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Mesencephalic Astrocyte-Derived Neurotrophic Factor (Manf) Regulates Neurite Outgrowth Through The Activation Of Akt/Mtor And Erk/Mtor Signaling Pathways, Wen Wen, Yongchao Wang, Hui Li, Hong Xu, Mei Xu, Jacqueline A. Frank, Murong Ma, Jia Luo Sep 2020

Mesencephalic Astrocyte-Derived Neurotrophic Factor (Manf) Regulates Neurite Outgrowth Through The Activation Of Akt/Mtor And Erk/Mtor Signaling Pathways, Wen Wen, Yongchao Wang, Hui Li, Hong Xu, Mei Xu, Jacqueline A. Frank, Murong Ma, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Neurite outgrowth is essential for brain development and the recovery of brain injury and neurodegenerative diseases. In this study, we examined the role of the neurotrophic factor MANF in regulating neurite outgrowth. We generated MANF knockout (KO) neuro2a (N2a) cell lines using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 and demonstrated that MANF KO N2a cells failed to grow neurites in response to RA stimulation. Using MANF siRNA, this finding was confirmed in human SH-SY5Y neuronal cell line. Nevertheless, MANF overexpression by adenovirus transduction or addition of MANF into culture media facilitated the growth of longer neurites in RA-treated N2a …


Repurposing Anti-Inflammasome Nrtis For Improving Insulin Sensitivity And Reducing Type 2 Diabetes Development, Jayakrishna Ambati, Joseph Magagnoli, Hannah Leung, Shao-Bin Wang, Chris A. Andrews, Dongxu Fu, Akshat Pandey, Srabani Sahu, Siddharth Narendran, Shuichiro Hirahara, Shinichi Fukuda, Jian Sun, Lekha Pandya, Meenakshi Ambati, Felipe Pereira, Akhil Varshney, Tammy Cummings, James W. Hardin, Babatunde Edun, Charles L. Bennett, Kameshwari Ambati, Benjamin J. Fowler, Nagaraj Kerur, Christian Röver, Norbert Leitinger, Brian C. Werner, Joshua D. Stein, S. Scott Sutton, Bradley D. Gelfand Sep 2020

Repurposing Anti-Inflammasome Nrtis For Improving Insulin Sensitivity And Reducing Type 2 Diabetes Development, Jayakrishna Ambati, Joseph Magagnoli, Hannah Leung, Shao-Bin Wang, Chris A. Andrews, Dongxu Fu, Akshat Pandey, Srabani Sahu, Siddharth Narendran, Shuichiro Hirahara, Shinichi Fukuda, Jian Sun, Lekha Pandya, Meenakshi Ambati, Felipe Pereira, Akhil Varshney, Tammy Cummings, James W. Hardin, Babatunde Edun, Charles L. Bennett, Kameshwari Ambati, Benjamin J. Fowler, Nagaraj Kerur, Christian Röver, Norbert Leitinger, Brian C. Werner, Joshua D. Stein, S. Scott Sutton, Bradley D. Gelfand

Ophthalmology and Visual Science Faculty Publications

Innate immune signaling through the NLRP3 inflammasome is activated by multiple diabetes-related stressors, but whether targeting the inflammasome is beneficial for diabetes is still unclear. Nucleoside reverse-transcriptase inhibitors (NRTI), drugs approved to treat HIV-1 and hepatitis B infections, also block inflammasome activation. Here, we show, by analyzing five health insurance databases, that the adjusted risk of incident diabetes is 33% lower in patients with NRTI exposure among 128,861 patients with HIV-1 or hepatitis B (adjusted hazard ratio for NRTI exposure, 0.673; 95% confidence interval, 0.638 to 0.710; P < 0.0001; 95% prediction interval, 0.618 to 0.734). Meanwhile, an NRTI, lamivudine, improves insulin sensitivity and reduces inflammasome activation in diabetic and insulin resistance-induced human cells, as well as in mice fed with high-fat chow; mechanistically, inflammasome-activating short interspersed nuclear element (SINE) transcripts are elevated, whereas SINE-catabolizing DICER1 is reduced, in diabetic cells and mice. These data suggest the possibility of repurposing an approved class of drugs for prevention of diabetes.


