797 research outputs found
Introduction: Christos Tsiolkas and Contemporary Australia — The Outsider Artist
No full textChristos Tsiolkas is regularly acknowledged as one of the most important writers working in Australia—indeed, the world—today. However, his proclivity for the public essay (in venues such as The Monthly), as well as his willingness to speak out on important social and political issues (such as refugees and marriage equality), casts him not only as an important writer, but also as a critical public figure in contemporary Australia. This collection of articles takes the range of Tsiolkas’s works (both fiction and non-fiction, as well as their television and cinematic adaptations) as their impetus, using these as a model to explore the significance of Tsiolkas’s intellectual contribution to Australian public life. As such, these articles work across genre, across theories, across national and international borders, and across disciplines in order to make clear Tsiolkas’s contemporary significance. Building on recent book-length studies on the author, including Andrew McCann’s Christos Tsiolkas and the Fiction of Critique: Politics, Obscenity, Celebrity (2015) and my own Christos Tsiolkas: The Utopian Vision (2017), what these articles hold in common is an assertion that Tsiolkas’s fiction and non-fiction always and everywhere serve a political and social purpose. As I have argued elsewhere, Tsiolkas’s writing ultimately suggests the ways in which we can shape a better future for Australia
The early development of the thought of Christos Yannaras
No full textEThOS - Electronic Theses Online ServiceGBUnited Kingdo
Helix pomatia Lectin, an inducer of Drosophila immune response, binds to Hemomucin, a novel surface Mucin
No full textWe describe the isolation and initial characterization of hemomucin, a novel Drosophila surface mucin that is likely to be involved in the induction of antibacterial effector molecules after binding a snail lectin (Helix pomatia A hemagglutinin). Two proteins of 100 and 220 kDa were purified from the membrane fraction of a Drosophila blood cell line using lectin columns. The two proteins are products of the same gene, as demonstrated by peptide sequencing. The corresponding cDNAs code for a product that contains an amino-terminal putative transmembrane domain, a domain related to the plant enzyme strictosidine synthase, and a mucin-like domain in the carboxyl-terminal part of the protein. The gene is expressed throughout development. In adult flies, high expression is found in hemocytes, in specialized regions of the gut, and in the ovary, where the protein is deposited onto the egg surface. In the gut, the mucin co-localizes with the peritrophic membrane. The cytogenetic location of the gene is on the third chromosome in the region 97F-98A.Ulrich Theopold, Christos Samakovlis, Hediye Erdjument-Bromage, Natalie Dillon, Bernt Axelsson, Otto Schmidt, Paul Tempst, and Dan Hultmar
BHLHE40 positively regulates the differentiation of human airway basal cells
No full textAirway basal cells are multipotent stem cell progenitors, which are crucial to maintaining the pseudostratified epithelium. Understanding the molecular mechanisms that regulate their differentiation is essential to unravel how normal and pathological airway epithelial regeneration occurs. With this aim, we performed single-cell RNA sequencing and pseudotime analysis of primary human bronchial epithelial cells (pHBECs) differentiated on air-liquid-interface (ALI) culture, revealing a selective upregulation of the transcription factor BHLHE40 in differentiating intermediate epithelial cells. Using our ALI cultures in combination with lentiviral-based gene transfer, we show that the overexpression of BHLHE40 in human basal cells increased their differentiation into club, goblet, and ciliated cells. Consistent with the overexpression results, the knockdown of BHLHE40 in the ALI cultures reduced basal epithelial cell differentiation. Interestingly, we demonstrate that BHLHE40-mediated loss of basal cell fate through increased differentiation was preceded earlier in the culture by an increase in Notch signaling on day 5. Previous studies have shown that Notch1 signaling activation in basal cells of the murine airway epithelium is associated with the downregulation of basal cell genes and upregulation of luminal differentiation markers. Furthermore, N1ICD overexpression in primary epithelial cells from the human mammary epithelium reduced TP63 expression. Taken together, we propose that BHLHE40-induced loss of basal cells and transition to an intermediate state involves Notch signaling.
