Chronic stress can induce hippocampus injury such as neuron loss and dendrite atrophy,but its mechanism and molecular basis remain unclear up to now.To understand the molecular mechanism on protein level and find the ...Chronic stress can induce hippocampus injury such as neuron loss and dendrite atrophy,but its mechanism and molecular basis remain unclear up to now.To understand the molecular mechanism on protein level and find the crucial proteins which correlated with chronic展开更多
An assay was described for measures of adducts of styrene oxide (SO) with molecules of hemoglobin(Hb) which have been modified at residues containing either carboxylic acid or sulfhydryl groups. The method employs tw...An assay was described for measures of adducts of styrene oxide (SO) with molecules of hemoglobin(Hb) which have been modified at residues containing either carboxylic acid or sulfhydryl groups. The method employs two steps. In the first, SO carboxylic acid adducts are hydrolyzed in basic medium to liberate styrene glycol(SG). Then, the remaining residues are reacted with a reductive catalyst (Raney nickel) to liberate the two positional isomers of SO cysteine adducts, i.e., 1 phenylethanol (1 PE) and 2 phenylethanol (2 PE). The liberated products are derivatized with pentafluorobenzoyl chloride and measured by GC NICI MS. The assay was evaluated with SO adducts of Hb which had been produced in the blood of Sprague Dawley rats following (a) in vitro modification(0—300m mol/L SO) or (b) i.p administration of either SO(0—1 mmol/kg) or styrene (0—3 mmol/kg). Levels of each of the three analytes (SG, 1 PE, and 2 PE) increased with dose in hemoglobin. The ratios of cysteine adducts to carboxylic acid adducts varied significantly among experiments. Ratios of 2 PE to 1 PE were much more consistent (2 PE/1 PE=6.9 (SE=1.5)) suggesting that binding of SO to cysteine residues of blood proteins is greatly preferred at the α position rather than the β position both in vitro and in vivo. The lowest detectable adduct concentration, using 10 mg of protein, was 8 pmol/g protein for SG,5 pmol/g protein for 1 PE, and 0.6 pmol/g protein for 2 PE. No significant change of adduct level was found during storage of proteins at -80℃ for 1 year.展开更多
This paper proposes a novel application of cohomology to protein structure analysis. Since proteins interact each other by forming transient protein complexes, their shape (e.g., shape complementarity) plays an import...This paper proposes a novel application of cohomology to protein structure analysis. Since proteins interact each other by forming transient protein complexes, their shape (e.g., shape complementarity) plays an important role in their functions. In our mathematical toy models, proteins are represented as a loop of triangles (2D model) or tetrahedra (3D model), where their interactions are defined as fusion of loops. The purpose of this paper is to describe the conditions for loop fusion using the language of cohomology. In particular, this paper uses cohomology to describe the conditions for “allosteric regulation”, which has been attracted attention in safer drug discovery. I hope that this paper will provide a new perspective on the mechanism of allosteric regulation. Advantages of the model include its topological nature. That is, we can deform the shape of loops by deforming the shape of triangles (or tetrahedra) as long as their folded structures are preserved. Another advantage is the simplicity of the “allosteric regulation” mechanism of the model. Furthermore, the effect of the “post-translational modification” can be understood as a resolution of singularities of a flow of triangles (or tetrahedra). No prior knowledge of either protein science, exterior calculus, or cohomology theory is required. The author hopes that this paper will facilitate the interaction between mathematics and protein science.展开更多
A strain B34 against Thanatephorus cucumeris was screened from rice plants. Lab and field experiments showed that the control effects of this fungal strain were better than that of Jinggangmycin on PDA plate. Based on...A strain B34 against Thanatephorus cucumeris was screened from rice plants. Lab and field experiments showed that the control effects of this fungal strain were better than that of Jinggangmycin on PDA plate. Based on the chemical components of cell wall and physiological and biochemical characters of B34, the fungal was named as Pseudomonas aureofaciens. It was a new antagonistic strain against Thanatephorus cucumeris.展开更多
Many eukaryotic genes are members of multi-gene families due to gene duplications, which generate new copies that allow functional divergence. However, the relationship between
