특 집 논 문 : 도시의 시대와 그 불만

브랜던글리슨 ( Brendan Gleeson ) 서울시립대학교 도시인문학연구소 2015 도시인문학연구 Vol.7 No.2

바야흐로 도시의 시대이다. 근대화 과정의 핵심에 있던 도시화 계획은 놀라울 정도의 발전을 거두었다. 그러나 이러한 발전에도 불구하고 도시의 시대에 인류의 미래에는 어두운 그늘이 드리워져 있다. 그 근거는 어디에서 찾을 수 있을 것인가? 환경이 파괴되고 경제가 몰락하는 소리가 도시의 시대 너머로 들리고 있다. 지젝이 말한 ‘묵시록의 기수’가 위험에 처한 근대성에 대해 경고하고 있지만 주의를 기울이는 이들은 많지 않다. 정치 이론가 한나 아렌트는 가장 심각한 위기의 순간에도 갱생을 꿈꿀 수 있는 인간의 능력에 대한 신념을 지니고 있었다. 아렌트는 인간의 ‘탄생성’, 즉 언제나 새로운 발전의 가능성을 열어놓는 죽음과 다시 태어남의 끊임없는 순환에서 희망을 보았다. 아렌트가 맞는다면, 우리는 죽어가는 산업적 근대성이 곧 새로이 태어나야만 할 위급한 시기를 앞에 두고 있다. 기후 변화의 위협 앞에 과학자들은 ‘운명의 시계’를 자정 2분전까지 당겨놓았다. 영국 과학자 제임스 러브록이 예견했던 끔찍한 ‘후세’는 이미 도래해 있다. 아렌트의 탄생성은 정치적 질서 대신 전지구적 자본주의가 지배하고 있는 불모의 질서 안에 존재하지 않는 것처럼 보인다. 신자유주의의 ‘어두운 탄생성’, 긴축 정부와 반과학은 아렌트도 예상하지 못했던 인류의 죽음 충동을 드러내는 듯하다. 이러한 상황에서 조금이라도 낙관주의를 꿈꿀 수 있을까? 오직 파괴의 확실성을 끌어안는 것만이 미래를 받아들이는 유일한 길일 것이다. 그렇다면, 현재의 폐허 뒤에는 무엇이 놓여 있는가? 이는 작금의 힘겨운 변화 과정에서 우리가 무엇을 배울 수 있는지, 그리고 이 배운 바를 인간의 재건을 위해 어떻게 써야 할지에 분명 달려 있다. 필자는 이것이 근대성의 이상과 가능성을 부정하는 것이 아니라 새롭게 함을 의미한다고 주장한다. 우리에게 근대적 이상의 중심에 놓여 있는 ‘좋은 도시’가 무엇인지 기술할 수 있는 용기가, 더 중요하게는 상상력이 있는가? 이것은 산업적 근대성이 성취하지 못한 ‘도시의 공기가 우리를 자유롭게 한다’는 오래된 도시의 약속을 재인식하는 일일 것이다. 나는 미래 세계에 도시의 공기가 우리를 자유롭게 할 수 있지만 오직 ‘성장 이후’의 세계에서만 가능함을 주장한다. 현재의 생태학적 (그리고 인간의) 위기에서 배울 수 있는 교훈은 성장 중심의 경제는 자연적 필요와 결코 공존할 수 없다는것이다. 아렌트가 근대성의 근본적인 원리라고 생각했던 의구심의 중요성을 복권시켜야만 한다. 제멋대로의 테크노크라시적(的)인 지식과 권력을 생산한 근대성은 그 이름의 진정한 의미에서의 근대성이 아니었다. 우리가 진정한 근대인이 될 수 있는 기회가 다가오는 세계에 열려 있다. (국문초록 번역: 정희원, 서울시립대학교 도시인문학연구소 HK교수) An urban age has been declared and celebrated by global institutions and in expert commentary. There is triumph in the air. To be sure, the urbanisation project that has been central to modernisation has reached new level of species’ significance. And yet, despite the enthusiasm of experts, the new urban ascendancy also marks a dangerous unravelling of human prospect. But where is this acknowledged? The testimonies of environmental and economic collapse struggle to be heard above the chorusing of the urban age. ‘The Horsemen of the Apocalypse’(Slavoj zizek) are the unheeded town criers of an endangered modernity. The political theorist Hannah Arendt had faith in the human capacity for renewal,even in the face of the gravest epochal dangers. For her, hope lay in the fact of human ‘natality’, the endless cycle of death and rebirth that always opens new possibilities for flourishing. If this is true, we await the rebirth of a dying industrial modernity with great urgency. Acknowledging the immense unchecked threat of climate change, science has recently reset the ‘Doomsday Clock’, two minutes closer to midnight.1) The awful ‘next world’ foreseen by British scientist James Lovelock is already upon us. Arendt’s natality seems absent in the arid post-political order of global capitalism. The ‘dark natalities’ of neo-liberalism, austerity governance and anti-science suggest a species death wish that even Arendt did not anticipate. What are the grounds for any optimism at all? Perhaps only by embracing the certainty of destruction can a future be entertained. Even so, what lies beyond the ruins of the present? It surely depends upon what we learn from the current terrible transition and how we use this knowledge in quest for human reconstruction. I argue that this means renewing not rejecting the ideals and possibilities of modernity. Do we have the courage and, more importantly, the imagination to describe the ‘good city’ which surely lay at the heart of the modern ideal? This would recognise the old urban promise-stadt luft macht frei (‘city air makes us free’)- that industrial modernity failed to deliver. I argue that city air can make us free again in the next world but only in a ‘post-growth’ world. One lesson to be learned from the present ecological (and human) crisis is that an economy hard wired to growth can never be made compatible with natural necessity. We must also reinstate the importance of doubt, which Arendt recognised as a fundamental postulate of modernity. Modernities which produced unrestrained technocratic knowledge and power were not modernities in the true sense of the name. In the next world we have the chance to be true moderns.

