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Madison, WI, United States

The University of Wisconsin–Madison is a selective public research university located in Madison, Wisconsin, United States. Founded when Wisconsin achieved statehood in 1848, UW–Madison is the official state university of Wisconsin, and the flagship campus of the University of Wisconsin System. It was the first public university established in Wisconsin and remains the oldest and largest public university in the state. It became a land-grant institution in 1866. The 933-acre main campus includes four National Historic Landmarks.UW–Madison is organized into 20 schools and colleges, which enrolled 29,504 undergraduate, 9,430 graduate, and 2,526 professional students and granted 6,494 bachelor's, 3,560 graduate and professional degrees in 2012-2013. The University employs over 21,727 faculty and staff. Its comprehensive academic program offers 132 undergraduate majors, along with 149 master's degree programs and 120 doctoral programs.The UW is categorized as an RU/VH Research University in the Carnegie Classification of Institutions of Higher Education. In 2012, it had research expenditures of more than $1.1 billion, the third highest among universities in the country. Wisconsin is a founding member of the Association of American Universities.The Wisconsin Badgers compete in 25 intercollegiate sports in the NCAA's Division I Big Ten Conference and have won 28 national championships. Wikipedia.

Hein P.P.,University of Wisconsin - Madison
Nature Structural and Molecular Biology | Year: 2014

The rates of RNA synthesis and the folding of nascent RNA into biologically active structures are linked via pausing by RNA polymerase (RNAP). Structures that form within the RNA-exit channel can either increase pausing by interacting with RNAP or decrease pausing by preventing backtracking. Conversely, pausing is required for proper folding of some RNAs. Opening of the RNAP clamp domain has been proposed to mediate some effects of nascent-RNA structures. However, the connections among RNA structure formation and RNAP clamp movement and catalytic activity remain uncertain. Here, we assayed exit-channel structure formation in Escherichia coli RNAP with disulfide cross-links that favor closed- or open-clamp conformations and found that clamp position directly influences RNA structure formation and RNAP catalytic activity. We report that exit-channel RNA structures slow pause escape by favoring clamp opening through interactions with the flap that slow translocation. Source

Kent K.C.,University of Wisconsin - Madison
New England Journal of Medicine | Year: 2014

A 76-year-old woman presents with a 2-day history of left-lower-quadrant pain. A computed tomographic (CT) scan reveals diverticulitis and an incidental 5.6-cm infrarenal abdominal aortic aneurysm. Her medical history is notable for hypertension, hypercholesterolemia, and obesity. She is a current smoker, with an 80 pack-year history. How should her case be managed? Copyright © 2014 Massachusetts Medical Society. Source

Frey P.A.,University of Wisconsin - Madison
Accounts of Chemical Research | Year: 2014

