Synaptic Vesicle Docking: Sphingosine Regulates Syntaxin1 Interaction with Munc18

Consensus exists that lipids must play key functions in synaptic activity but precise mechanistic information is limited. Acid sphingomyelinase knockout mice (ASMko) are a suitable model to address the role of sphingolipids in synaptic regulation as they recapitulate a mental retardation syndrome, Niemann Pick disease type A (NPA), and their neurons have altered levels of sphingomyelin (SM) and its derivatives. Electrophysiological recordings showed that ASMko hippocampi have increased paired-pulse facilitation and post-tetanic potentiation. Consistently, electron microscopy revealed reduced number of docked vesicles. Biochemical analysis of ASMko synaptic membranes unveiled higher amounts of SM and sphingosine (Se) and enhanced interaction of the docking molecules Munc18 and syntaxin1. In vitro reconstitution assays demonstrated that Se changes syntaxin1 conformation enhancing its interaction with Munc18. Moreover, Se reduces vesicle docking in primary neurons and increases paired-pulse facilitation when added to wt hippocampal slices. These data provide with a novel mechanism for synaptic vesicle control by sphingolipids and could explain cognitive deficits of NPA patients

Upregulation of the cell-cycle regulator RGC-32 in Epstein-Barr virus-immortalized cells

Epstein-Barr virus (EBV) is implicated in the pathogenesis of multiple human tumours of lymphoid and epithelial origin. The virus infects and immortalizes B cells establishing a persistent latent infection characterized by varying patterns of EBV latent gene expression (latency 0, I, II and III). The CDK1 activator, Response Gene to Complement-32 (RGC-32, C13ORF15), is overexpressed in colon, breast and ovarian cancer tissues and we have detected selective high-level RGC-32 protein expression in EBV-immortalized latency III cells. Significantly, we show that overexpression of RGC-32 in B cells is sufficient to disrupt G2 cell-cycle arrest consistent with activation of CDK1, implicating RGC-32 in the EBV transformation process. Surprisingly, RGC-32 mRNA is expressed at high levels in latency I Burkitt's lymphoma (BL) cells and in some EBV-negative BL cell-lines, although RGC-32 protein expression is not detectable. We show that RGC-32 mRNA expression is elevated in latency I cells due to transcriptional activation by high levels of the differentially expressed RUNX1c transcription factor. We found that proteosomal degradation or blocked cytoplasmic export of the RGC-32 message were not responsible for the lack of RGC-32 protein expression in latency I cells. Significantly, analysis of the ribosomal association of the RGC-32 mRNA in latency I and latency III cells revealed that RGC-32 transcripts were associated with multiple ribosomes in both cell-types implicating post-initiation translational repression mechanisms in the block to RGC-32 protein production in latency I cells. In summary, our results are the first to demonstrate RGC-32 protein upregulation in cells transformed by a human tumour virus and to identify post-initiation translational mechanisms as an expression control point for this key cell-cycle regulator

Insidious procedures: diversity awards legitimize unfair organizational practices

This is the author's version of an article subsequently published in Social Justice Research in final format. The final publication is available at Springer via http://dx.doi.org/10.1007/s11211-015-0240-zDoes the presence (versus absence) of an organizational diversity award increase the perceived fairness of biased personnel procedures? Participants examined fair or unfair personnel procedures at a company that had received a diversity award or an award unrelated to diversity. When the company had received a diversity award (versus a control award), participants perceived the unfair personnel procedure as fairer for minorities, and White participants were more supportive of enacting the biased procedure. These findings suggest that organizations perceived as successfully supporting diversity might be afforded particular legitimacy to enact policies and procedures that disadvantage the very groups they are perceived as valuing.National Science Foundatio

