Néstor-Guillermo Progeria Syndrome: a biochemical insight into Barrier-to-Autointegration Factor 1, alanine 12 threonine mutation

Background Premature aging syndromes recapitulate many aspects of natural aging and provide an insight into this phenomenon at a molecular and cellular level. The progeria syndromes appear to cause rapid aging through disruption of normal nuclear structure. Recently, a coding mutation (c.34G > A [p.A12T]) in the Barrier to Autointegration Factor 1 (BANF1) gene was identified as the genetic basis of Néstor-Guillermo Progeria syndrome (NGPS). This mutation was described to cause instability in the BANF1 protein, causing a disruption of the nuclear envelope structure. Results Here we demonstrate that the BANF1 A12T protein is indeed correctly folded, stable and that the observed phenotype, is likely due to the disruption of the DNA binding surface of the A12T mutant. We demonstrate, using biochemical assays, that the BANF1 A12T protein is impaired in its ability to bind DNA while its interaction with nuclear envelope proteins is unperturbed. Consistent with this, we demonstrate that ectopic expression of the mutant protein induces the NGPS cellular phenotype, while the protein localizes normally to the nuclear envelope. Conclusions Our study clarifies the role of the A12T mutation in NGPS patients, which will be of importance for understanding the development of the disease.

The Venice Architecture Biennale avoids lessons from the past

This article reviews the 14th Architectural Biennale in Venice.

Book Review: "Metal Rules the Globe: Heavy Metal Music around the World". Durham, NC: Duke University Press.

It is rare to find an anthology that realizes the possibilities of the form. We tend to regard our edited collections as lesser siblings, and forget their special value. But at times, a subject seems to require an edited collection much more than it does a classic monograph. So it is with the subject showcased here, which concerns the global circulation, performance and consumption of heavy metal. This is a relatively new and emerging body of work, hitherto scattered disparately in the broader popular music studies, but quickly gaining status as a “studies” with the establishment of a global conference, a journal, and publication of this anthology, all in recent years. Metal Rules the Globe took the editors’ a decade to compile. That they have thought deeply about how they want the collection to speak shows through in the book’s thoughtful arrangement and design, and in the way in which they draw on the contributions herein to develop for the field a research agenda that will take it forward...

Students’ perceptions of their own victimization: A youth voice perspective

This article investigates the perceptions of 156 students who were victims of both traditional and cyberbullying (117 female, 45 male), ages 10 to 17 years, as to which form of bullying was more hurtful. Overall, students perceived traditional victimization to be more hurtful than cyber victimization. Reasons identified in the data to explain the different perceptions of victims were categorized and found to relate to: the bully, the bystanders, the bullying incidents, the emotional impact on the victim, and the victim’s ability to respond. The perceptions of these students challenge a number of suppositions presented in the literature that attempt to explain why cyberbullying is associated with more negative outcomes than traditional bullying. The implications for antibullying programs to address these issues are discussed.

A rare view: Barbara Hatley’s new book documents a career-long study of, and passion for performance in Central Java

Javanese Performances on an Indonesian Stage: Contesting Culture, Embracing Change, is Barbara Hatley’s first book about the performing arts in Indonesia, a topic that piqued her interest while undergoing a masters program at Yale University in the late 1960s. In this sense, it is a landmark study, for Hatley has since become very well known in Indonesianist circles, especially among those with an interest in matters of culture, popular and elite. Until recently, her writings on Indonesian performing arts have only been available in the form of journal articles and book chapters...

Sustainability

One normally understands sustainability as a term connoting the capacity of an Initiative to raise or seek funds that enable It to continue. However, as we shall show in this chapter, in the initiatives with which we work, the question of how to sustain Is a multifaceted one. It is more, that is, than simply a question of how the initiatives can continue to be 11nanclally sustainable. There Is a need, rather, to 11nd ways to marry social (including organisational), technical and financial sustalnablllty...

Cosmopatriatism in Indonesian pop music imagings

In this article, cosmopatriotism is seen to describe an effect of transnational capitalism’s need to “settle down” in particular localities. The self-imaging of female singer Krisdayanti and punk band Superman is Dead serve as agentive forces in the working out of novel, post-New Order modernities. The body, in particular, is an important site to inscribe a sense of authenticity and social mobility, as well as to work out a sense of post-Suharto Indonesian-ness.

Reggae borderzones, reggae graveyards: Bob Marley fandom in Bali

The road from Bali’s international airport to the island’s most renowned tourist area, Kuta Beach, leads past a number of establishments claiming affiliation to reggae music and Rastafarianism in large, appropriately coloured billboards. A sign outside a tee shirt shop bears the words RASTA MANIA within a green, yellow and red border, and a stick figure caricaturing negritude, the logo of this clothing label. In the window display hangs a tee shirt, and upon it Bob Marley’s wizened face. His lips pinch a cone-shaped spliff, and he squints behind a veil of airbrushed smoke. A leanto sign on the sidewalk outside Apache Bar announce REGGAE BANDS NIGHTLY. This barn of coconut wood and thatch nestles behind Wendy’s Ice Cream Parlour and Chi Chi’s Mexican Bar. Its timber walls emulate a rustic, spaghetti Western aesthetic and are adorned with portraits of native Americans. In addition to the reggae bands, nightly, Apache bar unites young Japanese women with local ‘guides’.2

