Contribution of inter-site variations in architecture to trabecular bone apparent yield strains

Apparent yield strains for trabecular bone are uniform within an anatomic site but can vary across site. The overall goal of this study was to characterize the contribution of inter-site differences in trabecular architecture to corresponding variations in apparent yield strains. High-resolution, small deformation finite element analyses were used to compute apparent compressive and tensile yield strains in four sites (n = 7 specimens per site): human proximal tibia, greater trochanter, femoral neck, and bovine proximal tibia. These sites display differences in compressive, but not tensile, apparent yield strains. Inter-site differences in architecture were captured implicitly in the model geometries, and these differences were isolated as the sole source of variability across sites by using identical tissue properties in all models. Thus, the effects inter-site variations in architecture on yield strain could be assessed by comparing computed yield strains across site. No inter-site differences in computed yield strains were found for either loading mode (p > 0.19), indicating that, within the context of small deformations, inter-site variations in architecture do not affect apparent yield strains. However, results of ancillary analyses designed to test the validity of the small deformation assumption strongly suggested that the propensity to undergo large deformations constitutes an important contribution of architecture to inter-site variations in apparent compressive yield strains. Large deformations substantially reduced apparent compressive, but not tensile, yield strains. These findings indicate the importance of incorporating large deformation capabilities in computational analyses of trabecular bone. This may be critical when investigating the biomechanical consequences of trabecular thinning and loss.     

Periportal fibrosis in human Schistosoma mansoni infection is associated with low IL-10, low IFN-gamma, high TNF-alpha, or low RANTES, depending on age and gender

Schistosoma mansoni infection is highly endemic in parts of Uganda, and periportal fibrosis is common in communities along the shore of Lake Albert. In this study, we have identified cellular immune responses associated with fibrosis. A cohort of 199 individuals aged 6-50, resident in the village for at least 10 years or since birth, were examined for evidence of periportal fibrosis by ultrasound using the Niamey protocol. Whole-blood samples were assayed for levels of nine cellular immune molecules (IL-3, IL-4, IL-5, IL-10, IL-13, TNF-alpha, IFN-gamma, IL-1beta, and RANTES) in the absence of in vitro Ag stimulation, and after stimulation with egg and worm Ags. A lack of Ag specificity allowed the number of variables in the analysis to be reduced by factor analysis. The resulting factor scores were then entered into a risk analysis using a classification tree algorithm. Children, adult males, and adult females had different factors associated with fibrosis. Most cases of fibrosis in children (eight of nine) were associated with low (<47th percentile) IL-10 factor scores. Adult females at lowest risk had relatively high IFN-gamma factor scores (>83rd percentile), whereas those at highest risk had a combination of intermediate (32nd to 83rd percentile) IFN-gamma and relatively high (>60th percentile) TNF-alpha factor scores. Adult males at lowest risk of fibrosis had moderate TNF-alpha factor scores (55th to 82nd percentile), and a high risk was associated with either high TNF-alpha factor scores (>82nd percentile), or intermediate TNF-alpha combined with low RANTES factor scores (<58th percentile). These results demonstrate that periportal fibrosis is associated with cytokine production profiles that vary with both age and gender.     

Abrogation of transforming growth factor-beta signaling by SMAD7 inhibits collagen gel contraction of human dermal fibroblasts

Human fibroproliferative disorders like hypertrophic scarring of the skin are characterized by increased contractility and excess extracellular matrix synthesis. A beneficial role of transforming growth factor (TGF)-beta in wound healing was proposed; however, chronic stimulation by this cytokine leads to fibrosis. In the present report, the intracellular TGF-beta signaling in fibroblasts derived from hypertrophic scars and normal skin was examined. In an attempt to intervene in profibrogenic TGF-beta functions, ectopic expression of Smad7 or dominant negative Smads3/4 completely inhibited contractility of scar-derived and normal fibroblasts after suspension in collagen gels. Both cell types displayed constitutive Smad2/3 phosphorylation and (CAGA)9-MLP-Luc activity with expression and phosphorylation of Smad3 being predominant in hypertrophic scar-derived fibroblasts. Down-regulation of intrinsic signaling with various TGF-beta antagonists, e.g. soluble TGF-beta receptor, latency-associated peptide, and anti-TGF-beta1 antibodies, confirms autocrine TGF-beta stimulation of both cell populations. Further, Smad7 expression inhibited alpha1 (I) collagen and alpha-smooth muscle actin expression. In summary, our data indicate that autocrine TGF-beta/Smad signaling is involved in contractility and matrix gene expression of fibroblasts from normal and hypertrophic scars. Smad7 inhibits these processes and may exert beneficial effects on excessive scar formation.     

Web-based two-dimensional database of Saccharomyces cerevisiae proteins using immobilized pH gradients from pH 6 to pH 12 and matrix-assisted laser desorption/ionization-time of flight mass spectrometry

An image based two-dimensional (2-D) reference map of very alkaline yeast cell proteins was established by using immobilized pH gradients (IPG) up to pH 12 (IPG 6-12, IPG 9-12 and IPG 10-12) for 2-D electrophoresis and by using matrix-assisted laser desorption/ionization-time of flight mass spectrometry peptide mass fingerprinting for spot identification. Up to now 106 proteins with theoretical isoelectric points up to pH 11.15 and molecular mass between 7.5 and 115 kDa were localized and identified. Additionally, due to the improved resolution of steady-state isoelectric focussing with IPGs, even low copy number proteins with codon bias below 0.02 were detected and identified.     

