Digital Commons Network^™

Tmem27 Suppresses Tumor Development By Promoting Ret Ubiquitination, Positioning, And Degradation, Qianjin Guo, Zi-Ming Cheng, Hector Gonzalez-Cantú, Matthew Rotondi, Gabriela Huelgas-Morales, Purushoth Ethiraj, Zhijun Qiu, Jonathan Lefkowitz, Wan Song, Bethany N Landry, Hector Lopez, Cynthia M Estrada-Zuniga, Shivi Goyal, Mohammad Aasif Khan, Timothy J Walker, Exing Wang, Faqian Li, Yanli Ding, Lois M Mulligan, Ricardo C T Aguiar, Patricia L M Dahia

Faculty, Staff and Student Publications

The TMEM127 gene encodes a transmembrane protein of poorly known function that is mutated in pheochromocytomas, neural crest-derived tumors of adrenomedullary cells. Here, we report that, at single-nucleus resolution, TMEM127-mutant tumors share precursor cells and transcription regulatory elements with pheochromocytomas carrying mutations of the tyrosine kinase receptor RET. Additionally, TMEM127-mutant pheochromocytomas, human cells, and mouse knockout models of TMEM127 accumulate RET and increase its signaling. TMEM127 contributes to RET cellular positioning, trafficking, and lysosome-mediated degradation. Mechanistically, TMEM127 binds to RET and recruits the NEDD4 E3 ubiquitin ligase for RET ubiquitination and degradation via TMEM127 C-terminal PxxY motifs. Lastly, increased cell …

Pet Imaging Of Microglia Using Pbr28suv Determines Therapeutic Efficacy Of Autologous Bone Marrow Mononuclear Cells Therapy In Traumatic Brain Injury, Supinder S Bedi, Michael C Scott, Max A Skibber, Akshita Kumar, Henry W Caplan, Hasen Xue, David Sequeira, Alison L Speer, Fanni Cardenas, Franciska Gudenkauf, Karen Uray, Amit K. Srivastava, Alan R Prossin, Charles S Cox

Cardeza Foundation for Hematologic Research

Traumatic brain injury (TBI) results in activated microglia. Activated microglia can be measured in vivo by using positron emission topography (PET) ligand peripheral benzodiazepine receptor standardized uptake values (PBR28suv). Cell based therapies have utilized autologous bone marrow mononuclear cells (BMMNCs) to attenuate activated microglia after TBI. This study aims to utilize in vivo PBR28suv to assess the efficacy of BMMNCs therapy after TBI. Seventy-two hours after CCI injury, BMMNCs were harvested from the tibia and injected via tail-vein at 74 h after injury at a concentration of 2 million cells per kilogram of body weight. There were three groups of …

Pet Imaging Of Microglia Using Pbr28suv Determines Therapeutic Efficacy Of Autologous Bone Marrow Mononuclear Cells Therapy In Traumatic Brain Injury, Supinder S Bedi, Michael C Scott, Max A Skibber, Akshita Kumar, Henry W Caplan, Hasen Xue, David Sequeira, Alison L Speer, Fanni Cardenas, Franciska Gudenkauf, Karen Uray, Amit K Srivastava, Alan R Prossin, Charles S Cox

Faculty, Staff and Student Publications

Traumatic brain injury (TBI) results in activated microglia. Activated microglia can be measured in vivo by using positron emission topography (PET) ligand peripheral benzodiazepine receptor standardized uptake values (PBR28suv). Cell based therapies have utilized autologous bone marrow mononuclear cells (BMMNCs) to attenuate activated microglia after TBI. This study aims to utilize in vivo PBR28suv to assess the efficacy of BMMNCs therapy after TBI. Seventy-two hours after CCI injury, BMMNCs were harvested from the tibia and injected via tail-vein at 74 h after injury at a concentration of 2 million cells per kilogram of body weight. There were three groups of …

Pet Imaging Of Microglia Using Pbr28suv Determines Therapeutic Efficacy Of Autologous Bone Marrow Mononuclear Cells Therapy In Traumatic Brain Injury, Supinder S Bedi, Michael C Scott, Max A Skibber, Akshita Kumar, Henry W Caplan, Hasen Xue, David Sequeira, Alison L Speer, Fanni Cardenas, Franciska Gudenkauf, Karen Uray, Amit K Srivastava, Alan R Prossin, Charles S Cox

