Hard red spring wheat in North America must be high in protein in order to avoid costly discounts when marketed. Many newer cultivars have higher yield potential but produce relatively lower grain protein levels. A po...Hard red spring wheat in North America must be high in protein in order to avoid costly discounts when marketed. Many newer cultivars have higher yield potential but produce relatively lower grain protein levels. A post-anthesis foliar application of urea-ammonium nitrate mixed with equal part water at 33 kg·ha<sup>-1</sup> nitrogen (N) can increase grain protein levels by up to one percent. This increase can be profitable when market premiums/discounts for protein are moderate to high. Nitrogen applied post-anthesis consistently increased grain protein content more than the application of the same rate of N to the soil prior to planting. Milling and baking analysis reveals augmenting the protein in this way does not diminish its functionality.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
The liver is the site of synthesis of the majority of circulating proteins.Besides initial polypeptide synthesis,sophisticated machinery is involved in the further processing of proteins by removing parts of them and/...The liver is the site of synthesis of the majority of circulating proteins.Besides initial polypeptide synthesis,sophisticated machinery is involved in the further processing of proteins by removing parts of them and/or adding functional groups and small molecules tailoring the final molecule to suit its physiological purpose.Posttranslational modifications(PTMs)design a network of molecules with the common protein ancestor but with slightly or considerably varying activity/localization/purpose.PTMs can change under pathological conditions,giving rise to aberrant or overmodified proteins.Undesired changes in the structure of proteins most often accompany undesired changes in their function,such as reduced activity or the appearance of new effects.Proper protein processing is essential for the reactions in living beings and crucial for the overall quality control.Modifications that occur on proteins synthesized in the liver whose PTMs are cirrhosis-related are oxidation,nitration,glycosylation,acetylation,and ubiquitination.Some of them predominantly affect proteins that remain in liver cells,whereas others predominantly occur on proteins that leave the liver or originate from other tissues and perform their function in the circulation.Altered PTMs of certain proteins are potential candidates as biomarkers of liver-related diseases,including cirrhosis.This review will focus on PTMs on proteins whose structural changes in cirrhosis exert or are suspected to exert the most serious functional consequences.展开更多
OBJECTIVE:To study the functional mechanism of Pingchuanning Decoction in treatment of airway remodeling in asthmatic rats.METHODS:Eighty healthy Wistar male rats were randomized into eight groups(n=10 rats each):Norm...OBJECTIVE:To study the functional mechanism of Pingchuanning Decoction in treatment of airway remodeling in asthmatic rats.METHODS:Eighty healthy Wistar male rats were randomized into eight groups(n=10 rats each):Normal group,Asthma model group,Dexamethasone group,Guilong Kechuanning group,Xiaoqinglong Decoction group,and Pingchuanning Decoction low-,middle-,and high-dose groups.The rats of all but the Normal group were made into asthma models through intraperitoneal injection and aerosol inhalation of ovalbumin.All treatments were administered at the first stimulation of asthma onset(third week of modeling),and the rats were killed after stimulating asthma attacks for 4 weeks.The general conditions of rats and pathomorphological changes of the lung tissues were observed.The expression of nerve growth factor(NGF) of the lung tissues was measured with immunohistochemical methods,and the content of Clara cell secretory protein(CCSP) mRNA was determined with RT-PCR.RESULTS:Compared with the Normal group,the contents of NGF and CCSP mRNA in the lung tissues of the Model group were significantly changed(P<0.01).Compared with the Model group,the indices of Pingchuanning Decoction and other treatment groups were improved to some extent(P<0.05 or P<0.01).CONCLUSIONS:Pathological changes of airway inflammation and remodeling were present in these rat asthma models.Pingchuanning Decoction had an intervention effect on these experimental models.Its functional mechanism may be related to multiple factors,including alleviation of airway inflammation,relief of bronchial smooth muscle spasm,and inhibition of airway remodeling.展开更多
In this paper, a new hybrid model of amino acid substitution is developed and compared with the others in previous works. The results show that the new hybrid model can characterize the protein sequences very well by ...In this paper, a new hybrid model of amino acid substitution is developed and compared with the others in previous works. The results show that the new hybrid model can characterize the protein sequences very well by calculating Fisher weights, which can denote how much the variants contribute to the classification.展开更多
The thermodynamic properties of linear protein solutions are discussed by a statistical me-chanics theory with a lattice model. The numerical results show that the Gibbs function of the solution decreases, and the pro...The thermodynamic properties of linear protein solutions are discussed by a statistical me-chanics theory with a lattice model. The numerical results show that the Gibbs function of the solution decreases, and the protein chemical potential is enhanced with increase of the protein concentration for dilute solutions. The influences of chain length and temperature on the Gibbs function of the solution as well as the protein chemical potential are analyzed.As an application of the theory, the chemical potentials of some mutants of type I antifreeze proteins are computed and discussed.展开更多
