Giant cell formation: the way to cell death or cell survival?

The study of giant cells in populations of different tumor cells and evaluation of their role in cancer development is an expanding field. The formation of giant cells has been shown to be followed by mitotic catastrophe, apoptosis, necrosis, and other types of cell elimination. Reports also demonstrate that giant cells can escape cell death and give rise to new cancer cells. However, it is not known if the programmed cell death is involved in this type of cell cycle disorders. Here we describe principal events that are observed during giant cell formation. We also consider the role of giant cells in cancer development, taking into account both published work and our own recent data in this field.     

PH-dependent cell–cell interactions in the green alga Chara

Protoplasma - Characean internodal cells develop alternating patterns of acid and alkaline zones along their surface in order to facilitate uptake of carbon required for photosynthesis. In this...     

What befalls the proteins and water in a living cell when the cell dies?

The solvency of solutes of varying molecular size in the intracellular water of freshly-killed Ehrlich carcinoma cells fits the same theoretical curve that describes the solvency of similar solutes in a 36% solution of native bovine hemoglobin--a protein found only in red blood cells and making up 97.3% of the red cell's total intracellular proteins. The merging of the two sets of data confirms the prediction of the AI Hypothesis that key intracellular protein(s) in dying cells undergo(es) a transition from: (1) one in which the polypeptide NHCO groups assume a fully-extended conformation with relatively strong power of polarizing and orienting the bulk-phase water in multilayers; to (2) one in which most of the polypeptide NHCO groups are engaged in alpha-helical and other "introvert" conformations (see below for definition) with much weaker power in polarizing-orienting multilayers of bulk-phase water. This concordance of the two sets of data also shows that what we now call native hemoglobin--supposedly denoting hemoglobin found in its natural state in living red blood cells--, in fact, more closely resembles the water-polarizing, and -orienting intracellular proteins in dead cells. Although in the dead Ehrlich carcinoma cells as well as in the 36% solution of native hemoglobin, much of the protein's polypeptide NHCO groups are engaged in alpha-helical and other "introvert" conformation (Perutz 1969; Weissbluth 1974), both systems produce a weak but nonetheless pervasive and "long-range" water polarization and orientation. It is suggested that in both the dead Ehrlich carcinoma ascites cells and in the 36% native bovine hemoglobin solution, enough polypeptide NHCO groups assume the fully-extended conformation to produce the weak but far-reaching multilayer water polarization and orientation observed.     

When and how does cell division order influence cell allocation to the inner cell mass of the mouse blastocyst?

Aggregate 8-cell embryos were constructed from four 2/8 pairs of blastomeres, one of which was marked with a short-term cell lineage marker and was also either 4 h older (derived from an early-dividing 4-cell) or 4 h younger (derived from a late-dividing 4-cell) than the other three pairs. The aggregate embryos were cultured to the 16-cell stage, at which time a second marker was used to label the outside cell population. The embryos were then disaggregated and each cell was examined to determine its labelling pattern. From this analysis, we calculated the relative contributions to the inside cell population of the 16-cell embryo of older and younger cells. Older cells were found to contribute preferentially. However, if the construction of the aggregate 8-cell embryo was delayed until each of the contributing 2/8 cell pairs had undergone intercellular flattening and then had been exposed to medium low in calcium to reverse this flattening immediately prior to aggregation, the advantage possessed by the older cells was lost. These results support the suggestion that older cells derived from early-dividing 4-cell blastomeres contribute preferentially to the inner cell mass as a result of being early-flattening cells.     

Cilia and the cell cycle?

A recent convergence of data indicating a relationship between cilia and proliferative diseases, such as polycystic kidney disease, has revived the long-standing enigma of the reciprocal regulatory relationship between cilia and the cell cycle. Multiple signaling pathways are localized to cilia in mammalian cells, and some proteins have been shown to act both in the cilium and in cell cycle regulation. Work from the unicellular alga Chlamydomonas is providing novel insights as to how cilia and the cell cycle are coordinately regulated.     

What makes the cell differentiate?

