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Medical Sciences

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2021

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Articles 1 - 28 of 28

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Chemical And Biological Characterization Of The Anticancer Potency Of Salvia Fruticosa In A Model Of Human Malignant Melanoma, Sotiris Kyriakou, Venetia Tragkola, Michael Plioukas, Ioannis Anestopoulos, Paschalina S. Chatzopoulou, Eirini Sarrou, Dimitrios T. Trafalis, Maria V. Deligiorgi, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidi Nov 2021

Chemical And Biological Characterization Of The Anticancer Potency Of Salvia Fruticosa In A Model Of Human Malignant Melanoma, Sotiris Kyriakou, Venetia Tragkola, Michael Plioukas, Ioannis Anestopoulos, Paschalina S. Chatzopoulou, Eirini Sarrou, Dimitrios T. Trafalis, Maria V. Deligiorgi, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidi

School of Veterinary and Biomedical Sciences: Faculty Publications

Malignant melanoma is one of the most aggressive types of skin cancer with an increasing incidence worldwide. Thus, the development of innovative therapeutic approaches is of great importance. Salvia fruticosa (SF) is known for its anticancer properties and in this context, we aimed to investigate its potential anti-melanoma activity in an in vitro model of human malignant melanoma. Cytotoxicity was assessed through a colorimetric-based sulforhodamine-B (SRB) assay in primary malignant melanoma (A375), non-malignant melanoma epidermoid carcinoma (A431) and non-tumorigenic melanocyte neighbouring keratinocyte (HaCaT) cells. Among eight (8) different fractions of S. fruticosa extracts (SF1-SF8) tested, SF3 was found to possess …


Mt10-Cvb3 Vaccine Virus Protects Against Cvb4 Infection By Inducing Cross-Reactive, Antigen-Specific Immune Responses, Ninaad Lasrado, Rajkumar Arumugam, Mahima T. Rasquinha, Meghna Sur, David Steffen, Jay Reddy Nov 2021

Mt10-Cvb3 Vaccine Virus Protects Against Cvb4 Infection By Inducing Cross-Reactive, Antigen-Specific Immune Responses, Ninaad Lasrado, Rajkumar Arumugam, Mahima T. Rasquinha, Meghna Sur, David Steffen, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Group B coxsackieviruses (CVB) containing six serotypes, B1–B6, affect various organs, and multiple serotypes can induce similar diseases such as myocarditis and pancreatitis. Yet, no vaccines are currently available to prevent these infections. Translationally, the derivation of vaccines that offer protection against multiple serotypes is highly desired. In that direction, we recently reported the generation of an attenuated strain of CVB3, termed Mt10, which completely protects against both myocarditis and pancreatitis induced by the homologous wild-type CVB3 strain. Here, we report that the Mt10 vaccine can induce cross-protection against multiple CVB serotypes as demonstrated with CVB4. We note that the …


Untargeted Lipidomics Of Non-Small Cell Lung Carcinoma Demonstrates Differentially Abundant Lipid Classes In Cancer Vs. Non-Cancer Tissue, Joshua M. Mitchell, Robert M. Flight, Hunter N. B. Moseley Oct 2021

Untargeted Lipidomics Of Non-Small Cell Lung Carcinoma Demonstrates Differentially Abundant Lipid Classes In Cancer Vs. Non-Cancer Tissue, Joshua M. Mitchell, Robert M. Flight, Hunter N. B. Moseley

Molecular and Cellular Biochemistry Faculty Publications

Lung cancer remains the leading cause of cancer death worldwide and non-small cell lung carcinoma (NSCLC) represents 85% of newly diagnosed lung cancers. In this study, we utilized our untargeted assignment tool Small Molecule Isotope Resolved Formula Enumerator (SMIRFE) and ultra-high-resolution Fourier transform mass spectrometry to examine lipid profile differences between paired cancerous and non-cancerous lung tissue samples from 86 patients with suspected stage I or IIA primary NSCLC. Correlation and co-occurrence analysis revealed significant lipid profile differences between cancer and non-cancer samples. Further analysis of machine-learned lipid categories for the differentially abundant molecular formulas identified a high abundance sterol, …


