Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Functional differentiation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 271 records · Page 15Linked to original sources
PubMed1985

Pre- and postnatal development of differentiated functions in rat intestinal epithelial cells.

A panel of monoclonal antibodies to intestinal cell surface components has been used to compare the expression of differentiation-specific antigens in the epithelial cells of fetal, suckling, and adult rat small intestine. Indirect immunofluorescence staining, and immunopurification of detergent-solubilized membrane proteins, followed by single- and two-dimensional slab gel electrophoretic analysis, have demonstrated that fetal intestinal cells (at day 21 of gestation) express most differentiation-specific markers typical of adult absorptive villus cells. A marked heterogeneity in antigen expression was observed among different villus cell populations in suckling rat intestine, and three cell surface components were identified which are exclusively present during this period of intestinal development. Striking changes in the patterns of antigen expression in crypt and villus cells, and variations in the apparent isoelectric points for most luminal membrane components, were associated with the maturation of the intestinal mucosa at weaning. These changes could not be prematurely induced by cortisone injection in newborn rats, suggesting that factors other than glucocorticoids are responsible for the postnatal development of the intestinal epithelium. These results suggest that basic differences in biological properties and regulatory mechanisms exist among intestinal epithelial cells at different stages of pre- and postnatal maturation.

Animals↗
PubMed1985

Expression of tracheal differentiated functions in serum-free hormone-supplemented medium.

Most dissociated airway epithelial cells in culture express few of their in vivo functions and only to a limited degree. In this report, we demonstrate that hamster tracheal epithelial (HTE) cells cultured on a collagen gel substratum in a serum-free hormone-supplemented medium differentiate to cilia-beating and mucus-secreting cell types. The medium is Ham's F-12 supplemented with insulin, epidermal growth factor, transferrin, hydrocortisone, cholera toxin, bovine hypothalamus extract, and vitamin A. Under these culture conditions, HTE cells exhibit a growth rate of 24 h/population doubling and reach confluency, at a density of 2-5 X 10(4) cells/cm2, within 2 weeks. Both the collagen gel substratum and vitamin A of this culture system are important to the growth and differentiation of HTE cells in vitro. Evidence of HTE cell differentiation has been obtained at both the ultrastructural and the histochemical levels. In addition, a variety of biochemical studies (gel filtration, ion exchange column chromatography, enzyme digestion, nitrous acid treatment, and composition analysis) indicate the production of mucin-like glycoprotein in the HTE cultures. The levels of mucin-like glycoprotein were found to closely correlate with the histochemically quantitated levels of the mucous cell type. Kinetic studies demonstrate that HTE cells rapidly lose their differentiated features during the attachment stage of primary culture but redifferentiation occurs after the cultures reach confluency. The ability of HTE cells to grow and differentiate in this serum-free culture system in the absence of other cell types should greatly facilitate the study of mucociliary functions in vitro.

Animals↗
PubMed1994

Septal neuron cholinergic and GABAergic functions: differential regulation by basic fibroblast growth factor and epidermal growth factor.

Numerous studies suggest that growth and trophic factors play roles in the development and mature function of brain neurons. Recently, growth factors whose actions were previously characterized on non-neuronal cells have been localized to the brain. We sought to determine whether these factors influence septal cholinergic function. Initially, we defined the effects of basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) on septal cholinergic cells in dissociated neuronal culture. Both factors elevated activity of the acetylcholine synthetic enzyme, choline acetyltransferase (CAT). To determine whether the factors acted directly on neurons or whether glia mediated the effects, a mitotic inhibitor, 5-fluorodeoxyuridine (FDUR), was added to the cultures to eliminate dividing glia. The action of EGF was completely blocked by the addition of FDUR. However, bFGF elevated CAT activity even in the presence of FDUR. Consequently, bFGF may regulate septal cholinergic function directly, whereas EGF may affect cholinergic cells indirectly through glia. To determine whether increases in CAT activity reflect increased enzyme activity per neuron or an increase in the number of cholinergic cells, bFGF-treated cultures were stained for acetylcholinesterase (AChE) to determine numbers of cholinergic cells. No differences in AChE-positive cells were noted, suggesting that bFGF increased CAT activity per cholinergic neuron. To determine whether bFGF regulates other populations in the septum, we examined GABAergic neurons by monitoring the activity of glutamic acid decarboxylase (GAD), a GABA synthetic enzyme. Basic FGF significantly increased GAD activity; however, the effect was completely abolished by addition of FDUR. Thus, bFGF may act directly on cholinergic neurons and indirectly on GABA cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed2000

