Medical Specialties Commons^™

Age-Associated Spinal Stenosis In The Turquoise Killifish, Su-Hyeon Cho, Seongsin Lee, Jae-Il Park, Yoon La Yang, Song-Rae Kim, Hoibin Jeong, Nayoung Gwak, Kil-Nam Kim, Yumi Kim

Faculty, Staff and Student Publications

Aging triggers spinal degeneration, including common spinal stenosis, which causes back and leg pain in older individuals, significantly impacting their quality of life. Here, we explored aging traits in turquoise killifish spines, potentially offering a model for age-linked spinal stenosis in humans. Aged turquoise killifish exhibited body shape deformation and increased vertebral collapse, which was further accelerated by spawning. High-resolution CT scans revealed suppressed cortical bone thickness and hemal arch area in vertebrae due to spawning, and osteophyte formation was observed in both aged and breeding fish populations. Scale mineralization mirrored these changes, increasing with age but being suppressed by …

Focalizing Regions Of Biomarker Relevance Facilitates Biomarker Prediction On Histopathological Images, Jiefeng Gan, Hanchen Wang, Hui Yu, Zitong He, Wenjuan Zhang, Lianghui Zhu, Zongwei Zhou, Alan Yullie, Xiang Bai, Mingwei Wang, Dehua Yang, Yanyan Chen, Guoan Chen, Joan Lasenby, Chao Cheng, Jia Wu, Jianjun Zhang, Xinggang Wang, Yaobing Chen, Guoping Wang, Tian Xia

Faculty, Staff and Student Publications

Image-based AI has thrived as a potentially revolutionary tool for predicting molecular biomarker statuses, which aids in categorizing patients for appropriate medical treatments. However, many methods using hematoxylin and eosin-stained (H&E) whole-slide images (WSIs) have been found to be inefficient because of the presence of numerous uninformative or irrelevant image patches. In this study, we introduced the region of biomarker relevance (ROB) concept to identify the morphological areas most closely associated with biomarkers for accurate status prediction. We actualized this concept within a framework called saliency ROB search (SRS) to enable efficient and effective predictions. By evaluating various lung adenocarcinoma …

Actinide-Lanthanide Single Electron Metal-Metal Bond Formed In Mixed-Valence Di-Metallofullerenes, Yingjing Yan, Laura Abella, Rong Sun, Yu-Hui Fang, Yannick Roselló, Meihe Jin, Coen De Graaf, Qingyu Meng, Yang-Rong Yao, Luis Echegoyen, Bing-Wu Wang, Song Gao, Josep M Poblet, Ning Chen

Faculty, Staff and Student Publications

Understanding metal-metal bonding involving f-block elements has been a challenging goal in chemistry. Here we report a series of mixed-valence di-metallofullerenes, ThDy@C2n (2n = 72, 76, 78, and 80) and ThY@C2n (2n = 72 and 78), which feature single electron actinide-lanthanide metal-metal bonds, characterized by structural, spectroscopic and computational methods. Crystallographic characterization unambiguously confirmed that Th and Y or Dy are encapsulated inside variably sized fullerene carbon cages. The ESR study of ThY@D3h(5)-C78 shows a doublet as expected for an unpaired electron interacting with Y, and a SQUID magnetometric study of ThDy@ …

Early Resveratrol Treatment Mitigates Joint Degeneration And Dampens Pain In A Mouse Model Of Pseudoachondroplasia (Psach), Frankie Chiu

Faculty, Staff and Student Publications

Pseudoachondroplasia (PSACH), a severe dwarfing condition associated with early-onset joint degeneration and lifelong joint pain, is caused by mutations in cartilage oligomeric matrix protein (COMP). The mechanisms underlying the mutant-COMP pathology have been defined using the MT-COMP mouse model of PSACH that has the common D469del mutation. Mutant-COMP protein does not fold properly, and it is retained in the rough endoplasmic reticulum (rER) of chondrocytes rather than being exported to the extracellular matrix (ECM), driving ER stress that stimulates oxidative stress and inflammation, driving a self-perpetuating cycle. CHOP (ER stress signaling protein) and TNFα inflammation drive high levels of mTORC1 …

