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Science China(Life Sciences) 2010年第2期53卷 234-240页

作者： Rajasekaran R rao sethumadhavan Bioinformatics Division School of BiotechnologyChemical and Biomedical EngineeringVellore Institute of Technology

In this study,we identified the most deleterious nsSNP in RB1 gene through structural and functional properties of its protein (pRB) and investigated its binding affinity with *** of 956 SNPs,we investigated 12 nsSNPs in coding region in which three of them (SNPids rs3092895,rs3092903 and rs3092905) are commonly found to be damaged by I-Mutant 2.0,SIFT and PolyPhen *** this effort,we modeled the mutant pRB proteins based on these deleterious *** a comparison of total energy,stabilizing residues and RMSD of these three mutant proteins with native pRB protein,we identified that the major mutation is from Glutamic acid to Glycine at the residue position of 746 of ***,we compared the binding efficiency of both native and mutant pRB (E746G) with *** found that mutant pRB has less binding affinity with E2F-2 as compared to native *** is due to sixteen hydrogen bonding and two salt bridges that exist between native type and E2F-2,whereas mutant type makes only thirteen hydrogen bonds and one salt bridge with *** on our investigation,we propose that the SNP with an id rs3092905 could be the most deleterious nsSNP in RB1 gene causing retinoblastoma.

关键词： retinoblastoma non synonymous SNP RB1 gene pRB E2F-2

Selection of effective and highly thermostable Bacillus subtilis lipase A template as an industrial biocatalyst-A modern computational approach

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Frontiers in Biology 2015年第6期10卷 508-519页

作者： B. Senthilkumar D. Meshachpaul rao sethumadhavan R. Rajasekaran School of Biosciences and Technology Bioinformatics Division VIT University Vellore 632014 Tamil Nadu India

Biocatalysts are intrinsically reactive and hence their operational stability is of vital significance for any bioprocess. The setback in biocatalyst stability has been tackled from diverse prospects. Inherently, stable biocatalysts are markedly realized and a regular attempt is being made to seek out new organisms that harbor them. Here, we analyzed the industrial biocatalyst lipase A （Native） of Bacillus subtilis and its six thermostable mutants （2M, 3M, 4M, 6M, 9M and 12M） computationally using conformational sampling technique. Consequently, the various structural events deciphering thermostability like root mean square deviation, root mean square fluctuation, radius of gyration and polar surface area showed mutant 12M to be highly stable with statistical validation. Besides, static model analysis involving intra-molecular interactions, secondary structure, solvent accessibility, hydrogen bond pattern, simulated thermal denaturation and desolvation energy also supported 12M comparatively. Of note, the presence of high secondary structural rigidity and hydrogen bonds increased thermostability and functionality of 12M, thus selecting it as a best template for designing thermostable lipases in future. Also, this study has a significant implication toward a better understanding of conformational sampling in enzyme catalysis and enzyme engineering.

关键词： thermophilic Bacillus subtilis lipase A conformational analysis docking

Identification of structurally and functionally significant deleterious nsSNPs of GSS gene: in silico analysis

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Advances in Bioscience and Biotechnology 2010年第4期1卷 361-366页

作者： Ramavartheni Kanthappan rao sethumadhavan 不详

It is becoming more and more apparent that most genetic disorders are caused by biochemical abnormalities. Recent advances in human genome project and related research have showed us to detect and understand most of the inborn errors of metabolism. These are often caused by point mutations manifested as single-nucleotide-polymorphisms (SNPs). The GSS gene inquested in this work was analyzed for potential mutations with the help of computational tools like SIFT, PolyPhen and UTRscan. It was noted that 84.38% nsSNPs were found to be deleterious by the sequence homology based tool (SIFT), 78.13% by the structure homology based tool (PolyPhen) and 75% by both the SIFT and PolyPhen servers. Two major mutations occurred in the native protein (2HGS) coded by GSS gene at positions R125C and R236Q. Then a modeled structure for the mutant proteins (R125C and R236Q) was proposed and compared with that of the native protein. It was found that the total energy of the mutant (R125C and R236Q) proteins were -31893.846 and -31833.818 Kcal/mol respectively and that of the native protein was -31977.365 Kcal/mol. Also the RMSD values between the native and mutant (R125C and R236Q) type proteins were 1.80? and 1.54?. Hence, we conclude based on our study that the above mutations could be the major target mutations in causing the glutathione synthetase deficiency.

