A new invertebrate member of the p53 gene family is developmentally expressed and responds to polychlorinated biphenyls.

The cell-cycle checkpoint protein p53 both directs terminal differentiation and protects embryos from DNA damage. To study invertebrate p53 during early development, we identified three differentially expressed p53 family members (p53, p97, p120) in the surf clam, Spisula solidissima. In these mollusks, p53 and p97 occur in both embryonic and adult tissue, whereas p120 is exclusively embryonic. We sequenced, cloned, and characterized p120 cDNA. The predicted protein, p120, resembles p53 across all evolutionarily conserved regions and contains a C-terminal extension with a sterile alpha motif (SAM) as in p63 and p73. These vertebrate forms of p53 are required for normal inflammatory, epithelial, and neuronal development. Unlike clam p53 and p97, p120 mRNA and protein levels are temporally expressed in embryos, with mRNA levels decreasing with increasing p120 protein (R(2) = 0.97). Highest surf clam p120 mRNA levels coincide with the onset of neuronal growth. In earlier work we have shown that neuronal development is altered by exposure to polychlorinated biphenyls (PCBs), a neurotoxic environmental contaminant. In this study we show that PCBs differentially affect expression of the three surf clam p53 family members. p120 mRNA and protein are reduced the most and earliest in development, p97 protein shows a smaller and later reduction, and p53 protein levels do not change. For the first time we report that unlike p53 and p97, p120 is specifically embryonic and expressed in a time-dependent manner. Furthermore, p120 responds to PCBs by 48 hr when PCB-induced suppression of the serotonergic nervous system occurs

The Grizzly, November 9, 2000

Student Spearheads Effort to Save Local Dam • Cause of Deer\u27s Death a Concern to Police • Incident in Duryea Sparks Policy Change • Hostage Situation Unspools at Local Theater • A Nation Divided • Campus Survey Gauges Students\u27 Political Preferences • Collegeville has a New Sheriff in Town • Best Buddies Have Phantastic Time in Philly • Seniors Have Devil of a Time at Halloween Bash • GSA a Blur of Activity • Opinions: Campus Going to Waste; False Fire Alarms Annoying, Unsafe; CIE II a Must for Students at UC; Did Students Vote on Election Day?; Unwelcome Present Left for Reimert Residents; UC\u27s Athletic Internet Site not Living up to Potential; Confessions of a Political Junkie: An Intern\u27s Insights Into Y2K Campaigning • Ursinus Junior on \u27College Jeopardy!\u27 • Elijah a True Choral Masterpiece • Scudera\u27s Modern-day Everyman to Open Nov. 15th • Results are in: It\u27s Walking Woman in Runaway Victory • Rock & Roll Reception at Berman Today • Let the Winter Games Begin • Soccer Closes out Season with Loss to Mules • Deadly Virus Ravages African Population • Meningitis Vaccination to be Held on Campus Nov.15 • College Students Need Sleep • Muhlenberg Blanks Bears in Women\u27s Soccer Finale • Wrestler\u27s Quest for National Title Continues • Lacrosse\u27s McGovern Refuses to be Held Back • Centennial Conference Academic Honor Roll • Bears Blank Cougars, Keep Playoff Hopes Alive • Intramural Basketball Hoopla Already Underwayhttps://digitalcommons.ursinus.edu/grizzlynews/1478/thumbnail.jp