As a graduate student under Professor R. H. Abeles, I began my journey with 5′-deoxyadenosine, studying the coenzyme B12 (adenosylcobalamin)-dependent dioldehydrase (DDH). I proved that suicide inactivation of dioldehydrase by glycolaldehyde proceeded with irreversible cleavage of adenosylcobalamin to 5′-deoxyadenosine. I further showed that suicide inactivation by [2-3H]glycolaldehyde produced 5′-deoxy[3H]adenosine, the first demonstration of hydrogen transfer to adenosyl-C5′ of adenosylcobalamin. The tritium kinetic isotope effect Tk was 15, which correlated well with the measurement Dk = 12 for transformation of [1-2H]propane-1,2-diol to [2-2H]propionaldehyde by DDH. After establishing my own research program, I returned to the glycolaldehyde inactivation of DDH, showing by EPR that suicide inactivation produced glycolaldehyde-2-yl. In retrospect, suicide inactivation involved scission of adenosylcobalamin to 5′-deoxyadenosine- 5′-yl, which abstracted a hydrogen from glycolaldehyde. Captodative-stabilized glycolaldehyde-2-yl could not react further, leading to suicide inactivation.In 1986, my colleagues and I took up the problem of the mechanism by which lysine 2,3-aminomutase (LAM) catalyzes S-adenosylmethionine (SAM) and pyridoxal-5′-phosphate (PLP)-dependent interconversion of l-lysine and l-β-lysine. Because the reaction followed the pattern of adenosylcobalamin-dependent rearrangements, I postulated that SAM might be an evolutionary predecessor to adenosylcobalamin. Testing this hypothesis, we traced hydrogen transfer from lysine through the adenosyl-C5′ of SAM to β-lysine. Thus, the 5′-deoxyadenosyl of SAM mediated hydrogen transfer by LAM exactly as in adenosylcobalamin mediated hydrogen transfer in B12-dependent isomerizations. The mechanism postulated that SAM cleaves to form 5′-deoxyadenosine-5′-yl followed by abstraction of C3(H) from PLP-α-lysine aldimine to form PLP-α-lysine-3-yl. PLP-α-lysine-3-yl isomerizes to pyridoxal-β-lysine-2-yl, and a hydrogen abstraction from 5′-deoxyadenosine regenerates 5′-deoxyadenosine-5′-yl and releases β-lysine. Of four radicals in the postulated mechanism, three have been characterized by EPR spectroscopy as kinetically competent intermediates.The analysis of the role of iron allowed researchers to elucidate the mechanism by which SAM is cleaved to 5′-deoxyadenosine-5′-yl. LAM contains one [4Fe-4S] cluster ligated by three cysteine residues. As shown by ENDOR spectroscopy and X-ray crystallography, the fourth ligand to the cluster is SAM, through the methionyl carboxylate and amino groups. Inner sphere electron transfer within the [4Fe-4S]1+-SAM complex leads to [4Fe-4S]2+-Met and 5′-deoxyadenosine-5′-yl.The iron-binding motif in LAM, CxxxCxxC, found by other groups in four other SAM-dependent enzymes, is the founding motif for the radical SAM superfamily. These enzymes number in the tens of thousands and are responsible for highly diverse and chemically difficult transformations in the biosphere. Available information supports the hypothesis that this superfamily provides the chemical context from which the much more structurally complex adenosylcobalamin evolved. © 2013 American Chemical Society. Source

Hittinger C.T.,University of Wisconsin - Madison
Trends in Genetics | Year: 2013

Saccharomyces cerevisiae is one of the best-understood and most powerful genetic model systems. Several disciplines are now converging to turn Saccharomyces into an exciting model genus for evolutionary genetics and genomics. Yeast taxonomists and ecologists have dramatically expanded and clarified Saccharomyces diversity, more than doubling the number of bona fide species since 2000. High-quality genome sequences are available (or soon will be) for all seven known species. Haploid laboratory strains are enabling a deep integration of classic genetic approaches with modern genomic tools. Population genomic surveys and quantitative trait mapping of variation within species are underway across the genus. Finally, several case studies have illuminated general and novel genetic mechanisms of evolution. Expanding strain collections, low-cost genome sequencing, and tools for precise genetic manipulation promise to usher in a golden era for this surprisingly diverse genus as an evolutionary model. © 2013 Elsevier Ltd. Source

McFall-Ngai M.J.,University of Wisconsin - Madison
Annual Review of Microbiology | Year: 2014

Developmental biology is among the many subdisciplines of the life sciences being transformed by our increasing awareness of the role of coevolved microbial symbionts in health and disease. Most symbioses are horizontally acquired, i.e., they begin anew each generation. In such associations, the embryonic period prepares the animal to engage with the coevolved partner(s) with fidelity following birth or hatching. Once interactions are underway, the microbial partners drive maturation of tissues that are either directly associated with or distant from the symbiont populations. Animal alliances often involve complex microbial communities, such as those in the vertebrate gastrointestinal tract. A series of simpler-model systems is providing insight into the basic rules and principles that govern the establishment and maintenance of stable animal-microbe partnerships. This review focuses on what biologists have learned about the developmental trajectory of horizontally acquired symbioses through the study of the binary squid-vibrio model. Copyright © 2014 by Annual Reviews. All rights reserved. Source

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