Effects of Full-Length Borealin on the Composition and Protein-Protein Interaction Activity of a Binary Chromosomal Passenger Complex

The chromosomal passenger complex (CPC) comprises at least four protein components and functions at various cellular localizations during different mitotic stages to ensure correct chromosome segregation and completion of cytokinesis. Borealin, the most recently identified member of the CPC, is an intrinsically unstructured protein of low solubility and stability. Recent reports have demonstrated the formation binary or ternary CPC sub-complexes incorporating short Borealin fragments in vitro. Using isothermal titration calorimetry, we show that full-length Borealin, instead of a Borealin fragment possessing the complete Survivin and INCENP-recognition sequence, is required for the composition of a Borealin-Survivin complex competent to interact with INCENP. In addition, we show evidence that full-length Borealin, which forms high-order oligomers in its isolated form, is a monomer in the Borealin-Survivin CPC sub-complex

Aurora B phosphorylates spatially distinct targets to differentially regulate the kinetochore-microtubule interface

Accurate chromosome segregation requires carefully regulated interactions between kinetochores and microtubules, but how plasticity is achieved to correct diverse attachment defects remains unclear. Here we demonstrate that Aurora B kinase phosphorylates three spatially distinct targets within the conserved outer kinetochore KNL1/Mis12 complex/Ndc80 complex (KMN) network, the key player in kinetochore-microtubule attachments. The combinatorial phosphorylation of the KMN network generates graded levels of microtubule-binding activity, with full phosphorylation severely compromising microtubule binding. Altering the phosphorylation state of each protein causes corresponding chromosome segregation defects. Importantly, the spatial distribution of these targets along the kinetochore axis leads to their differential phosphorylation in response to changes in tension and attachment state. In total, rather than generating exclusively binary changes in microtubule binding, our results suggest a mechanism for the tension-dependent fine-tuning of kinetochore-microtubule interactions.Smith Family FoundationMassachusetts Life Sciences CenterKinship Foundation. Searle Scholars ProgramNational Institute of General Medical Sciences (U.S.) (Grant number GM088313

Contrasting roles of condensin I and condensin II in mitotic chromosome formation

© 2012. Published by The Company of Biologists LtdIn vertebrates, two condensin complexes exist, condensin I and condensin II, which have differing but unresolved roles in organizing mitotic chromosomes. To dissect accurately the role of each complex in mitosis, we have made and studied the first vertebrate conditional knockouts of the genes encoding condensin I subunit CAP-H and condensin II subunit CAP-D3 in chicken DT40 cells. Live-cell imaging reveals highly distinct segregation defects. CAP-D3 (condensin II) knockout results in masses of chromatin-containing anaphase bridges. CAP-H (condensin I)-knockout anaphases have a more subtle defect, with chromatids showing fine chromatin fibres that are associated with failure of cytokinesis and cell death. Super-resolution microscopy reveals that condensin-I-depleted mitotic chromosomes are wider and shorter, with a diffuse chromosome scaffold, whereas condensin-II-depleted chromosomes retain a more defined scaffold, with chromosomes more stretched and seemingly lacking in axial rigidity. We conclude that condensin II is required primarily to provide rigidity by establishing an initial chromosome axis around which condensin I can arrange loops of chromatin.This work was supported by an Australian Research Council discovery project [grant number DP110100784 to D.F.H., K.H.A.C. and W.C.E.]; National Health and Medical Research Council (NHMRC) project grants [APP1030358 and 546454]; an NHMRC RD Wright Fellowship to P.K.; an NHMRC Senior Research Fellowship to C.B.W.; an NHMRC Senior Principal Research Fellowship to K.H.A.C.; and by the Victorian Government’s Operational Infrastructure Support Progra

Narradores do Monte Serrat

Este ensaio propõe reflexões sobre o campo da narratividade enquanto instância da vida política das cidades a partir de uma pesquisa etnográfica realizada na comunidade do Monte Serrat, em Florianópolis. A partir da leitura e interpretação de narrativas produzidas e compartilhadas por pessoas e entidades com papel de mediação na comunidade, procuro discutir o gesto de narrar em associação com os modos de produzir o próprio território na cidade, sempre em um complexo campo de disputas com as representações hegemônicas da cidade sobre suas periferias

De l'intérêt de faire appel à un vétérinaire spécialisé lors de l'acquisition d'un cheval

L’intérêt de faire appel à un vétérinaire spécialisé lors de l’acquisition d’un cheval réside dans trois actions principales. Avant l’acquisition, le vétérinaire a un rôle de conseil et se doit de connaître les différentes modalités de la vente, les types de contrats possibles et doit insister sur le fait qu’un contrat écrit est essentiel. Le vétérinaire effectue ensuite une expertise d’achat afin de faire un bilan de l’état de santé du cheval au jour de la visite. Il conclue alors sur l’aptitude du cheval en fonction de l’utilisation future envisagée. Enfin, une fois la vente conclue, le vétérinaire maîtrise les différentes modalités de rupture d’un contrat de vente et peut conseiller ses clients le cas échéant. Il peut y avoir annulation de la vente lorsque qu’une irrégularité dans la formation du contrat est constatée ou résolution de la vente lorsque les garanties dues par le vendeur ne sont pas respectées

