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"Hook, Peter"
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Substance : inside New Order
1980. Resurrected from the ashes of Joy Division after the suicide of its lead singer, Ian Curtis, New Order would become one most critically acclaimed bands of the decade. Peter Hook and company quickly rose to the top of the alternative music scene, their sound would influence acts that followed in their wake. Hook focuses on the 1980s New Wave and Dance Punk scene to tells the unvarnished story of New Order's founding, evolution, rapid rise to international fame, and its eventual rancorous dissolution.
Book
Strong Binding of Platelet Integrin αIIbβ3 to Fibrin Clots: Potential Target to Destabilize Thrombi
The formation of platelet thrombi is determined by the integrin αIIbβ3-mediated interactions of platelets with fibrinogen and fibrin. Blood clotting
in vivo
is catalyzed by thrombin, which simultaneously induces fibrinogen binding to αIIbβ3 and converts fibrinogen to fibrin. Thus, after a short time, thrombus formation is governed by αIIbβ3 binding to fibrin fibers. Surprisingly, there is little understanding of αIIbβ3 interaction with fibrin polymers. Here we used an optical trap-based system to measure the binding of single αIIbβ3 molecules to polymeric fibrin and compare it to αIIbβ3 binding to monomeric fibrin and fibrinogen. Like αIIbβ3 binding to fibrinogen and monomeric fibrin, we found that αIIbβ3 binding to polymeric fibrin can be segregated into two binding regimes, one with weaker rupture forces of 30–60 pN and a second with stronger rupture forces >60 pN that peaked at 70–80 pN. However, we found that the mechanical stability of the bimolecular αIIbβ3-ligand complexes had the following order: fibrin polymer > fibrin monomer > fibrinogen. These quantitative differences reflect the distinct specificity and underlying molecular mechanisms of αIIbβ3-mediated reactions, implying that targeting platelet interactions with fibrin could increase the therapeutic indices of antithrombotic agents by focusing on the destabilization of thrombi rather than the prevention of platelet aggregation.
Journal Article
How myosin VI traps its off-state, is activated and dimerizes
Myosin VI (Myo6) is the only minus-end directed nanomotor on actin, allowing it to uniquely contribute to numerous cellular functions. As for other nanomotors, the proper functioning of Myo6 relies on precise spatiotemporal control of motor activity via a poorly defined off-state and interactions with partners. Our structural, functional, and cellular studies reveal key features of myosin regulation and indicate that not all partners can activate Myo6. TOM1 and Dab2 cannot bind the off-state, while GIPC1 binds Myo6, releases its auto-inhibition and triggers proximal dimerization. Myo6 partners thus differentially recruit Myo6. We solved a crystal structure of the proximal dimerization domain, and show that its disruption compromises endocytosis in HeLa cells, emphasizing the importance of Myo6 dimerization. Finally, we show that the L926Q deafness mutation disrupts Myo6 auto-inhibition and indirectly impairs proximal dimerization. Our study thus demonstrates the importance of partners in the control of Myo6 auto-inhibition, localization, and activation.
Canon et al. offer insights into the auto-inhibition and activation of the minus-end directed motor myosin VI. The work highlights how differential relief of auto-inhibition allows for fine control of myosin VI activity in vivo.
Journal Article
Semantics and Pragmatics of Non-Canonical Word Order in South Asian Languages: of lag- ‘Begin’ as an Attitude-Marker in Hindi-Urdu
This paper examines possible motivations for departures from canonical clause-final word order observed for the finite verb in Hindi-Urdu and other modern Indo-Aryan languages. Depiction of speaker attitude in Premchand's novel godān and the imperatives of journalistic style in TV newscasts are shown to be prime factors. The emergence of V-2 word-order in Kashmiri and other Himalayan languages may have had a parallel history.
Journal Article
Control of cytoplasmic dynein force production and processivity by its C-terminal domain
Cytoplasmic dynein is a microtubule motor involved in cargo transport, nuclear migration and cell division. Despite structural conservation of the dynein motor domain from yeast to higher eukaryotes, the extensively studied
S. cerevisiae
dynein behaves distinctly from mammalian dyneins, which produce far less force and travel over shorter distances. However, isolated reports of yeast-like force production by mammalian dynein have called interspecies differences into question. We report that functional differences between yeast and mammalian dynein are real and attributable to a C-terminal motor element absent in yeast, which resembles a ‘cap’ over the central pore of the mammalian dynein motor domain. Removal of this cap increases the force generation of rat dynein from 1 pN to a yeast-like 6 pN and greatly increases its travel distance. Our findings identify the CT-cap as a novel regulator of dynein function.
Cytoplasmic dynein from the yeast
S. cerevisiae
behaves distinctly from mammalian dyneins, despite structural conservation. Here, Nicholas
et al
. identify a C-terminal domain in mammalian dynein that restricts force generation and travel distance, which, when removed, allows mammalian dynein to behave like its yeast counterpart.
Journal Article
Prenominal Participial Phrases in Marathi, the Noun Phrase Accessibility Hierarchy, and Picture Nouns
An introduction to Keenan and Comrie’s NPAH (noun phrase accessibility hierarchy) is followed by data showing to what extent Marathi’s PPP s (prenominal participial phrases) do and do not conform to it. The range of constructional variety inside a PPP is shown to be related to the tightness or looseness of the relation of the predicate inside the PPP to the nulled element. Examples are presented of the puzzling absence of Agent and Experiencer noun phrases inside PPP s. The paper ends with examples and discussion of the mismatch or transfer of PPP modifiers away from the NP denoting the ‘imagee’ or entity depicted in an image to the NP denoting the image itself.
Journal Article
A magnificent machine
Electron-microscope studies of the motor protein dynein reveal fascinating details of the movements of its various structural regions. Vallee and Hook assert that the protein displays a degree of gymnastic ability that is rarely seen.
Journal Article