Gotowa bibliografia na temat „Runt related transcription factor”
Utwórz poprawne odniesienie w stylach APA, MLA, Chicago, Harvard i wielu innych
Spis treści
Zobacz listy aktualnych artykułów, książek, rozpraw, streszczeń i innych źródeł naukowych na temat „Runt related transcription factor”.
Przycisk „Dodaj do bibliografii” jest dostępny obok każdej pracy w bibliografii. Użyj go – a my automatycznie utworzymy odniesienie bibliograficzne do wybranej pracy w stylu cytowania, którego potrzebujesz: APA, MLA, Harvard, Chicago, Vancouver itp.
Możesz również pobrać pełny tekst publikacji naukowej w formacie „.pdf” i przeczytać adnotację do pracy online, jeśli odpowiednie parametry są dostępne w metadanych.
Artykuły w czasopismach na temat "Runt related transcription factor"
1
Saikia, Snigdha, Asad Ur Rehman, Prajjalendra Barooah, Preeti Sarmah, Mallika Bhattacharyya, Muktanjalee Deka, Manab Deka, Bhabadev Goswami, Syed Akhtar Husain i Subhash Medhi. "Alteration in the expression of MGMT and RUNX3 due to non-CpG promoter methylation and their correlation with different risk factors in esophageal cancer patients". Tumor Biology 39, nr 5 (maj 2017): 101042831770163. http://dx.doi.org/10.1177/1010428317701630.
Pełny tekst źródłaStreszczenie:
Promoter methylation reflects in the inactivation of different genes like O6-methylguanine-DNA methyltransferase DNA repair gene and runt-related transcription factor 3, a known tumor suppressor gene in various cancers such as esophageal cancer. The promoter methylation was evaluated for O6-methylguanine-DNA methyltransferase and runt-related transcription factor 3 in CpG, CHH, and CHG context (where H is A, T, or C) by next-generation sequencing. The methylation status was correlated with quantitative messenger RNA expression. In addition, messenger RNA expression was correlated with different risk factors like tobacco, alcohol, betel nut consumption, and smoking habit. CpG methylation of O6-methylguanine-DNA methyltransferase promoter had a positive association in the development of esophageal cancer (p < 0.05), whereas runt-related transcription factor 3 promoter methylation showed no significant association (p = 1.0) to develop esophageal cancer. However, the non-CpG methylation, CHH, and CHG were significantly correlated with O6-methylguanine-DNA methyltransferase (p < 0.05) and runt-related transcription factor 3 (p < 0.05) promoters in the development of esophageal cancer. The number of cytosine converted to thymine (C→T) in O6-methylguanine-DNA methyltransferase promoter showed a significant correlation between cases and controls (p < 0.05), but in runt-related transcription factor 3 no such significant correlation was observed. Besides, messenger RNA expression was found to be significantly correlated with promoter hypermethylation of O6-methylguanine-DNA methyltransferase and runt-related transcription factor 3 in the context of CHG and CHH (p < 0.05). The CpG hypermethylation in O6-methylguanine-DNA methyltransferase showed positive (p < 0.05) association, whereas in runt-related transcription factor 3, it showed contrasting negative association (p = 0.23) with their messenger RNA expression. Tobacco, betel nut consumption, and smoking habits were associated with altered messenger RNA expression of O6-methylguanine-DNA methyltransferase (p < 0.05) and betel nut consumption and smoking habits were associated with runt-related transcription factor 3 (p < 0.05). There was no significant association between messenger RNA expression of O6-methylguanine-DNA methyltransferase and runt-related transcription factor 3 with alcohol consumption (p = 0.32 and p = 0.15). In conclusion, our results suggest that an aberrant messenger RNA expression may be the outcome of CpG, CHG, and CHH methylation in O6-methylguanine-DNA methyltransferase, whereas outcome of CHG and CHH methylation in runt-related transcription factor 3 promoters along with risk factors such as consumption of tobacco, betel nut, and smoking habits in esophageal cancer from Northeast India.
2
Yu, Shibing, Yu Jiang, Deborah L. Galson, Min Luo, Yumei Lai, Yi Lu, Hong-Jiao Ouyang, Jian Zhang i Guozhi Xiao. "General Transcription Factor IIA-γ Increases Osteoblast-specificOsteocalcinGene Expression via Activating Transcription Factor 4 and Runt-related Transcription Factor 2". Journal of Biological Chemistry 283, nr 9 (2.01.2008): 5542–53. http://dx.doi.org/10.1074/jbc.m705653200.
Pełny tekst źródła
3
Thirunavukkarasu, Kannan, Muktar Mahajan, Keith W. McLarren, Stefano Stifani i Gerard Karsenty. "Two Domains Unique to Osteoblast-Specific Transcription Factor Osf2/Cbfa1 Contribute to Its Transactivation Function and Its Inability To Heterodimerize with Cbfβ". Molecular and Cellular Biology 18, nr 7 (1.07.1998): 4197–208. http://dx.doi.org/10.1128/mcb.18.7.4197.
Pełny tekst źródłaStreszczenie:
ABSTRACT Osf2/Cbfa1, hereafter called Osf2, is a member of the Runt-related family of transcription factors that plays a critical role during osteoblast differentiation. Like all Runt-related proteins, it contains a runt domain, which is the DNA-binding domain, and a C-terminal proline-serine-threonine-rich (PST) domain thought to be the transcription activation domain. Additionally, Osf2 has two amino-terminal domains distinct from any other Runt-related protein. To understand the mechanisms of osteoblast gene regulation by Osf2, we performed an extensive structure-function analysis. After defining a short Myc-related nuclear localization signal, a deletion analysis revealed the existence of three transcription activation domains and one repression domain. AD1 (for activation domain 1) comprises the first 19 amino acids of the molecule, which form the first domain unique to Osf2, AD2 is formed by the glutamine-alanine (QA) domain, the second domain unique to Osf2, and AD3 is located in the N-terminal half of the PST domain and also contains sequences unique to Osf2. The transcription repression domain comprises the C-terminal 154 amino acids of Osf2. DNA-binding, domain-swapping, and protein interaction experiments demonstrated that full-length Osf2 does not interact with Cbfβ, a known partner of Runt-related proteins, whereas a deletion mutant of Osf2 containing only the runt and PST domains does. The QA domain appears to be responsible for preventing this heterodimerization. Thus, our results uncover the unique functional organization of Osf2 by identifying functional domains not shared with other Runt-related proteins that largely control its transactivation and heterodimerization abilities.
4
Coller, Hilary A. "The Runt-related transcription factor 1 in prostate cancer-associated fibroblasts". Proceedings of the National Academy of Sciences 111, nr 46 (10.11.2014): 16238–39. http://dx.doi.org/10.1073/pnas.1418976111.
Pełny tekst źródła
5
Boström, Kristina I. "DNA Damage Response, Runx2 (Runt-Related Transcription Factor 2), and Vascular Calcification". Arteriosclerosis, Thrombosis, and Vascular Biology 41, nr 4 (kwiecień 2021): 1358–59. http://dx.doi.org/10.1161/atvbaha.121.315836.
Pełny tekst źródła
6
Chi, Xin-Zi, Jiyeon Kim, Yong-Hee Lee, Jung-Won Lee, Kyeong-Sook Lee, Heejun Wee, Wun-Jae Kim i in. "Runt-Related Transcription Factor RUNX3 Is a Target of MDM2-Mediated Ubiquitination". Cancer Research 69, nr 20 (6.10.2009): 8111–19. http://dx.doi.org/10.1158/0008-5472.can-09-1057.
Pełny tekst źródła
7
Huang, Shu-Pin, Yu-Hsuan Lan, Te-Ling Lu, Jiunn-Bey Pao, Ta-Yuan Chang, Hong-Zin Lee, Wen-Hui Yang i in. "Clinical significance of runt-related transcription factor 1 polymorphism in prostate cancer". BJU International 107, nr 3 (24.08.2010): 486–92. http://dx.doi.org/10.1111/j.1464-410x.2010.09512.x.
Pełny tekst źródła
8
DU, FEIYA, HUILING WU, ZHIQIN ZHOU i YU LIU. "microRNA-375 inhibits osteogenic differentiation by targeting runt-related transcription factor 2". Experimental and Therapeutic Medicine 10, nr 1 (7.05.2015): 207–12. http://dx.doi.org/10.3892/etm.2015.2477.
Pełny tekst źródła
9
Tanaka, Shigetomi, Hidenori Shiraha, Yutaka Nakanishi, Shin-Ichi Nishina, Minoru Matsubara, Shigeru Horiguchi, Nobuyuki Takaoka i in. "Runt-related transcription factor 3 reverses epithelial-mesenchymal transition in hepatocellular carcinoma". International Journal of Cancer 131, nr 11 (24.04.2012): 2537–46. http://dx.doi.org/10.1002/ijc.27575.
Pełny tekst źródła
10
Gil-Yarom, Naama, Lihi Radomir, Lital Sever, Matthias P. Kramer, Hadas Lewinsky, Chamutal Bornstein, Ronnie Blecher-Gonen i in. "CD74 is a novel transcription regulator". Proceedings of the National Academy of Sciences 114, nr 3 (28.12.2016): 562–67. http://dx.doi.org/10.1073/pnas.1612195114.
Pełny tekst źródłaStreszczenie:
CD74 is a cell-surface receptor for the cytokine macrophage migration inhibitory factor. Macrophage migration inhibitory factor binding to CD74 induces its intramembrane cleavage and the release of its cytosolic intracellular domain (CD74–ICD), which regulates cell survival. In the present study, we characterized the transcriptional activity of CD74–ICD in chronic lymphocytic B cells. We show that following CD74 activation, CD74–ICD interacts with the transcription factors RUNX (Runt related transcription factor) and NF-κB and binds to proximal and distal regulatory sites enriched for genes involved in apoptosis, immune response, and cell migration. This process leads to regulation of expression of these genes. Our results suggest that identifying targets of CD74 will help in understanding of essential pathways regulating B-cell survival in health and disease.
Rozprawy doktorskie na temat "Runt related transcription factor"
1
Mümmler, Carlo [Verfasser], i Melanie [Akademischer Betreuer] Königshoff. "Runt-related transcription factor 2 in pulmonary fibrosis / Carlo Mümmler ; Betreuer: Melanie Königshoff". München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2019. http://d-nb.info/1180285786/34.
Pełny tekst źródła
2
Curinga, Gabrielle Mercedes. "The role of runt-related transcription factor 2 in arterial smooth muscle cell mineralization /". Thesis, Connect to this title online; UW restricted, 2003. http://hdl.handle.net/1773/6353.
Pełny tekst źródła
3
Isehaq, Saif Said Al-Huseini. "Deletion of IκB-Kinase β in Smooth Muscle Cells Induces Vascular Calcification Through β-Catenin-Runt-Related Transcription Factor 2 Signaling". Kyoto University, 2018. http://hdl.handle.net/2433/232306.
