Structure-function Relationships in Human Hypoxanthine-guanine Phosphoribosyltransferase(HGPRT) by Random Mutagenesis

Hypoxanthine-guanine phosphoribosyltransferase （ HGPRT, EC 2.4.2.8） is a key enzyme of the purine salvage pathway, which allows recycling of purine bases into DNA and RNA. It is widely distributed in nature and has been studied both in prokaryotes and eukaryotes. In humans, a complete lack of HGPRT activity causes the Lesch-Nyhan syndrome, which is characterized by hyperuricaemia and neural disorders,

Relationship of Naturally Occurring Antisperm Antibodies in Blood Serum and Seminal Plasma of Cattle Bulls with Sperm Function and Fertility Tests

The study was planned with an objective to assess the level of antisperm antibodies (ASA) in the blood serum and seminal plasma of breeding cow bulls and their relationship with sperm function and fertility tests. ASA was analyzed in blood serum and seminal plasma by SpermMar test, Immuno peroxidase assay (IPA) and Enzyme linked immunoabsorbant assay (ELISA). In SpermMar test, about 54% bulls were with >40% IgG in blood serum against sperm surface antigens, whereas none of the bulls were with >10% IgG in seminal plasma. More than 20% and >10% IgA against sperm surface antigens were detected in the blood serum and seminal plasma of 65.8% and 37% bulls, respectively. Out of 26 bulls, seminal plasma of 21 bulls reacted with spermatozoa both in IPA and IgA latex particles and that of only 12 bulls reacted with IgG. In IPA, about 50% of the bulls had >40% ASA against head surface antigens, whereas, there were 23% bulls with >10% ASA in seminal plasma. Also ELISA indicated a higher antibody titre in blood serum (3200 - 6400) and seminal plasma (40 - 80) of 50% and 42% bulls, respectively. There were 11 bulls with low values of HOST/in vitro acrosome reaction/cervical mucus penetration assay and higher level of either serum or seminal plasma ASA. Our study revealed that a significant level of ASA in serum or seminal plasma may have effect on the fertility of bulls by affecting the sperm function.

甲状腺功能水平与肌少症相关特征表型的关联

背景:多项观察性研究发现甲状腺功能水平与肌少症之间存在密切关系,但是甲状腺功能水平与肌少症发病之间的因果关系尚不明确。目的:采用两样本孟德尔随机化方法研究甲状腺功能水平与肌少症的因果关系。方法:利用促甲状腺激素、游离三碘甲状腺原氨酸、游离四碘甲状腺原氨酸、亚临床甲状腺功能亢进症、亚临床甲状腺功能减退症和肌少症的4种相关表型——左手握力、右手握力、四肢瘦体质量、步速的全基因组关联研究汇总数据进行两样本孟德尔随机化分析,分别采用逆方差加权法、加权中位数法、简单模式法、加权中值方法和MR-Egger回归法作为分析方法,同时采用异质性检验、多效性检验、MR-PRESSO、留一法、漏斗图等方法进行敏感性分析。结果与结论:促甲状腺激素的增高会增加左手握力(β=0.02,SE=0.01,P=0.01)、右手握力(β=0.02,SE=0.01,P=0.01),游离三碘甲状腺原氨酸的增高会降低左手握力(β=-0.06,SE=0.02,P=9.5×10^(-5))、右手握力(β=-0.07,SE=0.02,P=9.3×10^(-5)),亚临床甲状腺功能亢进症会降低步速(β=-4.4×10^(-3),SE=1.7×10^(-3),P=0.01)。敏感性分析结果与主要分析基本一致。结果表明:促甲状腺激素上升是肌少症保护因素,游离三碘甲状腺原氨酸上升和亚临床甲状腺功能亢进症可能导致肌少症发生风险增加。

A study on deep structure using teleseismic receiver function in Western Yunnan

s Western Yunnan is located at the boundary of collision or underthrusting zone of Eurasian plate and is influenced by many times tectonic movements. With very complex geological environment and tectonic background, it is one of the seismically active areas. In the paper, the teleseismic records were selected from 16 national, local and mo-bile stations, including 4 very-wide-band mobile stations of PASSCAL. And nearly 2 000 receiver functions were extracted. Two measuring lines are 650 km and 450 km, respectively and across some major tectonic units in Western Yunnan. It is indicated that Nujiang might be a seam characterized by underthrusting. The western and eastern boundaries of Sichuan-Yunnan rhombus block, i.e., Honghe and Xiaojiang faults, might be an erection seam or collision belt. Panxi tectonic zone still has the characteristics of continental rift valley, that is, the surface is hollow and the upper mantle is upwarping. The tectonic situation in Western Yunnan is of certain regulation with the interlacing distribution of orogenic zone and seam. The crustal thickness decreases gradually from the north to the south and the S wave velocity is globally lower here.

