Digital Commons Network^™

B Cell-Derived Il-4 Acts On Podocytes To Induce Proteinuria And Foot Process Effacement, Alfred Hj Kim, Jun-Jae Chung, Shreeram Akilesh, Ania Koziell, Sanjay Jain, Jeffrey B. Hodgin, Mark J. Miller, Thaddeus S. Stappenbeck, Jeffrey H. Miner, Andrey S. Shaw

Open Access Publications

The efficacy of B cell depletion therapies in diseases such as nephrotic syndrome and rheumatoid arthritis suggests a broader role in B cells in human disease than previously recognized. In some of these diseases, such as the minimal change disease subtype of nephrotic syndrome, pathogenic antibodies and immune complexes are not involved. We hypothesized that B cells, activated in the kidney, might produce cytokines capable of directly inducing cell injury and proteinuria. To directly test our hypothesis, we targeted a model antigen to the kidney glomerulus and showed that transfer of antigen-specific B cells could induce glomerular injury and proteinuria. …

Cerebrospinal Fluid And Blood Biomarkers For Neurodegenerative Dementias: An Update Of The Consensus Of The Task Force On Biological Markers In Psychiatry Of The World Federation Of Societies Of Biological Psychiatry, Piotr Lewczuk, Anne M. Fagan, Brian A. Gordon, Et Al

Open Access Publications

No abstract provided.

Interleukin-17 Limits Hypoxia-Inducible Factor 1Α And Development Of Hypoxic Granulomas During Tuberculosis, Racquel Domingo-Gonzalez, Shibali Das, Kristin L. Griffiths, Mushtaq Ahmed, Monika Bambouskova, Suhas Gondi, Noor Al-Hammadi, Reid Townsend, Maxim N. Artyomov, Shabaana A. Khader, Et Al.

Open Access Publications

Mycobacterium tuberculosis (Mtb) is a global health threat, compounded by the emergence of drug-resistant strains. A hallmark of pulmonary tuberculosis (TB) is the formation of hypoxic necrotic granulomas, which upon disintegration, release infectious Mtb. Furthermore, hypoxic necrotic granulomas are associated with increased disease severity and provide a niche for drug-resistant Mtb. However, the host immune responses that promote the development of hypoxic TB granulomas are not well described. Using a necrotic Mtb mouse model, we show that loss of Mtb virulence factors, such as phenolic glycolipids, decreases the production of the proinflammatory cytokine IL-17 (also referred to as IL-17A). IL-17 …

N-3 Pufas Induce Inflammatory Tolerance By Formation Of Keap1-Containing Sqstm1/P62-Bodies And Activation Of Nfe2l2, Jennifer Mildenberger, Ida Johansson, Ismail Sergin, Eli Kjøbli, Jan Kristian Damås, Babak Razani, Trude Helen Flo, Geir Bjørkøy

Open Access Publications

Inflammation is crucial in the defense against infections but must be tightly controlled to limit detrimental hyperactivation. Our diet influences inflammatory processes and omega-3 polyunsaturated fatty acids (n-3 PUFAs) have known anti-inflammatory effects. The balance of pro- and anti-inflammatory processes is coordinated by macrophages and macroautophagy/autophagy has recently emerged as a cellular process that dampens inflammation. Here we report that the n-3 PUFA docosahexaenoic acid (DHA) transiently induces cytosolic speckles of the autophagic receptor SQSTM1/p62 (sequestosome 1) (described as SQSTM1/p62-bodies) in macrophages. We suggest that the formation of SQSTM1/p62-bodies represents a fast mechanism of NFE2L2/Nrf2 (nuclear factor, erythroid 2 like …

Redefining The Endophenotype Concept To Accommodate Transdiagnostic Vulnerabilities And Etiological Complexity, Theodore P. Beauchaine, John N. Constantino

Open Access Publications

In psychopathology research, endophenotypes are a subset of biomarkers that indicate genetic vulnerability independent of clinical state. To date, an explicit expectation is that endophenotypes be specific to single disorders. We evaluate this expectation considering recent advances in psychiatric genetics, recognition that transdiagnostic vulnerability traits are often more useful than clinical diagnoses in psychiatric genetics, and appreciation for etiological complexity across genetic, neural, hormonal and environmental levels of analysis. We suggest that the disorder-specificity requirement of endophenotypes be relaxed, that neural functions are preferable to behaviors as starting points in searches for endophenotypes, and that future research should focus on …

