• 제목/요약/키워드: mutant virus

검색결과 95건 처리시간 0.029초

A Gene Encoding Phosphatidyl Inositol-specific Phospholipase C form Cryphonectria parasitica Modulates the Hypoviral-modulated Laccase1 Expression

  • Kim, Dae-Hyuk
    • 한국미생물학회:학술대회논문집
    • /
    • 한국미생물학회 2005년도 International Meeting of the Microbiological Society of Korea
    • /
    • pp.159-161
    • /
    • 2005
  • Hypovirus infection of the chestnut blight fungus Cryphonectria parasitica is a useful model system to study the hypoviral regulation of fungal gene expression. The hypovirus is known to downregulate the fungal laccase1 (lac 1), the modulation of which is tightly governed by the inositol triphosphate ($IP_3$) and calcium second messenger system in a virus-free strain. We cloned the gene cplc1 encoding a phosphatidyl inositol-specific phospholipase C (PLC), in order to better characterize the fungal gene regulation by hypovirus. Sequence analysis of the cplc1 gene indicated that the protein product contained both the X and Y domains, which are the two conserved regions found in all known PLCs, with a 133 amino acid extension between the 2nd ${\beta}$-strand and the ${\alpha}$-helix in the X domain. In addition, the gene organization appeared to be highly similar to that of a ${\delta}$ type PLC. Disruption of the cplc1 gene resulted in slow growth and produced colonies characterized by little aerial mycelia and deep orange in color. In addition, down regulation of lac1 expression was observed. However, temperature sensitivity, osmosensitivity, virulence, and other hypovirulence-associated characteristics did not differ from the wild-type strain. Functional complementation of the cplc1-null mutant with the PLC1 gene from Saccharomyces cerevisiae restored lac1 expression, which suggests that the cloned gene encodes PLC activity. The present study indicates that the cplc1 gene is required for appropriate mycelial growth, and that it regulates the lac1 expression, which is also modulated by the hypovirus. Although several PLC genes have been identified in various simple eukaryotic organisms, the deletion analysis of the cplc1 gene in this study appears to be the first report on the functional analysis of PLC in filamentous fungi.

  • PDF

정신과의 분자생물학 적용 (Molecular Application in Psychiatry)

  • 최인근
    • 생물정신의학
    • /
    • 제7권2호
    • /
    • pp.115-122
    • /
    • 2000
  • The development of molecular biology has brought many changes in psychiatry. Molecular biology makes us possible to know the cause of mental disorders that provide the way to prevent the disorders, and to develop various accurate diagnostic and treatment methods for mental disorders. The author discusses the concept, cause, and treatment of mental disorders in the aspect of molecular biology. Importing the methods of molecular biology into psychiatry, we can anticipate to get a number of the goals of psychiatric genetics, including identification of specific susceptibility genes, clarification of the pathophysiological processes whereby these genes lead to symptoms, establishment of epigenetic factors that interact with these genes to produce disease, validation of nosological boundaries that more closely reflect the actions of these genes, and development of effective preventive and therapeutic interventions based on genetic counseling, gene therapy, and modification of permissive or protective environmental influences. In addition to their capacity to accelerate the discovery of new molecules participating in the nervous system's response to disease or to self-administered drugs, molecular biological strategies can also be used to determine how critical a particular gene product may be in mediating a cellular event with behavioral importance. Molecular biology probably enables us discover the environmental factors of mental disorders and allow rational drug design and gene therapies for mental disorders, by isolation of gene products that facilitate a basic understanding of the pathogenesis of these disorders. A specific genetic linkage may suggest a novel class of drugs that has not yet been tried. With respect to gene therapy, the hypothetical method would use a gene delivery system, most likely a modified virus, to insert a functional copy of a mutant gene into those brain cells that require the gene for normal function.

