Ablation of CNTN2+Pyramidal Neurons During Development Results in Defects in Neocortical Size and Axonal Tract Formation

Corticothalamic axons express Contactin-2 (CNTN2/TAG-1), a neuronal recognition molecule of the immunoglobulin superfamily involved in neurogenesis, neurite outgrowth, and fasciculation. TAG-1, which is expressed transiently by cortical pyramidal neurons during embryonic development, has been shown to be fundamental for axonal recognition, cellular migration, and neuronal proliferation in the developing cortex. Although Tag-1(-/-) mice do not exhibit any obvious defects in the corticofugal system, the role of TAG-1+ neurons during the development of the cortex remains elusive. We have generated a mouse model expressing EGFP under the Tag-1 promoter and encompassing the coding sequence of Diptheria Toxin subunit A (DTA) under quiescence with no effect on the expression of endogenous Tag-1. We show that while the line recapitulates the expression pattern of the molecule, it highlights an extended expression in the forebrain, including multiple axonal tracts and neuronal populations, both spatially and temporally. Crossing these mice to the Emx1-Cre strain, we ablated the vast majority of TAG-1+ cortical neurons. Among the observed defects were a significantly smaller cortex, a reduction of corticothalamic axons as well as callosal and commissural defects. Such defects are common in neurodevelopmental disorders, thus this mouse could serve as a useful model to study physiological and pathophysiological cortical development

'Islamic' consumers, markets, and marketing : a critique of El-Bassiouny's (2014) "The one-billion-plus marginalization"

In her article entitled 'The one-billion-plus marginalization: Toward a scholarly understanding of Islamic consumers', El-Bassiouny (2014) attempts to provide 'a comprehensive conceptualization for Islamic marketing and its foundational principles within the context of the Islamic faith' (p. 48). The present essay critiques some of the key assumptions that underpin El-Bassiouny’s discussion and her subsequent propositions for “future testing”, which are meant to offer an 'enlightened understanding of Islamic consumers' and 'benefit academics, practitioners, and policy makers' (pp. 42-43). This critical account argues: (1) apolitical and ahistorical analyses of markets and marketing phenomena in relation to Moslem geographies will only replicate imaginary juxtapositions between the West and Islam; (2) exceptionalist depictions of Moslem consumers can exacerbate inter- and/or intra-cultural misunderstandings; (3) theological and ethnocentric definitions of Islam and the oversimplification of Islamicness are less likely to help advance marketing theory, practice, and education in a global era

Digital imaging of tempratures in the Island of Chios (areas of Thimiana - Nenita)

105 σ.Αντικείμενο της έρευνας στο πλαίσιο της διπλωματικής εργασίας, είναι η μελέτη των θερμικών ανωμαλιών που παρουσιάζονται στο νησί της Χίου. Με την αύξηση της ενεργειακής ζήτησης που παρουσιάζεται παγκόσμια και τη στροφή που επιχειρείται προς ηπιότερες μορφές ενέργειας, η γεωθερμία αναμένεται να παίξει πρωταγωνιστικό ρόλο με τις πολλαπλές εφαρμογές της. Αρχικά γίνεται εισαγωγή στα πετρώματα και την τεκτονική του νησιού προκειμένου να είναι σαφές το υπόβαθρο το οποίο μελετάται. Στη συνέχεια γίνεται αναφορά στον τρόπο με τον οποίο δημιουργείται η θερμική ενέργεια στο εσωτερικό της γής, η δομή ενός γεωθερμικού συστήματος και οι τρόποι λειτουργίας του. Σημαντική ενότητα αποτελεί η αναφορά στο αντικείμενο της οπτικοποίησης, η οποία εστιάζει στην απεικόνιση μοντέλων τριών διαστάσεων. Ακολουθεί η υλοποίηση, με την απόδοση ψηφιακού μοντέλου του υπεδάφους σε διαφορετικά βάθη, από γωλογικά δεδομένα τα οποία προέρχονται από το Ι.Γ.Μ.Ε. Η δημιουργία των ψηφιακών μοντέλων γίνεται με την χρήση του λογισμικού πακέτου Surfer, μέσω των μεθόδων Kriging και Moving Average, βάσει των οποίων προέκυψαν χάρτες και εποπτικά σχέδια τα οποία σχολιάζονται και αναλύνονται στο τέλος της εργασίας.This thesis focuses on the study of thermal anomalies observed in Chios island. Geothermics is expected to play a key role in the near future due to its multiple applications, as the increasing demand for energy is turning towards renewable sources. The thesis introduction concertrates on the island's rocks ana\d tectonics with the aim to provide an explicit picture of the underground examined. The generation of thermal energy in earth's interior, the structure of a geothermal system and thw ways of this system's establishment are further elements of consideration in this paper. Another important point is the visualization, which focuses in the three dimensional imaging of models. The implementation with the digital imaging of the underground model in several depths follows, based on geological data from the Institute of Geology and Mineral Exploration. Digital models are produced eith the use of Surfer software through the "Kriging" and "Moving Average" methods. The maps and charts resulting from these two mapping methods are commented at the end of the thesisΑντώνιος Δ. Μαριάτο

