Fibulin-5/DANCE is essential for elastogenesis in vivo.

The elastic fibre system has a principal role in the structure and function of various types of organs that require elasticity, such as large arteries, lung and skin. Although elastic fibres are known to be composed of microfibril proteins (for example, fibrillins and latent transforming growth factor (TGF)-beta-binding proteins) and polymerized elastin, the mechanism of their assembly and development is not well understood. Here we report that fibulin-5 (also known as DANCE), a recently discovered integrin ligand, is an essential determinant of elastic fibre organization. fibulin-5-/- mice generated by gene targeting exhibit a severely disorganized elastic fibre system throughout the body. fibulin-5-/- mice survive to adulthood, but have a tortuous aorta with loss of compliance, severe emphysema, and loose skin (cutis laxa). These tissues contain fragmented elastin without an increase of elastase activity, indicating defective development of elastic fibres. Fibulin-5 interacts directly with elastic fibres in vitro, and serves as a ligand for cell surface integrins alphavbeta3, alphavbeta5 and alpha9beta1 through its amino-terminal domain. Thus, fibulin-5 may provide anchorage of elastic fibres to cells, thereby acting to stabilize and organize elastic fibres in the skin, lung and vasculature.     

Cephalosporin antibiotics can be modified to inhibit human leukocyte elastase

Several laboratories, including our own have reported the synthesis and activity of certain low relative molecular mass inhibitors of mammalian serine proteases, especially human leukocyte elastase (HLE, EC 3.4.21.37), an enzyme whose degradative activity on lung elastin has been implicated as a major causative factor in the induction of pulmonary emphysema, and which is present in the azurophil granules of human polymorphonuclear leukocytes (PMN). Normally, these granules fuse with phagosomes containing engulfed foreign material (such as bacteria), and HLE, in combination with other lysosomal enzymes, catabolizes the particles. Under certain pathological conditions, however, PMN become attached to host protein (elastin fibres, basement membrane, connective tissue, immune complexes), and in response to this adherence, the granules may fuse with the PMN outer membrane and release their contents, including HLE, directly onto the tissue. Besides emphysema, HLE may also contribute to the pathogenesis of disease states such as adult respiratory distress syndrome, and its potential involvement in rheumatoid arthritis makes HLE inhibitors of considerable interest. It is known that cephalosporin antibiotics (for example, cephalothin (compound I, Table 2)) are acylating inhibitors of bacterial serine proteases which help synthesize the cell wall by performing a transpeptidation reaction on a peptidyl substrate bearing a D-Ala-D-Ala terminus. We now report that neutral cephalosporins (that is, compounds not bearing a free carboxyl at position C-4) can be modified to become potent time-dependent inhibitors of HLE.     

Synthesis and properties of crosslinked recombinant pro-resilin

Resilin is a member of a family of elastic proteins that includes elastin, as well as gluten, gliadin, abductin and spider silks. Resilin is found in specialized regions of the cuticle of most insects, providing low stiffness, high strain and efficient energy storage; it is best known for its roles in insect flight and the remarkable jumping ability of fleas and spittle bugs. Previously, the Drosophila melanogaster CG15920 gene was tentatively identified as one encoding a resilin-like protein (pro-resilin). Here we report the cloning and expression of the first exon of the Drosophila CG15920 gene as a soluble protein in Escherichia coli. We show that this recombinant protein can be cast into a rubber-like biomaterial by rapid photochemical crosslinking. This observation validates the role of the putative elastic repeat motif in resilin function. The resilience (recovery after deformation) of crosslinked recombinant resilin was found to exceed that of unfilled synthetic polybutadiene, a high resilience rubber. We believe that our work will greatly facilitate structural investigations into the functional properties of resilin and shed light on more general aspects of the structure of elastomeric proteins. In addition, the ability to rapidly cast samples of this biomaterial may enable its use in situ for both industrial and biomedical applications.     

沥青路面温度应力分析

把沥青路面视为多层弹性半空间轴对称体,利用热弹性力学以及Hankel和Laplace积分变换等数学方法,首先推导出任意一层沥青路面温度应力的刚度矩阵,然后按传统的有限元方法组成总体刚度矩阵.通过求解由总体刚度矩阵所构成的代数方程和Hankel及Laplace积分逆变换就可解出外荷载和温度联合作用下沥青路面温度应力的精确解.由于刚度矩阵的元素中不含有正指数项,计算时不会出现溢出现象,从而克服了传递矩阵法的缺点.在推导过程中不用人为选择应力函数,使得问题的求解更加合理,同时也为进一步研究沥青路面的湿度场、动力学等问题奠定了理论基础.计算实例证明了推导结果的正确性.     

