Inflammatory bowel disease addressed by Caco-2 and monocyte-derived macrophages : an opportunity for an in vitro drug screening assay

Infammatory bowel disease (IBD) is a widespread disease, afecting a growing demographic. The treatment of chronic infammation located in the GI-tract is dependent on the severity; therefore, the IBD treatment pyramid is commonly applied. Animal experimentation plays a key role for novel IBD drug development; nevertheless, it is ethically questionable and limited in its throughput. Reliable and valid in vitro assays ofer the opportunity to overcome these limitations. We combined Caco-2 with monocyte-derived macrophages and exposed them to known drugs, targeting an in vitro-in vivo correlation (IVIVC) with a focus on the severity level and its related drug candidate. This co-culture assay addresses namely the intestinal barrier and the immune response in IBD. The drug efcacy was analyzed by an LPS-infammation of the co-culture and drug exposure according to the IBD treatment pyramid. Efcacy was defned as the range between LPS control (0%) and untreated co-culture (100%) independent of the investigated read-out (TEER, Papp, cytokine release: IL-6, IL-8, IL-10, TNF-α). The release of IL-6, IL-8, and TNF-α was identifed as an appropriate readout for a fast drug screening (“yes–no response”). TEER showed a remarkable IVIVC correlation to the human treatment pyramid (5-ASA, Prednisolone, 6-mercaptopurine, and infiximab) with an R2 of 0.68. Similar to the description of an adverse outcome pathway (AOP) framework, we advocate establishing an “Efcacy Outcome Pathways (EOPs)” framework for drug efcacy assays. The in vitro assay ofers an easy and scalable method for IBD drug screening with a focus on human data, which requires further validation

The Lantern, 2021-2022

No More Buses through El Paso • A Woman\u27s World • The Angel of Tragedy • A Victim of Circumstance • Ace of Hearts • Ghost Light • Missing Diamonds • The Upside-Down House: A Dialogue with the Self • What is Chronic Pain? • A Sunny Day in Sinkhole • Extra Marshmallows • Fourth Wall Broken • Hemlock • In the Comfort of Others • Lasting Impressions • Let\u27s Do the Time Warp Again • One Last Afternoon • Space Invaders • The Dogwood Tree • An Ode to Poppies • Charlotte\u27s Web • Crab • Crossing • Dandelions • Dandelion Sandwich • Grizzly Hood • Help Wanted • I Gave Way • I\u27m not who you wanted but maybe one day I can be • Kneeling • Lemon Cookies • Lies • Method Acting • Moment of Tranquility • Our Home • Overthinking • Sea Glass • Seasonal • Thirty-Two (No Spares) • The Autumn Beast • The Miller\u27s Daughter • Theodore • To the Earring I Left Behind in Your Carpet • Virginia • Waltzing • Yellow House • 1/25 British Monarch • Cracked • In the Shadows • Jewelwing • Life on the Wing • O\u27 Captain my Captain • Stars Above the Bay • The Common Fall • Tom • Cats + Crowshttps://digitalcommons.ursinus.edu/lantern/1190/thumbnail.jp

The Lantern, 2020-2021

One Thousand and One is Never Enough • House on Hazel Ave. • Crooked Men at Crooked Alley • Home • Honeybee • The Witch\u27s Daughter • Traveling to Reyu • December 31st, 2019 • The Dominator Rolls the Dice Again • Red Flowers • Military Ball • Drowning in Color • Early Bird • Introspection • Hot Water • Reaching Into Space • Floating Marigolds Before COVID-19 • Smokestack 4 • Longing • His Fifth Year on Amstel Road • Wonderful Moments • Clean Glass • Betty, the Debutante • Teakettles Have it Easy • Fuimos, Somos y Seramos Parte de la Historia de la Isla • Kitchen Table • She Couldn\u27t • Cooling Down • Not so Precious Stones • Domestic Wild • Violet Eater • I Will be Sweet • Flavor of Life • Clogged Artery • All Twenty-Six • The Greatest • From Ashes of War to Golden Cities • A Good Thing • Introduction • Devotion • Life of the Gambler • Impressions: Or a Dining Table\u27s Soliloquy • Looking Glass • Montgomery Pie • Under the Hill • Paperback Lesbian • Girl With Pearl Earring • Your Mirror • Jacket • Illusions • Strawberry Girl (Raw Sugar, Shattered Glass) • I Don\u27t Jam With Instagram • The Morning After Saturday • A Brisk Monday Morning • Emergence • Politeness and Pattern Recognition • Douglas Adams\u27 Guide to Florida • A Love Story With Femininity • Roots • Dysmorphia IIIhttps://digitalcommons.ursinus.edu/lantern/1189/thumbnail.jp

