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1
Lemarchandel, V., J. Ghysdael, V. Mignotte, C. Rahuel, and P. H. Roméo. "GATA and Ets cis-acting sequences mediate megakaryocyte-specific expression." Molecular and Cellular Biology 13, no. 1 (January 1993): 668–76. http://dx.doi.org/10.1128/mcb.13.1.668.
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The human glycoprotein IIB (GPIIB) gene is expressed only in megakaryocytes, and its promoter displays cell type specificity. We show that this specificity involved two cis-acting sequences. The first one, located at -55, contains a GATA binding site. Point mutations that abolish protein binding on this site decrease the activity of the GPIIB promoter but do not affect its tissue specificity. The second one, located at -40, contains an Ets consensus sequence, and we show that Ets-1 or Ets-2 protein can interact with this -40 GPIIB sequence. Point mutations that impair Ets binding decrease the activity of the GPIIB promoter to the same extent as do mutations that abolish GATA binding. A GPIIB 40-bp DNA fragment containing the GATA and Ets binding sites can confer activity to a heterologous promoter in megakaryocytic cells. This activity is independent of the GPIIB DNA fragment orientation, and mutations on each binding site result in decreased activity. Using cotransfection assays, we show that c-Ets-1 and human GATA1 can transactive the GPIIB promoter in HeLa cells and can act additively. Northern (RNA) blot analysis indicates that the ets-1 mRNA level is increased during megakaryocyte-induced differentiation of erythrocytic/megakaryocytic cell lines. Gel retardation assays show that the same GATA-Ets association is found in the human GPIIB enhancer and the rat platelet factor 4 promoter, the other two characterized regulatory regions of megakaryocyte-specific genes. These results indicate that GATA and Ets cis-acting sequences are an important determinant of megakaryocytic specific gene expression.
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Lemarchandel, V., J. Ghysdael, V. Mignotte, C. Rahuel, and P. H. Roméo. "GATA and Ets cis-acting sequences mediate megakaryocyte-specific expression." Molecular and Cellular Biology 13, no. 1 (January 1993): 668–76. http://dx.doi.org/10.1128/mcb.13.1.668-676.1993.
Full textAbstract:
The human glycoprotein IIB (GPIIB) gene is expressed only in megakaryocytes, and its promoter displays cell type specificity. We show that this specificity involved two cis-acting sequences. The first one, located at -55, contains a GATA binding site. Point mutations that abolish protein binding on this site decrease the activity of the GPIIB promoter but do not affect its tissue specificity. The second one, located at -40, contains an Ets consensus sequence, and we show that Ets-1 or Ets-2 protein can interact with this -40 GPIIB sequence. Point mutations that impair Ets binding decrease the activity of the GPIIB promoter to the same extent as do mutations that abolish GATA binding. A GPIIB 40-bp DNA fragment containing the GATA and Ets binding sites can confer activity to a heterologous promoter in megakaryocytic cells. This activity is independent of the GPIIB DNA fragment orientation, and mutations on each binding site result in decreased activity. Using cotransfection assays, we show that c-Ets-1 and human GATA1 can transactive the GPIIB promoter in HeLa cells and can act additively. Northern (RNA) blot analysis indicates that the ets-1 mRNA level is increased during megakaryocyte-induced differentiation of erythrocytic/megakaryocytic cell lines. Gel retardation assays show that the same GATA-Ets association is found in the human GPIIB enhancer and the rat platelet factor 4 promoter, the other two characterized regulatory regions of megakaryocyte-specific genes. These results indicate that GATA and Ets cis-acting sequences are an important determinant of megakaryocytic specific gene expression.
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Lutsyuk, Iryna, Yaroslav Vakhula, Iryna Tupis, and Iryna Iliuchok. "Catalytic Action of Nitric Acid on The Hydrolysis of ETS-40 Ethyl Silicate." Chemistry & Chemical Technology 15, no. 4 (November 25, 2021): 475–78. http://dx.doi.org/10.23939/chcht15.04.475.
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The effect of concentrated nitric acid on the hydrolysis rate of ETS-40 ethyl silicate hasbeen studied. The duration and maximum temperature of ethyl silicate hydrolysis at different temperatures of the components have been determined. The formation of silica particles in the xerogel structure is shown. The influence of the ETS-40 hydrolysis on the particles size and concentration has been examined. The structure of the xerogel and the composition of the formed particles have been investigated using scanning electron microscopy (SEM) and energy dispersion analysis (EDX).
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Rushton, Lesley. "Health Impact of Environmental Tobacco Smoke in the Horne." Reviews on Environmental Health 19, no. 3-4 (July 1, 2004): 291–310. http://dx.doi.org/10.1515/reveh-2004-19-3-408.
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Abstract Environmental tobacco smoke (ETS) can be a major constituent of air pollution in indoor environments, including the home. Regulation on smoking in the workplace and public places has made the home the dominant unregulated source of ETS, with important potential impacts on children. Between 40% and 60% of cbildren in the United Kingdom are exposed to ETS in the home. Many experimental and human and studies have investigated the adverse health effects of ETS. Substantial evidence shows that in adults ETS is associated with increased risk of chronic respiratory illness, including lung cancer, nasal cancer, and cardiovascular disease. In children, ETS increases the risk of sudden infant death syndrome, middle ear disease, lower respiratory tract illness, prevalence of wheeze and cough, and exacerbates asthma. Although banning smoking in the home would be the optimal reduction strategy, several barrier and ventilation methods can be effective. Nevertheless, such methods are not always practical or acceptable, particularly when social pressures contribute to a lack of support for ETS control in the home. Smoking cessation interventions have bad limited success. Research is needed to explore the barriers to adopting ETS risk-reducing behaviors.
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Perfume, Guadalupe, Sabrina L. Nabhen, Karla Riquelme Barrera, María G. Otero, Liliana G. Bianciotti, and Marcelo S. Vatta. "Long-term modulation of tyrosine hydroxylase activity and expression by endothelin-1 and -3 in the rat anterior and posterior hypothalamus." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 294, no. 3 (March 2008): R905—R914. http://dx.doi.org/10.1152/ajpregu.00555.2007.
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Brain catecholamines are involved in the regulation of biological functions, including cardiovascular activity. The hypothalamus presents areas with high density of catecholaminergic neurons and the endothelin system. Two hypothalamic regions intimately related with the cardiovascular control are distinguished: the anterior (AHR) and posterior (PHR) hypothalamus, considered to be sympathoinhibitory and sympathoexcitatory regions, respectively. We previously reported that endothelins (ETs) are involved in the short-term tyrosine hydroxylase (TH) regulation in both the AHR and PHR. TH is crucial for catecholaminergic transmission and is tightly regulated by well-characterized mechanisms. In the present study, we sought to establish the effects and underlying mechanisms of ET-1 and ET-3 on TH long-term modulation. Results showed that in the AHR, ETs decreased TH activity through ETB receptor activation coupled to the nitric oxide, phosphoinositide, and CaMK-II pathways. They also reduced total TH level and TH phosphorylated forms (Ser 19 and 40). Conversely, in the PHR, ETs increased TH activity through a G protein-coupled receptor, likely an atypical ET receptor or the ETC receptor, which stimulated the phosphoinositide and adenylyl cyclase pathways, as well as CaMK-II. ETs also increased total TH level and the Ser 19, 31, and 40 phosphorylated sites of the enzyme. These findings support that ETs are involved in the long-term regulation of TH activity, leading to reduced sympathoinhibition in the AHR and increased sympathoexcitation in the PHR. Present and previous studies may partially explain the cardiovascular effects produced by ETs when applied to the brain.
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Lawlor, E. R., J. A. Mathers, T. Bainbridge, D. E. Horsman, A. Kawai, J. H. Healey, A. G. Huvos, J. A. Bridge, M. Ladanyi, and P. H. Sorensen. "Peripheral primitive neuroectodermal tumors in adults: documentation by molecular analysis." Journal of Clinical Oncology 16, no. 3 (March 1998): 1150–57. http://dx.doi.org/10.1200/jco.1998.16.3.1150.
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PURPOSE The Ewing tumor (ET) family of peripheral primitive neuroectodermal tumors (pPNETs) are primitive small round-cell tumors (SRCTs) of the bone and soft tissue that occur predominantly in children and adolescents. However, pPNETs only rarely enter the differential diagnosis of bone and soft tissue SRCTs in adults. Recently, gene fusions between the EWS gene and different members of the ETS transcription factor family have been shown to occur in virtually all pPNETs and thus constitute a pathognomonic marker for this tumor subclass. The aim of the present study was to document EWS/ETS fusion gene expression in suspected pPNETs of adults as objective evidence for the existence of this tumor family in older patients. PATIENTS AND METHODS The three contributing molecular diagnostic laboratories retrospectively compiled a cohort of all SRCT cases in which EWS/ETS gene fusions had been shown by molecular analysis. This cohort was surveyed for cases that occurred in patients aged 40 years or older, which were then analyzed for their clinical and pathologic features. RESULTS Nine patients between 40 and 65 years of age were found to have tumors positive for EWS/ETS gene fusions. Standard histopathologic and clinical features of these cases, other than age, were similar to those of childhood pPNETs. Patients were initiated on appropriate therapy after molecular analysis confirmed the diagnosis of pPNET. CONCLUSION Identification of an EWS/ETS gene fusion is useful in providing objective evidence of the diagnosis of pPNET in patients over the age of 40 years. This diagnosis should be considered in adults who present with bone and soft tissue SRCTs and appropriate biopsy specimens should be collected for molecular analysis at the time of diagnosis.
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Whittam, Thomas S., M. L. Wolfe, and R. A. Wilson. "Genetic relationships amongEscherichia coliisolates causing urinary tract infections in humans and animals." Epidemiology and Infection 102, no. 1 (February 1989): 37–46. http://dx.doi.org/10.1017/s0950268800029666.
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SUMMARYGenetic variation in isolates ofEscherichia coliobtained mostly from urinary tract infections in humans and domesticated animals (dogs and cats) was assessed for 16 enzymes using multilocus enzyme electrophoresis to characterize chromosomal genotypes. A total of 148 isolates comprised 63 distinct electrophoretic types (ETs) and about half of the isolates belonged to one of 9 common ETs. A bootstrap analysis of genetic distance between ETs revealed three significant groups of strains. Variation in allele frequencies among groups accounted for 40% of the total genetic diversity. The majority of the common ETs fell into a major cluster of closely related strains. The recovery of multiple isolates of the same electrophoretic types and serotypes from unassociated hosts suggests that these bacteria represent uropathogenic clones that are widely disseminated in humans and animals
8
Fleischman, L. F., L. Holtzclaw, J. T. Russell, G. Mavrothalassitis, and R. J. Fisher. "ets-1 in astrocytes: expression and transmitter-evoked phosphorylation." Molecular and Cellular Biology 15, no. 2 (February 1995): 925–31. http://dx.doi.org/10.1128/mcb.15.2.925.
