Digital Commons Network^™

Immunomodulatory Roles Of Polysaccharide Capsules In The Intestine, Samantha A Hsieh, Paul M Allen

Open Access Publications

The interplay between the immune system and the microbiota in the human intestine dictates states of health vs. disease. Polysaccharide capsules are critical elements of bacteria that protect bacteria against environmental and host factors, including the host immune system. This review summarizes the mechanisms by which polysaccharide capsules from commensal and pathogenic bacteria in the gut microbiota modulate the innate and adaptive immune systems in the intestine. A deeper understanding of the roles of polysaccharide capsules in microbiota-immune interactions will provide a basis to harness their therapeutic potential to advance human health.

Investigating The Ferric Ion Binding Site Of Magnetite Biomineralisation Protein Mms6, Andrea E. Rawlings, Panah Liravi, Sybilla Corbett, Alex S. Holehouse, Sarah S. Staniland

Open Access Publications

The biomineralization protein Mms6 has been shown to be a major player in the formation of magnetic nanoparticles both within the magnetosomes of magnetotactic bacteria and as an additive in synthetic magnetite precipitation assays. Previous studies have highlighted the ferric iron binding capability of the protein and this activity is thought to be crucial to its mineralizing properties. To understand how this protein binds ferric ions we have prepared a series of single amino acid substitutions within the C-terminal binding region of Mms6 and have used a ferric binding assay to probe the binding site at the level of individual …

Pancreatic Triglyceride Lipase Mediates Lipotoxic Systemic Inflammation, Cristiane De Oliveira, Mark E Lowe, Et Al

Open Access Publications

Visceral adipose tissue plays a critical role in numerous diseases. Although imaging studies often show adipose involvement in abdominal diseases, their outcomes may vary from being a mild self-limited illness to one with systemic inflammation and organ failure. We therefore compared the pattern of visceral adipose injury during acute pancreatitis and acute diverticulitis to determine its role in organ failure. Acute pancreatitis-associated adipose tissue had ongoing lipolysis in the absence of adipocyte triglyceride lipase (ATGL). Pancreatic lipase injected into mouse visceral adipose tissue hydrolyzed adipose triglyceride and generated excess nonesterified fatty acids (NEFAs), which caused organ failure in the absence …

Metabolic Dysfunction In Hutchinson-Gilford Progeria Syndrome, Ray Kreienkamp, Susana Gonzalo

Open Access Publications

Hutchinson-Gilford Progeria Syndrome (HGPS) is a segmental premature aging disease causing patient death by early teenage years from cardiovascular dysfunction. Although HGPS does not totally recapitulate normal aging, it does harbor many similarities to the normal aging process, with patients also developing cardiovascular disease, alopecia, bone and joint abnormalities, and adipose changes. It is unsurprising, then, that as physicians and scientists have searched for treatments for HGPS, they have targeted many pathways known to be involved in normal aging, including inflammation, DNA damage, epigenetic changes, and stem cell exhaustion. Although less studied at a mechanistic level, severe metabolic problems are …

Lipin-1 Contributes To Il-4 Mediated Macrophage Polarization, Sunitha Chandran, Robert M Schilke, Cassidy M R Blackburn, Aila Yurochko, Rusella Mirza, Rona S Scott, Brian N Finck, Matthew D Woolard

Open Access Publications

Macrophage responses contribute to a diverse array of pathologies ranging from infectious disease to sterile inflammation. Polarization of macrophages determines their cellular function within biological processes. Lipin-1 is a phosphatidic acid phosphatase in which its enzymatic activity contributes to macrophage pro-inflammatory responses. Lipin-1 also possesses transcriptional co-regulator activity and whether this activity is required for macrophage polarization is unknown. Using mice that lack only lipin-1 enzymatic activity or both enzymatic and transcriptional coregulator activities from myeloid cells, we investigated the contribution of lipin-1 transcriptional co-regulator function toward macrophage wound healing polarization. Macrophages lacking both lipin-1 activities did not elicit IL-4 …