Organic Field-Effect Transistors As Flexible, Tissue-Equivalent Radiation Dosimeters In Medical Applications, Andrew M. Zeidell, Tong Ren, David S. Filston, Hamna F. Iqbal, Emma Holland, J. Daniel Bourland, John E. Anthony, Oana D. Jurchescu Sep 2020

Organic Field-Effect Transistors As Flexible, Tissue-Equivalent Radiation Dosimeters In Medical Applications, Andrew M. Zeidell, Tong Ren, David S. Filston, Hamna F. Iqbal, Emma Holland, J. Daniel Bourland, John E. Anthony, Oana D. Jurchescu

Chemistry Faculty Publications

Radiation therapy is one of the most prevalent procedures for cancer treatment, but the risks of malignancies induced by peripheral beam in healthy tissues surrounding the target is high. Therefore, being able to accurately measure the exposure dose is a critical aspect of patient care. Here a radiation detector based on an organic field‐effect transistor (RAD‐OFET) is introduced, an in vivo dosimeter that can be placed directly on a patient's skin to validate in real time the dose being delivered and ensure that for nearby regions an acceptable level of low dose is being received. This device reduces the errors …


Creating Space For Youth Voice: Implications Of Youth Disclosure Experiences For Youth-Centered Research, Roberta Lynn Woodgate, Pauline Tennent, Sarah C. Barriage Sep 2020

Creating Space For Youth Voice: Implications Of Youth Disclosure Experiences For Youth-Centered Research, Roberta Lynn Woodgate, Pauline Tennent, Sarah C. Barriage

Information Science Faculty Publications

This paper examines youth’s disclosure experiences within the context of chronic illness, drawing on examples from IN•GAUGE, an on-going research program led by Dr. Roberta L. Woodgate. Youth’s descriptions of their disclosure experiences provide valuable insights into the ways in which they use their voice in everyday life. This examination of the disclosure experiences of youth offers a lens through which the concept of youth voice in the research process can be understood and youth’s agency foregrounded. We present implications for researchers, ethics boards, funding agencies, and others who engage in youth-centered research, and offer alternative terminology to use in …


Rna Nanoparticle For Treatment Of Gastric Cancer, Peixuan Guo, Daxiang Cui, Dan Shu, Yi Shu, Chunlei Zhang Sep 2020

Rna Nanoparticle For Treatment Of Gastric Cancer, Peixuan Guo, Daxiang Cui, Dan Shu, Yi Shu, Chunlei Zhang

Pharmaceutical Sciences Faculty Patents

The presently-disclosed subject matter relates to RNA-based composition and method to treat gastric cancer in a subject. More particularly, the presently disclosed subject matter relates to a RNA nanostructure and composition containing a multiple branched RNA nanoparticle, a gastric cancer targeting module, and an effective amount of a therapeutic agent. Further, the presently disclosed subject matter relates to a method of using the RNA nanoparticle composition to treat gastric cancer in a subject having or at risk of having gastric cancer.


The Impact Of Feeding Cannabidiol (Cbd) Containing Treats On Canine Response To A Noise-Induced Fear Response Test, Elizabeth M. Morris, Susanna E. Kitts-Morgan, Dawn M. Spangler, Kyle R. Mcleod, Joao H. C. Costa, David L. Harmon Sep 2020

The Impact Of Feeding Cannabidiol (Cbd) Containing Treats On Canine Response To A Noise-Induced Fear Response Test, Elizabeth M. Morris, Susanna E. Kitts-Morgan, Dawn M. Spangler, Kyle R. Mcleod, Joao H. C. Costa, David L. Harmon

Animal and Food Sciences Faculty Publications

Interest is increasing regarding use of Cannabidiol (CBD) in companion animals due to anecdotal evidence of beneficial behavioral and health effects. The purpose of this investigation was to evaluate the influence of CBD on behavioral responses to fear-inducing stimuli in dogs. Sixteen dogs (18.1 ± 0.2 kg) were utilized in a replicated 4 × 4 Latin square design experiment with treatments arranged in a 2 × 2 factorial, consisting of control, 25 mg CBD, trazodone (100 mg for 10–20 kg BW, 200 mg for 20.1–40 kg BW), and the combination of CBD and trazodone. A fireworks model of noise-induced fear …


