The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor.

Mammalian Toll-like receptors (TLRs) 3, 7, 8 and 9 initiate immune responses to infection by recognizing microbial nucleic acids; however, these responses come at the cost of potential autoimmunity owing to inappropriate recognition of self nucleic acids. The localization of TLR9 and TLR7 to intracellular compartments seems to have a role in facilitating responses to viral nucleic acids while maintaining tolerance to self nucleic acids, yet the cell biology regulating the transport and localization of these receptors remains poorly understood. Here we define the route by which TLR9 and TLR7 exit the endoplasmic reticulum and travel to endolysosomes in mouse macrophages and dendritic cells. The ectodomains of TLR9 and TLR7 are cleaved in the endolysosome, such that no full-length protein is detectable in the compartment where ligand is recognized. Notably, although both the full-length and cleaved forms of TLR9 are capable of binding ligand, only the processed form recruits MyD88 on activation, indicating that this truncated receptor, rather than the full-length form, is functional. Furthermore, conditions that prevent receptor proteolysis, including forced TLR9 surface localization, render the receptor non-functional. We propose that ectodomain cleavage represents a strategy to restrict receptor activation to endolysosomal compartments and prevent TLRs from responding to self nucleic acids

The Grizzly, March 21, 2002

Wynton Marsalis Brings Down the House at Ursinus • The True History of St. Patrick\u27s Day • Music Series set for Berman Museum • Ursinus Women\u27s History Month Dedicated to Late Professor • Meistersingers to Perform at Ursinus College • Berman Museum of Art to Feature Hans Moller Retrospective • SERV and Campus Safety to the Rescue • The New Fad Drug that Might be a Thinly Veiled Disaster • Girls Lacrosse Starts out Strong after a Productive Southern Swinghttps://digitalcommons.ursinus.edu/grizzlynews/1510/thumbnail.jp

The Grizzly, August 30, 2001

Construction on Campus: Residents Return to Numerous Campus Improvement Projects • What is a Watson? • Lending a Helping Hand: Class of 2005 Volunteers at Philadelphia\u27s Cobb Creek Park • UC Students Complete Summer Research • Class of 2005 Receives Dell Laptops • Tumultuous Tuition? • Opinions: Potty Improvement?; Pet for a New Age; Mind the Dust: A Student Perspective of Construction on Campus • More Bang for Your Buck: A Comparative Report on the Prices of Condoms in Collegeville • What is There to do in Collegeville? • Francoise Gilot Exhibit in Berman Museum of Art • Art Fair Coming to Berman Museum of Art • Looking Back: The Life of an Ursinus Student in 1870 • What\u27s in a Name? • Drug-Testing for College Athletes • New Fitness Area Not Quite Ready for Students • Ursinus College Football Head Coach Peter Gallagher • Dog Days of Summer May Lead to Heat-Related Illnesseshttps://digitalcommons.ursinus.edu/grizzlynews/1491/thumbnail.jp

The Grizzly, September 6, 2001

Activities Fair Helps Students Get Involved on Campus • Ursinus Leadership Scholar Program Teaches Students Skills to Succeed • Students Express Concern About Unsafe Campus Pathways • Opinions: Roommate: Friend or Foe?; Is our Campus Safe?; Homesickness not so Uncommon • Former UC Professor to Perform in Seven Stars Music and Art Festival • Free Museums on the Philly Parkway! • Wash, Cut, Blow Dry: It Doesn\u27t Have to Empty Your Wallet! • A Face From the Past: Dr. John Henry Augustus Bomberger • Women\u27s Soccer Team Victorious at UC Invitational • La Roche College Men\u27s Soccer Invitational Champions • Soggy Soccer Field Creates Muddy Waters • Women\u27s Volleyball Defeats Hood in their own Tournament • Bears Fall to Presidents in Heated Battle at Patterson Field • Blood, Sweat and Tearshttps://digitalcommons.ursinus.edu/grizzlynews/1492/thumbnail.jp

Sex differences in pharmacological interventions and their effects on lifespan and healthspan outcomes: a systematic review

With an increasing aging population, the burden of age-related diseases magnifies. To alleviate this burden, geroprotection has been an area of intense research focus with the development of pharmacological interventions that target lifespan and/or healthspan. However, there are often sex differences, with compounds mostly tested in male animals. Given the importance of considering both sexes in preclinical research, this neglects potential benefits for the female population, as interventions tested in both sexes often show clear sexual dimorphisms in their biological responses. To further understand the prevalence of sex differences in pharmacological geroprotective intervention studies, we performed a systematic review of the literature according to the PRISMA guidelines. Seventy-two studies met our inclusion criteria and were classified into one of five subclasses: FDA-repurposed drugs, novel small molecules, probiotics, traditional Chinese medicine, and antioxidants, vitamins, or other dietary supplements. Interventions were analyzed for their effects on median and maximal lifespan and healthspan markers, including frailty, muscle function and coordination, cognitive function and learning, metabolism, and cancer. With our systematic review, we found that twenty-two out of sixty-four compounds tested were able to prolong both lifespan and healthspan measures. Focusing on the use of female and male mice, and on comparing their outcomes, we found that 40% of studies only used male mice or did not clarify the sex. Notably, of the 36% of pharmacologic interventions that did use both male and female mice, 73% of these studies showed sex-specific outcomes on healthspan and/or lifespan. These data highlight the importance of studying both sexes in the search for geroprotectors, as the biology of aging is not the same in male and female mice.Systematic Review Registration: [website], identifier [registration number]

