Kinematic analysis of a multi-segment foot model for research and clinical applications: a repeatability analysis

An unbiased understanding of foot kinematics has been difficult to achieve due to the complexity of foot structure and motion. We have developed a protocol for evaluation of foot kinematics during barefoot walking based on a multi-segment foot model. Stereophotogrammetry was used to measure retroreflective markers on three segments of the foot plus the tibia. Repeatability was evaluated between-trial, between-day and between-tester using two subjects and two testers. Subtle patterns and ranges of motion between segments of the foot were consistently detected. We found that repeatability between different days or different testers is primarily subject to variability of marker placement more than inter-tester variability or skin movement. Differences between inter-segment angle curves primarily represent a shift in the absolute value of joint angles from one set of trials to another. In the hallux, variability was greater than desired due to vibration of the marker array used. The method permits objective foot measurement in gait analysis using skin-mounted markers. Quantitative and objective characterisation of the kinematics of the foot during activity is an important area of clinical and research evaluation. With this work we hope to have provided a firm basis for a common protocol for in vivo foot study.     

Resistance training enhances the stability of sensorimotor coordination

Strategies for the control of human movement are constrained by the neuroanatomical characteristics of the motor system. In particular, there is evidence that the capacity of muscles for producing force has a strong influence on the stability of coordination in certain movement tasks. In the present experiment, our aim was to determine whether physiological adaptations that cause relatively long-lasting changes in the ability of muscles to produce force can influence the stability of coordination in a systematic manner. We assessed the effects of resistance training on the performance of a difficult coordination task that required participants to synchronize or syncopate movements of their index finger with an auditory metronome. Our results revealed that training that increased isometric finger strength also enhanced the stability of movement coordination. These changes were accompanied by alterations in muscle recruitment patterns. In particular, the trained muscles were recruited in a more consistent fashion following the programme of resistance training. These results indicate that resistance training produces functional adaptations of the neuroanatomical constraints that underlie the control of voluntary movement.     

Limited proteolysis of the coxsackievirus and adenovirus receptor (CAR) on HeLa cells exposed to trypsin

Trypsin treatment of HeLa cells results in a limited proteolysis of the coxsackievirus and adenovirus receptor (CAR) after which the cleaved CAR remains cell-associated and tryptic peptides remain associated through disulfide bonds. Trypsin-treated HeLa cells remain susceptible to infection with coxsackievirus B and produce progeny virus at 8 h post-infection in amounts comparable to cells with intact CAR. HeLa cells remove the proteolysed CAR within 15 h and require over 24 h to restore intact CAR to control levels. As turnover is relatively slow, physiological functions that require intact CAR protein may be compromised for more than 24 h following trypsin treatment. Moreover, since removal of proteolysed CAR proceeds at more than twice the replacement rate, trypsin treatment disrupts the receptor-per-cell steady state for at least 24 h.     

New structural motifs on the chymotrypsin fold and their potential roles in complement factor B

Factor B and C2 are two central enzymes for complement activation. They are multidomain serine proteases and require cofactor binding for full expression of proteolytic activities. We present a 2.1 A crystal structure of the serine protease domain of factor B. It shows a number of structural motifs novel to the chymotrypsin fold, which by sequence homology are probably present in C2 as well. These motifs distribute characteristically on the protein surface. Six loops surround the active site, four of which shape substrate-binding pockets. Three loops next to the oxyanion hole, which typically mediate zymogen activation, are much shorter or absent. Three insertions including the linker to the preceding domain bulge from the side opposite to the active site. The catalytic triad and non-specific substrate-binding site display active conformations, but the oxyanion hole displays a zymogen-like conformation. The bottom of the S1 pocket has a negative charge at residue 226 instead of the typical 189 position. These unique structural features may play different roles in domain-domain interaction, cofactor binding and substrate binding.     

