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Articles de revues sur le sujet "ATL gene family"
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Joseph, Meera, Faiza Rab, Karen Panabaker et Jeff Nisker. « ATL ». International Journal of Gynecologic Cancer 25, no 4 (mai 2015) : 584–92. http://dx.doi.org/10.1097/igc.0000000000000403.
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ObjectiveFamily physicians in Canada as reported in several studies do not recognize the importance of family history in relation to breast/ovarian cancer and thus Canadian women with strong family histories continue to develop early-onset breast cancer without the knowledge of or ability to make choices regarding increased surveillance or preventative strategies. This study explored the feelings of women who learned about their hereditary risk only after their diagnosis younger than 52 years and who eventually tested positive for a BRCA gene mutation.MethodsThirty-four such women were mailed an invitation to participate in this research including a letter of information, consent form, and discussion prompts for their written narrative response. Rigorous mixed method analyses were performed using Charmaz-based qualitative analyses as well as quantitative analyses.ResultsThirteen women (38.2%) responded with narratives for qualitative analysis from which 4 themes were coconstructed as follows: I, types of emotions; II, emotional response; III, coping with emotions; and IV, advice to women at similar risk. Women felt they should have learned about their hereditary risk from their family physician and through public education before their diagnosis. Although not experienced at the time of diagnosis, anger, frustration, and regret were experienced after receiving their BRCA results. These emotions arose from our research participants’ lack of opportunity for prior genetic counseling and testing opportunity for genetic counseling and testing.ConclusionsWith increased public and physician education, it is hoped that women with significant family histories of breast/ovarian cancer will be identified before diagnosis and given options regarding cancer surveillance and risk reduction strategies.
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Furukawa, Yoshitaka, Ryuji Kubota, Mitsutoshi Tara, Shuji Izumo et Mitsuhiro Osame. « Existence of escape mutant in HTLV-I tax during the development of adult T-cell leukemia ». Blood 97, no 4 (15 février 2001) : 987–93. http://dx.doi.org/10.1182/blood.v97.4.987.
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Abstract Although Tax protein is the main target of cytotoxic T lymphocyte (CTL) on human T-cell lymphotropic virus type I (HTLV-I)–infected cells, and Tax peptide 11 through 19 binding to HLA-A*02 has been shown to elicit a strong CTL response, there are patients with adult T-cell leukemia (ATL) bearing HLA-A*02. To explore whether there is genetic variation in HTLV-I tax that can escape CTL recognition during the development of ATL, the HTLV-I tax gene was sequenced in 55 patients with ATL, 61 patients with HTLV-I–associated myelopathy/tropical spastic paraparesis (HAM/TSP), and 62 healthy carriers, and it was correlated with the presence of HLA-A*02. First, a premature stop codon in the 5′ half of the tax gene that looses transactivation activity on the viral enhancer was observed in 3 patients with acute and 1 patient with chronic ATL. This stop codon was revealed to emerge after the viral transmission to the patient from sequence analysis in family members with ATL. Second, amino acid change in Tax peptide 11-19 was observed in 3 patients with ATL. CTL assays demonstrated that this altered Tax 11-19 peptide, observed in ATL patients with HLA-A*02, was not recognized by Tax 11-19–specific CTL. Two patients with ATL had large deletions in tax by sequencing, and 5 patients with ATL had deletions in HTLV-I by Southern blotting. These findings suggest that at some stage of ATL development, HTLV-I–infected cells that can escape the host immune system are selected and have a chance to accumulate genetic alterations for further malignant transformation, leading to acute ATL.
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Yamagata, T., J. Nishida, R. Sakai, T. Tanaka, H. Honda, N. Hirano, H. Mano, Y. Yazaki et H. Hirai. « Of the GATA-binding proteins, only GATA-4 selectively regulates the human interleukin-5 gene promoter in interleukin-5-producing cells which express multiple GATA-binding proteins. » Molecular and Cellular Biology 15, no 7 (juillet 1995) : 3830–39. http://dx.doi.org/10.1128/mcb.15.7.3830.
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Interleukin-5 (IL-5) is produced by T lymphocytes and known to support B-cell growth and eosinophilic differentiation of the progenitor cells. Using ATL-16T cells which express IL-5 mRNA, we have identified a region within the human IL-5 gene promoter that regulates IL-5 gene transcription. This cis-acting sequence contains the core binding motif, (A/T)GATA(A/G), for GATA-binding family proteins and thus suggests the involvement of this family members. In this report, we describe the cloning of human GATA-4 (hGATA-4) and show that hGATA-4 selectively interacts with the -70 GATA site within the IL-5 proximal promoter region. By promoter deletion and mutation analyses, we established this region as a positive regulatory element. Cotransfection experiments revealed that both hGATA-4 and phorbol-12-myristate-13-acetate (PMA)-A23187 stimulation are necessary for IL-5 promoter activation. The requirement for another regulatory element called CLE0, which lies downstream of the -70 GATA site, was also demonstrated. ATL-16T cells express mRNAs of three GATA-binding proteins, hGATA-2, hGATA-3, and hGATA-4, and each of them has a potential to bind to the consensus (A/T)GATA(G/A) motif. However, using ATL-16T nuclear extract, we demonstrated that GATA-4 is the only GATA-binding protein that forms a specific DNA-protein complex with the -70 GATA site. An electrophoretic mobility shift assay with extracts of COS cells expressing GATA-binding proteins showed that GATA-4 has the highest binding affinity for the -70 GATA site among the three GATA-binding proteins. When the transactivation abilities were compared among the three, GATA-4 showed the highest activity. These results demonstrate the selective role of GATA-4 in the transcriptional regulation of the IL-5 gene in a circumstance where multiple members of the GATA-binding proteins are expressed.
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Tatewaki, M., K. Yamaguchi, M. Matsuoka, T. Ishii, M. Miyasaka, S. Mori, K. Takatsuki et T. Watanabe. « Constitutive overexpression of the L-selectin gene in fresh leukemic cells of adult T-cell leukemia that can be transactivated by human T- cell lymphotropic virus type 1 Tax ». Blood 86, no 8 (15 octobre 1995) : 3109–17. http://dx.doi.org/10.1182/blood.v86.8.3109.3109.
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Abstract L-selectin is an adhesion molecule of the selectin family that mediates the initial step of leukocyte adhesion to vascular endothelium. Upon cellular activation, expression of the L-selectin gene is downregulated at both the protein and mRNA levels. To understand the mechanism of leukemic cell infiltration into organs, we studied the expression and regulation of L-selectin mRNA in fresh leukemic cells of adult T-cell leukemia (ATL) patients and investigated the response of the L-selectin promoter to human T-cell lymphotropic virus type 1 (HTLV-1) Tax, which is a viral transcriptional transactivator. Flow cytometry showed that L-selectin was expressed on fresh ATL cells along with other activation antigens. Northern blot analysis showed that ATL cells overexpressed that L-selectin mRNA and that the level was aberrantly upregulated after PMA stimulation. Studies using in situ hybridization showed expression of the L-selectin mRNA in the infiltrating leukemic cells in the liver of two ATL patients. Intravenous injection of a rat T-cell line that overexpresses L-selectin showed increased organ infiltration. The induction of Tax expression in JPX9 cells resulted in about a twofold increase in the mRNA expression levels compared with the basal level. Chloramphenicol acetyltransferase (CAT) assay after transient cotransfection showed about a fivefold transactivation of the L-selectin promoter by Tax. The serum level of the shed form of L-selectin was significantly increased in ATL patients (mean +/- SD, 4,215.4 +/- 4,111 ng/mL) compared with those of asymptomatic carriers and healthy blood donors (mean +/- SD, 1,148.0 +/- 269.0 ng/mL and 991.9 +/- 224 ng/mL, respectively). These results indicated that ATL cells constitutively overexpress the L-selectin gene that can be transactivated by HTLV-1 Tax. The overexpression of L-selectin, as well as of inflammatory cytokines, by ATL cells may provide a basis for ATL cells to attach the vascular endothelium, leading to transmigration and organ infitration.
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Tatewaki, M., K. Yamaguchi, M. Matsuoka, T. Ishii, M. Miyasaka, S. Mori, K. Takatsuki et T. Watanabe. « Constitutive overexpression of the L-selectin gene in fresh leukemic cells of adult T-cell leukemia that can be transactivated by human T- cell lymphotropic virus type 1 Tax ». Blood 86, no 8 (15 octobre 1995) : 3109–17. http://dx.doi.org/10.1182/blood.v86.8.3109.bloodjournal8683109.
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L-selectin is an adhesion molecule of the selectin family that mediates the initial step of leukocyte adhesion to vascular endothelium. Upon cellular activation, expression of the L-selectin gene is downregulated at both the protein and mRNA levels. To understand the mechanism of leukemic cell infiltration into organs, we studied the expression and regulation of L-selectin mRNA in fresh leukemic cells of adult T-cell leukemia (ATL) patients and investigated the response of the L-selectin promoter to human T-cell lymphotropic virus type 1 (HTLV-1) Tax, which is a viral transcriptional transactivator. Flow cytometry showed that L-selectin was expressed on fresh ATL cells along with other activation antigens. Northern blot analysis showed that ATL cells overexpressed that L-selectin mRNA and that the level was aberrantly upregulated after PMA stimulation. Studies using in situ hybridization showed expression of the L-selectin mRNA in the infiltrating leukemic cells in the liver of two ATL patients. Intravenous injection of a rat T-cell line that overexpresses L-selectin showed increased organ infiltration. The induction of Tax expression in JPX9 cells resulted in about a twofold increase in the mRNA expression levels compared with the basal level. Chloramphenicol acetyltransferase (CAT) assay after transient cotransfection showed about a fivefold transactivation of the L-selectin promoter by Tax. The serum level of the shed form of L-selectin was significantly increased in ATL patients (mean +/- SD, 4,215.4 +/- 4,111 ng/mL) compared with those of asymptomatic carriers and healthy blood donors (mean +/- SD, 1,148.0 +/- 269.0 ng/mL and 991.9 +/- 224 ng/mL, respectively). These results indicated that ATL cells constitutively overexpress the L-selectin gene that can be transactivated by HTLV-1 Tax. The overexpression of L-selectin, as well as of inflammatory cytokines, by ATL cells may provide a basis for ATL cells to attach the vascular endothelium, leading to transmigration and organ infitration.
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Kozako, Tomohiro, Makoto Yoshimitsu, Yohann White, Akiyoshi Aikawa, Teruhisa Shoji, Shinichiro Honda, Hiroshi Shimeno, Shinji Soeda et Naomichi Arima. « Overexpression of SIRT1, a Longevity Gene-Encoded Protein, and Induction of Apoptosis by Its Inhibition In Adult T-Cell Leukemia Cells ». Blood 116, no 21 (19 novembre 2010) : 2768. http://dx.doi.org/10.1182/blood.v116.21.2768.2768.
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Abstract Abstract 2768 Adult T-cell leukemia-lymphoma (ATL) is an aggressive peripheral T-cell neoplasm developing after a long-term infection with human T-cell leukemia virus (HTLV-1), in which NF-kB is also implicated as an exacerbation factor. Despite recent progress in both chemotherapy and supportive care for hematological malignancies, the prognosis of ATL is still poor; overall survival at 3 years is only 24%. New strategies for the therapy and prophylaxis of ATL (e.g., vaccines and novel molecular target agents) are still required. SIRT1, an NAD+-dependent histone/protein deacetylase, plays a crucial role in various physiological processes, such as aging, metabolism, neurogenesis and apoptosis, due to its ability to deacetylate numerous substrates, such as histone and NF-kB. Here, we assessed how SIRT1 is regulated in primary ATL cells and leukemic cell lines. SIRT1 expression in ATL patients was significantly higher than that in healthy controls, especially in the acute type. Sirtinol, a SIRT1 inhibitor, induced significant growth inhibition or apoptosis in cells from ATL patients and leukemic cell lines, especially HTLV-1-related cell lines (S1T and MT-2). Sirtinol-induced apoptosis was mediated by activation of the caspase family, and inactivation of NF-kB, reducing IkBα phosphorylation. Interestingly, NAD+ augmented sirtinol-induced apoptosis following deacetylation of NF-kB via NAD+-dependent deacetylase. Thus, the SIRT1 inhibitor acted as a tumor suppressor, where NAD+ accelerated the SIRT1 inhibitor-induced apoptosis. These results suggest that SIRT1 is a crucial antiapoptotic molecule in ATL cells, and that SIRT1 inhibitors may be useful therapeutic agents for leukemia, especially in patients with ATL. Figure 1. SIRT1 inhibitor reduces viability of leukemic cell lines. Cell lines were incubated at 1×105 cells/mL in the presence of various concentrations of sirtinol for 72 h. Proliferation of cell lines in the absence or presence of the indicated concentrations of sirtinol was assessed by WST-8 assay. Data are means ± S.D. from 3 independent experiments. Figure 1. SIRT1 inhibitor reduces viability of leukemic cell lines. Cell lines were incubated at 1×105 cells/mL in the presence of various concentrations of sirtinol for 72 h. Proliferation of cell lines in the absence or presence of the indicated concentrations of sirtinol was assessed by WST-8 assay. Data are means ± S.D. from 3 independent experiments. Disclosures: No relevant conflicts of interest to declare.
