University of Saint Mary

About: University of Saint Mary is a education organization based out in Leavenworth, Kansas, United States. It is known for research contribution in the topics: Population & Galaxy. The organization has 2276 authors who have published 2399 publications receiving 58990 citations. The organization is also known as: University of St. Mary & University of St Mary.

Cardiomyopathy and Worsened Ischemic Heart Failure in SM22-α Cre-Mediated Neuropilin-1 Null Mice: Dysregulation of PGC1α and Mitochondrial Homeostasis

Abstract: Objective— Neuropilin-1 (NRP-1) is a multidomain membrane receptor involved in angiogenesis and development of neuronal circuits, however, the role of NRP-1 in cardiovascular pathophysiology remains elusive. Approach and Results— In this study, we first observed that deletion of NRP-1 induced peroxisome proliferator–activated receptor γ coactivator 1α in cardiomyocytes and vascular smooth muscle cells, which was accompanied by dysregulated cardiac mitochondrial accumulation and induction of cardiac hypertrophy- and stress-related markers. To investigate the role of NRP-1 in vivo, we generated mice lacking Nrp-1 in cardiomyocytes and vascular smooth muscle cells (SM22-α- Nrp-1 KO), which exhibited decreased survival rates, developed cardiomyopathy, and aggravated ischemia-induced heart failure. Mechanistically, we found that NRP-1 specifically controls peroxisome proliferator–activated receptor γ coactivator 1 α and peroxisome proliferator–activated receptor γ in cardiomyocytes through crosstalk with Notch1 and Smad2 signaling pathways, respectively. Moreover, SM22-α- Nrp-1 KO mice exhibited impaired physical activities and altered metabolite levels in serum, liver, and adipose tissues, as demonstrated by global metabolic profiling analysis. Conclusions— Our findings provide new insights into the cardioprotective role of NRP-1 and its influence on global metabolism. # Significance {#article-title-62}

Molecular dynamics and mutational analysis of the catalytic and translocation cycle of RNA polymerase

Abstract: During elongation, multi-subunit RNA polymerases (RNAPs) cycle between phosphodiester bond formation and nucleic acid translocation. In the conformation associated with catalysis, the mobile “trigger loop” of the catalytic subunit closes on the nucleoside triphosphate (NTP) substrate. Closing of the trigger loop is expected to exclude water from the active site, and dehydration may contribute to catalysis and fidelity. In the absence of a NTP substrate in the active site, the trigger loop opens, which may enable translocation. Another notable structural element of the RNAP catalytic center is the “bridge helix” that separates the active site from downstream DNA. The bridge helix may participate in translocation by bending against the RNA/DNA hybrid to induce RNAP forward movement and to vacate the active site for the next NTP loading. The transition between catalytic and translocation conformations of RNAP is not evident from static crystallographic snapshots in which macromolecular motions may be restrained by crystal packing. All atom molecular dynamics simulations of Thermus thermophilus (Tt) RNAP reveal flexible hinges, located within the two helices at the base of the trigger loop, and two glycine hinges clustered near the N-terminal end of the bridge helix. As simulation progresses, these hinges adopt distinct conformations in the closed and open trigger loop structures. A number of residues (described as “switch” residues) trade atomic contacts (ion pairs or hydrogen bonds) in response to changes in hinge orientation. In vivo phenotypes and in vitro activities rendered by mutations in the hinge and switch residues in Saccharomyces cerevisiae (Sc) RNAP II support the importance of conformational changes predicted from simulations in catalysis and translocation. During simulation, the elongation complex with an open trigger loop spontaneously translocates forward relative to the elongation complex with a closed trigger loop. Switching between catalytic and translocating RNAP forms involves closing and opening of the trigger loop and long-range conformational changes in the atomic contacts of amino acid side chains, some located at a considerable distance from the trigger loop and active site. Trigger loop closing appears to support chemistry and the fidelity of RNA synthesis. Trigger loop opening and limited bridge helix bending appears to promote forward nucleic acid translocation.

Detailed evidence for flare-to-flare variations of the coronal calcium abundance

Abstract: The analysis of X-ray solar flare spectra obtained by the Bent Crystal Spectrometer on board the Solar Maximum Mission satellite is presented. The ratio of the Ca XIX resonance line intensity to the nearby continuum is used to measure the calcium abundance relative to hydrogen (ACa). A description of the spectroscopic method of determining the absolute calcium abundance is given. Possible instrumental and solar effects that might influence the abundance estimates are evaluated. Over 5000 spectra from more than 100 flares are analyzed. We find a flare-to-flare variation for ACa that is not correlated with flare size, Hα importance, or with several other flare characteristics. For flares observed from two active regions, the observed value of ACa increases as a function of time. The average for all flares is ACa = (5.77 ± 1.41) × 10-6. A discussion of investigated correlations of derived ACa values with several flare characteristics is presented.