Faculty, Staff and Student Publications

Traumatic brain injury (TBI) results in activated microglia. Activated microglia can be measured in vivo by using positron emission topography (PET) ligand peripheral benzodiazepine receptor standardized uptake values (PBR28suv). Cell based therapies have utilized autologous bone marrow mononuclear cells (BMMNCs) to attenuate activated microglia after TBI. This study aims to utilize in vivo PBR28suv to assess the efficacy of BMMNCs therapy after TBI. Seventy-two hours after CCI injury, BMMNCs were harvested from the tibia and injected via tail-vein at 74 h after injury at a concentration of 2 million cells per kilogram of body weight. There were three groups of …

In Vivo Crispr/Cas9 Screening Identifies Pbrm1 As A Regulator Of Myeloid Leukemia Development In Mice, Bin E Li, Grace Y Li, Wenqing Cai, Qian Zhu, Davide Seruggia, Yuko Fujiwara, Christopher R Vakoc, Stuart H Orkin

Faculty, Staff and Students Publications

CRISPR/Cas9 screening approaches are powerful tool for identifying in vivo cancer dependencies. Hematopoietic malignancies are genetically complex disorders in which the sequential acquisition of somatic mutations generates clonal diversity. Over time, additional cooperating mutations may drive disease progression. Using an in vivo pooled gene editing screen of epigenetic factors in primary murine hematopoietic stem and progenitor cells (HSPCs), we sought to uncover unrecognized genes that contribute to leukemia progression. We, first, modeled myeloid leukemia in mice by functionally abrogating both Tet2 and Tet3 in HSPCs, followed by transplantation. We, then, performed pooled CRISPR/Cas9 editing of genes encoding epigenetic factors and …

A Peptide-Binding Domain Shared With An Antarctic Bacterium Facilitates, Cameron J Lloyd, Shuaiqi Guo, Brett Kinrade, Hossein Zahiri, Robert Eves, Syed Khalid Ali, Fitnat Yildiz, Ilja K Voets, Peter L Davies, Karl E Klose

Faculty, Staff and Student Publications

No abstract provided.

Axl-Initiated Paracrine Activation Of Pstat3 Enhances Mesenchymal And Vasculogenic Supportive Features Of Tumor-Associated Macrophages, Chia-Nung Hung, Meizhen Chen, Daniel T Dearmond, Cheryl H-L Chiu, Catherine A Limboy, Xi Tan, Meena Kusi, Chih-Wei Chou, Li-Ling Lin, Zhao Zhang, Chiou-Miin Wang, Chun-Liang Chen, Kohzoh Mitsuya, Pawel A Osmulski, Maria E Gaczynska, Nameer B Kirma, Ratna K Vadlamudi, Don L Gibbons, Steve Warner, Andrew J Brenner, Daruka Mahadevan, Joel E Michalek, Tim H-M Huang, Josephine A Taverna

Faculty, Staff and Student Publications

Tumor-associated macrophages (TAMs) are integral to the development of complex tumor microenvironments (TMEs) and can execute disparate cellular programs in response to extracellular cues. However, upstream signaling processes underpinning this phenotypic plasticity remain to be elucidated. Here, we report that concordant AXL-STAT3 signaling in TAMs is triggered by lung cancer cells or cancer-associated fibroblasts in the cytokine milieu. This paracrine action drives TAM differentiation toward a tumor-promoting "M2-like" phenotype with upregulation of CD163 and putative mesenchymal markers, contributing to TAM heterogeneity and diverse cellular functions. One of the upregulated markers, CD44, mediated by AXL-IL-11-pSTAT3 signaling cascade, enhances macrophage ability to …

Novel Genetic And Phenotypic Expansion In Gosr2-Related Progressive Myoclonus Epilepsy, Lea Hentrich, Mered Parnes, Timothy Edward Lotze, Rohini Coorg, Tom J De Koning, Kha M Nguyen, Calvin K Yip, Heinz Jungbluth, Anne Koy, Hormos Salimi Dafsari