Assessing Resource Condition In Grazing Lands: How Do Different Indicators Compare?, John G. Mcivor, C. K. Mcdonald, Neil D. Macleod Sep 2020

Assessing Resource Condition In Grazing Lands: How Do Different Indicators Compare?, John G. Mcivor, C. K. Mcdonald, Neil D. Macleod

IGC Proceedings (1977-2023)

No abstract provided.


Sustainability Assessment Of Animal Production Systems In The (Sub)Tropics: Review And Prospectson Combining Life Cycle Assessment (Lca) With Other Environmental Impact Assessment Methods, Andrea C. Mayer Sep 2020

Sustainability Assessment Of Animal Production Systems In The (Sub)Tropics: Review And Prospectson Combining Life Cycle Assessment (Lca) With Other Environmental Impact Assessment Methods, Andrea C. Mayer

IGC Proceedings (1977-2023)

No abstract provided.


Fluorometry--An Evolving Methodology For Range Animal Ecologists, Dean M. Anderson, Gary D. Rayson Sep 2020

Fluorometry--An Evolving Methodology For Range Animal Ecologists, Dean M. Anderson, Gary D. Rayson

IGC Proceedings (1977-2023)

No abstract provided.


Case Studies In Developing Rangeland Sustainability Indicators: Scale Matters, B. H. Allen‐Diaz, Lynn Huntsinger, J. W. Bartolome, L. D. Ford Sep 2020

Case Studies In Developing Rangeland Sustainability Indicators: Scale Matters, B. H. Allen‐Diaz, Lynn Huntsinger, J. W. Bartolome, L. D. Ford

IGC Proceedings (1977-2023)

No abstract provided.


Rats Genetically Selected For High Aerobic Exercise Capacity Have Elevated Plasma Bilirubin By Upregulation Of Hepatic Biliverdin Reductase-A (Bvra) And Suppression Of Ugt1a1, Terry D. Hinds Jr., Justin F. Creeden, Darren M. Gordon, Adam C. Spegele, Steven L. Britton, Lauren G. Koch, David E. Stec Sep 2020

Rats Genetically Selected For High Aerobic Exercise Capacity Have Elevated Plasma Bilirubin By Upregulation Of Hepatic Biliverdin Reductase-A (Bvra) And Suppression Of Ugt1a1, Terry D. Hinds Jr., Justin F. Creeden, Darren M. Gordon, Adam C. Spegele, Steven L. Britton, Lauren G. Koch, David E. Stec

Pharmacology and Nutritional Sciences Faculty Publications

Exercise in humans and animals increases plasma bilirubin levels, but the mechanism by which this occurs is unknown. In the present study, we utilized rats genetically selected for high capacity running (HCR) and low capacity running (LCR) to determine pathways in the liver that aerobic exercise modifies to control plasma bilirubin. The HCR rats, compared to the LCR, exhibited significantly higher levels of plasma bilirubin and the hepatic enzyme that produces it, biliverdin reductase-A (BVRA). The HCR also had reduced expression of the glucuronyl hepatic enzyme UGT1A1, which lowers plasma bilirubin. Recently, bilirubin has been shown to activate the peroxisome …


Assessing The Affect Of Distance From Settlements On Landscape Function Analysis Indices In Central Mongolia, J. Addison, M. Nyamtseren Sep 2020

Assessing The Affect Of Distance From Settlements On Landscape Function Analysis Indices In Central Mongolia, J. Addison, M. Nyamtseren

IGC Proceedings (1977-2023)

No abstract provided.


The Use Of Criteria And Indicator Monitoring Of Ecosystem Sustainability To Assess Ecosystem Services On Grasslands/Rangelands, R. Dennis Child, Janette Kaiser, Ralph Crawford Sep 2020

The Use Of Criteria And Indicator Monitoring Of Ecosystem Sustainability To Assess Ecosystem Services On Grasslands/Rangelands, R. Dennis Child, Janette Kaiser, Ralph Crawford

IGC Proceedings (1977-2023)

No abstract provided.


