Differentiation Of Others Research Articles

Clonal Origin and Lineage Ambiguity in Mixed Neuroendocrine Carcinoma of the Uterine Cervix

Small cell neuroendocrine carcinoma of the cervix (SCNEC/cervix) is a rare disease characterized by a high incidence of mixed tumors with other types of cancer. The mechanism underlying this mixed phenotype is not well understood. In this study, a panel of organoid lines from patients with SCNEC/cervix was established and focused on one line, which retained a mixed tumor phenotype, both in vitro and in vivo. Histologically, both organoids and xenograft tumors showed distinct differentiation into either SCNEC or adenocarcinoma in some regions and ambiguous differentiation in others. By tracking single cells, the existence of cells with bipotential differentiation towards SCNEC and adenocarcinomas was revealed. Single-cell transcriptional analysis identified three distinct clusters: SCNEC-like, adenocarcinoma-like, and a cluster lacking specific differentiation markers. The expression of neuroendocrine markers was enriched in the SCNEC-like cluster but not exclusively. Human papillomavirus 18 E6 was enriched in the SCNEC-like cluster, which showed higher proliferation and lower levels of the p53 pathway. After treatment with anticancer drugs, the expression of adenocarcinoma markers increased, whereas that of SCNEC decreased. Using a reporter system for KRT19 expression, changes in the differentiation of each cell were revealed to be associated with the shift in differentiation induced by drug treatment. These data suggest that mixed SCNEC/cervical tumors have a clonal origin and are characterized by an ambiguous and flexible differentiation state.

Task Environments and Pressures to Conform to Corporate Social Performance Norms

Recent studies describe the degree to which variance in corporate social performance (CSP) is determined by firm-level choices versus constrained by industry pressures. However, the degree to which each matters likely varies across industries. We construct a theoretical framework grounded in institutional theory that explains how organizational task environment dimensions impact the relative importance of firm and industry effects on CSP. Hypotheses are tested using hierarchical linear modeling with longitudinal data from 4,109 firms in 378 industries between 1991 and 2009. Results show that industry effects increase and firm effects decrease in stable, hostile, and complex environments. The study helps explain why CSP serves as a legitimating mechanism in some industries but as a source of differentiation in others.

The Prospects of Intercultural Education in Bosnia and Herzegovina

Throughout history, education has not only been a carrier of culture, but also an integral part of communication between different cultures. Challenges faced by educational and cultural institutions in most modern pluralistic societies are higher than in earlier societies. The legacy of ethnic conflict in the war in Bosnia and Herzegovina, in which traditional value of multicultural and multi-religious life was undermined, had immediate implications for social, cultural and educational policies. Educational policy, based on the assumption of a national culture that promotes national exclusivity through textbooks and educational practice, should overcome in recognition of cultural diversity and dialogue in a globalized world where differences should be considered an advantage and not deemed an obstacle to common life and cooperation. The paper highlights the importance of introducing interculturalism as an important component of the overall educational practice. Teaching the value of diversity, the affirmation of universal values that underlie a democratic society, a sense of responsibility to themselves and to each other, the rejection of exclusion and differentiation of others on any basis, solidarity and cooperation, are current issues of the modern pedagogical and sociological discourse. These concerns must receive a stronger affirmation and application in the educational process of Bosnia and Herzegovina.