Mechanism of KMT5B haploinsufficiency in neurodevelopment in humans and mice.

Pathogenic variants in KMT5B, a lysine methyltransferase, are associated with global developmental delay, macrocephaly, autism, and congenital anomalies (OMIM# 617788). Given the relatively recent discovery of this disorder, it has not been fully characterized. Deep phenotyping of the largest (n = 43) patient cohort to date identified that hypotonia and congenital heart defects are prominent features that were previously not associated with this syndrome. Both missense variants and putative loss-of-function variants resulted in slow growth in patient-derived cell lines. KMT5B homozygous knockout mice were smaller in size than their wild-type littermates but did not have significantly smaller brains, suggesting relative macrocephaly, also noted as a prominent clinical feature. RNA sequencing of patient lymphoblasts and Kmt5b haploinsufficient mouse brains identified differentially expressed pathways associated with nervous system development and function including axon guidance signaling. Overall, we identified additional pathogenic variants and clinical features in KMT5B-related neurodevelopmental disorder and provide insights into the molecular mechanisms of the disorder using multiple model systems

Mutations in KEOPS-Complex Genes Cause Nephrotic Syndrome with Primary Microcephaly

Galloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibited cell proliferation, which human mutations did not rescue. Furthermore, knockdown of these genes impaired protein translation, caused endoplasmic reticulum stress, activated DNA-damage-response signaling, and ultimately induced apoptosis. Knockdown of OSGEP or TP53RK induced defects in the actin cytoskeleton and decreased the migration rate of human podocytes, an established intermediate phenotype of SRNS. We thus identified four new monogenic causes of GAMOS, describe a link between KEOPS function and human disease, and delineate potential pathogenic mechanisms

A Memory of a Memory

A short documentary exploring the recreation of memories and emotions through film using old home footage to tell the story of Alzheimer\u27s disease

Tidal Forces : The Old Wave : An Exhibition of Pre-Columbian Pottery and Lithics, 28 March - 10 April 2011, Nelson Poynter Memorial Library, University of South Florida St. Petersburg

20 p. booklet and a brochure created for this event. Included are 30 photographic images documenting this exhibit that were taken by Jim Schnur on 8 April 2011

Tidal Forces : The Old Wave : An Exhibition of Pre-Columbian Pottery and Lithics, 28 March - 10 April 2011, Nelson Poynter Memorial Library, University of South Florida St. Petersburg

20 p. booklet and a brochure created for this event. Included are 30 photographic images documenting this exhibit that were taken by Jim Schnur on 8 April 2011

Tidal Forces : The Old Wave : An Exhibition of Pre-Columbian Pottery and Lithics, 28 March - 10 April 2011, Nelson Poynter Memorial Library, University of South Florida St. Petersburg

20 p. booklet and a brochure created for this event. Included are 30 photographic images documenting this exhibit that were taken by Jim Schnur on 8 April 2011

Tidal Forces : The Old Wave : An Exhibition of Pre-Columbian Pottery and Lithics, 28 March - 10 April 2011, Nelson Poynter Memorial Library, University of South Florida St. Petersburg

20 p. booklet and a brochure created for this event. Included are 30 photographic images documenting this exhibit that were taken by Jim Schnur on 8 April 2011