A new parametric approach for modeling hip forces during gait

An analytical parametric model was developed to estimate the natural biological variations in muscle forces and their effect on the hip forces subject only to physiological constraints and not predefined optimization criterion. Force predictions are based on the joint kinematics and kinetics of each subject, a previously published muscle model, and physiological constraints on the muscle force distributions. The model was used to determine the hip contact forces throughout the stance phase of gait of a subject with a total hip replacement (THR). The parametrically modeled peak hip force without antagonistic muscle activity varied from 2.7 to 3.2 Body Weights (mean 2.9 Body Weights), which agreed well with published in vivo measurements from instrumented THRs in other subjects. For every 10% increase in antagonistic activity, the mean peak hip force increased by 0.2 Body Weights. The parametric model allows one to examine the effect of specific muscle weaknesses or increased antagonistic muscle activity on the hip forces. The model also provides a tool for studying the effect of gait adaptations on hip forces, as predictions are based on each individual's gait data. Differences in peak forces between subjects can then be evaluated relative to the uncertainty in not knowing the precise muscle force distributions.     

Discovery of biomarker candidates for coronary artery disease from an APOE-knock out mouse model using iTRAQ-based multiplex quantitative proteomics

Due to the lack of precise markers indicative of its occurrence and progression, coronary artery disease (CAD), the most common type of heart diseases, is currently associated with high mortality in the United States. To systemically identify novel protein biomarkers associated with CAD progression for early diagnosis and possible therapeutic intervention, we employed an iTRAQ‐based quantitative proteomic approach to analyze the proteome changes in the plasma collected from a pair of wild‐type versus apolipoprotein E knockout (APOE^?/?) mice which were fed with a high fat diet. In a multiplex manner, iTRAQ serves as the quantitative ‘in‐spectra’ marker for ‘cross‐sample’ comparisons to determine the differentially expressed/secreted proteins caused by APOE knock‐out. To obtain the most comprehensive proteomic data sets from this CAD‐associated mouse model, we applied both MALDI and ESI‐based mass spectrometric (MS) platforms coupled with two different schemes of multidimensional liquid chromatography (2‐D LC) separation. We then comparatively analyzed a series of the plasma samples collected at 6 and 12 wk of age after the mice were fed with fat diets, where the 6‐ or 12‐wk time point represents the early or intermediate phase of the fat‐induced CAD, respectively. We then categorized those proteins showing abundance changes in accordance with APOE depletion. Several proteins such as the γ and β chains of fibrinogen, apolipoprotein B, apolipoprotein C‐I, and thrombospondin‐4 were among the previously known CAD markers identified by other methods. Our results suggested that these unbiased proteomic methods are both feasible and a practical means of discovering potential biomarkers associated with CAD progression.     

A new approach for heparin standardization: combination of scanning UV spectroscopy, nuclear magnetic resonance and principal component analysis

The year 2007 was marked by widespread adverse clinical responses to heparin use, leading to a global recall of potentially affected heparin batches in 2008. Several analytical methods have since been developed to detect impurities in heparin preparations; however, many are costly and dependent on instrumentation with only limited accessibility. A method based on a simple UV-scanning assay, combined with principal component analysis (PCA), was developed to detect impurities, such as glycosaminoglycans, other complex polysaccharides and aromatic compounds, in heparin preparations. Results were confirmed by NMR spectroscopy. This approach provides an additional, sensitive tool to determine heparin purity and safety, even when NMR spectroscopy failed, requiring only standard laboratory equipment and computing facilities.     

Computational and serologic analysis of novel and known viruses in species human adenovirus D in which serology and genomics do not correlate

In November of 2007 a human adenovirus (HAdV) was isolated from a bronchoalveolar lavage (BAL) sample recovered from a biopsy of an AIDS patient who presented with fever, cough, tachycardia, and expiratory wheezes. To better understand the isolated virus, the genome was sequenced and analyzed using bioinformatic and phylogenomic analysis. The results suggest that this novel virus, which is provisionally named HAdV-D59, may have been created from multiple recombination events. Specifically, the penton, hexon, and fiber genes have high nucleotide identity to HAdV-D19C, HAdV-D25, and HAdV-D56, respectively. Serological results demonstrated that HAdV-D59 has a neutralization profile that is similar yet not identical to that of HAdV-D25. Furthermore, we observed a two-fold difference between the ability of HAdV-D15 and HAdV-D25 to be neutralized by reciprocal antiserum indicating that the two hexon proteins may be more similar in epitopic conformation than previously assumed. In contrast, hexon loops 1 and 2 of HAdV-D15 and HAdV-D25 share 79.13 and 92.56 percent nucleotide identity, respectively. These data suggest that serology and genomics do not always correlate.     