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Morosetti, R., N. Kawamata, AF Gombart, CW Miller, Y. Hatta, T. Hirama, JW Said, M. Tomonaga et HP Koeffler. « Alterations of the p27KIP1 gene in non-Hodgkin's lymphomas and adult T- cell leukemia/lymphoma ». Blood 86, no 5 (1 septembre 1995) : 1924–30. http://dx.doi.org/10.1182/blood.v86.5.1924.bloodjournal8651924.
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The protein p27KIP1 belongs to a recently identified family of proteins termed cyclin-dependent kinase inhibitors (CDKIs). These proteins play an important role in regulating cell-cycle progression and loss of their function has been implicated in tumorigenesis. Transforming growth factor beta (TGF-beta) may induce cell growth arrest through p27 activation. TGF-beta often loses its ability to arrest growth of transformed cells; this could potentially occur through a defect in p27. To determine the role of p27 in tumorigenesis, we examined its mutational status in 74 non-Hodgkin's lymphomas (NHLs) (52 of B-cell phenotype, 22 of T-cell phenotype), 5 lymphoma cell lines, and 42 adult T-cell leukemias/lymphomas (ATLs) using polymerase chain reaction- single strand conformational polymorphism (PCR-SSCP) and Southern blot analyses. A nonsense mutation (stop codon) that could result in expression of a truncated nonfunctional p27 protein was detected at codon 76 in one case of acute lymphomatous ATL, but not in matched normal tissues. Previously undescribed polymorphisms were also identified at codon 109 in the lymphomas and at codon 55 in the ATLs. Two homozygous deletions of the p27 gene were detected in one case of B- immunoblastic NHL and in one case of acute ATL by Southern blot hybridization. These results indicate that p27 gene alterations are rare events in NHLs and ATLs, but may play an important role in the pathogenesis of some hematologic malignancies.
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Serrano, Mario, Socorro Parra, Luis D. Alcaraz et Plinio Guzmán. « The ATL Gene Family from Arabidopsis thaliana and Oryza sativa Comprises a Large Number of Putative Ubiquitin Ligases of the RING-H2 Type ». Journal of Molecular Evolution 62, no 4 (22 mars 2006) : 434–45. http://dx.doi.org/10.1007/s00239-005-0038-y.
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Huang, Yan, Peifang Jiang, Jiazheng Li, Yanxin Chen, Zhengjun Wu, Lingyan Wang, Ting Yang et Jianda Hu. « Single-Cell RNA Sequencing Unveils the Hallmarks of Populations at Different Stages of HTLV-1 Infection ». Blood 138, Supplement 1 (5 novembre 2021) : 3323. http://dx.doi.org/10.1182/blood-2021-152438.
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Abstract Background Adult T-cell leukemia-lymphoma (ATL) is an aggressive mature T-cell neoplasm caused by human T -cell leukemia virus type 1 (HTLV-1). Up to 5% of infected individuals develop to ATL. HTLV-1 preferentially infects CD4 + T cells, and stimulates cell proliferation and prevents cell death by apoptosis. The viral oncogene-encoded proteins, Tax and HBZ, play important roles in viral infection and cell immortalization. However, the host factor of developing from carrier to patient is not clear. Results To characterize the heterogeneity of ATL patients, we performed single-cell RNA-sequencing (10x Genomics) analysis on single cell suspensions isolated from PBMCs of nine samples, including three ATL patients, three HTLV-1 asymptomatic carriers as well as three healthy donors (HD). We acquired 82977 high-quality cells with a median of 1718 genes detected per cell. Unsupervised clustering using Seurat followed by visualization in t-Stochastic Neighbor Embedding (t-SNE) identified 29 distinct cell clusters (Figure 1A). The single cell profiling of ATL patients were significantly different from that of carriers and healthy donors, while the latter two had little difference (Figure 1B). Based on singleR packages and marker genes of each cluster, 4 major cell populations (T cells, NK cells, B cells and myeloid cells) and other rare cell types were annotated, such as erythrocyte cluster and eosinophils cluster. We observed an enrichment of CD4 + T cell from patients in 4 cluster (Figure 1C), which proportion of cells was higher than that of carriers and healthy donors. According to cell type annotation, cells from cluster 11 were CD4 + CD25 + Foxp3 + Treg cells. Based on the increasing proportion of cluster 11 in healthy people, carriers and patients, without significant statistical differences, we assumed that Foxp3 + Treg cells were involved in the evolution of ATL tumor cells. That was identical with published literatures. To investigate the differences between tumor and normal CD4 + T cell, the gene expression was compared among 7 clusters of CD4 + T cell from three groups. Using a threshold of p value < 0.05 and | fold change| >2. Through integrated analysis, we identified 26 commonly upregulated genes (gene expression level: patients > carriers > HD) and 9 downregulated genes (gene expression level: patients < carriers < HD. To further analyze the biological function of the common DEGs, gene ontology (GO) analysis showed that these genes could be mainly categorized into plasma membrane and protein binding. Subsequently, we validated the mRNA expression level of upregulated common DEGs among three groups by qRT-PCR. The isolated CD4 + T cell using CD4 microbeads of a total of 6 patients, 3 carriers and 9 normal specimens were included. The result showed that the mRNA expression levels of gene CADM1 and RGS13 in patients were higher than those in carriers and healthy donors, although there was no statistical difference between patients and carriers, and the expression levels of carriers tended to be higher than those in normal people (Figure 1D and E). Previously, CADM1 has been revealed to be highly expressed in HTLV-1-infected CD4 + T cells. Our study confirmed this result by single-cell profiling. RGS13, a member of the regulators of G protein signaling (RGS) family, participates in cellular communication. The role of RGS13 in ATL needs to be investigated. Conclusions This study is the first time to analyze the single-cell RNA level of ATL patients, HTLV-1 virus carriers and normal people. The peripheral blood cell composition of the patient is significantly different from that of the carriers and healthy donors, while it is similar between carriers and normal people. CD4 + T cells are the main cell population of patients. The proportion of CD4 + CD25 + Foxp3 + Treg cells increased gradually in healthy people, carriers and patients. DEGs analysis showed that CADM1 and RGS13 were highly expressed in CD4 + T cells of patients, followed by carriers, validated by 18 clinical samples. However, the molecular mechanism of RGS13 in the process from HTLV-1 infection to ATL needs to be further studied. Figure 1 Figure 1. Disclosures Hu: Astellas Pharma, Inc.: Research Funding.
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Kurita, Daisuke, Jun-ichirou Yasunaga, Azusa Tanaka, Mahgoub Mohamed et Masao Matsuoka. « Dynamic Changes of Chromatin Structure and Transcriptome By Transient Expression of HTLV-1 Tax in ATL Cells ». Blood 132, Supplement 1 (29 novembre 2018) : 4094. http://dx.doi.org/10.1182/blood-2018-99-111125.
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Abstract Adult T-cell leukemia-lymphoma (ATL) is a fatal malignancy of CD4+ T cells, which is caused by human T-cell leukemia virus type 1 (HTLV-1). HTLV-1 encodes two oncogenic viral factors, Tax and HTLV-1 bZIP factor (HBZ) in the sense and antisense of the provirus respectively. HBZ is constitutively expressed in infected cells and plays critical roles for cell proliferation. Tax potently promotes viral replication and activates various oncogenic signaling pathways in HTLV-1 infected cells; however, Tax expression is generally suppressed in infected cells owing to its high immunogenicity. Therefore, the dynamics of Tax expression and contribution of oncogenic transformation by Tax in HTLV-1 infected cells have not been well elucidated. Recently, we have reported that Tax is transiently expressed in a small subpopulation of ATL cells, which induces drastic changes in the host transcriptional profile (Mahgoub M., et al. Proc Natl Acad Sci USA. 2018). Moreover, the single cell analysis showed that expression of anti-apoptotic and NF-kB related genes were upregulated in Tax-expressing cells compared to Tax-non-expressing cells. HBZ expression was increased in Tax-non-expressing cells than Tax-expressing cells, suggesting that HBZ may regulate cell proliferation in a different time phase from Tax. On the other hand, precise mechanisms for regulation of host gene expression by transient Tax expression are not well known. In this study, we analyzed structural change of host chromatin accompanied by transient Tax expression to clarify the transcriptional dynamics of host genes in ATL cells. ATL cell lines (MT-1 and KK-1), which express EGFP under the control of Tax, were used to sort Tax-expressing and -non-expressing cells by a cell sorter, and each population was subjected to H3K27ac ChIP-seq and ATAC-seq analyses. DNA libraries were quantified and sequenced on Illumina NextSeq 500 (single-end) for ChIP-seq, and on Illumina Hiseq 4000 (paired-end) for ATAC-seq, respectively. H3K27ac ChIP-seq data showed that the peaks correlated with Tax expression were observed in many genetic loci including NF-kB related genes. Among Tax-expressing MT-1 cells, H3K27ac were highly enriched super-enhancers, such as IL2RA, TRAF3, TNFRSF8, PHF13 loci, compared to Tax-non-expressing cells. There were more H3K27ac-marked active enhancers in Tax-expressing cells than Tax-non-expressing cells across the entire region, suggesting that global structural change may occur in Tax-expressing cells. Using the data of ATAC-seq, pathway analyses were performed by GREAT. This analysis revealed that the pathways associated with immune activation, such as Toll-like receptor signaling, TNFR2 signaling, IL-2 signaling, and Th1/Th2 differentiation pathways were significantly enriched in Tax-expressing cells. Analysis of genome-wide distribution of motifs in open chromatin region, were carried out with HOMER, and result showed that motifs of NF-kB, and AP-1 family (e.g., JunB, Fra1, Fra2) were significantly enriched in Tax-expressing cells compared to Tax-non-expressing cells, which is consistent with the results of pathway analyses of RNA-seq. The genome-wide motif footprinting analysis was performed using Protein interaction quantitation (PIQ) methods. It was found that motifs of NF-kB, and AP-1 family (e.g., JunB, Fra1, Fra2) were occupied in large number of regions and showed higher DNA accessibility in Tax-expressing cells. In contrast, motif of CTCF was likely occupied in large number of regions and exhibit higher DNA accessibility in Tax-non-expressing cells. Importantly, mRNA levels of NF-kB and AP-1 transcription factors were significantly higher in Tax-expressing than Tax-non-expressing cells. These findings suggest that structural changes of NF-kB and AP-1 family recognition sites, and activation of pathways related to these factors could trigger global transcriptional changes in host genome by transient Tax expression, which is the critical event for persistent infection of HTLV-1 and leukemogenesis of ATL. Disclosures Matsuoka: Bristol Myers Squibb: Research Funding.
Thèses sur le sujet "ATL gene family"
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Moussawi, Jihad. « PtaRHE1, a poplar RING-H2 protein of ATL family, with a regulatory role in vascular tissues development ». Doctoral thesis, Universite Libre de Bruxelles, 2014. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209344.
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Les protéines possédant un domaine RING (REALLY INTERESTING NEW GENE) avec une activité E3 ligase sont largement présentes chez les plantes, jouent des rôles importants dans la régulation de plusieurs processus par la reconnaissance d’une protéine cible pour l’ubiquitination. Auparavant, il a été montré que l'expression de PtaRHE1, codant une protéine contenant un domaine RING-H2 avec une activité E3 ligase, est associée à la mise en place de la croissance secondaire chez le peuplier. Dans le cadre de cette thèse, nous avons démontré que PtaRHE1 est mono-ubiquitiné in vitro en présence de l’E2 du peuplier PtaUbC5a. Par hydridation in situ et Western blot, nous montrons que PtaRHRE1 et la protéine correspondante sont exprimés dans les tissus vasculaires de la tige, c'est-à-dire le phloème, le cambium et le xylème. Par comparaison avec les plantes de type sauvage, la sous-expression de PtaRHE1 suite à l’expression d’un microARN (i) a donné lieu à une modification dans la morphologie des fibres secondaire de phloème avec une plus forte densité cellulaire et des paroi de fibres plus mince, (ii) à une modification de la qualité de lignine avec moins d’unité S au niveau des tissus de l’écorce, ces résultats suggèrent un rôle de PtaRHE1 dans la formation et / ou la maturation des fibres. La sur-expression de PtaRHE1 chez les peupliers engendre un phénotype pléiotropique caractérisé par l’enroulement des feuilles et une inhibition du développement racinaire. L’expression du gène codant pour le facteur de transcription WRKY23 est positivement corrélée à celui de PtaRHE1 dans le xylème de la tige des lignées sur-exprimant ou sous-exprimant PtaRHE1. Sur base d’un modèle, nous suggérons un rôle pour le couple PtaRHE1/PtaWRKY23 dans le développement des tissus vasculaires. De plus, nous avons montré que l'expression de PtaRHE1 et l'accumulation de la protéine correspondante sont modulées par l'humidité de l’air et du sol ainsi que par l'acide abscissique. Les informations présentées dans ce travail indiquent un rôle de PtaRHE1 au cours de développement de la plante ainsi que pendant la réponse au stress biotique et abiotiqueDoctorat en Sciences agronomiques et ingénierie biologique
info:eu-repo/semantics/nonPublished
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Bryson, Christen. « The "All-American" Couple. Dating, Marriage and the Family during the long 1950s with a Foray into Boise, Idaho and Portland, Oregon ». Thesis, Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCA106.
