Digital Commons Network^™

Infammatory Bowel Disease-Associated Ubiquitin Ligase Rnf183 Promotes Lysosomal Degradation Of Dr5 And Trail-Induced Caspase Activation, Yan Wu, Yuka Kimura, Takumi Okamoto, Koji Matsuhisa, Rie Asada, Atsushi Saito, Fumika Sakaue, Kazunori Imaizumi, Masayuki Kaneko

Open Access Publications

No abstract provided.

Vaccine-Induced Skewing Of T Cell Responses Protects Against Chikungunya Virus Disease, Rebecca M Broeckel, Nicole Haese, Takeshi Ando, Igor Dmitriev, Craig N Kreklywich, John Powers, Michael Denton, Patricia Smith, Thomas E Morrison, Mark Heise, Victor Defilippis, Ilhem Messaoudi, David T Curiel, Daniel N Streblow

Open Access Publications

Chikungunya virus (CHIKV) infections can cause severe and debilitating joint and muscular pain that can be long lasting. Current CHIKV vaccines under development rely on the generation of neutralizing antibodies for protection; however, the role of T cells in controlling CHIKV infection and disease is still unclear. Using an overlapping peptide library, we identified the CHIKV-specific T cell receptor epitopes recognized in C57BL/6 infected mice at 7 and 14 days post-infection. A fusion protein containing peptides 451, 416, a small region of nsP4, peptide 47, and an HA tag (CHKVf5) was expressed using adenovirus and cytomegalovirus-vectored vaccines. Mice vaccinated with …

Attribution Of Ghrelin To Cancer; Attempts To Unravel An Apparent Controversy, Saeed Soleyman-Jahi, Fatemeh Sadeghi, Amin Pastaki Khoshbin, Leila Khani, Venus Roosta, Kazem Zendehdel

Open Access Publications

Ghrelin is an endogenous peptide hormone mainly produced in the stomach. It has been known to regulate energy homeostasis, stimulate secretion of growth hormone, and mediate many other physiologic effects. Various effects attributed to ghrelin contribute to many aspects of cancer development and progression. Accordingly, a large body of evidence has emerged about the association of ghrelin with several types of cancer in scales of cell-line, animal, and human studies. However, existing data are controversial. This controversy occurs in two main domains: one is the controversial results in local effects of ghrelin on different types of human cancer cell-lines; the …

Proteomic And Phosphoproteomic Analysis Reveals That Neurokinin-1 Receptor (Nk1r) Blockade With Aprepitant In Human Keratinocytes Activates A Distinct Subdomain Of Egfr Signaling: Implications For The Anti-Pruritic Activity Of Nk1r Antagonists, Shawn G Kwatra, Emily Boozalis, Amy H Huang, Cory Nanni, Raveena Khanna, Kyle A Williams, Yevgeniy R Semenov, Callie M Roberts, Robert F Burns, Madison Krischak, Madan M Kwatra

Open Access Publications

No abstract provided.

Mechanisms Of Reactivation Of Latent Tuberculosis Infection Due To Siv Coinfection, Allison N Bucşan, Ayan Chatterjee, Dhiraj K Singh, Taylor W Foreman, Tae-Hyung Lee, Breanna Threeton, Melanie G Kirkpatrick, Mushtaq Ahmed, Nadia Golden, Xavier Alvarez, James A Hoxie, Smriti Mehra, Jyothi Rengarajan, Shabaana A Khader, Deepak Kaushal

Open Access Publications

HIV is a major driver of tuberculosis (TB) reactivation. Depletion of CD4+ T cells is assumed to be the basis behind TB reactivation in individuals with latent tuberculosis infection (LTBI) coinfected with HIV. Nonhuman primates (NHPs) coinfected with a mutant simian immunodeficiency virus (SIVΔGY) that does not cause depletion of tissue CD4+ T cells during infection failed to reactivate TB. To investigate the contribution of CD4+ T cell depletion relative to other mechanisms of SIV-induced reactivation of LTBI, we used CD4R1 antibody to deplete CD4+ T cells in animals with LTBI without lentiviral infection. The mere depletion of CD4+ T …

The Human Milk Protein-Lipid Complex Hamlet Disrupts Glycolysis And Induces Death In Streptococcus Pneumoniae, Hazeline Roche-Hakansson, Goutham Vansarla, Laura R. Marks, Anders P. Hakansson

Open Access Publications

No abstract provided.

