Improved execution efficiency of model-based roentgen stereophotogrammetric analysis: simplification and segmentation of model meshes

Recently, the model-based roentgen stereophotogrammetric analysis (RSA) method has been developed as an in vivo tool to estimate static pose and dynamic motion of the instrumented prostheses. The two essential inputs for the RSA method are prosthetic models and roentgen images. During RSA calculation, the implants are often reversely scanned and input in the form of meshes to estimate the outline error between prosthetic projection and roentgen images. However, the execution efficiency of the RSA iterative calculation may limit its clinical practicability, and one reason for inefficiency may be very large number of meshes in the model. This study uses two methods of mesh manipulation to improve the execution efficiency of RSA calculation. The first is to simplify the model meshes and the other is to segment and delete the meshes of insignificant regions. An index (i.e. critical percentage) of an optimal element number is defined as the trade-off between execution efficiency and result accuracy. The predicted results are numerically validated by total knee prosthetic system. The outcome shows that the optimal strategy of the mesh manipulation is simplification and followed by segmentation. On average, the element number can even be reduced to 1% of the original models. After the mesh manipulation, the execution efficiency can be increased about 75% without compromising the accuracy of the predicted RSA results (the increment of rotation and translation error: 0.06° and 0.02 mm). In conclusion, prosthetic models should be manipulated by simplification and segmentation methods prior to the RSA calculation to increase the execution efficiency and then to improve clinical applicability of the RSA method.     

NMR Studies of the Tautomerism in Pseudoisocytidine

Abstract

The structure of pseudoisocytidine may have two isomers. We would like to designate them as K1 and K3 for N₁H and N₃H, respectively. The authenticity of these two isomers was judged by ¹H NMR. The chemical shift value of N₁H in K1 is found more upfield than N₃H in K3, whereas the chemical shifts of rest protons remain the same. Theoretical calculations show that K1 is less stable than K3 by ca. 9 Kcal/mol in gas phase while a methyl group replaces the furanose moiety. This energy reduces as low as 2 Kcal/mol in solution depending on the polarity of the solvent. Thus, the equilibrium of two tautomers occurs most likely in solution. The ¹H and ¹³C NMR studies have been carried out in the pH range of 1 to 12. The pKa's of deprotonation of N₁ and N₃ sites are found to be 9.36 and 9.42, for K1 and K3, respectively. On the other hand, the pKa's of protonation of the same sites corresponding to these two isomers are 3.79 and 3.69, respectively. A critical analysis of line broadening of C₂ in K1 and K3 in the pH range of 5 to 7 establishes the proton exchange phenomenon. The exchange rate, catalyzed by both [H⁺] and [OH^?], depends on the pH.     

Dipeptidyl Peptidase-4 Inhibitor Decreases Abdominal Aortic Aneurysm Formation through GLP-1-Dependent Monocytic Activity in Mice

Abdominal aortic aneurysm (AAA) is a life-threatening situation affecting almost 10% of elders. There has been no effective medication for AAA other than surgical intervention. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been shown to have a protective effect on cardiovascular disease. Whether DPP-4 inhibitors may be beneficial in the treatment of AAA is unclear. We investigated the effects of DPP-4 inhibitor sitagliptin on the angiotensin II (Ang II)-infused AAA formation in apoE-deficient (apoE^-/-) mice. Mice with induced AAA were treated with placebo or 2.5, 5 or 10 mg/kg/day sitagliptin. Ang II-infused apoE^-/- mice exhibited a 55.6% incidence of AAA formation, but treatment with sitagliptin decreased AAA formation. Specifically, administered sitagliptin in Ang II-infused mice exhibited decreased expansion of the suprarenal aorta, reduced elastin lamina degradation of the aorta, and diminished vascular inflammation by macrophage infiltration. Treatment with sitagliptin decreased gelatinolytic activity and apoptotic cells in aorta tissues. Sitaglipitn, additionally, was associated with increased levels of plasma active glucagon-like peptide-1 (GLP-1). In vitro studies, GLP-1 decreased reactive oxygen species (ROS) production, cell migration, and MMP-2 as well as MMP-9 activity in Ang II-stimulated monocytic cells. The results conclude that oral administration of sitagliptin can prevent abdominal aortic aneurysm formation in Ang II-infused apoE^-/-mice, at least in part, by increasing of GLP-1 activity, decreasing MMP-2 and MMP-9 production from macrophage infiltration. The results indicate that sitagliptin may have therapeutic potential in preventing the development of AAA.     