Machine intelligence,is out of the system by the artificial intelligence shown.It is usually achieved by the average computer intelligence.Rough sets and Information Granules in uncertainty management and soft computi...Machine intelligence,is out of the system by the artificial intelligence shown.It is usually achieved by the average computer intelligence.Rough sets and Information Granules in uncertainty management and soft computing and granular computing is widely used in many fields,such as in protein sequence analysis and biobasis determination,TSM and Web service classification Etc.展开更多
Homogenates prepared from S. japonicum adult worms ofdifferent isolates from Anhui, Hubei, Guangxi, Yunnan andSichuan Provinces were analyzed by SDS-PAGE and enzymelinked immunoelectrotransfer blot (EITB) tested with ...Homogenates prepared from S. japonicum adult worms ofdifferent isolates from Anhui, Hubei, Guangxi, Yunnan andSichuan Provinces were analyzed by SDS-PAGE and enzymelinked immunoelectrotransfer blot (EITB) tested with rabbitanti-snails antibody. The results of SDS-PAGE indicated thatwith silver staining both male and female worms of Guangxiisolate showed some definite differences in their protein profile,namely, absence of one band between 50-75 kDa in maleworms and marked reduction in quantity of > 110 and 30 kDabands in female worms. There was no obvious differenceamong other isolates both in male and female worms. TheEITB patterns were similar in S. japonicum of Anhui andHubei, and it was also the case with isolates from Yunnan andSichuau, except that Yuunan female worms had a distinct band展开更多
Background Von HippeI-Lindau disease (VHL),a heritable autosomal dominant disease characterized by neoplasia in multiple organ systems,has rarely been reported in Asia.We genetically investigated a unique Chinese fa...Background Von HippeI-Lindau disease (VHL),a heritable autosomal dominant disease characterized by neoplasia in multiple organ systems,has rarely been reported in Asia.We genetically investigated a unique Chinese family with VHL disease and performed an analysis of the VHL protein stability.Methods Genomic deoxyribonucleic acid (DNA) extracted from peripheral blood was amplified by polymerase chain reaction (PCR) to three exons of the VHL gene in 9 members of the Chinese family with VHL disease.PCR products were directly sequenced.We estimated the effects of VHL gene mutation on the stability of pVHL,which is indicated by the free energy difference between the wild-type and the mutant protein (△△G).Results The Chinese family was classified as VHL type 1.Three family members,including two patients and a carrier,had a T to G heterozygotic missense mutation at nucleotide 515 of the VHL gene exon 1.This missense mutation resulted in the transition from leucine to arginine in amino acid 101 of the VHL protein.There was low stability of the VHL protein (the △△G was 12.71 kcal/mol) caused by this missense mutation.Conclusions We first reported a family with this VHL gene mutation in Asia.This missense mutation is predicted to significantly reduce the stability of the VHL protein and contribute to the development of the renal cell carcinoma (RCC) phenotype displayed by this family.The genetic characterization and protein stability analysis of families with VHL disease are important for early diagnosis and prevention of the disease being passed on to their offspring.展开更多
Mitotic catastrophe(MC)is a form of programmed cell death induced by mitotic process disorders,which is very important in tumor prevention,development,and drug resistance.Because rapidly increased data for MC is vigor...Mitotic catastrophe(MC)is a form of programmed cell death induced by mitotic process disorders,which is very important in tumor prevention,development,and drug resistance.Because rapidly increased data for MC is vigorously promoting the tumor-related biomedical and clinical study,it is urgent for us to develop a professional and comprehensive database to curate MC-related data.Mitotic Catastrophe Database(MCDB)consists of 1214 genes/proteins and 5014 compounds collected and organized from more than 8000 research articles.Also,MCDB defines the confidence level,classification criteria,and uniform naming rules for MC-related data,which greatly improves data reliability and retrieval convenience.Moreover,MCDB develops protein sequence alignment and target prediction functions.The former can be used to predict new potential MC-related genes and proteins,and the latter can facilitate the identification of potential target proteins of unknown MC-related compounds.In short,MCDB is such a proprietary,standard,and comprehensive database for MC-relate data that will facilitate the exploration of MC from chemists to biologists in the fields of medicinal chemistry,molecular biology,bioinformatics,oncology and so on.The MCDB is distributed on http://www.combio-lezhang.online/MCDB/indexhtml/.展开更多