In this paper are reported the local minimum problem by means of current greedy algorithm for training the empirical potential function of protein folding on 8623 non-native structures of 31 globular proteins and a so...In this paper are reported the local minimum problem by means of current greedy algorithm for training the empirical potential function of protein folding on 8623 non-native structures of 31 globular proteins and a solution of the problem based upon the simulated annealing algorithm. This simulated annealing algorithm is indispensable for developing and testing highly refined empirical potential functions.展开更多
Bone morphogenetic proteins （BMPs） have multiple roles in skeletal development, homeostasis and regeneration. BMPs signal via type I and type II serine/threonine kinase receptors （BMPRI and BMPRII）. In recent deca...Bone morphogenetic proteins （BMPs） have multiple roles in skeletal development, homeostasis and regeneration. BMPs signal via type I and type II serine/threonine kinase receptors （BMPRI and BMPRII）. In recent decades, genetic studies in humans and mice have demonstrated that perturbations in BMP signaling via BMPRI resulted in various diseases in bone, cartilage, and muscles. In this review, we focus on all three types of BMPRI, which consist of activin-like kinase 2 （ALK2, also called type IA activin receptor）, activin- llke kinase 3 （ALK3, also called BMPRIA）, and activin-like kinase 6 （ALK6, also called BMPRIB）. The research areas covered include the current progress regarding the roles of these receptors during myogenesis, chondrogenesis, and osteogenesis. Understanding the physiological and pathological functions of these receptors at the cellular and molecular levels will advance drug development and tissue regeneration for treating musculoskeletal diseases and bone defects in the future.展开更多
Investigating the biological function of proteins is a key aspect of protein studies. Bioinformatic methods become important for studying the biological function of proteins. In this paper, we first give the chaos gam...Investigating the biological function of proteins is a key aspect of protein studies. Bioinformatic methods become important for studying the biological function of proteins. In this paper, we first give the chaos game representation （CGR） of randomly-linked functional protein sequences, then propose the use of the recurrent iterated function systems （RIFS） in fractal theory to simulate the measure based on their chaos game representations. This method helps to extract some features of functional protein sequences, and furthermore the biological functions of these proteins. Then multifractal analysis of the measures based on the CGRs of randomly-linked functional protein sequences are performed. We find that the CGRs have clear fractal patterns. The numerical results show that the RIFS can simulate the measure based on the CGR very well. The relative standard error and the estimated probability matrix in the RIFS do not depend on the order to link the functional protein sequences. The estimated probability matrices in the RIFS with different biological functions are evidently different. Hence the estimated probability matrices in the RIFS can be used to characterise the difference among linked functional protein sequences with different biological functions. From the values of the Dq curves, one sees that these functional protein sequences are not completely random. The Dq of all linked functional proteins studied are multifractal-like and sufficiently smooth for the Cq （analogous to specific heat） curves to be meaningful. Furthermore, the Dq curves of the measure μ based on their CCRs for different orders to link the functional protein sequences are almost identical if q 〉 0. Finally, the Ca curves of all linked functional proteins resemble a classical phase transition at a critical point.展开更多
Considering huge number of insect species in the world,studies of heat shock proteins on insects are still very limited.Special focus of＂Insect heat shock proteins and their underlying functions＂provides a comprehen...Considering huge number of insect species in the world,studies of heat shock proteins on insects are still very limited.Special focus of＂Insect heat shock proteins and their underlying functions＂provides a comprehensive knowledge for the given topics,which focuses on the heat shock proteins from four insect species：i）Five heat shock proteins（HSPs）from Cotesia chilonis were identified,and their expressional patterns under different temperatures were examined.展开更多
Previous molecular analyses of human astrocytomas have identified many genetic changes associated with astrocy-toma formation and progression.In an effort to identify novel gene expression changes associated with astr...Previous molecular analyses of human astrocytomas have identified many genetic changes associated with astrocy-toma formation and progression.In an effort to identify novel gene expression changes associated with astrocytomaformation,which might reveal new potential targets for glioma therapeutic drug design,we used the B8-RAS-transgenic mouse astrocytoma model.Using multiplex gene expression profiling,we found that展开更多
The realization of protein functional movement is usually accompanied by specific conformational changes,and there exist some key residues that mediate and control the functional motions of proteins in the allosteric ...The realization of protein functional movement is usually accompanied by specific conformational changes,and there exist some key residues that mediate and control the functional motions of proteins in the allosteric process.In the present work,the perturbation-response scanning method developed by our group was combined with the molecular dynamics(MD)simulation to identify the key residues controlling the functional movement of proteins.In our method,a physical quantity that is directly related to protein specific function was introduced,and then based on the MD simulation trajectories,the perturbation-response scanning method was used to identify the key residues for functional motions,in which the residues that highly correlated with the fluctuation of the function-related quantity were identified as the key residues controlling the specific functional motions of the protein.Two protein systems,i.e.,the heat shock protein 70 and glutamine binding protein,were selected as case studies to validate the effectiveness of our method.Our calculated results are in good agreement with the experimental results.The location of the key residues in the two proteins are similar,indicating the similar mechanisms behind the performance of their biological functions.展开更多