Canonical Notch signalling is inactive in urothelial carcinoma

BackgroundNotch signalling regulates cell fate in most tissues, promoting precursor cell proliferation in some, but differentiation in others. Accordingly, downregulation or overactivity variously contributes to cancer development. So far, little is known about Notch pathway activity and function in the normal urothelium and in urothelial carcinoma (UC). We have therefore investigated expression of Notch pathway components in UC tissues and cell lines and studied the function of one receptor, NOTCH1, in detail.MethodsExpression of canonical Notch pathway components were studied in UC and normal bladder tissues by immunohistochemistry and quantitative RT-PCR and in UC cell lines and normal cultured urothelial cells by qRT-PCR, immunocytochemistry and Western blotting. Pathway activity was measured by reporter gene assays. Its influence on cell proliferation was investigated by γ-secretase inhibition. Effects of NOTCH1 restoration were followed by measuring cell cycle distribution, proliferation, clonogenicity and nuclear morphology.ResultsNOTCH1 and its ligand, DLL1, were expressed at plasma membranes and in the cytoplasm of cells in the upper normal urothelium layer, but became downregulated in UC tissues, especially in high-stage tumours. In addition, the proteins were often delocalized intracellularly. According differences were observed in UC cell lines compared to normal urothelial cells. Canonical Notch pathway activity in reporter assays was repressed in UC cell lines compared to normal cells and a mammary carcinoma cell line, but was induced by transfected NOTCH1. Inhibitors of Notch signalling acting at the γ-secretase step did not affect UC cell proliferation at concentrations efficacious against a cell line with known Notch activity. Surprisingly, overexpression of NOTCH1 into UC cell lines did not significantly affect short-term cell proliferation, but induced nuclear abnormalities and diminished clonogenicity.ConclusionOur data indicate that canonical Notch signalling is suppressed in urothelial carcinoma mainly through downregulation of NOTCH1. These findings can be explained by proposing that canonical Notch signalling may promote differentiation in the urothelium, like in many squamous epithelia, and its suppression may therefore be advantageous for tumour progression. As an important corollary, inhibition of canonical Notch signalling is unlikely to be efficacious and might be counter-productive in the treatment of urothelial carcinoma.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-628) contains supplementary material, which is available to authorized users.

CBDR&RC in a regime applicable to all

The principle of common, but differentiated, responsibilities and respective capabilities (CBDR&RC) is fundamental to the UNFCCC. Some options for a nuanced model of differentiation that addresses both responsibility and capability in a changing world are explored, such as new categories of countries, and some of the political issues that such a model might face are considered. The strengths and limitations of options for graduation based on ‘objective’ criteria such that countries could move between categories or ‘graduate’ – an option provided by the UNFCCC – are discussed. Countries could also choose to join another club (e.g. the G20), self-elect into categories or differentiate among themselves implicitly by accepting different commitments and actions. CBDR&RC will form part of the overall legally binding agreement, and must apply symmetry in some respects and differentiation in others to the commitments and actions contained therein. Some possible characteristics of CBDR&RC of relevance in a regime ‘applicable to all’ are outlined. These include promoting climate action and using mechanisms available in the UNFCCC to instil dynamism. Differentiation on mitigation must consider the distinctions between absolute and relative reductions, as well as commitments to outcomes and implementation. CBDR&RC should be applied to mitigation, adaptation, and the means of implementation.Policy relevanceIn Durban, Parties agreed to negotiate a regime ‘applicable to all’, which sent a political signal that there should be greater symmetry between nations. The world has changed since the UNFCCC was negotiated in 1992. It is now less helpful to think only in terms of two groups of countries (e.g. Annex I and non-Annex I), and evident that there are significant differences between member states. This requires a more nuanced interpretation of the principles of equity and CBDR&RC, which is an integral part of the UNFCCC. The options for the different approaches outlined in this article might help in the construction of a more nuanced model. All must do more, while some must do more still than others. To achieve this, some defining characteristics of CBDR&RC in a regime applicable to all are suggested.

Product differentiation and film-programming choice: do first-run movie theatres show the same films?

We present an empirical analysis of product differentiation using a new panel data set on film-programming choice in a major U.S. metropolitan motion-pictures exhibition market. Using these data, we compute two measures of product similarity, which allow us to investigate the determinants of strategic product differentiation in a multi-characteristics space. Our evidence is consistent with the idea that the degree of product differentiation between theatre pairs reflects a balance between strategic concerns and contractual constraints. Similarity in one dimension is offset by differentiation in others. Our results further suggest that the degree of product differentiation is negatively related to market size. Finally, we find that ownership matters: theatres under common ownership make more similar programming choices than theatres with different owners.