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The ets-1 protein has been primarily studied as a sequence-specific transcriptional regulator that is predominately expressed in lymphoid cells. In this report, we show that ets-1 is also expressed in astrocytes and astrocytoma cells and is regulated during both signal transduction and differentiation. Both isoforms of ets-1, p51 and p42, were found in astrocytes and astrocytoma cells, but whereas expression of p51 was strong, p42, the alternate splice product previously shown to lack the phosphorylation domain, was difficult to detect and was present at a level 10- to 40-fold lower than that of p51. This differed by roughly an order of magnitude from the ratio generally observable in T cells and thymocytes. In two astrocytoma lines of human origin, CCF and 1321N1, ets-1 phosphorylation was stimulated by bradykinin and carbachol, respectively. Glutamate, norepinephrine, and bradykinin elicited phosphorylation of p51 in cultures of primary rat type 1 astrocytes. ets-1 phosphorylation was dramatically blocked by KT5926, an inhibitor of myosin light-chain kinase, suggesting that this kinase may be involved in phosphorylation of ets-1 in vivo. Investigations of retinoic acid-induced differentiation in P19 cells provided further support for a strong correlation of ets-1 with the pathway for astrocyte differentiation.
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Protano, Carmela, Vittoria Cammalleri, Arianna Antonucci, Alexandra Sabina Ungureanu, Francesa Santilli, Stefano Martellucci, Vincenzo Mattei, and Matteo Vitali. "Further Insights on Predictors of Environmental Tobacco Smoke Exposure during the Pediatric Age." International Journal of Environmental Research and Public Health 16, no. 21 (October 23, 2019): 4062. http://dx.doi.org/10.3390/ijerph16214062.
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Background: The smoking ban in public places has reduced Environmental Tobacco Smoke (ETS) exposure for non-smokers, but despite this, domestic environments still remain places at high risk of exposure, and, today, about 40% of children worldwide are exposed to ETS at home. The aims of the study are to investigate the contribution of several factors on ETS exposure among a group of Italian children and to evaluate the changes in smoking precautions adopted at home when the smoker is the mother, the father, or both parents, respectively. Methods: A cross-sectional study was performed on a sample of 519 Italian schoolchildren. Information was collected via a questionnaire. Results: 41.4% of the participants lived with at least one smoker. Almost half of the children exposed to ETS lived with one or more smokers who do not observe any home smoking ban. Lower maternal or paternal educational levels significantly increase the risk of ETS exposure at home and the “worst case” is represented by both parents who smoke. Conclusions: More effective preventive interventions are needed to protect children from ETS exposure. Some interventions should be specifically dedicated to smokers with a low educational level and to mothers that smoke.
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Lapinskas, Erika J., Suzanne Svobodova, Ian D. Davis, Jonathan Cebon, Paul J. Hertzog, and Melanie A. Pritchard. "The Ets Transcription Factor ELF5 Functions as a Tumor Suppressor in the Kidney." Twin Research and Human Genetics 14, no. 4 (August 1, 2011): 316–22. http://dx.doi.org/10.1375/twin.14.4.316.
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Renal cell carcinoma is an important clinical disease with poorly understood etiology. ELF5 is an epithelial-specific member of the Ets family of transcription factors, characterized by the 80 amino acid Ets domain that binds the purine-rich GGAA/T Ets motif found in the promoter regions of a variety of genes. Since ELF5 is highly expressed in kidney and has been postulated to function as a tumor suppressor, at least in the context of the breast, we investigated its role in kidney cancer. In renal cell carcinoma ELF5 expression was consistently decreased in tumor samples versus normal. ELF5 mRNA was decreased in 94% of lesions tested and ELF5 protein was undetectable in 40/40 kidney-derived carcinomas. Re-expression of the ELF5 gene in 786-O renal carcinoma cells suppressed their tumorigenic capacity in vitro and in vivo. This work is the first to suggest that ELF5 has tumor suppressor activity in the kidney.
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Oey, J., RW Lau, and HJ Roethig. "Determination of Environmental Tobacco Smoke from a Second-Generation Electrically Heated Cigarette Smoking System and Conventional Cigarettes." Beiträge zur Tabakforschung International/Contributions to Tobacco Research 23, no. 1 (April 1, 2008): 1–7. http://dx.doi.org/10.2478/cttr-2013-0843.
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AbstractThis substudy of a randomized, controlled, forced switching, open-label, parallel-group clinical study in a total of 100 healthy adult male and female smokers compared environmental tobacco smoke (ETS) produced from smoking a second generation electrically heated cigarette smoking system (EHCSS), two conventional cigarettes, and no-smoking. Concentrations of air constituents including respirable suspended particulate matter (RSP), carbon monoxide (CO), and total volatile organic compounds (TVOCs) and ETS markers including solanesol-related particulate matter (Sol-PM), ultraviolet absorbing particulate matter (UVPM), fluorescing particulate matter (FPM), nicotine and 3-ethenylpyridine (3-EP) were measured in a ventilated, furnished conference room over a period of 2 hours on separate occasions. Except for TVOCs, concentrations of air constituents and ETS markers were reduced by 40% to more than 90% when adult smokers were smoking the EHCSS as compared to smoking conventional cigarettes. CO and most ETS marker concentrations were in the same range as no-smoking.
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Powers, William J., Richard H. Haas, Thuy Le, Tom O. Videen, Joanne Markham, and Joel S. Perlmutter. "Platelet Mitochondrial Complex I and I+III Activities Do Not Correlate with Cerebral Mitochondrial Oxidative Metabolism." Journal of Cerebral Blood Flow & Metabolism 31, no. 1 (October 20, 2010): e1-e5. http://dx.doi.org/10.1038/jcbfm.2010.179.
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Assays of mitochondrial electron transport system (ETS) activity in circulating blood platelets have been used to investigate the cause of neurodegenerative diseases. However, the correspondence between platelet ETS function and cerebral mitochondrial metabolism is not well characterized. To assess the validity of using platelet ETS activity to infer cerebral mitochondrial metabolism, we measured platelet ETS activity (complex I and complex I+III), cerebral metabolic rate of oxygen (CMRO2), and the CMRO2/cerebral metabolic rate for glucose ratio in 40 subjects: 7 with never-medicated Parkinson's disease, 13 with genetically proved Huntington's disease, and 20 normal controls. We found no correlation between in vivo measures of cerebral mitochondrial oxidative metabolism and ex vivo assays of platelet complex I and complex I+III activity performed on blood collected immediately before cerebral metabolism studies. We saw no evidence of a threshold effect when comparing platelet complex I and complex I+III activity with cerebral oxidative metabolism across a 4- to 10-fold range of platelet ETS activity. On the basis of these data, we conclude that measures of mitochondrial complex I and I+III activity in platelets within the ranges we have studied do not correlate with oxidative function of cerebral mitochondria.
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CHOU, CHUNG-HSI, JUAN L. SILVA, and CHINLING WANG. "Prevalence and Typing of Listeria monocytogenes in Raw Catfish Fillets†." Journal of Food Protection 69, no. 4 (April 1, 2006): 815–19. http://dx.doi.org/10.4315/0362-028x-69.4.815.
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Raw channel catfish fillets collected from three processing plants during four time periods were tested for the presence of Listeria species. Listeria monocytogenes was the predominant Listeria species found in these catfish fillets, with 25 to 47% prevalence. Other Listeria species, such as L. welshimeri, L. innocua, L. ivanovii, L. grayi, and L. seeligeri, were also found. L. monocytogenes isolates were further fingerprinted by a repetitive element PCR. Forty distinctive electrophoretic types (ETs) and three genetic clusters were determined by Dice coefficient analysis and UPGMA (unweighted pair group method using arithmetic averages). Twenty of 40 ETs were represented by a single isolate, and the other 20 ETs were represented by 2 to 11 isolates. Thirty-five ETs, represented by 76 isolates, were found in processing plant A, B, or C and designated plant-specific types. The remaining five ETs, represented by 21 isolates, were found in multiple plants and designated nonplant-specific types. In addition, 10 ETs from 52 isolates were found repeatedly during different seasons. Plant-specific and nonplant-specific L. monocytogenes coexisted in processed catfish fillets. Some isolates were persistently found in processed fillets, suggesting that either the current sanitation procedures used by these plants are inadequate or that these isolates originated from the natural habitats of the catfish. The results also suggest that the repetitive element PCR is a useful tool for differentiating L. monocytogenes subtypes and can be used for tracing the source of a contamination.
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Okano, Naohiro, Chigusa Morizane, Takuji Okusaka, Ryo Sadachi, Tomoko Kataoka, Makoto Ueno, Masafumi Ikeda, et al. "Analysis of early tumor shrinkage and depth of response in patients with advanced biliary tract cancer treated with gemcitabine plus cisplatin or gemcitabine plus S-1: An exploratory analysis of JCOG1113." Journal of Clinical Oncology 39, no. 3_suppl (January 20, 2021): 301. http://dx.doi.org/10.1200/jco.2021.39.3_suppl.301.
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301 Background: JCOG1113 is a randomized phase III trial to confirm the non-inferiority of gemcitabine (GEM) plus S-1 (GS) compared with GEM plus cisplatin (GC) regarding overall survival (OS) in patients with advanced biliary tract cancer (BTC). Although the non-inferiority of GS to GC was demonstrated, the difference in the nature of tumor shrinkage effects between GC and GS is not clear. Early tumor shrinkage (ETS) and depth of response (DpR) are considered as on-treatment markers that reflect the anti-tumor effect to chemotherapy and have been reported to be associated with survival in metastatic colorectal cancer. However, there are few studies assessing ETS or DpR in advanced BTC. Therefore, we evaluated the association between ETS, DpR, and clinical outcomes in JCOG1113. Methods: We conducted an exploratory analysis of JCOG1113, which included chemotherapy-naïve patients with recurrent or unresectable BTC. ETS was defined as tumor reduction in the sum of the longest diameters of the target lesions at week 6 when compared with that at baseline. DpR was defined as the maximum tumor shrinkage observed until 12 weeks from enrollment. Survival curves were estimated using the Kaplan–Meier method. Progression-free survival (PFS) and OS for ETS and DpR were estimated from week 6 and 12 (landmarks) after enrollment, respectively. Multivariable analyses for PFS and OS, adjusted for baseline factors, were performed using a stratified Cox regression model. Results: Of the 354 registered patients in JCOG1113, 277 patients in the ETS group and 230 patients in the DpR group were included in this study. Seventy-seven patients (27.8%) achieved ETS ≥ 20% (ETS high group) and 52 patients (22.6%) achieved DpR ≥ 40% (DpR high group). The proportion of ETS high group (GC, 25.4%; GS, 30.4%) and DpR high group (GC, 21.2%; GS, 24.1%) was similar between the arms. The patient characteristics of ETS high group were not different between GC and GS. The hazard ratio (HR) of the ETS high group compared with the ETS low group for PFS and OS was 0.76 (95% confidence interval [CI] 0.58–1.00) and 0.80 (95% CI 0.60–1.07), respectively. The impact of ETS was higher in GC (HR 0.64, 95% CI 0.43–0.95) than GS (HR 0.88, 95% CI 0.60–1.28) in PFS. The HR of DpR high group compared with DpR low group for PFS and OS was 0.75 (95% CI 0.55–1.03) and 0.79 (95% CI 0.57–1.09), respectively. The impact of DpR was higher in GC (HR 0.63, 95% CI 0.40–0.998) than GS (HR 0.88, 95% CI 0.57–1.37) in PFS. ETS and DpR were significantly associated with both PFS and OS in the multivariable analyses. Conclusions: ETS and DpR may be useful as on-treatment markers associated with PFS and OS in patients with advanced BTC, especially in those treated with GC. Clinical trial information: UMIN000010667.