Gardnerella Vaginalis As A Cause Of Bacterial Vaginosis: Appraisal Of The Evidence From In Vivo Models, Sydney Morrill, Nicole M Gilbert, Amanda L Lewis

Open Access Publications

Koch's postulates dictate the use of experimental models to illustrate features of human disease and provide evidence for a singular organism as the cause. The underlying cause(s) of bacterial vaginosis (BV) has been debated in the literature for over half a century. In 1955, it was first reported that a bacterium now known as

Co-Occurrence Of Campylobacter Species In Children From Eastern Ethiopia, And Their Association With Environmental Enteric Dysfunction, Diarrhea, And Host Microbiome, Yitagele Terefe, Mark J Manary, Maria Isabel Ordiz, Et Al

Open Access Publications

High

Multiple Network Disconnection In Anosognosia For Hemiplegia, Elena Monai, Francesca Bernocchi, Marta Bisio, Antonio Luigi Bisogno, Alessandro Salvalaggio, Maurizio Corbetta

Open Access Publications

Anosognosia for hemiplegia (AHP) is a complex syndrome whose neural correlates are still under investigation. One hypothesis, mainly based on lesion mapping studies, is that AHP reflects a breakdown of neural systems of the right hemisphere involved in motor function. However, more recent theories have suggested that AHP may represent a disorder of cognitive systems involved in belief updating, self-referential or body processing. Two recent studies, using a method to estimate the degree of white matter disconnection from lesions, have indeed shown that patients with AHP suffer from damage of several long-range white matter pathways in association cortex. Here, we …

Development Of Volumetric Independent Dose Calculation System For Verification Of The Treatment Plan In Image-Guided Adaptive Brachytherapy, Sang-Won Kang, Jin-Beom Chung, Kyeong-Hyeon Kim, Ji-Yeon Park, Hae-Jin Park, Woong Cho, Sven Olberg, Tae Suk Suh, Justin C Park

Open Access Publications

No abstract provided.

Sequencing-Based Measurable Residual Disease Testing In Acute Myeloid Leukemia, Jennifer M Yoest, Cara Lunn Shirai, Eric J Duncavage

Open Access Publications

Next generation sequencing (NGS) methods have allowed for unprecedented genomic characterization of acute myeloid leukemia (AML) over the last several years. Further advances in NGS-based methods including error correction using unique molecular identifiers (UMIs) have more recently enabled the use of NGS-based measurable residual disease (MRD) detection. This review focuses on the use of NGS-based MRD detection in AML, including basic methodologies and clinical applications.

Dopamine Buffering Capacity Imaging: A Pharmacodynamic Fmri Method For Staging Parkinson Disease, Kevin J Black, Haley K Acevedo, Jonathan M Koller

Open Access Publications

We propose a novel pharmacological fMRI (phMRI) method for objectively quantifying disease severity in Parkinson disease (PD). It is based on the clinical observation that the benefit from a dose of levodopa wears off more quickly as PD progresses. Biologically this has been thought to represent decreased buffering capacity for dopamine as nigrostriatal cells die. Buffering capacity has been modeled based on clinical effects, but clinical measurements are influenced by confounding factors. The new method proposes to measure the effect objectively based on the timing of the known response of several brain regions to exogenous levodopa. Such responses are robust …

Motor Unit Discharge Variability Is Increased In Mild-To-Moderate Parkinson's Disease, Jessica M Wilson, Christopher K Thompson, Laura Miller Mcpherson, Cindy Zadikoff, C J Heckman, Colum D Mackinnon

Open Access Publications

Individuals with Parkinson's disease (PD) demonstrate deficits in muscle activation such as decreased amplitude and inappropriate bursting. There is evidence that some of these disturbances are more pronounced in extensor vs. flexor muscles. Surface EMG has been used widely to quantify muscle activation deficits in PD, but analysis of discharge of the underlying motor units may provide greater insight and be more sensitive to changes early in the disease. Of the few studies that have examined motor unit discharge in PD, the majority were conducted in the first dorsal interosseous, and no studies have measured motor units from extensor and …