The earliest Timematids in Burmese amber reveal diverse tarsal pads of stick insects in the mid‐Cretaceous

Many extant insects have developed pad structures, euplantulae or arolia on their tarsi to increase friction or enhance adhesion for better mobility. Many polyneopteran insects with euplantulae, for example, Grylloblattodea, Mantophasmatodea and Orthoptera, have been described from the Mesozoic. However, the origin and evolution of stick insects' euplantulae are poorly understood due to rare fossil records. Here, we report the earliest fossil records of Timematodea hitherto, Tumefactipes prolongates gen. et sp. nov. and Granosicorpes Urates gen. et sp. nov., based on three specimens from mid-Cretaceous Burmese amber. Specimens of Tumefactipes prolongates gen. et sp. nov. have extremely specialized and expanded euplantulae on their tarsomere II. These new findings are the first known and the earliest fossil records about euplantula structure within Phasmatodea, demonstrating the diversity of euplantulae in Polyneoptera during the Mesozoic. Such tarsal pads might have increased friction and helped these mid-Cretaceous stick insects to climb more firmly on various surfaces, such as broad leaves, wetted tree branches or ground. These specimens provide more morphological data for us to understand the relationships of Timematodea, Euphasmatodea, Orthoptera and Embioptera, suggesting that Timematodea might be monophyletic with Euphasmatodea rather than Embioptera and Phasmatodea should have a closer relationship with Orthoptera rather than Embioptera.     

Differential effect of cholesterol on two types of 5-hydroxytryptamine binding sites

The specific binding of [3H]5-hydroxytryptamine ([3H]5-HT, [3H]serotonin) to rat cerebral cortex is increased approximately 1.5 to 2.0 fold by cholesterol hydrogen succinate (CHS) and is solubilized into the supernatant fraction by 12 mM CHS. [3H]5-HT binding sites can be constituted by incubating the supernatant fraction obtained from CHS-treated cerebral cortex with cerebellum in which no significant [3H]5-HT binding is detectable. The constituted [3H]5-HT binding could be displaced by unlabeled 5-HT, d-lysergic acid diethylamide (d-LSD) and spiperone as could the binding to cortex membranes. Unlabeled 5-HT, d-LSD and spiperone each inhibited specific [3H]5-HT binding to constituted binding sites by 50% at about 1 X 10(-9) M. Specific [3H]spiperone binding was not detectable in the constituted membranes. Stearic acid which is reported to have similar effects on membrane fluidity as cholesterol also increased specific [3H]5-HT binding in cortical membranes. Stearic acid does not affect specific [3H]spiperone binding. These results suggest that [3H]5-HT and [3H]spiperone binding sites are affected differently by membrane fluidity.     

A FRET-based sensor reveals large ATP hydrolysis-induced conformational changes and three distinct states of the molecular motor myosin

The molecular motor myosin is proposed to bind to actin and swing its light-chain binding region through a large angle to produce an approximately 10 nm step in motion coupled to changes in the nucleotide state at the active site. To date, however, direct dynamic measurements have largely failed to show changes of that magnitude. Here, we use a cysteine engineering approach to create a high resolution, FRET-based sensor that reports a large, approximately 70 degree nucleotide-dependent angle change of the light-chain binding region. The combination of steady-state and time-resolved fluorescence resonance energy transfer measurements unexpectedly reveals two distinct prestroke states. The measurements also show that bound Mg.ADP.Pi, and not bound Mg.ATP, induces the myosin to adopt the prestroke states.     

On the relationship between the sequence conservation and the packing density profiles of the protein complexes

We have recently showed that the weighted contact number profiles (or the packing density profiles) of proteins are well correlated with those of the corresponding sequence conservation profiles. The results suggest that a protein structure may contain sufficient information about sequence conservation comparable to that derived from multiple homologous sequences. However, there are ambiguities concerning how to compute the packing density of the subunit of a protein complex. For the subunits of a complex, there are different ways to compute its packing density – one including the packing contributions of the other subunits and the other one excluding their contributions. Here we selected two sets of enzyme complexes. Set A contains complexes with the active sites comprising residues from multiple subunits, while set B contains those with the active sites residing on single subunits. In Set A, if the packing density profile of a subunit is computed considering the contributions of the other subunits of the complex, it will agree better with the sequence conservation profile. But in Set B the situations are reversed. The results may be due to the stronger functional and structural constraints on the evolution processes on the complexes of Set A than those of Set B to maintain the enzymatic functions of the complexes. The comparison of the packing density and the sequence conservation profiles may provide a simple yet potentially useful way to understanding the structural and evolutionary couplings between the subunits of protein complexes. Proteins 2013; 81:1192–1199. © 2013 Wiley Periodicals, Inc.