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At least 145 records · Page 8Linked to original sources

From cell structure to transcription: Hippo forges a new path.

The control of cell number during animal development is a longstanding puzzle. Recent studies in the fruit fly Drosophila melanogaster have defined a new signaling pathway that restricts cell proliferation in differentiating epithelia. The cytoskeletal proteins Merlin and Expanded, which play a role in cell adhesion and structure, control the activation of the Hippo/Salvador kinase complex, which in turn activates the Warts/Mats kinase complex. Warts/Mats kinase phosphorylates and inhibits Yorkie, a transcriptional coactivator that positively regulates cell growth, survival, and proliferation. This conserved signaling pathway contains several tumor-suppressor genes and regulates the contact inhibition of proliferation in cultured cells.

Animals↗

The malaria-infected red blood cell: structural and functional changes.

The asexual stage of malaria parasites of the genus Plasmodium invade red blood cells of various species including humans. After parasite invasion, red blood cells progressively acquire a new set of properties and are converted into more typical, although still simpler, eukaryotic cells by the appearance of new structures in the red blood cell cytoplasm, and new proteins at the red blood cell membrane skeleton. The red blood cell undergoes striking morphological alterations and its rheological properties are considerably altered, manifesting as red blood cells with increased membrane rigidity, reduced deformability and increased adhesiveness for a number of other cells including the vascular endothelium. Elucidation of the structural changes in the red blood cell induced by parasite invasion and maturation and an understanding of the accompanying functional alterations have the ability to considerably extend our knowledge of structure-function relationships in the normal red blood cell. Furthermore, interference with these interactions may lead to previously unsuspected means of reducing parasite virulence and may lead to the development of novel antimalarial therapeutics.

Animals↗

Bidirectional compartmental approximation of realistic nerve cell structures.

Passive electrotonic activity of anatomically complex nerve cells has been computed through a simplified anisotropic "smoothing" of the original structures. The algorithm for this "smoothing" involves a recursive matching of the amplitude, zero and pole of the input impedances for each segment. This algorithm can be used for both spatially and/or electrically inhomogeneous cables. The directional sensitivity of the voltage transfer in non-smooth dendrites has been characterized by a decomposition which reveals the bidirectional segmentation of the core geometry according to the opposite wave fronts of electronic potentials in dendrites. The impedance diagrams can be used to estimate the goodness of the whole procedure in the frequency domain. The bidirectional segmentation of the core geometry may serve as a basis of the compartment simulations of those excitable nerve cells where the voltage spread is modulated by irregular dendritic structures, such as spines.

Algorithms↗

Heterogeneous endothelial cell structure along the porcine retinal microvasculature.

The pivotal role of the endothelial cell in the regulation of vascular tone has been well demonstrated in many vascular beds, including the retina. However, in the retina, little is known about how the structural elements of the endothelial cells are arranged along the arborisation pathway from artery to vein, the nature of which has been linked to functional heterogeneity in other vascular beds. The relative vulnerability of the retina to vascular based diseases, and the heavy reliance on local regulation of the retinal vasculature makes an improved understanding of such local regulatory mechanisms of significant clinical importance. The present study focuses on identifying differences in endothelial cells along the arborisation pathway in the porcine retinal vasculature. Enucleated pig eyes were arterially cannulated and perfused with fixative followed by double staining for F-actin microfilaments (rhodamine phalloidin) and nucleic acid (YO-PRO-1). The intact retina was then viewed by confocal microscopy. The distribution of F-actin, vessel diameter, endothelial cell size and shape, nucleus size and shape, and position within the cell were determined as a function of location along the vascular tree. The main retinal arterioles (A1) contained full length F-actin internal stress fibers which lay parallel to the long axis of the endothelial cell. Subsequent branches from the A1 arteriole (A2 and A3) showed fewer, shorter fibers, with none visible in the A4 and A5 branches, the capillaries, or in the venous side of the vasculature. All endothelial cells showed peripheral border staining of F-actin microfilaments which allowed the shape of the cell to be determined. All endothelial cells were elongated with the long axis parallel to the vessel, but the mean aspect ratio decreased from 10.9+/-0.5, s.e.m. in the A1 arterioles to 3.2+/-0.2 in the major veins (V1). The position of the endothelial cell nucleus relative to the cell was eccentric in the downstream direction in the A2-A5 arterioles, whilst centrally placed in the A1 arterioles and veins. The structural heterogeneity of endothelial cells along the pig retinal circulation suggests that functional heterogeneity of the endothelium may be involved in regulation of retinal blood flow.

