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51. Mechanistic and therapeutic relationships of traumatic brain injury and γ-amino-butyric acid (GABA)
- Title Tesim:
- Mechanistic and therapeutic relationships of traumatic brain injury and γ-amino-butyric acid (GABA)
- Creatore:
- Witkin, J., Shafique, H., Cerne, R., Smith, J., Marini, A., Lipsky, R., and Delery, Elizabeth
- Related Url Tesim:
- Available from the publisher: https://www.sciencedirect.com/science/article/abs/pii/S0163725824000299 and Available from the library catalog: https://marianunivindianapolis.on.worldcat.org/oclc/10179327578
- Descrizione:
- Traumatic brain injury (TBI) is a highly prevalent medical condition for which no medications specific for the prophylaxis or treatment of the condition as a whole exist. The spectrum of symptoms includes coma, headache, seizures, cognitive impairment, depression, and anxiety. Although it has been known for years that the inhibitory neurotransmitter γ-amino-butyric acid (GABA) is involved in TBI, no novel therapeutics based upon this mechanism have been introduced into clinical practice. We review the neuroanatomical, neurophysiological, neurochemical, and neuropharmacological relationships of GABA neurotransmission to TBI with a view toward new potential GABA-based medicines. The long-standing idea that excitatory and inhibitory (GABA and others) balances are disrupted by TBI is supported by the experimental data but has failed to invent novel methods of restoring this balance. The slow progress in advancing new treatments is due to the complexity of the disorder that encompasses multiple dynamically interacting biological processes including hemodynamic and metabolic systems, neurodegeneration and neurogenesis, major disruptions in neural networks and axons, frank brain lesions, and a multitude of symptoms that have differential neuronal and neurohormonal regulatory mechanisms. Although the current and ongoing clinical studies include GABAergic drugs, no novel GABA compounds are being explored. It is suggested that filling the gap in understanding the roles played by specific GABAA receptor configurations within specific neuronal circuits could help define new therapeutic approaches. Further research into the temporal and spatial delivery of GABA modulators should also be useful. Along with GABA modulation, research into the sequencing of GABA and non-GABA treatments will be needed.
- Dichiarazione dei diritti:
- http://rightsstatements.org/vocab/InC/1.0/
- Lingua:
- English
- Editore:
- Elsevier
- Identifier:
- DOI: https://doi.org/10.1016/j.pharmthera.2024.108609
- Tipo di risorsa:
- Article
- Parola chiave:
- Traumatic brain injury (TBI), γ-amino-butyric acid (GABA), inhibitory neurotransmitter, GABA-based medicines, and GABA neurotransmission
- data di creazione:
- 2024
52. Medical student research opportunities: a survey of osteopathic medical schools in the United States
- Title Tesim:
- Medical student research opportunities: a survey of osteopathic medical schools in the United States
- Creatore:
- Wilson, D., Hamby, T., Basha, R., Lowery, Jonathan, and Bui, P.
- Related Url Tesim:
- available from publisher at: https://www.degruyter.com/document/doi/10.1515/jom-2021-0242/html, Available from library catalog: https://marianunivindianapolis.on.worldcat.org/oclc/9432460093, and Available from pubmed at: https://pubmed.ncbi.nlm.nih.gov/35245010/
- Descrizione:
- Context: It is important for colleges of osteopathic medicine (COMs) to provide opportunities for osteopathic medical students (OMSs) to conduct research under the guidance of professional researchers. However, COMs historically lag behind allopathic medical schools in research offerings for medical students. The literature would benefit from a synopsis of research opportunities for OMSs at COMs. Objectives: This study aims to assess the availability of research opportunities currently offered to OMSs and to identify structured research programs (SRPs) to provide data that may help COMs expand such opportunities. Methods: Two online surveys were developed. The General Survey asked about general research opportunities, research requirements, and SRPs, which we define as optional, intramural, and mentored research programs. The follow-up SRP Survey sought to understand the history, funding, and organizational structure of SRPs. Between February and June 2021, the General and SRP Surveys were sent to all COMs in the United States. Response data were analyzed descriptively. Results: Responses were received from 32 (84.2%) of 38 COMs. Nearly all COMs offered research symposia, offered third- or fourth-year research elective rotations, and provided some form of funding for OMSs to participate in research. Fourteen (43.8%) COMs had mandatory research requirements. Twenty COMs (62.5%) offered 31 SRPs, and surveys were completed for 25 (80.6%) SRPs. SRPs were founded a median (range) of 7 (1-43) years prior and accommodated 20 (4-50) OMSs annually. Among the responding SRPs, 12.0% had external funding, 96.0% required applications, 50.0% interviewed applicants prior to acceptance into the program, 72.0% required OMSs to identify their own mentors, 68.0% offered stipends to OMSs, 28.0% offered course credits, 96.0% had clinical research opportunities, and 68.0% offered research-oriented didactics. In 84.0% of SRPs, OMSs worked predominantly in the summer after OMS-I; for these SRPs, students had 4-10 weeks of dedicated time for participation in research. Conclusions: Findings from our surveys provide a synopsis of the research opportunities currently provided by COMs in the United States. Our data demonstrated wide variability of research opportunities among COMs.
