A p34cdc2 survival checkpoint in cancer

AbstractA checkpoint surveying the entry into mitosis responds to defects in spindle microtubule assembly/stability. This has been used to trigger apoptosis in cancer cells, but how the spindle checkpoint couples to the cell survival machinery has remained elusive. Here, we report that microtubule stabilization engenders a survival pathway that depends on elevated activity of p34cdc2 kinase and increased expression of the apoptosis inhibitor and mitotic regulator, survivin. Pharmacologic, genetic, or molecular ablation of p34cdc2 kinase after microtubule stabilization resulted in massive apoptosis independent of p53, suppression of tumor growth, and indefinite survival without toxicity in mice. By ablating this survival checkpoint, inhibitors of p34cdc2 kinase could safely improve the efficacy of microtubule-stabilizing agents used to treat common cancers

The Dilemma of Using Sward Height as a Management Tool for Intensively Grazed Sheep Pasture in Spring

Sward height is often used as a tool for both animal and pasture management, especially when continuously grazing pasture. For example, sward height has been used to define the conditions for optimal feed intake of multiple-bearing ewes, both before and after lambing (Everett-Hincks et al.2005; Morris and Kenyon 2004). Sward height is easily applied by the grazier and so becomes an effective tool. However, changes in the leaf distribution and relative species makeup of the sward both seasonally (Thomson et al. 2001) and in response to grazing management (Webby and Pengelly 1986) mean that the amount of pasture per unit height will change. When these changes occur a dilemma is presented to the grazier. How do they manage the trade-off between a simple indicator for management decisions and the lost opportunity of harvesting pasture mass that may be accumulating below the assigned sward height? This paper presents data from an experiment that investigated the impacts of defoliation strategies on sward of differing starting masses, with defoliation management based on height rather than mass. The paper quantifies the accumulation of herbage below defoliation height and highlights the dilemma of using sward height as a management tool when aiming to maximise the utilisation of our pasture resource

Personality profiles and persuasion: An exploratory study investigating the role of the Big-5, Type D personality and the Dark Triad on susceptibility to persuasion

The present study investigated the relationship between personality profiles and susceptibility to persuasion.
 Participants (N = 316) were recruited for an online questionnaire and asked to complete self-reported measures of their personality – Big-5, Dark Triad and Type D. Individual differences in susceptibility to persuasion were also explored using Cialdini's model of persuasion. Latent profile analysis identified three distinct profiles which were labelled Socially Apt, Fearful and Malevolent. These profiles were correlated with scores on the persuasion sub-scales – authority, commitment, liking, scarcity, reciprocity, consensus – and a number of interesting associations were identified. The malevolent profile self-reported as more susceptible to a higher use of scarcity relative to the other principles of persuasion, and was least susceptible to reciprocity and authority. The socially apt profile appear to be more inclined to be persuaded to do something if it is consistent with their beliefs or a prior act whereas individuals in the Fearful profile were more likely to report obeying those in authority and going along with a crowd. Implications for persuasion are discussed along with research on personality types

Balancing Pastoral and Plantation Forestry Options in New Zealand and the Role of Agroforestry

Pastoral agriculture and forestry enterprises are key features of New Zealand’s landscape and are very important economically. They are competing landuses, particularly on moderate to steep hill country. Agroforestry involving spaced trees of Pinus radiata on pasture was developed in the 1970s to provide dual incomes from livestock enterprises and the later tree crop. In contrast, wide-spaced trees of predominantly Populus and Salix spp. are planted mainly for erosion control. Characteristics of pastoralism and plantation forestry are reviewed, including trends in conversions between these landuses. Roles, challenges and opportunities with wide-spaced trees are presented, together with current and future research initiatives. Pastoralism and forestry will continue to compete strongly for hill country sites and at present there is an increasing trend of converting previously forested areas to pasture, particularly in the central North Island. Agroforestry involving Pinus radiata has virtually ceased because of adverse effects on wood quality, pasture production and animal performance. There are millions of wide-spaced trees of Populus and Salix spp. on hill country and their planting is expected to continue unabated because they are the most practical and efficient means of enabling pastoralism on erodible slopes and they provide multiple ecosystem services. The species have significant advantages compared to other woody species but many older trees have grown very large because they have received negligible or no silviculture. This is an increasing problem, requiring development and implementation of appropriate management strategies. There is growing interest by landowners in the environmental outcomes of spaced-tree plantings

Synthetic Spin-Orbit Coupling in an Optical Lattice Clock.