Pre-mRNA splicing is a dynamic process. It is catalyzed by the spliceosome which is a large machine formed by an ordered interactions of several small nuclear ribonucleoproteins, U1,
We find that a conserved mutation residue Glu to residue Asp （E303D）, which both have the same polar and charged properties, makes Kit2.1 protein lose its function. To understand the mechanism, we identify three int...We find that a conserved mutation residue Glu to residue Asp （E303D）, which both have the same polar and charged properties, makes Kit2.1 protein lose its function. To understand the mechanism, we identify three interactions which control the conformation change and maintain the function of the Kit2.1 protein by combining homology modeling and molecular dynamics with targeted molecular dynamics. We find that the E303D mutation weakens these interactions and results in the loss of the related function. Our data indicate that not only the amino residues but also the interactions determine the function of proteins.展开更多
In the past two decades, extensive studies have focused on a group of so-called polarity proteins that play conserved and essential functions in establishing and maintaining cell polarity in epithelial cells. Among th...In the past two decades, extensive studies have focused on a group of so-called polarity proteins that play conserved and essential functions in establishing and maintaining cell polarity in epithelial cells. Among them, Crumbs （Crb） is the only trans- membrane polarity protein characterized to date （Tepass et al.,展开更多
Computational methods have significantly transformed biomedical research,offering a comprehensive exploration of disease mechanisms and molecular protein functions.This article reviews a spectrum of computational tools...Computational methods have significantly transformed biomedical research,offering a comprehensive exploration of disease mechanisms and molecular protein functions.This article reviews a spectrum of computational tools and network analysis databases that play a crucial role in identifying potential interactions and signaling networks contributing to the onset of disease states.The utilization of protein/gene interaction and genetic variation databases,coupled with pathway analysis can facilitate the identification of potential drug targets.By bridging the gap between molecular-level information and disease understanding,this review contributes insights into the impactful utilization of computational methods,paving the way for targeted interventions and therapeutic advancements in biomedical research.展开更多
Improving grain amino acid content of rice(Oryza sativa L.)is essential for the health of consumers.This study was conducted to identify the physiological processes that contribute to the higher grain amino acid conte...Improving grain amino acid content of rice(Oryza sativa L.)is essential for the health of consumers.This study was conducted to identify the physiological processes that contribute to the higher grain amino acid content in hybrid rice cultivar Lingliangyou 268 compared to Luliangyou 996.The results showed that total amino acid content in grains was 9%higher in Lingliangyou 268 than in Luliangyou 996.There was no significant difference in grain nitrogen(N)content between Lingliangyou 268 and Luliangyou 996,while ratio of amino acid to N was 6%higher in Lingliangyou 268 compared to Luliangyou 996.A total of 16 differentially expressed proteins related to amino acid metabolism(e.g.,erythronate-4-phosphate dehydrogenase domain containing protein)were identified in grains between Lingliangyou 268 and Luliangyou 996.The identified proteins were involved in 10 molecular functions.Six of the 10 defined functions were related to binding(heterocyclic compound binding,nucleoside phosphate binding,nucleotide binding,organic cyclic compound binding,protein binding,and small molecule binding)and the other 4 defined functions were catalytic activity,enzyme regulator activity,hydrolase activity,and transferase activity.These results indicate that the higher grain amino acid content in Lingliangyou 268 compared to Luliangyou 996 is attributed to increased efficiency of converting N to amino acid that results from altered expression of proteins related to amino acid metabolism.展开更多
AIM:To look at a comprehensive picture of etiology- dependent gene abnormalities in hepatocellular carcinoma in Western Europe. METHODS:With a liver-oriented microarray,transcript levels were compared in nodules and c...AIM:To look at a comprehensive picture of etiology- dependent gene abnormalities in hepatocellular carcinoma in Western Europe. METHODS:With a liver-oriented microarray,transcript levels were compared in nodules and cirrhosis from a training set of patients with hepatocellular carcinoma (alcoholism,12;hepatitis C,10)and 5 controls.Loose or tight selection of informative transcripts with an abnormal abundance was statistically valid and the tightly selected transcripts were next quantified by qRTPCR in the nodules from our training set(12+10) and a test set(6+7). RESULTS:A selection of 475 transcripts pointed to significant gene over-representation on chromosome 8 (alcoholism)or-2(hepatitis C)and ontology indicated a predominant inflammatory response(alcoholism)or changes in cell cycle regulation,transcription factors and interferon responsiveness(hepatitis C).A stringent selection of 23 transcripts whose differences betweenetiologies were significant in nodules but not in cirrhotic tissue indicated that the above dysregulations take place in tumor but not in the surrounding cirrhosis.These 23 transcripts separated our test set according to etiologies. The inflammation-associated transcripts pointed to limited alterations of free iron metabolism in alcoholic vs hepatitis C tumors. CONCLUSION:Etiology-specific abnormalities(chromo- some preference;differences in transcriptomes and related functions)have been identified in hepatocellular carcinoma driven by alcoholism or hepatitis C.This may open novel avenues for differential therapies in this disease.展开更多