Faculty, Staff and Students Publications

Biallelic variants in the Golgi SNAP receptor complex member 2 gene (GOSR2) have been reported in progressive myoclonus epilepsy with neurodegeneration. Typical clinical features include ataxia and areflexia during early childhood, followed by seizures, scoliosis, dysarthria, and myoclonus. Here, we report two novel patients from unrelated families with a GOSR2-related disorder and novel genetic and clinical findings. The first patient, a male compound heterozygous for the GOSR2 splice site variant c.336+1G>A and the novel c.364G>A,p.Glu122Lys missense variant showed global developmental delay and seizures at the age of 2 years, followed by myoclonus at the age …

Dopamine Signaling From Ganglion Cells Directs Layer-Specific Angiogenesis In The Retina, Justine H Liang, Viktor Akhanov, Anthony Ho, Mohamed Tawfik, Shane P D'Souza, Morven A Cameron, Richard A Lang, Melanie A Samuel

Faculty, Staff and Students Publications

During central nervous system (CNS) development, a precisely patterned vasculature emerges to support CNS function. How neurons control angiogenesis is not well understood. Here, we show that the neuromodulator dopamine restricts vascular development in the retina via temporally limited production by an unexpected neuron subset. Our genetic and pharmacological experiments demonstrate that elevating dopamine levels inhibits tip-cell sprouting and vessel growth, whereas reducing dopamine production by all retina neurons increases growth. Dopamine production by canonical dopaminergic amacrine interneurons is dispensable for these events. Instead, we found that temporally restricted dopamine production by retinal ganglion cells (RGCs) modulates vascular development. RGCs …

Blockade Of Interferon Signaling Decreases Gut Barrier Integrity And Promotes Severe West Nile Virus Disease, Shih-Ching Lin, Fang R Zhao, Hana Janova, Adrian Gervais, Summer Rucknagel, Kristy O Murray, Jean-Laurent Casanova, Michael S Diamond

Faculty, Staff and Students Publications

The determinants of severe disease caused by West Nile virus (WNV) and why only ~1% of individuals progress to encephalitis remain poorly understood. Here, we use human and mouse enteroids, and a mouse model of pathogenesis, to explore the capacity of WNV to directly infect gastrointestinal (GI) tract cells and contribute to disease severity. At baseline, WNV poorly infects human and mouse enteroid cultures and enterocytes in mice. However, when STAT1 or type I interferon (IFN) responses are absent, GI tract cells become infected, and this is associated with augmented GI tract and blood-brain barrier (BBB) permeability, accumulation of gut-derived …

A Rare Cause Of Diarrhea: Intestinal Spirochetosis In An Hiv-Positive Patient., Lacey Falgout, Shilpa Kailas, Supraja Sridhar, Nisha Loganantharaj

School of Medicine Faculty Publications

Intestinal spirochetosis (IS) is a rare gastrointestinal infection with vague presenting symptoms. Diagnosis is confirmed histopathologically. Risk factors include homosexuality and HIV. Antibiotic treatment with metronidazole usually leads to resolution of symptoms. We present the case of a 56-year-old HIV-positive man with chronic, watery diarrhea who was diagnosed with IS. This case highlights the importance of considering IS in the differential in HIV-positive patients with nonspecific gastrointestinal symptoms after more common etiologies have been ruled out.

A Retrospective Review Of 30-Day Hospital Readmission Risk After Open Heart Surgery In Patients With Atrial Fibrillation, Varun Ashutosh Rao, Genaro Deleon, Aish Thamba, Mindy Flanagan, Kathleen Nickel, Douglas Gray Md

Medical Student Research

Introduction

Readmission rates after open heart surgery (OHS) remain an important clinical issue. The causes are varied, with identifying risk factors potentially providing valuable information to reduce healthcare costs and the rate of post-operative complications. This study aimed to characterize the reasons for 30-day hospital readmission rates of patients after open heart surgery.

Methods

All patients over 18 years of age undergoing OHS at a community hospital from January 2020 through December 2020 were identified. Demographic data, medical history, operative reports, post-operative complications, and telehealth interventions were obtained through chart review. Descriptive statistics and readmission rates were calculated, along with …

Comparative Genomics Analysis Of Three Conserved Plasmid Families In The Western Hemisphere Soft Tick-Borne Relapsing Fever Borreliae Provides Insight Into Variation In Genome Structure And Antigenic Variation Systems, Alexander R Kneubehl, Job E Lopez