  • PDF

HIV/AIDS Management: Dolutegravir Based Antiretroviral Drug Therapy

  • John, Ikpeama Osita;Emmanuel, Okoh Emeka;Anthonia, Ikpeama Chizoba;Joy, Ikpeama Chinwe;Adimabua, Okafor Patrick;Osazuwa, Igbineweka Osa;Andrew, Ikpeama Emeka;Mariam, Onuzulike Nonye;Gami, Hilary Tumba
    • 식품보건융합연구
    • /
    • 제6권4호
    • /
    • pp.17-19
    • /
    • 2020
  • HIV/AIDS disease still remain a global pandemic and it's management has undergone series of treatment changes and improvement although there is still no permanent cure.Dolutegravir belongs to a group of HIV drugs called integrase inhibitors. Integrase inhibitors block an HIV enzyme called integrase. By blocking integrase, integrase inhibitors prevent HIV from multiplying and can reduce the amount of HIV in the body.Dolutegravir combination based regimen has turned out to be very effective (antiviral) with negligible rare side effects on clients. This drug (Dolutegravir based regimen) combination has successfully increased the appetite for food of all the clients, unlike others and has shown to reduce viral load in the most shortest period ever. It can be deduced that development of resistant mutant virus will be reduced if not eliminated with dolutogravir based regimen.The role of Continuous adherence counseling has shown to improve clients treatment management. It is important to note that the availability of food has direct effect on the economic status or financial weight on the client. Hence the progress that is increase in body mass index (BMI) is a direct impact of the availability of food for the clients.

Spike protein D614G and RdRp P323L: the SARS-CoV-2 mutations associated with severity of COVID-19

  • Biswas, Subrata K.;Mudi, Sonchita R.
    • Genomics & Informatics
    • /
    • 제18권4호
    • /
    • pp.44.1-44.7
    • /
    • 2020
  • The severity of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), greatly varies from patient to patient. In the present study, we explored and compared mutation profiles of SARS-CoV-2 isolated from mildly affected and severely affected COVID-19 patients in order to explore any relationship between mutation profile and disease severity. Genomic sequences of SARS-CoV-2 were downloaded from Global Initiative on Sharing Avian Influenza Data (GISAID) database. With the help of Genome Detective Coronavirus Typing Tool, genomic sequences were aligned with the Wuhan seafood market pneumonia virus reference sequence and all the mutations were identified. Distribution of mutant variants was then compared between mildly and severely affected groups. Among the numerous mutations detected, 14408C>T and 23403A>G mutations resulting in RNA-dependent RNA polymerase (RdRp) P323L and spike protein D614G mutations, respectively, were found predominantly in severely affected group (>82%) compared with mildly affected group (<46%, p < 0.001). The 241C>T mutation in the non-coding region of the genome was also found predominantly in severely affected group (p < 0.001). The 3037C>T, a silent mutation, also appeared in relatively high frequency in severely affected group compared with mildly affected group, but the difference was not statistically significant (p = 0.06). We concluded that spike protein D614G and RdRp P323L mutations in SARS-CoV-2 are associated with severity of COVID-19. Further studies will be required to explore whether these mutations have any impact on the severity of disease.

Epigenetic control of LTR retrotransposons in plant germline and somatic cells

  • Lee, Seung Cho;Parent, Jean-Sebastien;Ernst, Evan;Berger, Frederic;Grimanelli, Daniel;Martienssen, Robert A.
    • 한국작물학회:학술대회논문집
    • /
    • 한국작물학회 2017년도 9th Asian Crop Science Association conference
    • /
    • pp.20-20
    • /
    • 2017
  • Plant genomes include heterochromatic loci that consist of repetitive sequences and transposable elements. LTR retrotransposon is the major class of transposons in advanced plants in terms of proportion in plant genome. The elements contribute not only to genome size but also to genome stability and gene expression. A number of cases have been reported transposon insertions near genic regions affect crop traits such as fruit pigments, stress tolerance, and yields. Functional LTR retrotransposons produce extrachromosomal DNA from genomic RNA by reverse transcription that takes place within virus-like-particles (VLPs). DECREASED DNA METHYLATION 1 (DDM1) plays important roles in maintaining DNA methylation of heterochromatin affecting all sequence contexts, CG, CHG, and CHH. Previous studies showed that ddm1 mutant exhibits massive transcription of retrotransposons in Arabidopsis, but only few of them were able to create new insertions into the genome. RNA-dependent RNA POLYMERASE 6 (RDR6) is known to function in restricting accumulation of transposon RNA by processing the transcripts into 21-22 nt epigenetically activated small interfering RNA (easiRNA). We purified VLPs and sequence cDNA to identify functional LTR retrotransposons in Arabidopsis ddm1 and ddm1rdr6 plants. Over 20 LTR copia and gypsy families were detected in ddm1 and ddm1rdr6 sequencing libraries and most of them were not reported for mobility. In ddm1rdr6, short fragments of ATHILA gypsy elements were detected. It suggests easiRNAs might regulate reverse transcription steps. The highest enriched element among transposon loci was previously characterized EVADE element. It has been reported that active EVADE element is more efficiently silenced through female germline than male germline. By genetic analyses, we found ddm1 and rdr6 mutation affect maternal silencing of active EVADE elements. DDM1-GFP protein accumulated in megaspore mother cell but was not found in mature egg cell. The fusion protein was also found in early embryo and maternal DDM1-GFP allele was more dominantly expressed in the embryo. We observed localization of DDM1-GFP in Arabidopsis and DDM1-YFP in maize and found the proteins accumulated in dividing zone of root tips. Currently we are looking at cell cycle dependency of DDM1 expression using maize system. Among 10 AGO proteins in Arabidopsis, AGO9 is specifically expressed in egg cell and shoot meristematic cells. In addition, mutation of AGO9 and RDR6 caused failure in maternal silencing, implying 21-22 nt easiRNA pathway is important for retrotransposon silencing in female gametophyte or/and early embryo. On the other hand, canonical 24 nt sRNA-directed DNA methylation (RdDM) pathways did not contribute to maternal silencing as confirmed by this study. Heat-activated LTR retrotransposon, ONSEN, was not silenced by DDM1 but the silencing mechanisms require RdDM pathways in somatic cells. We will propose distinct mechanisms of LTR retrotransposons in germline and somatic stages.