Microglial-Associated Responses To Comorbid Amyloid Pathology And Hyperhomocysteinemia In An Aged Knock-In Mouse Model Of Alzheimer's Disease, David J. Braun, Edgardo R. Dimayuga, Josh M. Morganti, Linda J. Van Eldik Sep 2020

Microglial-Associated Responses To Comorbid Amyloid Pathology And Hyperhomocysteinemia In An Aged Knock-In Mouse Model Of Alzheimer's Disease, David J. Braun, Edgardo R. Dimayuga, Josh M. Morganti, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Elevated blood homocysteine levels, termed hyperhomocysteinemia (HHcy), is a prevalent risk factor for Alzheimer's disease (AD) in elderly populations. While dietary supplementation of B-vitamins is a generally effective method to lower homocysteine levels, there is little if any benefit to cognition. In the context of amyloid pathology, dietary-induced HHcy is known to enhance amyloid deposition and certain inflammatory responses. Little is known, however, about whether there is a more specific effect on microglia resulting from combined amyloid and HHcy pathologies.

METHODS: The present study used a knock-in mouse model of amyloidosis, aged to 12 months, given 8 weeks of …


Sequential Order Of Swing Phase Initiation In Baseball, Ethan Stewart, Megan Stewart, Jeffrey Simpson, Adam Knight, Harish Chander, Robert Shapiro Sep 2020

Sequential Order Of Swing Phase Initiation In Baseball, Ethan Stewart, Megan Stewart, Jeffrey Simpson, Adam Knight, Harish Chander, Robert Shapiro

Kinesiology and Health Promotion Faculty Publications

In order to successfully hit a baseball, hitters must utilize a series of preparatory movements (swing phases) which include shifting their body weight, stepping, landing, and swinging. The purpose of this study was to examine the differences between start times for swing phases (shifting, stepping, landing, and swinging)for currently active baseball players. Participants (n = 12) were all current collegiate baseball athletes. Retroreflective markers, surface electromyography (EMG) and two force platforms were utilized to complete a swing analysis. Each participant completed five swinging trials off a tee. All dependent variables were compared using a repeated measures 1×4 ANOVA with …


Experiences With Grazing The New Annual Pasture Legume Biserrula Pelecinus L. In Southern Australia Production Benefits And Risk Of Photosensitisation, Clinton K. Revell, N. Robertson, I. Williams Sep 2020

Experiences With Grazing The New Annual Pasture Legume Biserrula Pelecinus L. In Southern Australia Production Benefits And Risk Of Photosensitisation, Clinton K. Revell, N. Robertson, I. Williams

IGC Proceedings (1977-2023)

No abstract provided.


Testing Non‐Equilibrium Theory: Effects Of Grazing On Plant Community Composition And Soil Nutrient Availability In Dry Southern Mongolian Steppes, Karsten Wesche, Katrin Ronnenberg Sep 2020

Testing Non‐Equilibrium Theory: Effects Of Grazing On Plant Community Composition And Soil Nutrient Availability In Dry Southern Mongolian Steppes, Karsten Wesche, Katrin Ronnenberg

IGC Proceedings (1977-2023)

No abstract provided.


Indicators Of Sustainability For Production And Biodiversity Conservation In Australian Rangelands, Margaret H. Friedel, G. N. Bastin, A. K. Smyth Sep 2020

Indicators Of Sustainability For Production And Biodiversity Conservation In Australian Rangelands, Margaret H. Friedel, G. N. Bastin, A. K. Smyth

IGC Proceedings (1977-2023)

No abstract provided.


Ethics And Economics Of The Covid-19 Pandemic In The United States, Peter Hilsenrath, Tyrone F. Borders Sep 2020

Ethics And Economics Of The Covid-19 Pandemic In The United States, Peter Hilsenrath, Tyrone F. Borders

Health Management and Policy Faculty Publications

The Covid-19 experience provides a natural experiment in personal and social ethics. Difficult decisions are routinely made to optimize lives and livelihoods. This commentary provides background and insight into the ethical and economic foundations underpinning dilemmas of this historic pandemic.