Mitochondria, Energetics, Epigenetics, and Cellular Responses to Stress

Background: Cells respond to environmental stressors through several key pathways, including response to reactive oxygen species (ROS), nutrient and ATP sensing, DNA damage response (DDR), and epigenetic alterations. Mitochondria play a central role in these pathways not only through energetics and ATP production but also through metabolites generated in the tricarboxylic acid cycle, as well as mitochondria–nuclear signaling related to mitochondria morphology, biogenesis, fission/fusion, mitophagy, apoptosis, and epigenetic regulation. Objectives: We investigated the concept of bidirectional interactions between mitochondria and cellular pathways in response to environmental stress with a focus on epigenetic regulation, and we examined DNA repair and DDR pathways as examples of biological processes that respond to exogenous insults through changes in homeostasis and altered mitochondrial function. Methods: The National Institute of Environmental Health Sciences sponsored the Workshop on Mitochondria, Energetics, Epigenetics, Environment, and DNA Damage Response on 25–26 March 2013. Here, we summarize key points and ideas emerging from this meeting. Discussion: A more comprehensive understanding of signaling mechanisms (cross-talk) between the mitochondria and nucleus is central to elucidating the integration of mitochondrial functions with other cellular response pathways in modulating the effects of environmental agents. Recent studies have highlighted the importance of mitochondrial functions in epigenetic regulation and DDR with environmental stress. Development and application of novel technologies, enhanced experimental models, and a systems-type research approach will help to discern how environmentally induced mitochondrial dysfunction affects key mechanistic pathways. Conclusions: Understanding mitochondria–cell signaling will provide insight into individual responses to environmental hazards, improving prediction of hazard and susceptibility to environmental stressors. Citation: Shaughnessy DT, McAllister K, Worth L, Haugen AC, Meyer JN, Domann FE, Van Houten B, Mostoslavsky R, Bultman SJ, Baccarelli AA, Begley TJ, Sobol RW, Hirschey MD, Ideker T, Santos JH, Copeland WC, Tice RR, Balshaw DM, Tyson FL. 2014. Mitochondria, energetics, epigenetics, and cellular responses to stress. Environ Health Perspect 122:1271–1278; http://dx.doi.org/10.1289/ehp.140841

The Protein Maker: an automated system for high-throughput parallel purification

The Protein Maker instrument addresses a critical bottleneck in structural genomics by allowing automated purification and buffer testing of multiple protein targets in parallel with a single instrument. Here, the use of this instrument to (i) purify multiple influenza-virus proteins in parallel for crystallization trials and (ii) identify optimal lysis-buffer conditions prior to large-scale protein purification is described

The Grizzly, November 2, 2000

Students Rally to End Sexual Assault, Violence • Homecoming Case Closed, all Charges Dropped • Scuffle at Duryea Still Being Investigated • UC House of Horrors: Children Enjoy Ghoulish Experience • Operation Christmas Child • Goldstein Appointed Hillel Director • Study Abroad in London, Florence Next Fall • Annual Halloween Decorating Contest Winners Announced • Opinions: Where\u27s the Rush? Shortening of Rushing Activities has Some Greeks Angry, Upset; Up in Smoke: Non-smokers Fed up with UC Students Lighting up; Gore Does More to Combat Hate Crimes; Are we too old for Halloween?; A Vote for Al Gore is a Vote for our Future; Don\u27t Waste Your Vote on Majority Party Candidates, Elect Nader Nov. 7; Amidst Campus Safety Concerns, are IDs the Answer?; Rewards of Mideast Outweigh Risks for one UC Student • Students Make MTV Debut on \u27Total Request Live\u27 • Gone with the Wind: Bears Drop Heartbreaker to Mules on Blustery Day • It\u27s Madness!: Hoops Squad Scores Big with Annual Slam-dunk, Kick-off Festivities • Volleyball Drops Season Finale to Conference Rival • Men\u27s Soccer Falls to Fords • Men\u27s Lacrosse Gears up for Spring Season • Breast Cancer: What College Students Need to Know • Annual Health Fair Acquires new Name, Attitude • Tips for Female Lifters to Make it big in the Weight Room • Bears Field Hockey Rocks Rider, Finishes Season with Patriot League Win • XC Takes on WMC Course at Conference Champshttps://digitalcommons.ursinus.edu/grizzlynews/1477/thumbnail.jp

Inhibitor-bound complexes of dihydrofolate reductase-thymidylate synthase from Babesia bovis

Structural characterization of the bifunctional enzyme dihydrofolate reductase-thymidylate synthase from B. bovis in the apo state and complexed with antifolate inhibitors in both enzymatic active sites is reported