We propose the use of optical lattice clocks operated with fermionic alkaline-earth atoms to study spin-orbit coupling (SOC) in interacting many-body systems. The SOC emerges naturally during the clock interrogation, when atoms are allowed to tunnel and accumulate a phase set by the ratio of the "magic" lattice wavelength to the clock transition wavelength. We demonstrate how standard protocols such as Rabi and Ramsey spectroscopy that take advantage of the sub-Hertz resolution of state-of-the-art clock lasers can perform momentum-resolved band tomography and determine SOC-induced s-wave collisions in nuclear-spin-polarized fermions. With the use of a second counterpropagating clock beam, we propose a method for engineering controlled atomic transport and study how it is modified by p- and s-wave interactions. The proposed spectroscopic probes provide clean and well-resolved signatures at current clock operating temperatures

Protocol for a single-centre randomised controlled trial of multimodal periarticular anaesthetic infiltration versus single-agent femoral nerve blockade as analgesia for total knee arthroplasty: Perioperative Analgesia for Knee Arthroplasty (PAKA)

Introduction: Total knee arthroplasty (TKA) surgery causes postoperative pain. The use of perioperative injections around the knee containing local anaesthetic, opiates and non-steroidal anti-inflammatory drugs has increased in popularity to manage pain. Theoretical advantages include reduced requirements for analgesia and earlier mobilisation. We propose a single-centre randomised controlled trial of multimodal periarticular anaesthetic infiltration versus femoral nerve anaesthetic blockade as analgesia for TKA. The aim is to determine, in patients undergoing TKA, if there is a difference in patient-reported pain scores on the visual analogue scale (VAS) prior to physiotherapy on day 1 postoperatively between treatment groups. Methods and analysis: Patients undergoing a primary unilateral TKA at University Hospitals Coventry and Warwickshire Hospitals will be assessed for eligibility. A total of 264 patients will provide 90% power to detect a difference of 12 mm on the VAS on day 1 postoperatively at the 5% level. The trial will use 1:1 randomisation, stratified by mode of anaesthetic. Primary outcome measure will be the VAS for pain prior to physiotherapy on day 1. Secondary outcome measures include VAS on day 2, total use of opiate analgesia up to 48 h, ordinal pain scores up to 40 min after surgery, independent functional knee physiotherapist assessment on days 1 and 2. Oxford knee Scores (OKS), EuroQol (EQ-5D) and Douleur Neuropathic Pain Scores (DN2) will be recorded at baseline, 6 weeks and 12 months. Adverse events will be recorded up to 12 months. Analysis will investigate differences in VAS on day 1 between the two treatment groups on an intention-to-treat basis. Tests will be two-sided and considered to provide evidence for a significant difference if p values are less than 0.05. Ethics and dissemination: NRES Committee West Midlands, 23 September 2013 (ref: 13/WM/0316). The results will be disseminated via peer-reviewed publications and conference presentations. Trial registration numbers: ISRCTN 60611146 and EUDRACT Number 2013-002439-10 (protocol code number PAKA-33601-AS117013); Pre-results

Neurophysiology

Contains a report on a research project

<i>Plasmodium </i>Condensin Core Subunits SMC2/SMC4 Mediate Atypical Mitosis and Are Essential for Parasite Proliferation and Transmission

Condensin is a multi-subunit protein complex regulating chromosome condensation and segregation during cell division. In Plasmodium spp., the causative agent of malaria, cell division is atypical and the role of condensin is unclear. Here we examine the role of SMC2 and SMC4, the core subunits of condensin, during endomitosis in schizogony and endoreduplication in male gametogenesis. During early schizogony, SMC2/SMC4 localize to a distinct focus, identified as the centromeres by NDC80 fluorescence and chromatin immunoprecipitation sequencing (ChIP-seq) analyses, but do not form condensin I or II complexes. In mature schizonts and during male gametogenesis, there is a diffuse SMC2/SMC4 distribution on chromosomes and in the nucleus, and both condensin I and condensin II complexes form at these stages. Knockdown of smc2 and smc4 gene expression reveals essential roles in parasite proliferation and transmission. The condensin core subunits (SMC2/SMC4) form different complexes and may have distinct functions at various stages of the parasite life cycle

