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Metabolomic evidence of independent biotransformation pathways for terpenes in two specialist mammalian herbivores (genus Neotoma)

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Integrative Zoology 2024年第1期19卷 143-155页

作者： Katharina SCHRAMM Michele SKOPEC Denise DEARING Department of Biology University of UtahSalt Lake CityUtahUSA Department of Zoology Weber State UniversityOgdenUtahUSA

Herbivory is common in mammals,yet our understanding of detoxification processes used by mammals to biotrans-form plant secondary compounds(PSCs)is limited.Specialist herbivores are thought to have evolved detoxifica-tion mechanisms that rely more heavily on energetically cheap Phase I biotransformation reactions to process high levels of PSCs in their diets.We explored this hypothesis by comparing the urinary metabolite patterns of two spe-cialist herbivores(genus Neotoma).Neotoma stephensi is an obligate specialist on one-seeded juniper(Juniperus monosperma).Neotoma lepida is a generalist forager across its range,yet populations in the Great Basin specialize on utah juniper(J.osteosperma).While both juniper species have high levels of terpenes,the terpene profiles and quantities differ between the two.Individuals from both woodrat species were fed diets of each juniper in a cross-over design.Urine,collected over a 24-h period,was extracted and analyzed in an untargeted metabolomics approach using both GC-MS and HPLC-MS/MS.The obligate specialist N.stephensi excreted a unique pattern of Phase I metabolites when fed its native juniper,while N.lepida excreted a unique pattern of Phase II metabolites when fed its native juniper.Both woodrat species utilized the Phase II metabolic pathway of glucuronidation more heavily when consuming the more chemically diverse J.osteosperma,and N.stephensi utilized less glucuronida-tion than N.lepida when consuming J.monosperma.These results are consistent with the hypothesis that obligate specialists may have evolved unique and efficient biotransformation mechanisms for dealing with PSCs in their diet.

关键词： dietary specialization herbivory juniper metabolomics Neotoma

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Controlled release of FK506 from micropatterned PLGA films:potential for application in peripheral nerve repair

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Neural Regeneration Research 2018年第7期13卷 1247-1252页

作者： Brett Davis Susan Wojtalewicz Pratima Labroo Jill Shea Himanshu Sant Bruce Gale Jayant Agarwal Department of Bioengineering University of Utah Department of Surgery University of Utah Department of Mechanical Engineering University of Utah

After decades of research,peripheral nerve injury and repair still frequently results in paralysis,chronic pain and neuropathies leading to severe disability in patients.Current clinically available nerve conduits only provide crude guidance of regenerating axons across nerve gap without additional functionality.FK506（Tacrolimus）,an FDA approved immunosuppressant,has been shown to enhance peripheral nerve regeneration but carries harsh side-effects when delivered systemically.The objective of this study was to develop and evaluate a bioresorbable drug delivery system capable of local extended delivery of FK506 that also provides topological guidance cues to guide axon growth via microgrooves.Photolithography was used to create micropatterned poly（lactide-co-glycolic acid）（PLGA） films embedded with FK506.Non-patterned,10/10 μm（ridge/groove width）,and 30/30 μm patterned films loaded with 0,1,and 3 μg/cm2 FK506 were manufactured and characterized.In vitro FK506 rate of release testing indicated that the films are capable of an extended（at least 56 days）,controlled,and scalable release of FK506.Neurite extension bioactivity assay indicated that FK506 released from the films（concentration of samples tested ranged between 8.46–19.7 ng/m L） maintained its neural bioactivity and promoted neurite extension similar to control FK506 dosages（10 ng/m L FK506）.The multi-functional FK506 embedded,micropatterned poly（lactide-co-glycolic acid） films developed in this study have potential to be used in the construction of peripheral nerve repair devices.

