An antigen encoded by the latency-associated transcript in neuronal cell cultures latently infected with herpes simplex virus type 1.

During latent infection of neurons with herpes simplex virus type 1, viral transcription is restricted to the latency-associated transcripts (LATs). These RNAs contain open reading frames, but detection of a protein encoded by the LATs has not been reported. We used immunocytochemical techniques to demonstrate that an antiserum directed against a bacterially expressed fusion protein containing part of a LAT-encoded polypeptide recognized an antigen present in primary neurons latently infected in vitro. This antigen (called LAA, for latency-associated antigen) was not detected in mock-infected neurons, in productively infected Vero cells, or in neurons latently infected with a mutant virus carrying a deletion in the LAT gene. By Western immunoblot analysis, we demonstrated the presence of a protein with an apparent molecular mass of 80 kDa recognized by the anti-LAA antiserum in latently infected neurons

The deubiquitylase USP31 controls the Chromosomal Passenger Complex and spindle dynamics

We have identified USP31 as a microtubule and centrosome associated deubiquitylase, depletion of which leads to an increase in individual cell mass and defective proliferation. We have examined its dynamics and impact during mitosis. GFP-USP31 associates with the mitotic and central spindles, its levels are increased 2-3-fold in prometaphase compared to asynchronous cells and it is dynamically phosphorylated in a CDK1 dependent manner. We find that USP31 depleted cells display altered spindle morphology and chromosomal segregation errors, whilst stable expression of a catalytically inactive form of USP31 leads to polyploidy. At prometaphase, levels of multiple CPC components are destabilised, most prominently INCENP. Under anaphase conditions, depletion of USP31 impairs the translocation of both endogenous and ectopically expressed INCENP to the spindle mid-zone, whilst expression of catalytically inactive USP31 results in multiple ectopic cleavage furrows. In summary, our data indicate a multifaceted regulatory role for USP31 during mitosis, with a profound impact on chromosomal passenger complex abundance, dynamics and function

Efficacy of a Non-Hypercalcemic Vitamin-D2 Derived Anti-Cancer Agent (MT19c) and Inhibition of Fatty Acid Synthesis in an Ovarian Cancer Xenograft Model

BACKGROUND:Numerous vitamin-D analogs exhibited poor response rates, high systemic toxicities and hypercalcemia in human trials to treat cancer. We identified the first non-hypercalcemic anti-cancer vitamin D analog MT19c by altering the A-ring of ergocalciferol. This study describes the therapeutic efficacy and mechanism of action of MT19c in both in vitro and in vivo models. METHODOLOGY/PRINCIPAL FINDING:Antitumor efficacy of MT19c was evaluated in ovarian cancer cell (SKOV-3) xenografts in nude mice and a syngenic rat ovarian cancer model. Serum calcium levels of MT19c or calcitriol treated animals were measured. In-silico molecular docking simulation and a cell based VDR reporter assay revealed MT19c-VDR interaction. Genomewide mRNA analysis of MT19c treated tumors identified drug targets which were verified by immunoblotting and microscopy. Quantification of cellular malonyl CoA was carried out by HPLC-MS. A binding study with PPAR-Y receptor was performed. MT19c reduced ovarian cancer growth in xenograft and syngeneic animal models without causing hypercalcemia or acute toxicity. MT19c is a weak vitamin-D receptor (VDR) antagonist that disrupted the interaction between VDR and coactivator SRC2-3. Genome-wide mRNA analysis and western blot and microscopy of MT19c treated xenograft tumors showed inhibition of fatty acid synthase (FASN) activity. MT19c reduced cellular levels of malonyl CoA in SKOV-3 cells and inhibited EGFR/phosphoinositol-3kinase (PI-3K) activity independently of PPAR-gamma protein. SIGNIFICANCE:Antitumor effects of non-hypercalcemic agent MT19c provide a new approach to the design of vitamin-D based anticancer molecules and a rationale for developing MT19c as a therapeutic agent for malignant ovarian tumors by targeting oncogenic de novo lipogenesis

And now for something completely different? The impact of group membership on perceptions of creativity