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Cette thèse espère contribuer à l’histoire socio-culturelle du couple américain durant la période d’après-guerre. En discutant du récit national au travers d’aspects qui sont souvent considérés comme évident – génération, âge, situation géographique, individu et institution ainsi que cultures locales et nationales – ce travail essaie de nuancer ces définitions catégoriques qui en sont venues à représenter les années 1950 et 1960 tout comme l’ubiquité du discours sur la culture nationale. Le mariage, la famille, le genre, la sexualité, faire la cour (dating), les pratiques sexuelles et la culture des jeunes forment le cadre par lequel cette étude essaie d’éclairer la norme incarnée par le couple blanc, hétérosexuel, de classe moyenne. En introduisant deux villes du nord-ouest des Etats-Unis – Boise dans l’Etat d’Idaho et Portland dans l’Etat d’Oregon – dans une réflexion portant sur le récit national, cet essai tente d’élargir l’histoire locale de ces deux villes et de complexifier l’analyse des conventions sociales. L’histoire orale associée à des documents issus des archives d’universités locales et d’annuaires étudiants (yearbooks) ont permis à cette étude d’observer comment l’expérience d’américains « ordinaires » diffère et s’accorde avec le récit national dans des villes qui n’ont reçus que peu d’attention universitaire durant cette période et sur ces thèmes. Les informations des recensements, les documents et les discours politiques de l’époque étayent le modèle répandu d’un couple cent pour cent américain, alors que les films éducatifs, les livres de bonnes manières et les rubriques de chroniqueurs ont permis à ce travail d’explorer le processus au travers duquel cet idéal s’est imposé. Ce modèle connait un âge d’or pendant la « longue décennie » des années 1950. La mémoire collective nous dit qu’il constitue alors le dernier phare de la tradition familiale mais aussi peut-être son point de rupture. Cet essai défend l’idée que cet archétype n’était ni traditionnel ni catalyseur de bouleversements. Le couple blanc et hétérosexuel de classe moyenne était plutôt le point culminant de facteurs politiques, sociaux, économiques et culturels qui ont finalement ébranlés le couple « traditionnel », ce modèle ayant échoué à véritablement incarner les idéaux de la nation qu’il était supposé représenter. A la fin de la « longue décennie » des années 1950 cette norme représentait un statu quo, alors que les jeunes qui devaient perpétuer son héritage avaient consciemment et inconsciemment déjà commencé à saper ses fondationsThis thesis hopes to contribute to the postwar socio-cultural historiography on the American couple. In putting the national narrative into a discussion with some of its oft taken for granted aspects—generation, age, location, the individual and the institution, and local and national cultures—, this work attempts to provide nuance to the categorical definitions that have come to characterize the 1950s and the 1960s as well as the pervasiveness of the national culture’s voice. Marriage, family, gender, sexuality, dating, sexual activity, and youth culture are the framework through which this study has tried to elucidate the standard embodied in the white, middle-class, heterosexual couple. In incorporating two cities in the northwest United States—Boise, Idaho and Portland, Oregon—into a discussion about the national narrative, this dissertation tries to widen their local histories and complexify national convention. Oral histories paired with documents from the local universities’ archives and yearbooks have allowed for this work to look at how “average” Americans’ experiences differed from and coincided with the national narrative in places that have received very little scholarly attention on this time and these themes. Census data, scientific studies, political documents and speeches substantiate the pervasiveness of the “All-American couple,” while educational films, etiquette books, and advice columns have helped this thesis explore the process through which the ideal came into being. This model experienced a heyday during the long 1950s. Dominant memory tells us that either it was the last beacon of familial tradition or the breaking point for change. This dissertation contends that the archetype was neither traditional nor the catalyst for change. Rather the white, heterosexual middle-class couple was a culmination of political, social, economic, and cultural factors that ultimately undermined the “traditional” couple because it failed to truly embody the ideals of the nation it was purported to represent. By the end of the long 1950s, this model had become the status quo, but the young people who were to carry it into the future had consciously and unconsciously began chipping away at its foundations
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PEKÁČOVÁ, Aneta. « Characterisation of \kur{Drosophila melanogaster} mutated for all genes of the Sirtuin family ». Master's thesis, 2019. http://www.nusl.cz/ntk/nusl-394803.
Texte intégralRésumé :
The aim of my study was to create a Drosophila line lacking the expression of all Sirtuin genes, check its developmental phenotype and characterise its response in stress conditions. The flies had bigger weight than controls, they had decreased fertility and fecundity and they developed more slowly. They showed a trend towards increased resistance to chill coma, but they did not show a significant difference in starvation or oxidative stress assay. Its effect on lifespan is being investigated.
Livres sur le sujet "ATL gene family"
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Cassel, Daniel Kolb. A genea-biographical history of the Rittenhouse family and all its branches in America : With sketches of their descendants, from the earliest available records to the present time, including the birth of Wilhelm in 1644. Philadelphia, Pa : Rittenhouse Memorial Assoc., 1985.
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Powell, Craig M. SHANK Gene Family and Autism. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199744312.003.0011.
Texte intégralRésumé :
SHANK3 deletion/mutation is an independently replicated, genetic cause of autism (Durand et al., 2007; Gauthier et al., 2009; Moessner et al., 2007) and is the major causative gene in the 22q13 deletion syndrome known as Phelan-McDermid syndrome (Bonaglia et al., 2011; Bonaglia et al., 2001; Bonaglia et al., 2006; Chen et al., 2011; Delahaye et al., 2009; Dhar et al., 2010; Jeffries et al., 2005; Misceo et al., 2011; Sarasua et al., 2011; Wilson et al., 2003). Patients with Phelan-McDermid syndrome uniformly have delayed or absent speech and many carry the diagnosis of autism spectrum disorder (Cusmano-Ozog, Manning, & Hoyme, 2007; Havens, Visootsak, Phelan, & Graham, 2004). More recently, mutations in SHANK2 have been implicated in autism and intellectual disability (Berkel et al., 2010; Pinto et al., 2010). These recent human genetic findings provide a compelling rationale for developing a comprehensive understanding of SHANK3 function in synapses, circuits, and behavior, resulting in three different novel genetic mouse models published by more than four independent laboratories (Bangash et al., 2011; Bozdagi et al., 2010; Peca et al., 2011; Wang et al., 2011). Such studies shed light on the underlying biology of autism caused by SHANK3 mutations. This chapter examines in detail the evidence supporting a role for SHANK genes in autism and intellectual disability as well as insights from the recent genetic animal models of SHANK3 mutations.
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Johnston, Trevin. Gene Simmons PhotoBook : Compelling Photos of Gene Simmons Collection As a Perfect Gift Idea for Fans Family Relatives Friends Lover All Age. Independently Published, 2022.
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Alves, Ines Teles, Jan Trapman et Guido Jenster. Molecular biology of prostate cancer. Sous la direction de James W. F. Catto. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199659579.003.0059.
Texte intégralRésumé :
Prostate cancer is a heterogeneous disease that arises through the acquisition of key malignant hallmarks. At the molecular level, prostate tumours are dependent upon the androgen receptor pathway, which affects cell function, growth, and behaviour through downstream androgen-regulated genes. Prostate cancer requires this activity and manipulates the AR pathway to maintain signalling. For example, mutation of the AR (to bind ligands other than androgens) or amplification/duplication of the AR allows signalling to continue in the absence of testosterone. Around 50% of prostate cancers have a gene fusion between the androgen-regulated component of the TMPRSS2 gene and a transcription factor (e.g. ETS family members ERG and ETV1). This results in aberrant androgen stimulated cell growth. Current research is using molecular knowledge to identify biomarkers, such as PCA3, and new therapies, such as enzalutamide or abiraterone acetate.
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Nielsen, François. Genes and Status Achievement. Sous la direction de Rosemary L. Hopcroft. Oxford University Press, 2018. http://dx.doi.org/10.1093/oxfordhb/9780190299323.013.22.
Texte intégralRésumé :
A number of human traits that are predictive of socioeconomic success (e.g., intelligence, certain personality traits, and educational attainment) or reflective of success (e.g., occupational prestige and earnings) have been found to be substantially affected by individual genetic endowments; some outcomes, such as educational attainment, are also affected by the family environment, although usually to a lesser extent. The associations among status-related traits are themselves largely due to genetic causes. By reshuffling the genes of parents at each generation, sexual reproduction produces a regression of status-relevant traits of offspring toward the population mean—downward for high-status parents, upward for low-status parents—generating social mobility in an achievement-oriented society. Incorporating the quantitative genetic decomposition of trait variance into genetic, shared environmental, and nonshared environmental sources into the classic sociological model of status achievement allows for a better understanding and measurement of central social stratification concepts, such as opportunity and ascription.
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Syrris, Petros, et Alexandros Protonotarios. Arrhythmogenic right ventricular cardiomyopathy : genetics. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198784906.003.0359.
Texte intégralRésumé :
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disorder of the heart muscle which is typically inherited in an autosomal dominant manner. It is believed to be familial in over 50% of cases. A recessive mode of inheritance has also been reported in syndromic cases with cardiocutaneous features. The classic form of the disorder is considered to be ‘a disease of the desmosome’ as pathogenic variants have been identified in five genes encoding key desmosomal proteins: plakoglobin, desmoplakin, plakophilin-2, desmoglein-2, and desmocollin-2. Mutations in these genes account for 30–50% of ARVC cases. A further eight non-desmosomal genes have also been implicated in the pathogenesis of the disorder but only account for rare cases. Studies of patients with ARVC-associated gene mutations have revealed marked genetic heterogeneity and very limited genotype–phenotype correlation. Disease expression often varies significantly amongst individuals carrying the same mutation. It has been proposed that the presence of more than one sequence variant is required to determine overt clinical disease and patients with multiple variants have a more severe phenotype compared to single variant carriers. Identification of a potentially pathogenic variant comprises a major criterion in the diagnosis of ARVC but informative integration of genetic testing into clinical practice remains challenging. Gene testing should be used to identify asymptomatic family members at risk and only aids diagnosis in cases of high suspicion for ARVC, along with other evident features of the disease already present. However, genetic findings should be used with caution in clinical practice and their interpretation must be performed in expert centres.
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Pezzini, Alessandro. Genetics. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198722366.003.0011.
Texte intégralRésumé :
Ischaemic stroke is a heterogeneous multifactorial disorder. Although epidemiological data from twin and family studies provide substantial evidence for a genetic basis for stroke, the contribution of genetic factors identified so far is small. Large progress has been made in single-gene disorders associated with ischaemic stroke, particularly at young age. By contrast, little is known about the genes associated with multifactorial stroke. The reported genome-wide association studies of ischaemic stroke have shown that no single common genetic variant imparts major risk, but data on early-onset disease are scarce in this regard. Larger studies with samples numbering in the thousands are ongoing to identify common variants with smaller effects on risk. This approach, in addition with new analytic techniques, will likely contribute to the identification of additional genes, novel pathways, and eventually novel therapeutic approaches to cerebrovascular disorders in the near future. The aims of this review are to summarize data on clinical, genetic, and epidemiologic aspects of monogenic conditions associated with juvenile ischaemic stroke, to discuss recent findings and methodological limitations regarding the genetics of sporadic ischaemic stroke in this age category, and to provide a brief overview of the potential future approaches to stroke genetics.
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Ingles, Jodie, Charlotte Burns et Laura Yeates. Genetic counselling. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198784906.003.0145.
