The Grizzly, December 8, 1998

Actual Implications of Student Evaluations • Students Debate Greek Life on Campus • Opinion: Letter to the Editor; Greek Life Controversy; Who\u27s Recycling? • Final Exam Schedule • Baseball Coach Discusses Return to Vietnam • New Law Helps College Students Manage Debt • WVOU Benefit a Success • High-Tech Cheating, For a Price • Panelists Square Off on Global Warming • Women\u27s Basketball Setting Their Mark • Men\u27s Basketball Opens League Play With Win • UC Swimming in Full Swinghttps://digitalcommons.ursinus.edu/grizzlynews/1430/thumbnail.jp

The Grizzly, October 13, 1998

Drunk Driving Hits the Campus • A Tale of Two Teams • Wismer Lower Library? • As the World Communicates • Friday Night Fights • GALA Makes Changes, Seeks Broader Support • Wellness to Promote Alcohol Awareness • Berman Quilt Exhibit • Sculptures on Campus • Field Hockey Falls to 0-11 • Women\u27s Soccer at .500 • Football Downed at Homecoming • Cross Country Competes in Dickinson Invitational • UC Volleyball Keeps Steady Pace • Faculty Coaches Give New Edge on Footballhttps://digitalcommons.ursinus.edu/grizzlynews/1426/thumbnail.jp

The Grizzly, November 17, 1998

Bring in the New Year with a New Problem • Airband: Still Searching for a Cause • Update: New Gym • Opinion: Opportunity to Gain a Degree Should be for Everyone • Full-time Students, Part-time Jobs • Is Anyone Listening?: WVOU • Swing Night at Ursinus • Eden Cinema: Paradise • Cross Country Sprints to End • Women\u27s Soccer Season Concludes • Seniors Step-Up on the Volleyball Court • UC Swimming Drops Home Opener • Ursinus Wrestlers Hungry to Regain Title • Field Hockey Struggles Through Rebuilding • UC Football Loses Final Battle of Season • UC Football Players Honored • Donahue and Bailey Represent UChttps://digitalcommons.ursinus.edu/grizzlynews/1429/thumbnail.jp

The Grizzly, October 27, 1998

Mischief and Mayhem Night • Big Brother\u27s in the Library • Rewind: Homecoming Alterations • Racism: One Piece of the Puzzle • The Democratic Dilemma of Legislating Hate • Are We Creatures of Habit? • A Look at What Ursinus Terms as Security • Students Voice Security Concerns • Borsdorf Spreads Fitness Message Over East Coast • Sculpture Depicts Trauma, Unity and Sacrifice of War Years • Ursinus Welcomes Savadove • Jeffrey Gaines Entertains Ursinus • Church on Film • McKellen Teaches Us a Thing or Two in Apt Pupil • The Big Fella\u27s Forum • Ursinus Destroys Gettysburg • Linebacker Vecchio Shines for Ursinus • Women\u27s Soccer Makes History • Cross Country Runs Over Competition • Soccer Falls Against Gettysburg • UC Volleyball Evens Out at .500 • Field Hockey Chalks Up First Victoryhttps://digitalcommons.ursinus.edu/grizzlynews/1991/thumbnail.jp

The Grizzly, November 10, 1998

Financial Aid: Who Here Gets It? • President Pleased with Success of Roundtable • Upperclassman Mentors • Opinion: Letter to the Editor; New Athletic Facility; Reflection on Mid-term Elections; U.S. Policy Makers, Look Before you Leap; Cashing in on the Past • Betting, Off-Track and On-Campus • Kidnapped? Grizzly Uncovers Surprising Truth About Missing Corson Statue • War Years Classes Dedicate Promise-Anthem • Remembering War Years Life at Ursinus • Eden Cinema at Ursinus • Waiting for the World to Catch Up • Swimming Takes First Plunge • UC Field Hockey Finishes Strong • Bears\u27 Future: Contenders or Pretenders? • NCAA Sets to Control Wrestling Tragedies • Men\u27s Basketball Prepares for Tough Schedule • Ursinus Athletes Honored • UC Soccer Finishes Season with Tough Losshttps://digitalcommons.ursinus.edu/grizzlynews/1428/thumbnail.jp