关键词： GSS Gene SNP Glutathione Synthetase SIFT PolyPhen UTRScan

A computational approach to explore the functional missense mutations in the spindle check point protein Mad1

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Frontiers in Biology 2013年第6期8卷 618-625页

作者： Merlin LOPUS rao sethumadhavan P. CHANDRASEKARAN K. SREEVISHNUPRIYA A.W. VARSHA V. SHANTHI K. RAMANATHAN R. RAJASEKARAN Bioinformatics Division School of Biosciences and Technology Vellore Institute of Technology Vellore 632014 Tamil Nadu India Industrial Biotechnology Division School of Biosciences and Technology Vellore Institute of Technology Vellore 632014 Tamil Nadu India

In this work, the most detrimental missense mutations of Madl protein that cause various types of cancer were identified computationally and the substrate binding efficiencies of those missense mutations were analyzed. Out of 13 missense mutations, I Mutant 2.0, SIFT and PolyPhen programs identified 3 variants that were less stable, deleterious and damaging respectively. Subsequently, modeling of these 3 variants was performed to understand the change in their conformations with respect to the native Madl by computing their root mean squared deviation （RMSD）. Furthermore, the native protein and the 3 mutants were docked with the binding partner Mad2 to explain the substrate binding efficiencies of those detrimental missense mutations. The docking studies identified that all the 3 mutants caused lower binding affinity for Mad2 than the native protein. Finally, normal mode analysis determined that the loss of binding affinity of these 3 mutants was caused by altered flexibility in the amino acids that bind to Mad2 compared with the native protein. Thus, the present study showed that majority of the substrate binding amino acids in those 3 mutants displayed loss of flexibility, which could be the theoretical explanation of decreased binding affinity between the mutant Madl and Mad2.

关键词： missense mutation Madl Mad2 spindle check point cancer

Computational and Structural Investigation of Deleterious Functional SNPs in Breast Cancer BRCA2 Gene

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生物工程学报 2008年第5期24卷 851-856页

作者： Rajasekaran R George Priya Doss Sudandiradoss C Ramanathan K Rituraj Purohit rao sethumadhavan School of Biotechnology Chemical and Biomedical Engineering Bioinformatics Division Vellore Institute of Technology University Vellore 632014Tamil Nadu India.

In this work, we have analyzed the genetic variation that can alter the expression and the function in BRCA2 gene using computational methods. Out of the total 534 SNPs, 101 were found to be non synonymous (nsSNPs). Among the 7 SNPs in the untranslated region, 3 SNPs were found in 5′ and 4 SNPs were found in 3′ un-translated regions (UTR). Of the nsSNPs 20.7% were found to be damaging by both SIFT and PolyPhen server among the 101 nsSNPs investigated. UTR resource tool suggested that 2 SNPs in the 5′ UTR region and 4 SNPs in the 3′ UTR regions might change the protein expression levels. The mutation from asparagine to isoleucine at the position 3124 of the native protein of BRCA2 gene was most deleterious by both SIFT and PolyPhen servers. A structural analysis of this mutated protein and the native protein was made which had an RMSD value of 0.301 nm. Based on this work, we proposed that this most deleterious nsSNP with an SNPid rs28897759 is an important candidate for the cause of breast cancer by BRCA2 gene.

关键词：乳癌治疗方法临床分析基因

Passive activity enhances residual control ability in patients with complete spinal cord injury

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Neural Regeneration Research 2025年第8期20卷 2337-2347页

作者： Yanqing Xiao Mingming Gao Zejia He Jia Zheng Hongming Bai Jia-Sheng rao Guiyun Song Wei Song Xiaoguang Li Beijing Key Laboratory for Biomaterials and Neural Regeneration Beijing Advanced Innovation Center for Biomedical EngineeringSchool of Biological Science and Medical EngineeringBeihang UniversityBeijingChina Department of Rehabilitation Evaluation China Rehabilitation Research CenterBeijingChina Cardiac Center Beijing Children’s HospitalCapital Medical UniversityBeijingChina The State Key Laboratory of Virtual Reality Technology and Systems Beihang UniversityBeijingChina Department of Rehabilitation Engineering China Rehabilitation Science InstituteBeijingChina