The proinflammatory phenotype of senescent cells: The p53-mediated ICAM-1 expression

Senescent cells are characterized by the activation of the tumor suppressor protein p53 and consequently their inability to proliferate. However, their phenotype is not restricted to the exhaustion of their replicative potential, as they also exhibit a proinflammatory phenotype, which could possibly contribute to the aging process. Intercellular adhesion molecule-1 (ICAM-1) is one of the molecules involved in inflammatory response that is overexpressed in senescent cells and aged tissues. Although the role of the nuclear factor-kappaB (NF-κB) signaling cascade is crucial in ICAM-1 activation, we have shown that p53 directly activates the expression of ICAM-1 in an NF-κB- independent manner. This may link p53 to ICAM-1 function and consequently to the aging process and to various age-related pathologies

Absence of mutations in the functional domains of the human MDM2 oncogene in non-small cell lung carcinomas

Increasing evidence suggests that MDM2 oncoprotein participates in a complex array of interactions with a plethora of molecules, including cell-cycle and transcriptional regulators, as well as determinants of the cell differentiation and senescence. The tumorigenic potential of MDM2 is mainly determined by overexpression due to gene amplification, mRNA overexpression and possibly translational enhancement. Although artificially created mutations have been demonstrated to abolish normal MDM2 function, there is little information concerning its mutational status in human tissues. In this study, we screened all the functional domains of MDM2 for mutations in a series of 58 non-small cell lung carcinomas (NSCLCs), but none was found. Therefore, we report that MDM2 mutations are an extremely rare phenomenon of non-small cell lung carcinogenesis. A putative explanation for this observation may be the labyrinth of interactions necessary for cell viability, in which MDM2 takes part, a finding also supported by its stringent interspecies conservation. Copyright (C) 2000 Elsevier Science B.V

p53 activates ICAM-1 (CD54) expression in an NF-κB-independent manner

Intercellular adhesion molecule-1 (ICAM-1) is a crucial receptor in the cell-cell interaction, a process central to the reaction to all forms of injury. Its expression is upregulated in response to a variety of inflammatory/immune mediators, including cellular stresses. The NF-κB signalling pathway is known to be important for activation of ICAM-1 transcription. Here we demonstrate that ICAM-1 induction represents a new cellular response to p53 activation and that NF-κB inhibition does not prevent the effect of p53 on ICAM-1 expression after DNA damage. Induction of ICAM-1 is abolished after treatment with the specific p53 inhibitor pifithrin-α and is abrogated in p53-deficient cell lines. Furthermore, we map two functional p53-responsive elements to the introns of the ICAM-1 gene, and show that they confer inducibility to p53 in a fashion similar to other p53 target genes. These results support an NF-κB-independent role for p53 in ICAM-1 regulation that may link p53 to ICAM-1 function in various physiological and pathological settings