Off-Target Effect of doublecortin Family shRNA on Neuronal Migration Associated with Endogenous MicroRNA Dysregulation

Baek, S.,Kerjan, G.,Bielas, Stephanie L.,Lee, J.,Fenstermaker, Ali G.,Novarino, G.,Gleeson, Joseph G. Cell Press 2014 Neuron Vol.82 No.6

Acute gene inactivation using short hairpin RNA (shRNA, knockdown) in developing brain is a powerful technique to study genetic function; however, discrepancies between knockdown and knockout murine phenotypes have left unanswered questions. For example, doublecortin (Dcx) knockdown but not knockout shows a neocortical neuronal migration phenotype. Here we report that in utero electroporation of shRNA, but not siRNA or miRNA, to Dcx demonstrates a migration phenotype in Dcx knockouts akin to the effect in wild-type mice, suggesting shRNA-mediated off-target toxicity. This effect was not limited to Dcx, as it was observed in Dclk1 knockouts, as well as with a fraction of scrambled shRNAs, suggesting a sequence-dependent but not sequence-specific effect. Profiling RNAs from electroporated cells showed a defect in endogenous let7 miRNA levels, and disruption of let7 or Dicer recapitulated the migration defect. The results suggest that shRNA-mediated knockdown can produce untoward migration effects by altering endogenous miRNA pathways.

CCDC41 is required for ciliary vesicle docking to the mother centriole

Joo, Kwangsic,Kim, Chang Gun,Lee, Mi-Sun,Moon, Hyun-Yi,Lee, Sang-Hee,Kim, Mi Jeong,Kweon, Hee-Seok,Park, Woong-Yang,Kim, Cheol-Hee,Gleeson, Joseph G.,Kim, Joon National Academy of Sciences 2013 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.110 No.15

<P>The initiation of primary cilium assembly entails the docking of ciliary vesicles presumably derived from the Golgi complex to the distal end of the mother centriole. Distal appendages, which anchor the mother centriole to the plasma membrane, are thought to be involved in the docking process. However, little is known about the molecular players and mechanisms that mediate the vesicle–centriole association. Here we report that coiled-coil domain containing 41 (CCDC41) is required for the docking of ciliary vesicles. CCDC41 specifically localizes to the distal end of the mother centriole and interacts with centrosomal protein 164 (Cep164), a distal appendage component. In addition, a pool of CCDC41 colocalizes with intraflagellar transport protein 20 (IFT20) subunit of the intraflagellar transport particle at the Golgi complex. Remarkably, knockdown of CCDC41 inhibits the recruitment of IFT20 to the centrosome. Moreover, depletion of CCDC41 or IFT20 inhibits ciliogenesis at the ciliary vesicle docking step, whereas intraflagellar transport protein 88 (IFT88) depletion interferes with later cilium elongation steps. Our results suggest that CCDC41 collaborates with IFT20 to support the vesicle–centriole association at the onset of ciliogenesis.</P>