Population Structure and Mitochondrial Polyphyly in North American Gadwalls (Anas Strepera)

AbstractWe examined population genetic structure in Gadwalls (Anas strepera) to test the prediction that female philopatry and fidelity to migratory flyways have contributed to the partitioning of mitochondrial variation across North America. Sequencing a 658–659 base-pair fragment of the mitochondrial DNA (mtDNA) control region from 348 Gadwalls, we found two distinct clades that were broadly intermixed across both breeding and nonbreeding populations. Clade A was abundant in North America as well as among published sequences from Eurasia. Clade B was sequenced from 5.5% of North American Gadwalls and was more similar to Asian Falcated Duck (A. falcata) haplotypes than to clade A haplotypes. Maximum likelihood indicated that Gadwall clade B haplotypes were a monophyletic group nested within Falcated Duck haplotypes, which suggests mtDNA introgression of clade B into Gadwalls. However, that topology was weakly supported, and we could not reject topologies that were consistent with incomplete lineage-sorting as the cause of mitochondrial polyphyly. Migratory flyways did not contribute significantly to population structure and, in general, we found a lack of genetic structure among most populations. However, Gadwalls sampled in Alaska and Washington were well differentiated from other populations. Coalescent analyses supported a historical population expansion for clade A, and this expansion could have contributed to the high genetic similarity among some populations but the strong differentiation of others. Female-mediated gene flow, along with both historical and contemporary population and range expansions, has likely contributed to the overall weak mtDNA structure in North American Gadwalls.Estructura Poblacional y Polifilia Mitocondrial en Anas strepera

The role of Notch in tumorigenesis: oncogene or tumour suppressor?

Notch signalling participates in the development of multicellular organisms by maintaining the self-renewal potential of some tissues and inducing the differentiation of others. Involvement of Notch in cancer was first highlighted in human T-cell leukaemia, fuelling the notion that aberrant Notch signalling promotes tumorigenesis. However, there is mounting evidence that Notch signalling is not exclusively oncogenic. It can instead function as a tumour suppressor.

PRL-1 PTPase expression is developmentally regulated with tissue-specific patterns in epithelial tissues.

The mechanisms controlling tyrosine phosphorylation of cellular proteins are important in the regulation of many cellular processes, including development and differentiation. Protein tyrosine phosphatases (PTPases) may be as important as protein tyrosine kinases (PTKs) in these processes. PRL-1 is a distinct PTPase originally identified as an immediate-early gene in liver regeneration whose expression is associated with growth in some tissues but with differentiation in others. We now demonstrate that the PRL-1 protein is expressed during development in a number of digestive epithelial tissues. It is expressed at variable time points in the developing intestine, but its expression is limited to the developing villus enterocytes. In the gastric epithelium, PRL-1 expression in the adult is restricted to zymogen cells. PRL-1 is also expressed in the developing liver and esophagus and in the epithelia of the kidney and lung. In each of these contexts, the expression of PRL-1 is associated with terminal differentiation, suggesting that it may play a role in this important developmental process.

Inhibition by TGF-beta 1 of the in vitro thymulin-stimulated proliferation of gonocytes from fetal rat testes.

The cytokine transforming growth factor beta 1 (TGF-beta 1) inhibits the growth of certain cells and the differentiation of others. A thymus hormone, thymulin, stimulated the proliferation of fetal male germ cells in explants of testes from 13.5 gestation day rat fetuses. The way in which thymulin acts is unknown. Adding TGF-beta 1 to the culture medium blocked the response of the fetal male rat germ cells to thymulin. We suggest that TGF-beta 1 and thymulin may thus influence the same metabolic chain of events.

Semantic Differentiation in the Acquisition of English as a Second Language

I analyzed the mental organizations of two sets of fuzzy lexical items by 70 native speakers (NSs) of English and 185 learners of English as a second language (ESL). They provided pair‐wise comparisons of a set of degree adverbs and a set offrequency terms, respectively. I subjected their judgments to unidimensional scaling and circular triad analysis, which indicated that: (a) despite their apparent familiarity with the items, ESL learners' semantic organizations deviated from the NSs' model; (b) the location and extent of semantic mismatch can be identified at different levels of ESL proficiency; (c) consistent approximation to the target model improved as ESL proficiency improves; (d) the structural stability of an individual's private semantic model is not readily generalizable between sets of lexical items or levels of proficiency; and (el consensus among ESL learners improves as proficiency increases. The findings suggest that a discernible approximative pattern exists in the acquisition of ESL semantics, with the differentiation of certain words acquired before the differentiation of others.