Tonic And Phasic Amperometric Monitoring Of Dopamine Using Microelectrode Arrays In Rat Striatum, Martin Lundblad, David A. Price, Jason J. Burmeister, Jorge E. Quintero, Peter Huettl, Francois Pomerleau, Nancy R. Zahniser, Greg A. Gerhardt Sep 2020

Tonic And Phasic Amperometric Monitoring Of Dopamine Using Microelectrode Arrays In Rat Striatum, Martin Lundblad, David A. Price, Jason J. Burmeister, Jorge E. Quintero, Peter Huettl, Francois Pomerleau, Nancy R. Zahniser, Greg A. Gerhardt

Neuroscience Faculty Publications

Here we report a novel microelectrode array recording approach to measure tonic (resting) and phasic release of dopamine (DA) in DA-rich areas such as the rat striatum and nucleus accumbens. The resulting method is tested in intact central nervous system (CNS) and in animals with extensive loss of the DA pathway using the neurotoxin, 6-hydroxyDA (6-OHDA). The self-referencing amperometric recording method employs Nafion-coated with and without m-phenylenediamine recording sites that through real-time subtraction allow for simultaneous measures of tonic DA levels and transient changes due to depolarization and amphetamine-induced release. The recording method achieves low-level measures of both tonic and …


Neurotropic Lineage Iii Strains Of Listeria Monocytogenes Disseminate To The Brain Without Reaching High Titer In The Blood, Taylor E. Senay, Jessica L. Ferrell, Filip G. Garrett, Taylor M. Albrecht, Jooyoung Cho, Katie L. Alexander, Tanya Myers-Morales, Olivia F. Grothaus, Sarah E. F. D'Orazio Sep 2020

Neurotropic Lineage Iii Strains Of Listeria Monocytogenes Disseminate To The Brain Without Reaching High Titer In The Blood, Taylor E. Senay, Jessica L. Ferrell, Filip G. Garrett, Taylor M. Albrecht, Jooyoung Cho, Katie L. Alexander, Tanya Myers-Morales, Olivia F. Grothaus, Sarah E. F. D'Orazio

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Listeria monocytogenes is thought to colonize the brain using one of three mechanisms: direct invasion of the blood-brain barrier, transportation across the barrier by infected monocytes, and axonal migration to the brain stem. The first two pathways seem to occur following unrestricted bacterial growth in the blood and thus have been linked to immunocompromise. In contrast, cell-to-cell spread within nerves is thought to be mediated by a particular subset of neurotropic L. monocytogenes strains. In this study, we used a mouse model of foodborne transmission to evaluate the neurotropism of several L. monocytogenes isolates. Two strains preferentially colonized the brain …


Timing Of Maximal Weight Reduction Following Bariatric Surgery: A Study In Chinese Patients, Ting Xu, Chen Wang, Hongwei Zhang, Xiaodong Han, Weijie Liu, Junfeng Han, Haoyong Yu, Jin Chen, Pin Zhang, Jianzhong Di Sep 2020

Timing Of Maximal Weight Reduction Following Bariatric Surgery: A Study In Chinese Patients, Ting Xu, Chen Wang, Hongwei Zhang, Xiaodong Han, Weijie Liu, Junfeng Han, Haoyong Yu, Jin Chen, Pin Zhang, Jianzhong Di

Computer Science Faculty Publications

Introduction: Bariatric surgery is a well-received treatment for obesity with maximal weight loss at 12–36 months postoperatively. We investigated the effect of early bariatric surgery on weight reduction of Chinese patients in accordance with their preoperation characteristics.

Materials and Methods: Altogether, 409 patients with obesity from a prospective cohort in a single bariatric center were enrolled retrospectively and evaluated for up to 4 years. Measurements obtained included surgery type, duration of diabetic condition, besides the usual body mass index data tuple. Weight reduction was expressed as percent total weight loss (%TWL) and percent excess weight loss (%EWL).

