The Grizzly, November 19, 1982

Dorm Intrusion: Attack Prompts Security Changes • Council Approves Precalc • Student Apathy: Who Cares? • Elephants and Donkeys Revived on Campus • President\u27s Corner • Pledging Changes Planned • Commentary: Be a Good Boy, Johnny - Take Back Your Tray • Lewis on Wall Street • Applying for the Job • Robert Hazard: The Grizzly Interview • Final Exam Schedule • Grizzly Paws Boost Football Program • Women\u27s Basketball Set to Have Big Season • X-Country Takes a Disappointing Sixth • Soccer Team Was Tough All Year • Men\u27s Swimming Falls to Dickinson in Openerhttps://digitalcommons.ursinus.edu/grizzlynews/1089/thumbnail.jp

The Grizzly, January 28, 1983

Break-in Over Break: Olevian Burglarized • New Faculty Added • Wilder Play at Ritter • Retention Number Assessed • Soviet Policy Analyzed • News Briefs: Lantern Anniversary; ISC Has a Baby • President\u27s Corner • The New Valley Girl • Back at College • New Ski Club Formed at U.C. • Grizzly Football Banquet a Very Rewarding Night • Despite Tough Performances, Aquabears Fall to Lycoming • Early Breaks Diving Record: Lady Swimmers Stroke to 3-1 Record • Grapplers Dump Mules to Up Record to 3-1-1 • Badminton Tops F&M; Set Back by Temple • Lehigh Comeback Sinks Lady Bears • Men\u27s Hoops Tops Haverford • Christmas not a Good Time for Bearshttps://digitalcommons.ursinus.edu/grizzlynews/1091/thumbnail.jp

The Grizzly, February 11, 1983

Bookstore Explains Pricing Policy • Scottish Scholarships Offered to Sophomores • Weekend Alcohol Policy: Campus is Dry • Ursinus Gets Bucks From Sears Roebuck • President\u27s Corner • Visser Fills Exhibits in Corson • Letters to the Editor: Professor Laments Social Conditions at UC; I.F.C. President Irate; President\u27s Response; Bitter About Policy • Varying Viewpoints • Stravinsky to End Winterfest • U.C. Flu Flattens Students • Reaganomics Forum • Key Shooting Aids Lady Hoopsters\u27 Record • Basketball Laments Second Half Loss • Swimmers Glide to Third Straight Victory • Grapplers Deemed Tough • Basketball: End of an Era?? • Swimmers Stroke for Two Wins • Gymnasts Win by 0.75https://digitalcommons.ursinus.edu/grizzlynews/1093/thumbnail.jp

The Grizzly, February 4, 1983

Trouble at Cutillo\u27s: Frats Earn Reputation as Animals • Drinking Concerns Richter • Economics Council Sponsors Entrepreneur-Related Forum • President\u27s Corner • Wismer Tries Again • Pfacelift at Pfahler • Bear Blades Burnished Beat Wilmington Twice • Serendipity Celebration Features Films • Writing Center Welcomes Students • Who\u27s Who in Who\u27s Who? • Commentary: Speak Up for Coed Housing • Didja Ever Wonder • Wrestlers Earn Split • Lewis on Wall Street • Disruptive Fans Cause Flare-up at Widener • Top Individual Efforts Mark Gymnastics Team • Interview: Chupein Named to All-League Team • Lady Hoops Still Struggling • Men\u27s Basketball Find Road a Bit Bumpy • Swimmers Maul Terrors of Western Marylandhttps://digitalcommons.ursinus.edu/grizzlynews/1092/thumbnail.jp

The Grizzly, February 25, 1983

USGA Plans Communication Revision • Foley, D\u27Alesio First Place Winners at Talent Show • College Union Holds Tenth Anniversary • Ritter Production Opens: Skin of Our Teeth • Mass is Popular: Newman Society Links U.C. • Small Heads Alcohol Committee • SPC Seeks Editors • Union Calendar • Grizzly Looks For New Business Manager • Winterfest 1983: International Desserts Festival Tonight • Winterfest Schedule • Letters to the Editor: Admissions Dean Corrects Errors; Hoop Club President Responds; Student Reacts Negatively • Social Life at Ursinus Should be Improved • In the Gates • Registrar Announces Pre-Registration • President\u27s Corner • Roving Reporter: Do You Think the New Alcohol Policy Proposed by the Administration was the Correct Way to Handle the Situations That Occurred on Campus? • Bears Drown Monarchs • Women\u27s Swimming Ends 10-1 • MAC Competition: Wrestlers Take Seventh • Gymnasts Move up a Rank • Lady Hoopsters Finish With Victoryhttps://digitalcommons.ursinus.edu/grizzlynews/1095/thumbnail.jp