Occupancy models including local and landscape variables are useful to assess the distribution of a salamander species at risk

Numerous amphibian species are at risk of extinction worldwide. Therefore, reliable estimations of the distribution and abundance of these species are necessary for their conservation. Generally, amphibians are difficult to detect in the wild, which compromises the accuracy of long-term population monitoring and management. Occupancy models are useful tools to assess how environmental variables, at a local and at a landscape scale, affect the distribution and abundance of organisms taking into account species imperfect detectability. In this study, we evaluated with an environmental multiscale approach the seasonal variation of the occupation area of the threatened salamander, Ambystoma ordinarium along its distribution range. We obtained readings in 60 streams of physicochemical variables associated with habitat quality and landscape features. We found that detection and occupation probability of A. ordinarium are seasonally associated with different environmental variables. During the dry season, detectability was positively associated with temperature and stream depth, whereas occupancy was positively associated with the proportion of crops in the landscape and stream elevation. In the rainy season, the detection probability was not explained by any variable considered, and occupancy was negatively associated with stream's electrical conductivity and dissolved oxygen. Based on the estimation of occupied sites, we showed that A. ordinarium presents a more restricted distribution range than previously projected. Therefore, our results reveal the importance of evaluating the accuracy of distribution estimates for the conservation of threatened species as A. ordinarium.     

A Hybrid One-Way ANOVA Approach for the Robust and Efficient Estimation of Differential Gene Expression with Multiple Patterns

Background

Identifying genes that are differentially expressed (DE) between two or more conditions with multiple patterns of expression is one of the primary objectives of gene expression data analysis. Several statistical approaches, including one-way analysis of variance (ANOVA), are used to identify DE genes. However, most of these methods provide misleading results for two or more conditions with multiple patterns of expression in the presence of outlying genes. In this paper, an attempt is made to develop a hybrid one-way ANOVA approach that unifies the robustness and efficiency of estimation using the minimum β-divergence method to overcome some problems that arise in the existing robust methods for both small- and large-sample cases with multiple patterns of expression.

Results

The proposed method relies on a β-weight function, which produces values between 0 and 1. The β-weight function with β = 0.2 is used as a measure of outlier detection. It assigns smaller weights (≥ 0) to outlying expressions and larger weights (≤ 1) to typical expressions. The distribution of the β-weights is used to calculate the cut-off point, which is compared to the observed β-weight of an expression to determine whether that gene expression is an outlier. This weight function plays a key role in unifying the robustness and efficiency of estimation in one-way ANOVA.

Conclusion

Analyses of simulated gene expression profiles revealed that all eight methods (ANOVA, SAM, LIMMA, EBarrays, eLNN, KW, robust BetaEB and proposed) perform almost identically for m = 2 conditions in the absence of outliers. However, the robust BetaEB method and the proposed method exhibited considerably better performance than the other six methods in the presence of outliers. In this case, the BetaEB method exhibited slightly better performance than the proposed method for the small-sample cases, but the the proposed method exhibited much better performance than the BetaEB method for both the small- and large-sample cases in the presence of more than 50% outlying genes. The proposed method also exhibited better performance than the other methods for m > 2 conditions with multiple patterns of expression, where the BetaEB was not extended for this condition. Therefore, the proposed approach would be more suitable and reliable on average for the identification of DE genes between two or more conditions with multiple patterns of expression.     

Pentacyclic Triterpenoids Inhibit IKKβ Mediated Activation of NF-κB Pathway: In Silico and In Vitro Evidences

Pentacyclic Triterpenoids (PTs) and their analogues as well as derivatives are emerging as important drug leads for various diseases. They act through a variety of mechanisms and a majority of them inhibit the nuclear factor kappa-beta (NF-κB) signaling pathway. In this study, we examined the effects of the naturally occurring PTs on IκB kinase-β (IKKβ), which has great scientific relevance in the NF-κB signaling pathway. On virtual screening, 109 PTs were screened through the PASS (prediction of activity spectra of substances) software for prediction of NF-κB inhibitory activity followed by docking on the NEMO/IKKβ association complex (PDB: 3BRV) and testing for compliance with the softened Lipinski’s Rule of Five using Schrodinger (LLC, New York, USA). Out of the projected 45 druggable PTs, Corosolic Acid (CA), Asiatic Acid (AA) and Ursolic Acid (UA) were assayed for IKKβ kinase activity in the cell free medium. The UA exhibited a potent IKKβ inhibitory effect on the hotspot kinase assay with IC50 of 69 μM. Whereas, CA at 50 μM concentration markedly reduced the NF-κB luciferase activity and phospho-IKKβ protein expressions. The PTs tested, attenuated the expression of the NF-κB cascade proteins in the LPS-stimulated RAW 264.7 cells, prevented the phosphorylation of the IKKα/β and blocked the activation of the Interferon-gamma (IFN-γ). The results suggest that the IKKβ inhibition is the major mechanism of the PTs-induced NF-κB inhibition. PASS predictions along with in-silico docking against the NEMO/IKKβ can be successfully applied in the selection of the prospective NF-κB inhibitory downregulators of IKKβ phosphorylation.     

Tip60 might be a candidate for the acetylation of hepatic carbonic anhydrase I and III in mice

Molecular Biology Reports - Carbonic anhydrases (CAs) play a significant role in maintaining pH balance by catalyzing the conversion of carbon dioxide to bicarbonate. The regulation of pH is...     

Fluid–structure interaction (FSI) modeling of bone marrow through trabecular bone structure under compression

Biomechanics and Modeling in Mechanobiology - The present study has sought to investigate the fluid characteristic and mechanical properties of trabecular bone using fluid–structure...     

Spatial pattern of foliar hydrogen peroxide concentration and its implication in riparian vegetation management

Landscape and Ecological Engineering - Riparian vegetation is constantly subjected to environmental stresses and reactive oxygen species (ROS) are generated in the plant tissue due to the stress....