Evaluation of the influence of muscle deactivation on other muscles and joints during gait motion

When any muscle in the human musculoskeletal system is damaged, other muscles and ligaments tend to compensate for the role of the damaged muscle by exerting extra effort. It is beneficial to clarify how the roles of the damaged muscles are compensated by other parts of the musculoskeletal system from the following points of view: From a clinical point of view, it will be possible to know how the abnormal muscle and joint forces caused by the acute compensations lead to further physical damage to the musculoskeletal system. From the viewpoint of rehabilitation, it will be possible to know how the role of the damaged muscle can be compensated by extra training of the other muscles. A method to evaluate the influence of muscle deactivation on other muscles and joints is proposed in this report. Methodology based on inverse dynamics and static optimization, which is applicable to arbitrary motion was used in this study. The evaluation method was applied to gait motion to obtain matrices representing (1) the dependence of muscle force compensation and (2) the change to bone-on-bone contact forces. These matrices make it possible to evaluate the effects of deactivation of one of the muscles of the musculoskeletal system on the forces exerted by other muscles as well as the change to the bone-on-bone forces when the musculoskeletal system is performing the same motion. Through observation of this matrix, it was found that deactivation of a muscle often results in increment/decrement of force developed by muscles with completely different primary functions and bone-on-bone contact force in different parts of the body. For example, deactivation of the iliopsoas leads to a large reduction in force by the soleus. The results suggest that acute deactivation of a muscle can result in damage to another part of the body. The results also suggest that the whole musculoskeletal system must go through extra retraining in the case of damage to certain muscles.     

Role of the Msh2 gene in genome maintenance and development in mouse fetuses

In an attempt to evaluate the roles of the mismatch repair gene Msh2 in genome maintenance and in development during the fetal stage, spontaneous mutations and several developmental indices were studied in Msh2-deficient lacZ-transgenic mouse fetuses. Mutation levels in fetuses were elevated at 9.5dpc (days post coitum) when compared to wild-type mice, and the level of mutations continued to increase until the fetuses reached the newborn stage. The mutation levels in 4 different tissues of newborns showed similar magnitudes to those in the whole body. The levels remained similar after birth until 6 months of age. The molecular nature of the mutations examined in 12.5dpc fetuses of Msh2(+/+) and Msh2(-/-) revealed unique spectra which reflect errors produced during the DNA replication process, and those corrected by a mismatch repair system. Most base substitutions and simple deletions were reduced by the presence of the Msh2 gene, whereas G:C to A:T changes at CpG sequences were not affected, suggesting that the latter change was not influenced by mismatch repair. On the other hand, analysis of developmental indices revealed that there was very little effect, including the presence of malformations, resulting from Msh2-deficiencies. These results indicate that elevated mutation levels have little effect on the development of the fetus, even if a mutator phenotype appears at the organogenesis stage.     

Deficiency of inducible nitric oxide synthase exacerbates hepatic fibrosis in mice fed high-fat diet

The role of inducible nitric oxide synthase (iNOS) in the progression of fibrosis during nonalcoholic steatohepatitis remains to be elucidated. This study examined the role of iNOS in the progression of fibrosis during steatohepatitis by comparing iNOS knockout (iNOS^−/−) and wild-type (iNOS^+/+) mice that were fed a high-fat diet. Severe fatty metamorphosis developed in the liver of iNOS^+/+ and iNOS^−/− mice. Fibrotic changes were marked in iNOS^−/− mice. Gelatin zymography showed that pro MMP-2 and pro MMP-9 protein expressions were more highly induced in iNOS^+/+ mice than in iNOS^−/− mice. Active forms of MMP-2 and MMP-9 were clearly present only in the liver tissue of iNOS^+/+ mice. In situ zymography showed strong gelatinolytic activities in the liver tissue of iNOS^+/+ mice, but only spotty activity in iNOS^−/−mice. iNOS may attenuate the progression of liver fibrosis in steatohepatitis, in part by inducing MMP-2 and MMP-9 expression and augmenting their activity.     

Effects of the length ratio between the contractile element and the series elastic element on an explosive muscular performance.

Effects of the length ratio between the contractile element (CE) and the series elastic element (SEE) on the behavior of the muscle tendon complex were investigated during stretch-shortening cycles. A computer simulation model of the Hill-type muscle tendon complex was constructed. The proximal end of the CE was affixed to a point in the gravitational field, and a massless supporting object was affixed to the distal end of the SEE. A mass was held on the supporting object. Initially, the muscle tendon complex was fixed at a certain length, and the CE was activated at 100%. Through this process, the CE contracted as much as the SEE was stretched. Thereafter, the supporting object was released, which caused the muscle tendon complex to propel the mass upward, simulating a stretch-shortening cycle. The length ratio between the CE and the SEE, the size of the mass and the initial length of the CE were sequentially changed. As a result, it was found that a higher performance is obtained with a longer SEE when the mass is small, while with a shorter SEE when the mass is large.     