Neural stem cells have great potential for the development of novel therapies for nervous system diseases.However,the proliferation of endogenous neural stem cells following brain ischemia is insufficient for central ...Neural stem cells have great potential for the development of novel therapies for nervous system diseases.However,the proliferation of endogenous neural stem cells following brain ischemia is insufficient for central nervous system self-repair.Ginkgolide B has a robust neuroprotective effect.In this study,we investigated the cell and molecular mechanisms underlying the neuroprotective effect of ginkgolide B on focal cerebral ischemia/reperfusion injury in vitro and in vivo.Neural stem cells were treated with 20,40 and 60 mg/L ginkgolide B in vitro.Immunofluorescence staining was used to assess cellular expression of neuron-specific enolase,glial fibrillary acid protein and suppressor of cytokine signaling 2.After treatment with 40 and 60 mg/L ginkgolide B,cells were large,with long processes.Moreover,the proportions of neuron-specific enolase-,glial fibrillary acid protein-and suppressor of cytokine signaling 2-positive cells increased.A rat model of cerebral ischemia/reperfusion injury was established by middle cerebral artery occlusion.Six hours after ischemia,ginkgolide B（20 mg/kg） was intraperitoneally injected,once a day.Zea Longa＇s method was used to assess neurological function.Immunohistochemistry was performed to evaluate the proportion of nestin-,neuron-specific enolase-and glial fibrillary acid protein-positive cells.Real-time quantitative polymerase chain reaction was used to measure m RNA expression of brain-derived neurotrophic factor and epidermal growth factor.Western blot assay was used to analyze the expression levels of brain-derived neurotrophic factor and suppressor of cytokine signaling 2.Ginkgolide B decreased the neurological deficit score,increased the proportion of nestin-,neuron-specific enolase-and glial fibrillary acid protein-positive cells,increased the m RNA expression of brain-derived neurotrophic factor and epidermal growth factor,and increased the expression levels of brain-derived neurotrophic factor and suppressor of cytokine signaling 2 in the ischemic penumbra.Together,the in vivo and in vitro findings suggest that ginkgolide B improves neurological function by promoting the proliferation and differentiation of neural stem cells in rats with cerebral ischemia/reperfusion injury.展开更多
We used Drosophila melanogaster as an experimental model to express mouse and pig BM88/CEND1(cell cycle exit and neuronal differentiation 1) in order to investigate its potential functional effects on Drosophila neuro...We used Drosophila melanogaster as an experimental model to express mouse and pig BM88/CEND1(cell cycle exit and neuronal differentiation 1) in order to investigate its potential functional effects on Drosophila neurogenesis. BM88/CEND1 is a neuron-specific protein whose function is implicated in triggering cells to exit from the cell cycle and differentiate towards a neuronal phenotype. Transgenic flies expressing either mouse or pig BM88/CEND1 in the nervous system had severe neuronal phenotypes with variable expressivity at various stages of embryonic development. In early embryonic stage 10,BM88/CEND1 expression led to an increase in the neuralspecific antigenicity of neuroectoderm at the expense of precursor cells [neuroblasts(Nbs) and ganglion mother cells(GMCs)] including the defective formation and differentiation of the MP2 precursors, whereas at later stages(12–15), protein accumulation induced gross morphological defects primarily in the CNS accompanied by a reduction of Nb and GMC markers. Furthermore, the neuronal precursor cells of embryos expressing BM88/CEND1 failed to carry out proper cell-cycle progression as revealed by the disorganized expression patterns of specific cell-cycle markers. BM88/CEND1 accumulation in the Drosophila eye affected normal eye disc development by disrupting the ommatidia. Finally, we demonstrated that expression of BM88/CEND1 modified/reduced the levels of activated MAP kinase indicating a functional effect of BM88/CEND1 on the MAPK signaling pathway. Our findings suggest that the expression of mammalian BM88/CEND1 in Drosophila exerts specific functional effects associated with neuronal precursor cell formation during embryonic neurogenesis and proper eye disc development.This study also validates the use of Drosophila as a powerful model system in which to investigate gene function and the underlying molecular mechanisms.展开更多
文摘Hard red spring wheat in North America must be high in protein in order to avoid costly discounts when marketed. Many newer cultivars have higher yield potential but produce relatively lower grain protein levels. A post-anthesis foliar application of urea-ammonium nitrate mixed with equal part water at 33 kg·ha<sup>-1</sup> nitrogen (N) can increase grain protein levels by up to one percent. This increase can be profitable when market premiums/discounts for protein are moderate to high. Nitrogen applied post-anthesis consistently increased grain protein content more than the application of the same rate of N to the soil prior to planting. Milling and baking analysis reveals augmenting the protein in this way does not diminish its functionality.