  • PDF

Epigenetic control of LTR retrotransposons in plant germline and somatic cells

  • Lee, Seung Cho;Parent, Jean-Sebastien;Ernst, Evan;Berger, Frederic;Grimanelli, Daniel;Martienssen, Robert A.
    • 한국작물학회:학술대회논문집
    • /
    • 한국작물학회 2017년도 9th Asian Crop Science Association conference
    • /
    • pp.97-97
    • /
    • 2017
  • Plant genomes include heterochromatic loci that consist of repetitive sequences and transposable elements. LTR retrotransposon is the major class of transposons in advanced plants in terms of proportion in plant genome. The elements contribute not only to genome size but also to genome stability and gene expression. A number of cases have been reported transposon insertions near genic regions affect crop traits such as fruit pigments, stress tolerance, and yields. Functional LTR retrotransposons produce extrachromosomal DNA from genomic RNA by reverse transcription that takes place within virus-like-particles (VLPs). DECREASED DNA METHYLATION 1 (DDM1) plays important roles in maintaining DNA methylation of heterochromatin affecting all sequence contexts, CG, CHG, and CHH. Previous studies showed that ddm1 mutant exhibits massive transcription of retrotransposons in Arabidopsis, but only few of them were able to create new insertions into the genome. RNA-dependent RNA POLYMERASE 6 (RDR6) is known to function in restricting accumulation of transposon RNA by processing the transcripts into 21-22 nt epigenetically activated small interfering RNA (easiRNA). We purified VLPs and sequence cDNA to identify functional LTR retrotransposons in Arabidopsis ddm1 and ddm1rdr6 plants. Over 20 LTR copia and gypsy families were detected in ddm1 and ddm1rdr6 sequencing libraries and most of them were not reported for mobility. In ddm1rdr6, short fragments of ATHILA gypsy elements were detected. It suggests easiRNAs might regulate reverse transcription steps. The highest enriched element among transposon loci was previously characterized EVADE element. It has been reported that active EVADE element is more efficiently silenced through female germline than male germline. By genetic analyses, we found ddm1 and rdr6 mutation affect maternal silencing of active EVADE elements. DDM1-GFP protein accumulated in megaspore mother cell but was not found in mature egg cell. The fusion protein was also found in early embryo and maternal DDM1-GFP allele was more dominantly expressed in the embryo. We observed localization of DDM1-GFP in Arabidopsis and DDM1-YFP in maize and found the proteins accumulated in dividing zone of root tips. Currently we are looking at cell cycle dependency of DDM1 expression using maize system. Among 10 AGO proteins in Arabidopsis, AGO9 is specifically expressed in egg cell and shoot meristematic cells. In addition, mutation of AGO9 and RDR6 caused failure in maternal silencing, implying 21-22 nt easiRNA pathway is important for retrotransposon silencing in female gametophyte or/and early embryo. On the other hand, canonical 24 nt sRNA-directed DNA methylation (RdDM) pathways did not contribute to maternal silencing as confirmed by this study. Heat-activated LTR retrotransposon, ONSEN, was not silenced by DDM1 but the silencing mechanisms require RdDM pathways in somatic cells. We will propose distinct mechanisms of LTR retrotransposons in germline and somatic stages.