Faculty, Staff and Students Publications

Borrelia spirochetes, causative agents of Lyme disease and relapsing fever (RF), have uniquely complex genomes, consisting of a linear chromosome and both circular and linear plasmids. The plasmids harbor genes important for the vector-host life cycle of these tick-borne bacteria. The role of plasmids from Lyme disease causing spirochetes is more refined compared to RF Borrelia because of limited plasmid-resolved genome assemblies for the latter. We recently addressed this limitation and found that three linear plasmid families (F6, F27, and F28) were syntenic across all the RF Borrelia species that we examined. Given this conservation, we further investigated the three …

Boosting Glycolysis To Combat Fragile Bone In Type 1 Diabetes, Zixue Jin, Brendan Lee

Faculty, Staff and Students Publications

Individuals with type 1 diabetes (T1D) have an increased risk of osteoporosis and fracture. In this issue of Cell Chemical Biology, Ji et al.1 show that impaired glucose metabolism in the bone-forming osteoblast drives diabetic osteoporosis in Akita mice, a mouse model of T1D.

Epichaperome Inhibition Targets Tp53-Mutant Aml And Aml Stem/Progenitor Cells, Bing Z Carter, Po Yee Mak, Muharrem Muftuoglu, Wenjing Tao, Baozhen Ke, Jingqi Pei, Andrea D Bedoy, Lauren B Ostermann, Yuki Nishida, Sevinj Isgandarova, Mary Sobieski, Nghi Nguyen, Reid T Powell, Margarita Martinez-Moczygemba, Clifford Stephan, Mahesh Basyal, Naveen Pemmaraju, Steffen Boettcher, Benjamin L Ebert, Elizabeth J Shpall, Barbara Wallner, Robert A Morgan, Georgios I Karras, Ute M Moll, Michael Andreeff

Faculty, Staff and Student Publications

TP 53-mutant acute myeloid leukemia (AML) remains the ultimate therapeutic challenge. Epichaperomes, formed in malignant cells, consist of heat shock protein 90 (HSP90) and associated proteins that support the maturation, activity, and stability of oncogenic kinases and transcription factors including mutant p53. High-throughput drug screening identified HSP90 inhibitors as top hits in isogenic TP53-wild-type (WT) and -mutant AML cells. We detected epichaperomes in AML cells and stem/progenitor cells with TP53 mutations but not in healthy bone marrow (BM) cells. Hence, we investigated the therapeutic potential of specifically targeting epichaperomes with PU-H71 in TP53-mutant AML based on its preferred binding to …

Nlrp3 Selectively Drives Il-1Β Secretion By Pseudomonas Aeruginosa Infected Neutrophils And Regulates Corneal Disease Severity, Martin S Minns, Karl Liboro, Tatiane S Lima, Serena Abbondante, Brandon A Miller, Michaela E Marshall, Jolynn Tran Chau, Alicia Roistacher, Arne Rietsch, George R Dubyak, Eric Pearlman

Faculty, Staff and Student Publications

Macrophages infected with Gram-negative bacteria expressing Type III secretion system (T3SS) activate the NLRC4 inflammasome, resulting in Gasdermin D (GSDMD)-dependent, but GSDME independent IL-1β secretion and pyroptosis. Here we examine inflammasome signaling in neutrophils infected with Pseudomonas aeruginosa strain PAO1 that expresses the T3SS effectors ExoS and ExoT. IL-1β secretion by neutrophils requires the T3SS needle and translocon proteins and GSDMD. In macrophages, PAO1 and mutants lacking ExoS and ExoT (ΔexoST) require NLRC4 for IL-1β secretion. While IL-1β release from ΔexoST infected neutrophils is also NLRC4-dependent, infection with PAO1 is instead NLRP3-dependent and driven by the ADP ribosyl transferase activity …

Chronic Cough Relief By Allosteric Modulation Of P2x3 Without Taste Disturbance, Chang-Run Guo, Zhong-Zhe Zhang, Xing Zhou, Meng-Yang Sun, Tian-Tian Li, Yun-Tao Lei, Yu-Hao Gao, Qing-Quan Li, Chen-Xi Yue, Yu Gao, Yi-Yu Lin, Cui-Yun Hao, Chang-Zhu Li, Peng Cao, Michael X Zhu, Ming-Qiang Rong, Wen-Hui Wang, Ye Yu