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
基金Supported by the Ministry of Education,Science and Technological Development of the Republic of Serbia,No.451-03-9/2021-14/200019.
文摘The liver is the site of synthesis of the majority of circulating proteins.Besides initial polypeptide synthesis,sophisticated machinery is involved in the further processing of proteins by removing parts of them and/or adding functional groups and small molecules tailoring the final molecule to suit its physiological purpose.Posttranslational modifications(PTMs)design a network of molecules with the common protein ancestor but with slightly or considerably varying activity/localization/purpose.PTMs can change under pathological conditions,giving rise to aberrant or overmodified proteins.Undesired changes in the structure of proteins most often accompany undesired changes in their function,such as reduced activity or the appearance of new effects.Proper protein processing is essential for the reactions in living beings and crucial for the overall quality control.Modifications that occur on proteins synthesized in the liver whose PTMs are cirrhosis-related are oxidation,nitration,glycosylation,acetylation,and ubiquitination.Some of them predominantly affect proteins that remain in liver cells,whereas others predominantly occur on proteins that leave the liver or originate from other tissues and perform their function in the circulation.Altered PTMs of certain proteins are potential candidates as biomarkers of liver-related diseases,including cirrhosis.This review will focus on PTMs on proteins whose structural changes in cirrhosis exert or are suspected to exert the most serious functional consequences.
基金Supported by the National Natural Science Fund(No. 81173187)the Natural Science Fund of Anhui Province (No.11040606M217)
文摘OBJECTIVE:To study the functional mechanism of Pingchuanning Decoction in treatment of airway remodeling in asthmatic rats.METHODS:Eighty healthy Wistar male rats were randomized into eight groups(n=10 rats each):Normal group,Asthma model group,Dexamethasone group,Guilong Kechuanning group,Xiaoqinglong Decoction group,and Pingchuanning Decoction low-,middle-,and high-dose groups.The rats of all but the Normal group were made into asthma models through intraperitoneal injection and aerosol inhalation of ovalbumin.All treatments were administered at the first stimulation of asthma onset(third week of modeling),and the rats were killed after stimulating asthma attacks for 4 weeks.The general conditions of rats and pathomorphological changes of the lung tissues were observed.The expression of nerve growth factor(NGF) of the lung tissues was measured with immunohistochemical methods,and the content of Clara cell secretory protein(CCSP) mRNA was determined with RT-PCR.RESULTS:Compared with the Normal group,the contents of NGF and CCSP mRNA in the lung tissues of the Model group were significantly changed(P<0.01).Compared with the Model group,the indices of Pingchuanning Decoction and other treatment groups were improved to some extent(P<0.05 or P<0.01).CONCLUSIONS:Pathological changes of airway inflammation and remodeling were present in these rat asthma models.Pingchuanning Decoction had an intervention effect on these experimental models.Its functional mechanism may be related to multiple factors,including alleviation of airway inflammation,relief of bronchial smooth muscle spasm,and inhibition of airway remodeling.
基金supported by the National Natural Science Foundation of China(No 29877016).
文摘In this paper, a new hybrid model of amino acid substitution is developed and compared with the others in previous works. The results show that the new hybrid model can characterize the protein sequences very well by calculating Fisher weights, which can denote how much the variants contribute to the classification.
基金This work was supported by the National Natural Science Foundation of China （No.10764003 and No.30560039）.
文摘The thermodynamic properties of linear protein solutions are discussed by a statistical me-chanics theory with a lattice model. The numerical results show that the Gibbs function of the solution decreases, and the protein chemical potential is enhanced with increase of the protein concentration for dilute solutions. The influences of chain length and temperature on the Gibbs function of the solution as well as the protein chemical potential are analyzed.As an application of the theory, the chemical potentials of some mutants of type I antifreeze proteins are computed and discussed.