Authors' draft; final version published in Social influence; available online at http://www.informaworld.com/ Embargo until 1 July 2010A wealth of historical, cultural, and biographical evidence points to the fact that there is considerable variation in different people's judgments of creative products. What is creative to one person is deviant to another, and creative efforts often fail to be given the enthusiastic reception that their creators anticipate and think they deserve. Unpacking the roots of these discrepancies, this paper develops an analysis of creativity that is informed by the social identity approach. This analysis is supported by a review of previous research that points to the way in which perceptions of creativity are structured by both self-categorization and social norms (and their interaction). Further support for the analysis is provided by two experiments (Ns = 100, 125) which support the hypothesis that ingroup products are perceived to be more creative than those of outgroups independently of other factors with which group membership is typically correlated in the world at large (e.g., quality). The studies also indicate that this pattern is not simply a manifestation of generic ingroup bias since judgments of creativity diverge from those of both likeability (Experiment 1) and beauty (Experiment 2). The theoretical and practical significance of these findings is discussed with particular reference to innovation resistance and the “not invented here” syndrome.This research was supported by a grant from the Economic and Social Research Council (RES-062-23-0135)

Factors Associated With Sexual Coercion in a Representative Sample of Men in Australian Prisons

Very little research has focused on men or prisoners as victims of sexual violence. This study provides the first population-based analysis of factors associated with sexual coercion of men in Australian prisons, and the first to use a computer-assisted telephone interview to collect this information in a prison setting. A random sample of men in New South Wales and Queensland prisons were surveyed using computer-assisted telephone interviewing. We asked participants about sexual coercion, defined as being forced or frightened into doing something sexually that was unwanted while in prison. Associations between sexual coercion in prison and sociodemographics, sexual coercion history outside of prison, and prison-related factors were examined. Logistic regression was used to estimate adjusted odds ratios in examining factors associated with sexual coercion in prisons. Of 2626 eligible men, 2000 participated. Participants identifying as non-heterosexual and those with a history of sexual coercion outside prison were found to be most at risk. Those in prison for the first time and those who had spent more than 5 years in prison ever were also more likely to report sexual coercion. Although prison policies and improving prison officer training may help address immediate safety and health concerns of those at risk, given the sensitivity of the issue and likely under-reporting to correctional staff, community-based organizations and prisoner peer-based groups arguably have a role too in providing both preventive and trauma-focused support

Fossil energy in economic growth: A study of the energy direction of technical change, 1950-2012

Climate change mitigation challenges national economies to increase productivity while reducing fossil energy consumption. Fossil energy-saving technical change has been assumed to accomplish this, yet empirical evidence is scarce. This paper investigates the long-run relationship between the rate and direction of technical change with respect to fossil energy and labor in the world economy. Growth rates of labor productivity and the fossil energy-labor ratio are examined for more than 95 of world output between 1950 and 2012. The average elasticity of the energy-labor ratio with respect to labor productivity is close to one, implying highly energy-using technical change, but no trade-o between factor productivity growth rates. This stylized fact suggests the importance of a cheap, abundant energy supply for robust global growth, and a more important role for renewable energy. Integrated assessment models do not incorporate this restriction which may result in poorly speci ed baseline scenarios

Supersingular isogeny graphs and endomorphism rings:reductions and solutions

In this paper, we study several related computational problems for supersingular elliptic curves, their isogeny graphs, and their endomorphism rings. We prove reductions between the problem of path finding in the -isogeny graph, computing maximal orders isomorphic to the endomorphism ring of a supersingular elliptic curve, and computing the endomorphism ring itself. We also give constructive versions of Deuring’s correspondence, which associates to a maximal order in a certain quaternion algebra an isomorphism class of supersingular elliptic curves. The reductions are based on heuristics regarding the distribution of norms of elements in quaternion algebras. We show that conjugacy classes of maximal orders have a representative of polynomial size, and we define a way to represent endomorphism ring generators in a way that allows for efficient evaluation at points on the curve. We relate these problems to the security of the Charles-Goren-Lauter hash function. We provide a collision attack for special but natural parameters of the hash function and prove that for general parameters its preimage and collision resistance are also equivalent to the endomorphism ring computation problem.SCOPUS: cp.kinfo:eu-repo/semantics/published37th Annual International Conference on the Theory and Applications of Cryptographic Techniques, EUROCRYPT 2018; Tel Aviv; Israel; 29 April 2018 through 3 May 2018ISBN: 978-331978371-0Volume Editors: Nielsen J.B.Rijmen V.Publisher: Springer Verla