The Grizzly, November 3, 1998

President\u27s Proposal Summons Bears to the Roundtable • Pay...Now or Later • Myrin Security a Necessity • Close of Olin\u27s Open Door Policy • Opinion: Random Rudeness and Senseless Acts of Destruction; Why This Election Matters; College Students: Get Out and Vote! • Group Helps Students Cope with Loss • Kicking the Habit, One Habit at a Time • New Course Tackles The Big Questions • A Night of Jazz • Intercollegiate Choir • Graffiti Tribe Returns • Men\u27s Soccer Dominates Swarthmore • Season High for UC Volleyball • Field Hockey Victorious Over Colgate • UC Swimmers Test the Water • Women\u27s Soccer Season Ends Its Third Year • Football Loses to Muhlenberg in Overtimehttps://digitalcommons.ursinus.edu/grizzlynews/1427/thumbnail.jp

Discovery of Sulfonamidebenzamides as Selective Apoptotic CHOP Pathway Activators of the Unfolded Protein Response

Cellular proteins that fail to fold properly result in inactive or disfunctional proteins that can have toxic functions. The unfolded protein response (UPR) is a two-tiered cellular mechanism initiated by eukaryotic cells that have accumulated misfolded proteins within the endoplasmic reticulum (ER). An adaptive pathway facilitates the clearance of the undesired proteins; however, if overwhelmed, cells trigger apoptosis by upregulating transcription factors such as C/EBP-homologous protein (CHOP). A high throughput screen was performed directed at identifying compounds that selectively upregulate the apoptotic CHOP pathway while avoiding adaptive signaling cascades, resulting in a sulfonamidebenzamide chemotype that was optimized. These efforts produced a potent and selective CHOP inducer (AC₅₀ = 0.8 μM; XBP1 > 80 μM), which was efficacious in both mouse embryonic fibroblast cells and a human oral squamous cell cancer cell line, and demonstrated antiproliferative effects for multiple cancer cell lines in the NCI-60 panel

Discovery of a Plasmodium falciparum Glucose-6-phosphate Dehydrogenase 6‑phosphogluconolactonase Inhibitor (<i>R</i>,<i>Z</i>)‑<i>N</i>‑((1-Ethylpyrrolidin-2-yl)methyl)-2-(2-fluorobenzylidene)-3-oxo-3,4-dihydro‑2<i>H</i>‑benzo[<i>b</i>][1,4]thiazine-6-carboxamide (ML276) That Reduces Parasite Growth in Vitro

A high-throughput screen of the NIH’s MLSMR collection of ∼340000 compounds was undertaken to identify compounds that inhibit Plasmodium falciparum glucose-6-phosphate dehydrogenase (<i>Pf</i>G6PD). <i>Pf</i>G6PD is important for proliferating and propagating P. falciparum and differs structurally and mechanistically from the human orthologue. The reaction catalyzed by glucose-6-phosphate dehydrogenase (G6PD) is the first, rate-limiting step in the pentose phosphate pathway (PPP), a key metabolic pathway sustaining anabolic needs in reductive equivalents and synthetic materials in fast-growing cells. In P. falciparum, the bifunctional enzyme glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase (<i>Pf</i>GluPho) catalyzes the first two steps of the PPP. Because P. falciparum and infected host red blood cells rely on accelerated glucose flux, they depend on the G6PD activity of <i>Pf</i>GluPho. The lead compound identified from this effort, (<i>R</i>,<i>Z</i>)-<i>N</i>-((1-ethylpyrrolidin-2-yl)­methyl)-2-(2-fluorobenzylidene)-3-oxo-3,4-dihydro-2<i>H</i>-benzo­[<i>b</i>]­[1,4]­thiazine-6-carboxamide, <b>11</b> (ML276), is a submicromolar inhibitor of <i>Pf</i>G6PD (IC₅₀ = 889 nM). It is completely selective for the enzyme’s human isoform, displays micromolar potency (IC₅₀ = 2.6 μM) against P. falciparum in culture, and has good drug-like properties, including high solubility and moderate microsomal stability. Studies testing the potential advantage of inhibiting <i>Pf</i>G6PD in vivo are in progress