Pełny tekst źródła
4
Alsabeelah, Nimer Fehaid N. "Vascular calcification in rat cultured smooth muscle cells : a role for nitric oxide". Thesis, University of Hertfordshire, 2016. http://hdl.handle.net/2299/17217.
Pełny tekst źródłaStreszczenie:
The underlying inflammatory storm in renal or diabetic disease may induce expression of inducible nitric oxide synthase (iNOS). Similarly, expression of iNOS or nitric oxide (NO) production in vascular smooth muscle cells (VSMCs) in a calcifying environment, may promote vascular calcification (VC) (Zaragoza et al., 2006). However, emerging data suggests that NO generated by either endothelial nitric oxide synthase (eNOS) or iNOS may protect VSMCs from VC (Kanno et al., 2008). Thus, the role of NO and its associated enzymes in the development of VC is unclear. The aim of this study was to identify whether NO produced by iNOS regulates calcification in VSMCs, and to further understanding of potential mechanisms that may mediate the actions of NO/iNOS. A significant and sustained production of NO by iNOS, which peaked at day 3 and declined thereafter was found in rat aortic smooth muscle cells (RASMCs) that were preactivated with lipopolysaccharide (LPS; 100μg ml-1) and interferon gamma (IFN-γ;100U ml-1) in the presence of calcification buffer (CB) containing calcium chloride (CaCl2; 7mM) and β-glycerophosphate (β-GP; 7mM). This was associated with formation of hydroxyapatite crystals (HA) or calcification plaques, observed via alizarin red staining (ARS) and/or fourier transform infrared (FT-IR) analysis. However, when RASMCs were incubated with the iNOS inhibitor GW274150 at 10 μM, together with LPS + IFN-γ + CB, HA crystal formation was abolished. When RASMCs were pretreated with diethylenetriamine/nitric oxide adduct (NOC 18) at either 30 or 50 μM for an hour prior to addition of CB, to generate NO; calcium levels were elevated leading to form HA crystals. However, the elevation of calcium caused by the presence of NO generated via iNOS, did not result in phosphorylation of mitogen activated protein kinases (p38 MAPK), extracellular signal-regulated kinases (Erks), and protein kinase B. Furthermore, there was a reduction of Runx2 levels (pro-calcific factor) which could be another pro-calcific factor involved in this mechanism. These findings suggest that NO may indeed play a fundamental role in calcification, enhancing mineralisation of smooth muscle cells. Furthermore, the expression of iNOS/ NO appears to be enhanced under conditions that favour calcification and these together may contribute to enhanced calcification with potential detrimental consequences in vivo.
5
Vaughan, Tanya, i n/a. "Identifying Genes Influencing Bone Mineral Density". Griffith University. School of Health Science, 2004. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20040430.161453.
Pełny tekst źródłaStreszczenie:
Bone mineral density (BMD) is a reflection of the action of osteoblasts compared to osteoclasts. An imbalance in the activity of osteoblasts or osteoclasts, results in bone disease such as osteoporosis caused by overactive osteoclasts. BMD is influenced by genetic and environmental factors as demonstrated through twin studies, association studies and linkage analysis (Ralston, 1999). Several polymorphisms involved in the determination of BMD have been identified, with Vitamin D receptor and Collagen Type 1 showing reproducible associations. To identify genes influencing BMD two distinct strategies have been employed: 1) To determine if DNA polymorphism within the runt related transcription factor (RUNX2) gene is a determinant of BMD and fracture in women. 2) The identification of RANKL target genes in osteoclastogenesis. RUNX2 is a runt domain transcription factor (Werner et al., 1999) essential for osteoblast differentiation (Lee et al., 1997). RUNX2 gene knock-out mice have no osteoblasts due to a failure in osteoblast differentiation and consequently unmineralised skeletons, (Komori et al., 1997; Otto et al., 1997). In humans, mutations in RUNX2 cause cleidocranial dysplasia (CCD), a disorder characterised by hypoplasia or aplasia of the clavicles, short stature, supernumerary teeth, patent fontanelles and other changes in skeletal patterning and growth (Mundlos et al., 1997). RUNX2 contains a poly-glutamine poly-alanine (polyQ/polyA) repeat where mutations causing cleidocranial dysplasia have been observed. BMD has not been routinely examined in CCD, two studies have identified CCD patients with lower BMD with one fracture case identified (Quack et al., 1999; Bergwitz et al., 2001). The central role of RUNX2 in determining osteoblast differentiation makes RUNX2 a prime candidate gene for regulating adult bone density. To determine if polymorphism was present in the polyQ/polyA tract the repeat was amplified within the upper and lower deciles of femoral neck (FN) BMD in the Geelong Osteoporosis study (GOS). The upper and lower deciles of FN BMD acted as a surrogate for genotyping the entire cohort. This study identified two common variants within the polyA repeat: an 18 base pair deletion (11Ala) and a synonymous alanine codon polymorphism with alleles, GCA and GCG (noted as A and G alleles, respectively). The 11Ala and SNP polymorphism are found on codon 64 and 66 respectively (RUNX2 MRIPV variant). A allele frequencies were significantly different in a comparison of the upper and lower deciles of FN BMD (p=0.019). In 495 randomly selected women of the Geelong Osteoporosis Study (GOS), the A allele was associated with higher BMD at all sites tested. The association was maximal at the ultra-distal radius (p=0.001). In a separate fracture study, the A allele was significantly protective against Colles' fracture in elderly women but not spine and hip fracture. The 11Ala polymorphism was not related to BMD in GOS. To further decipher the role of the RUNX2 A allele we genotyped 992 women from a Scottish cohort. The alleles of RUNX2 within the glutamine/alanine repeat were determined by MspA1I restriction digest. To examine the possible influence on estrogen related therapies or estrogen status on the potential genetic effect conferred by RUNX2, we divided the cohort by menopausal and hormone replacement therapy status. Within postmenopausal Scottish women the RUNX2 A allele was associated with significantly higher FN BMD (p=0.028, n=312) but not lumbar spine (LS) BMD. The A allele was associated with higher FN BMD (p=0.035) within a postmenopausal subgroup of the population (n=312). To investigate the effect of weight on the RUNX2 alleles the Scottish cohort was segregated into thin/normal (BMI ≥ 25 kg/m2) and overweight /obese (BMI > 25 kg/m2). RUNX2 A allele showed a stronger effect on FN BMD in postmenopausal women above the median BMI. The 11Ala RUNX2 deletion allele was significantly associated with decreased LS BMD (p=0.018) within overweight/obese women (n=546). The 11Ala allele was significantly associated with increased levels of pyridinoline (p=0.014) and deoxypyridinoline (p=0.038) in the HRT treated subgroup of the population (n=492). Glutamine variants and an alanine insertion were identified within the group. These data suggest that the RUNX2 11Ala and A alleles exert differing affects on BMD showing preference for different skeletal sites in a weight dependent manner. We genotyped 78 individuals from an osteoarthritic population to elucidate the role of the RUNX2 alleles on markers of bone turnover and inflammation. The RUNX2 11Ala allele was significantly associated with decreased osteocalcin (OC) serum levels (p = 0.01). The RUNX2 A allele was significantly related to reduced tumor necrosis factor alpha (TNF-alpha) serum levels (p = 0.004). RUNX2 is known to bind to the OC promoter. An OC promoter polymorphism is found 7bp upstream from a putative RUNX2 binding site. We hypothesized that OC polymorphism may effect the RUNX2 transactivation of the OC gene and thus affect OC serum levels. OC promoter polymorphism was not related to OC serum levels (n=78). These data present a novel link between RUNX2 alleles and OC and TNF serum levels, providing putative mechanisms of action for the RUNX2 alleles. Further studies in larger populations are required to confirm these findings. Ten individuals within the GOS and the Scottish cohort were found to carry rare mutations of the polyQ/polyA repeat. All polyQ variants had a normal polyA repeat (17 amino acids) and were heterozygous for a normal 23Q/17A allele. Variants observed were 15, 16, 24 and 30Q. One individual was observed with an extended polyA repeat (24A). Patient records indicated otherwise unremarkable clinical history except for fracture in 4/10 individuals from GOS (hip and spine). BMD data from the LS and the FN were expressed as T-scores, a measure that relates BMD in terms of standard deviations below the young normal value. In addition, BMD data were also expressed as Z-scores around the age-mean. Under the null hypothesis, where RUNX2 Q repeat variation has no effect on BMD, Z scores would be expected to be distributed around a mean of zero. However, when all variants were pooled the BMD was significantly lower than expected. This effect persisted when deletion variants were considered alone. The effect was stronger on FN BMD (p=0.001) rather than LS BMD (p=0.096), reflecting either difference in precision of BMD measurements at these sites or perhaps a differential genetic effect on different skeletal sites. These data suggest that polyQ and polyA variants are associated with significantly lower BMD, and may be an important determinant for fracture. Glutamine variants exist at high frequency (~0.7%): this rate of mutation could be important when considering large populations at risk of age related osteoporosis. Considering that these subjects are heterozygous for a normal allele, it suggests that a more severe phenotype might be expected in rare subjects homozygous for glutamine repeat variants. In summary, this study investigated the role of novel polymorphisms and rare variants of the RUNX2 gene in influencing BMD, fracture and markers of bone turnover. Two common polymorphisms were identified within the polyA repeat: an 18 base pair deletion and a synonymous alanine codon polymorphism with alleles, A and G. The A allele was associated with increased BMD and was protective against a common form of osteoporotic fracture within a Geelong population. To verify these findings the RUNX2 alleles were genotyped in 992 women from a Scottish cohort. The magnitude and the direction of the effect of the A allele was maintained in the Scottish cohort. Interestingly, the A allele was shown to exert a menopause specific effect, with postmenopausal women showing the strongest effect. On re-analysis of the GOS data the post-menopausal women were found to drive the significance identified in the cohort. The magnitude of the effect of the A allele on BMD was greater in overweight/obese postmenopausal women indicating a gene-weight interaction for RUNX2. The RUNX2 11Ala allele showed a significant relationship with decreased LS BMD in overweight/obese Scottish women. The 11Ala allele was also associated with higher levels of urinary PYD and DPD in women treated with HRT, indicating higher levels of bone turnover in carriers of the 11Ala allele. In contrast to the Scottish cohort, no significant association with heterozygous carriers of 11Ala was observed in GOS, although a significant association was detected for homozygous carriers and LS BMAD. The 11 Ala RUNX2 allele was significantly associated with decreased serum osteocalcin levels and the A allele was significantly associated with TNF in OA patients. Glutamine variants and an alanine insertion were identified within Geelong and Scottish cohorts, which showed low Z and T scores suggesting that RUNX2 variants may be related to genetic effects on BMD and osteoporosis. Polymorphism of the polyQ/polyA region of RUNX2 were identified within this study were shown to associate with significant differences in BMD. The A allele showed a significant association with increased BMD in postmenopausal women from a Geelong and Scottish cohort, with a decreased frequency of the A allele observed in Colles' fracture patients from Geelong. The 11Ala deletion allele was significantly associated with decreased LS BMD and increases in markers of bone turnover in the Scottish cohort. A significant decrease in OC serum levels was observed in OA patients suggesting a direct effect of the allele on the transactivation of the RUNX2 gene. Rare variants of RUNX2 were identified which showed low BMD. These studies have provided insight into the role of RUNX2 in influencing BMD, further studies are required to verify the role of the A allele on BMD and fracture, the role of the rare variants and to identify the precise mechanisms behind the observed changes in BMD. - 2) The identification of RANKL target genes in osteoclastogenesis. Osteoclastogenesis is regulated in vivo by the action of osteoblast/stromal cells that express membrane bound, receptor activator of NF-kB ligand (RANKL). Monocytes treated in vitro with a soluble form of RANKL and macrophage colony stimulating factor (M-CSF) differentiate to osteoclasts, whereas monocytes treated with M-CSF alone differentiate to macrophage-like cells. The gene expression profile of human osteoclasts has not been extensively explored. Genes highly expressed by rabbit osteoclasts were identified through random sequencing of an osteoclast cDNA library (Sakai et al., 1995). Differential gene expression of mouse osteoclastogenesis was elucidated by array analysis (Cappellen et al., 2002). To identify genes important for human osteoclastogenesis, total RNA was isolated from monocytes treated for three weeks with either M-CSF alone or with RANKL and M-CSF. RANKL treatment for 3 weeks and 12 hours was investigated in this study, to complement previous data. Differential display was performed on RNA (12 hour treatment with RANKL) and differential gene expression profiles examined. The differential display products were pooled to generate a probe for screening a gene array system derived from a human osteoclast cDNA library. cDNA (3 week treatment with RANKL) hybridisation experiments against the array revealed additional regulated genes. Gene clones that showed significant regulation in M-CSF and RANKL treated cells compared M-CSF treated cells represent genes that are targets for RANKL-specific regulation. Osteopontin, creatine kinase and various mitochondrial genes were up regulated by the treatment of RANKL. Changes in gene expression observed in the array data were confirmed with real-time PCR using mRNA derived from in vitro induced osteoclasts. Cathepsin K gene expression was more than 300 fold greater in osteoclasts compared to macrophage-like cells after one week treatment with RANKL and M-CSF. Cystatin C expression showed a six-fold induction at two weeks of RANKL and M-CSF treatment and cystatin B showed a steady increase in expression. Some of these regulated genes may provide useful targets for influencing BMD.
