BACKGROUND: The level of the inactive N-terminal fragment of pro-brain(B-type) natriuretic peptide(BNP)-is a strong predictor of mortality among patients with acute coronary syndromes and may be a strong prognostic ma...BACKGROUND: The level of the inactive N-terminal fragment of pro-brain(B-type) natriuretic peptide(BNP)-is a strong predictor of mortality among patients with acute coronary syndromes and may be a strong prognostic marker in patients with chronic coronary heart disease as well. We assessed the relationship between N-terminal pro-BNP(NT-pro-BNP) levels and long-term mortality from all causes in a large cohort of patients with stable coronary heart disease. METHODS: NT-pro-BNP was measured in baseline serum samples from 1034 patients referred for angiography because of symptoms or signs of coronary heart disease. The rate of death from all causes was determined after a median follow-up of nine years. RESULTS: At follow-up, 288 patients had died. The median NT-pro-BNP level was significantly lower among patients who survived than among those who died(120 pg per milliliter[interquartile range, 50 to 318] vs. 386 pg per milliliter[interquartile range, 146 to 897], P< 0.001). Patients with NT-pro-BNP levels in the highest quartile were older, had a lower left ventricular ejection fraction(LVEF) and a lower creatinine clearance rate, and were more likely to have a history of myocardial infarction, clinically significant coronary artery disease, and diabetes than patients with NT-pro-BNP levels in the lowest quartile. In a multivariable Cox regression model, the hazard ratio for death from any cause for the patients with NT-pro-BNP levels in the fourth quartile as compared with those in the first quartile was 2.4(95 percent confidence interval, 1.5 to 4.0; P< 0.001); the NT-pro-BNP level added prognostic information beyond that provided by conventional risk factors, including the patients age; sex; family history with respect to ischemic heart disease; the presence or absence of a history of myocardial infarction, angina, hypertension, diabetes, or chronic heart failure; creatinine clearance rate; body-mass index; smoking status; plasma lipid levels; LVEF; and the presence or absence of clinically significant coronary展开更多
Bat SARS-Iike coronavirus （SL-CoV） has a genome organization almost identical to that of SARS-CoV, but the N-terminus of the Spike （S） proteins, which interacts with host receptor and is a major target of neutrali...Bat SARS-Iike coronavirus （SL-CoV） has a genome organization almost identical to that of SARS-CoV, but the N-terminus of the Spike （S） proteins, which interacts with host receptor and is a major target of neutralizing antibodies against CoVs, of the two viruses has only 63-64% sequence identity. Although there have been reports studying the overall immunogenicity of SsL, knowledge on the precise location of immunodominant determinants for SSL is still lacking. In this study, using a series of truncated expressed SsL fragments and SsL specific mouse sera, we identified two immunogenic determinants for SSL. Importantly, one of the two regions seems to be located in a region not shared by known immunogenic determinants of the SSARS. This finding will be of potential use in future monitoring of SL-CoV infection in bats and spillover animals and in development of more effective vaccine to cover broad protection against this new group of coronaviruses.展开更多
The Kaposi's Sarcoma-associated Herpesvirus (KSHV)-encoded G-protein coupled receptor (vGPCR) is an oncoprotein that is implicated in KSHV-associated malignancies. We previously revealed vGPCR incorporates sulfate...The Kaposi's Sarcoma-associated Herpesvirus (KSHV)-encoded G-protein coupled receptor (vGPCR) is an oncoprotein that is implicated in KSHV-associated malignancies. We previously revealed vGPCR incorporates sulfate groups within its extracellular N-terminal tyrosine residues (Y26 and Y28) and that this tyrosine sulfation is crucial for its tumorigenicity in nude mice. hGRO-binds vGPCR in a sulfotyrosine-dependent manner and promotes its tumorigenicity through autocrine signaling. Interestingly, an unsulfated vGPCR mutant (yydd-vGPCR) attenuated the tumor growth triggered by hGRO-α . In this study, the extracellular N-terminus of vGPCR (wt-vGN) and an unsulfated vGPCR mutant (yydd-vGN) were individually secreted, expressed and purified. A radioactive labeling assay demonstrated that wt-vGN but not yydd-vGN incorporated [ 35 S]-sulfate. In nude mice, NIH3T3 cells expressing yydd-vGN but not wt-vGN could significantly inhibit the tumor growth triggered by hGRO-α . All our data support the conclusion that the unsulfated extracellular N-terminus of vGPCR reduces the tumorigenicity of hGRO-α .展开更多
By means of the reaction between a DOTA-NHS-ester bifunctional reagent and N-terminal peptides of proteins, and then che- lation of lanthanide metal ions as tags, we established a novel method for the identification o...By means of the reaction between a DOTA-NHS-ester bifunctional reagent and N-terminal peptides of proteins, and then che- lation of lanthanide metal ions as tags, we established a novel method for the identification of N-terminal peptides of proteins and their relative quantification using metal-element-chelated tags coupled with mass spectrometry. The experimental results indicate that metal elements are able to completely label N-terminal peptides at the protein level. The N-terminal peptides are enriched as the peptides digested with trypsin are selectively eliminated by isothiocyanate-coupled silica beads. We success- fully identified the N-terminal peptides of 158 proteins of Thermoanaerobacter tengcongensis incubated at 55 and 75 ℃, among which N-terminal peptides of 24 proteins are partially acetylated. Moreover, metal-element tags with high molecule weights make it convenient for N-terminal peptides consisting of less than 6 amino acids to be identified; these make up 55 percent of the identified proteins. Finally, we developed a general approach for the relative quantification of proteins based on N-terminal peptides. We adopted lysozyme and ribonuclease B as model proteins; the correlation coefficients （R2） of the standard curves for the quantitative method were 0.9994 and 0.9997, respectively, with each concentration ratio ranging from 0.1 to 10 and both relative standard derivations （RSD） measured at less than 5%. In T. tengcongensis at two incubation tem- peratures, 80 proteins possess quantitative information. In addition, compared with the proteins of T. tengcongensis incubated at 55 ℃, in T. tengcongensis incubated at 75 ℃, 7 proteins upregulate whereas 16 proteins downregulate, and most differential proteins are related to protein synthesis.展开更多
Aims: Assessment of N- terminal brain natriuretic peptide(NTBNP) as a screening tool for heart failure in patients with a permanent pacemaker. Methods and results: Consecutive patients undergoing a routine permanent p...Aims: Assessment of N- terminal brain natriuretic peptide(NTBNP) as a screening tool for heart failure in patients with a permanent pacemaker. Methods and results: Consecutive patients undergoing a routine permanent pacemaker assessment were enrolled. Patients underwent medical history and examination, echocardiography and blood sampling for NT- BNP. Analysis was performed on 261 patients(132 DDD, 121 VVI, eight others), mean age 73± 12 years, range 34- 99 years. Seventy two subjects(27% ) had heart failure as defined by left ventricular ejection fraction(LVEF) ≤ 40% and symptoms of heart failure(NYHA class II, III, or IV). Screening with NT- BNP gave a sensitivity of 73% and specificity of 72% for detecting heart failure in all patients [area under the curve(AUC) 0.76, P< 0.001, 95% CI 0.69- 0.83]. This increased in subjects with a DDD type pacemaker(sensitivity 80% , specificity 66% , AUC=0.8, CI 0.7- 0.90) and reduced in subjects with a VVI type pacemaker(sensitivity 66% , specificity 61% , AUC 0.68 CI 0.57- 0.78). Conclusion: Symptoms of heart failure are common in patients with pacemakers. Screening with NT- BNP is feasible and assists in the detection of important cardiac co- morbidity, particularly in patients with a DDD type pacemaker.展开更多
文摘BACKGROUND: The level of the inactive N-terminal fragment of pro-brain(B-type) natriuretic peptide(BNP)-is a strong predictor of mortality among patients with acute coronary syndromes and may be a strong prognostic marker in patients with chronic coronary heart disease as well. We assessed the relationship between N-terminal pro-BNP(NT-pro-BNP) levels and long-term mortality from all causes in a large cohort of patients with stable coronary heart disease. METHODS: NT-pro-BNP was measured in baseline serum samples from 1034 patients referred for angiography because of symptoms or signs of coronary heart disease. The rate of death from all causes was determined after a median follow-up of nine years. RESULTS: At follow-up, 288 patients had died. The median NT-pro-BNP level was significantly lower among patients who survived than among those who died(120 pg per milliliter[interquartile range, 50 to 318] vs. 386 pg per milliliter[interquartile range, 146 to 897], P< 0.001). Patients with NT-pro-BNP levels in the highest quartile were older, had a lower left ventricular ejection fraction(LVEF) and a lower creatinine clearance rate, and were more likely to have a history of myocardial infarction, clinically significant coronary artery disease, and diabetes than patients with NT-pro-BNP levels in the lowest quartile. In a multivariable Cox regression model, the hazard ratio for death from any cause for the patients with NT-pro-BNP levels in the fourth quartile as compared with those in the first quartile was 2.4(95 percent confidence interval, 1.5 to 4.0; P< 0.001); the NT-pro-BNP level added prognostic information beyond that provided by conventional risk factors, including the patients age; sex; family history with respect to ischemic heart disease; the presence or absence of a history of myocardial infarction, angina, hypertension, diabetes, or chronic heart failure; creatinine clearance rate; body-mass index; smoking status; plasma lipid levels; LVEF; and the presence or absence of clinically significant coronary
基金funded by the State Key Program for Basic Research Grant (2010CB530100,2011CB504700)special project for infectious diseases(2009ZX10004-109) from the Chinese Ministry of Science and Technology
文摘Bat SARS-Iike coronavirus （SL-CoV） has a genome organization almost identical to that of SARS-CoV, but the N-terminus of the Spike （S） proteins, which interacts with host receptor and is a major target of neutralizing antibodies against CoVs, of the two viruses has only 63-64% sequence identity. Although there have been reports studying the overall immunogenicity of SsL, knowledge on the precise location of immunodominant determinants for SSL is still lacking. In this study, using a series of truncated expressed SsL fragments and SsL specific mouse sera, we identified two immunogenic determinants for SSL. Importantly, one of the two regions seems to be located in a region not shared by known immunogenic determinants of the SSARS. This finding will be of potential use in future monitoring of SL-CoV infection in bats and spillover animals and in development of more effective vaccine to cover broad protection against this new group of coronaviruses.
