Adsorption of liquid-phase alkane mixtures in silicalite: simulations and experiment.

A combination of experimental and computational studies of adsorption from liquid-phase mixtures of linear alkanes in the zeolite silicalite is presented here. Configurational biased grand canonical Monte Carlo simulations combined with identity-swap moves are used to equilibrate the simulations in reasonable times. Interesting trends observed in experiments have been captured quantitatively by simulations. A siting analysis of the simulation data reveals that, during adsorption from a liquid mixture, shorter alkanes prefer the zigzag channels and longer alkanes concentrate in the straight channels of silicalite.

Hyperphosphorylated tau and paired helical filament-like structures in the brains of mice carrying mutant amyloid precursor protein and mutant presenilin-1 transgenes.

Senile plaques composed mainly of beta-amyloid (Abeta) and neurofibrillary tangles principally composed of hyperphosphorylated tau are the major pathological features of Alzheimer's disease (AD). Despite the fact that increased expression of amyloid precursor protein (APP) and presenilin-1 (PS1) transgenes in mice lead to increased Abeta deposition in plaquelike structures in the brain, little is known about the nature and distribution of tau in these mice. Therefore the relationship between Abeta and hyperphosphorylated tau was investigated in mice carrying mutant APP and mutant PS1 transgenes using both light (LM) and electron microscopy (EM) with immunocytochemistry. LM immunocytochemistry revealed cerebral Abeta deposits to be present from 8 weeks of age, whereas hyperphosphorylated tau was not detected until 24 weeks of age, when it appeared as punctate deposits in close association with the Abeta deposits in the cortex and hippocampus. However, dystrophic neurites were not as heavily immunolabeled as they are in AD brain. EM revealed that aggregations of straight filaments (10-12 nm wide) were present in some cellular processes at the periphery of Abeta plaques in 8-month-old APP/PS1 mice. In one such mouse, single filaments and paired filaments showing a helical configuration (50-55 nm half-period, 25 nm max. width) were present in a dark, atrophic hippocampal neuron. Immunogold labeling of APP/PS1 mouse brain revealed hyperphosphorylated tau epitopes in some dystrophic neurites from 24 weeks of age that were similar to those present in AD. These results suggest that hyperphosphorylated tau appears in APP/PS1 mouse brain after the onset of Abeta deposition and although it is associated with Abeta deposits, its distribution is not identical to that in AD.

Neurodegenerative changes associated with beta-amyloid deposition in the brains of mice carrying mutant amyloid precursor protein and mutant presenilin-1 transgenes.

Mutations of amyloid precursor protein (APP) and presenilin-1 (PS1) lead to an increase in beta-amyloid (Abeta) production. Despite the fact that a number of transgenic mice develop cerebral Abeta plaques, few have been subjected to ultrastructural investigation and the sequence of events leading to Abeta plaque formation is unclear. We therefore investigated the doubly transgenic (mutant APP(K670N,M671L)-mutant PS1(M146L)) mouse, which develops Abeta deposits much earlier than singly transgenic littermates. Widespread Abeta plaques with or without a distinct core were found in gray matter. Abeta plaques were also present in white matter. Astrocytosis was greater around gray matter plaques than around white matter plaques. In some plaques, Abeta cores were associated with cell profiles containing prominent endoplasmic reticulum and a homogeneous cytoplasm that appeared to be neuronal. The morphology and location of other profiles indicated them to be microglia or oligodendrocytes. Some Abeta fibrils appeared to lie within these profiles, but they may have been simply surrounded by the cell profile since the profile membrane was not always visible. Dark atrophic neurons, whose morphology suggested that they were apoptotic, were present around gray matter plaques. Cerebrovascular Abeta deposition was also observed in the brains of APP/PS1 transgenic mice. Thus, the amyloid deposition and neuropathology observed in APP/PS1 mouse brain are similar to those in Alzheimer's disease and they appear to develop earlier and become more severe than in the other transgenic models currently available.

Synaptic deficit in the temporal cortex of partial trisomy 16 (Ts65Dn) mice.

Down syndrome results from triplication of human chromosome 21. The distal end of mouse chromosome 16 shares a large region of genetic homology with the Down syndrome 'critical region' of human chromosome 21. Therefore, a partially trisomic mouse (Ts65Dn) that possesses a triplication of the distal region of chromosome 16 has been developed as a putative model for Down syndrome. Ts65Dn mice display learning and memory deficits. However, despite the importance of preserved synaptic integrity for learning and memory, the ultrastructure of neural connectivity has not yet been studied in Ts65Dn mice. Therefore, the density and apposition zone length of synapses in the temporal cortex of aged Ts65Dn mice (n=4) were compared with those in diploid controls (n=4), using quantitative electron microscopy. There were significantly less (30%) asymmetric synapses in the temporal cortex of Ts65Dn mice than in controls (t=-5.067; p=0.023). However, there was no significant difference between the mean density of symmetric synapses in Ts65Dn mice and control mice. In addition, the mean synaptic apposition lengths of both asymmetric (15%; t=9.812, p<0.0001) and symmetric (11%; t=5. 582; p<0.0001) synapses were significantly larger in Ts65Dn mice than in controls. These results suggest that excitatory synapses are preferentially affected in Ts65Dn mice and that there is an attempt to compensate for the deficit of asymmetric synapses by increasing the contact zone area of existing synapses. The results may also reveal the morphological basis for the learning and memory deficits observed in Ts65Dn mice and have a bearing on the cognitive deficits in Down syndrome in old age.

