strain P. stutzeri OX1, as well as in a Pseudomonas putida PaW340 host harboring the reconstructed tou regulatory circuit. Regulator-promoter swapping experiments demonstrated that the presence of TouR is necessary and sufficient for imposing gratuitous activation on the Ptou promoter, as well as on other σ54-dependent catabolic promoters, whereas the highly similar phenol-responsive activator DmpR is unable to activate the Ptou promoter in the absence of effectors. We show that this phenomenon is specifically triggered by carbon source exhaustion but not by nitrogen starvation. An updated model of the tou regulatory circuit is presented.

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NK-DC crosstalk controls the autopathogenic Th17 response through an innate IFN-γ–IL-27 axis

Journal of Experimental Medicine ◽

10.1084/jem.20141678 ◽

2015 ◽

Vol 212 (10) ◽

pp. 1739-1752 ◽

Cited By ~ 37

Author(s):

Wai Po Chong ◽

Nicholas van Panhuys ◽

Jun Chen ◽

Phyllis B. Silver ◽

Yingyos Jittayasothorn ◽

...

Keyword(s):

Nk Cells ◽

Feedback Loop ◽

Dependent Manner ◽

Autoimmune Encephalomyelitis ◽

Th17 Response ◽

Regulatory Circuit ◽

Draining Lymph Node ◽

Ifn Γ ◽

Necessary And Sufficient ◽

Experimental Autoimmune

IFN-γ is a pathogenic cytokine involved in inflammation. Paradoxically, its deficiency exacerbates experimental autoimmune encephalomyelitis, uveitis, and arthritis. Here, we demonstrate using IFN-γ−/− mice repleted with IFN-γ+/+ NK cells that innate production of IFN-γ from NK cells is necessary and sufficient to trigger an endogenous regulatory circuit that limits autoimmunity. After immunization, DCs recruited IFN-γ-producing NK cells to the draining lymph node and interacted with them in a CXCR3-dependent fashion. The interaction caused DCs to produce IL-27, which in turn enhanced IFN-γ production by NK cells, forming a self-amplifying positive feedback loop. IL-10, produced by the interacting cells themselves, was able to limit this process. The NK-DC–dependent IL-27 inhibited development of the adaptive pathogenic IL-17 response and induced IL-10–producing Tr1-like cells, which ameliorated disease in an IL-10-dependent manner. Our data reveal that an early NK-DC interaction controls the adaptive Th17 response and limits tissue-specific autoimmunity through an innate IFN-γ–IL-27 axis.

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Interest rate option hedging portfolios without bank account

Studies in Economics and Finance ◽

10.1108/sef-02-2019-0058 ◽

2019 ◽

Vol 37 (1) ◽

pp. 134-142

Author(s):

Alberto Bueno-Guerrero

Keyword(s):

Design Methodology ◽

Contingent Claim ◽

Necessary And Sufficient Condition ◽

Barrier Option ◽

Bank Account ◽

Content Type ◽

Option Hedging ◽

Hedging Portfolio ◽

Necessary And Sufficient ◽

First Time

Purpose This paper aims to study the conditions for the hedging portfolio of any contingent claim on bonds to have no bank account part. Design/methodology/approach Hedging and Malliavin calculus techniques recently developed under a stochastic string framework are applied. Findings A necessary and sufficient condition for the hedging portfolio to have no bank account part is found. This condition is applied to a barrier option, and an example of a contingent claim whose hedging portfolio has a bank account part different from zero is provided. Originality/value To the best of the authors’ knowledge, this is the first time that this issue has been addressed in the literature.

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Secreted KIAA1199 promotes the progression of rheumatoid arthritis by mediating hyaluronic acid degradation in an ANXA1-dependent manner

Cell Death and Disease ◽

10.1038/s41419-021-03393-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Wei Zhang ◽