The Telomere-Binding Protein Rif2 And Atp-Bound Rad50 Have Opposing Roles In The Activation Of Yeast Tel1atm Kinase, Sarem Hailemariam, Paolo De Bona, Roberto Galletto, Marcel Hohl, John H. Petrini, Peter M. Burgers

Open Access Publications

No abstract provided.

Mutant P53 Drives Clonal Hematopoiesis Through Modulating Epigenetic Pathway, Sisi Chen, Terrence N. Wong, Daniel C. Link, Et Al.

Open Access Publications

No abstract provided.

Lxr-Inverse Agonism Stimulates Immune-Mediated Tumor Destruction By Enhancing Cd8 T-Cell Activity In Triple Negative Breast Cancer, Katherine J. Carpenter, Aurore-Cecile Valfort, Nick Steinauer, Arindam Chatterjee, Suomia Abuirqeba, Shabnam Majidi, Monideepa Sengupta, Richard J. Di Paolo, Laurie P. Shornick, Jinsong Zhang, Colin A. Flaveny

Open Access Publications

No abstract provided.

Edematous Severe Acute Malnutrition Is Characterized By Hypomethylation Of Dna, Katharina V. Schulze, Mark J. Manary, Indi Trehan, Et Al.

Open Access Publications

No abstract provided.

A Targeted Gene Panel That Covers Coding, Non-Coding And Short Tandem Repeat Regions Improves The Diagnosis Of Patients With Neurodegenerative Diseases, Allen Chi-Shing Yu, Aldrin Kay-Yuen Yim, Anne Yin-Yan Chan, Liz Y P Yuen, Wing Chi Au, Timothy H T Cheng, Xiao Lin, Jing-Woei Li, Larry W L Chan, Vincent C T Mok, Ting-Fung Chan, Ho Yin Edwin Chan

Open Access Publications

Genetic testing for neurodegenerative diseases (NDs) is highly challenging because of genetic heterogeneity and overlapping manifestations. Targeted-gene panels (TGPs), coupled with next-generation sequencing (NGS), can facilitate the profiling of a large repertoire of ND-related genes. Due to the technical limitations inherent in NGS and TGPs, short tandem repeat (STR) variations are often ignored. However, STR expansions are known to cause such NDs as Huntington's disease and spinocerebellar ataxias type 3 (SCA3). Here, we studied the clinical utility of a custom-made TGP that targets 199 NDs and 311 ND-associated genes on 118 undiagnosed patients. At least one known or likely pathogenic …

A Brief Review Of Low-Dose Rate (Ldr) And High-Dose Rate (Hdr) Brachytherapy Boost For High-Risk Prostate, Benjamin W Fischer-Valuck, Hiram A Gay, Sagar Patel, Brian C Baumann, Jeff M Michalski

Open Access Publications

For patients with unfavorable or high-risk prostate cancer, dose escalated radiation therapy leads to improved progression free survival but attempts to deliver increased dose by external beam radiation therapy (EBRT) alone can be limited by late toxicities to nearby genitourinary and gastrointestinal organs at risk. Brachytherapy is a method to deliver dose escalation in conjunction with EBRT with a potentially improved late toxicity profile and improved prostate cancer related outcomes. At least three randomized controlled trials have demonstrated improved biochemical control with the addition of either low-dose rate (LDR) or high-dose rate (HDR) brachytherapy to EBRT, although only ASCENDE-RT compared …

Classification Of Human Ovarian Cancer Using Functional, Spectral, And Imaging Features Obtained From In Vivo Photoacoustic Imaging, Eghbal Amidi, Atahar Mostafa, Sreyankar Nandy, Guang Yang, William Middleton, Cary Siegel, Quing Zhu

Open Access Publications

No abstract provided.

Veliparib With First-Line Chemotherapy And As Maintenance Therapy In Ovarian Cancer, Robert L. Coleman, Andrea R. Hagemann, Et Al.