Functional differentiation of multiple perilesional zones after focal cerebral ischemia.

Transient and permanent focal cerebral ischemia results in a series of typical pathophysiologic events. These consequences evolve in time and space and are not limited to the lesion itself, but they can be observed in perilesional (penumbra) and widespread ipsi- and sometimes contralateral remote areas (diaschisis). The extent of these areas is variable depending on factors such as the type of ischemia, the model, and the functional modality investigated. This review describes some typical alterations attributable to focal cerebral ischemia using the following classification scheme to separate different lesioned and perilesional areas: (1) The lesion core is the brain area with irreversible ischemic damage. (2) The penumbra is a brain region that suffers from ischemia, but in which the ischemic damage is potentially, or at least partially, reversible. (3) Remote brain areas are brain areas that are not directly affected by ischemia. With respect to the etiology, several broad categories of remote changes may be differentiated: (3a) remote changes caused by brain edema; (3b) remote changes caused by waves of spreading depression; (3c) remote changes in projection areas; and (3d) remote changes because of reactive plasticity and systemic effects. The various perilesional areas are not necessarily homogeneous; but a broad differentiation of separate topographic perilesional areas according to their functional state and sequelae allows segregation into several signaling cascades, and may help to understand the functional consequences and adaptive processes after focal brain ischemia.

Brain↗
PubMed2026

Comparative genomics reveals population structure and functional differentiation in Limosilactobacillus fermentum.

Limosilactobacillus fermentum is a widely distributed lactic acid bacterium frequently detected in fermented foods and host-associated microbiota, yet its global genomic diversity and functional variability remain insufficiently characterized. Here, we performed a large-scale comparative genomic analysis of 336 high-quality L. fermentum genomes curated from public databases. Species identity was validated using average nucleotide identity (ANI), and population structure was examined using pairwise ANI comparisons together with Mash-based phylogenetic reconstruction. Clustering at ≥ 99% ANI resolved the dataset into 15 genomic clusters, with four dominant lineages comprising the majority of genomes. Pangenome reconstruction identified 5,853 gene clusters, including 1,325 core genes (22.6%) and a large accessory component dominated by low-frequency genes. Heap's law modeling (λ = 0.19) indicated a weakly open pangenome, suggesting ongoing gene acquisition as additional genomes are sampled. Functional annotation revealed that core genes were primarily associated with essential cellular processes, whereas accessory genes were enriched in carbohydrate metabolism, membrane-associated functions, and defense-related systems. Variation in carbohydrate-active enzymes (CAZymes), transport systems, and stress-response genes was observed across lineages, indicating strain-level functional diversity. Although genomes from human and food sources were broadly distributed across phylogenetic lineages, multivariate analysis showed that gene-content variation was more strongly associated with genomic lineage than with isolation source. These results provide a population genomic framework for understanding genomic diversity and functional potential in L. fermentum.

Phylogeny↗
PubMed1995

N-terminal variants of thyroid hormone receptor beta: differential function and potential contribution to syndrome of resistance to thyroid hormone.