6
Vaughan, Tanya. "Identifying Genes Influencing Bone Mineral Density". Thesis, Griffith University, 2004. http://hdl.handle.net/10072/366470.
Pełny tekst źródłaStreszczenie:
In summary, this study investigated the role of novel polymorphisms and rare variants of the RUNX2 gene in influencing BMD, fracture and markers of bone turnover. Two common polymorphisms were identified within the polyA repeat: an 18 base pair deletion and a synonymous alanine codon polymorphism with alleles, A and G. The A allele was associated with increased BMD and was protective against a common form of osteoporotic fracture within a Geelong population. To verify these findings the RUNX2 alleles were genotyped in 992 women from a Scottish cohort. The magnitude and the direction of the effect of the A allele was maintained in the Scottish cohort. Interestingly, the A allele was shown to exert a menopause specific effect, with postmenopausal women showing the strongest effect. On re-analysis of the GOS data the post-menopausal women were found to drive the significance identified in the cohort. The magnitude of the effect of the A allele on BMD was greater in overweight/obese postmenopausal women indicating a gene-weight interaction for RUNX2. The RUNX2 11Ala allele showed a significant relationship with decreased LS BMD in overweight/obese Scottish women. The 11Ala allele was also associated with higher levels of urinary PYD and DPD in women treated with HRT, indicating higher levels of bone turnover in carriers of the 11Ala allele. In contrast to the Scottish cohort, no significant association with heterozygous carriers of 11Ala was observed in GOS, although a significant association was detected for homozygous carriers and LS BMAD. The 11 Ala RUNX2 allele was significantly associated with decreased serum osteocalcin levels and the A allele was significantly associated with TNF in OA patients. Glutamine variants and an alanine insertion were identified within Geelong and Scottish cohorts, which showed low Z and T scores suggesting that RUNX2 variants may be related to genetic effects on BMD and osteoporosis. Polymorphism of the polyQ/polyA region of RUNX2 were identified within this study were shown to associate with significant differences in BMD. The A allele showed a significant association with increased BMD in postmenopausal women from a Geelong and Scottish cohort, with a decreased frequency of the A allele observed in Colles’ fracture patients from Geelong. The 11Ala deletion allele was significantly associated with decreased LS BMD and increases in markers of bone turnover in the Scottish cohort. A significant decrease in OC serum levels was observed in OA patients suggesting a direct effect of the allele on the transactivation of the RUNX2 gene. Rare variants of RUNX2 were identified which showed low BMD. These studies have provided insight into the role of RUNX2 in influencing BMD, further studies are required to verify the role of the A allele on BMD and fracture, the role of the rare variants and to identify the precise mechanisms behind the observed changes in BMD.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Health Sciences
Full Text
7
Taber, Thomas Howland. "Thyroid Hormone Receptor SS (trß) Regulation Of Runt-Related Transcription Factor 2 (runx2) In Thyroid Tumorigenesis: Determination Of The Trß Nuclear Protein Complexes That Associate With The Runx2 Gene". ScholarWorks @ UVM, 2017. http://scholarworks.uvm.edu/graddis/820.
Pełny tekst źródłaStreszczenie:
Thyroid Tumorigenesis is typically a well understood process, with well delineated oncogenic factors. Follicular and papillary thyroid cancers are typically survivable, with 5-year survival rates being >95% for Stage I-III of both cancer types. Anaplastic thyroid cancer, in contrast, lacks this prognosis, and is the most lethal of all endocrine-related cancers. The median survival time after a diagnosis is generally between 6-8 months, with a 5-year survival rate of <10%. Current treatment for anaplastic thyroid cancers routinely meet roadblocks, as resistance is quickly developed. Even non-discriminatory kinase inactivators, such as sorafenib, which are generally considered a drug of last resort, are unable to effect survival rates. As such, there is a clear need for further investigation of the causes of anaplastic thyroid cancer mechanisms.
Previous work in the Carr lab revealed a novel regulatory pathway of an oncogene that is associated with several other endocrine-related cancers, as well as other non-endocrine-related cancers. Specifically, the Runt-related transcription factor 2 (Runx2) was found to be suppressed via direct binding of the thyroid hormone receptor beta 1 isoform (TRß1) to its proximal promotor. Runx2 was previously shown to be associated with increasing malignancy, with Runx2 occurring at low-levels in indolent cell lines, whilst occurring at high-levels in more malignant cell lines. TRß1, conversely, exhibited the opposite relationship. Endogenous levels of TRß1 were found to be high in indolent cell lines and were depleted in malignant cell lines. These findings were further confirmed via tissue microarrays. Restoration of TRß1 in malignant cell lines diminished Runx2 mRNA and protein levels, which was corroborated by evidence from electrophoretic mobility-shift assays, and chromatin immunoprecipitations that TRß1 was able to directly bind Runx2 promotor 1.
Current studies have investigated the nuclear protein profile that associates with TRß1 to alter Runx2 transcription. Through EMSA-to-Mass Spectrometry methodologies, as well as novel DNA pulldown techniques, binding partners have been elucidated. Findings have also been confirmed via classical immunoprecipitations. Specifically, our findings show that TRß1 complexes with the brahma-related gene 1 (BRG1) protein, the nuclear co-repressor (NCOR), and BRG1-associated protein 60 (BAF60). BRG1 functions by preferentially recruiting histone deacetylases (HDAC), with BRG1 and the HDAC’s acting to alter chromatin, and thus transcription. Future studies aim at examining whether other proteins complex with TRß1 to alter Runx2 transcription, and whether these complexes are altered in aggressive cell lines.
8
Cardoso, Camila Lopes. "Análise morfométrica e molecular da alveolite induzida em ratos com diferentes modalidades de tratamento". Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/25/25132/tde-27052009-102252/.
Pełny tekst źródłaStreszczenie:
A alveolite é uma complicação pós-operatória de carácter inflamatório que acomete alvéolos de dentes recém-extraídos. A incidência dessa complicação varia de 1 a 4% e pode chegar a 30%. O objetivo deste estudo foi analisar os mecanismos biológicos envolvidos no processo de reparo de alvéolos intencionalmente infectados, em ratos; comparar diferentes modalidades de tratamento e correlacionar os resultados encontrados através de duas análises (microscópica e molecular). Foram utilizados 84 ratos, divididos nos grupos: I: alvéolo não infectado; II: alvéolo infectado sem nenhum tratamento; III: alvéolo infectado tratado com irrigação de solução de iodeto de sódio a 2% e peróxido de hidrogênio a 3% na proporção de 1:1; e IV: alvéolo infectado submetido à curetagem, irrigação com soro fisiológico e preenchimento com uma pasta à base de metronidazol. Os animais foram eutanasiados aos 6, 15 e 28 dias pós-operatório. Foi realizada a análise quantitativa da expressão de genes envolvidos no processo de reparo [colágeno tipo I (COL-I), fator de crescimento do endotélio vascular (VEGF), osteocalcina (OCN), fosfatase alcalina (ALP), runt-related transcription factor 2 (RUNX2) e fator de necrose tumoral alfa (TNF-\'alfa\')], através da RealTimePCR, correlacionando sua expressão com as características microscópicas observadas qualitativa e quantitativamente. Com base nos resultados da análise microscópica e molecular, podemos concluir que os marcadores RUNX2, OCN e TNF-\'alfa\' podem ser usados como indicadores para avaliar a neoformação óssea e a quantidade de infiltrado inflamatório em alveolite. Os marcadores ALP e VEGF não representaram adequadamente o que se observou microscopicamente. Embora o tratamento da alveolite com a pasta à base de metronidazol promova maior densidade de neoformação óssea aos 28 dias, não há diferenças entre os tratamentos.Dry socket is an inflammatory postoperative complication that undertakes sockets of recently extracted teeth. The incidence of such complication varies from 1 to 4% and might reach up to 30%. The objective of this study was to analyze the biological mechanisms involved in the repair process of intentionally infected sockets in mice; compare different treatment conditions and correlate the results of two different analysis (microscopic and molecular). 84 mice were used in this study, divided according the following groups: I: uninfected socket; II: infected socket without any treatment; III: infected socket treated with irrigation of 2% sodium iodide and 3% hydrogen peroxide solution at 1:1 proportion; and IV: infected socket submitted to curettage, physiological saline solution irrigation and fulfillment with metronidazole base paste. The animals were killed at a postoperative period of 6, 15 and 28 days. A quantitative analysis was performed using a RealTimePCR to evaluate the genes expression involved [Collagen Type I (COL-I), vascular endothelial growth factor (VEGF), osteocalcin (OCN), alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2) and tumor necrosis factor-alpha (TNF-\'alpha\')], in the repair process, correlating its expression with the microscopic characteristics observed in both qualitative and quantitative manner. Based in the results of the microscopic and molecular analysis, it can be concluded that the RUNX2, OCN and TNF-\'alpha\' markers can be used as indicators to evaluate the dry socket bone neoformation and inflammatory infiltrate quantity. The ALP and VEGF markers did not represented appropriately what was observed microscopically. Although the dry socket treatment with metronidazole base paste promotes an increase in the bone neoformation density at 28 days, no difference was found among the treatments.
