Digital Commons Network^™

Severe Central Nervous System Demyelination In Sanfilippo Disease, Mahsa Taherzadeh, Erjun Zhang, Irene Londono, Benjamin De Leener, Sophie Wang, Jonathan D Cooper, Timothy E Kennedy, Carlos R Morales, Zesheng Chen, Gregory A Lodygensky, Alexey V Pshezhetsky

2020-Current year OA Pubs

INTRODUCTION: Chronic progressive neuroinflammation is a hallmark of neurological lysosomal storage diseases, including mucopolysaccharidosis III (MPS III or Sanfilippo disease). Since neuroinflammation is linked to white matter tract pathology, we analyzed axonal myelination and white matter density in the mouse model of MPS IIIC

METHODS: Brain and spinal cord tissues of human MPS III patients, 6-month-old

RESULTS: Analyses of CC and spinal cord tissues by immunohistochemistry revealed substantially reduced levels of myelin-associated proteins including Myelin Basic Protein, Myelin Associated Glycoprotein, and Myelin Oligodendrocyte Glycoprotein. Furthermore, ultrastructural analyses revealed disruption of myelin sheath organization and reduced myelin thickness in the brains …

Diffusion Basis Spectrum Imaging Detects Subclinical Traumatic Optic Neuropathy In A Closed-Head Impact Mouse Model Of Traumatic Brain Injury, Hsin-Chieh Yang, Raj Swaroop Lavadi, Andrew D Sauerbeck, Michael Wallendorf, Terrance T Kummer, Sheng-Kwei Song, Tsen-Hsuan Lin

2020-Current year OA Pubs

INTRODUCTION: Traumatic optic neuropathy (TON) is the optic nerve injury secondary to brain trauma leading to visual impairment and vision loss. Current clinical visual function assessments often fail to detect TON due to slow disease progression and clinically silent lesions resulting in potentially delayed or missed treatment in patients with traumatic brain injury (TBI).

METHODS: Diffusion basis spectrum imaging (DBSI) is a novel imaging modality that can potentially fill this diagnostic gap. Twenty-two, 16-week-old, male mice were equally divided into a sham or TBI (induced by moderate Closed-Head Impact Model of Engineered Rotational Acceleration device) group. Briefly, mice were anesthetized …

Defining Solute Carrier Transporter Signatures Of Murine Immune Cell Subsets, Tania Løve Aaes, Javier Burgoa Cardás, Kodi S Ravichandran

2020-Current year OA Pubs

Solute carrier (SLC) transporters are membrane-bound proteins that facilitate nutrient transport, and the movement across cellular membranes of various substrates ranging from ions to amino acids, metabolites and drugs. Recently, SLCs have gained increased attention due to their functional linkage to innate immunological processes such as the clearance of dead cells and anti-microbial defense. Further, the druggable nature of these transporters provides unique opportunities for improving outcomes in different immunological diseases. Although the SLCs represent the largest group of transporters and are often identified as significant hits in omics data sets, their role in immunology has been insufficiently explored. This …

The Actin-Bundling Protein, Pls3, Is Part Of The Mechanoresponsive Machinery That Regulates Osteoblast Mineralization, Samantha M Chin, Carmela Unnold-Cofre, Teri Naismith, Silvia Jansen

2020-Current year OA Pubs

Plastin-3 (PLS3) is a calcium-sensitive actin-bundling protein that has recently been linked to the development of childhood-onset osteoporosis. Clinical data suggest that PLS3 mutations lead to a defect in osteoblast function, however the underlying mechanism remains elusive. To investigate the role of PLS3 in bone mineralization, we generated MC3T3-E1 preosteoblast cells that are stably depleted of PLS3. Analysis of osteogenic differentiation of control and PLS3 knockdown (PLS3 KD) cells showed that depletion of PLS3 does not alter the first stage of osteoblast mineralization in which a collagen matrix is deposited, but severely affects the subsequent mineralization of that matrix. During …

Whole Genome Sequence Analysis Of Apparent Treatment Resistant Hypertension Status In Participants From The Trans-Omics For Precision Medicine Program, Nicole D Armstrong, Dabeeru C Rao, Et Al.

2020-Current year OA Pubs

No abstract provided.