NATURAL HYBRIDIZATION BETWEEN THE SYMPATRIC HAWAIIAN SPECIES DROSOPHILA SILVESTRIS AND DROSOPHILA HETERONEURA

Two newly formed, morphologically distinct species of Drosophila from the island of Hawaii have been found to form fertile hybrids in two areas of sympatry. Both F₁ and backcross hybrids have been recognized in nature; in one case, the hybridization events extended over three years. Original hybridizations involved one or more D. silvestris females mating with D. heteroneura males. Female F₁ hybrids from this cross have participated in backcrosses to D. silvestris. In any one locality, less than 2% hybrids have been found in nature. A hybrid swarm was not formed; selection appears to favor a strict maintenence of morphologies characteristic of the separate species. This result is attributed to pervasive sexual selection, which serves to preserve the syndromes of sexual characteristics that arose during past allopatric divergence. Populations of D. silvestris both within and outside the present range of D. heteroneura often display heritable variation in color patterns involving the abdomen, pleurae, legs, and wings. Genes effecting variation in these characters may be derived from genes involved in a past introgression from D. heteroneura. Independent evidence for past hybridization between these species comes from study of mitochondrial DNA. Although the inferred direction of the cross is the opposite of that observed in the recent case described here, both reciprocal crosses have been obtained experimentally in the laboratory. Accordingly, we suggest that these species may have been open to hybridization since their first sympatic encounters following their inception in allopatry. That they remain as strictly recognizable morphological entities is due both to their current partial allopatry and to the action of sexual selection in maintaining two separate major modes of efficient reproduction. There is no reason to invoke specific reinforcing selection that has imposed reproductive isolation.     

Expression of heparin/heparan sulfate interacting protein/ribosomal protein l29 during the estrous cycle and early pregnancy in the mouse

Using a variety of approaches, we have examined the expression of the heparin/heparan sulfate (Hp/HS) interacting protein/ribosomal protein L29 (HIP/RPL29) in mouse uteri during the estrous cycle and early pregnancy. HIP/RPL29 selectively binds heparin and HS and may promote HS-dependent embryo adhesion. HIP/RPL29 was prominently expressed in both luminal and glandular epithelia under almost all conditions, including the phase of embryo attachment. In contrast, differences were noted in HIP/RPL29 expression in the stromal compartment both during the estrous cycle and during early pregnancy. Most notably, HIP/RPL29 accumulated in decidua, where it displayed a pattern complementary to that of pericellular deposition of the HS proteoglycan, perlecan. HIP/RPL29 protein was detected in implanted embryos at both initial and later stages of implantation; however, embryonic HIP/RPL29 mRNA accumulation was more pronounced at later stages (Day 7.5 postcoitum). In situ hybridization revealed similar spatial changes for HIP/RPL29 mRNA during these different physiological states. Whereas differences in the spatial pattern of HIP/RPL29 protein and mRNA expression were demonstrable, little change was detected in the level of HIP/RPL29 mRNA or protein in total endometrial extracts. Mouse blastocysts attached, but did not outgrow, on surfaces coated with recombinant murine HIP/RPL29. Surprisingly, soluble glycosaminoglycans including heparin, low molecular weight heparin, or chondroitin sulfate were not able to inhibit embryo attachment to HIP/RPL29-coated surfaces. These latter observations indicate that embryonic cell surface components other than HS proteoglycans can promote binding to HIP/RPL29 expressed by uterine cells.     

Rational design, synthesis and structure-activity relationships of antitumor (E)-2-benzylidene-1-tetralones and (E)-2-benzylidene-1-indanones

Novel substituted 6,7-dimethoxy-1-tetralones and 5,6-dimethoxy-1-indanones have been synthesized and evaluated for their cytotoxicity. Compounds with 3'-lipophilic, 3',5'-dilipophilic, or 3',5'-dilipophilic-4'-hydrophilic substituents on (E)-2-benzylidene moiety showed highly cytotoxic effects. The unique structure of 42 possibly matches the pharmacophore features for these cytotoxic compounds.     

Functional magnetic resonance imaging of semantic memory as a presymptomatic biomarker of Alzheimer's disease risk

Extensive research efforts have been directed toward strategies for predicting risk of developing Alzheimer's disease (AD) prior to the appearance of observable symptoms. Existing approaches for early detection of AD vary in terms of their efficacy, invasiveness, and ease of implementation. Several non-invasive magnetic resonance imaging strategies have been developed for predicting decline in cognitively healthy older adults. This review will survey a number of studies, beginning with the development of a famous name discrimination task used to identify neural regions that participate in semantic memory retrieval and to test predictions of several key theories of the role of the hippocampus in memory. This task has revealed medial temporal and neocortical contributions to recent and remote memory retrieval, and it has been used to demonstrate compensatory neural recruitment in older adults, apolipoprotein E ε4 carriers, and amnestic mild cognitive impairment patients. Recently, we have also found that the famous name discrimination task provides predictive value for forecasting episodic memory decline among asymptomatic older adults. Other studies investigating the predictive value of semantic memory tasks will also be presented. We suggest several advantages associated with the use of semantic processing tasks, particularly those based on person identification, in comparison to episodic memory tasks to study AD risk. Future directions for research and potential clinical uses of semantic memory paradigms are also discussed. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.