基金Supported by the National Nataral Science Foundation of China(No.39980 0 0 5 )
文摘In this paper are reported the local minimum problem by means of current greedy algorithm for training the empirical potential function of protein folding on 8623 non-native structures of 31 globular proteins and a solution of the problem based upon the simulated annealing algorithm. This simulated annealing algorithm is indispensable for developing and testing highly refined empirical potential functions.
基金supported by the National Natural Science Foundation of China (No. 81500814) (SXL)the National Natural Science Foundation of China (No. 81430012 and No. 81170939) (XJ)+2 种基金the National Basic Research Program of China (973 Program, 2012CB933604)the National Science Fund for Distinguished Young Scholars of China (No. 81225006)the National Institutes of Health Grants DE025014 and R56DE022789 (JQF)
文摘Bone morphogenetic proteins （BMPs） have multiple roles in skeletal development, homeostasis and regeneration. BMPs signal via type I and type II serine/threonine kinase receptors （BMPRI and BMPRII）. In recent decades, genetic studies in humans and mice have demonstrated that perturbations in BMP signaling via BMPRI resulted in various diseases in bone, cartilage, and muscles. In this review, we focus on all three types of BMPRI, which consist of activin-like kinase 2 （ALK2, also called type IA activin receptor）, activin- llke kinase 3 （ALK3, also called BMPRIA）, and activin-like kinase 6 （ALK6, also called BMPRIB）. The research areas covered include the current progress regarding the roles of these receptors during myogenesis, chondrogenesis, and osteogenesis. Understanding the physiological and pathological functions of these receptors at the cellular and molecular levels will advance drug development and tissue regeneration for treating musculoskeletal diseases and bone defects in the future.
基金Project partially supported by the National Natural Science Foundation of China (Grant No.30570426)the Chinese Program for New Century Excellent Talents in University (Grant No.NCET-08-06867)+1 种基金Fok Ying Tung Education Foundation (Grant No.101004)Australian Research Council (Grant No.DP0559807)
文摘Investigating the biological function of proteins is a key aspect of protein studies. Bioinformatic methods become important for studying the biological function of proteins. In this paper, we first give the chaos game representation （CGR） of randomly-linked functional protein sequences, then propose the use of the recurrent iterated function systems （RIFS） in fractal theory to simulate the measure based on their chaos game representations. This method helps to extract some features of functional protein sequences, and furthermore the biological functions of these proteins. Then multifractal analysis of the measures based on the CGRs of randomly-linked functional protein sequences are performed. We find that the CGRs have clear fractal patterns. The numerical results show that the RIFS can simulate the measure based on the CGR very well. The relative standard error and the estimated probability matrix in the RIFS do not depend on the order to link the functional protein sequences. The estimated probability matrices in the RIFS with different biological functions are evidently different. Hence the estimated probability matrices in the RIFS can be used to characterise the difference among linked functional protein sequences with different biological functions. From the values of the Dq curves, one sees that these functional protein sequences are not completely random. The Dq of all linked functional proteins studied are multifractal-like and sufficiently smooth for the Cq （analogous to specific heat） curves to be meaningful. Furthermore, the Dq curves of the measure μ based on their CCRs for different orders to link the functional protein sequences are almost identical if q 〉 0. Finally, the Ca curves of all linked functional proteins resemble a classical phase transition at a critical point.
文摘Considering huge number of insect species in the world,studies of heat shock proteins on insects are still very limited.Special focus of＂Insect heat shock proteins and their underlying functions＂provides a comprehensive knowledge for the given topics,which focuses on the heat shock proteins from four insect species：i）Five heat shock proteins（HSPs）from Cotesia chilonis were identified,and their expressional patterns under different temperatures were examined.
文摘Previous molecular analyses of human astrocytomas have identified many genetic changes associated with astrocy-toma formation and progression.In an effort to identify novel gene expression changes associated with astrocytomaformation,which might reveal new potential targets for glioma therapeutic drug design,we used the B8-RAS-transgenic mouse astrocytoma model.Using multiplex gene expression profiling,we found that
文摘The realization of protein functional movement is usually accompanied by specific conformational changes,and there exist some key residues that mediate and control the functional motions of proteins in the allosteric process.In the present work,the perturbation-response scanning method developed by our group was combined with the molecular dynamics(MD)simulation to identify the key residues controlling the functional movement of proteins.In our method,a physical quantity that is directly related to protein specific function was introduced,and then based on the MD simulation trajectories,the perturbation-response scanning method was used to identify the key residues for functional motions,in which the residues that highly correlated with the fluctuation of the function-related quantity were identified as the key residues controlling the specific functional motions of the protein.Two protein systems,i.e.,the heat shock protein 70 and glutamine binding protein,were selected as case studies to validate the effectiveness of our method.Our calculated results are in good agreement with the experimental results.The location of the key residues in the two proteins are similar,indicating the similar mechanisms behind the performance of their biological functions.