A Myeloid Program Associated With Covid-19 Severity Is Decreased By Therapeutic Blockade Of Il-6 Signaling, Chris Overall, Luz Orozco, Xia Gao, Eugene Kim, Nathan West, Aditi Qamra, Diana Chang, Arindam Chakrabarti, David F Choy, Alexis J Combes, Tristan Courau, Gabriela K Fragiadakis, Arjun Arkal Rao, Arja Ray, Jessica Tsui, Kenneth Hu, Nicholas F Kuhn, Matthew F Krummel, David J Erle, Kirsten Kangelaris, Aartik Sarma, Zoe Lyon, Carolyn S Calfee, Prescott G Woodruff, Rajani Ghale, Eran Mick, Ashley Byrne, Beth Shoshana Zha, Charles Langelier, Carolyn M Hendrickson, Monique G P Van Der Wijst, George C Hartoularos, Tianna Grant, Raymund Bueno, David S Lee, John R Greenland, Yang Sun, Richard Perez, Anton Ogorodnikov, Alyssa Ward, Chun Jimmie Ye, Thiru Ramalingam, Jacqueline M Mcbride, Fang Cai, Anastasia Teterina, Min Bao, Larry Tsai, Ivan O Rosas, Aviv Regev, Sharookh B Kapadia, Rebecca N Bauer, Carrie M Rosenberger

Faculty, Staff and Students Publications

Altered myeloid inflammation and lymphopenia are hallmarks of severe infections. We identified the upregulated EN-RAGE gene program in airway and blood myeloid cells from patients with acute lung injury from SARS-CoV-2 or other causes across 7 cohorts. This program was associated with greater clinical severity and predicted future mechanical ventilation and death. EN-RAGEhi myeloid cells express features consistent with suppressor cell functionality, including low HLA-DR and high PD-L1. Sustained EN-RAGE program expression in airway and blood myeloid cells correlated with clinical severity and increasing expression of T cell dysfunction markers. IL-6 upregulated many EN-RAGE program genes in monocytes in vitro. …

Liposome Synthesis And Evaluation In The Hek-293 Cell Line, Christine Skibinski

Harrisburg University Research Symposium: Highlighting Research, Innovation, & Creativity

Liposomes were synthesized using the thin film method. A lyophilized power of egg-derived phosphatidylcholine, stearylamine, and cholesterol were added to ethanol and dried under argon to form a lipid cake. The lipid cake was rehydrated with dPBS and sonicated at 60°C forming a heterogenous batch of liposomes. Our results revealed the average size of the liposomes, determined by Dynamic Light Scattering, was approximately 223.1nm, while demonstrating a weakly positive zeta-potential of 1.9± 8.07mv. Next, we tested the antitumor action of the liposomes in the HEK-293 cell line via an MTT assay. We observed that the liposomes were able to inhibit …

Tumor-Resident Lactobacillus Iners Confer Chemoradiation Resistance Through Lactate-Induced Metabolic Rewiring, Lauren E. Colbert, Molly B. El Alam, Rui Wang, Tatiana Karpinets, David Lo, Erica J. Lynn, Timothy A. Harris, Jacob H. Elnaggar, Kyoko Yoshida-Court, Katarina Tomasic, Julianna K. Bronk, Julie Sammouri, Ananta V. Yanamandra, Adilene V. Olvera, Lily G. Carlin, Travis Sims, Andrea Y. Delgado Medrano, Tatiana Cisneros Napravnik, Madison O'Hara, Daniel Lin, Chike O. Abana, Hannah X. Li, Patricia J. Eifel, Anuja Jhingran, Melissa Joyner, Lilie Lin, Lois M. Ramondetta, Andrew M. Futreal

