Unique Transcriptional Profile of Sustained Ligand-Activated Preconditioning in Pre- and Post-Ischemic Myocardium

BACKGROUND: Opioidergic SLP (sustained ligand-activated preconditioning) induced by 3–5 days of opioid receptor (OR) agonism induces persistent protection against ischemia-reperfusion (I-R) injury in young and aged hearts, and is mechanistically distinct from conventional preconditioning responses. We thus applied unbiased gene-array interrogation to identify molecular effects of SLP in pre- and post-ischemic myocardium. METHODOLOGY/PRINCIPAL FINDINGS: Male C57Bl/6 mice were implanted with 75 mg morphine or placebo pellets for 5 days. Resultant SLP did not modify cardiac function, and markedly reduced dysfunction and injury in perfused hearts subjected to 25 min ischemia/45 min reperfusion. Microarray analysis identified 14 up- and 86 down-regulated genes in normoxic hearts from SLP mice (≥1.3-fold change, FDR≤5%). Induced genes encoded sarcomeric/contractile proteins (Myh7, Mybpc3,Myom2,Des), natriuretic peptides (Nppa,Nppb) and stress-signaling elements (Csda,Ptgds). Highly repressed genes primarily encoded chemokines (Ccl2,Ccl4,Ccl7,Ccl9,Ccl13,Ccl3l3,Cxcl3), cytokines (Il1b,Il6,Tnf) and other proteins involved in inflammation/immunity (C3,Cd74,Cd83, Cd86,Hla-dbq1,Hla-drb1,Saa1,Selp,Serpina3), together with endoplasmic stress proteins (known: Dnajb1,Herpud1,Socs3; putative: Il6, Gadd45g,Rcan1) and transcriptional controllers (Egr2,Egr3, Fos,Hmox1,Nfkbid). Biological themes modified thus related to inflammation/immunity, together with cellular/cardiovascular movement and development. SLP also modified the transcriptional response to I-R (46 genes uniquely altered post-ischemia), which may influence later infarction/remodeling. This included up-regulated determinants of cellular resistance to oxidant (Mgst3,Gstm1,Gstm2) and other forms of stress (Xirp1,Ankrd1,Clu), and repression of stress-response genes (Hspa1a,Hspd1,Hsp90aa,Hsph1,Serpinh1) and Txnip. CONCLUSIONS: Protection via SLP is associated with transcriptional repression of inflammation/immunity, up-regulation of sarcomeric elements and natriuretic peptides, and modulation of cell stress, growth and development, while conventional protective molecules are unaltered

Linda Williams Collection - Accession 1751

The Linda Williams Collection primarily includes memorabilia featuring the art work of Vernon Grant collected by author, educator, and school administrator Linda Driggers Williams (Winthrop Class of 1964, ‘69, ‘82). Contents of the collection includes items such as posters, Come See Me buttons, Christmas cards, magazines, and advertisements. There are many toys featuring the illustrations of Vernon Grant as well. For example, there is a xylophone, a record player, pick-up-stix set, and paper dolls. Also included is a Hershey’s mascot doll, plate, and mug; a Rice Krispies bowl, mug, and plate; and a Rice Krispies jigsaw puzzle. There are also copies of Linda Williams’ book on Vernon Grant as well as letters of correspondence concerning its creation and copyright permissions. Other material included in the collection includes some political t-shirts, Linda William’s Do’s and Don’ts of Etiquette book, and some personal correspondence.https://digitalcommons.winthrop.edu/manuscriptcollection_findingaids/2776/thumbnail.jp

Supersymmetry and the relationship between a class of singular potentials in arbitrary dimensions

The eigenvalues of the potentials $V_{1}(r)=\frac{A_{1}}{r}+\frac{A_{2}}{r^{2}}+\frac{A_{3}}{r^{3}}+\frac{A_{4 }}{r^{4}}$ and $V_{2}(r)=B_{1}r^{2}+\frac{B_{2}}{r^{2}}+\frac{B_{3}}{r^{4}}+\frac{B_{4}}{r^ {6}}$, and of the special cases of these potentials such as the Kratzer and Goldman-Krivchenkov potentials, are obtained in N-dimensional space. The explicit dependence of these potentials in higher-dimensional space is discussed, which have not been previously covered.Comment: 13 pages article in LaTEX (uses standard article.sty). Please check "http://www1.gantep.edu.tr/~ozer" for other studies of Nuclear Physics Group at University of Gaziante

Writing in Britain and Ireland, c. 400 to c. 800

No abstract available

Quantitative evidence for the effects of multiple drivers on continental-scale amphibian declines.

Since amphibian declines were first proposed as a global phenomenon over a quarter century ago, the conservation community has made little progress in halting or reversing these trends. The early search for a "smoking gun" was replaced with the expectation that declines are caused by multiple drivers. While field observations and experiments have identified factors leading to increased local extinction risk, evidence for effects of these drivers is lacking at large spatial scales. Here, we use observations of 389 time-series of 83 species and complexes from 61 study areas across North America to test the effects of 4 of the major hypothesized drivers of declines. While we find that local amphibian populations are being lost from metapopulations at an average rate of 3.79% per year, these declines are not related to any particular threat at the continental scale; likewise the effect of each stressor is variable at regional scales. This result - that exposure to threats varies spatially, and populations vary in their response - provides little generality in the development of conservation strategies. Greater emphasis on local solutions to this globally shared phenomenon is needed