The Grizzly, March 29, 1985

St. Joe\u27s to Offer MBA Program on Ursinus Campus • New Poli Sci Professor Hired • Main St. Renovations Scheduled • Co-ed Housing to Start Next Year in Reimert Complex • Community Opposes Vigilantes • Dining Committee Presents New Recipe Program • Car Stairs, S.P.E.C.T.E.R. Undefeated in College Bowl • Student Relates German Experience • Defending Champs Open Lax Season with Win • Baseball Squad Off to Sluggish Start • New Coach Readies Golfers for Tough Week • Senior Diver Finishes 19th in NCAA Championshipshttps://digitalcommons.ursinus.edu/grizzlynews/1137/thumbnail.jp

The Grizzly, April 18, 1986

The Bomb is Dropped; Policy Could Can Kegs • Admissions Video to Draw High School Seniors • CAB Spring Weekend Twists Around the Corner! • Administration\u27s Letter: Clearing Up the Cloudy Water • Get Your Ruby • Proposed Alcohol Regulations • Political Science\u27s Fitzpatrick to Focus on Constitution • Richter Joins Pavarotti • Greek Week Results • College Republicans Meet in Harrisburg • Perreten in Select Group to Interpret Humanities • Novack to Study Technology\u27s Effects on French Life • Lift-A-Thon: Pressing Weights for Progress • Women\u27s LAX Takes Two • Linksters Drive to 7-1 Record • Men\u27s LAX Strong at 5-2 • Rowson a Threat for Gold in Five Events • A Sterling Suggestion! Brown to be Tattooed • O\u27Toole Hurdles School Record • Men\u27s Tennis • Bears Battle Back • Hadler\u27s Medical Serieshttps://digitalcommons.ursinus.edu/grizzlynews/1988/thumbnail.jp

25-Hydroxyvitamin D Depletion Does Not Exacerbate MPTP-Induced Dopamine Neuron Damage in Mice

Recent clinical evidence supports a link between 25-hydroxyvitamin D insufficiency (serum 25-hydroxyvitamin D [25(OH)D] levels <30 ng/mL) and Parkinson’s disease. To investigate the effect of 25(OH)D depletion on neuronal susceptibility to toxic insult, we induced a state of 25(OH)D deficiency in mice and then challenged them with the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We found there was no significant difference between control and 25(OH)D-deficient animals in striatal dopamine levels or dopamine transporter and tyrosine hydroxylase expression after lesioning with MPTP. Additionally, we found no difference in tyrosine hydroxylase expression in the substantia nigra pars compacta. Our data suggest that reducing 25(OH)D serum levels in mice has no effect on the vulnerability of nigral dopaminergic neurons in vivo in this model system of parkinsonism

The Grizzly, April 26, 1985

Greek Week Comes to a Close • Economics Council Hosts Speakers • Class Attendance • Airbands Raise Money for Hungry • Letters: Teachers Needed • Outstanding Educators • Seniors Honored as Chapter Scholars • Shorts: Giunta Named Truman Scholar; Comet Looked at; Voices Called For; Pick-a-prof; U.C. Sees D.C.; Spring Concert; 550 Fast! • U2 Unforgettable at Spectrum • Fans Grateful Band is Still Alive • Day Shines the Light on Winning • UC Beats Div.I Delaware • Heading Toward a Winning Season • Politics is Just Another Goal Scored • Bravo Performs on Both Decks • Bears Look Good: MACs Coming • Flyers Quest for Cup • Cordes Scores Big at Temple • Intramural Softballhttps://digitalcommons.ursinus.edu/grizzlynews/1141/thumbnail.jp

The Grizzly, April 11, 1986

Collegeville Water: Poison • Toombs Speaks on Real Estate • The Time has Come • Wismer, be Realistic! • Letter: Administration Housing Plans are Unfair • Former U.C. Graduate Plays Important Role in Recovery of Challenger Debris • Hair Sneak Preview • Take C and C and See the Progress of Humanity • Greeks Flail Booze Curtail • Looking for Alternatives to the Joys of Alcohol • Women\u27s Lacrosse Wins Five in a Row • Linksters Off to a Great Start • Bears Drop to 4-8 • Women\u27s Track • Profile: Marc Dervishian • Women\u27s Softball Season Heats Up • Women\u27s Tennis Falls to 1-4 • Profile: Leigh Garrison • Gung Ho for Howard • Music: It gets the Irish in me Goinghttps://digitalcommons.ursinus.edu/grizzlynews/1163/thumbnail.jp

ALS-linked FUS exerts a gain of toxic function involving aberrant p38 MAPK activation

© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 7 (2017): 115, doi:10.1038/s41598-017-00091-1.Mutations in Fused in Sarcoma/Translocated in Liposarcoma (FUS) cause familial forms of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by progressive axonal degeneration mainly affecting motor neurons. Evidence from transgenic mouse models suggests mutant forms of FUS exert an unknown gain-of-toxic function in motor neurons, but mechanisms underlying this effect remain unknown. Towards this end, we studied the effect of wild type FUS (FUS WT) and three ALS-linked variants (G230C, R521G and R495X) on fast axonal transport (FAT), a cellular process critical for appropriate maintenance of axonal connectivity. All ALS-FUS variants impaired anterograde and retrograde FAT in squid axoplasm, whereas FUS WT had no effect. Misfolding of mutant FUS is implicated in this process, as the molecular chaperone Hsp110 mitigated these toxic effects. Interestingly, mutant FUS-induced impairment of FAT in squid axoplasm and of axonal outgrowth in mammalian primary motor neurons involved aberrant activation of the p38 MAPK pathway, as also reported for ALS-linked forms of Cu, Zn superoxide dismutase (SOD1). Accordingly, increased levels of active p38 MAPK were detected in post-mortem human ALS-FUS brain tissues. These data provide evidence for a novel gain-of-toxic function for ALS-linked FUS involving p38 MAPK activation.We are grateful for funding from NIH/NINDS (R01 NS078145, R01 NS090352, and R21 NS091860 to D.A.B., R01 NS066942A and R21 NS096642 to G.M., R01NS023868 and R01NS041170 to S.T.B.), the ALS Therapy Alliance/CVS Pharmacy (to D.A.B. and G.M.) and the ALS Association (to C.F. and J.M.)

The Grizzly, May 3, 1985

Reimert Hall Will Welcome Girls in the Fall • Fraternities Are Still Alive at Ursinus • Ursinus Applicants Improve • Letters: Greek Week Disappointing; Radio Offers Thanks • Drinking Age of 21 Should Not Be a Standard • Profile: Dr. Coggers Says Farewell • Greek Week\u27s Final Results • Lacrosse Looks to Repeat Division III Title • Successful Year for Lacrosse Club • Gasser Retires • Sally Grim Shines As Star Pitcher • Griffin Worth Far More than Gold • Trackmen Head to MAC\u27s • Stormy Baver is Pilot Behind the Plate • Golf Team Optimistic • Visit the Writing Center • 1985 Baseball Wraps it Up • 1985 Lacrosse Stats • St. Joseph\u27s M.B.A Courses Offered at Ursinus • Open Dialog On Intervention • Area Residents Share College Memories • Shorts: Faculty Members to Retire; Open Dialog; Color Analysis Held on Campus; Evening Concert Announced; Voices ; Art Show • Dead Kennedys • WVOU Conducts Survey • Luau on Sat. • Weekend Highlights • It Will Be a Fantasy Weekendhttps://digitalcommons.ursinus.edu/grizzlynews/1142/thumbnail.jp

ALS-linked PFN1 variants exhibit loss and gain of functions in the context of formin-induced actin polymerization

International audienceProfilin-1 (PFN1) plays important roles in modulating actin dynamics through binding both monomeric actin and proteins enriched with polyproline motifs. Mutations in PFN1 have been linked to the neurodegenerative disease amyotrophic lateral sclerosis (ALS). However, whether ALS-linked mutations affect PFN1 function has remained unclear. To address this question, we employed an unbiased proteomics analysis in mammalian cells to identify proteins that differentially interact with mutant and wild-type (WT) PFN1. These studies uncovered differential binding between two ALS-linked PFN1 variants, G118V and M114T, and select formin proteins. Furthermore, both variants augmented formin-mediated actin assembly relative to PFN1 WT. Molecular dynamics simulations revealed mutation-induced changes in the internal dynamic couplings within an alpha helix of PFN1 that directly contacts both actin and polyproline, as well as structural fluctuations within the actin- and polyproline-binding regions of PFN1. These data indicate that ALS-PFN1 variants have the potential for heightened flexibility in the context of the ternary actin–PFN1–polyproline complex during actin assembly. Conversely, PFN1 C71G was more severely destabilized than the other PFN1 variants, resulting in reduced protein expression in both transfected and ALS patient lymphoblast cell lines. Moreover, this variant exhibited loss-of-function phenotypes in the context of actin assembly. Perturbations in actin dynamics and assembly can therefore result from ALS-linked mutations in PFN1. However, ALS-PFN1 variants may dysregulate actin polymerization through different mechanisms that depend upon the solubility and stability of the mutant protein

Human C9ORF72 Hexanucleotide Expansion Reproduces RNA Foci and Dipeptide Repeat Proteins but Not Neurodegeneration in BAC Transgenic Mice

A non-coding hexanucleotide repeat expansion in the C9ORF72 gene is the most common mutation associated with familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). To investigate the pathological role of C9ORF72 in these diseases, we generated a line of mice carrying a bacterial artificial chromosome containing exons 1 to 6 of the human C9ORF72 gene with approximately 500 repeats of the GGGGCC motif. The mice showed no overt behavioral phenotype but recapitulated distinctive histopathological features of C9ORF72 ALS/FTD, including sense and antisense intranuclear RNA foci and poly(glycine-proline) dipeptide repeat proteins. Finally, using an artificial microRNA that targets human C9ORF72 in cultures of primary cortical neurons from the C9BAC mice, we have attenuated expression of the C9BAC transgene and the poly(GP) dipeptides. The C9ORF72 BAC transgenic mice will be a valuable tool in the study of ALS/FTD pathobiology and therapy

25(OH)D depletion does not exacerbate loss of tyrosine hydroxylase staining in the striatum and nigra after MPTP lesion.

<p>A) Representative TH staining of the striatum. B) Representative TH staining of the nigra.</p