关键词： nerve regeneration FK506 controlled release micropatterns topological cues PLGA

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Development of a field enhanced photocatalytic device for biocide of coliform bacteria

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Journal of Environmental Sciences 2016年第6期28卷 38-44页

作者： Jeff M.Huber Krista L.Carlson Otakuye Conroy-Ben Mano Misra Swomitra K.Mohanty Departments of Civil Engineering University of Utah Departments of Metallurgical Engineering University of Utah Departments of Chemical Engineering University of Utah

A field enhanced flow reactor using bias assisted photocatalysis was developed for bacterial disinfection in lab-synthesized and natural waters. The reactor provided complete inactivation of contaminated waters with flow rates of 50 mL/min. The device consisted of titanium dioxide nanotube arrays, with an externally applied bias of up to 6 V. Light intensity, applied voltage, background electrolytes and bacteria concentration were all found to impact the device performance. Complete inactivation of Escherichia coli W3110（- 8 × 10^3CFU/mL） occurred in 15 sec in the reactor irradiated at 25 mW/cm^2 with an applied voltage of 4 V in a 100 ppm NaCl solution. Real world testing was conducted using source water from Emigration Creek in Salt Lake City, utah. Disinfection of natural creek water proved more challenging, providing complete bacterial inactivation after 25 sec at 6 V. A reduction in bactericidal efficacy was attributed to the presence of inorganic and organic species, as well as the increase in robustness of natural bacteria.

关键词： Titanium dioxide Nanotubes Immobilized Photocatalysis Escherichia coli Inactivation

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Determinants of the impact of blood pressure variability on neurological outcome after acute ischaemic stroke

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Stroke & Vascular Neurology 2017年第1期2卷 1-6页

作者： Adam de Havenon Alicia Bennett Gregory J Stoddard Gordon Smith Lee Chung Steve O’Donnell J Scott McNally David Tirschwell Jennifer J Majersik Department of Neurology University of UtahSaltLake CityUtahUSA university of utah SaltLake CityUtahUSA university of Washington SeattleWashingtonUSA

Introduction: Increased blood pressure variability (BPV) is detrimental after acute ischaemic stroke, but the interaction between BPV and neuroimaging factors that directly influence stroke outcome has not been explored. Methods: We retrospectively reviewed inpatients from 2007 to 2014 with acute anterior circulation ischaemic stroke, CT perfusion and angiography at hospital admission, and a modified Rankin Scale (MRS) 30- 365 days after stroke onset. BPV indices included SD, coefficient of variation and successive variation of the systolic blood pressure between 0 and 120 hours after admission. Ordinal logistic regression models were fitted to MRS with predictor variables of BPV indices. Models were further stratified by CT perfusion volumetric measurements, proximal vessel occlusion and collateral score. Results: 110 patients met the inclusion criteria. The likelihood of a 1-point rise in the MRS increased with every 10 mm Hg increase in BPV (OR for the 3 BPV indices ranged from 2.27 to 5.54), which was more pronounced in patients with larger ischaemic core volumes (OR 8.37 to 18.0) and larger hypoperfused volumes (OR 6.02 to 15.4). This association also held true for patients with larger mismatch volume, proximal vessel occlusion and good collateral vessels. Conclusions: These results indicate that increased BPV is associated with worse neurological outcome after stroke, particularly in patients with a large lesion core volume, concurrent viable ischaemic penumbra, proximal vessel occlusion and good collaterals. This subset of patients, who are often not candidates for or fail acute stroke therapies such as intravenous tissue plasminogen activator or endovascular thrombectomy, may benefit from interventions aimed at reducing BPV.

关键词： impaired perfusion cerebral

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Plasmonic-enhanced electrochemical detection of volatile biomarkers with gold functionalized TiO_2 nanotube arrays

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Journal of Materials Science & Technology 2018年第6期34卷 905-913页

作者： Dhiman Bhattacharyya Pankaj Kumar York R.Smith Swomitra K.Mohanty Mano Misra Department of Metallurgical Engineering University of Utah Department of Chemical Engineering University of Utah

Titania nanotubular arrays （TNA） synthesized via electrochemical anodization is a stable and versatile material, widely studied for photocatalytic and sensing applications, whereas nano-sized gold particles are a known plasmonic material. Semiconductor-metal nanocomposites in isolated, embedded, or encapsulated form, when irradiated with proper light frequency can exhibit localized surface plasmon resonance （LSPR） effect. This effect can result in improved light adsorption and electrical properties of a material. In this study, we report the enhanced visible light photo-response of LSPR induced volatile organic biomarker vapor sensing at room temperature using a Au-embedded TNA electrochemical sensor. Two mechanisms are proposed. One based on classical physics （band theory）, which explains operation under non-irradiated conditions. The second mechanism is based on the coupling of classical and quantum physics （molecular orbitals）, and explains sensor operation under irradiated conditions.