- Dichiarazione dei diritti:
- http://rightsstatements.org/vocab/InC/1.0/
- Licenza:
- https://creativecommons.org/licenses/by/4.0/
- Lingua:
- English
- Editore:
- De Gruyter
- Identifier:
- PMID: 35245010, PMCID: PMC9131179 , and DOI: 10.1515/jom-2021-0242
- Tipo di risorsa:
- Article
- Parola chiave:
- medical education, colleges of osteopathic medicine, medical student research, and survey study
- data di creazione:
- 2022
53. The Metabolic Bone Disease X-linked Hypophosphatemia: Case Presentation, Pathophysiology and Pharmacology
- Title Tesim:
- The Metabolic Bone Disease X-linked Hypophosphatemia: Case Presentation, Pathophysiology and Pharmacology
- Creatore:
- Vincze, Jon, Hum, Julia, Conaway, Kory, Skinner, Brian, Tucker, Katherine, and Lowery, Jonathan
- Related Url Tesim:
- Available from the publisher: https://www.mdpi.com/2075-1729/11/6/563 and Available from PubMed Central: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232744/
- Descrizione:
- The authors present a stereotypical case presentation of X-linked hypophosphatemia (XLH) and provide a review of the pathophysiology and related pharmacology of this condition, primarily focusing on the FDA-approved medication burosumab. XLH is a renal phosphate wasting disorder caused by loss of function mutations in the PHEX gene (phosphate-regulating gene with homologies to endopeptidases on the X chromosome). Typical biochemical findings include elevated serum levels of bioactive/intact fibroblast growth factor 23 (FGF23) which lead to (i) low serum phosphate levels, (ii) increased fractional excretion of phosphate, and (iii) inappropriately low or normal 1,25-dihydroxyvitamin D (1,25-vitD). XLH is the most common form of heritable rickets and short stature in patients with XLH is due to chronic hypophosphatemia. Additionally, patients with XLH experience joint pain and osteoarthritis from skeletal deformities, fractures, enthesopathy, spinal stenosis, and hearing loss. Historically, treatment for XLH was limited to oral phosphate supplementation, active vitamin D supplementation, and surgical intervention for cases of severe bowed legs. In 2018, the United States Food and Drug Administration (FDA) approved burosumab for the treatment of XLH and this medication has demonstrated substantial benefit compared with conventional therapy. Burosumab binds circulating intact FGF23 and blocks its biological effects in target tissues, resulting in increased serum inorganic phosphate (Pi) concentrations and increased conversion of inactive vitamin D to active 1,25-vitD.