文摘Pre-mRNA splicing is a dynamic process. It is catalyzed by the spliceosome which is a large machine formed by an ordered interactions of several small nuclear ribonucleoproteins, U1,
基金Supported by the National Natural Science Foundation of China under Grant Nos 11247010,11175055,11475053 and 11347017the Natural Science Foundation of Hebei Province under Grant Nos C2012202079 and C201400305
文摘We find that a conserved mutation residue Glu to residue Asp （E303D）, which both have the same polar and charged properties, makes Kit2.1 protein lose its function. To understand the mechanism, we identify three interactions which control the conformation change and maintain the function of the Kit2.1 protein by combining homology modeling and molecular dynamics with targeted molecular dynamics. We find that the E303D mutation weakens these interactions and results in the loss of the related function. Our data indicate that not only the amino residues but also the interactions determine the function of proteins.
基金supported by the grants from the National Institutes of Health of USA(NCRR R21RR024869, NIGMS RO1GM086423 and RO1GM121534 to Y.H.)the Start-up Foundation from Nanjing Medical University (2012RC04 to J.H.)University of Pittsburgh Medical School Center for Biologic Imaging was supported by the grant 1S100D019973-01 from NIH, USA
文摘In the past two decades, extensive studies have focused on a group of so-called polarity proteins that play conserved and essential functions in establishing and maintaining cell polarity in epithelial cells. Among them, Crumbs （Crb） is the only trans- membrane polarity protein characterized to date （Tepass et al.,
基金This work was supported by EU funding within the NextGenerationEU-MUR PNRR Extended Partnership Initiative on Emerging Infectious Diseases(Project No.PE00000007,INF-ACT)。
文摘Computational methods have significantly transformed biomedical research,offering a comprehensive exploration of disease mechanisms and molecular protein functions.This article reviews a spectrum of computational tools and network analysis databases that play a crucial role in identifying potential interactions and signaling networks contributing to the onset of disease states.The utilization of protein/gene interaction and genetic variation databases,coupled with pathway analysis can facilitate the identification of potential drug targets.By bridging the gap between molecular-level information and disease understanding,this review contributes insights into the impactful utilization of computational methods,paving the way for targeted interventions and therapeutic advancements in biomedical research.
文摘Improving grain amino acid content of rice(Oryza sativa L.)is essential for the health of consumers.This study was conducted to identify the physiological processes that contribute to the higher grain amino acid content in hybrid rice cultivar Lingliangyou 268 compared to Luliangyou 996.The results showed that total amino acid content in grains was 9%higher in Lingliangyou 268 than in Luliangyou 996.There was no significant difference in grain nitrogen(N)content between Lingliangyou 268 and Luliangyou 996,while ratio of amino acid to N was 6%higher in Lingliangyou 268 compared to Luliangyou 996.A total of 16 differentially expressed proteins related to amino acid metabolism(e.g.,erythronate-4-phosphate dehydrogenase domain containing protein)were identified in grains between Lingliangyou 268 and Luliangyou 996.The identified proteins were involved in 10 molecular functions.Six of the 10 defined functions were related to binding(heterocyclic compound binding,nucleoside phosphate binding,nucleotide binding,organic cyclic compound binding,protein binding,and small molecule binding)and the other 4 defined functions were catalytic activity,enzyme regulator activity,hydrolase activity,and transferase activity.These results indicate that the higher grain amino acid content in Lingliangyou 268 compared to Luliangyou 996 is attributed to increased efficiency of converting N to amino acid that results from altered expression of proteins related to amino acid metabolism.