Neurofibromatosis Type 1: Pathology, Clinical Features and Molecular Genetics

Neurofibromatosis type 1 (NF1) or von Recklinghausen neurofibomatosis, is a common heritable neurocutaneous disorder. This disorder appears to affect all races, with a prevalence estimated to be 1 in 3000. Approximately half of all cases of NF1 represent new mutations. The characteristics of NF1, which include cafe-au-lait spots, neurofibromas, Lisch nodules, optic glioma, osseous lesions, macrocephaly, short stature and mental retardation suggest that the genetic lesion affects the proper development of multiple organ systems. Within the past few years, the gene causing NF1 has been identified and the protein encoded by this gene, neurofibromin, has been the subject of detailed investigation. The NF1 gene spans over 350 kb of genomic DNA and encodes a protein product of 2818 amino acids. Neurofibromin is expressed in many different tissues. It is now known that one role of neurofibromin is as a GTPase activating protein (GAP), very likely in the same pathway of signal transduction as ras. Absence of neurofibromin in mice homozygously mutant for the NF1 gene results in profound developmental abnormalities. In mice that are heterozygous for NF1, an accelerated onset of tumor formation is observed. Combined with studies of tumors from NF1 patients showing homozygous deletions in the NF1 gene, these data suggest a role for NF1 as a "tumor suppressor". Evidence suggesting other roles played by neurofibromin, in control of proliferation in some situations and differentiation in others, is gradually bringing the previously hazy picture of this genetic disorder into sharper focus.

Heregulin Stimulates Mitogenesis and Phosphatidylinositol 3-Kinase in Mouse Fibroblasts Transfected with erbB2/neu and erbB3

Heregulin (HRG) is a pluripotent growth factor that can stimulate the growth of some human mammary tumor cells and the differentiation of others. Two members of the epidermal growth factor receptor family of receptor/tyrosine kinases, p180erbB3 and p180erbB4, serve as receptors for the HRG ligand. While HRG appears to be capable of stimulating the autophosphorylation activity of p180erbB4, the co-expression of p185erbB2/neu with p180erbB3 is necessary for the HRG-stimulated tyrosine phosphorylation of both of these receptors. On the basis of the sequences surrounding their putative tyrosine phosphorylation sites, we predict that the different HRG-responsive receptors couple to different intracellular SH2 domain-containing proteins. Hence, the different receptors may mediate different cellular responses to the HRG ligand. In the present study we show that HRG beta 1 is mitogenic for erbB3-transfected DHFR/G8 cells, an NIH3T3 mouse fibroblast derivative that over-expresses p185erbB2/neu. HRG stimulated the incorporation of [3H]thymidine into the DNA of these cells with an EC50 of 70 +/- 7 pM. HRG was not mitogenic for parental DHFR/G8 cells that do not express the ErbB3 protein. Phosphatidylinositol (PI) 3-kinase, an enzyme believed to be important in cellular growth regulation by growth factors and oncogenes, is predicted to couple to tyrosine-phosphorylated ErbB3. We observed that HRG stimulated the association of PI 3-kinase with both p185erbB2/neu and ErbB3 in transfected DHFR/G8 cells, but not in the parental cell line. We conclude that the ErbB3 protein is capable of mediating a proliferative response of fibroblasts to HRG, and that the activation of PI 3-kinase is an integral part of the growth signaling mechanism.

Contrasting Morphological Changes in PC12 Flat Cells Expressing Two Different Forms of Exogenous Oncogenic Ras

Oncogenic ras is known to transform certain cells, whereas it induces terminal differentiation of others, e.g., neuronal differentiation of PC12 cells. MPT1 is a PC12 flat cell variant that extends glial-like processes and exhibits some properties of noncancer cells in culture, e.g., absence of anchorage-independent growth. Expression of oncogenic ras by MPT1 cells failed to result in neuronal differentiation, but such cells exhibited two contrasting morphological changes under certain conditions. First, they retained their extended processes in the presence of dexamethasone, unlike MPT1 cells not expressing oncogenic ras. Second, confluent cultures of ras -expressing MPT1 cells contained foci of transformed-looking cells that were refractile and grew in multiple layers. Thus, ras seemed to induce both a kind of differentiation and transformation of MPT1 cells. MPT1 cells were transfected with a plasmid carrying an oncogenic Harvey ras gene under transcriptional control of the metallothionein promoter. Two subclones of the transfected cells exhibited different responses to the induction of ras and expressed two different forms of the ras gene product. One clone extended dexamethesone-resistant processes and the second clone exhibited a more transformed phenotype. The ras gene product expressed in these two clones differed in migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and in the extent of phosphorylation. These results suggest that ras protein phosphorylation may be important in determining whether a ras-mediated response is differentiation or transformation.