The human syndrome of resistance to thyroid hormone (RTH) is associated with dominant mutations in the thyroid hormone receptor beta (TR beta) gene that generate mutant receptors with impaired binding for T3. Although the TR beta gene differentially expresses two N-terminal variant receptors, TR beta 1 and TR beta 2, functional analyses of RTH mutants have focused exclusively on TR beta 1. Since TR beta 2 is expressed in tissues that are malfunctional in RTH, the role of mutations in the context of TR beta 2 was examined. We compared the functional properties of corresponding RTH mutations in the common C-terminal domain of both TR beta 1 and TR beta 2. Wild type TR beta 1 and TR beta 2 bound similarly as homodimers and as heterodimers with retinoid X receptors to T3-responsive elements consisting of a direct repeat with 4-base pair spacing or an everted repeat. Homodimers, but not monomers or heterodimers, of both receptor subtypes were dissociated by the addition of T3. However, TR beta 2 formed at least 10-fold more stable homodimers than TR beta 1 on a palindromic repeat element, indicating that the N termini of TR beta 1 and TR beta 2 differentially influence dimerization on DNA. The RTH-like mutants of both TR beta 1 and TR beta 2 were equally insensitive to T3. They were defective in T3 binding but still bound DNA like their wild type counterparts except that the T3-dependent dissociation of homodimers from DNA was severely reduced. Wild type TR beta 1 and TR beta 2 mediated T3-inducible transactivation in cotransfection assays; this, however, was abolished in both mutants. TR beta 1 mediated more sensitive T3-dependent transcriptional suppression than TR beta 2 through the negative T3 response region of the TSH beta gene. Again, the mutation abolished T3-dependent suppression by both mutants. Furthermore, both mutants inhibited T3-inducible transcriptional activation by different wild type TR alpha and beta variants. These results indicate that both mutants have the potential to contribute to the pathogenesis of RTH and suggest that a reassessment of previous models of RTH is required to take into account the inhibitory activity of both TR beta 2 and TR beta 1 mutants.

3T3 Cells↗
PubMed1972

Expression of differentiated functions in hepatoma cell hybrids: induction of mouse albumin production in rat hepatoma-mouse fibroblast hybrids.

The synthesis of serum albumin has been studied in hybrids between well-differentiated rat hepatoma cells, which synthesize serum albumin, and mouse fibroblasts (3T3) that do not synthesize albumin. By immunodiffusion techniques with noncrossreacting antisera, the production of both rat and mouse albumin by the hybrids has been examined. Karyologically identified hybrids were produced between 3T3 cells and cells of a 1s hepatoma (Fu5) clone, and of a 2s hepatoma (2s Fu5-5cl.lE) clone. Each of the 3T3 x Fu5 hybrids produces only rat albumin. Among five 3T3 x 2s Fu5-5cl.lE hybrid clones isolated, one produces both rat and mouse albumin, two produce only mouse albumin, and two do not produce rat or mouse albumin.

Animals↗
PubMed1987

Early functional differentiation in the chick embryonic disc: interaction between mechanical activity and extracellular matrix.

The mechanical behaviour of ectodermal cells in the area opaca and the supracellular organization of fibronectin in the adjacent extracellular matrix were studied in whole chick blastoderms developing in vitro. The pattern of spontaneous mechanical activity and its modification by immunoglobulins against fibronectin were determined using a real-time image-analysis system. The pattern of fibronectin was studied using immunocytochemical techniques. It was found that the ectodermal cells in the area opaca actively develop a radially oriented contraction, which leads to a distension of the area pellucida from which the embryo develops. Abnormally increased tension resulted in perturbations of gastrulation and neurulation. An optimized mechanical equilibrium within the blastoderm seems to be necessary for normal development. Anti-fibronectin antibodies applied to the basal side of the blastoderm led rapidly and reversibly to an increase of tension in the contracted cells. This observation indicates that modifications of the extracellular matrix can be transmitted to cytoskeletal elements within adjacent cells. The extracellular matrix of the area opaca contains fibronectin arranged in radially oriented fibrils. This orientation corresponds to the direction of migration of the mesodermal cells. Interestingly, the radial pattern of fibronectin is found in the regions where the ectodermal cells are contracted and develop radially oriented forces. This observation suggests that the supracellular assembly of the extracellular materials could be influenced by the mechanical activity of adjacent cells. Possible modulations of the supracellular organization of extracellular matrix by other factors, e.g. diffusible metabolites, is also discussed. The presence of characteristically organized extracellular matrix components, of spatially differentiated cell activities and of reciprocal interactions between them makes the young chick blastoderm an excellent system for physiological studies of the coordinated cellular activities that lead to changes in form, complexity and function.

