Nonindependence of mammalian dental characters

Studies of mammalian evolution frequently use data derived from the dentition. Dental characters are particularly central for inferring phylogenetic relationships of fossil taxa, of which teeth are often the only recovered part. The use of different aspects of dental morphology as phylogenetic signals implies the independence of dental characters from each other. Here we report, however, that, at least developmentally, most dental characters may be nonindependent. We investigated how three different levels of the cell signalling protein ectodysplasin (Eda) changed dental characters in mouse. We found that with increasing expression levels of this one gene, the number of cusps increases, cusp shapes and positions change, longitudinal crests form, and number of teeth increases. The consistent modification of characters related to lateral placement of cusps can be traced to a small difference in the formation of an early signalling centre at the onset of tooth crown formation. Our results suggest that most aspects of tooth shape have the developmental potential for correlated changes during evolution which may, if not taken into account, obscure phylogenetic history.     

牙髓治疗的后牙纵折451例分析

分析牙髓治疗的后牙发生纵折的原因,并探讨预防措施。对门诊451例牙髓治疗的后牙发生牙纵折的牙齿特点和牙折情况进行检查和分析。牙髓治疗的后牙发生纵折处,有高尖陡坡或／和牙壁薄弱的牙体特征者占80．71％之多。说明高尖陡坡、薄弱牙壁是后牙纵折的重要原因,调[牙合]和冠套修复是对牙髓治疗后牙进行保护和预防纵折的重要措施。     

High-level similarity of dentitions in carnivorans and rodents

The study of mammalian evolution depends greatly on understanding the evolution of teeth and the relationship of tooth shape to diet. Links between gross tooth shape, function and diet have been proposed since antiquity, stretching from Aristotle to Cuvier, Owen and Osborn. So far, however, the possibilities for exhaustive, quantitative comparisons between greatly different tooth shapes have been limited. Cat teeth and mouse teeth, for example, are fundamentally distinct in shape and structure as a result of independent evolutionary change over tens of millions of years. There is difficulty in establishing homology between their tooth components or in summarizing their tooth shapes, yet both carnivorans and rodents possess a comparable spectrum of dietary specializations from animals to plants. Here we introduce homology-free techniques to measure the phenotypic complexity of the three-dimensional shape of tooth crowns. In our geographic information systems (GIS) analysis of 441 teeth from 81 species of carnivorans and rodents, we show that the surface complexity of tooth crowns directly reflects the foods they consume. Moreover, the absolute values of dental complexity for individual dietary classes correspond between carnivorans and rodents, illustrating a high-level similarity between overall tooth shapes despite a lack of low-level similarity of specific tooth components. These results suggest that scale-independent forces have determined the high-level dental shape in lineages that are widely divergent in size, ecology and life history. This link between diet and phenotype will be useful for inferring the ecology of extinct species and illustrates the potential of fast-throughput, high-level analysis of the phenotype.     

电动车高速轮边减速器传动效率建模与分析

以某电动车高速轮边减速器为研究对象,考虑齿轮啮合损失、搅油损失、风阻损失及轴承损失等因素,建立了该减速器的总效率计算模型,研究了工况参数和设计参数对减速器各种损失及总效率的影响规律。结果表明,随着工况参数转速、转矩、摩擦系数、齿高倍数和运动黏度的增大,系统效率均减小,其中转速、转矩和摩擦系数对总效率影响较大,齿高倍数和运动黏度对总效率的影响较小;减速器设计参数主动轮齿数和法面模数的变化均导致总效率先增加再减小,螺旋角的增加可明显提高系统效率。     

Signal relay by BMP antagonism controls the SHH/FGF4 feedback loop in vertebrate limb buds.