Substrate specificity within a family of outer membrane carboxylate channels

Many Gram-negative bacteria, including human pathogens such as Pseudomonas aeruginosa, do not have large-channel porins. This results in an outer membrane (OM) that is highly impermeable to small polar molecules, making the bacteria intrinsically resistant towards many antibiotics. In such microorganisms, the majority of small molecules are taken up by members of the OprD outer membrane protein family. Here we show that OprD channels require a carboxyl group in the substrate for efficient transport, and based on this we have renamed the family Occ, for outer membrane carboxylate channels. We further show that Occ channels can be divided into two subfamilies, based on their very different substrate specificities. Our results rationalize how certain bacteria can efficiently take up a variety of substrates under nutrient-poor conditions without compromising membrane permeability. In addition, they explain how channel inactivation in response to antibiotics can cause resistance but does not lead to decreased fitness.     

Kinship on the Kibbutz: coresidence duration predicts altruism, personal sexual aversions and moral attitudes among communally reared peers

The natural experiments created by the Israeli Kibbutzim and Taiwanese minor marriages provide unique testing grounds for investigating the mechanisms governing sibling detection, inbreeding avoidance and kin-selected altruism. Here we present two studies conducted on the coreared peers of Israeli Kibbutzim. We examined how coresidence duration — a cue that would have indicated genetic relatedness in ancestral environments — impacts the development of kin-directed behaviors. In both studies, we found that coresidence duration predicts levels of altruism and sexual aversions directed toward peers. We also investigated the relationship between personal sexual aversions and moral attitudes relating to peer sexual behavior. The absence of norms proscribing sex between peers on the Kibbutz allows for a more tightly controlled investigation of this relationship. We found that total coresidence duration with opposite-sex peers predicts the intensity of moral wrongness associated with third-party peer sexual behavior, but not other behaviors, including sibling incest. More directly, we found that the summed sexual aversion felt toward all opposite-sex peers predicts levels of moral wrongness associated with third-party peer sex. Mediation analyses confirmed that personal sexual aversions mediate the relationship between coresidence duration and moral attitudes regarding peer sex. These results bolster Westermarck's original claims that childhood coresidence serves as a kinship cue, leading to greater sexual aversions and altruistic motivations, and that personal sexual aversions shape attitudes relating to third-party sexual behavior.     

Eyes absent: A gene family found in several metazoan phyla

Genes related to the Drosophila eyes absent gene were identified in vertebrates (mouse and human), mollusks (squid), and nematodes (C. elegans). Proteins encoded by these genes consist of conserved C-terminal and variable N-terminal domains. In the conserved 271-amino acid C-terminal region, Drosophila and vertebrate proteins are 65–67% identical. A vertebrate homolog of eyes absent, designated Eya2, was mapped to Chromosome (Chr) 2 in the mouse and to Chr 20q13.1 in human. Eya2 shows a dynamic pattern of expression during development. In the mouse, expression of Eya2 was first detected in 8.5-day embryos in the region of head ectoderm fated to become the forebrain. At later stages of development, Eya2 is expressed in the olfactory placode and in a variety of neural crest derivatives. In the eye, expression of Eya2 was first detected after formation of the lens vesicle. At day 17.5, the highest level of Eya2 mRNA was observed in primary lens fibers. Low levels of Eya2 expression was detected in retina, sclera, and cornea. By postnatal day 10, Eya2 was expressed in secondary lens fibers, cornea, and retina. Although Eya2 is expressed relatively late in eye development, it belongs to the growing list of factors that may be essential for eye development across metazoan phyla. Like members of the Pax-6 gene family, eyes absent gene family members were probably first involved in functions not related to vision, with recruitment for visual system formation and function occurring later. Received: 23 November 1996 / Accepted: 25 February 1997