Guoyu Yin ◽

Heping Zhao ◽

Hanzhi Ling ◽

Zhen Xie ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Hyaluronic Acid ◽

Dependent Manner ◽

Collagen Induced Arthritis ◽

Intracellular Degradation ◽

Main Pathway ◽

First Time

AbstractIn inflamed joints, enhanced hyaluronic acid (HA) degradation is closely related to the pathogenesis of rheumatoid arthritis (RA). KIAA1199 has been identified as a hyaladherin that mediates the intracellular degradation of HA, but its extracellular function remains unclear. In this study, we found that the serum and synovial levels of secreted KIAA1199 (sKIAA1199) and low-molecular-weight HA (LMW-HA, MW < 100 kDa) in RA patients were significantly increased, and the positive correlation between them was shown for the first time. Of note, treatment with anti-KIAA1199 mAb effectively alleviated the severity of arthritis and reduced serum LMW-HA levels and cytokine secretion in collagen-induced arthritis (CIA) mice. In vitro, sKIAA1199 was shown to mediate exogenous HA degradation by attaching to the cell membrane of RA fibroblast-like synoviosytes (RA FLS). Furthermore, the HA-degrading activity of sKIAA1199 depended largely on its adhesion to the membrane, which was achieved by its G8 domain binding to ANXA1. In vivo, kiaa1199-KO mice exhibited greater resistance to collagen-induced arthritis. Interestingly, this resistance could be partially reversed by intra-articular injection of vectors encoding full-length KIAA1199 instead of G8-deleted KIAA119 mutant, which further confirmed the indispensable role of G8 domain in KIAA1199 involvement in RA pathological processes. Mechanically, the activation of NF-κB by interleukin-6 (IL-6) through PI3K/Akt signaling is suggested to be the main pathway to induce KIAA1199 expression in RA FLS. In conclusion, our study supported the contribution of sKIAA1199 to RA pathogenesis, providing a new therapeutic target for RA by blocking sKIAA1199-mediated HA degradation.

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Brassinolide Enhances the Level of Brassinosteroids, Protein, Pigments, and Monosaccharides in Wolffia arrhiza Treated with Brassinazole

Plants ◽

10.3390/plants10071311 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1311

Author(s):

Magdalena Chmur ◽

Andrzej Bajguz

Keyword(s):

Plant Growth ◽

Growth And Development ◽

Inhibitory Effect ◽

Dependent Manner ◽

Plant Growth And Development ◽

Concentration Dependent Manner ◽

Spectrophotometric Methods ◽

Synthetic Inhibitor ◽

Wolffia Arrhiza ◽

First Time

Brassinolide (BL) represents brassinosteroids (BRs)—a group of phytohormones that are essential for plant growth and development. Brassinazole (Brz) is as a synthetic inhibitor of BRs’ biosynthesis. In the present study, the responses of Wolffia arrhiza to the treatment with BL, Brz, and the combination of BL with Brz were analyzed. The analysis of BRs and Brz was performed using LC-MS/MS. The photosynthetic pigments (chlorophylls, carotenes, and xanthophylls) levels were determined using HPLC, but protein and monosaccharides level using spectrophotometric methods. The obtained results indicated that BL and Brz influence W. arrhiza cultures in a concentration-dependent manner. The most stimulatory effects on the growth, level of BRs (BL, 24-epibrassinolide, 28-homobrassinolide, 28-norbrassinolide, catasterone, castasterone, 24-epicastasterone, typhasterol, and 6-deoxytyphasterol), and the content of pigments, protein, and monosaccharides, were observed in plants treated with 0.1 µM BL. Whereas the application of 1 µM and 10 µM Brz caused a significant decrease in duckweed weight and level of targeted compounds. Application of BL caused the mitigation of the Brz inhibitory effect and enhanced the BR level in duckweed treated with Brz. The level of BRs was reported for the first time in duckweed treated with BL and/or Brz.

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Cytotoxic Effects of Ferula Latisecta on Human Glioma U87 Cells

Drug Research ◽

10.1055/a-0986-6543 ◽

2019 ◽

Vol 69 (12) ◽

pp. 665-670 ◽

Cited By ~ 6

Author(s):

Mohammad Jalili-Nik ◽

Hamed Sabri ◽

Ehsan Zamiri ◽

Mohammad Soukhtanloo ◽

Mostafa Karimi Roshan ◽

...

Keyword(s):

Enzymatic Activity ◽

Gelatin Zymography ◽

Annexin V ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Ic50 Values ◽

Induced Apoptosis ◽

Natural Herb ◽

First Time ◽

U87 Cells

AbstractGlioblastoma multiforme (GBM) is the fatal type of astrocytic tumors with a survival rate of 12 months. The present study, for the first time, evaluated the cytotoxic impacts of Ferula latisecta (F. latisecta) hydroalcoholic extract on U87 GBM cell line. The MTT assay measured the cellular toxicity following 24- and 48 h treatment with various doses of F. latisecta (0–800 μg/mL). Apoptosis was evaluated by an Annexin V/propidium iodide (PI) staining 24 h after treatment by F. latisecta. Moreover, to determine the cellular metastasis of U87 cells, we used a gelatin zymography assay (matrix metalloproteinase [MMP]-2/-9 enzymatic activity). The outcomes showed that F. latisecta mitigated the viability of U87 cells in a concentration- and time-dependent manner with IC50 values of 145.3 and 192.3 μg/mL obtained for 24- and 48 h treatments, respectively. F. latisecta induced apoptosis in a concentration-dependent manner after 24 h. Also, MMP-9 activity was significantly decreased following 24 h after treatment concentration-dependently with no change in MMP-2 enzymatic activity. This study showed that F. latisecta induced cytotoxicity and apoptosis, and mitigated metastasis of U87 GBM cells. Hence, F. latisecta could be beneficial as a promising natural herb against GBM after further studies.

