The importance of craniofacial sutures in biomechanical finite element models of the domestic pig

Craniofacial sutures are a ubiquitous feature of the vertebrate skull. Previous experimental work has shown that bone strain magnitudes and orientations often vary when moving from one bone to another, across a craniofacial suture. This has led to the hypothesis that craniofacial sutures act to modify the strain environment of the skull, possibly as a mode of dissipating high stresses generated during feeding or impact. This study tests the hypothesis that the introduction of craniofacial sutures into finite element (FE) models of a modern domestic pig skull would improve model accuracy compared to a model without sutures. This allowed the mechanical effects of sutures to be assessed in isolation from other confounding variables. These models were also validated against strain gauge data collected from the same specimen ex vivo. The experimental strain data showed notable strain differences between adjacent bones, but this effect was generally not observed in either model. It was found that the inclusion of sutures in finite element models affected strain magnitudes, ratios, orientations and contour patterns, yet contrary to expectations, this did not improve the fit of the model to the experimental data, but resulted in a model that was less accurate. It is demonstrated that the presence or absence of sutures alone is not responsible for the inaccuracies in model strain, and is suggested that variations in local bone material properties, which were not accounted for by the FE models, could instead be responsible for the pattern of results.     

Fc Gamma Receptor IIIB (FcγRIIIB) Polymorphisms Are Associated with Clinical Malaria in Ghanaian Children

Plasmodium falciparum malaria kills nearly a million people annually. Over 90% of these deaths occur in children under five years of age in sub-Saharan Africa. A neutrophil mediated mechanism, the antibody dependent respiratory burst (ADRB), was recently shown to correlate with protection from clinical malaria. Human neutrophils constitutively express Fc gamma receptor-FcγRIIA and FcγRIIIB by which they interact with immunoglobulin (Ig) G (IgG)-subclass antibodies. Polymorphisms in exon 4 of FCGR2A and exon 3 of FCGR3B genes encoding FcγRIIA and FcγRIIIB respectively have been described to alter the affinities of both receptors for IgG. Here, associations between specific polymorphisms, encoding FcγRIIA p.H166R and FcγRIIIB-NA1/NA2/SH variants with clinical malaria were investigated in a longitudinal malaria cohort study. FcγRIIA-p.166H/R was genotyped by gene specific polymerase chain reaction followed by allele specific restriction enzyme digestion. FCGR3B-exon 3 was sequenced in 585 children, aged 1 to 12 years living in a malaria endemic region of Ghana. Multivariate logistic regression analysis found no association between FcγRIIA-166H/R polymorphism and clinical malaria. The A-allele of FCGR3B-c.233C>A (rs5030738) was significantly associated with protection from clinical malaria under two out of three genetic models (additive: p = 0.0061; recessive: p = 0.097; dominant: p = 0.0076) of inheritance. The FcγRIIIB-SH allotype (CTGAAA) containing the 233A-allele (in bold) was associated with protection from malaria (p = 0.049). The FcγRIIIB-NA2*03 allotype (CTGCGA), a variant of the classical FcγRIIIB-NA2 (CTGCAA) was associated with susceptibility to clinical malaria (p = 0.0092). The present study is the first to report an association between a variant of FcγRIIIB-NA2 and susceptibility to clinical malaria and provides justification for further functional characterization of variants of the classical FcγRIIIB allotypes. This would be crucial to the improvement of neutrophil mediated functional assays such as the ADRB assay aimed at assessing the functionality of antibodies induced by candidate malaria vaccines.     

Silver as a Residual Disinfectant To Prevent Biofilm Formation in Water Distribution Systems

Biofilms can have deleterious effects on drinking water quality and may harbor pathogens. Experiments were conducted using 100 μg/liter silver to prevent biofilm formation in modified Robbins devices with polyvinyl chloride and stainless steel surfaces. No significant difference was observed on either surface between the silver treatment and the control.     

Influence of contraction intensity, muscle, and gender on median frequency of the quadriceps femoris.

