Is the evolutionary history of the O-type P element in the saltans and willistoni groups of Drosophila similar to that of the canonical P element?

We studied the occurrence of O-type P elements in at least one species of each subgroup of the saltans group, in order to better understand the phylogenetic relationships among the elements within the saltans group and with those of species belonging to the willistoni group. We found that the O-type subfamily has a patchy distribution within the saltans group (it does not occur in D. neocordata and D. emarginata), low sequence divergence among species of the saltans group as well as in relation to species of the willistoni group, a lower rate of synonymous substitution for coding sequences compared to Adh, and phylogenetic incongruities. These findings suggest that the evolutionary history of the O-type subfamily within the saltans and willistoni groups follows the same model proposed for the canonical subfamily of P elements, i.e., events of horizontal transfer between species of the saltans and willistoni groups.     

Finite element modeling of superelastic nickel–titanium orthodontic wires

Thanks to its good corrosion resistance and biocompatibility, superelastic Ni–Ti wire alloys have been successfully used in orthodontic treatment. Therefore, it is important to quantify and evaluate the level of orthodontic force applied to the bracket and teeth in order to achieve tooth movement. In this study, three dimensional finite element models with a Gibbs-potential-based-formulation and thermodynamic principles were used. The aim was to evaluate the influence of possible intraoral temperature differences on the forces exerted by NiTi orthodontic arch wires with different cross sectional shapes and sizes. The prediction made by this phenomenological model, for superelastic tensile and bending tests, shows good agreement with the experimental data. A bending test is simulated to study the force variation of an orthodontic NiTi arch wire when it loaded up to the deflection of 3 mm, for this task one half of the arch wire and the 3 adjacent brackets were modeled. The results showed that the stress required for the martensite transformation increases with the increase of cross-sectional dimensions and temperature. Associated with this increase in stress, the plateau of this transformation becomes steeper. In addition, the area of the mechanical hysteresis, measured as the difference between the forces of the upper and lower plateau, increases.     

Finite element analysis of the pressure-induced deformation of Schlemm’s canal endothelial cells

The endothelial cells lining the inner wall of Schlemm’s canal (SC) in the eye are relatively unique in that they support a basal-to-apical pressure gradient that causes these cells to deform, creating giant vacuoles and transendothelial pores through which the aqueous humor flows. Glaucoma is associated with an increased resistance to this flow. We used finite element modeling and estimates of cell modulus made using atomic force microscopy to characterize the pressure-induced deformation of SC cells and to estimate the maximum pressure drop that SC cells can support. We examined the effects of cell geometry, cell stiffness, and the contribution of the cell cortex to support the pressure-generated load. We found that the maximum strain generated by this loading occurs at the points of cell–substrate attachment and that the cortex of the cells bears nearly all of this load. The ability of these cells to support a significant transcellular pressure drop is extremely limited (on the order of 5 mmHg or less) unless these cells either stiffen very considerably with increasing deformation or have substantial attachments to their substratum away from their periphery. This puts limits on the flow resistance that this layer can generate, which has implications regarding the site where the bulk of the flow resistance is generated in healthy and glaucomatous eyes.     

β-arrestin-2 regulation of the cAMP response element binding protein

Previous work demonstrated that cystic fibrosis (CF) cells exhibit an increase in cAMP-mediated signaling as a characteristic response to lost CFTR function. Evidence for increased cAMP-mediated signaling in CF included increased phosphorylation of the cAMP response element binding protein (CREB) and elevated β-arrestin-2 (βarr2) expression. However, subsequent studies reveal that CREB activation in CF cells is independent of protein kinase-A (PKA). The goal of this study is to test the hypothesis that elevated βarr2 expression leads to increased CREB activation in a PKA-independent mechanism. βarr2-GFP expressing tracheal epithelial cells (βarr2-GFP) exhibit an increase of pCREB content and subsequent CRE activation compared to GFP expressing control cells. βarr2 activation of the ERK cascade represents a candidate mechanism leading to CREB activation. ERK exhibits increased activation in βarr2-GFP cells compared to cont-GFP cells, and ERK inhibition diminishes CRE activation in both GFP and βarr2-GFP cells. To test directly whether CREB regulation in CF is βarr2-dependent, nasal epithelium excised from wt mice (Cftr +/+; βarr2 +/+), CF mice (Cftr -/-; βarr2 +/+), and DKO mice (Cftr -/-; βarr2 -/-) were analyzed for pCREB protein content. Removal of βarr2 expression from CF mice reduces both pCREB and pERK content to wt levels. These data indicate that CF-related CREB regulation is mediated directly through βarr2 expression via the ERK pathway.     

