Predicting long bone loading from cross-sectional geometry

Long bone loading histories are commonly evaluated using a beam model by calculating cross-sectional second moments of areas (SMAs). Without in vivo strain data, SMA analyses commonly make two explicit or implicit assumptions. First, while it has long been known that axial compression superimposed on bending shifts neutral axes away from cross-sectional area centroids, most analyses assume that cross-sectional properties calculated through the area centroid approximate cross-sectional strength. Second, the orientation of maximum bending rigidity is often assumed to reflect the orientation of peak or habitual bending forces the bone experiences. These assumptions are tested in sheep in which rosette strain gauges mounted at three locations around the tibia and metatarsal midshafts measured in vivo strains during treadmill running at 1.5 m/sec. Calculated normal strain distributions confirm that the neutral axis of bending does not run through the midshaft centroid. In these animals, orientations of the principal centroidal axes around which maximum SMAs (Imax) are calculated are not in the same planes in which the bones experienced bending. Cross-sectional properties calculated using centroidal axes have substantial differences in magnitude (up to 55%) but high correlations in pattern compared to cross-sectional properties calculated around experimentally determined neutral axes. Thus interindividual comparisons of cross-sectional properties calculated from centroidal axes may be useful in terms of pattern, but are subject to high errors in terms of absolute values. In addition, cross-sectional properties do not necessarily provide reliable data on the orientations of loads to which bones are subjected.     

A common polygenic basis for quinine and PROP avoidance in mice

Inbred strains of mice (Mus musculus) differ greatly in ability to taste various bitter compounds. For some compounds, the differences result from allelic variation at a single locus. However, segregation patterns incompatible with monogenic inheritance have been found for quinine avoidance. The Soa bitter sensitivity locus exerts some influence on this phenotype, but an unknown number of other loci also contribute. Relative avoidance patterns for quinine sulfate in panels of naive inbred strains resembled avoidance patterns for 6-n-propyl-2- thiouracil (PROP), suggesting a common genetic basis. In particular, C57BL/6J mice strongly avoided both 0.1 mM quinine sulfate and 1 mM PROP in two-bottle preference tests, whereas C3H/HeJ mice were indifferent to both. Therefore, 12 BXH/Ty recombinant inbred strains, derived from these strains, were tested with both solutions to begin identification of the unknown bitter loci. Naive mice were tested for four consecutive days with each compound (order counterbalanced). Some BXH/Ty strain means resembled those of the parent strains, but others were intermediate. This indicated recombination among loci affecting avoidance, and therefore polygenic inheritance. The strain means were highly correlated across compounds (r = 0.98), suggesting that the same polygenes controlled both phenotypes. The BXH/Ty means for both compounds were then compared with the strain genotypes at 212 chromosome position markers distributed throughout the genome. Eight markers on five chromosomes (3, 6, 7, 8 and 9) yielded significant correlations. Six of the markers were correlated with both phenotypes, again suggesting common polygenic inheritance. The marker with the highest correlation was Prp, tightly linked to Soa on chromosome 6. The correlated marker regions likely contain quantitative trait loci affecting bitter avoidance. The phenotypic similarity of PROP to quinine, rather than to phenylthiourea, apparently stemming from a common polygenic basis, indicates a difference between mice and humans in gustatory organization related to bitters.      

Effects of extremely-low-frequency magnetic fields on biological magnetite

Adair [Bioelectromagnetics 14:1–4, 1993] writes that “the effects of 60 Hz magnetic fields of 5 μT (50 mG) or less on biological structures holding magnetite (Fe₃O₄) are shown to be much smaller than those from thermal agitation; hence such interactions cannot be expected to be biologically significant.” This conclusion is questioned, because it appears to be based on a model that probably has very limited validity for pertinent biological systems. Furthermore, biologically plausible parameters can be selected to show that even this particular model does not exclude biologically significant effects of 60 Hz magnetic fields below 5 μT. Reported experimental results indicate effects in mammals of 50 Hz fields at the 1 μT level. © 1994 Wiley-Liss, Inc.     

Sampling frequencies and measurement error for linear and temporal gait parameters in primate locomotion

Quantitative analyses of animal motion are increasingly easy to conduct using simple video equipment and relatively inexpensive software packages. With careful use, such analytical tools have the potential to quantify differences in movement between individuals or species and to allow insights into the behavioral consequences of morphological differences between taxa. However, as with any other type of measurement, there are errors associated with kinematic measurements. Because normative kinematic data on human and nonhuman primate locomotion are used to model aspects of gait of fossil hominins, errors in the extant data influence the accuracy of fossil gait reconstructions. The principal goal of this paper is to illustrate the effect of camera speeds (frame rates) on kinematic measurement errors, and to demonstrate how these errors vary with subject size, movement velocity, and sample size. Kinematic data for human walking and running (240 Hz), as well as data for primate quadrupedal walking and running (180 Hz) were used as inputs for a simulation of the measurement errors associated with various linear and temporal kinematic variables. Measurement errors were shown to increase as camera speed, subject body size, and interval duration all decrease, and as movement velocity increases. These results have implications for the methods used to calculate subject velocity and suggest that using a moving marker to measure the linear displacements of the body is preferable to the use of a stationary marker. Finally, while slower camera speeds will always result in higher measurement errors than do faster camera speeds, this effect can be moderated to some extent by collecting sufficiently large samples of data.     

