The Grizzly, November 3, 1978

Task Force Proposes Curricular Revisions: Faculty Discusses Broad Academic Changes • Computer Programs To Be Studied • Reed This Message • Liberal Education for a Modern World • Letters to the Editor • Campus Committees Graded • Springsteen Revisited • Halloween Horrors! • Annual Messiah Rehearsal • French Club Wined and Dined • GM: Looking Good For \u2779 • Soccer Trounces Widener • Founders\u27 Convocation • Harriers Cap 12-1 Season • Mermaids Anticipate Slick Season • Hockey J. V.s With No Losses • Zetans Take Intramural Football Championship • News in Brief: Egdon Heath to Rock T. G.; Forum Presents Workshop, Performance; Ursinus Appoints Band Directorhttps://digitalcommons.ursinus.edu/grizzlynews/1005/thumbnail.jp

The Grizzly, October 13, 1978

Frat Takes Charge: ZX To Clean New Men\u27s Dorm • Seniors Attack Teaching • News in Brief: Frosh Elections; Bause Gets Alumni Award; Espadas Presents Paper • Open Board Meeting • Portrait Of The Professor: Blanche Schultz • Yes and ELO: New Looks on Stage • Exhibit Coming • The Blue Oyster Cult -- Highly Underrated • The T.G. Party: A New Option At Ursinus • New Music Officers • Pancoast Honored by PACU • Byerly Speaks on Computer Innovations • Homecoming Excitement Builds • Harriers Overcome Injuries, Opposition • Hockey Gets A Lift • Football - Heartbreaker on Parent\u27s Day • Volleyball Rounduphttps://digitalcommons.ursinus.edu/grizzlynews/1002/thumbnail.jp

The Grizzly, October 20, 1978

Homecoming \u2778 Promises Color, Excitement • Judiciary Board Convicts Two • Shopping Center to Expand • On Personal Expression • Is Pledging All Fun and Games? • Ursinus\u27 Financial Aid Structure • SFARC Repairs Damage Policy • Gallagher Explores Amish • Springsteen & Dylan: Poet Laureates or Veritable Zeros? • The World\u27s Largest Hamburger • Paradise Lost: College Woods Gone Junkyard? • X-C: Dual Wins • Bears Fall Prey Again • Soccer Wins Five • News in Brief: Our New Look; Remember to Vote; Yom Kippur Celebration; Ursinus Announces Business Workshop; Library News Shortshttps://digitalcommons.ursinus.edu/grizzlynews/1003/thumbnail.jp

The Grizzly, October 27, 1978

Bomberger Tower Razed • Homecoming Brings Crowning, Presentations • Self Study Continues • Hockey Ties Nation\u27s Best • No Tickets at Door • Campus Sunshine to Set? • Ravine Paradise Revisited • Portrait of the Professor: Randy Davidson • Letters to the Editor • Springsteen & Dylan: Poet Laureates or Veritable Zeroes? • Art is a Math is an Art is a Math... • Escher Takes On New Dimension • Commencement Speaker Announced • Plea From the Press • GM: Looking Good For \u2779 • Soccer Splits: 2-2 • Sports Profile: Don Paolicelli • Thin Clads Receive Treat • Swarthmore Superior In Homecoming Game • J.V.s Romp to Win • Hockey Returns Home • News in Brief: Fire Alarm Installations Near Completion; ProTheatre to Present The Good Doctor ; Art Exhibit to Open Soonhttps://digitalcommons.ursinus.edu/grizzlynews/1004/thumbnail.jp

The Grizzly, October 27, 1978

Bomberger Tower Razed • Homecoming Brings Crowning, Presentations • Self Study Continues • Hockey Ties Nation\u27s Best • No Tickets at Door • Campus Sunshine to Set? • Ravine Paradise Revisited • Portrait of the Professor: Randy Davidson • Letters to the Editor • Springsteen & Dylan: Poet Laureates or Veritable Zeroes? • Art is a Math is an Art is a Math... • Escher Takes On New Dimension • Commencement Speaker Announced • Plea From the Press • GM: Looking Good For \u2779 • Soccer Splits: 2-2 • Sports Profile: Don Paolicelli • Thin Clads Receive Treat • Swarthmore Superior In Homecoming Game • J.V.s Romp to Win • Hockey Returns Home • News in Brief: Fire Alarm Installations Near Completion; ProTheatre to Present The Good Doctor ; Art Exhibit to Open Soonhttps://digitalcommons.ursinus.edu/grizzlynews/1004/thumbnail.jp

Pennsylvania Folklife Vol. 32, No. 4

• Frakturs • Apple Head Dolls are Unique • Tableware and Dutch Folklore • The Pipemaker • Wheat Weaving • Beekeeping: Past and Present • The Pennsylvania Longrifle • Festival Focus • Folk Festival Programs • Quilts • The Country Butcher • Stained Glass • Metal Casting in Sand • Is This Pure Leather? • The Horse and Carriage • Marquetry, Parquetry and Intarsia • Pennsylvania Dutch Cookinghttps://digitalcommons.ursinus.edu/pafolklifemag/1100/thumbnail.jp