Exonic DNA Sequencing of ERBB4 in Bipolar Disorder

The Neuregulin-ErbB4 pathway plays a crucial role in brain development and constitutes one of the most biologically plausible signaling pathways implicated in schizophrenia and, to a lesser extent, in bipolar disorder (BP). However, recent genome-wide association analyses have not provided evidence for common variation in NRG1 or ERBB4 influencing schizophrenia or bipolar disorder susceptibility. In this study, we investigate the role of rare coding variants in ERBB4 in BP cases with mood-incongruent psychotic features, a form of BP with arguably the greatest phenotypic overlap with schizophrenia. We performed Sanger sequencing of all 28 exons in ERBB4, as well as part of the promoter and part of the 3′UTR sequence, hypothesizing that rare deleterious variants would be found in 188 cases with mood-incongruent psychosis from the GAIN BP study. We found 42 variants, of which 16 were novel, although none were non-synonymous or clearly deleterious. One of the novel variants, present in 11.2% of cases, is located next to an alternative stop codon, which is associated with a shortened transcript of ERBB4 that is not translated. We genotyped this variant in the GAIN BP case-control samples and found a marginally significant association with mood-incongruent psychotic BP compared with controls (additive model: OR = 1.64, P-value = 0.055; dominant model: OR = 1.73. P-value = 0.039). In conclusion, we found no rare variants of clear deleterious effect, but did uncover a modestly associated novel variant that could affect alternative splicing of ERBB4. However, the modest sample size in this study cannot definitively rule out a role for rare variants in bipolar disorder and studies with larger sample sizes are needed to confirm the observed association

Genome-Wide DNA Methylation Scan in Major Depressive Disorder

While genome-wide association studies are ongoing to identify sequence variation influencing susceptibility to major depressive disorder (MDD), epigenetic marks, such as DNA methylation, which can be influenced by environment, might also play a role. Here we present the first genome-wide DNA methylation (DNAm) scan in MDD. We compared 39 postmortem frontal cortex MDD samples to 26 controls. DNA was hybridized to our Comprehensive High-throughput Arrays for Relative Methylation (CHARM) platform, covering 3.5 million CpGs. CHARM identified 224 candidate regions with DNAm differences >10%. These regions are highly enriched for neuronal growth and development genes. Ten of 17 regions for which validation was attempted showed true DNAm differences; the greatest were in PRIMA1, with 12–15% increased DNAm in MDD (p = 0.0002–0.0003), and a concomitant decrease in gene expression. These results must be considered pilot data, however, as we could only test replication in a small number of additional brain samples (n = 16), which showed no significant difference in PRIMA1. Because PRIMA1 anchors acetylcholinesterase in neuronal membranes, decreased expression could result in decreased enzyme function and increased cholinergic transmission, consistent with a role in MDD. We observed decreased immunoreactivity for acetylcholinesterase in MDD brain with increased PRIMA1 DNAm, non-significant at p = 0.08

PTEN Is a Potent Suppressor of Small Cell Lung Cancer

UnlabelledSmall cell lung carcinoma (SCLC) is a highly metastatic tumor type with neuroendocrine features and a dismal prognosis. PTEN mutations and PIK3CA activating mutations have been reported in SCLC but the functional relevance of this pathway is unknown. The PTEN/PIK3CA pathway was interrogated using an AdenoCre-driven mouse model of SCLC harboring inactivated Rb and p53. Inactivation of one allele of PTEN in Rb/p53-deleted mice led to accelerated SCLC with frequent metastasis to the liver. In contrast with the high mutation burden reported in human SCLC, exome analyses revealed a low number of protein-altering mutations in mouse SCLC. Inactivation of both alleles of PTEN in the Rb/p53-deleted system led to nonmetastatic adenocarcinoma with neuroendocrine differentiation. This study reveals a critical role for the PTEN/PI3K pathway in both SCLC and lung adenocarcinoma and provides an ideal system to test the phosphoinositide 3-kinase (PI3K) pathway inhibitors as targeted therapy for subsets of patients with SCLC.ImplicationsThe ability of PTEN inactivation to accelerate SCLC in a genetic mouse model suggests that targeting the PTEN pathway is a therapeutic option for a subset of human patients with SCLC. VISUAL OVERVIEW: http://mcr.aacrjournals.org/content/early/2014/04/28/1541-7786.MCR-13-0554/F1.large.jpg

PTEN Is a Potent Suppressor of Small Cell Lung Cancer

Small cell lung carcinoma (SCLC) is a highly metastatic tumor type with neuroendocrine features and a dismal prognosis. PTEN mutations and PIK3CA activating mutations have been reported in SCLC but the functional relevance of this pathway is unknown. The PTEN/PIK3CA pathway was interrogated using an AdenoCre-driven mouse model of SCLC harboring inactivated Rb and p53. Inactivation of one allele of PTEN in Rb/p53-deleted mice led to accelerated SCLC with frequent metastasis to the liver. In contrast to the high mutation burden reported in human SCLC, exome analyses revealed a low number of protein-altering mutations in mouse SCLC. Inactivation of both alleles of PTEN in the Rb/p53-deleted system led to non-metastatic adenocarcinoma with neuroendocrine differentiation. This study reveals a critical role for the PTEN/PI3-kinase pathway in both SCLC and lung adenocarcinoma and provides an ideal system to test PI3-kinase pathway inhibitors as targeted therapy for subsets of SCLC patients