Texte intégralRésumé :
Cardiac genetic counselling is an emerging but important subspecialty. The qualifications of cardiac genetic counsellors depend on the country of practice, but at a minimum they are Master’s-level trained health professionals with expertise in genetics, and are integral members of the multidisciplinary inherited cardiovascular disease clinic. Though the framework is diverse in different countries, key roles include investigation and confirmation of family history details, discussion of inheritance risks and facilitation of cardiac genetic testing, communication with at-risk relatives, and increasingly, curation of genetic test results. The use of next-generation sequencing technologies has seen a recent shift in the uptake of genetic testing, due to greater availability and lowered costs. As these gene tests become more comprehensive, including large panels of genes and even whole exome or whole genome sequencing, the need for cardiac genetic counsellors to provide informed consent, appropriate pre- and post-test genetic counselling, and ongoing curation of the variants identified is evident. Finally, given the improved understanding of the psychological implications of living with a cardiovascular genetic disease, cardiac genetic counsellors are integral in delivering psychosocial care and identifying patients requiring intervention with a clinical psychologist.
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Cassel, Daniel Kolb. A Genea-Biographical History Of The Rittenhouse Family V1 : And All Its Branches In America, With Sketches Of Their Descendants (1893). Kessinger Publishing, LLC, 2010.
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Hertz, Rosanna, et Margaret K. Nelson. Random Families. Oxford University Press, 2018. http://dx.doi.org/10.1093/oso/9780190888275.001.0001.
Texte intégralRésumé :
This is a book about unprecedented families—networks of strangers linked by genes, medical technology, and the human desire for affinity and identity. It chronicles the chain of choices that couples and single mothers make—how to conceive, how to place sperm donors in their family tree, and what to do when it suddenly becomes clear that there are children out there that share half their child’s DNA. Do shared genes make you family? Do children find anything in common? What becomes of the random networks that arise once the members of the families of donor siblings find one another? Based on over 350 interviews with children and parents from all over the United States, Hertz and Nelson explore what it means to children to be a donor sibling and what it’s like to be a parent who discovers four, six, or even a dozen children who share half the DNA of one’s own child. At the heart of their investigation are remarkable relationships woven from tenuous bits of information and fueled by intense curiosity. The authors suggest that donor siblings are expanding the possibilities for extended kinship in the United States.
Chapitres de livres sur le sujet "ATL gene family"
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Andisi, Kivisi C., et Abdirahman I. Abdi. « Analysis of var Gene Transcription Pattern Using DBLα Tags ». Dans Methods in Molecular Biology, 173–84. New York, NY : Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2189-9_14.
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AbstractThe Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) antigens, which are encoded by a multigene family called var genes, are exported and inserted onto the surface of the infected erythrocytes. PfEMP1 plays a key role in the pathogenesis of severe malaria and are major targets of naturally acquired immunity. Studying the expression pattern of var genes in P. falciparum clinical isolates is crucial for understanding disease mechanism and immunity to malaria. However, var genes are highly variable, which makes it difficult to study their expression in clinical isolates obtained directly from malaria patients. In this chapter, we describe an approach for analysis of var gene expression that targets a region referred to as DBLα tag, which is relatively conserved in all var genes.
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Reed, John C. « Roles of Apoptosis-Regulating Bcl-2 Family Genes in AML ». Dans Targeted Therapy of Acute Myeloid Leukemia, 47–65. New York, NY : Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-1393-0_3.
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Ravelonandro, Michel, et Pascal Briard. « Biogenesis and functional RNAi in fruit trees. » Dans RNAi for plant improvement and protection, 40–46. Wallingford : CABI, 2021. http://dx.doi.org/10.1079/9781789248890.0005.
Texte intégralRésumé :
Abstract In plants, genome expression is linked to the transcribed mRNAs that are synthesized by RNA polymerase. Following its move to the cytoplasm, the generated mRNA is briefly translated to the encoded protein. If transcription and translation are dependent on the family of RNA polymerase, these two phenomena could be interfered with through the process designated as gene regulation. Thus, large molecules of RNA (single-stranded or double-stranded) consequently sliced into small molecules produce nascent small interfering RNA ranging from 21 to 27 nucleotides. This chapter revisits the biogenesis of these two types of RNAi, miRNA and siRNA, and notably their involvement in plant gene regulation. Following their sequential transcription and their specific involvement, we will consider the sources and roles of RNA interference in plants and we will look at their detection in fruit crops. We discuss their applications and the risk assessment studies in fruit crops.
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Ravelonandro, Michel, et Pascal Briard. « Biogenesis and functional RNAi in fruit trees. » Dans RNAi for plant improvement and protection, 40–46. Wallingford : CABI, 2021. http://dx.doi.org/10.1079/9781789248890.0040.
Texte intégralRésumé :
Abstract In plants, genome expression is linked to the transcribed mRNAs that are synthesized by RNA polymerase. Following its move to the cytoplasm, the generated mRNA is briefly translated to the encoded protein. If transcription and translation are dependent on the family of RNA polymerase, these two phenomena could be interfered with through the process designated as gene regulation. Thus, large molecules of RNA (single-stranded or double-stranded) consequently sliced into small molecules produce nascent small interfering RNA ranging from 21 to 27 nucleotides. This chapter revisits the biogenesis of these two types of RNAi, miRNA and siRNA, and notably their involvement in plant gene regulation. Following their sequential transcription and their specific involvement, we will consider the sources and roles of RNA interference in plants and we will look at their detection in fruit crops. We discuss their applications and the risk assessment studies in fruit crops.
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Guimaraes, Claudia Teixeira, et Jurandir Vieira de Magalhaes. « Recent molecular breeding advances for improving aluminium tolerance in maize and sorghum. » Dans Molecular breeding in wheat, maize and sorghum : strategies for improving abiotic stress tolerance and yield, 318–24. Wallingford : CABI, 2021. http://dx.doi.org/10.1079/9781789245431.0018.
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Abstract Citrate transporters belonging to the multidrug and toxic compound extrusion (MATE) family of membrane transporters in sorghum and maize, SbMATE and ZmMATE1, respectively, play a major role in aluminium (Al) tolerance. However, these MATE members show regulatory differences, as well as peculiarities in their genetic effect and mode of action. These aspects, which are discussed in this chapter, have to be considered to design successful breeding programmes in order to achieve maximum Al tolerance and, consequently, to improve grain and biomass production in regions of the world with Al toxicity. As shown in this chapter, target genes with major effects and molecular tools are available for marker-assisted breeding for improving Al tolerance both in sorghum and maize. However, wide adaptation to acid soils should be sought by pyramiding genes controlling different traits such as drought tolerance, P acquisition, resistance to diseases and other stresses commonly found in each agroecological environment.
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Pintzas, Alex. « Signal Regulated Gene Expression Mediated by Transcription Factors-Members of AP-1 and ETS/SRF Family Members : Pathways for Potential Therapeutic Intervention ». Dans Chemical Probes in Biology Science at the Interface of Chemistry, Biology and Medicine, 35–38. Dordrecht : Springer Netherlands, 2003. http://dx.doi.org/10.1007/978-94-007-0958-4_3.
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« Molecular and medical genetics ». Dans Oxford Assess and Progress : Medical Sciences, sous la direction de Jade Chow, John Patterson, Kathy Boursicot et David Sales. Oxford University Press, 2012. http://dx.doi.org/10.1093/oso/9780199605071.003.0015.
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Genetics has come a long way since the pioneering work on plant inheritance patterns by the Augustinian monk, Gregor Mendel, in the mid-nineteenth century. In the first decades of the twentieth century, Archibald Garrod, a London physician, was studying a class of diseases which came to be called ‘inborn errors of metabolism’. As a result of studies on conditions such as alkaptonuria (a rare disease involving altered phenylalanine and tyrosine metabolism, with production of dark urine and a rare form of arthritis), Garrod postulated the ‘one gene – one enzyme’ hypothesis, namely that most inborn errors of metabolism result from errors in single genes that code for enzymes. This showed remarkable foresight, since the actual nature of DNA and the way genes are transcribed and translated was not fully established until the work of Watson and Crick and others in the 1950s and beyond. One gene – one enzyme (or one protein) has now been modified to become one gene – one peptide, but the principle holds. As more has been learned about human genetics and genetic mutation, especially following the Human Genome Project, the number of genetic defects known to underpin diseases and predisposition to disease has burgeoned. All this new knowledge is adding to earlier knowledge of diseases that were detected by studying chromosome number (cytogenetics) or by examining family pedigrees for the patterns of disease inheritance. Studies of family pedigrees exposed the genetic nature of diseases as diverse as cystic fibrosis, haemophilia, sickle-cell disease, and Huntington’s disease. Nowadays, a doctor’s training in medical genetics will cover the genetic code, gene expression, gene regulation and mutation, cancer genetics, chromosomal abnormalities, abnormalities at the gene level, genetic polymorphism, the principles of gene therapy, and the emerging science of pharmacogenetics. As it has become evident not only that diseases are a direct expression of particular genes or mutations, but that genetic predisposition can be identified for a great number of diseases, both ethical and therapeutic questions arise. For example, will every healthy person want or need to have knowledge of his or her own future risk for specific diseases? To what extent will gene therapies or pharmacogenetics have to be tailored to an individual’s genetic constitution, and at what financial cost?
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Thapar, Anita, et Peter McGuffin. « Quantitative genetics ». Dans New Oxford Textbook of Psychiatry, 212–22. Oxford University Press, 2012. http://dx.doi.org/10.1093/med/9780199696758.003.0028.
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In this chapter the authors consider the theoretical basis of inheritance and possible sources of phenotypic variation and familial resemblance. The investigation of the genetic basis of psychiatric disorders first requires us to examine to what extent genes and environment contribute to a given disorder or trait. Secondly, we need to know how genes and environmental influences exert their risk effects and finally we have to investigate the genetic basis of disorders at a molecular level. Traditional methods in psychiatric genetics research include family, twin, and adoption studies. Family studies enable us to examine to what extent a disorder or trait aggregates in families. Familiality of a disorder can of course by explained by shared environmental influences as well as by shared genes. Twin and adoption studies allow us to disentangle the effects of genes and shared environment. The statistical methods used in quantitative genetics may seem complex, the principles are straightforward. Here the authors consider the methods of analyses that are most commonly used for examining the contribution of genetic and environmental factors, to psychiatric disorders and traits. Finally, they discuss gene mapping, and molecular genetic studies investigating gene–environment interplay and intermediate phenotypes.
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Abdullah, Samaa. « Colorectal Cancer Stages, Progress, Genetic Predisposition, and Immune Surveillance ». Dans Recent Understanding of Colorectal Cancer Treatment [Working Title]. IntechOpen, 2022. http://dx.doi.org/10.5772/intechopen.105982.
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Colon cancer (CC) is highly malignant and is considered the second cause of death worldwide. However, the overall CC survival rate is improving due to the rapid development of screening tools and improved treatment options. This raised the need to develop effective approaches for medical intervention. Moreover, CC is classified into four stages: stages I, II, III, and IV. On the other hand, the driver genes played vital regulatory roles in essential pathways for cellular division, cell survival, fate, and genome stability. For example, the RAS mitogen-activated protein kinase is essential for cellular division. Additionally, carcinogenesis is linked to the mutations, which are reported in the Kirsten rat sarcoma viral oncogene homolog gene, Adenomatous Polyposis Coli gene, Tumor Protein 53 gene, and SMAD family member 4 genes, Mothers against decapentaplegic homolog 4 gene. In addition, the immune system reactions have different impacts on CC growth and management. The inflammation process is described as one of the innate responses. The inflammation process is initiated and exacerbated by various types of immune cells included the macrophages, and neutrophils for their activation, margination, extravasation, and migration to the damaged tissue. The preferred role of inflammation against cancer is at stages I and II.
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Felice, Daniela, Anand Gururajan, Olivia F. O’Leary et John F. Cryan. « Gene–environment interactions in animal models of depression and anxiety ». Dans Genes, brain, and emotions, 63–76. Oxford University Press, 2019. http://dx.doi.org/10.1093/oso/9780198793014.003.0006.
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Depression and anxiety disorders cause the greatest global disability in terms of impact on the individual, family, and society at large. The etiology of these disorders is multifactorial and includes complex interactions between genetic and environmental risk factors. This chapter reviews preclinical studies assessing the importance of gene–environment (G×E) interaction. Specifically, we focus on G×E studies assessing the roles of the hypothalamic–pituitary–adrenal (HPA) axis, serotonergic system, GABAergic system, and brain-derived neurotrophic factor (BDNF) system. Finally, novel candidate target genes for the treatment of depression and anxiety disorders are considered.
Actes de conférences sur le sujet "ATL gene family"
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Pannekoek, H., M. Linders, J. Keijer, H. Veerman, H. Van Heerikhuizen et D. J. Loskutoff. « THE STRUCTURE OF THE HUMAN ENDOTHELIAL PLASMINOGEN ACTIVATOR INHIBITOR (PAI-1) GENE : NON-RANDOM POSITIONING OF INTRONS ». Dans XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644767.
