1,607 research outputs found

    Anaphase B.

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    Anaphase B spindle elongation is characterized by the sliding apart of overlapping antiparallel interpolar (ip) microtubules (MTs) as the two opposite spindle poles separate, pulling along disjoined sister chromatids, thereby contributing to chromosome segregation and the propagation of all cellular life. The major biochemical "modules" that cooperate to mediate pole-pole separation include: (i) midzone pushing or (ii) braking by MT crosslinkers, such as kinesin-5 motors, which facilitate or restrict the outward sliding of antiparallel interpolar MTs (ipMTs); (iii) cortical pulling by disassembling astral MTs (aMTs) and/or dynein motors that pull aMTs outwards; (iv) ipMT plus end dynamics, notably net polymerization; and (v) ipMT minus end depolymerization manifest as poleward flux. The differential combination of these modules in different cell types produces diversity in the anaphase B mechanism. Combinations of antagonist modules can create a force balance that maintains the dynamic pre-anaphase B spindle at constant length. Tipping such a force balance at anaphase B onset can initiate and control the rate of spindle elongation. The activities of the basic motor filament components of the anaphase B machinery are controlled by a network of non-motor MT-associated proteins (MAPs), for example the key MT cross-linker, Ase1p/PRC1, and various cell-cycle kinases, phosphatases, and proteases. This review focuses on the molecular mechanisms of anaphase B spindle elongation in eukaryotic cells and briefly mentions bacterial DNA segregation systems that operate by spindle elongation

    The microtubule cross-linker Feo controls the midzone stability, motor composition, and elongation of the anaphase B spindle in Drosophila embryos.

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    Chromosome segregation during anaphase depends on chromosome-to-pole motility and pole-to-pole separation. We propose that in Drosophila embryos, the latter process (anaphase B) depends on a persistent kinesin-5-generated interpolar (ip) microtubule (MT) sliding filament mechanism that "engages" to push apart the spindle poles when poleward flux is turned off. Here we investigated the contribution of the midzonal, antiparallel MT-cross-linking nonmotor MAP, Feo, to this "slide-and-flux-or-elongate" mechanism. Whereas Feo homologues in other systems enhance the midzone localization of the MT-MT cross-linking motors kinesin-4, -5 and -6, the midzone localization of these motors is respectively enhanced, reduced, and unaffected by Feo. Strikingly, kinesin-5 localizes all along ipMTs of the anaphase B spindle in the presence of Feo, including at the midzone, but the antibody-induced dissociation of Feo increases kinesin-5 association with the midzone, which becomes abnormally narrow, leading to impaired anaphase B and incomplete chromosome segregation. Thus, although Feo and kinesin-5 both preferentially cross-link MTs into antiparallel polarity patterns, kinesin-5 cannot substitute for loss of Feo function. We propose that Feo controls the organization, stability, and motor composition of antiparallel ipMTs at the midzone, thereby facilitating the kinesin-5-driven sliding filament mechanism underlying proper anaphase B spindle elongation and chromosome segregation

    Self-rated everyday prospective memory abilities of cigarette smokers and non-smokers: a web based study

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    The present study examined self-ratings of two aspects of everyday memory performance: long-term prospective memory—measured by the prospective memory questionnaire (PMQ), and everyday memory—measured by the everyday memory questionnaire (EMQ). Use of other substances was also measured and used as covariates in the study. To ensure confidentiality and to expand the numbers used in previous studies, an Internet study was carried out and data from 763 participants was gathered. After controlling for other drug use and strategy use, the data from the PMQ revealed that smokers reported a greater number of long-term prospective memory errors than non-smokers. There were also differences between light and heavier smokers in long-term prospective memory, suggesting that nicotine may have a dose-dependent impact upon long-term prospective memory performance. There was also a significant ANOVA group effect on the EMQ, although the trend for more memory errors amongst the heavier smokers was statistically only borderline (p = .057). These findings suggest there are selective memory deficits associated with smoking and that long-term prospective memory deficits should be added to the growing list of problems associated with cigarette use

    The Role of Dopamine on Central Neuromuscular Activation during Passive Hyperthermia

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    Acute methylphenidate (MPH) (dopamine reuptake inhibitor) ingestion improves cycling time trial performance and power output in hot conditions (30 C), while also allowing for tolerance of higher core temperatures. However, the mechanisms for why this occurs have not been isolated. One potential explanation for this ergogenic benefit is that MPH intake was enhancing neuromuscular activation. Thus, this research project examined the influence of MPH on neuromuscular activation during hyperthermia. Participants ingested either placebo (PLA; 20mg) or MPH (Ritalin; 20mg) 1 hour prior to a passive heating protocol. 6 participants were passively heated until volitional cessation, or after 3 hours of heating had passed. Neuromuscular responses, as indicated by maximal voluntary contraction (MVC) force, and voluntary activation (VA) percentage were assessed prior to drug ingestion, 1 hour after MPH wash-in, throughout the heating protocol and at cessation of heating. A primary non-significant finding of this research project was that participants reached higher rectal temperatures (Tre) by ~0.3 C in trials where they ingested MPH (p = 0.065). This effect occurred in absence of any differences in thermal comfort or sensation ratings or heating durations. However, while MPH improves thermal tolerance, it was not able to attenuate the decreases in MVC force and VA that occurred during passive heating. Therefore, the aforementioned ergogenic benefits that MPH has in hot conditions are not occurring as a result of enhanced neuromuscular activation

    Alcohol Hangover and Multitasking: Effects on Mood, Cognitive Performance, Stress Reactivity, and Perceived Effort

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    The aim of this study was to examine the effects of hangover on mood, multitasking ability, and psychological stress reactivity to cognitive demand. Using a crossover design and semi-naturalistic methodology, 25 participants attended the laboratory in the morning following a night of (i) alcohol abstinence and (ii) alcohol self-administration during a typical night out (with order counterbalanced across participants). They completed a four-module multitasking framework (MTF, a widely used laboratory stressor) and a battery of questionnaires assessing mood, hangover symptom severity, and previous night’s sleep. The effects of the MTF on mood and perceived workload were also assessed. Participants in the hangover condition reported significantly lower alertness and contentment coupled with a higher mental fatigue and anxiety. Multitasking ability was also significantly impaired in the hangover condition. Completion of the cognitive stressor increased reported levels of mental demand, effort, and frustration, and decreased perceived level of performance. MTF completion did not differentially affect mood. Lastly, participants rated their sleep as significantly worse during the night prior to the hangover compared with the control condition. These findings confirm the negative cognitive and mood effects of hangover on mood. They also demonstrate that hangover is associated with greater perceived effort during task performance

    Prometaphase spindle maintenance by an antagonistic motor-dependent force balance made robust by a disassembling lamin-B envelope

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    The lamin-B nuclear envelope stabilizes spindle microtubules by keeping the competitive motility of opposing-force kinesins in check
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