Mutational Analysis of the Arf1•GTP/Arf GAP Interface Reveals an Arf1 Mutant that Selectively Affects the Arf GAP ASAP1

SummaryArf1 is a GTP binding protein that functions at a number of cellular sites to control membrane traffic and actin remodeling. Arf1 is regulated by site-specific GTPase-activating proteins (GAPs). The combined results of crystallographic and biochemical studies [1–3] have led to the proposal that Arf1 GAPs differ in the specific interface formed with Arf1. To test this hypothesis, we have used mutagenesis to examine the interaction of three Arf GAPs (ASAP1, AGAP1, and ArfGAP1) with switch 1, switch 2, and α helix3 of Arf1. The GAPs were similar in being affected by mutations in switch 1 and 2. However, effects of a mutation within α helix3 and specific mutations within switch 1 and 2 differed among the GAPs. The largest differences were observed with a change of isoleucine 46 to aspartate ([I46D]Arf1), which reduced ASAP1-induced catalysis by ∼10,000-fold but had a 3-fold effect on AGAP1. The reduction was due to an isolated effect on the catalytic rate, kcat. In vivo [I46D]Arf1 had no detectable effect on the Golgi apparatus but, instead, functioned as a constitutively active mutant in the cell periphery, affecting the localization of ASAP1 and paxillin. Based on our results, we conclude that the contribution of specific residues within switch 1 of Arf to binding and achieving a transition state toward GTP hydrolysis differs among Arf GAPs

Writers (Un)Block Grip Expander

Poster is of the Writers (Un)Block Grip Expander that aids in writing for prolonged periods for those with a weakened grasp.https://jdc.jefferson.edu/id/1009/thumbnail.jp

1995 Ruby Yearbook

A digitized copy of the 1995 Ruby, the Ursinus College yearbook.https://digitalcommons.ursinus.edu/ruby/1098/thumbnail.jp

The Grizzly, September 19, 1995

The Myth of Masculinity • Fairley in Custody • What am I Gonna do After College? • Helping Inmates Read • SAO: The Old and The New! • U.S. Calls for Peace • A Major Problem • Debate: Drinking • Oscar Needs a Home • Spotlight: Reverend Scott Landis • Chi Rho Psi to Feed the Homeless • Zack\u27s: New and Improved • Women 1, Men 0 in the Battle of the Sexes • Sigma Chi Delta is Here • Get a Kick Out of the Martial Arts Club • F&M Blanks Bears • Let\u27s Make Love • Men\u27s Soccer Wins • Spotlight: Brian Hamrick • Field Hockey Wins Two Straight • Volleyball Team Places Fifthhttps://digitalcommons.ursinus.edu/grizzlynews/1362/thumbnail.jp

The Lantern Vol. 63, No. 1, Fall 1995

• The Birthday Celebration • Surprise! Surprise! • Oregold • Future of Parenthood #2 • Seeds • How I Spent My Summer Vacation • Random Scenes From 1/2 Hour at Work • Life in the Coal Mines • Driveway • Midnight in the Court of Kings • The Black Quadrilateral • People I Hate to See, But Refuse to Dismiss • Metropolized • Poetry in Motion • Dream #3 • Rhythms • Mercykilling • Untitled • Lupine Lord • At the Bottom of the Cup • House of Commons • Poetry I Can\u27t Standhttps://digitalcommons.ursinus.edu/lantern/1147/thumbnail.jp

The Lantern Vol. 63, No. 2, Spring 1996

• Poet, Lead Me On • St. Patrick\u27s Day • The Last Three Days • The Impressionable • Roundabout • The Bench • Carnivorous • Kyrie • Second Glance • Porch • Cruel Design • A Mime • Flaxen Crown • My Embryonic Ocean of Love • Stone Matrix • Voices from the Past • Skipping the Bullfight: Toreadors and Gaudi • Another Part of My Lacolonialism • Translucent Pane • Linguistics • Treehouse • A Disagreeable Music Piece • Vigil • A Brief History of American Poetry in Englishhttps://digitalcommons.ursinus.edu/lantern/1148/thumbnail.jp

Observation of large and all-season ozone losses over the tropics” [AIP Adv. 12, 075006 (2022)]