Nanoscale chemical tomography of buried organic-inorganic interfaces in the chiton tooth

Biological organisms possess an unparalleled ability to control the structure and properties of mineralized tissues. They are able, for example, to guide the formation of smoothly curving single crystals or tough, lightweight, self-repairing skeletal elements. In many biominerals, an organic matrix interacts with the mineral as it forms, controls its morphology and polymorph, and is occluded during mineralization. The remarkable functional properties of the resulting composites-such as outstanding fracture toughness and wear resistance-can be attributed to buried organic-inorganic interfaces at multiple hierarchical levels. Analysing and controlling such interfaces at the nanometre length scale is critical also in emerging organic electronic and photovoltaic hybrid materials. However, elucidating the structural and chemical complexity of buried organic-inorganic interfaces presents a challenge to state-of-the-art imaging techniques. Here we show that pulsed-laser atom-probe tomography reveals three-dimensional chemical maps of organic fibres with a diameter of 5-10?nm in the surrounding nano-crystalline magnetite (Fe(3)O(4)) mineral in the tooth of a marine mollusc, the chiton Chaetopleura apiculata. Remarkably, most fibres co-localize with either sodium or magnesium. Furthermore, clustering of these cations in the fibre indicates a structural level of hierarchy previously undetected. Our results demonstrate that in the chiton tooth, individual organic fibres have different chemical compositions, and therefore probably different functional roles in controlling fibre formation and matrix-mineral interactions. Atom-probe tomography is able to detect this chemical/structural heterogeneity by virtue of its high three-dimensional spatial resolution and sensitivity across the periodic table. We anticipate that the quantitative analysis and visualization of nanometre-scale interfaces by laser-pulsed atom-probe tomography will contribute greatly to our understanding not only of biominerals (such as bone, dentine and enamel), but also of synthetic organic-inorganic composites.     

Effect of Post Spinning Modification on the PAN Precursors and Resulting Carbon Fibres

The impregnation of a special grade polyacrylonitrile(PAN) precursor fibres was carried out in a 8 wt.% KMnO4 aqueous solution to obtain modified PAN precusor fibres.The focus is primarily on the effects of modification on the structure and the pbysical properties of precursor fibres,thermal stabilised and their resulting carbon fibres,which were characterized by the combination use of densities,wide-angle X-ray diffraction(WAXD),X-ray photoelectron spectroscopy(XPS),Elemental analysis(EA),Fourier transform infrared(FT-IR) and seaming electron microscope(SEM),etc.KMnO4 as a strong oxidizer can swell,oxidize and corrode the skin of a precursor ibre,transform partly C≡N groups to C=N ones,decrease the crystal size,increase the orientation index,increase the crystallinity irdex,furthemore ircrease the densities of modified PAN precursors and resulting thermal stabilised fibres.As a result,the carbon fibres dcveloped from modified PAN fibres show,an improvment in tensile strength of 31.25% and an improvement in elongation of 77.78%,but a decrease of 16.52% in Young's modulus.     

A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25

Lung cancer is the most common cause of cancer death worldwide, with over one million cases annually. To identify genetic factors that modify disease risk, we conducted a genome-wide association study by analysing 317,139 single-nucleotide polymorphisms in 1,989 lung cancer cases and 2,625 controls from six central European countries. We identified a locus in chromosome region 15q25 that was strongly associated with lung cancer (P = 9 x 10(-10)). This locus was replicated in five separate lung cancer studies comprising an additional 2,513 lung cancer cases and 4,752 controls (P = 5 x 10(-20) overall), and it was found to account for 14% (attributable risk) of lung cancer cases. Statistically similar risks were observed irrespective of smoking status or propensity to smoke tobacco. The association region contains several genes, including three that encode nicotinic acetylcholine receptor subunits (CHRNA5, CHRNA3 and CHRNB4). Such subunits are expressed in neurons and other tissues, in particular alveolar epithelial cells, pulmonary neuroendocrine cells and lung cancer cell lines, and they bind to N'-nitrosonornicotine and potential lung carcinogens. A non-synonymous variant of CHRNA5 that induces an amino acid substitution (D398N) at a highly conserved site in the second intracellular loop of the protein is among the markers with the strongest disease associations. Our results provide compelling evidence of a locus at 15q25 predisposing to lung cancer, and reinforce interest in nicotinic acetylcholine receptors as potential disease candidates and chemopreventative targets.     