Physiological Roles Of Mammalian Transmembrane Adenylyl Cyclase Isoforms, Katrina F. Ostrom, Justin E. Lavigne, Tarsis F. Brust, Roland Seifert, Carmen Dessauer, Val J. Watts, Rennolds S. Ostrom Oct 2021

Physiological Roles Of Mammalian Transmembrane Adenylyl Cyclase Isoforms, Katrina F. Ostrom, Justin E. Lavigne, Tarsis F. Brust, Roland Seifert, Carmen Dessauer, Val J. Watts, Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

Adenylyl cyclases (ACs) catalyze the conversion of ATP to the ubiquitous second messenger cAMP. Mammals possess nine isoforms of transmembrane ACs, dubbed AC1-9, that serve as major effector enzymes of G protein-coupled receptors. The transmembrane ACs display varying expression patterns across tissues, giving potential for them having a wide array of physiologic roles. Cells express multiple AC isoforms, implying that ACs have redundant functions. Furthermore, all transmembrane ACs are activated by Gαs so it was long assumed that all ACs are activated by Gαs-coupled GPCRs. AC isoforms partition to different microdomains of the plasma membrane and form …


Inheritance Of A Mutation Causing Neuropathy With Splayed Forelimbs In Jersey Cattle, A. Al-Khudhair, D. J. Null, J. B. Cole, C. W. Wolfe, David J. Steffen, P. M. Vanraden Oct 2021

Inheritance Of A Mutation Causing Neuropathy With Splayed Forelimbs In Jersey Cattle, A. Al-Khudhair, D. J. Null, J. B. Cole, C. W. Wolfe, David J. Steffen, P. M. Vanraden

School of Veterinary and Biomedical Sciences: Faculty Publications

A new undesirable genetic factor, neuropathy with splayed forelimbs (JNS), has been identified recently in the Jersey breed. Calves affected with JNS are unable to stand on splayed forelimbs that exhibit significant extensor rigidity and excessive lateral abduction at birth. Affected calves generally are alert at birth but exhibit neurologic symptoms, including spasticity of head and neck and convulsive behavior. Other symptoms reported include dislocated shoulders, congenital craniofacial anomalies, and degenerative myelopathy. Inheritance of an undesirable genetic factor was determined from a study of 16 affected calves reported by Jersey breeders across the United States. All of their pedigrees traced …


The Novel Orfv Protein Orfv113 Activates Lpa-P38 Signaling, Sushil Khatiwad, Gustavo Delho, Sabal Chaulagai, Daniel L. Rock Oct 2021

The Novel Orfv Protein Orfv113 Activates Lpa-P38 Signaling, Sushil Khatiwad, Gustavo Delho, Sabal Chaulagai, Daniel L. Rock

School of Veterinary and Biomedical Sciences: Faculty Publications

Viruses have evolved mechanisms to subvert critical cellular signaling pathways that regulate a wide range of cellular functions, including cell differentiation, proliferation and chemotaxis, and innate immune responses. Here, we describe a novel ORFV protein, ORFV113, that interacts with the G protein-coupled receptor Lysophosphatidic acid receptor 1 (LPA1). Consistent with its interaction with LPA1, ORFV113 enhances p38 kinase phosphorylation in ORFV infected cells in vitro and in vivo, and in cells transiently expressing ORFV113 or treated with soluble ORFV113. Infection of cells with virus lacking ORFV113 (OVIA82Δ113) significantly decreased p38 phosphorylation and viral plaque size. …


Apoε4 Lowers Energy Expenditure In Females And Impairs Glucose Oxidation By Increasing Flux Through Aerobic Glycolysis, Brandon C. Farmer, Holden C. Williams, Nicholas A. Devanney, Margaret A. Piron, Grant K. Nation, David J. Carter, Adeline E. Walsh, Rebika Khanal, Lyndsay E. A. Young, Jude C. Kluemper, Gabriela Hernandez, Elizabeth J. Allenger, Rachel Mooney, Lesley R. Golden, Cathryn T. Smith, J. Anthony Brandon, Vedant A. Gupta, Philip A. Kern, Matthew S. Gentry, Josh M. Morganti, Ramon C. Sun, Lance A. Johnson Sep 2021