Injury-Induced Actin Cytoskeleton Reorganization In Podocytes Revealed By Super-Resolution Microscopy, Hani Y. Suleiman, Robyn Roth, Sanjay Jain, John E. Heuser, Andrey S. Shaw, Jeffrey H. Miner

Open Access Publications

The architectural integrity of tissues requires complex interactions, both between cells and between cells and the extracellular matrix. Fundamental to cell and tissue homeostasis are the specific mechanical forces conveyed by the actomyosin cytoskeleton. Here we used super-resolution imaging methods to visualize the actin cytoskeleton in the kidney glomerulus, an organized collection of capillaries that filters the blood to make the primary urine. Our analysis of both mouse and human glomeruli reveals a network of myosin IIA-containing contractile actin cables within podocyte cell bodies and major processes at the outer aspects of the glomerular tuft. These likely exert force on …

Whole Tumor Rna-Sequencing And Deconvolution Reveal A Clinically-Prognostic Pten/Pi3k-Regulated Glioma Transcriptional Signature, Yuan Pan, Erin C. Bush, Joseph A. Toonen, Yu Ma, Anne C. Solga, Peter A. Sims, David H. Gutmann

Open Access Publications

The concept that solid tumors are maintained by a productive interplay between neoplastic and non-neoplastic elements has gained traction with the demonstration that stromal fibroblasts and immune system cells dictate cancer development and progression. While less studied, brain tumor (glioma) biology is likewise influenced by non-neoplastic immune system cells (macrophages and microglia) which interact with neoplastic glioma cells to create a unique physiological state (glioma ecosystem) distinct from that found in the normal tissue. To explore this neoplastic ground state, we leveraged several preclinical mouse models of neurofibromatosis type 1 (NF1) optic glioma, a low-grade astrocytoma whose formation and maintenance …

Sexual Dimorphism In Glioma Glycolysis Underlies Sex Differences In Survival, Joseph E. Ippolito, Aldrin Kay-Yuen Yim, Jingqin Luo, Prakash Chinnaiyan, Joshua B. Rubin

Open Access Publications

The molecular bases for sex differences in cancer remain undefined and how to incorporate them into risk stratification remains undetermined. Given sex differences in metabolism and the inverse correlation between fluorodeoxyglucose (FDG) uptake and survival, we hypothesized that glycolytic phenotyping would improve glioma subtyping. Using retrospectively acquired lower-grade glioma (LGG) transcriptome data from The Cancer Genome Atlas (TCGA), we discovered male-specific decreased survival resulting from glycolytic gene overexpression. Patients within this high-glycolytic group showed significant differences in the presence of key genomic alterations (i.e., 1p/19q codeletion, CIC, EGFR, NF1, PTEN, FUBP1, and IDH mutations) compared with the low-glycolytic group. Although …

Pediatric And Adult Dilated Cardiomyopathy Represent Distinct Pathological Entities, Meghna D. Patel, Jayaram Mohan, Caralin Schneider, Geetika Bajpai, Enkhsaikhan Purevjav, Charles E. Canter, Jeffrey Towbin, Andrea Bredemeyer, Kory J. Lavine

Open Access Publications

Pediatric dilated cardiomyopathy (DCM) is the most common indication for heart transplantation in children. Despite similar genetic etiologies, medications routinely used in adult heart failure patients do not improve outcomes in the pediatric population. The mechanistic basis for these observations is unknown. We hypothesized that pediatric and adult DCM comprise distinct pathological entities, in that children do not undergo adverse remodeling, the target of adult heart failure therapies. To test this hypothesis, we examined LV specimens obtained from pediatric and adult donor controls and DCM patients. Consistent with the established pathophysiology of adult heart failure, adults with DCM displayed marked …

Chemoembolization Versus Radioembolization For The Treatment Of Unresectable Intrahepatic Cholangiocarcinoma In A Single Institution Image-Based Efficacy And Comparative Toxicity, Olaguoke Akinwande, Veer Shah, Abigail Mills, Christopher Noda, Eric Weiner, Gretchen Foltz, Nael Saad

Open Access Publications

Aim: Compare radioembolization (Y90) and chemoembolization (CE) for the treatment of unresectable intrahepatic cholangiocarcinoma (UICC).