In the present paper, I propose a hypothesis whereby the necessity to maintain the permanent energy-dissipating metabolic flux represents the primary force that determines the eukaryotic cell's choice to grow, divide and/or differentiate. This view is based on the universal structure and the strict redox neutrality of the core metabolic network. I propose that the direct substrate level coupling between metabolism and gene expression through epigenetic mechanisms provides a mechanistic explanation of how this control is implemented.     

ATP-mediated cell–cell signaling in the organ of Corti: the role of connexin channels

Connexin 26 (Cx26) and connexin 30 (Cx30) form hemichannels that release ATP from the endolymphatic surface of cochlear supporting and epithelial cells and also form gap junction (GJ) channels that allow the concomitant intercellular diffusion of Ca²⁺ mobilizing second messengers. Released ATP in turn activates G-protein coupled P2Y₂ and P2Y₄ receptors, PLC-dependent generation of IP₃, release of Ca²⁺ from intracellular stores, instigating the regenerative propagation of intercellular Ca²⁺ signals (ICS). The range of ICS propagation is sensitive to the concentration of extracellular divalent cations and activity of ectonucleotidases. Here, the expression patterns of Cx26 and Cx30 were characterized in postnatal cochlear tissues obtained from mice aged between P5 and P6. The expression gradient along the longitudinal axis of the cochlea, decreasing from the basal to the apical cochlear turn (CT), was more pronounced in outer sulcus (OS) cells than in inner sulcus (IS) cells. GJ-mediated dye coupling was maximal in OS cells of the basal CT, inhibited by the nonselective connexin channel blocker carbenoxolone (CBX) and absent in hair cells. Photostimulating OS cells with caged inositol (3,4,5) tri-phosphate (IP₃) resulted in transfer of ICS in the lateral direction, from OS cells to IS cells across the hair cell region (HCR) of medial and basal CTs. ICS transfer in the opposite (medial) direction, from IS cells photostimulated with caged IP₃ to OS cells, occurred mostly in the basal CT. In addition, OS cells displayed impressive rhythmic activity with oscillations of cytosolic free Ca²⁺ concentration ([Ca²⁺]_i) coordinated by the propagation of Ca²⁺ wavefronts sweeping repeatedly through the same tissue area along the coiling axis of the cochlea. Oscillations evoked by uncaging IP₃ or by applying ATP differed greatly, by as much as one order of magnitude, in frequency and waveform rise time. ICS evoked by direct application of ATP propagated along convoluted cellular paths in the OS, which often branched and changed dynamically over time. Potential implications of these findings are discussed in the context of developmental regulation and cochlear pathophysiology.     

Cell–cell contact and signaling in the muscle stem cell niche

Muscle stem cells (also called satellite cells or SCs) rely on their local niche for regulatory signals during homeostasis and regeneration. While a number of cell types communicate indirectly through secreted factors, here we focus on the significance of direct contact between SCs and their neighbors. During quiescence, SCs reside under a basal lamina and receive quiescence-promoting signals from their adjacent skeletal myofibers. Upon injury, the composition of the niche changes substantially, enabling the formation of new contacts that mediate proliferation, self-renewal, and differentiation. In this review, we summarize the latest work in understanding cell–cell contact within the satellite cell niche and highlight areas of open questions for future studies.     

Effect of theβ-d-galactoside-binding lectin on cell to substratum and cell to cell adhesion of cells from the extraembryonic endoderm of the early chick blastoderm

Summary Cells from the extraembryonic endoderm of the gastrulating chick embryo contain a -d-galactoside-binding lectin inhibited by thiodigalactoside (TDG). When cell suspensions are cultured in stationary culture in the presence of exogenously added purified blastoderm lectin or TDG, their attachment to the substratum is delayed and decreased compared to controls. The cells take on a fibroblastic-like morphology and cell to cell contact becomes limited to localized areas of the cell surface. Many lectin or TDG-treated cells appear to be migrating over the substratum. This is in contrast to control cultures where the cells appear epithelial in morphology and tend to maximize their areas of apposition. These data suggest that the endogenous lectin may have a role to play in cell to substratum and cell to cell adhesion.     