Actin Cytoskeleton↗

Langerhans cells: structure, function and role in oral pathological conditions.

Langerhans cells (LCs) are dendritic bone marrow derived cells situated suprabasally in most stratified squamous epithelia, such as the epidermis and the epithelium of oral mucosa, including the gingiva. Langerhans cells are thought to act as antigen-presenting cells (APC) during induction of immune responses. The exact role of Langerhans cells in the oral mucosa is not fully understood although several investigations suggest that these cells are involved in reactions to antigen challenge under both normal and pathological situations. In this paper the structure, phenotypic markers and derivation of Langerhans cells are reviewed. In view of recent findings, the immunological characteristics and the implications of Langerhans cells in pathologic oral reactions are discussed.

Antigens, Surface↗

Mathematical models of hierarchically structured cell populations under equilibrium with application to the epidermis.

There are three categories of keratinocytes in the germinative compartment of the epidermis - stem, transit-amplifying and post-mitotic. Their population structure is hierarchical. This means that stem cells differentiate into transit-amplifying cells which, after a few rounds of division, become post-mitotic cells. The cell processes of birth, differentiation, death and migration affect the composition and proliferation rate of the germinative compartment. These phenomena are quantified by various cell kinetic parameters. In this paper we derive equations that relate these parameters for different models of hierarchically structured cell populations in equilibrium. We include in the models asymmetric and symmetric division, variations in cell-cycle times, apoptosis and variation in the number of transit generations. We conclude that variation in cell-cycle times need only be considered if apoptosis is not negligible. If it is negligible, then only average cell-cycle times are needed. Unfortunately, it is impossible to predict the importance of apoptosis from the available experimental data. However, the strength of its effect is determined by the other parameters, especially the fraction of cycling stem cells. We show that variation in the number of transit generations can have a potentially large effect on cell birth rate. We also show that cell birth rate does not directly depend on the mean transit-amplifying cell-cycle time, only on the mean stem cell-cycle time. We argue that 'homogeneous cell population' equations should not be used to study hierarchical cell populations as has been done in the past. Finally we argue that stem cell parameters and transit-amplifying cell parameters should not be lumped together.

Animals↗

N-methyl-D-aspartate receptor activation and Ca2+ account for poor pyramidal cell structure in hippocampal slices.

The CA1 pyramidal cells appear damaged in micrographs of guinea pig hippocampal slices incubated in normal physiological buffer at 36-37 degrees C. This is remedied if slices are incubated in modified buffers for the first 45 min. Cell morphology is improved if this buffer is devoid of added Ca2+ and much improved if it contains N-methyl-D-aspartate (NMDA) receptor antagonists or 0 mM Ca2+ and 10 mM Mg2+. The cells then appear similar to CA1 pyramidal cells in situ. These findings support the notion that NMDA receptor activation and Ca2+, acting in the period immediately after slice preparation, permanently damage CA1 pyramidal cells in vitro.

Adenosine Triphosphate↗

Spermidine requirement for cell proliferation in eukaryotic cells: structural specificity and quantitation.