To investigate the molecular mechanisms of BHLHE40-induced basal-to-intermediate cell transition and identify its direct transcriptional targets involved in Notch signaling activation driving this transition, we did a 3-step selection by performing a comparative analysis of three datasets: the data from the published BHLHE40 A549 ChIP-sequencing, our differentially expressed transcription factors in the differentiation trajectory of the Submucosal glands (SMGs)-like basal cells toward secretory cells, and our Real-Time qPCR analysis of transduced A549 cells overexpressing GFP or BHLHE40-GFP. We ended up with 8 potential BHLHE40 targets: FOS, HIF1a, MYC, HMGA2, BNC1, ZFP36L1, FOSL1, and SOX9. To confirm that they are transcriptional targets of BHLHE40 in our pHBECs-derived ALI culture, we used CUT&RUN DNA enrichment combined with gene expression analysis of transduced cells overexpressing BHLHE40-GFP from ALI day 14. We show that, although BHLHE40 has bound to HIF1a, BNC1, FOSL1, MYC, HMGA2, and ZFP36L1 genomic regions, it only repressed BNC1 gene expression without affecting the other targets. Consistently, we show that BHLHE40 overexpression reduced the number of BNC1- expressing cells in the basal layer and that BNC1 expression was exclusive to basal cells, further confirming BHLHE40-mediated transcriptional repression of BNC1 in basal cells.
Previous studies showed that BNC1 has a selectively high expression in basal cells of the skin epithelium, which goes down in the Suprabasal and differentiated layers. Consistently, its reduction was associated with the appearance of keratinocytes differentiation marker, suggesting its role in maintaining the undifferentiated basal cell state. In line with our results, we show a correlation between the downregulation of BNC1, the reduction of basal cell markers, and the increase in epithelial cell differentiation following BHLHE40 overexpression on day 14. Taken together, our data indicate that BHLHE40 transcriptionally represses BNC1 expression, which in turn induces the loss of basal cells and their differentiation. We hypothesized that BNC1 is the solely transcriptional target of BHLHE40 that is needed to maintain the undifferentiated basal cell state by negatively regulating Notch signaling in basal cells (e.g., by activating Notch inhibitor). Bulk RNA sequencing of sorted BHLHE40-GFP cells from ALI day 14 identified LFNG, a basal cell-specific Notch inhibitor, as a potential downstream target of BNC1, as its expression decreased following BHLHE40 overexpression. However, it remains unclear whether LFNG or other mediators contribute to the BHLHE40-BNC1-induced transition from basal to intermediate cells.
Additionally, since TP63 expression is regulated by multiple signaling pathways in addition to Notch signaling, further investigation is needed to deepen our understanding of the molecular mechanisms driving BHLHE40-BNC1-mediated loss of TP63+ basal cells, focusing on identifying BNC1 downstream targets, which our findings suggest as a promising starting point for future studies. This will determine how BNC1 maintains TP63 expression in the human airway epithelium and whether Notch signaling is solely involved in BHLHE40-mediated regulation of basal cell differentiation.