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The endothelium plays a crucial role in the regulation of the fibrinolytic process, since it synthesizes and secretes tissue-type plasminogen activator (t-PA) as well as the fast-acting plasminogen activator inhibitor (PAI-1). Molecular cloning of full-length PAI-1 cDNA, employing a human endothelial cDNA expression library, and a subsequent determination of the complete nucleotide sequence, allowed a prediction of the amino-acid sequence of the PAI-1 glycoprotein. It was observed that the amino-acid sequence is significantly homologous to those of members of the serine protease inhibitor ("Serpin") family, e.g. αl-antitrypsin and antithrombin III. Serpins are regulators of various processes, such as coagulation, inflammatory reactions, complement activation and share a common functional principle and a similar structure, indicative for a common primordial gene. The intron-exon arrangement of Serpin genes may provide a record for the structure of a primordial gene. A comparison of the location of introns among members of the Serpin family reveals that some introns are indeed present at identical or almost identical positions, however in many other cases there is no correspondence between the intron positions among different Serpin genes.Obviously, more data on the chromosomal gene structure of members of this family are required to formulate a scheme for the evolutionary creation of the Serpins. To that end, we have established the number and the precise location of the introns in the PAI-1 gene and have compared these data with those reported on other Serpin genes. For that purpose a human genomic cosmid DNA library of about 340.000 independent colonies was screened with radiolabelled full-length PAI-1 cDNA as probe. Two clones were found which contain the entire PAI-1 gene. Restriction site mapping, electron microscopic inspection of heteroduplexes and nucleotide sequence analysis demonstrate that the PAI-1 gene comprises about 12.2kilo basepairs and consists of nine exons and eight introns. Intron-exon boundaries are all in accord with the "GT-AG" rule, including a cryptic acceptor splice site found in intron 7. Furthermore, it is observed that intron 3 of the PAI-1 gene occupies an identical position as intron E of chicken ovalbumin and intron E of the ovalbumin-related gene Y. The location of the other seven introns is unrelated to the known location of introns in the genes encoding the Serpins, rat angiotensin, chicken ovalbumin (and gene Y), human antithrombin III and human al-antitrypsin. The 3' untranslated region of the PAI-1 gene is devoid of introns, indicating that the two mRNA species detected in cultured endothelial cells which share an identical 5' untranslated segment and codogenic region, but differ in the length of the 3' untranslated region, arise by alternative polyadenylation. An extrapolation of the position of the introns to the amino-acid sequence of PAI-1, and adaption of the view that the subdomain structure of the Serpins is analogous, shows that the introns of PAI-1 are non-randomly distributed. Except for intron 7, the position of the other seven introns corresponds with randon-coil regions of the protein or with the borders of β-sheets and a-helices. Extrapolation of the position of introns in the genes of other Serpins to their respective amino-acid sequences and subdomain structures also reveals a preference for random-coil regions and borders of subdomains. These observations are reminiscent of an evolutionary model, called "intron sliding", that accounts for variations in surface loops of the same protein in different species by aberrant splicing (Craik et al., Science 220 (1983) 1125). The preferential presence of introns in gene segments, encoding these variable regions, and absence in regions determining the general folding of these proteins would explain conservation of the structure during the evolution of those genes.
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Feijão, Maria Clara Tomaz, Fernanda Pimentel Arraes Maia, Mateus Coelho Gondim de Oliveira Lima, Vitória Moreira Soares et Luiz Gonzaga Porto Pinheiro. « CONCERNING A FAMILY WITH BRCA2 MUTATION ». Dans XXIV Congresso Brasileiro de Mastologia. Mastology, 2022. http://dx.doi.org/10.29289/259453942022v32s1019.
Texte intégralRésumé :
Introduction: Breast cancer is the most common malignancy in women and represents a major obstacle to public health worldwide. The molecular diagnosis of this type of cancer is one of the main contemporary challenges in oncology, since it is hampered by a complex inheritance pattern, characterized by both genetic and environmental factors. Only a minority of breast cancers are explained by the presence of high penetrance gene mutations, such as those in the BRCA1 and BRCA2 genes, which together with mutations in intermediate penetrance genes explain only up to 25% of the risk. In fact, much of the genetic influence is elucidated by low penetrance variants. Mutations in the germline BRCA1 and BRCA2 are the most common alterations in cases of early onset or of family history of breast cancer. It is also important to acknowledge that BRCA2 mutations can increase the risk of developing other cancers. Some studies show a relation between BRCA2 mutations and the development of leukemia, especially acute myeloid leukemia (AML). Also, some of these mutations, when inherited from both parents, cause a rare form of Fanconi anemia, a syndrome associated with the development of AML. In addition, there are studies evaluating a higher risk of pancreatic and esophageal cancer in carriers of BRCA2 mutations. The risk of colorectal cancer is also increased in patients with BRCA1 mutations. However, there are also some authors who defend that BRCA2 mutations could also be related. The specific statistics are not well defined because of the lack of data focusing on the relationship with the aforecited types of cancers, demonstrating the need for further analysis. This study aims to report the case of a woman with breast cancer at an early age. Such malignancy is associated and was somehow induced by the rich family history, represented by the high prevalence of cancer in the ancestry. We report a 34-year-old woman with an extensive history of carcinoma in the family, who was diagnosed with breast cancer in July 2016. In order to confirm the diagnosis, it was required an ultrasound, which resulted in a 2.2×1.5 cm node on the right breast’s left superior quadrant, classified as BIRADS 4A. It also performed an ultrasound-guided biopsy that showed a tubular carcinoma on the right breast with the following characteristics: positive for estrogen and progesterone receptor, positive for KI 67 (5%), and negative for HER2, with staging of T1cN0M0. During anamnesis, the patient mentioned menarche at 12 years old, history of birth control pills use for 10 years, no pregnancy, and no breastfeeding. When it comes to family history, a great number of relatives were previously diagnosed with some type of cancer. Her paternal grandfather had rectum cancer at 42 years old and breast cancer at 62 years old. The paternal grandmother passed away because of a fast-progression leukemia at the age of 68. It is important to mention that her progenitors were first cousins. Furthermore, the patient’s dad was diagnosed with breast cancer at 62 years, alongside his three brothers who were also diagnosed with cancer: one with prostatic cancer at the age of 64 years and the other two with intestinal cancer at the ages of 64 and 68 years old. Considering such a family history, a genetic panel was performed, analyzing the genes related to hereditary cancer risk, and it identified mutations in the patient’s BRCA2 gene. Then, firstly, she performed a bilateral mastectomy in January 2017 with sentinel lymph node investigation, which was negative for neoplastic cells in the lymph nodes. Later, considering the BRCA2 mutation, in August 2017, the patient had to undergo prophylactic surgery: oophorectomy with salpingectomy.
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Aleev, Vladislav S., et Elena G. Plotnikova. « GENETIC AND ECOLOGICAL-PHYSIOLOGICAL CHARACTERISTICS OF BACTERIA OF THE GENUS SALINISPHAERA (CLASS GAMMAPROTEOBACTERIA) ISOLATED FROM THE VERKHNEKAMSKY SALT MINER ». Dans Фундаментальные и прикладные исследования в биологии и экологии. Пермский государственный национальный исследовательский университет, 2021. http://dx.doi.org/10.17072/fpibe-2021-4-7.
Texte intégralRésumé :
5 strains of halophilic bacteria were isolated from clay deposits of brine-diverting workings and brine tanks of the mine of the Verkhnekamskoye salt deposit (Solikamsk, Perm Territory). Because of phylogenetic analysis based on a comparison of the 16S rRNA gene sequences, it was found that the isolated cultures are members of the Salinisphaeraceae family. Three halophilic strains SHV2, RV14, and SWV1 had a similarity with the closest type strain of the Salinisphaera hydrothermalis species at the level of 95.94-96.62% (16S rRNA gene), which indicates that these strains belong to a new taxon. All isolated bacteria are halophiles: they grow at high salinity (up to 270-300 g / l NaCl).
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Matthews, R. J., D. S. Anson, I. R. Peake et A. L. Bloom. « GENE DELETIONS IN THE FACTOR IX LOCUS ». Dans XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643871.
Texte intégralRésumé :
Previous studies have indicated that the majority of haemophilia B patients who produce anti-factor IX inhibitors (antibodies) have some kind of deletion of the factor IX gene. We have analysed DNA from nine haemophilia B inhibitor patients using the Southern blotting method and hybridisation with (i) factor IX cDNA and intragenomic probes (ii) probes originating from flanking sequences up to 60kb 5' and 170kb 3' to the factor IX gene that have been isolated by gene walking experiments (D.S.Anson and G.G.Brownlee, unpublished observations).Two patients who are brothers (haemophilia B (Chicago I)) were shown to have a presumably identical complex rearrangement of the factor IX gene involving two separate deletions. The first deletion is approx. 5.0kb and removes exon e. The second deletion is between 9 and 29kb and removes exons g and h but leaves exon f intact. An abnormal TaqI fragment at one end of the deletions junctions acted as a marker for the inheritance of haemophilia B in the patients' family. Furthermore, an abnormal llkb Bglll fragment (detected with an intragenomic probe containing exon f) in DNA from both patients and their mother acted as a marker for the presence of both deletions. Since the patients' grandmother only showed the normal 12kb Bgl II fragment then both deletions appear to have arisen at the same time. We believe that haemophilia B (Chicago 1) is the first observation of a natural gene rearrangement involving two separate deletions within the same gene.Patient haemophilia B (Jersey 1) was revealed to have a deletion of at least 170kb including the entire factor IX gene and > 60kb of 5' flanking sequence. The 3' breakpoint of this deletion was mapped to between 80 and 140kb 3' to the factor IX gene. One further patient, haemophilia B (Boston I) was shown to have a deletion of > 230kb including the factor IX gene, > 60kb of 5' flanking sequence and >140kb of 3' flanking sequence. Five other inhibitor patients had a structurally intact gene as detected by this method.Although all nine haemophilia B inhibitor patients studied did not have a detectable plasma factor IX only in four of them is this absence due to a large deletion of the factor IX gene.
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Braga, Vinícius Lopes, Wladimir Bocca Vieira de Rezende Pinto, Bruno de Mattos Lombardi Badia, José Marcos Vieira de Albuquerque Filho, Igor Braga Farias, Paulo Victor Sgobbi de Souza et Acary Souza Bulle Oliveira. « Spastic paraplegia type 73 : expanding phenotype of the first two Brazilian families ». Dans XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.552.
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Context: Hereditary spastic paraplegias (HSPs) represent an expanding group of neurodegenerative diseases characterized mainly by progressive spastic paraparesis of the lower limbs. More than 80 different genetic loci have been associated with HSPs. In 2015, heterozygous pathogenic variants in the CPT1C gene were first associated with SPG73, not yet described in Brazilian patients. Objective: We present clinical, neuroimaging and genetic features of three Brazilian patients with SPG73. Cases reports: We report one male and two female patients, age range 36 to 78 years old. Case 1 presented with a 4-year-history of spasticity, predominantly crural tetraplegia, bladder incontinence, dysphagia and dysphonia. Family history disclosed a sister with epilepsy. Whole-exome sequencing (WES) disclosed a heterozygosis variant c.863G>A (p.Arg288His) in exon 9 of the CPT1C. Cases 2 and 3 are first degree relatives (mother and son). Both presented with long-standing slowly progressive spastic paraplegia. Case 3 presented bladder incontinence, constipation, dysphagia and dysphonia at late stages. Cases 2 and 3 WES disclosed the heterozygosis variant c.196T>G (p.Phe66Val) in exon 4 of the CPT1C. Discussion: Previous literature described six patients from an Italian family with pure HSPs phenotype and the pathogenic variant c.109C>G (p.Arg3. 7Cys) in CPT1C gene. Another group described three patients associated with pure HSPs phenotype and the pathogenic variant (c.226C>T) in the CPT1C gene. All previous reported cases had benign clinical course and bulbar involvement was not described before. One of our cases presented with a de novo variant and rapidly progressive motor and bulbar compromise. Conclusion: our cases expand the current knowledge about SPG73, including a rapidly progressive phenotype with bulbar involvement and cognitive compromise at late stages of disease course.
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Liddell, M. B., D. S. Anson, D. P. Lillicrap et I. R. Peake. « SEARCH FOR AND USE OF RESTRICTION FRAGMENT LENGTH POLYMORPHISMS (RFLPs) IN AND AROUND THE HUMAN FACTOR IX GENE ». Dans XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644078.
