Promissory Note, 21 October 1842

https://egrove.olemiss.edu/aldrichcorr_b/1042/thumbnail.jp

The Role of Molecular Microtubule Motors and the Microtubule Cytoskeleton in Stress Granule Dynamics

Stress granules (SGs) are cytoplasmic foci that appear in cells exposed to stress-induced translational inhibition. SGs function as a triage center, where mRNAs are sorted for storage, degradation, and translation reinitiation. The underlying mechanisms of SGs dynamics are still being characterized, although many key players have been identified. The main components of SGs are stalled 48S preinitiation complexes. To date, many other proteins have also been found to localize in SGs and are hypothesized to function in SG dynamics. Most recently, the microtubule cytoskeleton and associated motor proteins have been demonstrated to function in SG dynamics. In this paper, we will discuss current literature examining the function of microtubules and the molecular microtubule motors in SG assembly, coalescence, movement, composition, organization, and disassembly

Mitotic slippage in non-cancer cells induced by a microtubule disruptor, disorazole C1

<p>Abstract</p> <p>Background</p> <p>Disorazoles are polyene macrodiolides isolated from a myxobacterium fermentation broth. Disorazole C₁was newly synthesized and found to depolymerize microtubules and cause mitotic arrest. Here we examined the cellular responses to disorazole C₁in both non-cancer and cancer cells and compared our results to vinblastine and taxol.</p> <p>Results</p> <p>In non-cancer cells, disorazole C₁induced a prolonged mitotic arrest, followed by mitotic slippage, as confirmed by live cell imaging and cell cycle analysis. This mitotic slippage was associated with cyclin B degradation, but did not require p53. Four assays for apoptosis, including western blotting for poly(ADP-ribose) polymerase cleavage, microscopic analyses for cytochrome C release and annexin V staining, and gel electrophoresis examination for DNA laddering, were conducted and demonstrated little induction of apoptosis in non-cancer cells treated with disorazole C₁. On the contrary, we observed an activated apoptotic pathway in cancer cells, suggesting that normal and malignant cells respond differently to disorazole C₁.</p> <p>Conclusion</p> <p>Our studies demonstrate that non-cancer cells undergo mitotic slippage in a cyclin B-dependent and p53-independent manner after prolonged mitotic arrest caused by disorazole C₁. In contrast, cancer cells induce the apoptotic pathway after disorazole C₁treatment, indicating a possibly significant therapeutic window for this compound.</p

A Cross-National Investigation into the Marketing Department\u27s Influence Within the Firm: Toward Initial Empirical Generalizations

This study of the influence of the marketing department (MD), as well as its relationship with firm performance, includes seven industrialized countries and aims to generalize the conceptual model presented by Verhoef and Leeflang (2009). This investigation considers the antecedents of perceived MD influence, top management respect for the MD, and MD decision influence, as well as the relationships of these three influence variables with market orientation (MO) and business performance (BP). Meta-analytic procedures reveal initial empirical generalizations: Accountability, MD innovativeness, and the customer connection capabilities of the MD relate consistently to all three studied MD influence measures. The generalization also shows that MD influence contributes to BP indirectly through its positive relationship with MO and directly through its positive direct relationship with BP

Structural and Electronic Properties of Small Neutral (MgO)n Clusters

Ab initio Perturbed Ion (PI) calculations are reported for neutral stoichiometric (MgO)n clusters (n<14). An extensive number of isomer structures was identified and studied. For the isomers of (MgO)n (n<8) clusters, a full geometrical relaxation was considered. Correlation corrections were included for all cluster sizes using the Coulomb-Hartree-Fock (CHF) model proposed by Clementi. The results obtained compare favorably to the experimental data and other previous theoretical studies. Inclusion of correlaiotn is crucial in order to achieve a good description of these systems. We find an important number of new isomers which allows us to interpret the experimental magic numbers without the assumption of structures based on (MgO)3 subunits. Finally, as an electronic property, the variations in the cluster ionization potential with the cluster size were studied and related to the structural isomer properties.Comment: 24 pages, LaTeX, 7 figures in GIF format. Accepted for publication in Phys. Rev.