As discussed above, and supported by extensive literature, there is no robust, credible observational evidence for substantial ozone depletion (i.e., an “ozone hole”) in the tropics. It is well known that climatological total ozone in the tropics is much lower than that in the mid-latitudes (e.g., Sahai et al., 2000; Weber et al., 2022). Satellite and ozonesonde measurements indicate a 3%–5% per decade decline of tropical lower stratosphere ozone prior to 2000, far smaller than that reported by L2022. The stronger decline reported by L2022 is caused by inappropriate use of the gap-filled version of the TOST ozone dataset, which is based on sparse tropical ozone sondes before the 1990s. This misuse of data (TOST and total column ozone) shows the importance of collaboratively engaging with groups who obtain the measurements and create climatological datasets before performing such analyses. Furthermore, the study by L2022 has multiple flaws in its discussion of atmospheric chemistry and dynamics, particularly in the proposed, and previously refuted (see Sec. III A), cosmicray- driven electron induced (CRE) mechanism. Evidence for the occurrence of tropical stratospheric clouds, as needed for the tropical CRE mechanism, is lacking, nor do CFC-12 observations show signatures of depletion in the tropical lower stratosphere, which could be associated with dissociative electron attachment-induced loss of CFC-12 on particulate matter (i.e., the CRE mechanism). Finally, it is worth reiterating that the CRE mechanism is also not responsible for polar LS ozone depletion. Polar ozone loss can be well explained by the gas phase and heterogeneous chemistry, based on extensive observations and modeling studies documented in many thousands of scientific papers on the topic [e.g., see WMO (2018) and references therein], which is not acknowledged by L2022. L2022’s research paper is a severely flawed one. There is no tropical ozone hole, and the CRE mechanism does not explain observed changes in stratospheric ozone either in the polar regions or in the tropics

SN 2019ehk: A Double-peaked Ca-rich Transient with Luminous X-Ray Emission and Shock-ionized Spectral Features

We present panchromatic observations and modeling of the Calcium-rich supernova (SN) 2019ehk in the star-forming galaxy M100 (d ≈ 16.2 Mpc) starting 10 hr after explosion and continuing for ~300 days. SN 2019ehk shows a double-peaked optical light curve peaking at t = 3 and 15 days. The first peak is coincident with luminous, rapidly decaying Swift-XRT–discovered X-ray emission (L_x ≈ 10⁴¹ erg s⁻¹ at 3 days; L_x ∝ t⁻³), and a Shane/Kast spectral detection of narrow Hα and He II emission lines (v ≈ 500 km s⁻¹) originating from pre-existent circumstellar material (CSM). We attribute this phenomenology to radiation from shock interaction with extended, dense material surrounding the progenitor star at r (0.1–1) × 10¹⁷ cm. The photometric and spectroscopic properties during the second light-curve peak are consistent with those of Ca-rich transients (rise-time of t_r = 13.4 ± 0.210 days and a peak B-band magnitude of M_B = −15.1 ± 0.200 mag). We find that SN 2019ehk synthesized (3.1 ± 0.11) × 10⁻² M_⊙ of ⁵⁶Ni and ejected M_(ej) = (0.72 ± 0.040) M⊙ total with a kinetic energy E_k = (1.8 ± 0.10) × 10⁵⁰ erg. Finally, deep HST pre-explosion imaging at the SN site constrains the parameter space of viable stellar progenitors to massive stars in the lowest mass bin (~10 M_⊙) in binaries that lost most of their He envelope or white dwarfs (WDs). The explosion and environment properties of SN 2019ehk further restrict the potential WD progenitor systems to low-mass hybrid HeCO WD+CO WD binaries

Altered gene expression profiles define pathways in colorectal cancer cell lines affected by celecoxib

It is well established that celecoxib, a selective inhibitor of cyclooxygenase-2 (COX-2) and a tested chemopreventive agent, has several COX-2-independent activities. In an attempt to better understand COX-2-independent molecular mechanisms underlying the chemopreventive activity of celecoxib, we did global transcription profiling of celecoxib-treated COX-2-positive and COX-2-deficient colorectal cancer cell lines. Celecoxib treatment resulted in significantly altered expression levels of over 1,000 to 3,000 transcripts in these cell lines, respectively. A pathway/functional analysis of celecoxib-affected transcripts, using Gene Ontology and Biocarta Pathways and exploring biological association networks, revealed that celecoxib modulates expression of numerous genes involved in a variety of cellular processes, including metabolism, cell proliferation, apoptotic signaling, cell cycle check points, lymphocyte activation, and signaling pathways. Among these processes, cell proliferation and apoptotic signaling consistently ranked as the highest-scoring Gene Ontology terms and Biocarta Pathways in both COX-2 expresser and nonexpresser cell lines. Altered expression of many of the genes by celecoxib was confirmed by quantitative PCR and at the protein level by Western blotting. Many novel genes emerged from our analysis of global transcription patterns that were not previously reported to be affected by celecoxib. In the future, in-depth work on selected genes will determine if these genes may serve as potential molecular targets for more effective chemopreventive strategies