Apoε4 Lowers Energy Expenditure In Females And Impairs Glucose Oxidation By Increasing Flux Through Aerobic Glycolysis, Brandon C. Farmer, Holden C. Williams, Nicholas A. Devanney, Margaret A. Piron, Grant K. Nation, David J. Carter, Adeline E. Walsh, Rebika Khanal, Lyndsay E. A. Young, Jude C. Kluemper, Gabriela Hernandez, Elizabeth J. Allenger, Rachel Mooney, Lesley R. Golden, Cathryn T. Smith, J. Anthony Brandon, Vedant A. Gupta, Philip A. Kern, Matthew S. Gentry, Josh M. Morganti, Ramon C. Sun, Lance A. Johnson

Physiology Faculty Publications

BACKGROUND: Cerebral glucose hypometabolism is consistently observed in individuals with Alzheimer's disease (AD), as well as in young cognitively normal carriers of the Ε4 allele of Apolipoprotein E (APOE), the strongest genetic predictor of late-onset AD. While this clinical feature has been described for over two decades, the mechanism underlying these changes in cerebral glucose metabolism remains a critical knowledge gap in the field.

METHODS: Here, we undertook a multi-omic approach by combining single-cell RNA sequencing (scRNAseq) and stable isotope resolved metabolomics (SIRM) to define a metabolic rewiring across astrocytes, brain tissue, mice, and human subjects expressing APOE4.

RESULTS: Single-cell …


Targeting The Cdk6 Dependence Of Ph+ Acute Lymphoblastic Leukemia, Patrizia Porazzi, Marco De Dominici, Joseph Salvino, Bruno Calabretta Sep 2021

Targeting The Cdk6 Dependence Of Ph+ Acute Lymphoblastic Leukemia, Patrizia Porazzi, Marco De Dominici, Joseph Salvino, Bruno Calabretta

Department of Cancer Biology Faculty Papers

Ph+ ALL is a poor-prognosis leukemia subtype driven by the BCR-ABL1 oncogene, either the p190-or the p210-BCR/ABL isoform in a 70:30 ratio. Tyrosine Kinase inhibitors (TKIs) are the drugs of choice in the therapy of Ph+ ALL. In combination with standard chemotherapy, TKIs have markedly improved the outcome of Ph+ ALL, in particular if this treatment is followed by bone marrow transplantation. However, resistance to TKIs develops with high frequency, causing leukemia relapse that results in


African Swine Fever Virus Cd2v Protein Induces Β-Interferon Expression And Apoptosis In Swine Peripheral Blood Mononuclear Cells, Sabal Chaulangain, Gustavo A. Delhon, Sushil Khatiwada, Daniel L. Rock Jul 2021

African Swine Fever Virus Cd2v Protein Induces Β-Interferon Expression And Apoptosis In Swine Peripheral Blood Mononuclear Cells, Sabal Chaulangain, Gustavo A. Delhon, Sushil Khatiwada, Daniel L. Rock

School of Veterinary and Biomedical Sciences: Faculty Publications

African swine fever (ASF) is a hemorrhagic disease of swine characterized by massive lymphocyte depletion in lymphoid tissues due to the apoptosis of B and T cells, a process likely triggered by factors released or secreted by infected macrophages. ASFV CD2v (EP402R) has been implicated in viral virulence and immunomodulation in vitro; however, its actual function(s) remains unknown. We found that CD2v expression in swine PK15 cells induces NF-κB-dependent IFN-β and ISGs transcription and an antiviral state. Similar results were observed for CD2v protein treated swine PBMCs and macrophages, the major ASFV target cell. Notably, treatment of swine PBMCs and …


Attenuated Strain Of Cvb3 With A Mutation In The Car‑Interacting Region Protects Against Both Myocarditis And Pancreatitis, Ninaad Lasrado, Arunakumar Gangaplara, Chandirasegaran Massilamany, Rajkumar Arumugam, Allison Shelbourn, Mahima T. Rasquinha, Rakesh H. Basavalingappa, Gustavo Delhon, Shi-Hua Xiang, Asit K. Pattnaik, David Steffen, Jay Reddy Jun 2021