Results: RYGB or …


Cocaine Hydrolase-Fc Fusion Proteins For Cocaine And Methods For Utilizing The Same, Chang-Guo Zhan, Fang Zheng, Hsin-Hsiung Tai, Xiabin Chen, Liu Xue, Shurong Hou Sep 2020

Cocaine Hydrolase-Fc Fusion Proteins For Cocaine And Methods For Utilizing The Same, Chang-Guo Zhan, Fang Zheng, Hsin-Hsiung Tai, Xiabin Chen, Liu Xue, Shurong Hou

Pharmaceutical Sciences Faculty Patents

The presently-disclosed subject matter includes isolated polypeptides that comprise a butyrylcholinestrase (BChE) polypeptide and a second polypeptide. The BChE polypeptide as well as the second polypeptide can be variants and/or fragments thereof. The presently-disclosed subject matter also includes a pharmaceutical composition that comprises the present isolated polypeptide and a suitable pharmaceutical carrier. Further still, methods are provided for treating cocaine-induced conditions, and comprise administering the isolated polypeptide and/or pharmaceutical compositions thereof to an individual.


David S. Miller: Scientist, Mentor, Friend--A Tribute And Thank You, Björn Bauer, J. Larry Renfro, Karl J. Karnaky, Rosalinde Masereeuw, Gert Fricker, Ron E. Cannon, Anika M. S. Hartz Sep 2020

David S. Miller: Scientist, Mentor, Friend--A Tribute And Thank You, Björn Bauer, J. Larry Renfro, Karl J. Karnaky, Rosalinde Masereeuw, Gert Fricker, Ron E. Cannon, Anika M. S. Hartz

Pharmaceutical Sciences Faculty Publications

David S. Miller was Acting Scientific Director of the Division of Intramural Research at the National Institute of Environmental Health Sciences, National Institutes of Health, and Head of the Intracellular Regulation Group in the Laboratory of Toxicology and Pharmacology before he retired in 2016. David received his Ph.D. in biochemistry from the University of Maine in 1973. David was a Group Leader at the Michigan Cancer Foundation before joining the NIEHS in 1985. His research covered a wide range from renal excretory transport mechanisms to regulation of transporters at the blood-CSF and blood-brain barriers, from fish, amphibians and birds to …


The Effects Of Fermentation And Split Application Of Liquid Swine Manure On Dry Matter Yield Of Italian Ryegrass And Subsequent Soil Quality, M. C. Kim, K. J. Hwang, S. T. Song, C. H. Hyun, T. H. Kang Sep 2020

The Effects Of Fermentation And Split Application Of Liquid Swine Manure On Dry Matter Yield Of Italian Ryegrass And Subsequent Soil Quality, M. C. Kim, K. J. Hwang, S. T. Song, C. H. Hyun, T. H. Kang

IGC Proceedings (1977-2023)

No abstract provided.


Multilocular Radiolucency Of The Mandibular Ramus And Body, Galal Omami Sep 2020

Multilocular Radiolucency Of The Mandibular Ramus And Body, Galal Omami

Oral Health Practice Faculty Publications

No abstract provided.


From Twisting To Settling Down As A Nurse In China: A Qualitative Study Of The Commitment To Nursing As A Career, Jiao Ye, Aimei Mao, Jialin Wang, Chizimuzo T. C. Okoli, Yuan Zhang, Huiqiong Shuai, Min Lin, Bo Chen, Linli Zhuang Sep 2020

From Twisting To Settling Down As A Nurse In China: A Qualitative Study Of The Commitment To Nursing As A Career, Jiao Ye, Aimei Mao, Jialin Wang, Chizimuzo T. C. Okoli, Yuan Zhang, Huiqiong Shuai, Min Lin, Bo Chen, Linli Zhuang

Nursing Faculty Publications

Background

The nurse workforce shortage, partially caused by high work turnover, is an important factor influencing the quality of patient care. Because previous studies concerning Chinese nurse work turnover were predominantly quantitative, they lacked insight into the challenges faced by nurses as they transition from university to their career. A successful transition can result in new nurses’ commitment to the career. As such, this study sought to understand how new nurses commit to the career, and focused on identifying facilitators and barriers to such commitment.

