原核细胞骨架蛋白的结构与功能

长期以来,人们认为细胞骨架仅为真核生物所特有的结构,但近年来的研究发现它也存在于细菌等原核生物中。目前已经在细菌中发现的FtsZ、MreB和CreS依次与真核细胞骨架蛋白中的微管蛋白、肌动蛋白丝及中间丝类似。FtsZ能在细胞分裂位点装配形成Z环结构,并通过该结构参与细胞分裂的调控;MreB能形成螺旋丝状结构,其主要功能有维持细胞形态、调控染色体分离等;CreS存在于新月柄杆菌中,它在细胞凹面的细胞膜下面形成弯曲丝状或螺旋丝状结构,该结构对维持新月柄杆菌细胞的形态具有重要作用。     

植物早期光诱导蛋白的结构、功能及表达模式研究进展

早期光诱导蛋白(earlylight-induced protein,ELIPs)属于叶绿素结合蛋白(chlorophyll a/b binding proteins,Cabs)超家族,是一类定位于叶绿体类囊体膜上的跨膜蛋白,在蓝藻、苔藓、高等微管植物中都有发现,具有悠久的进化历史。其最早在黄化的豌豆幼苗转绿过程中被发现,因其受诱导的时间比其它光诱导蛋白都早,并在光合器官发育完整后迅速消失,具有瞬时积累的特性而得名。它含有三个跨膜α螺旋,其中第1、3螺旋高度同源并通过谷氨酸和精氨酸之间的离子键交叉相连形成双重对称结构;通过充当色素临时载体或抑制叶绿素的合成等方式行使其光保护和非生物胁迫抗性等功能;它能够受多种非生物胁迫的诱导,如干旱、高盐、低温、高温、强光、UV等;它根据跨膜螺旋数的不同可以分为4个不同的组,且螺旋数变化与环境的变换同步,预示着其功能的不断发展。     

葛仙米血红素氧合酶基因Ns-HO1异源表达及其蛋白结构模拟

为明确葛仙米(Nostoc sphaeroides)中血红素氧合酶(Heme oxygenase, HO)基因编码蛋白的分子进化地位和高级结构, 克隆该基因并进行原核细胞表达, 氨基酸序列比对与分子进化分析和Swiss-model高级结构模拟。结果显示: 葛仙米血红素氧合酶基因Ns-HO1密码区全长为678 bp, 预编码一含225个氨基酸的蛋白质; Ns-HO1与同源蛋白氨基酸相似性达90.3%, 存在少部分位点替换突变, 但底物血红素的预结合位点(如Arg10和Tyr125)及金属离子结合位点(His17)等关键位点的氨基酸保持稳定。 构建表达载体, 葛仙米Ns-HO1在大肠杆菌中成功诱导表达, SDS-PAGE检测目的蛋白大小近26.0 kD; 分子进化树分析显示Ns-HO1与普通念珠藻、发状念珠藻中同源蛋白聚类于同一分支, 并与点状念珠藻中同源蛋白具有共同祖先。Ns-HO1蛋白多肽链形成8个主要α-螺旋,其中N和C末端的两个α-螺旋与第四螺旋共同为Ns-HO1高级结构提供底面支撑, 其他螺旋围绕该底面进一步延展并充填其中, 形成Ns-HO1分子的类夹心式结构。在高级结构中, 含血红素预结合位点氨基酸的几个螺旋(第一、 五和七螺旋)位于Ns-HO1分子外围, 这些分支螺旋为形成Ns-HO1夹心空间以利于底物血红素锚定和产物及时释放提供了条件。总之, 研究为深入了解与运用葛仙米血红素氧合酶基因的生物学功能和资源提供了基础。     

螺旋-环区-螺旋蛋白质—DNA 结合蛋白的新类型

最近发现了一种特殊的蛋白质结构域,它广泛地存在于动、植物体的 DNA 结合蛋白(DBP)中.此结构称为螺旋-环区-螺旋(helix-loop-helix,HLH)结构.c-myc 基因和 MyoD 基因的蛋白质产物有此结构.在增强子结合蛋白(EBP)中也发现了 HLH 结构,如 E2A 基因的产物——E12/E47.已报道的20多种 HLH蛋白质几乎全与转录的调节和肿瘤的发生有关.     