The Golgi apparatus of goblet cells in the mouse descending colon: three-dimensional visualization using a confocal laser scanning microscope

The three-dimensional structure of the Golgi apparatus was studied in goblet cells in lectin-stained sections of the mouse descending colon by using a confocal laser scanning microscope. In the lower part of the crypt, the Golgi apparatus formed a dome- or globe-like structure in the supranuclear region. The wall of the dome had some holes, one of which usually faced toward the nucleus and others toward the apical cytoplasm. Mucous granules seemed to be initially released into the interior of the dome and transported toward the apical cytoplasm through the holes. In the upper part of the crypt, on the other hand, the Golgi apparatus formed a cup- or funnel-like structure with a larger opening toward the cell apex and a smaller opening toward the nucleus. A large mass of mucous granules occupied the inside of the cup to the apical cytoplasm. It is thought that the accumulation of mucous granules enlarges holes at the ceiling of the dome to form a large opening, which makes the configuration of the Golgi apparatus cup-shaped.     

Growth dynamics of domains in ternary fluid vesicles

We have studied the growth dynamics of domains on ternary fluid vesicles composed of saturated (dipalmitoylphosphatidylcholine), unsaturated (dioleoylphosphatidylcholine) phosphatidylcholine lipids, and cholesterol using a fluorescence microscopy. The domain coarsening processes are classified into two types: normal coarsening and trapped coarsening. For the normal coarsening, the domains having flat circular shape grow in a diffusion-and-coalescence manner and phenomenologically the mean size grows as a power law of approximately t(2/3). The observed growth law is not described by a two-dimensional diffusion-and-coalescence growth mechanism following the Saffman and Delbrück theory, which may originate from the two-body hydrodynamic interactions between domains. For trapped coarsening, on the other hand, the domain coarsening is suppressed at a certain domain size because the repulsive interdomain interactions obstruct the coalescence of domains. The two-color imaging of the trapped domains reveals that the repulsive interactions are induced by the budding of domains. The model free energy consisting of the bending energy of domains, the bending energy of matrix, the line energy of domain boundary, and the translation energy of domains can describe the observed trapped coarsening. The trapping of domains is caused by the coupling between the phase separation and the membrane elasticity under the incompressibility constraint.     

Impaired development of mammary glands in scorbutic rats unable to synthesize ascorbic acid

The effects of ascorbic acid (AsA)-deficiency on the development of mammary glands were investigated using mutant rats (osteogenic disorder syndrome rats; ODS rats) with hereditary inability to synthesize AsA. Female ODS rats of 21 days old were castrated and divided into two groups. One group was given AsA in their drinking water, and the other was not. All the rats received a daily injection of oestradiol-17 beta and progesterone (EP) from day 28 to day 49 of age. After EP treatment, the concentrations of AsA in the mammary glands of rats not given AsA were less than one tenth of those of rats given AsA and the contents of hydroxyproline in the mammary glands of the former rats were about half of those in the latter. Furthermore, the concentration of serum prolactin in rats not given AsA was reduced to about one third of that in rats given AsA. After EP treatment, whole mounts of mammary glands showed that in rats not given AsA the development of ducts was impaired and there was extensive accumulation of endbuds. Consistent with this finding, EP injections did not increase the area of parenchyma in the mammary glands of rats not given AsA, whereas they increased it about 2-fold in rats given AsA. Moreover, after EP treatment the amount of alpha-lactalbumin was significantly less in the mammary parenchyma of rats not given AsA than in that of rats given AsA. On the other hand, AsA deficiency did not impair the response of the mammary cells to insulin or prolactin in terms of DNA synthesis and alpha-lactalbumin production. These findings indicate that AsA deficiency impaired the development of mammary glands. This effect may be partly attributable to a defect in collagen synthesis in the mammary glands and a decrease in the concentration of serum prolactin.     

Peptide antibiotic subtilin is synthesized via precursor proteins

Biogenesis of subtilin, an antimicrobial peptide produced by Bacillus subtilis ATCC 6633, was studied in growing cells. Pulse-chase labeling experiments with [35S]cysteine revealed the presence of precursor proteins of subtilin. The synthesis of both precursor proteins and subtilin was inhibited by inhibitors of protein and RNA synthesis. When the precursor proteins were incubated with crude extracts of the organism in vitro, they were converted to subtilin. Pepstatin and phenylmethylsulfonyl fluoride in combination inhibited this conversion.