Outgrowth and patterning of the vertebrate limb are controlled by reciprocal interactions between the posterior mesenchyme (polarizing region) and a specialized ectodermal structure, the apical ectodermal ridge (AER). Sonic hedgehog (SHH) signalling by the polarizing region modulates fibroblast growth factor (FGF)4 signalling by the posterior AER, which in turn maintains the polarizing region (SHH/FGF4 feedback loop). Here we report that the secreted bone-morphogenetic-protein (BMP) antagonist Gremlin relays the SHH signal from the polarizing region to the AER. Mesenchymal Gremlin expression is lost in limb buds of mouse embryos homozygous for the limb deformity (Id) mutation, which disrupts establishment of the SHH/FGF4 feedback loop. Grafting Gremlin-expressing cells into ld mutant limb buds rescues Fgf4 expression and restores the SHH/FGF4 feedback loop. Analysis of Shh-null mutant embryos reveals that SHH signalling is required for maintenance of Gremlin and Formin (the gene disrupted by the ld mutations). In contrast, Formin, Gremlin and Fgf4 activation are independent of SHH signalling. This study uncovers the cascade by which the SHH signal is relayed from the posterior mesenchyme to the AER and establishes that Formin-dependent activation of the BMP antagonist Gremlin is sufficient to induce Fgf4 and establish the SHH/FGF4 feedback loop.     

Interpretation of the sonic hedgehog morphogen gradient by a temporal adaptation mechanism

Morphogens act in developing tissues to control the spatial arrangement of cellular differentiation. The activity of a morphogen has generally been viewed as a concentration-dependent response to a diffusible signal, but the duration of morphogen signalling can also affect cellular responses. One such example is the morphogen sonic hedgehog (SHH). In the vertebrate central nervous system and limbs, the pattern of cellular differentiation is controlled by both the amount and the time of SHH exposure. How these two parameters are interpreted at a cellular level has been unclear. Here we provide evidence that changing the concentration or duration of SHH has an equivalent effect on intracellular signalling. Chick neural cells convert different concentrations of SHH into time-limited periods of signal transduction, such that signal duration is proportional to SHH concentration. This depends on the gradual desensitization of cells to ongoing SHH exposure, mediated by the SHH-dependent upregulation of patched 1 (PTC1), a ligand-binding inhibitor of SHH signalling. Thus, in addition to its role in shaping the SHH gradient, PTC1 participates cell autonomously in gradient sensing. Together, the data reveal a novel strategy for morphogen interpretation, in which the temporal adaptation of cells to a morphogen integrates the concentration and duration of a signal to control differential gene expression.     

Mammal teeth from the Cretaceous of Africa

We report here the discovery of two mammal teeth from the early Cretaceous of Cameroon. These, and some jaw fragments, all from Cameroon, are the only fossil evidence of mammalian evolution from Africa between late Jurassic and Paleocene, a span of at least 85 million years. A triangular upper tooth lacks the principal internal cusp of marsupials and placentals and is therefore of a similar evolutionary grade to most Jurassic and early Cretaceous therian mammals, but more primitive than the metatherian-eutherian grade. Early Cretaceous, or older, therian mammals are now known from all southern continents except Antarctica. The new find from Cameroon is consistent with the hypothesis that marsupials, the dominant living mammals of South America and Australia, were not present on any Gondwana continents until after the early Cretaceous separation of Africa by the opening of the South Atlantic.     

有限元法在口腔种植修复中的应用

采用ANSYS软件对口腔种植修复上部结构进行有限元静力分析 .建立了下颌骨、邻牙、种植体及上部构造的三维正交各向异性模型 .由应力云图分析了单颗种植义齿在 3种不同牙尖斜度设计的条件下对种植修复的影响 ,为指导种植修复临床 ,提高种植修复的成功率 ,提供了理论依据 .     

圆柱齿轮弯曲应力数值模拟与影响因素分析

以直齿圆柱齿轮为研究对象,首先利用ANSYS有限元软件建立模型,对齿轮弯曲应力进行数值模拟。然后采用正交实验设计方法设计实验,通过直观和方差分析方法研究齿宽、齿数、扭矩对弯曲应力的影响。最后利用多元线性回归原理建立齿轮弯曲应力数学模型。结果表明,ANSYS数值模拟所得的齿轮弯曲应力与传统理论公式计算结果接近,说明仿真实验可信。在正交实验设计中,扭矩的极差最大,即对齿轮弯曲应力的影响最大,齿数次之,齿宽对齿轮弯曲应力的影响程度最小,可忽略不计。计算结果验证了回归方程的可靠性。该研究为变速器齿轮传动装置设计提供了有益参考。     

A truncated activin receptor inhibits mesoderm induction and formation of axial structures in Xenopus embryos.

