A cancer-associated, genome protective programme engaging PKCε.

Associated with their roles as targets for tumour promoters, there has been a long-standing interest in how members of the protein kinase C (PKC) family act to modulate cell growth and division. This has generated a great deal of observational data, but has for the most part not afforded clear mechanistic insights into the control mechanisms at play. Here, we review the roles of PKCε in protecting transformed cells from non-disjunction. In this particular cell cycle context, there is a growing understanding of the pathways involved, affording biomarker and interventional insights and opportunities

Direct Observation of the Superfluid Phase Transition in Ultracold Fermi Gases

Water freezes into ice, atomic spins spontaneously align in a magnet, liquid helium becomes superfluid: Phase transitions are dramatic phenomena. However, despite the drastic change in the system's behaviour, observing the transition can sometimes be subtle. The hallmark of Bose-Einstein condensation (BEC) and superfluidity in trapped, weakly interacting Bose gases is the sudden appearance of a dense central core inside a thermal cloud. In strongly interacting gases, such as the recently observed fermionic superfluids, this clear separation between the superfluid and the normal parts of the cloud is no longer given. Condensates of fermion pairs could be detected only using magnetic field sweeps into the weakly interacting regime. The quantitative description of these sweeps presents a major theoretical challenge. Here we demonstrate that the superfluid phase transition can be directly observed by sudden changes in the shape of the clouds, in complete analogy to the case of weakly interacting Bose gases. By preparing unequal mixtures of the two spin components involved in the pairing, we greatly enhance the contrast between the superfluid core and the normal component. Furthermore, the non-interacting wings of excess atoms serve as a direct and reliable thermometer. Even in the normal state, strong interactions significantly deform the density profile of the majority spin component. We show that it is these interactions which drive the normal-to-superfluid transition at the critical population imbalance of 70(5)%.Comment: 16 pages (incl. Supplemental Material), 5 figure

Tracking ultrafast non-adiabatic dissociation dynamics of the deuterated water dication molecule

We applied reaction microscopy to elucidate fast non-adiabatic dissociation dynamics of deuterated water molecules after direct photo-double ionization at 61 eV with synchrotron radiation. For the very rare D+ + O+ + D breakup channel, the particle momenta, angular, and energy distributions of electrons and ions, measured in coincidence, reveal distinct electronic dication states and their dissociation pathways via spin-orbit coupling and charge transfer at crossings and seams on the potential energy surfaces. Notably, we could distinguish between direct and fast sequential dissociation scenarios. For the latter case, our measurements reveal the geometry and orientation of the deuterated water molecule with respect to the polarization vector that leads to this rare 3-body molecular breakup channel. Aided by multi-reference configuration-interaction calculations, the dissociation dynamics could be traced on the relevant potential energy surfaces and particularly their crossings and seams. This approach also unraveled the ultrafast time scales governing these processes

Heterozygote Advantage for Fecundity

Heterozygote advantage, or overdominance, remains a popular and persuasive explanation for the maintenance of genetic variation in natural populations in the face of selection. However, despite being first proposed more than 80 years ago, there remain few examples that fit the criteria for heterozygote advantage, all of which are associated with disease resistance and are maintained only in the presence of disease or other gene-by-environment interaction. Here we report five new examples of heterozygote advantage, based around polymorphisms in the BMP15 and GDF9 genes that affect female fecundity in domesticated sheep and are not reliant on disease for their maintenance. Five separate mutations in these members of the transforming growth factor β (TGFβ) superfamily give phenotypes with fitness differentials characteristic of heterozygous advantage. In each case, one copy of the mutant allele increases ovulation rate, and ultimately litter size per ewe lambing, relative to the wildtype. However, homozygous ewes inheriting mutant alleles from both parents have impaired oocyte development and maturation, which results in small undeveloped ovaries and infertility. Using data collected over many years on ovulation rates, litter size, and lambing rates, we have calculated the equilibrium solution for each of these polymorphisms using standard population genetic theory. The predicted equilibrium frequencies obtained for these mutant alleles range from 0.11 to 0.23, which are amongst the highest yet reported for a polymorphism maintained by heterozygote advantage. These are amongst the most frequent and compelling examples of heterozygote advantage yet described and the first documented examples of heterozygote advantage that are not reliant on a disease interaction for their maintenance

Individual Readiness for Change in the Context of Enterprise Resource Planning Systems Implementation

The present study takes a bottom-up approach and investigates the organizational implications of ERP systems implementation in organizations. We adopt a likely point of view of employees and study the ERP integration process along 3 dimensions: people, processes, and information. In this manner we discover the ERP-specific sources of resistance that could affect negatively the deployment of the software. Then, we argue that a general set of beliefs shapes employees readiness to change to ERP use and provides the foundation for resistance or for adoptive behavior. We define the concept of readiness for change in the context of ERP and introduce a readiness for change assessment approach. Then, we test empirically the study hypotheses upon which the research model was build. The results obtained offer insights into factors that can improve the effectiveness of ERP implementation strategies and underline the importance of change management for the success of such projects

