Oncometabolites: tailoring our genes

Increased glucose metabolism in cancer cells is a phenomenon that has been known for over 90 years, allowing maximal cell growth through faster ATP production and redistribution of carbons towards nucleotide, protein and fatty acid synthesis. Recently, metabolites that can promote tumorigeneis by altering the epigenome have been identified. These ‘oncometabolites’ include the tricarboxylic acid cycle metabolites succinate and fumarate, whose levels are elevated in rare tumours with succinate dehydrogenase and fumarate hydratase mutations, respectively. 2-Hydroxyglutarate is another oncometabolite; it is produced de novo as a result of the mutation of isocitrate dehydrogenase, and is commonly found in gliomas and acute myeloid leukaemia. Interestingly, the structural similarity of these oncometabolites to their precursor metabolite, α-ketoglutarate, explains the tumorigenic potential of these metabolites, by competitive inhibition of a superfamily of enzymes called the α-ketoglutarate-dependent dioxygenases. These enzymes utilize α-ketoglutarate as a cosubstrate, and are involved in fatty acid metabolism, oxygen sensing, collagen biosynthesis, and modulation of the epigenome. They include enzymes that are involved in regulating gene expression via DNA and histone tail demethylation. In this review, we will focus on the link between metabolism and epigenetics, and how we may target oncometabolite-induced tumorigenesis in the future

Characterization of Knots and Links Arising From Site-specific Recombination on Twist Knots

We develop a model characterizing all possible knots and links arising from recombination starting with a twist knot substrate, extending previous work of Buck and Flapan. We show that all knot or link products fall into three well-understood families of knots and links, and prove that given a positive integer $n$, the number of product knots and links with minimal crossing number equal to $n$ grows proportionally to $n^5$. In the (common) case of twist knot substrates whose products have minimal crossing number one more than the substrate, we prove that the types of products are tightly prescribed. Finally, we give two simple examples to illustrate how this model can help determine previously uncharacterized experimental data.Comment: 32 pages, 7 tables, 27 figures, revised: figures re-arranged, and minor corrections. To appear in Journal of Physics

Targeted industry engagement was ‘spot-on’ for pasture dieback

Pasture Dieback (PD) is a condition that has been sporadically affecting sown pasture production in high rainfall zones of eastern Queensland for about 100 years. In recent years, there has been a large increase in the pasture species and area affected by PD. Affected pastures display progressive symptoms of stress which results in otherwise unexplained death, during what should be high growth periods. Currently, pathogenic organisms are the focus of multiple diagnostic research projects (Buck et. al 2021). Our objective was to increase graziers’ capability to accurately identify PD and implement appropriate management practices by conducting an industry engagement program

Folding model analysis of alpha radioactivity

Radioactive decay of nuclei via emission of $\alpha$ particles has been studied theoretically in the framework of a superasymmetric fission model using the double folding (DF) procedure for obtaining the $\alpha$-nucleus interaction potential. The DF nuclear potential has been obtained by folding in the density distribution functions of the $\alpha$ nucleus and the daughter nucleus with a realistic effective interaction. The M3Y effective interaction has been used for calculating the nuclear interaction potential which has been supplemented by a zero-range pseudo-potential for exchange along with the density dependence. The nuclear microscopic $\alpha$-nucleus potential thus obtained has been used along with the Coulomb interaction potential to calculate the action integral within the WKB approximation. This subsequently yields microscopic calculations for the half lives of $\alpha$ decays of nuclei. The density dependence and the exchange effects have not been found to be very significant. These calculations provide reasonable estimates for the lifetimes of $\alpha$ radioactivity of nuclei.Comment: 7 pages including 1 figur

Physical demand but not dexterity is associated with motor flexibility during rapid reaching in healthy young adults

