Self-organization of an oscillatory neural system

Hebbian dynamics is used to derive the differential equations for the synaptic strengths in the neural circuitry of the locomotive oscillator. Initially, neural connection are random. Under a specified arborization hypothesis relating to the density of neural connections, the differential equations are shown to model the self-organization and the stability of the oscillator.     

Instrumented Indentation Investigation on the Viscoelastic Properties of Porcine Cartilage

Articular cartilage lubricates the contact surfaces in human joints and provides a shock-absorbing effect which protects the joint under dynamic loading. However, this shock-absorbing effect is gradually reduced as the result of normal wear, tear and aging-related cartilage loss. Thus, with the increasing average human life expectancy, the issue of joint health has attracted significant interest in recent decades. In developing new materials for the repair or regeneration of damaged articular cartilage, it is essential that the difference in the mechanical properties of healthy and damaged cartilages is well-understood. In the present study, the hardness and Young＇s modulus of damaged and healthy porcine articular cartilage samples are evaluated via a quasi-static nanoindentation technique. A dynamic mechanical analysis method is then applied to determine the viscoelastic properties of the two samples. The results presented in this study provide a useful insight into the mechanical properties of articular cartilage at the mesoscale, and therefore fill an important gap in the literature.     

The effect of contaminants on the adhesion of the spatulae of a gecko

Many researchers have reported that the robust adhesion that enables geckos to move quickly and securely across a range of vertical and horizontal surfaces is provided by the hierarchical structure of their feet (i.e. lamellae, setae, spatulae, etc.). Maintaining this robust adhesion requires an intimate contact between the terminal tips of the spatulae and the surface. The aim of this study was to investigate the effect on the adhesive properties of the spatulae when a particle becomes trapped at the contact surface. Using the Johnson, Kendall and Roberts (JKR) theory, a model was constructed to assist in the analysis of the interactions between the spatula tip, the particle and the surface. The results showed that the keratin (the natural material of the spatula) provides a robust system for adhesion even when there is a particle in the contact area, and the effective contact area of spatulae will be 80%. When the particle is significantly harder than the surface, the adhesion properties of the contact surface influenced by the particle will be more obvious. The results also reveal that the generated adhesion is considerably higher when the spatula is in contact with a softer surface, such as wood or concrete, rather than a hard surface, such as glass or SiO₂.     

Macrophage insulin receptor deficiency increases ER stress-induced apoptosis and necrotic core formation in advanced atherosclerotic lesions

Insulin resistance in diabetes and metabolic syndrome is thought to increase susceptibility to atherosclerotic cardiovascular disease, but the underlying mechanisms are poorly understood. To evaluate the possibility that decreased insulin signaling in macrophage foam cells might worsen atherosclerosis, Ldlr(-/-) mice were transplanted with insulin receptor Insr(+/+) or Insr(-/-) bone marrow. Western diet-fed Insr(-/-) recipients developed larger, more complex lesions with increased necrotic cores and increased numbers of apoptotic cells. Insr(-/-) macrophages showed diminished Akt phosphorylation and an augmented ER stress response, leading to induction of scavenger receptor A and increased apoptosis when challenged with cholesterol loading or nutrient deprivation. These studies suggest that defective insulin signaling and reduced Akt activity impair the ability of macrophages to deal with ER stress-induced apoptosis within atherosclerotic plaques.     

Pruning an axon piece by piece: a new mode of synapse elimination

The process by which excess axons are pruned during development has remained unclear. In this issue of Neuron, Bishop et al. use time-lapse imaging and serial electron microscopy of developing neuromuscular junctions to describe a novel cellular mechanism in which retracting axon branches shed fragments rich in normal synaptic organelles. These "axosomes" are engulfed by adjacent Schwann cells and may be assimilated into the glial cytoplasm. Shedding of axosomes and glial engulfment may represent a widespread mechanism of synapse elimination.     