Electron microscope evidence for an 80 A unit in collagen fibrils.

Connective tissues are composite structures containing collagen, elastin, glycosaminoglycans, minerals, water and other minor components. In all cases the collagen exists predominantly in fibrillar form. The size distribution of the fibrils does, however, vary markedly with both age and the mechanical requirements of the tissue. Little is known about the mechanism of fibril formation in vivo, although some information is now available form in vitro polymerisation studies. We have now collected new and extensive electron microscope data on the size of collagen fibrils from tendon, skin, cornea and other tissues from both fetal and immature animals. The results reported here show that the diameters of the collagen fibrils thus measured lie close to a multiple of 80 A, a result which may be simply and readily interpreted in terms of the collagen microfibril and its mode of packing.     

基于连续最大流的三维肺实质快速分割算法

肺结节是肺癌的表征形式,形状结构多样且易与正常组织产生粘连,使分割存在困难.提出了一种基于空间约束的三维肺实质分割算法,实现对肺实质组织的分割及目标区域的获取.首先使用SLIC方法将二维CT序列图像构建成超像素图像矩阵,并对矩阵进行稀疏化处理,降低矩阵维度.然后连接相邻切片间的超像素构造肺实质组织的三维结构.最后采用连续最大流方法对构造的三维肺部结构进行分割.实验结果表明,所提算法能够快速准确地分割三维肺实质组织,对不同类型肺结节的分割均取得较好结果,具有一定的临床应用价值.     

Reduced airway surface pH impairs bacterial killing in the porcine cystic fibrosis lung

Cystic fibrosis (CF) is a life-shortening disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Although bacterial lung infection and the resulting inflammation cause most of the morbidity and mortality, how the loss of CFTR function first disrupts airway host defence has remained uncertain. To investigate the abnormalities that impair elimination when a bacterium lands on the pristine surface of a newborn CF airway, we interrogated the viability of individual bacteria immobilized on solid grids and placed onto the airway surface. As a model, we studied CF pigs, which spontaneously develop hallmark features of CF lung disease. At birth, their lungs lack infection and inflammation, but have a reduced ability to eradicate bacteria. Here we show that in newborn wild-type pigs, the thin layer of airway surface liquid (ASL) rapidly kills bacteria in vivo, when removed from the lung and in primary epithelial cultures. Lack of CFTR reduces bacterial killing. We found that the ASL pH was more acidic in CF pigs, and reducing pH inhibited the antimicrobial activity of ASL. Reducing ASL pH diminished bacterial killing in wild-type pigs, and, conversely, increasing ASL pH rescued killing in CF pigs. These results directly link the initial host defence defect to the loss of CFTR, an anion channel that facilitates HCO(3)(-) transport. Without CFTR, airway epithelial HCO(3)(-) secretion is defective, the ASL pH falls and inhibits antimicrobial function, and thereby impairs the killing of bacteria that enter the newborn lung. These findings suggest that increasing ASL pH might prevent the initial infection in patients with CF, and that assaying bacterial killing could report on the benefit of therapeutic interventions.     

远端剪切作用下正交各向异性介质中椭圆夹杂的弹性场分析

求解一类正交各向异性介质中平面椭圆夹杂在远端作用与椭圆主轴呈任意角度均匀剪切力情况下,内受非弹性特征应变引起的弹性场。采用各向异性平面问题的复变函数解法,结合保角变换方法,将远端剪切作用转化为在基体内边界上的初始应变,根据最小应变能原理,获得夹杂/基体系统弹性应力和应变场的封闭形式解析解。     

蟾蜍和麻蜥肝脏及肺组织中低分子蛋白的SDS-PAGE比较分析

用SDS-聚丙烯酰胺凝胶电泳和银染显色法对花背蟾蜍和密点麻蜥肝脏和肺组织中的低分子蛋白质进行了分析．结果表明，花背蟾蜍和密点麻蜥的肝脏和肺组织中蛋白务带分别为21、14、23、16.二者肝脏和肺组织均有各自的特异性务带，且肝脏中蛋白务带多于肺组织．密点麻蜥肝脏和肺组织中蛋白质务带均多于花背蟾蜍．     