Open Access Publications

No abstract provided.

Structural And Functional Abnormities Of Amygdala And Prefrontal Cortex In Major Depressive Disorder With Suicide Attempts, Lifei Wang, Yimeng Zhao, Elliot K Edmiston, Fay Y Womer, Ran Zhang, Pengfei Zhao, Xiaowei Jiang, Feng Wu, Lingtao Kong, Yifang Zhou, Yanqing Tang, Shengnan Wei

Open Access Publications

Finding neural features of suicide attempts (SA) in major depressive disorder (MDD) may be helpful in preventing suicidal behavior. The ventral and medial prefrontal cortex (PFC), as well as the amygdala form a circuit implicated in emotion regulation and the pathogenesis of MDD. The aim of this study was to identify whether patients with MDD who had a history of SA show structural and functional connectivity abnormalities in the amygdala and PFC relative to MDD patients without a history of SA. We measured gray matter volume in the amygdala and PFC and amygdala-PFC functional connectivity using structural and functional magnetic …

Regional Differences In The Expression Of Tetrodotoxin-Sensitive Inward Ca2+ And Outward Cs+ /K+ Currents In Mouse And Human Ventricles, Wei Wang, Rebecca L. Mellor, Jeanne M. Nerbonne, C. William Blake

Open Access Publications

No abstract provided.

High Myc Mrna Expression Is More Clinically Relevant Than Myc Dna Amplification In Triple-Negative Breast Cancer, Eriko Katsuta, Li Yan, Takashi Takeshita, Kerry-Ann Mcdonald, Subhamoy Dasgupta, Mateusz Opyrchal, Kazuaki Takabe

Open Access Publications

DNA abnormalities are used in inclusion criteria of clinical trials for treatments with specific targeted molecules. MYC is one of the most powerful oncogenes and is known to be associated with triple-negative breast cancer (TNBC). Its DNA amplification is often part of the targeted DNA-sequencing panels under the assumption of reflecting upregulated signaling. However, it remains unclear if MYC DNA amplification is a surrogate of its upregulated signaling. Thus, we investigated the difference between MYC DNA amplification and mRNA high expression in TNBCs utilizing publicly available cohorts. MYC DNA amplified tumors were found to have various mRNA expression levels, suggesting …

Nanotherapy Targeting Nf-Κb Attenuates Acute Pain After Joint Injury, Huimin Yan, Xin Duan, Kelsey H Collins, Luke E Springer, Farshid Guilak, Samuel A Wickline, M Farooq Rai, Hua Pan, Christine T N Pham

Open Access Publications

Inflammation after joint injury leads to joint responses that result in eventual osteoarthritis development. Blockade of inflammation, by suppressing NF-κB expression, has been shown to reduce joint injury-induced chondrocyte apoptosis and reactive synovitis

Validation Of A Commercial Antibody To Detect Endogenous Human Nicastrin By Immunoblot, Rosana A Mesa, Elisha D O Roberson

Open Access Publications

Nicastrin (NCSTN) is a transmembrane glycoprotein that is part of the gamma-secretase complex. Gamma-secretase is a protease complex that cleaves type-I single-pass transmembrane proteins. There are many potential substrates for this complex, including NOTCH receptors and amyloid precursor proteins (APP). There are a number of commercial antibodies to nicastrin, but they do not agree on expected peptide size. We confirmed the specificity of a C-terminal binding rabbit anti-human antibody from Sigma-Aldrich (#N1660) using wildtype HEK293 cells and HEK293 cells deleted for nicastrin. The wildtype cells showed a prominent band at approximately 110 kDa. We confirmed this larger than expected sized …

Glioblastoma Treated With Magnetic Resonance Imaging-Guided Laser Interstitial Thermal Therapy: Safety, Efficacy, And Outcomes, Ashwin A. Kamath, Daniel D. Friedman, S Hassan A. Akbari, Albert H. Kim, Yu Tao, Jinqin Luo, Eric C. Leuthardt

Open Access Publications

BACKGROUND: Despite the multitude of available treatments, glioblastoma (GBM) remains an aggressive and uniformly fatal tumor. Laser interstitial thermal therapy (LITT) is a novel, minimally invasive treatment that holds promise for treating patients with GBM who are not candidates for traditional open craniotomy. However, due to the recent introduction of LITT into clinical practice, large series that evaluate safety and long-term outcomes after LITT are lacking.

