Disordered aggregates

Ginsberg, M. H., Frelinger, A. L., Lam, S. C. T., Forsyth, J., McMillan, R., Plow, E. F., and Shattil, S. J., Analysis of platelet aggregation disorders based on flow cytometric analysis of membrane glycoprotein llb-llla with conformation specific monoclonal antibodies. Blood 76, 2017—2023... 

Gentleman SM (2013) Review microglia in protein aggregation disorders friend or foe Nemopathol Appl Nemobiol 39 45-50... 

Two point defects may aggregate to give a defect pair (such as when the two vacanc that constitute a Schottky defect come from neighbouring sites). Ousters of defects ( also form. These defect clusters may ultimately give rise to a new periodic structure oi an extended defect such as a dislocation. Increasing disorder may alternatively give j to a random, amorphous solid. As the properties of a material may be dramatically alte by the presence of defects it is obviously of great interest to be able to imderstand th relationships and ultimately predict them. However, we will restrict our discussion small concentrations of defects. 

Gels are viscoelastic bodies that have intercoimected pores of submicrometric dimensions. A gel typically consists of at least two phases, a soHd network that entraps a Hquid phase. The term gel embraces numerous combinations of substances, which can be classified into the following categories (2) (/) weU-ordered lamellar stmctures (2) covalent polymeric networks that are completely disordered (2) polymer networks formed through physical aggregation that are predominantly disordered and (4) particular disordered stmctures. 

Muscle biopsy with full histochemical and ultrastructural investigation is necessary for the confirmation of a diagnosis of IBM. The inclusions which are the hallmark of this disorder are to be found in three locations (a) basophilic granular inclusions are found at the periphery of vacuoles within the cytoplasm of muscle fibers (b) eosinophilic hyaline inclusions are also found in the cytoplasm but are not associated with vacuoles and (c) intranuclear inclusions consisting of aggregates of filamentous microtubules are found in a variable percentage of muscle nuclei. Inclusions of the first two types are visible at light microscope level, whereas the third type is detectable at the electron microscope level only. Ultrastructural... 

The major mineralocorticoid, aldosterone, is secreted by cells of the zona glomerulosa. Primary hyperaldosteronism (Conn s syndrome) is associated with potassium depletion which is, in mm, responsible for the observed neuromuscular abnormalities seen in the disorder. These are similar to those seen in hypokalemic periodic paralysis (PP), with episodic and severe exacerbations of fixed muscle weakness. Muscle biopsy shows occasional muscle necrosis and vacuoles often these feamres are accompanied by mbular aggregates as in hypokalemic PP. All these changes can be attributed to the hypokalemia and not to excess aldosterone production per se. 

Corticosteroids a chronic painless myopathy associated with the long-term use of corticosteroids is a particularly common example of drug-induced muscle disorder. It is almost certain that mild cases are overlooked because steroids are so frequently used to treat inflammatory myopathies such as polymyositis. Fluorinated steroids are particularly frequently implicated, and the incidence of drug-induced muscle disease is dose and time-related. The presence of muscle weakness can even complicate topical steroid therapy. Corticosteroid-induced myopathy is mediated via intramuscular cytosolic steroid receptors. The steroid-receptor complexes inhibit protein synthesis and interfere with oxidative phosphorylation. The myopathy is associated with vacuolar changes in muscle, and the accumulation of cytoplasmic glycogen and mitochondrial aggregations. 

Coacervation occurs in tropoelastin solutions and is a precursor event in the assembly of elastin nanofibrils [42]. This phenomenon is thought to be mainly due to the interaction between hydro-phobic domains of tropoelastin. In scanning electron microscopy (SEM) picmres, nanofibril stmc-tures are visible in coacervate solutions of elastin-based peptides [37,43]. Indeed, Wright et al. [44] describe the self-association characteristics of multidomain proteins containing near-identical peptide repeat motifs. They suggest that this form of self-assembly occurs via specific intermolecular association, based on the repetition of identical or near-identical amino acid sequences. This specificity is consistent with the principle that ordered molecular assembhes are usually more stable than disordered ones, and with the idea that native-like interactions may be generally more favorable than nonnative ones in protein aggregates. 

Tarek et al. [388] studied a system with some similarities to the work of Bocker et al. described earlier—a monolayer of n-tetradecyltrimethylammonium bromide. They also used explicit representations of the water molecules in a slab orientation, with the mono-layer on either side, in a molecular dynamics simulation. Their goal was to model more disordered, liquid states, so they chose two larger molecular areas, 0.45 and 0.67 nm molecule Density profiles normal to the interface were calculated and compared to neutron reflectivity data, with good agreement reported. The hydrocarbon chains were seen as highly disordered, and the diffusion was seen at both areas, with a factor of about 2.5 increase from the smaller molecular area to the larger area. They report no evidence of a tendency for the chains to aggregate into ordered islands, so perhaps this work can be seen as a realistic computer simulation depiction of a monolayer in an LE state. 

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