- Dichiarazione dei diritti:
- http://rightsstatements.org/vocab/InC/1.0/
- Lingua:
- English
- Editore:
- MDPI
- Identifier:
- PMID: 34203792 and DOI: 10.3390/life11060563
- Tipo di risorsa:
- Article
- Parola chiave:
- burosumab, Crysvita®, KRN23, metabolic bone disease, and X-linked hypophosphatemia
- data di creazione:
- 2021
54. Metastatic Melanoma of an Unknown Primary Site: A Case Report
- Title Tesim:
- Metastatic Melanoma of an Unknown Primary Site: A Case Report
- Alternative title:
- American Association of Neuropathologists, Inc. Abstracts of the 99th Annual Meeting June 8–11, 2023 Monterey, California
- Creatore:
- Vila, Annabel and Sakthi-Velavan, Sumathilatha
- Related Url Tesim:
- Available from the publisher: https://academic.oup.com/jnen/article/82/6/489/7174288
- Descrizione:
- Background Metastatic melanoma (MM) is refractory to treatment, and patients with MM have a median survival of 6 months. A donor in the anatomy laboratory was reported to have MM as the cause of death. However, the findings were unique, suggestive of a rare presentation or a co-existing pathological entity. The case report explores the unique combination of cutaneous and visceral lesions that may be inadvertently interpreted to be of non-malignant etiology. Methods The study investigated the pathology noted in a 75-year-old female donor, with MM as the reported cause of death, during routine dissection in the anatomy laboratory. Detailed dissection, examination, biopsy, and histopathological examination (HPE) of the lesions were done. Photographs of the lesions on the skin and viscera were taken. Results Multiple slightly elevated lesions of 2-3 cm diameter were found on the gluteal region and anterior abdominal wall. Several firm and smooth nodules of around 1 cm diameter were found on the pericardium, pleura, peritoneum, diaphragm, lungs, heart, stomach, intestines, liver, spleen, kidneys, uterus, retroperitoneal region, and mediastinum. HPE of skin lesions showed basaloid proliferation and dermal hyperplasia. The visceral lesions showed multifocal tumors with small, loosely arranged eosinophilic cells and dense triangular nuclei. Immunohistochemical staining (pan-cytokeratin AE1/AE3, Melan A, and Ki-67) were performed, and the results are awaited. Conclusions The most common sites of metastasis of cutaneous melanoma are lymph nodes, liver, lungs, and brain; however, lesions were not found in the brain of this donor. Extensive visceral involvement and generalized distribution of nodules of MM may be inadvertently interpreted to be of non-neoplastic origin. In immunosuppressed patients, the multisystemic visceral lesions may be confused for granulomatous diseases such as sarcoidosis, brucellosis, histoplasmosis, or miliary tuberculosis. Since melanoma is immunogenic and more common in immunosuppressed patients, the clinical presentation warrants further evaluation.
- Dichiarazione dei diritti:
- http://rightsstatements.org/vocab/InC/1.0/
- Lingua:
- English
- Editore:
- American Association of Neuropathologists and Oxford University Press
- Identifier:
- DOI: https://doi.org/10.1093/jnen/nlad029
- Tipo di risorsa:
- Other
- Parola chiave:
- Metastatic melanoma (MM), co-existing pathological entity, non-malignant etiology, and cutaneous and visceral lesions
- data di creazione:
- 2023
55. Molecular Characterization of Bacterial Community Composition in the Rhizosphere of Invasive Plant Species Amur Honeysuckle (Lonicera Maackii) in an Urban Wetland Forest
- Title Tesim:
- Molecular Characterization of Bacterial Community Composition in the Rhizosphere of Invasive Plant Species Amur Honeysuckle (Lonicera Maackii) in an Urban Wetland Forest
- Creatore:
- Ahmad, Azeem and Akbar, Samina
- Related Url Tesim:
- Available from the Publisher: https://www.scirp.org/journal/paperinformation.aspx?paperid=112114
- Descrizione:
- The goal of this research was to determine the effects of the growth of invasive plant Amur Honeysuckle (Lonicera maackii) on the rhizosphere bacterial community composition, and diversity in an urban wetland forest ecosystem. Bacterial communities from the rhizosphere of 5 L. maackii plants and control bulk soils that did not have any L. maackii were investigated at Nina Mason Pulliam EcoLab (NMPE) using a culture-independent pipeline. Bacterial communities were characterized by PCR amplification and cloning 16S rRNA gene fragments following total DNA isolation from the soil samples. Microbial communities associated with both L. maackii rhizosphere and control sites showed high bacterial diversity within each site and taxa unique to individual sites were observed. Phylogenetic analyses revealed 80% of 400 16S rDNA clones were classified as α-, β- and γ-Proteobacteria, Acidobacteria, Actinobacteria, Cytophaga-Flexibacter-Bacteroides (CFB) group, and Verrucomicrobia. Members of the Proteobacteria and Acidobacterium represented 66.5% and 14.5% of the clone library, respectively, whereas the remaining bacterial divisions each comprised less than 7% of the clone library. Twenty-five 16S rDNA clones could not be classified into any known bacterial divisions. Statistical analyses showed significant differences in the presence of L. maackii on the proportions of 16S rDNA clones affiliated with Proteobacteria and Acidobacterium, suggesting bacterial community composition and structure does significantly change in the presence of L. maackii. However, sequence-based community analysis and the corresponding lack of intact microbial cultures limit understanding of the potential influences of enriched microbial taxa on plant hosts and their roles in ecosystem functioning.