翻译速率与蛋白质二级结构的关系

统计分析了人的 119种蛋白质和大肠杆菌的 92种蛋白质密码子翻译速率和蛋白质二级结构的关系。据m 密码子片段在不同二级结构中的频数分布 ,我们发现人和大肠杆菌中翻译速率与蛋白质二级结构之间有一定关系 :高翻译速率时倾向编码α螺旋、不倾向编码线团 (coil) ;低翻译速率时倾向编码线团、不倾向编码α螺旋 ;β折叠结构则随翻译速率表现出明显的振荡。同时 ,密码子的使用在不同片段内一般也是不均匀的 :在α螺旋片段内 ,结构尾部偏向使用高翻译速率密码子 ;中部倾向使用中翻译速率密码子 ;而头部使用的密码子翻译速率偏低。这样的倾向性不大可能归结为随机起伏的影响。     

模拟α-螺旋多肽类似物抑制剂设计的研究进展

抑制剂筛选主要是通过反复、高通量地筛选化合物库,这个过程存在着对已有化合物库的依赖性和一定的机遇性。通过分析蛋白质数据库(PDB)发现,大多数蛋白质-蛋白质相互作用(PPI)界面以α-螺旋结构为主体。α-螺旋多肽的骨架结构及其热点氨基酸残基(hotspots)为高效理性设计小分子抑制剂提供了模板。对近几年来依据多肽类似物和小分子化合物模拟α-螺旋结构设计抑制剂的研究进展进行了概述,同时对依据模拟α-螺旋设计抑制剂骨架的结构原理进行了讨论。     

耐热甜味蛋白brazzein的溶液NMR结构研究——二级结构和分子骨架

brazzein是从非洲西部野生植物PentadiplandrabrazzeanaBaillon的果实中提取的一种甜味蛋白 .在所有已知的甜味蛋白质中 ,brazzein的分子量最小 ,水溶性最好 ,并且具有很好的热稳定性 .利用二维核磁共振 ( 2DNMR)技术研究brazzein的溶液三维结构 ,完成了包括主链和侧链在内的所有质子共振峰的序列归属 .brazzein的二级结构包含一段α螺旋 ( 2 1～ 2 9) ,一段较短的 310 螺旋 ( 1 4～ 1 7)和两股反平行 β折叠 ( 34～ 39,44～ 5 0 ) ,分子N端可能形成了第 3股 β链 ( 5～ 7) .比较研究发现 ,该甜味分子骨架CSαβ与蝎毒、昆虫防卫素和植物抗菌蛋白γ 硫素的分子支架基本相同 .以此为基础 ,讨论了这种多功能分子支架的意义 ,可能的甜味活性中心及其热稳定性的结构基础 .     

鸡胚发育中染色体长度的变化及螺旋结构

对孵育3-72小时家鸡胚胎染色体长度及螺旋结构进行了比较研究,同时还考察了染色体DNA含量的变化。结果表明：(1)家鸡染色体的最高一级结构是螺旋结构。(2）随胚胎发育的进展,染色体绝对长度逐渐缩短。(3）伴随染色体的缩短,其螺旋数目亦相应地减少,而螺旋直径却有一定程度增加。(4）每个中期板的染色体DNA含量并不随发育进展而变化。本文还讨论了发育中染色体缩短与螺旋结构间的相互关系。     