关键词： TiO2 nanotube arrays Au particles Surface plasmon resonance Electrochemical sensor

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Adult mammalian neurogenesis and motivated behaviors

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Integrative Zoology 2018年第6期13卷 655-672页

作者： Claudia JORGENSEN Behavioral Science Department Utah Valley UniversityOremUtahUSA

Adult neurogenesis continues to captivate the curiosity of the scientific community;and researchers seem to have a particular interest in identifying the functional implications of such plasticity.While the majority of research focuses on the association between adult neurogenesis and learning and memory(including spatial learning associated with hippocampal neurogenesis and olfactory discrimination associated with neurogenesis in the olfactory system),the following review will explore the link to motivated behaviors.In particular,goal-directed behaviors such as sociosexual,parental,aggressive,as well as depression-and anxiety-like behaviors and their reciprocal association to adult neurogenesis will be evaluated.The review will detail research in humans and other mammalian species.Furthermore,the potential mechanisms underlying these neurogenic alterations will be highlighted.Lastly,the review will conclude with a discussion on the functional significance of these newly generated cells in mediating goal-directed behaviors.

关键词： adult neurogenesis aggression anxiety depression reproduction

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Metallacycles,metallacages,and their aggregate/optical behavior

Aggregate

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Aggregate 2021年第5期2卷 1-21页

作者： Yan Sun Peter J.Stang Department of Chemistry University of UtahSalt Lake CityUtahUSA

Since the first metallacycle was prepared by Verkade in 1983,various metallacycles and metallacages with controllable nanoscale shapes and sizes have been created by modular design and synthesis,showing unique properties that enable applications in catalysis,sensors,and biomedicine.Everything from their photophysical properties to their antitumor activities and catalysis was found to be influenced by their suprastructures.Thus,it is necessary and helpful to develop a systematic understanding of the relationships among the micro/nanostructures,the resultant photophysical/chemical properties,and the corresponding applications.In this review,we summarized the latest progress in this area in approximately the past 5 years.

关键词： aggregation coordination-driven assembly emission

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CYP1B1-derived epoxides modulate the TRPA1channel in chronic pain

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Acta Pharmaceutica Sinica B 2023年第1期13卷 68-81页

作者： Lili Sun Jie Zhang Changshan Niu Cassandra E.Deering-Rice Ronald W.Hughen John G.Lamb Katherine Rose Kevin M.Chase Marysol Almestica-Roberts Markel Walter Eric W.Schmidt Alan R.Light Baldomero M.Olivera Christopher A.Reilly Department of Pharmacology and Toxicology Center for Human ToxicologyUniversity of UtahSalt Lake CityUT84112USA Department of Anesthesiology School of MedicineUniversity of UtahSalt Lake CityUT 84112USA Department of Medicinal Chemistry University of UtahSalt Lake CityUT 84112USA School of Biological Sciences University of UtahSalt Lake CityUT 84112USA