Background The non-hemodynamic effects of angiotensin receptor blocker (ARB) in the delay of progression of chronic kidney disease (CKD) remain unclear. In this study, we investigated the influence of irbesartan o...Background The non-hemodynamic effects of angiotensin receptor blocker (ARB) in the delay of progression of chronic kidney disease (CKD) remain unclear. In this study, we investigated the influence of irbesartan on the urinary excretion of cytokines in patients with CKD. Methods In this randomized perspective clinical trial, different doses of irbesartan (150 mg/d and 300 mg/d) were given to two groups of patients in a cross-over design. Blood pressure (BP), creatinine clearance (Ccr) and 24-hour proteinuria were examined. Urinary excretion of cytokines was determined by human inflammatory cytokine antibody array. A two-fold change in spot intensity was considered significant. Results Urinary excretion of cytokines (granulocyte colony stimulating factor (GCSF), intercellular cell adhesion molecule-1 (ICAM-1), interferon y (IFN-y), interleukin 1β (IL-1β), IL-2, IL-6, IL-8, IL-11, IL-15 and macrophage inflammatory protein 1δ (MIP-Iδ) in group B (irbesartan 300 mg/d) was significantly decreased in comparison to group A (irbesartan 150 mg/d) after 8-week treatment. In group A, 8 weeks of treatment induced a two- to nine-fold reduction in urinary cytokine levels (GCSF, GM-CSF, IFN-γ, IL-1α, IL-11, IL-12p40, MCP-2, MIP-1α), while increasing the dosage to 300 mg/d further decreased the excretion of GCSF, GM-CSF, IL-12p40, MCP-2 and MIP-1α by week 18. There was no significant difference in BP or Ccr between the two groups. However, 24-hour proteinuria was significantly reduced in both groups, and in group A the reduction was dose dependent.Conclusion Irbesartan offers additional renoprotection in a dose-dependent manner by reducing pro-inflammatory cvtokines excretion in the urine of CKD patients.展开更多
Background Neuroblastoma (NB) is one of the most common malignant solid tumors of childhood.It is still not clear whether the apoptosis of tumor cells or the non-tumor cells contributes to the increase of concentrat...Background Neuroblastoma (NB) is one of the most common malignant solid tumors of childhood.It is still not clear whether the apoptosis of tumor cells or the non-tumor cells contributes to the increase of concentration of cytochrome c (Cyt c) in the serum of the cancer patients.The aim of this research was to identify the source of the Cyt c in the serum when the tumor grows up by subcutaneous inoculation of human NB cells into nude mice.Methods We subcutaneously inoculated human NB cells (KP-N-NS) into nude mice and collected the sera of tumor-bearing mice (n=14) and control mice (n=25) 4 weeks later in order to screen for and identify differentially expressed proteins in the serum.Differentially expressed proteins in the serum were screened by surface-enhanced laser desorption/ionization-time-of-fiight (SELDI-TOF) mass spectrometry.Results The relative intensity of a protein having a mass-to-charge ratio (m/z) of 11 609 was 3338.37±3410.85 in the tumor group and 59.84±40.74 in the control group,indicating that the expression level of this protein in the tumor group was 55.8 times higher than that in the control group.Serum proteins were separated and purified by high-performance liquid chromatography (HPLC).Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was performed to produce peptide mass fingerprints (PMFs).Spectrum analysis and a database search revealed that the highly expressed protein (m/z=11605.4) from the serum of tumor-bearing mice was the mouse Cyt c.Conclusions Increased concentration of Cyt c in the serum of tumor-bearing nude mice might be partially attributed to the secretion of this protein by non-tumor cells.展开更多
Numerous transmethylation reactions are required for normal plant growth and development. S-adenosylhomocysteine hydrolase (SAHH) and adenosine kinase (ADK) act coordinately to recycle the by-product of these reac...Numerous transmethylation reactions are required for normal plant growth and development. S-adenosylhomocysteine hydrolase (SAHH) and adenosine kinase (ADK) act coordinately to recycle the by-product of these reactions, S-adenosylhomocysteine (SAH) that would otherwise competitively inhibit methyltransferase (MT) activities. Here, we report on investigations to understand how the SAH produced in the nucleus is metabolized by SAHH and ADK. Localization analyses using green fluorescent fusion proteins demonstrated that both enzymes are capable of localizing to the cytoplasm and the nucleus, although no obvious nuclear localization signal was found in their sequences. Deletion analysis revealed that a 41-amino-acid segment of SAHH (GlylS^-Lys19~) is required for nuclear targeting of this enzyme. This segment is surface exposed, shows unique sequence conservation patterns in plant SAHHs, and possesses additional features of protein-protein interaction motifs. ADK and SAHH interact in Arabidopsb via this segment and also interact with an mRNA cap MT. We propose that the targeting of this complex is directed by the nuclear localization signal of the MT; other MTs may similarly target SAHH/ADK to other subcellular compartments to ensure uninterrupted transmethylation.展开更多
