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The Faculty E-Portfolio Summer Seminar Day 4
No full textDay 4: 05-16-2019
Using ePortfolios in class and ePortfolios examples created by workshop participants
The Faculty E-Portfolio Summer Seminar Day 3
No full textDay 3: 05-15-2019 -
Part 1: Debrief about Faculty Portfolios;
Part 2: Student Portfolios;
Part 3: Exploring ePortfolio platforms (Google Sites, Wix and Weebly)
Website: http://patricklowenthal.co
McNair Scholar, Auriel Jasper Morris, receiving Dr. Rivera Award, 2019
No full textA photograph of Auriel Jasper Morris, McNair scholar receiving Dr. Rivera Award in 2019.https://digitalcommons.xula.edu/mcnair_schol/1004/thumbnail.jp
Transactivation of Human Endogenous Retroviruses by Tumor Viruses and Their Functions in Virus-Associated Malignancies.
Get PDFHuman endogenous retroviruses (HERVs), viral-associated sequences, are normal components of the human genome and account for 8–9% of our genome. These original provirus sequences can be transactivated to produce functional products. Several reactivated HERVs have been implicated in cancers and autoimmune diseases. An emerging body of literature supports a potential role of reactivated HERVs in viral diseases, in particular viral-associated neoplasms. Demystifying studies on the mechanism(s) of HERV reactivation could provide a new framework for the development of treatment and prevention strategies targeting virus-associated tumors. Although available data suggest that coinfection by other viruses, such as Kaposi’s Sarcoma-associated herpesvirus (KSHV) and Epstein–Barr virus (EBV), may be a crucial driving force to transactivate HERV boom, the mechanisms of action of viral infection-induced HERV transactivation and the contributions of HERVs to viral oncogenesis warrant further studies. Here, we review viral coinfection contributes to HERVs transactivation with focus on human viral infection associated oncogenesis and diseases, including the abilities of viral regulators involved in HERV reactivation, and physiological effects of viral infection response on HERV reactivation
Cellular Recruitment by Podocyte-Derived Pro-migratory Factors in Assembly of the Human Renal Filter.
No full textAnalysis of kidney disease-causing genes and pathology resulting from systemic diseases highlight the importance of the kidney\u27s filtering system, the renal corpuscles. To elucidate the developmental processes that establish the renal corpuscle, we performed single-nucleus droplet-based sequencing of the human fetal kidney. This enabled the identification of nephron, interstitial, and vascular cell types that together generate the renal corpuscles. Trajectory analysis identified transient developmental gene expression, predicting precursors or mature podocytes express FBLN2, BMP4, or NTN4, in conjunction with recruitment, differentiation, and modeling of vascular and mesangial cell types into a functional filter. In vitro studies provide evidence that these factors exhibit angiogenic or mesangial recruiting and inductive properties consistent with a key organizing role for podocyte precursors in kidney development. Together these studies define a spatiotemporal developmental program for the primary filtration unit of the human kidney and provide novel insights into cell interactions regulating co-assembly of constituent cell types
The in vitro Effects of Pentamidine Isethionate on Coagulation and Fibrinolysis
No full textPentamidine is bis-oxybenzamidine-based antiprotozoal drug. The parenteral use of pentamidine appears to affect the processes of blood coagulation and/or fibrinolysis resulting in rare but potentially life-threatening blood clot formation. Pentamidine was also found to cause disseminated intravascular coagulation syndrome. To investigate the potential underlying molecular mechanism(s) of pentamidine’s effects on coagulation and fibrinolysis, we studied its effects on clotting times in normal and deficient human plasmas. Using normal plasma, pentamidine isethionate doubled the activated partial thromboplastin time at 27.5 µM, doubled the prothrombin time at 45.7 µM, and weakly doubled the thrombin time at 158.17 µM. Using plasmas deficient of factors VIIa, IXa, XIa, or XIIa, the concentrations to double the activated partial thromboplastin time were similar to that obtained using normal plasma. Pentamidine also inhibited plasmin-mediated clot lysis with half-maximal inhibitory concentration (IC50) value of ~3.6 µM. Chromogenic substrate hydrolysis assays indicated that pentamidine inhibits factor Xa and plasmin with IC50 values of 10.4 µM and 8.4 µM, respectively. Interestingly, it did not significantly inhibit thrombin, factor XIa, factor XIIIa, neutrophil elastase, or chymotrypsin at the highest concentrations tested. Michaelis-Menten kinetics and molecular modeling studies revealed that pentamidine inhibits factor Xa and plasmin in a competitive fashion. Overall, this study provides quantitative mechanistic insights into the in vitro effects of pentamidine isethionate on coagulation and fibrinolysis via the disruption of the proteolytic activity of factor Xa and plasmin
Mardi Gras Indians Downtown Super Sunday Parade
No full textMen, women and children in Mardi Gras Indian suits parading in the Downtown streets of New Orleans during Super Sunday celebration. Super Sunday is an important day for Mardi Gras Indians and is usually celebrated during St. Joseph\u27s Feast Day. This particular parade is through the streets of Downtown New Orleans, an area bound by bordered by Iberville Street, the Pontchartrain Expressway, Claiborne Avenue, Iberville Street and the Mississippi River.https://digitalcommons.xula.edu/masked/1018/thumbnail.jp
O-Aminoalkyl-O-trimethyl-2,3-dehydrosilybins: Synthesis and In Vitro Effects Towards Prostate Cancer Cells.