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INTEGRINS MEDIATE PLACENTAL EXTRACELLULAR VESICLE TRAFFICKING TO LUNG AND LIVER IN VIVO

10.1101/2020.09.22.309047 ◽

2020 ◽

Author(s):

Sean L. Nguyen ◽

Soo Hyun Ahn ◽

Jacob W. Greenberg ◽

Benjamin W. Collaer ◽

Dalen W. Agnew ◽

...

Keyword(s):

Immune Cells ◽

Extracellular Vesicle ◽

Dependent Manner ◽

Cellular Phenotype ◽

Reporter Mouse ◽

Membrane Bound ◽

First Time

ABSTRACTMembrane-bound extracellular vesicles (EVs) mediate intercellular communication in all organisms, and those produced by placental mammals have become increasingly recognized as significant mediators of fetal-maternal communication. Here, we aimed to identify maternal cells targeted by placental EVs and elucidate the mechanisms by which they traffic to these cells. Exogenously administered pregnancy-associated EVs traffic specifically to the lung; further, placental EVs associate with lung interstitial macrophages and liver Kupffer cells in an integrin-dependent manner. Localization of EV to maternal lungs was confirmed in unmanipulated pregnancy using a transgenic reporter mouse model, which also provided in situ and in vitro evidence that fetally-derived EVs, rarely, may cause genetic alteration of maternal cells. These results provide for the first time direct in vivo evidence for targeting of placental EVs to maternal immune cells, and further, evidence that EVs can alter cellular phenotype.

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Regulatory B cells (Bregs) inhibit osteoclastogenesis and prevent bone loss in osteoporotic mice model

10.1101/2021.03.10.434751 ◽

2021 ◽

Author(s):

Leena Sapra ◽

Asha Bhardwaj ◽

Pradyumna K. Mishra ◽

Bhupendra K. Verma ◽

Rupesh K. Srivastava

Keyword(s):

B Cells ◽

Bone Marrow Cells ◽

Dependent Manner ◽

Regulatory B Cells ◽

Mice Model ◽

Post Menopausal Osteoporosis ◽

Post Menopausal ◽

First Time

AbstractIncreasing evidences in recent years have suggested that regulatory B cells (Bregs) are crucial modulator in various inflammatory disease conditions. However, the role of Bregs in case of postmenopausal osteoporosis remains unknown. Also, no study till date have ever investigated the significance of Bregs in modulating osteoclastogenesis. In the present study, we for the first time examined the anti-osteoclastogenic potential of Bregs under in vitro conditions and we observed that Bregs suppressed RANKL mediated osteoclastogenesis in bone marrow cells in a dose dependent manner. We further elucidated the mechanism behind the suppression of osteoclasts differentiation by Bregs and found that Bregs inhibit osteoclastogenesis via IL-10 production. To further confirm the bone health modulating potential of Bregs we employed post-menopausal osteoporotic mice model. Remarkably, our in vivo data clearly suggest a significant reduction (p < 0.01) in both CD19+IL-10+ and CD19+CD1dhiCD5+IL-10+ B10 Bregs in case of osteoporotic mice model. Moreover, our serum cytokine data further confirms the significant reduction of IL-10 levels in osteoporotic mice. Taken together, the present study for the first time unravels and establish the unexplored role of regulatory B cells in case of osteoporosis and provide new insight into Bregs biology in the context of post-menopausal osteoporosis.

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MyoR Modulates Cardiac Conduction by Repressing Gata4

Molecular and Cellular Biology ◽

10.1128/mcb.00860-14 ◽

2014 ◽

Vol 35 (4) ◽

pp. 649-661 ◽

Cited By ~ 5

Author(s):

John P. Harris ◽

Minoti Bhakta ◽

Svetlana Bezprozvannaya ◽

Lin Wang ◽

Christina Lubczyk ◽

...