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Gu, Ting-Lei, Tamara L. Goetz, Barbara J. Graves, and Nancy A. Speck. "Auto-Inhibition and Partner Proteins, Core-Binding Factor β (CBFβ) and Ets-1, Modulate DNA Binding by CBFα2 (AML1)." Molecular and Cellular Biology 20, no. 1 (January 1, 2000): 91–103. http://dx.doi.org/10.1128/mcb.20.1.91-103.2000.
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ABSTRACT Core-binding factor α2 (CBFα2; otherwise known as AML1 or PEBP2αB) is a DNA-binding subunit in the family of core-binding factors (CBFs), heterodimeric transcription factors that play pivotal roles in multiple developmental processes in mammals, including hematopoiesis and bone development. The Runt domain in CBFα2 (amino acids 51 to 178) mediates DNA binding and heterodimerization with the non-DNA-binding CBFβ subunit. Both the CBFβ subunit and the DNA-binding protein Ets-1 stimulate DNA binding by the CBFα2 protein. Here we quantify and compare the extent of cooperativity between CBFα2, CBFβ, and Ets-1. We also identify auto-inhibitory sequences within CBFα2 and sequences that modulate its interactions with CBFβ and Ets-1. We show that sequences in the CBFα2 Runt domain and sequences C terminal to amino acid 214 inhibit DNA binding. Sequences C terminal to amino acid 214 also inhibit heterodimerization with the non-DNA-binding CBFβ subunit, particularly heterodimerization off DNA. CBFβ rescinds the intramolecular inhibition of CBFα2, stimulating DNA binding approximately 40-fold. In comparison, Ets-1 stimulates CBFα2 DNA binding 7- to 10-fold. Although the Runt domain alone is sufficient for heterodimerization with CBFβ, sequences N terminal to amino acid 41 and between amino acids 190 and 214 are required for cooperative DNA binding with Ets-1. Cooperative DNA binding with Ets-1 is less pronounced with the CBFα2-CBFβ heterodimer than with CBFα2 alone. These analyses demonstrate that CBFα2 is subject to both negative regulation by intramolecular interactions, and positive regulation by two alternative partnerships.
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Aydın, Sevcan, Bahar Ince, and Orhan Ince. "The joint acute effect of tetracycline, erythromycin and sulfamethoxazole on acetoclastic methanogens." Water Science and Technology 71, no. 8 (February 13, 2015): 1128–35. http://dx.doi.org/10.2166/wst.2015.046.
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In this study, we aimed to develop an understanding of the triple effects of sulfamethoxazole–erythromycin–tetracycline (ETS) and the dual effects of sulfamethoxazole–tetracycline (ST), erythromycin–sulfamethoxazole (ES) and erythromycin–tetracycline (ET) on the anaerobic treatment of pharmaceutical industry wastewater throughout a year of operation. Concentrations of the antibiotics in the influent were gradually increased until the metabolic collapse of the anaerobic sequencing batch reactors (SBRs), which corresponded to ETS (40 + 3 + 3 mg/L) and ST (25 + 2.5 mg/L), ET (4 + 4 mg/L) and ES (3 + 40 mg/L). Acetate accumulation in the anaerobic SBRs, acetoclastic activity of the anaerobic sludge taken from different antibiotic feeding stages and also expression of acetyl-coA synthetase from the acetoclastic methanogenic pathway on the mRNA level were assessed. The results indicated that, while acetate accumulation and decrease of acetoclastic activity were observed after stage 3 in the ST and ES reactors, and stage 7 in the ETS and ET reactors, the expression of acetyl-coA synthetase was mostly decreased in the last stages in all SBRs, in which antibiotic mixture feeding was terminated. It might be speculated that acetoclastic methanogens have an important role in acetate degradation by expressing acetyl-coA synthetase.
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Martinelli, Angela M. "Development and Validation of the Avoidance of Environmental Tobacco Smoke Scale." Journal of Nursing Measurement 6, no. 1 (January 1998): 75–86. http://dx.doi.org/10.1891/1061-3749.6.1.75.
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The Avoidance of Environmental Tobacco Smoke (ETS) scale is a self-report measure of the avoidance of ETS by young adults. Initial use of the scale with 30 undergraduate students showed an internal consistency of .84 across 40 items and .90 in a refined 28-item instrument. In a sample of 241 students, a 20-item scale had an internal consistency reliability of .94 and a refined 10-item scale had an internal consistency of .86. In a sample of 95 mothers with a mean age of 36, the 10-item scale had an internal consistency of .81. In three distinct samples, significant known groups’ discrimination was found between smokers and nonsmokers. Psychometric analysis indicates that the scale merits further testing using a more heterogeneous sample from community and clinical populations to ensure its usefulness by clinicians and researchers interested in explaining, predicting, and preventing exposure to ETS.
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Bradford, A. P., K. E. Conrad, C. Wasylyk, B. Wasylyk, and A. Gutierrez-Hartmann. "Functional interaction of c-Ets-1 and GHF-1/Pit-1 mediates Ras activation of pituitary-specific gene expression: mapping of the essential c-Ets-1 domain." Molecular and Cellular Biology 15, no. 5 (May 1995): 2849–57. http://dx.doi.org/10.1128/mcb.15.5.2849.
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The mechanism by which activation of common signal transduction pathways can elicit cell-specific responses remains an important question in biology. To elucidate the molecular mechanism by which the Ras signaling pathway activates a cell-type-specific gene, we have used the pituitary-specific rat prolactin (rPRL) promoter as a target of oncogenic Ras and Raf in GH4 rat pituitary cells. Here we show that expression of either c-Ets-1 or the POU homeo-domain transcription factor GHF-1/Pit-1 enhance the Ras/Raf activation of the rPRL promoter and that coexpression of the two transcription factors results in an even greater synergistic Ras response. By contrast, the related GHF-1-dependent rat growth hormone promoter fails to respond to Ras or Raf, indicating that GHF-1 alone is insufficient to mediate the Ras/Raf effect. Using amino-terminal truncations of c-Ets-1, we have mapped the c-Ets-1 region required to mediate the optimal Ras response to a 40-amino-acid segment which contains a putative mitogen-activated protein kinase site. Finally, dominant-negative Ets and GHF constructs block Ras activation of the rPRL promoter, and each blocks the synergistic activation mediated by the other partner protein, further corroborating that a functional interaction between c-Ets-1 and GHF-1 is required for an optimal Ras response. Thus, the functional interaction of a pituitary-specific transcription factor, GHF-1, with a widely expressed nuclear proto-oncogene product, c-Ets-1, provides one important molecular mechanism by which the general Ras signaling cascade can be interpreted in a cell-type-specific manner.
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Yamaguchi, Hiroshi, Naoya Sakamoto, Yasuhide Watanabe, Toshihiro Saito, Yoshiaki Masuda, and Haruaki Nakaya. "Dual effects of endothelins on the muscarinic K+ current in guinea pig atrial cells." American Journal of Physiology-Heart and Circulatory Physiology 273, no. 4 (October 1, 1997): H1745—H1753. http://dx.doi.org/10.1152/ajpheart.1997.273.4.h1745.
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Effects of endothelins (ETs) on the acetylcholine receptor-operated K+current ( I K ACh) were examined in isolated guinea pig atrial cells using patch-clamp techniques. ET-1 or ET-3 produced a transient activation of I K ACh in atrial cells held at −40 mV. When I K ACh was preactivated by 1 μM carbachol, however, both ETs produced a transient potentiation followed by a sustained inhibition of the current. When I K ACh was maximally activated by 10 μM carbachol or 100 μM adenosine, these ETs produced only a sustained inhibition of the I K ACh. Their inhibitory effects on the preactivated I K ACh were concentration dependent, and the half-maximal effective concentrations were 314 pM for ET-1 and 1.13 nM for ET-3. The inhibitory effect of ET-1 was antagonized by BQ-485, a specific ETA receptor antagonist, but not by BQ-788, a specific ETB receptor antagonist, indicating that the ET-1 effect is mediated by ETA receptors. On the other hand, the inhibitory effect of ET-3 was antagonized by BQ-788 and more effectively by BQ-485, suggesting the involvement of “atypical” ET receptors. Both ETs partly reversed the carbachol-induced shortening of the action potential recorded in the current-clamp mode. Inhibitory effects of ET-1 and ET-3 on the preactivated I K ACh may contribute to the positive inotropic and chronotropic effects of ETs in atrial tissues.
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Yu, ShunJiang, Sylvia L. Asa, and Shereen Ezzat. "Fibroblast Growth Factor Receptor 4 Is a Target for the Zinc-Finger Transcription Factor Ikaros in the Pituitary." Molecular Endocrinology 16, no. 5 (May 1, 2002): 1069–78. http://dx.doi.org/10.1210/mend.16.5.0832.
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Abstract Fibroblast growth factor receptors (FGFRs) have been implicated in a multitude of endocrine cell hormonal and proliferative properties, and FGFR4 is differentially expressed in normal and neoplastic pituitary. We therefore examined the functionally important cis-DNA elements and multiprotein complexes implicated in the cooperative control of expression of the human FGFR4 gene in pituitary cells. Using deletional mapping, we defined a 214-bp (−115/+99) promoter that was functional in pituitary GH4 and PRL 235 cells. Overlapping 40- to 50-bp fragments of this minimal promoter were examined by EMSA. Interestingly, fragment C (−64/−26) included potential binding sites for the hematopoietic zinc finger-containing transcription factor Ikaros (Ik) flanked by binding sites for Sp and Ets-type factors. DNA binding by Ik, Sp, and Ets-like factors was confirmed by oligonucleotide competition and supershifting with specific antibodies. Transcriptional regulation of FGFR4 by Ik was demonstrated by cotransfection of Ik1 with or without Sp1 or Ets overexpression and by disruption of the Ik binding site. Although both Ets-1 and Sp1 overexpression stimulated promoter activity, mutation of the Ik-binding site completely eliminated the Ik1 effect. Specific Ik expression was identified by Western blotting of pituitary GH4 and PRL235 cells and localized in primary mouse hormone-producing anterior pituitary cells by immunocytochemistry. Our findings point to a new role for Ik outside the hematopoietic system and suggest a novel transcriptional contribution with Ets and Sp1 in regulation of FGFR4 in the pituitary.
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Szewczyk, Aleksandra, Mirosław Zagaja, Joanna Szala-Rycaj, Maciej Maj, and Marta Andres-Mach. "Effect of Lacosamide and Ethosuximide Chronic Treatment on Neural Precursor Cells and Cognitive Functions after Pilocarpine Induced Status Epilepticus in Mice." Brain Sciences 11, no. 8 (July 30, 2021): 1014. http://dx.doi.org/10.3390/brainsci11081014.