Six structural homologs of spermidine and five of its precursor, putrescine, were studied for their ability to prevent cytostasis of cultured L1210 leukemia cells induced by alpha-difluoromethylornithine (DFMO), a specific inhibitor of putrescine biosynthesis. High-performance liquid chromatography and competition studies with spermidine indicated that the homologs, which vary in the length of the carbon chain separating the amines, penetrated the cells. The structural specificity of the spermidine carrier was defined. Three of the six spermidine homologs supported cell growth during a 48-hour incubation in the presence of DFMO, indicating that a two-carbon extension of spermidine structure was tolerated for biological function. Two of the five putrescine homologs supported growth after being converted by the cells to their respective spermidine homologs. The central nitrogen of spermidine appears to be essential for function since diamines of chain length comparable to that of spermidine did not prevent DFMO cytostasis. No more than 15 percent of the spermidine normally present in L1210 cells was required for cell proliferation in the presence of DFMO.

Animals↗

Invadopodia: specialized cell structures for cancer invasion.

The spread of cancer cells to distant sites in the body is the major cause of cancer patient death. Growing evidence connects specialized subcellular structures, invadopodia, to cancer invasion and metastasis. Invadopodia, or invasive foot processes, are actin-rich protrusions that localize matrix-degrading activity to cell-substratum contact points and represent sites where cell signaling, proteolytic, adhesive, cytoskeletal, and membrane trafficking pathways physically converge. Understanding how invadopodia form and function should aid in the identification of novel targets for anti-invasive therapy.

Actins↗

Stromal cell structure and relationships in perimedullary spaces of chick embryo shaft bones.

Structure and relationships of stromal cells were studied by light (LM) and transmission electron microscopy (TEM) in the perimedullary spaces that form the growing cortex of the chick embryo tibia. Observation under LM showed that in all perimedullary spaces the interstices between the cells carpeting the bone surface and the endothelial lining contain stromal cells surrounded by an amorphous matrix. Two types of stromal cells were distinguished: stellate and spindle-shaped. All stromal cells are alkaline phosphatase-positive. TEM showed that both types of stromal cells have cytoplasmic processes of various length and calibre, coming into contact with each other as well as with endothelial cells and osteoblasts or bone lining cells. Capillaries were found to have a continuous endothelial lining; occasionally endothelial cells radiate cytoplasmic processes towards stromal cells. Along all the above-mentioned cellular contacts adherens and/or gap junctions were often observed. The results of the present study, together with our previous findings on osteoblast-osteocyte relationships, show that the cells of the osteogenic lineage form a continuous protoplasmic network that extends from the osteocytes to the vascular endothelium, passing through osteoblasts (or bone lining cells) and stromal cells. The occurrence of gap junctions among this cytoplasmic network, namely of junctions enabling metabolic and electric coupling, indicates that it forms a functional syncytium, suggesting the hypothesis that the activity of the cells pertaining to the osteogenic lineage might be regulated not only by diffusion (volume transmission) through the intercellular fluids of systemic (hormones) and local factors (cytokines, etc.) but also by signals issued through the cytoplasmic network of the osteogenic cells (wiring transmission).

Alkaline Phosphatase↗

Cell structure and cytokinesis alterations in multidrug-resistant Leishmania (Leishmania) amazonensis.

Multidrug-resistant Leishmania (Leishmania) amazonensis may be obtained by in vitro selection with vinblastine. In order to determine whether this phenotype is linked to structural alterations, we analyzed the cell architecture by electron microscopy. The vinblastine resistant CL2 clone of L. (L.) amazonensis, but not wild-type parasites, showed a cytokinesis dysfunction. The CL2 promastigotes had multiple nuclei, kinetoplasts and flagella, suggesting that vinblastine resistance may be associated with truncated cell division. The subpellicular microtubule plasma membrane connection was also affected. Wild-type parasites treated with vinblastine displayed similar alterations, presenting lobulated and multinucleated cells. Taken together, these data indicate that antimicrotubule drug-selected parasites may show evidence of the mutation of cytoskeleton proteins, impairing normal cell function.

Animals↗

Seasonal adaptations of the tuberous roots of Ranunculus asiaticus to desiccation and resurrection by changes in cell structure and protein content.