氧化处理的炭纤维表面性能

用反相色谱法、电子天平法和ESCA对氧化前后炭纤维的表面性能作了研究。以炭纤维为固定相,正烷烃作探针分子进行了反相色谱实验,求得了炭纤维的吸附等温线。等温线属BrunauerⅡ型,比表面积因氧化而增大。用电子天平法,以正烷烃-甲酰胺-炭纤维体系间接地求得了炭纤维的表面自由能及其分量。表面自由能的极性分量因氧化处理而增大。ESCA的结果表明,经氧化处理后炭纤维表面的[O]/[C]比增大,但氧化影响仅限于表面,而对距表面5nm以下没有影响。     

Horses damp the spring in their step.

The muscular work of galloping in horses is halved by storing and returning elastic strain energy in spring-like muscle-tendon units.These make the legs act like a child's pogo stick that is tuned to stretch and recoil at 2.5 strides per second. This mechanism is optimized by unique musculoskeletal adaptations: the digital flexor muscles have extremely short fibres and significant passive properties, whereas the tendons are very long and span several joints. Length change occurs by a stretching of the spring-like digital flexor tendons rather than through energetically expensive length changes in the muscle. Despite being apparently redundant for such a mechanism, the muscle fibres in the digital flexors are well developed. Here we show that the mechanical arrangement of the elastic leg permits it to vibrate at a higher frequency of 30-40 Hz that could cause fatigue damage to tendon and bone. Furthermore, we show that the digital flexor muscles have minimal ability to contribute to or regulate significantly the 2.5-Hz cycle of movement, but are ideally arranged to damp these high-frequency oscillations in the limb.     

Nucleation and growth of fibres and gel formation in sickle cell haemoglobin

Deoxygenated sickle haemoglobin polymerizes into long 210-A diameter fibres that distort and decrease the deformability of red blood cells, and cause sickle cell disease. The fibres consist of seven intertwined double strands. They can form birefringent nematic liquid crystals (tactoids) and spherulites. Rheologically, the system behaves as a gel. The equilibria show a phase separation and a solubility. The reaction kinetics show a delay time, are then roughly exponential and are highly dependent on concentration and temperature, and accord with the double nucleation model. But these conclusions are derived from macroscopic data, without direct observation of individual fibres. We have now used non-invasive video-enhanced differential interference contrast (DIC) and dark-field microscopy to observe nucleation, growth and interaction of sickle deoxyhaemoglobin fibres in real time. The fibres originate both from centres that produce many radially distributed fibres and on the surface of pre-existing fibres, from which they then branch. The resulting network is cross-linked and dynamic in that it is flexible and continues to grow and cross-link. Our results support most aspects of the double nucleation model.     

Nonlinear material behaviour of spider silk yields robust webs

Natural materials are renowned for exquisite designs that optimize function, as illustrated by the elasticity of blood vessels, the toughness of bone and the protection offered by nacre. Particularly intriguing are spider silks, with studies having explored properties ranging from their protein sequence to the geometry of a web. This material system, highly adapted to meet a spider's many needs, has superior mechanical properties. In spite of much research into the molecular design underpinning the outstanding performance of silk fibres, and into the mechanical characteristics of web-like structures, it remains unknown how the mechanical characteristics of spider silk contribute to the integrity and performance of a spider web. Here we report web deformation experiments and simulations that identify the nonlinear response of silk threads to stress--involving softening at a yield point and substantial stiffening at large strain until failure--as being crucial to localize load-induced deformation and resulting in mechanically robust spider webs. Control simulations confirmed that a nonlinear stress response results in superior resistance to structural defects in the web compared to linear elastic or elastic-plastic (softening) material behaviour. We also show that under distributed loads, such as those exerted by wind, the stiff behaviour of silk under small deformation, before the yield point, is essential in maintaining the web's structural integrity. The superior performance of silk in webs is therefore not due merely to its exceptional ultimate strength and strain, but arises from the nonlinear response of silk threads to strain and their geometrical arrangement in a web.     