Positive Allosteric Modulation Of Cd11b As A Novel Therapeutic Strategy Against Lung Cancer, Terese Geraghty, Anugraha Rajagopalan, Rabail Aslam, Alexander Pohlman, Ishwarya Venkatesh, Andrew Zloza, David Cimbaluk, David G Denardo, Vineet Gupta

Open Access Publications

Lung cancer is one of the leading causes of cancer-related deaths in the United States. A major hurdle for improved therapies is immune suppression mediated by the tumor and its microenvironment. The lung tumor microenvironment (TME) contains large numbers of tumor-associated macrophages (TAMs), which suppress the adaptive immune response, increase neo-vascularization of the tumor, and provide pro-tumor factors to promote tumor growth. CD11b is highly expressed on myeloid cells, including TAMs, where it forms a heterodimeric integrin receptor with CD18 (known as CD11b/CD18, Mac-1, CR3, and αMβ2), and plays an important role in recruitment and biological functions of these cells, …

High Prevalence Of Radiographic Outliers And Revisions With Unicompartmental Knee Arthroplasty, Gregory S Kazarian, Toby N Barrack, Louis Okafor, Robert L Barrack, Ryan M Nunley, Charles M Lawrie

Open Access Publications

BACKGROUND: Alignment outcomes and their impact on implant survival following unicompartmental knee arthroplasty (UKA) are unclear. The purpose of this study was to assess the implant survival and radiographic outcomes after UKA as well as the impact of component alignment and overhang on implant survival.

METHODS: We performed a retrospective analysis of 253 primary fixed-bearing and mobile-bearing medial UKAs from a single academic center. All UKAs were performed by 2 high-volume fellowship-trained arthroplasty surgeons. UKAs comprised <10% of their knee arthroplasty practices, with an average of 14.2 medial UKAs per surgeon per year. Implant survival was assessed. Femoral coronal (FCA), femoral sagittal (FSA), tibial coronal (TCA), and tibial sagittal (TSA) angles as well as implant overhang were radiographically measured. Outliers were defined for FCA (>±10° deviation from neutral), FSA (>15° of flexion), TCA (>±5° deviation from neutral), and TSA (>±5° deviation from 7°). "Far outliers" …

Stable Readout Of Observed Actions From Format-Dependent Activity Of Monkey’S Anterior Intraparietal Neurons, Marco Lanzilotto, Monica Maranesi, Alessandro Livi, Carolina Giulia Ferroni, Guy A. Orban, Luca Bonini

Open Access Publications

No abstract provided.

Aerococcus Urinae Isolated From Women With Lower Urinary Tract Symptoms: In Vitro Aggregation And Genome Analysis, Evann E Hilt, Catherine Putonti, Krystal Thomas-White, Amanda L Lewis, Karen L Visick, Nicole M Gilbert, Alan J Wolfe

Open Access Publications

No abstract provided.

In Situ Detection Of Endogenous Hiv Activation By Dynamic Nuclear Polarization Nmr And Flow Cytometry, Sarah A Overall, Lauren E Price, Brice J Albert, Chukun Gao, Nicholas Alaniva, Patrick T Judge, Erika L Sesti, Paul A Wender, George B Kyei, Alexander B Barnes

Open Access Publications

We demonstrate for the first time in-cell dynamic nuclear polarization (DNP) in conjunction with flow cytometry sorting to address the cellular heterogeneity of in-cell samples. Utilizing a green fluorescent protein (GFP) reporter of HIV reactivation, we correlate increased

Contribution Of Immune Cells To Glucocorticoid Receptor Expression In Breast Cancer, Shipra Gandhi, Ahmed Elkhanany, Masanori Oshi, Tao Dai, Mateusz Opyrchal, Hemn Mohammadpour, Elizabeth A Repasky, Kazuaki Takabe

Open Access Publications

Breast cancer (BC) patients experience increased stress with elevated cortisol levels, increasing risk of cancer recurrence. Cortisol binds to a cytoplasmic receptor, glucocorticoid receptor (GR) encoded by GR gene (

Methylation-Directed Glycosylation Of Chromatin Factors Represses Retrotransposon Promoters, Mathieu Boulard, Sofia Rucli, John R. Edwards, Timothy H. Bestor

Open Access Publications

No abstract provided.