Book review: "Hip Hop Japan: Rap and the Paths of Cultural Globalization’ by Ian Condry, Durham: Duke University Press

Had it been published a decade earlier, Hip-hop Japan might have been cited as a good example of the kind of multi-sited ethnography George Marcus (1998) proposes. Hip-hop Japan is a critical study of cultural globalisation. It presents as much theoretical interpretation, discussions of Japanese popular culture in general, and reviews of formulations of the Japanese self by Japanese scholars, as it does of Japanese hip-hop per se. In fact, the latter is relatively thinly described, as Condry’s project is to demonstrate how Japanese hip-hop’s particularities are made up from a mix of US hip-hop, Japanese modes of fandom, contestatory uses of the Japanese language and the specific logics of the Japanese popular music recording industry. The book journeys into these worlds as much as it does into the world of Japanese hip-hop.

Book review: Politics and the media in twenty-first century Indonesia: Decade of democracy

This is the third (but first edited) volume in Sen and Hill’s corpus on Indonesian media. An anthology built from contributions to a 2006 workshop, it is necessarily more fragmented than the editors’ earlier monographs. While this fragmented character helps to evoke a fractured context, it also makes for unwieldiness...

Dietary intake in Australian children aged 4–24 months: Consumption of meat and meat alternatives

Meat/meat alternatives (M/MA) are key sources of Fe, Zn and protein, but intake tends to be low in young children. Australian recommendations state that Fe-rich foods, including M/MA, should be the first complementary foods offered to infants. The present paper reports M/MA consumption of Australian infants and toddlers, compares intake with guidelines, and suggests strategies to enhance adherence to those guidelines. Mother–infant dyads recruited as part of the NOURISH and South Australian Infants Dietary Intake studies provided 3 d of intake data at three time points: Time 1 (T1) (n 482, mean age 5·5 (SD 1·1) months), Time 2 (T2) (n 600, mean age 14·0 (SD 1·2) months) and Time 3 (T3) (n 533, mean age 24 (SD 0·7) months). Of 170 infants consuming solids and aged greater than 6 months at T1, 50 (29 %) consumed beef, lamb, veal (BLV) or pork on at least one of 3 d. Commercial infant foods containing BLV or poultry were the most common form of M/MA consumed at T1, whilst by T2 BLV mixed dishes (including pasta bolognaise) became more popular and remained so at T3. The processed M/MA increased in popularity over time, led by pork (including ham). The present study shows that M/MA are not being eaten by Australian infants or toddlers regularly enough; or in adequate quantities to meet recommendations; and that the form in which these foods are eaten can lead to smaller M/MA serve sizes and greater Na intake. Parents should be encouraged to offer M/MA in a recognisable form, as one of the first complementary foods, in order to increase acceptance at a later age.

Refining prognosis and identifying targetable pathways for high-risk endometrial cancer; a TransPORTEC initiative

This study aimed to investigate whether molecular analysis can be used to refine risk assessment, direct adjuvant therapy, and identify actionable alterations in high-risk endometrial cancer. TransPORTEC, an international consortium related to the PORTEC3 trial, was established for translational research in high-risk endometrial cancer. In this explorative study, routine molecular analyses were used to detect prognostic subgroups: p53 immunohistochemistry, microsatellite instability and POLE proofreading mutation. Furthermore, DNA was analyzed for hotspot mutations in 13 additional genes (BRAF, CDKNA2, CTNNB1, FBXW7, FGFR2, FGFR3, FOXL2, HRAS, KRAS, NRAS, PIK3CA, PPP2R1A, and PTEN) and protein expression of ER, PR, PTEN, and ARID1a was analyzed. Rates of distant metastasis, recurrence-free, and overall survival were calculated using the Kaplan-Meier method and log-rank test. In total, samples of 116 high-risk endometrial cancer patients were included: 86 endometrioid; 12 serous; and 18 clear cell. For endometrioid, serous, and clear cell cancers, 5-year recurrence-free survival rates were 68%, 27%, and 50% (P=0.014) and distant metastasis rates 23%, 64%, and 50% (P=0.001), respectively. Four prognostic subgroups were identified: (1) a group of p53-mutant tumors; (2) microsatellite instable tumors; (3) POLE proofreading-mutant tumors; and (4) a group with no specific molecular profile (NSMP). In group 3 (POLE-mutant; n=14) and group 2 (microsatellite instable; n=19) patients, no distant metastasis occurred, compared with 50% distant metastasis rate in group 1 (p53-mutant; n=36) and 39% in group 4 (NSMP; P<0.001). Five-year recurrence-free survival was 93% and 95% for group 3 (POLE-mutant) and group 2 (microsatellite instable) vs 42% (group 1, p53-mutant) and 52% (group 4, NSMP; P<0.001). Targetable FBXW7 and FGFR2 mutations (6%), alterations in the PI3K-AKT pathway (60%) and hormone receptor positivity (45%) were frequently found. In conclusion, molecular analysis of high-risk endometrial cancer identifies four distinct prognostic subgroups, with potential therapeutic implications. High frequencies of targetable alterations were identified and may serve as targets for individualized treatment