A Small Family of Elements with Long Inverted Repeats is Located Near Sites of Developmentally Regulated DNA Rearrangement in \u3cem\u3eTetrahymena thermophila\u3c/em\u3e

Extensive DNA rearrangement occurs during the development of the somatic macronucleus from the germ line micronucleus in ciliated protozoans. The micronuclear junctions and the macronuclear product of a developmentally regulated DNA rearrangement in Tetrahymena thermophila, Tlr1, have been cloned. The intrachromosomal rearrangement joins sequences that are separated by more than 13 kb in the micronucleus with the elimination of moderately repeated micronucleus-specific DNA sequences. There is a long, 825-bp, inverted repeat near the micronuclear junctions. The inverted repeat contains two different 19-bp tandem repeats. The 19-bp repeats are associated with each other and with DNA rearrangements at seven locations in the micronuclear genome. Southern blot analysis is consistent with the occurrence of the 19-bp repeats within pairs of larger repeated sequences. Another family member was isolated. The 19-mers in that clone are also in close proximity to a rearrangement junction. We propose that the 19-mers define a small family of developmentally regulated DNA rearrangements having elements with long inverted repeats near the junction sites. We discuss the possibility that transposable elements evolve by capture of molecular machinery required for essential cellular functions

Loop quantum cosmology of Bianchi type IX models

The loop quantum cosmology "improved dynamics" of the Bianchi type IX model are studied. The action of the Hamiltonian constraint operator is obtained via techniques developed for the Bianchi type I and type II models, no new input is required. It is shown that the big bang and big crunch singularities are resolved by quantum gravity effects. We also present the effective equations which provide modifications to the classical equations of motion due to quantum geometry effects.Comment: 20 page

Inhibition of protein geranylgeranylation induces apoptosis in synovial fibroblasts

Statins, competitive inhibitors of hydroxymethylglutaryl-CoA reductase, have recently been shown to have a therapeutic effect in rheumatoid arthritis (RA). In RA, synovial fibroblasts in the synovial lining, are believed to be particularly important in the pathogenesis of disease because they recruit leukocytes into the synovium and secrete angiogenesis-promoting molecules and proteases that degrade extracellular matrix. In this study, we show a marked reduction in RA synovial fibroblast survival through the induction of apoptosis when the cells were cultured with statins. Simvastatin was more effective in RA synovial fibroblasts than atorvastatin, and both statins were more potent on tumor necrosis factor-α-induced cells. In contrast, in osteoarthritis synovial fibroblasts, neither the statin nor the activation state of the cell contributed to the efficacy of apoptosis induction. Viability of statin-treated cells could be rescued by geranylgeraniol but not by farnesol, suggesting a requirement for a geranylgeranylated protein for synovial fibroblast survival. Phase partitioning experiments confirmed that in the presence of statin, geranylgeranylated proteins are redistributed to the cytoplasm. siRNA experiments demonstrated a role for Rac1 in synovial fibroblast survival. Western blotting showed that the activated phosphorylated form of Akt, a protein previously implicated in RA synovial fibroblast survival, was decreased by about 75%. The results presented in this study lend further support to the importance of elevated pAkt levels to RA synovial fibroblast survival and suggest that statins might have a beneficial role in reducing the aberrant pAkt levels in patients with RA. The results may also partly explain the therapeutic effect of atorvastatin in patients with RA

HIV-1 Coreceptor Activity of CCR5 and Its Inhibition by Chemokines: Independence from G Protein Signaling and Importance of Coreceptor Downmodulation

AbstractHIV-1 infection requires the presence of specific chemokine receptors on CD4+ target cells to enable the fusion reactions involved in virus entry. CCR5 is a major fusion coreceptor for macrophage-tropic HIV-1 isolates. HIV-1 entry and fusion are mediated by the viral envelope glycoprotein (Env) and are inhibited by CCR5 ligands, but the mechanisms are unknown. Here, we test the role of G protein signaling and CCR5 surface downmodulation by two separate approaches: direct inactivation of CCR5 signaling by mutagenesis and inactivation of Gi-type G proteins with pertussis toxin. A CCR5 mutant lacking the last 45 amino acids of the cytoplasmic C-terminus (CCR5306) was created that was expressed on transfected cells at levels comparable to cells expressing CCR5 and displayed normal chemokine binding affinity. CCR5 ligands induced calcium flux and receptor downmodulation in cells expressing CCR5, but not in cells expressing CCR5306. Nevertheless, CCR5 or CCR5306, when coexpressed with CD4, supported comparable HIV-1 Env-mediated cell fusion. Consistent with this, treatment of CCR5-expressing cells with pertussis toxin completely blocked ligand-induced transient calcium flux, but did not affect Env-mediated cell fusion or HIV-1 infection. Also, pertussis toxin did not block chemokine inhibition of Env-mediated cell fusion or HIV-1 infection. However, chemokines inhibited Env-mediated cell fusion less efficiently for CCR5306than for CCR5. We conclude that the C-terminal domain of CCR5 is critical for G protein signaling and receptor downmodulation from the surface, but that neither function is required for CCR5 fusion coreceptor activity. The contrasting phenotypes of CCR5 and CCR5306suggest that coreceptor downmodulation and direct blockage of Env interaction sites both contribute to chemokine inhibition of HIV-1 infection

