Physical Sciences and Mathematics Commons^™

A Review Of Baobab (Adansonia Digitata) Products: Effect Of Processing Techniques, Medicinal Properties And Uses, Donatien Kabore, Hagrétou Sawadogo-Lingani, Bréhima Diawara, Clarise Compaoré, Mamoudou H. Dicko Prof., Mogens Jacobsen

Pr. Mamoudou H. DICKO, PhD

A general literature review including the effect of processing techniques, medicinal value and uses of baobab tree is reported in this manuscript. Baobab tree has multi-purpose uses, as it produces food and non-food products such as medicines, fuel, timber, fodder. Every part of the baobab tree is reported to be useful. The seeds, leaves, roots, flowers, fruit pulp and bark of baobab are edible. Baobab leaves are used in the preparation of soup. Seeds are used as a thickening agent in soups, but they can be fermented and used as a flavouring agent or roasted and eaten as snacks. The …

Promise Of Advances In Simulation Methods For Protein Crystallography: Implicit Solvent Models, Time-Averaging Refinement, And Quantum Mechanical Modeling, Celia Schiffer, Jan Hermans

Celia A. Schiffer

No abstract provided.

Competition Between Ski And Creb-Binding Protein For Binding To Smad Proteins In Transforming Growth Factor-Beta Signaling, Weijun Chen, Suvana Lam, Hema Srinath, Celia Schiffer, William Royer, Kai Lin

Celia A. Schiffer

The family of Smad proteins mediates transforming growth factor-beta (TGF-beta) signaling in cell growth and differentiation. Smads repress or activate TGF-beta signaling by interacting with corepressors (e.g. Ski) or coactivators (e.g. CREB-binding protein (CBP)), respectively. Specifically, Ski has been shown to interfere with the interaction between Smad3 and CBP. However, it is unclear whether Ski competes with CBP for binding to Smads and whether they can interact with Smad3 at the same binding surface on Smad3. We investigated the interactions among purified constructs of Smad, Ski, and CBP in vitro by size-exclusion chromatography, isothermal titration calorimetry, and mutational studies. Here, …

Viral Protease Inhibitors, Jeffrey Anderson, Celia Schiffer, Sook-Kyung Lee, Ronald Swanstrom

Celia A. Schiffer

This review provides an overview of the development of viral protease inhibitors as antiviral drugs. We concentrate on HIV-1 protease inhibitors, as these have made the most significant advances in the recent past. Thus, we discuss the biochemistry of HIV-1 protease, inhibitor development, clinical use of inhibitors, and evolution of resistance. Since many different viruses encode essential proteases, it is possible to envision the development of a potent protease inhibitor for other viruses if the processing site sequence and the catalytic mechanism are known. At this time, interest in developing inhibitors is limited to viruses that cause chronic disease, viruses …

Mutation Patterns And Structural Correlates In Human Immunodeficiency Virus Type 1 Protease Following Different Protease Inhibitor Treatments, Thomas Wu, Celia Schiffer, Matthew Gonzales, Jonathan Taylor, Rami Kantor, Sunwen Chou, Dennis Israelski, Andrew Zolopa, W. Jeffrey Fessel, Robert Shafer

Celia A. Schiffer

Although many human immunodeficiency virus type 1 (HIV-1)-infected persons are treated with multiple protease inhibitors in combination or in succession, mutation patterns of protease isolates from these persons have not been characterized. We collected and analyzed 2,244 subtype B HIV-1 isolates from 1,919 persons with different protease inhibitor experiences: 1,004 isolates from untreated persons, 637 isolates from persons who received one protease inhibitor, and 603 isolates from persons receiving two or more protease inhibitors. The median number of protease mutations per isolate increased from 4 in untreated persons to 12 in persons who had received four or more protease inhibitors. …

Curling Of Flap Tips In Hiv-1 Protease As A Mechanism For Substrate Entry And Tolerance Of Drug Resistance, Walter Scott, Celia Schiffer

Celia A. Schiffer

BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) protease is an essential viral protein that is a major drug target in the fight against Acquired Immune Deficiency Syndrome (AIDS). Access to the active site of this homodimeric enzyme is gained when two large flaps, one from each monomer, open. The flap movements are therefore central to the function of the enzyme, yet determining how these flaps move at an atomic level has not been experimentally possible.