The annual developmental cycle of tuberous roots of Ranunculus asiaticus was studied with respect to structure and content of their cells, to understand how these roots are adapted to desiccation, high temperature and rehydration. Light microscopy, histochemical analysis, and protein analyses by SDS-PAGE were employed at eight stages of annual root development. During growth and maturation of the roots, cortical cells increased in size and their cell walls accumulated pectin materials in a distinct layer to the inside of the primary walls, with pits between adjoining cells. The number of starch granules and protein bodies also increased within the cells. Several discrete proteins accumulated. Following quiescence and rehydration of the roots there was a loss of starch and proteins from the cells, and cell walls decreased in thickness. The resurrection geophyte R. asiaticus possesses desiccation-tolerant annual roots. They store carbon and nitrogen reserves within their cells, and pectin within the walls to support growth of the plant following summer quiescence and rehydration.

Adaptation, Physiological↗

Cadmium-induced changes in parietal cell structure and functions of rats.

The aim of this study was to determine the cadmium (Cd)-induced functional and structural changes in gastric parietal cells of male rats exposed to high Cd for 30 d. In the present study, control animals were fed with normal food and tap water; the remaining animals received Cd (15 ppm CdCl2) in drinking water for the same period. Receiving Cd for 30 d increased the mean blood Cd level, the mean tissue Cd content, and the mean blood pressure (p < 0.01, p < 0.001, p < 0.01, respectively). The basal acid output fell; however, the increases in stimulated acid output were not statistically significant. Light and electron microscopic examination revealed respectively that (1) Cd decreases the mean parietal cell number per unit from the control value of 23.46 +/- 3.84 to 19.46 +/- 2.12 (p < 0.05) and it affected preferentially the cells located at the distal half of the zymogenic unit and (2) in parietal cells, the Cd-induced alterations were characterized with swollen canalicular profiles, broken-down tubulovesicles, or degenerated mitochondria. We concluded that Cd augments the elimination rate of parietal cells by increasing the alteration rate and reduced basal acid output can be explained easily with the loss of parietal cell population.

Animals↗

[Mesangial kidney cells: structure and function under normal and pathological conditions].

A review of the data on the structure and functions of mesangial cells (MC) and mesangial matrix of the kidneys in normal subjects under experimental conditions and in human pathology is presented. An important role of MC in purification of the glomerular filter is emphasized, their participation in regulation of the glomerular blood flow, the possibility of renin production by them and other functions are considered. Most frequent lesions of MC and their importance in the development of glomerular pathology of the kidneys are described. The nature of MC is discussed.

Cell Membrane↗

Dynamic aspects of the structured cell population in a swarming colony of Proteus mirabilis.

Proteus mirabilis forms a concentric-ring colony by undergoing periodic swarming. A colony in the process of such synchronized expansion was examined for its internal population structure. In alternating phases, i.e., swarming (active migration) and consolidation (growth without colony perimeter expansion), phase-specific distribution of cells differing in length, in situ mobility, and migration ability on an agar medium were recognized. In the consolidation phase, the distribution of mobile cells was restricted to the inner part of a new ring and a previous terrace. Cells composing the outer part of the ring were immobile in spite of their ordinary swimming ability in a viscous solution. A sectorial cell population having such an internal structure was replica printed on fresh agar medium. After printing, a transplant which was in the swarming phase continued its ongoing swarming while a transplanted consolidation front continued its scheduled consolidation. This shows that cessation of migration during the consolidation phase was not due to substances present in the underlying agar medium. The ongoing swarming schedule was modifiable by separative cutting of the swarming front or disruption of the ring pattern by random mixing of the pattern-forming cell population. The structured cell population seemed to play a role in characteristic colony growth. However, separation of a narrow consolidation front from a backward area did not induce disturbance in the ongoing swarming schedule. Thus, cells at the frontal part of consolidation area were independent of the internal cell population and destined to exert consolidation and swarming with the ongoing ordinary schedule.

Culture Media↗