Interaction of glycoprotein H of human herpesvirus 6 with the cellular receptor CD46.

Human herpesvirus 6 (HHV-6) employs the complement regulator CD46 (membrane cofactor protein) as a receptor for fusion and entry into target cells. Like other known herpesviruses, HHV-6 encodes multiple glycoproteins, several of which have been implicated in the entry process. In this report, we present evidence that glycoprotein H (gH) is the viral component responsible for binding to CD46. Antibodies to CD46 co-immunoprecipitated an approximately 110-kDa protein band specifically associated with HHV-6-infected cells. This protein was identified as gH by selective depletion with an anti-gH monoclonal antibody, as well as by immunoblot analysis with a rabbit hyperimmune serum directed against a gH synthetic peptide. In reciprocal experiments, a monoclonal antibody against HHV-6 gH was found to co-immunoprecipitate CD46. Studies using monoclonal antibodies directed against specific CD46 domains, as well as engineered constructs lacking defined CD46 regions, demonstrated a close correspondence between the CD46 domains involved in the interaction with gH and those previously shown to be critical for HHV-6 fusion (i.e. short consensus repeats 2 and 3)

Adaptive computation of gravitational waves from black hole interactions

We construct a class of linear partial differential equations describing general perturbations of non-rotating black holes in 3D Cartesian coordinates. In contrast to the usual approach, a single equation treats all radiative $\ell -m$ modes simultaneously, allowing the study of wave perturbations of black holes with arbitrary 3D structure, as would be present when studying the full set of nonlinear Einstein equations describing a perturbed black hole. This class of equations forms an excellent testbed to explore the computational issues of simulating black spacetimes using a three dimensional adaptive mesh refinement code. Using this code, we present results from the first fully resolved 3D solution of the equations describing perturbed black holes. We discuss both fixed and adaptive mesh refinement, refinement criteria, and the computational savings provided by adaptive techniques in 3D for such model problems of distorted black holes.Comment: 16 Pages, RevTeX, 13 figure

Event horizons and apparent horizons in spherically symmetric geometries

Spherical configurations that are very massive must be surrounded by apparent horizons. These in turn, when placed outside a collapsing body, must propagate outward with a velocity equal to the velocity of radially outgoing photons. That proves, within the framework of (1+3) formalism and without resorting to the Birkhoff theorem, that apparent horizons coincide with event horizons.Comment: 5 pages, plainte

Studying Underlying Characteristics of Computing and Engineering Student Success (SUCCESS) Survey

This survey was developed to measure underlying factors that may influence student success including personality, community, grit, thriving, identity, mindset, motivation, perceptions of faculty caring, stress, gratitude, self-control, mindfulness, and belongingness. We measure these underlying factors because each engineering and computing student admitted to a university has clear potential for academic and personal success in their undergraduate curriculum based upon admissions criteria. However, while some thrive academically, others struggle in a variety of ways. In our NSF-funded project (1626287/1626185/1626148), we posit that some collection of characteristics—apparently not visible on their admission applications and perhaps not related to their talent or intelligence—is an important piece of the student performance puzzle. We developed a survey to measure various non-cognitive and affective factors that we believe are important for student achievement, academically, personally, and professionally. These non-cognitive and affective factors are representative of multifaceted aspects of undergraduate student success in prior literature. Each of the constructs we chose had validity evidence from prior studies, some within an engineering population. An exploratory and confirmatory factor analysis have been conducted on the original list of items to develop this finalized survey (Scheidt et al., 2018). The survey takes approximately 30 minutes for students to complete. Scheidt, M., & Godwin, A., & Senkpeil, R. R., & Ge, J. S., & Chen, J., & Self, B. P., & Widmann, J. M., & Berger, E. J. (2018, June), Validity Evidence for the SUCCESS Survey: Measuring Non-Cognitive and Affective Traits of Engineering and Computing Students. Paper presented at 2018 ASEE Annual Conference & Exposition, Salt Lake City, Utah. https://peer.asee.org/3122