A Bone To Pick-Cellular And Molecular Mechanisms Of Bone Pain In Sickle Cell Disease, Jahnavi Gollamudi, Kristine A Karkoska, Oluwabukola T Gbotosho, Wei Zou, Hyacinth I Hyacinth, Steven L Teitelbaum

2020-Current year OA Pubs

The bone is one of the most commonly affected organs in sickle cell disease (SCD). Repeated ischemia, oxidative stress and inflammation within the bone is largely responsible for promoting bone pain. As more individuals with SCD survive into adulthood, they are likely to experience a synergistic impact of both aging and SCD on their bone health. As bone health deteriorates, bone pain will likely exacerbate. Recent mechanistic and observational studies emphasize an intricate relationship between bone remodeling and the peripheral nervous system. Under pathological conditions, abnormal bone remodeling plays a key role in the propagation of bone pain. In this …

Evaluating The Efficacy Of Purchased Antisense Oligonucleotides To Reduce Mouse And Human Tau In Vivo, Pranav Vemula, Kathleen M Schoch, Timothy M Miller

2020-Current year OA Pubs

Many preclinical and clinical studies support the use of antisense oligonucleotides (ASOs) as effective therapeutic strategies. However, acquiring ASOs for research purposes may be limited by partnerships with the pharmaceutical companies. Our lab previously developed an effective ASO strategy to lower human tau and reverse pathology in aged tauopathy model mice. Testing the efficacy of purchased tau lowering ASOs would provide support for these reagents as broad research tools. Purchased mouse and human tau lowering ASOs were infused or injected intracerebroventricularly into wildtype and tau transgenic mice. Following treatment, brain tissue evaluated for ASO distribution and levels of tau mRNA, …

Changes In Distribution Of Severe Neurologic Involvement In Us Pediatric Inpatients With Covid-19 Or Multisystem Inflammatory Syndrome In Children In 2021 Vs 2020, Kerri L Larovere, Amanda R Kolmar, Et Al.

2020-Current year OA Pubs

IMPORTANCE: In 2020 during the COVID-19 pandemic, neurologic involvement was common in children and adolescents hospitalized in the United States for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related complications.

OBJECTIVE: To provide an update on the spectrum of SARS-CoV-2-related neurologic involvement among children and adolescents in 2021.

DESIGN, SETTING, AND PARTICIPANTS: Case series investigation of patients reported to public health surveillance hospitalized with SARS-CoV-2-related illness between December 15, 2020, and December 31, 2021, in 55 US hospitals in 31 states with follow-up at hospital discharge. A total of 2253 patients were enrolled during the investigation period. Patients suspected of having …

Plasma And Cerebrospinal Fluid Proteomic Signatures Of Acutely Sleep-Deprived Humans: An Exploratory Study, Ana Vaquer-Alicea, Jinsheng Yu, Haiyan Liu, Brendan P Lucey

2020-Current year OA Pubs

STUDY OBJECTIVES: Acute sleep deprivation affects both central and peripheral biological processes. Prior research has mainly focused on specific proteins or biological pathways that are dysregulated in the setting of sustained wakefulness. This exploratory study aimed to provide a comprehensive view of the biological processes and proteins impacted by acute sleep deprivation in both plasma and cerebrospinal fluid (CSF).

METHODS: We collected plasma and CSF from human participants during one night of sleep deprivation and controlled normal sleep conditions. One thousand and three hundred proteins were measured at hour 0 and hour 24 using a high-scale aptamer-based proteomics platform (SOMAscan) …

Development Of An In-Vitro High-Throughput Screening System To Identify Modulators Of Genitalia Development, Yan Yin, Meade Haller, Tian Li, Liang Ma

2020-Current year OA Pubs

Sexually dimorphic outgrowth and differentiation of the embryonic genital tubercles (GTs) give rise to the penis in males and the clitoris in females. Defects in androgen production or in response to androgen signaling can lead to various congenital penile anomalies in both mice and humans. Due to lack of a high-throughput screening system, identification of crucial regulators of GT sexual differentiation has been slow. To overcome this research barrier, we isolated embryonic GT mesenchymal (GTme) cells to model genitalia growth and differentiation in vitro. Using either a mechanical or fluorescence-activated cell sorting-assisted purification method, GTme cells were isolated and assayed …

A Just Transition For Collie That Leaves No One Behind: A Community-Led Social Justice Analysis Of Collie’S Transition, Naomi Joy Godden, Georgia Beardman, Mehran Nejati, Evonne Scott, Jaime Yallup Farrant, Leonie Scoffern, Joseph Northover, James Khan, Lynette Winmar, Phillip Ugle, Kiera Mulholland, Jayla Parkin, Stevie Anderson, Angus Morrison-Saunders

Research outputs 2022 to 2026

No abstract provided.