The purpose of this study was to assess the effects of contraction intensity, gender, and muscle on median frequency of the three superficial portions of the quadriceps femoris muscle. Thirty healthy volunteers were assessed for isometric electromyogram activity of the vastus medialis (VM), vastus lateralis (VL), and rectus femoris (RF) muscles with the knee at 60 degrees flexion. Subjects performed 5-s isometric contractions at 10, 20, 30, 40, 50, 60, 70, 80, and 90% of the average of three maximal voluntary contractions. Median frequency (f(med)) of the three muscles was assessed through a power spectral analysis performed over 11 consecutive 512-ms epochs overlapping each other by one-half their length. The f(med) for each of the 11 epochs was then determined, followed by calculation of the mean and SD. The major findings of this study demonstrated that overall f(med) was significantly highest for the VL and lowest for the VM, whereas RF f(med) was between that of the other two muscles. Similar findings were observed for f(med) variability as the VL was significantly higher than the VM and RF, with no gender differences or differences between the latter two muscles. The results demonstrate that the largest change in f(med) as a function of contraction intensity occurred for the VL in men (18.6%) and women (7.6%). These findings suggest that muscle fiber-type homogeneity may exist in the VM and RF, which displayed negligible changes in f(med), whereas the VL may possess greater morphological variability.     

Retinoic Acid and Vitamin E Modulate Expression and Release of CD178 in Carcinoma Cells: Consequences for Induction of Apoptosis in CD95-Sensitive Cells

CD178 (CD95-ligand) is expressed on several tumor cells and likely influences the interaction of the tumor with the host immune system. However, little is known about the mechanisms that regulate its expression on the cell surface. We have evaluated the ability of various compounds and cytokines to regulate cell surface expression and release of soluble CD178 in various carcinoma cell lines. Vitamin E succinate (VES) and retinoic acid (RA) were found to reduce CD178 surface expression, whereas interferon-gamma stimulated a slight upregulation. At 48 h, the regulation of surface CD178 by VES and RA arose from a small decrease in CD178 mRNA and to a greater extent due to an increase in the release of soluble CD178; the latter was blocked by addition of a metalloproteinase inhibitor. Accordingly, VES and RA treatment diminished the ability of tumor cells to kill CD95-sensitive cells and this effect was markedly reduced by the presence of a metalloproteinase inhibitor. Our results indicate that, in vitro, CD178 expression on the cell surface of tumor cells can be regulated by agents that alter both expression and release of the ligand. In vivo, such treatments may play an important role in the outcome of tumor sensitivity or resistance to host immune mechanisms.     

Species differences in methaemoglobin production after addition of 4-dimethylaminophenol, a cyanide antidote, to blood in vitro: a comparative study

Methaemoglobin production after addition of DMAP to blood of various species, has been studied in vitro. The study was undertaken both with blood, as taken, and after equilibration with atmospheric oxygen. Considerable interspecies variation in methaemoglobin production was found. When the initial rate of methaemoglobin formation was considered only marmoset and human blood showed any marked degree of inhibition by equilibration with atmospheric oxygen.     

In situ studies of protein conformation in supercritical fluids: trypsin in carbon dioxide.

The conformation of the monomeric enzyme trypsin has been studied in supercritical carbon dioxide. Steady-state fluorescence spectroscopy is used to follow the conformation of trypsin in situ as a function of CO2 density. Our results show for the first time that protein denaturation can occur during the fluid compression step and that the native trypsin is only slightly more stable (1.2 kcal/mol) than the unfolded form. These results demonstrate the power of fluorescence spectroscopy as a tool for studying protein conformation and dynamics in supercritical fluids.     

Nitro analogs of substrates for adenylosuccinate synthetase and adenylosuccinate lyase

The reactivities of the nitro analogs of the substrates of adenylosuccinate synthetase and adenylosuccinate lyase, the enzymes which catalyze the penultimate and last step, respectively, in the pathway for AMP biosynthesis have been examined. Alanine-3-nitronate, an aspartate analog, was a substrate for the synthetase from Azotobacter vinelandii, having a $\text{k}{}_{\mathrm{<mtext>cat</mtext>}}\text{K}{}_{\mathrm{m}}$ which was ~30% that for aspartate. The product of this reaction was N⁶-(l-1-carboxy-2-nitroethyl)-AMP. Of nine other substrate analogs tested, only cysteine sulfinate (having 5.5% of the activity of aspartate) was reactive. These results demonstrate the strict requirement of the synthetase for a negatively charged substituent, with a carboxylate-like geometry, at the β-carbon of the α-amino acid substrate. The lyase, purified to homogeneity from brewer's yeast by a new procedure, did not utilize N⁶-(l-1-carboxy-2-nitroethyl)-AMP as a substrate. However, the nitronate form of this analog was a good inhibitor of the lyase ($\text{K}{}_{\mathrm{m}}\text{K}{}_{\mathrm{i}}\text{= 28}$ when compared to adenylosuccinate), suggesting that it mimics a carbanionic intermediate in the reaction pathway. The avid binding of bromphenol blue by the lyase (_i = 0.95 μM) was used for active site titrations and for displacement of the enzyme, in the purification protocol, from blue Sepharose.