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Seizures in about 40% of patients with epilepsy fail to respond to anti-seizure medication (ASM) and may lead to uncontrolled and prolonged seizures often inducing status epilepticus (SE). The aim of the study was to evaluate the impact of a long-term treatment with two different generation ASMs: ethosuximide (ETS, a classic ASM) and lacosamide (LCM, a 3rd generation ASM) on neural stem cells’ (NSCs’) proliferation and learning and memory functions after pilocarpine (PILO)-induced SE in mice. The following drugs were used: LCM (10 mg/kg), ETS (20 mg/kg), and PILO (300 mg/kg). Cell counting was done using confocal microscope and ImageJ software. Cognitive functions were evaluated with the Morris water maze (MWM) test. The level of several selected neurometabolites was measured with magnetic resonance spectroscopy (MRS). Obtained results indicated no significant impact of ETS treatment on the neurogenesis process in PILO mice. Interestingly, LCM significantly decreased the total amount of newborn neurons. The MWM test indicated no significant changes in the time and distance traveled by the ETS and LCM groups compared to PILO control mice, although all measured parameters were more favorable for the PILO mice treated with ASM. Conclusions: The presented results show that long term treatment with LCM and ETS seems to be safe for the cognitive functions and the proper course of neurogenesis in the mouse PILO-induced SE model, although one should remember that LCM administered chronically may act to reduce new neurons’ formation.
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Meng, Y., S. Suppiah, L. Gonen, G. Klironomos, F. Gentili, and G. Zadeh. "Factors associated with recurrence after endoscopic transphenoidal surgery for Cushing’s disease." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 42, S1 (May 2015): S41. http://dx.doi.org/10.1017/cjn.2015.186.
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Introduction: Surgical removal is the standard treatment for Cushing’s disease. Although endoscopic transsphenoidal surgical (ETS) approach has grown in popularity, its efficacy has not yet been established. Furthermore, achieving long-term remission remains challenging. Methods: We conducted a retrospective chart review of 39 consecutive patients who underwent ETS for Cushing’s disease at our institution between 2005 and 2014. Univariate analysis using Pearson’s χ2 test was carried out on variables of patient demographics, radiology, pathology, biochemical markers versus recurrence. Results: The mean age was 40, with 82% females. Average length of follow-up was 44.8 months. Based on serum cortisol level, 28 patients (71%) achieved mid to long-term remission after ETS. Of them, 25 experienced an immediate remission, and 3 achieved a delayed remission as long as 4 months postoperatively. MRI findings of (1) microadenomas or no detectable abnormality, (2) adjacency to the cavernous sinus wall were associated with significantly higher recurrence rate (p<0.05). Histologically, MIB-1 >5% was not a significant variable (p=0.55). Conclusion: We found ETS resection to be an effective and safe procedure for majority of the ACTH-secreting adenomas, with remission rates >70%. Additionally, patients with microadenomas, negative preoperative MR, and cavernous sinus adjacency were less likely to achieve remission.
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Alhetheli, Ghadah. "Outcome Using Either Intradermal Botox Injection or Endoscopic Thoracic Sympathectomy for Patients with Primary Palmar Hyperhidrosis: A Comparative Study." Cosmetics 8, no. 2 (May 25, 2021): 41. http://dx.doi.org/10.3390/cosmetics8020041.
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Hyperhidrosis, or excessive sweating, negatively impacts patients both physically and psychologically. It may be primary or secondary: the primary form is a benign condition, with its growing prevalence reaching 5% recently. Its medical treatments are transitory. Objectives: Comparison of the outcomes of patients with primary palmar hyperhidrosis (PPH) after intradermal Botox injection (IBI) versus endoscopic thoracic sympathectomy (ETS). Methods: Forty patients were randomly divided into two equal groups. Patients in the IBI group received an intradermal injection of a botulinum toxin A. Patients in the EST group received endoscopic electrocautery of the sympathetic chain. The patients were evaluated biweekly for 12 weeks, and patient satisfaction by outcome was evaluated using a 4-point satisfaction score. Results: At 12 weeks, 60% of the IBI group patients had maintained an improvement. Meanwhile, 40% of the patients were improved compared to pre-intervention scores, despite deterioration after remarkable improvement. On the other hand, 80% of ETS group patients maintained their Hyperhidrosis Disease Severity Scale (HDSS) up until the end of follow-up. Patient satisfaction scores were significantly higher for the IBI group compared to the ETS group. Conclusions: Intradermal Botox injection is a simple, safe, non-invasive, and effective therapeutic modality for PPH and achieved higher patient satisfaction compared to ETS.
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Flores Morales, Rogelio, Liliana Souza Colín, Ángela Oviedo Mireles, and Jorge Fernando Bonilla Allende. "Estrés Traumático Secundario (ETS) en Periodistas Mexicanos y Defensores de Derechos Humanos." Summa Psicológica 13, no. 1 (July 15, 2016): 101–11. http://dx.doi.org/10.18774/448x.2016.13.290.
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El objetivo del presente estudio descriptivo fue identificar la prevalencia de síntomas de estrés traumático secundario (ETS) en una muestra conjunta de periodistas mexicanos y defensores de derechos humanos (N=88), cuyo trabajo profesional regularmente demanda un contacto cercano con víctimas de violencia. Se encontró que 36.4% de los participantes presentaron sintomatología "alta” o “severa” de ETS, sin embargo, no se ubicaron diferencias significativas entre ambos grupos. Por otra parte, las mujeres y quienes laboraban más de 40 horas a la semana, sí mostraron síntomas significativamente más altos. Los resultados de esta investigación transversal reflejan el considerable desgaste psicológico que pueden generar las exposiciones secundarias en profesionistas que documentan y establecen vínculos sistemáticos con personas traumatizadas por la violencia social en México.
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Juric, Dejan, Sibylle Loibl, Fabrice Andre, J. Ignacio Delgado Mingorance, Frederic Forget, Christelle Levy, Norikazu Masuda, et al. "Alpelisib (ALP) with fulvestrant (FUL) in patients (pts) with PIK3CA-mutated hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancer (ABC): Primary or secondary resistance to prior endocrine therapy (ET) in the SOLAR-1 trial." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 1038. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.1038.
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1038 Background: A contributor to ETR, phosphatidylinositol 3-kinase (PI3K) pathway hyperactivation can result from mutations to PIK3CA; ~40% of pts with HR+, HER2– ABC exhibit tumors with this mutation. Use of the oral α-specific PI3K inhibitor ALP + FUL significantly improved progression-free survival (PFS) in pts with a PIK3CA mutation (HR 0.65; 95% CI, 0.50-0.85; P<0.001) in SOLAR-1, which included both ET sensitive (ETS) and ETR pts (Table). ETS pts were later excluded by a protocol amendment. ETR was further defined as primary (1R) or secondary (2R) per ESMO criteria in both 1L and 2L pts. This subgroup analysis evaluated pts with a PIK3CA mutation based on tx line and endocrine status. Methods: SOLAR-1 was a phase 3, randomized, double-blind study of ALP 300 mg QD or PBO Q28d + FUL 500 mg Q28d + C1d15 in men and postmenopausal women with HR+, HER2– ABC whose disease progressed on/after an aromatase inhibitor. PFS was estimated by Kaplan-Meier method and median PFS (mPFS) presented by tx arm. A stratified Cox proportional hazards model estimated HR and 2-sided 95% CI. Results: Of 341 pts in the PIK3CA mutant cohort, 39 (11%) were ETS; 302 (89%) were ETR. mPFS in the ALP vs PBO arms was 22.1 vs 19.1 mo (HR 0.87; 95% CI, 0.35-2.17) for ETS pts and 9.4 vs 4.2 mo (HR 0.64; 95% CI, 0.48-0.84) for ETR pts. For ETR pts, mPFS for 1L (n=138) was 9.0 vs 4.7 mo (HR 0.69; 95% CI, 0.46-1.05) and for 2L (n=161) was 10.9 vs 3.7 mo (HR 0.61; 95% CI, 0.42-0.89). Conclusions: In SOLAR-1, mPFS was improved with ALP + FUL vs PBO + FUL across ETR pts in 1L and 2L. Representation of ETS pts was low in SOLAR-1, which included more ETR pts. Analysis of the PI3K pathway in ETS pts is warranted in future studies. Clinical trial information: NCT02437318. [Table: see text]
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Zhang, Tiejun, Yaohui Li, Haixia Duan, Yuanpu Liu, Dingwen Zeng, Cailing Zhao, Chongshui Gong, Ganlin Zhou, Linlin Song, and Pengcheng Yan. "Development and Evaluation of a WRF-Based Mesoscale Numerical Weather Prediction System in Northwestern China." Atmosphere 10, no. 6 (June 25, 2019): 344. http://dx.doi.org/10.3390/atmos10060344.
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Based on the U.S. Weather Research and Forecasting (WRF) numerical model, this study has developed the Northwest Mesoscale Numerical Prediction Service and Experimental System (NW-MNPS). Surface and sounding data assimilation has been introduced for this system. Effects of model vertical layers and land-use data replacement have been assessed. A year-long forecast validation and analysis have been performed. The following results have been obtained: (1) Data assimilation can improve the performance of regional numerical forecasting. (2) Compared to simulations with 40 vertical layers, simulations with 55 vertical layers are more accurate. The average absolute error and root-mean-square error of the 48 h surface element forecast decrease. The analysis of threat score (TS) and equitable threat score (ETS) shows that there are higher TS and ETS values for various precipitation intense levels, in particular for heavy rainfall when comparing a 55-vertical-layer test with a 40-vertical-layer test. (3) Updating the database to include vegetation coverage can more accurately reflect actual surface conditions. The updated land-use data reduce prediction errors in all domains of the NW-MNPS.
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Feng, Jie, Fang Liao, Deying Kong, Ruihua Ren, Tao Sun, Wei Liu, Yanyan Yin, Haoyu Ma, Jiahao Tang, and Guanrong Li. "Genetic diversity of the cultivated Salvia miltiorrhiza populations revealed by four intergenic spacers." PLOS ONE 17, no. 4 (April 6, 2022): e0266536. http://dx.doi.org/10.1371/journal.pone.0266536.
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For better understanding the genetic diversity and phylogeny of the cultivated Salvia miltiorrhiza populations, four intergenic spacer sequences, ETS, psbA-trnH, trnL-trnF, and ycf1-rps15 of the 40 populations collected from China were Polymerase Chain Reaction (PCR) amplified, analyzed both individually and in combination. Haplotype diversity analysis showed that the cultivated S. miltiorrhiza populations had a very rich genetic diversity and an excellent capacity to resist environmental pressure. The best-fit nucleotide substitution models for ETS, psbA-trnH, trnL-trnF, ycf1-rps15, and their combined sequences were HKY+I, T92, T92, T92+G, and T92+G, respectively; the nucleotide conversion frequency in the combined sequences was lower than the transversion, and the relatively high nucleotide substitution frequencies suggests its high genetic variability. Neutral tests showed that the spacer sequences of the populations conform with the neutral evolution model, and there has been no current expansion events occurred. Phylogeny analyses based on both the individual and the combined sequences showed that the 40 populations were clustered in two clades with a very similar topological structure. The discrimination rate of the combined sequence marker is significantly increased to 52.5% (21 populations) over the highest 35% (13 populations) by the single marker of ETS, though still inadequate but a big step forward. Further exploration of more DNA markers is needed. This study for the first time revealed the rich genetic diversity and phylogeny of the currently cultivated S. miltiorrhiza populations in China and provides novel alternative molecular markers for the genetic identification and resources evaluation of the cultivated S. miltiorrhiza populations.