Gait Asymmetry, And Bilateral Coordination Of Gait During A Six‑Minute Walk Test In Persons With Multiple Sclerosis, Meir Plotnik, Joanne M. Wagner, Gautam Adusumilli, Amihai Gottlieb, Robert T. Naismith

Open Access Publications

No abstract provided.

Federated Learning In Medicine: Facilitating Multi‑Institutional Collaborations Without Sharing Patient Data, Micah J. Sheller, Brandon Edwards, G. Anthony Reina, Jason Martin, Sarthak Pati, Aikaterini Kotrotsou, Mikhail Milchenko, Weilin Xu, Daniel Marcus, Rivka R. Colen, Spyridon Bakas

Open Access Publications

No abstract provided.

The Role Of Ct-Quantified Body Composition On Longitudinal Health-Related Quality Of Life In Colorectal Cancer Patients: The Colocare Study, Biljana Gigic, Graham A Colditz, Adetunji T Toriola, Et Al

Open Access Publications

BACKGROUND: Obesity, defined by body mass index (BMI), measured at colorectal cancer (CRC) diagnosis has been associated with postoperative complications and survival outcomes. However, BMI does not allow for a differentiation between fat and muscle mass. Computed tomography (CT)-defined body composition more accurately reflects different types of tissue and their associations with health-related quality of life (HRQoL) during the first year of disease, but this has not been investigated yet. We studied the role of visceral and subcutaneous fat area (VFA and SFA) and skeletal muscle mass (SMM) on longitudinally assessed HRQoL in CRC patients.

METHODS: A total of 138 …

Genomics Of Mpnst (Gem) Consortium: Rationale And Study Design For Multi-Omic Characterization Of Nf1-Associated And Sporadic Mpnsts, David T Miller, Angela C Hirbe, Et Al

Open Access Publications

The Genomics of Malignant Peripheral Nerve Sheath Tumor (GeM) Consortium is an international collaboration focusing on multi-omic analysis of malignant peripheral nerve sheath tumors (MPNSTs), the most aggressive tumor associated with neurofibromatosis type 1 (NF1). Here we present a summary of current knowledge gaps, a description of our consortium and the cohort we have assembled, and an overview of our plans for multi-omic analysis of these tumors. We propose that our analysis will lead to a better understanding of the order and timing of genetic events related to MPNST initiation and progression. Our ten institutions have assembled 96 fresh frozen …

Multi-System Factors Associated With Metatarsophalangeal Joint Deformity In Individuals With Type 2 Diabetes, Jennifer A Zellers, Michael J Mueller, Paul K Commean, Ling Chen, Hyo-Jung Jeong, Mary K Hastings

Open Access Publications

The underlying factors contributing to metatarsophalangeal joint deformity, a known precursor to skin breakdown in individuals with diabetes mellitus (DM), is likely to involve multiple body systems. The purpose of this cross-sectional study was to identify multi-system factors associated with metatarsophalangeal joint deformity in individuals with type 2 DM and peripheral neuropathy (

Cell Profiling Of Mouse Acute Kidney Injury Reveals Conserved Cellular Responses To Injury, Yuhei Kirita, Haojia Wu, Kohei Uchimura, Parker C. Wilson, Benjamin D. Humphreys

Open Access Publications

No abstract provided.

