275 research outputs found
Protein Tpr is required for establishing nuclear pore-associated zones of heterochromatin exclusion
Amassments of heterochromatin in somatic cells occur in close contact with the nuclear envelope (NE) but are gapped by channel- and cone-like zones that appear largely free of heterochromatin and associated with the nuclear pore complexes (NPCs). To identify proteins involved in forming such heterochromatin exclusion zones (HEZs), we used a cell culture model in which chromatin condensation induced by poliovirus (PV) infection revealed HEZs resembling those in normal tissue cells. HEZ occurrence depended on the NPC-associated protein Tpr and its large coiled coil-forming domain. RNAi-mediated loss of Tpr allowed condensing chromatin to occur all along the NE's nuclear surface, resulting in HEZs no longer being established and NPCs covered by heterochromatin. These results assign a central function to Tpr as a determinant of perinuclear organization, with a direct role in forming a morphologically distinct nuclear sub-compartment and delimiting heterochromatin distribution
Study of the collagen structure in the superficial zone and physiological state of articular cartilage using a 3D confocal imaging technique
Steatosis of indeterminate cause in a pediatric group: is it a primary mitochondrial hepatopathy?
Intestinal fibrovascular nodules caused by Schistosoma mansoni infection in Calomys callosus Rengger, 1830 (Rodentia: Cricetidae): a model of concomitant fibrosis and angiogenesis
Lysosomes in iron metabolism, ageing and apoptosis
The lysosomal compartment is essential for a variety of cellular functions, including the normal turnover of most long-lived proteins and all organelles. The compartment consists of numerous acidic vesicles (pH ∼4 to 5) that constantly fuse and divide. It receives a large number of hydrolases (∼50) from the trans-Golgi network, and substrates from both the cells’ outside (heterophagy) and inside (autophagy). Many macromolecules contain iron that gives rise to an iron-rich environment in lysosomes that recently have degraded such macromolecules. Iron-rich lysosomes are sensitive to oxidative stress, while ‘resting’ lysosomes, which have not recently participated in autophagic events, are not. The magnitude of oxidative stress determines the degree of lysosomal destabilization and, consequently, whether arrested growth, reparative autophagy, apoptosis, or necrosis will follow. Heterophagy is the first step in the process by which immunocompetent cells modify antigens and produce antibodies, while exocytosis of lysosomal enzymes may promote tumor invasion, angiogenesis, and metastasis. Apart from being an essential turnover process, autophagy is also a mechanism by which cells will be able to sustain temporary starvation and rid themselves of intracellular organisms that have invaded, although some pathogens have evolved mechanisms to prevent their destruction. Mutated lysosomal enzymes are the underlying cause of a number of lysosomal storage diseases involving the accumulation of materials that would be the substrate for the corresponding hydrolases, were they not defective. The normal, low-level diffusion of hydrogen peroxide into iron-rich lysosomes causes the slow formation of lipofuscin in long-lived postmitotic cells, where it occupies a substantial part of the lysosomal compartment at the end of the life span. This seems to result in the diversion of newly produced lysosomal enzymes away from autophagosomes, leading to the accumulation of malfunctioning mitochondria and proteins with consequent cellular dysfunction. If autophagy were a perfect turnover process, postmitotic ageing and several age-related neurodegenerative diseases would, perhaps, not take place
Lipid droplets: a classic organelle with new outfits
Lipid droplets are depots of neutral lipids that exist virtually in any kind of cell. Recent studies have revealed that the lipid droplet is not a mere lipid blob, but a major contributor not only to lipid homeostasis but also to diverse cellular functions. Because of the unique structure as well as the functional importance in relation to obesity, steatosis, and other prevailing diseases, the lipid droplet is now reborn as a brand new organelle, attracting interests from researchers of many disciplines
Characterization of Granulations of Calcium and Apatite in Serum as Pleomorphic Mineralo-Protein Complexes and as Precursors of Putative Nanobacteria
Calcium and apatite granulations are demonstrated here to form in both human and
fetal bovine serum in response to the simple addition of either calcium or
phosphate, or a combination of both. These granulations are shown to represent
precipitating complexes of protein and hydroxyapatite (HAP) that display marked
pleomorphism, appearing as round, laminated particles, spindles, and films.
These same complexes can be found in normal untreated serum, albeit at much
lower amounts, and appear to result from the progressive binding of serum
proteins with apatite until reaching saturation, upon which the mineralo-protein
complexes precipitate. Chemically and morphologically, these complexes are
virtually identical to the so-called nanobacteria (NB) implicated in numerous
diseases and considered unusual for their small size, pleomorphism, and the
presence of HAP. Like NB, serum granulations can seed particles upon transfer to
serum-free medium, and their main protein constituents include albumin,
complement components 3 and 4A, fetuin-A, and apolipoproteins A1 and B100, as
well as other calcium and apatite binding proteins found in the serum. However,
these serum mineralo-protein complexes are formed from the direct chemical
binding of inorganic and organic phases, bypassing the need for any biological
processes, including the long cultivation in cell culture conditions deemed
necessary for the demonstration of NB. Thus, these serum granulations may result
from physiologically inherent processes that become amplified with calcium
phosphate loading or when subjected to culturing in medium. They may be viewed
as simple mineralo-protein complexes formed from the deployment of
calcification-inhibitory pathways used by the body to cope with excess calcium
phosphate so as to prevent unwarranted calcification. Rather than representing
novel pathophysiological mechanisms or exotic lifeforms, these results indicate
that the entities described earlier as NB most likely originate from calcium and
apatite binding factors in the serum, presumably calcification inhibitors, that
upon saturation, form seeds for HAP deposition and growth. These calcium
granulations are similar to those found in organisms throughout nature and may
represent the products of more general calcium regulation pathways involved in
the control of calcium storage, retrieval, tissue deposition, and disposal
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