双黄莲促进冲击波致严重层头皮和脑损伤修复实验研究

探索双黄莲液对冲击波导致的严重全层头皮和脑损伤的自体组织修复的促进作用，对爆炸冲击波致伤的并已污染的实验家兔进行暴露疗法治疗，切除损伤的头皮，用自体颅骨膜或帽状腱膜粘贴于颅骨面上，双黄莲液喷雾，同时日服2ml双黄莲3次，观察疗效，12d后，10只受伤家兔神经症状和体症消失，修复的头皮不同程度地长出头发，说明双黄莲液具有活血化瘀、调节机体免疫功能、抗感染及诱导组织产生超氧化物歧化酶等多种作用，对冲击波损伤的自体组织的重建和修复具有促进作用。     

Biomimetic self-templating supramolecular structures

In nature, helical macromolecules such as collagen, chitin and cellulose are critical to the morphogenesis and functionality of various hierarchically structured materials. During tissue formation, these chiral macromolecules are secreted and undergo self-templating assembly, a process whereby multiple kinetic factors influence the assembly of the incoming building blocks to produce non-equilibrium structures. A single macromolecule can form diverse functional structures when self-templated under different conditions. Collagen type I, for instance, forms transparent corneal tissues from orthogonally aligned nematic fibres, distinctively coloured skin tissues from cholesteric phase fibre bundles, and mineralized tissues from hierarchically organized fibres. Nature's self-templated materials surpass the functional and structural complexity achievable by current top-down and bottom-up fabrication methods. However, self-templating has not been thoroughly explored for engineering synthetic materials. Here we demonstrate the biomimetic, self-templating assembly of chiral colloidal particles (M13 phage) into functional materials. A single-step process produces long-range-ordered, supramolecular films showing multiple levels of hierarchical organization and helical twist. Three distinct supramolecular structures are created by this approach: nematic orthogonal twists, cholesteric helical ribbons and smectic helicolidal nanofilaments. Both chiral liquid crystalline phase transitions and competing interfacial forces at the interface are found to be critical factors in determining the morphology of the templated structures during assembly. The resulting materials show distinctive optical and photonic properties, functioning as chiral reflector/filters and structural colour matrices. In addition, M13 phages with genetically incorporated bioactive peptide ligands direct both soft and hard tissue growth in a hierarchically organized manner. Our assembly approach provides insight into the complexities of hierarchical assembly in nature and could be expanded to other chiral molecules to engineer sophisticated functional helical-twisted structures.     

Slc24a5在不同毛色绵羊皮肤中的表达和定位研究

为研究阳离子交换体(solute carrier family 24member 5,Slc24a5)在不同毛色绵羊皮肤中的表达情况,探究其与毛色形成之间的关系采用实时荧光定量PCR(qRT-PCR)技术分析黑色和白色绵羊皮肤中Slc24a5的相对表达量,并运用Western blot和免疫组织化学方法对不同体色绵羊皮肤中Slc24a5蛋白的表达和定位情况进行分析.结果显示:Slc24a5基因在黑色绵羊皮肤组织中的相对表达量是白色绵羊皮肤组织的20.53倍(P0.01);Western blot印迹结果证实绵羊皮肤组织总蛋白中存在分子量约为51kD的蛋白质条带,且黑色绵羊皮肤平均蛋白表达量显著高于白色绵羊(P0.01).免疫组织化学结果显示,Slc24a5在绵羊皮肤毛囊外根鞘和毛基质处均呈阳性表达,且根据光密度值分析显示,Slc24a5在黑色绵羊中的平均蛋白质表达量显著高于白色绵羊.以上研究结果显示Slc24a5可能与绵羊毛色形成具有一定的相关性.     

Avoiding obstacles by using a proximity infrared sensor skin

Placement and wiring of vast amount of sensor elements on the 3-dimensionally configured robot surface to form soft sensor skin is very difficult with the traditional technology. In this paper we propose a new method to realize such a skin. By implanting infrared sensors array in an elastic body, we obtain an elastic and tough sensor skin that can be shaped freely. The developed sensor skin is a large-area, flexible array of infrared sensors with data processing capabilities. Depending on the skin electronics, it endows its carrier with an ability to sense its surroundings. The structure, the method of infrared sensor signal processing, and basic experiments of sensor skin are presented. The validity of the infrared sensor skin is investigated by preliminary obstacle avoidance trial.