cAMP phosphodiesterase-4A1 (PDE4A1) has provided the paradigm for the intracellular targeting of phosphodiesterases, a process that underpins compartmentalized cAMP signalling

2006 ◽  
Vol 34 (4) ◽  
pp. 504-509 ◽  
Author(s):  
E. Huston ◽  
T.M. Houslay ◽  
G.S. Baillie ◽  
M.D. Houslay

Specificity of cAMP signalling pathways has shown that the intracellular targeting of the individual components confers a three-dimensional context to the signalling paradigms in which they can exquisitely control the specificity of the outcome of the signal. Pivotal to this paradigm is degradation of cAMP by sequestered PDEs (phosphodiesterases). cAMP rapidly diffuses within cells and, without the action of spatially confined PDE populations, cAMP gradients could not be formed and shaped within cells so as to regulate targeted effector proteins. Of particular importance in regulating compartmentalized cAMP signalling are isoforms of the PDE4 family, which are individually defined by unique N-terminal regions. We have developed and pioneered the concept that a major function of this N-terminal region is to confer intracellular targeting of particular PDE4 isoforms on specific signalling complexes and intracellular locations. The paradigm for this concept developed from our original studies on the PDE4A1 (RD1) isoform. The N-terminal region unique to PDE4A1 consists of two well-defined helical regions separated by a mobile hinge region. Helix-2 provides the core membrane-insertion module, with helix-1 facilitating membrane association and fidelity of targeting in living cells. The irreversible, Ca2+-dependent insertion of the N-terminal region of PDE4A1 into membranes provides ‘long-term’ memory of cell activation.

Author(s):  
B. Carragher ◽  
M. Whittaker

Techniques for three-dimensional reconstruction of macromolecular complexes from electron micrographs have been successfully used for many years. These include methods which take advantage of the natural symmetry properties of the structure (for example helical or icosahedral) as well as those that use single axis or other tilting geometries to reconstruct from a set of projection images. These techniques have traditionally relied on a very experienced operator to manually perform the often numerous and time consuming steps required to obtain the final reconstruction. While the guidance and oversight of an experienced and critical operator will always be an essential component of these techniques, recent advances in computer technology, microprocessor controlled microscopes and the availability of high quality CCD cameras have provided the means to automate many of the individual steps.During the acquisition of data automation provides benefits not only in terms of convenience and time saving but also in circumstances where manual procedures limit the quality of the final reconstruction.


2010 ◽  
Vol 3 (2) ◽  
pp. 156-180 ◽  
Author(s):  
Renáta Gregová ◽  
Lívia Körtvélyessy ◽  
Július Zimmermann

Universals Archive (Universal #1926) indicates a universal tendency for sound symbolism in reference to the expression of diminutives and augmentatives. The research ( Štekauer et al. 2009 ) carried out on European languages has not proved the tendency at all. Therefore, our research was extended to cover three language families – Indo-European, Niger-Congo and Austronesian. A three-step analysis examining different aspects of phonetic symbolism was carried out on a core vocabulary of 35 lexical items. A research sample was selected out of 60 languages. The evaluative markers were analyzed according to both phonetic classification of vowels and consonants and Ultan's and Niewenhuis' conclusions on the dominance of palatal and post-alveolar consonants in diminutive markers. Finally, the data obtained in our sample languages was evaluated by means of a three-dimensional model illustrating the place of articulation of the individual segments.


2011 ◽  
Vol 77 (13) ◽  
pp. 4669-4675 ◽  
Author(s):  
Dawn C. Bisi ◽  
David J. Lampe

ABSTRACTThe insect-vectored disease malaria is a major world health problem. New control strategies are needed to supplement the current use of insecticides and medications. A genetic approach can be used to inhibit development of malaria parasites (Plasmodiumspp.) in the mosquito host. We hypothesized thatPantoea agglomerans, a bacterial symbiont ofAnophelesmosquitoes, could be engineered to express and secrete anti-Plasmodiumeffector proteins, a strategy termed paratransgenesis. To this end, plasmids that include thepelBorhlyAsecretion signals from the genes of related species (pectate lyase fromErwinia carotovoraand hemolysin A fromEscherichia coli, respectively) were created and tested for their efficacy in secreting known anti-Plasmodiumeffector proteins (SM1, anti-Pbs21, and PLA2) inP. agglomeransandE. coli.P. agglomeranssuccessfully secreted HlyA fusions of anti-Pbs21 and PLA2, and these strains are under evaluation for anti-Plasmodiumactivity in infected mosquitoes. Varied expression and/or secretion of the effector proteins was observed, suggesting that the individual characteristics of a particular effector may require empirical testing of several secretion signals. Importantly, those strains that secreted efficiently grew as well as wild-type strains under laboratory conditions and, thus, may be expected to be competitive with the native microbiota in the environment of the mosquito midgut.