beta-Amyloid immunoreactivity in astrocytes in Alzheimer's disease brain biopsies: an electron microscope study.

The deposition of amyloid beta (A beta) protein plays a central role in the neuropathology of Alzheimer's disease (AD) and it constitutes the core of classical senile plaques. However, little is known about its intracellular distribution. An immunogold electron microscope study was therefore carried out on biopsies of brain tissue from patients with AD using a monoclonal antibody raised against residues 8 to 17 of the A beta protein. Specific A beta immunogold labeling was observed over extracellular amyloid fibrils associated with senile plaques. In addition, widespread intracellular A beta immunolabeling was observed adjacent to granular structures (30-40 nm in diameter) within membrane-bound processes. Pretreatment of some sections with amylase or omission of lead citrate staining from others strongly suggests that the electron-dense granular structures associated with A beta immunoreactivity are glycogen. Some of the A beta-immunolabeled processes contained gliofilaments and immunolabeling of alternate sections for glial fibrillary acidic protein confirmed that the A beta-immunolabeled processes were astrocytic. A beta immunolabeling was not observed over neuronal or microglial processes. Whether the presence of A beta protein in astrocytes is the result of synthetic or degradation processes requires further investigation.

Squatting facets on the neck of the talus and extensions of the trochlear surface of the talus in late Byzantine males.

Remodelling of bone occurs in response to physical stress. Habitual squatting is associated with modifications of the neck of the talus (squatting facets) and its trochlear/malleolar surfaces (trochlear extensions), and individual populations exhibit different incidences of these modifications that reflect their lifestyle. The occurrence of talar modifications was therefore investigated in a population of late Byzantine (13th century AD) adult male skeletons. Lateral squatting facets occurred most frequently (37.7%), but medial (0.6%), combined (0.6%) and continuous (gutter-like) facets (0.6%) were also observed. Lateral (8.0%), medial (10.9%) and continuous (lateral/central/medial) extensions (4.6%) of the trochlear surface were all present in the late Byzantine population. There was no evidence of side dimorphism. The occurrence of lateral squatting facets in the late Byzantine population was greater than that reported for modern Europeans, but similar to that reported for some populations of modern Indians. The frequency of occurrence of trochlear extensions in the late Byzantine population was substantially less than in modern Indian populations, but similar to modern Europeans. Therefore, it is unlikely that precisely the same factors determine the expression of squatting facets and trochlear extensions.

A case with coincidence of aberrant right subclavian artery and common origin of the carotid arteries.

An aortic arch variant was found in a 63 year-old male cadaver during routine dissection. An aberrant right subclavian artery (ARSA) arose from the distal aortic arch after the left subclavian artery and coursed to the right and upward behind the trachea and esophagus. A common origin for the carotid arteries (COCA) accompanied this variant of the right subclavian artery.

A rare case of a multiple variation of the muscles in the upper and lower extremities.

In an anatomy class, dissection led to the discovery of a hitherto unreported multiple variation of the muscles in the upper and lower extremities of a Turkish male cadaver. The variant muscles were the palmaris longus of the reverse type in the right and a double reverse palmaris longus in the left forearm, and the extensor medius proprius in the left forearm and a supernumerary muscle slip originating from the posterior tibialis in the left crus.

Paired helical filament morphology varies with intracellular location in Alzheimer's disease brain.

Paired helical filaments (PHFs) are one of the hallmark pathologies of Alzheimer's disease (AD). PHFs occur in three intracellular locations, although hitherto, it was not known whether all PHFs are structurally homogeneous. Parietal cortex biopsies were taken from five patients with a clinical and histopathological diagnosis of AD and processed for electron microscopy. Photomicrographs were then taken of PHFs in neurofibrillary tangles (NFTs), neuropil threads (NTs) and neuritic plaque (NP) neurites and their dimensions measured. The mean half period, maximum and minimum widths of PHFs in NFTs were significantly smaller than those in NTs or NP neurites. The mean half period and maximum width of PHFs in NTs were similar to those in NP neurites. These results reveal the presence of two distinct PHF populations and investigation of their relationship may shed light on the pathogenesis of AD.