Massive Ellipticals at High Redshift: NICMOS Imaging of Z~1 Radio Galaxies

We present deep, continuum images of eleven high-redshift (0.811 < z < 1.875) 3CR radio galaxies observed with NICMOS. Our images probe the rest-frame optical light where stars are expected to dominate the galaxy luminosity. The rest-frame UV light of eight of these galaxies demonstrates the well-known ``alignment effect''. Most of the radio galaxies have rounder, more symmetric morphologies at rest-frame optical wavelengths. Here we show the most direct evidence that in most cases the stellar hosts are normal elliptical galaxies with de Vaucouleurs law light profiles. For a few galaxies very faint traces of the UV-bright aligned component are also visible in the infrared images. We derive both the effective radius and surface-brightness for nine of eleven sample galaxies by fitting surface-brightness models to them. We find their sizes are similar to those of local FRII radio source hosts and are in general larger than other local galaxies. The derived host galaxy luminosities are very high and lie at the bright end of luminosity functions constructed at similar redshifts. The galaxies in our sample are also brighter than the rest-frame size--surface-brightness locus defined by the low-redshift sources. Passive evolution roughly aligns the z ~ 1 galaxies with the low-redshift samples. The optical host is sometimes centered on a local minimum in the rest-frame UV emission, suggesting the presence of substantial dust obscuration. We also see good evidence of nuclear point sources in three galaxies. Overall, our results are consistent with the hypothesis that these galaxies have already formed the bulk of their stars at redshifts greater than z >~ 2, and that the AGN phenomenon takes place within otherwise normal, perhaps passively evolving, galaxies. (abridged)Comment: 28 pages, 14 figures, accepted to ApJ. Uses AASTEX and emulateapj

Prey Nutritional Quality Interacts With Chemical Defenses to Affect Consumer Feeding and Fitness

Numerous studies have assessed the individual effects of prey nutritional quality or chemical defenses on consumer feeding behavior. However, little is known about how these traits interact to affect consumer feeding and performance. We tested the separate and interactive effects of prey chemical defenses and nutritional quality on the feeding behavior and fitness of six sympatric crustacean mesograzers. Natural concentrations of diterpene alcohols (dictyols) from the brown alga Dictyota menstrualis were incorporated, or not incorporated, into lower quality and higher quality foods to create artificial diets mimicking prey of variable value and defense. Five amphipods (Ampithoe longimana, A. valida, Cymadusa compta, Gammarus mucronatus, and Elasmopus levis) and one isopod (Paracerceis caudata), representing a continuum of closely to distantly related organisms, were fed intact algae or lower and higher quality diets containing or lacking dictyols. All six mesograzers preferred the green alga Enteromorpha intestinalis to the dictyol producing alga Dictyota menstrualis. In assays allowing consumers to choose between simultaneously available foods, dictyols deterred feeding by all five amphipods, but not the isopod; this occurred for both lower and higher quality foods. In no-choice assays, where consumers were confined with only one of our four treatment diets, effects on feeding became more complex. Nutritional quality alone affected feeding by five of the six species. These grazers compensated for lower quality by increasing consumption. Dictyols suppressed feeding for four of the six species. More interestingly, there were significant dictyol X quality interactions for three species. Dictyols decreased feeding more when placed in lower quality foods than higher quality foods. Two amphipods deterred by dictyols in the choice assays readily consumed dictyol-containing foods in no-choice situations and suffered few negative effects of doing so. Although all amphipods were deterred by dictyols in choice assays, dictyols decreased fitness (survivorship, growth, or reproduction) for only four of the five species. These effects included large and immediate decreases in survivorship, dramatic effects on reproduction, and modest effects on female growth. Dictyols enhanced survivorship of the isopod. Thus, the effects of secondary metabolites on feeding in choice situations vs. fitness in long-term assays were inconsistent. For three amphipods, certain effects of food quality, dictyols, or their interaction were detected only for females. In general, negative effects of dictyols on fitness were greater in lower than in higher quality foods, suggesting that prey nutritional value may counteract the effects of defensive metabolites. For example, when G. mucronatus consumed dictyols in lower quality foods, mortality was \u3e80% by day 5; for dictyols in higher quality foods, 80% mortality took 28 days to develop. Lower quality foods alone significantly decreased growth for the isopod, three of the amphipods, and the females of a fourth amphipod, concomitantly reducing fecundity for four of the five amphipods studied. The effects of both chemical defenses and nutritional quality were unrelated to consumer phylogeny; responses of congeners varied as much, or more, than responses of more distantly related consumers. Understanding mechanisms and consequences of food selection requires that the interactive effects of both chemical defenses and prey nutritional characteristics be considered explicitly