School of Medicine Faculty Publications

Tumor microbiota can produce active metabolites that affect cancer and immune cell signaling, metabolism, and proliferation. Here, we explore tumor and gut microbiome features that affect chemoradiation response in patients with cervical cancer using a combined approach of deep microbiome sequencing, targeted bacterial culture, and in vitro assays. We identify that an obligate L-lactate-producing lactic acid bacterium found in tumors, Lactobacillus iners, is associated with decreased survival in patients, induces chemotherapy and radiation resistance in cervical cancer cells, and leads to metabolic rewiring, or alterations in multiple metabolic pathways, in tumors. Genomically similar L-lactate-producing lactic acid bacteria commensal to other …

Integrating Clinical Decision Support Into Electronic Health Record Systems Using A Novel Platform (Evidencepoint): Developmental Study, Sera Levy, Sundas Khan, Benjamin Coleman, Rupert Persaud, John Chelico, D'Arcy King, Alex Spyropoulos, Thomas Mcginn

Faculty, Staff and Students Publications

Background: Through our work, we have demonstrated how clinical decision support (CDS) tools integrated into the electronic health record (EHR) assist providers in adopting evidence-based practices. This requires confronting technical challenges that result from relying on the EHR as the foundation for tool development; for example, the individual CDS tools need to be built independently for each different EHR.

Objective: The objective of our research was to build and implement an EHR-agnostic platform for integrating CDS tools, which would remove the technical constraints inherent in relying on the EHR as the foundation and enable a single set of CDS tools …

Adaptive Design Of Mrna-Loaded Extracellular Vesicles For Targeted Immunotherapy Of Cancer, Shiyan Dong, Xuan Liu, Ye Bi, Yifan Wang, Abin Antony, Kristin Huntoon, Yifan Ma, Xuefeng Li, Weiye Deng, Benjamin R Schrank, Adam J Grippin, Jonghoon Ha, Minjeong Kang, Mengyu Chang, Yarong Zhao, Rongze Sun, Xiangshi Sun, Jie Yang, Jiayi Chen, Sarah K Tang, L James Lee, Andrew S Lee, Lirong Teng, Shengnian Wang, Lesheng Teng, Betty Y S Kim, Zhaogang Yang, Wen Jiang

Faculty, Staff and Student Publications

The recent success of mRNA therapeutics against pathogenic infections has increased interest in their use for other human diseases including cancer. However, the precise delivery of the genetic cargo to cells and tissues of interest remains challenging. Here, we show an adaptive strategy that enables the docking of different targeting ligands onto the surface of mRNA-loaded small extracellular vesicles (sEVs). This is achieved by using a microfluidic electroporation approach in which a combination of nano- and milli-second pulses produces large amounts of IFN-γ mRNA-loaded sEVs with CD64 overexpressed on their surface. The CD64 molecule serves as an adaptor to dock …

The Effect Of Heat-Moisture Treatment Changed The Binding Of Starch, Protein And Lipid In Rice Flour To Affect Its Hierarchical Structure And Physicochemical Properties, Won-Joong Kim

Faculty, Staff and Student Publications

Dexmedetomidine prevents postoperative cognitive dysfunction by inhibiting high-mobility group box 1 (HMGB1), which acts as an inflammatory marker. This study investigated the HMGB1 levels and the cognitive function using a Mini-Cog© score in elderly patients undergoing orthopedic surgery with dexmedetomidine infusion. In total, 128 patients aged ≥ 65 years were analyzed. The patients received saline in the control group and dexmedetomidine in the dexmedetomidine group until the end of surgery. Blood sampling and the Mini-Cog© test were performed before the surgery and on postoperative days 1 and 3. The primary outcomes were the effect of dexmedetomidine on the HMGB1 levels …

Reprogramming Of Cis-Regulatory Networks During Skeletal Muscle Atrophy In Male Mice, Meijun Si, Jiao Wu, Yanlin Wang, Sandhya S Thomas, Zheng Sun, Zhaoyong Hu