Matriptase Cleaves Epcam And Trop2 In Keratinocytes, Destabilizing Both Proteins And Associated Claudins, Chuan-Jin Wu, Michael Lu, Xu Feng, Gaku Nakato, Mark C Udey

Open Access Publications

The homologs EpCAM and TROP2, which both interact with claudin-1 and claudin-7, are frequently coexpressed in epithelia including skin. Intestine uniquely expresses high levels of EpCAM but not TROP2. We previously identified EpCAM as a substrate of the membrane-anchored protease matriptase and linked HAI-2, matriptase, EpCAM and claudin-7 in a pathway that is pivotal for intestinal epithelial cells (IEC) homeostasis. Herein, we reveal that TROP2 is also a matriptase substrate. Matriptase cleaved TROP2 when purified recombinant proteins were mixed in vitro. TROP2, like EpCAM, was also cleaved after co-transfection of matriptase in 293T cells. Neither EpCAM nor TROP2 cleavage was …

Development And Evaluation Of Machine Learning Models For Voxel Dose Predictions In Online Adaptive Magnetic Resonance Guided Radiation Therapy, M Allan Thomas, Yabo Fu, Deshan Yang

Open Access Publications

PURPOSE: Daily online adaptive plan quality in magnetic resonance imaging guided radiation therapy (MRgRT) is difficult to assess in relation to the fully optimized, high quality plans traditionally established offline. Machine learning prediction models developed in this work are capable of predicting 3D dose distributions, enabling the evaluation of online adaptive plan quality to better inform adaptive decision-making in MRgRT.

METHODS: Artificial neural networks predicted 3D dose distributions from input variables related to patient anatomy, geometry, and target/organ-at-risk relationships in over 300 treatment plans from 53 patients receiving adaptive, linac-based MRgRT for abdominal cancers. The models do not include any …

Myeloid-Specific Asxl2 Deletion Limits Diet-Induced Obesity By Regulating Energy Expenditure, Wei Zou, Nidhi Rohatgi, Jonathan R Brestoff, John R Moley, Yongjia Li, Jesse W Williams, Yael Alippe, Hua Pan, Terri A Pietka, Gabriel Mbalaviele, Elizabeth P Newberry, Nicholas O Davidson, Anwesha Dey, Kooresh I Shoghi, Richard D Head, Samuel A Wickline, Gwendalyn J Randolph, Nada A Abumrad, Steven L Teitelbaum

Open Access Publications

We previously established that global deletion of the enhancer of trithorax and polycomb (ETP) gene, Asxl2, prevents weight gain. Because proinflammatory macrophages recruited to adipose tissue are central to the metabolic complications of obesity, we explored the role of ASXL2 in myeloid lineage cells. Unexpectedly, mice without Asxl2 only in myeloid cells (Asxl2ΔLysM) were completely resistant to diet-induced weight gain and metabolically normal despite increased food intake, comparable activity, and equivalent fecal fat. Asxl2ΔLysM mice resisted HFD-induced adipose tissue macrophage infiltration and inflammatory cytokine gene expression. Energy expenditure and brown adipose tissue metabolism in Asxl2ΔLysM mice were protected from the …

Focal Dynamic Thermal Imaging For Label‑Free High‑Resolution Characterization Of Materials And Tissue Heterogeneity, Christine M. O'Brien, Hongyu Meng, Leonid Shmuylovich, Julia Carpenter, Praneeth Gogineni, Haini Zhang, Kevin Bishop, Suman B. Mondal, Gail P. Sudlow, Cheryl Bethea, Clyde Bethea, Samuel Achilefu

Open Access Publications

No abstract provided.

Applying Dimensional Psychopathology: Transdiagnostic Associations Among Regional Homogeneity, Leptin And Depressive Symptoms, Yan-Ge Wei, Jia Duan, Fay Y. Womer, Yue Zhu, Zhiyang Yin, Lingling Cui, Chao Li, Zhuang Liu, Shengnan Wei, Xiaowei Jiang, Yanbo Zhang, Xizhe Zhang, Yanqing Tang, Fei Wang

Open Access Publications

No abstract provided.