- Dichiarazione dei diritti:
- http://rightsstatements.org/vocab/InC/1.0/
- Licenza:
- https://creativecommons.org/licenses/by/4.0/
- Lingua:
- English
- Editore:
- Scientific Research Publishing
- Identifier:
- DOI: 10.4236/aim.2021.119035
- Tipo di risorsa:
- Article
- Parola chiave:
- Rhizosphere, Bacterium, 16S rRNA, Forest Soils, and Lonicera maackii
- data di creazione:
- 2021
56. Muscle Regulatory Factors Regulate T1R3 Taste Receptor Expression
- Title Tesim:
- Muscle Regulatory Factors Regulate T1R3 Taste Receptor Expression
- Creatore:
- Sato, T., Enoki, Y., Okubo, M., Kokabu, S, Yoda, T., Seta, Y, Toyono, T., Hitomi, S., Fukushima, Y., and Lowery, Jonathan W.
- Descrizione:
- T1R3 is a T1R class of G protein-coupled receptors, composing subunit of the umami taste receptor when complexed with T1R1. T1R3 was originally discovered in gustatory tissue but is now known to be expressed in a wide variety of tissues and cell types such the intestine, pancreatic ?-cells, skeletal muscle, and heart. In addition to taste recognition, the T1R1/T1R3 complex functions as an amino acid sensor and has been proposed to be a control mechanism for the secretion of hormones, such as cholecystokinin, insulin, and duodenal HCO3(-) and activates the mammalian rapamycin complex 1 (MTORC1) to inhibit autophagy. T1R3 knockout mice have increased rate of autophagy in the heart, skeletal muscle and liver. Thus, T1R3 has multiple physiological functions and is widely expressed in vivo. However, the exact mechanisms regulating T1R3 expression are largely unknown. Here, we used comparative genomics and functional analyses to characterize the genomic region upstream of the annotated transcriptional start of human T1R3. This revealed that the T1R3 promoter in human and mouse resides in an evolutionary conserved region (ECR). We also identified a repressive element located upstream of the human T1R3 promoter that has relatively high degree of conservation with rhesus macaque. Additionally, the muscle regulatory factors MyoD and Myogenin regulate T1R3 expression and T1R3 expression increases with skeletal muscle differentiation of murine myoblast C2C12 cells. Taken together, our study raises the possibility that MyoD and Myogenin might control skeletal muscle metabolism and homeostasis through the regulation of T1R3 promoter activity.