Faculty, Staff and Students Publications

A comprehensive atlas of cis-regulatory elements and their dynamic activity is necessary to understand the transcriptional basis of cellular structure maintenance, metabolism, and responses to the environment. Here we show, using matched single-nucleus chromatin accessibility and RNA-sequencing from juvenile male C57BL6 mice, an atlas of accessible chromatin regions in both normal and denervated skeletal muscles. We identified cell-type-specific cis-regulatory networks, highlighting the dynamic regulatory circuits mediating transitions between myonuclear types. Through comparison of normal and perturbed muscle, we delineated the reprogramming of cis-regulatory networks in response to denervation, described the interplay of promoters/enhancers and target genes. We further unveil a …

Standardization Of An Antiviral Pipeline For Human Norovirus In Human Intestinal Enteroids Demonstrates Nitazoxanide Has No To Weak Antiviral Activity, Ketki Patil, Gurpreet Kaur, Frederick H Neill, Robert L Atmar, Sasirekha Ramani, Mary K Estes

Faculty, Staff and Students Publications

Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis. In immunocompetent hosts, symptoms usually resolve within 3 days; however, in immunocompromised persons, HuNoV infection can become persistent, debilitating, and sometimes life-threatening. There are no licensed therapeutics for HuNoV due to a near half-century delay in its cultivation. Treatment for chronic HuNoV infection in immunosuppressed patients anecdotally includes nitazoxanide, a broad-spectrum antimicrobial licensed for treatment of parasite-induced gastroenteritis. Despite its off-label use for chronic HuNoV infection, nitazoxanide has not been clearly demonstrated to be an effective treatment. In this study, we standardized a pipeline for antiviral testing using multiple human …

Neuromyelitis Optica Spectrum Disorder: Redefining An Old Disease Present And Future Challenges

Faculty, Staff and Students Publications

No abstract provided.

Biomechanical Origins Of Proprioceptor Feature Selectivity And Topographic Maps In The Drosophila Leg, Yanyan Qi, Tzu-Chiao Lu, Pralaksha Gurung, Chenghao Chen, Jasper S Phelps, Aaron T Kuan, Alexandra Pacureanu, Wei-Chung Allen Lee, Hongjie Li, Natasha Mhatre, John C Tuthill

Faculty, Staff and Students Publications

Our ability to sense and move our bodies relies on proprioceptors, sensory neurons that detect mechanical forces within the body. Different subtypes of proprioceptors detect different kinematic features, such as joint position, movement, and vibration, but the mechanisms that underlie proprioceptor feature selectivity remain poorly understood. Using single-nucleus RNA sequencing (RNA-seq), we found that proprioceptor subtypes in the Drosophila leg lack differential expression of mechanosensitive ion channels. However, anatomical reconstruction of the proprioceptors and connected tendons revealed major biomechanical differences between subtypes. We built a model of the proprioceptors and tendons that identified a biomechanical mechanism for joint angle selectivity …

International Consensus On Differential Diagnosis And Management Of Patients With Danon Disease: Jacc State-Of-The-Art Review, Alessia Argirò, Michela Brambatti, Quan Bui, Oren Caspi, Fernando De Frutos, Barry Greenberg, Carolyn Y Ho, Juan Pablo Kaski, Iacopo Olivotto, Matthew R G Taylor, Abigail Yesso, Pablo Garcia-Pavia, Eric D Adler

Faculty, Staff and Students Publications

Danon disease is a rare X-linked autophagic vacuolar cardioskeletal myopathy associated with severe heart failure that can be accompanied with extracardiac neurologic, skeletal, and ophthalmologic manifestations. It is caused by loss of function variants in the LAMP2 gene and is among the most severe and penetrant of the genetic cardiomyopathies. Most patients with Danon disease will experience symptomatic heart failure. Male individuals generally present earlier than women and die of either heart failure or arrhythmia or receive a heart transplant by the third decade of life. Herein, the authors review the differential diagnosis of Danon disease, diagnostic criteria, natural history, …