9
Bäckström, Stefan. "The hematopoietic transcription factor RUNX1 : a structural view". Doctoral thesis, Umeå University, Umeå Centre for Molecular Pathogenesis (UCMP), 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-192.
Pełny tekst źródłaStreszczenie:
The malfunction of the transcriptional regulator RUNX1 is the major cause of several variants of acute human leukemias and its normal function is to regulate the development of the blood system in concert with other transcriptional co-regulators. RUNX1 belongs to a conserved family of heterodimeric transcription factors that share a conserved DNA binding domain, the Runt domain (RD), named after the first member of this group – Runt - found in Drosophila melanogaster. The binding partner CBFβ serves as a regulator of RUNX by enhancing its DNA binding affinity through an allosteric mechanism.
The main focus ofo my thesis work has been the crystallization and structural analysis of the RUNX1 RD and involved also more technical methodological aspects that can be applied to X-ray crystallography in general.
The high resolution crystal structure of the free RD shows that this immunoglobulin-like molecule undergoes significant structural changes upon binding to both CBFβ and DNA. This involves a large flip of the L11 loop from a closed conformation in the free protein to an open conformation when CBFβ and/or DNA are bound. We refer to this transition as the “S-switch”. Smaller but significant conformational changes in other parts of the RD accompany the “S-switch”. We suggest that CBFβ triggers and stabilizes the “S-switch” which leads to the conversion of the RD into a conformation enhanced for DNA binding.
During the structural analysis of the RD we identified two chloride ions that are coordinated by residues otherwise involved in DNA binding. In electrophoretic mobility-shift analyses (EMSA) we demonstrated a chloride ion concentration dependent stimulation of the DNA binding affinity of RUNX1. We further showed by NMR line width broadening experiments that the chloride binding occurred within the physiological range. A comparable DNA binding stimulation of RUNX1 was seen in the presence of negative amino acids. This suggests a regulation of the DNA binding activity of RUNX1 proteins through acidic amino acid residues possibly provided by activation domains of transcriptional co-regulators that interact with RUNX1.
The use of the anomalous signal from halide ions has become a powerful technique for obtaining phase information. By replacing the sodium chloride with potassium bromide in the crystallisation conditions of the RD, we could demonstrate in a single wavelength anomalous diffraction (SAD) experiment that the anomalous signal from 2 bromide ions were sufficient to phase a 16 kDa protein. Due to lack of completeness in the low-resolution shells caused by overloaded intensities, density modification schemes failed and the resulting electron density maps were not interpretable. By combining the highresolution
synchrotron data with low-resolution data from a native data set collected on a home X-ray source, the density modified bromide phases gave easily traceable maps.
10
Yu, Wai Man C. Y. O. L. "Targeting the Myocardin-related transcription factor/serum response factor (MRTF/SRF) pathway in conjunctival fibrosis". Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/1559574/.
Pełny tekst źródłaStreszczenie:
Glaucoma is the leading cause of irreversible blindness and its prevalence is estimated to reach 79.6 million people by 2020. Wound contraction and scarring are the principal causes of blockage of aqueous flow at the drainage site in glaucoma filtration surgery. The cytotoxic antimetabolites, mitomycin-C and 5-fluorouracil, are widely used but have potentially blinding complications. There is thus a large unmet need for alternative agents with more targeted physiological effects and less cytotoxicity. The myocardin-related transcription factor/serum response factor (MRTF/SRF) pathway is a master regulator of cytoskeletal gene expression and thus represents a promising therapeutic target to prevent fibrosis. The MRTF/SRF pathway in human conjunctival fibroblasts responds to actin dynamics but as human conjunctival fibroblasts have constitutively high MRTF-A and MRTF-B nuclear concentrations, they show a relatively small response to serum stimulation and actin binding drugs, such as latrunculin B and cytochalasin D. The localisation of MRTF-A and MRTF-B is also conserved across species in mouse and rabbit conjunctival fibroblasts. As the MRTF/SRF pathway is a master regulator of many key cytoskeletal genes in fibrosis, we next studied the effects of downregulating the MRTF/SRF pathway in human conjunctival fibroblasts using three-dimensional in vitro collagen contraction assays. MRTF-A and MRTF-B siRNA silencing significantly decreased collagen matrix contraction, the cell protrusive activity, matrix degradation, and the expression of key matrix metalloproteinase genes. Liposome-peptide-siRNA nanoparticles also represent an efficient and safe siRNA delivery system for MRTF silencing in conjunctival fibrosis. We further compared the contractility of fibrotic and non-fibrotic human conjunctival fibroblasts from glaucoma patients with and without previous glaucoma surgery, respectively. Fibrotic human conjunctival fibroblasts were significantly more contractile than non-fibrotic human conjunctival fibroblasts, and the increased contractility was linked to the upregulation of alpha smooth muscle actin, a marker of myofibroblast differentiation. We finally validated in vivo the effects of inhibiting the MRTF/SRF pathway in conjunctival fibrosis using a rabbit model of experimental glaucoma filtration surgery. We have identified a new MRTF/SRF pathway inhibitor CCG-222740, which was more potent in the fibroblast-mediated collagen contraction assay, less cytotoxic, and a more potent inhibitor of alpha smooth muscle actin expression than inhibitor CCG-203971. Local delivery of CCG-222740 and CCG-203971 in a rabbit model of conjunctival fibrosis significantly increased the long-term success of the surgery and decreased scar tissue formation histologically. Unlike mitomycin-C, neither CCG-222740 nor CCG- 203971 caused any epithelial toxicity or systemic side effects with very low drug levels measured in the aqueous, vitreous and serum. In conclusion, our in vitro and in vivo results support that inhibiting the MRTF/SRF pathway represents a potential new therapeutic target to prevent conjunctival fibrosis in glaucoma and other contractile scarring conditions in the eye.
Książki na temat "Runt related transcription factor"
1
Soliman, Karam F. A., i Yashwant Pathak. Flavonoids and Anti-Aging: The Role of Transcription Factor Nuclear Erythroid 2-Related Factor2. Taylor & Francis Group, 2023.
Znajdź pełny tekst źródła
2
Soliman, Karam F. A., i Yashwant Pathak. Flavonoids and Anti-Aging: The Role of Transcription Factor Nuclear Erythroid 2-Related Factor2. Taylor & Francis Group, 2023.
Znajdź pełny tekst źródła
3
Soliman, Karam F. A., i Yashwant Pathak. Flavonoids and Anti-Aging: The Role of Transcription Factor Nuclear Erythroid 2-Related Factor2. Taylor & Francis Group, 2023.
Znajdź pełny tekst źródła
4
Structure-function analysis of the immediate early transcription factor Egr-1 and identification of a gene repressed by a related zinc finger protein, the Wilms tumor suppressor WT1. 1992.
Znajdź pełny tekst źródła
5
Chess, Andrew, i Schahram Akbarian. The Human Brain and its Epigenomes. Redaktorzy Dennis S. Charney, Eric J. Nestler, Pamela Sklar i Joseph D. Buxbaum. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190681425.003.0003.
Pełny tekst źródłaStreszczenie:
Conventional psychopharmacology elicits an insufficient therapeutic response in more than one half of patients diagnosed with schizophrenia, bipolar disorder, depression, anxiety, or related disorders. This underscores the need to further explore the neurobiology and molecular pathology of mental disorders in order to develop novel treatment strategies of higher efficacy. One promising avenue of research is epigenetics.Deeper understanding of genome organization and function in normal and diseased human brain will require comprehensive charting of neuronal and glial epigenomes. This includes DNA cytosine and adenine methylation, hundred(s) of residue-specific post-translational histone modifications and histone variants, transcription factor occupancies, and chromosomal conformations and loopings. Epigenome mappings provide an important avenue to assign function to many risk-associated DNA variants and mutations that do not affect protein-coding sequences. Powerful novel single cell technologies offer the opportunity to understand genome function in context of the vastly complex cellular heterogeneity and neuroanatomical diversity of the human brain.
Części książek na temat "Runt related transcription factor"
1
Will, Thorsten. "Related work". W Predicting Transcription Factor Complexes, 25–43. Wiesbaden: Springer Fachmedien Wiesbaden, 2014. http://dx.doi.org/10.1007/978-3-658-08269-7_2.
Pełny tekst źródła
2
Ikeda, Kazuhiro, Kuniko Horie-Inoue i Satoshi Inoue. "Analysis of TFRNs Associated with Steroid Hormone-Related Cancers". W Transcription Factor Regulatory Networks, 197–209. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-0805-9_16.
Pełny tekst źródła
3
Ito, Yoshiaki, i Suk-Chul Bae. "The Runt Domain Transcription Factor, PEBP2/CBF, and its Involvement in Human Leukemia". W Oncogenes as Transcriptional Regulators, 107–32. Basel: Birkhäuser Basel, 1997. http://dx.doi.org/10.1007/978-3-0348-8934-6_4.
Pełny tekst źródła
4
Grant, Struan F. A., i Leif Groop. "Transcription Factor 7-Like 2 (TCF7L2)". W The Genetics of Type 2 Diabetes and Related Traits, 297–316. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-01574-3_14.
Pełny tekst źródła
5
Lambros, Mandy L., i Scott M. Plafker. "Oxidative Stress and the Nrf2 Anti-Oxidant Transcription Factor in Age-Related Macular Degeneration". W Retinal Degenerative Diseases, 67–72. Cham: Springer International Publishing, 2015. http://dx.doi.org/10.1007/978-3-319-17121-0_10.
Pełny tekst źródła
6
Gilmore, Thomas D., i Céline Gélinas. "Methods for Assessing the In Vitro Transforming Activity of NF-κB Transcription Factor c-Rel and Related Proteins". W Methods in Molecular Biology, 427–46. New York, NY: Springer New York, 2015. http://dx.doi.org/10.1007/978-1-4939-2422-6_26.
Pełny tekst źródła
7
"Runt-Related Transcription Factor 3". W Encyclopedia of Signaling Molecules, 4773. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-67199-4_103376.
Pełny tekst źródła
8
Panovska-Stavridis, Irina. "Molecular Monitoring in Acute Myeloid Leukemia Patients Undergoing Matched Unrelated Donor: Hematopoietic Stem Cell Transplantation". W Acute Leukemias [Working Title]. IntechOpen, 2020. http://dx.doi.org/10.5772/intechopen.94830.
