Patient specific finite element analysis results in more accurate prediction of stent fractures: Application to percutaneous pulmonary valve implantation

Stent fracture is a recognised complication following device implantation. Magnetic resonance data from a patient who underwent percutaneous pulmonary valve implantation (PPVI) and had subsequent stent fractures was used to create a finite element (FE) model of the patient's implantation site. Simulated expansion of the PPVI stent into this right ventricular outflow tract (RVOT) geometry was compared with free expansions of the PPVI stent up to a uniformly deployed configuration (conventional method employed in bench testing protocols), using FE analysis. PPVI biplane fluoroscopy images from the same patient were used to reconstruct the 3D shape and deformation of the stent in-situ and verify the FE geometrical results. Asymmetries were measured in all 3 orthogonal directions, in early systole and diastole.Although a simplified FE modelling of stent/implantation site interaction was adopted, this analysis gave useful information about the influence of the RVOT on the final geometry and mechanical performance of the stent. When deployed into the RVOT, the FE stent showed a non-uniform shape, similar to the geometry seen in the “real” fluoroscopy reconstructed stent, where the most expanded cells corresponded to the fracture locations. This asymmetrical geometry, when compared to the free-expanded stent, resulted in higher stresses in the portion of the stent where fractures occurred. Furthermore, fatigue fractures that were not predicted in the free-deployed stents, developed in the asymmetrically expanded device.In conclusion, the interaction between the PPVI device and the patient's RVOT is likely to be the crucial factor involved with this undesired event.     

Canonical Wnt3a Modulates Intracellular Calcium and Enhances Excitatory Neurotransmission in Hippocampal Neurons

A role for Wnt signal transduction in the development and maintenance of brain structures is widely acknowledged. Recent studies have suggested that Wnt signaling may be essential for synaptic plasticity and neurotransmission. However, the direct effect of a Wnt protein on synaptic transmission had not been demonstrated. Here we show that nanomolar concentrations of purified Wnt3a protein rapidly increase the frequency of miniature excitatory synaptic currents in embryonic rat hippocampal neurons through a mechanism involving a fast influx of calcium from the extracellular space, induction of post-translational modifications on the machinery involved in vesicle exocytosis in the presynaptic terminal leading to spontaneous Ca²⁺ transients. Our results identify the Wnt3a protein and a member of its complex receptor at the membrane, the low density lipoprotein receptor-related protein 6 (LRP6) coreceptor, as key molecules in neurotransmission modulation and suggest cross-talk between canonical and Wnt/Ca²⁺ signaling in central neurons.     

Effect of sexual segregation on host-parasite interaction: Model simulation for abomasal parasite dynamics in alpine ibex (Capraibex)

We investigated whether sexual segregation might affect parasite transmission and host dynamics, hypothesising that if males are the more heavily infected sex and more responsible for the transmission of parasite infections, female avoidance of males and the space they occupy could reduce infection rates. A mathematical model, simulating the interaction between abomasal parasites and a hypothetical alpine ibex (Capraibex) host population composed of its two sexes, was developed to predict the effect of different degrees of sexual segregation on parasite intensity and on host abundance. The results showed that when females tended to be segregated from males, and males were distributed randomly across space, the impact of parasites was the lowest, resulting in the highest host abundance, with each sex having the lowest parasite intensity. The predicted condition that minimises the impact of parasites in our model was the one closest to that observed in nature where females actively seek out the more segregated sites while males are less selective in their ranging behaviour. The overlapping of field observation with the predicted optimal strategy lends support to our idea that there might be a connection between parasite transmission and sexual segregation. Our simulations provide the biological boundaries of host-parasite interaction needed to determine a parasite-mediated effect on sexual segregation and a formalised null hypothesis against which to test future field experiments.     

The urokinase receptor: Focused cell surface proteolysis, cell adhesion and signaling

Plasma membrane urokinase-type plasminogen activator (uPA)-receptor (uPAR) is a GPI-anchored protein that binds with high-affinity and activates the serine protease uPA, thus regulating proteolytic activity at the cell surface. In addition, uPAR is a signaling receptor that often does not require its protease ligand or its proteolytic function.uPAR is highly expressed during tissue reorganization, inflammation, and in virtually all human cancers. Since its discovery, in vitro and in vivo models, as well as retrospective clinical studies have shown that over-expression of components of the uPA/uPAR-system correlates with increased proliferation, migration, and invasion affecting the malignant phenotype of cancer. uPAR regulates the cells-extracellular matrix interactions promoting its degradation and turnover through the plasminogen activation cascade.     