Macrocephaly And Developmental Delay Caused By Missense Variants In Rab5c, Wilmer R Rodriguez-Polanco, Jeremy Grubbs, Bo Zhang, Matt Osmond, Gail Graham, Sarah Sawyer, Erin Conboy, Francesco Vetrini, Kayla Treat, Rafal Płoski, Victor Murcia Pienkowski, Anna Kłosowska, Elizabeth Fieg, Joel Krier, Coralie Mallebranche, Ziegler Alban, Kimberly A Aldinger, Deborah Ritter, Ellen Macnamara, Bonnie Sullivan, John Herriges, Joseph T Alaimo, Catherine Helbig, Colin A Ellis, Clare Van Eyk, Jozef Gecz, Daniel Farrugia, Ikeoluwa Osei-Owusu, Lesley Adès, Marie-Jose Van Den Boogaard, Sabine Fuchs, Jeroen Bakker, Karen Duran, Zachary D Dawson, Anika Lindsey, Huiyan Huang, Dustin Baldridge, Gary A Silverman, Barth D Grant, David Raizen, Undiagnosed Diseases Network, Gijs Van Haaften, Stephen C Pak, Holger Rehmann, Tim Schedl, Peter Van Hasselt

Faculty, Staff and Students Publications

Rab GTPases are important regulators of intracellular vesicular trafficking. RAB5C is a member of the Rab GTPase family that plays an important role in the endocytic pathway, membrane protein recycling and signaling. Here we report on 12 individuals with nine different heterozygous de novo variants in RAB5C. All but one patient with missense variants (n = 9) exhibited macrocephaly, combined with mild-to-moderate developmental delay. Patients with loss of function variants (n = 2) had an apparently more severe clinical phenotype with refractory epilepsy and intellectual disability but a normal head circumference. Four missense variants were investigated experimentally. In vitro biochemical …

Impairment Of Serine Transport Across The Blood-Brain Barrier By Deletion Of Slc38a5 Causes Developmental Delay And Motor Dysfunction, Inna Radzishevsky, Maali Odeh, Oded Bodner, Salman Zubedat, Lihi Shaulov, Kayoko Esaki, Bella Agranovich, Wen-Hong Li, Alex Radzishevsky, Eyal Gottlieb, Avi Avital, Herman Wolosker

Faculty, Staff and Student Publications

Brain L-serine is critical for neurodevelopment and is thought to be synthesized solely from glucose. In contrast, we found that the influx of L-serine across the blood-brain barrier (BBB) is essential for brain development. We identified the endothelial Slc38a5, previously thought to be a glutamine transporter, as an L-serine transporter expressed at the BBB in early postnatal life. Young Slc38a5 knockout (KO) mice exhibit developmental alterations and a decrease in brain L-serine and D-serine, without changes in serum or liver amino acids. Slc38a5-KO brains exhibit accumulation of neurotoxic deoxysphingolipids, synaptic and mitochondrial abnormalities, and decreased neurogenesis at the dentate gyrus. …

Author Correction: Global Proteomic Identifies Multiple Cancer-Related Signaling Pathways Altered By A Gut Pathobiont Associated With Colorectal Cancer, Ewa Pasquereau-Kotula, Giulia Nigro, Florent Dingli, Damarys Loew, Patrick Poullet, Scott Kopetz, Lucie Peduto, Catherine Robbe-Masselot, Philippe Sansonetti, Patrick Trieu-Cuot, Shaynoor Dramsi

Faculty, Staff and Student Publications

No abstract provided.