Faculty, Staff and Student Publications

P2X receptors are cation channels that sense extracellular ATP. Many therapeutic candidates targeting P2X receptors have begun clinical trials or acquired approval for the treatment of refractory chronic cough (RCC) and other disorders. However, the present negative allosteric modulation of P2X receptors is primarily limited to the central pocket or the site below the left flipper domain. Here, we uncover a mechanism of allosteric regulation of P2X3 in the inner pocket of the head domain (IP-HD), and show that the antitussive effects of quercetin and PSFL2915 (our nM-affinity P2X3 inhibitor optimized based on quercetin) on male mice and guinea pigs …

Critical Functions Of Extracellular Matrix In Brain Metastasis Seeding, Arseniy E Yuzhalin, Dihua Yu

Faculty, Staff and Student Publications

Human brain is characterized by extremely sparse extracellular matrix (ECM). Despite its low abundance, the significance of brain ECM in both physiological and pathological conditions should not be underestimated. Brain metastasis is a serious complication of cancer, and recent findings highlighted the contribution of ECM in brain metastasis development. In this review, we provide a comprehensive outlook on how ECM proteins promote brain metastasis seeding. In particular, we discuss (1) disruption of the blood-brain barrier in brain metastasis; (2) role of ECM in modulating brain metastasis dormancy; (3) regulation of brain metastasis seeding by ECM-activated integrin signaling; (4) functions of …

Evaluation Of Acceptability, Functionality, And Validity Of A Passive Image-Based Dietary Intake Assessment Method In Adults And Children Of Ghanaian And Kenyan Origin Living In London, Uk, Modou L Jobarteh, Megan A Mccrory, Benny Lo, Konstantinos K Triantafyllidis, Jianing Qiu, Jennifer P Griffin, Edward Sazonov, Mingui Sun, Wenyan Jia, Tom Baranowski, Alex K Anderson, Kathryn Maitland, Gary Frost

Children’s Nutrition Research Center Staff Publications

Background: Accurate estimation of dietary intake is challenging. However, whilst some progress has been made in high-income countries, low- and middle-income countries (LMICs) remain behind, contributing to critical nutritional data gaps. This study aimed to validate an objective, passive image-based dietary intake assessment method against weighed food records in London, UK, for onward deployment to LMICs.

Methods: Wearable camera devices were used to capture food intake on eating occasions in 18 adults and 17 children of Ghanaian and Kenyan origin living in London. Participants were provided pre-weighed meals of Ghanaian and Kenyan cuisine and camera devices to automatically capture images …

Kcnq2/3 Gain-Of-Function Variants And Cell Excitability: Differential Effects In Ca1 Versus L2/3 Pyramidal Neurons, Nissi Varghese, Bruno Moscoso, Ana Chavez, Kristen Springer, Erika Ortiz, Heun Soh, Sabato Santaniello, Atul Maheshwari, Anastasios V Tzingounis

Faculty, Staff and Students Publications

Gain-of-function (GOF) pathogenic variants in the potassium channels KCNQ2 and KCNQ3 lead to hyperexcitability disorders such as epilepsy and autism spectrum disorders. However, the underlying cellular mechanisms of how these variants impair forebrain function are unclear. Here, we show that the R201C variant in KCNQ2 has opposite effects on the excitability of two types of mouse pyramidal neurons of either sex, causing hyperexcitability in layer 2/3 (L2/3) pyramidal neurons and hypoexcitability in CA1 pyramidal neurons. Similarly, the homologous R231C variant in KCNQ3 leads to hyperexcitability in L2/3 pyramidal neurons and hypoexcitability in CA1 pyramidal neurons. However, the effects of KCNQ3 …

Mir-146a Inhibits Ovarian Tumor Growth In Vivo Via Targeting Immunosuppressive Neutrophils And Enhancing Cd8+ T Cell Infiltration, Rui Chen, Elaina Coleborn, Chintan Bhavsar, Yue Wang, Louisa Alim, Andrew N Wilkinson, Michelle A Tran, Gowri Irgam, Sharat Atluri, Kiefer Wong, Jae-Jun Shim, Siddharth Adityan, Ju-Seog Lee, Willem W Overwijk, Raymond Steptoe, Da Yang, Sherry Y Wu