Pełny tekst źródłaStreszczenie:
Minimal residual disease (MRD) in acute myeloid leukemia (AML) is a complex, multi-modality assessment and much as its clinical implications at different points are extensively studied, it remains even now a challenging area. It is the disease biology that governs the modality of MRD assessment; in patients harboring specific molecular targets, high sensitivity techniques can be applied. In AML patients undergoing allogenic hematopoietic stem cell transplantation (alloHSCT), relapse in considered as leading cause for treatment failure. In post-transplant setting, regular MRD status assessment enables to identify patients at risk of impending relapse when early therapeutic intervention may be beneficent. We analyzed data of AML patients who underwent matched unrelated donor (MUD) HSCT since the introduction of this procedure in the Republic of North Macedonia. Chimeric fusion transcripts were identified in three patients; two of them positive for RUNX-RUNX1T1 transcript and one for CBFB-MYH11. One patient harbored mutation in the transcription factor CCAAT/enhancer binding protein α (CEBPA). Post-transplant MRD kinetics was measured by quantitative polymerase chain or multiplex fluorescent-PCR every three months after the transplantation during the first two years after the transplant. MRD negativity was achieved in three patients by the sixth month of HSCT, who were pre-transplant MRD positive. They sustained hematological and molecular remission for 19, 9 and 7 months, respectively. The forth patient died due to transplant-related complication. Our experience suggests, when molecularly-defined AML patients undergo HSCT, regular MRD monitoring helps predict impending relapse and direct future treatment strategies.
9
Tarı Selçuk, Kevser. "Epidemiology of Inflammation-Related Diseases". W Role of Nutrition in Providing Pro-/Anti-Inflammatory Balance, 24–44. IGI Global, 2020. http://dx.doi.org/10.4018/978-1-7998-3594-3.ch002.
Pełny tekst źródłaStreszczenie:
Inflammation, a vital defense mechanism for health, is defined as the immune system's response to harmful stimuli such as pathogens, damaged cells, toxic compounds or irradiation. Inflammation is usually examined in two groups: acute and chronic. Chronic inflammation instigates various kinds of diseases that cause premature mortality and morbidity such us cardiovascular diseases, cancer, diabetes mellitus (DM), asthma-chronic obstructive pulmonary disease (COPD), obesity, metabolic syndrome (METs), inflammatory bowel disease (IBD), rheumatoid arthritis (RA), multiple sclerosis (MS), osteoporosis, and neurological diseases via dysregulation of various signaling pathways such as nuclear factor kappa-B (NF-κB), signal transducer, activator of transcription 3 (STAT3), etc. These inflammation-related diseases are among the major causes of mortality and morbidity in almost every region of the world. Studies have shown that these diseases associated with inflammation have tended to increase worldwide.
10
Isomura, Hiroki. "DNA Polymerase Processivity Factor of Human Cytomegalovirus May Be a Key Molecule for Molecular Coupling of Viral DNA Replication to Transcription". W DNA Replication and Related Cellular Processes. InTech, 2011. http://dx.doi.org/10.5772/18144.
Pełny tekst źródłaStreszczenia konferencji na temat "Runt related transcription factor"
1
Liu, Ka, Richard L. Smith, Trang Nguyen-Vu, Nicholes R. Candelaria, Colin M. Rogerson, W. Evan Johnson, Edwin Cheung i in. "Abstract 3107: Runt-related transcription factor 1 (RUNX1) is involved in transcriptional repression by estrogen receptor and breast cancer cell proliferation." W Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-3107.
Pełny tekst źródła
2
Rada, Miran, Audrey Kapelanski-Lamoureux, Stephanie Petrillo, Sébastien Tabariès, Peter Siegel, Anthoula Lazaris i Peter Metrakos. "Abstract 3935: Runt related transcription factor-1 (runx1) plays a central role in vessel co-option of colorectal cancer liver metastases". W Proceedings: AACR Annual Meeting 2020; April 27-28, 2020 and June 22-24, 2020; Philadelphia, PA. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1538-7445.am2020-3935.
Pełny tekst źródła
3
Lestari, Citra, Eryati Darwin, Deddi Prima Putra i Netti Suharti. "The Effect of α-Mangosteen on Runt-Related Transcription Factor 2 and Tartrate-Resistant Acid Phosphatase 5b Expressions on Bone Remodeling in Periodontitis (An Experimental Research on Wistar Rats)". W 1st International Conference on Health Sciences and Biotechnology (ICHB 2021). Paris, France: Atlantis Press, 2022. http://dx.doi.org/10.2991/ahsr.k.220303.007.
Pełny tekst źródła
4
Huang, Xiangwei, Ying Gai, Rajesh Thouta, Naiheng Yang, Miao Mi, Victor Thannickal i Yong Zhou. "Mechanotransduction-Induced Myofibroblast Differentiation And Survival Is Mediated By Myocardin-Related Transcription Factor (MRTF)-A". W American Thoracic Society 2011 International Conference, May 13-18, 2011 • Denver Colorado. American Thoracic Society, 2011. http://dx.doi.org/10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a3569.
Pełny tekst źródła
5
Arima, Yoshimi, Mari Hosonaga i Hideyuki Saya. "Abstract 522: The epithelial-mesenchymal transition-related transcription factor ZEB suppressesClaudinexpression in breast cancer cells." W Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-522.
Pełny tekst źródła
6
Hasegawa, Reika. "A homeodomain transcription factor, BRASSISTEORID-RELATED HOMEOBOX 1, act as a negative regulator for Brassisteroid feedback loop". W ASPB PLANT BIOLOGY 2020. USA: ASPB, 2020. http://dx.doi.org/10.46678/pb.20.1052915.
Pełny tekst źródła
7
Huang, Xiangwei, Naiheng Yang, Vincent F. Fiore, Thomas Barker, Yi Sun, Stephan W. Morris, Victor J. Thannickal i Yong Zhou. "Matrix Stiffness-Induced Myofibroblast Differentiation Is Regulated By Actin Dynamics And Myocardin-Related Transcription Factor (MRTF)-A-Mediated Intrinsic Mechanotransduction". W American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California. American Thoracic Society, 2012. http://dx.doi.org/10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a1032.
Pełny tekst źródła
8
Homps-Legrand, M., M. Jaillet, L. Deneuville, B. Crestani i A. Mailleux. "Lineage Tracing of Cells Expressing the Mesenchymal Profibrotic Transcription Factor Prrx1 (Paired Related Homeobox Protein 1) in Normal and Fibrotic Lung". W American Thoracic Society 2022 International Conference, May 13-18, 2022 - San Francisco, CA. American Thoracic Society, 2022. http://dx.doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a5231.
Pełny tekst źródła
9
Li, Mingzhe, Zhenyu Wang, Zhongyi Xie, Jing Luo, Dongsun Cao i Tongcun Zhang. "CREB-binding Protein (CBP) p300 Enhanced the Expression of Cardiac Hypertrophy-Specific Genes Activated by Myocardin-Related Transcription Factor-A (MRTF-A)". W 2012 International Conference on Biomedical Engineering and Biotechnology (iCBEB). IEEE, 2012. http://dx.doi.org/10.1109/icbeb.2012.118.
Pełny tekst źródła
10
Shikata, Tetsuo, Toshihiko Shiraishi, Shin Morishita i Ryohei Takeuchi. "Effects of Acceleration Amplitude and Frequency of Mechanical Vibration on Cultured Osteoblasts". W ASME 2008 International Mechanical Engineering Congress and Exposition. ASMEDC, 2008. http://dx.doi.org/10.1115/imece2008-67221.
Pełny tekst źródłaStreszczenie:
This paper describes the effects of the frequency and acceleration amplitude of mechanical vibration on osteoblasts, the bone cells that generate the bone matrix. Their cell proliferation and bone matrix generation were investigated when sinusoidal inertia force was applied to the cells. Bone formation is subject in vivo to mechanical stimulation. Although many researches for bone cells of osteoblastic lineage sensing and responding to mechanical stimulation have been reported mainly in the biochemical field, effects of mechanical stimulation on bone cells are not well understood. After the cells were cultured in culture plates in a CO2 incubator for one day and adhered on the cultured plane, vibrating groups of the culture plates were set on an aluminum plate attached to a exciter and cultured under sinusoidal excitation in another incubator separated from non-vibrating groups of the culture plates. Acceleration amplitude and frequency were set to several kinds of conditions. The time evolution of cell density was obtained by counting the number of cells with a hemocytometer. Calcium salts generated by the cells were observed by being stained with alizarin red S solution and their images were captured with a CCD camera. The vibrating groups for the cell proliferation and the calcium salts staining were sinusoidally excited for 24 hours a day during 28 days of culture. Gene expression of alkaline phosphatase (ALP) and runt-related gene 2 (Runx2) was measured by a real-time reverse transcription polymerase chain reaction (real-time RT-PCR) method. After the vibrating groups for the PCR were excited for 4 days, the total RNAs were extracted. After reverse transcription, real-time RT-PCR was performed. Gene expression for ALP, Runx2, and a housekeeping gene were determined simultaneously for each sample. ALP and Runx2 gene level in each sample was normalized to the measured housekeeping gene level. The following experimental results of sinusoidal excitation of osteoblasts have been shown: (a) Cell density decreased at 0.5 G with increasing frequency in the range from 12.5 to 1000 Hz and increased at 25 Hz with increasing acceleration amplitude from 0 to 0.5 G at 14 days of culture. (b) No calcium salts were observed in the non-vibrating group and the areas of calcium salts observed in the 0.5 G vibration group were larger than those in the 0.25 G group at 25 Hz at 21 days of culture. (c) The mRNA level of ALP at 0.5 G showed the peak at 50 Hz in the range from 12.5 to 1000 Hz and that at 50 Hz showed the peak at 0.5 G in the range from 0.25 to 1 G at 4 days of culture. In the case of Runx2, the same tendency was found. It has been shown that it is important to consider mechanical vibration as well as biochemical aspects in studies of the functional adaptation of cells to mechanical stimulation.
Raporty organizacyjne na temat "Runt related transcription factor"
1
Funkenstein, Bruria, i Shaojun (Jim) Du. Interactions Between the GH-IGF axis and Myostatin in Regulating Muscle Growth in Sparus aurata. United States Department of Agriculture, marzec 2009. http://dx.doi.org/10.32747/2009.7696530.bard.