OBJECTIVE: To present our institution's series of over 50 GBM patients treated with LITT, with regard to safety, efficacy, and outcomes.

METHODS: We performed a retrospective descriptive study of patients with histologically proven GBM …

Ctcf Variants In 39 Individuals With A Variable Neurodevelopmental Disorder Broaden The Mutational And Clinical Spectrum, Enrico D. H. Konrad, Marwan Shinawi, Emily Fassi, Et Al.

Open Access Publications

No abstract provided.

Recommendations And Alerting For Delirium Alleviation In Real-Time (Radar): Protocol For A Pilot Randomized Controlled Trial, Phillip E Vlisides, Jacqueline W Ragheb, Aleda Leis, Amanda Schoettinger, Kim Hickey, Amy Mckinney, Joseph Brooks, Mackenzie Zierau, Alexandra Norcott, Shirley Yang, Michael S Avidan, Lillian Min

Open Access Publications

No abstract provided.

Retinoic Acid Receptors In Acute Myeloid Leukemia Therapy, Orsola Di Martino, John S Welch

Open Access Publications

Retinoic acid (RA) signaling pathways regulate fundamental biological processes, such as cell proliferation, development, differentiation, and apoptosis. Retinoid receptors (RARs and RXRs) are ligand-dependent transcription factors. All-trans retinoic acid (ATRA) is the principal endogenous ligand for the retinoic acid receptor alpha (RARA) and is produced by the enzymatic oxidation of dietary vitamin A, whose deficiency is associated with several pathological conditions. Differentiation therapy using ATRA revolutionized the outcome of acute promyelocytic leukemia (APL), although attempts to replicate these results in other cancer types have been met with more modest results. A better knowledge of RA signaling in different leukemia contexts …

Genomic Characterization Of Antibiotic Resistant Escherichia Coli Isolated From Domestic Chickens In Pakistan, Muhammad Rafique, Robert F Potter, Aura Ferreiro, Meghan A Wallace, Abdul Rahim, Akbar Ali Malik, Naila Siddique, Muhammad Athar Abbas, Alaric W D'Souza, Carey-Ann D Burnham, Naeem Ali, Gautam Dantas

Open Access Publications

Poultry husbandry is important for the economic health of Pakistan, but the Pakistani poultry industry is negatively impacted by infections from

Membrane Potential Determined By Flow Cytometry Predicts Fertilizing Ability Of Human Sperm, Lis C Puga Molina, Stephanie Gunderson, Joan Riley, Pascal Lybaert, Aluet Borrego-Alvarez, Emily S Jungheim, Celia M Santi

Open Access Publications

Infertility affects 10 to 15% of couples worldwide, with a male factor contributing up to 50% of these cases. The primary tool for diagnosing male infertility is traditional semen analysis, which reveals sperm concentration, morphology, and motility. However, 25% of infertile men are diagnosed as normozoospermic, meaning that, in many cases, normal-appearing sperm fail to fertilize an egg. Thus, new information regarding the mechanisms by which sperm acquire fertilizing ability is needed to develop a clinically feasible test that can predict sperm function failure. An important feature of sperm fertilization capability in many species is plasma membrane hyperpolarization (membrane potential …

The Interplay Between Tissue Niche And Macrophage Cellular Metabolism In Obesity, Sabine Daemen, Joel D Schilling

Open Access Publications

Obesity is associated with the development of metabolic diseases such as type 2 diabetes and non-alcoholic fatty liver disease. The presence of chronic, low-grade inflammation appears to be an important mechanistic link between excess nutrients and clinical disease. The onset of these metabolic disorders coincides with changes in the number and phenotype of macrophages in peripheral organs, particularly in the liver and adipose tissue. Macrophage accumulation in these tissues has been implicated in tissue inflammation and fibrosis, contributing to metabolic disease progression. Recently, the concept has emerged that changes in macrophage metabolism affects their functional phenotype, possibly triggered by distinct …