Effect of N-substituents on performance of thiourea collectors by density functional theory calculations

Using density functional methods,some properties were studied such as the energies and compositions of frontier molecular orbitals and the atomic charges,which are related to the reactive behavior of thioureas containing different N-substituent groupings.The calculation results indicate that the N-substituent groupings have significant effect on the flotation performance of thiourea collectors.The order of electron-donating ability is N-propyl-N'-benzyl-thiourea(PBZYTU)>N-propyl-N'-ethyl-thiourea (PETU)>N-propyl-N'-allyl-thiourea(PALTU)>>N-propyl-N'-acetyl-thiourea(PACTU)>N-propyl-N'-ethoxycarbonyl-thiourea (PECTU)>N-propyl-N'-benzoyl-thiourea(PBZOYTU),and the order of feedback-electron-accepting ability is PBZOYTU> PACTU>PECTU>>PALTU>PETU>PBZYTU.This implies that PBZOYTU,PACTU or PECTU can react with copper atoms having(t2g) 6 (eg) 3Cu(II)or t 6e 4Cu(I)configuration on the surfaces of copper sulfide minerals through normal covalent bond and back donation covalent bond,and exhibit excellently collecting performance for copper sulfide minerals.These are consistent with the experimental data reported in the literatures.

Studies of n-Octanol/water Partition Coefficients (lgK_(ow)) for Organophosphate Compounds by Density Functional Theory

Optimized calculation of 35 dialkyl phenyl phosphate compounds （OPs） was carded out at the B3LYP/6-31G^＊ level in Gaussian 98 program. Based on the theoretical linear solvation energy relationship （TLSER） model, the obtained parameters were taken as theoretical descriptors to establish the novel QSPR model for predicting n-octanol/water partition coefficients （lgKow） of OPs. The new model achieved in this work contains three variables, i.e., molecular volume （Vm）, dipole moment of the molecules （μ） and enthalpy （H^0）. For this model, R^2 = 0.9167 and SD = 0.31 at large t values. In addition, the variation inflation factors （VIF） of variables are all close to 1.0, suggesting high accuracy of the predicting model. And the results of cross-validation test （q^2 = 0.8993） and method validation also showed the model of this study exhibited optimum stability and better predictive power than that from semi-empirical method. The model achieved can be used to predict IgKow of congeneric compounds.

GOMA:functional enrichment analysis tool based on GO modules

Analyzing the function of gene sets is a critical step in interpreting the results of high-throughput experiments in systems biology. A variety of enrichment analysis tools have been developed in recent years, but most output a long list of significantly enriched terms that are often redundant, making it difficult to extract the most meaningful functions. In this paper, we present GOMA, a novel enrichment analysis method based on the new concept of enriched functional Gene Ontology (GO) modules. With this method, we systematically revealed functional GO modules, i.e., groups of functionally similar GO terms, via an optimization model and then ranked them by enrichment scores. Our new method simplifies enrichment analysis results by reducing redundancy, thereby preventing inconsistent enrichment results among functionally similar terms and providing more biologically meaningful results.

Function S-Rough sets and its applications

Based on S-rough sets（singular rough sets）, this paper presents function S-rough sets （function singular rough sets）and its mathematical structures and features. Function S-rough sets has two forms： function one direction S-rough sets （function one direction singular rough sets） and function two direction S-rough sets （function two direction singular rough sets）. This paper advances the relationship theorem of function S-rough sets and S-rough sets. Function S-rough sets is the general form of S-rough sets, and S-rough sets is the special ease of function S-rough sets. In this paper, applications of function S-rough sets in rough law mining-discovery of system are given. Function S-rough sets is a new research direction of rough sets and rough system.