Characteristic Evolution and Matching

I review the development of numerical evolution codes for general relativity based upon the characteristic initial value problem. Progress in characteristic evolution is traced from the early stage of 1D feasibility studies to 2D axisymmetric codes that accurately simulate the oscillations and gravitational collapse of relativistic stars and to current 3D codes that provide pieces of a binary black hole spacetime. Cauchy codes have now been successful at simulating all aspects of the binary black hole problem inside an artificially constructed outer boundary. A prime application of characteristic evolution is to extend such simulations to null infinity where the waveform from the binary inspiral and merger can be unambiguously computed. This has now been accomplished by Cauchy-characteristic extraction, where data for the characteristic evolution is supplied by Cauchy data on an extraction worldtube inside the artificial outer boundary. The ultimate application of characteristic evolution is to eliminate the role of this outer boundary by constructing a global solution via Cauchy-characteristic matching. Progress in this direction is discussed.Comment: New version to appear in Living Reviews 2012. arXiv admin note: updated version of arXiv:gr-qc/050809

Lattice Boltzmann simulations of soft matter systems

This article concerns numerical simulations of the dynamics of particles immersed in a continuum solvent. As prototypical systems, we consider colloidal dispersions of spherical particles and solutions of uncharged polymers. After a brief explanation of the concept of hydrodynamic interactions, we give a general overview over the various simulation methods that have been developed to cope with the resulting computational problems. We then focus on the approach we have developed, which couples a system of particles to a lattice Boltzmann model representing the solvent degrees of freedom. The standard D3Q19 lattice Boltzmann model is derived and explained in depth, followed by a detailed discussion of complementary methods for the coupling of solvent and solute. Colloidal dispersions are best described in terms of extended particles with appropriate boundary conditions at the surfaces, while particles with internal degrees of freedom are easier to simulate as an arrangement of mass points with frictional coupling to the solvent. In both cases, particular care has been taken to simulate thermal fluctuations in a consistent way. The usefulness of this methodology is illustrated by studies from our own research, where the dynamics of colloidal and polymeric systems has been investigated in both equilibrium and nonequilibrium situations.Comment: Review article, submitted to Advances in Polymer Science. 16 figures, 76 page

Quasi-Normal Modes of Stars and Black Holes

Perturbations of stars and black holes have been one of the main topics of relativistic astrophysics for the last few decades. They are of particular importance today, because of their relevance to gravitational wave astronomy. In this review we present the theory of quasi-normal modes of compact objects from both the mathematical and astrophysical points of view. The discussion includes perturbations of black holes (Schwarzschild, Reissner-Nordstr\"om, Kerr and Kerr-Newman) and relativistic stars (non-rotating and slowly-rotating). The properties of the various families of quasi-normal modes are described, and numerical techniques for calculating quasi-normal modes reviewed. The successes, as well as the limits, of perturbation theory are presented, and its role in the emerging era of numerical relativity and supercomputers is discussed.Comment: 74 pages, 7 figures, Review article for "Living Reviews in Relativity

Resilience in education: An example from primary school in Fiji and technical vocational education and training

In the Pacific, the capacity of curriculum writers for integrating the content of climate change into their curricula and/or taught Resilience [Climate Change Adaptation (CCA) & Disaster Risk Reduction (DRR)] in education is limited. This paper described the findings of a 2018 study on the integration of climate change into primary and secondary schools’ curricula and taught resilience in education in TVET. It involves teachers (n = 30) from Kadavu and Levuka islands, curriculum writers and editors from the Ministry of Education, GIZ, SPC, and USP—in Fiji. An exploratory design was used to explore the curricula for Fiji and the EU PacTVET project at SPC. Information was collected from workshops and training events, interviews and project documents. Using BEKA (Benchmarking, Evidencing, Knowing, Applying) and the concept of ako (e.g. to study or educate), a model of climate change and resilience in education was designed as part of this research to help Pacific schools with their curricula. These results indicate how behavioural changes may shape Resilience, thus placing them in a better position to achieve the UNFCCC, the SDGs, the Sendai Framework and the Framework for Resilient Development in the Pacific (FRDP) targets and objectives by 2030 and beyond