Attenuated Strain Of Cvb3 With A Mutation In The Car‑Interacting Region Protects Against Both Myocarditis And Pancreatitis, Ninaad Lasrado, Arunakumar Gangaplara, Chandirasegaran Massilamany, Rajkumar Arumugam, Allison Shelbourn, Mahima T. Rasquinha, Rakesh H. Basavalingappa, Gustavo Delhon, Shi-Hua Xiang, Asit K. Pattnaik, David Steffen, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Coxsackievirus B3 (CVB3), is commonly implicated in myocarditis, which can lead to dilated cardiomyopathy, in addition to causing acute pancreatitis and meningitis. Yet, no vaccines are currently available to prevent this infection. Here, we describe the derivation of a live attenuated vaccine virus, termed mutant (Mt) 10, encoding a single amino acid substitution H790A within the viral protein 1, that prevents CVB3 infection in mice and protects from both myocarditis and pancreatitis in challenge studies. We noted that animals vaccinated with Mt 10 developed virus neutralizing antibodies, predominantly containing IgG2a and IgG2b, and to a lesser extent IgG3 and IgG1. …


Synphilin-1 And Its Effects On Pathogenesis Of Parkinson’S Disease, Mirghani Mohamed Jun 2021

Synphilin-1 And Its Effects On Pathogenesis Of Parkinson’S Disease, Mirghani Mohamed

Honors Scholar Theses

Parkinson's Disease (PD) is a progressive neurodegenerative and movement disorder primarily caused by the degradation of dopaminergic neurons. Known markers of neurodegeneration in PD are Lewy Bodies, which are fibrillar aggregates that are found in the brains of PD patients. Lewy Bodies can accumulate from specific mutations in the SNCA gene that codes for alpha-synuclein, a protein enriched in presynaptic neurons. A mutated SNCA gene can cause conformational aggregates of alpha-synuclein to form toxic species mediating neuronal death. Research into alpha-synuclein has led to the discovery of a binding partner known as synphilin-1 that is also found in protein aggregates …


Component Causes Of Infectious Bovine Keratoconjunctivitis—Non-Moraxella Organisms In The Epidemiology Of Infectious Bovine Keratoconjunctivitis, John Dustin Loy, Kristin A. Clothier, Gabriele Maier May 2021

Component Causes Of Infectious Bovine Keratoconjunctivitis—Non-Moraxella Organisms In The Epidemiology Of Infectious Bovine Keratoconjunctivitis, John Dustin Loy, Kristin A. Clothier, Gabriele Maier

School of Veterinary and Biomedical Sciences: Faculty Publications

• Non-Moraxella organisms are associated with infectious bovine keratoconjunctivitis (IBK).

Mycoplasma bovoculi can cause conjunctivitis and has a potential role in IBK pathogenesis.

• Other Non-Mycoplasma agents can cause disease that resembles IBK but is clinically different.

• Genomics and molecular technology are advancing research in this area.

• Classification and determination of pathogenesis potential of these organisms may be better understood through metagenomics and whole genome sequencing.


A Screen Of Fda-Approved Drugs Identifies Inhibitors Of Protein Tyrosine Phosphatase 4a3 (Ptp4a3 Or Prl-3), Dylan R. Rivas, Mark Vincent C. Dela Cerna, Caroline N. Smith, Shilpa Sampathi, Blaine G. Patty, Donghan Lee, Jessica S. Blackburn May 2021

A Screen Of Fda-Approved Drugs Identifies Inhibitors Of Protein Tyrosine Phosphatase 4a3 (Ptp4a3 Or Prl-3), Dylan R. Rivas, Mark Vincent C. Dela Cerna, Caroline N. Smith, Shilpa Sampathi, Blaine G. Patty, Donghan Lee, Jessica S. Blackburn

Molecular and Cellular Biochemistry Faculty Publications

Protein tyrosine phosphatase 4A3 (PTP4A3 or PRL-3) is highly expressed in a variety of cancers, where it promotes tumor cell migration and metastasis leading to poor prognosis. Despite its clinical significance, small molecule inhibitors of PRL-3 are lacking. Here, we screened 1443 FDA-approved drugs for their ability to inhibit the activity of the PRL phosphatase family. We identified five specific inhibitors for PRL-3 as well as one selective inhibitor of PRL-2. Additionally, we found nine drugs that broadly and significantly suppressed PRL activity. Two of these broad-spectrum PRL inhibitors, Salirasib and Candesartan, blocked PRL-3-induced migration in human embryonic kidney cells …


Component Causes Of Infectious Bovine Keratoconjunctivitis - The Role Of Moraxella Species In The Epidemiology Of Infectious Bovine Keratoconjunctivitis, John Dustin Loy, Matthew Hille, Gabriele Maier, Michael L. Clawson May 2021

Component Causes Of Infectious Bovine Keratoconjunctivitis - The Role Of Moraxella Species In The Epidemiology Of Infectious Bovine Keratoconjunctivitis, John Dustin Loy, Matthew Hille, Gabriele Maier, Michael L. Clawson

School of Veterinary and Biomedical Sciences: Faculty Publications

Moraxella bovis can cause infectious bovine keratoconjunctivitis (IBK).

