21 research outputs found
Liminal Consumption within Nigerian wedding rituals: The interplay between bridal identity and Liminal Gatekeepers
Get PDFFagbola, L., Raftopoulou, C., & McEachern, M., Liminal consumption within Nigerian wedding rituals: The interplay between bridal identity and liminal gatekeepers, Marketing Theory (Journal Volume Number 23 and Issue Number 3) 437–462. Copyright © [2023] (The Authors). Reprinted by permission of SAGE Publications.This article combines the theoretical lenses of bridal identity and liminal consumption to illustrate the processes of problem-solving, negotiation and reconciliation through which the bride creates her bridal identity, in the Global South context of Nigeria. Most wedding ritual studies typically emphasise the processes of creating and negotiating a successful bridal identity, but few acknowledge the possibilities of failure and its effect upon the liminars. In addition, within liminal consumption studies, the role of liminars’ mentors is often under-theorised. Thus, we contribute to the field by expanding on the concept of ‘liminal gatekeepers’ as the individuals and institutions who control and enforce certain norms associated with the liminal experience. Following an interpretivist approach, the article also advances our understanding of the ways in which the demands of liminal gatekeepers affect the liminars’ experiences and identifies three novel bridal identity outcomes, namely: i) Embedded Bridal Identity; ii) Synthesised Bridal Identity; and iii) Marginalisation. In this way, we advance marketing research around how a liminal consumer identity such as bridal identity is co-constructed between liminars and gatekeepers
The Roles of Telomerase in the Generation of Polyploidy during Neoplastic Cell Growth
Get PDFAbstractPolyploidy contributes to extensive intratumor genomic heterogeneity that characterizes advanced malignancies and is thought to limit the efficiency of current cancer therapies. It has been shown that telomere deprotection in p53-deficient mouse embryonic fibroblasts leads to high rates of polyploidization. We now show that tumor genome evolution through whole-genome duplication occurs in ∼15% of the karyotyped human neoplasms and correlates with disease progression. In a panel of human cancer and transformed cell lines representing the two known types of genomic instability (chromosomal and microsatellite), as well as the two known pathways of telomere maintenance in cancer (telomerase activity and alternative lengthening of telomeres), telomere dysfunction-driven polyploidization occurred independently of the mutational status of p53. Depending on the preexisting context of telomere maintenance, telomerase activity and its major components, human telomerase reverse transcriptase (hTERT) and human telomerase RNA component (hTERC), exert both reverse transcriptase-related (canonical) and noncanonical functions to affect tumor genome evolution through suppression or induction of polyploidization. These new findings provide a more complete mechanistic understanding of cancer progression that may, in the future, lead to novel therapeutic interventions
A Non-Canonical Function of Zebrafish Telomerase Reverse Transcriptase Is Required for Developmental Hematopoiesis
Get PDFAlthough it is clear that telomerase expression is crucial for the maintenance of telomere homeostasis, there is increasing evidence that the TERT protein can have physiological roles that are independent of this central function. To further examine the role of telomerase during vertebrate development, the zebrafish telomerase reverse transcriptase (zTERT) was functionally characterized. Upon zTERT knockdown, zebrafish embryos show reduced telomerase activity and are viable, but develop pancytopenia resulting from aberrant hematopoiesis. The blood cell counts in TERT-depleted zebrafish embryos are markedly decreased and hematopoietic cell differentiation is impaired, whereas other somatic lineages remain morphologically unaffected. Although both primitive and definitive hematopoiesis is disrupted by zTERT knockdown, the telomere lengths are not significantly altered throughout early development. Induced p53 deficiency, as well as overexpression of the anti-apoptotic proteins Bcl-2 and E1B-19K, significantly relieves the decreased blood cells numbers caused by zTERT knockdown, but not the impaired blood cell differentiation. Surprisingly, only the reverse transcriptase motifs of zTERT are crucial, but the telomerase RNA-binding domain of zTERT is not required, for rescuing complete hematopoiesis. This is therefore the first demonstration of a non-canonical catalytic activity of TERT, which is different from “authentic” telomerase activity, is required for during vertebrate hematopoiesis. On the other hand, zTERT deficiency induced a defect in hematopoiesis through a potent and specific effect on the gene expression of key regulators in the absence of telomere dysfunction. These results suggest that TERT non-canonically functions in hematopoietic cell differentiation and survival in vertebrates, independently of its role in telomere homeostasis. The data also provide insights into a non-canonical pathway by which TERT functions to modulate specification of hematopoietic stem/progenitor cells during vertebrate development. (276 words