No full textAs part of our ongoing silybin project, this study aims to introduce a basic nitrogen-containing group to 7-OH of 3,5,20-O-trimethyl-2,3-dehydrosilybin or 3-OH of 5,7,20-O-trimethyl- 2,3-dehydrosilybin via an appropriate linker for in vitro evaluation as potential anti-prostate cancer agents. The synthetic approaches to 7-O-substituted-3,5,20-O-trimethyl-2,3-dehydrosilybins through a five-step procedure and to 3-O-substituted-5,7,20-O-trimethyl-2,3-dehydrosilybins via a four-step transformation have been developed. Thirty-two nitrogen-containing derivatives of silybin have been achieved through these synthetic methods for the evaluation of their antiproliferative activities towards both androgen-sensitive (LNCaP) and androgen-insensitive prostate cancer cell lines (PC-3 and DU145) using the WST-1 cell proliferation assay. These derivatives exhibited greater in vitro antiproliferative potency than silibinin. Among them, 11, 29, 31, 37, and 40 were identified as five optimal derivatives with IC 50 values in the range of 1.40–3.06 µM, representing a 17- to 52-fold improvement in potency compared to silibinin. All these five optimal derivatives can arrest the PC-3 cell cycle in the G 0 /G 1 phase and promote PC-3 cell apoptosis. Derivatives 11, 37, and 40 are more effective than 29 and 31 in activating PC-3 cell apoptosis
Two Tryptophans Are Better Than One in Accelerating Electron Flow through a Protein
No full textWe have constructed and structurally characterized a Pseudomonas aeruginosa azurin mutant Re126WWCu I , where two adjacent tryptophan residues (W124 and W122, indole separation 3.6-4.1 Å) are inserted between the Cu I center and a Re photosensitizer coordinated to the imidazole of H126 (Re I (H126)(CO) 3 (4,7-dimethyl-1,10-phenanthroline) + ). Cu I oxidation by the photoexcited Re label (∗Re) 22.9 Å away proceeds with a ∼70 ns time constant, similar to that of a single-tryptophan mutant (∼40 ns) with a 19.4 Å Re-Cu distance. Time-resolved spectroscopy (luminescence, visible and IR absorption) revealed two rapid reversible electron transfer steps, W124 →∗Re (400-475 ps, K 1 3.5-4) and W122 → W124 •+ (7-9 ns, K 2 0.55-0.75), followed by a rate-determining (70-90 ns) Cu I oxidation by W122 •+ ca. 11 Å away. The photocycle is completed by 120 μs recombination. No photochemical Cu I oxidation was observed in Re126FWCu I , whereas in Re126WFCu I , the photocycle is restricted to the ReH126W124 unit and Cu I remains isolated. QM/MM/MD simulations of Re126WWCu I indicate that indole solvation changes through the hopping process and W124 →∗Re electron transfer is accompanied by water fluctuations that tighten W124 solvation. Our finding that multistep tunneling (hopping) confers a ∼9000-fold advantage over single-step tunneling in the double-tryptophan protein supports the proposal that hole-hopping through tryptophan/tyrosine chains protects enzymes from oxidative damage