• 제목/요약/키워드: Double regulating

검색결과 64건 처리시간 0.03초

Post-Translational Regulation of the RSF1 Chromatin Remodeler under DNA Damage

  • Min, Sunwoo;Choi, Yong Won;Yun, Hansol;Jo, Sujin;Ji, Jae-Hoon;Cho, Hyeseong
    • Molecules and Cells
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    • 제41권2호
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    • pp.127-133
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    • 2018
  • Chromatin remodeling factors are involved in many cellular processes such as transcription, replication, and DNA damage response by regulating chromatin structure. As one of chromatin remodeling factors, remodeling and spacing factor 1 (RSF1) is recruited at double strand break (DSB) sites and regulates ataxia telangiectasia mutated (ATM) -dependent checkpoint pathway upon DNA damage for the efficient repair. RSF1 is overexpressed in a variety of cancers, but regulation of RSF1 levels remains largely unknown. Here, we showed that protein levels of RSF1 chromatin remodeler are temporally upregulated in response to different DNA damage agents without changing the RSF1 mRNA level. In the absence of SNF2h, a binding partner of RSF1, the RSF1 protein level was significantly diminished. Intriguingly, the level of RSF1-3SA mutant lacking ATM-mediated phosphorylation sites significantly increased, and upregulation of RSF1 levels under DNA damage was not observed in cells overexpressing ATM kinase. Furthermore, failure in the regulation of RSF1 level caused a significant reduction in DNA repair, whereas reconstitution of RSF1, but not of RSF1-3SA mutants, restored DSB repair. Our findings reveal that temporal regulation of RSF1 levels at its post-translational modification by SNF2h and ATM is essential for efficient DNA repair.

Probiotic supplementation has sex-dependent effects on immune responses in association with the gut microbiota in community-dwelling older adults: a randomized, double-blind, placebo-controlled, multicenter trial

  • Chong-Su Kim;Min Ho Jung;Eun Young Choi;Dong-Mi Shin
    • Nutrition Research and Practice
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    • 제17권5호
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    • pp.883-898
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    • 2023
  • BACKGROUND/OBJECTIVES: Probiotics have been suggested as potent modulators of age-related disorders in immunological functions, yet little is known about sex-dependent effects of probiotic supplements. Therefore, we aimed to investigate sex-dependent effects of probiotics on profiles of the gut microbiota and peripheral immune cells in healthy older adults. SUBJECTS/METHODS: In a randomized, double-blind, placebo-controlled, multicenter trial, healthy elderly individuals ≥ 65 yrs old were administered probiotic capsules (or placebo) for 12 wk. Gut microbiota was analyzed using 16S rRNA gene sequencing and bioinformatic analyses. Peripheral immune cells were profiled using flow cytometry for lymphocytes (natural killer, B, CD4+ T, and CD8+ T cells), dendritic cells, monocytes, and their subpopulations. RESULTS: Compared with placebo, phylum Firmicutes was significantly reduced in the probiotic group in women, but not in men. At the genus level, sex-specific responses included reductions in the relative abundances of pro-inflammatory gut microbes, including Catabacter and unclassified_Coriobacteriales, and Burkholderia and unclassified Enterobacteriaceae, in men and women, respectively. Peripheral immune cell profiling analysis revealed that in men, probiotics significantly reduced the proportions of dendritic cells and CD14+ CD16- monocytes; however, these effects were not observed in women. In contrast, the proportion of total CD4+ T cells was significantly reduced in women in the probiotic group. Additionally, serum lipopolysaccharide-binding protein levels showed a decreasing tendency that were positively associated with changes in gut bacteria, including Catabacter (ρ = 0.678, P < 0.05) and Burkholderia (ρ = 0.673, P < 0.05) in men and women, respectively. CONCLUSIONS: These results suggest that probiotic supplementation may reduce the incidence of inflammation-related diseases by regulating the profiles of the gut microbiota and peripheral immune cells in healthy elders in a sex-specific manner.

Analysis of C. elegans VIG-1 Expression

  • Shin, Kyoung-Hwa;Choi, Boram;Park, Yang-Seo;Cho, Nam Jeong
    • Molecules and Cells
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    • 제26권6호
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    • pp.554-557
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    • 2008
  • Double-stranded RNA (dsRNA) induces gene silencing in a sequence-specific manner by a process known as RNA interference (RNAi). The RNA-induced silencing complex (RISC) is a multi-subunit ribonucleoprotein complex that plays a key role in RNAi. VIG (Vasa intronic gene) has been identified as a component of Drosophila RISC; however, the role VIG plays in regulating RNAi is poorly understood. Here, we examined the spatial and temporal expression patterns of VIG-1, the C. elegans ortholog of Drosophila VIG, using a vig-1::gfp fusion construct. This construct contains the 908-bp region immediately upstream of vig-1 gene translation initiation site. Analysis by confocal microscopy demonstrated GFP-VIG-1 expression in a number of tissues including the pharynx, body wall muscle, hypodermis, intestine, reproductive system, and nervous system at the larval and adult stages. Furthermore, western blot analysis showed that VIG-1 is present in each developmental stage examined. To investigate regulatory sequences for vig-1 gene expression, we generated constructs containing deletions in the upstream region. It was determined that the GFP expression pattern of a deletion construct (${\Delta}-908$ to -597) was generally similar to that of the non-deletion construct. In contrast, removal of a larger segment (${\Delta}-908$ to -191) resulted in the loss of GFP expression in most cell types. Collectively, these results indicate that the 406-bp upstream region (-596 to -191) contains essential regulatory sequences required for VIG-1 expression.