Healthy humans are able to place light and heavy objects in small and large target locations with remarkable accuracy. Here we examine how dexterity demand and physical demand affect flexibility in joint coordination and end-effector kinematics when healthy young adults perform an upper extremity reaching task. We manipulated dexterity demand by changing target size and physical demand by increasing external resistance to reaching. Uncontrolled manifold analysis was used to decompose variability in joint coordination patterns into variability stabilizing the end-effector and variability de-stabilizing the end-effector during reaching. Our results demonstrate a proportional increase in stabilizing and de-stabilizing variability without a change in the ratio of the two variability components as physical demands increase. We interpret this finding in the context of previous studies showing that sensorimotor noise increases with increasing physical demands. We propose that the larger de-stabilizing variability as a function of physical demand originated from larger sensorimotor noise in the neuromuscular system. The larger stabilizing variability with larger physical demands is a strategy employed by the neuromuscular system to counter the de-stabilizing variability so that performance stability is maintained. Our findings have practical implications for improving the effectiveness of movement therapy in a wide range of patient groups, maintaining upper extremity function in old adults, and for maximizing athletic performance

alpha-nucleus potentials for the neutron-deficient p nuclei

alpha-nucleus potentials are one important ingredient for the understanding of the nucleosynthesis of heavy neutron-deficient p nuclei in the astrophysical gamma-process where these p nuclei are produced by a series of (gamma,n), (gamma,p), and (gamma,alpha) reactions. I present an improved alpha-nucleus potential at the astrophysically relevant sub-Coulomb energies which is derived from the analysis of alpha decay data and from a previously established systematic behavior of double-folding potentials.Comment: 6 pages, 3 figures, accepted for publication in Phys. Rev.

Relationships between the multiplication of chronic bee-paralysis virus and its associate particle

The amounts of chronic bee-paralysis virus associate (CPVA) produced in bees injected with purified chronic bee-paralysis virus (CPV) were negatively associated with the amounts, lengths of particles and maximum sedimentation coefficients of CPV. The ratio of the amounts of CPV/CPVA varied widely between individuals, but more CPVA was produced and CPV/CPVA ratios were smaller when CPVA was injected with the CPV preparations than when the latter were injected alone. The multiplication of the RNAs of CPV and of CPVA were also negatively correlated. The nature of the relationship between CPV and CPVA and the packaging arrangement of CPV RNA are discussed

Space construction system analysis. Part 2: Construction analysis

The construction methods specific to the end to end construction process for building the ETVP in low Earth orbit, using the space shuttle orbiter as a construction base, are analyzed. The analyses concerned three missions required to build the basic platform. The first mission involved performing the fabrication of beams in space and assembling the beams into a basic structural framework. The second mission was to install the forward support structure and aft support structure, the forward assembly, and a TT&C antenna. The third mission plan was to complete the construction of the platform and activate it to begin operations in low Earth orbit. The integration of the activities for each mission is described along with the construction requirements and construction logic

Evidence for transfer followed by breakup in 7Li + 65Cu

The observation of a large cross-section for the alpha + d channel compared to breakup into the alpha + t channel from an exclusive measurement for the 7Li+65Cu system at 25 MeV is presented. A detailed analysis of the angular distribution using coupled channels Born approximation calculations has provided clear evidence that the observed alpha + d events arise from a two step process, i.e. direct transfer to the 2.186 MeV (3+) resonance in the alpha + d continuum of 6Li followed by breakup, and are not due to final state interaction effects.Comment: 12 pages, 3 figures, To be published in Phys. Letts.

Zero-modes of Non-Abelian Solitons in Three Dimensional Gauge Theories

We study non-Abelian solitons of the Bogomol'nyi type in N=2 (d=2+1) supersymmetric Chern-Simons (CS) and Yang-Mills (YM) theory with a generic gauge group. In CS theory, we find topological, non-topological and semi-local (non-)topological vortices of non-Abelian kinds in unbroken, broken and partially broken vacua. We calculate the number of zero-modes using an index theorem and then we apply the moduli matrix formalism to realize the moduli parameters. For the topological solitons we exhaust all the moduli while we study several examples of the non-topological and semi-local solitons. We find that the zero-modes of the topological solitons are governed by the moduli matrix H_0 only and those of the non-topological solitons are governed by both H_0 and the gauge invariant field \Omega. We prove local uniqueness of the master equation in the YM case and finally, compare all results between the CS and YM theories.Comment: 54 pages, 1 figur