The Grizzly, May 3, 2001

Xenadrine Evidence Points Towards Addictive Nature • Class of 2004 Offers Words of Wisdom to Class of 2005 • Public Radio Personality Ira Glass Hosts Lecture at Ursinus • Fountain Expected to be Completed Soon • Saying Goodbye: Grizzly Editor Signoffs • Opinions: National Missile Defense Still a Bad Idea; Greek Week Unites Local Organizations; Awards Ceremony an Enriching Experience • Stalin\u27s Daughter Steals the Stage • Annual Student Art Show Arrives at Berman • Women\u27s Lacrosse Wins CC Title; Looks Ahead to NCAA\u27s • Girls Rugby Finishes Spring Season • Tennis Teams Lose in First Round at CCC • A Weekend of CCC Playoffs and Tournaments Sees Success for Few • Final Exams Schedulehttps://digitalcommons.ursinus.edu/grizzlynews/1490/thumbnail.jp

Antibiotic prophylaxis in transurethral resection of bladder tumours: study protocol for a systematic review and meta-analysis

The necessity of antibiotic prophylaxis for postoperative urinary tract infections (UTIs) after transurethral resection of bladder tumours is controversial. This potentially leads to the overuse of antibiotic prophylaxis and rising antimicrobial resistance rates. The objective of this systematic review and meta-analysis is to compare the impact of different antimicrobial prophylaxis schemes versus placebo on the prevention of postoperative UTI and asymptomatic bacteriuria.; We designed and registered a study protocol for a systematic review and meta-analysis of randomized controlled trials and non-randomized (e.g. cohort, case-control) studies examining any form of antibiotic prophylaxis in patients with transurethral resection of bladder tumours. Literature searches will be conducted in several electronic databases (from inception onwards), including MEDLINE (Ovid), EMBASE (Ovid), and the Cochrane Central Register of Controlled Trials (CENTRAL). Grey literature will be identified through searching conference abstracts. The primary outcome will be postoperative urinary tract infections. The secondary outcome will be asymptomatic bacteriuria. Two reviewers will independently screen all citations, full-text articles, and abstract data. Potential conflicts will be resolved through discussion. The study methodological quality (or bias) will be appraised using appropriate tools (e.g. Risk of Bias 2.0 tool and Newcastle-Ottawa Scale). If feasible, we will conduct random-effects meta-analysis of outcome data. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g. study design, publication year, the setting of the study, and antibiotics regimen). We will also search, identify, and discuss potential risk factors for urinary tract infections following transurethral resection of bladder tumours. This may serve as basis for a scoping review.; In times of rising antimicrobial resistance rates, sound evidence on the necessity of antibiotic prophylaxis is essential for implementation into guideline recommendations and for decision-making in clinical practice

The Grizzly, November 8, 2001

Construction on Campus Continues as Scheduled • UC Leadership Scholars Attend Annual Halloween Concert • An Evening with Alice Parker a Musical Success • Peace Corps and City Year Representatives Speak About Careers in Common Good • Anthrax Vaccine at Center of Controversy • Opinions: Closed Courses and Wait Lists: Nightmares of Registration; Pop Goes the Quiz! • Gospel Choir Sings out for Peace, Prayer and Healing; Concert a Great Success • Judy Chicago is Coming! World-famous Artist to Visit Ursinus • Influenza Season is Upon Us • Comparative Prices on Museums • Self Protection Facts: What You Need to Know • Power of Dance • Rushing Season Begins Again • Gettysburg Becomes New CC Men\u27s Soccer Champion • UC Women\u27s Rugby Fighting the Good Fight • NCAA Volleyball Semi-finals • UC Downs FDUhttps://digitalcommons.ursinus.edu/grizzlynews/1500/thumbnail.jp

The Grizzly, April 25, 2002

Pesta Appeals College\u27s Action • O\u27Flaherty Speaks to Ursinus about Human Rights • Diverse and Abundant Research Continues • Sex for Sale: What Drives the Porn Industry? • Final Exam Schedule • Jon Volkmer Named Montgomery County Poet Laureate • Greek Week Change Bad: An Opinion • Commencement and Baccalaureate Speakers Announced • Hockey Intramurals • Family or no Family: That is the Question for Many Career Womenhttps://digitalcommons.ursinus.edu/grizzlynews/1515/thumbnail.jp

The Grizzly, September 27, 2001

Fitness Center Opens After Slight Delay • Two Women Recognized with Honorary Doctorate Degrees • Helping Campus Deal with Tragedy: President Strassburger Responds to the Crisis • The Decline of the Airplane Industry • Planning for the Future: Utilizing Career Services\u27 Online Resources • Learning the Ins and Outs of Criminology • Pennsylvania Governor Ridge to Head Office of Homeland Security • In Sorrow • Opinions: Professors Speak Out: Faculty Opinions About the Terrorist Attacks on America; Will There be a Draft? Is the Army Big Enough? • The Lantern Starts a New Year of Publications • New Kickboxing Class Takes a Swing at Fitness • Artist Speaks with Freshmen CIE Students • Trip to College Day on the Parkway Disappointing, but Free! • Fringe Festival Comes to Ursinus! • Student Profile: A Runner • Comparing the Prices of Cigarettes in Collegeville • Ursinus Dive Team • Dougherty Breezes to Second win at Philly Championships • Bears Fall to Terror, 35-9 • DC\u27s Berggren Dominates UC • Ursinus\u27s Liz Umbro Equalizes Dickinson • Hopkins Erupts on Ursinus • Shearer and Nolan are Making the Kills for UChttps://digitalcommons.ursinus.edu/grizzlynews/1495/thumbnail.jp