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Fuhrer, D., M. Eszlinger, S. Karger, K. Krause, C. Engelhardt, D. Hasenclever, H. Dralle, and R. Paschke. "Evaluation of insulin-like growth factor II, cyclooxygenase-2, ets-1 and thyroid-specific thyroglobulin mRNA expression in benign and malignant thyroid tumours." European Journal of Endocrinology 152, no. 5 (May 2005): 785–90. http://dx.doi.org/10.1530/eje.1.01912.
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Objective: We evaluated three markers (insulin-like growth factor II (IGF-II), cyclooxygenase-2 (COX-2) and ets-1) of thyroid growth stimulation and cell transformation together with a thyroid-specific marker (thyroglobulin (Tg)) for their potential to differentiate benign and malignant follicular thyroid neoplasia (FN). Design and methods: mRNA expression levels were determined by real-time PCR in 100 snap-frozen thyroid samples: 36 benign thyroid nodules with different histology and function (19 cold (CTN) and 17 toxic thyroid nodules (TTN)), 36 corresponding normal thyroid tissues of the same patients, eight Graves’ disease (GD) thyroids, 10 follicular thyroid carcinomas (FTC) and 10 papillary thyroid carcinomas (PTC). Results: Mean IGF-II and COX-2 levels were not significantly altered between benign and malignant thyroid nodules (IGF-II) or nodular (FTC, TTN, CTN) and normal thyroid tissues (COX-2). In contrast, eight- to tenfold upregulation of ets-1 was observed in PTC and three- to fourfold upregulation of ets-1 was observed in FTC (and GD) compared with benign thyroid nodules and normal thyroid tissues. In addition, thyroglobulin mRNA expression was markedly downregulated (50- to 100-fold) in FTC, PTC and GD samples compared with benign nodular and normal thyroid tissues. Hence an ets-1/Tg ratio >20 distinguished differentiated thyroid cancer from benign nodular or normal thyroid tissue. We then studied ets1- and Tg mRNA expression levels in fine needle aspiration cytology (FNAC) samples. However, in a consecutive series of 40 FNAC samples only equivocal results were obtained on 38 benign and two malignant (FTC) thyroid tumour samples. Conclusions: Upregulation of ets-1 and downregulation of Tg mRNA expression occur in differentiated thyroid cancer and may facilitate pre-operative identification of thyroid malignancy depending on further evaluation of these potentially promising markers in a larger series of benign and malignant thyroid tumours and their FNAC samples.
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NORDENTOFT, Iver, and Poul JØRGENSEN. "The acetyltransferase 60 kDa trans-acting regulatory protein of HIV type 1-interacting protein (Tip60) interacts with the translocation E26 transforming-specific leukaemia gene (TEL) and functions as a transcriptional co-repressor." Biochemical Journal 374, no. 1 (August 15, 2003): 165–73. http://dx.doi.org/10.1042/bj20030087.
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The translocation E26 transforming-specific (ETS) leukaemia (TEL), alias the ETS variant (ETV6), gene is expressed in most human tissues and encodes a transcriptional repressor. The TEL gene is involved in more than 40 different chromosomal translocations associated with haematological malignancies. As little is known about the function of intact TEL, we searched for TEL-interacting proteins by yeast two-hybrid screening. Among the interacting partners, we identified the histone acetyltransferase protein Tip60 [60 kDa trans-acting regulatory protein of HIV type 1 (Tat)-interacting protein]. The interaction was reproduced in vitro, and in mammalian cells we mapped the interaction regions in TEL to the ETS domain and those in Tip60 to the MYST (‘MOZ, Ybf2/Sas3, SAS2 and Tip60’, where MOZ stands for male absent on the first, SAS for something about silencing and Ybf2 for identical with SAS2) region. Detailed analysis of the Tip60 MYST domain by introduction of point mutations revealed that an N-terminal C2HC zinc finger was essential for interaction with TEL. Finally, we showed that Tip60 functions in a reporter system as a co-repressor in TEL-mediated transcription repression.
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Kushwaha, Satish Chandra, and Pradyuman Kumar. "Acceptability of ellagitannin powder as an additive in preparation of sharbet." Nutrition & Food Science 46, no. 6 (November 14, 2016): 753–65. http://dx.doi.org/10.1108/nfs-01-2016-0011.
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Purpose The purpose of this study is to look at the application of ellagitannin (ET) powder in sharbet (sugar syrup-based drink) as an additive to produce a polyphenol-enriched drink. ETs are important polyphenols extracted from pomegranate peel (an underutilized juice industry waste). ETs are known for many functional properties such as antioxidative, antibacterial and coloring agent. Naturally, sharbet lacks in polyphenol content; hence, there is a large scope to enhance the functional property of sharbet by addition of ellagitannin powder (ETP) as an additive. Design/methodology/approach ETP at different concentrations (2, 10, 20, 30, 40 and 50 mg/100 ml sharbet) was applied in plain sharbet (EPS) and lemon-flavored sharbet (ELS). Each concentration of both types of sharbet was analyzed for physicochemical parameters and sensory attributes by sensory panel. Data were analyzed by using statistical tools (t-test, ANOVA, PCA and graphs) and finding the acceptability of ETP application in sharbet. Findings Each concentration of both sharbets was analyzed for chemical attributes, i.e. color (L, a, b) ranges (65.81-51.33, −0.24-0.24, −1.57-2.06, respectively), pH (6.30-3.95), titrable acidity as citric acid (0.01-0.1 per cent), total soluble solids (14.7-14.9 per cent), antioxidant activity as DPPH (12.6-71.6 per cent in EPS and 15.5-75.3 per cent in ELS) and sensory analysis (on Hedonic Scale) for sensory attributes, i.e. color, odor, taste and overall acceptability by a sensory panel (n = 24) of food technologists. Principal component analysis and sensory evaluation score have revealed that sharbet-flavored with lemon extract was liked more in comparison to plain sharbet. ELS containing 30 and 40 mg ETP per 100 ml sharbet was showed to have the highest acceptability index (92.13 and 91.67 per cent) in terms of overall acceptability by sensory panel. It is evident that the addition of ET in polyphenol-deficient beverages could be a market potential toward production of neutraceutical beverages which have antioxidative effects, good taste and are widely accepted. Originality/value In view of the neutraceutical food development, ETs could be a major polyphenolic component to fulfill the human health requirement. This research can be helpful for commercialization of ETs by the beverage industry.
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Hussain, Maha, Stephanie Daignault, Przemyslaw Twardowski, Costantine Albany, Mark N. Stein, Lakshmi Priya Kunju, Dan R. Robinson, et al. "Abiraterone + prednisone (Abi) +/- veliparib (Vel) for patients (pts) with metastatic castration-resistant prostate cancer (CRPC): NCI 9012 updated clinical and genomics data." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 5001. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.5001.
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5001 Background: In preclinical CRPC models, PARP1 inhibition synergizes with AR targeted therapy, especially in ETS fusion-positive tumors. We hypothesized: 1. Co-targeting PARP-1 + AR is superior to AR inhibition and 2. ETS +ve predicts response. Methods: Pts had metastatic (mets) disease biopsy (bx), stratified by IHC-ETS status and randomized to Abi (Arm A) or Abi + Vel (Arm B). Primary endpoint: PSA response rate (RR > = 50% decline). Secondary endpoints: safety, objective RR (ORR), progression free survival (PFS), and molecular analysis including if DNA repair gene deficiency (DRD: BRCA 1, BRCA 2, ATM, FANCA, PALB2, RAD51B, RAD51C) predicts response. 148 pts stratified by IHC-ETS status were randomized to detect a 20% PSA RR improvement assuming a 5% 1-sided type I error and 80% power. An elastic net multivariable Cox model was used to analyze PFS. Mets bx underwent targeted exon sequencing and capture transcriptome analysis. Results: 72 pts were randomly assigned to Arm A and 76 to Arm B. PSA RR: Arm A 63.9%, Arm B 72.4% (p = 0.27). ORR: Arm A 45%, Arm B 52.2%, p = 0.51. Median PFS: Arm A 10.1 months (m), Arm B 11.3 m, p = 0.95. More Arm-B pts were on therapy for 12+ (45% vs 38%) and 18+ cycles (22% vs 17%). ETS status had no impact. Mets tissue sequencing (N = 80): 42 pts (53%) were ETS +ve, 19 (25%) had DRD, 47 (59%) had AR amplification/copy gain, 32 (40%) had PTEN mutation (mut), 33 (41%) had TP53 mut, 37 (46%) had PIK3CA activation (a) and 12 (15%) had WNT-a. Irrespective of arm pts with DRD had a higher PSA and ORR ( > = 87%) vs wild type (58%, 39%; p = 0.013, p = 0.002, respectively), higher PSA decline rate of > = 90% (74% vs 26%, p = 0.0004) and longer median PFS (95% CI): DRD 16.6 m (11 - NR) vs wild type: 8 m (5.4 – 13.3); p = 0.02. PFS was longer in pts with normal PTEN (13.5 vs 6.2 m, p = 0.02), TP53 (13.3 vs 7.8 m, p = 0.04) and PIK3CA (10.3 vs 8.3 m, p = 0.03). Controlling for clinical factors, DRD, PTEN, TP53 and PIK3CA are associated with PFS in this order of importance. Conclusions: There was a modest trend in favor of Abi + Vel but no difference by ETS. Pts with DRD, normal PTEN,TP53 and PIK3CA had better PFS raising new hypotheses regarding the importance of integrating molecular analysis in therapeutic trials. Clinical trial information: NCT01576172.
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Prescott, Jason D., Karen S. N. Koto, Meenakshi Singh, and Arthur Gutierrez-Hartmann. "The ETS Transcription Factor ESE-1 Transforms MCF-12A Human Mammary Epithelial Cells via a Novel Cytoplasmic Mechanism." Molecular and Cellular Biology 24, no. 12 (June 15, 2004): 5548–64. http://dx.doi.org/10.1128/mcb.24.12.5548-5564.2004.
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ABSTRACT Several different transcription factors, including estrogen receptor, progesterone receptor, and ETS family members, have been implicated in human breast cancer, indicating that transcription factor-induced alterations in gene expression underlie mammary cell transformation. ESE-1 is an epithelium-specific ETS transcription factor that contains two distinguishing domains, a serine- and aspartic acid-rich (SAR) domain and an AT hook domain. ESE-1 is abundantly expressed in human breast cancer and trans-activates epithelium-specific gene promoters in transient transfection assays. While it has been presumed that ETS factors transform mammary epithelial cells via their nuclear transcriptional functions, here we show (i) that ESE-1 protein is cytoplasmic in human breast cancer cells; (ii) that stably expressed green fluorescent protein-ESE-1 transforms MCF-12A human mammary epithelial cells; and (iii) that the ESE-1 SAR domain, acting in the cytoplasm, is necessary and sufficient to mediate this transformation. Deletion of transcriptional regulatory or nuclear localization domains does not impair ESE-1-mediated transformation, whereas fusing the simian virus 40 T-antigen nuclear localization signal to various ESE-1 constructs, including the SAR domain alone, inhibits their transforming capacity. Finally, we show that the nuclear localization of ESE-1 protein induces apoptosis in nontransformed mammary epithelial cells via a transcription-dependent mechanism. Together, our studies reveal two distinct ESE-1 functions, apoptosis and transformation, where the ESE-1 transcription activation domain contributes to apoptosis and the SAR domain mediates transformation via a novel nonnuclear, nontranscriptional mechanism. These studies not only describe a unique ETS factor transformation mechanism but also establish a new paradigm for cell transformation in general.
