DNA methylation and DNA methyltransferases

The prevailing views as to the form, function, and regulation of genomic methylation patterns have their origin many years in the past, at a time when the structure of the mammalian genome was only dimly perceived, when the number of protein-encoding mammalian genes was believed to be at least five times greater than the actual number, and when it was not understood that only ~10% of the genome is under selective pressure and likely to have biological function. We use more recent findings from genome biology and whole-genome methylation profiling to provide a reappraisal of the shape of genomic methylation patterns and the nature of the changes that they undergo during gametogenesis and early development. We observe that the sequences that undergo deep changes in methylation status during early development are largely sequences without regulatory function. We also discuss recent findings that begin to explain the remarkable fidelity of maintenance methylation. Rather than a general overview of DNA methylation in mammals (which has been the subject of many reviews), we present a new analysis of the distribution of methylated CpG dinucleotides across the multiple sequence compartments that make up the mammalian genome, and we offer an updated interpretation of the nature of the changes in methylation patterns that occur in germ cells and early embryos. We discuss the cues that might designate specific sequences for demethylation or de novo methylation during development, and we summarize recent findings on mechanisms that maintain methylation patterns in mammalian genomes. We also describe the several human disorders, each very different from the other, that are caused by mutations in DNA methyltransferase genes

THE INFLUENCE OF EFFECTIVE MASS ON IMPACT FORCE AND ACCELERATION

Accelerometry is often used as a means to quantify the osteogenic or injury potential of impacts. This paper uses a series of four experiments to demonstrate theoretically, mechanically, and experimentally that increasing the effective mass of an impact can lead to an increase in impact force with a corresponding decrease in acceleration. The four experiments included: 1) mass spring models, 2) shoe impact testing, 3) cadaver impact simulation, and 4) an in vivo study manipulating knee angle during running. Results were consistent with the aim, illustrating a limitation for the use of accelerometers for impact assessment. In order to appropriately interpret the results from accelerometry it is necessary to quantify the effective mass of the impact. Failure to account for the influence of effective mass can lead to erroneous conclusions about impact severity

Moderated Mediation Analysis: A Review and Application to School Climate Research

Moderated mediation analysis is a valuable technique for assessing whether an indirect effect is conditional on values of a moderating variable. We review the basis of moderation and mediation and their integration into a combined model of moderated mediation within a regression framework. Thereafter, an analytic and interpretive illustration of the technique is provided in the context of a substantive school climate research question. The illustration is based on a sample of 318 high schools that examines whether school-wide student engagement mediates the association between the prevalence of teasing and bullying (PTB) and academic achievement on a state-mandated reading exam; and whether this indirect effect was moderated by student perceptions of teacher support

Inspiring Change Agents through Technology

A capstone submitted in partial fulfillment of the Requirements for the degree of Doctor of Education in the College of Education at Morehead State University by Edith J. Bostic and Timothy R. Edwards Gallipolis on April 1, 2016

Non-Perturbative Improvement of the Anisotropic Wilson QCD Action

We describe the first steps in the extension of the Symanzik O($a$) improvement program for Wilson-type quark actions to anisotropic lattices, with a temporal lattice spacing smaller than the spatial one. This provides a fully relativistic and computationally efficient framework for the study of heavy quarks. We illustrate our method with accurate results for the quenched charmonium spectrum.Comment: LATTICE98(improvement), 3 pages, 4 figure

Abnormal X chromosome inactivation and sex-specific gene dysregulation after ablation of FBXL10

BACKGROUND: Almost all CpG-rich promoters in the mammalian genome are bound by the multidomain FBXL10 protein (also known as KDM2B, JHDM1B, CXXC2, and NDY1). FBXL10 is expressed as two isoforms: FBXL10-1, a longer form that contains an N-terminal histone demethylase domain with C-terminal F-box, CXXC, PHD, RING, and leucine-rich repeat domains, and FBXL10-2, a shorter form that initiates at an alternative internal exon and which lacks the histone demethylase domain but retains all other annotated domains. Selective deletion of Fbxl10-1 had been reported to produce a low penetrance and variable phenotype; most of the mutant animals were essentially normal. We constructed mutant mouse strains that were either null for Fbxl10-2 but wild type for Fbxl10-1 or null for both Fbxl10-1 and Fbxl10-2. RESULTS: Deletion of Fbxl10-2 (in a manner that does not perturb expression of Fbxl10-1) produced a phenotype very different from the Fbxl10-1 mutant, with craniofacial abnormalities, neural tube defects, and increased lethality, especially in females. Mutants that lacked both FBXL10-1 and FBXL10-2 showed embryonic lethality and even more extreme sexual dimorphism, with more severe gene dysregulation in mutant female embryos. X-linked genes were most severely dysregulated, and there was marked overexpression of Xist in mutant females although genes that encode factors that bind to Xist RNA were globally downregulated in mutant female as compared to male embryos. CONCLUSIONS: FBXL10 is the first factor shown to be required both for the normal expression and function of the Xist gene and for normal expression of proteins that associate with Xist RNA; it is proposed that FBXL10 coordinates the expression of Xist RNA with proteins that associate with this RNA. The function of FBXL10 is largely independent of the histone demethylase activity of the long form of the protein. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13072-016-0069-1) contains supplementary material, which is available to authorized users