文摘Chronic stress can induce hippocampus injury such as neuron loss and dendrite atrophy,but its mechanism and molecular basis remain unclear up to now.To understand the molecular mechanism on protein level and find the crucial proteins which correlated with chronic
文摘An assay was described for measures of adducts of styrene oxide (SO) with molecules of hemoglobin(Hb) which have been modified at residues containing either carboxylic acid or sulfhydryl groups. The method employs two steps. In the first, SO carboxylic acid adducts are hydrolyzed in basic medium to liberate styrene glycol(SG). Then, the remaining residues are reacted with a reductive catalyst (Raney nickel) to liberate the two positional isomers of SO cysteine adducts, i.e., 1 phenylethanol (1 PE) and 2 phenylethanol (2 PE). The liberated products are derivatized with pentafluorobenzoyl chloride and measured by GC NICI MS. The assay was evaluated with SO adducts of Hb which had been produced in the blood of Sprague Dawley rats following (a) in vitro modification(0—300m mol/L SO) or (b) i.p administration of either SO(0—1 mmol/kg) or styrene (0—3 mmol/kg). Levels of each of the three analytes (SG, 1 PE, and 2 PE) increased with dose in hemoglobin. The ratios of cysteine adducts to carboxylic acid adducts varied significantly among experiments. Ratios of 2 PE to 1 PE were much more consistent (2 PE/1 PE=6.9 (SE=1.5)) suggesting that binding of SO to cysteine residues of blood proteins is greatly preferred at the α position rather than the β position both in vitro and in vivo. The lowest detectable adduct concentration, using 10 mg of protein, was 8 pmol/g protein for SG,5 pmol/g protein for 1 PE, and 0.6 pmol/g protein for 2 PE. No significant change of adduct level was found during storage of proteins at -80℃ for 1 year.
文摘This paper proposes a novel application of cohomology to protein structure analysis. Since proteins interact each other by forming transient protein complexes, their shape (e.g., shape complementarity) plays an important role in their functions. In our mathematical toy models, proteins are represented as a loop of triangles (2D model) or tetrahedra (3D model), where their interactions are defined as fusion of loops. The purpose of this paper is to describe the conditions for loop fusion using the language of cohomology. In particular, this paper uses cohomology to describe the conditions for “allosteric regulation”, which has been attracted attention in safer drug discovery. I hope that this paper will provide a new perspective on the mechanism of allosteric regulation. Advantages of the model include its topological nature. That is, we can deform the shape of loops by deforming the shape of triangles (or tetrahedra) as long as their folded structures are preserved. Another advantage is the simplicity of the “allosteric regulation” mechanism of the model. Furthermore, the effect of the “post-translational modification” can be understood as a resolution of singularities of a flow of triangles (or tetrahedra). No prior knowledge of either protein science, exterior calculus, or cohomology theory is required. The author hopes that this paper will facilitate the interaction between mathematics and protein science.
文摘A strain B34 against Thanatephorus cucumeris was screened from rice plants. Lab and field experiments showed that the control effects of this fungal strain were better than that of Jinggangmycin on PDA plate. Based on the chemical components of cell wall and physiological and biochemical characters of B34, the fungal was named as Pseudomonas aureofaciens. It was a new antagonistic strain against Thanatephorus cucumeris.
文摘Many eukaryotic genes are members of multi-gene families due to gene duplications, which generate new copies that allow functional divergence. However, the relationship between
文摘Machine intelligence,is out of the system by the artificial intelligence shown.It is usually achieved by the average computer intelligence.Rough sets and Information Granules in uncertainty management and soft computing and granular computing is widely used in many fields,such as in protein sequence analysis and biobasis determination,TSM and Web service classification Etc.