Pełny tekst źródłaStreszczenie:
Growth rate of cultured fish from hatching to commercial size is a major factor in the success of aquaculture. The normal stimulus for muscle growth in growing fish is not well understood and understanding the regulation of muscle growth in fish is of particular importance for aquaculture. Fish meat constitutes mostly of skeletal muscles and provides high value proteins in most people's diet. Unlike mammals, fish continue to grow throughout their lives, although the size fish attain, as adults, is species specific. Evidence indicates that muscle growth is regulated positively and negatively by a variety of growth and transcription factors that control both muscle cell proliferation and differentiation. In particular, growth hormone (GH), fibroblast growth factors (FGFs), insulin-like growth factors (IGFs) and transforming growth factor-13 (TGF-13) play critical roles in myogenesis during animal growth. An important advance in our understanding of muscle growth was provided by the recent discovery of the crucial functions of myostatin (MSTN) in controlling muscle growth. MSTN is a member of the TGF-13 superfamily and functions as a negative regulator of skeletal muscle growth in mammals. Studies in mammals also provided evidence for possible interactions between GH, IGFs, MSTN and the musclespecific transcription factor My oD with regards to muscle development and growth. The goal of our project was to try to clarify the role of MSTNs in Sparus aurata muscle growth and in particular determine the possible interaction between the GH-IGFaxis and MSTN in regulating muscle growth in fish. The steps to achieve this goal included: i) Determining possible relationship between changes in the expression of growth-related genes, MSTN and MyoD in muscle from slow and fast growing sea bream progeny of full-sib families and that of growth rate; ii) Testing the possible effect of over-expressing GH, IGF-I and IGF-Il on the expression of MSTN and MyoD in skeletal muscle both in vivo and in vitro; iii) Studying the regulation of the two S. aurata MSTN promoters and investigating the possible role of MyoD in this regulation. The major findings of our research can be summarized as follows: 1) Two MSTN promoters (saMSTN-1 and saMSTN-2) were isolated and characterized from S. aurata and were found to direct reporter gene activity in A204 cells. Studies were initiated to decipher the regulation of fish MSTN expression in vitro using the cloned promoters; 2) The gene coding for saMSTN-2 was cloned. Both the promoter and the first intron were found to be polymorphic. The first intron zygosity appears to be associated with growth rate; 3) Full length cDNA coding for S. aurata growth differentiation factor-l I (GDF-II), a closely related growth factor to MSTN, was cloned from S. aurata brain, and the mature peptide (C-terminal) was found to be highly conserved throughout evolution. GDF-II transcript was detected by RT -PCR analysis throughout development in S. aurata embryos and larvae, suggesting that this mRNA is the product of the embryonic genome. Transcripts for GDF-Il were detected by RT-PCR in brain, eye and spleen with highest level found in brain; 4) A novel member of the TGF-Bsuperfamily was partially cloned from S. aurata. It is highly homologous to an unidentified protein (TGF-B-like) from Tetraodon nigroviridisand is expressed in various tissues, including muscle; 5) Recombinant S. aurata GH was produced in bacteria, refolded and purified and was used in in vitro and in vivo experiments. Generally, the results of gene expression in response to GH administration in vivo depended on the nutritional state (starvation or feeding) and the time at which the fish were sacrificed after GH administration. In vitro, recombinantsaGH activated signal transduction in two fish cell lines: RTHI49 and SAFI; 6) A fibroblastic-like cell line from S. aurata (SAF-I) was characterized for its gene expression and was found to be a suitable experimental system for studies on GH-IGF and MSTN interactions; 7) The gene of the muscle-specific transcription factor Myogenin was cloned from S. aurata, its expression and promoter activity were characterized; 8) Three genes important to myofibrillogenesis were cloned from zebrafish: SmyDl, Hsp90al and skNAC. Our data suggests the existence of an interaction between the GH-IGFaxis and MSTN. This project yielded a great number of experimental tools, both DNA constructs and in vitro systems that will enable further studies on the regulation of MSTN expression and on the interactions between members of the GHIGFaxis and MSTN in regulating muscle growth in S. aurata.
2
Grumet, Rebecca, Rafael Perl-Treves i Jack Staub. Ethylene Mediated Regulation of Cucumis Reproduction - from Sex Expression to Fruit Set. United States Department of Agriculture, luty 2010. http://dx.doi.org/10.32747/2010.7696533.bard.
Pełny tekst źródłaStreszczenie:
Reproductive development is a critical determinant of agricultural yield. For species with unisexual flowers, floral secualdifferentation adds additional complexity, that can influenec productivity. The hormone ethylene has long, been known to play a primary role in sex determination in the Cucumis species cucumber (C. sativus) and melon (C. melo). Our objectives were to: (1) Determine critical sites of ethylene production and perception for sex determination; (2) Identify additional ethylene related genes associated with sex expression; and (3) Examine the role of environment ami prior fruit set on sex expression, pistillate flower maturation, and fruit set. We made progress in each of these areas. (1) Transgenic melon produced with the Arabidopsis dominant negative ethylene perception mutant gene, etrl-1, under the control of floral primordia targeted promoters [AP3 (petal and stamen) and CRC (carpel and nectary)], showed that ethylene perception by the stamen primordia, rather than carpel primordia, is critical for carpel development at the time of sex determination. Transgenic melons also were produced with the ethylene production enzyme gene. ACS, encoding l-aminocyclopropane-lcarboylate synthase, fused to the AP3 or CRC promoters. Consistent with the etr1-1 results, CRC::ACS did not increase femaleness; however, AP3::ACS reduced or eliminated male flower production. The effects of AP3:ACS were stronger than those of 35S::ACS plants, demonstratin g the importance of targeted expression, while avoiding disadvantages of constitutive ethylene production. (2) Linkage analysis coupled with SNP discovery was per formed on ethylene and floral development genes in cucumber populations segregating for the three major sex genes. A break-through towards cloning the cucumber M gene occurred when the melon andromonoecious gene (a), an ACS gene, was cloned in 2008. Both cucumber M and melon a suppress stamen development in pistillate flowers. We hypothesized that cucumber M could be orthologous to melon a, and found that mutations in CsACS2 co-segregated perfectly with the M gene. We also sought to identify miRNA molecules associated with sex determination. miRNA159, whose target in Arabidopsis is GAMYB[a transcription factor gene mediating response to10 gibberellin (GA)], was more highly expressed in young female buds than male. Since GA promotes maleness in cucumber, a micro RNA that counteracts GAMYB could promote femaleness. miRNA157, which in other plants targets transcription factors involved in flower development , was expressed in young male buds and mature flower anthers. (3) Gene expression profiling showed that ethylene-, senescence-, stress- and ubiquitin-related genes were up-regulated in senescing and inhibited fruits, while those undergoing successful fruit set up-regulated photosynthesis, respiration and metabolic genes. Melon plants can change sex expression in response to environmental conditions, leading to changes in yield potential. Unique melon lines with varying sex expression were developed and evaluated in the field in Hancock, Wisconsin . Environmental changes during the growing season influenced sex expression in highly inbred melon lines. Collectively these results are of significance for understanding regulation of sex expression. The fact that both cucumber sex loci identified so far (F and M) encode isoforms of the same ethylene synthesis enzyme, underscores the importance of ethylene as the main sex determining hormone in cucumber. The targeting studies give insight into developmental switch points and suggest a means to develop lines with earlier carpel-bearing flower production and fruit set. These results are of significance for understanding regulation of sex expression to facilitate shorter growing seasons and earlier time to market. Field results provide information for development of management strategies for commercial production of melon cultivars with different sex expression characteristics during fruit production.
3
Casey, Therese, Sameer J. Mabjeesh, Avi Shamay i Karen Plaut. Photoperiod effects on milk production in goats: Are they mediated by the molecular clock in the mammary gland? United States Department of Agriculture, styczeń 2014. http://dx.doi.org/10.32747/2014.7598164.bard.
Pełny tekst źródłaStreszczenie:
US scientists, Dr. Theresa Casey and Dr. Karen Plaut, collaborated with Israeli scientists, Dr. SameerMabjeesh and Dr. AviShamay to conduct studies proposed in the BARD Project No. US-4715-14 Photoperiod effects on milk production in goats: Are they mediated by the molecular clock in the mammary gland over the last 3 years. CLOCK and BMAL1 are core components of the circadian clock and as heterodimers function as a transcription factor to drive circadian-rhythms of gene expression. Studies of CLOCK-mutant mice found impaired mammary development in late pregnancy was related to poor lactation performance post-partum. To gain a better understanding of role of clock in regulation of mammary development studies were conducted with the mammary epithelial cell line HC11. Decreasing CLOCK protein levels using shRNA resulted in increased mammary epithelial cell growth rate and impaired differentiation, with lower expression of differentiation markers including ad herens junction protein and fatty acid synthesis genes. When BMAL1 was knocked out using CRISPR-CAS mammary epithelial cells had greater growth rate, but reached stationary phase at a lower density, with FACS indicating cells were growing and dying at a faster rate. Beta-casein milk protein levels were significantly decreased in BMAL1 knockout cells. ChIP-seq analysis was conducted to identify BMAL1 target genes in mammary epithelial cells. Studies conducted in goats found that photoperiod duration and physiological state affected the dynamics of the mammary clock. Effects were likely independent of the photoperiod effects on prolactin levels. Interestingly, circadian rhythms of core body temperature, which functions as a key synchronizing cue sent out by the central clock in the hypothalamus, were profoundly affected by photoperiod and physiological state. Data support that the clock in the mammary gland regulates genes important to development of the gland and milk synthesis. We also found the clock in the mammary is responsive to changes in physiological state and photoperiod, and thus may serve as a mechanism to establish milk production levels in response to environmental cues.
4
Crisosto, Carlos, Susan Lurie, Haya Friedman, Ebenezer Ogundiwin, Cameron Peace i George Manganaris. Biological Systems Approach to Developing Mealiness-free Peach and Nectarine Fruit. United States Department of Agriculture, 2007. http://dx.doi.org/10.32747/2007.7592650.bard.
Pełny tekst źródłaStreszczenie:
Peach and nectarine production worldwide is increasing; however consumption is flat or declining because of the inconsistent eating quality experienced by consumers. The main factor for this inconsistent quality is mealiness or woolliness, a form of chilling injury that develops following shipping periods in the global fruit market today. Our research groups have devised various postharvest methods to prolong storage life, including controlled atmosphere and delayed storage; however, these treatments only delay mealiness. Mealiness texture results from disruption of the normal ripening process involving disassembly of cell wall material, and creates a soft fruit texture that is dry and grainy instead of juicy and smooth. Solving this problem is a prerequisite for increasing the demand for fresh peach and nectarine. Two approaches were used to reveal genes and their associated biochemical processes that can confer resistance to mealiness or wooliness. At the Volcani Center, Israel, a nectarine cultivar and the peach cultivar (isogenetic materials) from which the nectarine cultivar spontaneously arose, and at the Kearney Agricultural Center of UC Davis, USA, a peach population that segregates for quantitative resistance to mealiness was used for dissecting the genetic components of mealiness development. During our project we have conducted research integrating the information from phenotypic, biochemical and gene expression studies, proposed possible candidate genes and SNPs-QTLs mapping that are involved in reducing peach mealiness susceptibility. Numerous genes related to ethylene biosynthesis and its signal transduction, cell wall structure and metabolism, stress response, different transcription factor families were detected as being differentially accumulated in the cold-treated samples of these sensitive and less sensitive genotypes. The ability to produce ethylene and keep active genes involved in ethylene signaling, GTP-binding protein, EIN-3 binding protein and an ethylene receptor and activation of ethyleneresponsive fruit ripening genes during cold storage provided greater resistance to CI. Interestingly, in the functional category of genes differentially expressed at harvest, less chilling sensitive cultivar had more genes in categories related to antioxidant and heat sock proteins/chaperones that may help fruit to adapt to low temperature stress. The specific objectives of the proposed research were to: characterize the phenotypes and cell wall components of the two resistant systems in response to mealiness- inducing conditions; identify commonalities and specific differences in cell wall proteins and the transcriptome that are associated with low mealiness incidence; integrate the information from phenotypic, biochemical, and gene expression studies to identify candidate genes that are involved in reducing mealiness susceptibility; locate these genes in the Prunus genome; and associate the genes with genomic regions conferring quantitative genetic variation for mealiness resistance. By doing this we will locate genetic markers for mealiness development, essential tools for selection of mealiness resistant peach lines with improved fruit storability and quality. In our research, QTLs have been located in our peach SNPs map, and proposed candidate genes obtained from the integrated result of phenotypic, biochemical and gene expression analysis are being identified in our QTLs as an approach searching for consistent assistant markers for peach breeding programs.
