Modelling motor units in 3D: influence on muscle contraction and joint force via a proof of concept simulation

Functional heterogeneity is a skeletal muscle’s ability to generate diverse force vectors through localised motor unit (MU) recruitment. Existing 3D macroscopic continuum-mechanical finite element (FE) muscle models neglect MU anatomy and recruit muscle volume simultaneously, making them unsuitable for studying functional heterogeneity. Here, we develop a method to incorporate MU anatomy and information in 3D models. Virtual fibres in the muscle are grouped into MUs via a novel “virtual innervation” technique, which can control the units’ size, shape, position, and overlap. The discrete MU anatomy is then mapped to the FE mesh via statistical averaging, resulting in a volumetric MU distribution. Mesh dependency is investigated using a 2D idealised model and revealed that the amount of MU overlap is inversely proportional to mesh dependency. Simultaneous recruitment of a MU’s volume implies that action potentials (AP) propagate instantaneously. A 3D idealised model is used to verify this assumption, revealing that neglecting AP propagation results in a slightly less-steady force, advanced in time by approximately 20 ms, at the tendons. Lastly, the method is applied to a 3D, anatomically realistic model of the masticatory system to demonstrate the functional heterogeneity of masseter muscles in producing bite force. We found that the MU anatomy significantly affected bite force direction compared to bite force magnitude. MU position was much more efficacious in bringing about bite force changes than MU overlap. These results highlight the relevance of MU anatomy to muscle function and joint force, particularly for muscles with complex neuromuscular architecture.

     

Effect of dietary caffeine and zinc on the activity of antioxidant enzymes,zinc, and copper concentration of the heart and liver in fast-growing rats

The purpose of this study was to determine the relationship between concentrations of Zn and Cu and the activities of superoxide dismutase and glutathione peroxidase in the heart and liver of young rat pups whose dams were fed a diet supplemented with caffeine and/or Zn. Four groups of dams with their newborn pups were fed one of the following diets for 22 d: 20% protein basal diet; the basal diet supplemented with caffeine (2 mg/100 body wt); the basal diet supplemented with Zn (300 mg/kg diet); or the basal diet supplemented with caffeine plus Zn. The Cu levels in the livers of the pups were decreased by maternal intake of the caffeine and Zn diet. The maternal intake of the caffeine diet increased Mn-superoxide dismutase (MnSOD) activity and Cu, Zn-superoxide dismutase (CUZnSOD) in the heart of the pups. On the other hand, the activity of Cu,ZnSOD was significantly reduced in the liver of pups whose dams consumed a caffeine, Zn, or caffeine plus Zn diet. Cu, ZnSOD activity in the liver of the pups seems to be correlated with Cu levels in the tissue. Selenium-dependent glutathione peroxidase (GSH-Px) activities in the heart and liver showed no difference among the groups. The effect of dietary caffeine and/or Zn on the activity of antioxidant enzymes in the heart and liver were different in young rats. The activities of these enzymes in the heart were lower than in the liver of 22-d-old rats. Our experiments indicate that the heart has limited defenses against the toxic effects of peroxides when compared to the liver.     

An autosomal dominant retinitis pigmentosa family with close linkage to D7S480 on 7q

Retinitis pigmentosa is the most prevalent inherited disorder of the retina. It can be autosomal dominant (adRP), autosomal recessive (arRP) or X-linked (XLRP). A form of adRP mapping to chromosome 7q was reported in a large Spanish pedigree. We have typed DNA from the members of another Spanish family for polymorphic markers from the known candidate genes. Positive lod scores were obtained only for the markers located on 7q31-35, giving a maximum lod score of 2.98 (3.01 by multipoint analysis) at = 0.00 for D7S480. A brief clinical evaluation is given.     

Plasmodium falciparum protein associated with the invasion junction contains a conserved oxidoreductase domain

The merozoite cap protein-1 (MCP-1) of Plasmodium falciparum follows the distribution of the moving Junction during invasion of erythrocytes. We have cloned the gene encoding this protein from a cDNA library using a monoclonal antibody. The protein lacks a signal sequence and has no predicted trans-membrane domains; none of the antisera reacts with the surfaces of intact merozoites, indicating that the cap distribution is submembranous. MCP-1 is divided into three domains. The N-terminal domain includes a 52-amino-acid region that is highly conserved in a large family of bacterial and eukaryotic proteins. Based on the known functions of two proteins of this family and the pattern of amino acid conservation, it is predicted that this domain may possess oxido-reductase activity, since the active cysteine residue of this domain is invariant in all proteins of the family. The other two domains of MCP-1 are not found in any other members of this protein family and may reflect the specific function of MCP-1 in invasion. The middle domain is negatively charged and enriched in glutamate; the C-terminal domain is positively charged and enriched in lysine. By virtue of its positive charge, the C-terminal domain resembles domains in some cytoskeleton-associated proteins and may mediate the interaction of MCP-1 with cytoskeleton in Plasmodium.     

Vasotocin, melatonin and narcolepsy: Possible involvement of the pineal gland in its patho-physiological mechanism

Both the pineal nonapeptide hormone arginine vasotocin (AVT) (2.5 μg) administered intra-nasally and the pineal indole melatonin (50 mg) administered intravenously to three male narcoleptics (two with auxiliary symptoms and one with sleep attacks only), dramatically increased the amount of REM sleep and decreased REM sleep latency. The duration of the sleep onset REM periods in the two narcoleptics with auxiliary symptoms increased by more than 100 percent after AVT and melatonin administration. In the narcoleptic with sleep attacks only both AVT and melatonin induced REM periods at sleep onset. The hypothesis is advanced that narcolepsy represents an impairment of the melatonin-AVT control in the induction and circadian organization of REM sleep associated with an immaturity of REM triggering centers.     

Catalysis by modified polyethylenimine of nucleophilic substitution reactions of azide ions

The reactions of azide ion with 4-chloro-3,5-dinitrobenzoate and with 4-acetoxy-3-nitrobenzoate catalyzed by laurylethyl polyethylenimine were examined at pH 5.72 and 25°C. In the presence of the polymer, marked accelerations were observed for nucleophilic attack of azide ion in the aromatic substitution reaction, but only small enhancements appeared in the acylation reaction. A detailed rate analysis indicates that the intrinsic reactivity of the reactants in the aromatic substitution reaction is increased in the environment of the polymer about 100 times more than is the reactivity of reactants in the acylation reaction. This difference is ascribed to the influence of the apolar environment of the polymer matrix on the more delocalized charge distribution in the transition state of the aromatic substitution reaction.     

On the kinetics of enzyme reactions

The Abel type differential equation governing the kinetics of the enzyme reactions is derived. Approximate solutions of this equation corresponding to the transient phase of the reaction, before a steady state is reached, are considered. It is shown that in several cases it is possible to obtain explicit, approximate solutions to the transient phase.     

Monoclonal antibodies directed against the sugar sequence of lacto-N-fucopentaose III are obtained from mice immunized with human tumors

Four hybridomas obtained from mice immunized with human adenocarcinomas of colon or stomach produce antibodies that bind specifically in solid-phase radioimmunoassay to the ceramide pentasaccharide that contains the lacto-N-fucopentaose III sequence of sugars. Binding of the antibodies to the glycolipid is inhibited by lacto-N-fucopentaose III,

but not by structurally related oligosaccharides. The antibodies bind to glycolipids of erythrocytes, granulocytes, and certain normal and malignant tissues.