scholarly journals Amyloid Beta Annular Protofibrils in Cell Processes and Synapses Accumulate with Aging and Alzheimer-Associated Genetic Modification

2009 ◽  
Vol 2009 ◽  
pp. 1-7 ◽  
Author(s):  
Hideko Kokubo ◽  
Rakez Kayed ◽  
Charles G. Glabe ◽  
Matthias Staufenbiel ◽  
Takaomi C. Saido ◽  
...  

Amyloidβ(Aβ) annular protofibrils (APFs) have been described where the structure is related to that ofβbarrel pore-forming bacterial toxins and exhibits cellular toxicity. To investigate the relationship of AβAPFs to disease and their ultrastructural localization in brain tissue, we conducted a pre-embedding immunoelectron microscopic study using anti-annular protofibril antiserum. We examined brain tissues of young- and old-aged amyloid precursor protein transgenic mice (APP23), neprilysin knockout APP23 mice, and nontransgenic littermates.αAPF-immunoreactions tended to be found (1) on plasma membranes and vesicles inside of cell processes, but not on amyloid fibrils, (2) with higher density due to aging, APP transgene, and neprilysin deficiency, and (3) with higher positive rate at synaptic compartments in aged APP23, especially in neprilysin knockout APP23 mice. These findings imply that APFs are distinct from amyloid fibrils, interact with biological membranes, and might be related to synaptic dysfunction in Alzheimer model mouse brains.

Author(s):  
Bruce R. Stevenson ◽  
Matthew B. Heintzelman ◽  
James Melvin Anderson ◽  
Sandra Citi ◽  
I. Deborah Braun ◽  
...  

The tight junction (zonula occludens) constitutes a selectively permeable barrier in the paracellular pathway of most epithelia. It is also thought to play a role in the maintenance of the cell surface compositional asymmetry characteristic of epithelial cells. The identification of ZO-1 and cingulin, the first two proteins found to be exclusively associated with the tight junction, permits novel investigations of this important epithelial cell structure at the biochemical level.ZO-1 is a high molecular weight polypeptide (>200 kD) found at the tight junctions of a variety of epithelia as well as endothelia, and ultrastructural localization studies on isolated liver plasma membranes indicate that this molecule is clustered at the points of membrane contact on the cytoplasmic surface of the junction. Physical analysis demonstrates ZO-1 to be an elongated, monomeric, phosphorylated protein, peripherally associated with the junctional membrane. Cingulin was originally isolated from chicken intestine, and, like ZO-1, is a peripheral membrane component of the junction which exhibits an elongated shape. Antibodies directed against this molecule show two primary bands at 140 kD and 108 kD on immunoblots of several epithelial tissues, although the relationship between these two elements remains undefined. Little information currently exists regarding the relationship of ZO-1 and cingulin to each other or to tight junction structure or function. We report here a comparison of the immunocytochemical properties of these junctional components as well as an examination of the phosphorylation state of ZO-1.


Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 880
Author(s):  
Tuanyuan Shi ◽  
Xinlei Yan ◽  
Hongchao Sun ◽  
Yuan Fu ◽  
Lili Hao ◽  
...  

Cyniclomyces guttulatus is usually recognised as an inhabitant of the gastrointestinal (GI) tract in rabbits. However, large numbers of C. guttulatus are often detected in the faeces of diarrhoeic rabbits. The relationship of C. guttulatus with rabbit diarrhoea needs to be clearly identified. In this study, a C. guttulatus Zhejiang strain was isolated from a New Zealand White rabbit with severe diarrhoea and then inoculated into SPF New Zealand white rabbits alone or co-inoculated with Eimeriaintestinalis, another kind of pathogen in rabbits. Our results showed that the optimal culture medium pH and temperature for this yeast were pH 4.5 and 40–42 °C, respectively. The sequence lengths of the 18S and 26S ribosomal DNA fragments were 1559 bp and 632 bp, respectively, and showed 99.8% homology with the 18S ribosomal sequence of the NRRL Y-17561 isolate from dogs and 100% homology with the 26S ribosomal sequence of DPA-CGR1 and CGDPA-GP1 isolates from rabbits and guinea pigs, respectively. In animal experiments, the C. guttulatus Zhejiang strain was not pathogenic to healthy rabbits, even when 1 × 108 vegetative cells were used per rabbit. Surprisingly, rabbits inoculated with yeast showed a slightly better body weight gain and higher food intake. However, SPF rabbits co-inoculated with C. guttulatus and E. intestinalis developed more severe coccidiosis than rabbits inoculated with C. guttulatus or E. intestinalis alone. In addition, we surveyed the prevalence of C. guttulatus in rabbits and found that the positive rate was 83% in Zhejiang Province. In summary, the results indicated that C. guttulatus alone is not pathogenic to healthy rabbits, although might be an opportunistic pathogen when the digestive tract is damaged by other pathogens, such as coccidia.


Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769224 ◽  
Author(s):  
Ioannis A Voutsadakis

Proteasome is a multi-protein organelle that participates in cellular proteostasis by destroying damaged or short-lived proteins in an organized manner guided by the ubiquitination signal. By being in a central place in the cellular protein complement homeostasis, proteasome is involved in virtually all cell processes including decisions on cell survival or death, cell cycle, and differentiation. These processes are important also in cancer, and thus, the proteasome is an important regulator of carcinogenesis. Cancers include a variety of cells which, according to the cancer stem cell theory, descend from a small percentage of cancer stem cells, alternatively termed tumor-initiating cells. These cells constitute the subsets that have the ability to propagate the whole variety of cancer and repopulate tumors after cytostatic therapies. Proteasome plays a role in cellular processes in cancer stem cells, but it has been found to have a decreased function in them compared to the rest of cancer cells. This article will discuss the transcriptional regulation of proteasome sub-unit proteins in cancer and in particular cancer stem cells and the relationship of the proteasome with the pluripotency that is the defining characteristic of stem cells. Therapeutic opportunities that present from the understanding of the proteasome role will also be discussed.


Author(s):  
Himanshu Suman ◽  
Yash Sharma ◽  
Puneet Kumar Acharya ◽  
Jyoti Krishna ◽  
Nilesh Kumar Patidar

Background: Avascular necrosis (AVN) or osteonecrosis is the death of bone tissues due to decreased blood flow of femoral head, it is a major orthopaedic disease with many risk factors including the chronic alcohol and tobacco consumption.  Aims and objectives: To study the relationship of alcohol and tobacco with AVN of femoral head in adult population. Materials and Methods: This study included 72 patients of AVN of femoral head (ONFH) who attending our hospital between Sept 2018 to Sept 2020. History of alcoholism and tobacco consumption, detailed information of the amount and duration of smoking and alcohol intake was recorded. Results: Majority of the AVN patients were working age groups males (72%) and 28% were females. Out of 72 patient 55% had history of alcohol consumption and 60% were smokers which indicates a positive correlation of cellular toxicity with AVN of femoral head. Conclusion: Present study conclude that the alcohol ingestion and tobacco smoking are the major cause of cellular toxicity and AVN of femoral heads. Keywords: alcohol drinking, femur head necrosis, smoking


2020 ◽  
Vol 117 (22) ◽  
pp. 12087-12094 ◽  
Author(s):  
Alexander J. Dear ◽  
Thomas C. T. Michaels ◽  
Georg Meisl ◽  
David Klenerman ◽  
Si Wu ◽  
...  

The spontaneous assembly of proteins into amyloid fibrils is a phenomenon central to many increasingly common and currently incurable human disorders, including Alzheimer’s and Parkinson’s diseases. Oligomeric species form transiently during this process and not only act as essential intermediates in the assembly of new filaments but also represent major pathogenic agents in these diseases. While amyloid fibrils possess a common, defining set of physicochemical features, oligomers, by contrast, appear much more diverse, and their commonalities and differences have hitherto remained largely unexplored. Here, we use the framework of chemical kinetics to investigate their dynamical properties. By fitting experimental data for several unrelated amyloidogenic systems to newly derived mechanistic models, we find that oligomers present with a remarkably wide range of kinetic and thermodynamic stabilities but that they possess two properties that are generic: they are overwhelmingly nonfibrillar, and they predominantly dissociate back to monomers rather than maturing into fibrillar species. These discoveries change our understanding of the relationship between amyloid oligomers and amyloid fibrils and have important implications for the nature of their cellular toxicity.


2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Silvia Lorena Montes-Fonseca ◽  
Erasmo Orrantia-Borunda ◽  
Alberto Duarte-Möller ◽  
Antonia Luna-Velasco ◽  
Manuel Román-Aguirre ◽  
...  

The cytotoxicity of the carbon nanotubes (CNTs) is an important factor for the manufacture of nanovaccines. The aim of this work was to evaluate the relationship of the purification method of CNTs in cellular toxicity using macrophages (MOs) from the J774 cell line. Viability test was performed with MTT assays at 24 h of exposure at concentrations of 0.06, 0.6, and 6 mg/L of unpurified (UP-CNTs) or purified (P-CNTs) CNTs by two different methods: (1) reflux with 3M HNO3and (2) sonication in H2SO4/HNO3. Characterization and COOH content of CNTs was performed using scanning electron microscopy, raman spectroscopy, and titration with NaHCO3. P-CNTs1had lengths >100 μm and 2.76% COOH content, while P-CNTs2had lengths >1 μm and 7% COOH content. This last particle showed a lower toxic effect. The results suggest that the lenght and COOH content are important factors in the toxicity of the CNTs.