Receptors for the TGF-β Ligand Family

This chapter summarizes the current status of research in the transforming growth factor-β (TGF-β) receptor field. The TGF-β is a group of multi-functional peptide hormones that regulate many aspects of cellular function. TGF-β is identified as a protein that induced normal rat kidney fibroblasts to proliferate in soft agar in the presence of epidermal growth factor (EGF). TGF-β can inhibit the differentiation of certain mesodermal cells, induce the differentiation of others, and inhibit proliferation of cells derived from epithelial, endothlial, neuronal, hematopoietic, lymphoid, and fibroblastic origins. The effects of TGF-β on individual cells, is also important in many biological processes. TGF-β is an important regulator of immune responses, wound healing, cell adhesion, cell-cell recognition, and extracellular matrix deposition. Deregulation of TGF-β function is implicated in the pathological processes of several diseases including arthritis, atheosclerosis, and glomerulonephritis. The cells that lose the ability to respond to TGF-β may exhibit uncontrolled proliferation and become tumorigenic. The TGF-β receptors transduce signals that result in TGF-β-induced gene responses and growth inhibition. The type I, II, and III receptors, are focused in the chapter as they are widely expressed and the most biologically relevant mediators of TGF-β signal transduction.

Differentiation in judgements of self and others: The role of self-consciousness

This study investigated the role of individual differences in Private and Public self-consciousness (SC) on differentiation of self and others in judgements of personality. Ss judged themselves and six other familiar persons on personality constructs derived from a modified Rep Grid procedure. Results showed that the judgements of high scorers on Private SC exhibited greater within-self and self-other differentiation than those of low scorers. There was no significant influence of Private SC on differentiation of other stimulus persons. Public SC had no significant influence on any of the measures of differentiation. The findings were discussed in terms of previous research on self-awareness, the specificity of measures of self-consciousness, and Duval and Wicklund's attentional model of self-awareness.

Metamorphic History of the Blue Ridge Province of Tennessee and North Carolina

A study of metamorphic index minerals in 354 panned alluvial samples has enabled delineation of metamorphic isograds in the Blue Ridge province of Tennessee and North Carolina. A well-defined axis of maximum metamorphic intensity (sillimanite and kyanite grades) is flanked to the southeast and northwest by lower metamorphic zones. Based on radiometric age determinations, metamorphic isograds are interpreted to have formed during the 320 to 375 m.y. event. In northeastern Tennessee and northwestern North Carolina, the isograds form a retrograde sequence in rocks previously metamorphosed during the Granville orogeny (≅1000 m.y.). In the southeastern Blue Ridge, a classical prograde sequence of the Barrovian type has developed in the Late Precambrian Ocoee Series. Mid-Paleozoic granites and pegmatites are essentially confined to the kyanite and sillimanite zones. The granites are interpreted to have formed by anatexis. Pegmatites may have formed by differentiation of granitic magmas in some areas, and by local anatexis or metamorphic differentiation in others. Ultramafic rocks are also confined mainly to the kyanite and sillimanite zones. These rocks were probably implaced during an early stage of regional metamorphism. The relationships between metamorphic isograds and faults indicate that the major period of movement of the Blue Ridge thrust sheet took place after mid-Paleozoic metamorphism.

Congenital testicular deficiency. II. Defective Sertoli cell differentiation in hypogonadism of so-called obscure origin.

WE (1, 2) have recently called attention to certain forms of congenital testicular disease associated with androgen deficiency. In one type (1) there was a complete absence of spermatogonia (germinal aplasia) with preservation of Sertoli and Ley dig cells. In another form (2) a rudimentary cryptorchid testis was entirely devoid of germinal, Sertoli and Leydig cells. It was composed essentially of small solid tubules containing only undifferentiated cells. The purpose of the present communication is to record still another variety of testicular dysgenesis. In this instance Leydig cells are absent, but the Sertoli cells show variable development ranging from complete absence in some tubules to full differentiation in others. At the same time, spermatogonia are preserved, although there is no evidence of germ cell maturation. Tubular fibrosis is conspicuous and could easily obscure the primarily congenital nature of the testicular lesion.