The Anisotropic Wilson Gauge Action

Anisotropic lattices, with a temporal lattice spacing smaller than the spatial one, allow precision Monte Carlo calculations of problems that are difficult to study otherwise: heavy quarks, glueballs, hybrids, and high temperature thermodynamics, for example. We here perform the first step required for such studies with the (quenched) Wilson gauge action, namely, the determination of the renormalized anisotropy $\xi$ as a function of the bare anisotropy $\xi_0$ and the coupling. By, essentially, comparing the finite-volume heavy quark potential where the quarks are separated along a spatial direction with that where they are separated along the time direction, we determine the relation between $\xi$ and $\xi_0$ to a fraction of 1% for weak and to 1% for strong coupling. We present a simple parameterization of this relation for $1\leq \xi \leq 6$ and $5.5 \leq \beta \leq \infty$, which incorporates the known one-loop result and reproduces our non-perturbative determinations within errors. Besides solving the problem of how to choose the bare anisotropies if one wants to take the continuum limit at fixed renormalized anisotropy, this parameterization also yields accurate estimates of the derivative $\partial\xi_0/\partial\xi$ needed in thermodynamic studies.Comment: 24 pages, LaTeX, 15 ps figures (added high statistics simulations confirming our results; to appear in Nucl. Phys. B

Effects of Stride Length and Running Mileage on a Probabilistic Stress Fracture Model

The fatigue life of bone is inversely related to strain magnitude. Decreasing stride length is a potential mechanism of strain reduction during running. If stride length is decreased, the number of loading cycles will increase for a given mileage. It is unclear if increased loading cycles are detrimental to skeletal health despite reductions in strain. Purpose: To determine the effects of stride length and running mileage on the probability of tibial stress fracture. Methods: Ten male subjects ran overground at their preferred running velocity during two conditions: preferred stride length and 10% reduction in preferred stride length. Force platform and kinematic data were collected concurrently. A combination of experimental and musculoskeletal modeling techniques was used to determine joint contact forces acting on the distal tibia. Peak instantaneous joint contact forces served as inputs to a finite element model to estimate tibial strains during stance. Stress fracture probability for stride length conditions and three running mileages (3, 5, and 7 miles·d−1) were determined using a probabilistic model of bone damage, repair, and adaptation. Differences in stress fracture probability were compared between conditions using a 2 × 3 repeated-measures ANOVA. Results: The main effects of stride length (P = 0.017) and running mileage (P = 0.001) were significant. Reducing stride length decreased the probability of stress fracture by 3% to 6%. Increasing running mileage increased the probability of stress fracture by 4% to 10%. Conclusions: Results suggest that strain magnitude plays a more important role in stress fracture development than the total number of loading cycles. Runners wishing to decrease their probability for tibial stress fracture may benefit from a 10% reduction in stride length

Suitability of a GPS Collar for Grazing Studies

The traditional means of tracking animal location in a field is by visual observation. Not only is this method labor intensive, it is also prone to error as the observer can alter cattle movement, observation periods are often too short to obtain confidence in general daily behavior patterns, and observer fatigue becomes an issue. In the 1990s, the University of Kentucky began using GPS collars on cattle to track their position with the goal of incorporating this information into cattle management practices. One of the key unanswered questions regarding the GPS collars is the accuracy of the position data recorded by the collar. The objective of this work was to assess the capabilities and limitations of using GPS collars to track animal movement in grazed watersheds. Static tests were conducted in an open field, under trees, and near fence lines to ascertain the impacts of various field features on collar performance. Dynamic tests were carried out to examine the errors associated with the collars while operated under real-world conditions. Results from these tests indicate that the collars generally provide data with horizontal accuracies of 4 to 5 m. This information will assist researchers in the development of experiments based on collar capabilities and limitations