Potential of some traditionally used edible plants for prevention and cure of diabesity associated comorbidities

  • Kumar, Vikas;Thakur, Ajit Kumar;Verma, Suruchi;Yadav, Vaishali;Chatterjee, Shyam Sunder
    • 셀메드
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    • 제5권2호
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    • pp.8.1-8.22
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    • 2015
  • Medicinal uses of edible and other plants for prevention and cure of obesity and overweight associated metabolic and mental health problems have since long been known to scholars and practitioners of Ayurvedic and other traditionally known system of medicine. Modernized versions of numerous edible plant derived formulations mentioned in ancient Ayurvedic texts are at present some of the most popular, or best selling, herbal remedies in India and numerous other countries suffering from double burden of diseases caused by malnutrition and obesity. Preclinical and clinical information now available on edible plants and their bioactive constituents justify traditionally known medicinal uses of products derived from them for prevention and cure of obesity associated type-2 diabetes, psychopathologies and other health problems. Such information now available on a few edible Ayurvedic plants and their formulations and suggesting that their stress response regulating effects are involved in their broad spectrums of bioactivity profiles are summarized in this communication. Implications of recent physiological and pharmacological observations made with numerous phytochemicals isolated from edible plants for better understanding of traditionally known medicinal uses of herbal remedies are also pointed out.

A Technique of Segment Expression and RNA Interference (SERI) Reveals a Specific Physiological Function of a Cysteine-Rich Protein Gene Encoded in Cotesia plutellae Bracovirus

  • Barandoc, Karen;Kim, Yong-Gyun
    • Journal of Microbiology and Biotechnology
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    • 제19권6호
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    • pp.610-615
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    • 2009
  • As a provirus, polydnavirus has a segmented DNA genome on chromosome(s) of host wasp. It contains several genes in each segment that presumably play critical roles in regulating physiological processes of target insect parasitized by the wasp. A cysteine-rich protein 1 (CRP1) is present in the polydnavirus Cotesia plutellae bracovirus (CpBV) genome, but its expression and physiological function in Plutella xylostella parasitized by the viral host C. plutellae is not known. This CpBV-CRP1 encoding 189 amino acids with a putative signal peptide (20 residues) was persistently expressed in parasitized P. xylostella with gradual decrease at the late parasitization period. Expression of CpBV-CRP1 was tissue-specific in the fat body/epidermis and hemocyte, but not in the gut. Its physiological function was analyzed by inducing transient expression of a CpBV segment containing CpBV-CRP1 and its promoter, which caused significant reduction in hemocyte -spreading and delayed larval development. When the treated larvae were co-injected with double-stranded RNA of CpBV-CRP1, the expression of CpBV-CRP1 disappeared, whereas other genes encoded in the CpBV segment was expressed. These co-injected larvae significantly recovered the hemocyte-spreading capacity and larval development rate. This study reports that CpBV-CRP1 is expressed in P. xylostella parasitized by C. plutellae and its physiological function is to alter the host immune and developmental processes.

Disruption of the Myostatin Gene in Porcine Primary Fibroblasts and Embryos Using Zinc-Finger Nucleases

  • Huang, Xian-Ju;Zhang, Hong-Xiao;Wang, Huili;Xiong, Kai;Qin, Ling;Liu, Honglin
    • Molecules and Cells
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    • 제37권4호
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    • pp.302-306
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    • 2014
  • Myostatin represses muscle growth by negatively regulating the number and size of muscle fibers. Myostatin loss-of-function can result in the double-muscling phenotype and increased muscle mass. Thus, knockout of myostatin gene could improve the quality of meat from mammals. In the present study, zinc finger nucleases, a useful tool for generating gene knockout animals, were designed to target exon 1 of the myostatin gene. The designed ZFNs were introduced into porcine primary fibroblasts and early implantation embryos via electroporation and microinjection, respectively. Mutations around the ZFNs target site were detected in both primary fibroblasts and blastocysts. The proportion of mutant fibroblast cells and blastocyst was 4.81% and 5.31%, respectively. Thus, ZFNs can be used to knockout myostatin in porcine primary fibroblasts and early implantation embryos.