A Schwann cell matrix component of neuromuscular junctions and peripheral nerves

Molecules localized to the synapse are potential contributors to processes unique to this specialized region, such as synapse formation and maintenance and synaptic transmission. We used an immunohistochemical strategy to uncover such molecules by generating antibodies that selectively stain synaptic regions and then using the antibodies to analyse their antigens. In this study, we utilized a monoclonal antibody, mAb 6D7, to identify and characterize an antigen concentrated at frog neuromuscular junctions and in peripheral nerves. In adult muscle, immunoelectron microscopy indicates that the antigen is located in the extracellular matrix around perisynaptic Schwann cells at the neuromuscular junction and in association with myelinated and nonmyelinated axons in peripheral nerves. The maintenance of the mAb 6D7 epitope is innervation-dependent but is muscle-independent; it disappears from the synaptic region within 2 weeks after denervation, but persists after muscle damage when the nerve is left intact. mAb 6D7 immunolabelling is also detected at the neuromuscular junction in developing tadpoles. Biochemical analyses of nerve extracts indicate that mAb 6D7 recognizes a glycoprotein of 127 kDa with both N- and O-linked carbohydrate moieties. Taken together, the results suggest that the antigen recognized by mAb 6D7 may be a novel component of the synaptic extracellular matrix overlying the terminal Schwann cell. The innervation-sensitivity of the epitope at the neuromuscular junction suggests a function in the interactions between nerves and Schwann cells.     

Reducing plasma membrane sphingomyelin increases insulin sensitivity

It has been shown that inhibition of de novo sphingolipid synthesis increases insulin sensitivity. For further exploration of the mechanism involved, we utilized two models: heterozygous serine palmitoyltransferase (SPT) subunit 2 (Sptlc2) gene knockout mice and sphingomyelin synthase 2 (Sms2) gene knockout mice. SPT is the key enzyme in sphingolipid biosynthesis, and Sptlc2 is one of its subunits. Homozygous Sptlc2-deficient mice are embryonic lethal. However, heterozygous Sptlc2-deficient mice that were viable and without major developmental defects demonstrated decreased ceramide and sphingomyelin levels in the cell plasma membranes, as well as heightened sensitivity to insulin. Moreover, these mutant mice were protected from high-fat diet-induced obesity and insulin resistance. SMS is the last enzyme for sphingomyelin biosynthesis, and SMS2 is one of its isoforms. Sms2 deficiency increased cell membrane ceramide but decreased SM levels. Sms2 deficiency also increased insulin sensitivity and ameliorated high-fat diet-induced obesity. We have concluded that Sptlc2 heterozygous deficiency- or Sms2 deficiency-mediated reduction of SM in the plasma membranes leads to an improvement in tissue and whole-body insulin sensitivity.     

Dihydrotestosterone ameliorates degeneration in muscle, axons and motoneurons and improves motor function in amyotrophic lateral sclerosis model mice

Amyotrophic lateral sclerosis (ALS) is a lethal disease characterized by a progressive loss of motoneurons. The clinical symptoms include skeletal muscle weakness and atrophy, which impairs motor performance and eventually leads to respiratory failure. We tested whether dihydrotestosterone (DHT), which has both anabolic effects on muscle and neuroprotective effects on axons and motoneurons, can ameliorate clinical symptoms in ALS. A silastic tube containing DHT crystals was implanted subcutaneously in SOD1-G93A mice at early symptomatic age when decreases in body weight and grip-strength were observed as compared to wild-type mice. DHT-treated SOD1-G93A mice demonstrated ameliorated muscle atrophy and increased body weight, which was associated with stronger grip-strength. DHT treatment increased the expression of insulin-like growth factor-1 in muscle, which can exert myotrophic as well as neurotrophic effects through retrograde transport. DHT treatment attenuated neuromuscular junction denervation, and axonal and motoneuron loss. DHT-treated SOD1-G93A mice demonstrated improvement in motor behavior as assessed by rota-rod and gait analyses, and an increased lifespan. Application of DHT is a relatively simple and non-invasive procedure, which may be translated into therapy to improve the quality of life for ALS patients.