Texte intégralRésumé :
5 previously described RFLPs within the factor IX gene have been used for family studies (carrier detection) in 10 haemophilia B kindred. In all DNA from 91 individuals, including 25 obligate or possible carriers, was analysed by digestion with TaqI and XmnI and probing with the intragenomic probe VIII (all probes were provided by Professor G. G. Brownlee, Oxford). When noninformative, additional RFLPs (DdeI;probe XIII and MspI;probe II) were used. Of 12 possible carriers, 11 were diagnosed (6 as carriers, 5 normal). Of the confirmed carriers (6 diagnosed, 13 obligate) 15 were informative (heterozygous and phase known), and the overall incidence of heterozygosity was 72%. The recently reported BamHI RFLP was not found to be useful ( <1.0% frequency).Further RFLPs in and flanking the factor IX gene were sought by two procedures. Firstly cosmid pCHIXα, containing a 40kb insert including the 3' end of the factor IX gene and stretching some 35kb 3' to the gene was used as a large probe, with repetitive sequences being blocked by preannealing the probe with an excess of sonicated, denatured human DNA (Litt and White, PNAS 82, 6206). Results with 25 restriction enzymes (covering an estimated 1038 nucleotides) and DNA from 7 unrelated females were obtained, but only one low frequency PvuII RFLP (frequency about 1%) was identified. Similar experiments with further cosmid probes 3' to the gene are underway. The second technique was developed to analyse small DNA fragments (<1.0kb) generated by frequently cutting restriction enzymes. These fragments were separated on 3.5% polyacrylamide/0.5% agarose composite gels and then electroblotted onto hybond-N. Fragments of 150bp were readily visualised by this procedure. 3 frequently cutting enzymes have been used (Hinfl, Rsal and Mbol), and the blots probed with a factor IX c-DNA probe, or a unique sequence subclone of cosmid pCHIXα. To date no RFLPs have been identified. This search for further useful RFLP has illustrated the paucity of detectable sequence variation within this region of the X-chromosome.
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Standen, G., P. Moodie, H. Pannekoek, C. L. Verweij et I. R. Peake. « ANALYSIS OF THE VON WILLEBRAND FACTOR (vWF) GENE IN 6 PATIENTS WITH SEVERE TYPE III VON WILLEBRANDS DISEASE ». Dans XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644641.
Texte intégralRésumé :
DNA from 6 unrelated patients with severe type III von Willebrands disease (vWF antigen < 0.01u/dl) was studied with a cDNA probe for the 3' end of the vWF gene. DNA was extracted from peripheral blood leucocytes using standard techniques and was digested with a range of restriction enzymes. DNA fragments were separated by electrophoresis in 0.7% agarose and were southern blotted onto hybond-N (Amersham). The probe used was pvWF1100, a 1.1kb PstI fragment derived from the 2.28kb vWFcDNA insert of pvWF2280 isolated from a human endothelial cell cDNA expression library (Verweij et al, Nucleic Acids Res 13 (1985) 4699-4717). The probe corresponds to nucleotides 7083 to 8191 of the vWF cDNA (first nucleotide of initiator methionine as 1).When digested with Bglll and probed with pvWF11000, normal DNA showed two invariant bands (13 and 4.9kb) and polymorphic bands of 9 and/or 7.4kb. This pattern was also seen in 5 of the 6 severe vWD patients DNA suggesting that in this 3' area of the gene they had no major deletions or rearrangements. In the 6th case however the band of 4.9kb was not seen and did not appear to be replaced by any novel fragments, suggesting a partial deletion including some of the 3' end of the gene. This patient had the clinically severest form of the condition in that the patient had developed, some 10 years ago, an antibody (inhibitor) to vWF as detected by the ability of the patients plasma to inhibit restocetin cofactor activity in normal plasma. His parents were related (his mother was his father's second cousin) and had levels of vWFAg, considerably lower than those of factor VIII activity. This situation has been previously reported in carriers of recessive severe vWD. vWD was also present in a second family member, but in a less severe form (vWFAg 3u/dl). This patient and all other members of the family have, to date, given normal restriction fragment patterns with the vWF probe and several enzymes, including BgIII.
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Hassan, H. J., L. Cianetti, P. M. Mannucci, V. Vicente, R. Cortese et C. Peschle. « HEREDITARY THROMBOPHILIA CAUSED BY MISSENSE MUTATION IN PROTEIN C GENE ». Dans XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1642944.
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The structure of the gene for protein C was analyzed in 13 protein C deficient unrelated patients (11 heterozygous, 2 homozygous), who showed an equivalent reduction of this serine protease at both enzymatic and antigen level. No deletion(s) or rearrangement(s) was demonstrated by Southern blot after hybridization to a cDNA probe. One patient showed a variant restriction pattern after Bam HI digestion, characterized by an abnormal 9.6 kb band in addition to the 8.3 and 1.3 normal ones. Extensive family studies, including 7 heterozygotes with the same clinical phenotype, showed the same abnormal pattern in all and only these heterozygotes. Protein C gene from the propositus was cloned in EMBL3 lambda vector. A 411 bp PstI - SacI fragment from exon 9 encompassing the mutation in the Bam HI site was subcloned in M13mpl8. Its sequence showed a single transversion in the Bam HI palyndrome (GGATCC -> GCATCC) : this causes a substitution of the 402 thryptophan residue with a cystein. The 402 thryptophan residue is constantly conserved in a biochemical domain present in all eukaryotic serine proteases: substitution of the large thryptophan aromatic ring with the small cysteine hydrophilic side-chain conceivably leads to destabilization of the tertiary structure of protein C in these heterozygotes. Thus, the point mutation reported here is sufficient to explain the protein C deficiency in these subjects, and is apparently responsible for their clinical phenotype.
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Gomes, Martha Velloso Murta, Nadya Alves de Sousa Guimarães, Thais Karla Vivan et Vinicius Xavier de Santana. « SECOND BREAST CANCER IN A WOMAN WITH GENETIC SYNDROME ». Dans XXIV Congresso Brasileiro de Mastologia. Mastology, 2022. http://dx.doi.org/10.29289/259453942022v32s1074.
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Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disease and is the most common neurocutaneous syndrome. It results from a defect in the gene located on chromosome number 17 that produces the protein neurofibromin, involved in controlling cell growth. Women with NF1 have a higher risk of developing breast and contralateral breast cancers. There is a relationship between high estrogen receptor (ER) and worse survival, which is also affected by the low overall life expectancy of patients with neurofibromatosis. Given that data also suggest that there are genes that interact with the NF1 gene, particularly in relation to the Breast Cancer gene 1 (BRCA1) subset. The interaction of altered expression of the NF1 neurofibromin protein in breast cell lines with upregulation of Ras is not inhibited through the PI3K and Raf/MAPK/ERK pathways. Increased PI3K activity has often been related to poor survival and resistance to hormone treatment in ER-negative breast cancer, while elevated Ras/MAPK/ERK activity has been related to metastasis and poor survival in both ER positive and negative. Mutations and deletions in NF1 are even more prevalent in HER2-amplified breast cancer subtypes and in basal tumor subtypes. In fact, all women with NF1, such as the case reported below, should start screening for breast cancer from the age of 30 and not from the age of 50 as in women not affected by the disease, as well as adequate and early counseling of oncogenetic. MSF, 56 years old, female, with neurofibromatosis was treated for invasive ductal carcinoma (ICD) in the left breast, RH negative in 2006, with mastectomy and axillary emptying, followed by adjuvant chemotherapy and radiotherapy. Menarche at age 17, menopause around age 41, at which time she underwent chemotherapy, was nulliparous, and denied hormone use. She had a negative family history. She was admitted to the Mastology Unit of the HBDF in March 2021 with an ultrasound examination of the right breast on February 19, 2021, BIRADs 4 at the expense of a solid, irregular nodular image and imprecise limits at 12 o’clock, measuring 21×16 mm. On physical examination, nodular lesions (neurofibromas) of varying sizes were observed, distributed throughout the trunk and limbs, and a 3 cm nodulation was palpated in the upper internal quadrante (QSM) of the right breast, close to the NAC with a negative axillae and plastron on the left, staging cT2N0M0 — IIA. Core biopsy confirms CDI, grade II, with ductal carcinoma in situ present, and luminal B-like immunohistochemistry (IHC). Staging tests without an evidence of distant disease. In July 2021, a mastectomy was performed with a sentinel lymph node biopsy (SLNB) on the right in view of the clinical staging and IHC profile, but of the four lymph nodes stained with patent blue, three were positive in intraoperative frozen section biopsy; therefore, the axilla was completed with dissection. The patient was discharged on the first postoperative day with weekly follow-up at an outpatient clinic, and the dressing was discharged in August 2021. Biopsy results confirmed a 6.5-cm ICD, grade III, ICD present with intermediate nuclear grade, and with all diseasefree margins. The patient was referred to a clinical oncology but arrived at the oncology more than 120 days after surgery, with time loss for adjuvant treatment.
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Albuquerque Filho, José Marcos Vieira de, Natália Merten Athayde, Alzira Alves de Siqueira Carvalho, Igor Braga Farias, Roberta Ismael Lacerda Machado et Marco Antônio Troccoli Chieia. « Familial ALS Type 25 – A Brazillian Case Serie ». Dans XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.186.
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Introduction: Familial Amyotrophic Lateral Sclerosis (fALS) represent 5-10% of ALS patients. Different mutations in the N-terminal motor or coiled-coil domains of the kinesin family member 5A (KIF5A) cause Hereditary Spastic Paraplegia Type 10 (HSP10), Charcot-Marie-Tooth 2 (CMT2), Neonatal Intractable Myoclonus and more recently described fALS Type 25. Previous described phenotypes are very similar to the sporadic type, except from the long course of disease. Methods: We describe four Brazillian patients, under clinical follow-up on two Neuromuscular services with genetic diagnosis of fALS25. Results: Four diferent fALS25 are described. Two brothers and two unrelated patients, with distinct features, three males and one female, age range from 72 to 24; age of onset ranged from 62 to 22. The genetic mutations were the following: simple heterozygous pathogenic variant c.1651C>G (p. Leu551Val), simple heterozygous pathogenic variant c.2953G>A (p. Gly985Ser) and pathogenic variant c.484C>T (p.Arg162Trp); all of KIF5A gene (fALS25). Only one patient presented with similar phenoptype and age of onset as sporadic ALS (sALS), the two brothers presented the symptoms at the ages of 28 and 30, the female patient at 22. All patients still walk without assistence after the diagnosis. All patients showed classic superior and inferior motor neuron involvement signs, but one brother had a mild limb ataxia. The three younger patients had MRI with no specific findings, except from subtle cortical atrophy in one brother, and mild vermis and corpus callosum atrophy on the other brother. Only the female patient had negative familiar history. Conclusions: fALS25 should be suspected in patient with fALS and longer course disease. Mutations KIF5A gene must be remembered either in juvenile form of ALS.
Rapports d'organisations sur le sujet "ATL gene family"
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Sessa, Guido, et Gregory Martin. Role of GRAS Transcription Factors in Tomato Disease Resistance and Basal Defense. United States Department of Agriculture, 2005. http://dx.doi.org/10.32747/2005.7696520.bard.
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The research problem: Bacterial spot and bacterial speck diseases of tomato are causedby strains of Xanthomonas campestris pv. vesicatoria (Xcv) and Pseudomonas syringae pv.tomato (Pst), respectively. These bacteria colonize aerial parts of the plant and causesignificant losses in tomato production worldwide. Protection against Xcv and Pst bycultural practices or chemical control has been unsuccessful and there are only limitedsources of genetic resistance to these pathogens. In previous research supported in part byBARD IS-3237-01, we extensively characterized changes in tomato gene expression uponthe onset of spot and speck disease resistance. A remarkable finding of these studies wasthe inducibility in tomato leaves by both Xcv and Pst strains of genes encodingtranscriptional activator of the GRAS family, which has not been previously linked todisease resistance. Goals: Central goals of this research were to investigate the role of GRAS genes in tomatoinnate immunity and to assess their potential use for disease control.Specific objectives were to: 1. Identify GRAS genes that are induced in tomato during thedefense response and analyze their role in disease resistance by loss-of-function experiments.2. Overexpress GRAS genes in tomato and characterize plants for possible broad-spectrumresistance. 3. Identify genes whose transcription is regulated by GRAS family. Our main achievements during this research program are in three major areas:1. Identification of tomato GRAS family members induced in defense responses andanalysis of their role in disease resistance. Genes encoding tomato GRAS family memberswere retrieved from databases and analyzed for their inducibility by Pst avirulent bacteria.Real-time RT-PCR analysis revealed that six SlGRAS transcripts are induced during theonset of disease resistance to Pst. Further expression analysis of two selected GRAS genesshowed that they accumulate in tomato plants in response to different avirulent bacteria orto the fungal elicitor EIX. In addition, eight SlGRAS genes, including the Pst-induciblefamily members, were induced by mechanical stress in part in a jasmonic acid-dependentmanner. Remarkably, SlGRAS6 gene was found to be required for tomato resistance to Pstin virus-induced gene silencing (VIGS) experiments.2. Molecular analysis of pathogen-induced GRAS transcriptional activators. In aheterologous yeast system, Pst-inducible GRAS genes were shown to have the ability toactivate transcription in agreement with their putative function of transcription factors. Inaddition, deletion analysis demonstrated that short sequences at the amino-terminus ofSlGRAS2, SlGRAS4 and SlGRAS6 are sufficient for transcriptional activation. Finally,defense-related SlGRAS proteins were found to localize to the cell nucleus. 3. Disease resistance and expression profiles of transgenic plants overexpressing SlGRASgenes. Transgenic plants overexpressing SlGRAS3 or SlGRAS6 were generated. Diseasesusceptibility tests revealed that these plants are not more resistant to Pst than wild-typeplants. Gene expression profiles of the overexpressing plants identified putative direct orindirect target genes regulated by SlGRAS3 and SlGRAS6. Scientific and agricultural significance: Our research activities established a novel linkbetween the GRAS family of transcription factors, plant disease resistance and mechanicalstress response. SlGRAS6 was found to be required for disease resistance to Pstsuggesting that this and possibly other GRAS family members are involved in thetranscriptional reprogramming that takes place during the onset of disease resistance.Their nuclear localization and transcriptional activation ability support their proposed roleas transcription factors or co-activators. However, the potential of utilizing GRAS familymembers for the improvement of plant disease resistance in agriculture has yet to bedemonstrated.