Methods

This was a qualitative study using a grounded theory design. Through purposive sampling, clinical …


Atom Identifiers Generated By A Neighborhood-Specific Graph Coloring Method Enable Compound Harmonization Across Metabolic Databases, Huan Jin, Joshua M. Mitchell, Hunter N. B. Moseley Sep 2020

Atom Identifiers Generated By A Neighborhood-Specific Graph Coloring Method Enable Compound Harmonization Across Metabolic Databases, Huan Jin, Joshua M. Mitchell, Hunter N. B. Moseley

Molecular and Cellular Biochemistry Faculty Publications

Metabolic flux analysis requires both a reliable metabolic model and reliable metabolic profiles in characterizing metabolic reprogramming. Advances in analytic methodologies enable production of high-quality metabolomics datasets capturing isotopic flux. However, useful metabolic models can be difficult to derive due to the lack of relatively complete atom-resolved metabolic networks for a variety of organisms, including human. Here, we developed a neighborhood-specific graph coloring method that creates unique identifiers for each atom in a compound facilitating construction of an atom-resolved metabolic network. What is more, this method is guaranteed to generate the same identifier for symmetric atoms, enabling automatic identification of …


Efficient Cocaine Degradation By Cocaine Esterase-Loaded Red Blood Cells, Luigia Rossi, Francesca Pierigè, Marco Agostini, Noemi Bigini, Veronica Termopoli, Yingting Cai, Fang Zheng, Chang-Guo Zhan, Donald W. Landry, Mauro Magnani Sep 2020

Efficient Cocaine Degradation By Cocaine Esterase-Loaded Red Blood Cells, Luigia Rossi, Francesca Pierigè, Marco Agostini, Noemi Bigini, Veronica Termopoli, Yingting Cai, Fang Zheng, Chang-Guo Zhan, Donald W. Landry, Mauro Magnani

Molecular Modeling and Biopharmaceutical Center Faculty Publications

Recombinant bacterial cocaine esterase (CocE) represents a potential protein therapeutic for cocaine use disorder treatment. Unfortunately, the native enzyme was highly unstable and the corresponding mutagenized derivatives, RBP-8000 and E196-301, although improving in vitro thermo-stability and in vivo half-life, were a partial solution to the problem. For cocaine use disorder treatment, an efficient cocaine-metabolizing enzyme with a longer residence time in circulation would be needed. We investigated in vitro the possibility of developing red blood cells (RBCs) loaded with RBP-8000 and E196-301 as a biocompatible system to metabolize cocaine for a longer period of time. RBP 8000 stability within human …


Develop A High-Throughput Screening Method To Identify C-P4h1 (Collagen Prolyl 4-Hydroxylase 1) Inhibitors From Fda-Approved Chemicals, Shike Wang, Kuo-Hao Lee, Nathália Victoria Araujo, Chang-Guo Zhan, Vivek M. Rangnekar, Ren Xu Sep 2020

Develop A High-Throughput Screening Method To Identify C-P4h1 (Collagen Prolyl 4-Hydroxylase 1) Inhibitors From Fda-Approved Chemicals, Shike Wang, Kuo-Hao Lee, Nathália Victoria Araujo, Chang-Guo Zhan, Vivek M. Rangnekar, Ren Xu

Pharmaceutical Sciences Faculty Publications

Collagen prolyl 4-hydroxylase 1 (C-P4H1) is an α-ketoglutarate (α-KG)-dependent dioxygenase that catalyzes 4-hydroxylation of proline on collagen. C-P4H1-induced prolyl hydroxylation is required for proper collagen deposition and cancer metastasis. Therefore, targeting C-P4H1 is considered a potential therapeutic strategy for collagen-related cancer progression and metastasis. However, no C-P4H1 inhibitors are available for clinical testing, and the high content assay is currently not available for C-P4H1 inhibitor screening. In the present study, we developed a high-throughput screening assay by quantifying succinate, a byproduct of C-P4H-catalyzed hydroxylation. C-P4H1 is the major isoform of collagen prolyl 4-hydroxylases (CP4Hs) that contributes the majority prolyl 4-hydroxylase …