DynaCT对肝转移瘤介入治疗具有指导意义

为了探讨锥形束CT (DynaCT)在肝癌患者实施经导管肝动脉化疗栓塞(TACE)手术治疗中的指导作用、栓塞效果评估中的价值,本研究选取了2012年3月至2015年5月在本院实施TACE手术治疗的102例原发性肝癌或转移性肝癌患者进行研究。通过对102例患者病灶进行手术前螺旋CT检测、术中数字减影血管造影(DSA)及DynaCT检测,并对比DSA与DynaCT对肝癌病灶、供血动脉、术后栓塞效果的检测结果。本研究发现术前普通螺旋CT共计检出病灶105个,术中DSA检出病灶数目176个,DynaCT术中检出肿瘤病灶285个;DynaCT和DSA的平均检出病灶数目均显著的高于普通螺旋CT (p<0.05),DynaCT平均检出病灶数目均显著的高于DSA (p<0.05);DynaCT的病灶供血动脉检出率为86.67%,显著地高于DSA (55.68%)(p<0.05);DynaCT检出的285个病灶对栓塞效果评估结果与实际栓塞效果一致的有271个病灶(95.09%),DSA评估结果与实际结果一致的有138个病灶(78.41%),DynaCT对于TACE术后效果评估的一致性高于DSA (p<0.05)。本研究表明,DynaCT在肝癌患者实施TACE手术治疗中能够更有效的发现病灶,指导栓塞操作。     

肋螺距对管式微藻反应器光暗循环性能的影响

对一种新型带螺旋肋的光生物反应器进行数值模拟,采用粒子追踪模型模拟微藻在反应器中的运动情况,分析微藻细胞经历的光暗循环频率f_(av)、反应器光暗循环强化效率η随螺旋肋螺距P_s的变化情况。结果表明,随着P_s的增加,f_(av)、η出现峰值。f_(av)在P_s=400mm的反应器中最大,为0.5794Hz;η的峰值则出现在P_s=800mm的反应器中。分析发现,在0.5m/s的进口速度下,P_s=400mm、600mm、800mm时,螺旋肋的存在对提高f_(av)有正面作用,P_s=200mm、1000mm时,螺旋肋的存在限制了f_(av)的提高。可通过调整螺旋肋的结构参数达到对流场的调整,从而改变微藻所受光暗循环的情况。     

Analysis and prediction of functionally important sites in proteins

The rapidly increasing volume of sequence and structure information available for proteins poses the daunting task of determining their functional importance. Computational methods can prove to be very useful in understanding and characterizing the biochemical and evolutionary information contained in this wealth of data, particularly at functionally important sites. Therefore, we perform a detailed survey of compositional and evolutionary constraints at the molecular and biological function level for a large set of known functionally important sites extracted from a wide range of protein families. We compare the degree of conservation across different functional categories and provide detailed statistical insight to decipher the varying evolutionary constraints at functionally important sites. The compositional and evolutionary information at functionally important sites has been compiled into a library of functional templates. We developed a module that predicts functionally important columns (FIC) of an alignment based on the detection of a significant "template match score" to a library template. Our template match score measures an alignment column's similarity to a library template and combines a term explicitly representing a column's residue composition with various evolutionary conservation scores (information content and position-specific scoring matrix-derived statistics). Our benchmarking studies show good sensitivity/specificity for the prediction of functional sites and high accuracy in attributing correct molecular function type to the predicted sites. This prediction method is based on information derived from homologous sequences and no structural information is required. Therefore, this method could be extremely useful for large-scale functional annotation.     

Developing synthetic conical nanopores for biosensing applications

In this review we bring together recent results from our group focused towards the development of biosensors from single conically-shaped artificial nanopores. The nanopores, used in the work presented here, were prepared using the track-etch process. The fabrication of track-etched conical nanopores has been optimized to allow for single nanopores with reproducible dimensions to be prepared. We have also demonstrated techniques that allow for easy and controllable manipulation of nanopore geometry (e.g., cone angle). We will consider the ion transport properties of the conical nanopores and factors that affect these properties. Methods for introducing functions that mimic biological ion channels, such as voltage-gating, into these nanopores will also be addressed. Three prototype sensors developed from single conical nanopores will be presented. In the first two sensors, the single conical nanopores function as resistive-pulse sensors and detect the presence of analytes as current-blockade events in the ion current. The third sensor functions in an on/off mode, much like a ligand-gated ion channel. In the presence of a target analyte, the ion current permanently shuts off.     