Patients with complete spinal cord injury retain the potential for volitional muscle activity in muscles located below the spinal injury ***,because of prolonged inactivity,initial attempts to activate these muscles may not effectively engage any of the remaining neurons in the descending pathway.A previous study unexpectedly found that a brief clinical round of passive activity significantly increased volitional muscle activation,as measured by surface *** this study,we further explored the effect of passive activity on surface electromyographic signals during volitional control tasks among individuals with complete spinal cord *** patients with chronic complete thoracic spinal cord injury were *** electromyography data from eight major leg muscles were acquired and compared before and after the passive activity *** results indicated that the passive activity led to an increased number of activated volitional muscles and an increased frequency of *** the cumulative root mean square of surface electromyography amplitude for volitional control of movement showed a slight increase after passive activity,the difference was not statistically *** findings suggest that brief passive activity may enhance the ability to initiate volitional muscle activity during surface electromyography tasks and underscore the potential of passive activity for improving residual motor control among patients with motor complete spinal cord injury.

关键词： complete spinal cord injury cycle training epidural electrical stimulation motor training passive activity physiological state spinal cord circuit surface electromyography volitional control task

Infiltration by monocytes of the central nervous system and its role in multiple sclerosis: reflections on therapeutic strategies

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Neural Regeneration Research 2025年第3期20卷 779-793页

作者： Guangyong Zhang Qing Yao Chubing Long Pengcheng Yi Jiali Song Luojia Wu Wei Wan Xiuqin rao Yue Lin Gen Wei Jun Ying Fuzhou Hua Department of Anesthesiology the Second Affiliated Hospital of Nanchang UniversityNanchangJiangxi ProvinceChina Key Laboratory of Anesthesiology of Jiangxi Province NanchangJiangxi ProvinceChina

Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple roles of mononuclear macrophages in the neuroinflammatory process. Monocytes play a significant role in neuroinflammation, and managing neuroinflammation by manipulating peripheral monocytes stands out as an effective strategy for the treatment of multiple sclerosis, leading to improved patient outcomes. This review outlines the steps involved in the entry of myeloid monocytes into the central nervous system that are targets for effective intervention: the activation of bone marrow hematopoiesis, migration of monocytes in the blood, and penetration of the blood–brain barrier by monocytes. Finally, we summarize the different monocyte subpopulations and their effects on the central nervous system based on phenotypic differences. As activated microglia resemble monocyte-derived macrophages, it is important to accurately identify the role of monocyte-derived macrophages in disease. Depending on the roles played by monocyte-derived macrophages at different stages of the disease, several of these processes can be interrupted to limit neuroinflammation and improve patient prognosis. Here, we discuss possible strategies to target monocytes in neurological diseases, focusing on three key aspects of monocyte infiltration into the central nervous system, to provide new ideas for the treatment of neurodegenerative diseases.

关键词： blood–brain barrier macrophages monocytes multiple sclerosis neuroinflammation review therapy

Systematical identification of regulatory GPCRs by single-cell trajectory inference reveals the role of ADGRD1 and GPR39 in adipogenesis

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Science China Life Sciences 2025年

作者： Chuan Ye Xuemei Wang Jun Lin Chenyang Wu Yuhua Gao Chenghao Guo Yunxi Liao Ziyan rao Shaodong Huang Weixuan Chen Ying Huang Jinpeng Sun Dongyu Zhao Changtao Jiang Center of Basic Medical Research Institute of Medical Innovation and ResearchPeking University Third Hospital Department of Physiology and Pathophysiology School of Basic Medical SciencesPeking University Department of Biomedical Informatics School of Basic Medical SciencesPeking University State Key Laboratory of Vascular Homeostasis and Remodeling Peking University Center for Obesity and Metabolic Disease Research School of Basic Medical SciencesPeking University State Key Laboratory of Female Fertility Promotion Center for Reproductive MedicineDepartment of Obstetrics and GynecologyPeking University Third Hospital National Clinical Research Center for Obstetrics and Gynecology Peking University Third Hospital Department of Endocrinology and Metabolism Peking University Third Hospital Key Laboratory Experimental Teratology of the Ministry of Education Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesCheeloo College of MedicineShandong University Department of Immunology School of Basic Medical SciencesPeking University

