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Urbana, IL, United States

The University of Illinois at Urbana–Champaign is a public research-intensive university in the U.S. state of Illinois. A land-grant university, it is the flagship campus of the University of Illinois system. The University of Illinois at Urbana–Champaign is the second oldest public university in the state , and is a founding member of the Big Ten Conference. It is a member of the Association of American Universities and is designated as a RU/VH Research University . The campus library system possesses the second-largest university library in the United States after Harvard University.The university comprises 17 colleges that offer more than 150 programs of study. Additionally, the university operates an extension that serves 2.7 million registrants per year around the state of Illinois and beyond. The campus holds 647 buildings on 4,552 acres in the twin cities of Champaign and Urbana ; its annual operating budget in 2011 was over $1.7 billion. Wikipedia.

Ha T.,University of Illinois at Urbana - Champaign
Cell | Year: 2013

Enormous mechanistic insight has been gained by studying the behavior of single molecules. The same approaches used to study proteins in isolation are now being leveraged to examine the changes in functional behavior that emerge when single molecules have company. © 2013 Elsevier Inc.

Oldfield E.,University of Illinois at Urbana - Champaign
Accounts of Chemical Research | Year: 2010

The isoprenoid biosynthesis pathways produce the largest class of small molecules in Nature: isoprenoids (also called terpenoids). Not surprisingly then, isoprenoid biosynthesis is a target for drug discovery, and many drugs-such as Lipitor (used to lower cholesterol), Fosamax (used to treat osteoporosis), and many anti-infectives-target isoprenoid biosynthesis. However, drug resistance in malaria, tuberculosis, and staph infections is rising, cheap and effective drugs for the neglected tropical diseases are lacking, and progress in the development of anticancer drugs is relatively slow. Isoprenoid biosynthesis is thus an attractive target, and in this Account, I describe developments in four areas, using in each case knowledge derived from one area of chemistry to guide the development of inhibitors (or drug leads) in another, seemingly unrelated, area. First, I describe mechanistic studies of the enzyme IspH, which is present in malaria parasites and most pathogenic bacteria, but not in humans. IspH is a 4Fe-4S protein and produces the five-carbon (C5) isoprenoids IPP (isopentenyl diphosphate) and DMAPP (dimethylallyl diphosphate) from HMBPP (E-1-hydroxy-2-methyl-but-2-enyl-4-diphosphate) via a 2H +/2e- reduction (of an allyl alcohol to an alkene). The mechanism is unusual in that it involves organometallic species: "metallacycles" (n2-alkenes) and n1/n 3-allyls. These observations lead to novel alkyne inhibitors, which also form metallacycles. Second, I describe structure-function-inhibition studies of FPP synthase, the macromolecule that condenses IPP and DMAPP to the sesquiterpene farnesyl diphosphate (FPP) in a "head-to-tail" manner. This enzyme uses a carbocation mechanism and is potently inhibited by bone resorption drugs (bisphosphonates), which I show are also antiparasitic agents that block sterol biosynthesis in protozoa. Moreover, "lipophilic" bisphosphonates inhibit protein prenylation and invasiveness in tumor cells, in addition to activating γΔ T-cells to kill tumor cells, and are important new leads in oncology. Third, I describe structural and inhibition studies of a "head-to-head" triterpene synthase, dehydrosqualene synthase (CrtM), from Staphylococcus aureus. CrtM catalyzes the first committed step in biosynthesis of the carotenoid virulence factor staphyloxanthin: the condensation of two FPP molecules to produce a cyclopropane (presqualene diphosphate). The structure of CrtM is similar to that of human squalene synthase (SQS), and some SQS inhibitors (originally developed as cholesterol-lowering drugs) block staphyloxanthin biosynthesis. Treated bacteria are white and nonvirulent (because they lack the carotenoid shield that protects them from reactive oxygen species produced by neutrophils), rendering them susceptible to innate immune system clearance-a new therapeutic approach. And finally, I show that the heart drug amiodarone, also known to have antifungal activity, blocks ergosterol biosynthesis at the level of oxidosqualene cyclase in Trypanosoma cruzi, work that has led to its use in the clinic as a novel antiparasitic agent. In each of these four examples, I use information from one area (organometallic chemistry, bone resorption drugs, cholesterol-lowering agents, heart disease) to develop drug leads in an unrelated area: a "knowledge-based" approach that represents an important advance in the search for new drugs. © 2010 American Chemical Society.

Freund J.B.,University of Illinois at Urbana - Champaign
Annual Review of Fluid Mechanics | Year: 2014

The cellular detail of blood is an essential factor in its flow, especially in vessels or devices with size comparable to that of its suspended cells. This article motivates and reviews numerical simulation techniques that provide a realistic description of cell-scale blood flow by explicitly representing its coupled fluid and solid mechanics. Red blood cells are the principal focus because of their importance and because of their remarkable deformability, which presents particular simulation challenges. Such simulations must couple discretizations of the large-deformation elasticity of the cells with the viscous flow mechanics of the suspension. The Reynolds numbers are low, so the effectively linear fluid mechanics is amenable to a wide range of simulation methods, although the constitutive models and geometric factors of the coupled system introduce challenging nonlinearity. Particular emphasis is given to the relative merits of several fundamentally different simulation methods. The detailed description provided by such simulations is invaluable for advancing our scientific understanding of blood flow, and their ultimate impact will be in the design of biomedical tools and interventions. Copyright © 2014 by Annual Reviews. All rights reserved.

Single-cell mass spectrometry (MS) empowers metabolomic investigations by decreasing analytical dimensions to the size of individual cells and subcellular structures. We describe a protocol for investigating and quantifying metabolites in individual isolated neurons using single-cell capillary electrophoresis (CE) coupled to electrospray ionization (ESI) time-of-flight (TOF) MS. The protocol requires ∼2 h for sample preparation, neuron isolation and metabolite extraction, and 1 h for metabolic measurement. We used the approach to detect more than 300 distinct compounds in the mass range of typical metabolites in various individual neurons (25-500 μm in diameter) isolated from the sea slug (Aplysia californica) central and rat (Rattus norvegicus) peripheral nervous systems. We found that a subset of identified compounds was sufficient to reveal metabolic differences among freshly isolated neurons of different types and changes in the metabolite profiles of cultured neurons. The protocol can be applied to the characterization of the metabolome in a variety of smaller cells and/or subcellular domains.

Simons D.J.,University of Illinois at Urbana - Champaign
Perspectives on Psychological Science | Year: 2014

Trying to remember something now typically improves your ability to remember it later. However, after watching a video of a simulated bank robbery, participants who verbally described the robber were 25% worse at identifying the robber in a lineup than were participants who instead listed U.S. states and capitals—this has been termed the “verbal overshadowing” effect (Schooler & Engstler-Schooler, 1990). More recent studies suggested that this effect might be substantially smaller than first reported. Given uncertainty about the effect size, the influence of this finding in the memory literature, and its practical importance for police procedures, we conducted two collections of preregistered direct replications (RRR1 and RRR2) that differed only in the order of the description task and a filler task. In RRR1, when the description task immediately followed the robbery, participants who provided a description were 4% less likely to select the robber than were those in the control condition. In RRR2, when the description was delayed by 20 min, they were 16% less likely to select the robber. These findings reveal a robust verbal overshadowing effect that is strongly influenced by the relative timing of the tasks. The discussion considers further implications of these replications for our understanding of verbal overshadowing. © The Author(s) 2014

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