ATP dependent charge movement in ATP7B Cu+-ATPase is demonstrated by pre-steady state electrical measurements

ATP7B is a copper dependent P-type ATPase, required for copper homeostasis. Taking advantage of high yield heterologous expression of recombinant protein, we investigated charge transfer in ATP7B. We detected charge displacement within a single catalytic cycle upon ATP addition and formation of phosphoenzyme intermediate. We attribute this charge displacement to movement of bound copper within ATP7B. Based on specific mutations, we demonstrate that enzyme activation by copper requires occupancy of a site in the N-terminus extension which is not present in other transport ATPases, as well as of a transmembrane site corresponding to the cation binding site of other ATPases.     

Adrenergic origin of very low-frequency blood pressure oscillations in the unanesthetized rat

Spectral analysis of cardiovascular signals has been extensively used to investigate circulatory homeostatic mechanisms. However, the nature of very low-frequency (VLF) fluctuations remains unclear. Because we previously observed enhanced VLF fluctuations in blood pressure (BP) in the sympathectomized rat (a model characterized by markedly increased plasma epinephrine levels), the aims of our study were to assess whether the genesis of VLF fluctuations in BP depends on circulating catecholamines and to determine which adrenergic receptor(s) and which membrane ion channel(s) are involved. We used continuous intra-arterial BP recordings from unanesthetized unrestrained rats to compute the power of VLF fluctuations in BP in the intact condition, during acute ganglionic blockade with hexamethonium, and after restoration of BP levels by infusion (in addition to hexamethonium) of adrenergic agonists (epinephrine, norepinephrine, and clonidine) or nonadrenergic vasoconstrictors (vasopressin). Effects of infusion of specific adrenergic receptor blockers (propranolol, prazosin, and yohimbine) with hexamethonium and catecholamines and infusion of various membrane ion channel blockers on VLF fluctuations in BP were also evaluated. Our results are as follows. 1) Ganglionic blockade drastically reduced BP levels and VLF fluctuations. 2) All vasoconstrictors restored BP levels, but only adrenergic vasoconstrictors generated striking VLF fluctuations in BP. 3) Catecholamine-induced fluctuations were abolished by alpha2-, but not alpha1- or beta-, adrenergic receptor blockade and by Ba2+-sensitive K+ channel or L-type Ca2+ channel, but not by other ion channel, blockers. We conclude that, in the conscious, unrestrained ganglion-blocked rat, catecholamine infusion generates VLF fluctuations in BP through stimulation of alpha2-receptors and activation of Ba2+-sensitive K+ channels. These fluctuations may have (patho)physiological relevance under conditions of disrupted circulatory homeostasis.     

Evaluation of intra-specific diversities in Oenococcus oeni through analysis of genomic and expressed DNA

In winemaking Oenococcus (O.) oeni is the most frequent species of lactic acid bacteria (LAB) associated with malolactic fermentation (MLF). Several studies have demonstrated that O. oeni is a quite homogeneous species and strains are difficult to differentiate especially when isolates from the same region are analyzed. In this study, the molecular biodiversity of O. oeni isolated from wines of the same region (Aglianico produced in Basilicata Region, Southern Italy) was evaluated with the aim of designing a molecular approach for discrimination and characterization of the isolates at the strain level. Three molecular techniques were applied: random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR), restriction endonucleases analysis-pulsed field gel electrophoresis (REA-PFGE) and differential display PCR (DD-PCR). The results obtained by RAPD-PCR confirmed the difficulty in differentiating isolates. By means of REA-PFGE a higher polymorphism, often related to the origin (winery) of strains, was revealed. However, on analyzing strains isolated from the same winery, only in some cases was more than one REA-PFGE pattern obtained. By analyzing dendrograms constructed on the basis of DD-PCR profiles differentiation of strains isolated from the same winery, in some cases, could be accomplished. The reliability of the DD-PCR in the differentiation of closely related strains suggests that this method could represent an alternative and/or additional tool to other molecular methods, such as REA-PFGE, for fine characterization of oenococcal strains.