Oncolytic Virus M1 Functions As A Bifunctional Checkpoint Inhibitor To Enhance The Antitumor Activity Of Dc Vaccine, Jia Dan, Jing Cai, Yingqian Zhong, Chaoqun Wang, Shanyu Huang, Zhen Fan, Linyi Hu, Jiayu Zhang, Jun Hu, Ying Liu, Xingwen Su, Wenbo Zhu, Guangmei Yan, Jiankai Liang, Yuan Lin

Faculty, Staff and Student Publications

Although promising, dendritic cell (DC) vaccines still provide limited clinical benefits, mainly due to the immunosuppressive tumor microenvironment (TME) and the lack of tumor-associated antigens (TAAs). Oncolytic virus therapy is an ideal strategy to overcome immunosuppression and expose TAAs; therefore, they may work synergistically with DC vaccines. In this study, we demonstrate that oncolytic virus M1 (OVM) can enhance the antitumor effects of DC vaccines across diverse syngeneic mouse tumor models by increasing the infiltration of CD8+ effector T cells in the TME. Mechanically, we show that tumor cells counteract DC vaccines through the SIRPα-CD47 immune checkpoint, while OVM can …

Isospectral Intermediates In The Photochemical Reaction Cycle Of Anion Channelrhodopsin Gtacr1, John L Spudich

Faculty, Staff and Student Publications

The most effective tested optogenetic tools available for neuronal silencing are the light-gated anion channel proteins found in the cryptophyte alga Guillardia theta (GtACRs). Molecular mechanisms of GtACRs, including the photointermediates responsible for the open channel state, are of great interest for understanding their exceptional conductance. In this study, the photoreactions of GtACR1 and its D234N, A75E, and S97E mutants were investigated using multichannel time-resolved absorption spectroscopy. For each of the proteins, the analysis showed two early microsecond transitions between K-like and L-like forms and two late millisecond recovery steps. Spectral forms associated with potential molecular intermediates of the proteins …

Emotional Barriers And Facilitators Of Deprescribing For Older Adults With Cancer And Polypharmacy: A Qualitative Study, Jinjiao Wang

Faculty, Staff and Student Publications

Purpose: To describe emotional barriers and facilitators to deprescribing (the planned reduction or discontinuation of medications) in older adults with cancer and polypharmacy.

Methods: Virtual focus groups were conducted over Zoom with 5 key informant groups: oncologists, oncology nurses, primary care physicians, pharmacists, and patients. All groups were video- and audio-recorded and transcribed verbatim. Focus group transcripts were analyzed using inductive content analysis, and open coding was performed by two coders. A codebook was generated based on the initial round of open coding and updated throughout the analytic process. Codes and themes were discussed for each transcript until consensus was …

Molecular And Sequencing Study And Identification Of Novel Sem-Type In Beta-Hemolytic Streptococci Involving The Upper Respiratory Tract In Iran, Ali Hassanpour, Hamid Tavanaei Manesh, Iraj Ashrafi Tamai

Faculty, Staff and Students Publications

BACKGROUND: Beta-hemolytic streptococci involving the upper respiratory tract cause strangles and strangles-like diseases in horses and cause severe economic damage to the equestrian club each year. Therefore, careful epidemiological study of these bacteria, evaluation of phylogenetic connections and SeM-typing can be useful to determine the source and epidemiological characteristics of the disease outbreak. Isolates were analyzed using molecular and phylogenetic methods and to determine antibiotic resistance pattern in Iranian isolates. Molecular and phylogenetic methods were used to evaluate Iranian streptococcal isolates, and the similarity of the Iranian SeM-97 sequence with other alleles was assessed using the Neighbor-joining method with the …

Orthostatic Hypotension, Hypertension Treatment, And Cardiovascular Disease: An Individual Participant Meta-Analysis, Anthony M Ishak, Carol Mita, Lewis A Lipsitz, Lawrence J Appel, Nigel S Beckett, Ruth L Coleman, William C Cushman, Barry R Davis, Greg Grandits, Rury R Holman, Edgar R Miller, Ruth Peters, Jan A Staessen, Addison A Taylor, Lutgarde Thijs, Jackson T Wright, Kenneth J Mukamal

Faculty, Staff and Students Publications

IMPORTANCE: There are ongoing concerns about the benefits of intensive vs standard blood pressure (BP) treatment among adults with orthostatic hypotension or standing hypotension.