基金supported by the National Natural Science Foundation of China (81171583,31272634)the Program for New Century Excellent Talents in University (NCET-11-0971)+2 种基金the Scientific Research Foundation for the Returned Overseas Chinese Scholars/State Education Ministry(2011-1568-1)funds from Hunan Province (12JJ1005,12A088)the Excellent Talent Program of Hunan Normal University (ET31004)
文摘The Kaposi's Sarcoma-associated Herpesvirus (KSHV)-encoded G-protein coupled receptor (vGPCR) is an oncoprotein that is implicated in KSHV-associated malignancies. We previously revealed vGPCR incorporates sulfate groups within its extracellular N-terminal tyrosine residues (Y26 and Y28) and that this tyrosine sulfation is crucial for its tumorigenicity in nude mice. hGRO-binds vGPCR in a sulfotyrosine-dependent manner and promotes its tumorigenicity through autocrine signaling. Interestingly, an unsulfated vGPCR mutant (yydd-vGPCR) attenuated the tumor growth triggered by hGRO-α . In this study, the extracellular N-terminus of vGPCR (wt-vGN) and an unsulfated vGPCR mutant (yydd-vGN) were individually secreted, expressed and purified. A radioactive labeling assay demonstrated that wt-vGN but not yydd-vGN incorporated [ 35 S]-sulfate. In nude mice, NIH3T3 cells expressing yydd-vGN but not wt-vGN could significantly inhibit the tumor growth triggered by hGRO-α . All our data support the conclusion that the unsulfated extracellular N-terminus of vGPCR reduces the tumorigenicity of hGRO-α .
基金supported by the National Basic Research Program of China(2012CB910603,2010CB912701)the National Key Scientific Instrument Development Program of China(2011YQ09000504,2012YQ-12004407,2011YQ06008408)+1 种基金the High-Technology Research and Development Programme of China(2012AA020202)the National Natural Science Foundation of China(20735005,21275159,31100591)
文摘By means of the reaction between a DOTA-NHS-ester bifunctional reagent and N-terminal peptides of proteins, and then che- lation of lanthanide metal ions as tags, we established a novel method for the identification of N-terminal peptides of proteins and their relative quantification using metal-element-chelated tags coupled with mass spectrometry. The experimental results indicate that metal elements are able to completely label N-terminal peptides at the protein level. The N-terminal peptides are enriched as the peptides digested with trypsin are selectively eliminated by isothiocyanate-coupled silica beads. We success- fully identified the N-terminal peptides of 158 proteins of Thermoanaerobacter tengcongensis incubated at 55 and 75 ℃, among which N-terminal peptides of 24 proteins are partially acetylated. Moreover, metal-element tags with high molecule weights make it convenient for N-terminal peptides consisting of less than 6 amino acids to be identified; these make up 55 percent of the identified proteins. Finally, we developed a general approach for the relative quantification of proteins based on N-terminal peptides. We adopted lysozyme and ribonuclease B as model proteins; the correlation coefficients （R2） of the standard curves for the quantitative method were 0.9994 and 0.9997, respectively, with each concentration ratio ranging from 0.1 to 10 and both relative standard derivations （RSD） measured at less than 5%. In T. tengcongensis at two incubation tem- peratures, 80 proteins possess quantitative information. In addition, compared with the proteins of T. tengcongensis incubated at 55 ℃, in T. tengcongensis incubated at 75 ℃, 7 proteins upregulate whereas 16 proteins downregulate, and most differential proteins are related to protein synthesis.
文摘Aims: Assessment of N- terminal brain natriuretic peptide(NTBNP) as a screening tool for heart failure in patients with a permanent pacemaker. Methods and results: Consecutive patients undergoing a routine permanent pacemaker assessment were enrolled. Patients underwent medical history and examination, echocardiography and blood sampling for NT- BNP. Analysis was performed on 261 patients(132 DDD, 121 VVI, eight others), mean age 73± 12 years, range 34- 99 years. Seventy two subjects(27% ) had heart failure as defined by left ventricular ejection fraction(LVEF) ≤ 40% and symptoms of heart failure(NYHA class II, III, or IV). Screening with NT- BNP gave a sensitivity of 73% and specificity of 72% for detecting heart failure in all patients [area under the curve(AUC) 0.76, P< 0.001, 95% CI 0.69- 0.83]. This increased in subjects with a DDD type pacemaker(sensitivity 80% , specificity 66% , AUC=0.8, CI 0.7- 0.90) and reduced in subjects with a VVI type pacemaker(sensitivity 66% , specificity 61% , AUC 0.68 CI 0.57- 0.78). Conclusion: Symptoms of heart failure are common in patients with pacemakers. Screening with NT- BNP is feasible and assists in the detection of important cardiac co- morbidity, particularly in patients with a DDD type pacemaker.