Probabilistic failure analysis of bone using a finite element model of mineral–collagen composites

Microdamage accumulation is a major pathway for energy dissipation during the post-yield deformation of bone. In this study, a two-dimensional probabilistic finite element model of a mineral–collagen composite was developed to investigate the influence of the tissue and ultrastructural properties of bone on the evolution of microdamage from an initial defect in tension. The probabilistic failure analyses indicated that the microdamage progression would be along the plane of the initial defect when the debonding at mineral–collagen interfaces was either absent or limited in the vicinity of the defect. In this case, the formation of a linear microcrack would be facilitated. However, the microdamage progression would be scattered away from the initial defect plane if interfacial debonding takes place at a large scale. This would suggest the possible formation of diffuse damage. In addition to interfacial debonding, the sensitivity analyses indicated that the microdamage progression was also dependent on the other material and ultrastructural properties of bone. The intensity of stress concentration accompanied with microdamage progression was more sensitive to the elastic modulus of the mineral phase and the nonlinearity of the collagen phase, whereas the scattering of failure location was largely dependent on the mineral to collagen ratio and the nonlinearity of the collagen phase. The findings of this study may help understanding the post-yield behavior of bone at the ultrastructural level and shed light on the underlying mechanism of bone fractures.     

Three-dimensional finite element analysis of stress distribution in retention screws of different crown–implant ratios

The retaining screw of the implant-supported dental prosthesis is the weakest point of the crown/implant system. Furthermore, crown height is another important factor that may increase the lever arm. Therefore, the aim of this study was to assess the stress distribution in implant prosthetic screws with different heights of the clinical crown of the prosthesis using the method of three-dimensional finite element analysis. Three models were created with implants (3.75 mm × 10 mm) and crowns (heights of 10, 12.5 and 15 mm). The results were visualised by means of von Mises stress maps that increased the crown heights. The screw structure exhibited higher levels of stresses in the oblique load. The oblique loading resulted in higher stress concentration when compared with the axial loading. It is concluded that the increase of the crown was damaging to the stress distribution on the screw, mainly in oblique loading.     

Boron — Key element in the actions of phytochrome and gravity?

Hypocotyl sections from dark-grown mung bean (Vigna radiata (L.) Wilczek) seedlings grown without boron exhibit little or no increase in the translocation of fluorescein in phloem cells following gravitational stimulation or red irradiation. In contrast, pretreatment of the hypocotyl sections with low concentrations of boric acid before red irradiation or gravitational stimulation results in a rapid increase in fluorescein movement. Mung bean root tips without boron fail to remain attached to a negativelycharged glass surface after several minutes of red irradiation. A low boron concentration in the solution induces tip attachment. The suggestion is made that boron is required to stabilize a positive electrostatic charge in the plasma membrane that is generated by the actions of phytochrome and gravity.     

Genetic control of mitosis. Mast(v40) protein--an element of checkpoints system?

The effect of the mastv40 mutation was studied using neural ganglion cells of third-instar larvae of Drosophila melanogaster. The distributions of the cells by the interphase nucleus diameter and by the distance between the sister chromosome sets in anaphase were analyzed. Three following types of defects induced by the mutation were described: (1) Monopolar mitosis or, in the case of bipolar mitosis, an abnormally short distance between the sister chromosome sets in anaphase and early telophase. We believe that these abnormalities are caused by damage of the start and (or) motor mechanisms of centrosome separation at the beginning and in the end of mitosis. (2) Lagging and bridging of chromosomes in anaphase and early telophase. These defects seem to be related to the disruption of functioning of mitotic spindle microtubules and (or) their defective attachment to the appropriate kinetochores. (3) Unlimited division of aneuploid and polyploid cells, which may be explained either by inactivation of the checkpoint system controlling the genome ploidy or by checkpoint adaptation. Taken collectively, our results and literature data suggest that the MAST protein is an element of the checkpoint system and that division of aneuploid and polyploid cells results from inactivation of the checkpoints.     