Animals↗
PubMed2001

Differential functions of members of the low density lipoprotein receptor family suggested by their distinct endocytosis rates.

The low density lipoprotein receptor (LDLR) family is composed of a class of cell surface endocytic receptors that recognize extracellular ligands and internalize them for degradation by lysosomes. In addition to LDLR, mammalian members of this family include the LDLR-related protein (LRP), the very low density lipoprotein receptor (VLDLR), the apolipoprotein E receptor-2 (apoER2), and megalin. Herein we have analyzed the endocytic functions of the cytoplasmic tails of these receptors using LRP minireceptors, its chimeric receptor constructs, and full-length VLDLR and apoER2 stably expressed in LRP-null Chinese hamster ovary cells. We find that the initial endocytosis rates mediated by different cytoplasmic tails are significantly different, with half-times of ligand internalization ranging from less than 30 s to more than 8 min. The tail of LRP mediates the highest rate of endocytosis, whereas those of the VLDLR and apoER2 exhibit least endocytosis function. Compared with the tail of LRP, the tails of the LDLR and megalin display significantly lower levels of endocytosis rates. Ligand degradation analyses strongly support differential endocytosis rates initiated by these receptors. Interestingly apoER2, which has recently been shown to mediate intracellular signal transduction, exhibited the lowest level of ligand degradation efficiency. These results thus suggest that the endocytic functions of members of the LDLR family are distinct and that certain receptors in this family may play their main roles in areas other than receptor-mediated endocytosis.

Animals↗
PubMed2000

'Where' depends on 'what': a differential functional anatomy for position discrimination in one- versus two-dimensions.

Line bisection is widely used as a clinical test of spatial cognition in patients with left visuospatial neglect after right hemisphere lesion. Surprisingly, many neglect patients who show severe impairment on marking the center of horizontal lines can accurately mark the center of squares. That these patients with left neglect are also typically poor at judging whether lines are correctly prebisected implies that the deficit can be perceptual rather than motoric. These findings suggest a differential neural basis for one- and two-dimensional visual position discrimination that we investigated with functional neuroimaging (fMRI). Normal subjects judged whether, in premarked lines or squares, the mark was placed centrally. Line center judgements differentially activated right parietal cortex, while square center judgements differentially activated the lingual gyrus bilaterally. These distinct neural bases for one- and two-dimensional visuospatial judgements help explain the observed clinical dissociations by showing that as a stimulus becomes a better, more 'object-like' gestalt, the ventral visuoperceptive route assumes more responsibility for assessing position within the object.

Adult↗
PubMed2001

Differential functional relevance of a plasma membrane ganglioside sialidase in cholinergic and adrenergic neuroblastoma cell lines.

Gangliosides located in the outer leaflet of the plasma membrane are important modulators of cellular functions. Our previous work has shown that in cultured human SK-N-MC neuroblastoma cells a sialidase residing in the same membrane selectively desialylates gangliosides with terminal sialic acid residues, causing a shift from higher species to GM1 and a conversion of GM3 to lactosylceramide. Inhibition of this sialidase by 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (NeuAc2en) resulted in increased cell proliferation and a loss of differentiation markers. In this study, we examined the occurrence and function of this ganglioside sialidase in other neuronal cells. Subcellular fractionation showed the sialidase to be located in the plasma membrane of all cell lines studied. The presence of the inhibitor NeuAc2en led to a profound decrease in the amount of the differentiation marker 200 kDa/70 kDa neurofilaments and an increase in cell proliferation in the cholinergic SK-N-MC and mixed cholinergic/adrenergic SK-N-FI and SK-N-DZ neuroblastoma lines, but had little or no effect in the human adrenergic SK-N-SH and SK-N-AS and the adrenergic/cholinergic PC12 cells from rat. The influence of the inhibitor on cell behaviour was paralleled by a diminished number of cholera toxin B-binding GM1 sites. The findings demonstrate that the plasma membrane ganglioside sialidase is an important element of proliferation and differentiation control in some, but not all, neuroblastoma cells and suggest that there might be a relationship between plasma membrane sialidase activity and cholinergic differentiation.