p53 activates ICAM-1 (CD54) expression in an NF-kappaB-independent manner

Intercellular adhesion molecule-1 (ICAM-1) is a crucial receptor in the cell-cell interaction, a process central to the reaction to all forms of injury. Its expression is upregulated in response to a variety of inflammatory/immune mediators, including cellular stresses. The NF-kappaB signalling pathway is known to be important for activation of ICAM-1 transcription. Here we demonstrate that ICAM-1 induction represents a new cellular response to p53 activation and that NF-kappaB inhibition does not prevent the effect of p53 on ICAM-1 expression after DNA damage. Induction of ICAM-1 is abolished after treatment with the specific p53 inhibitor pifithrin-alpha and is abrogated in p53-deficient cell lines. Furthermore, we map two functional p53- responsive elements to the introns of the ICAM-1 gene, and show that they confer inducibility to p53 in a fashion similar to other p53 target genes. These results support an NF-kappaB-independent role for p53 in ICAM-1 regulation that may link p53 to ICAM-1 function in various physiological and pathological settings

Transcription factor E2F-1 acts as a growth-promoting factor and is associated with adverse prognosis in non-small cell lung carcinomas

Numerous upstream stimulatory and inhibitory signals converge to the pRb/E2F pathway, which governs cell-cycle progression, but the information concerning alterations of E2F-1 in primary malignancies is very limited. Several in vitro studies report that E2F-1 can act either as an oncoprotein or as a tumour suppressor protein. In view of this dichotomy in its functions and its critical role in cell cycle control, this study examined the following four aspects of E2F-1 in a panel of 87 non-small cell lung carcinomas (NSCLCs), previously analysed for defects in the pRb-p53-MDM2 network: firstly, the status of E2F-1 at the protein, mRNA and DNA levels; secondly, its relationship with the kinetic parameters and genomic instability of the tumours; thirdly, its association with the status of its transcriptional co-activator CBP, downstream target PCNA and main cell cycle regulatory and E2F-1-interacting molecules pRb, p53 and MDM2; and fourthly, its impact on clinical outcome. The protein levels of E2F-1 and its co-activator CBP were significantly higher in the tumour area than in the corresponding normal epithelium (p < 0.001). E2F-1 overexpression was associated with increased E2F-1 mRNA levels in 82% of the cases examined. The latter finding, along with the low frequency of E2F-1 gene amplification observed (9%), suggests that the main mechanism of E2F-1 protein overexpression in NSCLCs is deregulation at the transcriptional level. Mutational analysis revealed only one sample with a somatic mutation at codon 371 (Glu –> Asp) and one carrying a polymorphism at codon 393 (Gly –> Ser). Carcinomas with increased E2F-1 positivity demonstrated a significant increase in their growth indexes (r = 0.402, p = 0.001) and were associated with adverse prognosis (P = 0.033 by Cox regression analysis). The main determinant of the positive association with growth was the parallel increase between E2F-1 staining and proliferation (r = 0.746, p < 0.001), whereas apoptosis was not influenced by the status of E2F-1. Moreover, correlation with the status of the pRb-p53-MDM2 network showed that the cases with aberrant pRb expression displayed significantly higher E2F-1 indexes (p = 0.033), while a similar association was noticed in the group of carcinomas with deregulation of the p53-MDM2 feedback loop. In conclusion, the results suggest that E2F-1 overexpression may contribute to the development of NSCLCs by promoting proliferation and provide evidence that this role is further enhanced in a genetic background with deregulated pRb-p53-MDM2 circuitry. Copyright (C) 2002 John Wiley & Sons, Ltd

Low levels of p27 in association with deregulated p53-pRb protein status enhance tumor proliferation and chromosomal instability in non-small cell lung carcinomas