Kinetics of the hydrogen abstraction ·C2H5 + alkane → C2H6 + alkyl reaction class: an application of the reaction class transition state theory

This paper presents an application of the reaction class transition state theory (RC-TST) to predict thermal rate constants for hydrogen abstraction reactions at alkane by the C2H5 radical on-the-fly. The linear energy relationship (LER), developed for acyclic alkanes, was also proven to hold for cyclic alkanes. We have derived all RCTST parameters from rate constants of 19 representative reactions, coupling with LER and the barrier height grouping (BHG) approach. Both the RC-TST/LER, where only reaction energy is needed, and the RC-TST/BHG, where no other information is needed, can predict rate constants for any reaction in this reaction class with satisfactory accuracy for combustion modeling. Our analysis indicates that less than 50% systematic errors on the average exist in the predicted rate constants using either the RC-TST/LER or RC-TST/BHG method, while in comparison with explicit rate calculations, the differences are within a factor of 2 on the average. The results also show that the RC-TST method is not sensitive to the choice of density functional theory used

Tetraspanin (TSP-17) Protects Dopaminergic Neurons against 6-OHDA-Induced Neurodegeneration in <i>C. elegans</i>

Parkinson's disease (PD), the second most prevalent neurodegenerative disease after Alzheimer's disease, is linked to the gradual loss of dopaminergic neurons in the substantia nigra. Disease loci causing hereditary forms of PD are known, but most cases are attributable to a combination of genetic and environmental risk factors. Increased incidence of PD is associated with rural living and pesticide exposure, and dopaminergic neurodegeneration can be triggered by neurotoxins such as 6-hydroxydopamine (6-OHDA). In C. elegans, this drug is taken up by the presynaptic dopamine reuptake transporter (DAT-1) and causes selective death of the eight dopaminergic neurons of the adult hermaphrodite. Using a forward genetic approach to find genes that protect against 6-OHDA-mediated neurodegeneration, we identified tsp-17, which encodes a member of the tetraspanin family of membrane proteins. We show that TSP-17 is expressed in dopaminergic neurons and provide genetic, pharmacological and biochemical evidence that it inhibits DAT-1, thus leading to increased 6-OHDA uptake in tsp-17 loss-of-function mutants. TSP-17 also protects against toxicity conferred by excessive intracellular dopamine. We provide genetic and biochemical evidence that TSP-17 acts partly via the DOP-2 dopamine receptor to negatively regulate DAT-1. tsp-17 mutants also have subtle behavioral phenotypes, some of which are conferred by aberrant dopamine signaling. Incubating mutant worms in liquid medium leads to swimming-induced paralysis. In the L1 larval stage, this phenotype is linked to lethality and cannot be rescued by a dop-3 null mutant. In contrast, mild paralysis occurring in the L4 larval stage is suppressed by dop-3, suggesting defects in dopaminergic signaling. In summary, we show that TSP-17 protects against neurodegeneration and has a role in modulating behaviors linked to dopamine signaling

The untapped potential of the gaming community: Narrative review.

Background: Video gamers are a population at heightened risk of developing obesity due to the sedentary nature of gaming, increased energy intake, and the disruption caused to their sleep. This increases their risk of developing a number of noncommunicable diseases. To date, research seeking to improve health behaviors has focused on developing novel video games to promote behavior change. Although positive results have emerged from this research, large-scale success has been limited due to the lack of transferability to mainstream games and the focus on children and adolescents. The gaming community has a number of unique aspects, which have received comparatively less attention than the development of new video games. Objective: The purpose of this paper is to highlight under-researched areas that have the potential to encourage positive health behavior among this community. Methods: A narrative review of the lay and academic literature was conducted to provide context and support to our claims that further research could be beneficial in this area. Results: Research has found that advertising can have implicit effects on an individual’s memories, which could influence later decisions. However, the effect of the exponential growth of in-game advertisements and the brand sponsorship of gaming events and professional gamers have not been explored in the gaming community. The possibility of using advertising techniques to encourage positive health behaviors within games or at these events has also not been explored. Research suggests that virtual communities can be effective at disseminating health information, but the efficacy of this needs to be explored using known community influencers within the gaming community. Conclusions: This paper has highlighted a number of potential avenues for the development of interventions within the gaming community. Further research must be conducted alongside game developers to ensure that any in-game developed interventions do not deter gameplay and gamers to ensure that potential approaches are acceptable