Activins can induce mesoderm in embryonic explants and have been proposed as the natural inducer in Xenopus. A mutant activin receptor that inhibits activin signalling is used to show that activin is required for the induction of mesoderm in vivo and the patterning of the embryonic body plan. Blocking the activin signal transduction pathway also reveals autonomous induction of a neural marker and unmasks a relationship between activin and fibroblast growth factor.     

Fringe is a glycosyltransferase that modifies Notch

Notch receptors function in highly conserved intercellular signalling pathways that direct cell-fate decisions, proliferation and apoptosis in metazoans. Fringe proteins can positively and negatively modulate the ability of Notch ligands to activate the Notch receptor. Here we establish the biochemical mechanism of Fringe action. Drosophila and mammalian Fringe proteins possess a fucose-specific beta1,3 N-acetylglucosaminyltransferase activity that initiates elongation of O-linked fucose residues attached to epidermal growth factor-like sequence repeats of Notch. We obtained biological evidence that Fringe-dependent elongation of O-linked fucose on Notch modulates Notch signalling by using co-culture assays in mammalian cells and by expression of an enzymatically inactive Fringe mutant in Drosophila. The post-translational modification of Notch by Fringe represents a striking example of modulation of a signalling event by differential receptor glycosylation and identifies a mechanism that is likely to be relevant to other signalling pathways.     

Gene defect in ectodermal dysplasia implicates a death domain adapter in development.

Members of the tumour-necrosis factor receptor (TNFR) family that contain an intracellular death domain initiate signalling by recruiting cytoplasmic death domain adapter proteins. Edar is a death domain protein of the TNFR family that is required for the development of hair, teeth and other ectodermal derivatives. Mutations in Edar-or its ligand, Eda-cause hypohidrotic ectodermal dysplasia in humans and mice. This disorder is characterized by sparse hair, a lack of sweat glands and malformation of teeth. Here we report the identification of a death domain adapter encoded by the mouse crinkled locus. The crinkled mutant has an hypohidrotic ectodermal dysplasia phenotype identical to that of the edar (downless) and eda (Tabby) mutants. This adapter, which we have called Edaradd (for Edar-associated death domain), interacts with the death domain of Edar and links the receptor to downstream signalling pathways. We also identify a missense mutation in its human orthologue, EDARADD, that is present in a family affected with hypohidrotic ectodermal dysplasia. Our findings show that the death receptor/adapter signalling mechanism is conserved in developmental, as well as apoptotic, signalling.     

同步带传动的计算机辅助设计

利用计算机辅助设计，设计程序ＳＢＤＡＰ，完成了同步带传动设计及带齿间的载荷分配计算。在传动设计基础上，通过对齿间载荷分配分析，可以调整齿形参数，以达到提高带的传动寿命。     

正弦齿条所生成的齿轮副的重合度

提出正弦齿条所生成的齿轮副的重合度定义及其计算式,并且讨论有关设计参数对于重合度的影响效果.正弦齿轮的重合度定义为齿轮副作用角(即一对轮齿从进入啮合到脱离啮合过程中齿轮所转过的角度)与齿轮的单个齿距转角的比值,正弦齿轮副的重合度随齿顶高系数和齿轮齿数的增大而增大,随设计压力角的增大而减小.在相同的设计参数下,正弦齿轮副的重合度要略小于渐开线齿轮副的重合度.     

Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1

When telomeres are rendered dysfunctional through replicative attrition of the telomeric DNA or by inhibition of shelterin, cells show the hallmarks of ataxia telangiectasia mutated (ATM) kinase signalling. In addition, dysfunctional telomeres might induce an ATM-independent pathway, such as ataxia telangiectasia and Rad3-related (ATR) kinase signalling, as indicated by the phosphorylation of the ATR target CHK1 in senescent cells and the response of ATM-deficient cells to telomere dysfunction. However, because telomere attrition is accompanied by secondary DNA damage, it has remained unclear whether there is an ATM-independent pathway for the detection of damaged telomeres. Here we show that damaged mammalian telomeres can activate both ATM and ATR and address the mechanism by which the shelterin complex represses these two important DNA damage signalling pathways. We analysed the telomere damage response on depletion of either or both of the shelterin proteins telomeric repeat binding factor 2 (TRF2) and protection of telomeres 1 (POT1) from cells lacking ATM and/or ATR kinase signalling. The data indicate that TRF2 and POT1 act independently to repress these two DNA damage response pathways. TRF2 represses ATM, whereas POT1 prevents activation of ATR. Unexpectedly, we found that either ATM or ATR signalling is required for efficient non-homologous end-joining of dysfunctional telomeres. The results reveal how mammalian telomeres use multiple mechanisms to avoid DNA damage surveillance and provide an explanation for the induction of replicative senescence and genome instability by shortened telomeres.     

Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer

Embryonic signalling pathways regulate progenitor cell fates in mammalian epithelial development and cancer. Prompted by the requirement for sonic hedgehog (Shh) signalling in lung development, we investigated a role for this pathway in regeneration and carcinogenesis of airway epithelium. Here we demonstrate extensive activation of the hedgehog (Hh) pathway within the airway epithelium during repair of acute airway injury. This mode of Hh signalling is characterized by the elaboration and reception of the Shh signal within the epithelial compartment, and immediately precedes neuroendocrine differentiation. We reveal a similar pattern of Hh signalling in airway development during normal differentiation of pulmonary neuroendocrine precursor cells, and in a subset of small-cell lung cancer (SCLC), a highly aggressive and frequently lethal human tumour with primitive neuroendocrine features. These tumours maintain their malignant phenotype in vitro and in vivo through ligand-dependent Hh pathway activation. We propose that some types of SCLC might recapitulate a critical, Hh-regulated event in airway epithelial differentiation. This requirement for Hh pathway activation identifies a common lethal malignancy that may respond to pharmacological blockade of the Hh signalling pathway.     

非标准复合齿轮插齿刀设计方法

研究加工不等齿厚的非标准参数渐开线齿形,与非渐开线齿形复合的锁闭齿轮插齿刀刀齿的排列、刀具齿数的选择以及刀具设计的基本方法,介绍用限制区域选择插齿刀变位系数的新方法,并给出刀具齿顶后角与侧螺旋角的关系曲线,为插齿刀参数的选择提供依据,结果表明,采用上述方法设计非标准复合齿轮插齿刀,可简化计算和提高设计效率。     

Derivation of pluripotent epiblast stem cells from mammalian embryos

Although the first mouse embryonic stem (ES) cell lines were derived 25 years ago using feeder-layer-based blastocyst cultures, subsequent efforts to extend the approach to other mammals, including both laboratory and domestic species, have been relatively unsuccessful. The most notable exceptions were the derivation of non-human primate ES cell lines followed shortly thereafter by their derivation of human ES cells. Despite the apparent common origin and the similar pluripotency of mouse and human embryonic stem cells, recent studies have revealed that they use different signalling pathways to maintain their pluripotent status. Mouse ES cells depend on leukaemia inhibitory factor and bone morphogenetic protein, whereas their human counterparts rely on activin (INHBA)/nodal (NODAL) and fibroblast growth factor (FGF). Here we show that pluripotent stem cells can be derived from the late epiblast layer of post-implantation mouse and rat embryos using chemically defined, activin-containing culture medium that is sufficient for long-term maintenance of human embryonic stem cells. Our results demonstrate that activin/Nodal signalling has an evolutionarily conserved role in the derivation and the maintenance of pluripotency in these novel stem cells. Epiblast stem cells provide a valuable experimental system for determining whether distinctions between mouse and human embryonic stem cells reflect species differences or diverse temporal origins.     

基于计算机视觉的齿轮齿数、公法线长度变动检测

在基于计算机视觉的齿轮检测中，首次运用极坐标变换算法对预处理后的齿廓采样数据进行变换，将圆周上的齿廓曲线变换到水平方向，并将得到的齿廓看作正弦曲线，再采用Matlab工具箱中傅里叶变换函数得到正弦曲线的拟合表达式，对齿廓采样数据的总数（即列数）与拟合函数的周期比值取整，得到所检测齿轮的齿数。在检测公法线长度变动时，首先求得齿顶圆半径、模数，从而得到基圆半径，可求得基圆与齿廓交点的中点与斜率，利用点斜式方程求得与基圆相切的切线方程，该切线与跨过k个齿的齿廓相交的长度即为公法线长度，根据其最大值与最小值之差得到公法线长度变动。文中提出的基于计算机视觉系统的检测齿轮的齿数以及公法线长度的检测方法，实现了齿轮精度非接触式检测，且其检测精度能够满足工程实践的需求。