Materials & methods: Institutional Review Board-approved, retrospective search was performed. Forty patients with UICC were treated with either Y90 (n = 25, 39 treatments) or CE (n = 15, 35 treatments). Comparative analysis was performed using Student's

Results: Median ages were 60 and 64 years for CE and Y90 groups, respectively (p = 0.798). Patient variables including age, Eastern Cooperative Oncology Group score, tumor burden, extra-hepatic disease, prior chemotherapy and prior surgery were similar between groups. Adverse events were similar in both groups (CE 20%, …

Ca2+-Permeable Ampars Mediate Glutamatergic Transmission And Excitotoxic Damage At The Hair Cell Ribbon Synapse, Joy Y. Sebe, Soyoun Cho, Lavinia Sheets, Mark A. Rutherford, Henrique Von Gersdorff, David W. Raible

Open Access Publications

We report functional and structural evidence for GluA2-lacking Ca

Postoperative Atrial Fibrillation: The Role Of The Inflammatory Response, Yosuke Ishii, Richard B Schuessler, Sydney L Gaynor, Kiyomi Hames, Ralph J Damiano

Open Access Publications

OBJECTIVE: Abnormal atrial conduction has been shown to be a substrate for postoperative atrial fibrillation (POAF). This study aimed to determine the relationship between the location of the atrial reentry responsible for POAF, and degree of atrial inflammation.

METHODS: Normal mongrel dogs (n = 18) were divided into 3 groups: anesthesia alone (anesthesia), lateral right atriotomy (atriotomy), and lateral right atriotomy with anti-inflammatory therapy (steroid). Conduction properties of the right and left atria (RA and LA) were examined 3 days postoperatively by mapping. Activation was observed during burst pacing-induced AF. The RA and LA myeloperoxidase activity was measured to quantitate …

Gdf15 Is Elevated In Mice Following Retinal Ganglion Cell Death And In Glaucoma Patients, Norimitsu Ban, Carla J. Siegfried, Jonathan B. Lin, Ying-Bo Shui, Julia Sein, Wolfgang Pita-Thomas, Abdoulaye Sene, Andrea Santeford, Mae Gordon, Rachel Lamb, Zhenyu Dong, Shannon C. Kelly, Valeria Cavalli, Jun Yoshino, Rajendra S. Apte

Open Access Publications

Glaucoma is the second leading cause of blindness worldwide. Physicians often use surrogate endpoints to monitor the progression of glaucomatous neurodegeneration. These approaches are limited in their ability to quantify disease severity and progression due to inherent subjectivity, unreliability, and limitations of normative databases. Therefore, there is a critical need to identify specific molecular markers that predict or measure glaucomatous neurodegeneration. Here, we demonstrate that growth differentiation factor 15 (GDF15) is associated with retinal ganglion cell death. Gdf15 expression in the retina is specifically increased after acute injury to retinal ganglion cell axons and in a murine chronic glaucoma model. …

Cholinergic, But Not Dopaminergic Or Noradrenergic, Enhancement Sharpens Visual Spatial Perception In Humans, Caterina Gratton, Sahar Yousef, Esther Aarts, Deanna L. Wallace, Mark D'Esposito, Michael A. Silver

Open Access Publications

The neuromodulator acetylcholine modulates spatial integration in visual cortex by altering the balance of inputs that generate neuronal receptive fields. These cholinergic effects may provide a neurobiological mechanism underlying the modulation of visual representations by visual spatial attention. However, the consequences of cholinergic enhancement on visuospatial perception in humans are unknown. We conducted two experiments to test whether enhancing cholinergic signaling selectively alters perceptual measures of visuospatial interactions in human subjects. In Experiment 1, a double-blind placebo-controlled pharmacology study, we measured how flanking distractors influenced detection of a small contrast decrement of a peripheral target, as a function of target-flanker …

Mapk Signaling Promotes Axonal Degeneration By Speeding The Turnover Of The Axonal Maintenance Factor Nmnat2, Lauren J. Walker, Daniel W. Summers, Yo Sasaki, Ej Brace, Jeffrey Milbrandt, Aaron Diantonio

Open Access Publications

Injury-induced (Wallerian) axonal degeneration is regulated via the opposing actions of pro-degenerative factors such as SARM1 and a MAPK signal and pro-survival factors, the most important of which is the NAD

Aberrantly Activated Cox-2 And Wnt Signaling Interact To Maintain Cancer Stem Cells In Glioblastoma, Megan Wu, Jennifer Guan, Chris Li, Simon Gunter, Labeeba Nusrat, Sheena Ng, Karan Dhand, Cindi Morshead, Albert Kim, Sunit Das

Open Access Publications

No abstract provided.