The role of M bovoculi in IBK is not fully understood.

M bovis and M bovoculi appear to undergo genetic recombination with each other or other members of the Moraxellaceae.

Recombination complicates their classification and potential role(s) in IBK pathogenesis.

MALDI-TOF MS is used to identify M bovis, 2 major strains or genotypes of M bovoculi, M ovis, and other members of the Moraxellaceae.

Classification and determination of pathogenesis potential within Moraxella species may be better understood through whole genome sequencing.


A High-Androgen Microenvironment Inhibits Granulosa Cell Proliferation And Alters Cell Identity, Renee M. Mcfee, Sarah M. Romereim, Alexandria P. Snider, Adam F. Summers, William E. Pohlmeier, Scott G. Kurz, Robert A. Cushman, John S. Davis, Jennifer R. Wood, Andrea S. Cupp Apr 2021

A High-Androgen Microenvironment Inhibits Granulosa Cell Proliferation And Alters Cell Identity, Renee M. Mcfee, Sarah M. Romereim, Alexandria P. Snider, Adam F. Summers, William E. Pohlmeier, Scott G. Kurz, Robert A. Cushman, John S. Davis, Jennifer R. Wood, Andrea S. Cupp

School of Veterinary and Biomedical Sciences: Faculty Publications

A naturally occurring bovine model with excess follicular fluid androstenedione (High A4), reduced fertility, and polycystic ovary syndrome (PCOS)-like characteristics has been identified. We hypothesized High A4 granulosa cells (GCs) would exhibit altered cell proliferation and/or steroidogenesis. Microarrays of Control and High A4 GCs combined with Ingenuity Pathway Analysis indicated that High A4 GCs had cell cycle inhibition and increased expression of microRNAs that inhibit cell cycle genes. Granulosa cell culture confirmed that A4 treatment decreased GC proliferation, increased anti-Müllerian hormone, and increased mRNA for CTNNBIP1. Increased CTNNBIP1 prevents CTNNB1 from interacting with members of the WNT signaling pathway thereby …


Vitamin D3 Induces Mesenchymal-To-Endothelial Transition And Promotes A Proangiogenic Niche Through Igf-1 Signaling, Lei Chen, Anweshan Samanta, Lin Zhao, Nathaniel R. Dudley, Tanner Buehler, Robert J. Vincent, Jeryl Hauptman, Magdy Girgis, Buddhadeb Dawn Apr 2021

Vitamin D3 Induces Mesenchymal-To-Endothelial Transition And Promotes A Proangiogenic Niche Through Igf-1 Signaling, Lei Chen, Anweshan Samanta, Lin Zhao, Nathaniel R. Dudley, Tanner Buehler, Robert J. Vincent, Jeryl Hauptman, Magdy Girgis, Buddhadeb Dawn

School of Medicine Faculty Publications

Biological Sciences; Physiology; Molecular Biology; Cell Biology


Living With It: A Patient’S And A Biochemist’S Perspective On Kidney Disease; A Historical Review Of Alport Syndrome, Jacob Olson Apr 2021

Living With It: A Patient’S And A Biochemist’S Perspective On Kidney Disease; A Historical Review Of Alport Syndrome, Jacob Olson

WWU Honors College Senior Projects

A review paper on the origin of health studies around Alport Syndrome, including aspects of genetics, pharmacy, and biochemistry, from the past to today and beyond. This report deals with important aspects of health development with regards to kidney disease overall, but narrows its focus on Alport Syndrome specifically due to the personal nature of the topic for the author. While this paper includes no personal testimony, as it is strictly meant to be formal, the author shares a deep connection with the material.