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Raghothama, Kashchandra G., Avner Silber et Avraham Levy. Biotechnology approaches to enhance phosphorus acquisition of tomato plants. United States Department of Agriculture, janvier 2006. http://dx.doi.org/10.32747/2006.7586546.bard.
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Abstract: Phosphorus is one of the least available macronutrient in the soil. The high affinity phosphate transporters are known to be associated with phosphate acquisition under natural conditions. Due to unique interactions of phosphate with soil particles, up to 80% of the applied phosphates may be fixed forcing the farmers to apply 4 to 5 times the fertilizers necessary for crop production. Efficient uptake and utilization of this essential nutrient is essential for sustainability and profitability of agriculture. Many predictions point to utilization/exhaustion of high quality phosphate rocks within this century. This calls for efforts to improve the ability of plants to acquire and utilize limiting sources of phosphate in the rhizosphere. Two important molecular and biochemical components associated with phosphate efficiency are phosphate transporters and phosphatases. This research project is aimed at defining molecular determinants of phosphate acquisition and utilization in addition to generating phosphate uptake efficient plants. The main objectives of the project were; Creation and analysis of transgenic tomato plants over-expressing phosphatases and transporters Characterization of the recently identified members (LePT3 and LePT4) of the Pi transporter family Generate molecular tools to study genetic responses of plants to Pi deficiency During the project period we have successfully identified and characterized a novel phosphate transporter associated with mycorrhizal symbiosis. The expression of this transporter increases with mycorrhizal symbiosis. A thorough characterization of mutant tomato lacking the expression of this gene revealed the biological significance of LePT3 and another novel gene LePT4. In addition we have isolated and characterized several phosphate starvation induced genes from tomato using a combination of differential and subtractive mRNA hybridization techniques. One of the genes, LePS2 belongs to the family of phospho-protein phosphatase. The functionality of the recombinant protein was determined using synthetic phosphor-peptides. Over expression of this gene in tomato resulted in significant changes in growth, delay in flowering and senescence. It is anticipated that phospho-protein phosphatase may have regulatory role in phosphate deficiency responses of plants. In addition a novel phosphate starvation induced glycerol 3-phosphate permease gene family was also characterized. Two doctoral research students are continuing the characterization and functional analysis of these genes. Over expression of high affinity phosphate transporters in tobacco showed increased phosphate content under hydroponic conditions. There is growing evidence suggesting that high affinity phosphate transporters are crucial for phosphate acquisition even under phosphate sufficiency conditions. This project has helped train several postdoctoral fellows and graduate students. Further analysis of transgenic plants expressing phosphatases and transporters will not only reveal the biological function of the targeted genes but also result in phosphate uptake and utilization efficient plants.
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Sengupta-Gopalan, Champa, Shmuel Galili et Rachel Amir. Improving Methionine Content in Transgenic Forage Legumes. United States Department of Agriculture, février 2001. http://dx.doi.org/10.32747/2001.7580671.bard.
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Leguminous forage crops are high in proteins but deficient in S- amino acids. It has been shown that both wool quality and milk production can be limited by the post-ruminal supply of sulfur-containing amino acids. Efforts to use conventional plant breeding and cell selection techniques to increase the S-amino acid content of alfalfa have met with little success. With the objective to increase the S-amino acid content of forage legumes, the goal of this project was to co- express the methionine rich zein genes from corn along with a gene for a key enzyme in methionine biosynthesis, aspartate kinase(AK). The zeins are seed storage proteins from corn and are groupec into four distinct classes based on their amino acid sequence homologies. The b-zein (15kd) and the 6zein (10kD and 18kD) have proportionately high levels of methionine (10%, 22% and 28%, respectively). Initial studies from our lab had shown that while the 15kD zein accumulated to high levels in vegetative tissues of transgenic tobacco the l0kD zein did not. However, co-expression of the 10kD zein with the 15kD zein genes in tobacco showed stabilization of the 10kD zein and the co-localization of the 10kD and 15kD zein proteins in unique ER derived protein bodies. AK is the key enzyme for producing carbon skeletons for all amino acids of the aspartate family including methionine. It is, however, regulated by end-product feedback inhibition. The specific objectives of this proposal were: i. to co-express the 15kD zein with the 10/18kD zein genes in alfalfa in order to enhance the level of accumulation of the 10/18kD zein; ii. to increase methionine pools by expressing a feedback insensitive AK gene in transformants co-expressing the 15kD and 10/18kD zein genes. The Israeli partners were successful in expressing the AK gene in alfalfa which resulted in an increase in free and bound threonine but not in methionine (Galili et al., 2000). Since our target was to increase methionine pools, we changed our second objective to replace the AK gene with the gene for cystathionine gamma synthase (CGS) in the co-expression studies. The first methionine specific reaction is catalyzed by CGS. An additional objective was to develop a transformation system for Berseem clover, and to introduce the appropriate gene constructs into it with the goal of improving their methionine content. Genes for the 15kD zein along with the genes for either the 10kD or 18kD zein have been introduced into the same alfalfa plant both by sexual crosses and by re-transformation. Analysis of these zein co-expressors have shown that both the IOkD and 18kD zein levels go up 5 to 10 fold when co-expressed with the 15kD zein (Bagga et al., MS in preparation). Incubation of the leaves of transgenic alfalfa co-expressing the 15kD and 10kD zein genes, in the rumen of cows have shown that the zein proteins are stable in the rumen. To increase the level of zein accumulation in transgenic alfalfa different promoters have been used to drive the zein genes in alfalfa and we have concluded that the CaMV 35S promoter is superior to the other strong leaf -specific promoters. By feeding callus tissue of alfalfa plants co-expressing the 15kD and 10kD zein genes with methionine and its precursors, we have shown that the zein levels could be significantly enhanced by increasing the methionine pools. We have now introduced the CGS gene (from Arabidopsis; kindly provided to us by Dr. Leustek), into the 15kD zein transformants and experiments are in progress to check if the expression of the CGS gene indeed increases the level of zein accumulation in alfalfa. We were not successful in developing a transformation protocol for Berseem clover.
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Meir, Shimon, Michael Reid, Cai-Zhong Jiang, Amnon Lers et Sonia Philosoph-Hadas. Molecular Studies of Postharvest Leaf and Flower Abscission. United States Department of Agriculture, 2005. http://dx.doi.org/10.32747/2005.7696523.bard.
Texte intégralRésumé :
Original objectives: Understanding the regulation of abscission competence by exploring the nature and function of auxin-related gene expression changes in the leaf and pedicelAZs of tomato (as a model system), was the main goal of the previously submitted proposal. We proposed to achieve this goal by using microarray GeneChip analysis, to identify potential target genes for functional analysis by virus-induced gene silencing (VIGS). To increase the potential of accomplishing the objectives of the previously submitted proposal, we were asked by BARD to show feasibility for the use of these two modern techniques in our abscission system. Thus, the following new objectives were outlined for the one-year feasibility study: 1.to demonstrate the feasibility of the VIGS system in tomato to perform functional analysis of known abscission-related genes; 2. to demonstrate that by using microarray analysis we can identify target genes for further VIGS functional analysis. Background to the topic: It is a generally accepted model that auxin flux through the abscission zone (AZ) prevents organ abscission by rendering the AZ insensitive to ethylene. However, the molecular mechanisms responsible for acquisition of abscission competence and the way in which the auxin gradient modulates it are still unknown. Understanding this basic stage of the abscission process may provide us with future tools to control abscission for agricultural applications. Based on our previous study, performed to investigate the molecular changes occurring in leaf and stem AZs of MirabillisJalapaL., we have expanded our research to tomato, using genomic approaches that include modern techniques for gene discovery and functional gene characterization. In our one-year feasibility study, the US team has established a useful system for VIGS in tomato, using vectors based on the tobacco rattle virus (TRV), a Lcreporter gene for silencing (involved in regulation of anthocyanin biosynthesis), and the gene of interest. In parallel, the Israeli team has used the newly released Affymetrix Tomato GeneChip to measure gene expression in AZ and non-AZ tissues at various time points after flower removal, when increased sensitivity to ethylene is acquired prior to abscission (at 0-8 h), and during pedicelabscission (at 14 h). In addition, gene expression was measured in the pedicel AZ pretreated with the ethylene action inhibitor, 1-methylcyclopropene (1-MCP) before flower removal, to block any direct effects of ethylene. Major conclusions, solutions and achievements: 1) The feasibility study unequivocally established that VIGS is an ideal tool for testing the function of genes with putative roles in abscission; 2) The newly released Affymetrix Tomato GeneChip was found to be an excellent tool to identify AZ genes possibly involved in regulation and execution of abscission. The VIGS-based study allowed us to show that TAPG, a polygalacturonase specifically associated with the tomato AZ, is a key enzyme in the abscission process. Using the newly released Affymetrix Tomato GeneChip we have identified potential abscission regulatory genes as well as new AZ-specific genes, the expression of which was modified after flower removal. These include: members of the Aux/IAAgene family, ethylene signal transduction-related genes, early and late expressed transcription factors, genes which encode post-translational regulators whose expression was modified specifically in the AZ, and many additional novel AZ-specific genes which were previously not associated with abscission. This microarray analysis allowed us to select an initial set of target genes for further functional analysis by VIGS. Implications: Our success in achieving the two objectives of this feasibility study provides us with a solid basis for further research outlined in the original proposal. This will significantly increase the probability of success of a full 3-year project. Additionally, our feasibility study yielded highly innovative results, as they represent the first direct demonstration of the functional involvement of a TAPG in abscission, and the first microarray analysis of the abscission process. Using these approaches we could identify a large number of genes involved in abscission regulation, initiation and execution, and in auxin-ethylene cross-talk, which are of great importance, and could enable their potential functional analysis by VIGS.
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Weil, Clifford F., Anne B. Britt et Avraham Levy. Nonhomologous DNA End-Joining in Plants : Genes and Mechanisms. United States Department of Agriculture, juillet 2001. http://dx.doi.org/10.32747/2001.7585194.bard.
Texte intégralRésumé :
Repair of DNA breaks is an essential function in plant cells as well as a crucial step in addition of modified DNA to plant cells. In addition, our inability to introduce modified DNA to its appropriate locus in the plant genome remains an important hurdle in genetically engineering crop species.We have taken a combined forward and reverse genetics approach to examining DNA double strand break repair in plants, focusing primarily on nonhomologous DNA end-joining. The forward approach utilizes a gamma-plantlet assay (miniature plants that are metabolically active but do not undergo cell division, due to cell cycle arrest) and has resulted in identification of five Arabidopsis mutants, including a new one defective in the homolog of the yeast RAD10 gene. The reverse genetics approach has identified knockouts of the Arabidopsis homologs for Ku80, DNA ligase 4 and Rad54 (one gene in what proves to be a gene family involved in DNA repair as well as chromatin remodeling and gene silencing)). All these mutants have phenotypic defects in DNA repair but are otherwise healthy and fertile. Additional PCR based screens are in progress to find knockouts of Ku70, Rad50, and Mre11, among others. Two DNA end-joining assays have been developed to further our screens and our ability to test candidate genes. One of these involves recovering linearized plasmids that have been added to and then rejoined in plant cells; plasmids are either recovered directly or transformed into E. coli and recovered. The products recovered from various mutant lines are then compared. The other assay involves using plant transposon excision to create DNA breaks in yeast cells and then uses the yeast cell as a system to examine those genes involved in the repair and to screen plant genes that might be involved as well. This award supported three graduate students, one in Israel and two in the U.S., as well as a technician in the U.S., and is ultimately expected to result directly in five publications and one Masters thesis.