III型干扰素相关生物学功能的研究进展

干扰素（Interferon,IFN）是一类具有多功能生物活性的糖蛋白,包含3个家族（I型、II型和III型）。III型干扰素（Type III interferon,IFN-III）是近16年发现的新型干扰素,其诱导过程及生物学功能与I型干扰素（Type I interferon,IFN-I）相似,在抗病毒、免疫调节、抗肿瘤、抑制自身免疫病、抑制过敏性哮喘以及抗细菌和真菌等方面具有重要作用。本文将从IFN-I和IFN-III的分类、序列同源性和信号传导等方面进行阐述,并结合近年来IFN-III在疾病治疗过程中所取得的成就,综述IFN-III的生物学功能,旨在为IFN-III的深入研究以及在多种疾病的诊断和防控中提供参考。     

"F"型置钉与FNS固定术对成人创伤性Pauwels III型股骨颈骨折患者疗效、骨折愈合状况及髋关节功能的影响

摘要 目的：探讨"F"型置钉与新型股骨颈内固定系统（FNS）固定术对成人创伤性Pauwels III型股骨颈骨折疗效、骨折愈合状况及髋关节功能的影响。方法：选取2019年1月-2021年12月我院收治的78例成人创伤性Pauwels III型股骨颈骨折患者作为研究对象,采用随机数字表法将患者分为对照组及研究组,各36例。对照组采用FNS进行治疗,观察组采用"F"型置钉内固定术进行治疗。观察并比较两组患者治疗疗效、术后情况、骨折愈合情况、髋关节功能、骨折复位质量及并发症发生情况。结果：观察组治疗总有效率80.56%高于对照组52.78%（P<0.05）。观察组住院时间、下地行走时间及完全负重时间均短于对照组（P<0.05）。观察组骨折愈合状况优于对照组（P<0.05）。两组患者Harris评分随时间发展而逐渐升高,且观察组术后1个月、术后3个月及术后6个月评分均高于对照组（P<0.05）。观察组骨折复位率77.78%高于对照组41.67%（P<0.05）。观察组并发症发生率低于对照组（P<0.05）。结论："F"型置钉及FNS固定术均可以治疗成人创伤性Pauwels III型股骨颈骨折患者,但"F"型置钉治疗疗效更好,并且力学稳定性能更好,术后并发症较少,利于患者术后恢复,值得在临床治疗中推广使用。     

Plasmonic Fano Resonances in Single-Layer Gold Conical Nanoshells

Plasmonic Fano resonances arise in symmetric single-layer conical nanoshells, which can be switched on and off by changing the polarization of the incident electric field. By breaking the symmetry, higher-order dark hybridized modes emerge in the spectrum, which couple to the superradiant bright mode and induce higher-order plasmonic Fano resonances. From a comparison with spherical nanostructures, it comes out that single-layer conical nanoshells are found to be highly capable in the generation of higher-order Fano resonances with larger modulation depths in the optical spectra. Such nanostructures are also found to offer high values of figure of merit and contrast ratio due to which they are highly suitable for biological sensors.     

Structural investigations into the interaction of hemoglobin and part structures with bacterial endotoxins

An understanding of details of the interaction mechanisms of bacterial endotoxins (lipopolysaccharide, LPS) with the oxygen transport protein hemoglobin is still lacking, despite its high biological relevance. Here, a biophysical investigation into the endotoxin:hemoglobin interaction is presented which comprises the use of various rough mutant LPS as well as free lipid A; in addition to the complete hemoglobin molecule from fetal sheep extract, also the partial structure alpha-chain and the heme-free sample are studied. The investigations comprise the determination of the gel-to-liquid crystalline phase behaviour of the acyl chains of LPS, the ultrastructure (type of aggregate structure and morphology) of the endotoxins, and the incorporation of the hemoglobins into artificial immune cell membranes and into LPS. Our data suggest a model for the interaction between Hb and LPS in which hemoglobins do not react strongly with the hydrophilic or with the hydrophobic moiety of LPS, but with the complete endotoxin aggregate. Hb is able to incorporate into LPS with the longitudinal direction parallel to the lipid A double-layer. Although this does not lead to a strong disturbance of the LPS acyl chain packing, the change of the curvature leads to a slightly conical molecular shape with a change of the three-dimensional arrangement from unilamellar into cubic LPS aggregates. Our previous results show that cubic LPS structures exhibit strong endotoxic activity. The property of Hb on the physical state of LPS described here may explain the observation of an increase in LPS-mediating endotoxicity due to the action of Hb.     