Combining Multicolor Fish With Fluorescence Lifetime Imaging For Chromosomal Identification And Chromosomal Sub Structure Investigation, Archana Bhartiya, Ian Robinson, Mohammed Yousuf, Stanley W. Botchway Mar 2021

Combining Multicolor Fish With Fluorescence Lifetime Imaging For Chromosomal Identification And Chromosomal Sub Structure Investigation, Archana Bhartiya, Ian Robinson, Mohammed Yousuf, Stanley W. Botchway

Centre for Regenerative Medicine & Stem Cell Research

Understanding the structure of chromatin in chromosomes during normal and diseased state of cells is still one of the key challenges in structural biology. Using DAPI staining alone together with Fluorescence lifetime imaging (FLIM), the environment of chromatin in chromosomes can be explored. Fluorescence lifetime can be used to probe the environment of a fluorophore such as energy transfer, pH and viscosity. Multicolor FISH (M-FISH) is a technique that allows individual chromosome identification, classification as well as assessment of the entire genome. Here we describe a combined approach using DAPI as a DNA environment sensor together with FLIM and M-FISH …


Maldi-Tof Ms Biomarker Detection Models To Distinguish Rtx Toxin Phenotypes Of Moraxella Bovoculi Strains Are Enhanced Using Calcium Chloride Supplemented Agar, Matthew M. Hille, Michael L. Clawson, Aaron M. Dickey, Justin H. Lowery, John Dustin Loy Mar 2021

Maldi-Tof Ms Biomarker Detection Models To Distinguish Rtx Toxin Phenotypes Of Moraxella Bovoculi Strains Are Enhanced Using Calcium Chloride Supplemented Agar, Matthew M. Hille, Michael L. Clawson, Aaron M. Dickey, Justin H. Lowery, John Dustin Loy

School of Veterinary and Biomedical Sciences: Faculty Publications

Moraxella bovoculi is the bacterium most often cultured from ocular lesions of cattle with infectious bovine keratoconjunctivitis, also known as bovine pinkeye. Some strains of M. bovoculi contain operons encoding for a repeats-in-toxin (RTX) toxin, which is a known virulence factor of multiple veterinary pathogens. We explored the utility of MALDI-TOF MS and biomarker detection models to classify the presence or absence of an RTX phenotype in M. bovoculi. Ninety strains that had undergone whole genome sequencing were classified by the presence or absence of complete RTX operons and confirmed with a visual assessment of hemolysis on blood agar. Strains …


Arginase 1 Insufficiency Precipitates Amyloid-Β Deposition And Hastens Behavioral Impairment In A Mouse Model Of Amyloidosis, Chao Ma, Jerry B. Hunt, Maj-Linda B. Selenica, Awa Sanneh, Leslie A. Sandusky-Beltran, Mallory Watler, Rana Daas, Andrii Kovalenko, Huimin Liang, Devon Placides, Chuanhai Cao, Xiaoyang Lin, Michael B. Orr, Bei Zhang, John C. Gensel, David J. Feola, Marcia N. Gordon, Dave Morgan, Paula C. Bickford, Daniel C. Lee Jan 2021

Arginase 1 Insufficiency Precipitates Amyloid-Β Deposition And Hastens Behavioral Impairment In A Mouse Model Of Amyloidosis, Chao Ma, Jerry B. Hunt, Maj-Linda B. Selenica, Awa Sanneh, Leslie A. Sandusky-Beltran, Mallory Watler, Rana Daas, Andrii Kovalenko, Huimin Liang, Devon Placides, Chuanhai Cao, Xiaoyang Lin, Michael B. Orr, Bei Zhang, John C. Gensel, David J. Feola, Marcia N. Gordon, Dave Morgan, Paula C. Bickford, Daniel C. Lee

Sanders-Brown Center on Aging Faculty Publications

Alzheimer’s disease (AD) includes several hallmarks comprised of amyloid-β (Aβ) deposition, tau neuropathology, inflammation, and memory impairment. Brain metabolism becomes uncoupled due to aging and other AD risk factors, which ultimately lead to impaired protein clearance and aggregation. Increasing evidence indicates a role of arginine metabolism in AD, where arginases are key enzymes in neurons and glia capable of depleting arginine and producing ornithine and polyamines. However, currently, it remains unknown if the reduction of arginase 1 (Arg1) in myeloid cell impacts amyloidosis. Herein, we produced haploinsufficiency of Arg1 by the hemizygous deletion in myeloid cells using Arg1 …