Adrenergic Fibers↗
PubMed2005

Effect of isoliquiritigenin on viability and differentiated functions of human hepatocytes maintained on PEEK-WC-polyurethane membranes.

In this study, we tested the ability of microporous membranes synthesised from a polymeric blend of modified polyetheretherketone (PEEK-WC) and polyurethane (PU) to support long-term maintenance and differentiation of human liver cells. The effect of isoliquiritigenin (ISL), which is a component of liquorice extract, exhibiting growth stimulatory and antiproliferative dose-dependent effect was investigated by comparing cultures treated with ISL with those untreated. To this purpose, flat-sheet membranes were prepared by a blend of PEEK-WC and PU polymers by phase inverse technique. The morphological and physico-chemical properties were characterised, respectively, by scanning electron microscopy and water contact angle measurements. Human hepatocytes cultured on PEEK-WC-PU membranes were constant up to 1 month albumin production and urea synthesis as well as the synthesis of total proteins. The liver-specific functions were expressed at high levels when cells were cultured on membranes with respect to collagen. Also the biotransformation functions were maintained for all culture periods: the ISL elimination rate increased during the culture time and high values were measured up to 22 days. Thereafter, a decrease was observed. ISL stimulated the proliferation of hepatocytes cultured on both substrata but did not affect their liver-specific functions. Hepatocytes cultured on PEEK-WC-PU membranes responded very well to ISL and expressed high levels of P450 cytochrome. These results demonstrated that long-term maintenance of human liver differentiation can be achieved on PEEK-WC-PU membranes. The incubation with ISL at the investigated concentration could stimulate the proliferation of human hepatocytes in biohybrid systems.

Benzophenones↗
PubMed1973

Expression of differentiated functions in hepatoma cell hybrids: alanine aminotransferase.

The expression of alanine aminotransferase (EC 2.6.1.2), an enzyme that is inducible in the liver, has been examined in somatic hybrid cells formed by crossing well-differentiated rat hepatoma cells with rat diploid epithelial cells, the former characterized by high activity and inducibility of the enzyme, and the latter by the absence of detectable activity. The hybrid cells that contain essentially complete chromosomal sets of the two parents show only very low activity and little inducibility. Among numerous "segregated" hybrid subclones, which have lost up to 40% of the chromosomes initially present, several show expression of intermediate levels of enzyme activity and very little inducibility, and two independent subclones are characterized by full re-expression of both baseline and inducible enzyme activity. The electrophoretic mobility of the enzyme from the latter hybrids, from the hepatoma parental cells, and from rat liver is identical. The absence of a correlation between total chromosome number of the hybrid cells and re-expression of alanine aminotransferase suggests that the loss of specific chromosomes is required for re-expression. In these hybrid cells, the re-expression of alanine aminotransferase baseline and inducibility is independent of that of tyrosine aminotransferase inducibility.

Alanine Transaminase↗
PubMed1974

Expression of differentiated functions in hepatoma cell hybrids: high frequency of induction of mouse albumin production in rat hepatoma-mouse lymphoblast hybrids.

We have studied the production of serum albumin by somatic hybrids between well-differentiated 2s and 1s rat hepatoma cells (Faza), which produce serum albumin, and sub-diploid mouse leukemic lymphoblasts (Lc), which do not produce albumin. We determined the rat or mouse origin of the albumin by double immunodiffusion, using immuno-adsorbed noncrossreacting antisera. Each of 12 karyologically identified 2s hybrid clones (Lc2F) produces both rat and mouse albumin. Moreover, unlike 1s hybrids reported previously, eight of nine 1s hybrids (LcF) also produce mouse albumin; six of them produce rat albumin as well. One clone from the 1s cross produces only rat albumin.

Albumins↗