- Dichiarazione dei diritti:
- http://rightsstatements.org/vocab/InC/1.0/
- Lingua:
- English
- Identifier:
- 10.1016/j.bbrc.2015.10.142
- Tipo di risorsa:
- Article
- Parola chiave:
- G-Protein-Coupled, Gene Expression Regulation, Molecular Sequence Data, Species Specificity, Myoblasts, and Myogenic Regulatory Factors
- data di creazione:
- 12/25/2015
57. Muscle-derived factors influencing bone metabolism
- Title Tesim:
- Muscle-derived factors influencing bone metabolism
- Creatore:
- Zysik, Victoria S., Gries, Kevin, Jobe, Tyler K., Leeds, Benjamin P., Lowery, Jonathan W., and Griffin, Nicole
- Related Url Tesim:
- Available for request from the library catalog: https://marianunivindianapolis.on.worldcat.org/oclc/9415331686, Available from PubMed: https://pubmed.ncbi.nlm.nih.gov/34756782/, and Available from the publisher: https://www.sciencedirect.com/science/article/abs/pii/S108495212100272X?via%3Dihub
- Descrizione:
- A significant amount of attention has been brought to the endocrine-like function of skeletal muscle on various tissues, particularly with bone. Several lines of investigation indicate that the physiology of both bone and muscle systems may be regulated by a given stimulus, such as exercise, aging, and inactivity. Moreover, emerging evidence indicates that bone is heavily influenced by soluble factors derived from skeletal muscle (i.e., muscle-to-bone communication). The purpose of this review is to discuss the regulation of bone remodeling (formation and/or resorption) through skeletal muscle-derived cytokines (hereafter myokines) including the anti-inflammatory cytokine METRNL and pro-inflammatory cytokines (e.g., TNF-α, IL-6, FGF-2 and others). Our goal is to highlight possible therapeutic opportunities to improve muscle and bone health in aging.
- Dichiarazione dei diritti:
- http://rightsstatements.org/vocab/InC/1.0/
- Lingua:
- English
- Editore:
- Elsevier
- Identifier:
- PMID: 34756782 and DOI: 10.1016/j.semcdb.2021.10.009
- Tipo di risorsa:
- Article
- Parola chiave:
- anti-inflammatory cytokine METRNL, bone remodeling, muscle-to-bone communication, myokine, skeletal muscle-derived cytokines, and crosstalk
- data di creazione:
- 2022
58. N-linked Glycosylation of the Bone Morphogenetic Protein Receptor Type 2 (BMPR2) Enhances Ligand Binding
- Title Tesim:
- N-linked Glycosylation of the Bone Morphogenetic Protein Receptor Type 2 (BMPR2) Enhances Ligand Binding
- Creatore:
- Amich, J.M., Andonian, A., Rosen, V., and Lowery, Jonathan W.
- Descrizione:
- The bone morphogenetic protein (BMP) signaling pathway is essential for normal development and tissue homeostasis. BMP signal transduction occurs when ligands interact with a complex of type 1 and type 2 receptors to activate downstream transcription factors. It is well established that a single BMP receptor may bind multiple BMP ligands with varying affinity, and this has been largely attributed to conformation at the amino acid level. However, all three type 2 BMP receptors (BMPR2, ACVR2A/B) contain consensus N-glycosylation sites in their extracellular domains (ECDs), which could play a role in modulating interaction with ligand. Here, we show a differential pattern of N-glycosylation between BMPR2 and ACVR2A/B. Site-directed mutagenesis reveals that BMPR2 is uniquely glycosylated near its ligand binding domain and at a position that is mutated in patients with heritable pulmonary arterial hypertension. We further demonstrate using a cell-free pulldown assay that N-glycosylation of the BMPR2-ECD enhances its ability to bind BMP2 ligand but has no impact on binding by the closely-related ACVR2B. Our results illuminate a novel aspect of BMP signaling pathway mechanics and demonstrate a functional difference resulting from post-translational modification of type 2 BMP receptors. Additionally, since BMPR2 is required for several aspects of normal development and defects in its function are strongly implicated in human disease, our findings are likely to be relevant in several biological contexts in normal and abnormal human physiology.
- Dichiarazione dei diritti:
- http://rightsstatements.org/vocab/InC/1.0/
- Lingua:
- English
- Identifier:
- 10.1007/s00018-013-1541-8
- Tipo di risorsa:
- Article
- Parola chiave:
- Hypertension, Binding Sites, Bone Morphogenetic Protein Receptors, Amino Acid Sequence, Glycosylation, Molecular Sequence Data, Humans, Activin Receptors, Ligands, Type II, Mutagenesis, and Familial Primary Pulmonary Hypertension
- data di creazione:
- 8/1/2014
59. On the Emerging Role of the Taste Receptor Type 1 (T1R) Family of Nutrient-Sensors in the Musculoskeletal System.
- Title Tesim:
- On the Emerging Role of the Taste Receptor Type 1 (T1R) Family of Nutrient-Sensors in the Musculoskeletal System.