RESULTS: In the present study, we observe the flaps of HIV-1 protease completely opening during a 10 ns solvated molecular dynamics simulation starting from …

Resilience To Resistance Of Hiv-1 Protease Inhibitors: Profile Of Darunavir, Eric Lefebvre, Celia A. Schiffer

Celia A. Schiffer

The current effectiveness of HAART in the management of HIV infection is compromised by the emergence of extensively cross-resistant strains of HIV-1, requiring a significant need for new therapeutic agents. Due to its crucial role in viral maturation and therefore HIV-1 replication and infectivity, the HIV-1 protease continues to be a major development target for antiretroviral therapy. However, new protease inhibitors must have higher thresholds to the development of resistance and cross-resistance. Research has demonstrated that the binding characteristics between a protease inhibitor and the active site of the HIV-1 protease are key factors in the development of resistance. More …

Structural Analysis Of Human Immunodeficiency Virus Type 1 Crf01_Ae Protease In Complex With The Substrate P1-P6., Rajintha Bandaranayake, Moses Prabu-Jeyabalan, Junko Kakizawa, Wataru Sugiura, Celia Schiffer

Celia A. Schiffer

The effect of amino acid variability between human immunodeficiency virus type 1 (HIV-1) clades on structure and the emergence of resistance mutations in HIV-1 protease has become an area of significant interest in recent years. We determined the first crystal structure of the HIV-1 CRF01_AE protease in complex with the p1-p6 substrate to a resolution of 2.8 A. Hydrogen bonding between the flap hinge and the protease core regions shows significant structural rearrangements in CRF01_AE protease compared to the clade B protease structure.

Berberine-Inf55 (5-Nitro-2-Phenylindole) Hybrid Antimicrobials: Effects Of Varying The Relative Orientation Of The Berberine And Inf55 Components, Danuta Tomkiewicz, Gabriele Casadei, Jonah Larkins-Ford, Terence I. Moy, James A. Garner, John B. Bremner, Frederik M. Ausubel, Kim Lewis, Michael J. Kelso

Kim Lewis

Hybrid antimicrobials containing an antibacterial linked to a multidrug resistance (MDR) pump inhibitor make up a promising new class of agents for countering efflux-mediated bacterial drug resistance. This study explores the effects of varying the relative orientation of the antibacterial and efflux pump inhibitor components in three isomeric hybrids (SS14, SS14-M, and SS14-P) which link the antibacterial alkaloid and known substrate for the NorA MDR pump berberine to different positions on INF55 (5-nitro-2-phenylindole), an inhibitor of NorA. The MICs for all three hybrids against wild-type, NorA-knockout, and NorA-overexpressing Staphylococcus aureus cells were found to be similar (9.4 to 40.2 mu …

Antimicrobial And Antioxidant Activities Of Essential Oil And Methanol Extract Of Matricaria Chamomilla L. From Djibouti, Fatouma M. Abdoul-Latif, Mohamed Nabil, Prosper Edou, Adwa A. Ali, Samatar O. Djama, Louis-Clément Obamé, Mamoudou H. Dicko Prof.

Pr. Mamoudou H. DICKO, PhD

The essential oil and methanol extracts of Matricaria Chamomilla L. were subjected to screening for their possible antioxidant activity by two complementary test systems, namely 2,2-diphenykpicrylhydrazyl (DPPH) free radical scavenging and β-carotene-linoleic acid assays. BHT was used as positive control in both test systems. In the DPPH test system, the IC50 values of essential oil and methanol extracts were 4.18 and 1.83 μg/ml, respectively. In the β-carotene-linoleic acid system, oxidation was effectively inhibited by M. Chamomilla, the RAA value of essential oil and methanol extracts were 12.69 and 11.37 %, respectively. When compared to BHT, the essential oil and methanol …

Biodepollution Of Wastewater Containing Phenolic Compounds From Leather Industry By Plant Peroxidases, Mamounata Diao, Nafissetou Ouedraogo, Lamine Baba-Moussa, Paul W. Savadogo, Georges N'Guessan Amani, Mamoudou H. Dicko Prof.

Pr. Mamoudou H. DICKO, PhD

This study deals with the use of peroxidases (POXs) from Allium sativum, Ipomoea batatas, Raphanus sativus and Sorghum bicolor to catalyze the degradation of free phenolic compounds as well as phenolic compounds contained in wastewater from leather industry. Secretory plant POXs were able to catalyze the oxidation of gallic acid, ferulic acid, 4-hydroxybenzoic acid, pyrogallol and 1,4-tyrosol prepared in ethanol 2% (v:v). Efficiency of peroxidase catalysis depends strongly on the chemical nature of phenolic substrates and on the botanical source of the enzymes. It appeared that POX from Raphanus sativus had the highest efficiency. Results show that POXs can also …

Niche Of Harmful Alga Aureococcus Anophagefferens Revealed Through Ecogenomics, Christopher Gobler, Dianna Berry, Sonya Dyhrman, Steven Wilhelm

Steven Wilhelm

Harmful algal blooms (HABs) cause significant economic and ecological damage worldwide. Despite considerable efforts, a comprehensive understanding of the factors that promote these blooms has been lacking, because the biochemical pathways that facilitate their dominance relative to other phytoplankton within specific environments have not been identified. Here, biogeochemical measurements showed that the harmful alga Aureococcus anophagefferens outcompeted co-occurring phytoplankton in estuaries with elevated levels of dissolved organic matter and turbidity and low levels of dissolved inorganic nitrogen. We subsequently sequenced the genome of A. anophagefferens and compared its gene complement with those of six competing phytoplankton species identified through metaproteomics. …