Targeting Dendritic Cells To Accelerate T-Cell Activation Overcomes A Bottleneck In Tuberculosis Vaccine Efficacy, Kristin L. Griffiths, Mushtaq Ahmed, Shibali Das, Radha Gopal, William Horne, Terry D. Connell, Kelly D. Moynihan, Jay K. Kolls, Darrell J. Irvine, Maxim N. Artyomov, Javier Rangel-Moreno, Shabaana A. Khader

Open Access Publications

No abstract provided.

The Retina Visual Cycle Is Driven By Cis Retinol Oxidation In The Outer Segments Of Cones, Shinya Sato, Rikard Frederiksen, M. Carter Cornwall, Vladimir J. Kefalov

Open Access Publications

No abstract provided.

Diffusion Assessment Of Cortical Changes, Induced By Traumatic Spinal Cord Injury, Peng Sun, Rory K. Murphy, Paul Gamble, Ajit George, Sheng-Kwei Song, Wilson Z. Ray

Open Access Publications

No abstract provided.

Icd-9-Cm Coding For Multidrug Resistant Infection Correlates Poorly With Microbiologically Confirmed Multidrug Resistant Infection, Jason P. Burnham, Jennie H. Kwon, Hilary M. Babcock, Margaret A. Olsen, Marin H. Kollef

Open Access Publications

No abstract provided.

The Cyprinodon Variegatus Genome Reveals Gene Expression Changes Underlying Differences In Skull Morphology Among Closely Related Species, Ezra S. Lencer, Wesley C. Warren, Richard Harrison, Amy R. Mccune

Open Access Publications

No abstract provided.

Il-15 Sustains Il-7r-Independent Ilc2 And Ilc3 Development, Michelle L. Robinette, Jennifer K. Bando, Wilbur Song, Tyler K. Ulland, Susan Gilfillan, Marco Colonna

Open Access Publications

No abstract provided.

Fibulin-4 Is Essential For Maintaining Arterial Wall Integrity In Conduit But Not Muscular Arteries, Carmen M. Halabi, Thomas J. Broekelmann, Michelle Lin, Vivian S. Lee, Mon-Li Chu, Robert P. Mecham

Open Access Publications

No abstract provided.

Two Forms Of Death In Ageing Caenorhabditis Elegans, Yuan Zhao, Ann F. Gilliat, Matthias Ziehm, Mark Turmaine, Hongyuan Wang, Marina Ezcurra, Chenhao Yang, George Phillips, David Mcbay, William B. Zhang, Linda Partridge, Zachary Pincus, David Gems

Open Access Publications

No abstract provided.

Oscillatory Brain Activity In Spontaneous And Induced Sleep Stages In Flies, Melvyn H.W. Yap, Martyna J. Grabowska, Chelsie Rohrscheib, Rhiannon Jeans, Michael Troup, Angelique C. Paulk, Bart Van Alphen, Paul J. Shaw, Bruno Van Swinderen

Open Access Publications

No abstract provided.

Wormbase 2017: Molting Into A New Stage, Tim Schedl, Et Al

Open Access Publications

No abstract provided.

Selinexor Overcomes Hypoxia-Induced Drug Resistance In Multiple Myeloma, Barbara Muz, Feda Azab, Pilar De La Puente, Yosef Landesman, Abdel Kareem Azab

Open Access Publications

No abstract provided.

Epithelial Chloride Transport By Cftr Requires Tmem16a, Roberta Benedetto, Jiraporn Ousingsawat, Podchanart Wanitchakool, Yong Zhang, Michael J. Holtzman, Margarida Amaral, Jason R. Rock, Rainer Schreiber, Karl Kunzelmann

Open Access Publications

No abstract provided.

Long-Term Deficits In Cortical Circuit Function After Asphyxial Cardiac Arrest And Resuscitation In Developing Rats, Jason W. Middleton, Daniel J. Simons, Jennifer W. Simmons, Robert S.B. Clark, Patrick M. Kochanek, Michael Shoykhet

Open Access Publications

No abstract provided.

Organization Of The Dorsal Lateral Geniculate Nucleus In The Mouse, Daniel Kerschensteiner, William Guido

Open Access Publications

No abstract provided.