Faculty, Staff and Student Publications

Immunotherapies have emerged as promising strategies for cancer treatment. However, existing immunotherapies have poor activity in high-grade serous ovarian cancer (HGSC) due to the immunosuppressive tumor microenvironment and the associated low tumoral CD8+ T cell (CTL) infiltration. Through multiple lines of evidence, including integrative analyses of human HGSC tumors, we have identified miR-146a as a master regulator of CTL infiltration in HGSC. Tumoral miR-146a expression is positively correlated with anti-cancer immune signatures in human HGSC tumors, and delivery of miR-146a to tumors resulted in significant reduction in tumor growth in both ID8-p53−/− and IG10 murine HGSC models. Increasing miR-146a expression …

Abcc1 And Glutathione Metabolism Limit The Efficacy Of Bcl-2 Inhibitors In Acute Myeloid Leukemia, Jessica Ebner, Johannes Schmoellerl, Martin Piontek, Gabriele Manhart, Selina Troester, Bing Z Carter, Heidi Neubauer, Richard Moriggl, Gergely Szakács, Johannes Zuber, Thomas Köcher, Michael Andreeff, Wolfgang R Sperr, Peter Valent, Florian Grebien

Faculty, Staff and Student Publications

The BCL-2 inhibitor Venetoclax is a promising agent for the treatment of acute myeloid leukemia (AML). However, many patients are refractory to Venetoclax, and resistance develops quickly. ATP-binding cassette (ABC) transporters mediate chemotherapy resistance but their role in modulating the activity of targeted small-molecule inhibitors is unclear. Using CRISPR/Cas9 screening, we find that loss of ABCC1 strongly increases the sensitivity of AML cells to Venetoclax. Genetic and pharmacologic ABCC1 inactivation potentiates the anti-leukemic effects of BCL-2 inhibitors and efficiently re-sensitizes Venetoclax-resistant leukemia cells. Conversely, ABCC1 overexpression induces resistance to BCL-2 inhibitors by reducing intracellular drug levels, and high ABCC1 levels …

Epigenetic Induction Of Smooth Muscle Cell Phenotypic Alterations In Aortic Aneurysms And Dissections, Abhijit Chakraborty, Yanming Li, Chen Zhang, Yang Li, Kimberly R Rebello, Shengyu Li, Samantha Xu, Hernan G Vasquez, Lin Zhang, Wei Luo, Guangyu Wang, Kaifu Chen, Joseph S Coselli, Scott A Lemaire, Ying H Shen

Faculty, Staff and Students Publications

BACKGROUND: Smooth muscle cell (SMC) phenotypic switching has been increasingly detected in aortic aneurysm and dissection (AAD) tissues. However, the diverse SMC phenotypes in AAD tissues and the mechanisms driving SMC phenotypic alterations remain to be identified.

METHODS: We examined the transcriptomic and epigenomic dynamics of aortic SMC phenotypic changes in mice with angiotensin II-induced AAD by using single-cell RNA sequencing and single-cell sequencing assay for transposase-accessible chromatin. SMC phenotypic alteration in aortas from patients with ascending thoracic AAD was examined by using single-cell RNA sequencing analysis.

RESULTS: Single-cell RNA sequencing analysis revealed that aortic stress induced the transition of …

Narrative Review Of The Role Of Technology In Pediatric Diabetes: From Testing Blood Glucose To Subcutaneous Automated Therapy And Hope For Cure, Michael Yafi, Avni Shah, Katherine Velez

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVE: Type 1 diabetes, the most common cause of diabetes in pediatrics, is defined by the hyperglycemia that results from the permanent autoimmune damage to the pancreas. The Diabetes Control and Complications Trial (DCCT) demonstrated that strict glycemic control targeting lower HbA1c goals can both delay the onset and progression of its complications that include diabetic neuropathy, nephropathy, retinopathy, and increased cardiovascular events. Our primary objective is to review the literature available regarding the technology applied for the treatment of diabetes, not only aiding patients' quality of life but addressing its effects on hypoglycemia and reduced risk of …

Aspergillus Flavus And Fusarium Verticillioides And Their Main Mycotoxins: Global Distribution And Scenarios Of Interactions In Maize, Xiangrong Chen, Mohamed F Abdallah, Sofie Landschoot, Kris Audenaert, Sarah De Saeger, Xiangfeng Chen, Andreja Rajkovic

Faculty, Staff and Student Publications

Maize is frequently contaminated with multiple mycotoxins, especially those produced by Aspergillus flavus and Fusarium verticillioides. As mycotoxin contamination is a critical factor that destabilizes global food safety, the current review provides an updated overview of the (co-)occurrence of A. flavus and F. verticillioides and (co-)contamination of aflatoxin B1 (AFB1) and fumonisin B1 (FB1) in maize. Furthermore, it summarizes their interactions in maize. The gathered data predict the (co-)occurrence and virulence of A. flavus and F. verticillioides would increase worldwide, especially in European cold climate countries. Studies on the interaction of both fungi regarding their growth mainly showed antagonistic …

Specific Polysaccharide Antibody Deficiency, Daniel M Musher

Faculty, Staff and Students Publications

No abstract provided.