Of Pigs And Men: The Best-Laid Plans For Prevention And Control Of Swine Fevers, Jishu Shi, Lihua Wang, David Scott Mcvey Jan 2021

Of Pigs And Men: The Best-Laid Plans For Prevention And Control Of Swine Fevers, Jishu Shi, Lihua Wang, David Scott Mcvey

School of Veterinary and Biomedical Sciences: Faculty Publications

John Steinbeck drew the title of his novel “Of Mice and Men” from a line in a Robert Burns poem “To a mouse”: “The best-laid plans of mice and men/Go often awry.” Unlike John Steinbeck who used the title to mirror the characters who were struggling during the Great Depression to the mouse whose nest was accidentally destroyed by the poet (Burns 1785), we chose this line to emphasize that the best-laid plan can go wrong in infectious disease control and prevention. Here, we will discuss the contributing factors behind the global successes and failures in the prevention and control …


Covid19 Disease Map, A Computational Knowledge Repository Of Virus–Host Interaction Mechanisms, Marek Ostaszewski, Tomáš Helikar, Bhanwar Lal Puniya, A Host Of Co-Authors, Covid-19 Disease Map Community Jan 2021

Covid19 Disease Map, A Computational Knowledge Repository Of Virus–Host Interaction Mechanisms, Marek Ostaszewski, Tomáš Helikar, Bhanwar Lal Puniya, A Host Of Co-Authors, Covid-19 Disease Map Community

Department of Biochemistry: Faculty Publications

We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, …


Il-10 As A Th2 Cytokine: Differences Between Mice And Humans, Mahima T. Rasquinha, Meghna Sur, Ninaad Lasrado, Jay Reddy Jan 2021

Il-10 As A Th2 Cytokine: Differences Between Mice And Humans, Mahima T. Rasquinha, Meghna Sur, Ninaad Lasrado, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

The discovery of interleukin (IL)-10 more than 30 years ago marked the beginning of our understanding of how cytokines regulate immune responses, based on cross-regulation between T helper (Th)1 and Th2 cytokines. Although multiple cell types were shown to produce IL-10, its identity as a Th2 cytokine remained strong since it was rigidly associated with Th2 clones in mice, whereas both Th1 and Th2 clones could secrete IL-10 in humans. However, as new Th1/Th2 cell functionalities emerged, anti-inflammatory action of IL-10 gained more attention than its inhibitory effect on Th1 cells, which may occur as an indirect consequence of suppression …


Impact Of The Histidine‐Containing Phosphocarrier Protein Hpr On Carbon Metabolism And Virulence In Staphylococcus Aureus, Linda Pätzold, Anne-Christine Brausch, Evelyn-Laura Bielefeld, Lisa Zimmer, Greg A. Somerville, Markus Bischoff, Rosmarie Gaupp Jan 2021

Impact Of The Histidine‐Containing Phosphocarrier Protein Hpr On Carbon Metabolism And Virulence In Staphylococcus Aureus, Linda Pätzold, Anne-Christine Brausch, Evelyn-Laura Bielefeld, Lisa Zimmer, Greg A. Somerville, Markus Bischoff, Rosmarie Gaupp

School of Veterinary and Biomedical Sciences: Faculty Publications

Carbon catabolite repression (CCR) is a common mechanism pathogenic bacteria use to link central metabolism with virulence factor synthesis. In gram‐positive bacteria, catabolite control protein A (CcpA) and the histidine‐containing phosphocarrier protein HPr (encoded by ptsH) are the predominant mediators of CCR. In addition to modulating CcpA activity, HPr is essential for glucose import via the phosphotransferase system. While the regulatory functions of CcpA in Staphylococcus aureus are largely known, little is known about the function of HPr in CCR and infectivity. To address this knowledge gap, ptsH mutants were created in S. aureus that either lack the open reading …


An Evaluation Of The Anti-Carcinogenic Response Of Major Isothiocyanates In Non-Metastatic And Metastatic Melanoma Cells, Melina Mitsiogianni, Sotiris Kyriakou, Ioannis Anestopoulos, Dimitrios T. Trafalis, Maria V. Deligiorgi, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidi Jan 2021