Background: Down-regulation or overexpression of the cyclin-dependent kinase inhibitor p27 have been observed in a range of malignancies, including lung cancer. To further elucidate the role of the molecule in tumor growth regulation, we evaluated p27 expression in a series of non-small cell lung carcinomas (NSCLCs), and examined its relation with histology, kinetic parameters, ploidy, and overall survival. We extended our investigation into the association of p27 levels with the presence of Ki-ras mutations, as well as with the expression status of p53 and pRb in tumor cells. Material and Methods: p27, p53, and pRb status were immunohistochemically evaluated in a total of 69 NSCLCs. In situ assays were employed to assess the kinetic parameters (Ki-67 immunohistochemistry for proliferation index, Tdt-mediated dUTP nick end labeling assay for apoptotic index). The ploidy status of the tumors was assessed after staining nuclei with the Feulgen procedure, and the presence of Ki-ras mutations was examined by restriction fragment length polymorphisms. All possible associations were assessed with a series of statistical methods. Results: Immunoreactivity for p27 was observed in the entire series of specimens, with the mean percentage of positive cells being 33%. Adenocarcinomas (AdCs) exhibited higher p27 levels compared to squamous cell carcinomas (SqCCs) (p < 0.01). An inverse correlation was established between p27 expression and proliferation index (PI) (r = -0.834, p < 0.01) but not with apoptotic index (AI), whereas aneuploid tumors were characterized by lower p27 levels than diploid ones (p < 0.01). No difference in p27 immunostaining was observed with regard to the presence of Ki-ras mutations, whereas aberrant p53 and/or pRb expression patterns were associated with p27 underexpression (p < 0.01 for p53 status, p < 0.05 regarding pRb levels, and p < 0.01 for a combined deregulation of both proteins). Two or more alterations in the p27/p53/pRb protein network (i.e., p27 levels lower than the estimated mean value, overexpressed p53, and/or aberrant pRb) were associated with increased PI and aneuploidy (p < 0.001 and p < 0.01, respectively). A powerful trend was found between p27 expression and overall survival (p = 0.066). Conclusions: Our findings confirm the heterogeneity between AdCs and SqCCs, and are suggestive of an increased proliferative activity in NSCLCs underexpressing p27. Furthermore, our analysis supports the concept of p27 forming a functionally compact network with p53 and pRb, which is actively involved in the regulation of cellular proliferation and chromosomal stability

Expression of p16(INK4A) and alterations of the 9p21-23 chromosome region in non-small-cell lung carcinomas: Relationship with tumor growth parameters and ploidy status

The 9p21-23 chromosome region harbors a number of known and putative tumor-suppressor genes (TSGs). The best characterized gene in this area is p16(INK4A) (CDKN2A). Alterations of its product have been observed in various malignancies, including non-small-cell lung carcinomas (NSCLCs). We earlier investigated the mechanisms underlying p16(INK4A) inactivation. In the present study, we examined, in a series of 87 NSCLCs, its relationship with the kinetic parameters [proliferation index (PI) and apoptotic index (AI)] and the ploidy status of the tumors. In addition, we extended our previous LOH analysis of the 9p21-23 region by examining flanking areas of p16(INK4A). Aberrant p16 expression was observed in 41.4% of the carcinomas. A significant association was found with increased PI (p = 0.037), but not with apoptosis. Aneuploid tumors were more frequently correlated with abnormal p16 staining (p = 0.05), A high frequency of allelic imbalance (AIm) was noticed at: the D9S161 (51.3%) and D9S157 (64.5%) loci, which lie approximately 4cM centromeric and 7cM telomeric, respectively, to CDKN2A, Abnormal p16(INK4A) expression was strongly correlated with Aim at D9S161 (p = 0.004). Allelic losses at D9S157 occurred more frequently in early stages (p = 0.018) and were significantly associated with deletions at D9S161 (p = 0.035). We conclude that, in a sub-set of NSCLCs, (i) abnormal p16 expression contributes to tumor growth mainly by increasing the proliferative activity in the initial stages of carcinogenesis; (ii) the association with aneuploidy merely reflects the impact of aberrant p16 on proliferative activity; and (iii) other putative TSGs possibly reside within the 9p21-23 region that possibly co-operate in certain cases with CDKN2A in the development of NSCLCs. (C) 2000 Wiley-Liss, Inc