Amylose content and chemical modification effects on the extrusion of thermoplastic starch from maize

The effects of starch structural properties and starch modification on extruder operation were monitored via die pressure, motor torque, mean residence time and specific mechanical energy (SME). The structural properties studied involved variations in the ratios of amylose and amylopectin as well as the effect of a hydroxypropylated starch on the fore mentioned extruder properties. A full factorial design of experiments (DOE) was used to then determine the influence of starch type (unmodified starches with 0%, 28%, 50% and 80% amylose; 80% amylose hydroxypropylated starch) and screw speed (250, 300 and 350 rpm) on these processing parameters. The effects of starch type and screw speed on extrusion operation that were systematically investigated using the DOE and have provided valuable insight into the relationships between starch structure and processing. The design of experiments showed that starch type for both unmodified and modified maize had a statistically significant effect on parameters such as torque, die pressure and specific mechanical energy and that screw speed also significantly effected specific mechanical energy. Residence time distributions differed according to starch type (amylose content, hydroxypropylation) and screw speed. The additional study of residence time distribution also gave an indication of the degree of mixing in the extruder. Starch type variations were apparent at low screw speed however at higher screw speed the influence of starch type decreased significantly.     

血型与气质类型和疾病相关性的生物学机制

血型与气质类型关系的研究属于人格的生物学研究范畴,其最早的研究在日本,1927年日本学者古川竹二(Furukawa)提出气质血型学说,在学术界和社会上都产生很大影响。早期对气质血型论的研究主要是通过统计学方法进行研究,缺少对其相关生物学机制的探讨,从而引起较大的争论。上世纪五十年代血型与疾病相关性的研究也引起许多学者的关注。气质类型与遗传因素、机体生活环境和文化因素等都具有相关性,本文介绍了血型与气质类型和疾病现阶段的主要研究结果,重点是从生物学角度阐述血型与气质类型和疾病等方面具有相关性的原因。     

Studies of the type I cellular retinoic acid-binding protein mutants and their biological activities

We have mutated the type I cellular retinoic acid binding protein (CRABP-I), individually at the Arg131 (into Ala) and the Tyr 133 (into Phe) residues which have been predicted to make direct contact with retinoic acid (RA) based upon previous structural studies. The RA-binding affinities of these mutants are examined and their biological effects on RA induction of reporter genes are determined. The R131A mutation drastically affects its ligand-binding property, but the Y133F mutation has little effect. By using an RA-inducible reporter, it is found that the wild type CRABP-I exerts biphasic effects on RA induction of the reporter. The early (at 12 h) effect is to enhance RA induction, whereas the delayed (at 24 h) effect is to suppress RA induction. In consistence with their RA binding property, the R 131A mutant loses both its early and delayed biological activities, whereas the Y133F mutant remains as effective as the wild type. It is concluded that CRABP-I over-expression exerts biphasic effects on RA-mediated gene expression, and that Arg131, but not Tyr 133, is essential for a high RA-binding affinity of this protein as well as its biological activity.     

空心钉固定治疗骶骨骨折的临床疗效分析

目的:探讨空心钉固定治疗骶骨骨折的临床疗效及其安全性。方法:回顾性分析2010年1月至2013年1月骶骨骨折患者50例,其中男36例,女14例。按照Denis分类法,Ⅰ型22例,Ⅱ型14例,Ⅲ型14例,36例采用空心钉固定治疗,14例采用非手术保守治疗。结果:治疗后,根据Majeed评分标准进行评定,其中空心钉组优10例,良18例,可8例;非手术组优1例,良7例,可6例。全部患者经手术治疗后骨折均愈合,未出现断钉现象。结论:空心钉固定治疗骶骨骨折较保守治疗有更好的功能恢复及生活质量,空心钉固定具有术后恢复快,避免神经损伤,患者可尽早行功能锻炼,促进骨质愈合,改善患者预后,具有良好的临床疗效。