The Interplay Between Viral-Derived Mirnas And Host Immunity During Infection, Richa Mishra, Ashish Kumar, Harshad Ingle, Himanshu Kumar

Open Access Publications

MicroRNAs are short non-coding RNAs that play a crucial role in the regulation of gene expression during cellular processes. The host-encoded miRNAs are known to modulate the antiviral defense during viral infection. In the last decade, multiple DNA and RNA viruses have been shown to produce miRNAs known as viral miRNAs (v-miRNAs) so as to evade the host immune response. In this review, we highlight the origin and biogenesis of viral miRNAs during the viral lifecycle. We also explore the role of viral miRNAs in immune evasion and hence in maintaining chronic infection and disease. Finally, we offer insights into …

Ferroptotic Cell Death And Tlr4/Trif Signaling Initiate Neutrophil Recruitment After Heart Transplantation, Wenjun Li, Guoshuai Feng, Jason M Gauthier, Inessa Lokshina, Ryuji Higashikubo, Sarah Evans, Xinping Liu, Adil Hassan, Satona Tanaka, Markus Cicka, Hsi-Min Hsiao, Daniel Ruiz-Perez, Andrea Bredemeyer, Richard W Gross, Douglas L Mann, Yulia Y Tyurina, Andrew E Gelman, Valerian E Kagan, Andreas Linkermann, Kory J Lavine, Daniel Kreisel

Open Access Publications

Non-apoptotic forms of cell death can trigger sterile inflammation through the release of danger-associated molecular patterns, which are recognized by innate immune receptors. However, despite years of investigation the mechanisms which initiate inflammatory responses after heart transplantation remain elusive. Here, we demonstrate that ferrostatin-1 (Fer-1), a specific inhibitor of ferroptosis, decreases the level of pro-ferroptotic hydroperoxy-arachidonoyl-phosphatidylethanolamine, reduces cardiomyocyte cell death and blocks neutrophil recruitment following heart transplantation. Inhibition of necroptosis had no effect on neutrophil trafficking in cardiac grafts. We extend these observations to a model of coronary artery ligation-induced myocardial ischemia reperfusion injury where inhibition of ferroptosis resulted in …

Visualization Of Positive And Negative Sense Viral Rna For Probing The Mechanism Of Direct-Acting Antivirals Against Hepatitis C Virus, Dandan Liu, Philip R Tedbury, Shuiyun Lan, Andrew D Huber, Maritza N Puray-Chavez, Juan Ji, Eleftherios Michailidis, Mohsan Saeed, Tanyaradzwa P Ndongwe, Leda C Bassit, Raymond F Schinazi, Robert Ralston, Charles M Rice, Stefan G Sarafianos

Open Access Publications

RNA viruses are highly successful pathogens and are the causative agents for many important diseases. To fully understand the replication of these viruses it is necessary to address the roles of both positive-strand RNA ((+)RNA) and negative-strand RNA ((-)RNA), and their interplay with viral and host proteins. Here we used branched DNA (bDNA) fluorescence in situ hybridization (FISH) to stain both the abundant (+)RNA and the far less abundant (-)RNA in both hepatitis C virus (HCV)- and Zika virus-infected cells, and combined these analyses with visualization of viral proteins through confocal imaging. We were able to phenotypically examine HCV-infected cells …

Mobilized Peripheral Blood: An Updated Perspective, Darja Karpova, Michael P Rettig, John F Dipersio

Open Access Publications

Enforced egress of hematopoietic stem cells (HSCs) out of the bone marrow (BM) into the peripheral circulation, termed mobilization, has come a long way since its discovery over four decades ago. Mobilization research continues to be driven by the need to optimize the regimen currently available in the clinic with regard to pharmacokinetic and pharmacodynamic profile, costs, and donor convenience. In this review, we describe the most recent findings in the field and how we anticipate them to affect the development of mobilization strategies in the future. Furthermore, the significance of mobilization beyond HSC collection, i.e. for chemosensitization, conditioning, and …