基金This project was supported by the National Natural Science Foundation of China
文摘Homogenates prepared from S. japonicum adult worms ofdifferent isolates from Anhui, Hubei, Guangxi, Yunnan andSichuan Provinces were analyzed by SDS-PAGE and enzymelinked immunoelectrotransfer blot (EITB) tested with rabbitanti-snails antibody. The results of SDS-PAGE indicated thatwith silver staining both male and female worms of Guangxiisolate showed some definite differences in their protein profile,namely, absence of one band between 50-75 kDa in maleworms and marked reduction in quantity of > 110 and 30 kDabands in female worms. There was no obvious differenceamong other isolates both in male and female worms. TheEITB patterns were similar in S. japonicum of Anhui andHubei, and it was also the case with isolates from Yunnan andSichuau, except that Yuunan female worms had a distinct band
基金This research was supported by grants from the National Natural Science Foundation of China (No. 30901487, No. 81302223, No. 81070488 and No. 81172432), the Guangdong Natural Science Foundation (No. 10251008901000005), and the Guangdong Province Science and Technology Project (No. 2011 B031800115, No. 2011 B032000003 and No. 20101051500032).
文摘Background Von HippeI-Lindau disease (VHL),a heritable autosomal dominant disease characterized by neoplasia in multiple organ systems,has rarely been reported in Asia.We genetically investigated a unique Chinese family with VHL disease and performed an analysis of the VHL protein stability.Methods Genomic deoxyribonucleic acid (DNA) extracted from peripheral blood was amplified by polymerase chain reaction (PCR) to three exons of the VHL gene in 9 members of the Chinese family with VHL disease.PCR products were directly sequenced.We estimated the effects of VHL gene mutation on the stability of pVHL,which is indicated by the free energy difference between the wild-type and the mutant protein (△△G).Results The Chinese family was classified as VHL type 1.Three family members,including two patients and a carrier,had a T to G heterozygotic missense mutation at nucleotide 515 of the VHL gene exon 1.This missense mutation resulted in the transition from leucine to arginine in amino acid 101 of the VHL protein.There was low stability of the VHL protein (the △△G was 12.71 kcal/mol) caused by this missense mutation.Conclusions We first reported a family with this VHL gene mutation in Asia.This missense mutation is predicted to significantly reduce the stability of the VHL protein and contribute to the development of the renal cell carcinoma (RCC) phenotype displayed by this family.The genetic characterization and protein stability analysis of families with VHL disease are important for early diagnosis and prevention of the disease being passed on to their offspring.
基金supported by grants from National Natural Science Foundation of China(Grant Nos.81803755 and 81922064)National Science and Technology Major Project(Grant No.2018ZX10201002,China)+1 种基金China Postdoctoral ScienceFoundation(2018M640926 and 2020M673221)Sichuan University Postdoctoral Research and Development Foundation(2020SCU12062 and 2020SCU12056,China)。
文摘Mitotic catastrophe(MC)is a form of programmed cell death induced by mitotic process disorders,which is very important in tumor prevention,development,and drug resistance.Because rapidly increased data for MC is vigorously promoting the tumor-related biomedical and clinical study,it is urgent for us to develop a professional and comprehensive database to curate MC-related data.Mitotic Catastrophe Database(MCDB)consists of 1214 genes/proteins and 5014 compounds collected and organized from more than 8000 research articles.Also,MCDB defines the confidence level,classification criteria,and uniform naming rules for MC-related data,which greatly improves data reliability and retrieval convenience.Moreover,MCDB develops protein sequence alignment and target prediction functions.The former can be used to predict new potential MC-related genes and proteins,and the latter can facilitate the identification of potential target proteins of unknown MC-related compounds.In short,MCDB is such a proprietary,standard,and comprehensive database for MC-relate data that will facilitate the exploration of MC from chemists to biologists in the fields of medicinal chemistry,molecular biology,bioinformatics,oncology and so on.The MCDB is distributed on http://www.combio-lezhang.online/MCDB/indexhtml/.