Considering our pHBECs-derived ALI culture as a re-generation model, our data suggest a potential of BHLHE40 to enhance the regeneration of the human airway epithelium upon airway injury through increasing differentiation. Also, our single-cell RNA sequencing and pseudotime analysis of differentiating ALI culture suggested the involvement of BHLHE40 in the SMGs-like basal cell differentiation trajectory towards secretory cells. Since basal cells of the SMGs have been shown to contribute to the surface airway epithelium (SAE) regeneration upon injury, we propose a potential role of BHLHE40 in enhancing regeneration via increasing differentiation of basal progenitor cells, both in the SAE and the SMGs. Collectively, we propose that BHLHE40 could serve as a target for therapeutic strategies aimed at enhancing tissue repair and regeneration in the airway epithelium
Christos Tsiolkas: the utopian vision
No full textMore than two decades ago, Christos Tsiolkas’s his first novel Loaded was published and he had achieved a cult following in the short-lived grunge fiction scene of Australian writing. The novel was quickly adapted as the film Head On (1998), directed by Ana Kokkinos, and starring popular young Greek actor, Alex Dimitriades; like the novel, it was well-received by critics, if not by mainstream literary and cinematic culture. For the next few years, Tsiolkas worked on Jump Cuts, an experimental collaborative autobiography, with Sasha Soldatow (1996), as well as a number of theatre productions – Who’s Afraid of the Working Class? (1999, co-written with Andrew Bovell, Melissa Reeves and Patricia Cornelius, and adapted to film as Blessed, also directed by Kokkinos [2009]), Thug (1998, written with Spiro Economopolous), and Elektra AD (1999) – but when The Jesus Man (1999) was published, its violent depiction of depression and suicide received critical attention as offensive and unnecessary. Partly because of the reception of The Jesus Man, and partly because of the density of its subject matter, his next novel, Dead Europe (2005) took six years to write. In the interim, he published a critical study of the film The Devil’s Playground (2002), and several more plays and screenplays: Viewing Blue Poles (2000), Saturn’s Return (2000), Fever (2002, co-written with Bovell, Reeves and Cornelius), Dead Caucasians (2002), Non Parlo di Salo (2005, written with Economopoulous), and The Hit (2006, written with Netta Yashin). Dead Europe was a triumphant return: it won the Age Book of the Year and the Melbourne Best Writing Award in 2006.
But it was the extraordinary critical and commercial success of The Slap (2008) which entirely changed Tsiolkas’s personal and professional circumstances. It was the fourth-highest selling book by an Australian author in 2009, won the ALS Gold Medal, was longlisted for the Man Booker Prize, shortlisted for the Miles Franklin Literary Award, won the Commonwealth Writers’ Prize and was Book of the Year for both the Australian Booksellers Association and the Australian Book Industry Award. The Slap was also adapted as a popular television series for the ABC in 2011, and for NBC in the United States in 2015. For the first time in his career, Tsiolkas was able to dedicate himself to writing full-time, but the attention paid to the novel also meant that Tsiolkas was now a household name – no longer a cult writer, his opinions are now courted and offered in popular and political publications. Barracuda (2013) follows the social realism of The Slap, and sold similarly well, riding on the back of its extraordinary predecessor. Merciless Gods (2014), a collection of short stories, some new, some previously published, is only recently being taken up by popular critics.
Tsiolkas’s work has become increasingly popular and appealing to readers outside of the academy. Tsiolkas’s works adopt a Modernist attitude to the concept of a utopia – a negative politics which simultaneously draws attention to the insufficiency of the present, a pastoral nostalgia for the past, and a longing for the impossible future to come. This first in-depth study of his entire corpus provides an understanding of Tsiolkas’s position in relation to Modernism, thereby drawing out his points about character, setting and politics, thereby helping us to think about what place his ideas about the individual and the community might have in our reading of contemporary Australia and contemporary world literature
Author response
No full textDevelopmental potentials of cells are tightly controlled at multiple levels. The embryonic Drosophila airway tree is roughly subdivided into two types of cells with distinct developmental potentials: a proximally located group of multipotent adult precursor cells (P-fate) and a distally located population of more differentiated cells (D-fate). We show that the GATA-family transcription factor (TF) Grain promotes the P-fate and the POU-homeobox TF Ventral veinless (Vvl/Drifter/U-turned) stimulates the D-fate. Hedgehog and receptor tyrosine kinase (RTK) signaling cooperate with Vvl to drive the D-fate at the expense of the P-fate while negative regulators of either of these signaling pathways ensure P-fate specification. Local concentrations of Decapentaplegic/BMP, Wingless/Wnt, and Hedgehog signals differentially regulate the expression of D-factors and P-factors to transform an equipotent primordial field into a concentric pattern of radially different morphogenetic potentials, which gradually gives rise to the distal-proximal organization of distinct cell types in the mature airway.</p
Author self-citation in orthodontics is associated with author origin and gender.
No full textBACKGROUND
The aims of this bibliometric study were to determine author self-citation trends in high-impact orthodontic literature and to investigate possible association between self-citation and publication characteristics.
