Inactivation of Mandelate Racemase by 3-Hydroxypyruvate Reveals a Potential Mechanistic Link between Enzyme Superfamilies

Mandelate racemase (MR), a member of the enolase superfamily, catalyzes the Mg2+-dependent interconversion of the enantiomers of mandelate. Several α-keto acids are modest competitive inhibitors of MR [e.g., mesoxalate (Ki = 1.8 ± 0.3 mM) and 3-fluoropyruvate (Ki = 1.3 ± 0.1 mM)], but, surprisingly, 3-hydroxypyruvate (3-HP) is an irreversible, time-dependent inhibitor (kinact/KI = 83 ± 8 M–1 s–1). Protection from inactivation by the competitive inhibitor benzohydroxamate, trypsinolysis and electrospray ionization tandem mass spectrometry analyses, and X-ray crystallographic studies reveal that 3-HP undergoes Schiff-base formation with Lys 166 at the active site, followed by formation of an aldehyde/enol(ate) adduct. Such a reaction is unprecedented in the enolase superfamily and may be a relic of an activity possessed by a promiscuous progenitor enzyme. The ability of MR to form and deprotonate a Schiff-base intermediate furnishes a previously unrecognized mechanistic link to other α/β-barrel enzymes utilizing Schiff-base chemistry and is in accord with the sequence- and structure-based hypothesis that members of the metal-dependent enolase superfamily and the Schiff-base-forming N-acetylneuraminate lyase superfamily and aldolases share a common ancestor

Down East Partnership for Children: A Systems Approach to Improving Community Health

Improving community health is a highly complex endeavor that requires extensive analysis of and effective response to a wide array of factors. Utilizing a systems approach to improve community health is the most effective way to respond to these factors and lays a strong foundation for sustaining community health improvement. The Down East Partnership for Children (DEPC) in Rocky Mount, NC provides a model for delivering an assets-driven, evidence-based and community-centered systems approach to addressing health challenges faced by children and their families. This report provides an overview of the systems approach, an analysis of DEPC’s systems based approach to community health improvement, an analysis of why this model has proven successful, and recommendations for moving forward.Master of Public Healt

Down East Partnership for Children: A Systems Approach to Improving Community Health

Improving community health is a highly complex endeavor that requires extensive analysis of and effective response to a wide array of factors. Utilizing a systems approach to improve community health is the most effective way to respond to these factors and lays a strong foundation for sustaining community health improvement. The Down East Partnership for Children (DEPC) in Rocky Mount, NC provides a model for delivering an assets-driven, evidence-based and community-centered systems approach to addressing health challenges faced by children and their families. This report provides an overview of the systems approach, an analysis of DEPC’s systems based approach to community health improvement, an analysis of why this model has proven successful, and recommendations for moving forward.Master of Public Healt

A High-Throughput Screening Assay for Pyruvate Carboxylase

Pyruvate carboxylase (PC) catalyzes the conversion of pyruvate to oxaloacetate (OAA), an important metabolic reaction in a wide range of organisms. Small molecules directed against PC would enable detailed studies on the metabolic role of this enzyme and would have the potential to be developed into pharmacological agents. Currently, specific and potentsmall molecule regulators of PC are unavailable. To assist in efforts to find, develop, and characterize small molecule effectors of PC, a novel fixed-time assay has been developed based on the reaction of OAA with the diazonium salt, Fast Violet B (FVB), which produces a colored adduct with an absorbance maximum at 530 nm. This fixed time assay is reproducible, sensitive and responsive to known effectors of Rhizobium etli PC, Staphylococcus aureus PC, and Listeria monocytogenes PC, and is highly amenable to high-throughput screening. The assay was validated using a plate uniformity assessment test and a pilot screen of a library of 1280 compounds. The results indicate that the assay is suitable for screening small molecule libraries to find novel small molecule effectors of PC

Back to the Future: Re‐Examining the Need for Shelf‐Ready Processes in the E‐Book Environment

Shelf‐ready processing of print materials is a commonly available service from library book vendors, and many libraries outsource these services in order to help save staff time and costs, and to expedite the process. However, in the age where print monographs are increasingly replaced with e‐books, do these services still make fiscal sense? In the spring of 2015, the Texas Woman’s University Libraries were looking to expand shelf‐ready services to a second vendor, but before doing so opted to do a feasibility study to see if shelf‐ready services were still needed and economical. This paper presents the findings of a two‐month study done at the Texas Woman’s University Libraries on their outsourced and in‐house cataloging workflows. The study examined the amount of time it took to receive the materials after ordering, the various costs involved, including shelf‐ready fees and internal staff costs, as well as the number of print materials being purchased over the past three fiscal years

Evaluation of α-hydroxycinnamic Acids as Pyruvate Carboxylase Inhibitors

Through a structure-based drug design project (SBDD), potent small molecule inhibitors of pyruvate carboxylase (PC) have been discovered. A series of α-keto acids (7) and α-hydroxycinnamic acids (8) were prepared and evaluated for inhibition of PC in two assays. The two most potent inhibitors were 3,3′-(1,4-phenylene)bis[2-hydroxy-2-propenoic acid] (8u) and 2-hydroxy-3-(quinoline-2-yl)propenoic acid (8v) with IC50 values of 3.0 ± 1.0 μM and 4.3 ± 1.5 μM respectively. Compound 8v is a competitive inhibitor with respect to pyruvate (Ki = 0.74 μM) and a mixed-type inhibitor with respect to ATP, indicating that it targets the unique carboxyltransferase (CT) domain of PC. Furthermore, compound 8v does not significantly inhibit human carbonic anhydrase II, matrix metalloproteinase-2, malate dehydrogenase or lactate dehydrogenase

Forearm design for a myoelectric prosthetic hand

Due to the rapid growth of children and the complexity of myoelectric technology, children are often not given the same opportunities to use myoelectric prosthetics as adults. The Muscle Activated Prosthesis (MAP) team is working to create an affordable, transradial myoelectric prosthesis for a twelve-year-old girl. The basic mechanism by which this device operates is as follows: a muscle contraction emits an electrical signal that will be detected and processed through a microcontroller. Then the onboard software determines whether the hand opens or closes based on the level of muscle intensity. If the software determines to close or open the hand, a signal from the microcontroller is sent to linear actuators that control the tendon system running through the fingers. Currently the team has a working prototype that we plan to give to our client in the fall of 2020 to test.https://mosaic.messiah.edu/engr2020/1016/thumbnail.jp

The 2014 BFA Graduating Class Department of Visual Arts

Congratulations on the opening of this, your graduate exhibition. Your presence in this catalogue not only celebrates your achievements while you’ve been with us, but also serves to signal your transition to the next chapter of your life and career. Whatever your goals, whatever your desire in life, it is my hope that your studies with the visual arts program serve you well, that you continue to explore, search, question, and, it is also my hope that you keep making art. The Division of Fine Arts is extremely proud of all its graduates and this catalogue, and your presence in it, will serve as a reminder over the years that you were here, and that you made a contribution and a difference to the visual arts program. All the very best and please keep in touch