Multivariable Optimal Control of a Direct AC/AC Converter under Rotating dq Frames

  • Wan, Yun;Liu, Steven;Jiang, Jianguo
    • Journal of Power Electronics
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    • 제13권3호
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    • pp.419-428
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    • 2013
  • The modular multilevel cascade converter (MMCC) is a new family of multilevel power converters with modular realization and a cascaded pattern for submodules. The MMCC family can be classified by basic configurations and submodule types. One member of this family, the Hexverter, is configured as Double-Delta Full-Bridge (DDFB). It is a novel multilevel AC/AC converter with direct power conversion and comparatively fewer required components. It is appropriate for connecting two three-phase systems with different frequencies and driving an AC motor directly from a utility grid. This paper presents the dq model of a Hexverter with both of its AC systems by state-space representation, which then simplifies the continuous time-varying model into a periodic discrete time-invariant one. Then a generalized multivariable optimal control strategy for regulating the Hexverter's independent currents is developed. The resulting control structure can be adapted to other MMCCs and is flexible enough to include other control criterion while guaranteeing the original controller performance. The modeling method and control design are verified by simulation results.

RNases and their role in Cancer

  • Beeram, Eswari
    • 식품보건융합연구
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    • 제5권2호
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    • pp.27-34
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    • 2019
  • RNases plays a pivotal role in biological system and different RNases are known for their various functions like angiogenesis, immunological response, antiviral, antitumour activity and apoptosis. In which anti tumour activity of RNase is proved to improve genome stability in normal cells up to some extent. RNases like RNase L shows antiviral and antitumour activities against virus infected cells and cancer cells through 2'-5' oligo adenylate pathway and induces RNaseL dependent apoptosis where as RNase A modulates various proliferative pathways like MAP kinase, JNK, TGF-${\beta}$ and activates apoptosis in cancer cells and promotes immunological response through processing of Ags. IRE1 RNase acts as both tumour suppressor gene and oncogene in normal and cancer cells and involved in both antitumour and tumorigenic activities. RNase III upregulates miRNA in cancer cells there by acting via posttranscriptional level and proven to be effective against colorectal adeno carcinoma. In addition to this IRE1 RNase is a double edged sword through RIDD pathway in ER (18). To some of the cancers expressing c-myc IRE1 acts as tumour suppressor where as in cancers where myc is downregulated IRE1 acts as tumour provoking through RIDD pathway (18). Thus RNases play vital role in regulating the genome stability.

Molecular Tension Probes to Quantify Cell-Generated Mechanical Forces

  • Baek, Kyung Yup;Kim, Seohyun;Koh, Hye Ran
    • Molecules and Cells
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    • 제45권1호
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    • pp.26-32
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    • 2022
  • Living cells generate, sense, and respond to mechanical forces through their interaction with neighboring cells or extracellular matrix, thereby regulating diverse cellular processes such as growth, motility, differentiation, and immune responses. Dysregulation of mechanosensitive signaling pathways is found associated with the development and progression of various diseases such as cancer. Yet, little is known about the mechanisms behind mechano-regulation, largely due to the limited availability of tools to study it at the molecular level. The recent development of molecular tension probes allows measurement of cellular forces exerted by single ligand-receptor interaction, which has helped in revealing the hitherto unknown mechanistic details of various mechanosensitive processes in living cells. Here, we provide an introductory overview of two methods based on molecular tension probes, tension gauge tether (TGT), and molecular tension fluorescence microscopy (MTFM). TGT utilizes the irreversible rupture of double-stranded DNA tether upon application of force in the piconewton (pN) range, whereas MTFM utilizes the reversible extension of molecular springs such as polymer or single-stranded DNA hairpin under applied pN forces. Specifically, the underlying principle of how molecular tension probes measure cell-generated mechanical forces and their applications to mechanosensitive biological processes are described.

Unraveling the Role of Cytochrome P450 as a Key Regulator Lantipeptide Production in Streptomyces globisporus

  • Da-Ran Kim;Su In Lee;Youn-Sig Kwak
    • The Plant Pathology Journal
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    • 제39권6호
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    • pp.566-574
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    • 2023
  • The aim of this study was to investigate the regulation of lantipeptide production in Streptomyces globisporus SP6C4, which produces the novel antifungal lantipeptides conprimycin and grisin, and to identify the role of cytochrome P450 (P450) in tis regulation. To investigate the regulation of lantipeptide production, we created gene deletion mutants, including ΔP450, ΔtsrD, ΔlanM, ΔP450ΔtsrD, and ΔP450ΔlanM. These mutants were characterized in terms of their morphology, sporulation, attachment, and antifungal activity against Fusarium oxysporum. The gene deletion mutants showed distinct characteristics compared to the wild-type strain. Among them, the ΔP450ΔlanM double mutant exhibited a recovery of antifungal activity against F. oxysporum, indicating that P450 plays a significant role in regulating lantipeptide production in S. globisporus SP6C4. Our findings highlight the significant role of P450 in the regulation of lantipeptide production and morphological processes in S. globisporus. The results suggest a potential link between P450-mediated metabolic pathways and the regulation of growth and secondary metabolism in SP6C4, thereby highlighting P450 as a putative target for the development of new antifungal agents.