OBJECTIVE: To determine the effect of a lower BP treatment goal or active therapy vs a standard BP treatment goal or placebo on cardiovascular disease (CVD) or all-cause mortality in strata of baseline orthostatic hypotension or baseline standing hypotension.

DATA SOURCES: Individual participant data meta-analysis based on a systematic review of MEDLINE, EMBASE, and CENTRAL databases through May 13, 2022.

STUDY SELECTION: Randomized trials of BP pharmacologic treatment (more intensive BP goal or active agent) with …

Regulation Of Postnatal Cardiomyocyte Maturation By An Rna Splicing Regulator Rbfox1, Arash Pezhouman, Tomohiro Yokota, Hiromi Miwa, Matthew Feldman, Tsz Kin Kong, Ziyue Yang, Woan Ting Tay, Ivan Pushkarsky, Kyungsoo Kim, Shan S Parikh, Shreya Udani, Boon Seng Soh, Chen Gao, Linsey Stiles, Orian S Shirihai, Bjorn C Knollmann, Reza Ardehali, Dino Di Carlo, Yibin Wang

Faculty, Staff and Students Publications

No abstract provided.

Excretory/Secretory Products From Trichinella Spiralis Adult Worms Ameliorate Myocardial Infarction By Inducing M2 Macrophage Polarization In A Mouse Model, Shuying Wang, Huihui Li, Xiaoli Wang, Weixiao Zhang, Shuyao Duan, Qiuyu Zhu, Erhe Gao, Shili Wu, Bin Zhan, Rui Zhou, Xiaodi Yang

Faculty, Staff and Students Publications

BACKGROUND: Ischemia-induced inflammatory response is the main pathological mechanism of myocardial infarction (MI)-caused heart tissue injury. It has been known that helminths and worm-derived proteins are capable of modulating host immune response to suppress excessive inflammation as a survival strategy. Excretory/secretory products from Trichinella spiralis adult worms (Ts-AES) have been shown to ameliorate inflammation-related diseases. In this study, Ts-AES were used to treat mice with MI to determine its therapeutic effect on reducing MI-induced heart inflammation and the immunological mechanism involved in the treatment.

METHODS: The MI model was established by the ligation of the left anterior descending coronary artery, …

Sptan1/Numb Axis Senses Cell Density To Restrain Cell Growth And Oncogenesis Through Hippo Signaling, Dongxue Su, Yuxi Li, Weiji Zhang, Huan Gao, Yao Cheng, Junhong Li, Zhangjian Lai, Zhe Li, Haitao Huang, Jiaxin Li, Jinhuan Li, Mengyu Cheng, Cheng Nian, Na Wu, Zhien Zhou, Yunzhi Xing, Yu Zhao, He Liu, Jiayu Tang, Qinghua Chen, Lixin Hong, Wengang Li, Zhihai Peng, Bin Zhao, Randy L Johnson, Pingguo Liu, Wanjin Hong, Lanfen Chen, Dawang Zhou

Faculty, Staff and Student Publications

The loss of contact inhibition is a key step during carcinogenesis. The Hippo-Yes-associated protein (Hippo/YAP) pathway is an important regulator of cell growth in a cell density-dependent manner. However, how Hippo signaling senses cell density in this context remains elusive. Here, we report that high cell density induced the phosphorylation of spectrin α chain, nonerythrocytic 1 (SPTAN1), a plasma membrane-stabilizing protein, to recruit NUMB endocytic adaptor protein isoforms 1 and 2 (NUMB1/2), which further sequestered microtubule affinity-regulating kinases (MARKs) in the plasma membrane and rendered them inaccessible for phosphorylation and inhibition of the Hippo kinases sterile 20-like kinases MST1 and …

Genome-Wide Analysis Of The Interplay Between Chromatin-Associated Rna And 3d Genome Organization In Human Cells, Tri C Nguyen, Weizhong Chen, Zhangming Yan, Weixin Wu, Kathia Zaleta-Rivera, Rong Hu, Miao Yu, Yuchuan Wang, Wenbo Li, Jian Ma, Bing Ren, Sheng Zhong