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Mattison, Michelle, and Penny Cooper. "Witness Statements for Employment Tribunals in England and Wales: What are the ‘Issues’?" International Journal of Evidence & Proof 25, no. 4 (October 2021): 286–306. http://dx.doi.org/10.1177/13657127211046397.
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In England and Wales, Employment Tribunals (ETs) hear claims from persons who believe that an employer, or potential employer, has treated them unlawfully. Witness statements form part of the evidence considered by ETs, but research is lacking with regard to the methods used to produce ET witness statements. This study presents the findings from 40 semi-structured interviews with ET judges, panel members, employment lawyers (solicitors, barristers, advisers) and litigants. Our data revealed six themes: professional processes, enabling through case management, presentation preferences, challenges for litigants in person, availability and quality of resources, and lack of training. Participants felt that the quality of witness statements varied amongst those prepared by professional advisors and by litigants in person. Our interviews revealed almost no evidence of practitioner training on how best to prepare a witness statement. We make recommendations about guidance and training for those tasked with drafting witness statements.
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Mattison, Michelle, and Penny Cooper. "Witness Statements for Employment Tribunals in England and Wales: What are the ‘Issues’?" International Journal of Evidence & Proof 25, no. 4 (October 2021): 286–306. http://dx.doi.org/10.1177/13657127211046397.
Full textAbstract:
In England and Wales, Employment Tribunals (ETs) hear claims from persons who believe that an employer, or potential employer, has treated them unlawfully. Witness statements form part of the evidence considered by ETs, but research is lacking with regard to the methods used to produce ET witness statements. This study presents the findings from 40 semi-structured interviews with ET judges, panel members, employment lawyers (solicitors, barristers, advisers) and litigants. Our data revealed six themes: professional processes, enabling through case management, presentation preferences, challenges for litigants in person, availability and quality of resources, and lack of training. Participants felt that the quality of witness statements varied amongst those prepared by professional advisors and by litigants in person. Our interviews revealed almost no evidence of practitioner training on how best to prepare a witness statement. We make recommendations about guidance and training for those tasked with drafting witness statements.
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Brazhnik, D. A., G. D. Semchenko, G. N. Shabanova, I. N. Rozhko, and V. V. Makarenko. "Investigation of physicomechanical properties of carbide-silicon materials using the disten-sillimanite raw material of Ukraine." Scientific research on refractories and technical ceramics 118 (July 11, 2018): 49–55. http://dx.doi.org/10.35857/2663-3566.118.05.
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Structural destruction is less for products used in various furnaces of ferrous and non-ferrous metallurgy, on the surface of which a melt with a high viscosity is formed during service. With this in mind, it seems appropriate to use silicon carbide materials, the grains of which are coated with a quartz film that protects SiC from rapid destruction in an oxidizing medium. To form a quartz film on carborundum grains, it is necessary to introduce quartz-containing raw materials, in particular, disthen-sillimanite concentrate, which allows to create the necessary phase composition of the lining mass in the process of raising the temperature at the initial stage of the furnace operation. The article is considered the possibility of using the disthen-sillimanite raw materials of Ukraine in the development of carbide-silicon materials. Various types of binder (ethyl silicate ETS-40, ETS 40/60, TLS, thermoplastic), variants of their correlation among themselves, and also with a different amount of disthen-sillimanite concentrate, are given. The possibility of controlling the physical and mechanical characteristics of materials by adjustment of the components ratio of binder and disthen-sillimanite concentrate is shown. The best combination of characteristics of silicon carbide materials, which is achieved by using a specific amount of disthen-sillimanite concentrate, is established.
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Iliv, Vasyl, and Yarema Iliv. "STUDY OF FLUIDITY AND KINEMATIC VISCOSITY OF ORGANIC SILICONAL LIQUIDS AND MIXTURES BASED ON THEM." Theory and Building Practice 2021, no. 1 (June 22, 2021): 8–14. http://dx.doi.org/10.23939/jtbp2021.01.008.
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Preliminary studies have shown that hydrophobic materials ZDP "Silicon Polymer" 136-157 M, ETS-32, ETS-40, and a number of their analogs, in contrast to GKZh-11N and GKZh-11K, can withstand excess water pressure of 0.02 MPa when tested for methods developed based on standard methods for determining the water-resistance of concrete and tiles. The authors of the article developed experimental waterproofing liquids 1 K, 2 K, 1 N, and 2 N, based on GKZh-11 N and GKZh-11K. These liquids are ready for use for hydrophobization and silicatization of organosilicon compounds. The depth of penetration of waterproofing liquids into wall materials depends, in addition to the absorbency, on the value of the kinematic viscosity of such liquids. Therefore, the establishment of conditional and kinematic viscosity of waterproofing liquids is one of the tasks set in this article. Conditional (fluidity) and kinematic viscosity, due to their relationship, were determined using viscometers VZ-1, VZ-4, VZ-246, and a ball viscometer.
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Yang, Xia, An-Lei Guo, Yi-Peng Pang, Xiao-Jing Cheng, Ting Xu, Xin-Rui Li, Jiao Liu, Yu-Yun Zhang, and Yi Liu. "Astaxanthin Attenuates Environmental Tobacco Smoke-Induced Cognitive Deficits: A Critical Role of p38 MAPK." Marine Drugs 17, no. 1 (January 3, 2019): 24. http://dx.doi.org/10.3390/md17010024.
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Increasing evidence indicates that environmental tobacco smoke (ETS) impairs cognitive function and induces oxidative stress in the brain. Recently, astaxanthin (ATX), a marine bioactive compound, has been reported to ameliorate cognitive deficits. However, the underlying pathogenesis remains unclear. In this study, ATX administration (40 mg/kg and 80 mg/kg, oral gavage) and cigarette smoking were carried out once a day for 10 weeks to investigate whether the p38 MAPK is involved in cognitive function in response to ATX treatment in the cortex and hippocampus of ETS mice. Results indicated that ATX administration improved spatial learning and memory of ETS mice (p < 0.05 or p < 0.01). Furthermore, exposure to ATX prevented the increases in the protein levels of the p38mitogen-activated protein kinase (p38 MAPK; p < 0.05 or p < 0.01) and nuclear factor-kappa B (NF-κB p65; p < 0.05 or p < 0.01), reversed the decreases in the mRNA and protein levels of synapsin I (SYN) and postsynaptic density protein 95 (PSD-95) (all p < 0.05 or p < 0.01). Moreover, ATX significantly down-regulated the increased levels of pro-inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) (all p < 0.05 or p < 0.01). Meanwhile, the increased level of malondialdehyde (MDA) and the decreased activities of superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) were suppressed after exposure to ATX (all p < 0.05 or p < 0.01). Also, the results of the molecular docking study of ATX into the p38 MAPK binding site revealed that its mechanism was possibly similar to that of PH797804, a p38 MAPK inhibitor. Therefore, our results indicated that the ATX might be a critical agent in protecting the brain against neuroinflammation, synaptic plasticity impairment, and oxidative stress in the cortex and hippocampus of ETS mice.
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Willruth, Arne, Johannes Steinhard, Christian Enzensberger, Roland Axt-Fliedner, Ulrich Gembruch, Astrid Doelle, Ioanna Dimitriou, Rolf Fimmers, and Franz Bahlmann. "Color Tissue Doppler to Analyze Fetal Cardiac Time Intervals: Normal Values and Influence of Sample Gate Size." Ultraschall in der Medizin - European Journal of Ultrasound 39, no. 01 (February 4, 2016): 56–68. http://dx.doi.org/10.1055/s-0041-107765.
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Abstract Purpose To assess the time intervals of the cardiac cycle in healthy fetuses in the second and third trimester using color tissue Doppler imaging (cTDI) and to evaluate the influence of different sizes of sample gates on time interval values. Materials and Methods Time intervals were measured from the cTDI-derived Doppler waveform using a small and large region of interest (ROI) in healthy fetuses. Results 40 fetuses were included. The median gestational age at examination was 26 + 1 (range: 20 + 5 – 34 + 5) weeks. The median frame rate was 116/s (100 – 161/s) and the median heart rate 143 (range: 125 – 158) beats per minute (bpm). Using small and large ROIs, the second trimester right ventricular (RV) mean isovolumetric contraction times (ICTs) were 39.8 and 41.4 ms (p = 0.17), the mean ejection times (ETs) were 170.2 and 164.6 ms (p < 0.001), the mean isovolumetric relaxation times (IRTs) were 52.8 and 55.3 ms (p = 0.08), respectively. The left ventricular (LV) mean ICTs were 36.2 and 39.4 ms (p = 0.05), the mean ETs were 167.4 and 164.5 ms (p = 0.013), the mean IRTs were 53.9 and 57.1 ms (p = 0.05), respectively. The third trimester RV mean ICTs were 50.7 and 50.4 ms (p = 0.75), the mean ETs were 172.3 and 181.4 ms (p = 0.49), the mean IRTs were 50.2 and 54.6 ms (p = 0.03); the LV mean ICTs were 45.1 and 46.2 ms (p = 0.35), the mean ETs were 175.2 vs. 172.9 ms (p = 0.29), the mean IRTs were 47.1 and 50.0 ms (p = 0.01), respectively. Conclusion Isovolumetric time intervals can be analyzed precisely and relatively independent of ROI size. In the near future, automatic time interval measurement using ultrasound systems will be feasible and the analysis of fetal myocardial function can become part of the clinical routine.
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Dare, Richard A., and Elizabeth E. Ebert. "Latitudinal variations in the accuracy of model-generated forecasts of precipitation over Australia and south-east Asia." Journal of Southern Hemisphere Earth Systems Science 67, no. 1 (2017): 46. http://dx.doi.org/10.1071/es17005.
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Forecasts of precipitation produced by global and regional versions of the Bureau of Meteorology’s Australian Community Climate and Earth System Simulator (ACCESS) numerical weather prediction models are compared with Tropical Rainfall Measuring Mission (TRMM) observations for the period January 2011 to March 2014. The area considered covers longitudes 110° to 160°E within 40° latitude of the equator, and includes the Australian continent and part of south-east Asia. Forecast accuracy is assessed using objective measures: equitable threat score (ETS), frequency bias (FB), and the ratio of predicted to observed rain volume (RVR). For the assessment, the TRMM and model datasets are both interpolated to consistent grids defined by spacings of 1° longitude and 1° latitude. Assessments based on three-month seasons show that, in general, the volume of rain predicted by the models is too high, and rainfall is predicted to occur at more locations than observed. Latitudinal variations in values of the ETS reveal marked declines over the equatorial tropics, with minimum values near the equator from December to May and near 10°N from June to November. Differences in the ETS between 24-hour model and persistence forecasts show that the models produce useful predictions of rainfall away from the tropics, poleward of latitudes 5º-15º S and 15º-30º N, depending on the season and model. The 48-hour model predictions are more useful than the 24-hour forecasts, with improvements relative to persistence over most latitudes, although differences are close to zero at low latitudes. Varying the rain threshold used to compute skill metrics shows that the models produce excessive rainfall at low rain rates, generally less than approximately 15 mm day-1, while not enough precipitation is forecast at higher rain rates. Values of the ETS are generally highest at lower rain rates, coinciding with the excessive values of RVR and FB.