An Evaluation Of The Anti-Carcinogenic Response Of Major Isothiocyanates In Non-Metastatic And Metastatic Melanoma Cells, Melina Mitsiogianni, Sotiris Kyriakou, Ioannis Anestopoulos, Dimitrios T. Trafalis, Maria V. Deligiorgi, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidi

School of Veterinary and Biomedical Sciences: Faculty Publications

Malignant melanoma is one of the most deadly types of solid cancers, a property mainly attributed to its highly aggressive metastatic form. On the other hand, different classes of isothiocy- anates, a class of phytochemicals, present in cruciferous vegetables have been characterized by considerable anti-cancer activity in both in vitro and in vivo experimental models. In the current study, we investigated the anti-cancer response of five isothiocyanates in an in vitro model of melanoma consisting of non-metastatic (A375, B16F-10) and metastatic (VMM1, Hs294T) malignant melanoma as well as non-melanoma epidermoid carcinoma (A431) and non-tumorigenic melanocyte-neighboring keratinocyte (HaCaT) cells. Our aim …


Inhibition Of Zika Virus Replication By G-Quadruplex-Binding Ligands, Prativa Majee, Aryamav Pattnaik, Bikash R. Sahoo, Uma Shankar, Asit K. Pattnaik, Amit Kumar, Debasis Nayak Jan 2021

Inhibition Of Zika Virus Replication By G-Quadruplex-Binding Ligands, Prativa Majee, Aryamav Pattnaik, Bikash R. Sahoo, Uma Shankar, Asit K. Pattnaik, Amit Kumar, Debasis Nayak

School of Veterinary and Biomedical Sciences: Faculty Publications

Zika virus (ZIKV), a mosquito-transmitted Flavivirus, emerged in the last decade causing serious diseases and affecting human health globally. Currently, no licensed vaccines or antivirals are available to combat ZIKV, although several vaccine candidates are in the pipeline. In recent years, the presence of non-canon- ical G-quadruplex (GQ) secondary structures in viral genomes has ignited significant attention as potential targets for anti- viral strategy. In this study, we identified several novel conserved potential GQ structures by analyzing published ZIKV genome sequences using an in-house algorithm. Bio- physical and biochemical analysis of the RNA sequences con- taining these potential GQ sequences …


Female And Male-Controlled Livestock Holdings Impact Pastoralist Food Security And Women’S Dietary Diversity, Henriette Gitungwa, Christopher Gustafson, E.Y. Jimenez, E. Wesley F. Peterson, M. Mwanzalila, Asha Makweta, E. Komba, R.R. Kazwala, J.A.K. Mazet, Elizabeth Vanwormer Jan 2021

Female And Male-Controlled Livestock Holdings Impact Pastoralist Food Security And Women’S Dietary Diversity, Henriette Gitungwa, Christopher Gustafson, E.Y. Jimenez, E. Wesley F. Peterson, M. Mwanzalila, Asha Makweta, E. Komba, R.R. Kazwala, J.A.K. Mazet, Elizabeth Vanwormer

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: Food insecurity is a global problem that requires a One Health approach. As many households in low- and middle-income nations rely on crops and livestock that they produce to meet their household’s needs, food security and nutrition are closely linked to the health of animals and the environment. Resources controlled by women are more often allocated to uses that benefit the entire household, such as food, health, and educating children, than men’s resources. However, studies of gender control of resources among pastoralist societies are scant. We examined the effect of female and male control of livestock resources on food …


Special Issue: Shiga Toxin-Producing Escherichia Coli, Rodney A. Moxley Jan 2021

Special Issue: Shiga Toxin-Producing Escherichia Coli, Rodney A. Moxley

School of Veterinary and Biomedical Sciences: Faculty Publications

Globally, Shiga toxin-producing Escherichia coli (STEC) is an important cause of diarrheal disease, most notably hemorrhagic colitis, and post-diarrheal sequela, such as hemolytic-uremic syndrome (HUS) [1]. Cattle are a major reservoir of STEC, with approx- imately half of the cases in humans attributable to foodborne exposure [2]. Prevention of human illness has mainly been through food safety measures [2]. Despite extensive research, no other generally accepted and effective preventive measures or therapies for STEC infections in human patients are available [3]. Many questions remain about STEC virulence factors, pathogenesis, detection, and other aspects that necessitate a continua- tion of basic …