Abstracts from the 3rd Conference on Aneuploidy and Cancer: Clinical and Experimental Aspects
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Investigation of the role of the protein complex of shelterin in continuous cell proliferation and the appearance of chromosomal instability in neoplasia
No full textThe Alternative Lengthening of Telomeres (ALT-pathway) ischaracterized by continuous cellular growth in absence of telomerase andincreased telomeric DNA recombination(Bryan et al. 1995; Nebatani andIshikawa. 2011; Cesare and Reddel 2010; Muntoni and Reddel 2005).Several telomere interacting factors and proteins participating in DNADamage Responses (DDR) have been implicated in ALT telomeremaintenance(Bryan et al. 1995; Nebatani and Ishikawa. 2011). However,the molecular basis of the ALT pathway still remains elusive(Nebatani andIshikawa. 2011; Cesare and Reddel 2010; Muntoni and Reddel 2005). Thehomologous-recombination-mediated-DDR proteins BRCA1 and BARD1 areknown oncosuppressors involved in inherited predisposition to breast andovarian cancers(Irminger-Finger and Jefford, 2006). The two moleculesheterodimerize and acquire E3 ubiquitin ligase activity, that targetsproteins involved in cell cycle control, chromosome stability and DDR fordegradation(Drost et al. 2011; Shabbeer et al. 2012;Irminger-Finger andJefford, 2006). We show that in human ALT cells, BRCA1/BARD1 formnumerous nuclear foci that frequently co-localize with telomeric repeats,components of shelterin(de Lange, 2005)and the PML protein. Abundanceand telomeric localization of nuclear BRCA1/BARD1 foci correlated withALT activity but not with telomeric DDR. BRCA1/BARD1 showed lowphysical interaction with ALT telomeric repeats, while the amount of TRF2precipitating with BRCA1 was dependent upon proteasome activity but notupon DNA damage. Depletion of BRCA1/BARD1 reduced telomericrecombination, inducing telomere shortening, terminal dysfunction andcellular senescence. These effects were rescued by overexpression ofBRCA1/BARD1, but not by a BRCA1 allele deficient for E3-ligaseactivity(Drost et al. 2011; Shabbeer et al. 2012). Excessive expression ofBRCA1/BARD1 provoked accumulation of poly-ubiquitinated forms of TRF2,and rapid TRF2 degradation. In addition, reconstitution of telomerase activity in ALT cells decreased cytotoxicity and rescued telomeric defectsexerted by proteasome inhibition. We have uncovered a novel, function ofBRCA1/BARD1 E3 ubiquitin ligase, in the regulation of shelterin turnovervia TRF2 that is critical for alternative telomere elongation in neoplasia.Our results provide new insights into inherited predisposition to breast andovarian cancer, proposing in parallel novel oncotherapeutic strategies toefficiently target aggressive ALT-positive neoplasms such as sarcomas and brain tumors.Οι πρωτεΐνες BRCA1 και BARD1 είναι γνωστές για την οκγοκατασταλτική τους δράση και την εμπλοκή τους στην κληρονομική προδιάθεση του καρκίνου του μαστού και των ωοθηκών. Οι δύο πρωτεΐνες ετεροδιμερίζονται, αποκτούν ενεργότητα Ε3 λιγάσης της ουμπικουιτίνης και σηματοδοτούν την αποδόμηση πρωτεϊνών που συμμετέχουν στην ρύθμιση του κυτταρικού κύκλου και τον έλεγχο της ακεραιότητας του γονιδιώματος. Σκοπός της παρούσας μελέτης είναι η διερεύνηση του ρόλου της ενεργότητας Ε3-λιγάσης της ουμπικουιτίνης των BRCA1/BARD1, στην συγκρότηση της Σελτερίνης κατά τον εναλλακτικό μηχανισμό επιμήκυνσης των τελομερών στην ανθρώπινη νεοπλασία
Resilience as governance: building responsible citizenship through the example of Athens' Resilience Strategy
No full textΕθνικό Μετσόβιο Πολυτεχνείο. Μεταπτυχιακή εργασία. Διεπιστημονικό - Διατμηματικό Πρόγραμμα Μεταπτυχιακών Σπουδών (Δ.Π.Μ.Σ.) "Αρχιτεκτονική - Σχεδιασμός του Χώρου : Πολεοδομία - Χωροταξία (Κατ. Β')
Association between Telomere Length and Pediatric Obesity: A Systematic Review
No full textObjective: Telomere length (TL) is a robust marker of biological aging, and increased telomere attrition is noted in adults with obesity. The primary objective of this systematic review was to summarize current knowledge on the effects of childhood obesity in TL. The secondary objective was to assess the effect of weight management interventions in TL. Methods: The following databases were searched: PubMed, Scopus, Web of Science and Heal-link.gr from inception to September 2021. The search was performed using the following combinations of terms: “telomer*” [All Fields] AND (“length” [All Fields] OR “lengths” [All Fields]) AND “obes*” [All Fields] AND (“child*” [All Fields] OR “adolescen*” [All Fields]). Results: A total of 16 original articles were included in this systematic review. Eleven of them were cross-sectional and five were lifestyle interventions. Conclusions: There was a tendency towards a negative association between childhood obesity and TL. Life-style interventions in children have been associated with increased TL peripherally, indicating a possible association of the redistribution of younger cells in the periphery with the favorable effect of these interventions. Further prospective studies with larger sample sizes that employ other markers of cell aging would potentially elucidate this important mechanistic relation
