Glucose Metabolism through Pentose Phosphate Pathway: Effects on the Development of Congenital Heart Defects

Several studies have shown that genes related to cardiac muscle and function thrive in low glucose concentrations, whereas cells over actively replicate and do not reach full maturation in high glucose concentrations. Data suggests that blocking the pentose phosphate pathway induces cardiac maturation. The pentose phosphate pathway is responsible for generating ribose sugars that contribute to making nucleotides and NADP+/NADPH. Prolonged activation of the pentose phosphate pathway leads to excess nucleotide synthesis resulting in immature cardiomyocytes leading to congenital heart defects. This paper discussed how the pentose phosphate pathway is involved in the inhibition of fetal cardiomyocytes in high glucose conditions

AhrC and Eep are biofilm infection-associated virulence factors in enterococcus faecalis

Enterococcus faecalis is part of the human intestinal microbiome and is a prominent cause of health care-associated infections. The pathogenesis of many E. faecalis infections, including endocarditis and catheter-associated urinary tract infection (CAUTI), is related to the ability of clinical isolates to form biofilms. To identify chromosomal genetic determinants responsible for E. faecalis biofilm-mediated infection, we used a rabbit model of endocarditis to test strains with transposon insertions or in-frame deletions in biofilm-associated loci: ahrC, argR, atlA, opuBC, pyrC, recN, and sepF. Only the ahrC mutant was significantly attenuated in endocarditis. We demonstrate that the transcriptional regulator AhrC and the protease Eep, which we showed previously to be an endocarditis virulence factor, are also required for full virulence in murine CAUTI. Therefore, AhrC and Eep can be classified as enterococcal biofilm-associated virulence factors. Loss of ahrC caused defects in early attachment and accumulation of biofilm biomass. Characterization of ahrC transcription revealed that the temporal expression of this locus observed in wild-type cells promotes initiation of early biofilm formation and the establishment of endocarditis. This is the first report of AhrC serving as a virulence factor in any bacterial species

Paclitaxel-induced epithelial damage and ectopic MMP-13 expression promotes neurotoxicity in zebrafish

Paclitaxel is a microtubule-stabilizing chemotherapeutic agent that is widely used in cancer treatment and in a number of curative and palliative regimens. Despite its beneficial effects on cancer, paclitaxel also damages healthy tissues, most prominently the peripheral sensory nervous system. The mechanisms leading to paclitaxel-induced peripheral neuropathy remain elusive, and therapies that prevent or alleviate this condition are not available. We established a zebrafish in vivo model to study the underlying mechanisms and to identify pharmacological agents that may be developed into therapeutics. Both adult and larval zebrafish displayed signs of paclitaxel neurotoxicity, including sensory axon degeneration and the loss of touch response in the distal caudal fin. Intriguingly, studies in zebrafish larvae showed that paclitaxel rapidly promotes epithelial damage and decreased mechanical stress resistance of the skin before induction of axon degeneration. Moreover, injured paclitaxel-treated zebrafish skin and scratch-wounded human keratinocytes (HEK001) display reduced healing capacity. Epithelial damage correlated with rapid accumulation of fluorescein-conjugated paclitaxel in epidermal basal keratinocytes, but not axons, and up-regulation of matrix-metalloproteinase 13 (MMP-13, collagenase 3) in the skin. Pharmacological inhibition of MMP-13, in contrast, largely rescued paclitaxel-induced epithelial damage and neurotoxicity, whereas MMP-13 overexpression in zebrafish embryos rendered the skin vulnerable to injury under mechanical stress conditions. Thus, our studies provide evidence that the epidermis plays a critical role in this condition, and we provide a previously unidentified candidate for therapeutic interventions

Differential ability of Staphylococcus aureus to cause infective endocarditis and lethal sepsis in rabbits