The Antiferromagnetic Band Structure of La2CuO4 Revisited

Using the Becke-3-LYP functional, we have performed band structure calculations on the high temperature superconductor parent compound, La2CuO4. Under the restricted spin formalism (rho(alpha) equal to rho(beta)), the R-B3LYP band structure agrees well with the standard LDA band structure. It is metallic with a single Cu x2-y2/O p(sigma) band crossing the Fermi level. Under the unrestricted spin formalism (rho(alpha) not equal to rho(beta)), the UB3LYP band structure has a spin polarized antiferromagnetic solution with a band gap of 2.0 eV, agreeing well with experiment. This state is 1.0 eV (per formula unit) lower than that calculated from the R-B3LYP. The apparent high energy of the spin restricted state is attributed to an overestimate of on-site Coulomb repulsion which is corrected in the unrestricted spin calculations. The stabilization of the total energy with spin polarization arises primarily from the stabilization of the x2-y2 band, such that the character of the eigenstates at the top of the valence band in the antiferromagnetic state becomes a strong mixture of Cu x2-y2/O p(sigma) and Cu z2/O' p(z). Since the Hohenberg-Kohn theorem requires the spin restricted and spin unrestricted calculations give exactly the same ground state energy and total density for the exact functionals, this large disparity in energy reflects the inadequacy of current functionals for describing the cuprates. This calls into question the use of band structures based on current restricted spin density functionals (including LDA) as a basis for single band theories of superconductivity in these materials.Comment: 13 pages, 8 figures, to appear in Phys. Rev. B, for more information see http://www.firstprinciples.co

Disclosure, Privacy and Workplace Accommodation of Episodic Disabilities: Organizational Perspectives on Disability Communication-Support Processes to Sustain Employment

© 2020, The Author(s). Purpose Employers increasingly are asked to accommodate workers living with physical and mental health conditions that cause episodic disability, where periods of wellness are punctuated by intermittent and often unpredictable activity limitations (e.g., depression, anxiety, arthritis, colitis). Episodic disabilities may be challenging for workplaces which must comply with legislation protecting the privacy of health information while believing they would benefit from personal health details to meet a worker’s accommodation needs. This research aimed to understand organizational perspectives on disability communication-support processes. Methods Twenty-seven participants from diverse employment sectors and who had responsibilities for supporting workers living with episodic disabilities (e.g., supervisors, disability managers, union representatives, occupational health representatives, labour lawyers) were interviewed. Five participants also had lived experience of a physical or mental health episodic disability. Participants were recruited through organizational associations, community networks and advertising. Semi-structured interviews and qualitative content analysis framed data collection and analyses, and mapped communication-support processes. Results Seven themes underpinned communication-support process: (1) similarities and differences among physical and mental health episodic disabilities; (2) cultures of workplace support, including contrasting medical and biopsychosocial perspectives; (3) misgivings about others and their role in communication-support processes; (4) that subjective perceptions matter; (5) the inherent complexity of the response process; (6) challenges arising when a worker denies a disability; and (7) casting disability as a performance problem. Conclusions This study identifies a conceptual framework and areas where workplace disability support processes could be enhanced to improve inclusion and the sustainability of employment among workers living with episodic disabilities

1972: Abilene Christian College Bible Lectures - Full Text

THE CHURCH AND THE FUTURE Being the Abilene Christian College Annual Bible Lectures 1972 Published by ABILENE CHRISTIAN COLLEGE BOOK STORE ACC Station Abilene, Texas 7960

Exosomes Derived from M. Bovis BCG Infected Macrophages Activate Antigen-Specific CD4+ and CD8+ T Cells In Vitro and In Vivo

Activation of both CD4+ and CD8+ T cells is required for an effective immune response to an M. tuberculosis infection. However, infected macrophages are poor antigen presenting cells and may be spatially separated from recruited T cells, thus limiting antigen presentation within a granuloma. Our previous studies showed that infected macrophages release from cells small membrane-bound vesicles called exosomes which contain mycobacterial lipid components and showed that these exosomes could stimulate a pro-inflammatory response in naïve macrophages. In the present study we demonstrate that exosomes stimulate both CD4+ and CD8+ splenic T cells isolated from mycobacteria-sensitized mice. Although the exosomes contain MHC I and II as well as costimulatory molecules, maximum stimulation of T cells required prior incubation of exosomes with antigen presenting cells. Exosomes isolated from M. bovis and M. tuberculosis infected macrophages also stimulated activation and maturation of mouse bone marrow-derived dendritic cells. Interestingly, intranasal administration of mice with exosomes isolated from M. bovis BCG infected macrophages induce the generation of memory CD4+ and CD8+ T cells. The isolated T cells also produced IFN-γ upon restimulation with BCG antigens. The release of exosomes from infected macrophages may overcome some of the defects in antigen presentation associated with mycobacterial infections and we suggest that exosomes may be a promising M. tuberculosis vaccine candidate