Pain is often debilitating,and current treatments are neither universally efficacious nor without risks.Transient receptor potential(TRP)ion channels offer alternative targets for pain relief,but little is known about the regulation or identities of endogenous TRP ligands that affect inflammation and pain.Here,transcriptomic and targeted lipidomic analysis of damaged tissue from the mouse spinal nerve ligation(SNL)-induced chronic pain model revealed a time-dependent increase in Cyp1b1 mRNA and a concurrent accumulation of 8,9-epoxyeicosatrienoic acid(EET)and 19,20-EpDPA post injury.Production of 8,9-EET and 19,20-EpDPA by human/mouse CYP1B1 was confirmed in vitro,and 8,9-EET and 19,20-EpDPA selectively and dose-dependently sensitized and activated TRPA1 in overexpressing HEK-293 cells and Trpa1-expressing/AITC-responsive cultured mouse peptidergic dorsal root ganglia(DRG)neurons.TRPA1 activation by 8,9-EET and 19,20-EpDPA was attenuated by the antagonist A967079,and mouse TRPA1 was more responsive to 8,9-EET and 19,20-EpDPA than human TRPA1.This latter effect mapped to residues Y933,G939,and S921 of TRPA1.Intra-plantar injection of 19,20-EpDPA induced acute mechanical,but not thermal hypersensitivity in mice,which was also blocked by A967079.Similarly,Cyp1b1-knockout mice displayed a reduced chronic pain phenotype following SNL injury.These data suggest that manipulation of the CYP1B1-oxylipin-TRPA1 axis might have therapeutic benefit.

关键词： CYPIB1 Spinal nerve ligation Epoxides TRPA1 Calcium imaging Hyperalgesia Chronic pain Inflammation

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Establishing minimum clinically important difference values for the Patient-Reported Outcomes Measurement Information System Physical Function, hip disability and osteoarthritis outcome score for joint reconstruction, and knee injury and osteoarthritis out

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World Journal of Orthopedics 2018年第3期9卷 41-49页

作者： Man Hung Jerry Bounsanga Maren W Voss Charles L Saltzman Department of Orthopaedic Surgery Operations University of Utah Division of Public Health University of Utah Population Health Research Foundation University of Utah

AIM To establish minimum clinically important difference(MCID) for measurements in an orthopaedic patient population with joint disorders.METHODS Adult patients aged 18 years and older seeking care for joint conditions at an orthopaedic clinic took the Patient-Reported Outcomes Measurement Information System Physical Function(PROMIS~? PF) computerized adaptive test(CAT), hip disability and osteoarthritis outcome score for joint reconstruction(HOOS JR), and the knee injury and osteoarthritis outcome score for joint reconstruction(KOOS JR) from February 2014 to April 2017. MCIDs were calculated using anchorbased and distribution-based methods. Patient reports of meaningful change in function since their first clinic encounter were used as an anchor.RESULTS There were 2226 patients who participated with a mean age of 61.16(SD = 12.84) years, 41.6% male, and 89.7% Caucasian. Mean change ranged from 7.29 to 8.41 for the PROMIS~? PF CAT, from 14.81 to 19.68 for the HOOS JR, and from 14.51 to 18.85 for the KOOS JR. ROC cut-offs ranged from 1.97-8.18 for the PF CAT, 6.33-43.36 for the HOOS JR, and 2.21-8.16 for the KOOS JR. Distribution-based methods estimated MCID values ranging from 2.45 to 21.55 for the PROMIS~? PF CAT; from 3.90 to 43.61 for the HOOS JR, and from 3.98 to 40.67 for the KOOS JR. The median MCID value in the range was similar to the mean change score for each measure and was 7.9 for the PF CAT, 18.0 for the HOOS JR, and 15.1 for the KOOS JR.CONCLUSION This is the first comprehensive study providing a wide range of MCIDs for the PROMIS? PF, HOOS JR, and KOOS JR in orthopaedic patients with joint ailments.

关键词： Hhip disability and osteoarthritis outcome score for joint reconstruction Patient-Reported Outcomes Measurement Information System Physical Function Knee injury and osteoarthritis outcome score for joint reconstruction Minimum clinically important difference Joint Physical function Minimum detectable change Arthroplasty Orthopaedics Clinical outcomes

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ACC for generalized log canonical thresholds for complex analytic spaces

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Science China Mathematics 2024年

作者： Christopher D.Hacon Lingyao Xie university of utah Department of Mathematics

We show that generalized log canonical thresholds for complex analytic spaces satisfy the ACC(ascending chain condition) and we characterize the accumulation points.

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