Covid-19 Stress And Cognitive Failures In Daily Life: A Multilevel Examination Of Within- And Between-Persons Patterns, Nadyanna M. Majeed, K. T. A. Sandeeshwara Kasturiratna, Mingyao Li, Jonathan L. Chia, Verity Y. Q. Lua, Andree Hartanto

Research Collection School of Social Sciences

The COVID-19 pandemic has claimed an extremely high number of lives worldwide, causing widespread panic and stress. The current research examined whether COVID-19 stress was associated with everyday cognitive failures, using data from a seven-day daily diary study of 253 young adults in Singapore. Multilevel modeling revealed that COVID-19 stress was significantly associated with cognitive failures even after adjusting for demographic factors, both at the within-person and between-persons levels. Specifically, individuals experienced more cognitive failures on days they experienced more COVID-19 stress (as compared to their own average levels of COVID-19 stress), and individuals who experienced more COVID-19 stress overall …

Inhibition Of Mirna Associated With A Disease-Specific Signature And Secreted Via Extracellular Vesicles Of Systemic Lupus Erythematosus Patients Suppresses Target Organ Inflammation In A Humanized Mouse Model, Nicholas A Young, Emily Schwarz, Braden M Zeno, Shane Bruckner, Rosana A Mesa, Kyle Jablonski, Lai-Chu Wu, Elisha D O Roberson, Wael N Jarjour

2020-Current year OA Pubs

INTRODUCTION: Distinct, disease-associated intracellular miRNA (miR) expression profiles have been observed in peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematous (SLE) patients. Additionally, we have identified novel estrogenic responses in PBMCs from SLE patients and demonstrated that estrogen upregulates toll-like receptor (TLR)7 and TLR8 expression. TLR7 and TLR8 bind viral-derived single-stranded RNA to stimulate innate inflammatory responses, but recent studies have shown that miR-21, mir-29a, and miR-29b can also bind and activate these receptors when packaged and secreted in extracellular vesicles (EVs). The objective of this study was to evaluate the association of EV-encapsulated small RNA species in SLE …

Exercise Builds The Scaffold Of Life: Muscle Extracellular Matrix Biomarker Responses To Physical Activity, Inactivity, And Aging, Georgios Mavropalias, Marni Boppart, Kayley M. Usher, Miranda D. Grounds, Kazunori Nosaka, Anthony J. Blazevich

Research outputs 2022 to 2026

Skeletal muscle extracellular matrix (ECM) is critical for muscle force production and the regulation of important physiological processes during growth, regeneration, and remodelling. ECM remodelling is a tightly orchestrated process, sensitive to multi-directional tensile and compressive stresses and damaging stimuli, and its assessment can convey important information on rehabilitation effectiveness, injury, and disease. Despite its profound importance, ECM biomarkers are underused in studies examining the effects of exercise, disuse, or aging on muscle function, growth, and structure. This review examines patterns of short- and long-term changes in the synthesis and concentrations of ECM markers in biofluids and tissues, which may …

Skin-Derived Abcb5+ Mesenchymal Stem Cells For High-Medical-Need Inflammatory Diseases: From Discovery To Entering Clinical Routine, Elke Niebergall-Roth, Natasha Y. Frank, Christoph Ganss, Markus H. Frank, Mark A. Kluth

Research outputs 2022 to 2026

The ATP-binding cassette superfamily member ABCB5 identifies a subset of skin-resident mesenchymal stem cells (MSCs) that exhibit potent immunomodulatory and wound healing-promoting capacities along with superior homing ability. The ABCB5+ MSCs can be easily accessed from discarded skin samples, expanded, and delivered as a highly homogenous medicinal product with standardized potency. A range of preclinical studies has suggested therapeutic efficacy of ABCB5+ MSCs in a variety of currently uncurable skin and non-skin inflammatory diseases, which has been substantiated thus far by distinct clinical trials in chronic skin wounds or recessive dystrophic epidermolysis bullosa. Therefore, skin-derived ABCB5+ MSCs have the potential …

From Real Life To Story – And Back Again: Using Autobiographical Fiction Writing To Understand Self, Others And Family Generations, Alberta N. Adji

Research outputs 2022 to 2026

Writing autobiographically includes complicated responsibilities to the subjects involved: to family members, friends, colleagues, and even cultural communities. This article explores creative developments occurring during the process of writing an autobiographical novel called ‘The longing’, which is drawn from a recollection of intergenerational lived experiences of a middle-class Chinese Indonesian family from 1956 to 2018. I reflect on my strategies and approaches on tackling challenges that arose while using autobiographical material and autofictional techniques to write fiction and communicating cultural complexities for it allows agreeable distance between the author and her writing subject. In the article, I also argue that …