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Soukup, Alexandra A., Daniel R. Matson, Kirby D. Johnson, and Emery H. Bresnick. "GATA2 Enhancer Modules Governing Hematopoietic Regeneration." Blood 136, Supplement 1 (November 5, 2020): 15–16. http://dx.doi.org/10.1182/blood-2020-142867.
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The transcription factor GATA2 is essential for the generation and function of hematopoietic stem and progenitor cells (HSPCs), erythroid precursors, and endothelial cells. A conserved intronic GATA2 enhancer, 9.8 kb downstream of the transcriptional start site (+9.5 in the mouse), is mutated in patients with GATA2 deficiency syndrome. Patient mutations within this region include a c.1017+512del28 deletion, removing E-box and GATA motifs, c.1017+532T>A that disrupts the E-box, and, most frequently, C>T in a 3' Ets motif (c.1017+572C>T) (Soukup and Bresnick, 2020). Homozygous mutation of the Ets motif in mice allows normal developmental and steady-state hematopoiesis but impairs hematopoietic regeneration (Soukup et al., 2019). In addition to HSPCs, GATA2 is expressed in non-hematopoietic cells in the bone marrow niche, e.g. endothelial cells and neurons (Katsumura et al., 2017). As the +9.5(Ets) mutation is not hematopoietic cell-specific, we asked whether regenerative defects of +9.5(Ets)-/- mice reflect disruption of cell-intrinsic or -extrinsic activities. In a competitive transplant assay, +9.5(Ets)-/- HSPCs were 3-fold less effective at long-term reconstitution than WT, and mechanistic studies indicated that the motif functions in hematopoietic cells to promote regeneration (Soukup et al., 2019). We conducted a reciprocal transplant of WT HSPCs into irradiated WT or +9.5(Ets)-/- recipients and quantified reconstitution by peripheral blood counts 4, 8, 12, and 16 weeks post-transplant. This analysis revealed no significant differences between WT and mutant recipients. At week 16, donor-derived leukocytes were 92% (+9.5(Ets)-/- recipients) and 96% (WT recipients) of total; the contribution did not differ significantly at any time. After 16 weeks, animals were sacrificed and HSPCs analyzed, confirming no significant alterations in mutant recipients. These results rigorously establish the mutant microenvironment as competent to support WT HSPC functions, emphasizing the critical hematopoietic cell-intrinsic activity of the +9.5 Ets motif. As the +9.5 Ets motif promotes regenerative hematopoiesis, and the +9.5 E-box;GATA is essential for developmental hematopoiesis, we devised a strategy to leverage these activities to innovate new models for GATA2 function in adult HSPCs. We generated compound heterozygous (CH) mice containing a mutant E-box;GATA sequence on one allele and a mutant Ets motif on the other allele. CH mice survived past weaning, with adults exhibiting significant steady-state defects, including a 4.4-fold decrease in GATA2hi megakaryocytes (p < 0.0001) and 20% decrease (p = 0.02) in platelets. To test whether the CH mutations compromise regeneration, we quantified HSPC populations in bone marrow from mice treated with vehicle or 5-fluorouracil (FU) 9- and 10- days post treatment. Steady-state HSC (Lin−Sca1+Kit+CD48-CD150+) levels were unaltered in CH animals. Days 9 and 10 post-FU treatment, WT HSC levels increased 17- (p = 0.0006) and 18-fold (p = 0.0007) relative to vehicle-treated animals. CH HSCs did not expand and were <10% of the steady-state level. 7 days post-FU treatment, Gata2 expression increased 1.9-fold in WT HSCs (p = 0.029); this response was abrogated in CHs. We asked if CH HSCs were capable of reconstitution in a competitive transplant assay. Four weeks post-transplant, CH progeny were 40-fold lower than WT (p < 0.0001). At 8-, 12-, and 16-weeks post-transplant, CH contribution was reduced 90-, 266-, and 280-fold, respectively. Defects persisted upon secondary transplantation, demonstrating that the defects cannot be restored by passage through a WT microenvironment. Thus, CH and +9.5(Ets)-/- mice share phenotypes, but CH mutations more severely impair regeneration and long-term reconstituting activity. This supports a paradigm in which the Ets motif and additional +9.5 sequences are critical for regeneration. This study revealed molecular determinants for steady-state and regenerative enhancer functions to enable discovery of +9.5-like enhancers with common operating mechanisms. We predict that such enhancers reside at a GATA2-regulated gene cohort, including genes that will reveal new mechanisms in hematopoiesis. As CH mice are poised for hematopoietic collapse, but can be propagated as relatively normal adults, studies are underway with this unique model to identify triggers of bone marrow failure and leukemogenesis. Disclosures No relevant conflicts of interest to declare.
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OLSEN, Jørgen, Klaus KOKHOLM, Jesper T. TROELSEN, and Liselotte LAUSTSEN. "An enhancer with cell-type dependent activity is located between the myeloid and epithelial aminopeptidase N (CD 13) promoters." Biochemical Journal 322, no. 3 (March 15, 1997): 899–908. http://dx.doi.org/10.1042/bj3220899.
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The 5´ flanking region of the gene encoding the small intestinal brush-border peptidase aminopeptidase N (APN) was screened for the presence of enhancer regions. A 300 bp region with enhancer activity was identified 2.7 kb upstream of the transcriptional start site which is used in epithelial cells. The enhancer stimulated transcription from a heterologous promoter (the simian virus 40 early promoter) in a position- and orientation-independent manner. The activity of the enhancer is cell-type dependent and it is active in liver (HepG2), intestinal (Caco-2) and myeloid (K562) cells. As the epithelial APN promoter is active in the first two cell-types and the myeloid APN promoter in the last, the results may suggest that the enhancer, through a cooperation with either of the promoters, is important for the tissue-specific expression of APN. A detailed analysis of the enhancer led to the identification of four functionally important regions that are protected against DNase I digestion by Caco-2 nuclear extract. Sequence analysis suggests that two of the regions may interact with members of the Ets transcription factor family (Ets is a transformation-specific protein first discovered in the E26 avian erythroblastosis virus), one region with a CCAAT enhancer-binding protein and one region with Sp1, a transcriptional activator first described as a factor binding to the simian virus 40 early promoter.
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Santos, Sebastião Dos. "Teores de As, Cd e Pb em solos e sedimentos de áreas de garimpo de ouro nos municípios de Pontes e Lacerda e Nova Lacerda, Vale do Alto Guaporé, MT." Revista Brasileira de Geografia Física 9, no. 6 (November 28, 2016): 1805. http://dx.doi.org/10.26848/rbgf.v9.6.p1805-1814.
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Os solos funcionam como fonte ou dreno de elementos traço (ETs) no ambiente. O estudo foi realizado em três áreas de garimpo de ouro na região do Alto Guaporé, nos municípios de Pontes e Lacerda e Nova Lacerda, sudoeste do estado de Mato Grosso, tendo como finalidade avaliar a concentração de As, Cd e Pb em sedimentos e solos em duas profundidades de 0-20 e 20-40 cm. Os ETs foram determinados em forno de grafite após extração ácida conforme método USEPA SW-846-3050. Os resultados das analises de solo foram comparados com a resolução da CETESB nº 195/2005 e de sedimentos com CONAMA nº 344/2004 e CCME-EPC 1999. Os teores médios de ETs encontradas nos sedimentos foram (As 0,413; Cd 0,021; e Pb 1,618 mg kg-1) no garimpo da Lavrinha; (As 1,343; Cd 0,037; e Pb 3,198 mg kg-1) no garimpo Pau a Pique; e (As 1,093; Cd 0,020; e Pb: 2,060 mg kg-1) na mineração São Francisco. Nos solos os teores médios foram de (As 0,772; Cd 0,017 e Pb 2, 515, mg kg-1) no garimpo da Lavrinha; (As 2,579; Cd 0,021 e Pb 4,373 mg kg-1 ) no garimpo Pau a Pique; e (As 0,920; Cd 0,018 e Pb 3,198 mg kg-1) na mineração São Francisco. Os valores encontrados de As, Cd e Pb nos solos e sedimentos dessas áreas estão abaixo dos valores de referencia, de acordo com as legislações brasileira e canadense.
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Cho, YM, DA Lewis, PF Koltz, V. Richard, TA Gocken, TJ Rosol, RL Konger, DF Spandau, and J. Foley. "Regulation of parathyroid hormone-related protein gene expression by epidermal growth factor-family ligands in primary human keratinocytes." Journal of Endocrinology 181, no. 1 (April 1, 2004): 179–90. http://dx.doi.org/10.1677/joe.0.1810179.
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Cultured primary human keratinocytes were the first non-cancer-derived cell type reported to produce the humoral hypercalcemia factor, parathyroid hormone-related protein (PTHrP). Emerging evidence suggests that only a subset of keratinocytes produce high levels of PTHrP in vivo. We found that the PTHrP mRNA content of intact human skin was minimal, whereas transcripts were easily detectable in primary keratinocytes derived from those skin samples. We hypothesized that conditions associated with growth in culture activated PTHrP gene expression in primary keratinocytes. In culture, keratinocytes produce a number of epidermal growth factor (EGF)-like ligands (transforming growth factor-alpha, heparin binding-EGF and amphiregulin) and their receptor, ErbB1. Treatment of keratinocytes with a specific erbB1 inhibitor (PD153035) reduced PTHrP mRNA levels by >80% in rapidly growing keratinocytes. Treatment of keratinocytes with reagents that neutralize amphiregulin reduced PTHrP mRNA levels by approximately 60%. Blockade of erbB1 signaling reduces transcription from the endogenous PTHrP P3-TATA promoter. The Ets transcription factor-binding site, 40 bases upstream of the P3 promoter, is required for baseline expression of PTHrP reporter gene constructs in keratinocytes; in addition, cotransfection of Ets-1 and Ets-2 expression vectors activate the reporter gene constructs. Finally, disruption of both ras and raf signaling reduce reporter gene expression by 80%, suggesting that ErbB1 signaling is mediated by the classic ras/MAP kinase pathway. These findings suggest that acquisition of EGF-like ligand expression has the potential to substantially activate PTHrP gene expression in the epidermis.
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Gattini, Andrea. "BETWEEN SPLENDID ISOLATION AND TENTATIVE IMPERIALISM: THE EU'S EXTENSION OF ITS EMISSION TRADING SCHEME TO INTERNATIONAL AVIATION AND THE ECJ'S JUDGMENT IN THE ATA CASE." International and Comparative Law Quarterly 61, no. 4 (October 2012): 977–91. http://dx.doi.org/10.1017/s0020589312000395.