基金Grants from ANRS,ARC,IREB and ConseilRégional de Haute-Normandie to JPS
文摘AIM:To look at a comprehensive picture of etiology- dependent gene abnormalities in hepatocellular carcinoma in Western Europe. METHODS:With a liver-oriented microarray,transcript levels were compared in nodules and cirrhosis from a training set of patients with hepatocellular carcinoma (alcoholism,12;hepatitis C,10)and 5 controls.Loose or tight selection of informative transcripts with an abnormal abundance was statistically valid and the tightly selected transcripts were next quantified by qRTPCR in the nodules from our training set(12+10) and a test set(6+7). RESULTS:A selection of 475 transcripts pointed to significant gene over-representation on chromosome 8 (alcoholism)or-2(hepatitis C)and ontology indicated a predominant inflammatory response(alcoholism)or changes in cell cycle regulation,transcription factors and interferon responsiveness(hepatitis C).A stringent selection of 23 transcripts whose differences betweenetiologies were significant in nodules but not in cirrhotic tissue indicated that the above dysregulations take place in tumor but not in the surrounding cirrhosis.These 23 transcripts separated our test set according to etiologies. The inflammation-associated transcripts pointed to limited alterations of free iron metabolism in alcoholic vs hepatitis C tumors. CONCLUSION:Etiology-specific abnormalities(chromo- some preference;differences in transcriptomes and related functions)have been identified in hepatocellular carcinoma driven by alcoholism or hepatitis C.This may open novel avenues for differential therapies in this disease.
基金supported by the National Natural Science Foundation of China,No.81073082 to JSZ
文摘Neural stem cells have great potential for the development of novel therapies for nervous system diseases.However,the proliferation of endogenous neural stem cells following brain ischemia is insufficient for central nervous system self-repair.Ginkgolide B has a robust neuroprotective effect.In this study,we investigated the cell and molecular mechanisms underlying the neuroprotective effect of ginkgolide B on focal cerebral ischemia/reperfusion injury in vitro and in vivo.Neural stem cells were treated with 20,40 and 60 mg/L ginkgolide B in vitro.Immunofluorescence staining was used to assess cellular expression of neuron-specific enolase,glial fibrillary acid protein and suppressor of cytokine signaling 2.After treatment with 40 and 60 mg/L ginkgolide B,cells were large,with long processes.Moreover,the proportions of neuron-specific enolase-,glial fibrillary acid protein-and suppressor of cytokine signaling 2-positive cells increased.A rat model of cerebral ischemia/reperfusion injury was established by middle cerebral artery occlusion.Six hours after ischemia,ginkgolide B（20 mg/kg） was intraperitoneally injected,once a day.Zea Longa＇s method was used to assess neurological function.Immunohistochemistry was performed to evaluate the proportion of nestin-,neuron-specific enolase-and glial fibrillary acid protein-positive cells.Real-time quantitative polymerase chain reaction was used to measure m RNA expression of brain-derived neurotrophic factor and epidermal growth factor.Western blot assay was used to analyze the expression levels of brain-derived neurotrophic factor and suppressor of cytokine signaling 2.Ginkgolide B decreased the neurological deficit score,increased the proportion of nestin-,neuron-specific enolase-and glial fibrillary acid protein-positive cells,increased the m RNA expression of brain-derived neurotrophic factor and epidermal growth factor,and increased the expression levels of brain-derived neurotrophic factor and suppressor of cytokine signaling 2 in the ischemic penumbra.Together,the in vivo and in vitro findings suggest that ginkgolide B improves neurological function by promoting the proliferation and differentiation of neural stem cells in rats with cerebral ischemia/reperfusion injury.
基金supported by the General Secretariat of Research and Technology-EPAN (Competitiveness and Entepreneurship) Program
文摘We used Drosophila melanogaster as an experimental model to express mouse and pig BM88/CEND1(cell cycle exit and neuronal differentiation 1) in order to investigate its potential functional effects on Drosophila neurogenesis. BM88/CEND1 is a neuron-specific protein whose function is implicated in triggering cells to exit from the cell cycle and differentiate towards a neuronal phenotype. Transgenic flies expressing either mouse or pig BM88/CEND1 in the nervous system had severe neuronal phenotypes with variable expressivity at various stages of embryonic development. In early embryonic stage 10,BM88/CEND1 expression led to an increase in the neuralspecific antigenicity of neuroectoderm at the expense of precursor cells [neuroblasts(Nbs) and ganglion mother cells(GMCs)] including the defective formation and differentiation of the MP2 precursors, whereas at later stages(12–15), protein accumulation induced gross morphological defects primarily in the CNS accompanied by a reduction of Nb and GMC markers. Furthermore, the neuronal precursor cells of embryos expressing BM88/CEND1 failed to carry out proper cell-cycle progression as revealed by the disorganized expression patterns of specific cell-cycle markers. BM88/CEND1 accumulation in the Drosophila eye affected normal eye disc development by disrupting the ommatidia. Finally, we demonstrated that expression of BM88/CEND1 modified/reduced the levels of activated MAP kinase indicating a functional effect of BM88/CEND1 on the MAPK signaling pathway. Our findings suggest that the expression of mammalian BM88/CEND1 in Drosophila exerts specific functional effects associated with neuronal precursor cell formation during embryonic neurogenesis and proper eye disc development.This study also validates the use of Drosophila as a powerful model system in which to investigate gene function and the underlying molecular mechanisms.