Alternative Lengthening of Telomeres: Recurrent Cytogenetic Aberrations and Chromosome Stability under Extreme Telomere Dysfunction
No full textHuman tumors using the alternative lengthening of telomeres (ALT) exert high rates of telomere dysfunction. Numerical chromosomal aberrations are very frequent, and structural rearrangements are widely scattered among the genome. This challenging context allows the study of telomere dysfunction-driven chromosomal instability in neoplasia (CIN) in a massive scale. We used molecular cytogenetics to achieve detailed karyotyping in 10 human ALT neoplastic cell lines.We identified 518 clonal recombinant chromosomes affected by 649 structural rearrangements. While all human chromosomes were involved in random or clonal, terminal, or pericentromeric rearrangements and were capable to undergo telomere healing at broken ends, a differential recombinatorial propensity of specific genomic regions was noted.We show that ALT cells undergo epigenetic modifications rendering polycentric chromosomes functionally monocentric, and because of increased terminal recombinogenicity, they generate clonal recombinant chromosomes with interstitial telomeric repeats. Losses of chromosomes 13, X, and 22, gains of 2, 3, 5, and 20, and translocation/deletion events involving several common chromosomal fragile sites (CFSs) were recurrent. Long-term reconstitution of telomerase activity in ALT cells reduced significantly the rates of random ongoing telomeric and pericentromeric CIN. However, the contribution of CFS in overall CIN remained unaffected, suggesting that in ALT cells whole-genome replication stress is not suppressed by telomerase activation. Our results provide novel insights into ALT-driven CIN, unveiling in parallel specific genomic sites that may harbor genes critical for ALT cancerous cell growth
Respiratory mechanics in brain-damaged patients
No full textObjective: To assess respiratory mechanics on the 1st and 5th days of
mechanical ventilation in a cohort of brain-damaged patients on positive
end-expiratory pressure (PEEP) of 8 cmH(2)O or zero PEEP (ZEEP). Design
and setting: Physiological study with randomized control trial design in
a multidisciplinary intensive care unit of a university hospital.
Patients and measurements: Twenty-one consecutive mechanically
ventilated patients with severe brain damage and no acute lung injury
were randomly assigned to be ventilated with ZEEP (n=10) or with 8
cmH(2)O of PEEP (n=11). Respiratory mechanics and arterial blood gases
were assessed on days 1 and day 5 of mechanical ventilation. Results: In
the ZEEP group on day 1 static elastance and minimal resistance were
above normal limits (18.9 +/- 3.8 cmH(2)O/1 and 5.6 +/- 2.2 cmH(2)O/1
per second, respectively); on day 5 static elastance and iso-CO2 minimal
resistance values were higher than on day 1 (21.2 +/- 4.1 cmH(2)O/1; 7.0
+/- 1.9 cmH(2)O/1 per second, respectively). In the PEEP group these
parameters did not change significantly. One of the ten patients on ZEEP
developed acute lung injury. On day 5 there was a significant decrease
in PaO2/FIO2 in both groups. Conclusions: On day 1 of mechanical
ventilation patients with brain damage exhibit abnormal respiratory
mechanics. After 5 days of mechanical ventilation on ZEEP static
elastance and minimal resistance increased significantly, perhaps
reflecting “low lung volume” injury. Both could be prevented by
administration of moderate levels of PEEP
A Comprehensive, Multidisciplinary, Personalized, Lifestyle Intervention Program Is Associated with Increased Leukocyte Telomere Length in Children and Adolescents with Overweight and Obesity
No full textLeucocyte telomere length (LTL) is a robust marker of biological aging and is associated with obesity and cardiometabolic risk factors in childhood and adolescence. We investigated the effect of a structured, comprehensive, multidisciplinary, personalized, lifestyle intervention program of healthy diet and physical exercise on LTL in 508 children and adolescents (239 males, 269 females; 282 prepubertal, 226 pubertal), aged 10.14 ± 0.13 years. Participants were classified as obese (n = 267, 52.6%), overweight (n = 174, 34.2%), or of normal BMI (n = 67, 13.2%) according to the International Obesity Task Force (IOTF) cutoff points and were studied prospectively for one year. We demonstrated that LTL increased significantly after 1 year of the lifestyle interventions, irrespective of gender, pubertal status, or body mass index (BMI). Waist circumference was the best negative predictor of LTL at initial assessment. The implementation of the lifestyle interventions also resulted in a significant improvement in clinical (BMI, BMI z-score and waist to height ratio) and body composition indices of obesity, inflammatory markers, hepatic enzymes, glycated hemoglobin (HbA1C), quantitative insulin sensitivity check index (QUICKI), and lipid profile in all participants. These findings indicate that the increased LTL may be associated with a more favorable metabolic profile and decreased morbidity later in life