文摘Background The non-hemodynamic effects of angiotensin receptor blocker (ARB) in the delay of progression of chronic kidney disease (CKD) remain unclear. In this study, we investigated the influence of irbesartan on the urinary excretion of cytokines in patients with CKD. Methods In this randomized perspective clinical trial, different doses of irbesartan (150 mg/d and 300 mg/d) were given to two groups of patients in a cross-over design. Blood pressure (BP), creatinine clearance (Ccr) and 24-hour proteinuria were examined. Urinary excretion of cytokines was determined by human inflammatory cytokine antibody array. A two-fold change in spot intensity was considered significant. Results Urinary excretion of cytokines (granulocyte colony stimulating factor (GCSF), intercellular cell adhesion molecule-1 (ICAM-1), interferon y (IFN-y), interleukin 1β (IL-1β), IL-2, IL-6, IL-8, IL-11, IL-15 and macrophage inflammatory protein 1δ (MIP-Iδ) in group B (irbesartan 300 mg/d) was significantly decreased in comparison to group A (irbesartan 150 mg/d) after 8-week treatment. In group A, 8 weeks of treatment induced a two- to nine-fold reduction in urinary cytokine levels (GCSF, GM-CSF, IFN-γ, IL-1α, IL-11, IL-12p40, MCP-2, MIP-1α), while increasing the dosage to 300 mg/d further decreased the excretion of GCSF, GM-CSF, IL-12p40, MCP-2 and MIP-1α by week 18. There was no significant difference in BP or Ccr between the two groups. However, 24-hour proteinuria was significantly reduced in both groups, and in group A the reduction was dose dependent.Conclusion Irbesartan offers additional renoprotection in a dose-dependent manner by reducing pro-inflammatory cvtokines excretion in the urine of CKD patients.
文摘Background Neuroblastoma (NB) is one of the most common malignant solid tumors of childhood.It is still not clear whether the apoptosis of tumor cells or the non-tumor cells contributes to the increase of concentration of cytochrome c (Cyt c) in the serum of the cancer patients.The aim of this research was to identify the source of the Cyt c in the serum when the tumor grows up by subcutaneous inoculation of human NB cells into nude mice.Methods We subcutaneously inoculated human NB cells (KP-N-NS) into nude mice and collected the sera of tumor-bearing mice (n=14) and control mice (n=25) 4 weeks later in order to screen for and identify differentially expressed proteins in the serum.Differentially expressed proteins in the serum were screened by surface-enhanced laser desorption/ionization-time-of-fiight (SELDI-TOF) mass spectrometry.Results The relative intensity of a protein having a mass-to-charge ratio (m/z) of 11 609 was 3338.37±3410.85 in the tumor group and 59.84±40.74 in the control group,indicating that the expression level of this protein in the tumor group was 55.8 times higher than that in the control group.Serum proteins were separated and purified by high-performance liquid chromatography (HPLC).Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was performed to produce peptide mass fingerprints (PMFs).Spectrum analysis and a database search revealed that the highly expressed protein (m/z=11605.4) from the serum of tumor-bearing mice was the mouse Cyt c.Conclusions Increased concentration of Cyt c in the serum of tumor-bearing nude mice might be partially attributed to the secretion of this protein by non-tumor cells.
文摘Numerous transmethylation reactions are required for normal plant growth and development. S-adenosylhomocysteine hydrolase (SAHH) and adenosine kinase (ADK) act coordinately to recycle the by-product of these reactions, S-adenosylhomocysteine (SAH) that would otherwise competitively inhibit methyltransferase (MT) activities. Here, we report on investigations to understand how the SAH produced in the nucleus is metabolized by SAHH and ADK. Localization analyses using green fluorescent fusion proteins demonstrated that both enzymes are capable of localizing to the cytoplasm and the nucleus, although no obvious nuclear localization signal was found in their sequences. Deletion analysis revealed that a 41-amino-acid segment of SAHH (GlylS^-Lys19~) is required for nuclear targeting of this enzyme. This segment is surface exposed, shows unique sequence conservation patterns in plant SAHHs, and possesses additional features of protein-protein interaction motifs. ADK and SAHH interact in Arabidopsb via this segment and also interact with an mRNA cap MT. We propose that the targeting of this complex is directed by the nuclear localization signal of the MT; other MTs may similarly target SAHH/ADK to other subcellular compartments to ensure uninterrupted transmethylation.