Adipogenesis is the healthy expansion of white adipose tissue (WAT),serving as a compensatory response to maintain metabolic homeostasis in the presence of excess energy in the ***,the identification of novel regulatory molecules in adipogenesis,specifically membrane receptors such as G protein-coupled receptors (GPCRs),holds significant clinical *** receptors can serve as viable targets for pharmaceuticals,offering potential for restoring metabolic homeostasis in individuals with *** utilized trajectory inference methods to analyze three distinct single-nucleus sequencing (sNuc-seq) datasets of adipose tissue and systematically identified GPCRs with the potential to regulate *** verification in primary adipose progenitor cells (APCs) of mice,we discovered that ADGRD1 promoted the differentiation of APCs,while GPR39 inhibits this *** the obese mouse model induced by a high-fat diet(HFD),both gain-of-function and loss-of-function studies validated that ADGRD1 promoted adipogenesis,thereby improving metabolic homeostasis,while GPR39 inhibited adipogenesis,leading to metabolic ***,through the analysis of 2,400 ChIP-seq data and 1,204 bulk RNA-seq data,we found that the transcription factors (TFs) MEF2D and TCF12 regulated the expression of ADGRD1and GPR39,*** study revealed the regulatory role of GPCRs in adipogenesis,providing novel targets for clinical intervention of metabolic dysfunction in obese patients.

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现象学视域下农村集体经济的本质再诠释

西北农林科技大学学报（社会科学版） 2025年第1期25卷 60-68页

作者：李林峰刘启明饶静中国农业大学人文与发展学院北京100083 中共江西省委党校江西经济社会发展战略研究所南昌330108

鉴于当前政策、理论和实践领域对农村集体经济本质缺乏共识,本研究采用胡塞尔现象学的方法论,特别是一般现象学还原、本质还原和先验还原等技术,系统地审视了“农村集体经济应该是什么”这一核心议题。通过全面梳理当前对农村集体经济... 详细信息

鉴于当前政策、理论和实践领域对农村集体经济本质缺乏共识,本研究采用胡塞尔现象学的方法论,特别是一般现象学还原、本质还原和先验还原等技术,系统地审视了“农村集体经济应该是什么”这一核心议题。通过全面梳理当前对农村集体经济的多维认知,从而为其本质探索提供更为宽广的视角。在搁置既有认识的基础上,采用更加开放的态度识别出土地集体所有制是农村集体经济的共相,这一发现为理解其本质提供了关键线索。进一步从源初意向性与结构性剖析农村集体经济,揭示其本质在于注重公正,并凸显了其深厚的社会性和伦理性。这种本体论式反思既验证了马克思主义理论关于集体所有制经济的科学性及其生命力,更展示了中国农村集体经济独有的文化烙印。同时,跨学科的研究方法或为理解农村集体经济提供了新的视角,为推动其持续健康发展提供有益的思考。

关键词：农村集体经济现象学本质

Region-dependent micro damage of enamel under indentation

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Acta Mechanica Sinica 2012年第6期28卷 1651-1658页

作者： Bing-Bing An rao-rao Wang .Dong-Sheng Zhang rao-rao Wang Dong-Sheng Zhang Shanghai Institute of Applied Mathematics and Mechanics 200072 Shanghai China The Tenth People's Hospital of Tongji University 200072 Shanghai China Department of Mechanics Shanghai University200444 Shanghai China Shanghai Key Laboratory of Mechanics in Energy Engineering 200072 Shanghai China

The objective of this investigation is to explore the region-dependent damage behavior of enamel, as well as to develop a good understanding of the deformation mech- anisms of enamel with numerical modeling. Nanoinden- tation experiments have been performed to investigate the load-penetration depth responses for outer and inner enamel. Results show that the unloading curve does not follow the loading curve, and degradation of stiffness in the unloading curve is observed. Based on the experimental data, a physi- cal quantity, the chain density in protein, has been introduced to the Drucker-Prager plastic model. Numerical simulations show that the simulated load-penetration depth curves agree with the experiments, and the stiffness degradation behav- iors of outer and inner enamel are captured by the numerical model. The region-dependent damage behavior of enamel could be revealed by the numerical model. The micro dam- age affected area at inner enamel is larger than that at outer enamel, indicating that the inner enamel experiences more micro damage than the outer one. Compared with its outer counterpart, the inner enamel which is rich in organic protein could break more internal protein chains to dissipate energy and to enhance its resistance to fracture accordingly.

关键词： Enamel. Nanoindentation Damage. Numerical simulation