Identification of a hormone response element that mediates suppression of APOF by LXR and PPARα agonists

Apolipoprotein F (ApoF) regulates cholesteryl ester transfer protein activity. We previously observed that hepatic APOF mRNA levels are decreased by high fat, cholesterol-enriched diets. Here we show in human liver C3A cells that APOF mRNA levels are reduced by agonists of LXR and PPARα nuclear receptors. This negative regulation requires co-incubation with the RXR agonist, retinoic acid. Bioinformatic analysis of the ~2 kb sequence upstream of the APOF promoter identified one potential LXR and 4 potential PPARα binding sites clustered between nucleotides −2007 and −1961. ChIP analysis confirmed agonist-dependent binding of LXRα, PPARα, and RXRα to this hormone response element complex (HREc). A luciferase reporter containing the 2 kb 5′ APOF sequence was negatively regulated by LXR and PPARα ligands as seen in cells. This regulation was maintained in constructs lacking the ~1700 nucleotides between the HREc and the APOF proximal promoter. Mutations of the HREc that disrupted LXRα and PPARα binding led to the loss of reporter construct inhibition by agonists of these nuclear receptors. siRNA knockdown studies showed that APOF gene regulation by LXRα or PPARα agonists did not require an interaction between these two nuclear receptors. Thus, APOF is subject to negative regulation by agonist-activated LXR or PPARα nuclear receptors binding to a regulatory element ~1900 bases 5′ to the APOF promoter. High fat, cholesterol-enriched diets likely reduce APOF gene expression via these receptors interacting at this regulatory site.     

Finite element modeling of arachnid slit sensilla—I. The mechanical significance of different slit arrays

Arachnid strain sensitive slit sensilla are elongated openings in the cuticle with aspect ratios (slit length l / slit width b) of up to 100. Planar Finite Element (FE) models are used to calculate the relative slit face displacements, D _c, at the centers of single slits and of arrangements of mechanically interacting slits under uni-axial compressive far-field loads. Our main objective is to quantitatively study the role of the following geometrical parameters in stimulus transformation: aspect ratio, slit shape, geometry of the slits‘ centerlines, load direction, lateral distance S, longitudinal shift λ, and difference in slit length Δl between neighboring slits. Slit face displacements are primarily sensitive to slit length and load direction but little affected by aspect ratios between 20 and 100. In stacks of five parallel slits at lateral distances typical of lyriform organs (S = 0.03 l) the longitudinal shift λ substantially influences slit compression. A change of λ from 0 to 0.85 l causes changes of up to 420% in D _c. Even minor morphological variations in the arrangements can substantially influence the stimulus transformation. The site of transduction in real slit sensilla does not always coincide with the position of maximum slit compression predicted by simplified models. An erratum to this article can be found at     

A Fos-Jun element in the first intron of an α2u-globulin gene

The hepatic expression of the _2u gene family is controlled by a variety of hormones including steroids, growth hormone and insulin. The mechanisms by which these hormones affect -globulin expression are only partially understood. Recently we isolated and characterized clone RAP 01, an _2u-globulin gene expressed in the liver. In preliminary experiments we noted that partial hepatectomy, a procedure which results in a sharp rise in the level of the oncoproteins c-Fos and c-Jun, also causes a transient induction of the messenger RNA corresponding to clone RAP 01. Using the DNAseI footprinting technique we were able to show that this clone contains a TPA (phorbol 12-myristate 13-acetate)-responsive element (TRE) in its first intron. This element (denoted as element X) is identical to the consensus AP-1 binding site (TGACTCAG) and is protected by rat liver nuclear extracts as well as by purified c-Jun. Gel retardation experiments show that an oligonucleotide containing the TRE consensus sequence competes for binding of liver nuclear proteins to element X and that antibodies directed against the M₂ peptide of the mouse Fos protein or the PEP-2 peptide of Jun prevent the formation of specific complexes with the same element. Moreover, element X functions as a TRE in transfected BWTG₃ hepatoma cells treated with TPA. Co-transfection withfos andjun expression vectors mimics the effects of TPA suggesting that AP-1 is in fact the mediator of the observed response. It is concluded that the first intron of RAP 01 contains a functional Fos-Jun element.     