Neuroimmune Support Of Neuronal Regeneration And Neuroplasticity Following Cerebral Ischemia In Juvenile Mice, Ricaurte A Marquez-Ortiz, Vesna Tesic, Daniel R Hernandez, Bilkis Akhter, Nibedita Aich, Porter M Boudreaux, Garrett A Clemons, Celeste Yin-Chieh Wu, Hung Wen Lin, Krista M Rodgers

Faculty, Staff and Student Publications

Ischemic damage to the brain and loss of neurons contribute to functional disabilities in many stroke survivors. Recovery of neuroplasticity is critical to restoration of function and improved quality of life. Stroke and neurological deficits occur in both adults and children, and yet it is well documented that the developing brain has remarkable plasticity which promotes increased post-ischemic functional recovery compared with adults. However, the mechanisms underlying post-stroke recovery in the young brain have not been fully explored. We observed opposing responses to experimental cerebral ischemia in juvenile and adult mice, with substantial neural regeneration and enhanced neuroplasticity detected in …

Classification Of Missense Variants In The N-Methyl-D-Aspartate Receptor Grin Gene Family As Gain- Or Loss-Of-Function, Scott J Myers, Hongjie Yuan, Riley E Perszyk, Jing Zhang, Sukhan Kim, Kelsey A Nocilla, James P Allen, Jennifer M Bain, Johannes R Lemke, Dennis Lal, Timothy A Benke, Stephen F Traynelis

Faculty, Staff and Student Publications

Advances in sequencing technology have generated a large amount of genetic data from patients with neurological conditions. These data have provided diagnosis of many rare diseases, including a number of pathogenic de novo missense variants in GRIN genes encoding N-methyl-d-aspartate receptors (NMDARs). To understand the ramifications for neurons and brain circuits affected by rare patient variants, functional analysis of the variant receptor is necessary in model systems. For NMDARs, this functional analysis needs to assess multiple properties in order to understand how variants could impact receptor function in neurons. One can then use these data to determine whether the …

Characterization Of An Mtbp Hypomorphic Allele In A Diethylnitrosamine-Induced Liver Carcinogenesis Model, Atul Ranjan, Elizabeth A. Thoenen, Atsushi Kaida, Stephanie Wood, Terry Van Dyke, Tomoo Iwakuma

Manuscripts, Articles, Book Chapters and Other Papers

MTBP is implicated in cell cycle progression, DNA replication, and cancer metastasis. However, the function of MTBP remains enigmatic and is dependent on cellular contexts and its cellular localization. To understand the in vivo physiological role of MTBP, it is important to generate Mtbp knockout mice. However, complete deletion of the Mtbp gene in mice results in early embryonic lethality, while its heterozygous deletion shows modest biological phenotypes, including enhanced cancer metastasis. To overcome this and better characterize the in vivo physiological function of MTBP, we, for the first time, generated mice that carry an Mtbp hypomorphic allele (MtbpH …

A Review Of The Role Of Tendon Stem Cells In Tendon-Bone Regeneration, Junjie Chen, Chuanfeng Jiang, Lu Yin, Yingqi Liu, Yue He, Sen Li, Huarui Shen

Faculty, Staff and Student Publications

Tendon-bone injuries are a prevalent health concern associated with sports and other physically demanding activities. These injuries have a limited innate healing ability, often leading to the formation of scar tissue rather than the regeneration of healthy tendon tissue. This scar tissue results from excessive fibrosis during the early healing process and often leads to reduced tendon function and an increased risk of reinjury. Traditionally, surgical reconstruction has been the primary treatment for tendon-bone injuries. However, restoring the natural structure and mechanical properties of tendons after surgical reconstruction presents a considerable challenge. Recently, the potential of stem cell therapy has …