Staphylococcus aureus is a major cause of infective endocarditis (IE) and sepsis. In addition, 50% of IE survivors develop strokes and metastatic abscesses due to the release of emboli from infected valves. Both methicillin-resistant (MRSA) and methicillin-sensitive (MSSA) strains cause IE and sepsis, and they may be categorized by pulsed-field gel electrophoresis, for example clonal types USA200, 300, and 400. We hypothesize that secreted virulence factors contribute to their differential ability to cause IE and/or sepsis. Rabbits are an excellent model for studying IE, which over the course of 4 days are monitored for development of vegetations (the hallmark signs of IE), and sepsis, as S. aureus are administered intravenously. Rabbit cardiac physiology is similar to humans, and rabbits exhibit susceptibility to superantigens and cytolysins produced by these clonal types of S. aureus. We examined the differential ability of community-associated MRSA and MSSA strains (5 USA200 or related strain FRI1169, 3 USA300, and 2 USA400) to cause vegetations versus lethal sepsis in rabbits. USA200 and related strain FRI1169 exhibited intermediate LD50s in sepsis (5x106-5x108) colony-forming units (CFUs), and 4/5 caused significant IE. In contrast, USA300 strains were highly effective in causing lethal sepsis (LD50s of 1 x 106-5 x 107 CFUs) but were minimally capable of causing IE. USA300 variant strain Newman was not highly lethal (LD50 of 2 x 109 CFUs) but was highly effective in causing IE. USA400 strains were both highly lethal (LD50s of 1 x 107-5 x 107 CFUs) and highly effective causes of IE. Additional studies showed that phenol soluble modulins produced by FRI1169 were important for sepsis but did not contribute to IE. Our studies show that these clonal groups of S. aureus have differential abilities to cause IE and lethal sepsis and suggest that secreted virulence factors, including superantigens and cytolysins, account for these differences

Marquette Literary Review, Issue 13

Table of contents [cover] Andy Mayer, “Poet, Bound” 5 Margot Zamberlin, “Under the Rhododendron” 6 Lauren Demasek, “Mind Waves” 7 Will Scheueman, “At Home” 10 Jacob Riyeff, “Deer Camp” 12 Nikita Deep, “Hiraeth Lake” 13 Kayla DiFranco “An Ode to My Love” 14 Tommy Donahue, “Just Another Stat” 15 Olivia Cimino “A Full Swing” 17 Kelly Kennedy, “Winnie” 18 Meghan King, “Take Me There” 19 Lauren Demasek, “Soul of the Sea” 21 Sadaf Nasir, “Crystal Clear” 22 Grace Lambertson, “Fulfillment” 24 Peter Spaulding “Avylon Landing” 28 Sadaf Nasir, “Baldie” 29 Maggie Miller “The Charcoal Sky” 31 Nikki Deep, “Lost City” 32 Urwa Ahmad, “Pour Over” 34 Claire Carlson, “Moon Jelly” 35 Ross Bravo, “Warmth” 36 Hailey Wellner, “Our Past Lives” 37 Ryan Hagan, “Dead Weight Walking, or Trudge of the Somber Tumult” 39 Mia Gleason, “The Creek” 41 Andy Mayer, “Wilderness” 42 Ryan Hagan, “Auntie” 45 Sarah Aaron, “Starlit Sisters” 47 Spencer Kilapatrick, “The Loving Cup” 48 Lauren Demasek, “Sublime Dream” 49 Jack Murphy, “An African Serpent’s Song” 50 Sarah Aaron, “August” 56 Kelly Kennedy, “Elvis Blues” 57 Urwa Ahmad, “Other” 58 Margarita Buitrago, “Haughty Happenings” 59 Saul Lopez, “El Rey” 61 Riley Knapp, “Mother Earth and Father Yhwh” 63 Riley Ellison, “62523” 65 Ryan Hagan, “Snow Dune, Ice Tunnel” 66 Eren Joyce, “xolotl” 67 Kelsie Kasky, “But Let Them Fly” 68 Georgette Kouassi, “At Your Side” 69 Mia Gleason, “Mask of Art” 70 Jannea Thomason, “Condolences” 71 Ryan Hagan, “A Clockwork Orange” 72 Hailey Whetten, “A Child’s Brain” 75 Oluwappelumi Oguntade, “Dandy” 77 Jessica Diebold, “He Died in His Dreams” 79 Nikki Deep, “Unconditional” 80 Sarah Aaron, “Amber Summer Sunday” 81 Sadaf Nasir, “Fort Jefferson