- Creatore:
- Sato, T, Yoda, T, Kokabu, S, and Lowery, Jonathan W.
- Descrizione:
- The special sense of taste guides and guards food intake and is essential for body maintenance. Salty and sour tastes are sensed via ion channels or gated ion channels while G protein-coupled receptors (GPCRs) of the taste receptor type 1 (T1R) family sense sweet and umami tastes and GPCRs of the taste receptor type 2 (T2R) family sense bitter tastes. T1R and T2R receptors share similar downstream signaling pathways that result in the stimulation of phospholipase-C-?2. The T1R family includes three members that form heterodimeric complexes to recognize either amino acids or sweet molecules such as glucose. Although these functions were originally described in gustatory tissue, T1R family members are expressed in numerous non-gustatory tissues and are now viewed as nutrient sensors that play important roles in monitoring global glucose and amino acid status. Here, we highlight emerging evidence detailing the function of T1R family members in the musculoskeletal system and review these findings in the context of the musculoskeletal diseases sarcopenia and osteoporosis, which are major public health problems among the elderly that affect locomotion, activities of daily living, and quality of life. These studies raise the possibility that T1R family member function may be modulated for therapeutic benefit.
- Dichiarazione dei diritti:
- http://rightsstatements.org/vocab/InC/1.0/
- Lingua:
- English
- Identifier:
- 10.3390/molecules22030469
- Tipo di risorsa:
- Article
- Parola chiave:
- myogenesis, sarcopenia, T1R3, taste receptor, bone remodeling, osteoporosis, bone, and skeletal muscle
- data di creazione:
- 3/15/2017
60. Osilodrostat for the treatment of Cushing's disease
- Title Tesim:
- Osilodrostat for the treatment of Cushing's disease
- Creatore:
- Rasool, Syeda and Skinner, Brian
- Collaboratore:
- Hum, Julia
- Related Url Tesim:
- From the publisher website: https://www.tandfonline.com/doi/abs/10.1080/14656566.2021.1897106?journalCode=ieop20 and Available for request from the library catalog: https://marianunivindianapolis.on.worldcat.org/v2/oclc/8942652670
- Descrizione:
- Introduction The treatment of Cushing’s disease (CD) has been advanced well with the introduction of treatment options like transsphenoidal surgery, radiosurgery, bilateral adrenalectomy, and various classes of medication; however, many patients still fail to achieve disease remission. Osilodrostat, an orally bioavailable adrenal steroidogenesis inhibitor, was approved in the USA and EU in 2020 for the treatment of CD. Areas covered This review provides an overview of Cushing’s disease and the newly FDA approved 11β-hydroxylase inhibitor, osilodrostat, for CD with a focus on pharmacodynamics, pharmacokinetics, safety and efficacy data, and phase 2 and 3 clinical trials. Expert opinion Osilodrostat has proven clinical efficacy and tolerability in phase 2 and 3 trials with CD patients who had an inadequate or reoccurring response to transsphenoidal surgery (TSS) and conventional first-line treatment. The phase 3 trial (LINC3) had 86% of the treatment group respond with normal urinary free cortisol (UFC) level compared to 29% in the placebo group (p < 0.001). Deemed as well-tolerated in all current pivotal trials, oral osilodrostat provides a noninvasive option for patients who cannot undergo surgery or patients who have reoccurring hypercortisolemia.
- Dichiarazione dei diritti:
- http://rightsstatements.org/vocab/InC/1.0/
- Lingua:
- English
- Editore:
- Taylor & Francis
- Identifier:
- https://doi.org/10.1080/14656566.2021.1897106
- Tipo di risorsa:
- Article
- Parola chiave:
- osilodrostat, steroidogenesis inhibitor, hypercortisolism, LCI699, Cushing's Disease, and endocrinology
- data di creazione:
- 2021