5
Horwitz, Benjamin, i Barbara Gillian Turgeon. Secondary Metabolites, Stress, and Signaling: Roles and Regulation of Peptides Produced by Non-ribosomal Peptide Synthetases. United States Department of Agriculture, 2005. http://dx.doi.org/10.32747/2005.7696522.bard.
Pełny tekst źródłaStreszczenie:
Fungal pathogens of plants produce a diverse array of small molecules. Often referred to as secondary metabolites because they were thought to be dispensable for basic functions, they may indeed have central roles as signals for the fungal cell, and in interactions with the host. We have identified more than a dozen genes encoding nonribosomal peptide synthetases (NPS) in Cochliobolusheterostrophus, the agent of southern corn leaf blight. The aim of this project was to identify roles of these genes in stress responses and signaling. The first objective was to test a complete collection of C. heterostrophus nonribosomal peptide synthetase (NRPS)-encoding gene deletion mutant and wildtype (WT) strains for sensitivity to various agents of oxidative (ROS) and nitrosative (RNOS) stress, in vitro. The second objective and next step in this part of the project was to study the relevance of sensitivity to ROS and RNOS in the host pathogen interaction, by measuring the production of ROS and RNOS in planta, when plants are inoculated with wild type and mutant strains. A third objective was to study expression of any genes shown to be involved in sensitivity to ROS or RNOS, in vitro and in planta. Another objective was to determine if any of the genes involved in oxidative or nitrosative stress responses are regulated by components of signal transduction pathways (STP) that we have identified and to determine where mechanisms overlap. Study of the collection of nps mutants identified phenotypes relevant for virulence, development and oxidative stress resistance for two of the genes, NPS2 and NPS6. Mutants in genes related to RNOS stress have no virulence phenotypes, while some of those related to ROS stress have reduced virulence as well as developmental phenotypes, so we focused primarily on ROS stress pathways. Furthermore, the identification of NPS2 and NPS6 as encoding for NRPS responsible for siderophore biosynthesis lent a new focus to the project, regulation by Fe. We have not yet developed good methods to image ROS in planta and work in this direction is continuing. We found that NPS6 expression is repressed by Fe, responding over the physiological Fe concentration range. Studying our collection of mutants, we found that conserved MAPK and G protein signal transduction pathways are dispensable for Fe regulation of NPS6, and initiated work to identify other pathways. The transcription factor SreA is one candidate, and is responsible for part, but not all, of the control of NPS6 expression. The results of this project show that the pathogen contends with oxidative stress through several signaling pathways. Loss of the siderophore produced by Nps6 makes the fungus sensitive to oxidative stress, and decreases virulence, suggesting a central role of the ability to sequester and take up extracellular iron in the host-pathogen interaction. Siderophores, and manipulation of Fe levels, could be targets for new strategies to deal with fungal pathogens of maize and other plants.
6
Horwitz, Benjamin A., i Barbara Gillian Turgeon. Fungal Iron Acquisition, Oxidative Stress and Virulence in the Cochliobolus-maize Interaction. United States Department of Agriculture, marzec 2012. http://dx.doi.org/10.32747/2012.7709885.bard.
Pełny tekst źródłaStreszczenie:
Our project focused on genes for high affinity iron acquisition in Cochliobolus heterostrophus, a necrotrophic pathogen of maize, and their intertwined relationship to oxidative stress status and virulence of the fungus on the host. An intriguing question was why mutants lacking the nonribosomal peptide synthetase (NRPS) gene (NPS6) responsible for synthesis of the extracellular siderophore, coprogen, are sensitive to oxidative stress. Our overall objective was to understand the mechanistic connection between iron stress and oxidative stress as related to virulence of a plant pathogen to its host. The first objective was to examine the interface where small molecule peptide and reactive oxygen species (ROS) mechanisms overlap. The second objective was to determine if the molecular explanation for common function is common signal transduction pathways. These pathways, built around sensor kinases, response regulators, and transcription factors may link sequestering of iron, production of antioxidants, resistance to oxidative stress, and virulence. We tested these hypotheses by genetic manipulation of the pathogen, virulence assays on the host plant, and by following the expression of key fungal genes. An addition to the original program, made in the first year, was to develop, for fungi, a genetically encoded indicator of redox state based on the commercially available Gfp-based probe pHyper, designed for animal cell biology. We implemented several tools including a genetically encoded indicator of redox state, a procedure to grow iron-depleted plants, and constructed a number of new mutants in regulatory genes. Lack of the major Fe acquisition pathways results in an almost completely avirulent phenotype, showing how critical Fe acquisition is for the pathogen to cause disease. Mutants in conserved signaling pathways have normal ability to regulate NPS6 in response to Fe levels, as do mutants in Lae1 and Vel1, two master regulators of gene expression. Vel1 mutants are sensitive to oxidative stress, and the reason may be underexpression of a catalase gene. In nps6 mutants, CAT3 is also underexpressed, perhaps explaining the sensitivity to oxidative stress. We constructed a deletion mutant for the Fe sensor-regulator SreA and found that it is required for down regulation of NPS6 under Fe-replete conditions. Lack of SreA, though, did not make the fungus over-sensitive to ROS, though the mutant had a slow growth rate. This suggests that overproduction of siderophore under Fe-replete conditions is not very damaging. On the other hand, increasing Fe levels protected nps6 mutants from inhibition by ROS, implying that Fe-catalyzed Fenton reactions are not the main factor in its sensitivity to ROS. We have made some progress in understanding why siderophore mutants are sensitive to oxidative stress, and in doing so, defined some novel regulatory relationships. Catalase genes, which are not directly related to siderophore biosynthesis, are underexpressed in nps6 mutants, suggesting that the siderophore product (with or without bound Fe) may act as a signal. Siderophores, therefore, could be a target for intervention in the field, either by supplying an incorrect signal or blocking a signal normally provided during infection. We already know that nps6 mutants cause smaller lesions and have difficulty establishing invasive growth in the host. Lae1 and Vel1 are the first factors shown to regulate both super virulence conferred by T-toxin, and basic pathogenicity, due to unknown factors. The mutants are also altered in oxidative stress responses, key to success in the infection court, asexual and sexual development, essential for fungal dissemination in the field, aerial hyphal growth, and pigment biosynthesis, essential for survival in the field. Mutants in genes encoding NADPH oxidase (Nox) are compromised in development and virulence. Indeed the triple mutant, which should lack all Nox activity, was nearly avirulent. Again, gene expression experiments provided us with initial evidence that superoxide produced by the fungus may be most important as a signal. Blocking oxidant production by the pathogen may be a way to protect the plant host, in interactions with necrotrophs such as C. heterostrophus which seem to thrive in an oxidant environment.
7
Lers, Amnon, i Gan Susheng. Study of the regulatory mechanism involved in dark-induced Postharvest leaf senescence. United States Department of Agriculture, styczeń 2009. http://dx.doi.org/10.32747/2009.7591734.bard.
Pełny tekst źródłaStreszczenie:
Postharvest leaf senescence contributes to quality losses in flowers and leafy vegetables. The general goal of this research project was to investigate the regulatory mechanisms involved in dark-induced leaf senescence. The regulatory system involved in senescence induction and control is highly complex and possibly involves a network of senescence promoting pathways responsible for activation of the senescence-associated genes. Pathways involving different internal signals and environmental factors may have distinctive importance in different leaf senescence systems. Darkness is known to have a role in enhancement of postharvest leaf senescence and for getting an insight into its regulatory mechanism/s we have applied molecular genetics and functional genomics approaches. The original objectives were: 1. Identification of dark-induced SAGs in Arabidopsis using enhancer/promoter trap lines and microarray approaches; 2. Molecular and functional characterization of the identified genes by analyzing their expression and examining the phenotypes in related knockout mutant plants; 3. Initial studies of promoter sequences for selected early dark-induced SAGs. Since genomic studies of senescence, with emphasis on dark-induced senescence, were early-on published which included information on potential regulatory genes we decided to use this new information. This is instead of using the uncharacterized enhancer/promoter trap lines as originally planned. We have also focused on specific relevant genes identified in the two laboratories. Based on the available genomic analyses of leaf senescence 10 candidate genes hypothesized to have a regulatory role in dark-induced senescence were subjected to both expression as well as functional analyses. For most of these genes senescence-specific regulation was confirmed, however, functional analyses using knock-out mutants indicated no consequence to senescence progression. The transcription factor WARK75 was found to be specifically expressed during natural and dark-induced leaf senescence. Functional analysis demonstrated that in detached leaves senescence under darkness was significantly delayed while no phenotypic consequences could be observed on growth and development, including no effect on natural leaf senescence,. Thus, WARKY75 is suggested to have a role in dark-induced senescence, but not in natural senescence. Another regulatory gene identified to have a role in senescence is MKK9 encoding for a Mitogen-Activated Protein Kinase Kinase 9 which is upregulated during senescence in harvested leaves as well as in naturally senescing leaves. MKK9 can specifically phosphorylate another kinase, MPK6. Both knockouts of MKK9 and MPK6 displayed a significantly senescence delay in harvested leaves and possibly function as a phosphorelay that regulates senescence. To our knowledge, this is the first report that clearly demonstrates the involvement of a MAP kinase pathway in senescence. This research not only revealed a new signal transduction pathway, but more important provided significant insights into the regulatory mechanisms underlying senescence in harvested leaves. In an additional line of research we have employed the promoter of the senescence-induced BFN1 gene as a handle for identifying components of the regulatory mechanism. This gene was shown to be activated during darkinduced senescence of detached leaves, as well as natural senescence. This was shown by following protein accumulation and promoter activity which demonstrated that this promoter is activated during dark-induced senescence. Analysis of the promoter established that, at least some of the regulatory sequences reside in an 80 bps long fragment of the promoter. Overall, progress was made in identification of components with a role in dark-induced senescence in this project. Further studies should be done in order to better understand the function of these components and develop approaches for modulating the progress of senescence in crop plants for the benefit of agriculture.
8
Chen, Junping, Zach Adam i Arie Admon. The Role of FtsH11 Protease in Chloroplast Biogenesis and Maintenance at Elevated Temperatures in Model and Crop Plants. United States Department of Agriculture, maj 2013. http://dx.doi.org/10.32747/2013.7699845.bard.