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For the last 15 years the European Union (EU) has been particularly active, both internally and internationally, in the fight against global warming, and it is determined to continue to play a global leadership role in this strategic issue. Among the various market-based measures decided upon, the Emission Trading Scheme (ETS) for energy-intensive industrial sectors has been rightly described as the ‘flagship of the EU climate policy’.1 Even before proceeding to a general overhauling of Directive 2003/87 in the framework of the 2009 Climate and Energy package, the EU had decided to modify the Directive by including aviation activities in the ETS. Directive 2008/1012 provides that all flights from whichever aircraft operator taking off from or landing in the EU territory will be subjected to the ETS from 1 January 2012. For the year 2012 97 per cent of all emissions allowances will be freely assigned, from 2013 the amount will decrease to 95 per cent, whereas 15 per cent of all allowances will be auctioned. In reality the percentage of free allowances is much lower, about 60 per cent, because it takes as parameter the historical aviation emissions of the years 2004–06, when the air traffic was 40 per cent lower than it is now. The idea underlying the Directive is that aircraft operators will either purchase the necessary allowances in the market or will try to reduce their emissions by using bio-fuels (or else reducing the number of flights), with the second option becoming more economically attractive over time.
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Gerasimchuk, M. Yu. "CHARACTERISTICS OF DEPRESSION IN PATIENTS WITH DIFFERENT CHRONOTYPES." Annals of the Russian academy of medical sciences 72, no. 6 (November 22, 2017): 435–41. http://dx.doi.org/10.15690/vramn881.
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Background: Approximately 30−40% of depressive patients does not improve or show a partial response. Since biological rhythm involved in the pathogenesis of mood disorders is regarded as a unique characteristic of a person, it opens new opportunities for personalized medicine.Aim: to evaluate clinical characteristics and treatment effectiveness in depressive patients with different chronotypes.Materials and methods: In prospective, hospital-based study MADRS was performed weekly (dMADRS), therapeutic response (R) was defined as a 50% or greater decrease from baseline in the score. Chronotype was evaluated using the Morningness−Eveningness Questionnaire (MEQ). Participants completed a questionnaire package: HDRS-21, PSQI, ТОВ, «individual minute». Statistical analysis was performed using Excel for Windows, Statistica 13.0.Results: All patients (n=100, mean age 48±16 yrs) were divided into groups based on their circadian type: evening types (ETs) had more severe condition; antidepressants (SSRIs; R=72%) were effective given at morning in ETs, at evening (other; R=100%) ― in morning types (MTs) (p0.00001) with a greater reduction in depressive symptoms (p0.05). Prescribing drugs with balanced potency were effective in both groups (F=4.62, p=0.032). Cluster analysis on 25 clinical, biological, and therapeutic variables to establish the role of chronotype as a factor important for identifying patients with similar socio-demographic, clinical, and health characteristics was conducted. Cluster 1 achieved a reduction of depression severity (19% MTs; R=81%; 43.4±17.7 yrs; single episode; dMADRS 16.9±2.7; 23% monotherapy). Cluster 3 (80% ETs; R=50%; 40.4±15.2; early onset dMADRS 15.23±2.29; 7% monotherapy) was the most unfavorable prognostic group.Conclusions: Depressive patients with morning/evening chronotypes have significant differences in clinical presentation, the course of the illness and efficacy of antidepressants. Evening chronotype was found to be associated with poor prognosis. Circadian typology should be considered when choosing the appropriate therapeutic options.
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Dusser, Philippe. "The green-house gas (GHG) emission’s reduction mechanisms for biofuels in the European legislation." OCL 26 (2019): 45. http://dx.doi.org/10.1051/ocl/2019039.
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GHG reductions are a major focus of the EU policy. Several regulations have been set in order to meet the EU commitments under the Paris Agreement with an overall reduction of 40% from 1990 level. For the transport sector which is responsible for around 20% of the total GHG emissions, the GHG reductions obligations have been translated by i) reinforced GHG reduction thresholds for biofuels into the recast Renewable Energy Directive RED II; ii) an ambitious target of 30% GHG emission reduction target from 2005 level in the Effort Sharing Regulation (ESR) common to “non-ETS sector” (not covered by the Emission Trading System – ETS) as agriculture, building, waste… and transport. Furthermore, other EU regulations directed to Cars, Vans as well as Heavy Duty Vehicles set GHG emission reduction targets for new vehicle up to 2030. Finally, in its communication “A Clean Planet for All” the EU Commission describes A Strategy for 2050 to achieve a carbon neutral economy. This article addresses also the case of the German “GHG quota” which is a national support system for biofuels and as such is parallel to the European obligations stemming from the RED II renewable energy mandates that are to be met by Germany.
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Othman, Maha, Yvette Chirinian, Christine Brown, Colleen Notley, Nicholas Hickson, Daniel Hampshire, Suzanne Buckley, et al. "Functional characterization of a 13-bp deletion (c.-1522_-1510del13) in the promoter of the von Willebrand factor gene in type 1 von Willebrand disease." Blood 116, no. 18 (November 4, 2010): 3645–52. http://dx.doi.org/10.1182/blood-2009-12-261131.
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Abstract We have studied the effect of a 13-bp deletion in the promoter of the von Willebrand factor (VWF) gene in a patient with type 1 von Willebrand disease. The index case has a VWF:Ag of 0.49 IU/mL and is heterozygous for the deletion. The deletion is located 48 bp 5′ of the transcription start site, and in silico analysis, electrophoretic mobility shift assays, and chromatin immunoprecipitation studies all predict aberrant binding of Ets transcription factors to the site of the deletion. Transduction of reporter gene constructs into blood outgrowth endothelial cells showed a 50.5% reduction in expression with the mutant promoter (n = 16, P < .001). A similar 40% loss of transactivation was documented in transduced HepG2 cells. A similar marked reduction of transgene expression was shown in the livers of mice injected with the mutant promoter construct (n = 8, P = .003). Finally, in studies of BOEC mRNA, the index case showed a 4.6-fold reduction of expression of the VWF transcript associated with the deletion mutation. These studies show that the 13-bp deletion mutation alters the binding of Ets (and possibly GATA) proteins to the VWF promoter and significantly reduces VWF expression, thus playing a central pathogenic role in the type 1 von Willebrand disease phenotype in the index case.
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Kolluru, Mythili, and Tetiana Semenenko. "Income Inequalities in EU Countries: Gini Indicator Analysis." ECONOMICS 9, no. 1 (June 1, 2021): 125–42. http://dx.doi.org/10.2478/eoik-2021-0007.
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Abstract Franklin Delano Roosevelt said that “the test of our progress is not whether we add more to the abundance of those who have much; it is whether we provide enough for those who have too little.” According to the World Economic Forum (2021), income disparity is at the top of global risks in the coming years. The development of income inequality is a growing concern worldwide, particularly since the Great Recession. This study is based on available data on the Gini coefficient of equivalized disposable income from 2005 to 2019 for the 27 European Union countries. We found that the indicator’s value demonstrates a reasonably even distribution of income (not exceeding 40%) in all European Union countries, except Bulgaria. We used the FORECAST ETS function (Excel for Microsoft 365) that is based on the AAA version of the Exponential Smoothing (ETS) algorithm to conduct our analysis. We grouped the EU 27 countries to investigate income equality behavior. According to the interval’s median of the sample’s standard deviation, we selected Italy, Spain, Germany, Slovakia, Hungary, Bulgaria for further investigation. We conclude the absence of general trends in the inequality of income distribution in society due to the financial crisis factors. The research presents exploratory insights into income inequality in the European Union.
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Scimeca, Manuel, Manuela Montanaro, Rita Bonfiglio, Lucia Anemona, Enrico Finazzi Agrò, Anastasios D. Asimakopoulos, Roberto Bei, et al. "The ETS Homologous Factor (EHF) Represents a Useful Immunohistochemical Marker for Predicting Prostate Cancer Metastasis." Diagnostics 12, no. 4 (March 24, 2022): 800. http://dx.doi.org/10.3390/diagnostics12040800.
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The main aim of this study was to investigate the risk of prostate cancer metastasis formation associated with the expression of ETS homologous factor (EHF) in a cohort of bioptic samples. To this end, the expression of EHF was evaluated in a cohort of 152 prostate biopsies including primary prostate cancers that developed metastatic lesions, primary prostate cancers that did not develop metastasis, and benign lesions. Data here reported EHF as a candidate immunohistochemical prognostic biomarker for prostate cancer metastasis formation regardless of the Gleason scoring system. Indeed, our data clearly show that primary lesions with EHF positive cells ≥40% had a great risk of developing metastasis within five years from the first diagnosis. Patients with these lesions had about a 40-fold increased risk of developing metastasis as compared with patients with prostate lesions characterized by a percentage of EHF positive cells ≤30%. In conclusion, the immunohistochemical evaluation of EHF could significantly improve the management of prostate cancer patients by optimizing the diagnostic and therapeutic health procedures and, more important, ameliorating the patient’s quality of life.
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Kargi, Ahmet. "Plantar Sweating as an Indicator of Lower Risk of Compensatory Sweating after Thoracic Sympathectomy." Thoracic and Cardiovascular Surgeon 65, no. 06 (April 4, 2016): 479–83. http://dx.doi.org/10.1055/s-0036-1579680.
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Background Hyperhidrosis is a dysfunction of the autonomic nervous system that results in regional excessive sweating, mostly in the hands, armpits, and feet. A permanent and effective treatment of hyperhidrosis can be achieved by interruption of the thoracic sympathetic chain with endoscopic thoracic sympathectomy (ETS). However, some side effects, particularly compensatory sweating (CS), are the limitations of this procedure. The mechanism of CS and the associated risk factors are still controversial. The aim of this retrospective study was to determine the relationship with various parameters associated with CS in patients undergoing ETS. Materials and Methods ETS was performed on a total of 95 patients for palmar hyperhidrosis, axillary hyperhidrosis and facial blushing by the same surgeon. The mean age of the patients was 26.41 (± 7) years, and 54 (56.8%) were males. Palmar hyperhidrosis was present in 54 (56.8%) patients, axillary hyperhidrosis in 33 (34.7%) patients, and facial blushing in 8 (8.5%) patients. Moreover, 38 (40%) patients also had plantar sweating. The severity of CS was rated into three scales as less, moderate, and severe. Results Regarding the severity of CS, 55 (57.9%) patients had no or less CS, 28 (29.5%) had moderate CS, and 12 (12.6%) patients had severe CS. Higher age group had a significant increased risk of severe CS (p = 0.03) (r = 0.262). Patients with body mass index (BMI) > 25 kg/m2 had a statistically significantly increased risk of severe CS (p = 0.016). Facial blushing resulted in severe CS in a significantly higher proportion of patients than by palmar and axillary hyperhidrosis (p = 0.001). The level of surgery was another important risk factor for CS, with the T2 level showing an increased risk of severe CS compared with T3 level (p < 0.001). Furthermore, plantar sweating was inversely and significantly related to the development of CS. Patients with plantar sweating had a significantly decreased incidence of developing CS (p = 0.015). Conclusion CS after thoracic sympathectomy for primary hyperhidrosis is the most displeasing and restrictive side effect. This study demonstrates that older age, operation level, facial blushing, and high BMI are risk factors for CS, as have been shown in several similar studies. An interesting finding of the present study is that there was a decreased incidence of CS among patients with plantar sweating. This situation may help us to distinguish high risk for CS before ETS operation.