Keyword(s):

Transcriptional Repression ◽

Atrioventricular Node ◽

Electrical Activation ◽

Cardiac Conduction ◽

Specific Gene ◽

Dependent Manner ◽

Regulatory Circuit ◽

Genetic Deletion ◽

Repression Domain ◽

Av Delay

The cardiac conduction system coordinates electrical activation through a series of interconnected structures, including the atrioventricular node (AVN), the central connection point that delays impulse propagation to optimize cardiac performance. Although recent studies have uncovered important molecular details of AVN formation, relatively little is known about the transcriptional mechanisms that regulate AV delay, the primary function of the mature AVN. We identify here MyoR as a novel transcription factor expressed in Cx30.2+cells of the AVN. We show that MyoR specifically inhibits a Cx30.2 enhancer required for AVN-specific gene expression. Furthermore, we demonstrate that MyoR interacts directly with Gata4 to mediate transcriptional repression. Our studies reveal that MyoR contains two nonequivalent repression domains. While the MyoR C-terminal repression domain inhibits transcription in a context-dependent manner, the N-terminal repression domain can function in a heterologous context to convert the Hand2 activator into a repressor. In addition, we show that genetic deletion of MyoR in mice increases Cx30.2 expression by 50% and prolongs AV delay by 13%. Taken together, we conclude that MyoR modulates a Gata4-dependent regulatory circuit that establishes proper AV delay, and these findings may have wider implications for the variability of cardiac rhythm observed in the general population.

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Blastocystis ratti Contains Cysteine Proteases That Mediate Interleukin-8 Response from Human Intestinal Epithelial Cells in an NF-κB-Dependent Manner

Eukaryotic Cell ◽

10.1128/ec.00371-07 ◽

2007 ◽

Vol 7 (3) ◽

pp. 435-443 ◽

Cited By ~ 65

Author(s):

Manoj K. Puthia ◽

Jia Lu ◽

Kevin S. W. Tan

Keyword(s):

Gene Expression ◽

Epithelial Cells ◽

Intestinal Inflammation ◽

Experimental Studies ◽

Cysteine Proteases ◽

Interleukin 8 ◽

Dependent Manner ◽

Public Health Importance ◽

Wide Range ◽

First Time

ABSTRACT Blastocystis is a ubiquitous enteric protozoan found in the intestinal tracts of humans and a wide range of animals. Evidence accumulated over the last decade suggests association of Blastocystis with gastrointestinal disorders involving diarrhea, abdominal pain, constipation, nausea, and fatigue. Clinical and experimental studies have associated Blastocystis with intestinal inflammation, and it has been shown that Blastocystis has potential to modulate the host immune response. Blastocystis is also reported to be an opportunistic pathogen in immunosuppressed patients, especially those suffering from AIDS. However, nothing is known about the parasitic virulence factors and early events following host-parasite interactions. In the present study, we investigated the molecular mechanism by which Blastocystis activates interleukin-8 (IL-8) gene expression in human colonic epithelial T84 cells. We demonstrate for the first time that cysteine proteases of Blastocystis ratti WR1, a zoonotic isolate, can activate IL-8 gene expression in human colonic epithelial cells. Furthermore, we show that NF-κB activation is involved in the production of IL-8. In addition, our findings show that treatment with the antiprotozoal drug metronidazole can avert IL-8 production induced by B. ratti WR1. We also show for the first time that the central vacuole of Blastocystis may function as a reservoir for cysteine proteases. Our findings will contribute to an understanding of the pathobiology of a poorly studied parasite whose public health importance is increasingly recognized.

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Small Molecule Constituents of Periplaneta americana and Their IL-6 Inhibitory Activities

Natural Product Communications ◽

10.1177/1934578x211033180 ◽

2021 ◽

Vol 16 (9) ◽

pp. 1934578X2110331

Author(s):

Hua-Sheng Zhang ◽

Yong-Ming Yan ◽

Dai-Wei Wang ◽

Qing Lv ◽

Yong-Xian Cheng ◽

...

Keyword(s):

High Performance Liquid Chromatography ◽

High Performance ◽

Periplaneta Americana ◽

Ethanol Extract ◽

Biological Evaluation ◽

Dependent Manner ◽

Chemical Methods ◽

Concentration Dependent Manner ◽

Inhibitory Activities ◽

First Time

Two new glycosides, periplanosides A (1) and B (2), 3 compounds reported from a natural source for the first time (3 − 5), and 6 known compounds 6 − 11 were isolated from the ethanol extract of Periplaneta americana (Linnaeus). Their structures, including absolute configurations, were unambiguously identified by comprehensive spectroscopic and chemical methods. Compound 3 is a racemate whose enantiomers were purified by chiral high-performance liquid chromatography . The biological evaluation results showed that compound 7 (0 − 20 μM) did not affect the viability of RAW264.7 cells and could effectively inhibit the production of interleukin-6 stimulated by lipopolysaccharide in a concentration-dependent manner, indicating the potential to develop novel agents against inflammation-related diseases.

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