2013 ◽  
Vol 05 (01) ◽  
pp. 1350002 ◽  
Author(s):  
I. Benedetti ◽  
F. Barbe

A survey of recent contributions on three-dimensional grain-scale mechanical modelling of polycrystalline materials is given in this work. The analysis of material micro-structures requires the generation of reliable micro-morphologies and affordable computational meshes as well as the description of the mechanical behavior of the elementary constituents and their interactions. The polycrystalline microstructure is characterized by the topology, morphology and crystallographic orientations of the individual grains and by the grain interfaces and microstructural defects, within the bulk grains and at the inter-granular interfaces. Their analysis has been until recently restricted to two-dimensional cases, due to high computational requirements. In the last decade, however, the wider affordability of increased computational capability has promoted the development of fully three-dimensional models. In this work, different aspects involved in the grain-scale analysis of polycrystalline materials are considered. Different techniques for generating artificial micro-structures, ranging from highly idealized to experimentally based high-fidelity representations, are briefly reviewed. Structured and unstructured meshes are discussed. The main strategies for constitutive modelling of individual bulk grains and inter-granular interfaces are introduced. Some attention has also been devoted to three-dimensional multiscale approaches and some established and emerging applications have been discussed.


FEBS Letters ◽  
1996 ◽  
Vol 384 (2) ◽  
pp. 172-176 ◽  
Author(s):  
Niccolò Taddei ◽  
Francesca Magherini ◽  
Fabrizio Chiti ◽  
Monica Bucciantini ◽  
giovanni Raugei ◽  
...  

2017 ◽  
Vol 14 (1) ◽  
pp. 172988141769231 ◽  
Author(s):  
Ning An ◽  
Shi-Ying Sun ◽  
Xiao-Guang Zhao ◽  
Zeng-Guang Hou

Visual tracking is a challenging computer vision task due to the significant observation changes of the target. By contrast, the tracking task is relatively easy for humans. In this article, we propose a tracker inspired by the cognitive psychological memory mechanism, which decomposes the tracking task into sensory memory register, short-term memory tracker, and long-term memory tracker like humans. The sensory memory register captures information with three-dimensional perception; the short-term memory tracker builds the highly plastic observation model via memory rehearsal; the long-term memory tracker builds the highly stable observation model via memory encoding and retrieval. With the cooperative models, the tracker can easily handle various tracking scenarios. In addition, an appearance-shape learning method is proposed to update the two-dimensional appearance model and three-dimensional shape model appropriately. Extensive experimental results on a large-scale benchmark data set demonstrate that the proposed method outperforms the state-of-the-art two-dimensional and three-dimensional trackers in terms of efficiency, accuracy, and robustness.


2013 ◽  
Vol 796 ◽  
pp. 513-518
Author(s):  
Rong Jin ◽  
Bing Fei Gu ◽  
Guo Lian Liu

In this paper 110 female undergraduates in Soochow University are measured by using 3D non-contact measurement system and manual measurement. 3D point cloud data of human body is taken as research objects by using anti-engineering software, and secondary development of point cloud data is done on the basis of optimizing point cloud data. In accordance with the definition of the human chest width points and other feature points, and in the operability of the three-dimensional point cloud data, the width, thickness, and length dimensions of the curve through the chest width point are measured. Classification of body type is done by choosing the ratio values as classification index which is the ratio between thickness and width of the curve. The generation rules of the chest curve are determined for each type by using linear regression method. Human arm model could be established by the computer automatically. Thereby the individual model of the female upper body mannequin modeling can be improved effectively.


1998 ◽  
Vol 42 (03) ◽  
pp. 174-186
Author(s):  
C. J. Garrison

A method is presented for evaluation of the motion of long structures composed of interconnected barges, or modules, of arbitrary shape. Such structures are being proposed in the construction of offshore airports or other large offshore floating structures. It is known that the evaluation of the motion of jointed or otherwise interconnected modules which make up a long floating structure may be evaluated by three dimensional radiation/diffraction analysis. However, the computing effort increases rapidly as the complexity of the geometric shape of the individual modules and the total number of modules increases. This paper describes an approximate method which drastically reduces the computational effort without major effects on accuracy. The method relies on accounting for hydrodynamic interaction effects between only adjacent modules within the structure rather than between all of the modules since the near-field interaction is by far the more important. This approximation reduces the computational effort to that of solving the two-module problem regardless of the total number of modules in the complete structure.


2021 ◽  
Vol 77 (9) ◽  
pp. 1206-1215
Author(s):  
Norbert Schormann ◽  
Sangeetha Purushotham ◽  
Joshua L. Mieher ◽  
Manisha Patel ◽  
Hui Wu ◽  
...  

Streptococcus gordonii is a member of the viridans streptococci and is an early colonizer of the tooth surface. Adherence to the tooth surface is enabled by proteins present on the S. gordonii cell surface, among which SspB belongs to one of the most well studied cell-wall-anchored adhesin families: the antigen I/II (AgI/II) family. The C-terminal region of SspB consists of three tandemly connected individual domains that display the DEv-IgG fold. These C-terminal domains contain a conserved Ca2+-binding site and isopeptide bonds, and they adhere to glycoprotein 340 (Gp340; also known as salivary agglutinin, SAG). Here, the structural and functional characterization of the C123 SspB domain at 2.7 Å resolution is reported. Although the individual C-terminal domains of Streptococcus mutans AgI/II and S. gordonii SspB show a high degree of both sequence and structural homology, superposition of these structures highlights substantial differences in their electrostatic surface plots, and this can be attributed to the relative orientation of the individual domains (C1, C2 and C3) with respect to each other and could reflect their specificity in binding to extracellular matrix molecules. Studies further confirmed that affinity for Gp340 or its scavenger receptor cysteine-rich (SRCR) domains requires two of the three domains of C123 SspB, namely C12 or C23, which is different from AgI/II. Using protein–protein docking studies, models for this observed functional difference between C123 SspB and C123 AgI/II in their binding to SRCR1 are presented.


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