Faculty, Staff and Student Publications

The interphase genome is dynamically organized in the nucleus and decorated with chromatin-associated RNA (caRNA). It remains unclear whether the genome architecture modulates the spatial distribution of caRNA and vice versa. Here, we generate a resource of genome-wide RNA-DNA and DNA-DNA contact maps in human cells. These maps reveal the chromosomal domains demarcated by locally transcribed RNA, hereafter termed RNA-defined chromosomal domains. Further, the spreading of caRNA is constrained by the boundaries of topologically associating domains (TADs), demonstrating the role of the 3D genome structure in modulating the spatial distribution of RNA. Conversely, stopping transcription or acute depletion of RNA …

Priorities And Progress In Gram-Positive Bacterial Infection Research By The Antibacterial Resistance Leadership Group: A Narrative Review, Sarah B Doernberg, Cesar A Arias, Deena R Altman, Ahmed Babiker, Helen W Boucher, Sara E Cosgrove, Vance G Fowler, Stephanie A Fritz, Toshimitsu Hamasaki, Brendan J Kelly, Sixto M Leal, Catherine Liu, Thomas P Lodise, Loren G Miller, Jose M Munita, Barbara E Murray, Melinda M Pettigrew, Felicia Ruffin, Marc H Scheetz, Bo Shopsin, Truc T Tran, Nicholas A Turner, Derek J Williams, Smitha Zaharoff, Thomas L Holland

Faculty, Staff and Student Publications

The Antibacterial Resistance Leadership Group (ARLG) has prioritized infections caused by gram-positive bacteria as one of its core areas of emphasis. The ARLG Gram-positive Committee has focused on studies responding to 3 main identified research priorities: (1) investigation of strategies or therapies for infections predominantly caused by gram-positive bacteria, (2) evaluation of the efficacy of novel agents for infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci, and (3) optimization of dosing and duration of antimicrobial agents for gram-positive infections. Herein, we summarize ARLG accomplishments in gram-positive bacterial infection research, including studies aiming to (1) inform optimal vancomycin dosing, …

A Single Nanobody Neutralizes Multiple Epochally Evolving Human Noroviruses By Modulating Capsid Plasticity, Natthawan Chaimongkol, Khalil Ettayebi, Stanislav V Sosnovtsev, Kaundal Soni, B Vijayalakshmi Ayyar, Sreejesh Shanker, Frederick H Neill, Banumathi Sankaran, Robert L Atmar, Mary K Estes, Kim Y Green, Viviana Parreño, B V Venkataram Prasad

Faculty, Staff and Students Publications

Acute gastroenteritis caused by human noroviruses (HuNoVs) is a significant global health and economic burden and is without licensed vaccines or antiviral drugs. The GII.4 HuNoV causes most epidemics worldwide. This virus undergoes epochal evolution with periodic emergence of variants with new antigenic profiles and altered specificity for histo-blood group antigens (HBGA), the determinants of cell attachment and susceptibility, hampering the development of immunotherapeutics. Here, we show that a llama-derived nanobody M4 neutralizes multiple GII.4 variants with high potency in human intestinal enteroids. The crystal structure of M4 complexed with the protruding domain of the GII.4 capsid protein VP1 revealed …

Revisiting Asthma Obstructive Sleep Apnea Overlap: Current Knowledge And Future Needs

Faculty, Staff and Students Publications

Asthma and obstructive sleep apnea are highly prevalent conditions with a high cost burden. In addition to shared risk factors, existing data suggest a bidirectional relationship between asthma and OSA, where each condition can impact the other. Patients with asthma often complain of sleep fragmentation, nocturnal asthma symptoms, daytime sleepiness, and snoring. The prevalence of OSA increases with asthma severity, as evidenced by multiple large studies. Asthma may lower the threshold for arousal in OSA, resulting in the hypopnea with arousal phenotype. Epidemiologic studies in adults have shown that OSA is associated with worse asthma severity, increased frequency of exacerbation, …