Prevalence of tumor BRCA1 and BRCA2 dysfunction in unselected patients with ovarian cancer

( Roshni D Kalachand ),( Ciaran O’riain ),( Sinead Toomey ),( Aoife Carr¸ Bsc ),( Kirsten M Timms ),( Sharon O’toole ),( Stephen Madden ),( Mark Bates ),( John J O’leary ),( Noreen Gleeson ),( Dearbha 대한산부인과학회 2020 Obstetrics & Gynecology Science Vol.63 No.5

Objective The therapeutic benefits of poly(ADP-ribose) polymerase inhibitors highlight the need to evaluate BRCA1/2 defects in tubal/ovarian cancer (OC). We sought to determine the pattern and disease characteristics associated with tumor BRCA1/2 mutations and BRCA1 methylation in women with OC. Methods We obtained 111 OC specimens from 2 university hospitals and assessed BRCA1/2 mutations and BRCA1 methylation in tumor DNA. The frequency and pattern of BRCA1/2 defects were examined. Associations between patient/disease characteristics and BRCA1/2 defects were ascertained (Fisher’s exact test). Platinum-free interval (PFI), progressionfree survival (PFS), and overall survival (OS) based on the underlying BRCA1/2 defect were determined (Kaplan-Meier analysis [log-rank test]). Results We observed a BRCA1/2 dysfunction rate of 40% (28/70) in high-grade serous tubal/ovarian cancer (HGSC), including 14.3% BRCA1 methylation (n=10), 7.1% BRCA1 mutation (n=5), and 18.6% BRCA2 mutation (n=13). Defects in BRCA1/2 genes were associated with stage III/IV HGSC (BRCA1 methylation: P=0.005 [stage III/IV] and P=0.004 [HGSC]; BRCA1/2 mutation: P=0.03 [stage III/IV] and P<0.001 [HGSC]). Patients with BRCA1/2-mutated cancers showed improved OS (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.43-0.99; P=0.045) and a trend toward improved PFI (HR, 0.48; 95% CI, 0.22-1.06; P=0.07) and PFS (HR, 0.72; 95% CI, 0.51-1.03; P=0.07). No survival differences were observed between BRCA1-methylated and BRCA1/2 wild-type non-BRCA1-methylated cancers. Conclusion We observed a high tumor BRCA1/2 dysfunction rate in HGSC with a unique predominance of BRCA2 over BRCA1 mutations. While BRCA1/2 mutations conferred survival benefits in OC, no such association was observed with BRCA1 methylation.

Genome-wide screen identifies novel machineries required for both ciliogenesis and cell cycle arrest upon serum starvation

Kim, J.H.,Ki, S.M.,Joung, J.G.,Scott, E.,Heynen-Genel, S.,Aza-Blanc, P.,Kwon, C.H.,Kim, J.,Gleeson, J.G.,Lee, J.E. Elsevier Biomedical Press 2016 Biochimica et biophysica acta, Molecular cell rese Vol.1863 No.6

Biogenesis of the primary cilium, a cellular organelle mediating various signaling pathways, is generally coordinated with cell cycle exit/re-entry. Although the dynamic cell cycle-associated profile of the primary cilium has been largely accepted, the mechanism governing the link between ciliogenesis and cell cycle progression has been poorly understood. Using a human genome-wide RNAi screen, we identify genes encoding subunits of the spliceosome and proteasome as novel regulators of ciliogenesis. We demonstrate that 1) the mRNA processing-related hits are essential for RNA expression of molecules acting in cilia disassembly, such as AURKA and PLK1, and 2) the ubiquitin-proteasome systems (UPS)-involved hits are necessary for proteolysis of molecules acting in cilia assembly, such as IFT88 and CPAP. In particular, we show that these screen hit-associated mechanisms are crucial for both cilia assembly and cell cycle arrest in response to serum withdrawal. Finally, our data suggest that the mRNA processing mechanism may modulate the UPS-dependent decay of cilia assembly regulators to control ciliary resorption-coupled cell cycle re-entry.