Activation of peroxisome proliferator-activated receptor gamma suppresses nuclear factor kappa B-mediated apoptosis induced by Helicobacter pylori in gastric epithelial cells

Helicobacter pylori colonization leads to epithelial cell hyperproliferation within inflamed mucosa, but levels of apoptosis vary, suggesting that imbalances between rates of cell production and loss may contribute to differences in gastric cancer risk among infected populations. Peroxisome proliferator-activated receptor gamma (PPARgamma) regulates inflammatory and growth responses of intestinal epithelial cells. We determined whether activation of PPARgamma modified H. pylori-induced apoptosis in gastric epithelial cells. PPARgamma was expressed and functionally active in gastric epithelial cell lines sensitive to H. pylori-induced apoptosis. PPARgamma ligands 15d-PGJ(2) and BRL-49653 significantly attenuated H. pylomicronri-induced apoptosis, effects that could be reversed by co-treatment with a specific PPARgamma antagonist. Cyclopentanone prostaglandins that do not bind and activate PPARgamma had no effects on H. pylori-induced apoptosis. The ability of H. pylori to activate nuclear factor (NF)-kappaB and increase levels of the NF-kappaB target IL-8 was blocked by co-treatment with PPARgamma agonists, and direct inhibition of NF-kappaB also abolished H. pylori-stimulated apoptosis. These results suggest that activation of the PPARgamma pathway attenuates the ability of H. pylori to induce NF-kappaB-mediated apoptosis in gastric epithelial cells. Because PPARgamma regulates a multitude of host responses, activation of this receptor may contribute to varying levels of cellular turnover as well as the diverse pathologic outcomes associated with chronic H. pylori colonization.     

Diet-induced obesity in rats leads to a decrease in sperm motility

Background  

Obesity is rapidly becoming a worldwide epidemic that affects children and adults. Some studies have shown a relationship between obesity and infertility, but until now it remains controversial. Thus, the aim of the present study was to investigate the effect of high-fat diet-induced obesity on male reproductive parameters.     

Divergent patterns of integration and reduced constraint in the human hip and the origins of bipedalism

When compared to other hominids--great apes including humans--the human pelvis reveals a fundamental reorganization of bony morphology comprised of multiple trait-level changes, many of which are associated with bipedal locomotion. Establishing how patterns of integration--correlations and covariances among traits--within the pelvis have evolved in concert with morphology is essential to explaining this evolutionary transition because integration may facilitate or constrain morphological evolution. Here, we show that the human hip bone has significantly lower levels of integration and constraint overall when compared to other hominids, that the focus of these changes is on traits hypothesized to play major functional roles in bipedalism, and we provide evidence that the human hip was reintegrated in a pattern distinct from other members of this group. Additionally, the evolutionary transition from a nonhuman great ape-like to human hip bone morphology was significantly easier to traverse using the human integration pattern in each comparison, which suggests hominin patterns may have evolved to facilitate this transition. Our results suggest natural selection for bipedalism broke down earlier hominid integration patterns, allowing relevant traits to respond to separate selection pressures to a greater extent than was previously possible, and reintegrated traits in a way that could have facilitated evolution along the vector specifying ancestral hominid and hominin morphological differences.     

RhoA regulation of NF-kappaB activation is mediated by COX-2-dependent feedback inhibition of IKK in kidney epithelial cells

Numerous studies have demonstrated a central role of renal tubular epithelial cells in the etiology of kidney injury and disease through the elaboration of inflammatory mediators. However, little is known about the cellular signaling mechanisms involved in this process. In this study we employed normal rat kidney epithelial (NRK52E) cells to identify a novel LPS-induced signaling pathway in which RhoA-mediated AP-1 activity promotes expression of cyclooxygenase-2 (COX-2) with consequent feedback inhibition of NF-B activation through IKK. Inhibition of RhoA signaling using either the RhoA kinase inhibitor Y-27632 or a dominant negative mutant of RhoA (RhoA-DN) dramatically extended the duration of p65-DNA binding, IB phosphorylation, and IKK activity following LPS treatment. Prolongation of events associated with NF-B activation was also observed in cells pretreated and/or cotransfected with the JNK inhibitor SP600125 or deletion mutants of MEKK1 (MEKK1-KD) or Jun (Jun-DN). Conversely, constitutive expression of RhoA prevented NF-B activation by LPS, and this effect was reversed by cotransfection with MEKK1-KD. In addition, we found that the RhoA/AP-1 signaling axis plays a necessary role in COX-2 expression by LPS and that this effect is independent of NF-B activation. Moreover, inhibition of COX-2 activity results in persistent p65-DNA binding, IB phosphorylation, and IKK activity, similar to that observed after prevention of RhoA/AP-1 axis signaling. These findings suggest that COX-2 links the RhoA/AP-1 signaling cascade to NF-B activation, thereby defining a novel integrated model for regulation of the inflammatory response of kidney epithelial cells to LPS and potentially other external stimuli. AP-1; cyclooxygenase-2; inflammation; lipopolysaccharide, nuclear factor-B; IB kinase