Pełny tekst źródłaStreszczenie:
specific objectives of this proposal were to: 1) determine the location, topology, and oligomerization of FtsH11 protease; 2) identify the substrate/s of FtsH11 and the downstream components involved in maintaining thermostability of chloroplasts; 3) identify new elements involved in FtsH11 protease regulatory network related to HT adaptation processes in chloroplast; 4) Study the role of FtsH11 homologs from crop species in HT tolerance. Background to the topic: HT-tolerant varieties that maintain high photosynthetic efficiency at HT, and cope better with daily and seasonal temperature fluctuations are in great need to alleviate the effect of global warming on food production. Photosynthesis is a very complex process requiring accurate coordination of many complex systems and constant adjustments to the changing environments. Proteolytic activities mediated by various proteases in chloroplast are essential part of this process and critical for maintaining normal chloroplast functions under HT. However, little is known about mechanisms that contribute to adaptation of photosynthetic processes to HT. Our study has shown that a chloroplast-targeted Arabidopsis FtsH11 protease plays an essential and specific role in maintaining thermostability of thylakoids and normal photosynthesis at moderate HT. We hypothesized that FtsH11 homologs recently identified in other plant species might have roles similarly to that of AtFtsH1. Thus, dissecting the underlying mechanisms of FtsH11 in the adaptation mechanisms in chloroplasts to HT stress and other elements involved will aid our effort to produce more agricultural products in less favorable environments. Major conclusions, solutions, achievements - Identified the chloroplast inner envelope membrane localization of FtsH11. - Revealed a specific association of FtsH11 with the a and b subunits of CPN60. - Identified the involvement of ARC6, a protein coordinates chloroplast division machineries in plants, in FtsH11 mediated HT adaptation process in chloroplast. -Reveal possible association of a polyribonucleotide nucleotidyltransferase (cpPNPase), coded by At3G03710, with FtsH11 mediated HT adaptation process in chloroplast. - Mapped 4 additional loci in FtsH11 mediated HT adaptation network in chloroplast. - Demonstrated importance of the proteolytic activity of FtsH11 for thermotolerance, in addition to the ATPase activity. - Demonstrated a conserved role of plant FtsH11 proteases in chloroplast biogenesis and in maintaining structural and functional thermostability of chloroplast at elevated temperatures. Implications, both scientific and agricultural:Three different components interacting with FtsH11 were identified during the course of this study. At present, it is not known whether these proteins are directly involved in FtsH11mediated thermotolerance network in chloroplast and/or how these elements are interrelated. Studies aiming to connect the dot among biological functions of these networks are underway in both labs. Nevertheless, in bacteria where it was first studied, FtsH functions in heat shock response by regulating transcription level of σ32, a heat chock factor regulates HSPsexpression. FtsH also involves in control of biosynthesis of membrane components and quality control of membrane proteins etc. In plants, both Arc 6 and CPN60 identified in this study are essential in chloroplast division and developments as mutation of either one impairs chloroplast division in Arabidopsis. The facts that we have found the specific association of both α and β CPN60 with FtsH11 protein biochemically, the suppression/ enhancement of ftsh11 thermosensitive phenotype by arc6 /pnp allele genetically, implicate inter-connection of these networks via FtsH11 mediated network(s) in regulating the dynamic adaptation processes of chloroplast to temperature increases at transcriptional, translational and post-translational levels. The conserved role of FtsH11 proteases in maintaining thermostability of chloroplast at HT demonstrated here provides a foundation for improving crop photosynthetic performance at high temperatures.
9
Applebaum, Shalom W., Lawrence I. Gilbert i Daniel Segal. Biochemical and Molecular Analysis of Juvenile Hormone Synthesis and its Regulation in the Mediterranean Fruit Fly (Ceratitis capitata). United States Department of Agriculture, 1995. http://dx.doi.org/10.32747/1995.7570564.bard.
Pełny tekst źródłaStreszczenie:
Original Objectives and revisions: (1) "To determine the biosynthetic pathway of JHB3 in the adult C. capitata CA in order to establish parameters for the future choice and synthesis of suitable inhibitors". Modified: to determine the pattern of FR-7 biosynthesis during normal reproductive maturation, and identify enzymes potentially involved in its synthesis. (2) "To correlate allatal epoxidase activity to the biosynthesis of JHB3 at different stages of reproductive maturation/vitellogenesis and evaluate the hypothesis that a specific JH-epoxidase may be rate limiting". Modified: to study the effects of epoxidase inhibitors on the pattern of allatal JH biosynthesis in vitro and on female reproduction in vive. (3) "To probe and clone the gene homologous to ap from C. capitata, determine its exon-intron organization, sequence it and demonstrate its spatial and temporal expression in larvae, pupae and adults." The "Medfly" (Ceratitis capitata) is a serious polyphagous fruit pest, widely distributed in subtropical regions. Damage is caused by oviposition and subsequent development of larvae. JH's are dominant gonadotropic factors in insects. In the higher Diptera, to which the Medfly belongs, JHB3 is a major homolog. It comprises 95% of the total JH produced in vitro in D. melanogaster, with JH-III found as a minor component. The biosynthesis of both JH-III and JHB3 is dependent on epoxidation of double bonds in the JH molecule. The specificity of such epoxidases is unknown. The male accessory gland D. melanogaster produces a Sex Peptide, transferred to the female during copulation. SP reduces female receptivity while activating specific JH biosynthesis in vitro and inducing oviposition in vive. It also reduces pheromone production and activates CA of the moth Helicoverpa armigera. In a previous study, mutants of the apterous (ap) gene of D. melanogaster were analyzed. This gene induces previteilogenic arrest which can be rescued by external application of JH. Considerable progress has been made in recombinant DNA technology of the Medfly. When fully operative, it might be possible to effectively transfer D. melanogaster endocrine gene-lesions into the Medfly as a strategy for their genetic control. A marked heterogeneity in the pattern of JH homologs produced by Medfly CA was observed. Contrary to the anticipated biosynthesis of JHB;, significant amounts of an unknown JH-like compound, of unknown structure and provisionally termed FR-7, were produced, in addition to significant amounts of JH-III and JHB3. Inhibitors of monooxygenases, devised for their effects on ecdysteroid biosynthesis, affect Medfly JH biosynthesis but do not reduce egg deposition. FR-7 was isolated from incubation media of Medfly CA and examined by various MS procedures, but its structure is not yet resolved. MS analysis is being done in collaboration with Professor R.R.W. Rickards of the Australian National University in Canberra, Australia. A homologue of the ap gene of D. melanogaster exists in the Medfly. LIM domains and the homeo-domain, important for the function of the D. melanogaster ap gene, are conserved here too. Attempts to clone the complete gene were unsuccessful. Due to the complexity of JH homologs, presence of related FR-7 in the biosynthetic products of Medfly CA and lack of reduction in eggs deposited in the presence of monooxygenase inhibitors, inhibition of epoxidases is not a feasible alternative to control Medfly reproduction, and raises questions which cannot be resolved within the current dogma of hormonal control of reproduction in Diptera. The Medfly ap gene has similar domains to the D. melanogaster ap gene. Although mutant ap genes are involved in JH deficiency, ap is a questionable candidate for an endocrine lesion, especially since the D. melanogoster gene functions is a transcription factor.
10
Friedman, Haya, Julia Vrebalov, James Giovannoni i Edna Pesis. Unravelling the Mode of Action of Ripening-Specific MADS-box Genes for Development of Tools to Improve Banana Fruit Shelf-life and Quality. United States Department of Agriculture, styczeń 2010. http://dx.doi.org/10.32747/2010.7592116.bard.
Pełny tekst źródłaStreszczenie:
Fruit deterioration is a consequence of a genetically-determined fruit ripening and senescence programs, in which developmental factors lead to a climacteric rise of ethylene production in ethylene-sensitive fruits such as tomato and banana. Breeding of tomato with extended fruit shelf life involves the incorporation of a mutation in RIN, a MADS-box transcription factor participating in developmental control signalling of ripening. The RIN mode of action is not fully understood, and it may be predicted to interact with other MADS-box genes to execute its effects. The overall goal of this study was to demonstrate conservation of ripening control functions between banana and tomato and thus, the potential to genetically extend shelf-life in banana based on tools developed in tomato. The specific objectives were: 1. To increase the collection of potential RIN-like genes from banana; 2. To verify their action as developmental regulators; 3. To elucidate MADS-box gene mode of action in ripening control; 4. To create transgenic banana plants that express low levels of endogenous Le-RIN- like, MaMADS- gene(s). We have conducted experiments in banana as well as in tomato. In tomato we have carried out the transformation of the tomato rin mutant with the MaMADS1 and MaMADS2 banana genes. We have also developed a number of domain swap constructs to functionally examine the ripening-specific aspects of the RIN gene. Our results show the RIN-C terminal region is essential for the gene to function in the ripening signalling pathway. We have further explored the tomato genome databases and recovered an additional MADS-box gene necessary for fruit ripening. This gene has been previously termed TAGL1 but has not been functionally characterized in transgenic plants. TAGL1 is induced during ripening and we have shown via RNAi repression that it is necessary for both fleshy fruit expansion and subsequent ripening. In banana we have cloned the full length of six MaMADS box genes from banana and determined their spatial and temporal expression patterns. We have created antibodies to MaMADS2 and initiated ChI assay. We have created four types of transgenic banana plants designed to reduce the levels of two of the MaMADS box genes. Our results show that the MaMADS-box genes expression in banana is dynamically changing after harvest and most of them are induced at the onset of the climacteric peak. Most likely, different MaMADS box genes are active in the pulp and peel and they are differently affected by ethylene. Only the MaMADS2 box gene expression is not affected by ethylene indicating that this gene might act upstream to the ethylene response pathway. The complementation analysis in tomato revealed that neither MaMADS1 nor MaMADS2 complement the rin mutation suggesting that they have functionally diverged sufficiently to not be able to interact in the context of the tomato ripening regulatory machinery. The developmental signalling pathways controlling ripening in banana and tomato are not identical and/or have diverged through evolution. Nevertheless, at least the genes MaMADS1 and MaMADS2 constitute part of the developmental control of ripening in banana, since transgenic banana plants with reduced levels of these genes are delayed in ripening. The detailed effect on peel and pulp, of these transgenic plants is underway. So far, these transgenic bananas can respond to exogenous ethylene, and they seem to ripen normally. The response to ethylene suggest that in banana the developmental pathway of ripening is different than that in tomato, because rin tomatoes do not ripen in response to exogenous ethylene, although they harbor the ethylene response capability This study has a major contribution both in scientific and agricultural aspects. Scientifically, it establishes the role of MaMADS box genes in a different crop-the banana. The developmental ripening pathway in banana is similar, but yet different from that of the model plant tomato and one of the major differences is related to ethylene effect on this pathway in banana. In addition, we have shown that different components of the MaMADS-box genes are employed in peel and pulp. The transgenic banana plants created can help to further study the ripening control in banana. An important and practical outcome of this project is that we have created several banana transgenic plants with fruit of extended shelf life. These bananas clearly demonstrate the potential of MaMADS gene control for extending shelf-life, enhancing fruit quality, increasing yield in export systems and for improving food security in areas where Musaspecies are staple food crops.