Autoinhibition of TBCB regulates EB1-mediated microtubule dynamics

Tubulin cofactors (TBCs) participate in the folding, dimerization, and dissociation pathways of the tubulin dimer. Among them, TBCB and TBCE are two CAP-Gly domain-containing proteins that together efficiently interact with and dissociate the tubulin dimer. In the study reported here we showed that TBCB localizes at spindle and midzone microtubules during mitosis. Furthermore, the motif DEI/M-COO− present in TBCB, which is similar to the EEY/F-COO− element characteristic of EB proteins, CLIP-170, and α-tubulin, is required for TBCE–TBCB heterodimer formation and thus for tubulin dimer dissociation. This motif is responsible for TBCB autoinhibition, and our analysis suggests that TBCB is a monomer in solution. Mutants of TBCB lacking this motif are derepressed and induce microtubule depolymerization through an interaction with EB1 associated with microtubule tips. TBCB is also able to bind to the chaperonin complex CCT containing α-tubulin, suggesting that it could escort tubulin to facilitate its folding and dimerization, recycling or degradation.

Runtime Elision of Transactional Barriers for Captured Memory

In this paper, we propose a new technique that can identify transaction-local memory (i.e. captured memory), in managed environments, while having a low runtime overhead. We implemented our proposal in a well known STM framework (Deuce) and we tested it in STMBench7 with two different STMs: TL2 and LSA. In both STMs the performance improved significantly (4 times and 2.6 times, respectively). Moreover, running the STAMP benchmarks with our approach shows improvements of 7 times in the best case for the Vacation application.

CCTα and CCTδ chaperonin subunits are essential and required for cilia assembly and maintenance in Tetrahymena

Background - The eukaryotic cytosolic chaperonin CCT is a hetero-oligomeric complex formed by two rings connected back-to-back, each composed of eight distinct subunits (CCTalpha to CCTzeta). CCT complex mediates the folding, of a wide range of newly synthesised proteins including tubulin (alpha, beta and gamma) and actin, as quantitatively major substrates. Methodology/Principal findings - We disrupted the genes encoding CCTalpha and CCTdelta subunits in the ciliate Tetrahymena. Cells lacking the zygotic expression of either CCTalpha or CCTdelta showed a loss of cell body microtubules, failed to assemble new cilia and died within 2 cell cycles. We also show that loss of CCT subunit activity leads to axoneme shortening and splaying of tips of axonemal microtubules. An epitope-tagged CCTalpha rescued the gene knockout phenotype and localized primarily to the tips of cilia. A mutation in CCTalpha, G346E, at a residue also present in the related protein implicated in the Bardet Biedel Syndrome, BBS6, also caused defects in cilia and impaired CCTalpha localization in cilia. Conclusions/Significance - Our results demonstrate that the CCT subunits are essential and required for ciliary assembly and maintenance of axoneme structure, especially at the tips of cilia.

Optimizing memory transactions for large-scale programs

Even though Software Transactional Memory (STM) is one of the most promising approaches to simplify concurrent programming, current STM implementations incur significant overheads that render them impractical for many real-sized programs. The key insight of this work is that we do not need to use the same costly barriers for all the memory managed by a real-sized application, if only a small fraction of the memory is under contention lightweight barriers may be used in this case. In this work, we propose a new solution based on an approach of adaptive object metadata (AOM) to promote the use of a fast path to access objects that are not under contention. We show that this approach is able to make the performance of an STM competitive with the best fine-grained lock-based approaches in some of the more challenging benchmarks. (C) 2015 Elsevier Inc. All rights reserved.