The Grizzly, December 1, 1978

Task Force Reviews Health Services; Bookstore Also Discussed • New Curriculum Approved • SAC Discusses New Frat & Allocations • Biology Department Alters Curriculum • A Good Editorial • Let\u27s See Co-Ed Dorms • A Mutually Advantageous Symbiosis • Letters to the Editor: Sleeping Awareness; Disturbing Guyana Attitudes • Portrait of the Professor: Dr. Patrick J. Mulvanny • Parking: Problem At Ursinus • If Zacharias Could See Us Now... • Think Snow • The Rocky Horror Show: A Celluloid Wasteland • Audio Corner: Loudspeakers • Thompson-Gay Soon To Be Theater • Logic & Dance • Drinking Myths • Hopes High For Hoops • Football Ends On Good Note • Ursinus Girls Drown Dickinson • Marathon Men Compete • Bears Net .500 Against Florida Foes • First Winter Weather Day ; Stimeling Exhibit To Be Presentedhttps://digitalcommons.ursinus.edu/grizzlynews/1008/thumbnail.jp

TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age-related neurodegenerative disorders with shared genetic etiologies and overlapping clinical and pathological features. Here we studied a novel ALS/FTD family and identified the P362L mutation in the low-complexity domain (LCD) of T cell-restricted intracellular antigen-1 (TIA1). Subsequent genetic association analyses showed an increased burden of TIA1 LCD mutations in ALS patients compared to controls (p = 8.7 × 1

Nuclear import receptors are recruited by FG-nucleoporins to rescue hallmarks of TDP-43 proteinopathy

Background: Cytoplasmic mislocalization and aggregation of TAR DNA-binding protein-43 (TDP-43) is a hallmark of the amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD) disease spectrum, causing both nuclear loss-of-function and cytoplasmic toxic gain-of-function phenotypes. While TDP-43 proteinopathy has been associated with defects in nucleocytoplasmic transport, this process is still poorly understood. Here we study the role of karyopherin-β1 (KPNB1) and other nuclear import receptors in regulating TDP-43 pathology. Methods: We used immunostaining, immunoprecipitation, biochemical and toxicity assays in cell lines, primary neuron and organotypic mouse brain slice cultures, to determine the impact of KPNB1 on the solubility, localization, and toxicity of pathological TDP-43 constructs. Postmortem patient brain and spinal cord tissue was stained to assess KPNB1 colocalization with TDP-43 inclusions. Turbidity assays were employed to study the dissolution and prevention of aggregation of recombinant TDP-43 fibrils in vitro. Fly models of TDP-43 proteinopathy were used to determine the effect of KPNB1 on their neurodegenerative phenotype in vivo. Results: We discovered that several members of the nuclear import receptor protein family can reduce the formation of pathological TDP-43 aggregates. Using KPNB1 as a model, we found that its activity depends on the prion-like C-terminal region of TDP-43, which mediates the co-aggregation with phenylalanine and glycine-rich nucleoporins (FG-Nups) such as Nup62. KPNB1 is recruited into these co-aggregates where it acts as a molecular chaperone that reverses aberrant phase transition of Nup62 and TDP-43. These findings are supported by the discovery that Nup62 and KPNB1 are also sequestered into pathological TDP-43 aggregates in ALS/FTD postmortem CNS tissue, and by the identification of the fly ortholog of KPNB1 as a strong protective modifier in Drosophila models of TDP-43 proteinopathy. Our results show that KPNB1 can rescue all hallmarks of TDP-43 pathology, by restoring its solubility and nuclear localization, and reducing neurodegeneration in cellular and animal models of ALS/FTD. Conclusion: Our findings suggest a novel NLS-independent mechanism where, analogous to its canonical role in dissolving the diffusion barrier formed by FG-Nups in the nuclear pore, KPNB1 is recruited into TDP-43/FG-Nup co-aggregates present in TDP-43 proteinopathies and therapeutically reverses their deleterious phase transition and mislocalization, mitigating neurodegeneration. Graphical Abstract: [Figure not available: see fulltext.]

Homozygosity for the C9orf72 GGGGCC repeat expansion in frontotemporal dementia

An expanded hexanucleotide repeat in the C9orf72 gene is the most common genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis (c9FTD/ALS). We now report the first description of a homozygous patient and compare it to a series of heterozygous cases. The patient developed early-onset frontotemporal dementia without additional features. Neuropathological analysis showed c9FTD/ALS characteristics, with abundant p62-positive inclusions in the frontal and temporal cortices, hippocampus and cerebellum, as well as less abundant TDP-43-positive inclusions. Overall, the clinical and pathological features were severe, but did not fall outside the usual disease spectrum. Quantification of C9orf72 transcript levels in post-mortem brain demonstrated expression of all known C9orf72 transcript variants, but at a reduced level. The pathogenic mechanisms by which the hexanucleotide repeat expansion causes disease are unclear and both gain- and loss-of-function mechanisms may play a role. Our data support a gain-of-function mechanism as pure homozygous loss of function would be expected to lead to a more severe, or completely different clinical phenotype to the one described here, which falls within the usual range. Our findings have implications for genetic counselling, highlighting the need to use genetic tests that distinguish C9orf72 homozygosity