1972 ◽  
Vol 180 (1060) ◽  
pp. 247-271 ◽  

Eyes of the seatrout (Sciaenidae) contain a tapetum lucidum, located in processes of the pigment epithelial cells. The tapetum is a white diffuse reflector, occluded by black retinal pigment by day, and exposed by retreat of pigment at night; threshold for pigment migration is around 10 lx. Reflexion is caused by backscattering of light from a multitude of small spheres, each about 0.4 μ m in diameter, packing the cell processes. Material has been examined by electron microscopy, employing epoxide sections and freeze-etch techniques. The spheres have homogeneous, densely staining contents and are surrounded by thin boundary membranes. The reflecting material is a lipid, it has been extracted, purified by column and thin-layer chromatography, and characterized by TLC and GLC. On TLC it runs at the same rate as triglycerides, and is demarcated according to class from wax esters, sterols and diacyl glyceryl ethers. It contains predominantly one fatty acid, n — C22 : 6 ( ≥ 95%), and appears to be largely tridocosahexaenoin. The tapetum contains 1.5 mg of triglyceride per square cm. The relationship of the tapetum to the photoreceptors and some characteristics of the latter are described, and reference is made to the occurrence of similar lipid tapeta in other families of fishes.


1984 ◽  
Vol 224 (2) ◽  
pp. 677-680 ◽  
Author(s):  
L Lim ◽  
C Hall ◽  
T Leung ◽  
S Whatley

A protein of molecular mass 68 kDa and pI5.6 is a major translation product of rat brain mRNA [Hall, Mahadevan, Whatley, Biswas & Lim (1984) Biochem. J. 219, 751-761]. In the rat brain this protein was associated with microtubule preparations and was present together with tubulin as a component of the synaptosomal plasma membranes, synaptic vesicles and post-synaptic structures. The brain mRNA for this protein was found to hybridize specifically to the Drosophila gene for the 70 kDa heat-shock protein, thus enabling its rapid isolation.


Paleobiology ◽  
1980 ◽  
Vol 6 (02) ◽  
pp. 146-160 ◽  
Author(s):  
William A. Oliver

The Mesozoic-Cenozoic coral Order Scleractinia has been suggested to have originated or evolved (1) by direct descent from the Paleozoic Order Rugosa or (2) by the development of a skeleton in members of one of the anemone groups that probably have existed throughout Phanerozoic time. In spite of much work on the subject, advocates of the direct descent hypothesis have failed to find convincing evidence of this relationship. Critical points are:(1) Rugosan septal insertion is serial; Scleractinian insertion is cyclic; no intermediate stages have been demonstrated. Apparent intermediates are Scleractinia having bilateral cyclic insertion or teratological Rugosa.(2) There is convincing evidence that the skeletons of many Rugosa were calcitic and none are known to be or to have been aragonitic. In contrast, the skeletons of all living Scleractinia are aragonitic and there is evidence that fossil Scleractinia were aragonitic also. The mineralogic difference is almost certainly due to intrinsic biologic factors.(3) No early Triassic corals of either group are known. This fact is not compelling (by itself) but is important in connection with points 1 and 2, because, given direct descent, both changes took place during this only stage in the history of the two groups in which there are no known corals.


Author(s):  
D. F. Blake ◽  
L. F. Allard ◽  
D. R. Peacor

Echinodermata is a phylum of marine invertebrates which has been extant since Cambrian time (c.a. 500 m.y. before the present). Modern examples of echinoderms include sea urchins, sea stars, and sea lilies (crinoids). The endoskeletons of echinoderms are composed of plates or ossicles (Fig. 1) which are with few exceptions, porous, single crystals of high-magnesian calcite. Despite their single crystal nature, fracture surfaces do not exhibit the near-perfect {10.4} cleavage characteristic of inorganic calcite. This paradoxical mix of biogenic and inorganic features has prompted much recent work on echinoderm skeletal crystallography. Furthermore, fossil echinoderm hard parts comprise a volumetrically significant portion of some marine limestones sequences. The ultrastructural and microchemical characterization of modern skeletal material should lend insight into: 1). The nature of the biogenic processes involved, for example, the relationship of Mg heterogeneity to morphological and structural features in modern echinoderm material, and 2). The nature of the diagenetic changes undergone by their ancient, fossilized counterparts. In this study, high resolution TEM (HRTEM), high voltage TEM (HVTEM), and STEM microanalysis are used to characterize tha ultrastructural and microchemical composition of skeletal elements of the modern crinoid Neocrinus blakei.


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