Function S-rough sets and mining-discovery of rough law in systems

Function S-rough sets （function singular rough sets） is defined on a -function equivalence class [u]. Function S-rough sets is the extension form of S-rough sets. By using the function S-rough sets, this paper gives rough law generation model of a-function equivalence class, discussion on law mining and law discovery in systems, and application of law mining and law discovery in communication system. Function S-rough sets is a new theory and method in law mining research.

Disorder structural predictions of the native EWS and its oncogenic fusion proteins in rapport with the function

The Intrinsic structural disorder (ISD) of native EWS and its fusion oncogenic proteins, including EWS/FliI, EWS/ATF1 and EWS/ZSG, was estimated by different Predictors. The ISD difference between the wild type and the oncogenic fusions found in the CTD is due to the fusion partner, usually a transcription factor (TF). A disordered region was found in the sequence (AA 132 - 156) of the NTD (EAD) of EWS, consisting of the longest region free of Y motifs. The IQ domain (AA 258 - 280), a Y-free region, flanked by two Y-boxes, is also disordered by all used Predictors. The EWS functional regions RGG1, RGG2 and RGG3 are predominantly disordered. A strong dependence was found between the structure of EWS protein and its oncogenic fusions, and their estimated ISD. The oncogenic function of the fusions is related to a decreased ISD in the CTD, due to the fused TF. The Predictors shown that the different isoforms have similar profiles, shifted with some amino acids, due to the translocations. On the bases of the prediction results, an analysis was made of the EWS sequence and its functional regions with increased ISD to make a relationship sequence-disorder-function that could be helpful in the design of antitumor agents against the corresponding malignances.

Endorphins, oxytocin, sexuality and romantic relationships: An understudied area

Endorphins are the body's natural opioids that are created and released by the central nervous system, hypothalamus and pituitary gland. Endorphins have a reputation for pain reduction, enhancing excitement or satisfaction, boosting confidence, enabling control of emotions and generating feelings of euphoria, and are involved in the natural reward cycle. There is also evidence in the literature suggesting the role of endorphins in sexuality(including sexual function and sexual behaviours), as they may regulate the release of sex hormones, prolactin and growth hormone, which are involved in sexual function and love. Endogenous oxytocin is another intrinsic hormone whose role in inducing labour contractions, the delivery of the baby and stimulating lactation has been well studied. However, the potential impact of endorphins and oxytocin on sexuality and romantic relationships is not well understood. This article reviews the research on endorphins and endogenous oxytocin and how they relate to human sexuality and romantic relationships. Some animal studies report the effect of endorphin and oxytocin on sex hormones and mating behaviours, but these findings have not been supported by research into human behaviour, indicating many gaps in knowledge relating to the association between these hormones and human sexuality.

A study on deep structure using teleseismic receiver function in Western Yunnan

s Western Yunnan is located at the boundary of collision or underthrusting zone of Eurasian plate and is influenced by many times tectonic movements. With very complex geological environment and tectonic background, it is one of the seismically active areas. In the paper, the teleseismic records were selected from 16 national, local and mo-bile stations, including 4 very-wide-band mobile stations of PASSCAL. And nearly 2 000 receiver functions were extracted. Two measuring lines are 650 km and 450 km, respectively and across some major tectonic units in Western Yunnan. It is indicated that Nujiang might be a seam characterized by underthrusting. The western and eastern boundaries of Sichuan-Yunnan rhombus block, i.e., Honghe and Xiaojiang faults, might be an erection seam or collision belt. Panxi tectonic zone still has the characteristics of continental rift valley, that is, the surface is hollow and the upper mantle is upwarping. The tectonic situation in Western Yunnan is of certain regulation with the interlacing distribution of orogenic zone and seam. The crustal thickness decreases gradually from the north to the south and the S wave velocity is globally lower here.

Estimation of n-Octanol/water Partition Coeffi-cients(lgK_(ow)) and the Aqueous Solubility(-lg_(Sw)) of all PCDF Congeners by Density Functional Theory