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Steffens, John, Eithan Harel et Alfred Mayer. Coding, Expression, Targeting, Import and Processing of Distinct Polyphenoloxidases in Tissues of Higher Plants. United States Department of Agriculture, novembre 1994. http://dx.doi.org/10.32747/1994.7613008.bard.
Texte intégralRésumé :
Polyphenol oxidase (PPO) catalyzes the oxidation of phenols to quinones at the expense of O2. PPOs are ubiquitous in higer plants, and their role in oxidative browning of plant tissues causes large annual losses to food production. Despite the importance of PPOs to agriculture, the function(s) of PPOs in higher plants are not understood. Among other roles, PPOs have been proposed to participate in aspects of chloroplast metabolism, based on their occurrence in plastids and high Km for O2. Due to the ability of PPO to catalyze formation of highly reactive quinones, PPOs have also been proposed to be involved in a wide array of defensive interactions with insect, bacterial, and fungal pests. Physiological and biochemical studies of PPO have provided few answers to the major problems of PPO function, subcellular localization, and biochemical properties. This proposal achieved the following major objectives: cloning of PPO cDNAs in potato and tomato; characterization of the tomato PPO gene family; antisense downregulation of the tomato PPO gene family; and reduction in post-harvest enzymic browning of potato through expression of antisense PPO genes under the control of tuber-specific promoters. In addition, we established the lumenal localization of PPO, characterized and clarified the means by which PPOs are imported and processed by chloroplasts, and provided insight into the factors which control localization of PPOs. This proposal has thereby provided fundamental advances in the understanding of this enzyme and the control of its expression.
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Or, Etti, Tai-Ping Sun, Amnon Lichter et Avichai Perl. Characterization and Manipulation of the Primary Components in Gibberellin Signaling in the Grape Berry. United States Department of Agriculture, janvier 2010. http://dx.doi.org/10.32747/2010.7592649.bard.
Texte intégralRésumé :
Seedless cultivars dominate the table grape industry. In these cultivars it is mandatory to apply gibberellin (GA) to stimulate berry development to a commercially acceptable size. These cultivars differ in their sensitivity to GA application, and it frequently results in adverse effects such as decreased bud fertility and increased fruit drop. Our long term goals are to (1) understand the molecular basis for the differential sensitivity and identify markers for selection of sensitive cultivars (2) to develop new strategies for targeted manipulation of the grape berry response to GA that will eliminate the need in GA application and the undesirable effects of GA on the vine, while maintaining its desirable effects on the berry. Both strategies are expected to reduce production cost and meet growing consumer demand for reduced use of chemicals. This approach relies on a comprehensive characterization of the central components in the GA signaling cascade in the berry. Several key components in the GA signaling pathway were identified in Arabidopsis and rice, including the GA receptors, GID1s, and a family of DELLA proteins that are the major negative regulators of the GA response. GA activates its response pathway by binding to GID1s, which then target DELLAs for degradation via interaction with SLY, a DELLA specific F-box protein. In grape, only one DELLA gene was characterized prior to this study, which plays a major role in inhibiting GA-promoted stem growth and GA-repressed floral induction but it does not regulate fruit growth. Therefore, we speculated that other DELLA family member(s) may control GA responses in berry, and their identification and manipulation may result in GA-independent berry growth. In the current study we isolated two additional VvDELLA family members, two VvGID1 genes and two VvSLY genes. Arabidopsis anti-AtRGA polyclonal antibodies recognized all three purified VvDELLA proteins, but its interaction with VvDELLA3 was weaker. Overexpression of the VvDELLAs, the VvGID1s, and the VvSLYs in the Arabidopsis mutants ga1-3/rga-24, gid1a-2/1c-2 and sly1-10, respectively, rescued the various mutant phenotypes. In vitro GAdependent physical interaction was shown between the VvDELLAs and the VvGID1s, and GAindependent interaction was shown between the VvDELLAs and VvSLYs. Interestingly, VvDELLA3 did not interact with VvGID1b. Together, the results indicate that the identified grape homologs serve as functional DELLA repressors, receptors and DELLA-interacting F-box proteins. Expression analyses revealed that (1) VvDELLA2 was expressed in all the analyzed tissues and was the most abundant (2) VvDELLA1 was low expressed in berries, confirming former study (3) Except in carpels and very young berries, VvDELLA3 levels were the lowest in most tissues. (4) Expression of both VvGID1s was detected in all the grape tissues, but VvGID1b transcript levels were significantly higher than VvGID1a. (5) In general, both VvDELLAs and VvGID1s transcripts levels increased as tissues aged. Unfertilized and recently fertilized carpels did not follow this trend, suggesting different regulatory mechanism of GA signaling in these stages. Characterization of the response to GA of various organs in three seedless cultivars revealed differential response of the berries and rachis. Interestingly, VvDELLA3 transcript levels in the GA-unresponsive berries of cv. Spring blush were significantly higher compared to their levels in the highly responsive berries of cv. Black finger. Assuming that VvDELLA2 and VvDELLA3 are regulating berry size, constructs carrying potential dominant mutations in each gene were created. Furthermore, constitutive silencing of these genes by mIR is underway, to reveal the effect of each gene on the berry phenotype.
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Veilleux, Richard E., Jossi Hillel, A. Raymond Miller et David Levy. Molecular Analysis by SSR of Genes Associated with Alkaloid Synthesis in a Segregating Monoploid Potato Family. United States Department of Agriculture, mai 1994. http://dx.doi.org/10.32747/1994.7570550.bard.
Texte intégralRésumé :
More than 15,000 anthers of an interspecific hybrid (CP2) between two diploid (2n=2x=24) potato species, Solanum chacoense (weedy) and S. phureja (cultivated), were cultured to generate a family of monoploid (haploid, 2n-1x=12) plants. Of 260 regenerated plants, 34 were monoploid, 210 diploid and 16 tetraploid. SSR analysis revealed that six monoploids were genetically identical and 14 diploids were homozygous, thus limiting the population to 42 (28 monoploids and 14 homozygous diploids). New microsatellite loci were developed for potato from database sequences (15), a conventional genomic library (6), an enriched library (18) and tomato (11). Of these, 13 were polymorphic in the CP2 family and 11 were used to study genetic segregatin. Four of 11 exhibited skewed segregation in the monoploid family. Seven of 18 microsatellite markers were polymorphic and informative on a set of 12 tetraploid potato cultivars. Acetylleptinidine (ALD) is the aglycone of leptines, a natural defense against insects, especially the highly destructuve Colorado potato beetle. ALD is absend in S. phureja but highly expressed in the S. chacoense parent of CP2. A backcross population between CP2 and tis S. phureja parent was used to examine segregation for ALD. Bulks of 10 backcross individuals that expressed ALD and 10 that did not were used to identify putative RAPD markers associatd with the trait. Of 80 primers tested, one putative marker amplified by OPQ02 was present in eight of ten individuals comprising the high bulk and absent in all 10 individuals comprising the low bulk. This is a putative marker for ALD expression in potato.
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Newton, Ronald, Joseph Riov et John Cairney. Isolation and Functional Analysis of Drought-Induced Genes in Pinus. United States Department of Agriculture, septembre 1993. http://dx.doi.org/10.32747/1993.7568752.bard.
Texte intégralRésumé :
Drought is a common factor limiting timber production in the U.S. and Israel. Loblolly (Pinus taeda) and alleppo pine (Pinus halepensis) seedling survival is reduced when out planted, and growth and reproduction are often hindered by periodic droughts during later stages of tree development. Molecular and gene responses to drought stress have not been characterized. The objectives were to characterize drought-induced gene clones from these pines, to determine the effects of a growth regulator on drought tolerance, ABA levels, and drought-induced gene expression in alleppo pine, and to develop procedures for loblolly pine transformation. Nearly 20 cDNA clones influenced by gradual, prolonged drought stress have been isolated. Many of these have been shown to be induced by drought stress, whereas several others are down-regulated. These are the first drought-induced genes isolated from a pine species. Two genomic clones (lp5-1 and lp3-1) have been sequenced and characterized, and each has been found to be associated with a gene family. Clone lp5 appears to code for a cell wall protein, and clone lp3 codes for a nuclear protein. The former may be associated with changing the elastic properties of the cell wall, while the latter may be involved in signal transduction and/or protection from desiccation in the nucleus. Clone lp3 is similar to a drought-induced gene from tomato and is regulated by ABA. Several DNA sequences that are specific to induction during growth-retardation in alleppo pine by uniconazole have been identified. The active DNA species is now being identified. Promoters from genomic clones, lp3 and lp5, have been sequenced. Both are functional when fused with the gus reporter gene and transferred to other plant tissues as well as responding to a simulated drought stress. Through exodeletion analysis, it has been established that the promoter ABRE element of lp3 responds to ABA and that drought-induction of lp3 expression may also involve ABA. Stable tobacco transformants carrying either the lp5 or the lp3 promoter fused to a reporter gus gene have been obtained. The lp5lgus fusion was expressed at several stages of tobacco development and differentiation including the reproductive stage. There was no difference in phenotype between the transformants and the wild type. Embryogenesis procedures were developed for slash pine, but attempts to couple this process with gene transfer and plantlet transformation were not successful. Transformation of pine using Agrobacterium appears tractable, but molecular data supporting stable integration of the Agrobacterium-transferred gene are still inconclusive.
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Ohad, Nir, et Robert Fischer. Regulation of Fertilization-Independent Endosperm Development by Polycomb Proteins. United States Department of Agriculture, janvier 2004. http://dx.doi.org/10.32747/2004.7695869.bard.
Texte intégralRésumé :
Arabidopsis mutants that we have isolated, encode for fertilization-independent endosperm (fie), fertilization-independent seed2 (fis2) and medea (mea) genes, act in the female gametophyte and allow endosperm to develop without fertilization when mutated. We cloned the FIE and MEA genes and showed that they encode WD and SET domain polycomb (Pc G) proteins, respectively. Homologous proteins of FIE and MEA in other organisms are known to regulate gene transcription by modulating chromatin structure. Based on our results, we proposed a model whereby both FIE and MEA interact to suppress transcription of regulatory genes. These genes are transcribed only at proper developmental stages, as in the central cell of the female gametophyte after fertilization, thus activating endosperm development. To test our model, the following questions were addressed: What is the Composition and Function of the Polycomb Complex? Molecular, biochemical, genetic and genomic approaches were offered to identify members of the complex, analyze their interactions, and understand their function. What is the Temporal and Spatial Pattern of Polycomb Proteins Accumulation? The use of transgenic plants expressing tagged FIE and MEA polypeptides as well as specific antibodies were proposed to localize the endogenous polycomb complex. How is Polycomb Protein Activity Controlled? To understand the molecular mechanism controlling the accumulation of FIE protein, transgenic plants as well as molecular approaches were proposed to determine whether FIE is regulated at the translational or posttranslational levels. The objectives of our research program have been accomplished and the results obtained exceeded our expectation. Our results reveal that fie and mea mutations cause parent-of-origin effects on seed development by distinct mechanisms (Publication 1). Moreover our data show that FIE has additional functions besides controlling the development of the female gametophyte. Using transgenic lines in which FIE was not expressed or the protein level was reduced during different developmental stages enabled us for the first time to explore FIE function during sporophyte development (Publication 2 and 3). Our results are consistent with the hypothesis that FIE, a single copy gene in the Arabidopsis genome, represses multiple developmental pathways (i.e., endosperm, embryogenesis, shot formation and flowering). Furthermore, we identified FIE target genes, including key transcription factors known to promote flowering (AG and LFY) as well as shoot and leaf formation (KNAT1) (Publication 2 and 3), thus demonstrating that in plants, as in mammals and insects, PcG proteins control expression of homeobox genes. Using the Yeast two hybrid system and pull-down assays we demonstrated that FIE protein interact with MEA via the N-terminal region (Publication 1). Moreover, CURLY LEAF protein, an additional member of the SET domain family interacts with FIE as well. The overlapping expression patterns of FIE, with ether MEA or CLF and their common mutant phenotypes, demonstrate the versatility of FIE function. FIE association with different SET domain polycomb proteins, results in differential regulation of gene expression throughout the plant life cycle (Publication 3). In vitro interaction assays we have recently performed demonstrated that FIE interacts with the cell cycle regulatory component Retinobalsoma protein (pRb) (Publication 4). These results illuminate the potential mechanism by which FIE may restrain embryo sac central cell division, at least partly, through interaction with, and suppression of pRb-regulated genes. The results of this program generated new information about the initiation of reproductive development and expanded our understanding of how PcG proteins regulate developmental programs along the plant life cycle. The tools and information obtained in this program will lead to novel strategies which will allow to mange crop plants and to increase crop production.