Impaired Inhibitory Control in Recreational Cocaine Users

Chronic use of cocaine is associated with impairment in response inhibition but it is an open question whether and to which degree findings from chronic users generalize to the upcoming type of recreational users. This study compared the ability to inhibit and execute behavioral responses in adult recreational users and in a cocaine-free-matched sample controlled for age, race, gender distribution, level of intelligence, and alcohol consumption. Response inhibition and response execution were measured by a stop-signal paradigm. Results show that users and non users are comparable in terms of response execution but users need significantly more time to inhibit responses to stop-signals than non users. Interestingly, the magnitude of the inhibitory deficit was positively correlated with the individuals lifetime cocaine exposure suggesting that the magnitude of the impairment is proportional to the degree of cocaine consumed

Stressful situation if CENP-A not front and CENter

The exclusive localization of the histone H3 variant CENP-A to centromeres is essential for accurate chromosome segregation. Ubiquitin-mediated proteolysis helps to ensure that CENP-A does not mislocalize to euchromatin, which can lead to genomic instability. Consistent with this, overexpression of the budding yeast CENP-A(Cse4) is lethal in cells lacking Psh1, the E3 ubiquitin ligase that targets CENP-A(Cse4) for degradation. To identify additional mechanisms that prevent CENP-A(Cse4) misincorporation and lethality, we analyzed the genome-wide mislocalization pattern of overexpressed CENP-A(Cse4) in the presence and absence of Psh1 by chromatin immunoprecipitation followed by high throughput sequencing. We found that ectopic CENP-A(Cse4) is enriched at promoters that contain histone H2A.Z(Htz1) nucleosomes, but that H2A.Z(Htz1) is not required for CENP-A(Cse4) mislocalization. Instead, the INO80 complex, which removes H2A.Z(Htz1) from nucleosomes, promotes the ectopic deposition of CENP-A(Cse4). Transcriptional profiling revealed gene expression changes in the psh1Δ cells overexpressing CENP-A(Cse4). The down-regulated genes are enriched for CENP-A(Cse4) mislocalization to promoters, while the up-regulated genes correlate with those that are also transcriptionally up-regulated in an htz1Δ strain. Together, these data show that regulating centromeric nucleosome localization is not only critical for maintaining centromere function, but also for ensuring accurate promoter function and transcriptional regulation

Branching Random Walk: Seneta-Heyde norming

: In the discrete-time branching random walk, the martingale formed by taking the Laplace transform of the nth generation point process is known, for suitable values of the argument, to converge in L 1 under an X log X condition, and to converge to zero when this moment condition fails. This paper examines the strategy used in Biggins and Kyprianou (1996) to prove that, when the X log X condition fails, there exists a Seneta-Heyde renormalisation of the martingale that converges in probability to a nontrivial random variable. To bring out how the method works it is first discussed in the context of the Galton-Watson process. The paper is concluded by extending the results to the case of the continuous-time Markov branching random walk. R'esum'e: Dans une marche al'eatoire de branchement `a temps discret, on sait que pour des valeurs convenables de l'argument, la martingale obtenue en prenant la transform'ee de Laplace du processus ponctuel de la n-i`eme g'en'eration converge dans L 1 ..

Statutory occupational health and safety workplace arrangements for the modern labour market.

Over the past 20 years there has been a significant refashioning of the labour market within Australia and other industrialised countries. This paper examines the implications of the growth of more flexible work arrangements for mechanisms designed to facilitate worker involvement in occupational health and safety at the workplace—a pivotal feature of post-Robens OHS legislation in Australia. It is argued that the growth of subcontracting, casual and home-based work has undermined both coverage and the effectiveness of these provisions, especially in a context where union membership and influence has also been declining. Looking at international experience, the paper examines a number of ways of remedying these deficiencies

Tension directly stabilizes reconstituted kinetochore-microtubule attachments.

Kinetochores are macromolecular machines that couple chromosomes to dynamic microtubule tips during cell division, thereby generating force to segregate the chromosomes. Accurate segregation depends on selective stabilization of correct 'bi-oriented' kinetochore-microtubule attachments, which come under tension as the result of opposing forces exerted by microtubules. Tension is thought to stabilize these bi-oriented attachments indirectly, by suppressing the destabilizing activity of a kinase, Aurora B. However, a complete mechanistic understanding of the role of tension requires reconstitution of kinetochore-microtubule attachments for biochemical and biophysical analyses in vitro. Here we show that native kinetochore particles retaining the majority of kinetochore proteins can be purified from budding yeast and used to reconstitute dynamic microtubule attachments. Individual kinetochore particles maintain load-bearing associations with assembling and disassembling ends of single microtubules for >30 min, providing a close match to the persistent coupling seen in vivo between budding yeast kinetochores and single microtubules. Moreover, tension increases the lifetimes of the reconstituted attachments directly, through a catch bond-like mechanism that does not require Aurora B. On the basis of these findings, we propose that tension selectively stabilizes proper kinetochore-microtubule attachments in vivo through a combination of direct mechanical stabilization and tension-dependent phosphoregulation