Optimized calculation of dibenzofuran （DF） and 135 polychlorinated dibenzofurans （PCDFs） was carried out at the B3LYP/6-31G＊ level in GAUSSIAN 98 program. Based on the theoretical linear solvation energy relationship （TLSER） model, the obtained structural parameters were taken as theoretical descriptors to establish the novel quantitative structureproperty relationship （QSPR） model for predicting n-octanol/water partition coefficients （lgKow） of PCDFs. The new model of lgKow achieved in this work contains three variables： energy of the highest occupied molecular orbital （EHOMO）, the most negative atomic partial charge （q^-） and average molecular polarizability （a）, of which R^2= 0.9011 and SD = 0,17 with larger t values. In addition, the variation inflation factors （VIF） of variables in the present model are all less than 5.5, suggesting high accuracy of the lgKow model. And the results of cross-validation test （q^2 = 0.8688） and method validation also show this model exhibits optimum stability and better predictive power than semi-empirical method. At the same time, it is found that the aqueous solubility （-lgSw） has high relative correlation with constant volume molar heat capacity （Cv^0）, of which R^2 = 0.9777 and SD = 0.22. Moreover, lgKow and -lgSw values of all PCDF congeners were predicted respectively.

Structure-activity correlationship and folding of recombinant Escherichia coli dihydro folate reductase (DHFR) enzyme through biochemical and biophysical approaches

The design of any antagonist or inhibitor for any enzyme requires the knowledge of structure- function relationship of the protein and the optimum conformational states for maximum and minimum activities. Furthermore, designing of the inhibitors or drugs against an enzyme becomes easier if there is information available about various well characterized intermediate conformation of the molecule. In vivo folding pathway of any recombinant protein is an important parameter for understanding its ability to fold by itself inside the cell, which always dictates the downstream processing for the purification. In the present manuscript we have discussed about the in vivo and in vitro folding, and structure-function relationship of Dihydrofolate reductase enzyme. This is an important enzyme involved in the cell growth and hence inhibition or inactivation of the enzyme may reduce the cell growth. It was observed that the equilibrium unfolding transition of DHFR proceeds through the formation of intermediates having higher exposed surface hydrophobicity, unchanged enzymatic activity and minimum changes in the secondary structural elements. Because of enhanced surface hydrophobicity, and unchanged enzymatic activity, these intermediates could be a nice target for designing drugs against DHFR.

基于密度泛函理论研究聚醚类破乳剂的构效关系

油田采出液处理工艺中化学破乳剂的使用能够大大提升工作效率并且节约成本,其中聚醚类破乳剂的应用最为广泛,研究聚醚类破乳剂的构效关系对于新型破乳剂的研发及应用至关重要。本文首先对几种聚醚类破乳剂和反相破乳剂的破乳效果进行了评价和比较,然后根据沥青质分子的结构特点及现有聚醚类破乳剂和反相破乳剂的类型,选取了相应的模型分子,通过密度泛函理论(DFT)中B3LYP/6-31G基组得到其最优分子几何构型和静电势分布图,并利用泛函M062X/6-31G基组计算了聚醚类破乳剂模型分子分别与沥青质模型分子和水分子之间的相互作用能。结合聚醚类破乳剂和反相破乳剂的破乳性能评价结果,进而分析了聚醚类破乳剂的构效关系。结果表明,由理论化学计算结果所推测的破乳剂的破乳性能差异与其实际破乳效果相一致:具有支状结构、聚合度较高的聚醚类破乳剂的效果优于线型结构、聚合度较低的聚醚类破乳剂;酚醛树脂聚醚的破乳效果优于酚胺树脂聚醚,而反相破乳剂中则是多元醇聚醚类反相破乳剂的效果较优。该工作的开展表明采用密度泛函理论进行破乳剂的构效关系研究是可行的,能够为未来新型破乳剂的制备及选用奠定重要的理论基础和提供参考依据。

论能动司法视野下家事司法的人际关系调整功能

能动司法要求家事司法除了从法律上处理家事案件当事人之间的法律争议外,还应当发挥家事司法的人际关系调整功能。家事司法人际关系调整功能就是家事司法所发挥的帮助家事案件当事人修复或重建当事人之间人际关系的作用。家事司法人际关系调整功能是独立于纠纷解决功能之外的家事司法的一项基本功能。家事司法人际关系调整功能确立是应对家事案件的特殊性和实现家事司法正义的要求。为实现家事司法的人际关系调整功能,必须将能动司法理念贯穿于家事司法的始终,要求法院将人际关系调整贯穿于家事司法全过程,联合社会力量共同参与家事司法中当事人人际关系调整,采用家事调解、婚姻家庭辅导教育、心理疏导等多种机制帮助家事案件当事人调整人际关系,并建立相应的配套措施。