  • PDF

트랜스미디어 환경에서의 감성마케팅을 위한 사용자 경험디자인에 대한 고찰 (Study on the User Experience Design for Emotional Marketing in an Transmedia Environment)

  • 허진
    • 한국콘텐츠학회논문지
    • /
    • 제12권9호
    • /
    • pp.194-201
    • /
    • 2012
  • 미디어의 확장은 인식의 확장과 맞닿아 있다. 문자의 발명은 시공간을 넘게 하였다. 기계는 육체의 기능 확장으로 이어졌으며, 전기는 공간과 시간으로 확장되었다. 컴퓨터는 두뇌의 확장이며, 인터넷은 관계의 확장으로 이어졌다. 지금 이 순간에도 미디어는 바이러스의 변종증식처럼 끊임없이 진보하고 있으며, 컨버전스나 하이브리드와 같은 융 복합 현상으로 이어진다. 이제 미디어는 인간 의식을 대신하고 있다. 트랜스미디어는, '횡단', '초월', '관통', 변화' 등을 뜻하는 'Trans'와 'Media'의 합성어로 현대사회 모든 미디어를 수용하는 '미디어를 초월한 미디어'를 뜻한다. 그러나 다른 융 복합 미디어와 달리 기술과 기술의 결합이 아닌 기술과 감성을 융합한다는 차별성을 가진다. 따라서 트랜스미디어는 스마트사회에서 중요시되는 디지털기술에 의한 인간의 '의식적 자각'과 인간 감성에 호소하는 '정서적 자각'을 동시에 충족시켜야하는 '사용자 경험'이라는 측면에서 중요한 의미를 가진 미디어로 인식되어져야 할 것이다. 본 논문에서는 먼저 트랜스미디어의 개념을 알아보고 의식적 사고를 유발하는 사용자경험디자인의 역할과 감성마케팅에 대하여 살펴보고자 한다. 이러한 고찰이 앞으로 개발자와 디자이너, 그리고 사용자와의 원활한 소통관계를 이루기 위한 개발단계에 있어 고려해야할 개념으로 이해되기를 기대한다.

사람의 신경교종 세포주에서 아데노바이러스 벡터를 이용한 p16/INK4a 유전자 전달에 의한 종양성장 억제 (Growth Suppression by Adenovirus-mediated Gene Transfer of p16/INK4a in Glioma Cell Lines)

  • 김미숙;권희충;강희석;박인철;이창훈;김창민;이춘택;홍석일;이승훈
    • Journal of Korean Neurosurgical Society
    • /
    • 제29권4호
    • /
    • pp.471-476
    • /
    • 2000
  • Objective : p16/INK4a, a kind of tumor suppressor genes, encodes a specific inhibitor of the cyclin D-dependent kinases CDK4 and CDK6. This prevents the association of CDK4 with cyclin D1, and subsequently inhibits phosphorylation of retinoblastoma tumor suppressor protein(pRb), thus preventing exit from the G1 phase. According to previous reports, over 50% of glioma tissue and 80% of glioma cell lines have been demonstrated inactivation of p16/INK4a gene. The purpose of this study was to determine whether recombinant adenovirus-p16 virus is a suitable candidate for gene replacement therapy in cases of glioma. Methods : Three human glioma cell lines(U251MG, U87MG and U373MG) that express mutant p16 protein were used. Replication-deficient adenovirus was utilized as an expression vector to transfer exogenous p16 cDNA into the cells ; control cells were infected with the Ad-${\beta}$-gal expressing ${\beta}$-galactosidase. To monitor gene transfer and the expression of exogenous genes, we used Western Blotting analysis. Flow cytometry studies of cellular DNA content were performed to determine the cell cycle phenotype of the glioma cells before and after treatment. Results : We showed here that restoration of p16/INK4a expression in p16 negative U87MG, U251MG and partially deleted U373MG by Ad-CMV-p16 induced growth suppression in vitro. Flow cytometric study revealed that Ad-CMV-p16 infected U87MG cells were arrested during the G0-G1 phase of the cell cycle. Expression of p16 transferred by Ad-CMV-p16 in glioma cells was highly efficient and maintained for more than seven days. Conclusions : Our results suggest that Ad-CMV-p16 gene therapy strategy is potentially useful and warrants further clinical investigation for the treatment of gliomas.