METHODS
Six orthodontic journals with the highest impact factor as ranked by 2017 Journal Citation Reports were screened for a full publication year (2018) for original research articles, reviews, and case reports. Eligible articles were scrutinized for article and author characteristics and citation metrics. Univariable and multivariable negative binomial regression was used to examine associations between self-citation incidence and publication characteristics.
RESULTS
Medians for author self-citation rate of the most self-citing authors and self-citations were 3.03% (range 0-50) and 1 (range 0-19), respectively. In the univariable analysis, there was no association between self-citation counts and study type (P = 0.41), article topic (P = 0.61), number of authors (P = 0.62), and rank of authors (P = 0.56). Author origin (P = 0.001), gender (P = 0.001) and journal (P = 0.05) were associated with self-citation counts and in the multivariable analysis only origin and gender remained strong self-citation predictors. Asian authors and females self-cited significantly less often than all other regions and male authors.
CONCLUSIONS
Authors in orthodontics do not self-cite at a frequency that suggests potential citation manipulation. Author origin and gender were the only variables associated with citations counts. More bibliometric research is necessary to draw solid conclusions about author self-citation trends in orthodontic literature
Contemporary Australian masculinities and De Certeau’s concept of la perruqe in Christos Tsiolkas’ novel The Slap (2008)
No full textThis paper will focus on how Christos Tsiolkas the author of The Slap (2008) invites us to view the complex range of private lives of his male characters living in suburban Melbourne through their daily routines, conversations and innermost thoughts. On the surface most appear to be participating in and achieving a certain level of success in their lives. However, this novel reveals when we agitate and dig below the “practices of everyday life” there is often a disquiet simmering away under the facade of family harmony, male bravado and contentment. This paper will argue that as a result of dissatisfaction with the established order of their lives, each man has managed to create another level of meaning for himself, his own form of la perruque (De Certeau 2011: 29),the concept of living proposed by Michel De Certeau. A treatment of the characters in this article draws on, and is used to illustrate the paradigm
Regulation of the Drosophila hypoxia-inducible factor alpha Sima by CRM1-dependent nuclear export
No full textHypoxia-inducible factor alpha (HIF-alpha) proteins are regulated by oxygen levels through several different mechanisms that include protein stability, transcriptional coactivator recruitment, and subcellular localization. It was previously reported that these transcription factors are mainly nuclear in hypoxia and cytoplasmic in normoxia, but so far the molecular basis of this regulation is unclear. We show here that the Drosophila melanogaster HIF-alpha protein Sima shuttles continuously between the nucleus and the cytoplasm. We identified the relevant nuclear localization signal and two functional nuclear export signals (NESs). These NESs are in the Sima basic helix-loop-helix (bHLH) domain and promote CRM1-dependent nuclear export. Site-directed mutagenesis of either NES provoked Sima nuclear retention and increased transcriptional activity, suggesting that nuclear export contributes to Sima regulation. The identified NESs are conserved and probably functional in the bHLH domains of several bHLH-PAS proteins. We propose that rapid nuclear export of Sima regulates the duration of cellular responses to hypoxia.Fil: Romero, Nuria Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Irisarri, Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Roth, Peggy. Stockholms Universitet; SueciaFil: Cauerhff, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Samakovlis, Christos. Stockholms Universitet; SueciaFil: Wappner, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentin
Carcerals and Olympic Masculinities in Christos Tsiolkas’s Barracuda
No full textIn an effort to draw attention to the masculine crisis occurring in the era of globalisation, this paper elaborates on Australian author Christos Tsiolkas’s novel Barracuda and the central character’s self-discipline and struggle into reaching Olympic achievement. The course of his rise as a potential Olympic athlete but also his fall and crisis within an institutional framework of disciplines, which often symbolically turn into nightmarish prisons, resonate with Michel Foucault’s 1975 work Discipline and Punish. The latter’s ideas about discipline and the “carceral” will help interpret Tsiolkas’s novel and further understand how the Olympics work as a mechanism of discipline and compliance towards a kind of hegemonic masculinity and its inevitable crisis
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