Effect of sildenafil citrate (Viagra?) on trace element concentration in serum and brain of rats

As a vasodilator with good hemodynamic effects, sildenafil has been successfully used in the treatment of patients with pulmonary hypertension and cardiovascular diseases. By selectively inhibiting phosphodiestrase type 5 (PDE-5) and thus effectively reducing the breakdown of c GMP, sildenafil administration can markedly improve the erectile dysfunction. Sildenafil also elevates localized cerebral blood flow in rat brain. The objective of the present study was to investigate the effect of sildenafil on the level of trace elements (Zinc (Zn), copper (Cu), iron (Fe), selenium (Se), cobalt (Co), and chromium (Cr)) in blood and brain of rats. Sixteen male albino rats weighing 180-200 g were divided into two groups (8 rats/group). Sildenafil (Viagra, Pfizer Inc.) was dissolved in saline and administered at a dose of 10mg/kg i.p. (0.5 ml volume) to rats in the treated group every 72 h for 12 injections. Rats in the control group were administered the same volume of saline as in treated group. All rats were sacrificed 24h after the last injection. Blood samples were collected and serum was separated and stored at -20°C. Brains were dissected and stored frozen until analysis. Trace elements concentrations were determined by flame emission atomic absorption spectrophotometer. Results showed that sildenafil injection significantly (P<0.05) increased serum and brain Se and Cu concentrations. Moreover, sildenafil increased the Cr concentration in the brain tissue. It was concluded that sildenafil citrate administration increased serum Se and Cu as well as, increased brain Se, Cu, and Cr concentrations in rats.     

Deformation of articular cartilage during static loading of a knee joint – Experimental and finite element analysis

Novel conical beam CT-scanners offer high resolution imaging of knee structures with i.a. contrast media, even under weight bearing. With this new technology, we aimed to determine cartilage strains and meniscal movement in a human knee at 0, 1, 5, and 30 min of standing and compare them to the subject-specific 3D finite element (FE) model. The FE model of the volunteer?s knee, based on the geometry obtained from magnetic resonance images, was created to simulate the creep. The effects of collagen fibril network stiffness, nonfibrillar matrix modulus, permeability and fluid flow boundary conditions on the creep response in cartilage were investigated. In the experiment, 80% of the maximum strain in cartilage developed immediately, after which the cartilage continued to deform slowly until the 30 min time point. Cartilage strains and meniscus movement obtained from the FE model matched adequately with the experimentally measured values. Reducing the fibril network stiffness increased the mean strains substantially, while the creep rate was primarily influenced by an increase in the nonfibrillar matrix modulus. Changing the initial permeability and preventing fluid flow through noncontacting surfaces had a negligible effect on cartilage strains. The present results improve understanding of the mechanisms controlling articular cartilage strains and meniscal movements in a knee joint under physiological static loading. Ultimately a validated model could be used as a noninvasive diagnostic tool to locate cartilage areas at risk for degeneration.     

Influence of morphology and material properties on the range of motion of the costovertebral joint – a probabilistic finite element analysis

Abstract

The motion of the costovertebral joint (CVJ) is governed by the material properties and its morphology. The goal of this numerical study was to identify the material and morphology parameters with the greatest influence on the motion of the CVJ. A fully parametric finite element model of the anatomy and material properties of the CVJ was developed. The impact of five morphology and thirteen material parameters was investigated and compared to in vitro data. The motion was influenced in particular by the rotational stiffness of the articulatio capitis costae and the lateral position of the fovea costalis transveralis.