Fibril deposition

Significantly, the ordered pattern of fibril deposition in the secondary wall of Micrasterias367 was shown to be derived from the structure of the complexes located in the plasma membrane. The results indicated that the widest fibrils, those in the center of a band, are formed by the longest rows of rosettes, those in the center of arosette array. The shorter rows of rosettes within an array give rise to narrower fibrils. This proportionality between the width of a secondary cellulose fibril and the number of rosettes involved in its formation provides strong evidence that the rosette structure plays a significant role in the synthesis of cellulose fibrils. 

B. A Model of Cellulose-Fibril Deposition During Secondary-wall Formation in Microsterias.7 [Each rosette is believed to form one 5-nm microfibril. A row of rosettes forms a set of 5-nm microfibrils which aggregate laterally to form the larger fibrils of the secondary wall. Above side view. The stippled area in the center of a rosette represents the presumptive site of microfibril formation, although details of its structure, composition, and enzymic activity remain unclear. Below surface view, with expanded, cross-sectional view of cellulose fibrils.]... 

Based on these observations, it is clear that a close and highly complicated relationship exists between fibril deposition and oxidative stress during neurodegeneration. 

It was proved experimentally that immobilization period can be effectively used for variation of the density of the supramolecular structures on the surfaces. Influence of the immobilization time on die arrangement of the combined structures is illustrated in Fig. 2 by typical SPM images obtained for hen egg lysozyme fibrils deposited on mica surfaces. After deposition of the lysozyme fibrils under similar conditions, the fibrils were rare on the surfaces if immobilization was shorter... 

Oyler and Tycko have demonstrated that absolute, molecular-level structural information can be obtained from solid state NMR measurements on partially oriented amyloid fibrils.In particular, it has been shown that the direction of the fibril axis relative to a carbonyl CSA tensor can be determined from MAS sideband patterns in C NMR spectra of fibrils deposited on planar substrates. Deposition of fibrils on a planar substrate creates a highly anisotropic distribution of fibril orientations (hence, CSA tensor orientations) with most fibrils lying in the substrate plane. The anisotropic orientational distribution gives rise to distorted spinning sideband patterns in MAS spectra from which the fibril axis direction can be inferred. 

In a transgenic mouse model, which expressed a gene encoding 18 residues of signal peptide and 99 residues of carboxyl-terminal fi agment of the amyloid P protein precursor, this protein in the pancreas accumulated in an age-dependent manner (Shoji etal. 2000). Amyloid P protein fibril deposits closely correlated with degeneration of pancreatic acinar cells and macrophage activation. 

Many layered biological systems resemble cholesteric liquid crystals in the rotation of orientation from layer to layer. This has raised recent interest in whether they actually are liquid crystals, in that the rotation forms spontaneously as a result of interactions between fibers in successive layers. This would occur in a fluid state, which is subsequently embedded in a hard matrix. The core question is really whether the rotation pattern is directly controlled by some form of oriented extrusion during the deposition process or is controlled through the surface chemistry of fibrils deposited in successive layers. 

Within the scope of thermoelectric nanostructures, Sima et al. [161] prepared nanorod (fibril) and microtube (tubule) arrays of PbSei. , Tej by potentiostatic electrodeposition from nitric acid solutions of Pb(N03)2, H2Se03, and Te02, using a 30 fim thick polycarbonate track-etch membrane, with pores 100-2,000 nm in diameter, as template (Cu supported). After electrodeposition the polymer membrane was dissolved in CH2CI2. Solid rods were obtained in membranes with small pores, and hollow tubes in those with large pores. The formation of microtubes rather than nanorods in the larger pores was attributed to the higher deposition current. 

Figure 18.2 Production of senile plaque (S/A4 amyloid protein. Amyloid fS4 protein (/S/A4) is part of a 695, 751 or 770 amino-acid amyloid precursor protein APP. This is a transmembrane protein which is normally cleared within the fi/A4 amino acid sequence to give short 40 amino-acid soluble derivatives. It seems that under some circumstances as in Alzheimer s disease, APP is cleared either side of the fi/A4 sequence to release the 42/43 amino acid P/A4 which aggregates into the amyloid fibrils of a senile plaque (a). (See also Fig. 18.5.) Some factors, e.g. gene mutation, must stimulate this abnormal clearage leading to the deposition of P/A4 amyloid protein as plaques and tangles and the death of neurons (b)...

Neuritic or senile plaques are extracellular protein deposits of fibrils and amorphous aggregates of P-amyloid protein.11 This formed protein is central to the pathogenesis of AD. The P-amyloid protein is present in a non-toxic, soluble form in human brains. In AD, conformational changes occur that render it insoluble and cause it to deposit into amorphous diffuse plaques associated with dystrophic neuritis.14 Over time, these deposits become compacted into plaques and the P-amyloid protein becomes fibrillar and neurotoxic. Inflammation occurs secondary to clusters of astrocytes and microglia surrounding these plaques. 

To this list of protein misfolding diseases can be added rare familial amyloidoses in which the mutated proteins have the classic amyloid fibril congophilic birefringence and cross-(3-sheet structure (Table 3). Many of these deposits have an impact on the central nervous system (TTR, cystatin, lysozyme) as well as on other organ systems. A newly described disease, familial British dementia, is associated with the deposition of Abri, a 34 amino acid, 4 kDa peptide cleaved from a 277 amino acid precursor sequence, the last 10 amino acids of which are not normally translated [52]. Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is... 

Another prominent site of deposition of (5-amyloid fibrils with age and in AD is within the cerebrovasculature in areas of the brain prone to parenchymal amyloid deposition [137-139]. The peptide deposits along the surfaces of the smooth muscle cells of the vascular wall, resulting in the death of those cells and their replacement by amyloid fibrils, weakening the vascular wall. Endothelial cells are also affected [140]. The Dutch mutation in the APP precursor protein Q22E, within the (5-peptide sequence, produces a particularly fibrillogenic and toxic (to smooth muscle cells) peptide associated with primarily vascular deposition of mutant peptide and hemorrhagic vessel disease [137]. Thus, in addition to neuronal cells, the brain vascular smooth muscle cells are a pathologically relevant cell type. While the source of... 

The failure of proteins to fold into their functional forms can occasionally lead to "misfolding" or "conformational" diseases.140 Many of these diseases are associated with the formation of amyloid protein, an insoluble material that is deposited as fibrils or plaques in different tissues and organs of the body. They include amyloid Ap protein as the major constituent of the plaques in Alzheimer patients, PrPc associated with neuro-degenerative diseases, a-synuclein (AS) associated with Parkinson s diseases, transthyretin (TTR) as a homotetrameric protein that is involved in the transport of thyroid hormones and retinol in human serum. In particular, the Ap protein is a peptide of 39-43 amino acids that is the... 

Human amylin, or islet amyloid polypeptide (hlAPP), is a 37-residue peptide hormone which forms both intracellular and extracellular (EC) amyloid deposits in the pancreas of most type II diabetic subjects. The core of the structure in the SDS micelle is an ot-helix that runs from about residues 5-28. Although the basic structural unit in the fibrils in... 

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