Acteurs des transferts culturels en Méditerranée médiévale

Der Mittelmeerraum wies während des Mittelalters einen großen Reichtum an Transfer- und Austauschprozessen auf. Waren entsprechende Bedingungen (geographische Mobilität, eine kulturell grenzüberschreitende Lebenssituation oder ein entsprechendes Aktivitätsfeld etc.) gegeben, konnten Menschen zu Vermittlern von Kulturgütern werden, darunter Gesandte, Pilger, Seeleute, Händler, Schmuggler, Kriegsgefangene, Geiseln, Missionare, Ärzte, Gelehrte, Übersetzer, Dolmetscher, Bauleute, Söldner und viele andere mehr. Der Band bietet einen Überblick über verschiedene Milieus, Gruppen und Individuen, die auf jeweils unterschiedlich Art die Mobilität von Kulturgütern im mittelalterlichen Mediterraneum beförderten

Cidade, memória e narrativa: reflexões e propostas para a leitura e reconhecimento da história não-oficial

TCC (graduação) - Universidade Federal de Santa Catarina. Centro Tecnológico. ArquiteturaTCC sem resumo

A Presença do passado na produção da cidade: as narrativas do Monte Serrat em Florianópolis/SC

El pasado, reapropiado y resignificado, hace parte de la producci´ón de narrativas que logran la construcción de la noción de cultura para diferentes grupos. Al mismo tiempo en que ese fenómeno se puede observar en uma escala amplia, por medio de los aparatos de oficialidad como el Estado y la Academia, grupos a margen de eses procesos vienen recurriendo al pasado para construir sus propias narrativas. Así que la comunidad del Monte Serrat, ubicada en Florianópolis, se viene destacando en las últimas décadas. Por medio de una lectura crítica de los mecanismos de construcción de las narrativas oficialas y de una investigación etnográfica junto a la comunidad, este trabajo busca comprender las maneras por las que se configuran las narrativas locales del Monte Serrat en oposición a las oficiales de la ciudad, y como eses procesos vienen agenciando la producción de eses territorios.Past events, once re-interpreted and re-signified, has been made into part of the production of narratives which aim for the building of a notion of culture for different groups. As well as this phenomenon may be observed in a large scale, through official apparatus such as the State and the Academy, groups put apart of these processes have been recurring to its own past in order to construct their own narratives. In this sense, the community of Monte Serrat, located in Florianópolis, has had an important role in the last decades. Through a critical lecture of the mechanisms used to produce official narratives and an ethnographic investigation within the community, this works aims to understand how these local narratives have been produced in Monte Serrat, and how these processes have been part of the production of its territory itself.O passado, reapropriado e ressignificado, tem feito parte da produção de narrativas que buscam a construção da noção de cultura de diferentes grupos. Ao mesmo tempo em que esse fenômeno se observa em uma escala ampla, por meio de aparatos de oficialidade como o Estado e a Academia, grupos à margem desses processos vem recorrendo ao passado para construir suas próprias narrativas. Nesse sentido a comunidade do Monte Serrat, localizada em Florianópolis, tem se destacado nas últimas décadas. Por meio de uma leitura crítica dos mecanismos de construção de narrativas oficiais e de uma investigação etnográfica junto à comunidade, este trabalho busca compreender de que maneiras se configuram as narrativas locais do Monte Serrat frente às oficiais da cidade, e como esses processos tem agenciado a própria produção desses territórios

Bronchiectasis:new therapies and new perspectives

European Respiratory Society guidelines for the management of adult bronchiectasis highlight the paucity of treatment options available for patients with this disorder. No treatments have been licensed by regulatory agencies worldwide, and most therapies used in clinical practice are based on very little evidence. Development of new treatments is needed urgently. We did a systematic review of scientific literature and clinical trial registries to identify agents in early-to-late clinical development for bronchiectasis in adults. In this Review, we discuss the mechanisms and potential roles of emerging therapies, including drugs that target airway and systemic inflammation, mucociliary clearance, and epithelial dysfunction. To ensure these treatments achieve success in randomised clinical trials-and therefore reach patients-we propose a reassessment of the current approach to bronchiectasis. Although understanding of the pathophysiology of bronchiectasis is at an early stage, we argue that bronchiectasis is a heterogeneous disease with many different biological mechanisms that drive disease progression (endotypes), and therefore the so-called treatable traits approach used in asthma and chronic obstructive pulmonary disease could be applied to bronchiectasis, with future trials targeted at the specific disease subgroups most likely to benefit