  • PDF

구제역바이러스의 FMDV 2C 단백질은 소포체 스트레스를 통해서 염증 유도 사이토카인 TNFα의 발현을 증가시킴 (FMDV 2C Protein of Foot-and-mouth Disease Virus Increases Expression of Pro-inflammatory Cytokine TNFα via Endoplasmic Reticulum Stress)

  • 강효린;성미소;나진주;류소연;구복경;정재훈
    • 생명과학회지
    • /
    • 제30권3호
    • /
    • pp.285-290
    • /
    • 2020
  • 구제역바이러스(FMDV)는 Picornaviridae 과의 Aphthovirus 속의 한 종류이며, 야생과 가축의 소와 돼지에 감염한다. FMDV는 감염 조직에서 중증의 염증반응을 포함한 다양한 임상적 증후들을 일으킨다. FMDV 게놈 RNA는 약 8.3 kb 길이의 양성-단일 가닥을 가지고 있으며, 하나의 긴 단백질 번역틀(ORF)을 만든다. 이 ORF는 바이러스의 단백질가수분해효소에 의해서 구조단백질과 비구조단백질로 나누어진다. FMDV의 FMDV 2C 단백질은 FMDV 유전자에서 만들어지는 비구조단백질로서 염증과 세포사를 포함한 FMD 병리 과정과 바이러스 복제에서 중요한 역할을 한다. 이 연구에서 우리는 FMDV 2C가 염증 유도 사이토카인인 tumor necrosis factor alpha (TNFα)의 세포내 발현을 유도하는 가능성을 검토하였다. FMDV 2C의 돼지 세포인 IBRS-2 세포내 발현은 TNFα의 유전자 발현 조절 부위인 프로모터의 활성화를 이용하여 전사수준에서 TNFα의 mRNA와 단백질 생성을 증가시켰다. 추가적으로, 소포체 스트레스를 감소시키는 화학물질인 4-phenylbutyric acid (4-PBA) 처리는 FMDV 2C에 의해 유도된 TNFα 발현을 감소시켰다. 소포체 스트레스 반응을 매개하는 전사인자의 한 종류인 ATF4는 TNFα 프로모터의 활성을 유도하고, TNFα의 mRNA와 단백질 발현을 증가시켰다. 하지만, ATF4의 기능 결핍 돌연변이체 단백질의 발현은 FMDV 2C에 의한 TNFα 생성을 유도하지 못하였다. 이들 결과들은 FMDV FMDV 2C 단백질이 ATF4-매개 TNFα 발현을 통해 임상적 염증반응을 증가시키고, 이는 소포체 스트레스의 유도와 연관되어있음을 제시한다.

한국야생유래 행동이상 Mouse 에 있어서 체외수정에 의한 번식장애 개선과 정자의 동결보존 (Improvement of Reproductive Disturbances by In Vitro Fertilization and Spermatozoa Cryopreservation in a Mouse Strain Showing Behavior Abnormality Derived from Korean Wild Mouse (Mus musculus molossinus))

  • 남윤이;김상근;김명수;이철호;최양규;현병화
    • 한국가축번식학회지
    • /
    • 제23권3호
    • /
    • pp.247-256
    • /
    • 1999
  • 본 연구는 한국야생 유래 행동이상 마우스(M. m. molossinus-tt@Kist)의 혈액학 및 혈액생화학치와, 체외수정란과 정자동결보존법, 체외수정과 수정란 이식기법을 이용한 번식장애 개선과 병원성 미생물이 제거된 무병마우스 생산을 위하여 실시하였다. 1. 5주령의 혈액학치에서 RBC, platelet치는 근교계에 비해 높게 나타났다. 혈액생화학치에서는 total cholesterol치가 근교계에 비해 높게 나타났으나 triglyceride, total protein, albumin치는 유사하였다. 2. 과배란 유기시의 평균 채란 수는 PMSG/hCG를 2.5/2.5 lU 투여군에서 11.6개, 5.0/5.0 IU 투여군에서 12.7개로 통계학적 유의 차는 인정되지 않았다. 3. 2.5/2.5 lU 투여군과 5.0/5.0 lU 투여군의 수정율은 각각 87.9%와 52%로 2.5/2.5 lU 부여군이 유의성있게 높은 성적을 나타내었고(p<0.05), 2세포기로의 발달율도 각각 유의성이 인정되는 99.0%와 90.6%였다 (p<0.05). 4. 동결정자를 이용한 체외수정에서의 수정율은 24.8%로 신선정자를 사용했을 때의 87.9% 보다 낮은 성적이었다. 5. 체외 수정란의 이식후의 산자율은 동결 2세포기 체외수정란의 경우 5마리(6.6%), 동결 정사를 이용한 체외 수정란의 경우 6마리(19.4%)와 대조군의 체외수정란의 경우 10마리(21.7%)의 새끼를 얻었다. 6. 이식후 출산한 산자의 미생물학적 검사에서 MHV(Mouse hepatitis virus)와 Staphylo-coccus aureus 등의 병원성 미생물이 무병대리모를 이용한 수정란이식에 의해 제거되었음을 확인하였다.

  • PDF