基于原子/分子团簇结构的材料与器件制造

原子/分子团簇是物质结构的一种新形态,具有独特的本征性质。从原子/分子团簇到器件的跨尺度制造,将为国防高端装备和新兴电子等产业发展带来深刻变革。团簇的多物质构效关系、宏量制造、团簇结构跨尺度构筑以及团簇器件的高性能制造等是原子/分子团簇器件制造的关键发展方向,主导着从原子到产品制造的发展历程。把握这些发展背后的重要机遇,将有助于占领原子级制造研究的制高点,引领原子级制造方法的变革。本文从团簇新材料的宏量制造、新型功能器件的原子/分子团簇构筑、团簇—器件的跨尺度制造工艺和装备等三个方面概括了原子/分子团簇与器件制造领域的主要研究进展,总结了原子/分子团簇与器件领域的关键科学问题及面临的挑战,并对其未来发展方向和发展战略给出了建议。

刈割对滇西北退化高寒草甸植物化学计量特征的影响

为探究环境干扰对退化高寒草甸植物化学计量特征的影响,该研究于2018—2020年对香格里拉市3个退化程度[轻度退化(LD)、中度退化(MD)、重度退化(SD)]的高寒草甸开展刈割试验,进而分析退化高寒草甸植物C、N、P含量、C∶N∶P和N-P幂函数关系在不同刈割年限(0、1、2 a)之间的差异。结果表明:(1)除莎草科P含量外,草甸植物群落、禾本科和杂类草的C、N、P含量在退化程度间无显著差异(P>0.05)。随着刈割年限的增加,退化草甸植物C、N、P含量呈先增后降的趋势(P<0.05)。(2)草甸植物C∶N和C∶P在退化程度间无差异(P>0.05)。从LD到SD,植物群落、莎草科和杂类草的N∶P比先小幅下降再显著上升(P<0.05),禾本科的N∶P未发生显著变化(P>0.05)。(3)随刈割年限增加,草甸植物的C∶N和C∶P呈先降后增、N∶P呈先增后降的趋势。刈割0 a时,莎草科的C∶P和N∶P显著高于杂类草(P<0.05),与植物群落和禾本科无差异(P>0.05);刈割1 a和2 a时,莎草科的C∶P和N∶P高于植物群落和其他功能群(P<0.05);在各刈割年限,植物群落和各功能群植物间的C∶N无差异(P>0.05)。(4)随刈割年限增加,退化草甸植物的N-P幂函数关系由弱变强、幂指数趋于稳定。莎草科的N-P幂指数(小于0.1)与植物群落、禾本科和杂类草的幂指数(稳定在0.19~0.22之间)明显不同。该研究发现,刈割干扰下退化高寒草甸植物生态化学计量特征在退化程度间差异不大,但其随刈割年限增加发生显著变化,这说明滇西北不同退化程度高寒草甸对刈割干扰可能具有相似的响应过程。

Linear QSAR Regression Models for the Prediction of Bioconcentration Factors of Chloroanilines in Fish by Density Functional Theory

Density functional theory（DFT）-B3LYP level with the 6-311G＊＊（d,p） basis set was used to calculate a set of molecular quantum chemical descriptors of 12 chloroanilines. Quantitative structure-activity relationship（QSAR） models of the bioconcentration factors（BCF） of the anilines in fish were established using some of the following calculated descriptors： EHOMO, ENHOMO, ELUMO, ENLUMO, ΔE1（= ELUMO- EHOMO）, ΔE2（= ENLUMO- ENHOMO）, dipole moment（μ）, molecular volume（V）, vibrational energy of 0 K（Ev）, thermodynamic energy（E）, heat capacity（Cv）, entropy（Sm） and the charge of benzene ring（Qph）. Using the variable selection and leaps-and-bounds regression, the quantum chemical descriptors derived directly from the molecular structures were employed to develop a linear QSAR model between the bioconcentration factors（BCF） and two descriptors（Sm, ENHOMO） of 12 chloroanilines. Statistically, the most significant one is a two-parameter linear equation with the correlation coefficient（R^2） of 0.981 and cross-validated correlation coefficient（Rcv^2） of 0.967. The established QSAR model has good stability and predictability based on the results from Rcv2 of leave-one-out cross-validation, AIC, FIT and tα/2. The quantum chemical analyses were performed from two aspects of frontier molecular orbital and entropy. The results show that two structural describers are crucial to the bioconcentration activity of chloroanilines.