Malaria tolerance--for whom the cell tolls?

How is it that individuals exposed to intense malaria transmission can tolerate the presence of malaria parasites in their blood at levels that would produce fever in others? In light of evidence discounting a role for nitric oxide or antibodies to plasmodial glycosylphosphatidylinositols in maintaining this tolerant state, refractoriness to toxin-induced Toll-like receptor-mediated signalling has emerged as a likely explanation that links malarial and bacterial endotoxin tolerance. Understanding the mechanisms underlying tolerance and the potential for cross-tolerization has significant implications for understanding the potential for antitoxic vaccine strategies, as well as interactions between different malaria species and between malaria and other human parasites.     

Does the hematopoietic stem cell exist?

The hypothesis concerning the existence of a self-maintaining, i. e. "immortal" hemopoietic stem cell has no conclusive evidence. The data demonstrating the existence of hemopoietic cells with very high proliferative potentials, which are formed only during embryogenesis are discussed. Clonal expansion of these cells can support hemopoiesis during the entire life of the adult organism.     

How do cytokinins affect the cell?

The lecture presents modern knowledge of the mechanisms of cytokinin perception and signal transduction to the genes of primary and secondary responses. It also demonstrates the relations between the rapid cytokinin-induced processes and cytokinin-induced physiological effects. The characteristics of the cytokinin regulatory system and its role in the control of plant growth and development are discussed.     

Probing cell structure by controlling the mechanical environment with cell–substrate interactions

Recent results demonstrate the exquisite sensitivity of cell morphology and structure to mechanical stimulation. Mechanical stimulation is often coupled with cell–substrate interactions that can, in turn, influence molecular response and determine cellular fates including apoptosis, proliferation, and differentiation. To understand these effects as they specifically relate to compressive mechanical stimulation and topographic control, we developed a microfabricated system to grow cells on polydimethylsiloxane (PDMS) microchannel surfaces where we maintained compression stimulation. We also probed cellular response following compressive mechanical stimulation to PDMS substrates of varying stiffness. In these instances, we examined cytoskeletal and morphologic changes in living cells attached to our substrate following the application of localized compressive stimulation. We found that the overall morphology and cell structure, including the actin cytoskeleton, oriented in the direction of the compressive strain applied and along the topographic microchannels. Furthermore by comparing topographic response to material stiffness, we found a 40% increase in cell area for cells cultured on the microchannels versus softer PDMS as well as a decreased cell area of 30% when using softer PDMS over unmodified PDMS. These findings have implications for research in a diversity of fields including cell–material interactions, mechanotransduction, and tissue engineering.     

Characterization of Giardia cell nucleus：Its implication on the nature and origin of the primitive cell nucleus

Thecentralproblemoftheoriginandearlyevolutionoftheeukaryoticcel1istheoriginofthecellnucleus,becausethecellnucleus,withitsdouble-layerednuclearenvelope,isthemostprominentandimportantmorphologicalmarkdistinguishingeukaryoticcellsfromprokaryotes.Eukaryoticcellsmayhavenochloroplast,mito-chondriaorflagellum,buttheymustpossessacellnucleus.Thecellnucleusitselfisaverycomplicatedstructure-Ifwetrytomakecleartheoriginandearlyevolutionofthecellnucleus,weoughttoinvestigatetheoriginandevolutionofeachmorphol…     

Diabetes mellitus and the β cell: the last ten years

Diabetes is a major global problem. During the past decade, the genetic basis of various monogenic forms of the disease, and their underlying molecular mechanisms, have been elucidated. Many genes that increase type 2 diabetes (T2DM) risk have also been identified, but how they do so remains enigmatic. Nevertheless, defective insulin secretion emerges as the main culprit in both monogenic and polygenic diabetes, with environmental and lifestyle factors, via obesity, accounting for the current dramatic increase in T2DM. There also have been significant advances in therapy, particularly for some monogenic disorders. We review here what ails the β cell and how its function may be restored.