The speed of parietal theta frequency drives visuospatial working memory capacity

The speed of theta brain oscillatory activity is thought to play a key role in determining working memory (WM) capacity. Individual differences in the length of a theta cycle (ranging between 4 and 7 Hz) might determine how many gamma cycles (>30 Hz) can be nested into a theta wave. Gamma cycles are thought to represent single memory items; therefore, this interplay could determine individual memory capacity. We directly tested this hypothesis by means of parietal transcranial alternating current stimulation (tACS) set at slower (4 Hz) and faster (7 Hz) theta frequencies during a visuospatial WM paradigm. Accordingly, we found that 4-Hz tACS enhanced WM capacity, while 7-Hz tACS reduced WM capacity. Notably, these effects were found only for items presented to the hemifield contralateral to the stimulation site. This provides causal evidence for a frequency-dependent and spatially specific organization of WM storage, supporting the theta–gamma phase coupling theory of WM capacity

Harmful lifestyles' clustering among sexually active in-school adolescents in Zambia

<p>Abstract</p> <p>Background</p> <p>HIV is a leading cause of morbidity and mortality in Zambia. Like many other African nations with high HIV burden, heterosexual intercourse is the commonest mode of HIV spread. The estimation of prevalence and factors associated with sexual intercourse among in-school adolescents has potential to inform public health interventions aimed at reducing the burden of sex-related diseases in Zambia.</p> <p>Methods</p> <p>We carried out secondary analysis of the Zambia Global School-Based Health Survey (GSHS) 2004; a cross sectional survey that aims to study health-related behaviors among in-school adolescents. We estimated frequencies of relevant socio-demographic variables. The associations between selected explanatory variables and self-reported history of sexual intercourse within the last 12 months were assessed using logistic regression analysis.</p> <p>Results</p> <p>Data from 2136 in-school adolescents who participated in the Zambia Global School-Based Health Survey of 2004 were available for analysis. Out of these respondents, 13.4% reported that they had sexual intercourse in the past 12 months prior to the survey; 16.4% and 9.7% among males and females respectively. In multivariable logistic regression analysis, with age less than 15 years as the referent the adjusted odds ratio (AOR) of having engaged in sexual intercourse in adolescents of age 15 years, and those aged 16 years or more were 1.06 (95% CI 1.03–1.10) and 1.74 (95% 1.70–1.79) respectively. Compared to adolescents who had no close friends, adolescents who had one close friend were more likely to have had sexual intercourse, AOR = 1.28 (95% CI 1.24–1.32). Compared to adolescents who were not supervised by their parents, adolescents who were rarely or sometimes supervised by their parents were likely to have had sexual intercourse, and adolescents who were most of the time/always supervised by their parents were less likely to have had sexual intercourse; AORs 1.26 (95% CI 1.23–1.26) and 0.92 (95% CI 0.90–0.95) respectively. Compared to adolescents who did not smoke dagga, adolescents who smoked dagga 1 or 2 times, and those who smoked dagga 3 or more times in their lifetime were 70% and 25% more likely to have had sexual intercourse, respectively. Adolescents who drank alcohol in 1 or 2 days, and those who took alcohol in 3 or more days in a month preceding the survey were 12% and 9% more likely to have had sexual intercourse, respectively, compared to adolescents who did not drink alcohol in the 30 days prior to the survey. Furthermore, adolescents who had been drunk 1 or 2 times, and who had been drunk 3 or more times in a life time were 14% and 13% more likely to have had sexual intercourse compared to those who have never been drunk in their lifetime.</p> <p>Conclusion</p> <p>We identified a constellation of potentially harmful behaviours among adolescents in Zambia. Public health interventions aimed at reducing prevalence of sexual intercourse may be designed and implemented in a broader sense having recognized that sexually active adolescents may also be exposed to other problem behaviours.</p